ASSESSING THE ACTIVITY OF MYOPIC

CHOROIDAL NEOVASCULARIZATION
Comparison Between Optical Coherence
Tomography Angiography and Dye Angiography
SONGSHAN LI, MD, PHD, LIMEI SUN, MD, XIUJUAN ZHAO, MD, PHD, SIJIAN HUANG, BS,
XIAOLING LUO, BS, AIYUAN ZHANG, BS, CHONGLIN CHEN, MD, ZHIRONG WANG, MD,
CHENGXI LIU, MD, XIAOYAN DING, MD, PHD

Purpose: This study aims to suggest a novel strategy for assessing the activity of
myopic choroidal neovascularization (mCNV) based on optical coherence tomography
angiography (OCTA) and to compare it with traditional fundus fluorescein angiography as
the gold standard.
Methods: Macular OCTA images were obtained using RTVue XR Avanti with AngioVue.
Morphologic features of mCNV lesions were analyzed. Characteristics of OCTA in 41 eyes with
active mCNV and 41 eyes with inactive mCNV were analyzed. Optical coherence tomography
angiography parameters associated with mCNV activity and the clinical significance of their
sensitivity and specificity were analyzed using fundus fluorescein angiography as the reference.
Results: Of the total 108 patients, 82 had OCTA images with good quality which were
included in this study. Several anatomical features of the CNV lesions, including overall
appearance, branching with tiny vessels, presence of anastomoses/loops, and choroidal dark
halo, were considered the possible parameters associated with mCNV activity. The intra- and
interobserver agreements were substantial. To evaluate the CNV activity, sensitivity of overall
appearance, tiny vascular branching, and presence of anastomoses or loops were 65.9%,
82.9%, and 73.2%, respectively, whereas the specificity was 87.8%, 90.2%, and 92.7%,
respectively. However, the choroidal dark halo showed low specificity (46.3%) and failed in
terms of evaluating the activity of mCNV. A novel comprehensive procedure integrating
branching as a major parameter and overall appearance and presence of anastomoses/loops
as minor parameters was developed to evaluate mCNV activity with sensitivity of 95.1% and
specificity of 85.4%.
Conclusion: In mCNV, the acquisition rate of clear OCTA images was 75.9%. A novel
comprehensive diagnostic procedure combining mCNV appearance, vascular branching,
and anastomoses/loops by OCTA may be a valuable strategy to evaluate neovascular
activity in mCNV.
RETINA 40:1757–1764, 2020

M yopic choroidal neovascularization (mCNV) is

one of the most common vision-threatening com-
plications of pathologic myopia. It affects 5%–11% of
treatment has become the first-line treatment for
mCNV, leading to not only anatomical improvements
but also functional improvements.6 During anti-VEGF
patients with pathologic myopia and 0.04%–0.05% of treatment, monitoring neovascular activity is essential
the general population.1 It is particularly prevalent for a re-treatment decision making.
among young and middle-aged Asians.1,2 With- Fundus fluorescein angiography (FFA) with dye
out treatment, there have been very poor outcomes injection is considered the gold standard for detecting
for mCNV. Visual acuity may drop to 20/200 or less mCNV and assessing its activity.6,7 However, FFA is
within 5 years, with a tendency to progressively time consuming and invasive, resulting in varying de-
enlarge the lesion or CNV-related macular atrophy.3–5 grees of patient discomfort, including anaphylactic reac-
Anti–vascular endothelial growth factor (VEGF) tions that can occur during and/or after FFA. A total of

1757
1758 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2020  VOLUME 40  NUMBER 9

4.8% patients were reported to have experienced adverse (SE) , 26.00 D or axial length (AL) .26.5 mm; 3)
events after the FFA, including nausea (2.9%), vomiting accompanied by characteristic degenerative changes in
(1.2%), and flushing/itching (0.5%).8 Recently, optical the choroid and retina or by myopic-related sclera
coherence tomography angiography (OCTA) has been changed, such as staphyloma. The exclusion criteria
introduced in the clinical practice. Optical coherence were as follows: 1) other secondary choroidal neovas-
tomography angiography provides depth-resolved visu- cular diseases, such as wet AMD or angioid streaks; 2)
alization of the retinal and choroidal vasculature without poor FFA or OCTA image quality due to severe vit-
the need for dye injection. The technology has been reous hemorrhage; 3) poor FFA or OCTA image qual-
applied for the diagnosis and monitoring of CNV in ity due to posterior staphyloma or cataract, the
age-related macular degeneration (AMD). A recent case presence of other ocular diseases; 4) or evidence of
series analyzed the morphologic characteristics of any conditions other than CNV which may have
mCNV before and after anti-VEGF therapy by OCTA. affected the FFA and OCTA images. For patients with
Querques et al9 described the OCTA features of mCNV quiescent mCNV, the requirements included a history
and demonstrated its high sensitivity and specificity for of active mCNV treated with anti-VEGF previously or
neovascular detection. Nevertheless, studies of OCTA in confirmed with an image in the imaging bank.
monitoring mCNV activity remain very limited. The A comprehensive ophthalmic examination, includ-
present study aims to evaluate the presence and structural ing measurement of best-corrected visual acuity,
features of mCNV on OCTA, to estimate the sensitivity intraocular pressure, slit-lamp examination, FFA, and
and specificity of OCTA in assessing mCNV activity, SD-OCT (Spectralis + HRA; Heidelberg Engineering,
and to compare it with FFA as the gold standard. Heidelberg, Germany), was performed in each patient.
Optical coherence tomography angiography was per-
formed by the RTVue AngioVue System, XR Avanti
Methods
SD-OCT device (Optovue, Inc, Fremont, CA), based
on a high-speed SD-OCT platform that operates at
Patients
70,000 axial scans per second. A macula cube (3 ·
This retrospective case series was conducted in 3 mm) centered the fovea was acquired; in cases of
Zhongshan Ophthalmic Center with the permission of partial visualization of the entire CNV network,
the Institutional Review Board of the Zhongshan a larger (6 · 6 mm) image was obtained. The image
Ophthalmic Center, Sun Yat-sen University. All of the outer retina slab and choroid slab was collected
investigations followed the tenets of the Declaration and analyzed by the RTVue XR angio analytics soft-
of Helsinki. A total of 82 eyes from 82 patients with ware (2017.1.0.155). Manual adjustment was made by
active or quiescent mCNV were enrolled in this study two expert retina specialists (S.L. and L.S.) to ensure
from March 2014 to July 2018. The inclusion criteria accurate segmentation if necessary.
were as follows: 1) aged $18 years; 2) diagnosis of
pathologic myopia as defined by spherical equivalent
Imaging
From the State Key Laboratory of Ophthalmology, Retina Divi- Typical active mCNV was subfoveal or juxtafoveal
sion, Zhongshan Ophthalmic Center, Sun Yat-sen University,
Guangzhou, China. Type 2 neovascularization and “classic” on FFA, with
Supported in part by grants from the Fundamental Research well-defined hyperfluorescence on early frames and
Funds of State Key Laboratory of Ophthalmology, research funds dye leakage on late frames. The dye leakage was iden-
of Sun Yat-sen University (15ykjc22d; Guangzhou, Guangdong,
China) (18zxxt73; Guangzhou, Guangdong, China), Science and tified by an increased area of hyperfluorescence in the
Technology Program Guangdong, China (2016A020215096; late phase compared with the early phase. In addition,
Guangzhou, Guangdong, China) (2018A030310230; Guangzhou, active mCNV lesions appeared as elevation of the,
Guangdong, China), and the grant from the National Natural Sci-
ence Foundation of China (31800873). The sponsors and funding presenting subretinal or intraretinal hyporeflective or
organizations had no role in the design or conduct of this research. hyperreflective exudation, along with overlying fuzzy
None of the authors have any conflicting interests to disclose. areas and absence of external limiting membrane vis-
S. Li and L. Sun share the first authorship.
This is an open-access article distributed under the terms of the ibility on structural SD-OCT. In quiescent mCNV,
Creative Commons Attribution-Non Commercial-No Derivatives there are no signs of activity by FFA at the time of
License 4.0 (CCBY-NC-ND), where it is permissible to download OCTA acquisition. The lesions present as staining of
and share the work provided it is properly cited. The work cannot
be changed in any way or used commercially without permission a CNV scar on FFA and a well-defined profile with
from the journal. hyperreflective borders on structural SD-OCT. The
Reprint requests: Xiaoyan Ding, MD, PhD, State Key Labora- OCTA images were assessed for classification of sev-
tory of Ophthalmology, Retina Division, Zhongshan Ophthalmic
Center, Sun Yat-sen University, Guangzhou, China, 510000; eral anatomical descriptors that were considered to be
e-mail: [email protected] associated with the activity of the myopic neovascular
 OCTA IN ASSESSING THE ACTIVITY OF mCNV  LI ET AL 1759

lesion based on previous wAMD studies10: 1) overall preted as follows: less than 0, poor agreement; 0 to 0.20,
appearance, a well-defined medusa or a sea-fan-shaped slight agreement; 0.21 to 0.40, fair agreement; 0.41 to
CNV lesion versus an irregular CNV lesion with linear 0.60, moderate agreement; 0.61 to 0.80, substantial
vessels; 2) branching, numerous tiny capillaries versus agreement; and greater than 0.80, almost perfect agree-
rare, large, mature vessels; 3) the presence of anasto- ment. The level of significance was set at P = 0.05.
moses or loops; and 4) the presence of a perilesional
dark halo. Two independent investigators (S.L. and
L.S.) evaluated OCTA without visualization of the Results
corresponding FFA or SD-OCT B-scan independently.
Any discrepancies in the data were resolved through Study Population and Main Clinical Findings
reassessment and discussion with a senior researcher
(X.D.). Examples of overall appearance, branching, A total of 108 OCTA and FFA examinations in 108
presence of anastomoses/loops and dark halo are rep- mCNV eyes were checked by two retinal specialists.
resented in Figure 1. Twenty-six were excluded because of unsatisfactory
OCTA image quality. Of these 26 mCNVs, 15 could
not be detected in OCTA and showed as small CNV
Statistical Analysis
(diameter of CNV ,100 mm in OCT), 9 showed poor
Statistical analysis was performed using Graph Pad images due to staphyloma, 1 was excluded because of
(GraphPad Software, CA) or SPSS (SPSS Inc, Chicago, impaired eye fixation, and 1 was excluded due to
IL). Kappa analysis was performed to examine the intra- refractive opacity. Finally, 82 eyes from 82 patients
and interobserver agreement between the two readers. were included in this study. Of these, 42 patients
Diagnostic sensitivity, specificity, positive predictive (51.2%) were women; the mean age was 47.77 ±
value (PPV), negative predictive value, agreement 13.09 years (range, 20–74 years). The average SE
percentage, and Youden index were calculated for each was 211.71 ± 4.80 D, and the mean AL was 28.99
OCTA parameter. The level of agreement was deter- ± 1.22 mm. Active mCNVs were found in 41 eyes of
mined by Cohen k-analysis. Kappa values were inter- 41 patients (Group A), and quiescent mCNV was

Fig. 1. OCTA images and FA images of (A–D) a recurrent active mCNV in a 26-year-old woman with AL of 28.78 mm and SE of 29.875 D and (E–
H) a quiescent mCNV in a 54-year-old man with AL of 28.89 mm and SE of 211.375 D. A. The OCTA image shows the presence of neovascular
structure in the outer retina layer. The lesion is composed by numerous tiny capillaries (arrowhead) with clear anastomoses and loops (arrow). B. The
OCTA scan of the choroid layer under the mCNV shows a hyposignaling halo surrounding the lesion (arrow). C. Fluorescein angiography in the early
phase reveals the neovascular structure, whose shape is similar to the one showed by OCTA. The shape of this mCNV is angular, which usually is a sign
of previous treatment or shrunken lesion. D. The presence of mild leakage (arrowheads) of this lesion is observed in the late phase of FA. E. The OCTA
image of a quiescent mCNV appears as an irregular shape and is composed by large, rare, mature vessels which lacks anastomose or loop. F. The
choroid dark halo is absent in the choroid layer. G. On the early phase of fluorescein angiography, a hyperfluorescent vascular structure is clearly
visible. H. No leakage is observed on the late phase in this inactive lesion.
1760 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2020  VOLUME 40  NUMBER 9

identified in 41 eyes of 41 patients (Group Q). In Diagnostic Sensitivity and Specificity of Optical
Group A, 7 of the 41 patients received anti-VEGF Coherence Tomography Angiography Parameters
treatment 3 months ago. In Group Q, all patients Compared With Fundus Fluorescein Angiography
received anti-VEGF treatment previously. No statisti-
Four qualitative parameters, A (appearance)—B
cal differences were found in terms of age, AL, and SE
(branching)—A (anastomoses/loops)—D (dark halo),
between the groups (P = 0.17, 0.52, and 0.34, respec-
were used to evaluate mCNV activity. The overall
tively). Complete demographics are shown in Table 1.
appearance of medusa/sea fan on OCTA and leakage
on FFA achieved a moderate agreement in 63 of the
Intra- and Interobserver Agreement
82 cases (76.8%), with a k-value of 0.537, sensitivity
Four descriptive parameters, “A (appearance)—B of 65.9%, specificity of 87.8%, and PPV of 84.4%. In 19
(branching)—A (anastomoses/loops)—D (dark halo),” cases (23.2%), consensus was not reached; of these 19
were used in this study: overall Appearance of the cases, 14 presented leakage during FA but with an irreg-
neovascular lesion, Branching of vasculature, presence ular shape in OCTA and 5 cases were shaped as medusa/
of Anastomoses/loops, and presence of Dark halo. The sea fan on OCTA but without fluorescein leakage.
intraobserver agreement of A-B-A-D was substantial Lesions with tiny vascular branching also achieved
to almost perfect, with kappa values of 0.955, 0.892, good agreement in 71 of the 82 cases (86.6%), with a k-
0.876, and 0.937, respectively. Substantial to almost value of 0.732, sensitivity of 82.9%, specificity of 90.2%,
perfect interobserver agreement was also observed, and PPV of 89.5%. Consensus was not reached in 11
with kappa values of 0.933, 0.783, 0.744, and 0.905, cases (13.4%). In total, of these 11 cases, 4 were with tiny
respectively (Table 2). branching and capillaries on OCTA but no leakage on
FFA, whereas 7 cases showing only rare, large, mature
Morphology Findings in Active and Quiescent vessels on OCTA showed fluorescent leakage on FFA.
Myopic Choroidal Neovascularization on Optical The presence of anastomoses and loops was noted
Coherence Tomography Angiography with good agreement on OCTA compared with FFA in
The overall appearance of the neovascular lesions 68 of the 82 cases (82.8%), with a k-value of 0.659,
was defined as medusa or sea fan in 32 eyes, including sensitivity of 73.2%, specificity of 92.7%, and PPV of
27 in Group A (n = 41, 65.9%) and 5 in Group Q (n = 90.9%. A consensus was not reached in 14 cases
41, 12.2%) (P , 0.0001). Tiny vascular branching (17.1%). A diagnosis of anastomoses and loops was
was found in 38 eyes, including 34 in Group A (n = made in 30 of the 41 active mCNV cases but only in 3
41, 82.9%) and 4 in Group Q (n = 41, 9.8%) (P , of the 41 silent mCNV lesions.
0.0001). Multiple anastomoses and loops were identi- However, only fair agreement between choroid
fied in 33 eyes, with 30 in Group A (n = 41, 73.2%) dark halo on OCTA and FFA leakage was reached in
and 3 in Group Q (n = 41, 7.3%) (P , 0.0001). Cho- 52 of the 82 sessions (63.4%), with a k-value of
roid dark halo, the hypointense perilesional halo at the 0.268. The sensitivity was 80.5%, which is accept-
choroid layer, was considered in 55 eyes, including 33 able; however, the specificity was only 46.3%. A
in Group A (n = 41, 80.5%) and 22 in Group Q (n = consensus was not reached in 30 cases (36.6%).
41, 53.7%) (P = 0.01) (Table 3). Choroid dark halo was not identified in 8 of the 41

Table 1. Demographic Characteristics

Characteristic Active mCNV Group Quiescent mCNV Group P
No. of patients (no. of eyes) 41 (41) 41 (41)
Male/Female (n) 20/21 20/21 1.0
OD/OS 21/20 18/23 0.51
Mean age ± SD, years (min to max) 49.76 ± 13.64 (20 to 74) 45.78 ± 12.37 (21 to 69) 0.17
Mean AL, mm (min to max) 29.09 ± 1.20 (26.73 to 31.53) 28.88 ± 1.25 (26.09 to 32.26) 0.52
Mean SE, D (min to max) 212.35 ± 5.00 (220.75 to 26) 211.10 ± 4.62 (220.25 to 26.5) 0.34
Mean BCVA, ETDRS letters 49.2 ± 14.3 (40 to 72) 57.3 ± 13.3 (49 to 73) 0.01*
(min to max)
Area of CNV, mm2 (min to max) 0.62 ± 0.58 (0.23 to 1.26) 0.30 ± 0.43 (0.02 to 1.17) 0.01*
Subfoveal lesion/parafoveal 5/41 7/41 0.76
lesion (n)
BCVA, best-corrected visual acuity.
* P,0.05.
 OCTA IN ASSESSING THE ACTIVITY OF mCNV  LI ET AL 1761

Table 2. Interobserver Agreement Regarding the OCTA Characters

Observer 2
Character Observer 1 + 2 % Agreement Kappa ± SE Strength of Agreement
Medusa or sea-fan shape + 31 2 96.34 0.924 ± 0.043 Very good
2 1 48
Tiny branching + 31 5 86.59 0.728 ± 0.076 Good
2 6 40
Loop or anastomoses + 29 4 89.02 0.773 ± 0.071 Good
2 5 44
Choroid dark halo + 54 1 96.34 0.916 ± 0.047 Very good
2 2 25

active mCNV lesions (19.5%) and 22 cases with taneously, the CNV lesion is likely to be active (7 of
dark halo did not leak on FFA. the 44 eyes). If “no,” the CNV lesion is likely to be
inactive (Figures 3 and 4). In summary, an mCNV
lesion with the major parameter (branching) positive
A Noninvasive Accessing Strategy for Myopic or two minor parameters (appearance and anastomo-
Choroidal Neovascularization Activity by Optical ses/loops) positive should be considered an active
Coherence Tomography Angiography lesion. With this novel procedure to evaluate the lesion
Considering the re-treatment requirement during activity, the final sensitivity and specificity reached
anti-VEGF strategy and the poor prognosis of this 95.1% and 85.4%, respectively. The final agreement
disease if left untreated, a criterion with excellent was as high as 90.2% (74 of 82), with kappa value of
sensitivity and good specificity is highly recommen- 0.805, considered almost perfect agreement (Table 4).
ded to determine the treatment needed for active
mCNV lesions to the greatest extent possible. Among
the four OCTA parameters A-B-A-D, branching of Discussion
tiny vasculature appeared to have the highest sensitiv-
ity (82.9%). Five of seven active lesions that appeared Owing to the ability to visualize retinal and choroidal
with no branching of vessels showed medusa/sea-fan vasculature noninvasively with high resolution, several
shape and anastomoses/loops. In Group Q, only two studies have reported on the potential value of OCTA in
lesions appeared as medusa/sea-fan shape and anasto- a variety of ocular diseases, including AMD, polypoidal
moses/loops simultaneously. Therefore, we suggest choroidal vasculopathy (PCV), and mCNV. Several
branching could be used as the major parameter to studies showed that the sensitivity (75.7–100.0%) and
assess the mCNV activity. In addition to branching, specificity (67.6–100.0%) appear to be high for detect-
the presence of medusa or sea-fan shape and anasto- ing CNV in AMD by OCTA, especially for Type II
moses/loops should also be considered as minor CNV, compared with the gold standard FFA.11–16 As
parameters in the evaluation of lesion activity. most of the mCNVs appear as Type II CNV, located
We developed a novel comprehensive procedure above the retina pigment epithelial layer and can be
intergrading the major (branching) and minor (appear- easily imaged, the detection of mCNV in OCTA
ance and anastomoses/loops) parameters. First, the showed high sensitivity (90.5–94.1%) in several studies
major parameter (branching) is judged. If “yes” (38 as well as our own experience.17–19 Nevertheless, some
eyes), the CNV lesion is likely active (n = 82) (Figure features of pathologic myopia such as posterior staph-
2) and if “no” (44 eyes), the two minor parameters are yloma may diminish OCTA image quality and may
evaluated. If the lesion appears as medusa or sea-fan limit the interpretation of OCTA, especially for CNV
shaped in the presence of anastomoses or loops simul- located on the slope of staphyloma. As reported by

Table 3. OCTA Characters in Active mCNV and Inactive mCNV

Character Active mCNV (n = 41), n (%) Inactive mCNV (n = 41), n (%) P
Medusa or sea-fan shape 27 (65.9) 5 (12.2) ,0.0001
Tiny branching 34 (82.9) 4 (9.8) ,0.0001
Loop or anastomoses 30 (73.2) 3 (7.3) ,0.0001
Choroid dark halo 33 (80.5) 22 (53.7) 0.01
1762 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2020  VOLUME 40  NUMBER 9

Fig. 2. Typical OCTA image and traditional multimodal images in Fig. 3. Typical OCTA image and traditional multimodal images in
a 55-year-old woman with active mCNV (AL: 29.47 mm; SE: 212.25 a 43-year-old woman with inactive mCNV (AL: 29.70 mm; SE: 218.5
D). A. Typical medusa-shaped neovascular network with numerous tiny D). A. An irregular-shaped neovascular network with mature, large
capillaries (branching) and anastomoses/loops in OCTA. B–D. Tradi- linear vessels and absent anastomoses/loops in OCTA. B–D. Traditional
tional multimodal images confirm the lesion is an active mCNV by the multimodal images confirm the lesion is an inactive mCNV by the well-
fuzzy shape around the hyperreflective CNV in OCT (B) and late-phase defined boundary around the hyperreflective CNV in OCT (B) and
leakage of the neovascular lesion on FA (C–D). absent late-phase leakage of the neovascular lesion on FA (C–D).

Miyata et al,17 75% of the patients (21 of 28) achieved Coscas’ study in wAMD reported that the PPV of
OCTA images with sufficient quality, similar to the shape, branching, anastomoses, and choroid dark halo
75.9% (82 of the 108) achieved in the present study. was 59/59, 59/60, 59/60, and 53/65, respectively.10
Several studies have assessed the ability of non- Here, in mCNV, all these characteristics were easily
invasive methods, such as structure-OCT, in deter- identified and are repeatable in clinical practice with
mining the activity of CNV in AMD. The results were good inter- and intraobserver agreement. The number
quite positive for revealing the fuzzy border of the of eyes with each of these four characters in the active
lesion; SRF and IRF were good indexes for activity mCNV group was significantly larger than that of the
checking in OCT.7 In 2015, Coscas et al10 also dem-
onstrated that OCTA patterns with 1) a well-defined
lacy-wheel or sea-fan shape, 2) tiny capillaries branch-
ing, 3) anastomoses and loops, and 4) perilesional
hypointense choroid halo were more highly correlated
with active CNV in wAMD than with FA. Thus, OCT
and OCTA in patients with AMD could both serve as
a noninvasive alternative for monitoring CNV and for
making treatment decisions during follow-up. Never-
theless, according to previous studies and our previous
investigation,20 most mCNV cases feature less leakage
on FFA and noteless SRF and IRF on OCT when
compared with wAMD, limiting the application of
structure-OCT in mCNV activity assessments. To
date, very few studies have focused on OCTA charac-
teristics in active and inactive mCNV lesions. In 2017,
Querques et al18 classified mCNV lesions as “interlac-
ing” and “tangled” and proposed that the “interlacing”
Fig. 4. A case of an active mCNV diagnosed by the presence of two
pattern may correspond to neovascular activity, sug- minor characters in a 40-year-old man (AL: 28.49 mm; SE: 29.5 D). A.
gesting that OCTA could be considered a potentially The lesion is barely seen tiny branching, but is medusa shaped and
useful tool in characterizing CNV by its morphology present with anastomoses/loops (arrow) in OCTA. B–D. Traditional
multimodal images confirm the lesion is an active mCNV by the fuzzy
and detecting CNV activity in eyes with pathologic shape around the hyperreflective CNV in OCT (B) and late-phase
myopia. leakage of the neovascular lesion on FA (C–D).
 OCTA IN ASSESSING THE ACTIVITY OF mCNV  LI ET AL 1763

Table 4. Diagnostic Performance of OCTA Characters Compared With FFA

% Positive % Negative Youden
Character % Sensitivity % Specificity Predictive Value Predictive Value Index Kappa ± SE
Medusa or sea-fan shape 65.9 87.8 84.4 72.0 0.537 0.537 ± 0.091
Tiny branching 82.1 90.2 85.2 88.1 0.723 0.732 ± 0.075
Loop or anastomoses 75.0 92.7 87.5 84.4 0.677 0.659 ± 0.082
Choroid dark halo 80.5 46.3 50.0 76.0 0.249 0.268 ± 0.100
One major criterion and 95.1 85.4 86.7 94.6 0.805 0.805 ± 0.065
two minor criteria

inactive mCNV group. Among these four character- as a screen for mCNV lesions in terms of both diag-
istics, our study confirmed that branching with tiny nosis and monitoring.
vessels could help differentiate active mCNV with Our study has a number of limitations. First, due to
a sensitivity and specificity of 82.9% and 90.2%, the long AL, posterior scleral staphyloma, and opacity
respectively. Similar findings were also acquired in of the refractive media, some OCTA data with low
the analysis of appearance and anastomoses/loops, quality were excluded from the study, possibly
which may aid discrimination of active mCNV from weakening the findings. Furthermore, patients with
quiescent ones. Furthermore, we demonstrated that the poor fixation due to low vision and poorly perfused or
PPV of A (appearance), B (branching), and A (anas- small lesions could also limit the quality of the images
tomoses) was 84.4%, 89.5% and 90.0%, respectively, and be excluded, possibly increasing the selection bias
similar to that in wAMD. Nevertheless, D (dark halo) of the study. In addition, the mCNV detection rate and
failed to qualify for evaluating mCNV activity, with the image quality may limit the usefulness of OCTA in
the specificity of 46.4% and PPV of 60%. In 2017, Al- mCNV screening in assessing the CNV activity.
Sheikh et al21 reported the flow deficit in myopic eyes Second, the sample of patients was limited, and the
by OCTA, possibly explaining the presence of dark retrospective nature of the analysis restricts the
halo in both active and quiescent mCNV lesions. We integrality of the patient information. Further inves-
supposed the possible reason could be decreased/ tigations with larger samples in various cohorts are
injured choroid vascular perfusion. warranted to confirm our observations. Third, another
This comparative analysis, focused on the potential limitation of the current OCTA technology is the
correspondence between the OCTA pattern and gold accuracy of segmentation algorithms. Manual segmen-
standard FFA, was intended to evaluate the efficacy of tation to accurately locate the CNV lesion may induce
OCTA in guiding treatment decisions. To identify inaccuracy, especially between observers.
every patient needing treatment, a diagnosis test with In conclusion, the results of our study provided
high sensitivity and appropriate specificity is preferred. a detailed description and classification of OCTA
Nevertheless, any one feature may not be sufficient to characteristics in active and inactive mCNV lesions.
accurately demonstrate active mCNV. Similarly, Cos- As opposed to wAMD, choroid dark halo has low
cas et al10 previously reported that these OCTA fea- specificity for diagnosing active mCNV. Active
tures could serve as biomarkers of CNV activity, not mCNV primarily appears as medusa or sea-fan shaped,
by any single one but by combining multiple markers with tiny vascular branching and presence of loops/
on OCTA. Querques et al18 roughly classified the anastomoses. A novel comprehensive procedure in-
mCNV lesion as “interlacing” and “tangled,” also cludes one major parameter or two minor parameters,
including several parameters such as branching and showing excellent sensitivity and good specificity in
appearance. Based on our findings, we developed evaluating the mCNV activity based on noninvasive
a novel comprehensive procedure to identify mCNV OCTA.
activity according to three image biomarkers: branch- Key words: OCTA, OCT angiography, mCNV,
ing, overall appearance, and anastomoses/loops. myopic choroidal neovascularization, FFA, activity.
Branching is considered the major sign and the other
two are considered minor ones. An mCNV lesion with
one major sign or two minor signs should be consid- References
ered active by this criterion with the final agreement as
1. Wong TY, Ferreira A, Hughes R, et al. Epidemiology and
90.2% (74 of the 82) and the Kappa as 0.805, indicat- disease burden of pathologic myopia and myopic choroidal
ing an almost perfect agreement. We believe this novel neovascularization: an evidence-based systematic review. Am
procedure is easily conducted, noninvasive, and rapid J Ophthalmol 2014;157:9–25.e12.
1764 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2020  VOLUME 40  NUMBER 9

2. Soubrane G. Choroidal neovascularization in pathologic myo- 12. Gong J, Yu S, Gong Y, et al. The diagnostic accuracy of
pia: recent developments in diagnosis and treatment. Surv optical coherence tomography angiography for neovascular
Ophthalmol 2008;53:121–138. age-related macular degeneration: a comparison with fundus
3. Yoshida T, Ohno-Matsui K, Yasuzumi K, et al. Myopic cho- fluorescein angiography. J Ophthalmol 2016;2016:7521478.
roidal neovascularization: a 10-year follow-up. Ophthalmology 13. Carnevali A, Cicinelli MV, Capuano V, et al. Optical coher-
2003;110:1297–1305. ence tomography angiography: a useful tool for diagnosis of
4. Shih YF, Ho TC, Hsiao CK, Lin LL. Visual outcomes for high treatment-naïve quiescent choroidal neovascularization. Am J
myopic patients with or without myopic maculopathy: a 10 Ophthalmol 2016;169:189–198.
year follow up study. Br J Ophthalmol 2006;90:546–550. 14. Ahmed D, Stattin M, Graf A, et al. Detection OF treatment-
5. Verteporfin in Photodynamic Therapy Study Group. Photody- naive choroidal neovascularization IN age-related macular
namic therapy of subfoveal choroidal neovascularization in degeneration BY swept source optical coherence tomography
pathologic myopia with verteporfin. 1-year results of a random- angiography. Retina 2018;38:2143–2149.
ized clinical trial–VIP report no. 1. Ophthalmology 2001;108: 15. Nikolopoulou E, Lorusso M, Micelli Ferrari L, et al. Optical
841–852. coherence tomography angiography versus dye angiography in
6. Ohno-Matsui K, Ikuno Y, Lai TYY, Gemmy Cheung CM. age-related macular degeneration: sensitivity and specificity
Diagnosis and treatment guideline for myopic choroidal neo- analysis. Biomed Res Int 2018;2018:6724818.
vascularization due to pathologic myopia. Prog Retin Eye Res 16. Soomro T, Talks J; Medscape. The use of optical coherence
2018;63:92–106. tomography angiography for detecting choroidal neovasculari-
7. Lee DH, Kang HG, Lee SC, Kim M. Features of optical coher- zation, compared to standard multimodal imaging. Eye (Lond)
ence tomography predictive of choroidal neovascularisation 2018;32:661–672.
treatment response in pathological myopia in association with 17. Miyata M, Ooto S, Hata M, et al. Detection of myopic choroi-
fluorescein angiography. Br J Ophthalmol 2018;102:238–242. dal neovascularization using optical coherence tomography
8. Kwiterovich KA, Maguire MG, Murphy RP, et al. Frequency angiography. Am J Ophthalmol 2016;165:108–114.
of adverse systemic reactions after fluorescein angiography. 18. Querques G, Corvi F, Querques L, et al. Optical coherence
Results of a prospective study. Ophthalmology 1991;98: tomography angiography of choroidal neovascularization second-
1139–1142. ary to pathologic myopia. Dev Ophthalmol 2016;56:101–106.
9. Querques L, Giuffrè C, Corvi F, et al. Optical coherence 19. Bruyère E, Miere A, Cohen SY, et al. Neovascularization sec-
tomography angiography of myopic choroidal neovascularisa- ondary to high myopia imaged BY optical coherence tomog-
tion. Br J Ophthalmol 2017;101:609–615. raphy angiography. Retina 2017;37:2095–2101.
10. Coscas GJ, Lupidi M, Coscas F, et al. Optical coherence 20. Ding X, Zhan Z, Sun L, et al. Retinal pigmental epithelium
tomography angiography versus traditional multimodal imag- elevation and external limiting membrane interruption in myo-
ing in assessing the activity of exudative age-related macular pic choroidal neovascularization: correlation with activity.
degeneration: a new diagnostic challenge. Retina 2015;35: Graefes Arch Clin Exp Ophthalmol 2018;256:1831–1837.
2219–2228. 21. Al-Sheikh M, Phasukkijwatana N, Dolz-Marco R, et al. Quan-
11. Faridi A, Jia Y, Gao SS, et al. Sensitivity and specificity of titative OCT angiography of the retinal microvasculature and
OCT angiography to detect choroidal neovascularization. Oph- the choriocapillaris in myopic eyes. Invest Ophthalmol Vis Sci
thalmol Retina 2017;1:294–303. 2017;58:2063–2069.