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Table 28.3 Commercially available wide-eld OCT machines
NIDEK Mirante (NIDEK Co. Ltd., Gamagori,
Japan)
Heidelberg Spectralis OCT (Heidelberg
Engineering, Heidelberg, Germany)
Optos Silverstone (Optos PLC, Dunfermline, UK) cSLO/SS-OCT 200° FOV
Optos Monaco (Optos PLC, Dunfermline, UK) cSLO/SD-OCT 200° FOV
FOV eld of vision, HD high denition, OCT optical coherence tomography, SLO scanning laser ophthalmoscope,
cSLO confocal scanning laser ophthalmoscope
SLO/HD-OCT 160° FOV
Confocal SLO/SD-OCT
Combination with ocular Staurenghi 230
SLO retina lens
N. K. Sahoo et al.
55° FOV
150° FOV
deeper portions of the choroid are now closer to
the zero-delay line, there is enhanced imaging of
these structures.
28.1.4 OCT Artifacts
Some common artifacts include misidentication
of the inner and outer retinal layers, and issues
with mirrors, being out-of-register, degraded
images, cut edges, off-center images, and motion
and blink artifacts [3].
28.1.5 Principles ofOCTA
Optical coherence tomography angiography
(OCTA) is a noninvasive imaging modality that
evaluates the retinal and choroidal vasculature.
The OCTA images are generated using an
OCT- based system. Flow signals from the
OCTA arise from detecting changes in the
reectivity of light when the same location is
scanned over time, which is attributed to the
movement of red blood cells. A threshold
masking strategy can be used to block OCTA
signals from tissues below a threshold OCT
signal. If the threshold level is too low, areas of
low signal strength without true blood ow,
like the sclera and vitreous, can be incorrectly
displayed as having ow. Conversely, if the
threshold level is too high, areas of low ow
will be incorrectly displayed as having no ow.
While manufacturers set threshold values, it is
good practice to analyze OCTA data in conjunction with structural OCT to conrm the
validity of the OCTA signal [4].
Table 28.4 Commercially available OCTA machines
OCT
Manufacturer Device name
Carl-Zeiss
Meditech
Topcon DRI OCT
Optovue RTVue XR
Heidelberg
Engineering
Canon OCT-HS 100 Spectral-
Nidek RS-3000
OPTOPOL REVO NX
CODAA complex optical coherence tomography difference analysis angiography, SADA full-spectrum
amplitude- decorrelation angiography, OCTARA optical
coherence tomography angiography ratio analysis, OMAG
optical microangiography, SOA spectral domain optical
coherence tomography angiography, SSADA split-
spectrum amplitude-decorrelation angiography
Cirrus
HD-OCT
Angioplex
PLEX elite
9000
triton
Avanti
Angiovue
Spectralis
OCT
angiography
advance
Angioscan
OCTA
modality Algorithm
Spectral-
domain
Sweptsource
Sweptsource
Spectraldomain
Spectraldomain
domain
Spectral-
domain
Spectraldomain
OMAG
OMAG
OCTARA
SSADA
FSADA
Modied
FSADA
CODAA
SOA
28.1.5.1 OCTA Algorithms
(Table28.4)
Several strategies have been developed to analyze information related to both phase and intensity of the reected light. Most commercially
available instruments utilize complex signalbased algorithms based on both phase and intensity. These include optical microangiography
(OMAG), split-spectrum amplitude- decorrelation
angiography (SSADA),
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OCTA ratio analysis (OCTARA), and proba-
bilistic algorithms [4].
28.1.5.2 Scanning Protocols
andQuantitative Measures:
(Tables 28.5 and28.6)
Similar to OCT, commercial OCTA instruments
generally come with pre-set acquisition algorithms according to scan area, for example, 3×3
mm, 6×6mm, 9×9 mm, and 12×12mm. It is
also possible to produce montage images by
stitching together images to provide a wider eld
of view. In addition, pre-set segmentation strategies are also commonly available, with most
instruments being able to generate the supercial
and deep retinal plexus. There are some variations
in the pre-set segmentations for the outer retina
(e.g., the outer retina and choriocapillaris (ORCC)
slab, the outer retina slab). It is also important to
Table 28.5 Common terminology used in OCTA
Field of view 3×3mm, 6×6mm, 8×8mm,
9×9mm, 12×12mm,
15×9mm
The sampling density may or may
not change for different elds of
view, depending on the machine
Montage Enables elds of view of up to
100° by stitching together smaller
elds of view without sacricing
image resolution
Vitreous slab Above the ILM; normally
avascular
Supercial retinal
plexus
Deep retinal
plexus
Inner retina Combination of supercial and
Outer retina Outer border of OPL to RPE;
Choriocapillaris
Deeper choroid
Choroid Combination of the
ILM internal limiting membrane, IPL inner plexiform layer,
OPL outer plexiform layer, RPE retinal pigment epithelium
Supercial portion of the inner
retina; ILM to the outer border of
IPL
Deep portion of the inner retina;
outer border of IPL to the outer
border of OPL
deep retinal plexus
normally avascular
Bruch’s membrane to 10–20μm
below
Larger choroidal vessels, >20μm
below the Bruch’s membrane
choriocapillaris and deeper
choroid
understand that differences in the boundaries exist
between instruments, even for the same slab.
Several quantitative measures of the presence and
absence of ow (non-perfusion) can be derived
from OCTA.Metrics describing the presence of
ow include vessel density, perfusion density, and
vessel length density. Various metrics have been
used to describe the properties of the foveal avascular zone (FAZ), including FAZ area, circularity
and acircularity index, and axis ratio [5].
28.1.5.3 OCTA Artifacts
Accurate interpretation of OCTA requires a good
understanding of potential artifacts, including
those arising from motion, blink, projection, seg-
Table 28.6 OCTA measurements
Foveal
avascular zone
Acircularity
index
Circularity
index
Axis ratio Ratio between an ellipse’s major and
Vessel density The proportion of blood vessel area
Vessel length
density/
skeleton
density
Vessel
diameter index
Fractal
dimension
Vessel
tortuosity
FAZ foveal avascular zone, VD vessel density
The central area of the macula
devoid of retinal capillaries
Ratio of the perimeter of the FAZ to
the perimeter of a circle with an
equal area. Irregular FAZ perimeters
have a higher acircularity index
Ratio of the area of FAZ to the area
of a circle with an equal perimeter.
Irregular FAZ is associated with a
decreased circularity index
minor axes ts with second-order
moments. An elongated FAZ has a
greater axis ratio
over the total measured area based
on the binarized image for indicating
the perfusion of the retinal
microvasculature
Modication of VD which quanties
the vessel density by performing an
additional skeletonizing process
which reduces the width of each
blood vessel to 1 pixel, regardless of
the vessel diameter
Measure of the vessel caliber.
Calculated by dividing the area
occupied by blood vessels in the
binarized image by the length of
blood vessels in the skeletonized
image
Measures the complexity of a
vasculature branching pattern
Compares the length of a vessel’s
ow path to a straight line between
its path’s starting and ending points
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mentation, and shadow. Furthermore, the accuracy of quantitative measures such as vessel
density may be affected by vessel doubling,
media opacity, and stretch [4].
28.2 Applications ofOCT
andOCTA inRetinal
Conditions
28.2.1 Diabetic Retinopathy
28.2.1.1 Non-proliferative Diabetic
Retinopathy (NPDR)
Common features in DR include microaneurysms (MA), dot and blot hemorrhages, cotton
wool spots (CWS), and hard exudates (HE); MAs
typically appear as small, medium to high echoes
with minimal back-shadowing in the INL (inner
nuclear layer) and NFL (nerve ber layer). On en
face OCTA, they appear as focally dilated saccular and fusiform capillaries and may arise from
different layers of the choroidal plexus. Retinal
hemorrhages appear as areas of hyperreectivity
within the retina. Sub-hyaloid hemorrhage is
seen as a highly reective lesion above the ILM
(internal limiting membrane), causing the shadowing of the underlying retinal layers. HEs are
hyperreective spots, larger than 30μm, seen in
the outer retinal layers, most commonly the OPL
(outer plexiform layer), with associated backshadowing and a reectivity similar to the RPE–
BM (retinal pigment epithelium–Bruch’s
membrane) complex. Cotton wool spots appear
as hyperreective, nodular, or elongated lesions
in the NFL, which may also involve the GCL
(ganglion cell layer), with associated backshadowing [6]. OCTA may detect areas of nonperfusion within the retina. Quantitative measures
may demonstrate a reduction in vessel density or
perfusion density in eyes with NPDR compared
to eyes without DR.
28.2.1.2 Proliferative Diabetic
Retinopathy (PDR)
Extensive areas of non-perfusion can often be
seen on OCTA [Fig. 28.2]. On OCT, NVD (new
vessels on disc) is seen as hyperreective tissue
N. K. Sahoo et al.
Fig. 28.2 Wide-eld OCTA of a patient with proliferative diabetic retinopathy showing neovascularization of
the disc (white arrow), neovascularization elsewhere (red
arrow), and extensive areas of capillary non-perfusion
areas (yellow stars)
on the disc (attached posterior hyaloid) or protruding from the disc into the vitreous (detached
posterior hyaloid). The NVE (new vessels elsewhere) are seen as homogenous hyperreective
loops breaching the ILM and breaching the vitreous with posterior retinal shadowing [7]. On
OCTA, the ow signal can be detected by segmenting above the disc or peripapillary retinal
surface (NVD) and above the ILM (NVE) [7].
Accurate segmentation is critical because this
helps to differentiate it from intraretinal microvascular abnormalities (IRMA), which do not
show ow signals above the vitreoretinal interface slab. Exuberant vascular proliferation (EVP)
is seen as the proliferation of irregular, ne,
small-caliber vessels at the margin of new vessels, which is a sign of more active disease.
28.2.1.3 Diabetic Maculopathy
andDiabetic Macular Edema
Diabetic macular edema (DME) is the accumulation of excess uid in the extracellular space
within the retina in the macular area and the subretinal space [Fig. 28.3]. With OCT, DME can be
assessed quantitatively, and the location with
regard to the center of the fovea can be dened
more precisely. The International Council of
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a
b
c
Fig. 28.3 OCTA of an irregular foveal avascular zone
and reduced vessel density in the supercial plexus (a)
and the deep plexus (b). Microaneurysms (red arrows) can
Ophthalmology has classied DME into noncenter- involved DME, when the retinal thickening
in the macula does not involve the central subeld zone (1 mm in diameter), and centerinvolved DME, when the retinal thickening in the
macula involves the central subeld zone. Most
clinical trials for DME have used a quantitative
threshold for central retinal thickness (CRT) or
central subeld thickness (CSFT) with Protocol I
and Protocol T studies, including eyes where the
CSFT is above 320μm. In addition, various morphological forms of DME (e.g., cystoid, serous)
have been reported, but there is a lack of standardization for their denition. Identifying vitreomacular interface abnormalities in eyes with
DME may impact the management options.
be seen. (c) OCT shows intraretinal cysts and subretinal
uid in an eye with diabetic macular edema
In addition to macular edema, OCT is also
useful for assessing the integrity of the retinal
layers. Disorganization of retinal inner layers
(DRIL) may be seen in some eyes of diabetic
patients and has been associated with ischemia.
On OCT, DRIL is dened as the inability to
distinguish between the GCL-IPL complex,
INL, and OPL. DRIL is assessed on OCT B
scans by looking at the central 1 mm retinal
zone. Disorganization of more than 50%
or>500μm of this area is considered signicant and is associated with a worse visual
prognosis. The integrity of the ELM and EZ is
regarded as a good prognostic indicator in eyes
with DME; however, their assessment might be
difcult [8].
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N. K. Sahoo et al.
a
c
Fig. 28.4 (a) Horizontal OCT scan of a patient with Type
1 (occult) MNV showing a double layer sign, PED, and
intact RPE. (b) Horizontal OCT scan of a patient with
Type 2 (classic) MNV showing hyperreective material
above the RPE with subretinal uid and intraretinal uid.
(c) Horizontal OCT scan of a patient with Type 3 (RAP)
b
d
MNV showing PED with intraretinal anastomosis (red
arrow) and intraretinal uid. (d) Horizontal OCT scan of
a patient with PCV showing tall-peaked PED (yellow
arrow), notched PED (blue arrow), sub-RPE ring (green
arrow), and a double layer sign (white arrow)
On OCTA, it has been shown that vessel density and perfusion density are lower in eyes with
DME.Also, there is an increase in FAZ area and
acircularity index and a decrease in circularity
index in eyes with DME.The fractal dimension is
also lower in eyes with DME [9].
28.2.2 Age-Related Macular
Degeneration (AMD)
28.2.2.1 Early andIntermediate AMD
Drusen are hallmarks of AMD and can be
observed with clinical examination. However, the
depth of these extracellular deposits can be more
precisely assessed using OCT.In cross-sectional
OCT, soft drusen appear as reecting basallaminar deposits between the RPE and BM; the
reticular pseudodrusen appear as subretinal
drusenoid deposits (SDD) above the RPE.SDD
may be associated with extensive disruption of
the ellipsoid zone [10]. Conuent drusen may
coalesce and form drusenoid PED, which has a
smooth contour because of the detachment of the
hyperreective RPE with homogenous moderate
to high reectivity content. Pigment clumping on
top of the PED can be seen as hyperreective
foci.
28.2.2.2 Neovascular AMD
OCT and OCTA can detect the presence of new
vessels and determine the subtype based on its
relationship to the RPE (Fig.28.4). Type 1 macular neovascularization (MNV) typically appears
as a detachment of the RPE from the underlying
BM, and the sub-RPE space shows heterogeneous reectivity. Type 2 MNVs above the RPE
typically appear as subretinal hyperreective
material [11]. Type 3 MNV appears as a hyperreective lesion between the sub-RPE compartment and the neurosensory retina [12]. Type 3
MNV can be further classied into three stages.
Stage 1 is the stage of intraretinal neovascularization (IRN), wherein capillaries originate from
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a
ba
b
c
e
d
f
Fig. 28.5 Left Panel. (a) ICGA of a patient with PCV
showing polyp with branching vascular network (yellow
arrows) corresponding to the thumb-shaped PED on horizontal OCT in Fig. Right panel a (b) OCTA of the same
patient through the thumb- shaped PED (white arrow in
Fig. Right panel a) showing ow within the polyp along
with branching vascular network (yellow arrow). (c)
ICGA of the same patient showing a plaque suggestive of
classic MNV (green arrow) corresponding to the area of
the deep retinal capillary plexus; stage 2 is the
stage of subretinal neovascularization where the
IRN extends into the subretinal space, and stage
3 is the stage of choroidal neovascularization.
Finally, PCV (polypoidal choroidal vasculopathy) is considered a variant of type 1 MNV.The
branching neovascular network (BVN) has a
similar OCT appearance as a type 1 MNV, while
the polypoidal lesion(s) are associated with the
appearance of a sharp-peaked PED with a hyporeective sub- RPE ring. Based on the APOIS
(Asia Pacic Ocular Imaging Society) work-
subretinal hyperreective material on horizontal OCT in
Fig. Right panel b (d) OCTA of the same patient through
the subretinal hyperreective material (white arrow in
Fig. Right panel b) showing a corresponding large network (green arrow). (e) OCTA of a patient with RAP
lesion in the deep retinal plexus (yellow arrow). (f) En
face image of the same patient with RAP showing patchy
vessel atrophy (yellow arrow)
group recommendations, the combination of
sub-RPE ring-like lesion, en face OCT complex
RPE elevation, and sharp-peaked PED can differentiate PCV from typical neovascular AMD
with high sensitivity and specicity. OCTA can
detect ow signals within the MNV.By carefully
selecting the segmentation in relation to the RPE
in cross- sectional scans, OCTA can complement
OCT in determining the subtype of MNV
(Fig.28.5). The en face OCTA provides further
information related to the size and morphology
of the MNV. In PCV, however, reports have
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N. K. Sahoo et al.
found variable ow signals within the polypoidal
lesions; these have been attributed to turbulent or
slow ow.
The level of activity from the MNV can be
assessed with OCT based on intraretinal uid,
subretinal uid (SRF), and subretinal hyperreective material. The presence of SRF and IRF
(intraretinal uid) on OCT have been widely
used as markers of disease activity for guiding
retreatment decisions. Sub-RPE uid or PED
(pigment epithelial detachment) has been considered a less important marker for disease activity,
except in PCV.On the other hand, OCTA features
have not been consistently incorporated into
retreatment assessment. This is due to limitations
of repeatability and lack of quantitative comparison. While a progression to a more mature
branching pattern within the vascular network
has been described, a lack of objective, quantiable parameters has limited the current application of OCTA in retreatment decisions [13].
28.2.2.3 Geographic Atrophy
Geographic atrophy (GA) appears as a welldened circular or oval area of depigmentation
due to thinning of the outer retina and RPE.The
Classication of Atrophy Meeting (CAM) group
proposed a classication system of atrophy
based on SD-OCT and complimented by CFP
(color fundus photo), FAF (fundus autouorescence), and NIR (near infra-red). Based on CAM
classication, GA can be diagnosed in the presence of cRORA (complete RPE and outer retinal
atrophy) that is dened by a zone of RPE loss or
RPE attenuation of at least 250μm, a region of
choroidal hyper-transmission of at least 250μm
in diameter and loss of the interdigitation zone,
ellipsoid zone (EZ), or the external limiting
membrane and the absence of scrolled RPE or
signs of RPE tear [14]. Alterations in the choriocapillaris have been documented with OCTA in
eyes with GA.In addition, OCT can detect EZ
disruption, which apparently precedes the development of RPE atrophy. The prediction of individual conversion of early AMD to CNV or GA
using Articial Intelligence (AI) with automated
analysis of imaging biomarkers showed that the
critical features of conversion to GA were outer
retinal thinning with an associated
decreasedouter nuclear layer thickness and the
presence of hyperreective foci in the outer
nuclear layer [15].
28.2.2.4 The Choroid inAMD
EDI-OCT and SS-OCT can penetrate the choroid
better than the conventional spectral-domainOCT, allowing the evaluation of changes in choroidal thickness in AMD.The subfoveal choroidal
thickness correlates with the drusen and MNV
subtypes. Eyes with thicker choroids tend to
develop pachydrusen and PCV; those with thinner choroids tend to develop SDD and type 3
MNV [16]. Besides evaluating subfoveal choroidal thickness, en face OCT and OCTA allow the
evaluation of choroidal vasculature noninvasively. These have led to the description of
pachyvessels, inter-vortex anastomosis, and
unbalanced vortex drainage in eyes with MNV
and choroidal congestion. Together with the nding of choriocapillaris ow impairment, the
pachychoroid theory has been proposed as a
novel mechanism resulting in MNV.
28.3 Retinal Vascular Diseases
28.3.1 Retinal Arteriolar Occlusion or
Ischemia
During the acute phase of retinal artery occlusion,
there is increased thickness and reectivity of the
inner retinal layers with back-shadowing on
OCT. The area of swelling is well-demarcated,
which shows the area supplied by the occluded
artery. Macular edema, outer retinal layer thickening, and SRF may also be seen. ILM detachment
has been recently described as a feature of total
retinal artery occlusion and severe retinal ischemia
[Fig. 28.6]. In the chronic phase, thinning of the
inner and outer retinal layers with loss of stratica-
ab
cd
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tion of the retinal layers in the area of previous
hyperreectivity can be noted. On OCTA, vessel
density is reduced in the SCP and DCP [17].
Fig. 28.6 OCT scan of a case of acute central retinal
artery occlusion showing the increased retinal thickness
and reectivity of the inner retinal layers with backshadowing. There is also the presence of cystoid spaces in
the inner retina and internal limiting membrane
detachment
28.3.2 Retinal Vein Occlusion
In retinal vein occlusion (RVO), OCT is useful in
evaluating macular edema, SRF, hemorrhages,
and exudates. Macular edema is usually seen as a
combination of cystoid edema, sponge-like
retinal thickening, and serous retinal detachment
[18]. DRIL and disruption of ELM and EZ are
associated with a worse visual prognosis. The
presence of a prominent middle limiting membrane, a hyperreective line located in the outer
plexiform layer, is a marker of acute ischemia
and is also associated with poor visual outcomes
[Fig. 28.7].
OCTA can evaluate the presence of a nonperfusion area (NPA) [Fig. 28.8]. The relative
degree of NPA between the DCP (deep choroidal plexus) and SCP (supercial choroidal
plexus) has been suggested to have prognostic
implications. Ischemia affecting both the SCP
Fig. 28.7 (a) Vertical OCT of a case of inferotemporal
branch retinal vein occlusion showing increased retinal
thickness and cystoid macular edema. (b) Prominent mid-
dle limiting membrane. (c) Disorganization of retinal
inner layers. (d) Ganglion layer cysts
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Fig. 28.8 (a) Color fundus photo of en face OCTA. (b) Image of an eye with inferotemporal retinal vein occlusion.
Retinal non-perfusion and disrupted FAZ can be seen on OCTA
N. K. Sahoo et al.
and DCP is associated with the development of
atrophy. In contrast, eyes with a larger NPA seen
in the DCP than SCP may experience recurrent
edema due to impaired outow of uid through
the DCP. The FAZ and acircularity index can
also increase in the SCP and DCP. Other features the OCTA can detect are capillary telangiectasias, collateral vessels, microaneurysms,
and retinal new vessels [18].
ective middle retinal layer is another early
OCT feature, seen as increased reectivity and
thickness between the inner and outer plexiform layers. Other features seen in the nonproliferative stage of the disease include
hyporeective inner and outer retinal cavities,
the ILM drape sign, and outward bending of
the inner retinal layers. The pigment appears as
hyperreective foci with back- shadowing [Fig.
28.9]. Development of neovascularization may
lead to subretinal or intraretinal uid [19].
28.3.3 Macular Telangiectasia Type 2
(Mac Tel Type 2)
Epiretinal neovascularization is a recently
described feature which shows communication
with the intraretinal abnormal vascular plexus.
Mac Tel type 2 is a slowly progressive disease
of the macula, primarily involving the Muller
cells. In advanced cases, it may be complicated
by subretinal neovascularization. The earliest
sign of this condition seen on OCT is the temporal widening of the fovea due to thinning of
the temporal juxta foveal retina. The hyperre-
Features seen on OCTA include dilated bulbs
of perifoveal vessels, dilation of perifoveal vessels, rarefaction and increased intervascular
spaces, vessels distorting FAZ, bunching of vessels, and vascular network in the outer retina
[Fig. 28.9]. Right-angled veins can be seen associated with pigment plaques.
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a
b
c
Fig. 28.9 (a) Color fundus photograph of the left eye of
a patient with Mac Tel type-2. Pigment clumps can be
seen temporal to the fovea. (b) OCTA showing blunted
perifoveal vessels. (c) OCT shows a widening of the tem-
28.4 Vitreomacular Interface
Disorders
Vitreomacular interface disorders may cause
visual disturbance or loss. OCT is essential in
assessing vitreomacular interface disorders
and planning surgery. Vitreomacular adhesion
(VMA) is dened as a partially detached vitreous in the perifoveal area without retinal
abnormalities. There is an elevation of the cor-
poral fovea, hyporeective space beneath the ILM at the
fovea, outward bending of the inner retinal layers, and
hyperreective pigments clumps with back-shadowing
tical vitreous above the retinal surface with an
area of attachment within the 3mm radius of
the fovea. They can be sub-classied by the
size of the adhesion into focal (≤1500μm) and
broad (>1500 μm). Vitreomacular traction
(VMT) is present when the attached posterior
hyaloid is associated with retinal distortion
[Fig. 28.10b] [20]. Visual symptoms may result
from further complications such as macular
hole formation.
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