CLINICAL OPTOMETRY 4 (SO4004)

ADVANCED OPTOMETRIC
INVESTIGATION II
(OPTICAL COHERENCE TOMOGRAPHY -
POSTERIOR SEGMENT)

Dr. Vincent Ng
Associate Consultant Optometrist, HK PolyU
 THIS LECTURE

Clinical application of OCT on glaucoma

management

OCTA - clinical interpretation and application

 DEFINITION OF GLAUCOMA

Glaucoma is a degenerative optic neuropathy

characterized by a progressive loss of retinal ganglion
cells and their retinal nerve fibre layer axons, resulting
in loss of visual function and corresponding optic nerve
head anatomical change.
 THE GLAUCOMA CONTINUUM

Structural defect precedes functional defect.

But why?
(it has been widely thought that RGCs are “reductant”)
EARLY GLAUCOMA DIAGNOSIS

The best time to diagnosis glaucoma is in the pre-

perimetric phase.

Pre-perimetric glaucoma - glaucomatous damages

without visual field loss.

The basis of current glaucoma assessment – to

determine the structural loss associated with
glaucoma (e.g. measuring of RNFL thickness using
OCT)
 RETINAL GANGLION CELLS

RGC is a type of neuron

(nerve cell) near the inner
retinal surface

Having a long axon

(nerve fibre) that extends
into the brain.

Axons form the optic

nerve, optic chiasma &
optic tract

The longest cell in

human body
 STRUCTURAL DEFECTS IN
GLAUCOMA

Loss of retinal ganglion

cells

Loss of retinal nerve fibre

layer

Glaucomatous optic
nerve head (cupping)
COURSE OF THE RETINAL GANGLION CELL AXONS
WITHIN THE NERVE FIBRE LAYER OF THE RETINA

http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v8/v8c021.html
EARLY APPLICATION OF OCT ON
GLAUCOMA MANAGEMENT

Peripapillary region:

Average of 3 circular scans (RNFL Thickness (3.4) protocol) at

peripapillary region

Retinal nerve fibre layer (RNFL) thickness in TNSIT plot

Macular region:

Entire/total macular thickness mapping

Partial macular thickness (ganglion cell layer) analysis

EARLY APPLICATION OF OCT ON
GLAUCOMA MANAGEMENT
Average of 3 circular peripapillary scans (RNFL Thickness (3.4) protocol)

Automated segmentation of retinal nerve fibre layer (ILM and NF/GC

boundary)

RNFL thickness in TNSIT plot (compared with the color-coded normative data)

Normal distribution
Green: 95%
RFNL map (also known as TSNIT plot)
Yellow: 1-5%
Red: within <1 %
 RNFL (STRUCTURAL) VS VF
(FUNCTIONAL) DEFECTS

in agreement ?
Functional losses Structural losses
 MACULAR THICKNESS IN GLAUCOMA

Zeimer et al. (1998) first suggested that,

since a significant portion of retinal
ganglion cells reside in the macula, a
loss of tissue in this region should be a
sign of glaucomatous damage.

The ganglion cell layer is thickest at the

perimacular region.

Decreased total macular thickness in

glaucomatous eyes has been observed in
the earlier studies (using TD-OCT),
likely due to thinning of the ganglion
cell layer.
Zeimer R, Asrani S, Zou S, et al. Quantitative detection of glaucomatous damage at the posterior pole by retinal thickness mapping: a pilot study. Ophthalmology. 1998;105(2):224-231.
Lederer DE, Schuman JS, Hertzmark E, et al. Analysis of macular volume in normal and glaucomatous eyes using optical coherence tomography. Am J Ophthalmol. 2003;135(6):838-843.
Greenfield DS, Bagga H, Knighton RW. Macular thickness changes in glaucomatous optic neuropathy detected using optical coherence tomography. Arch Ophthalmol. 2003;121(1):41-46.
Wollstein G, Schuman JS, Price LL, et al. Optical coherence tomography (OCT) macular and peripapillary retinal nerve fiber layer measurements and automated visual fields. Am J Ophthalmol.
2004;138(2):218-225.
MACULAR THICKNESS IN GLAUCOMA

IPL+GCL+RNFL ≈ 40% of
total retinal thickness
 MACULAR THICKNESS IN GLAUCOMA

Earlier studies measured the full

macular thickness using TD-OCT,
trying to correlate with the findings of
peripapillary RNFLT and VF.

However, the sensitivity and specificity

of measuring full macular thickness are
low for detection of glaucoma.

Clinical use of TD-OCT macular-

thickness measurement alone in the
evaluation of glaucoma is
argumentative.
Zeimer R, Asrani S, Zou S, et al. Quantitative detection of glaucomatous damage at the posterior pole by retinal thickness mapping: a pilot study. Ophthalmology. 1998;105(2):224-231.
Lederer DE, Schuman JS, Hertzmark E, et al. Analysis of macular volume in normal and glaucomatous eyes using optical coherence tomography. Am J Ophthalmol. 2003;135(6):838-
843.
Greenfield DS, Bagga H, Knighton RW. Macular thickness changes in glaucomatous optic neuropathy detected using optical coherence tomography. Arch Ophthalmol. 2003;121(1):41-
46.
Wollstein G, Schuman JS, Price LL, et al. Optical coherence tomography (OCT) macular and peripapillary retinal nerve fiber layer measurements and automated visual fields. Am J
Ophthalmol. 2004;138(2):218-225.
(Source: www. meditec.zeiss.com)
 GANGLION CELL ANALYSIS

A new, complementary diagnostic parameter in glaucoma.

Under the macular scan with SD-OCT, segmentation of the ganglion

cell layer from the entire retinal layer is possible.
 GANGLION CELL ANALYSIS

Cirrus HD-OCT (Carl Zeiss Meditec)

‣ RGC+ = retinal ganglion cell layer (RGC) + inner plexiform layer (IPL)
RTVue-100 (Optovue Inc.)
‣ Ganglion cell complex (GCC) = RNFL + GCL + IPL
GANGLION CELL ANALYSIS (CIRRUS)
 EVIDENCE OF STRUCTURAL DEFECTS IN
MACULA

Early studies have shown that macular ganglion cell layer thickness
data provided similar diagnostic capability compared with RNFL
thickness analysis

Jeong et al. Macular ganglion cell imaging study: glaucoma diagnostic accuracy of
spectral-domain optical coherence tomography. IOVS 2013

• Full-thickness macular data generally underperformed vs RNFL,

with one exception

• Macular thickness asymmetry parameters compared favorably

with RNFL diagnostic capability

Sullivan-Mee et al. Diagnostic precision of retinal nerve fibre layer and macular
thickness asymmetry parameters for identifying early primary open-angle glaucoma.
Am J Ophthalmol 2013.
POSTERIOR POLE ASYMMETRY ANALYSIS
(HEIDELBERG SPECTRALIS-OCT)

PPAA maps retinal thickness across the posterior pole and graphs
asymmetric both between hemispheres and between eyes.

Black cells indicate mean difference ≥ 30 um.

http://www.heidelbergengineering.com/us/wp-content/uploads/2134_Info-Sheet_Posterior-Pole_Final-Low-Res.pdf
 POSTERIOR POLE ASYMMETRY ANALYSIS
(HEIDELBERG SPECTRALIS-OCT)

A case with a localized

RNFLD.

(A) A localized RNFLD is

observed by red-free RNFL
photography (white arrows).

(B) The defect was also

identified by PPAA (blue
arrow).

(C) The defect was not

detected by cpRNFL
measurement (black arrow).
 IS MACULAR THICKNESS OBTAINED
FROM OCT USEFUL FOR GLAUCOMA
EVALUATION?

Full macular thickness No

Ganglion cell complex (RNFL+ GCL+IPL) Yes

RGC+ (GCL+IPL) Yes

Macular thickness asymmetry (Posterior Pole

Yes (?)
Asymmetry analysis
Wong et al. Macular imaging for glaucoma using spectral-domain optical
coherence tomography: a review. Semin Ophthalmol 2012
Spectralis OCT (Heidelberg
Engineering)

Cirrus HD-OCT (Carl Zeiss

Meditec
CIRRUS HD-OCT
OPTIC DISC CUBE
200X200

A: RNFL thickness map

B: Infrared image with
deviation map
C: Color-coded statistical
parameters compared to
normative data
D: Neuroretinal rim
thickness & RNFL thickness
(in TSNIT plot)
E: Distribution of normal
Green - 95% normal
Yellow - 1-5% normal
Red - <1% normal
CIRRUS HD-OCT
GANGLION CELL ANALYSIS (MACULAR
CUBE 512X128

Thickness map of the

GCL-IPL
GCL-IPL thickness
averages for each sector
Color-coded distribution
of normals based on
normative data
Table of values for
average and minimal
thickness
Deviation maps - color-
coded compared to
normative data
SPECTRALIS OCT
RNFL THICKNESS ANALYSIS

Retinal fundus image with

delineation of circular scan (3.4 mm
peripapillary ring)
Tomogram (showing the
segmentation of RNFL)
TSNIT RNFL thickness in line graph
format with color-coded table
representing normative data
Pie graphs of quadrant and sector
RNFL thickness compared to
normative data (color-coded)
OD-OS asymmetry comparison
Classification whether the scan falls
within, borderline or outside
normative database
 ONH RIM ANALYSIS

In Spectralis OCT, Bruch’s membrane opening minimum rim width (BMO-

MRW) is a parameter that uses BMO as the anatomic reference point, and MRW
is defined as the shortest distance between BMO and the internal limiting
membrane, in effect, measuring the neuroretinal rim thickness.
 ONH RIM ANALYSIS

Totally 24 radial line B-scans centered on the ONH is acquired to provide neuro-
retinal rim plot

The results are compared to a reference database of healthy eyes and presented
in a sector format, which allows for better structure and function correlation.
EXTE NDED GLAU COMA AN ALYSES

Under the 24-radial line scans, Spectralis

OCT can extract different peripapillary
RNFL thickness datea in 3.4 mm, 4.1 mm
and 4.7 mm circles

RNFL thickness decreases as distance from

disc margin increases

Rate of RNFL loss can be faster or slower

depending on distance from optic disc

The combination of RNFL thickness from

three different distances may provide
complementary information

May consider the results from 4.1 or 4.7.

mm circular scan when px with
peripapillary atrophy or large disc diameter
 APS
Spectralis OCT has a specific module which combines
Anatomic Positioning System (APS) with a series of
scan patterns to assess ONH, RNFL and GC layer.

The software compares patients’ eyes to a reference

database of healthy eyes, and flags for any deviations

APS is based on 2 structural landmarks:

The center of fovea

The center of Bruch’s membrane opening

Fovea-to-Bruch’s membrane opening centre

(FoBMOC)
 APS
APS identifies 2 fixed
landmarks -
(1) the centre of BMO and
(2) the fovea - in order to
place and orient glaucoma
scans according to the
correct anatomic location in
each individual eye
 APS

APS helps to determine individual’s disc and fovea tilting

Automated APS guides examiners to ensure that scans are

aligned relative to the patient’s individual FoBMOC axis and
thereby enhances consistent, accurate placement of subsequent
scans and sectors for data analysis
WO/APS VS W/APS
 HOOD’S MODEL

A schematic developed by Professor D Hood showing the macula

areas of greatest vulnerability to glaucomatous damage

Traditional glaucoma
evaluation usually overlooked
macular region due to the
historical focus on cpRNFL
and the incorrected
assumption that glaucoma
does not affect the central 10º
until the end stage of disease.

Although this area represents

only 2% of the entire retina,
over 30% of all ganglion cells
is represented here.

Hood DC, Raza AS. On improving the use of OCT imaging for detecting glaucomatous damage. Br J Ophthalmol. 2014
Jul;98 Suppl 2(Suppl 2):ii1-9. doi: 10.1136/bjophthalmol-2014-305156. PMID: 24934219; PMCID: PMC4208344
HOOD’S MODEL
 Conventional
TSNIT plot

Hood’s
NSTIN plot

In NSTIN plot, the most important portion of the disc for visual function i.e.
the temporal quadrant, is in the middle. This allows for easier visualization of
the relationship between RNFL thinning and VF defects.

Display RNFL data in NSTIN format so that the Macular Vulnerability Zone is
represented centrally on the graph, and not divided between the two extremes
of the cpRNFL tomogram
THE HOOD GLAUCOMA REPORT
 ARTIFACTS IN RNFL ANALYSIS

Sclerosis of blood vessels around ONH

Haemorrhages or drusens at ONH

Vitreoretinal disorders at ONH (e.g.

dpiretinal membrane)
ARTIFACTS IN RNFL
ANALYSIS

High myopia

magnification of retinal image,

peripapillary atrophy,

tilted disc, displacement of the optic

nerve fibres

Intra-retinal splitting (retinoschisis)

RED & GREEN DISEASE

Based on normative databases -

red (abnormal), green (normal),
yellow (borderline)

“Red disease” - the OCT

mistakenly indicates that
something is abnormal

“Green disease” - the OCT data

shows normal, but in fact the
eye is abnormal
EME RGENT USE OF SD -OCT FOR GLAUCOMA
MANAGE MENT

Owing to fast scanning speed, SD-OCT allows multiple cross-sectional B-

scans to be captured over an area of interest

Multiple B-scans
in cube or circular way

Peripapillary region Macular region

”Extracted” RNFL map Neural rim Ganglion cell

RNFL circles Deviation map thickness analysis

TSNIT NSTIN

Correlate the structural defects with VF defects (24-2, 10-2)

Trend analysis – monitor progression over-time, differentiating the trend

from normal age-related thinning
Nowadays, OCT is a very useful and essential tool in
detecting and diagnosing retinal disorders and glaucoma.

However, this doesn’t mean OCT can replace the

conventional optometric examinations at all due to several
reasons:
OCT is relatively expensive which is still not readily
available in most optometric practices.

OCT is a supplementary test - you cannot solely use it to

examine every patient’s fundus.

Currently available OCT is still not able to examine the

peripheral fundus.

For glaucoma care, you cannot ignore the patient’s visual

function. Visual field test is still the essential part of
glaucoma management.
OCT ANGIOGRAPHY
(OCTA)
 TRADITIONAL ANGIOGRAPHY

Angiography - for qualitative

assessment of retinal and choroidal
circulations.

Traditional angiography (with

intravenous dye injection):

Fluorescein angiography (FA) - for

retinal circulation
FA of normal eye
Indocyanine green angiography
(ICGA) - for choroidal circulation
 TRADITIONAL ANGIOGRAPHY

Hyperfluorescence
Leakage
Staining
Pooling
Window defect
CONVENTIONAL ANGIOGRAPHY

Hypofluorescence
Blocking
Filling defect
CONVENTIONAL ANGIOGRAPHY

Disadvantages/limitations
Invasive (required intravenous dye injection)
Time-consuming
Potential risk/side effects (e.g. nausea, allergic
reactions)
IGC is contradicted in pregnancy and kidney disease.
2D images only - limited depth perception
 OCTA

OCTA is an extension of OCT technology

To image blood flow in the retinal and choroidal vasculature

OCTA images can be segmented to give an en face, depth-

encoded slab of the vasculature
 OCTA - ADVANTAGES

Non-invasive (no intravenous dye required)

Fast (images can be obtained within seconds)
Volumetic scans that can be segmented to specific
depths/layers
Provides accurate size and localization information
Visualizes both the retinal and choroidal vasculatures in
highly detailed
The OCTA images should be evaluated concurrently with
the structural OCT scans
 OCTA - LIMITATIONS

Limited field of view (could be improved using montage

of images)
Static view
Inability to view leakage/pooling
Inability to detect blood flow below the slowest
detectable flow
Image artifacts (segmentation errors, blinks, motion,
vessel ghosting)
 OCTA - BASIC PRINCIPLE

OCTA detects the motion of

scattered moving particles, e.g. red
blood cells, on the same retinal
location at different time points
rapidly in order to reveal the
retinal vasculature (repeated B-
scans at the same retinal location).
 OCTA - BASIC PRINCIPLE

Repeated B-scan acquired at the same retinal location in rapid

succession

Non-mobile tissue: the reflected signal will be stationary -

repeated B-scans will be identical

Moving RCBs: cause a time-dependent backscattering of the OCT

signal - repeated B-scans will be different
 OCTA - BASIC PRINCIPLE

Detecting the differences in the scattered light from moving particles

(RBCs in the vessels) - visualisation and quantification of
microcirculation in different retinal and choroidal layers.

The faster the blood flow > the greater the decorreclation signal > the
brighter the pixel values on the resultant en face OCTA images
COMMERCIALLY AVAILABLE
OCTA

Zeiss Angioplex OCTA

Optovue AngioVue

Topcon SS OCT Angio

Heidelberg Engineering
VASCULAR SYSTEM OF RETINA

Superficial retinal plexus

Deep retinal plexus
Choriocapillaris
Choroid
 SEGMENTED EN FACE
PRESENTATION OF OCTA
 SEGMENTED EN FACE
PRESENTATION OF OCTA

Visualization of separate
layers of microvascular
blood flow.

Simultaneous view of en
face OCTA images with
the corresponding
structural cross-sectional
OCT B-scans.
 CLINICAL APPLICATIONS

Diabetic retinopathy
Dry age-related macular degeneration
Wet age-related macular degeneration
Central serous chorioretinopathy
Vascular occlusions
Polypoidal choroidal vasculopathy
Choroidal neovascular membranes
Glaucoma
MACULAR SCANNING OPTIONS
ANGIOPLEX - VRI (VITREO-RETINAL
INTERFACE)

Hyper-reflective signal absent in the OCTA-

VRI but present in structural-VRI, indicating
that it is not abnormal blood vessels but
vitreous hemorrhage
 ANGIOPLEX - SUPERFICIAL (WITH
VESSEL DENSITY IN ETDRS GRID FOR
QUANTIFICATION
ANGIOPLEX - SUPERFICIAL (WITH
PERFUSION DENSITY FOR
QUANTIFICATION)
 ANGIOPLEX – DEEP
A deeper superficial layer where the blood vessels are finer
 ANGIOPLEX - AVASCULAR
As named, there should in absence of blood vessels in this layer
 ANGIOPLEX - OUTER RETINA TO
CHORIOCAPILLARIS (ORCC)
This is outer retina to choriocapillaris - the vessels size is smaller than
that in choroid
ANGIOPLEX - RPE-RPE FIT
This is RPE layer - supposed no BV to be seen here
 ANGIOPLEX - SUB RPE
Smaller sized blood vessels in both Sub RPE and Choriocapillaris layers
ANGIOPLEX - CHORIOCAPILLARIS
Smaller sized blood vessels in both Sub RPE and Choriocapillaris layers
 ANGIOPLEX - CHOROID
This is the outermost choroidal layer - the blood vessels size is largest
 SEGMENTATION OCTA - ISOLATE
MORE RETINA LAYERS OF INTEREST
AngioPlex Structure
ANGIOPLEX - MACULAR QUANTITATIVE
MEASUREMENT (LIMITED TO 3X3 & 6X6
SUPERFICIAL RETINA)

Vessel density
Total length of perfused
vasculature per unit area
Capillary perfusion density
Total area of perfused
vasculature per unit area
Foveal avascular zone (FAZ)
Perimeter
Circularity
Area
ANGIOPLEX - MACULAR QUANTITATIVE
MEASUREMENT (LIMITED TO 3X3 & 6X6
SUPERFICIAL RETINA)

Vessel density
Total length of perfused
vasculature per unit area
Capillary perfusion density
Total area of perfused
vasculature per unit area
Foveal avascular zone (FAZ)
Perimeter
Circularity
Area
ANGIOPLEX - MACULAR QUANTITATIVE
MEASUREMENT (LIMITED TO 3X3 & 6X6
SUPERFICIAL RETINA)

Vessel density
Total length of perfused
vasculature per unit area
Capillary perfusion density
Total area of perfused
vasculature per unit area
Foveal avascular zone (FAZ)
Perimeter
Circularity
Area
FOVEAL AVASCULAR ZONE (FAZ)

Other possible associated factors:

age, heart rate,
foveal thickness, choroidal thickness,
ocular perfusion pressure, IOP,
BCVA,
degree of myopia
DRY AMD - DRUSES
 DRY (NON-NEOVASULAR) AMD -
DRUSES

(A1) En-face structural OCT demonstrating areas of choriocapillaris alteration.

(A2-4) OCT angiograms of the choriocapillaris. The soft drusen shown are associated with areas of
decreased signal in the choriocapillaris, which could indicate impairment of blood flow.
 CNV IN NEOVASCULAR AMD
A circular net of abnormal vessels are shown surrounded by relatively homogenous
choriocapillaris. The abnormal vessels exist both below and above Bruch’s membrane

A: 6 x 6 mm OCT angiogram segmented at

choriocapillaris and the outer retina

B: En-face structural OCT

C: OCT b-scan

D1-3: IGC angiography – early, intermediate and late frames

E1-2: FA – intermediate and late frames

 DRY ARM - GEOGRAPHIC
ATROPHY
OCTA at the level of the choriocapillaris demonstrating flow impairment in a
similar area as the GA.
 NON-PROLIFERATIVE DIABETIC
RETINOPATHY

OCTA shows microvascular abnormalities such as areas of capillary non-

perfusion (yellow arrows), capillary loops, and microaneurysms.
EARLY, ASYMPTOMATIC NPDR
MONTAGE - EXPANDED VIEW
MONTAGE - EXPANDED VIEW
 OCTA IN AMD

Differentiate non-exduative (dry) from exudative (wet) AMD

Determines the size, depth and location of CNV

Visualization and classification of the CNV

Helps to decide the best treatment plan based on the

morphological features of CNV

Monitoring and quantifying the response to treatment.

GLAUCOMA (CASE #1)
GLAUCOMA (CASE #2)
 OCTA ON OPTIC NERVE HEAD

Enable visualization of the radial peripapillary

capillaries (RPC) of the RNFL to detect focal
glaucomatous perfusion defects.

Cannot be seen using traditional FA.

ANGIOPLEX - ONH
QUANTITATIVE
MEASUREMENT

Capillary perfusion

Total area of perfused vasculature per unit

area

Capillary flux index

Perfusion weight by the brightness

(intensity) of the flow signal
 OCTA IN GLAUCOMA

Decreased papillary, peripapillary and macular perfusion.

Significantly lower capillary perfusion and flux index.

Correlated well with functional and structural defects and

severity.

Comparable discrimination capillary as RNFL thickness

Reduced peripapillary and macular vessel density may be prior

to glaucomatous visual field defects and structural defects.

Early detection of normal tension glaucoma?

MAJOR ARTIFICERS IN OCTAL

3 common artifacts in OCTA imaging:

Motion artifacts

Projection artifacts

Segmentation errors
 MOTION ARTIFACT

OCTA depicts flow that is inferred by movement of red

blood cells between successive OCT scans.

OCTA images is very sensitive to “motion artifacts” induced

by patient motion (such as head movement, loss of fixation
and even microsaccades).
 PROJECTION ARTIFACT

Projection artifact refers to erroneous imaging of superficial

retinal vessels onto the deeper retinal capillary plexus, outer
retina, and choriocapillaris.
 PROJECTION ARTIFACT

Projection artefact due to vitreous floaters

SEGMENTATION ERROR

This is actually not new-vessels but just a

segmentation error on the avascular
retinal layer.
This focal OCTA signal is actually the
elevated choriocapillaries due to a
drusen.
 CONCLUSIONS

OCTA becomes the standard of care for the management of

various vascular-associated retinal diseases and glaucoma.

It is fast, non-invasive and safe, which can be repeatedly

performed for patients who required long-term monitoring.

Interpretation of results with cautions for the image artifacts.

While conventional angiography must be conducted by

ophthalmologists, OCTA can be performed by optometrists!
THE END

Q&A