OCT - In.neuro Ophthalmology - Practice

North American Neuro-Ophthalmology Society
36th Annual Meeting

March 6-11, 2010 • JW Starr Pass Marriott Resort & Spa, Tucson, AZ
Educational Program Schedule
T HURSDAY, MARCH 11 LOCATION
6:30 a.m. – 12:30 p.m. Registration Arizona Ballroom Foyer
6:30 a.m. – 7:30 a.m. Continental Breakfast Arizona Salon
8:30 a.m. – 10:30 a.m. Spouse/Guest Hospitality Suite Signature Grill
7:30 a.m. - 9:30 a.m. OCT IN NEURO-OPHTHALMOLOGY PRACTICE [2 CME] Arizona Salons 1-6
Moderators: Laura J. Balcer, MD, MSCE and Fiona Costello, MD
This half-morning symposium will review the current knowledge concerning the use of
optical coherence tomography (OCT) in patients with neuro-ophthalmologic disorders.
The session will discuss the history of OCT and the evolution of the underlying technology.
The currently available and future equipment will be discussed and evaluated. The
evidence regarding the use of OCT in the diagnosis and follow/up of optic neuritis,
chiasmal lesions, multiple sclerosis and other neurologic diseases will be reviewed.
A perspective on the clinical utilization of OCT drawing on experience from its place in
glaucoma management will be presented. The potential of OCT for monitoring possible
neuro-protective treatment of optic nerve and macular disease will be reviewed.
At the conclusion of the symposium, the attendees should be able to: 1) Describe the
principle of OCT and the forms of equipment available to perform the test; 2) Discuss the
currently available evidence about the use of OCT in evaluating optic neuritis, MS, chiasmal
lesions, and other neuro-ophthalmologic disorders; 3) Explain the lessons available from
the use of OCT in management of glaucoma; and 4) Discuss the potential use of OCT in
monitoring the effects of therapy of anterior visual pathway disease, including
neuroprotective agents.
PAGES
7:30 a.m. – 7:50 a.m. OCT Technologies: Past, Present, and What’s New? - Joel Schuman, MD 327
7:50 a.m. – 8:10 a.m. OCT in Neurologic Disease - Eric Eggenberger, DO, MSEpi 335
8:10 a.m. – 8:30 a.m. Lessons from Glaucoma: Use of OCT in the Clinic and Trials - Joel Schuman, MD 343
8:30 a.m. – 8:50 a.m. Linking Axons and Neurons: Unveiling Mysteries of the Macula and 369
Modeling Neuroprotection - Randy Kardon, MD, PhD
8:50 a.m. – 9:05 a.m. Platform Presentation: Ganglion Cell Layer Volume by Spectralis Optical Coherence 375
Tomography (OCT) in Multiple Sclerosis - Emma Davies, MD
9:05 a.m. – 9:20 a.m. Evidence Meets Practice: Take-Home Points on OCT - Thomas Hedges, III, MD 377
9:20 a.m. – 9:30 a.m. Questions and Discussion
9:30 a.m. – 10:00 a.m. Coffee Break
2010 Annual Meeting Syllabus | 325

LOCATION
10:00 a.m. – 12:00 p.m. THYROID EYE DISEASE UPDATE [2 CME] Arizona Salons 1-6
Moderators: Steven Feldon, MD and Madhu Agarwal, MD
This course will review the latest concepts in the evaluation and treatment of the often
vexing disease process of thyroid orbitopathy. The immunology of the condition as well as
potential new treatments and their indications will be discussed. Speakers will further
discuss newer modalities for assessing disease progression, evaluating strabismus, and
surgical and pharmacologic treatment options. A panel discussion will consider these
topics, as well as the potential for clinical trial in this area.
At the conclusion of the symposium, the attendees should be able to: 1) Understand the
latest diagnostic and assessment tools for thyroid eye disease; and 2) Discuss both
medical and surgical treatment options.
PAGES
10:00 a.m. – 10:30 a.m. Immunology of Thyroid Eye Disease: New Treatments on the Horizon? - 383
Raymond Douglas, MD, PhD
10:30 a.m. – 10:50 a.m. Objective Markers for Thyroid Eye Disease (TED) Activity, Severity 387
and Progression - Kim Cockerham, MD, FACS
10:50 a.m. – 11:20 am. Surgical Techniques for Anatomic Restoration - Raymond Douglas, MD, PhD 391
11:20 a.m. – 11:40 a.m. Ocular Motility in Thyroid Eye Disease –Evaluation and Surgery - 395
Steven Feldon, MD
11:40 a.m. – 12:00 p.m. Panel Discussion: Impediments to Formulating a Meaningful Clinical Trial
12:00 p.m. Meeting adjourns
326 | North American Neuro-Ophthalmology Society

OCT TECHNOLOGIES: PAST, PRESENT, AND WHAT’S NEW?
Joel S. Schuman, MD, FACS,1,2,3 Michelle Gabriele, BS, MS,1,2,3 Gadi Wollstein, MD1
1
UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center,
Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA;
2
Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh;
3
Center for the Neural Basis of Cognition, Carnegie Mellon University and University of Pittsburgh
LEARNING OBJECTIVES INTRODUCTION

• The attendee will be able to describe the basic The development of optical coherence tomography (OCT)
principles of optical coherence tomography. began with a team comprised of clinician-scientists and
a physicist at Massachusetts Eye and Ear Infirmary (MEEI),
• The attendee will be able to explain how OCT can be
Harvard University and engineers at the Massachusetts
used in the detection of ocular diseases.
Institute of Technology (MIT). Remarkably, one member
• The attendee will be know the utility and potential of this group was a graduate student, one a postdoctoral
utility of OCT in the assessment of longitudinal change fellow, and another was a predoctoral fellow. OCT actually
in diseases of the eye. began as optical coherence domain ranging (OCDR),
essentially a single A-scan in what we now know as OCT.
OCDR was being developed by James Fujimoto and
CME QUESTIONS AND ANSWERS Carmen Puliafito for corneal ranging. Joel Schuman was
1. What is the basic physical principle underlying optical a fellow in Puliafito’s laser laboratory at MEEI and David
coherence tomography (OCT)? Huang an MD, PhD student in the Harvard-MIT Health
Sciences Technology (HST) program, working in Fujimoto’s
2. How can OCT be used to detect eye disease, and is
laboratory at MIT. Eric Swanson was an engineer at MIT-
there any evidence that it can do so?
Lincoln Laboratories, Charles Lin a physicist in Puliafito’s
3. How can OCT be used to assess change over time in lab and William Stinson a preresidency fellow working in
eye disease? Puliafito’s lab as well. These seven people were the key
persons involved in the development of this technology.
Joel Schuman, while working on other projects in the laser

KEY WORDS
laboratory, became aware of the OCDR corneal ranging
• Optical Coherence Tomography (OCT) target. It occurred to Schuman that the near infrared
• Optic Nerve Head (ONH) wavelength of OCDR would be able to safely measure
retinal thickness, and would perhaps be useful for
• Retinal Nerve Fiber Layer (RNFL) measuring retinal layers. After discussing this idea with
• Macula Puliafito, Schuman pursued the concept together with
Fujimoto and Huang. Schuman, Huang, Lin and Stinson
• Ganglion Cell Complex (GCC) did the very first retinal ranging experiments in James
Fujimoto’s laboratory at MIT.
Supported in part by National Institutes of Health David Huang, while an MD-PhD student, had the insight
contracts R01-EY13178-10, R01-EY11289-24, and that an OCDR A-scan was similar to an ultrasound A-scan,
P30-EY08098-21 (Bethesda, MD), The Eye and Ear and that creating a tomographic cross-sectional image
Foundation (Pittsburgh, PA), and unrestricted grants from similar to an ultrasound B-scan would be possible. The
Research to Prevent Blindness, Inc. (New York, NY). technology was refined to create tomography, and was
Corresponding Author: Joel S. Schuman, MD, UPMC renamed Optical Coherence Tomography (OCT). In 1991
Eye Center, Eye and Ear Institute, Department of the first scientific paper regarding OCT was published,
Ophthalmology, University of Pittsburgh School of describing the use of an optical detection technique called
Medicine, 203 Lothrop Street, Suite 816, Pittsburgh, PA low coherence interferometry to acquire cross-sectional
15213; schumanjs@upmc.edu. images of the peripapillary region of the human retina ex
vivo.1 Low coherence tomography refers to the detection
Conflict of Interest Statement: Dr. Schuman receives
of light that has been split, reflected off of an object of
royalties for intellectual property licensed by
interest and a reference mirror and recombined. This
Massachusetts Institute of Technology to Carl Zeiss
recombination produces an interference pattern with an
Meditec. Dr. Wollstein received research funding from
amplitude proportional to the reflectivity of the
Carl Zeiss Meditec and Optovue. Dr. Schuman received
corresponding location (same optical path length) within
honoraria from Carl Zeiss Meditec, Heidelberg Engineering
tissue of interest. Individual axial scans, or A-scans, are
and Optovue. Ms. Gabriele reports no conflicts.

acquired at a given location in tissue and correspond to a acquisition speeds of 24,000 - 55,000 A-scans per
reflectivity profile in depth. Multiple neighboring A-scans second. Axial resolution improvements in these systems
can be acquired to build up a B-scan that represents an can be attributed to broader bandwidth light sources.
optical cross-section of the tissue.
OCT was described in vivo in 19932 and quickly used in

HEALTHY EYES
human subjects as a research tool to investigate retinal
and glaucomatous abnormalities.3-6 During this time the This section provides representative ocular OCT images,
technology was transferred to industry. The OCT patent both time-domain and spectral domain, from healthy
was granted in 1994 to Fujimoto, Huang, Lin, Puliafito, subjects. Figure 1a shows a representative SD-OCT image
Schuman and Swanson, and was licensed by what is now through the macular region of a healthy subject, while the
Carl Zeiss Meditec, Inc. (Dublin, CA), allowing the creation Figure 1b shows a representative TDOCT image from the
of a device that could be broadly used for patient care. same subject. Note that the time-domain image contains
128 Ascans and the SD-OCT image contains 1000 A-
The first commercial system became available in 1996 scans; however, the TD-OCT image required 0.32 seconds
and was a time-domain OCT system (TD-OCT). This to acquire, while the SD-OCT image, with eight times
means A-scans are acquired by moving the more Ascans, took 0.04 seco
interferometer’s reference mirror, which changes the
reference path length and enables the detection
FIGURE 1: (a) Vertical SD-OCT cross-section through the macula
reflectivity from different depths in a given structure.
of the same subject. The white box with vertical line indicates
Hence, in TD-OCT imaging, the time of flight of the light the orientation of SD-OCT image. (b) Vertical TDOCT
reflected from the retinal structures determines the OCT cross-section through the macula.
measurements. The commercial time-domain OCT system
has an axial resolution of approximately 10μm.
The first commercial two iterations of OCT were not

particularly successful, in part because of the novelty of
the technology, but also because systems were big, slow
and difficult to use. This changed in 2002 with the
introduction of Stratus OCT. The Stratus system acquired
400 A-scans per second, compared with 100 per second
a b
in prior versions. Stratus OCT also had a normative
database, making clinical use considerably more practical,
and the system was now ergonomically designed. Finally, Figure 2 shows spectral domain (left panel) and time-
a billing code for scanning computerized ocular diagnostic domain (right panel) OCT retinal nerve fiber layer (RNFL)
imaging was introduced around the time that Stratus came assessments. With time-domain devices, a 3.4-mm
to market. All of these factors contributed to the rapid circular scan centered on the optic nerve head (ONH) is
adoption of the technology; by 2008 10,000 OCT devices used to assess peripapillary RNFL thickness. Typically,
were in worldwide clinical use. three OCT scans (with 256 A-scans per scan) are acquired
OCT underwent further evolution with the clinical in succession, the RNFL is segmented, and thickness
availability in 2006 of spectral-domain OCT (SD-OCT).7-11 measurements along the scan are compared to a
SD-OCT introduced in 2006 was 40-60 times faster than normative database. Using spectral-domain three-
TD-OCT, allowing the collection of large amounts of dimensional tissue volumes from around the optic nerve,
clinical data, permitting increased scan densities and three one can reconstruct the RNFL peripapillary scan by
dimensional imaging. SD-OCT refers to the measurement resampling the tissue volume along a 3.4 mm circle
of tissue thickness using not time of flight but reflected centered on the ONH. An extracted RNFL scan can be seen
wavelengths (frequencies). Using SDOCT, an entire A-scan in Figure 2, bottom left. Above it, an RNFL thickness
can be collected simultaneously, and the optical overlay on a normative database is shown along with
frequencies analyzed using fast Fourier transformation clock-hour and quadrant RNFL thickness measurements.
and mathematical algorithms to create a tomographic One peripapillary TD-OCT scan, with RNFL segmentation
image and determine depth information, converting from (white line), is shown in Figure 2, bottom right. Above it
the frequency domain to the time domain. Because optical lie the normative database with an overlay of RNFL
frequencies from different depths are detected at once thickness and clock-hour and quadrant RNFL thickness
and used to determine the spatial locations of reflections measurements.
in the A-scans, a moving reference mirror is not required:
conversion from the frequency domain to the time domain
occurs after acquisition. This means SD-OCT systems can
acquire A-scans much faster than time-domain systems.
SD-OCT systems have recently been commercialized by
several companies, and most of these systems have an
axial resolution of approximately 3.5 - 6μm and

FIGURE 2: (Left) SD-OCT RNFL thickness clock-hour and When three-dimensional tissue volumes have been
quadrant measurements (top), comparison to normative acquired around the optic nerve head region using
database (middle), and resampled 3.4-mm RNFL B-scan
SD-OCT , RNFL thickness maps can be created by
(bottom). (Right) TD-OCT RNFL thickness measurements (top),
comparison to normative database (middle) and 3.4-mm RNFL segmenting the RNFL in each frame of the volume,
peripapillary scan (bottom). Both images were acquired from excluding the optic nerve head region. This provides easy
the same subject, same day. visualization of areas of thinning around the optic nerve.
Example RNFL thickness maps from a healthy subject can
be seen in Figure 4.
FIGURE 4: RNFL thickness map of the left eye of a healthy

subject created from a 200 x 200 A-scan scanning (6 x 6 mm)
of the optic nerve head region. Thicker areas are red and
thinner areas are blue. The uniform blue area towards the
center of each map indicates the optic nerve head region,
where no thickness measurements are made.
In SD-OCT , after multiple B-scans are acquired in raster

fashion and a three-dimensional volume of tissue is
acquired, en-face (OCT fundus) images can be generated
by summing intensity values along the z-direction (in
In addition to posterior segment imaging, images of the
depth). An example SD-OCT fundus image through the
cornea and anterior chamber can be acquired with OCT.
macular region of a healthy subject is seen in Figure 3.
Figure 5 shows a horizontal TD-OCT image through the
cornea of a healthy subject. Figure 6 shows an anterior
chamber TD-OCT image from the same subject.
FIGURE 3: SD-OCT fundus image of the macular region of the
left eye of a healthy subject, created by taking the sum of the
reflections along the direction of each individual A-scans in the FIGURE 5: TD-OCT image through the cornea of a
200 x 200 A-scan volume. This creates a picture-like image due healthy subject.
to the total reflection at each scan location being viewed in the
en-face composite, much the same as in a photograph.
FIGURE 6: TD-OCT image through the anterior

chamber of a healthy subject.

GLAUCOMA FIGURE 9: (Left) SD-OCT RNFL thickness clock-hour
and quadrant measurements (top), comparison to
A 58-year-old woman with a history of primary open normative database (middle), and resampled 3.4-mm
angle glaucoma presented with an IOP of 30 in the right RNFL B-scan (bottom) in patient with primary open
eye (VA 20/20). Visual field testing showed a superior angle glaucoma and inferior RNFL loss. (Right) TD-OCT
arcuate defect, with a glaucoma hemifield test outside RNFL thickness measurements (top), comparison to
normative database (middle) and 3.4-mm RNFL
normal limits, mean deviation of -1.25 dB, and pattern
peripapillary scan (bottom). Both images were
standard deviation of 4.37 dB (Figure 7). Widespread acquired from the same subject, same day.
inferior nerve fiber layer thinning can be seen in the
SD-OCT RNFL thickness map (Figure 8). Figure 9, top,
shows clock hour and quadrant thicknesses from SD-OCT
(left panel) and TD-OCT (right panel). A comparison to a
normative database is shown below the segment a b
measurements. Both spectral- and time-domain
measurements show inferior thinning of the RNFL, as
indicated by red quadrant and clock hour segments.
Looking at individual spectral- domain and time domain
OCT cross sections (bottom left and bottom right,
respectively), thinning of the RNFL can be seen (arrows).
Note that the white line outlining the RNFL in the time-
domain image indicates segmentation of the RNFL; this
line is not present in the spectral-domain image. In
addition, the spectral-domain image has not been
flattened using image filtering techniques while the
AGE-RELATED MACULAR DEGENERATION
time-domain image has. Figure 10 shows a fundus photograph and slow macular
(512 A-scans) TD-OCT scan from an 84-year-old female
FIGURE 7: Visual field test showing a superior arcuate with exudative age-related macular degeneration; she had
defect from a patient with primary open angle glaucoma. with 20/40 vision in the right eye. Drusen and RPE
changes were noted upon clinical examination. The
fundus photograph (Figure 10a) shows numerous drusen
in the macular region. Similarly, irregularities in the RPE
can be seen in the horizontal OCT crosssection though the
macular region (Figure 10b, arrows).
FIGURE 10: (a) Fundus photograph of

age-related macular degeneration patient with
drusen (b) Horizontal TD-OCT scan (512 A-scans).
Arrows indicate areas that are likely drusen.
FIGURE 8: RNFL thickness map of patient with primary open

angle glaucoma showing inferior thinning of the RNFL (map
created from 200 x 200 A-scans, 6x6 mm region around the
optic nerve head). The uniform blue region towards the
center of the image represents the optic nerve head while
black region is the result of RNFL detection algorithm failure.
a

MACULAR HOLE BRANCH RETINAL VEIN OCCLUSION
A 72-year-old male presented with a distorted vision in Figure 13a shows a late-phase angiograph from an
the right eye (VA 20/200) and 20/50 vision in the left eye. 82-year-old male with branch retinal vein occlusion in the
Both spectral-domain and TD-OCT images showed a large right eye. He presented with a visual acuity of 20/400 and
macular hole in the right eye with posterior hyaloid clinical examination showed hemorrhage and macular
partially attached to edge of the hole (Figure 11, spectral- edema in the right eye. A slow macular (512 A-scans)
domain horizontal and vertical cross-sections on left and horizontal TD-OCT image showed clinically significant
timedomain horizontal and vertical cross-sections on macular edema (Figure 13b).
right). Small cystoid changes with a vitreous traction were
seen in the left eye along with posterior hyaloid traction in
FIGURE 13: (a) Late-phase angiograph showing branch retinal
the foveal center (Figure 12). Three-dimensional vein occlusion (b) Horizontal TD-OCT image (512 A-scans)
reconstructions of the thickness maps of the macular through the macular region showing edematous changes.
region are also shown (Figure 11 and 12, top) and were
created by segmenting three-dimensional data volumes
(200 x 200 A-scans in a 6 x 6 mm region of the retina)
from the ILM to the RPE. The blues lines on each thickness
map correspond to the location of the horizontal spectral-
domain cross-sections (1000 A-scans each), while the
purple lines correspond to the location of vertical cross-
sections (1000 A-scans).
a
FIGURE 11: Right eye (Top) Three-dimensional reconstruction of

macular region showing foveal thickening (red) that corresponds
to the location of a macular hole and corresponding edema
(Middle and Bottom, left) Horizontal and vertical SD-OCT (1000
A-scans) cross-sections through the macular hole (Middle and
Bottom, right) Horizontal and vertical TD-OCT (512 A-scans)
cross-sections through the macular hole.
b
MACULAR PUCKER
A 60-year-old woman with 20/70 vision in the left eye
showed a pronounced epiretinal membrane with posterior
vitreous detachment. A three-dimensional reconstruction
of the macular thickness map illustrates the extent of
macular puckering (Figure 14a). The epiretinal membrane
can be seen in individual horizontal spectral-domain
(Figure 14b) and time-domain (Figure 14c) OCT images
(arrows).
FIGURE 12: Left eye. (Top) Three-dimensional reconstruction FIGURE 14: (a) Three-dimensional reconstruction of macular
of macular region showing slight foveal thickening (green) that region showing macular puckering (b) Horizontal SD-OCT (1000
corresponds to the location of small cystoids changes A-scans) and (c) time-domain (512 A-scans) OCT images through
(Middle and Bottom, left) Horizontal and vertical SD-OCT the macula, with arrows indicating epiretinal membrane.
(1000 A-scans) crosssections through the macular (Middle and
Bottom, right) Horizontal and vertical TDOCT (512 A-scans)
cross-sections through the macula.

DIABETIC MACULAR EDEMA POTENTIAL DIAGNOSTIC POWER
Figure 15 (a) and (b) show a fundus and red-free Since its commercialization in 1996, OCT has increasingly
photograph, respectively, from a 65-year-old male with become a valuable tool for ophthalmologists. Posterior
moderate nonproliferative diabetic retinopathy and segment imaging has improved the quantification of RNFL
clinically significant diabetic macular edema in the right damage in glaucoma and the visualization of changes due
eye. He presented with 20/160 vision in this eye. to age-related macular degeneration, macular hole,
Scattered blot hemorrhages and hard exudates can be epiretinal member and macular puckering, macular edema
seen in the fundus photograph, and microaneurysms in and more. In addition, anterior segment imaging allows
the red-free photograph. A SD-OCT macular thickness clinicians to monitor patients after LASIK (not shown here)
mapa(200 x 200 A-scans covering 6x6 mm region, and corneal injury, and provides a non-invasive alternative
segmented from the ILM to the RPE) superimposed on a to ultrasound biomicroscopy for anterior chamber
fundus photograph (Figure 15c) shows a region of imaging.
thickening that corresponds to the macular edema, with
While OCT offers several advantages to clinicians, certain
thicker areas represented as hotter colors. Horizontal
limitations need to be kept in mind. This technique,
(Figure 15 d) and vertical (Figure 15e) spectral-domain
especially spectral-domain imaging, is still rather new and
crosssectional OCT images show the extent of fluid
longitudinal studies are required to evaluate its objective
accumulation in the macular region.
monitoring capabilities. In addition, high-speed imaging
is very sensitive to eye motion and large movements may
FIGURE 15: (a) Fundus photograph of patient with make measurements inaccurate. Fortunately, however,
diabetic retinopathy and clinically significant macular solutions to these restrictions are currently being pursued
edema. (b) Red-free photograph. (c) SD-OCT thickness by several research groups.
map of macular region superimposed onto fundus
photograph, with thicker areas white/red. In sum, OCT offers clinicians a new perspective on
(d) Horizontal and (e) vertical SD-OCT images (1000 structural damage caused by disease. This may lead to
A-scans each), the location of each corresponding to enhanced diagnostic power — not only through objective
the blue and purple lines on the macular thickness map.
quantification but through synergy with other methods of
evaluation that are presently available to clinicians.
CME ANSWERS
1. OCT is based on interferometry
2. Measurements of various ocular structures demonstrate

a b differences in disease and health. There are numerous
articles showing the usefulness of OCT in disease
detection for glaucoma and other optic neuropathies,
macular degeneration and other retinal diseases, as well
as diseases of the anterior segment and anterior
chamber angle.
c 3. Change can be measured in the RNFL, macula and optic
nerve head using software algorithms, some of which
exist already and others in development. The relevant
tissue should be evaluated when investigating
longitudinally.
d e

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OCT IN NEUROLOGIC DISEASE
Fiona Costello, M.D.; Adnan Subie, D.O.; Eric Eggenberger, D.O., MSEpi
Michigan State University
East Lansing MI
LEARNING OBJECTIVES INTRODUCTION

The attendee will be able to: Optical coherence tomography (OCT) has evolved
dramatically since the first reports of this technology
1. Understand OCT as it applies to optic neuropathy-
in 1991, and has become an integral part of the
related neurologic diseases such as MS.
ophthalmology evaluation. In addition to providing an
2. Understand OCT applications to CNS diseases indispensible service for the retina physician, the ability to
associated with disc edema. quantify the retinal nerve fiber layer has begun to change
neuro-ophthalmic practice. In this regard, OCT has the
3. Understand relationships between OCT measures
potential to change qualitative, subjective descriptive
and other CNS measures including clinical optic nerve
reporting into reproducible quantitative science.
function.
Quantification of the RNFL has several clinical
applications, including numerous diseases of the optic
CME QUESTIONS nerve, both in documentation of edema and quantification
1. OCT works by: of optic atrophy; OCT has also become a viable study
outcome in treatment trials. This review will focus on
a. light reflectivity current OCT applications as they apply to neuro-
b. echo location ophthalmic clinical practice.
c. birefringence of the retinal axons
d. xray imaging RETINAL IMAGING METHODOLOGIES

In addition to OCT, commercially available retinal imaging
e. magnetic imaging
devises also include Heidelberg Retinal Tomography
2. OCT has demonstrated retinal nerve fiber loss in (HRT), and scanning laser polarimetry (GDx). Each of these
which of the following conditions: instruments has inherent advantages and disadvantages,
and results obtained from 1 instrument do not translate
a. optic neuritis
into results from another imaging technique. The
b. MS Heidelberg Retina Tomograph (HRT) is a confocal laser
scanning system to acquisition three dimensional retinal
c. Alzheimer’s disease
images. GDx relies on birefringence of the retinal ganglion
d. NAION cell axon microtubules and filaments. Monteiro and Moura
compared GDx with variable corneal compensation (VCC)
e. All of the above
against TD-OCT in patients with band atrophy (BA) from
3. OCT is an emerging non-invasive technology that at chiasmal compression, and reported GDx appeared to
present is a useful tool in the GROUP analysis of underestimated the temporal quadrant by an average of
neuro-ophthalmic conditions, rather than the basis 22µm; conversely, Zaveri et al found OCT and GDx-VCC
for INDIVIDUAL clinical decisions. True or False equally able to measure RNFL thickness in MS patients
experiencing acute optic neuritis; by virtues of assessing
retinal ganglion cell axon microtubule density, GDx
KEY WORDS changes appeared earlier than OCT-demonstrable RNFL
1. OCT thinning. The remainder of this review will focus on OCT
as the most common methodology employed in neuro-
2. Optic Neuritis ophthalmic practice.
3. Multiple Sclerosis
4. Papilledema OCT METHODOLOGY

Time-domain OCT (TD-OCT), the 3rd generation
instrument, is able to record a series of 512 x 1024
A-scan images within 2 seconds with approximately 10µm
resolution. Several studies have demonstrated TD-OCT’s
reproducibility in assessing the RNFL thickness in normal
eyes, glaucoma, and various non-glaucomatous optic

neuropathies. The next generation of OCT, Spectral- Bellusci et al documented RNFL edema followed by
domain OCT (SD-OCT), has significantly improved the thinning in the superior optic nerve among acute NAION
speed of image acquisition; the SD-OCT captures patients with inferior altitudinal defects; conversely,
approximately 27,000 scans per second with a resolution patient with diffuse visual field (VF) loss had extensive
of 5µm, and has the ability to form a 3-dimentional map RNFL thinning. Temporal quadrant RNFL thinning
of the retina and optic nerve, allowing more accurate (papillomacular fibers) correlated with central field
distinctions between retinal layers. In addition, SD-OCT defects. Chan et al used OCT to investigate the optic disc
automatically centers the scan on the optic disc with the in 22 NAION patients; smaller cups and C:D ratios were
use of optic nerve landmarks to decrease scan — rescan more common in NAION eyes compared to control eyes;
variability. Although measurements with the TD-OCT and additionally, a smaller cup was present in the non-
SD-OCT instruments correlate well, the RNFL and retinal affected fellow eye of NAION patients (C:D 0.103)
thickness results are not interchangeable. compared to the affected NAION eye (C:D 0.135; P=0.04),
suggesting a small degree of cup enlargement after
OCT VS Histology
NAION.
Blumenthal et al compared OCT-derived RNFL
measurements to histology-derived measurements These studies indicate that OCT-measured RNFL values
(exenterated orbit secondary to an infiltrative squamous correlate with the topographical representation of visual
cell carcinoma), and reported OCT outcomes mirrored the field defects in eyes with NAION. Further, reduced RNFL
histology, but actual measurements differed by 10-40µm. values can help predict recovered visual function in NAION
This discrepancy likely reflects identification of the RNFL patients.
layers via staining techniques versus optical reflectance.
Optic Neuritis (ON) & Multiple Sclerosis (MS)
Several investigators have demonstrated RNFL loss in
MS patients even without a history of optic neuritis, while
FACTORS INFLUENCING SCAN ACCURACY
superimposed optic neuritis produces additional RNFL
Several factors influence the quality of OCT images. decline. There is a clinical-OCT paradox concerning optic
The 3.4 mm laser reticule must be centered on the optic neuritis, similar to the MRI-clinical paradox within MS.
nerve; decentered scans preferentially affect quadrant MRI T2 lesion load does not correlate with overall
thicknesses, especially the vertical quadrants, while total neurologic function, with MS patients often exhibiting MRI
RNFL remains relatively stable. Surprisingly, use of the lesions out of proportion to their clinical condition
OCT scan tracking coordinates only provided a statistically (especially as assessed by the EDSS). Similarly, OCT RNFL
significant effect on the temporal quadrant. Signal loss appears out of proportion to the clinical visual
strength also positively correlates with the observed RNFL assessments. Although the majority of patients lose RNFL
thickness; many studies require signal strength of 7. Pupil following an episode of optic neuritis, most recover
size is not generally a significant factor as long as size is “normal” visual function (despite the patients’ perception
≥ 3mm. Lens opacities are inversely correlated with the that the ‘recovered’ eye is not normal). Costello et all
measurement of RNFL thickness (effect size <12%); documented an OCT injury threshold of 75µm before a
similarly, contact lenses use is associated with decrease in linear decline in visual field was apparent. Several studies
signal strength (7.8 to 7.1; P=0.011) and the measured have investigated RNFL quadrant data after optic neuritis,
average RNFL thickness (average RNFL 105.3 to 102.8µm; and there appears to be a predilection for the infero-
P=0.001). temporal quadrants.
Costello et al investigated OCT findings in CIS optic

OCT IN CNS DISEASE/OPTIC NEUROPATHIES neuritis. There was no significant difference in RNFL
thickness between CIS progressing to MS versus CIS
Anterior Ischemic Optic Neuropathy (AION)
without MS at 2 years follow up; however, progressive
AION is a disease characterized by disc edema at onset
RNFL thinning was more apparent in CIS patients
with subsequent optic atrophy. Contreras and colleagues
progressing to MS.
used OCT to study 27 patients with NAION at baseline,
6-weeks; and 3, 6, and 12 months after onset. The initial OCT has been used to investigate MS subtypes; RNFL
mean RNFL of 201µm represented a 96.4% increase loss is generally greater in progressive MS than RRMS
relative to the fellow eye. Percentages of RNFL loss 3, 6, (somewhat duration of disease dependent).
and 12 months after onset were 38.9%, 42.3%, and 43.9%,
Neuromyelitis Optica (NMO)
respectively. Regression analysis revealed a 2-dB decrease
In most reports, NMO is associated with greater RNFL loss
in visual field function for every 1-µm of mean RNFL
than optic neuritis or MS. De Seze et al reported RNFL
thickness loss, and a 1-line drop in Snellen visual acuity
thickness of 29 NMO patients had significantly reduced
for every 1.6µm deficit.
RNFL values (77.9 µm ) compared to controls. OCT is not
specific enough to distinguish NMO form ON/MS, but
NMO should be considered in ON patients with poor
recovery, or dramatic RNFL thinning <50µm.

Papilledema/Pseudotumor Cerebri (PTC)/Idiopathic mother. LHON is usually due to one of three pathogenic
Intracranial Hypertension (IIH) mitochondrial DNA (mtDNA) point mutations: at
Patients with idiopathic intracranial hypertension (IIH) nucleotide positions 11778 G to A, 3460 G to A and
typically present with headache, pulsatile tinnitus, 14484 T to C, respectively, in the ND4, ND1 and ND6
transient visual obscurations, and papilledema usually subunit genes of complex I of the oxidative
with relatively preserved visual acuity. phosphorylation chain in mitochondria. Clinically, patients
may develop often acute onset visual loss in one eye,
Intuitively, we expect elevated RNFL values at presentation
followed by fellow eye involvement months to weeks later.
when optic disc edema is maximal, and decreasing RNFL
Vision loss typically occurs in young adulthood. In the
elevation with effective treatment.
acute stage, the affected eye demonstrates telangectatic
Rebolleda and Munoz-Negrete studied 22 PTC patients, and tortuous peripapillary vessels; and with time, optic
and noted the initial increase in RNFL correlated well with atrophy ensues.
visual field mean deviation (MD) (P=0.002) and pattern
Seo et al. studied RNFL in LHON patients with the 11778
standard deviation (PSD; P=0.013). At 1 year follow-up,
and 14484 mutations. Patients were divided into early
perimetry demonstrated a 0.6dB MD decline with a 10µm
(≤6 months) and late (>6 months) categories. In the late
RNFL decrease. It should be noted that OCT alone is
stage, the RNFL thickness was greater in the 14484 group
unable to distinguish resolving edema from emerging
(average RNFL 81µm) compared to the 11778 (average
optic atrophy, and therefore OCT needs to be
RNFL 65.6µm; P=0.02), thus supporting severe atrophy
incorporated into the remainder of the clinical exam.
in the late 11778 group. Comparisons between the 2
Additional information on OCT in IIH will emerge from the
mutations in the early stage may be misleading, since
OCT substudy of the Idiopathic Intracranial Hypertension
there can be considerable variability within this time frame
Treatment Trial (IIHTT).
as thinning occurs. Overall, these OCT findings are in
Optic Nerve Head Drusen agreement with the clinical impression that the 11778
Johnson et al applied the TD-OCT “fast optic disc” mutation is associated with worse visual outcome than the
protocol to differentiate disc drusen from disc edema. 14484 mutation.
Drusen appeared more “lumpy-bumpy” with RNFL thinner
Savini et al used OCT to study RNFL thickness in
than 86µm nasally in contrast to the smooth and elevated
unaffected carriers with LHON mutations. Sixty-six
contour of true disc edema.
unaffected carriers (44 females and 22 males) were
Compressive Optic Neuropathy (CON) analyzed and compared with an age-matched control
Danesh-Meyer et al investigated OCT’s ability to predict group of 70 patients (40 females and 30 males). As
visual recovery from CON. Thirty five patients with various compared to the control group, unaffected male carriers
etiologies of CON were evaluated with OCT and visual showed thicker RNFL measurements in the temporal and
fields pre- and post-surgical decompression. The patients inferior RNFL quadrants and in the 360 degrees average
were divided into 2 groups: “normal” RNFL and “thin” RNFL measurements. These differences reached statistical
(defined as pre-op RNFL <97.5% of normal values). significance in subjects carrying the 11778 mutation,
Patients with reduced VA and VF but normal RNFL whereas only a trend was detected in those with the 3460
thickness had significant improvement of VA (mean of mutation. Unaffected female carriers had an increased
20/40 to 20/25; P=0.028) post-decompression than thickness in the temporal quadrant when compared with
those with “thin” RNFL (20/80 to 20/60; P=0.177). the control group (P = 0.003). The increase in temporal
Although the mean improvement in the “thin” RNFL group sectors was statistically significant in females with the
of 2 lines was statistically insignificant, this degree of 11778 mutation, whereas a trend was detected in those
improvement may well be clinically significant. The with the 3460 mutation. A thickening of the temporal
analysis found an increased likelihood of post-op fibers was detected in all subgroups of unaffected
improvement with a thicker pre-op RNFL until carriers.
approximately 85µm, after which there was no additional
Migraine
benefit was observed; this likely reflects the fact that
Martinez et al used OCT to study 70 patients with
patients with RNFL of 85µm have relatively preserved
migraine, and noted a significant RNFL reduction in the
visual function. While pre-op measurements of RNFL do
temporal quadrants of migraineurs compared to healthy
not necessarily change our management of patients with
controls; additionally, the RNFL in migraine with aura
CON, such studies enhance our ability to predict visual
(average RNFL 96.5µm) was significantly less than
outcome post decompression in CON.
migraine without aura (average RNFL of 102.9µm;
Hereditary Optic Neuropathies/Leber Hereditary P=0.0189). Significantly thinner RNFL was found in
Optic Neuropathy (LHON) patients with migraine ≥15 years. These investigators
Leber hereditary optic neuropathy (LHON) is a found a correlation between RNFL thickness and migraine
mitochondrially inherited degeneration of retinal ganglion disability assessment (MIDAS) scores.
cells and their axons that leads to an acute or subacute
loss of central vision. Affected patients are predominantly
males, mutations in the mitochondrial genome from their

Neurodegenerative disease/Alzheimer Disease 9. Blumenthal EZ, Williams JM, Weinreb RN, et al. Reproducibility
There is both histologic and retinal imaging evidence of of nerve fiber layer thickness measurements by use of optical
coherence tomography. Ophthalmology. 2000;107:2278-82.
retinal ganglionic cell (RGC) in patients with Alzheimer
disease (AD). Danesh-Meyer et al used HRT scanning laser 10. Budenz D, Chang R, Huang X, et al. Reproducibility of nerve
ophthalmoscopy (SLO) to investigate 40 patients with AD fiber thickness measurements using stratus OCT in normal
and glaucomatous eyes. Invest Ophthalmol Vis Sci.
compared to age- and sex-matched controls, and found
2005;46:2440-3.
that clinical and SLO vertical cup-to-disc ratio was
significantly different between the groups (AD 0.4, 11. Bulens C, Meerwaldt JD, Van der Wildt GJ, Van Deursen JB.
Effect of levodopa treatment on contrast sensitivity in
control 0.27-0.31); additionally, these authors reported Parkinson’s disease. Ann Neurol 1987;22:365-369.
decreased rim volume, RNFL thickness and rim area
in AD compared to controls. 12. Carpineto P, Ciancaglini M, Zuppardi E, et al. Reliability of
nerve fiber layer thickness measurements using optical
coherence tomography in normal and glaucomatous eyes.
Ophthalmology. 2003;110:190-5.
CONCLUSION
13. Cettomai D, Pulicken M, Gordon-Lipkin E, et al.
OCT has enhanced our assessment, management, and Reproducibility of optical coherence tomography in multiple
understanding of neuro-ophthalmic diseases, and has sclerosis. Arch Neurol. 2008;65:1218-22.
potential to further our understanding of other CNS-based 14. Cettomai D, Pulicken M, Gordon-Lipkin E, Salter A, Frohman
diseases. OCT has the advantages of reproducibility, T, Conger A, Zhang X, Cutter G, Balcer L, Frohman E,
ease of use, non-invasive nature and relatively low cost, Calabresi P. Cross center and inter-rater reproducibility of
optical coherence tomography in multiple sclerosis. Arch
makes it an asset to several clinical situations. With its
Neurol 2008;65:1218-1222.
advancement into spectral domain, OCT has wide use in
evaluating the optic nerve and the visual system. 15. Decreased retinal nerve fibre layer thickness detected by
optical coherence tomography in patients with ethambutol-
induced optic neuropathy. : 2007; 91(7):895-7.
CME ANSWERS 16. Chan CK, Cheng AC, Leung CK, et al. Quantitative
assessment of optic nerve head morphology and retinal
1. A nerve fibre layer in non-arteritic anterior ischaemic optic
neuropathy with optical coherence tomography and confocal
2. E scanning laser ophthalmoscopy. Br J Ophthalmol.
2009;93(6):731-5.
3. True
17. Chen J, Lee L. Clinical applications and new developments of
optical coherence tomography: an evidence-based review.
Clin Exp Optom. 2007;90(5):317-35.
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LESSONS FROM GLAUCOMA:
USE OF OCT IN THE CLINIC AND TRIALS
Joel S. Schuman, MD, FACS, Allison K. Ungar, Gadi Wollstein
Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute,
Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine,
Pittsburgh, PA
LEARNING OBJECTIVES care provider. The first-line diagnostic tools for

1. The participant will be able to describe the two types identifying glaucoma are clinical examination with direct
of optical coherence tomography devices. or indirect ophthalmoscopy and/or stereoscopic optic
nerve head photographs. Unfortunately, these tools are
2. The participant will be able to explain the advantages prone to high intra- and inter-observer variability.
of Spectral-Domain Optical Coherence Tomography in Recently, a number of imaging devices have been
comparison to Time-Domain Optical Coherence introduced with the goal of early detection and
Tomography. quantification of structural glaucomatous changes in the
3. The participant will be able to describe five different retinal nerve fiber layer and optic nerve head. One of the
scenarios where OCT would be clinically useful in commercially available glaucoma imaging devices is
glaucoma diagnosis and management. optical coherence tomography (OCT). OCT generates
cross-sectional and three-dimensional images of retinal
structures. Its application in glaucoma diagnostics and
monitoring will be discussed in this chapter.
CME QUESTIONS
1. What are the most clinically relevant parameters
collected from an OCT scan for glaucoma?
INTRODUCTION
2. Name the three main scans from time domain OCT. Glaucoma is the second leading cause of blindness
3. Name 4 advantages of Spectral-Domain Optical worldwide. It is characterized by the accelerated death
Coherence Tomography in comparison to Time- of retinal ganglion cells and presents as progressive
Domain Optical Coherence Tomography functional damage to the visual field. The World Health
Organization (WHO) has projected this disease to affect
60.5 million individuals by the year 2010, leaving 8.4
million blind. With the world’s aging population, the
KEY WORDS
burden of disease is predicted to grow exponentially,
• Optical Coherence Tomography (OCT)
affecting 80 million people by 20201.
• Time-Domain Optical Coherence Tomography
With this understanding, the WHO has made it a priority
(TD-OCT)
eye disease to address with their program Vision 2020,
• Spectral-Domain Optical Coherence Tomography which aims to prevent avoidable blindness. One of their
(SD-OCT) specific objectives is to develop adequate training
methods in the diagnosis of glaucoma, as early
• Retinal Nerve Fiber Layer (RNFL)
intervention has been shown to slow disease progression
• Circumpapillary Scan and preserve functional sight2. The NIH National Eye
Institute has also set improved glaucoma diagnostic
• Ganglion Cell Complex (GCC) measures as a part of their National Plan for Eye and
• Glaucoma Progression Analysis (GPA) Vision Research.
• Visual Field Index (VFI) Unfortunately, early detection of glaucoma remains a

challenge. No symptoms appear until there is advanced
• Pre-perimetric retinal ganglion cell death and visual field loss. Estimates
• Central Island of undiagnosed glaucoma range from 40 to 90%, with
higher percentages found in underdeveloped nations4.5.
There is no formal screening method for glaucoma.

ABSTRACT Disease detection is solely dependent on the clinical
Glaucoma is the second leading cause of blindness capabilities of the eye care provider. The first-line
worldwide. It is characterized by the accelerated death of diagnostic tools for identifying structural changes in
retinal ganglion cells and presents as progressive glaucoma are clinical examination with direct or indirect
functional damage to the visual field. There is no formal ophthamoscopy and/or stereoscopic ONH photographs.
screening method for glaucoma. Disease detection is These tools are mostly qualitative thus prone to high
solely dependent on the clinical capabilities of the eye intra- and inter-observer variability7-9. The functional
damage caused by glaucoma which causes characteristic COMMERCIAL TYPES OF OCT
patterns of VF loss is often quantified through the use of TD-OCT
standard automated perimetry (SAP). SAP is a threshold • Stratus (CZMI)
test that determines the eye’s sensitivity to light
throughout the central visual field (VF). This commonly SD-OCT
used clinical test has a high test-retest variability, and • Cirrus (CZMI)
multiple VF tests are required to confirm damage10,11. • Spectralis (Heidelberg Engineering, Heidelberg,
Also, significant structural loss may occur before changes Germany)
are detected by VF12.
• RTView (Optovue, Fairmont, CA)
A number of ocular imaging devices have been introduced
which provide reproducible quantification of the retinal • TopCon (Topcon Medical Systems, Inc, Paramus, NJ)
nerve fiber layer (RNFL) and ONH. The commercially • Bioptogen (Research Triangle Park, Durham, NC)
available glaucoma imaging devices (GIDs) include: optical
coherence tomography (OCT), confocal scanning laser
ophthalmoscopy (CSLO) and scanning laser polarimetry
FEATURED HIGHLIGHTS OF OCT DEVICES
(SLP).
When deciding on an device to use in the clinic or in
Using the best parameters of each GID has been shown to research, consider that different instruments have
have specificity and sensitivity similar to that of glaucoma different special features which make them unique.
experts in detecting glaucomatous ONH abnormalities40,41.
Various imaging devices emphasize:
Studies directly comparing these three technologies
have not found significant differences in their diagnostic • Tracking to control for eye motion.
ability42-46. In 2007, the American Academy of
• 3-Dimensional reconstruction.
Ophthalmology suggested that information from imaging
printouts is best used in conjunction with other clinical • Advanced visualization with cube data
parameters47.
• Averaging scan data to make for a visually appealing
image.
BASICS OF OCT • Fundus image either red-free or CSLO, which
OCT generates cross-sectional and three-dimensional provides information about orientation.
(3D) images of retinal structures by detecting coherent • Quantification of various parameters.
(non-scattered) light echoes with an interferometer. The
most important glaucoma application of the device is the • Comparison to a normative database to use clinically.
measurement of RNFL thickness. Thinning of the RNFL • A variety of scan patterns allowing for multiple means
has been well correlated with the fundamental of visualizing any pathology.
pathophysiology of glaucoma namely the destruction
of the ganglion cell layer of the retina20. • Automatic registration within a cube of data allowing
for more accurate change analyses.
The commercial time-domain OCT (TD-OCT) system
(StratusOCT, Carl Zeiss Meditec, Dublin, CA (CZMI)), has
an axial resolution of 8-10µm and obtains scans at a rate
OCT SCAN PATTERNS
of 400 axial scans/second. A newer model of OCT,
Spectral Domain OCT (SD-OCT), is able to detect all of the TD-OCT
light echoes simultaneously rather than sequentially, as in • Peripapillary Circle Scan
time domain detection. This enables a dramatic increase – This is relevant in glaucoma as it is a robust
in resolution and scanning speed, most offering a 5-7µm indicator of the nerve fiber layer thickness.
axial resolution and 25,000 scans per second. The • ONH
increase in resolution is advantageous in following small – Provides cup and disc parameters.
changes in progression.
• Macula
OCT provides reproducible quantification of the RNFL – This is an alternative to the circle scan which
thickness13-15. a measurement that correlates with the provides a statistically significant correlation with
fundamental pathophysiology of glaucoma, namely the glaucoma.
destruction of the ganglion cell layer of the retina. OCT
provides good glaucoma discrimatory power with an area – Note: Correlation r=.52 between overall mean
under the receiver operating curve of 0.79 to 0.97, macular thickness and peripapillary RNFL
depending on the referenced sector21-25. thickness

In a longitudinal study published in 2005 by Wollstein, FIGURE 2: HVF – Normal gray scale (left) and pattern
et al., OCT sensitivity using RNFL thickness was higher deviation (right).
than that of SAP. [Reference]
SD-OCT
• 3-Dimensional Cube (multiple B-scans compiled)
– Post-processing allows a misaligned scan to be

fixed, removing a limitation of TD-OCT.
– Increased reproducibility in comparison with

TD-OCT [Reference: Kim JS, Br J Ophthalmol 2009]
– Faster speed in comparison with TD-OCT reduces

the number of motion artifacts
FIGURE 3: HVF – VFI graph over 5 years showing no

progression.
CASE 1: NORMAL EYE
This was a 45 year old Caucasian man with
hypothyroidism and no ocular disease. Best corrected
visual acuity in the left eye is 20/16 wearing a prescription
of -2.00+1.50x174, intraocular pressure (IOP) was
12 millimeters of mercury (mmHg), and pachymetry
showed a central corneal thickness (CCT) of 586. The
anterior chamber was normal, and the dilated fundus
exam revealed a normal appearing ONH with no other
abnormalities (Fig. 1). Humphrey visual fields (HVF) were
full (Fig. 2) and showed no progression over the span of
5 years (Fig. 3).
Imaging with OCT, both TD (Fig. 4-9) and SD (Fig. 10-15)

revealed structures with parameters within the normal
distribution. Confocal scanning laser ophthalmoscopy FIGURE 4: Stratus OCT - Circumpaillary B scan with excellent
(CSLO) and scanning laser polimetry (SLP) confirmed signal strength showing a normal retinal nerve fiber layer
thickest in the superior and inferior regions.
normal ONH parameters (Fig. 17 and 18, respectively).
FIGURE 1: Normal color photo (left) and red-free photo (right)

of a normal optic nerve head. The white arrow points to the
normal coloration of the nerve fiber bundles in a red-free photo.
FIGURE 5: Stratus OCT Infrared Photo — Circumpaillary scan

properly placed around the ONH (left) and off-centered,
displaced nasally (right).

FIGURE 6: Stratus OCT circumpaillary thickness profiles for FIGURE 7: Well-centered Stratus OCT macula raster scan.
properly placed (A, B) and nasally displaced (C, D) scans (A) Infrared fundus image. (B) Normal vertical retinal B scan.
compared with normal distribution percentiles. Note that the Note the paucity of reflectance centrally at the foveal dip.
“double hump” pattern in C and D is spread apart. This changes (C) Thickness chart — overall retinal thickness compared to a
the thickness, although remaining in the normal distribution. normative database. (D) Retinal volume map quantitative color
map (top) and sectoral comparison to a normative database
(below). Note that the blue foveal thinning is placed centrally.
c
d
d
FIGURE 8: Nasally displaced Stratus OCT macula raster scan. FIGURE 9: Normal ONH Scan from Stratus TD-OCT. (A) Infrared
(A) Vertical macular B scan. Note that the foveal dip has ONH image. (B) ONH parameter outlining a small cup-to-disc
increased reflectance in comparison with the well-centered ratio (C/D). (C) ONH Analysis Results (D) Manually placed edges
scan shown in Figure 7B. (B) Thickness chart with the scan of retinal pigment epithelium (red-circles) allow for a computer
displaced nasally. (C) Retinal volume map quantitative color generated disc (blue shaded area). (E) Vertical ONH B scan
map (top) and sectoral comparison to a normative database without any graphics shows a thick RNFL at the ONH.
(below). Note that the blue foveal thinning is displaced. In this
case, the quantitative assessment of the macula overall has not
been compromised, however, the foveal thickness is
significantly different (in comparison with Figure 7D).
a a b
c
b

FIGURE 10: Normal Optic Disc Cube 200x200 from Cirrus
SD-OCT showing no progression. (A) RNFL Thickness Map.
(B) En-face fundus image showing the location of the
peripapillary circle scan location. (C) RNFL Tomogram extracted
from the cube. (D) RNFL thickness profile compared to a
normative database at the Temporal-Superior-Nasal-Inferior-
Temporal (TSNIT) locations. (E) RNFL Thickness — Average,
Quadrants, and Clock Hours. (F) Optic disc cube maps over
2 years showing no progression. These scan locations are
automatically registered within the cube with the intent to
have a consistent circle scan location in following progression.
(G) Progression graph of average, superior, and inferior g
measurements. (H) Progression graph of RNFL thickness profile.
a b
FIGURE 11: Normal Optic Disc Cube 200x200 from Cirrus

SD-OCT, advanced visualization function. (A) CSLO fundus
image showing the vertical (Purple line) and horizontal
(blue line) scans available for viewing in the cube. (B) Vertical B
Scan through the ONH. (C) Hortizontal B Scan through ONH.
c
a b
d

FIGURE 12: Normal Macular Cube 200x200 from Cirrus
SD-OCT. (A) Macular thickness map. (B) Progression
analysis map showing minimal change. (C) Hortizontal B
Scan from the macular cube.
d
a b
e
FIGURE 14: Normal Macula Images from Spectralis SD-OCT.

(A) Confocal Scanning Laser Ophthalmoscopy (CSLO)
background green lines indicating the individual B scans.
The brightest line is the scan location seen in the image below.
(B) Horizontal B-Scan through the macula.
FIGURE 13: Normal Optic Disc from Spectralis SD-OCT.

(A) Confocal Scanning Laser Ophthalmoscopy ONH image
(CSLO) overlay and background with a 3-Dimensional
horizontal B scan through the ONH. (B) SLO ONH Image
with peripapillary circle in green. (C) Sectoral RNFL
measurements compared to a normative database.
(D) Peripapillary Circle Scan. (E) RNFL thickness profile
compared to a normative database.
a
b c

FIGURE 15: Normal Images from TopCon SD-OCT.
(A) Peripapillary circle scan. (B) Vertical scan through ONH.
(C) Macular scan.
FIGURE 16: Normal Images from RTView SD-OCT. (A) En-face

ONH Image. (B) 3-Dimensional horizontal ONH scan cube data
with CLSO overlay. Green line in (A) indicating location of scan.
(C) ONH scan. (D) Peripapillary cirlcle scan. (E) Thickness map of
ONH compared to a normative database. (F) RNFL profile
compared to a normative database. (G) Horizontal cross-line
scan of macula. (H) Vertical cross-line scan of macula. (I) Ganglion
Cell Complex (GCC) Scan of the macula with thickness map (left)
and significance map (right).
g
FIGURE 18: Normal Images from CSLO. (A) Moorfields
Regression Analysis within normal limits within each sector.
(B) Topographic Change Analysis over 8 years showing normal
variation around blood vessels on a CSLO background.
(C) RNFL Profile compared to a normative database.
a b
h
i
c
FIGURE 17: Normal Images from Scanning Laser Polarimetry TAKE HOME POINTS
with the highest quality (10/10). (A)Nerve fiber layer thickness
map of the ONH. (B) Deviation map compared to a normative 1. Use OCT scans with a high quality signal strength.
database. 2. Use OCT scans with good alignment around the
ONH and on the macula.
3. It is beneficial to analyze data using the normative

database.
CASE 2: GLAUCOMA — THE FOCAL DEFECT

WITH EXCELLENT CORRESPONDENCE BETWEEN
STRUCTURE AND FUNCTION
This was the left eye of a 57 year old female with normal
tension glaucoma treated with Lumigan, Cosopt, and
Alphagan. Best corrected visual acuity was 20/30 wearing
a prescription of +0.75+0.50x90 and the IOP was 11 mm.
a b
The anterior segment examination was normal with wide
open angles. The dilated fundus exam revealed an ONH
with C/D = 0.85x0.6 with no other abnormalities
(Fig. 19 A).
Red-free photography reveals a RNFL wedge defect at

4:00 (Figure 19B black arrows). Humphrey visual fields
(HVF) showed a superior nasal step and superior
paracentral scotoma (Figure 20).

Imaging with OCT, both TD (Fig. 21-23) and SD (Fig. 24)
confirm this defect. Confocal scanning laser
ophthalmoscopy (CSLO) and Scaning Laser Polarimetry
also confirms this defect (Fig. 25 A and B, respectively).
FIGURE 19: Color disc photo (left) and Red-Free photo (right)
with discoloration indicating an area of defect (between black
arrow), better seen in the red-free photo.
b
a b
FIGURE 22: Stratus OCT macula raster scan. (A) Macular B scan
at 330 degrees. Note the thin RNFL indicated by the white
arrow. (B) Thickness chart – overall retinal thickness compared
FIGURE 20: HVF showing visual fields with a superior nasal step to a normative database. (C) Retinal volume map quantitative
and superior paracentral scotoma. Grey scale (left) and pattern color map (left) and sectoral comparison to a normative
deviation (right). Glaucoma Hemifield Test (GHT) is outside of database (right).
normal limits, visual field index (VFI)= 80%, mean deviation
(MD)=-4.66 dB with p<0.5%, pattern standard deviation
(PSD)=8.63dB with p<0.5%.
a b
FIGURE 21: Images from Stratus TD-OCT Peripapillary Circle

Scan. (A) B Scan showing focal RNFL inferiotemporal thinning
(white arrow). (B) RNFL thickness profile comparison to a
normative database confirming the inferiotemporal defect seen
in (A). (C) Clock-hours (left) and quadrants (right) comparison to
a normative database, again confirming the finding in (A).
b

FIGURE 23: Stratus OCT Images (A) Optic Nerve Head FIGURE 24: Images from RTView SD-OCT (A) “NHM4” ONH
Map. Black arrow indicating where the neuroretinal rim is Scan showing a neuroretinal rim thinnest inferiorly. (B) ONH
thinnest, 4:00. (B) Radial B Scan through ONH 4:00 with Scan with RNFL sector measurements along the 3.45mm
manually placed edges of retinal pigment epithelium diameter peripapillary circle. (C) RNFL Thickness Profile along
(red-circles) allow for a computer generated disc (blue the 3.45 mm circle. (D) Vertical Crossline through the macula
shaded area). (E) Identical B scan as (B) without any graphics. showing decreased reflectance of the inferior RNFL.

FIGURE 25: Other imaging modalities confirm the focal defect. FIGURE 26: HVF Grey Scale. Pattern deviation is not
(A) CSLO. (B) SLP. commuted by the technology for severely depressedfields.
GHT is outside of normal limits, VFI= 11%, MD=-29.59dB
with p<0.5%, PSD=7.89dB with p<0.5%.
TAKE HOME POINTS

1. Defects in the RNFL are displayed in the visual field
inverted and reversed. FIGURE 27: Images from Stratus TD-OCT Peripapillary Circle
Scan. (A) B Scan showing global RNFL thinning. (B) RNFL
2. Red free photos are the best type of photo to view thickness profile comparison to a normative database
a focal neurofiber bundle defect. showing the topography to have thinned predominantly
superiorly and inferiorly with relative temporal sparing.
3. The peripapillary circle, ONH, and macula scans can (C) Clock-hours (left) and quadrants (right) comparison to a
all provide information about RNFL wedge defects. normative database.
CASE 3: ADVANCED GLAUCOMA –

THE CENTRAL ISLAND
This was the right eye of a 56 year old male with a
primary open angle glaucoma (POAG) treated with a
trabeculectomy. All images are taken after the surgical
treatment. Best corrected visual acuity was 20/30 and
the IOP was 14 mm. The anterior segment examination
was normal other than a flat bleb without leak superiorly
and a patent peripheral iridotomy. The dilated fundus
exam revealed an ONH with a barely perceptible
neuroretinal rim (C/D = 0.99) with no other abnormalities.
Humphrey visual fields (HVF) showed a severly depressed

field with only central vision spared (Figure 26).
Imaging with OCT, both TD (Fig. 27) and SD (Fig. 28)

confirm this defect. Confocal scanning laser
ophthalmoscopy (CSLO) and Scaning Laser Polarimetry
also confirms this global defect (Fig. 30 and 31,
respectively). The macula RNFL thickness remains normal
(Figure 29), corresponding with the remaining central
vision.

FIGURE 28: (A) Optic Disc Cube 200x200 from Cirrus SD- FIGURE 29: Macular Cube 200x200 from Cirrus SD-OCT.
OCT. (A) RNFL Thickness Map displays global thinning (top). (A) Macular thickness map displaying that the macular has
En-face fundus image showing thinning most prominent been spared from the otherwise global RNFL damage.
superiorly and interiorly (bottom). (B) RNFL Thickness – (B) Horizontal (top) and vertical (bottom)B scans from the
Average (top), Quadrants (middle), and Clock Hours macular cube. (C) 3D segmentation of the macula showing
(bottom). (C) RNFL Tomogram extracted from the cube. the green circular island of retinal thickness at the macula
(D) RNFL thickness profile compared to a normative surrounded by sea of thin (blue) retina.
database at the TSNIT locations.
a b
c
b c
FIGURE 30: CLSO Moorfields Regression Analysis outside

normal limits for each sector.

FIGURE 31: SLP image nerve fiber layer thickness map of the Imaging with TD-OCT (Figure 35) shows a significant
ONH showing a globally thin RNFL (blue). progression globally from 2005 to 2009 (Figure 36).
The RNFL thins much more than the HVF would suggest.
The macula RNFL thickness remains normal (Figure 37),

corresponding with the remaining central vision.
FIGURE 32: Color and Red-free photography. In 2005, clear

neurofiber bundles are visualized following the vascular
arches (B, between white arrows). In 2009, these striations
have disappeared and the shadows of choroidal vessels are
clear (D, between white arrows).
TAKE HOME POINTS

1. The RNFL thickness “bottoms out” at 40 microns
in severe damage.
2. Although the TD- and SD-OCT are not

quantitatively identical, they can both provide
into a RNFL defect location and severity.
a b
CASE 4: GLAUCOMA — GLOBAL PROGRESSION

This was the left eye of a 52 year old female with juvenile
glaucoma secondary to juvenile rheumatory arthritis. She
was treated with a trabeculectomy in 2004. She also has
ocular rosacea and is psuedophakic. All images are taken
after the surgical treatments. From 2005 to 2009 she
progressed globally both structurally by OCT and \
functionally by HVF.
From 2005-2009, the patient’s exam remained stable.

Best corrected visual acuity was 20/30 and the IOP was
12 mm Hg, and remained stable without drops. External
exam was notable for telangiectasis on the lids. The
anterior segment examination was normal other than a
c d
flat bleb without leak superior and a patent peripheral
iridotomy. The posterior chamber intraocular lense was
in place. The dilated fundus exam revealed a pale ONH
with a thin neuroretinal rim (C/D = 0.9) with no other
abnormalities.
Red-free photography clearly shows a loss of the

neurofiber layer from 2005 to 2009. In 2005, clear
neurofiber bundles are visualized following the vascular
arches (Figure 32 B). In 2009, these striations have
disappeared and the shadows of choroidal vessels
are clear (Figure 32D).
In 2005 and 2009, HVF showed significantly depressed

fields with both superior and inferior arcuate scotomas
and superior and inferior nasal steps. (Figure 33).
Glaucoma progression analysis showed a significant VF
deterioration in the superior and inferior nasal step areas.
(Figure 34A). The VFI analysis shows non-significant
progression (Figure 34B).

FIGURE 33: HVF grey scale (left) and pattern deviation (right) FIGURE 35: Stratus OCT TD-OCT Images in in 2005 (A, C,
from 2005 (A and B) and 2009 (C and D) showing visual fields and E) and 2009 (B, D, and F). Images (A) and (B) show the
with a superior and inferior nasal step as well as a superior circumpaillary B scan in 2005 and 2009, respectively.
and inferior arcuate. In 2005, GHT is outside of normal limits, Comparing (A) and (B) one can see the RNFL thinning
VFI= 77%, MD=-9.82 dB with p<0.5%, PSD=7.28dB with globally. Images (C) and (D) show the RNFL thickness profile
p<0.5%. In 2009, GHT is outside of normal limits, VFI=73%, comparison to a normative database in 2005 and 2009,
MD=-11.53 dB with p<0.5%, PSD=8.13dB with p<0.5%. respectively. Images (E) and (F) show clock-hours (left) and
quadrants (right) in comparison to a normative database in
2005 and 2009, respectively.
a 2005
a 2005
b 2009
b 2009
FIGURE 34: Glaucoma progression analysis (A) showed a

significant VF deterioration in the superior and inferior nasal
step areas. The VFI progression analysis shows non-significant
progression (B).
c 2009
d 2009
e 2005

FIGURE 37: Vertical Macular B Scan (A) and Retinal Thickness
Map (B). The macula in this scenario has been preserved
despite the global damage.
f 2009
FIGURE 36: Stratus TD-OCT Progression Analysis. (A) RNFL

Profiles color coded by date (top) and graph of average
RNFL thickness (bottom) showing a significant rate of
change. (B) Dates of scans color coded along with signal
strengths and quantitative measurements of each scan.
TAKE HOME POINTS

1. OCT is a tool that is able to quantify progression,
even when a clinical fundus exam remains stable.
a CASE 5: GLAUCOMA — “PREPERIMETRIC”

This was the right eye of a 70 year old female with a
history of ocular hypertension since 1994, referred to the
glaucoma service in 2004 after a structural defect was
seen on imaging. No visual field defects appeared until
2006. She was treated in 2008 and 2009 with Selective
Laser Trabeculoplasty.
recorded as 24 mm Hg in 2004 and 13 mm Hg in 2009.
The anterior segment examination was normal with open
angles. The dilated fundus exam revealed an ONH with
C/D = 0.9x0.8 in 2004 and 0.9x0.9 in 2009 with no other
b
abnormalities (Figure 38 A and B, respectively).
Humphrey visual fields (HVF) in 2004 show a normal field

and in 2009 shows a superior nasal and a superior arcuate
scotoma. (Figure 39 A and B, respectively).
Imaging with TD-OCT (Figure 41) displays a progressing

inferior RNFL defect from 2004-2009. The RNFL changes
are significant and progressive (Figure 42). Confocal
scanning laser ophthalmoscopy (CSLO) confirmed thie
defect in 2004 (Fig. 45).
Imaging of the macula with OCT, both TD (Fig. 43) and SD

(Fig. 44) also show an inferior defect. Figure 44 displays
the progressive changes from 2006-2009.

FIGURE 38: Color ONH Photographs in 2004 (A) and 2009 FIGURE 40: Glaucoma progression analysis from 2004-2009
(B). Note the baring of the lamina cribrosa inferiorly from (A) showed a significant VF deterioration in the superior
and the superior neuroretinal thinning 2004 to 2009. nasal step area. The VFI progression analysis from 2004-
2009 shows non-significant progression (B).
a 2004 b 2009
FIGURE 39: HVF from 2004 and 2009. HVF grey scale (left)
and pattern deviation (right) from 2004 (A) and 2009 (B).
In 2004, GHT is outside of normal limits, VFI= 100%,
MD=+0.46 dB and PSD=1.78dB. In 2009, GHT is outside
of normal limits, VFI=94%, MD=-2.73 dB with p<2%, and
PSD=3.82dB with p<0.5%.
a 2004 FIGURE 41: Stratus OCT TD-OCT Images in in 2004 (A, C,

and E) and 2009 (B, D, and F). Images (A) and (B) show the
circumpaillary B scan in 2004 and 2009, respectively.
Comparing (A) and (B) one can see the RNFL thinning
inferiorly and inferiotemporally (between white arrows).
Images (C) and (D) show the RNFL thickness profile
comparison to a normative database in 2004 and 2009,
respectively. Images (E) and (F) show clock-hours (left) and
b 2009
a 2004

RNFL thickness (bottom) showing a significant rate of
change. In between the black arrows, the graph highlights
the inferior area that thins progressively from the first visit
(black line) to the last visit (red line). (B) Dates of scans color
coded along with signal strengths and quantitative
measurements of each scan.
b 2009
c 2004
a
d 2009
FIGURE 43: Macular Scan from Stratus TD-OCT. (A) Vertical

macular B Scan. (B) Retinal Thickness Chart. (C) Retinal
Thickness Map. The macula in this case shows some inferior
thinning.

TAKE HOME POINTS
1. OCT is capable of detecting damage to the RNFL
before functional change occurs.
2. OCT is a tool that is able to quantify progression,

even when a clinical fundus exam remains stable.
3. Some progression analyses are very useful in

visualizing damage, especially for explaining to
c
patients.
FIGURE 44: RTView SD-OCT Ganglion Cell Complex (GCC)

Progression Scans of the macula. (A) Deviation maps
CASE 6: GLAUCOMA — FLUCTUATING FUNCTION
showing thinning inferiorly in comparison with a normative BEFORE STRUCTURE
database. (B) Significance maps in comparison with a This was the left eye of a 75 year old male with a history
normative database. (C) Graphic change of average (red),
of ocular hypertension vs. POAG since 2000 treated with
superior (blue), and inferior (green) GCC thickness.
Brimonidine-Timolol drops. A small focal superionasal
scotoma appeared from 2002- 2005, disappeared from
2006-2008, and reappeared in 2009 with no overall
progression (Figure 46). Until 2006 when the OCT
showed a clock-hour defect at 5:00, this spot was
considered a patient–dependent error or lid line mark.
a 2006 2007 2008 2009 In retrospect, this mark was indicative of impending
corresponding structural changes.
recorded as 22 mm Hg in 2005 and 28 mm Hg in 2009.
The anterior segment examination was normal with open
angles. The dilated fundus exam revealed an ONH with
C/D = 0.8 in 2005 and 0.9 thinnest inferiorly in 2009 with
no other abnormalities. In 2006, a disc hemorrhage could
be seen at 5:00 (Figure 45).
b 2006 2007 2008 2009 Imaging with OCT, both TD (Fig. 48) and SD (Fig. 49)
display a progressive 5:00 defect (Figures 47 and 49).
FIGURE 45: Color ONH Photographs in 2006. The black

arrow points to a disc hemorrhage, which often indicates
progression at that location.
FIGURE 45: Other imaging modalities confirming the

pre-perimetric inferior defect in 2004 (A) CSLO. (B) SLP.
a b
FIGURE 46: HVF from 2002-2009. (A) HVF grey scale (top) FIGURE 47: Stratus TD-OCT Progression Analysis. (A) RNFL
and pattern deviation (bottom) shows a fluctuating focal Profiles color coded by date (top) and graph of average
superior scotoma. (B) VFI progression shows no progression. RNFL thickness (bottom) showing a significant rate of
change. The black arrow indicates the inferior area that thins
progressively from the first visits (black/purple line) to the
last visit (dark blue line). (B) Dates of scans color coded
along with signal strengths and quantitative measurements
of each scan.
2002 2004 2005
a 2007 2008 2009
FIGURE 48: Stratus OCT TD-OCT Images in 2004 (A, C,

and E) and 2008 (B, D, and F). Images (A) and (B) show the
circumpaillary B scan in 2004 and 2009, respectively.
Comparing (A) and (B) one can see the RNFL thinning
inferiorly and inferiotemporally (between white arrows).
Images (C) and (D) show the RNFL thickness profile
comparison to a normative database in 2004 and 2009,
b respectively. Images (E) and (F) show clock-hours (left) and
a 2005

FIGURE 49: RTView SD-OCT ONH Scan Progression from
2006-2009.
b 2008
c 2005
a 2006-2009
d 2008
e 2005 b
TAKE HOME POINTS

1. Beware of misleading HVF. Rely more on VF
progression analyses, as they necessitate a
greater number of exams.
2. Sometimes a focal scotoma will come and go

f 2005 because it is patient-dependent. OCT provides a
reproducible, quanitative measurement that is
less patient-dependent.
3. VF changes may occur before changes are seen

on OCT.

CASE 7: GLAUCOMA — STABLE HEMIFIELD
STRUCTURAL DAMAGE WITH BOTH STABLE
AND FLUCTUATING FUNCTIONAL CHANGES
This was the right eye of a 65 year old female with a
history of POAG treated with trabeculectomy in 2006. All
images are taken after the surgical treatment, 2007-2009.
6 mm Hg, and remained stable without drops. The
anterior segment examination was normal other than a
superior avascular bleb without leak and a patent
peripheral iridotomy at 1:00. The dilated fundus exam
revealed a, the increased cupping from 2007-2009
C/D = 0.8 to 0.9 with no other abnormalities.
b
From January 2007- February 2009, HVF displayed a
dense inferior nasal step and arcuate scotoma. It also
seemed that the patient’s glaucoma had progressed
functionally to include both a superior nasal step and FIGURE 52: Stratus OCT TD-OCT Images in 2009 and
arcuate scotoma. However, when the patient returned in progression analysis. Image (A) shows the circumpaillary
B Scan. Image (B) shows the RNFL thickness profile in
September 2009, the superior defects nearly disappeared.
comparison to a normative database. Image C shows clock-
Imaging with OCT, both TD (Fig. 52) displayed a stable hours (left) and quadrants (right) in comparison to a
normative database. (A)-(C) all correspond with HVF with
RNFL thickness through this time period (Figures 53).
more superior RNFL structural damage leading to a dense
Other SD-OCT technologies showed similar B scan inferior defect.
profiles (Figures 54-57).
FIGURE 50: Color ONH Photographs in 2009.
b
FIGURE 51: HVF from 2007-2009. (A) HVF grey scale (top)
and pattern deviation (bottom) shows a fluctuating superior
nasal step and arcuate scotoma. (B) VFI progression shows
no progression.
a 1/2007 10/2007 2/2009 9/2009

RNFL thickness (bottom) showing no change. (B) Dates of
scans color coded along with signal strengths and
quantitative measurements of each scan. Note, how stable
the measurements stay throughout the time period.
FIGURE 55: RTView SD-OCT NHM4 ONH Scan.

(A) neuroretinal rim thinnest inferiorly. (B) ONH Scan with
FIGURE 54: Optic Disc Cube 200x200 from Cirrus SD-OCT. RNFL sector measurements along the 3.45mm diameter
(A) RNFL Thickness Map. (B) En-face fundus image showing peripapillary circle. (C) RNFL Thickness Profile along the
the location of the peripapillary circle scan location and 3.45 mm circle.
coloration based upon deviation from a normative database.
(C) RNFL Tomogram extracted from the cube. (D) RNFL
thickness profile compared to a normative database at the
TSNITlocations. (E) RNFL Thickness – Average, Quadrants,
and Clock Hours.
a b

FIGURE 56: Spectralis SD-OCT. (A) Peripapillary circle CME ANSWERS
B scan highlighting the RNFL with red lines. (B) RNFL
thickness profile compared to a normative database. 1. Retinal Nerve Fiber Layer (RNFL) thickness, ganglion
(C) Sectoral RNFL measurements compared to a cell complex (GCC). Optic nerve head parameters
normative database. (ONH) may be useful as well, but there is insufficient
evidence base to validate at this time.
2. Circumpapillary Scan, Macular Scan, and ONH Scan.
3. Increase in scanning speed enabling 3D imaging,

a improved resolution, post-processing capabilities,
increased reproducibility, and better sensitivity and
specificity in disease detection.
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LINKING AXONS AND NEURONS: UNVEILING MYSTERIES
OF THE MACULA AND MODELING NEUROPROTECTION
Randy Kardon, M.D. Ph.D.
University of Iowa, Hospitals and Clinics
Iowa City, IA
LEARNING OBJECTIVES 3. Which of the following factors may significantly

1. Understand the linear relationship between retinal confound the correlation between ganglion cell layer
nerve fiber layer thickness and corresponding visual thickness and corresponding locations of visual
field areas of sensitivity. sensitivity?
2. Understand the limitations of using the retinal nerve a) the number of ganglion cell layers in the normal
fiber layer thickness to diagnose and monitor optic retina at the locations being evaluated
nerve disorders. b) peripheral field location of damage
3. Understand the advantages and disadvantages of c) spatial variability in the mapping of ganglion cell
using the retinal ganglion cell layer thickness location to corresponding visual field
determined by OCT for diagnosis and management of
optic neuropathy. d) extent of visual field damage
e) all of the above
CME QUESTIONS
1. Which of the following factors may confound the KEY WORDS
accurate OCT determination of RNFL thickness for Optical Coherence Tomography
diagnosing optic nerve damage?
Retinal Nerve Fiber Layer
a) Blood vessels
Ganglion Cells
b) Proliferation of glial elements in the retina
Glaucoma
c) Scan signal to noise
Anterior Ischemic Optic Neuropathy
d) Developmental differences in the distribution of
axon bundles in the retina Optic Neuritis
e) all of the above
2. Which of the following clinical conditions is likely to Most clinicians, especially neuro-ophthalmlogists and
show the highest correlation between structure and glaucoma specialists, have been trying to understand
function using OCT? whether the information yielded by optical coherence
tomography is really helping them to improve upon the
a) compressive optic neuropathy clinical care of their patients. In this context, clinical
b) NAION after 6 months decision-making has mainly focused on the status of the
retinal nerve fiber layer (RNFL) thickness in relation to the
c) optic neuritis after 6 months from the acute attack threshold sensitivity of the corresponding area of visual
d) visual field loss in a patient with idiopathic field (see review, reference 1). Theoretically, it is expected
intracranial hypertension that the degree of thinning of the RNFL will have a
meaningful correlation with optic nerve function in a
e) all of the above patient with loss of axons2-4 and less correlation of
structure with function in locations where axons are still
intact, but not functioning. In the latter case, either a
return of function may still be possible, as in the case
with some eyes with compressive optic neuropathy5,
acute optic neuritis6-9, or ischemic optic neuropathy.
Alternatively, the axons may have undergone irreversible
dysfunction but not enough time has elapsed to produce
atrophy and thinning of the RNFL1.

The clinical interpretation becomes even more difficult in While the relationship between RNFL thickness and visual
the setting of optic disc edema associated with visual field field sensitivity appears to correspond to a linear model,
loss, since there may be swelling of some axons with there are still between and within subject components of
atrophy of neighboring axons, confounding the measurement variability that impose limitations of this
relationship between RNFL thickness and corresponding framework and its application to individual patients (see
visual field sensitivity, as long as axon swelling is present Figure 2). In addition, the dynamic range of both the
and atrophy is not yet complete. Another potential RNFL and threshold sensitivity and their associated
confounding variable is the status of other components measurement variability limit meaningful relationships to
that make up the thickness of the RNFL, besides axons, be explored once 10 decibels of threshold loss have been
such as blood vessels and glial elements, which may exceeded or if the RNFL thickness drops below 60 microns
influence the measured thickness of the RNFL1,10,11. for arcuate field loss.
Attempts to quantify the relationship between structure

and function between RNFL thickness and visual threshold FIGURE 2: The ellipses are the 95% confidence boundaries of
at corresponding locations have discovered that there is a the linear model of structure vs function with variability
correlation (primarily studied in glaucoma and anterior component shown for different glaucoma disease states, d,
ischemic optic neuropathy), but not as great as one would expressed in decibels of field loss. The 95% ellipses for the
expect (refs). Factors such as measurement variability in combined within- and between-individual variability (green),
for between-individual variability excluding within-individual
both visual threshold and in RNFL thickness, the influence variability (red), and for within-individual variability excluding
of non-neuronal elements on the RNFL thickness such as between-individual variability (blue) are shown for six levels
blood vessels and glial elements, and the inter-individual of decibel visual field loss (from reference 4 with author
variation in mapping of RNFL bundles to their permission).
corresponding area of the visual field all confound the
correlation in an individual patient. We have recently
reviewed this topic1 and have provided evidence for a
linear model relating visual threshold (unlogged) and
RNFL thickness in glaucoma and AION2-4. This is depicted
in Fig 1 in semi-log plots.
FIGURE. 1: Relationship of the retinal nerve fiber layer

(RNFL) thickness to visual field loss in patients with glaucoma
and AION. (A) A schematic illustrating the location of the
corresponding disc sectors and field regions for the superior
arcuate field (left panel) and inferior arcuate field (right
panel). (B) RNFL thickness as a function of field loss for the
upper field/inferior disc (left panel) and the lower
field/superior disc (right panel). Data are shown for patients
with AION (n = 24; filled gray), asymmetric glaucoma (n =15;
filled black), and severe glaucoma (n =16; open symbols),
and for the mean of a group of 60 age-similar controls (open In glaucoma studies, the RNFL thickness has been shown
square). The theoretical structure-function curves are fitted to have a very good sensitivity and specificity for
to a linear function, but plotted here on a semi-log plot. For diagnosing glaucoma, using Receiver-Operator
the upper and lower visual field regions, three theoretical
Characteristic curve analysis (ROC). It is important to keep
curves are shown (50th percentile=solid line, 95th percentile,
and 5th percentile = dashed lines). From review reference 1 in mind that such analyses are always influenced by the
(with author permission). criteria that are chosen as the gold standard for the
presence or absence of the disease, the characteristics of
the population being studied in terms of the distribution
of severity of damage in the population included, and
whether structure (disc appearance) or function (visual
field sensitivity and the pattern of loss) is used as the
criteria for the presence of glaucomatous or optic nerve
disease.
A great deal of research has also been directed towards

using the RNFL thickness to detect progression of
glaucomatous damage over time (refs). Most of these
studies have applied techniques that have also been used
to study progression of visual field loss, namely a)
significant change in RNFL status at a given time point
from a prior baseline measurement or b) linear regression
analysis of RNFL thickness over time. The main problems
encountered in detecting progression using these

approaches are measurement variability and using 4. Papilledema: When the optic nerve appears swollen,
population statistics to determine what constitutes a the main questions applicable to OCT concern whether
significant change over time. Individuals appear to vary true papilledema is present vs. pseudopapilledema12,
considerably in their measurement variability, so applying whether the change in optic disc edema over time can
population statistics (defining the variability of a given be better quantified using thickening of the RNFL with
patient by applying the variability from a population of OCT compared to the fundus appearance of the optic
patients) to a given patient may not be optimal for nerve and whether axon loss can be detected while the
individualizing the analysis of progression for a given disc is still swollen and differentiated from a reduction
patient. In addition, defining a statistically significant in RNFL thickness due to lowering of intracranial
change over time may not always equate with what is a pressure.
clinically significant change — one that would warrant a
5. Differentiation of optic neuropathy from
deviation in treatment. Because the rate of glaucomatous
retinopathy and identifying disorders in which
visual field progression varies considerably among treated
both are present: OCT scans of other portions of the
and untreated patients and the rate is, in general, slow,
posterior pole besides the RNFL can be very revealing.
the challenge in the future will be to identify as early as
For example, acute or subacute visual field loss with a
possible which patients are at the most risk for
thickened macula on OCT but without obvious
progression and focus aggressive treatment on those
evidence of retinal edema on fundus exam may help
patients while not applying the same treatment to patients
point the diagnosis more correctly toward a branch or
who are at low risk for significant progression over their
central retinal artery occlusion (CRAO), and away from
remaining life expectancy.
anterior or posterior ischemic optic neuropathy,
For neuro-ophthalmology, the OCT landscape for optic inflammatory, or compressive optic neuropathy. In the
nerve diseases other than glaucoma pose similar chronic state, an abnormally reduced total macular
problems. These mostly encompass the following thickness keeping company with a thinned RNFL and
disorders and focus on questions regarding the pale nerve may also help make the diagnosis of a
application of OCT to diagnosis and treatment: previous retinal artery occlusion, without requiring an
electroretinogram (ERG) or neuro-imaging. Another
1. Multiple Sclerosis: In this setting OCT is being used to
example is a patient with possible neuroretinitis and
help substantiate the diagnosis of multiple sclerosis,
persistent visual field loss; the combination of an OCT
determine whether OCT can be used to monitor the
scan of the peripapillary RNFL and macula scan may
course and treatment of demyelinating disease and
help reveal the layer of the retina which is most likely
predict which patients are likely to progress at a faster
to be the source of pathology explaining the visual
rate, requiring a more tailored treatment approach6-9.
field loss.
There is also evidence that total macular thickness may
also reflect neuronal loss in multiple sclerosis13. The Most ophthalmologists use the macula OCT to
main interest at present is whether acute optic neuritis diagnose disorders causing loss of the photoreceptors
is a good model for evaluating the efficacy of new CNS in the outer retina or disorders causing fluid
multiple sclerosis treatment strategies, such as the use accumulation in the retina (e.g. cystoid macular
of neuro-protectants and whether the use of OCT is a edema, diabetic macular edema, vitreal traction,
valid surrogate for modeling the status of multiple perifoveal telangiectasia, choroidal neovascular
sclerosis and treatment strategy. membrane), or macular holes. Such patients may make
their way into a neuro-ophthalmology clinic and a
2. Non-arteritic anterior ischemic optic neuropathy
macular OCT may be an important diagnostic tool to
(NAION): Structural features on OCT are being
narrow the differential and reduce cost of a work-up.
identified (such as neural opening size in the sclera)
which might predict which patients are at the most The factors discussed above pose limitations on relating
risk for progressive visual field loss during the acute the retinal nerve fiber layer to visual threshold and axon
phase of NAION and who may respond to treatment loss. This has prompted an interest in going to the source
interventions during the first 2 weeks (e.g. steroids). of the axons – the soma of retinal ganglion cells, which
It may be possible to use OCT to help identify patients predominate in the macula. Here the question is whether
that are most likely to benefit from treatments aimed the ganglion cell layer can be accurately quantified within
at preserving axons. the macula scan using current OCT technology and
whether a change in the number of viable neurons can
3. Compressive optic neuropathy: The presumption is
accurately be detected with current software. This also
that the greater number of axons that are present at
presupposes that the ganglion cells in the macula are
the time of diagnosis, the higher potential for visual
adequate surrogates for disease affecting the visual field
recovery if decompression is successful5. Here the
outside of the macula.
confounding variables are how much time must elapse
before axonal degeneration is detectable on OCT at
the time of diagnosis and how many neurons/axons
are required to support adequate visual function which
may influence treatment decisions?

Segmentation of the ganglion cell layer within the FIGURE 4: Thickness and thickness variability (standard
central macula with spectral domain OCT has a deviation) maps of six macular intraretinal layers from the
right eye of 15 normal subjects. The micron thickness of the
number of potential advantages:
different macula layers is color coded (red=thickest,
1. The retinal ganglion cells are densest in the macula blue=thinnest).
and form a stratified multi-cellular layer within the
central 6 degrees of visual field. Therefore, loss of
axons and the corresponding soma in this location is
likely to cause a thinning of the retinal ganglion cell
layer.
2. The lack of large retinal vessels in this location makes

their confounding contribution to the thickness of the
ganglion cell layer very minimal, compared to the
peripapillary retina, where they do influence the RNFL
measurement. FIGURE 5: Example of a glaucoma patient whose visual field
defect came close to the center of their visual field and was
3. The mapping of visual field location to corresponding tested with a denser visual field testing program covering
ganglion cell soma is less complicated than the only 10 degrees of radius and which corresponds to the area
of retina covered by the macula scan on the corresponding
situation with the RNFL bundles and may show less spectral domain OCT. The gray scale map shows visual
inter-individual developmental variability. sensitivity loss that was worst in the top part of the visual
Simplistically, a focal light in the macula activates the field (dark areas), but also shows some loss in the inferior
ganglion cells directly underlying it. In the foveal and field. The visual field sensitivity di erence from normal plot is
perifoveal location this is not strictly the case and also shown below the gray scale with the abnormal area with
decrease in sensitivity surrounded by a red dotted line. The
some modification has to be made in this area of the statistical probability plot of the same visual field data is
visual field due to displaced ganglion cells. shown in the lower left corner. 3D-OCT was obtained on this
eye and segmented into the inner retinal layer (ganglion cells
4. Recent advances in OCT image analysis using both and axons) and outer retinal layer containing the
manual14 and automated analysis in three photoreceptors and bipolar cells. Note the high spatial
dimensions15,16 have provided a potential solution correlation between the thinned layer containing the
for delineation of the different neuronal layers in the ganglion cells in the inferior macula (thinned areas are red
macula (Figures 3-4). and yellow and depicted as di erence from normal) and the
corresponding superior (and inferior) areas of visual field
5. Preliminary attempts to quantify the correlation defect. However, there is no such thinning in the outer retina
between visual threshold and retinal ganglion cell which is known not to be a ected in most glaucomatous
damage.
thickness in the macula appear to subjectively
correlate with the spatial pattern of visual field loss
in the macula in patients with glaucoma (Figure 5)
and anterior ischemic optic neuropathy. However,
a quantitative correlation between ganglion cell
thickness and corresponding overlying visual threshold
has not yet been reported in detail.
FIGURE 3: Automated software 3D segmentation of the

retinal layers of the normal macula using spectral domain
SDOCT. Segmenation is shown for one of many successive
slices of the volume macula scan. The software uses all
surrounding volume image information to segment the layers.
Challenges associated with OCT analysis of the macula

that need to be overcome before clinical monitoring of
optic nerve function is useful:
1. Total macula thickness is a measurement that is not

likely to be specific and sensitive enough to detect
small changes in the ganglion cell layer associated
with optic neuropathy. This is why segmenting the
different layers is likely to be a better approach.

2. Current commercially available OCT and associated CME ANSWERS
software are not capable of segmenting the ganglion 1. e) all of the above; all of these factors may influence
cell layer in three dimensions. At best, one the ability to differentiate a normal RNFL from an
manufacturer (Optoview) purports to segment the abnormal thinning due to optic nerve damage
inner layers of the retina of the macula as a neural
complex layer (RNFL, ganglion cell layer and inner 2. b) thinning of the RNFL reaches a maximum at
pleximform layers), but this software analysis has not 6 months following acute injury from AION. The
yet been rigorously validated. Recently Don Hood and other conditions may not show as good a correlation
colleagues reported to have manually segmented two between structure and function.
dimensional line scans through the macula and have 3. e) all of the above.
shown correlation of thinning of the ganglion
cell+inner plexiform layer with corresponding loss of
visual threshold in glaucoma, so this approach does
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have promise14. Our group has reported automated
1. Hood DC, Kardon RH: A framework for comparing structural
segmentation of retinal layers using a 3D graph search and functional measures of glaucomatous damage. Prog
approach applied to volume OCT scans, as shown in Retin Eye Res 2007;26(6):688-710.
Figures 3-515,16.
2. Hood DC, Anderson SC, Wall M, Kardon RH: Structure versus
3. Outside of the central 6 degrees of the macula, the function in glaucoma: an application of a linear model. Invest
Ophthalmol Vis Sci 2007;48(8): 3662-3668.
ganglion cell layer is less of a multi-cellular layer. In
areas where there is only a single layer of ganglion 3. Hood DC, Anderson S, Rouleau J, Wenick AS, Grover LK,
cells it is not known if loss of soma will cause a Behrens MM, Odel JG, Lee AG, Kardon RH: Retinal nerve fiber
structure versus visual field function in patients with ischemic
measurable, significant thinning of the cellular layer or
optic neuropathy: a test of a linear model. Ophthalmology
whether it will just be replaced by glial and Mueller 2008;115(5):904-910.
cells, making structural thinning of the ganglion cell
4. Hood DC, Anderson SC, Wall M, Raza AS, Kardon RH. A test of
layer of the inner retina difficult to measure. a linear model of glaucomatous structure-function loss
4. Focal peripheral visual field damage would be unlikely reveals sources of variability in retinal nerve fiber and visual
field measurements. Invest Ophthalmol Vis Sci
to affect the retinal ganglion cell layer in the macula, 2009;50(9):4254-4266.
making it theoretically less sensitive to detection and
5. Danesh-Meyer HV, Papchenko T, Savino PJ, Law A, Evans J,
monitoring of peripheral field pathology. On the other
Gamble GD. In vivo retinal nerve fiber layer thickness
hand, most optic nerve diseases do show some degree measured by optical coherence tomography predicts visual
of diffuse loss and although significant abnormalities recovery after surgery for parachiasmal tumors. Invest
in visual threshold may not be detected, there still may Ophthalmol Vis Sci. 2008 May;49(5):1879-85. Epub 2008
be a measurable decrease in retinal ganglion cell Feb 8.
thickness in the macula, even though a visual field test 6. Costello F, Hodge W, Pan YI, Metz L, Kardon RH. Retinal nerve
may appear to show mainly extra-macular loss of fiber layer and future risk of multiple sclerosis. Can J Neurol
sensitivity. Sci 2008;35(4):482-487.
7. Costello F, Hodge W, Pan Y, Eggenberger E, Coupland S,

5. It is currently not known how much time it takes for a
Kardon R: Tracking retinal nerve fiber layer loss after optic
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occur after damage to the optic nerve at different tomography. Mult Scler 2008;14(7):893-905.
distances from the globe. The time delay between
8. Frohman EM, Fujimoto JG, Frohman TC, Calabresi PA, Cutter
permanent damage and atrophy of the ganglion cell G, Balcer LJ. Optical coherence tomography: a window into the
layer would provide a framework for dating the time mechanisms of multiple sclerosis. Nat Clin Pract Neurol. 2008
of injury. Dec;4(12):664-75. Review.
In summary, recent improvements in OCT resolution and 9. Frohman EM, Costello F, Stüve O, Calabresi P, Miller DH,
Hickman SJ, Sergott R, Conger A, Salter A, Krumwiede KH,
automated segmentation software has provided a means Frohman TC, Balcer L, Zivadinov R. Modeling axonal
of relating visual pathway damage to structural changes in degeneration within the anterior visual system: implications
the RNFL and corresponding soma of the ganglion cells in for demonstrating neuroprotection in multiple sclerosis. Arch
the macula. Ganglion cell layer analysis in volume OCT Neurol. 2008 Jan;65(1):26-35. Review.
data may provide yet another piece of the puzzle to 10. Hood DC, Salant JA, Arthur SN, Ritch R, Liebmann JM. The
understanding structure-function relationships and its Location of the Inferior and Superior Temporal Blood Vessels
application to diagnosis and monitoring of optic nerve and and Interindividual Variability of the Retinal Nerve Fiber Layer
Thickness. J Glaucoma. 2009 Aug 5. [Epub ahead of print]
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11. Hood DC, Fortune B, Arthur SN, Xing D, Salant JA, Ritch R,
Liebmann JM. Blood vessel contributions to retinal nerve fiber
layer thickness profiles measured with optical coherence
tomography. J Glaucoma. 2008 Oct-Nov;17(7):519-28.

12. Johnson LN, Diehl ML, Hamm CW, Sommerville DN, Petroski
GF. Differentiating optic disc edema from optic nerve head
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TC, Conger A, Ratchford JN, Warner C, Markowitz CE, Jacobs
DA, Galetta SL, Cutter GR, Maguire MG, Calabresi PA, Balcer LJ,
Frohman EM. Macular volume determined by optical
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14. Wang M, Hood DC, Cho JS, Ghadiali Q, De Moraes GV, Zhang
X, Ritch R, Liebmann JM. Measurement of local retinal
ganglion cell layer thickness in patients with glaucoma using
frequency-domain optical coherence tomography. Arch
Ophthalmol. 2009 Jul;127(7):875-81.
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coherence tomography images using optimal 3-D graph
search. IEEE Trans Med Imaging. 2008;27(10):1495-1505.

PLATFORM PRESENTATION
GANGLION CELL LAYER VOLUME BY SPECTRALIS OPTICAL
COHERENCE TOMOGRAPHY (OCT) IN MULTIPLE SCLEROSIS
Emma Davies1, Dina Jacobs1, James Wilson1, Clyde Markowitz1, Steven Galetta1,
Elliot Frohman2, Peter Calabresi3, Laura Balcer1
1
University of Pennsylvania School of Medicine, Philadelphia, PA, United States,
2
University of Texas Southwestern Medical Center, Dallas, TX, United States,
3
Johns Hopkins University School of Medicine, Baltimore, MD, United States
INTRODUCTION: CONCLUSION:
Anterior visual pathway neuronal loss in multiple sclerosis This exploratory study demonstrates thinning of the
(MS) has been suggested by optical coherence tomography retinal ganglion cell and associated layers in MS eyes.
(OCT) measurements of macular volume. Software This finding is most pronounced in the setting of a prior
programs that segment retinal layers are used but not yet history of ON, consistent with the occurrence of neuronal
widely available. The purpose of this study was to pilot a in addition to axonal loss in this setting. Low-contrast
manual method of estimating the retinal ganglion cell acuity is more sensitive than high-contrast VA to ganglion
layer volume by Spectral-Domain OCT, and to explore the cell layer loss in this small cohort. Ongoing longitudinal
relation of this volume to visual function and prior history studies piloting segmentation software will define the
of optic neuritis (ON). temporal relation of neuronal to axonal degeneration in
MS, ON, and other optic neuropathies.
METHODS:
Patients with MS and control subjects underwent fast REFERENCES:
macular OCT scans (25 frames/eye) obtained with 1. Burkholder B, Osborne B, Loguidice M, et al. Macular volume
by optical coherence tomography as a measure of neuronal
Spectral-Domain OCT technology. Ganglion cell layer
loss in multiple sclerosis. Archives of Neurology 2009, in
volume was determined by manually outlining these press.
structures for each frame of the OCT scan. Images were
2. Dijk H, Kok P, Garvin M, et al. Selective loss of inner retinal
magnified by 400-800%; contrast was enhanced to
layer thickness in type 1 diabetic patients with minimal
maximize the accuracy of layer delineation. Visual diabetic retinopathy. Investigative Ophthalmology & Visual
function testing was performed using low-contrast Science 50:3404-3409, 2009.
(1.25% level) and high-contrast visual acuity (VA).
3. Wolf-Schnurrbush U, Ceklic L, Brinkmann C, et al. Macular
thickness measurements in healthy eyes using six different
optical coherence tomography instruments. Investigative
RESULTS: Ophthalmology & Visual Science 50:3432-3437, 2008.
Eyes of patients with MS (n=16, age 50±6.3 years) had a

lower ganglion cell layer volumes than did control eyes
(MS: 0.76 mm3 vs. controls: 1.06 mm3; p=0.0001, t-test). KEY WORDS:
MS eyes with a prior history of ON had the greatest degree Multiple Sclerosis (MS), Optical Coherence Tomography
of ganglion cell layer thinning. Lower ganglion cell layer (OCT), Ganglion Cell Layer, Visual Function
volumes were associated with poorer performance on
tests of low-contrast letter acuity (r=0.60, p<0.001), but
not VA (r=0.10). FINANCIAL DISCLOSURE: NONE

EVIDENCE MEETS PRACTICE: TAKE-HOME POINTS ON OCT
Thomas R. Hedges III, MD
Tufts University
Boston, Massachusetts
LEARNING OBJECTIVES neuropathy, and this has had a significantly positive

1. To understand how OCT helps identify maculopathy impact on my practice.
that may mimic optic neuropathy.
HOW I USE OCT IN MY NEURO-OPHTHALMIC
2. To understand how OCT can aid in the management of PRACTICE
various optic neuropathies.
Proving Maculopathy That May Mimic Optic
3. To understand some of the limitations of OCT and how Neuropathy
to avoid misinterpretation of OCTs. Years ago, the diagnosis of occult maculopathy mimicking
optic neuropathy depended on subtle and often indirect
findings. Frequently, this also required ruling out optic
CME QUESTIONS
neuropathy, sometimes at significant expense. It was not
1. OCT can identify all but which of the following macular unusual for neuro-ophthalmologists to become engaged
lesions that may not be apparent clinically? in a dialogue with a retina specialist who insisted that a
a. Occult outer retinopathy, including MEWDS patient with unexplained visual loss had optic neuropathy,
when the neuro-ophthalmologist was sure that the
b. Stargardt’s disease problem was indeed macular, but had no clear way of
c. Cone dystrophy proving this. Central serous retinopathy was a common
maculopathy, which could mimic optic neuropathy yet
d. Solar maculopathy could easily be identified with fundus fluorescein
2. OCT can clearly distinguish improvement of angiography. However, now, with more refined OCT
papilledema from evolution of papilledema into techniques, other retinal conditions mimicking optic
atrophic papilledema. True or False? neuropathy are more easily proven.
3. Nerve fiber layer analysis by OCT can distinguish mild The diagnosis of macular hole and epiretinal membrane
papilledema from psuedopapilledema. True or False? often required considerable discussion between neuro-
ophthalmologists and retina colleagues in the past. Now
KEY WORDS macular hoe is a favorite diagnosis for retina specialists
now that it can be treated surgically. OCT reliably and
1. Optical Coherence Tomography
consistently demonstrates macular holes and epiretinal
2. Occult Maculopathy membranes.3 Another group of conditions, now more
easily identified using OCT, the occult outer retinopathies,
3. Optic Neuropathy
includes multiple evanescent white-dot syndrome, acute
4. Papilledema zonal occult outer retinopathy, and acute idiopathic blind
spot enlargement syndrome. These conditions are
5. Optic Neuritis
especially easy to identify with high-resolution OCT
6. Anterior Ischemic Optic Neuropathy whereby the inner segment/outer segment junction is
usually affected in the retinal areas corresponding to the
clinical findings.4-8 These diagnoses are also made with
INTRODUCTION more assurance using multifocal retinography. However,
I have been fortunate to have access to optical coherence OCT is much easier and quicker for the patient and usually
tomography (OCT) since its inception thanks to suffices.
collaboration between Joel Schuman and others at the New
England Eye Center1 with Jim Fugimoto at M.I.T.2 At first, We have also found that ultra-high resolution OCT helps
this appeared to be a tool primarily useful for retina in localizing the cause of microscotomas to the outer
specialists, but, as optic nerve analysis became more retina. However, we still do not have a better
refined for the use in glaucoma, its use in other types of understanding of the pathophysiology of this condition.
optic neuropathy became more apparent. However, there Hopefully, with more detailed OCT, the mechanism by
are still some difficulties with regard to this, which will be which these micro scotomas occur will become apparent.
reviewed below. What turns out to be most useful in The structural findings in some patients with
neuro-ophthalmic practice is the ability of OCT to identify microscotoma that we see with OCT do resemble those
and prove occult maculopathy mimicking optic which are seen with phototoxic maculopathy9-11 which can

result in a very discrete area of inner segment/outer OPTIC NEUROPATHY IN THE PRESENCE OF
segment loss in such individuals. It also resembles what is RETINOPATHY
occasionally seen in patients with epiretinal membrane.12
OCT can identify optic neuropathy when there is nerve
fiber layer loss, and this may be the first clue that there is
an insidious optic neuropathy occurring such as with optic
FIGURE 1. Inner segment/outer segment defect in a patient
with a paracentral microscotoma. nerve sheath meningiomas. In individuals with mild
decrease in visual acuity, mild visual field constriction,
mild color vision loss, and subtle visual field constriction,
finding nerve fiber layer thinning provides more objective
evidence that there is an optic neuropathy that requires
further investigation. We have been impressed with how
optic nerve head analysis by OCT will identify optic
neuropathy in the presence of a known maculopathy.
Even though such individuals may have visual field
characteristics that are more typical of optic neuropathy,
such as bitemporal hemianopia, frequently a concomitant
maculopathy makes interpretation of subjective
psychophysical tests difficult. Finding characteristic nerve
fiber layer changes on OCT does help motivate me at least
to obtain MRI scans when a retinal surgeon sends me a
Bilateral central visual loss in young people with
patient in whom the possibility of an optic neuropathy
apparently normal appearing retinas and optic nerves has
coexisting with maculopathy arises.
been a diagnostic dilemma until recently. Frequently,
these children have required a variety of rather expensive
investigations. Although multifocal electroretinography
can identify juvenile retinal degeneration or Stargardt’s
FUNCTIONAL LOSS OF VISION
disease when it does occur, OCT does show distinctive OCT can provide further objective evidence of normal
macular outer retinal changes early on, and I think OCT structure in patients suspected of having functional visual
will become the standard way of making this diagnosis in loss. However, one must remember that retinal nerve fiber
the future.13 Multifocal electroretinography may be layer degeneration does take time to develop, and a
difficult in young children, although we have been able to normal RNFL thickness does not always rule out a
use this approach in some individuals as young as six compressive optic neuropathy. However, in patients who
years of age. We have also found that OCT is as sensitive have had functional visual loss for many months or years,
in identifying hydroxychloroquine retinopathy as a normal RNFL thickness, along with a normal macular
multifocal ERG.14 OCT allows neuro-ophthalmologists to scan, is strong, objective evidence that there is no
make diagnosis of occult maculopathy much more structural pathology accounting for visual loss that is
efficiently and, this has saved me time and has saved likely functional in nature.
patients considerable expense.
OPTIC NERVE SWELLING

FIGURE 2. Perifoveal inner segment/outer segment loss in a We have attempted to use OCT to differentiate mild
patient with Plaquenil retinal toxicity. Note also the presence of
papilledema from pseudopapilledema. OCT can show
epiretinal membrane on the right portion of the inner retina.
optic nerve head drusen, and, when there are significant
drusen, one would expect the retinal nerve fiber layer to
be thin.15 However, in those individuals with congenitally
crowded optic nerve heads, without significant drusen, we
have been impressed that OCT shows thickening of the
nerve fiber layer, similar to that which occurs in mild
papilledema.16 Therefore, we now use OCT to observe
such individuals with suspected pseudopapilledema over
time, just the way we used to use photographs for this
purpose. If the OCT does not show any change in the
nerve fiber layer thickness over time, then we can assume
that such individuals were born with crowded nerves and
thicker nerve fiber layers. The finding of thickened nerve
fiber layer on circumferential OCTs in patients with
pseudopapilledema is not surprising, considering that
there is axoplasmic flow stasis in these individuals, just as
there is in those with true papilledema. Of course, one
must remember that patients with pseudopapilledema can

develop increased intracranial pressure and these two FIGURE 3. Foveal and peripapillary subretinal fluid in a patient
conditions may occur simultaneously. Recently, one report with acute nonarteritic AION. The patient’s vision spontaneously
recovered from 20/400 to 20/40 over 3 months.
showed evidence that peripapillary subretinal fluid may be
seen exclusively in patients with pathologic optic nerve
swelling either from increased intracranial pressure or
from ischemic optic neuropathy. Perhaps this may be the
best way to distinguish mild papilledema from
pseudopapilledema in the future.17
We also have been using OCT to followup patients with

papilledema. However, the main problem with this has
been in interpreting what appears to be normalization of
the retinal nerve fiber layer thickness when there is
concomitant optic atrophy, which also leads to reduction
VITREOPAPAPILLARY TRACTION
in the thickness of the nerve fiber layer over time.
However, we have some indication that there may be a OCT has also been very useful in our practice in patients
pattern of nerve fiber layer change, which may indicate with suspected optic disc swelling due to vitreopapillary
that there is optic atrophy superimposed upon traction.20 Vitreopapillary traction may be difficult to prove
papilledema. When the thickness of the superior nerve by ophthalmoscopy alone. However, OCT clearly shows
fiber layer diminishes while the thickness of the inferior vitreous adhesions to the optic nerve head, and in some
nerve fiber layer remains elevated, the likelihood of visual of these individuals, there may be simultaneous,
field loss appears to rise, indicating the onset of atrophic vitreomacular traction. When the latter occurs, the
papilledema, rather than improvement in the papilledema. resolution of the pseudopapilledema caused by
vitreopapillary traction can be relieved surgically.
One observation that OCT has allowed is the visualization
of subretinal fluid in patients with papilledema.18 This may
correlate with loss of visual acuity which is a reversible COMPRESSIVE OPTIC NEUROPATHY
phenomenon. The degree of subretinal fluid in the foveal There have been some interesting OCT findings in
region seems to correlate with the degree of visual acuity patients with compressive optic neuropathy.21, 22 However,
loss, and, just as in patients with central serous from a practical point of view, we have not found OCT to
retinopathy, the prognosis for recovery of visual acuity be all that useful in managing patients with compressive
remains good and, in my practice, when there is loss of optic neuropathy. We do not feel that OCT aids in the
visual acuity and this can be demonstrated to be due to prognosis any more than ophthalmoscopic observation
subretinal fluid by OCT, I do not feel that this is definitely of the retinal nerve fiber layer does. Our main goal in
an indication for urgent intervention surgically. The source managing patients with compressive optic neuropathy is
of the fluid is not entirely clear. Because there is to prevent any retinal nerve fiber layer loss, and visual
frequently a communication between the subfoveal fluid field testing remains the main tool in identifying
and the peripapillary subretinal fluid that we also compressive optic neuropathy before optic atrophy
described, the possibility that the fluid could be coming develops. As opposed to patients with optic nerve head
from the choroid remains the best possibility. There may disease, glaucoma being the main example, visual field
be disruption of the connections between Bruch’s changes usually precede nerve fiber layer changes and we
membrane and the optic nerve which is disturbed because continue to follow all of our patients with compressive
of the swelling of the nerve, allowing for serous fluid to optic neuropathy primarily monitoring their visual fields.
leak under the retina in the peripapillary space and then,
in some individuals, track into the subfoveal region.
OPTIC NEURITIS
Subretinal fluid has also been observed in patients with
From a practical point of view OCT is occasionally useful
anterior ischemic optic neuropathy.19 We believe that,
in managing patients with optic neuritis.23-29 Although
when there is loss of visual acuity in patients with AION
OCT can serve as a biomarker for the progression of
associated with subfoveal fluidfluid, this may have
demyelinating disease, it may not always reflect the
significant implications with regard to treatment. Patients
overall degree of demyelination occurring in such
with subretinal fluid from AION, like patients with
individuals. Certainly, OCT will be a useful in studies of
subretinal fluid from papilledema, also have a good
the effectiveness of various drugs in the treatment of
prognosis for spontaneous recovery of visual acuity as the
demyelinating disease from an investigational point of
subretinal fluid resorbs.
view, but for the day-to-day management of patients with
MS, OCT is probably only going to be as useful as MRI
scanning to monitor the overall condition of the patient.
Although there have been reports of OCT helping to
distinguish patients with neuromyelitis optica from those

with multiple sclerosis, the degree of nerve fiber layer CME ANSWERS
dropout is reflected by the degree of visual loss 1. C
demonstrated by visual acuity testing or visual field 2. False
testing, so OCT so in and of itself is not all that useful in 3. False
that regard.
REFERENCES
CAVEATS 1. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang
Although OCT has become very useful in my practice over W, et al. Optical coherence tomography. Science 1991 Nov
the last several years, I try to remain aware of some of the 22;254(5035):1178-81.
limitations of OCT. OCT can be normal in patients with 2. Fujimoto JG, Brezinski ME, Tearney GJ, Boppart SA, Bouma B,
compressive optic neuropathy, and visual field testing Hee MR, et al. Opticalbiopsy and imaging using optical
remains the most important diagnostic tool in the coherence tomography. Nat Med 1995 Sep;1(9):970-2.
diagnosis and followup of patients with compressive optic 3. Ko TH, Witkin AJ, Fujimoto JG, et al. Ultrahigh-resolution
neuropathy. OCT can be normal in patients with some optical coherence tomography of surgically closed macular
occult maculopathies, and multifocal electroretinography hole. Arch Ophthamol 2006;124:827-836.
may be needed to identify maculopathy in these patients 4. Witkin AJ, Ko TH, Fujimoto JG, et al. Ultra-high resolution
and to prevent extensive evaluations, searching for other optical coherence tomography assessment of photoreceptors
diagnoses. A bad OCT is like a bad MRI or a bad CT scan. in retinitis pigmentosa and related diseases. Am J Ophthlamol
2006;142:945-952.
There may be errors in retinal nerve fiber layer analysis.
Sometimes the algorithm used by the OCT machine will 5. Pieroni CG, Witkin AJ, Ko TH, et al. Ultrahigh resolution optical
fail and false measurements of the retinal nerve fiber layer coherence tomography in non-exudative age related macular
degeneration. Br J Ophthalmol 2006 Feb;90(2):19-17.
or the macula may occur. It is important to check the
alignment of the circular scans when analyzing retinal 6. Ko TH, Fujimoto JG, Duker JS, et al. Comparison of ultrahigh
nerve fiber layer measurements. If the scan is not properly and standard resolution optical coherence tomography for
imaging of macular pathology and repair. Ophthalmol
placed which respect to the optic nerve head, inaccurate 2004;111:2033–43.
measurements may follow. This is especially problematic
in patients with swollen optic nerves where the presence 7. Drexler W, Sattmann H, Hermann B, et al. Enhanced
visualization of macular pathology with the use of ultrahigh-
of subretinal fluid and marked elevation of the nerve fiber resolution optical coherence tomography. Arch Ophthalmol
layer may provide measurements which are inaccurate 2003;121(5):695-705.
because they are out of the range of the normal algorithm.
8. Srinivasan VJ, Wojtkowski M, Witkin AJ, et al. High-definition
Perhaps, in patients with optic nerve head swelling, a and 3-dimensional imaging of macular pathologies with
larger diameter should be used for retinal nerve fiber layer high-speed ultrahigh-resolution optical coherence
analysis. Also, there may be errors in macular analysis. To tomography. Ophthalmology 2006;113:2054-2065.
avoid this, because most macular diagnoses rely on a 9. Garg SJ, Martidis A, Nelson ML, et al. Optical coherence
more qualitative evaluation of the OCT, I always obtain tomography chronic solar retinopathy. Am J Ophthalmol
line scans, which incorporate the optic nerve head and the 2004;137:351-354.
macula. This allows for a better view of the anatomic 10. Chen RW, Gorczynska I, Srinivasan VJ, et al. High-speed
details of the macula, which are not always clear on the ultrahigh resolution optical coherence tomography findings in
typical macular scans. OCT may identify concurrent optic chronic solar retinopathy. Retin Cases Brief Rep
nerve and macular disease. Therefore, I image the macula 2008;2(2):101-102.
as well as the RNFL in every patient in whom I obtain OCT. 11. Kaushik, S, Gupta V, Gupta A. Optical coherence tomography
findings in solar retinopathy. Ophthlamic Surg Lasers Imaging
2004;35(1):52-5.
MY STANDARD PROTOCOL FOR OCT 12. Witkin AJ, Wojtkowski M, Reichel E, et al. Photoreceptor
disruption secondary to posterior vitreous detachment as
My standard protocol is to obtain a retinal nerve layer
visualized using high-speed ultrahigh resolution optical
scan, a macula scan, and a line scan of the macula and coherence tomography. Arch Ophthalmol 2007
nerve. I have not found that the optic nerve head protocol Nov;125(11):1579-1580.
is useful in analyzing optic nerve disease, and I have very
13. Ergun E, Hermann B, Wirtitsch M, et al. Assessment of Central
little experience with this. Spectral domain OCT appears Visual Function in Stargardt’s Disease/Fundus Flavimaculatus
better than time domain for evaluating macular disease. with Ultrahigh-Resolution Optical Coherence Tomography.
However, the time domain appears to be more consistent Investigative Ophthalmology and Visual Science.
with regard to retinal nerve fiber layer analysis, especially 2005;46:310-316.
for serial analysis over time. High-speed ultra-high 14. Rodriguez-Padilla JA, Hedges TR, Monson B, Srinivasan V, et
resolution OCT is best for occult maculopathy, especially al. High-Speed Ultra–High-Resolution Optical Coherence
for the occult outer retinopathies, and also in patients Tomography Findings in Hydroxychloroquine Retinopathy.
Arch Ophthalmol. 2007;125:775-780.
with micro scotomas.

15. Roh S, Noecker RJ, Schuman, JS, Hedges TR, Weiter JJ, Mattox
C. Effect of optic nerve head drusen on nerve fiber layer
thickness. Ophthalmology 1998; 105:878-885.
16. Karam EZ, Hedges TR. Optical coherence tomography of the

retinal nerve fibre layer in mild papilloedema and
pseudopapilloedema. Br J Ophthalmol 2005;89:294-298.
17. Johnson LN, Diehl ML, Hamm CW et al. Differentiating Optic

Disc Edema From Optic Nerve Head Drusen on Optical
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45-49.
18. Hoye VJ, Berrocal AM, Hedges TR, Amaro-Quireza ML. Optical
coherence tomography demonstrates subretinal macular
edema from papilledema. Arch Ophthalmol. 2001;119:
1287-1290.
19. Hedges TR, Vuong, LN, Gonzalez-Garcia AO, Mendoza-

Santiesteban CE, Amaro-Quiereza AL. Subretinal fluid from
anterior ischemic optic neuropathy demonstrated by optical
coherence tomography. Arch Ophthalmol 2008;126:812-815.
20. Hedges TR, Flattem NL, Bagga A. Vitreopapillary traction

confirmed by optical coherence tomography. Arch
Ophthalmol 124; 279-281: 2006.
21. Kanamori A, Nakamura M, Matsui N, et al. Optical coherence

tomography detects characteristic retinal nerve fiber layer
thickness corresponding to band atrophy of the optic discs
Ophthalmology 2004; 111: 2278-2283.
22. Monteiro MLR, Leal BC,Rosa AAM, Bronstein MD. Optical

coherence tomography analysis of axonal loss in band
atrophy of the optic nerve. Br J Ophthalmol 2004;88:896-899.
23. Zaveri MS, Conger A, Salter A, et al. Retinal imaging by laser

polarimetry and optical coherence tomography evidence of
axonal degeneration in multiple sclerosis. Arch Neurol 2008
Jul;65(7):924-8.
24. Frohman EM, Dwyer MG, Frohman T, et al. Relationship of

optic nerve and brain conventional and non-conventional MRI
measures and retinal nerve fiber layer thickness, as assessed
by OCT and GDx: a pilot study. J Neurol Sci 2009 Jul
15;282(1-2):96-105.
25. Costello F, Hodge W, Pan YI, et al. Tracking retinal nerve fiber
layer loss after optic neuritis: a prospective study using
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Aug;14(7):893-905.
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Garway-Heath DF, Plant GT, et al. An investigation of the
retinal nerve fibre layer in progressive multiple sclerosis using
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coherence tomography and disease subtype in multiple
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OCT - In.neuro Ophthalmology - Practice

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North American Neuro-Ophthalmology Society

36th Annual Meeting

T HURSDAY, MARCH 11 LOCATION

6:30 a.m. – 12:30 p.m. Registration Arizona Ballroom Foyer

6:30 a.m. – 7:30 a.m. Continental Breakfast Arizona Salon

8:30 a.m. – 10:30 a.m. Spouse/Guest Hospitality Suite Signature Grill

9:20 a.m. – 9:30 a.m. Questions and Discussion

9:30 a.m. – 10:00 a.m. Coffee Break

2010 Annual Meeting Syllabus | 325

12:00 p.m. Meeting adjourns

326 | North American Neuro-Ophthalmology Society

LEARNING OBJECTIVES INTRODUCTION

Joel Schuman, while working on other projects in the laser

2010 Annual Meeting Syllabus | 327

OCT was described in vivo in 19932 and quickly used in

The first commercial two iterations of OCT were not

328 | North American Neuro-Ophthalmology Society

FIGURE 4: RNFL thickness map of the left eye of a healthy

In SD-OCT , after multiple B-scans are acquired in raster

FIGURE 6: TD-OCT image through the anterior

2010 Annual Meeting Syllabus | 329

FIGURE 10: (a) Fundus photograph of

FIGURE 8: RNFL thickness map of patient with primary open

330 | North American Neuro-Ophthalmology Society

FIGURE 11: Right eye (Top) Three-dimensional reconstruction of

2010 Annual Meeting Syllabus | 331

2. Measurements of various ocular structures demonstrate

332 | North American Neuro-Ophthalmology Society

2. Fercher AF et al. In vivo optical coherence tomography. Am J

3. Schuman JS, Hee MR, Arya AV, Pedut-Kloizman T, Puliafito CA,

5. Hee MR, Puliafito CA, Wong C, Duker JS, Reichel E, Schuman

7. Leitgeb R, Wojtkowski M, Kowalczyk A, Hitzenberger CK,

10. Wojtkowski M, Bajraszewski T, Gorczyńska I, Targowski P,

11. Wojtkowski M, Srinivasan V, Fujimoto JG, Ko T, Schuman JS,

2010 Annual Meeting Syllabus | 333

LEARNING OBJECTIVES INTRODUCTION

c. birefringence of the retinal axons

d. xray imaging RETINAL IMAGING METHODOLOGIES

4. Papilledema OCT METHODOLOGY

2010 Annual Meeting Syllabus | 335

Costello et al investigated OCT findings in CIS optic

336 | North American Neuro-Ophthalmology Society

2010 Annual Meeting Syllabus | 337

338 | North American Neuro-Ophthalmology Society

2010 Annual Meeting Syllabus | 339

340 | North American Neuro-Ophthalmology Society

2010 Annual Meeting Syllabus | 341

132. Trip SA, Schlottmann PG, Jones SJ et al. Optic nerve

135. Tzamalis A, Kynigopoulos M, Schlote T, Haefliger I. Improved

136. Uc EY, Rizzo M, Anderson SW, et al. Impaired visual search in

138. Reversible dysfunction of retinal ganglion cells in non-

139. Vizzeri G, Bowd C, Medeiros FA, et al. Effect of improper

140. Vizzeri G, Bowd C, Medeiros FA, et al. Scan tracking

141. Vizzeri G, Bowd C, Medeiros FA, et al. Scan tracking

342 | North American Neuro-Ophthalmology Society

LEARNING OBJECTIVES care provider. The first-line diagnostic tools for

• Visual Field Index (VFI) Unfortunately, early detection of glaucoma remains a

There is no formal screening method for glaucoma.