Download Calibration of Fundus Images Using Spectral Domain Optical

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C L I N I C A L
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Calibration of Fundus Images Using Spectral
Domain Optical Coherence Tomography
Brandon J. Lujan, MD; Fenghua Wang, MD; Giovanni Gregori, PhD; Philip J. Rosenfeld, MD, PhD;
Robert W. Knighton, PhD; Carmen A. Puliafito, MD, MBA; Ronald P. Danis, MD;
Larry D. Hubbard, MAT; Robert T. Chang, MD; Donald L. Budenz, MD, MPH;
Michael I. Seider, BGS; O’Rese Knight, BS
BACKGROUND AND OBJECTIVE: Measurements performed on fundus images using current software are not accurate. Accurate measurements can be
obtained only by calibrating a fundus camera using
measurements between fixed retinal landmarks, such
as the dimensions of the optic nerve, or by relying on
a calibrated model eye provided by a reading center.
However, calibrated spectral domain OCT (SD-OCT)
could offer a convenient alternative method for the
calibration of any fundus image.
PATIENTS AND METHODS: The ability to measure exact distances on SD-OCT fundus images was
tested by measuring the distance between the center of
the fovea and the optic nerve. Calibrated SD-OCT scans
measuring 6 × 6 × 2 mm centered on the fovea and
the optic nerve were analyzed in 50 healthy right eyes.
The foveal center was identified using cross-sectional
SD-OCT images, and the center of the optic nerve was
identified manually. The SD-OCT scans were registered
to each other, and the distances between the center of
From the Bascom Palmer Eye Institute, University of Miami Miller School
of Medicine, Miami, Florida (BJL, FW, GG, PJR, RWK, CAP, RTC, DLB,
MIS); the Department of Ophthalmology, Shanghai Jiaotong University, First
People’s Hospital, Shanghai, China (FW); and the Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin
(RPD, LDH).
Accepted for publication March 13, 2008.
Supported by research grants from NEI (RO3 EY016420), NEI core center
grant P30 EY014801 to the University of Miami, and Research to Prevent
Blindness. Additional research funding was received from Carl Zeiss Meditec,
Inc. The researchers would also like to acknowledge research funding from the
2006 Allergan Horizon Grant Program and the H.A. & Mary K. Chapman
Charitable Trust.
CALIBRATING FUNDUS IMAGES WITH SD-OCT · Lujan et al.
the optic nerve and fovea were calculated. The overlay of
these SD-OCT fundus images on photographic fundus
images was performed.
RESULTS: Any image of the fundus could be calibrated by overlaying the SD-OCT fundus image, and the
measurements were consistent with previously defined
calibration methods. The mean distance between the center of the fovea and the center of the optic nerve was 4.32
± 0.32 mm. The line from the center of the optic nerve to
the foveal center had a mean declination of 7.67 ± 3.88°.
Mean horizontal displacement and vertical displacement
were 4.27 ± 0.29 mm and 0.58 ± 0.29 mm, respectively.
CONCLUSIONS: The overlay of the SD-OCT fundus image provides a convenient method for calibrating
any image of the fundus. This approach should provide
a uniform standard when comparing images from different devices and from different reading centers.
[Ophthalmic Surg Lasers Imaging 2008;39:S15-S20.]
Dr. Rosenfeld received a travel grant and honorarium from Carl Zeiss
Meditec, Inc. Drs. Gregori, Knighton, and Budenz received research support from Carl Zeiss Meditec, Inc. Drs. Gregori, Knighton, and Puliafito
own a patent that is licensed to Carl Zeiss Meditec, Inc. Dr. Puliafito
is also a consultant for Carl Zeiss Meditec, Inc. Drs. Lujan and Chang
received support from a grant to the University of Miami from Carl Zeiss
Meditec, Inc., and O’Rese Knight receives research support from Carl
Zeiss Meditec, Inc. None of the other researchers have commercial or
proprietary interest in the products and corporations referred to in this
article.
Address correspondence to Giovanni Gregori, PhD, McKnight Vision
Research Center, Bascom Palmer Eye Institute, 1638 NW 10th Ave., Miami,
FL 33136.
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INTRODUCTION
A convenient, reliable, and standardized method
for the accurate calibration of fundus images is not
widely available. Currently, the software accompanying
commercial fundus cameras “measures” distances on a
fundus image by setting the amount of image magnification that an individual camera produces. However,
in practice, inadvertent variation in magnification of
the retinal image can occur. This is due in part to the
variability of the relay lens magnification and due in
part to the camera’s wide depth of focus, in which the
incorrect position of an objective lens can be compensated for by the photographer using the focus knob.
Inadvertent changes in the magnification of the image
then occur, which directly result in inaccurate distance
measurements using the software supplied by the digital camera manufacturers.
The problem of calibrating fundus images is not
unique to digital photography but has been a problem
since the introduction of fundus photography. The
first widely recognized calibration technique based
on Duke-Elder’s review was that the average optic
disc was 1.5 mm in diameter.1 This later became the
“standard disc diameter” and was used to generate a
grading reticle in the Age-Related Eye Disease Study
(AREDS),2,3 the Early Treatment of Diabetic Retinopathy Study (ETDRS),4 and the Macular Photocoagulation Study (MPS).5 This standard was then used to
perform linear and area measurements on the fundus
image. However, an extensive postmortem study of
the nerve size6 as well as rigorous photographic studies
of the optic nerve head later demonstrated that this
was an underestimate of the average nerve diameter
and that there was significant variability in the size of
the optic disc.7-11
Another approach to calibrate a fundus image uses
the dimensions of other fundus features, most notably
the distance between the optic nerve and the fovea.8,12-16
The Fundus Photograph Reading Center (FPRC) at the
University of Wisconsin has found that this distance
between the fovea and the center of the optic nerve is
approximately 4.5 mm and that this is more consistent
across individuals than measurement of the optic disc itself (R.P. Danis, personal communication, 2008). However, the most significant obstacle to accurately measuring distances based on this approach is the reliable
identification of the foveal center.
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Another approach used by reading centers is to calculate distances on fundus photographs based on images obtained from a sample eye containing a reticle
of a known size. Once the reticle is imaged, a conversion factor is calculated between the known size of the
reticle and its dimensions on the image. This way, any
fundus image can be calibrated as long as the image is
obtained using the same camera. However, each camera will have a different conversion factor, and these
sample eyes are not readily available.
In this article, we report on the use of the calibrated
spectral domain optical coherence tomography (SDOCT) fundus image as a convenient universal technique
for the calibration of any fundus image. We also repeat
the measurements performed by the FPRC using the
geometric center of the optic nerve and the foveal center.
However, our approach uses the absolute anatomic foveal center defined cross-sectionally by SD-OCT.
PATIENTS AND METHODS
We initially evaluated the right eyes of 56 healthy
patients (27 men) with a mean age 47.1 ± 16.7 years
(range, 20-73 years). Approval to perform these evaluations was obtained from the Institutional Review Board
at the University of Miami Miller School of Medicine,
and informed consent was obtained from each patient
before all examinations. Each patient was refracted and
had best-corrected Snellen visual acuities ⩾ 20/30. The
range of the spherical equivalent of refractive error was
-10.375 diopters (D) to +3 D, with a mean of -0.52 ±
2.50 D and a median of zero D. To establish clinical
normalcy, each patient underwent slit-lamp examination, gonioscopy, and dilated fundus examination. Furthermore, each patient had intraocular pressure, central
corneal thickness, and axial length measurements that
were within the established normal ranges. Finally,
Humphrey visual field examinations were performed,
and all patients had a reliable test result without any
pathologic scotomas. Patients with tilted optic nerves,
signs of myopic degeneration, or a history of ocular disease were excluded from the study.
A single Cirrus high-definition (HD)-OCT unit
(Carl Zeiss Meditec, Inc., Dublin, CA) was used to acquire all SD-OCT images from both eyes of each patient. This machine uses a superluminescent diode laser
centered at a wavelength of 840 nm, which generates an
axial resolution of approximately 5 µm. The Cirrus HD-
OPHTHALMIC SURGERY, LASERS & IMAGING · JULY/AUGUST 2008 · VOL 34, NO 4 (SUPPLEMENT)
OCT is calibrated to scan a square 6 × 6 mm region of
the posterior pole by using a model eye. The model eye
has a curved back surface, and at 840 nm has a focal
length of 17.23 mm and a refractive error of 1.35 D.
We performed two sets of scans for each eye, one centered on the fovea by patient fixation and one centered
on the optic nerve using an internal fixation target. The
scan protocol for both the macula and optic nerve was
a 200 × 200 raster scan (the first number refers to the
number of A-scans in each horizontal B-scan, whereas
the second number is the total number of horizontal Bscans) and was acquired in approximately 1.5 seconds.
Multiple scans of each type were performed to reduce
the likelihood of motion artifact. If an entire set of one
type of image from the right eye had poor signal strength
or demonstrated a motion artifact, that patient was excluded. In this article, this technology will be referred to
generically as SD-OCT.
All macular cross-sectional SD-OCT B-scans were
reviewed by a retinal specialist (BJL) to ensure that
there was no pathology affecting the fovea and to confirm that there was an anatomically normal foveal depression. Three patients were excluded from the study
because of pathology on the macular B-scans that was
not revealed clinically or by fundus photography. Specifically, one patient showed retinal pigment epithelium
changes under the fovea, and two had abnormalities of
the vitreoretinal interface.
The horizontal and vertical B-scans that contained
the center of the fovea were then identified. This determination was based on the lowest point of the foveal
depression in both horizontal and vertical planes. The
location of these B-scans within the SD-OCT dataset could then be visualized en face by generating an
SD-OCT fundus image. This technique, which was
described previously,17 integrates the signal intensity
along each A-scan and then displays the intensity relative to other A-scans. The horizontal and vertical Bscans that included the foveal center were identified
by lines on the SD-OCT fundus image such that their
intersection was the foveal center.
The center of the optic nerve was identified on the
SD-OCT fundus image of the optic nerve by manually
centering the cross-hairs of a standard disc diameter as
defined by the ETDRS. In overlaying this circle over
the optic nerve, the amount of optic disc substance in
each of the four quadrants defined by a horizontal and
vertical cross-hair was visually equalized. The research-
CALIBRATION OF FUNDUS IMAGES WITH SD-OCT · Lujan et al.
ers were careful to use the neuroretinal rim as the outer
boundary and not peripapillary atrophy, scleral crescents, or other anatomic irregularities. This method
has been shown by the FPRC to be a reliable way to
identify the center of the optic nerve (R.P. Danis, personal communication, 2008).
The macular and optic nerve SD-OCT fundus
images with their respective centers identified were
then manually registered to each other. This was accomplished by an alignment of the optic nerve SDOCT fundus image with the macular SD-OCT fundus
image based on an overlap of the retinal vasculature.
Thus, a composite SD-OCT fundus image was generated that contained both the confirmed foveal center
and the manually identified center of the optic disc.
This alignment required a rotation in eight cases. There
were three eyes that could not be registered adequately
because of lack of overlapping features, and these were
excluded from the study. Therefore, we proceeded to
analyze distances on the remaining 50 eyes (25 men).
Once the composite SD-OCT fundus image was
formed, the horizontal and vertical displacement between the center of the optic nerve and the center of
the fovea could be directly measured in pixels. The
horizontal displacement was the horizontal distance
from the center of the optic nerve to a vertical line
that intersected the center of the fovea. Likewise,
the vertical displacement was the vertical distance
between the center of the fovea and its intersection
with the horizontal displacement line. The distance
between the foveal center and the center of the optic
disc was then calculated from these displacements.
This distance will be referred to as the fovea-nerve
distance. All distance measurements were then converted to millimeters using the known calibration of
the image. The angle between the horizontal displacement line and the fovea-nerve distance line will be
referred to as the angle of declination.
RESULTS
The foveal center could be identified by horizontal and vertical B-scans in all 50 macular SDOCT scans. The exact en face location of the intersection of B-scans passing through the foveal center
was identified on the SD-OCT fundus image using
the Cirrus HD-OCT 2.0 software (Fig. 1). The center of the optic nerve could be determined on the
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TABLE
Measurement of Parameters Between the Fovea and the Center of the Optic Nerve
Mean (mm)
Standard
Deviation (mm)
Coefficient of
Variability (%)
Median (mm)
Fovea–nerve distance
4.32
0.32
7.30
4.31
Angle of declination
7.67
3.88
50.50
7.55
Parameter
Horizontal displacement
4.27
0.29
6.76
4.27
Vertical displacement
0.58
0.29
50.35
0.59
Figure 1. Horizontal (H) and vertical (V) B-scans through the foveal center. The SD-OCT fundus image with the position of these
B-scans through the foveal center is identified.
SD-OCT fundus image using the standard disc diameter circle in each eye. The fovea-nerve distance,
the angle of declination, and the horizontal and vertical displacements between the fovea and the center of the optic nerve were successfully obtained in
all cases (Fig. 2), and the results are summarized in
the Table.
The fovea-nerve distance and the horizontal displacement followed a Gaussian distribution and showed
less variability compared with its mean (the coefficient
of variability) than the vertical displacement or the angle of declination. The lower and upper quartiles of the
fovea-nerve distance were 4.12 and 4.52 mm respectively, whereas 94% of our sample had a fovea-nerve
distance between 3.91 and 4.90 mm. Similarly, the
lower and upper quartiles of the horizontal displacement were 4.07 and 4.48 mm, and 94% of our sample
had values between 3.83 and 4.77 mm. The horizontal
displacement had the smallest coefficient of variability
of any of the parameters analyzed.
The measurements of the angle of declination and
the vertical displacement had coefficients of variability
that were significantly larger than the other two parameters. The lower and upper quartiles of the angle
of declination were 4.83° and 10.27° respectively, and
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Figure 2. Composite SD-OCT fundus image of the fovea centered
scan and the optic nerve centered scan showing the various measurements performed. H, horizontal displacement; V, vertical displacement.
The fovea-nerve distance can be computed from these horizontal and
vertical displacements. α, angle of declination between the horizontal
displacement line and the fovea-nerve distance line.
94% of measurements were between 0.38° and 13.75°.
The lower and upper quartiles of the vertical displacement were 0.38 and 0.73 mm, and 94% of vertical
displacements were between 0.03 and 1.08 mm. One
of the eyes had a negative vertical displacement, meaning that the imaged foveal center was located above the
optic nerve.
There was no correlation between the fovea-nerve
distance and the age of the patient (r = 0.11) and a moderate correlation between the refractive error (r = 0.47)
and the axial length (r = -0.42) was found.
DISCUSSION
One advantage of SD-OCT technology is the
ability to generate an SD-OCT fundus image directly
from the 6 × 6 mm calibrated scan. Precise distance
measurements can therefore be performed directly using this image. The ability to overlay the SD-OCT
OPHTHALMIC SURGERY, LASERS & IMAGING · JULY/AUGUST 2008 · VOL 34, NO 4 (SUPPLEMENT)
Figure 4. Reticle constructed from the mean dimensions determined by this study overlying the optic nerve head on the scanning
laser ophthalmoscope generated by the Cirrus HD-OCT. Use of the
reticle could allow the foveal center to be obtained without operator
judgment, even in the presence of severe macular pathology.
Figure 3. Composite SD-OCT fundus image registered to a digital
fundus photograph. Registration was performed by maximizing
blood vessel overlap.
fundus image on any other image of the fundus using shared landmarks permits the calibration of digital fundus photographs, fluorescein angiograms, and
fundus autofluorescence images obtained from any
system (Fig. 3). Moreover, these measurements will be
more accurate for an individual compared with presumed calibrations obtained from population-based
measurements.
One of the major strengths of this calibration
study was the ability to locate the foveal center directly from cross-sectional SD-OCT data and not
from a fundus photograph where this may be ambiguous. The distribution of macular pigment and
the geometry of retinal vessels may be proxies for the
foveal center, but the accuracy of these assumptions
has not been proven. Furthermore, the presence of
pathology can significantly limit the ability to recognize even these indirect clues regarding the location
of the foveal center. Because we used multiplanar
cross-sectional data in our study, the identification
of the foveal center was more anatomically accurate
than in any previously reported work.
Although we can obtain very precise fundus distance
measurements using SD-OCT, we found from the data
CALIBRATION OF FUNDUS IMAGES WITH SD-OCT · Lujan et al.
analyzed in this study that the fovea-nerve distance varies
little within this population of healthy individuals. These
results were in close agreement with other published results.6,18 Furthermore, the coefficients of variability for
the vertical dimension and for the angle of declination
were similar to those in a study that used a scanning laser
ophthalmoscope to functionally assess a patient’s preferred
retinal locus as a proxy for the fovea.19
As expected, the refractive error in a patient has a
role in the amount of magnification of the SD-OCT
fundus image.13 Despite this, the mean fovea-nerve distance varied by only 7.3% over a range of refractive errors in our study. The refractive error is generally stable
in a given eye, and this permits comparisons over time.
The parameters in this study with the greatest coefficient of variability were the vertical displacement
and, consequently, the angle of declination. This is due
either to biological variability or to angular rotation of
the eye. To register images from 16% of the eyes in our
study, the SD-OCT fundus image of the optic nerve
needed to be rotated relative to the SD-OCT fundus
image of the macula. This confirms that rotation of the
eye occurs during some SD-OCT scans and suggests
that rotation is a component of the variability.
Our data demonstrate that the fovea-nerve distance and the horizontal displacement between the
fovea and the optic nerve do not vary significantly
among patients. Furthermore, the range of both the
horizontal and vertical displacements was less than
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1.05 mm in 94% of the eyes in this study in each
dimension. Given these biometric data, we envision the creation of a simple reticle (Fig. 4) that
would use the optic nerve as a landmark to acquire
data centered on the fovea without the subjective
judgment of the SD-OCT operator. This reticle
would be useful when there is significant macular
pathology and no other means exist to identify the
foveal center.
In summary, we have developed a simple and direct approach for calibrating any fundus image using
an SD-OCT fundus image. Based on the measurements obtained in this study, we have also developed a
simple reticle that can be used to maximize the likelihood that an SD-OCT scan will be centered on the
fovea whenever macular pathology precludes accurate
identification of the foveal center.
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