Download Advantages of Anterior Segment Optical Coherence Tomography

MS NO: CORNEA-D-16-00706
CLINICAL SCIENCE
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Advantages of Anterior Segment Optical Coherence
Tomography Evaluation of the Kayser–Fleischer Ring in
Wilson Disease
Mittanamalli S. Sridhar, MD
Purpose: To present anterior segment optical coherence tomogra-
phy (AS-OCT) findings of the Kayser–Fleischer (KF) ring in Wilson
disease (WD) and to discuss the potential advantages of evaluating
the KF ring by AS-OCT.
Methods: This is a retrospective case series of 7 patients with WD
with the KF ring seen in our institute during the study period (August
2015 to June 2016). All patients underwent slit-lamp examination of
the cornea and AS-OCT (Optovue RTVue Premier). In 2 patients, the
length of the KF ring was measured using the gray scale of AS-OCT.
Results: The KF ring on the gray scale of AS-OCT was visualized
as a hyperreflective deep corneal layer at the level of Descemet
membrane in all eyes. The OCT color scale revealed the KF ring as
a greenish/greenish yellow/yellow/yellow-orange band. The gray
scale of AS-OCT could easily measure the length of the KF ring in
patients 6 and 7.
Conclusions: AS-OCT is an alternative method of evaluating the
KF ring in WD, which can be used in combination with slit-lamp
examination. The KF ring can be easily measured using the gray
scale of AS-OCT. Further studies are required to study the potential
advantages of AS-OCT including assessing the density of the KF
ring, as a tool to assess response to treatment in WD, in
differentiating the KF ring of WD disease from copper deposits in
other situations and pigmented corneal rings in non-Wilsonian
liver disease.
Key Words: Kayser–Fleischer ring, Wilson disease, slit-lamp
examination, optical coherence tomography
(Cornea 2016;00:1–4)
W
ilson disease (WD) is a genetic disorder in which there
is an inherited defect in the biliary excretion of copper.
WD has an autosomal recessive mode of inheritance.1 In this
condition, copper accumulates in the liver, brain, cornea, and
Received for publication August 2, 2016; revision received November 13,
2016; accepted November 14, 2016. Published online ahead of print XX
XX, XXXX.
From the Department of Ophthalmology, Krishna Institute of Medical
Sciences, Hyderabad, India.
The author has no funding or conflicts of interest to disclose.
Reprints: Mittanamalli S. Sridhar, MD, Department of Ophthalmology,
Krishna Institute of Medical Sciences, Minister Road, Hyderabad,
Telangana 500003, India (e-mail: [email protected]).
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Cornea Volume 00, Number 00, Month 2016
other organs, resulting in hepatic, neurological/psychiatric,
ocular, and other manifestations.2 Copper is deposited in the
inner part of Descemet membrane (DM) of the cornea, and
this copper chelate is called the Kayser–Fleischer (KF) ring.3
The worldwide prevalence of WD has been reported to be
approximately 1 in 30,000 with a carrier rate of 1 in 90.2
Identification of the KF ring remains the single most
important diagnostic sign in WD.4,5 The KF ring may be the
first detectable manifestation of WD.6 The ring is typically
seen in the peripheral cornea, copper deposited on DM as
a greenish yellow or golden brown ring. It is almost always
bilateral, starts superiorly first, followed by a similar inferior
arc and later becomes circumferential.3 In eye clinics, slitlamp (SL) examination of the cornea is performed routinely to
look for the KF ring.
In this case series, we present anterior segment optical
coherence tomography (AS-OCT) findings of the KF ring and
discuss the potential advantages of using AS-OCT in WD.
Optical coherence tomography has become an important
diagnostic tool in eye clinics. It is a noncontact optical device
that provides cross-sectional images of the eye and does
quantitative analysis of ocular tissues.7
MATERIALS AND METHODS
This is a retrospective case series of 7 patients with WD
with the KF ring seen in our institute during the study period
from August 2015 to June 2016. The Ethics Committee of the
Krishna Institute of Medical Sciences Foundation and
Research Center (KFRC) approved the study. Patient 1 was
an 8-year-old female child with chronic liver disease and
portal hypertension. The rest of the 6 patients had dysarthria
and tremors. Patient 3 had additional vitamin-resistant rickets.
Patient 4 was a 27-year-old woman with a history of 3
abortions. Patient 5 had dystonia and dysphagia. Patient 6
presented with an additional history of joint and bone pains.
Patient 7 had psychiatric symptoms.
All patients underwent SL examination of the cornea and
AS-OCT (Optovue RTVue Premier). AS-OCT of Optovue
RTVue is converted from a retinal scanner using 830 nm.7 The
cornea-anterior module lens was attached to the OCT machine,
and corneal OCT images were obtained. In patients 6 and 7, the
length of the KF ring was measured using the gray scale of ASOCT. With the patient’s eye aligned, the cursor was brought to
the center of the superior, inferior, temporal, and nasal cornea.
In patient 6, measurements were made by both SL (Haag-Streit
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Sridhar
FIGURE 1. A, Slit lamp—slit view of
patient 7 showing thin yellowish
green deposits in the inferior corneal
periphery. B, Slit lamp—diffuse view
of patient 6 showing a thick yellowbrown deposit in the superior corneal periphery.
International BM 900 slit lamp using ·1.6 magnification) and
AS-OCT. In patient 7, the length of the KF ring could be
measured only by AS-OCT. In this patient, SL measurement
was not possible because the patient had head movements.
Even AS-OCT examination was difficult and time was spent to
capture images.
RESULTS
F1
F2
Three patients were females and the remaining 4 were
males. The age of the patients ranged from 8 to 40 years. On
SL examination, the KF ring was seen as greenish/yellowish
green/yellowish brown deposits at the level of DM. In 6 of 7
patients, the KF ring was seen as greenish/yellowish deposits,
whereas in 1 patient, patient 6, it was seen as yellowish brown
deposits. The KF ring was thin in 2 patients (Fig. 1A) and was
thick in the rest of the 5 patients (Fig. 1B). The KF ring on the
gray scale of AS-OCT was visualized as a hyperreflective
deep corneal layer at the level of DM in all eyes (Figs. 2A,
3A). The color scale of AS-OCT showed the KF ring as
a greenish/greenish yellow/yellow/yellow-orange band at the
level of DM (Figs. 2B, 3B).
In patient 6, the length of the KF ring measured on the
gray scale of AS-OCT in the superior, inferior, temporal, and
nasal cornea in the right eye was 2.57 mm (Fig. 4), 1.77 mm,
1.06 mm, and 550 mm, respectively (Fig. 4). With SL, the
corresponding measurements were 1.9, 1.2, 1.2 mm, and less
than 1 mm. The length of the KF ring using the gray scale of
AS-OCT of the left eye in the superior, inferior, temporal, and
nasal cornea was 2.6 mm, 1.68 mm, 1.23 mm, and 720 mm,
respectively. The corresponding measurements with SL were
1.8, 1.1, 1 mm, and less than 1 mm.
In patient 7, the length of the KF ring on the gray scale
of AS-OCT in the right eye of the superior, inferior, temporal,
and nasal cornea was 1.87 mm, 1.55 mm, 1.05 mm, and
416 mm, respectively. A similar measurement in the left eye
of the superior, inferior, temporal, and nasal cornea was
1.74 mm, 1.43 mm, 1.13 mm, and 714 mm, respectively.
DISCUSSION
The KF ring has been considered an important diagnostic criterion for WD. Electron microscopy studies have
identified copper bound to sulfur-containing moiety in
electron-dense granules seen throughout the cornea in patients
with WD. It is 10–20 times higher in the corneal periphery.
These granules are arranged in multiple discrete layers with
the smallest granules closest to the endothelium.8
AS-OCT has been found to be useful in eye clinics
practicing corneal and anterior segment surgeries.9–13 According to the manufacturer of OCT used in this study
(Optovue RTVue Premier), gray scale images are intensity
image of backscattered light from the cornea and may vary
with several factors including alignment on the cornea,
curvature, and location of the B-scan within OCT. Color
scale images do not reflect tissue reflectivity, and normalization is not done by the company to account for the various
factors accounting for image brightness.
Methods of examination of the KF ring include naked
eye examination, direct ophthalmoscope examination, gonioscopy, and SL examination of the cornea. AS-OCT is an
alternative method of looking at the KF ring. The KF ring on
the gray scale of AS-OCT seems as a hyperreflective layer in
the corneal periphery at the level of DM. Localized deep
stromal opacities resulting from various causes (infection,
injury, and inflammation), copper deposits in other situations,
and pigmented corneal rings in non-Wilsonian liver disease
are differential diagnosis for the localized hyperreflective
layer in the deep peripheral cornea.5,14–18 Studies are required
to differentiate the KF ring of WD from deep corneal
opacities and other deposits.
Detection of the KF ring on SL requires experience of
a clinician. An ophthalmologist, who has not seen the KF ring
on SL before, may miss an early KF ring. However, in
a suspected case, hyperreflectivity of a deep corneal layer in
the periphery on AS-OCT may alert the clinician to do careful
SL examination to look for the early KF ring.
FIGURE 2. A, AS-OCT gray scale
analysis of patient 6 showing hyperreflectivity (arrow) at the level of
DM. B, Color scale of AS-OCT of
patient 6 showing orange-yellow
band (arrow) at the level of DM.
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Cornea Volume 00, Number 00, Month 2016
Evaluation of the Kayser–Fleischer Ring
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FIGURE 3. A, AS-OCT gray scale analysis of patient 7 showing hyperreflectivity (arrow) at the level of DM. B, Color scale of ASOCT of patient 6 showing orange-yellow band (arrow) at the level of DM.
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FIGURE 4. AS-OCT gray scale analysis of patient 6 showing measurement of the KF ring (superior cornea of the right eye).
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Sridhar
A difficult method of measuring the KF ring and
calculating the KF ring score has been suggested by Esmaeli
et al.19 Standard narrow-beam direct-illumination SL photographs (·20 magnification) were taken at 6-o’clock and 12-o’
clock vertical corneal meridians in each eye. After masking
and randomizing the photographic slides, a single observer
measured the length of the KF ring at 6-o’ clock and 12-o’
clock vertical corneal meridians using a Castroviejo caliper
under ·4 magnification. The average KF ring score was
obtained by summation of all vertical length measurements in
both eyes as per the number of meridians examined by SL
photomicrographs. Nasal and temporal rings were not
measured because of technical difficulty using SL photographs in these meridians. With the eye aligned properly and
cursor positioned, the KF ring can be easily measured using
the gray scale of AS-OCT. Even nasal and temporal measurements could be obtained, and when the measurement is less
than 1 mm, the KF ring measurement in microns is given on
the gray scale. An average KF ring score can be easily
obtained by adding the measurements in all 4 quadrants and
dividing it by 4.
There are other possible potential advantages of ASOCT in evaluating the KF ring in WD, although this study has
not looked at these aspects. AS-OCT can possibly determine
the density of the KF ring and hence help us to assess the
severity of disease. AS-OCT can be a good tool to assess
response to treatment in WD. Further studies are required to
confirm the advantages mentioned above.
To conclude, AS-OCT is an alternative method of
evaluating the KF ring in WD, which can be used in
combination with SL examination. The KF ring can be easily
measured using the gray scale of AS-OCT. Further studies are
required to study the potential advantages of AS-OCT
including assessing the density of the KF ring, as a tool to
assess the response to treatment in WD, in differentiating the
KF ring of WD from copper deposits in other situations and
pigmented corneal rings in non-Wilsonian liver disease.
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