Download 05.16.03 Ophthal`y Update

OphthalmologyUpdate
Winter 2004
A three-dimensional confocal microscopy
reconstruction of a corneal keratocyte that has
been transfected by intrastromal injection of an
enhanced green fluorescence reporter gene driven
by a keratocyte-specific promoter. Story, Page 2.
Page
4
GENETICS
Genetic Researchers
Identify Novel SOX2
Mutation Associated
with Multiple Ocular,
CNS Anomalies
5
COLOR VISION
Computer-based Test
Offers Many Advantages
in Diagnosis of Color
Discrimination Problems
6
HEALING
Bone Marrow-Derived
Inflammatory Cells May
Be Progenitor for New
Cell Type Involved in
Corneal Wound Healing
16
GOLD WEIGHT
Gold Weight Implantation Can Be Effective
Treatment for Exposure
Keratopathy
Important Advances in Ocular Surface
Gene Delivery and Imaging Achieved
RESEARCHERS AT THE COLE EYE INSTITUTE ARE CONTINUING ON A PATH OF PROGRESS DEVELOPING METHODS FOR GENE DELIVERY INTO THE CORNEA. MOST RECENTLY, THEY REPORTED
THEIR SUCCESS IN ACHIEVING TISSUE-SPECIFIC EXPRESSION OF AN EXOGENOUS GENE IN THE
CORNEAL STROMA. IN VIVO GENE DELIVERY WAS ACCOMPLISHED RAPIDLY, EFFICIENTLY AND
IN A RELATIVELY EASY FASHION USING AN INTRASTROMAL INJECTION TECHNIQUE, AND THE
LOCALIZATION OF GENE EXPRESSION WAS INVESTIGATED IN SITU USING A NOVEL METHOD
INVOLVING THREE-DIMENSIONAL (3-D) RECONSTRUCTION OF CONFOCAL MICROSCOPY IMAGES.
The research was described in
an article by Eric Carlson, Ph.D., a
researcher in the Perez Laboratory, in
the July issue of Investigative Ophthalmology & Visual Science, and it was
considered of such significance that it
was featured as the cover story.
“Our experiments represent not
only an advancement in gene therapy,
but the confocal 3-D reconstruction
method we developed for visualizing
the cornea provides a powerful new
tool for future use in studying corneal
architecture and cell biology,” says
Victor L. Perez, M.D., corneal specialist
and researcher in The Cole Eye Institute, who is the principal investigator.
The experiments were based on
delivery of an enhanced green fluorescent protein (EGFP) reporter gene into
the stroma of murine eyes. Some animals were treated with an adenovirus
construct with an EGFP reporter gene
driven by cytomegalovirus (adenoEGFP). In another group of mice, a
keratocan promoter was used to drive
keratocyte-specific EGFP expression.
Gene delivery was performed by
creating a tunnel from the corneal
epithelium to the anterior stroma with
a 33-gauge needle. Then, another
33-gauge needle attached to a syringe
containing 2 µl of the genetic material
was advanced through the tunnel into
the stroma.
After intrastromal injection of the
adeno-EGFP, animals were followed in
vivo using a stereomicroscope equipped
with a fluorescence filter. Those studies
showed EGFP gene expression occurred
as early as 11 hours after injection and
had decreased moderately by 1 week,
but was still evident in some animals
for up to 3 weeks.
“The methods in these experiments
address several of the limitations of
previous studies of direct gene transfer
into the cornea, which have included
low level, delayed, and very transient
gene expression as well as use of moderately invasive approaches to delivery.
Our success in achieving rapid and efficient expression of exogenous genes in
the cornea using the relatively simple
technique of intrastromal injection is
important as we think about moving
forward into the clinical arena where
we could even envision performing
gene delivery with the patient sitting
at the slit-lamp,” says Dr. Perez.
Conventional analyses of immunohistochemical-stained 5-µm frozen
sections demonstrated EGFP expression
throughout the corneal stroma. However,
it was apparent to Dr. Perez and his colleagues that limited information about
cornea cell population and presence of
EGFP-positive cells could be derived by
studying the 5-µm corneal sections.
Against that background, they
developed the confocal 3-D reconstruction
method. After obtaining full-thickness
fluorescence confocal micrographs of
wholemount corneas, 3-D reconstruction was achieved with image-stacking
software. The technique allows for 360º
visualization of 100-µm sections of
cornea with analyses from a variety of
angles and planes. Studies of adenoEGFP-transfected corneas confirmed
EGFP expression was localized to
corneal stroma cells and was absent
in the epithelium and endothelium.
To address the need for cell specificity in gene therapy, Dr. Perez and
colleagues used a keratocan promoter to
drive EGFP expression. Keratocan is a
keratan sulfate proteoglycan expressed
only by keratocytes in the corneal
stroma, and the 3.2-kb 5'-flanking
region of the keratocan gene they used
as a promoter had been previously
reported to drive cornea stroma-specific
expression of a reporter gene.
“Different populations of cells can
be found in the cornea, including keratocytes, nerve cells and inflammatory
cells. The success of gene therapy will
depend in part on development of
delivery techniques that will result in
targeted gene expression by a specific
cell of interest,” Dr. Perez explains.
Using the confocal 3-D imaging
method, Dr. Perez and colleagues
demonstrated that intrastromal injections
of EGFP with the keratocan promoter
resulted in corneal-specific gene delivery
to the stroma. Keratocan promoterdriven tissue-specific expression was
further confirmed in another experiment
that compared gene expression in eyes
treated with subconjunctival injections
of EGFP with the keratocan promoter
versus a CMV promoter. ■
2
Figure 1 Three-dimensional reconstructed confocal
images of a wholemount cornea 24 hours after an adenovirus construct with an enhanced green fluorescent
protein (EGFP) reporter gene was delivered to a mouse
corneal stroma by intrastromal injection. Three-dimensional reconstructed images of wholemount corneas can
be manipulated and viewed in a 360° manner as indicated by the top (A), bottom (B) and tilt (C) images.
Figure 3 Anterior to posterior
corneal stromal view of a DAPI
stained wholemount cornea
which was intrastromally
injected with a keratocyte-specific promoter driving an EGFP
reporter gene and imaged
using confocal microscopy.The
blue staining shows cell nuclei
and the green shows corneal
keratocytes expressing EGFP.
Figure 2 Three-dimensional reconstructed confocal
micrograph of a wholemount DAPI-stained mouse
cornea 24 hours after in vivo transfection by
intrastromal injection of an adenoviral vector
expressing an EGFP reporter gene. This image
shows a view of EGFP-positive transfected corneal
stromal cells (green) in front of epithelial cell nuclei
(blue) as viewed from the posterior aspect of the
corneal stroma.
3
Figures reprinted with permission, Investigative Ophthalmology and
Visual Sciences (Carlson EC, Liu C-Y, Yang X, et al. In vivo gene delivery
and visualization of corneal stromal cells using an adenoviral vector and
keratocyte-specific promoter. Invest Ophthal Vis Sci 2004; 45:2194-2200)
Genetic Researchers Identify Novel SOX2 Mutation
Associated with Multiple Ocular and CNS Anomalies
RESEARCHERS AT THE COLE EYE INSTITUTE
HAVE IDENTIFIED A NOVEL STOP MUTATION
IN THE SOX2 GENE THAT IS ASSOCIATED
WITH A NOVEL PHENOTYPE CHARACTERIZED
BY ANOPHTHALMIA AND BRAIN ANOMALIES.
Sequence analysis of the SOX2 mutation
and its segregation in the family.
A: The top sequence shows the heterozygous Gln155Ter mutation in the patient
with anophthalmia and other neurological abnormalities.The bottom sequence is
the normal sequence of the same region
in a control individual.
B: Schematic pedigree showing the segregation of the mutation in the family.The
filled symbol indicates the affected
patient.
SOX2 is a transcription factor
known to be expressed in the eye
and nervous system during embryonic
development. The newly discovered
SOX2 gene mutation is a nonsense
mutation involving a C to T transition
that creates a premature termination
codon early in the transcriptional activation domain. The affected individual
was a female child born with bilateral
anophthalmia who also had aplasia of
the optic nerve, chiasm and optic tract
along with bilateral sensorineural hearing loss and global development delay.
Her parents and normal brother did
not carry the mutation, and it was also
not found during screening of samples
obtained from 142 unrelated controls
without any known eye disease.
“A previous paper described three
nonsense mutations in SOX2 in four
patients with bilateral anophthalmia,
but that report provided no additional
details about the features of its cases.
The findings in our child with a SOX2
mutation tell us this gene is important
not only in the development of the eye,
but also in the embryogenesis of other
parts of the CNS, including some structures responsible for hearing,” says
Stephanie A. Hagstrom, Ph.D., a geneticist in the Department of Ophthalmic
Research at The Cole Eye Institute.
The child is a patient of pediatric
ophthalmologist Elias I. Traboulsi, M.D.,
and she was investigated in a study
that included 93 patients who have
severe ocular malformations. There
were 11 other individuals with anophthalmia in the population, as well as 17
patients with coloboma, 38 patients
with microphthalmia and 26 with optic
nerve hypoplasia. None of the other
patients was found to have a SOX2
sequence change.
“We knew SOX2 is an important
gene in ocular development. Having
accumulated this large series of patients
with a variety of ocular anomalies provided us with the power to investigate
if mutations in it might be responsible
for defects other than anophthalmia,”
Dr. Traboulsi explains.
“However, there are many other
examples in ophthalmology of transcription factor defects associated with
congenital malformations, including
anophthalmia. Considering genetic
heterogeneity – that the same clinical
abnormality can be caused by a number
of different genetic defects – we were
not too surprised to find that none of
these other children had a SOX2 mutation despite there being some overlap
in clinical features,” he says.
The Cole Eye Institute researchers
are continuing to search for genetic
mutations in other patients, and they
are currently focusing on another
transcription factor.
Considering the large array of
genes involved in ocular development,
a defect in any particular gene is likely
to cause only a small minority of disorders and anomalies. However, the
ultimate hope of the genetic research
is to identify genes that are more
commonly associated with problems
and therefore would be useful for
genetic screening.
“Particularly if we find a gene
associated with a familial defect, we
could use the information to provide
prenatal diagnosis. That application is
not relevant for our child who had an
isolated, sporadic mutation in SOX2.
However, by documenting her parents
and brother were not carriers, we could
reassure them that they would be highly
unlikely to have more children with the
same problems,” Dr. Traboulsi notes. ■
4
Computer-based Test Offers Many Advantages in
Diagnosis of Color Discrimination Problems
OPHTHALMOLOGISTS AT THE CLEVELAND CLINIC COLE EYE INSTITUTE ARE USING A NEW
COMPUTER-BASED TEST, THE PORTAL COLOR SORT TEST (PCST), FOR EVALUATING COLOR VISION
IN DAILY PRACTICE. INTRODUCTION OF THE PCST WAS BASED ON THEIR FINDINGS THAT IT IS A
VALID AND RELIABLE METHOD FOR INVESTIGATING COLOR DISCRIMINATION ABILITY AND THEIR
ASSESSMENT THAT IT OFFERS SEVERAL ADVANTAGES WHEN COMPARED TO EXISTING ALTERNATIVES FOR TESTING COLOR VISION.
The PCST is an arrangement test
requiring patients to complete a task
similar in nature to the gold standard
Farnsworth Munsell 100 hue test (FM
100-Hue). However, with the PCST,
patients move the colored chips into
a logical order on a touch-sensitive
computer screen. Since the computer
monitor has its own constant, internal
source of illumination, the test can be
performed in any darkened exam lane
without special lighting requirements,
avoiding the need to escort patients to
a separate color vision lab.
Like the FM 100-Hue, the PCST
can identify protan, deutan and tritan
color vision defects and it generates
similar results using a numerical discrimination scoring method. However,
the PCST scores are tabulated and
graphed automatically with rapid turnaround, adding an efficiency factor by
eliminating time spent by an administrator to score and graph the results.
Unaware of any previous studies
evaluating the performance of the PCST,
Alex Melamud, M.D., M.A., a resident
at The Cole Eye Institute, in collaboration with pediatric ophthalmologist
and geneticist Elias I. Traboulsi, M.D.,
undertook a clinical trial to determine
its validity and reliability. Their investigation demonstrated that the results of
the PCST were reproducible and correlated strongly with those measured by
the FM 100-Hue. In addition, the study
participants found the PCST easy to
take and they only needed three minutes to complete the test, compared
with 10 minutes for the FM 100-Hue.
“The Portal Color Sort Test fills the
niche for a rapid, accurate test of color
vision that can be readily used in the
5
office without any special laboratory
setting or trained technician. This computer-based method also overcomes
some of the other limitations of conventional arrangement tests, including
handling-related deterioration of the
test pieces and the need to manipulate
pieces that can make testing difficult
for individuals with limited manual
dexterity,” Dr. Melamud says.
“Color vision testing has an important role in a pediatric ophthalmology
practice for early detection of retinal
dystrophies and identification of congenital color vision defects that can be
associated with learning difficulties in
school. Because it provides accurate
results rapidly in an easy-to-perform
format, this new computer-based test
is a welcome and valuable addition to
our tools for evaluating color vision,”
Dr. Traboulsi says.
The study to measure the validity
and reliability of the PCST included 47
subjects with normal color vision and
12 with congenital color defects. All
underwent testing with the PCST and
FM 100-Hue, and they also completed
the 16 plate Ishihara Pseudo-Isochromatic Plates test and the D-15
Farnsworth Munsell test (D-15). To
assess the reliability of the PCST, 33
subjects re-took the test on another day.
Each of the evaluations was performed
under the testing conditions recommended by the manufacturer, and the
tests were completed in a random order.
The results of the study also showed
the PCST performed well in predicting
failure on the Ishihara plate and D-15
tests, indicating it could serve as an excel-
lent screening test. However, compared
with those two latter tools, the PCST
took longer for the subjects to complete.
Median times for completing the D-15
and Ishihara tests were approximately 1.4
and 1 minute, respectively. Nevertheless,
the PCST has other advantages relative
to those tests, Dr. Traboulsi explains.
“The Ishihara is only a screening
test for red-green color defects, but it
does not test color discrimination. The
D-15 identifies color blindness, but
does not provide information on color
discrimination ability, and it requires
special lighting conditions,” he notes.
Cole Eye Institute ophthalmologists
are continuing to evaluate the performance of the PCST in patients with
various acquired and congenital color
vision defects. Dr. Melamud believes
that despite its many desirable features,
the PCST is a complement to other testing methods and not a replacement.
“Although the PCST is quicker than
the FM-100 Hue, the latter test would be
preferable if one wants a more detailed
analysis of color discrimination, and
none of these tests is as precise as
the anomaloscope for diagnosing and
classifying color deficiency,” he says.
The PCST was developed by an
engineer at Accommodata, a Clevelandbased company. It is being distributed
by Haag-Streit, and marketed in a package that includes other ophthalmic
testing software.
Drs. Traboulsi and Melamud have
no financial interest in Accommodata
or the PCST. ■
Bone Marrow-Derived Inflammatory Cells May Be Progenitor
for New Cell Type Involved in Corneal Wound Healing
COLE EYE INSTITUTE RESEARCHERS INVESTIGATING THE CELLULAR AND MOLECULAR MECHANISMS
OF CORNEAL WOUND HEALING HAVE OBTAINED EVIDENCE SUPPORTING THEIR HYPOTHESIS THAT
INFLAMMATORY CELLS MIGRATING INTO THE CORNEA AFTER INJURY DIFFERENTIATE UNDER
CYTOKINE INFLUENCE INTO A NEW CELL TYPE THAT MAY PLAY AN IMPORTANT ROLE IN STROMAL
REMODELING AFTER INJURY.
That concept derives from recent major developments in the field of bone research
that demonstrated bone-resorbing osteoclasts do not arise from fibroblasts as previously
thought. Rather, they are generated from cytokine-driven differentiation of monocytes.
Having previously found that corneal injury resulted in monocyte influx, Cole
Eye Institute Director of Corneal Research Steven E. Wilson, M.D., and his colleagues
sought to explore their hypothesis that in addition to performing as phagocytic cells,
the monocytes may, in a process analogous to bone, be converted to a new cell type
that participates in corneal repair.
In a recent publication [Invest Ophthalmol Vis Sci 2004;45:2201-2211], the
researchers reported that corneal injury results in early influx of bone marrow-derived
monocytes. Their studies also show there is a simultaneous increase in expression of
the same cytokine systems that have been shown in bone to mediate the transition of
monocytes into osteoclasts.
“It has long been known that a variety of cell types can be found in the cornea
after wounding, and while multiple different types of cells are expected to participate
in the wound healing response, the contributions of individual cell types have not been
well characterized. With these findings, we believe we are on a track to determining
this bone marrow-derived cell is a key participant in the wound healing pathway, and
we are now working to characterize this new cell type and its function further so as to
confirm that theory,” says Dr. Wilson.
The presence of monocytes in the cornea of mice was studied using immunocytochemistry techniques to stain for the monocyte-specific antigen CD11b and in
experiments using chimeric animals expressing enhanced green fluorescent protein
(EGFP)-labeled bone marrow cells. The
immunocytochemistry studies showed
only a limited number of monocytes
were present in unwounded corneas,
but their numbers increased at 24 and
48 hours after injury caused by epithelial scraping.
Serial studies in the chimeric mice
showed appearance of the fluorescent
green protein-labeled, bone marrowderived monocytes in the cornea by
day 1 after epithelial scraping. The cells
increased in number thereafter, and
while they reached a peak within the
first few days after corneal injury, they
still persisted during ongoing follow-up,
which now extends to three months.
“Our findings indicate these cells
continue to function for many months
after the cornea is wounded. As we
continue our follow-up to 6 months
and 1 year, we expect to find these
cells will be present for a much longer
time,” Dr. Wilson says.
The cytokines studied included
receptor activator of NF-kappaB ligand
(RANKL), osteoprotegerin (OPG) and
monocyte chemotactic and stimulator
Figure 1 Immunocytochemistry
for detection of RANKL in
mouse corneas at 24 (A) and 48
(B) hours after epithelial scrape
injury. (C) An unwounded control cornea and (D) a control
cornea at 24 hours after epithelial scraping in which the
primary antibody was preabsorbed with RANKL antigen.
A large number of cells expressing RANKL (arrows) were
present in the corneal stroma
of 24- or 48-hour wounded
corneas, but not unwounded
control corneas. Background
staining was performed with
4’, 6’-diamino-2-phenylindole
(DAPI). Magnification, x400.
6
Ophthalmic Puzzler
factor (M-CSF), all of which are
expressed by osteoblasts and important
in modulating the transition of monocytes to osteoclasts. Using RT-PCR and
RNase protection assay techniques,
both the mRNA for those proteins and
the actual proteins were found to be
present in mouse fibroblasts in vitro.
In vivo studies showed those same
proteins were rarely present in normal
corneas, but were found in higher numbers in stromal cells between 24 and 48
hours after epithelial scraping. RANK,
which is expressed by monocytes and
interacts in bone with osteoblastexpressed RANKL, was first detected in
the cornea at 24 hours after injury. At
that time, RANK was mostly found in
the midstroma, whereas it could be
identified in the mid- and anterior
stroma at 48 hours post-injury.
“The pattern of expression of these
cytokines in the cornea is consistent
with our hypothesis that the same
cytokine systems operating in bone
remodeling are also upregulated in the
cornea in response to wounding. While
in the bone osteoblasts interact with
Figure 2 Immunocytochemistry
for detection of M-CSF in mouse
corneas at 24 (A) and 48 (B)
hours after epithelial scrape
injury. (C, D) Control mouse
corneas at 24 and 48 hours,
respectively, after epithelial
scraping in which the primary
antibody was preabsorbed with
M-CSF antigen. A large number
of cells expressing M-CSF were
present in the corneal stroma in
24-hour wounded corneas. (A,
arrows) M-CSF was also associated with epithelial basement
membrane at 24 hours after
epithelial scrape injury (A, *).
monocytes to produce osteoclasts,
we believe that in the corneal stroma,
the monocytes are interacting with
keratocytes to produce a new cell type
that is yet to be fully characterized,”
Dr. Wilson says.
Identification of the role of inflammatory cells in corneal wound healing
has important clinical implications,
notes Dr. Wilson.
“Acquiring an understanding of
the function of this cell and its role
in wound healing should enhance our
ability to control the corneal repair
process to our advantage. Based on
knowledge of the pathways of corneal
healing, we should be able to develop
better strategies for minimizing complications such as haze that can occur
following certain keratorefractive
procedures as well as improve the
predictability of our refractive surgery
outcomes to reduce the incidences of
under- and overcorrections,” he explains. ■
Also note heavy expression of
M-CSF in the endothelial cells
(A, arrowheads) at 24 hours after
epithelial scraping. M-CSF is a
soluble
cytokine.
There
appeared to be noncellular MCSF present in the anterior
stroma at 48 hours after epithelial injury (B, arrows). The
preabsorption control sections
(C, D) had little detectable
signal. Background staining
was performed with 4’, 6’diamino-2-phenylindole (DAPI).
Magnification, x400.
Figures reprinted with permission, Investigative Ophthalmology and
Visual Sciences (Wilson SE, Mohan RR, et al. RANK, RANKL, OPG and
M-CSF expression in stromal cells during corneal wound healing.
Invest Ophthalmol Vis Sci 2004;45:2201-2211)
7
Part 1
By Anat Galor, M.D., and
Arun D. Singh, M.D.
A 16-year-old white male presented
to The Cole Eye Institute after a retinal
lesion was incidentally discovered in
his left eye. The patient had a normal
eye exam one year prior. The patient
denied ocular history; medical history
was significant only for acne and
mild asthma.
Examination revealed uncorrected
visual acuity of 20/20 OU and normal
IOPs, pupils, peripheral fields and
extraocular movements. External
examination and slit-lamp microscopy
were unremarkable. Dilated funduscopy
revealed an amelanotic choroidal mass,
measuring 11 x 9 x 2.7 mm, with
brown pigment (Figure 1). The mass
was located 3 mm superior and nasal to
the optic disc. Overlying and dependent
subretinal fluid was evident. A clear
vitreous was present.
What is the differential diagnosis
and what further tests are required?
See Page 8.
Figure 1 Amelanotic choroidal mass OS, 11 x
9 x 2.7 mm, with brown pigmentation and
dependent subsensory fluid.
Ophthalmic Puzzler
Part 2
Treatment
(Continued from Page 7)
Differential diagnosis
The differential diagnosis for an amelanotic choroidal mass includes amelanotic melanoma,
metastasis, circumscribed hemangioma, granuloma, osteoma and other entities.
To differentiate among these entities, several tests were ordered. Fluorescein
angiography (IVFA) revealed early and diffuse hyperfluorescence which persisted into
late phases (Figures 2 and 3). Similar findings were seen on indocyanine green angiography (ICG). The mass demonstrated abnormal intrinsic choroidal vasculature (Figure
4). In addition, B-scan ultrasonography (US) revealed a low-medium reflective lesion, 2.7
mm in height, without extrascleral extension. No uptake was seen on the PET/CT scan.
Diagnosis
To arrive at a diagnosis, it is important to consider the clinical and imaging findings
of the other entities in the differential (Figure 5). Choroidal metastases show hypofluorescence in the early phases of IVFA and generally leak in the late phases. No intrinsic
vessels are seen on ICG and medium-high internal reflectivity is seen on US. Circumscribed choroidal hemangiomas have characteristic early hyperfluorescence with late
washout on IVFA and ICG and high internal reflectivity on US. Choroidal granulomas
are normally accompanied by ocular and systemic signs of inflammation.
Choroidal osteomas are flat lesions with high surface reflectivity and shadowing on
US. Combining the clinical picture and results of the ancillary studies, a final diagnosis
of choroidal melanoma was made.
Discussion
Pediatric (< 20 yrs) choroidal melanoma represents a small minority (< 1%) of all uveal
melanoma. Clinical findings are similar to those in adults. However, it is important to
exclude rare genetic associations such as familial uveal melanoma, dysplastic nevus
syndrome and oculo (dermal) melanocytosis in such cases.
The diagnosis, treatment and prognosis of these tumors are believed to be similar to
adults but long-term outcomes in young patients with uveal melanoma are not known.
Survival rates of 95% at 5 years and 77% at 10 years have been reported (Singh 2000).
There are several options for treatment
of choroidal melanoma, including
transpupillary thermotherapy, radiotherapy and surgery. Unfortunately, the
choice of treatment has little influence
on survival due to the presence of
micrometastases at the time of
ophthalmic diagnosis.
Our patient was not a good candidate for transpupillary thermotherapy
given the medium size of his lesion and
its lack of pigment. Brachytherapy is
widely used and is a good option for
our patient given the nasal location
and relatively small thickness of his
tumor. Proton beam radiation is also
a good option but this modality is not
available at The Cleveland Clinic. Local
resection is generally reserved for
tumors that are too bulky for radiotherapy (height > 6 mm). Enucleation is
similarly reserved for larger tumors.
Our patient was therefore treated
with brachytherapy based on the
Collaborative Ocular Melanoma Study
(COMS) protocol. A 16-mm iodine 125
plaque was placed behind the tumor and
8563 cGy of radiation was delivered
to the apex over 98 hours. The patient
tolerated surgery and radiation therapy
without complications and continues to
do well 4 months after surgery.
Prognosis
Figures 2 and 3 IVFA showing early and diffuse hyperfluorescence
that persists in late phases. Figure 2 is at 35 seconds and Figure 3 is
at 10 minutes, 19 seconds.
Figure 4 B-scan ultrasonography showing a low-medium reflective
lesion, 2.7 mm in height, with no extrascleral extension.
Figure 2
Figure 3
Figure 5 Differential diagnosis of an amelanotic choroidal mass.
COMS data have found excellent control
rates (~90% at 5 years) for medium-size
choroidal melanomas treated with
brachytherapy. However, 12.5% of
eyes with plaque required enucleation
at five years due to tumor recurrence
and radiation complications (Jampol
2002). Five-year tumor-specific mortality for medium melanomas was about
9% (Diener-West M 2001). In a study
of 289 patients with uveal melanoma in
which long-term follow-up information
was available, it was estimated that
62% of tumor-specific mortality occurs
in the first five years (Kujala 2002).
Figure 4
8
From this study, it can be extrapolated
that our patient has about a 14.5%
risk of melanoma-related death over
his lifetime.
In patients treated with brachytherapy
in the medium-size COMS trial, mean
visual acuity dropped from 20/32 to
20/125 three years after therapy. Fifty
percent of patients retained visual acuity
of 20/200 or better. Poor prognostic factors for vision loss included poor initial
visual acuity, greater tumor thickness,
proximity to foveal avascular zone,
history of diabetes, exudative retinal
detachment and a non-dome-shaped
tumor (Melia 2001). Given the location
of his tumor and lack of poor prognostic
factors, our patient’s visual prognosis
is good.
Follow-up will include an oncology
evaluation, liver US and liver function
tests every six months. ■
References
1. Singh AD, Shields CL, Shields JA,
Sato T. Uveal melanoma in young
patients. Arch Ophthalmol. 2000
Jul;118(7):918-23.
2. Melia BM, Abramson DH, Albert DM,
Boldt HC, Earle JD, Hanson WF,
Montague P, Moy CS, Schachat AP,
Simpson ER, Straatsma BR, Vine AK,
Weingeist TA; Collaborative Ocular
Melanoma Study Group. Collaborative
ocular melanoma study (COMS) randomized trial of I-125 brachytherapy
for medium choroidal melanoma.
I. Visual acuity after 3 years COMS
report no. 16. Ophthalmology. 2001
Feb;108(2):348-66.
3. Jampol LM, Moy CS, Murray TG,
Reynolds SM, Albert DM, Schachat AP,
Diddie KR, Engstrom RE Jr, Finger PT,
Hovland KR, Joffe L, Olsen KR, Wells
CG; Collaborative Ocular Melanoma
Study Group (COMS Group). The
COMS randomized trial of iodine
125 brachytherapy for choroidal
melanoma: IV. Local treatment failure
and enucleation in the first 5 years
after brachytherapy. COMS report
no.19. Ophthalmology. 2002
Dec;109(12):2197-206. Erratum in:
Ophthalmology. 2004 Aug;111(8):1514.
4. Diener-West M, Earle JD, Fine SL,
Hawkins BS, Moy CS, Reynolds SM,
Schachat AP, Straatsma BR; Collaborative Ocular Melanoma Study Group.
The COMS randomized trial of iodine
125 brachytherapy for choroidal
melanoma, III: initial mortality
findings. COMS Report No. 18. Arch
Ophthalmol. 2001 Jul;119(7):969-82.
5. Kujala E, Makitie T, Kivela T. Very
long-term prognosis of patients with
malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2003 Nov;44(11):4651-9.
Ophthalmic
Continuing Medical Education
Programs in
Ophthalmic Education
2004–2005
Saturday, December 4, 2004
PHYSICIANS ARE CORDIALLY INVITED TO
Course Director:
Elias I. Traboulsi, M.D.
Head, Department of Pediatric
Ophthalmology and Adult Strabismus
Cole Eye Institute
ATTEND THE FOLLOWING OPHTHALMIC CONTINUING MEDICAL EDUCATION COURSES AT
THE CLEVELAND CLINIC COLE EYE INSTITUTE.
ALL COURSES EXCEPT THE APRIL RETINA
SUMMIT WILL BE HELD IN THE JAMES P.
STORER CONFERENCE CENTER ON THE FIRST
FLOOR OF THE COLE EYE INSTITUTE.
For more information, contact Jane
Sardelle, program coordinator, at
216/444-2010 or 800/223-2273,
ext. 42010, or [email protected]. View
the entire 2004-2005 course catalog at
http://www.clevelandclinic.org/eye/
physician_info or go to Cleveland
Clinic continuing medical education web
site at www.clevelandclinicmeded.com.
9
CARDINAL OCULAR SIGNS OF INHERITED
SYSTEMIC DISEASES
Guest Faculty:
Arlene V. Drack, M.D.
Associate Professor
Department of Ophthalmology
University of Colorado Health
Sciences Center
Rocky Mountain Lions Eye Institute
Chief of Ophthalmology
Children’s Hospital
Aurora, CO
Richard A. Lewis, M.D., M.S.
Professor, Baylor College of Medicine
Cullen Eye Institute
Houston, TX
Cole Eye Faculty:
Arun D. Singh, M.D.
Director, Ophthalmic Oncology
Content & Objectives
Ocular abnormalities are present in up to
one-third of inherited systemic disorders,
and the ophthalmologist is often called
upon to assist in the diagnosis of genetic
diseases that involve the eye. Occasionally, patients with inherited systemic
diseases present primarily to the ophthalmologist, who then assumes the task of
recognizing the underlying disease and
referring to the appropriate specialists.
At the conclusion of this course,
participants should be able to:
• Recognize pathognomonic ocular
findings in inherited systemic diseases.
• Describe ocular lesions associated with
syndromes predisposing to cancer.
• Outline the work-up of patients with
ocular findings suggestive of an associated metabolic, connective tissue,
vascular or neurodegenerative disorder.
Ophthalmic
Continuing Medical Education
Saturday, January 22, 2005
NEURO-OPHTHALMOLOGIC EMERGENCIES
Course Directors:
Gregory S. Kosmorsky, D.O.
Department of Neuro-Ophthalmology
Cole Eye Institute
Michael S. Lee, M.D.
Department of Neuro-Ophthalmology
Cole Eye Institute
Guest Faculty:
Andrew G. Lee, M.D.
Professor of Ophthalmology, Neurology
and Neurosurgery
University of Iowa Hospital
Iowa City, IA
(continued)
Friday and Saturday,
March 25-26, 2005
CORNEA AND REFRACTIVE SURGERY SUMMIT
Course Directors:
Steven E. Wilson, M.D.
Director, Corneal Research
Cole Eye Institute
Ronald R. Krueger, M.D.
Medical Director, Refractive Surgery
Cole Eye Institute
Marguerite B. McDonald, M.D.
Director, Refractive Surgery Center
of the South
Professor of Ophthalmology
Tulane University
New Orleans, LA
Content & Objectives
This course will cover a broad range
of neuro-ophthalmologic disorders
encountered by the comprehensive
ophthalmologist. Diagnostic and management strategies will be presented.
At the conclusion of this course,
participants should be able to:
Stephen C. Pflugfelder, M.D.
Professor of Ophthalmology
Baylor University
Houston, TX
visual loss.
• Recognize implications of pupil
abnormalities.
• Assess a broad range of etiologies of
diplopia.
• Describe the pathophysiology and
clinical presentation of papilledema.
• Custom corneal wavefront analysis.
• Custom corneal ablation.
Guest Faculty:
Stephen Klyce, Ph.D.
Professor of Ophthalmology
Louisiana State University
New Orleans, LA
Peter J. Savino, M.D.
Director, Neuro-Ophthalmology Service
Attending Surgeon
Wills Eye Hospital
Thomas Jefferson University
Philadelphia, PA
• Identify different causes of transient
Content & Objectives
This program provides a forum for
presentation of the most advanced work
on refractive and corneal research for
comprehensive ophthalmologists and
refractive surgery specialists.
At the conclusion of this summit,
participants should be able to highlight
the most recent advances in refractive
and corneal surgery, including:
Karl G. Stonecipher, M.D.
South Eastern Laser and Refractive Center
Greensboro, NC
Mark A. Terry, M.D.
Devers Eye Institute
Chief/Cornea, Good Samaritan Hospital
Clinical Associate Professor
Oregon Health Sciences University
Portland, OR
Vance M. Thompson, M.D.
Ophthalmology LTD
Assistant Clinical Professor
University of South Dakota
Sioux Falls, SD
Cole Eye Faculty:
Williams J. Dupps, M.D.
Bennie H. Jeng, M.D.
Gregory S. Kosmorsky, M.D.
Roger H.S. Langston, M.D.
David M. Meisler, M.D.
Marcelo Netto, M.D.
Victor L. Perez, M.D.
• Corneal transplantation.
• Replacement of corneal endothelium.
• Femtosecond technology.
• Diseases of the cornea affecting
refractive and corneal surgery, such
as dry eye disease.
Friday and Saturday,
April 29-30, 2005
RETINA SUMMIT
Being held at the Cleveland Clinic InterContinental Hotel and Conference Center
Course Director:
Hilel Lewis, M.D.
Chairman, Division of Ophthalmology
Director, Cole Eye Institute
Guest Faculty:
Alan Bird, M.D.
Professor, Department of Clinical
Ophthalmology
Institute of Ophthalmology
Moorfields Eye Hospital
London, England
Stanley Chang, M.D.
Professor and Chairman
Department of Ophthalmology
Edward Harkness Eye Institute
Columbia University
New York, NY
Emily Y. Chew, M.D.
Medical Officer
Division of Biometry and Epidemiology
National Eye Institute
Bethesda, MD
10
Eugene de Juan, Jr, M.D.
President
Retina Institute
Doheny Eye Institute
University of Southern California
Los Angeles, CA
Cole Eye Faculty:
Bela Anand-Apte, Ph.D.
John W. Crabb, Ph.D.
Joe G. Hollyfield, Ph.D.
Peter K. Kaiser, M.D.
Jonathan E. Sears, M.D.
Alain A. Gaudric, M.D.
Sce Ophthalmologie
Hospital Lariboisiere
Professor, University of Paris
Paris, France
Content & Objectives
This fifth retina summit is intended to
provide ophthalmologists and vitreoretinal specialists with information about
issues relating to diagnosing and treating vitreoretinal diseases, utilizing the
full spectrum of medical and surgical
therapies currently available. Live
surgery and live laser sessions are part
of the summit format. We will examine
interesting case presentations, where
experts will advise on specific treatments for patients with vitreoretinal
diseases. This summit offers a great
opportunity for audience participation.
At the conclusion of the summit,
participants should be able to:
Anselm Kampik, M.D.
Professor and Chairman
University of Munich
Augenklinik Der LMU Munchen
Munich, Germany
Joan W. Miller, M.D., Ph.D.
Chief of Ophthalmology
Massachusetts Eye and Ear Infirmary
Chair, Department of Ophthalmology
Harvard Medical School
Boston, MA
Richard F. Spaide, M.D.
Assistant Clinical Professor
New York Medical College
Manhattan Eye, Ear and Throat Hospital
Vitreous, Retina, Macula Consultants of NY
New York, NY
Yasuo Tano, M.D.
Professor and Chairman
Ophthalmology Department
Osaka University Medical School
Suita, Japan
11
• Discuss the pathophysiology and
•
•
Michael T. Trese, M.D.
Professor, Oakland University
William Beaumont Hospital
Associated Retinal Consultants, PC
Royal Oak, MI
•
Marco A. Zarbin, M.D., Ph.D.
Professor and Chairman
Department of Ophthalmology
New Jersey Medical School
Newark, NJ
•
•
•
diagnosis of several vitreoretinal
diseases.
Review a variety of new treatments
for age-related macular degeneration,
diabetic retinopathy, complicated retinal detachment and other macular
and retinal diseases.
Examine new technology, including
state-of-the-art and experimental
imaging systems, drug-delivery
systems and new instrumentation.
Analyze cost-effective therapeutic
protocols.
Review publicized findings and ongoing clinical trials and assess new data
and discoveries.
Demonstrate live surgical procedures.
Examine interesting case presentations.
Thursday and Friday,
June 16-17, 2005
ANNUAL RESEARCH, RESIDENTS AND
ALUMNI MEETING
Course Directors:
Hilel Lewis, M.D.
Chairman, Division of Ophthalmology
Director, Cole Eye Institute
Careen Y. Lowder, M.D., Ph.D.
Director, Uveitis Department
Cole Eye Institute
Keynote Speaker:
Andrew P. Schachat, M.D.
Karl Hagen Professor of Ophthalmology
Wilmer Ophthalmological Institute
Johns Hopkins University
Editor-in-Chief, Ophthalmology
Baltimore, MD
Content & Objectives
This program provides a scientific forum
to present clinical and basic science
research of the Cole Eye Institute residents, fellows, staff, alumni and invited
ophthalmologists.
The goal of this meeting is to
pursue and present the highest-quality,
original, thought-provoking clinical
research papers. In addition to the
educational aspects of the program and
learning about new and ongoing investigations, this event offers an excellent
opportunity to meet current residents,
fellows, new faculty and invited ophthalmologists, and to make and renew
friendships.
Distinguished
Lecture Series
THE DISTINGUISHED LECTURE SERIES PROVIDES A FORUM FOR RENOWNED RESEARCHERS IN THE
June 23, 2005
VISUAL SCIENCES TO PRESENT THEIR LATEST RESEARCH FINDINGS. THIS SERIES OF LECTURES
SIGNALING FOR CELL SURVIVAL IN THE
RETINAL PIGMENT EPITHELIUM
Nicolas G. Bazan, M.D., Ph.D.
Boyd Professor
Ernest C. and Yvette C. Villere
Professor of Ophthalmology,
Biochemistry and Molecular Biology,
and Neurology
Director, Neuroscience Center of
Excellence
Louisiana State University Health
Sciences Center
New Orleans, LA
FEATURES ADVANCES IN MANY AREAS OF OPHTHALMIC RESEARCH PRESENTED BY NOTED BASIC
AND CLINICAL SCIENTISTS FROM THROUGHOUT THE WORLD. AMPLE OPPORTUNITY FOR QUESTIONS
AND ANSWERS IS PROVIDED.
ALL LECTURES ARE HELD ON THURSDAYS FROM 7:00 TO 8:00 AM IN THE JAMES P. STORER
CONFERENCE ROOM ON THE FIRST FLOOR AT THE COLE EYE INSTITUTE, CLEVELAND CLINIC FOUNDATION. FREE PARKING IS PROVIDED IN EITHER THE EAST 102ND STREET PARKING LOT (FACING
THE FRONT OF THE COLE EYE INSTITUTE) OR THE VISITORS’ PARKING GARAGE AT E. 100TH
STREET AND CARNEGIE AVENUE. PARKING TICKETS WILL BE VALIDATED. THERE IS NO REGISTRATION FEE; CME CREDITS ARE NOT PROVIDED.
FOR QUESTIONS, PLEASE CALL 216/444-5832
July 21, 2005
December 16, 2004
March 17, 2005
THE RETINOID CYCLE AND VISUAL PIGMENT
REGENERATION
MAKING SENSE OF NEURONAL DIVERSITY:
A BOTTOM-UP VIEW OF THE RETINA
Rosalie K. Crouch, Ph.D.
Professor of Ophthalmology and
Biochemistry
Provost Emerita
Research to Prevent Blindness Senior
Scientific Investigator
Medical University of South Carolina
Charleston, SC
January 20, 2005
NOVEL ROLES FOR MÜLLER CELLS IN
THE RETINA
Vijay Sarthy, Ph.D.
Magerstadt Professor of Ophthalmology
Professor of Cell and Molecular Biology
Northwestern University
Chicago, IL
February 17, 2005
TOLERANCE AND AUTOIMMUNITY TO
IMMUNOLOGICALLY PRIVILEGED
RETINAL ANTIGENS
Rachel R. Caspi, Ph.D.
Chief, Immunoregulation Section
Deputy Chief, Laboratory of Immunology
National Eye Institute, National
Institutes of Health
Bethesda, MD
Richard H. Masland, Ph.D.
Charles A. Pappas Professor of
Neuroscience
Harvard Medical School
Investigator, Howard Hughes Medical
Institute
Boston, MA
April 21, 2005
LIGHT DETECTION IN THE RETINA
King-Wai Yau, Ph.D.
Professor
Department of Neuroscience
The Johns Hopkins School of Medicine
Baltimore, MD
May 19, 2005
AN EYE ON REPAIR: LESSONS FROM
CONFOCAL MICROSCOPY
James V. Jester, Ph.D.
Professor
Department of Ophthalmology
University of California, Irvine
Irvine, CA
THE RETINAL PIGMENT EPITHELIUM: THE
BEST OF CELLS, THE WORST OF CELLS
Janice M. Burke, Ph.D.
Marjorie and Joseph Heil Professor
of Ophthalmology, and Cell Biology,
Neurobiology and Anatomy
Medical College of Wisconsin
The Eye Institute
Milwaukee, WI
September 15, 2005
USING EXPERIMENTAL GENETICS TO
UNDERSTAND MECHANISMS OF GLAUCOMA
Simon W.M. John, Ph.D.
Associate Investigator
Howard Hughes Medical Institute
Jackson Laboratory
Bar Harbor, ME
October 27, 2005
DYNAMIC REORGANIZATION AT THE CORNEAL
STROMAL CELL INTERFACE AFTER WOUNDING
Sandra K. Masur, Ph.D.
Professor, Ophthalmology
Associate Professor, Physiology/Biophysics and Center for Anatomy and
Functional Morphology
Associate Dean for Faculty
Development
Department of Ophthalmology
Mount Sinai School of Medicine
New York, NY
November 17, 2005
USE OF THE MOUSE MODEL TO
UNDERSTAND HERITABLE FORMS OF
RETINAL DEGENERATION
Patsy M. Nishina, Ph.D.
Staff Scientist
The Jackson Laboratory
Bar Harbor, ME
12
Cole Eye Institute
Clinical Trials
The following studies are currently enrolling.
All have been approved by the Institutional
Review Board.
For a complete list, go to www.clevelandclinic.org/eye/research
GENETICS
RETINAL DISEASES
STUDIES OF THE MOLECULAR GENETICS OF
EYE DISEASES
Objective: To map the genes for inherited
eye diseases. To screen candidate genes for
mutations in a variety of genetic ocular
disorders, including ocular malformations,
congenital cataracts and retinal dystrophies.
Contact: E. Traboulsi, M.D., at 216/444-4363
or S. Crowe, C.O.T., at 216/445-3840
A PHASE III, MULTI-CENTER, RANDOMIZED,
DOUBLE-MASKED, ACTIVE TREATMENT CONTROLLED STUDY OF THE EFFICACY AND
SAFETY OF RHUFAB V2 (RANIBIZUMAB)
COMPARED WITH VERTEPORFIN (VISUDYNE)
PHOTODYNAMIC THERAPY IN SUBJECTS WITH
PREDOMINANTLY CLASSIC SUBFOVEAL
NEOVASCULAR AGE-RELATED MACULAR
DEGENERATION
Objective: To evaluate the efficacy of
intravitreal injections of ranibizumab
administered monthly compared with
verteporfin PDT in preventing vision loss,
as measured by the proportion of subjects
who lose fewer than 15 letters in visual
acuity at 12 months compared with baseline.
Contact: P. Kaiser, M.D., at 216/444-6702 or
L. Holody, C.O.A., at 216/445-3762
PEDIATRICS
INFANT APHAKIA TREATMENT STUDY
Objective: To determine whether infants with
a unilateral congenital cataract are more
likely to develop better vision following
cataract extraction surgery if (1) they undergo
the primary implantation of an IOL or if (2)
they are treated primarily with a contact lens.
Contact: E. Traboulsi, M.D., at 216/444-4363
or S. Crowe, C.O.T., at 216/445-3840
REFRACTIVE SURGERY
LADARVISION SYSTEM USE OF THE REFRACTIVE
DATA FROM A WAVEFRONT MEASUREMENT
DEVICE (WMD) FOR THE CORRECTION OF
REFRACTIVE ERROR-LASIK
Rationale: In an effort to improve outcomes
in LASIK surgery, Alcon Surgical has developed a product, the LADARWave Custom
Cornea Wavefront System, designed to
measure refractive errors, including a
method of characterizing aberrations of the
visual system, generically referred to as a
Wavefront Measurement Device (WMD).
This clinical study is currently enrolling
only hyperopic patients.
Contact: R. Krueger, M.D., at 216/445-8585
or R. Scott at 216/444-0680
ACRYSOF ANGLE-SUPPORTED PHAKIC
INTRAOCULAR LENS
Objective: To collect information on the
safety and effectiveness of the artificial
lens ACRYSOF for the correction of severe
myopia. This study lens will be implanted
behind the cornea in the anterior chamber.
The lens is made of a soft acrylic material
that allows the lens to be folded for
implantation and therefore can be inserted
through a smaller incision than other rigid
lens designs. Participation in this study will
last about 3 years.
Contact: R. Krueger, M.D., at 216/445-8585
or R. Scott at 216/444-0680
13
PROTOCOL B7A-MC-MBDL REDUCTION IN
THE OCCURRENCE OF CENTER-THREATENING
DIABETIC MACULAR EDEMA
Objective: The primary objective of this
study is to test the hypothesis that oral
administration of 32 mg per day of Ruboxistaurin for approximately 36 months will
reduce, relative to placebo, the occurrence
of center-threatening diabetic macular
edema as assessed by fundus photography
in patients with non-clinically significant
macular edema and nonproliferative diabetic retinopathy at baseline.
Contact: P. Kaiser, M.D., at 216/444-6702
or C. Rosal, R.N., B.S.N., at 216/445-1256
A PHASE II RANDOMIZED, DOSE-RANGING,
DOUBLE-MASKED, MULTI-CENTER TRIAL, IN
PARALLEL GROUPS, TO DETERMINE THE SAFETY,
EFFICACY AND PHARMACOKINETICS OF
INTRAVITREOUS INJECTIONS OF PEGAPTANIB
SODIUM COMPARED TO SHAM INJECTION FOR
30 WEEKS IN PATIENTS WITH RECENT VISION
LOSS DUE TO MACULAR EDEMA SECONDARY
TO CRVO
Objective: To determine the effectiveness
of pegaptanib sodium in improving vision
in patients with CRVO. Injections or sham
will be every 6 weeks with one week postinjection checks throughout the study. The
study will last one year. Patients must have
been diagnosed with CRVO within the last
6 months.
Contact: H. Lewis, M.D., at 216/444-0430
or L. Schaaf, R.N., at 216/445-4086
AN EVALUATION OF EFFICACY AND SAFETY OF
POSTERIOR JUXTASCLERAL ADMINISTRATIONS
OF ANECORTAVE ACETATE FOR DEPOT SUSPENSION (15 MG OR 30 MG) VERSUS SHAM
ADMINISTRATION IN PATIENTS AT RISK FOR
DEVELOPING SIGHT-THREATENING CHOROIDAL
NEOVASCULARIZATION DUE TO EXUDATIVE
AGE-RELATED MACULAR DEGENERATION
(AMD) AART
Objective: To evaluate the effectiveness of
anecortave acetate in stopping the progression of the “dry” or early form of AMD to
the “wet” or advanced form. Depot administration or sham (like an injection) will be
every six months for four years for a total
of nine visits. Patients must have “wet”
AMD in one eye and “dry” AMD in the
other. Vision in the “dry” eye must be
equivalent to 20/40 or better.
Contact: P. Kaiser, M.D., at 216/444-6702
or L. Schaaf, R.N., at 216/445-4086
THE STANDARD CARE VERSUS CORTICOSTEROID
FOR RETINAL VEIN OCCLUSION STUDY
Objective: To evaluate the effectiveness
of triamcinolone acetonide injections for
treatment of macular edema versus standard treatment. Patients will have 11 to 13
visits over a period of up to three years.
Contact: P. Kaiser, M.D., at 216/444-6702
or L. Holody, C.O.A., at 216/445-3762
A SIX-MONTH PHASE 3, MULTICENTER, MASKED,
RANDOMIZED, SHAM-CONTROLLED TRIAL
(WITH SIX-MONTH OPEN-LABEL EXTENSION) TO
ASSESS THE SAFETY AND EFFICACY OF 700 µG
AND 350 µG DEXAMETHASONE POSTERIOR
SEGMENT DRUG DELIVERY SYSTEM
Objective: To evaluate the safety and efficacy of the 700 µg DEX PS DDS Applicator
System and 350 µg DEX PS DDS Applicator
System compared with a Sham DEX PS DDS
Applicator System (needle-less applicator)
for six months in patients with macular
edema following branch retinal vein occlusion or central retinal vein occlusion. The
safety of the 700 µg DEX PS DDS Applicator
System will be assessed for an additional 6
months in patients who qualify for treatment
in an open-label safety extension.
Contact: P. Kaiser, M.D., at 216/444-6702 or
L. Schaaf, R.N., at 216/445-4086
Continued on page 14
Clinical Trials
contd.
GLAUCOMA
ADVANCED IMAGING FOR GLAUCOMA
Objective: Advanced Imaging for
Glaucoma (AIG) is a multi-center bioengineering partnership sponsored by the
National Eye Institute. This partnership
includes four clinical centers: the Cleveland Clinic Foundation (CCF), University
of Pittsburgh Medical Center/University of
Pittsburgh School of Medicine (UPMC), the
University of Miami (Bascom Palmer Eye
Institute) and the University of Southern
California. The goal of the partnership is
to develop advanced imaging technologies
to improve the detection and management
of glaucoma. The advanced imagining
technologies include optical coherence
tomography, scanning laser polarimetry
and scanning laser tomography. The technologies will be evaluated in a longitudinal
five-year clinical trial composed of glaucoma suspects, glaucoma patients and
normal subjects.
Contact: S. Smith, M.D., M.P.H., at
216/444-4821 or R. Scott 216/444-0680
Retinal Dystrophy, Pediatric Cornea
and Cataract Clinics Available
A RETINAL DYSTROPHY CLINIC AND A
PEDIATRIC CORNEA AND CATARACT CLINIC
ARE NOW AVAILABLE TO PATIENTS BY
REFERRAL AT THE CLEVELAND CLINIC COLE
EYE INSTITUTE.
Each will be offered once a month
and will be overseen by Elias I. Traboulsi,
M.D., pediatric ophthalmologist and
clinical geneticist at the institute.
Both are set up to facilitate extended
appointments and testing for conditions
that can be difficult for less-specialized
ophthalmologists to manage.
The Retinal Dystrophy Clinic, open
to adults and children, offers patients
enhanced diagnostic capabilities, such
as access to electrophysiologic testing,
genetic screening and inclusion in studies.
The clinic ties together retina, genetic
and pediatric care, Dr. Traboulsi explains.
The Pediatric Cornea and Cataract
Clinic is designed to assess and treat
infants and young children with anterior segment and corneal problems,
including the need for penetrating
keratoplasty, infantile and congenital
cataracts and genetically determined
corneal disorders.
“We hope these clinics will assist
general and specialized ophthalmologists in the care of patients that they
may not be fully equipped to handle,”
says Dr. Traboulsi.
To schedule an appointment
for a patient, call 216/444-2020 or
800-223-2273 ext. 42020. To discuss
whether a specific patient is well-suited
for referral to one of these clinics,
please contact Dr. Traboulsi at
216/444-4363 or [email protected].
Book Highlights 2003 Research Efforts
The vision research conducted at The Cleveland Clinic Cole Eye Institute in 2003
has been published in a compendium that highlights the work of our physicians
and researchers.
It includes abstracts from all research published or presented in 2003 in a
broad range of subspecialty areas: retina, cornea, glaucoma, neuro-ophthalmology,
oculoplasty, ophthalmic genetics, ophthalmic oncology, pediatric ophthalmology,
refractive surgery and uveitis. The book also includes biographies and photographs
of our physicians and research leaders.
If you are interested in receiving a free copy, contact Sue Omori at 216/444-8838
or [email protected].
GLAUCOMA DIAGNOSIS BY OPTICAL
COHERENCE TOMOGRAPHY ANALYSIS OF
RETINA AND NERVE
Objective: The purpose of this study is
to evaluate the ability of the Optical
Coherence Tomography Unit model 2010 to
measure accurately and reproducibly optic
nerve head excavation, retinal fiber thickness layer and the perifoveal retinal
thickness in patients suspected of having
glaucoma or known to have glaucoma.
Contact: S. Smith, M.D., M.P.H., at
216/444-4821 or R. Scott 216/444-0680
The Cleveland Clinic
Medical Concierge
Assists Out-of-State
Patients
PHYSICIANS FROM ACROSS THE COUNTRY
REFER THEIR PATIENTS TO THE CLEVELAND
CLINIC FOR SPECIALIZED MEDICAL CARE.
TO MAKE YOUR PATIENTS’ EXPERIENCE
HERE AS EASY AS POSSIBLE, WE OFFER A
SPECIALIZED, COMPLIMENTARY CONCIERGE
SERVICE EXCLUSIVELY FOR OUT-OF-STATE
PATIENTS AND THEIR FAMILIES.
Members of our Medical Concierge
service will assist your patients before,
during and after their Cleveland visit.
Services provided include assistance
with coordination of multiple appointments, scheduling/confirmation of airline
reservations and access to discounted
air fares when available, help with hotel
and housing reservations with discounts
provided when available, arrangement
of taxi or car service between the airport
and hotel and communication with
family members regarding leisure-time
options. A Medical Concierge will meet
and accompany your patients to their
appointments, upon request.
Our Medical Concierge is available
every weekday from 8 a.m. to 5 p.m.
Eastern time at 800/223-2273, extension
55580, or [email protected]. If
you would like to receive a brochure(s)
regarding the Medical Concierge Program,
contact Debbie Durbin at 800/223-2273,
extension 58272, or [email protected].
14
Cole Eye Institute
Staff
Hilel Lewis, M.D.
Chairman, Division of Ophthalmology
Director, Cole Eye Institute
Specialty/Research Interests: Vitreoretinal
surgery for complicated retinal detachment
and trauma, age-related macular degeneration, diabetic retinopathy, retinal
photocoagulation, instrument development
Bela Anand-Apte, M.B.B.S., Ph.D.
Ophthalmic Research Department
Research Interest: Angiogenesis
John W. Crabb, Ph.D.
Ophthalmic Research Department
Research Interests: Age-related macular
degeneration, inherited retinal diseases
Marc A. Feldman, M.D.
Ophthalmic Anesthesia
Specialty Interests: Ophthalmic surgery
anesthesia, preoperative assessment,
resident education
Richard E. Gans, M.D., F.A.C.S.
Comprehensive Ophthalmology Department
Specialty Interests: Cataract, glaucoma,
diabetes
Philip N. Goldberg, M.D.
Comprehensive Ophthalmology Department
Specialty Interests: Cataract, glaucoma
Froncie A. Gutman, M.D.
Vitreoretinal Department
Specialty Interests: Retinal vascular diseases, laser therapy, diabetic retinopathy
Stephanie A. Hagstrom, Ph.D.
Ophthalmic Research Department
Research Interests: Inherited forms of
retinal degeneration, including macular
degeneration and retinitis pigmentosa
Joe G. Hollyfield, Ph.D.
Ophthalmic Research Department
Research Interests: Retinal degeneration,
retinal diseases
Bennie H. Jeng, M.D.
Cornea and External Disease Department
Specialty/Research Interests: Corneal transplantation, ocular surface disease, limbal
stem cell transplantation, artificial corneas,
eyebanking, cataracts
Peter K. Kaiser, M.D.
Vitreoretinal Department
Specialty/Research Interests: Vitreoretinal
diseases, age-related macular degeneration,
retinal detachment, diabetic retinopathy,
endophthalmitis, posterior segment complications of anterior segment surgery
Gregory S. Kosmorsky, D.O.
Neuro-Ophthalmology Department
Specialty Interests: Neuro-ophthalmology,
cataract, refractive surgery
15
Ronald R. Krueger, M.D.
Refractive Surgery Department
Specialty/Research Interests: Refractive
surgery, lasers, refractive corneal pathology,
lamellar corneal transplants, investigational
clinical trials
Roger H.S. Langston, M.D.
Cornea and External Disease Department
Specialty Interests: Cornea and external
disease, corneal transplantation
Michael S. Lee, M.D.
Neuro-Ophthalmology Department
Specialty Interests: Neuro-ophthalmology,
optic neuropathies, double vision
Careen Y. Lowder, M.D., Ph.D.
Uveitis Department
Specialty/Research Interests: Uveitis, intraocular inflammatory diseases, pathology
Andreas Marcotty, M.D.
Pediatric Ophthalmology and Strabismus
Department
Specialty Interests: Pediatric ophthalmology,
adult strabismus
Shari Martyn, M.D.
Comprehensive Ophthalmology Department
Specialty Interests: Cataract, glaucoma,
diabetes
David M. Meisler, M.D.
Cornea and External Disease Department
Specialty/Research Interests: Corneal
and external disease, inflammatory and
infectious diseases of the cornea, corneal
transplantation, refractive surgery
Michael Millstein, M.D.
Comprehensive Ophthalmology Department
Specialty Interests: Cataract, glaucoma,
refractive surgery
Neal S. Peachey, Ph.D.
Ophthalmic Research Department
Research Interests: Visual loss associated
with hereditary retinal degeneration
Victor L. Perez, M.D.
Cornea and External Disease Department
Specialty/Research Interests: Medical
and surgical treatments of autoimmune
inflammatory conditions of the cornea
and ocular surface, uveitis, corneal
transplantation, cataract surgery
Julian D. Perry, M.D.
Oculoplastic and Orbital Surgery Department
Specialty/Research Interests: Aesthetic
facial surgery/fat transplantation and
repositioning, acellular human dermal
graft matrix, new bovine hydroxyapatite
orbital implant, thyroid eye disease/rate
of strabismus after decompression surgery
for dysthyroid orbitopathy
Edward J. Rockwood, M.D.
Glaucoma Department
Specialty/Research Interests: Glaucoma,
glaucoma laser surgery, combined cataract
and glaucoma surgery, glaucoma filtering
surgery with antimetabolite therapy, glaucomatous optic nerve damage, congenital
glaucoma
Allen S. Roth, M.D.
Comprehensive Ophthalmology Department
Specialty Interests: Corneal transplantation, refractive surgery, cataract and
implant surgery
Jonathan E. Sears, M.D.
Vitreoretinal Department
Specialty/Research Interests: Pediatric
and adult vitreoretinal diseases, pediatric
retinal detachment, inherited vitreoretinal
disorders, retinopathy of prematurity, other
acquired proliferative diseases
David B. Sholiton, M.D.
Comprehensive Ophthalmology Department
Specialty Interests: Cataract and implant
surgery, glaucoma, oculoplastics
Arun D. Singh, M.D.
Ophthalmic Oncology Department
Specialty/Research Interests: Adult and
pediatric ocular tumors, uveal melanoma,
genetics of retinoblastoma, retinal capillary
hemangioma, von Hippel-Lindau disease
Scott D. Smith, M.D., M.P.H.
Glaucoma Department
Specialty/Research Interests: Glaucoma,
cataract, prevention of eye disease, international ophthalmology, congenital
glaucoma
Elias I. Traboulsi, M.D.
Pediatric Ophthalmology and
Strabismus Department
Center for Genetic Eye Diseases
Specialty/Research Interests: Ocular
diseases of children, genetic eye diseases,
strabismus, retinoblastoma, congenital
cataracts, childhood/congenital glaucoma
Steven E. Wilson, M.D.
Cornea and External Disease and
Refractive Surgery Departments
Specialty/Research Interests: Corneal and
external disease, corneal transplantation,
refractive surgery, corneal healing
216/444-2020
The Cleveland Clinic
Cole Eye Institute
www.clevelandclinic.org/eye
Ophthalmology Update, a publication of The Cleveland
Clinic Cole Eye Institute, provides information for
ophthalmologists about state-of-the-art diagnostic
and management techniques and current research.
Please direct any correspondence to:
Steven E. Wilson, M.D.
Cole Eye Institute / i32
The Cleveland Clinic Foundation
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone 216/444-5887
Fax 216/445-8475
Ophthalmic Pearl
Gold Weight Implantation Can Be Effective
Treatment for Exposure Keratopathy
WEIGHTING OF THE UPPER EYELID WITH A
GOLD WEIGHT TO IMPROVE LAGOPHTHALMOS
HAS BECOME A WIDELY ACCEPTED PROCEDURE
Director and Division Chairman
Hilel Lewis, M.D.
FOR TREATMENT OF EXPOSURE KERATOPATHY
Editor-in-Chief
Steven E. Wilson, M.D.
ALLOWS FOR IMPROVEMENT IN DOWNWARD
Editorial Board
Julian D. Perry, M.D.
Jonathan E. Sears, M.D.
THALMOS. THE SIZE OF THE WEIGHT IS
Managing Editor
Beth Thomas Hertz
Art Director
Barbara Ludwig Coleman
Photographers
Don Gerda
Deborah Ross, C.R.A.
The Cleveland Clinic Foundation is an independent,
not-for-profit, multispecialty academic medical center.
It is dedicated to providing quality specialized care
and includes an outpatient Clinic, a hospital with
approximately 927 staffed beds, an Education Division
and a Research Institute.
Ophthalmology Update is written for physicians and
should be relied upon for medical education purposes
only. It does not provide a complete overview of the
topics covered and should not replace the independent
judgment of a physician about the appropriateness or
risks of a procedure for a given patient.
Physicians who wish to share this information with
patients need to make them aware of any risks or
potential complications associated with any procedures.
© The Cleveland Clinic Foundation, 2004
9500 Euclid Avenue / W14
Cleveland, OH 44195
DUE TO 7TH NERVE PARESIS. THE EYELID LOAD
EYELID EXCURSION TO MINIMIZE LAGOPHDETERMINED PREOPERATIVELY BASED ON THE
AMOUNT OF LAGOPHTHALMOS, THE DEGREE
OF LEVATOR FUNCTION AND RESULTS OF TRIAL
WEIGHT TESTING IN THE EXAMINING SUITE.
Gold weight implantation is performed through an eyelid crease incision
and in most cases, the weight rests primarily upon tarsus. Most gold weights
have three holes to allow for suture fixation to the tarsus. Gold weights can be
removed easily if the 7th nerve paresis
and lagophthalmos improve.
Gold weights can be placed on a
more permanent basis, however, complications can occur, including migration,
extrusion, skin erosion, implant visability
or cosmetic dissatisfaction. Certain
patient factors may increase the risk
for these complications. A history of
extrusion, migration or tissue thinning,
radiation therapy or thin or atropic anterior lamellar structures as well as larger
weights may increase the risk of complications. Patients who require long-term
placement of the gold weight or who
have a complication related to previous
gold weight placement may benefit from
wrapping the gold weight in autogenous
or synthetic material.
Another common complication of
gold weight placement is ptosis. The ptosis can be corrected through conjunctival
mullerectomy-tarsectomy repair if the
gold weight must be placed on a more
permanent basis. Patients with 7th nerve
paresis resulting in paralytic ectropion
may require reconstruction of the lower
eyelid. Patients with severe 7th nerve
palsy may require tarsorrhaphy if gold
weight placement and lower lid reconstruction do not provide adequate
corneal protection.
In summary, gold weight placement
offers a straight-forward solution for
many patients who suffer from corneal
exposure due to 7th nerve paresis. The
procedure is safe and effective and allows
for better upper eyelid excursion. While
complications may occur, they can be
minimized by good surgical technique
and orbicularis muscle closure over the
implant. Eyelid loading with a gold weight
offers the surgeon a straight-forward
procedure to improve corneal protection
for patients suffering from paralytic
lagophthalmos.
—Julian D. Perry, M.D.
Non-Profit Org.
U.S. Postage
PAID
Cleveland, OH
Permit No. 4184