Ophthalmology Update - Cleveland Clinic

COLE EYE INSTITUTE

Ophthalmology

Update

Special Edition 2009

OPHTHALMOLOGY UPDATE 2009 SPECIAL EDITION

in this

Issue

02 Investigations

16 Innovation

20 Staff

28 Education

34 Research

D E A R C O L L E A G U E S

I am pleased to present the 2009 Cleveland Clinic Cole

Eye Institute Special Edition of Ophthalmology Update.

As you will see in the pages that follow, Cole Eye

Institute has enjoyed great success in the past year in

both clinical care and cutting-edge research. At the

same time, it also has been a year of significant change.

In December 2008, I was honored to join the Cole Eye

Institute as its new Chairman. The tradition of academic

and clinical excellence, as well as the people who

make up this great institute, were the primary reasons

that I accepted this position. I feel most fortunate to be

here working with this highly acclaimed staff.

In this year’s special edition, you can read about a non-invasive drug delivery system for

ocular disease that is under development by Dr. Rishi Singh in collaboration with Buckeye

Ocular (p.5) and a superiorly based bilobed flap for reconstruction of nasojugal fold

region defects being used by Dr. Julian Perry (p.7). We also provide an update on the three

largest ongoing multicenter randomized clinical trials evaluating treatments for neovascular

(wet) age-related macular degeneration, including (p.3) the Comparison of AMD

Treatments Trials (CATT), the DENALI trial and (p.10) the VEGF Trap-Eye Phase III study.

Members of our staff play leadership roles in all three of these studies.

I hope that you are able to spend some time reviewing Ophthalmology Update and find

it valuable and helpful in your practice. I look forward to sharing with you additional

updates as the year progresses regarding our ever-expanding research program and our

efforts to further improve patient care. Please feel free to contact us at 216.444.2020 if you

have any questions or would like to refer a patient. As always, we welcome the opportunity

to work with you.

Sincerely,

Daniel F. Martin, MD

Chairman, Cole Eye Institute

1


Investigations

STRIVING FOR ANSWERS


Two of the nation’s most important clinical trials

in age-related macular degeneration (AMD) are

now lead by retina specialists at Cleveland Clinic’s

Cole Eye Institute.

When Daniel F. Martin, MD, became Chairman

of Cole Eye Institute in late 2008, coming from

Emory University in Atlanta, he brought with him

his role as Study Chairman of the Comparison of

AMD Treatments Trials (CATT).

CLEVELAND CLINIC | COLE EYE INSTITUTE | CLEVELANDCLINIC.ORG/OUSPECIAL | INVESTIGATIONS

New Chairman Brings CATT Study to Cole Eye Institute

Colleague Peter K. Kaiser, MD, is chairman of the

DENALI trial, which is evaluating the combination

of injectable verteporfin (Visudyne ® ) photodynam-

ic therapy and ranibizumab (Lucentis ® ) for the

treatment of AMD. The 24-month study will

compare the ranibizumab combination therapy

with ranibizumab monotherapy in patients with

subfoveal choroidal neovascularization (CNV)

secondary to neovascular AMD. Dr. Kaiser also is

involved in the leadership of the VEGF Trap-Eye

Phase III study (see related article, p. 10).

The CATT study has generated much publicity

in recent months. Genentech’s ranibizumab is

approved by the FDA for treatment of AMD, but

many ophthalmologists believe that another of

the company’s drugs, bevacizumab (Avastin ® ),

delivers equal results for a fraction of the price.

“Two of the nation’s most important clinical

trials in age-related macular degeneration

(AMD) are now lead by retina specialists at

Cleveland Clinic’s Cole Eye Institute.”

Dr. Martin agrees that comparing the drugs in a

head-to-head trial is an important issue. However,

he believes that the study’s second question,

which addresses the issues of preferred dosing

frequency, is just as important.

“The clinical trials that led to FDA approval of

ranibizumab only evaluated a fixed monthly

dosing schedule. However, in clinical practice,

Continued

3

4


CATT Study continued

no one is using this drug or bevacizumab this way,”

he says. “Most retina specialists are using these

drugs on an as-needed basis. It is essential to

understand whether or not we are compromising

long-term visual outcomes with these reduced

dosing frequencies and whether or not we can

identify a subset of patients who do very well with

fewer injections.”

“Most retina specialists are using these drugs on an

as-needed basis, and we are eager to learn if that is

the optimal way to use them, or if a fixed schedule

would deliver superior outcomes,” he says.

To help answer both questions, patients are being

randomly assigned to one of four groups for

treatment during the first year (doses are 0.5 mg

for ranibizumab and 1.25 mg for bevacizumab):

• Ranibizumab on a fixed schedule of every

four weeks for a year.

• Bevacizumab on fixed schedule of every

four weeks for a year.

• Ranibizumab on variable schedule dosing;

i.e., after initial treatment, monthly evaluation

of the need for treatment based on signs of

lesion activity.

• Bevacizumab on variable schedule dosing;

i.e., after initial treatment, monthly evaluation

of the need for treatment based on signs of

lesion activity.

Optical coherence tomography will drive retreatment

decisions in the PRN groups, he explains. If

any subretinal, intraretinal or sub-retinal pigment

epithelium fluid is seen, the eye will receive an

injection. If there is no fluid but there are other

signs of active CNV, the eye will be treated as

well. Examples of signs include new or persistent

subretinal or intraretinal hemorrhage or unexplained

decreased visual acuity. Fluorescein

angiography results may be considered at the

physician’s discretion, and findings that would

elicit particular concern would include increased

lesion size or leakage.

The primary outcome measure is change in visual

acuity. Secondary outcome measures include

number of treatments, retinal thickness at the

fovea, adverse events and cost.

Dr. Martin expects the two-year trial to complete

enrollment — 1,200 participants at 43 sites — by

the fourth quarter of 2009. One-year outcomes are

expected to be released early in 2011.

For more information,

contact ophthalmologyupdate@ccf.org.

Non-invasive Drug Delivery System

for Ocular Disease Under Development

Rishi P. Singh, MD


The current method of delivery of ocular therapeutics

is through injections in the eye. In the case of

age-related macular degeneration (AMD), treatments

can be as frequent as every four weeks.

These injections have been associated with

significant side effects such as pain, infection,

bleeding and retinal detachment. Beyond the

socioeconomic impact of monthly patient visits,

intravitreal injections must be administered by an

ophthalmologist and place significant demands

on ophthalmic practices given the growth of the

number of patients with AMD.

At the Cleveland Clinic Cole Eye Institute, Rishi P.

Singh, MD, is collaborating with Buckeye Ocular,

Beachwood, Ohio, to develop a drug delivery system

that is non-invasive, low-cost and effective with

minimal side effects. Together, they are adapting

a proprietary technology and drug formulation

combination, Macroesis , which Buckeye Ocular’s

parent company, Buckeye Pharmaceuticals, had

developed to revolutionize the treatment of

onychomycosis and herpes labialis.

Nanodielectrophoresis

• AC signal applies a non-uniform electric field to a chemical

compound.

• This induces a dipole (areas of equal charge separated by a

distance) in the compound and generates an electrical field

gradient that provides an electromotive force.

• This forces varies in magnitude and direction with applied

frequency, among other factors.

“The delivery technology uses a series of optimallytuned

alternating current (AC) signals applied with

a custom-designed combination of successive

electrodes that induces temporary polarization,

preconcentrates and enhances mobility in AMD

drugs, making them candidates for active transcleral

delivery,” Dr. Singh says.

Two in-vitro models of drug delivery were used

for recent validity studies with ranibizumab and

triamcinolone acetonide. These studies, the results

of which were presented at the Retina Society and

Prototype Device Design

Continued

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6


Non-invasive Drug Delivery System continued

American Society of Retina Specialists annual

meetings in 2008, concluded that macroesis

can successfully deliver ranibizumab, an

FDA-approved intravitreal injection for treating

AMD, and triamcinolone acetonide, a topical

corticosteroid, in a non-invasive manner using

the Buckeye Ocular delivery system.

The technology is akin to iontophoresis, a delivery

platform for steroids to be transported to a joint

that uses direct current (DC), Dr. Singh explains.

“The beauty of macroesis is that you can actually

optimally tune the drug for the delivery,” he says.

“If I have a drug that is hard to diffuse to tissue, I

can use a certain wave length and voltage to fine

tune its delivery for a superior outcome. It’s almost

like iontophoresis on steroids.”

Dr. Singh and his collaborators recently received

$35,000 in product development funds from

Cleveland Clinic Innovations to conduct preclinical

studies. The study has two aims: 1) To transport

ranibizumab through an eye animal model to

a saline solution vitreous fluid analog using a

laboratory-generated electrical signal. 2) To build

an alpha prototype embodying the laboratorygenerated

signaling to transport the pharmacological

agents through the cadaver animal model.

Dr. Singh says the prototype will be like a contact

lens that is inserted on the patient’s eye and runs

off of four AA batteries. The consumable electrode

preloaded with the approved AMD drug would

be designed to be nurse-administered in a

clinical setting.

“If the device can succeed in being both

inexpensive and convenient, Dr. Singh says,

it has the potential to eliminate some existing

barriers to AMD treatment.”

Such a treatment, he says, could be performed

in as little as five to 10 minutes in an outpatient

setting, or perhaps even at home.

If the device can succeed in being both inexpensive

and convenient, Dr. Singh says, it has the potential

to reduce some existing barriers to AMD treatment.

“The gold standard for AMD treatment is monthly

injections,” he says. “But this is many times

prohibitive for patients. If we could use this

technology successfully, maybe we would have

better compliance and improved outcomes.”

Another exciting aspect of the technology is its

potential for pairing with any FDA-approved drug.

“Currently, we’re focusing on AMD, but it could

conceivably be used for any ocular disease.

Perhaps it could be used with anti-inflammatory

medications to treat uveitis or with chemotherapeutic

medication for ocular melanoma

or metastasis.”



Superiorly Based Bilobed Flap Effective for Inferior Medial Canthal and

Nasojugal Fold Defect Reconstruction

Julian D. Perry, MD


Reconstruction of the inferior medial canthal, nasal

sidewall and nasojugal fold after surgical resection

of cutaneous malignancy presents many challenges.

The medial canthal region represents a multi-contoured

area with great variation in skin thickness,

color, texture and appendage density, and it includes

contributions from the orbital and tarsal portions

of the upper and lower eyelids, the nasal sidewall

and the glabella. Local landmarks, including the

lacrimal drainage apparatus and eyebrows, limit

flap design, as does the lack of significant horizontal

tissue redundancy in this region.

To evaluate the use of a superiorly based bilobed flap

for reconstruction of nasojugal fold region defects,

Cole Eye Institute oculoplastic surgeon Julian D.

Perry, MD, and his team conducted a retrospective

review of all patients undergoing medial canthal,

nasal sidewall and nasojugal fold region reconstruction

using a superiorly based bilobed flap from

October 2000 through March 2008. Charts were

reviewed for patient age and gender, indication,

defect size and location, flap(s) used and follow-up

time. Outcome measures included ability to

completely close the defect without tension,

cosmetic appearance, complications and need

for further surgery.

Eighteen cases of medial canthal and nasojugal

fold area reconstruction were performed using a

superiorly based bilobed flap in 17 patients. There

were eight male and nine female patients with an

average age of 68.2 years (range, 11 to 88 years) and

mean follow-up time of 17.8 months (range, 1 to 60

months). Mean defect size measured 2.0 x 1.4 cm

(range, 0.7 to 4 cm). One patient underwent

simultaneous glabellar flap repair, two patients

underwent simultaneous lateral lower eyelid

rotational flap repair, and one patient underwent

simultaneous upper eyelid V-Y advancement flap.

All defects closed completely with no wound

tension. No cases of hemorrhage, infection,

a b c

Preoperative (a), immediate postoperative (b) and one-year postoperative (c) photographs of a patient who underwent successful

reconstruction of a typical nasojugal region defect using a superiorly based bilobed flap.

dehiscence or necrosis developed during the

follow-up period. Cosmetic satisfaction was

achieved in 16 of 17 patients. Complications

included mild medial ectropion (two patients) and

canalicular stenosis (one patient). None of these

patients elected re-operation. Trapdoor deformity

did not occur in any case. Two patients underwent

re-operation for local tumor recurrence.

Dr. Perry and the team concluded that a superiorly

based bilobed flap adequately reconstructs inferior

medial canthal, nasal sidewall and nasojugal

fold defects.



7

8


Case Study: DSAEK to Treat Amantadine-associated Corneal Edema

Christopher T. Hood, MD

Roger H.S. Langston, MD

William J. Dupps, Jr.,

MD, PhD

Presentation:

A 45-year-old Caucasian woman presented to the

Cole Eye Institute for management of corneal

edema. She described experiencing six months of

blurry vision in both eyes that was worse in the

morning and improved slightly throughout the day.

She denied redness, pain or photophobia. She was

being treated with Muro 128 ointment four times

daily in the right eye upon referral.

She denied any history of ocular trauma, surgery

or inflammatory disease. Her medical history was

significant for a longstanding diagnosis of multiple

sclerosis, for which she was taking baclofen, methyl-

phenidate, glatiramer acetate injection, neurontin,

amantadine, escitalopram oxalate and bupropion.

She denied any family history of eye disease.

Examination:

On examination, visual acuity was 20/800 in the right

eye and 20/400 in the left eye. Pupils were equal

in size and reactive, without an afferent pupillary

defect. Extraocular movements were full. Intraocular

pressures were 12 mm Hg in the right eye and 10

mm Hg in the left eye. Anterior segment examination

demonstrated normal eyelids, sclera and conjunc-

tiva. Bilateral diffuse stromal and epithelial edema

was observed with marked Descemet membrane

folds and pre-Descemet membrane opacification

without guttae (Figure 1). Ultrasound pachymetry

demonstrated a central corneal thickness of 867

µm in the right eye and 700 µm in the left eye. The

anterior chambers were deep and quiet. The iris

and lens were normal. Dilated fundus examination

of both eyes was unremarkable.

Diagnosis:

Diagnoses considered included Fuchs endothelial

dystrophy, endotheliitis, congenital hereditary

endothelial dystrophy and posterior polymorphous

dystrophy. In this case, a lack of guttae on examina-

tion combined with the historical features of no

previous intraocular surgery and amantadine use

led to the diagnosis of amantadine-associated

corneal edema. With the approval of the patient’s

neurologist, amantadine was discontinued and the

patient was followed for six weeks with minimal

improvement of the bilateral corneal edema.

Prednisolone acetate 1 percent was initiated four

times daily in both eyes and the patient was followed

for an additional six weeks. Although she demonstrated

initial improvement, best corrected vision

was 20/200 in both eyes.

The patient was offered Descemet’s stripping

automated endothelial keratoplasty (DSAEK) in the

right eye. After informed consent was obtained, she

underwent uncomplicated surgery. The patient, who

had no appreciable nuclear sclerosis, was left phakic

and was given topical pilocarpine 1 percent preoperatively.

Descemet stripping was performed under air,

and a donor lenticule was prepared on an artificial

anterior chamber and punched to 8.5 mm just prior to

insertion. Controlled tamponade of the graft against

the host stroma was performed with air infusion and

air-fluid exchange as described previously. 1 Three

months after surgery, the patient’s best corrected

visual acuity was 20/30+ in the right eye. Her cornea

was clear and compact with minimal anterior stromal

haze and the posterior donor lenticule was wellcentered

(Figure 2). DSAEK is planned in the left eye.

Discussion:

Amantadine was developed for short-term use as

an antiviral drug against influenza A, also is used

chronically to treat tremors and stiffness in Parkinson’s

disease and fatigue associated with multiple

sclerosis. The mechanism of its action is not well

understood. Reported ocular side effects include

visual loss, hallucination, oculogyric crises and

mydriasis. 2 Corneal side effects include superficial

punctuate keratitis, punctuate subepithelial opacities,

and epithelial and stromal edema. 2 Corneal edema

occurs from a few weeks to many years after commencing

amantadine therapy. 2-6 Clinical exam

demonstrates bilateral, diffuse stromal and microcystic

epithelial edema, without guttae or inflammatory


Figure 1a Figure 1b Figure 1c

signs. First-line management consists of discontinu-

ing amantadine, which results in the resolution of

corneal edema in most cases. 2-6 However, it has

recently been reported that corneal edema may be

irreversible, and penetrating keratoplasty has been

employed with good anatomic and visual outcomes. 2

The pathophysiology of amantadine-associated

corneal edema is not fully understood, but the

medication is thought to damage endothelial cells, as

evidenced by the presence of rare endothelial cells

on routine light microscopy and areas of denuded

endothelial cells on scanning electron microscopy. 2

The presence of a posterior collagenous layer by

transmission electron microscopy supports the

hypothesis that amantadine leads to endothelial

stress. 2 Other authors have demonstrated a low

endothelial cell density by specular microscopy after

discontinuation of amantadine, even in corneas

that cleared and returned to normal thickness. 3

It remains unclear why only a small fraction of patients

treated with amantadine develops corneal edema.

References

1. Meisler DM, Dupps WJ, Jr., Covert DJ, Koenig SB.

Use of an air-fluid exchange system to promote graft

adhesion during Descemet’s stripping automated

endothelial keratoplasty. J Cataract Refract Surg.

2007;33(5):770-2.

2. Jeng BH, Galor A, Lee MS, et al. Amantadineassociated

corneal edema potentially irreversible

even after cessation of the medication.

Ophthalmology. 2008;115(9):1540-4.

3. Chang KC, Kim MK, Wee WR, Lee JH. Corneal

endothelial dysfunction associated with amantadine

toxicity. Cornea. 2008;27(10):1182-5.

4. Hughes B, Feiz V, Flynn SB, Brodsky MC.

Reversible amantadine-induced corneal edema

in an adolescent. Cornea. 2004;23(8):823-4.

DSAEK, a partial thickness transplantation of

the posterior corneal surface, is emerging as the

preferred procedure for managing endothelial

dysfunction in the absence of stromal opacities

because of its more predictable refractive outcomes,

faster visual recovery, and maintenance of the

structural integrity of the eye. Although most com-

monly used for Fuch’s dystrophy and pseudophakic

or aphakic bullous keratopathy, DSAEK also has been

7, 8

used in cases of iridocorneal endothelial syndrome.

To our knowledge, this is the first patient in which

DSAEK was employed in amantadine-associated

corneal edema, and a successful outcome was

achieved for our patient. This case highlights the

importance of considering amantadine toxicity in the

differential diagnosis of corneal edema without an

identifiable ocular cause and suggests the utility of

DSAEK in the treatment of this rare condition.

Dr. Hood is a resident at Cole Eye Institute. For more

information, contact ophthalmologyupdate@ccf.org.

5. Kubo S, Iwatake A, Ebihara N, et al. Visual

impairment in Parkinson’s disease treated with

amantadine: case report and review of the literature.

Parkinsonism Relat Disord. 2008;14(2):166-9.

6. Pond A, Lee MS, Hardten DR, et al. Toxic corneal

oedema associated with amantadine use.

Br J Ophthalmol. 2009;93(3):281,413.

7. Price MO, Price FW, Jr. Descemet stripping with

endothelial keratoplasty for treatment of iridocorneal

endothelial syndrome. Cornea. 2007;26(4):493-7.

8. Jeng BH, Dupps WJ, Jr., Meisler DM, Schoenfield L.

Epithelial debridement for the treatment of

epithelial basement membrane abnormalities

coincident with endothelial disorders. Cornea.

2008;27(10):1207-11.

9

10


VEGF Trap-Eye for AMD in Phase III Trials

Phase II results promising; Cleveland Clinic Cole Eye Institute specialist on executive committee

Peter K. Kaiser, MD

Phase III trials of VEGF Trap-Eye, a promising new

treatment for age-related macular degeneration

(AMD), are under way nationally and a Cleveland

Clinic Cole Eye Institute retina specialist has a key

leadership role in the research.

Peter K. Kaiser, MD, who is on the Executive

Committee of the 150-plus site Phase III study,

explains that the results of the Phase II study of

VEGF Trap-Eye, for which the Cole Eye Institute

was the central reading center, were very positive.

“The number of treatments required to achieve the

desired results was considerably less than with our

current standards of care, ranibizumab injection

(Lucentis ® ) and bevacizumab (Avastin ® ),” he says.

VEGF Trap-Eye is a unique fusion protein that

binds all forms of VEGF (vascular endothelial

growth factor) and PLGF (placental growth factor),

which is another member of the VEGF family that

binds to the VEGF receptor 1 and activates VEGF

receptor signaling. PLGF indirectly increases VEGF

concentration, is upregulated in neovascularization

and is thought to be involved in the pathophysiology

of AMD.

Dr. Kaiser explains that VEGF Trap-Eye is a soluble

receptor decoy that works in a manner similar to

ranibizumab or bevacizumab but binds VEGF

tighter than these drugs and even the native

receptors, so it may last longer and/or achieve

better outcomes.

In the multicenter Phase II study, 157 patients

received an initial intravitreal injection and then

were randomly assigned to one of five VEGF Trap

dosing schedules:

-0.5 mg every four weeks

-2 mg every four weeks

-0.5 mg every 12 weeks

-2 mg every 12 weeks

-4 mg every 12 weeks

“VEGF Trap-Eye achieved clinically

meaningful and durable vision improvement

over one year with almost two lines gained

at week 52 and an excellent reduction in

central retinal lesion thickness at week 52

as measured by OCT.”

All patients were redosed no later than week 12.

As-needed (PRN) dosing began at week 16 and

continued through week 52. Criteria for the PRN

dosing after 16 weeks included persistent fluid as

visualized with optical coherence tomography

(OCT), a loss of ≥ 5 ETDRS letters with recurrent

fluid on OCT, new or persistent leakage seen via

fluorescein angiography, a new macular hemor-

rhage, central retinal thickness ≥100 µm as seen

on OCT or new onset classic neovascularization.

At 12 weeks, mean change central retinal/lesion

thickness (CR/LT), which was the study’s primary

endpoint, was best in the 2 mg every four weeks

group. Mean change in visual acuity, the secondary

endpoint, was best in the patients receiving

treatment every four weeks, with approximately a

1.5-line gain in vision, but even the patients treated

every 12 weeks gained around one line in vision.

The mean number of doses given during the PRN

phase averaged 2.1 across all treatment groups.

“Patients received, on average, only two addition-

al injections over the 40-week PRN-dosing phase.

No additional injections were used after week 12

in 19 percent of patients,” Dr. Kaiser says. “VEGF

Trap-Eye achieved clinically meaningful and

durable vision improvement over one year with

almost two lines gained at week 52 and an

excellent reduction in central retinal lesion

thickness at week 52 as measured by OCT.”

The drug was generally well tolerated, he adds.


Regeneron and Bayer HealthCare are collaborating on

the development of VEGF Trap-Eye for the treatment

of wet AMD, diabetic eye diseases and other eye

disorders. Bayer HealthCare will market VEGF

Trap-Eye outside the United States, while Regeneron

maintains exclusive rights in the United States.

The companies have initiated the Phase III trial

to evaluate dosing at 0.5 mg every four weeks,

2 mg every four weeks or 2 mg every eight weeks,

following three monthly doses, in direct comparison

with ranibizumab administered 0.5 mg every

four weeks. PRN dosing will be evaluated during

the second year. This study is ongoing throughout

AngioQuest

Peter K. Kaiser, MD, is Chief Medical Officer

of a new Cleveland Clinic-owned company,

AngioQuest.

The company has three anti-angiogenic platforms

that are in pre-clinical testing. One is based on

the work by Cole Eye Institute researcher Bela

Anand-Apte, PhD, with tissue inhibitor of

metalloproteinase (TIMP3). The second is based

on the work of Tatiana Byzova, PhD, in Cleveland

the world and at the Cole Eye Institute.

“We are always looking for better treatments for

macular degeneration that can offer our patients

the best outcomes with fewer treatments,” Dr.

Kaiser says. “We hope that the Phase III trials will

confirm that VEGF Trap-Eye is an incremental step

over what we currently have.”



Clinic’s Department of Molecular Cardiology,

regarding AlphavBeta3 integrin. The third

involves carboxyethyl pyrrole (CEP), work led

by Dr. Anand-Apte and John W. Crabb, PhD,

also of the Cole Eye Institute.

For more information about AngioQuest, please

contact Neema Mayhugh, PhD, at 216.445.7176 or

mayhugn@ccf.org.

11

12


Cole Eye Institute Researchers Describe a Difference

in the Biomechanical Impact of Hyperopic Versus Myopic LASIK

William J. Dupps, Jr.,

MD, PhD

By thinning the cornea and severing anterior

corneal lamellae, LASIK and other photoablative

keratorefractive procedures induce changes in

corneal material properties. In some patients,

these structural alterations can contribute to residual

postoperative refractive error or even biomechanical

instability in the form of ectasia. At the

Cole Eye Institute, William J. Dupps, Jr., MD, PhD,

has been actively involved in conducting research

in this field, including developing methods for

assessing the cornea’s biomechanical properties

and studies to determine how they are affected by

corneal pathology and surgery.

Results from a recent study using the Ocular

Response Analyzer (ORA, Reichert) to investigate

biomechanical changes early after myopic and

hyperopic LASIK support the hypothesis that

differences in the ablation pattern of these two

procedures leads to marked differences in their

biomechanical impact. The work was performed in

collaboration with Fabricio W. Medeiros, MD, and

Abhijit Sinha Roy, PhD, of the Cole Eye Institute

Laboratory of Ocular Biomechanics & Imaging.

Extrapolating these findings to clinical outcomes,

Dr. Dupps postulates they may account for the

observation that post-LASIK ectasia occurs more

often after myopic versus hyperopic keratorefractive

ablation procedures. The results also may explain

the greater artifactual decrease in IOP after myopic

versus hyperopic corneal ablative surgery.

“Interest in understanding the underlying mechanisms

of patient-specific outcomes after laser

vision refractive surgery has been one motivation

driving corneal biomechanics research. With the

ORA, researchers have for the first time a useful

tool for collecting in vivo data in a clinical setting,”

notes Dr. Dupps.

“Previous investigations using this instrument

have shown significant differences in the corneal

biomechanical properties of post-LASIK eyes

compared with normal, virgin corneas. To our

knowledge, ours is the first study investigating

how LASIK-induced changes in corneal material

properties are affected by the specific photo

ablation pattern.”

The study was a retrospective analysis of preop-

erative and one-week postoperative data extract-

ed from chart review of 13 eyes of 13 myopic

patients and 11 eyes of 11 hyperopic patients.

In order to isolate a potential influence of

differences in the photoablative pattern on

corneal biomechanics, other factors that might

affect the outcome were evaluated.

All myopic and hyperopic procedures were

performed with the same flap construction

method using the same femtosecond laser with

similar energy settings to create thin flaps of

similar attempted depth and diameter. In addition,

the ablations were performed with a single excimer

laser system, and the mean total number of fixed

spot-size photoablative pulses, which is a surro-

gate for ablated corneal volume, was comparable

in the myopic and hyperopic groups. Statistical

analyses showed the two groups also were similar

preoperatively with respect to mean values for

central corneal thickness as well as for the two

ORA-derived biomechanical measures, corneal

hysteresis (CH) and corneal resistance factor (CRF).

ORA measurements performed at one week after

surgery showed significant differences between

the myopes and hyperopes that demonstrated

the hyperopic procedures had less impact on the

ORA’s standard corneal viscoelastic parameters.

Compared with the hyperopes, the myopes had

both significantly lower mean CH and CRF values

and a significantly greater decrease in both

measures. In addition, there was a significantly

greater reduction in Goldmann-equivalent IOP

(IOPg) after surgery in the myopic group compared

with the hyperopes.


“Results from a recent study using the Ocular Response Analyzer (ORA, Reichert) to investigate

biomechanical changes early after myopic and hyperopic LASIK support the hypothesis that

differences in the ablation pattern of these two procedures leads to marked differences in

their biomechanical impact.”

“A tendency for IOP to be underestimated by

applanation tonometry in eyes that have undergone

myopic LASIK has been previously recognized

and was originally attributed to thinning

of the central cornea where the IOP measurement

is made. Our data corroborate this postoperative

change in IOP with central ablation but also

demonstrate that a change in the biomechanical

status of the cornea with little removal of tissue in

the central 3 mm impacts the IOP measurement

after surgery,” Dr. Dupps says.

Regression analyses performed to examine any

relationship between the number of laser pulses

delivered and the changes in CH and CRF values

showed no statistical correlations in the hyperopic

group or for change in CH in the myopic group.

However, there was a statistically significant inverse

relationship between change in CRF and the number

of laser pulses delivered for the myopic ablations.

Dr. Dupps observes that the lesser impact of the

hyperopic ablation on corneal biomechanics might

be predicted based on knowledge of regional

differences in corneal tissue architecture. Relative

to the central ablation of myopic corrections,

hyperopic procedures remove a paracentral annulus

of tissue and involve an area of the cornea that is

relatively thicker and biomechanically stronger.

“The cornea is thinnest in the center and becomes

thicker moving toward the periphery, and the

collagen lamellae become more tightly interwoven

moving anteriorly toward the epithelium and

outward toward the limbus. Therefore, hyperopic

LASIK removes proportionally less corneal

thickness than myopic corrections and leaves

a stronger underlying interlamellar network.

Together, these features may be important

in minimizing the biomechanical impact of

hyperopic ablation profiles,” he explains.

One other factor that could contribute to the

measured differences in the biomechanical impact

of myopic and hyperopic ablation profiles could be

that ORA data are derived from reflections of

infrared light off the central 3 mm of the cornea.

“Previous work from our laboratory, as well as

emerging clinical data, suggest that central

corneal biomechanical behavior and, therefore,

ORA measurements are affected by in the mechanical

conditions outside the central cornea, suggesting

that device spatial sampling bias may not be

sufficient to explain the measured differences,”

notes Dr. Dupps.

Continuing their research, Dr. Dupps and colleagues

are adding more patients to their study

groups. In addition, they have designed several

new variables based on custom signal waveform

analysis of the ORA measurements to try to gain

more sensitive and specific indicators of biomechanical

change. Preliminary analyses reveal

differences between several variables in their

responses to myopic versus hyperopic surgery.

“Currently, we are analyzing multiple candidate

variables not only for the purpose of identifying

additional predictors of the biomechanical and

optical responses to refractive surgery, but also

for early detection of keratoconus in a refractive

surgery screening setting,” says Dr. Dupps.



13

14


Reducing the Progression of Retinopathy of Prematurity

Jonathan E. Sears, MD

Two recent Cleveland Clinic publications highlight

the idea that stimulating angiogenesis can prevent

retinopathy of prematurity (ROP). 1,2

In the March 2009 issue of Ophthalmology,

Cleveland Clinic ophthalmologist Jonathan E.

Sears, MD, and Fairview Hospital neonatologist

Jeffrey Pietz, MD, reported that a modified oxygen

protocol showed not only a reduction in threshold

retinopathy, but more importantly, an increase in

the incidence of normal, orderly development of

the retina without the disease phenotype.

Adjusting Oxygen Saturation by Age

The new protocol calls for decreasing the oxygen

saturation targets when infants are less than 34

weeks, and increasing the saturation targets when

infants are 34 weeks or more. These targets appear

to match in utero saturations and thereby enable

the sequential development of the retina without

provoking the typical disease progression of ROP.

“Our findings in the clinic gave us the idea that we

could use pharmaceutical preconditioning in the

same way as oxygen,” notes Dr. Sears, Principal

Investigator and member of Cleveland Clinic’s

departments of Ophthalmic Research and Cell

Biology. In a study published in the December 2008

Proceedings of the National Academy of Sciences, he

reported that increasing the activity of hypoxiainducible

factor during early premature age

prevents ROP in a mouse model.

Preventing Many Complications

“The work of Drs. Sears and Pietz opens new

horizons for the prevention of ROP,” says Ricardo

Rodriguez, MD, Director of Neonatal Care at

Cleveland Clinic Children’s Hospital. “It demonstrates

that inducing normal development of

the retina — either pharmaceutically or by the

judicious use of oxygen — allows for sequential

and orderly retinal development. This has tremendous

implications for the systemic complications

of prematurity found in the lungs and brain.”

Currently, progressive disease is treated surgically,

through laser ablation of the avascular

retina. Advanced proliferative disease requires

more aggressive surgical intervention and has

mixed results.

Reversing Phases for Infants’ Benefit

Both of these studies by Dr. Sears’ group demonstrate

that “reversal” of these stages, either by

hypoxic or pharmaceutical preconditioning, may

benefit children. This process prevents ischemia

and may therefore have application to a wide

range of diseases, such as diabetes and stroke.

“In our NICUs, changes in oxygen administration

practices have significantly decreased the incidence

of ROP,” says Dr. Rodriguez. “We treat the

administration of oxygen just as we do any other

drugs. We are very careful in optimizing oxygen

delivery and monitoring oxygen saturation levels

in these tiny babies to avoid the detrimental effects

of wide blood oxygen level fluctuations on the

immature retina.”



References

1. Sears JE, Pietz J, Sonnie C, Dolcini D, Hoppe G. A

change in oxygen supplementation can decrease

the incidence of retinopathy of prematurity.

Ophthalmology. 2009 Mar;116(3):513-8.

2. Sears JE, Hoppe G, Ebrahem Q, Anand-Apte B.

Prolyl hydroxylase inhibition during hyperoxia

prevents oxygen-induced retinopathy. Proc Natl

Acad Sci USA. 2008 Dec 16;105(50):19898-903.

Case Study: Fundus Photography Useful

for Detecting AMD in Asymptomatic Patient

Rishi P. Singh, MD


Presentation:

The patient is a 68-year-old man with a medical

history significant for hypertension, hyperglyceridemia

and carotid occlusive disease. He presented for

his annual Executive Health physical examination

and was asked to undergo remote ophthalmology

screening evaluation.

Examination:

On examination, his visual acuity was 20/20 in both

eyes at both distance and near with correction.

Air puff tonometry measurements of intraocular

pressure showed measurements of 12 mm Hg in

the right eye and 11 mm Hg in the left eye. The

non-dilated funduscopic photograph was significant

for large, soft drusen in both eyes with retinal

pigment epithelial changes. The diagnosis of

age-related macular degeneration (AMD) was made

and the patient was referred for full ophthalmologic

evaluation with a retina specialist at Cole Eye

Institute. The follow-up examination confirmed the

diagnosis of dry AMD (category 3) and the patient

was asked to start Age-Related Eye Disease Study

(AREDS) vitamin therapy and monitor his vision

with an Amsler grid for acute changes.

Discussion:

Non-mydriatic fundus photography is a type of

medical imaging of the retina. A customized camera

is used to take high-resolution images, which can

be used to diagnose certain ocular diseases and

monitor disease progression. No medications or

dilation of the pupil is required for the exam.

Through our Cole Fundus Screening Network,

fundus photos of undilated eyes are taken by a

technician in a physician office. The process is

simple, painless and takes about five to seven

minutes. The images are remotely uploaded to the

electronic medical record for review by a fellowshiptrained

retina specialist at Cole Eye Institute.

Readings are performed within two business

days. The report can be shared with patients and

ophthalmologists when referrals are needed.

In the case of this patient, remote ophthalmology

examination resulted in the diagnosis of advanced

dry AMD in a patient with no clinical symptoms and

good vision. AREDS, sponsored by the National Eye

Institute, was designed to determine the clinical

course and prognosis of AMD and cataracts. In

addition, AREDS evaluated the possible risk factors

associated with the development of AMD and

cataracts; the nutritional risk factors were evaluated

and published in October 2001.

Study results showed that antioxidant vitamins and

zinc therapy reduced the risk of developing advanced

AMD in participants with intermediate and greater

risk of developing AMD (categories 3 and 4) by 25

percent. The risk of vision loss of three lines or more

on the logarithmic visual acuity charts was reduced

by 19 percent for these participants. For those who

developed AMD, their risk of vision loss was reduced

by 25 percent. Antioxidants and zinc are now

recommended for patients who have an intermediate

risk of developing advanced AMD.

This case is a prime example of how fundus photog-

raphy is being used at Cole Eye Institute to help

screen patients remotely. We are currently studying

whether this technology has the potential to screen

mass populations easily and effectively for AMD,

diabetic macular edema and glaucoma — conditions

in which timely diagnoses are key to optimal

vision outcomes.



15


Innovation

DEFINING WHAT MAKES US DIFFERENT

I N S T I T U T E O V E R V I E W

At Cleveland Clinic Cole Eye Institute, we have assembled a

team of the world’s foremost clinicians and researchers who

are committed not only to delivering the finest healthcare

available, but also to improving tomorrow’s care through

innovative basic, clinical and translational research.

We believe that research and patient care are interdependent.

Therefore, we forge synergistic relationships through analytical

and integrative processes, such as surgical outcomes analysis.

We are pioneering treatment protocols for complex vision-

threatening disorders through our clinical trials and aggressive

research programs to shorten the gap between the laboratory

discoveries of today and the patient care of tomorrow. Our goal:

Answering tomorrow’s medical problems through today’s

laboratory and research endeavors.

Clinical Expertise

As one of the leading comprehensive eye institutes in the world,

we are able to enhance the lives of our patients and serve our

referring physicians by providing early, accurate diagnosis and

excellent, efficient state-of-the-art care. Our program consis-

tently ranks amongst the highest in the U.S.News & World

Report annual survey. We have some of the largest patient

volumes in the United States, with more than 140,000 patient

visits and more than 5,000 surgeries per year. We offer primary,

CLEVELAND CLINIC | COLE EYE INSTITUTE | CLEVELANDCLINIC.ORG/OUSPECIAL | INNOVATIONS

secondary and tertiary ophthalmologic services for all ages.

Our internationally recognized staff of 33 ophthalmologists

and researchers is composed almost entirely of subspecialists,

and seven optometrists round out our comprehensive services.

Patient-Centered Facilities

We deliver care in a state-of-the-art building that demonstrates

our dedication to putting patients first. Our facilities deliver

maximum patient comfort, service and quality. We offer

one-stop care, with our exam lanes, diagnostic services suite

and operating rooms all in one building, which includes such

special features as:

• Windows with special filters to minimize light on dilated

or newly treated eyes.

• A comfortable waiting room that includes a special play area

for children.

• Amenities such as valet parking and an easy postoperative

pickup area.

• Conveniently located food services.

Our regional eye care program also brings care into the

community, providing services in six convenient suburban

locations and one ambulatory surgery center.

Continued

17

18


I N S T I T U T E O V E R V I E W continued

Fostering Innovation

Our institute is specially designed to enable clinicians to develop

tomorrow’s advances; our facility includes an Experimental

Surgery Suite — one of the few in the country with full operating

capacity. Training future eye specialists is greatly enhanced in

the Education Pavilion, with the James P. Storer Conference

Center (designed with tele-video technology), as well as video

rooms, resident carrels and ample conference space.

Unique Programs at Cole Eye Institute

The Center for Genetic Eye Diseases: The Center for Genetic Eye

Diseases provides multidisciplinary clinical diagnostic and

therapeutic services for patients with inherited eye conditions

such as corneal and retinal dystrophies and microphthalmia.

Patients with inherited disorders that involve the eye, such as

neurofibromatosis, albinism, neurodegenerative disorders

and Marfan syndrome, are referred to the Center by physicians

from around the country. A regular specialty clinic is dedicated

to patients with retinal dystrophies and their families.

A National Eye Donor Program: The Foundation Fighting Blind-

ness’ Center, a central collection agency for eyes donated by

individuals across the United States for blindness research,

shares tissue samples with researchers worldwide. Formally

known as the Retinal Degeneration Pathophysiology Facility,

the collection center accepts eye donations after death from

any person of any age who has normal vision or any degree of

vision loss resulting from a retinal-degenerative disease. Cole

Eye Institute staff members prepare a detailed medical report

about each donated eye to help researchers track the effects of

eye disease in different types of people and environments.

For more information or to refer a patient,

please call 216.444.2020 or 800.223.2273 ext. 42020

or visit clevelandclinic.org/OUspecial.

2008 Key Statistics

Total Clinic Visits ......................................... 144,929

Total Surgical Procedures ..................................8,171

Total Surgeries ................................................ 5,215

Total Cataract Procedures ................................. 2,545

Total Cornea Procedures .....................................253

Total Glaucoma Procedures ................................. 341

Total Retina Procedures ....................................3,191

Total Oncology Procedures ............................... 1,062

Total Oculoplastics Procedures .......................... 1,460

Total Strabismus Procedures ................................553

Total Refractive Procedures .............................. 1,498

Total Laser Procedures ..................................... 1,458

Total Intraocular Drug Procedures ...................... 2,248

O U T C O M E S : C R E AT I N G B E N C H M A R K S,

S T R I V I N G F O R I M P R O V E M E N T

Clinical outcomes allow us to understand and objectively measure

the success of our surgical results.

Cole Eye Institute has recently released its 2008 Outcomes

review. This is the third year we have shared our clinical

outcomes with referring physicians, alumni and potential

patients around the country.

Our key evaluatory measures continue to be visual acuity and

the rate of surgical complications, and we continue to use

ETDRS protocol refraction as the means of measuring visual

acuity. The key measurement variables are mentioned under

each section in the book. In addition to clinical outcomes,

world-class customer service is very important to us. Conse-

quently, we have spent significant time understanding patient

flow process and experience. We continue to seek best practice

measurement processes for both clinical and administrative

areas. We strive to set the standard for excellence by innovating

and by consistent follow-up and measurement to evaluate our

overall clinical proficiency.

The Outcomes book has data from across the full spectrum

of ophthalmic surgery, including:

• Cataract surgery

• Cornea surgery

• Glaucoma surgery

• Oculoplastic surgery

• Oncologic eye procedures

• Refractive surgery

• Vitreoretinal surgery

• Strabismus surgery

Almost all of the surgical procedures performed at the Cole Eye

Institute have been tracked and reported. As a regional, national

and international referral center, many of our patients are

followed by their local ophthalmologists, and the data do not

include patients who are not followed at the Cole Eye Institute.

CLEVELAND CLINIC | COLE EYE INSTITUTE | CLEVELANDCLINIC.ORG/OUSPECIAL | INNOVATIONS

The scope of the Cole Eye Institute outcomes project is signifi-

cant, our approach is innovative, and in spite of the complexity of

cases and lack of a clear benchmark, our outcomes are excellent.

Our physicians strive to push the boundaries of science and

technology to provide excellence for our patients. We hope that

by reviewing and analyzing information, we will continue to

improve and offer patients better outcomes.

Cleveland Clinic has created a series of outcomes books

for its institutes. The Outcomes books contain a summary

of our surgical and medical trends and approaches; data

on patient volume and outcomes; and a review of new

technologies and innovations.

To view all our outcomes books, or to download a copy of Cole Eye

Institute’s 2008 Clinical Outcomes book, visit Cleveland Clinic’s

Quality Web site at clevelandclinic.org/quality/outcomes.

19


Staff

IDENTIFYING WHO WE ARE

ARVO Awards Highest Honor to Cole Eye Institute Director of

Ophthalmic Research

Joe G. Hollyfield, PhD, the inaugural Director of Ophthalmic

Research at Cole Eye Institute, has earned the 2009 Proctor

Medal from the Association for Research in Vision and

Ophthalmology (ARVO).

Dr. Hollyfield, who joined Cleveland Clinic in 1995, also is

Professor of Ophthalmology at the Cleveland Clinic Lerner

College of Medicine of Case Western Reserve University and

Director of the Foundation Fighting Blindness Research Center

at the Cole Eye Institute.

He was awarded the prestigious medal for his significantly

advancing the understanding of the cell biology of photoreceptors,

interphotoreceptor matrix and the pigment epithelium.

The Proctor Medal is the oldest and highest award presented by

ARVO to honor an individual for exceptional contributions to

ophthalmology and visual science. The award was established

in 1949 as a memorial to Dr. Francis I. Proctor, an ophthalmologist

who conducted research on the etiology and treatment of

trachoma. The Proctor Medal was the first ophthalmology-related

award to honor both non-clinical and clinical scientists.

N E W C O L E E Y E IN S T I T U T E S TA F F IN 20 0 9

Paul J. Rychwalski, MD, joined Cole Eye

Institute’s Pediatric Ophthalmology and

Strabismus Department in January 2009.

Dr. Rychwalski is a graduate of the

Medical College of Wisconsin. He

completed his residency at the Saint Louis

University School of Medicine, Saint Louis,

Mo., and his fellowship in pediatric ophthalmology and adult

strabismus at the University of Kentucky School of Medicine.

His specialty interests include ocular diseases of children,

strabismus, retinopathy of prematurity, congenital cataracts,

pathogenesis of myopia, amblyopia and shaken

baby syndrome.

He can be reached at rychwap@ccf.org.

CLEVELAND CLINIC | COLE EYE INSTITUTE | CLEVELANDCLINIC.ORG/OUSPECIAL | STAFF

JOE G. HOLLYFIELD, PHD, RECEIVES PRO CTOR MEDAL

Dr. Hollyfield received the award and delivered the Proctor

Award Lecture “Progress in understanding the initiating

events in age-related macular degeneration” at the ARVO

Annual Meeting on May 3-6, 2009.

ARVO was founded in 1928 in Washington, DC, and was

originally named the Association for Research in Ophthalmology

(ARO). The word “vision” was added in 1970 to better reflect

the scientific profile of its members. ARVO’s membership is

comprised of more than 11,500 individuals from multiple

specialties, encompassing both clinical and basic researchers.

Jonathan A. Eisengart, MD, joined Cole

Eye Institute’s Glaucoma staff in July 2009.

Dr. Eisengart received his medical

degree from The Ohio State University,

Columbus, Ohio. He completed his

residency and fellowship in glaucoma

and anterior segment surgery at the

University of Michigan, Kellogg Eye Center, in Ann Arbor, Mich.

His specialty interests include medical, laser and surgical

glaucoma management, including filtering surgery with

antimetabolites, glaucoma tube shunts, cyclodestructive

procedures, combined cataract and glaucoma surgery and

anti-VEGF therapy in glaucoma.

He can be reached at eisengj@ccf.org.

21

22


L E A D E R S H I P R O L E S

ROLES IN PUBLISHING

American Journal of Ophthalmology

Executive Editor, Genetics Section

Elias I. Traboulsi, MD

Executive Editor, Oculoplastic Section

Julian D. Perry, MD

Editorial Board

Peter K. Kaiser, MD


Reviewers/Referees

Peter K. Kaiser, MD

Ronald R. Krueger, MD

Careen Y. Lowder, MD, PhD


Julian D. Perry, MD

Edward J. Rockwood, MD

Andrew P. Schachat, MD


Rishi P. Singh, MD

Steven E. Wilson, MD

Archives of Facial Plastic Surgery

Reviewer/Referee

Julian D. Perry, MD

Archives of Ophthalmology

Reviewers/Referees

William J. Dupps, Jr., MD, PhD

Peter K. Kaiser, MD

Gregory S. Kosmorsky, DO




Julian D. Perry, MD

Paul J. Rychwalski, MD



British Journal of Ophthalmology

Editor-in-Chief (U.S.)

Arun D. Singh, MD

Editorial Board


Reviewers/Referees


Peter K. Kaiser, MD

Rishi P. Singh, MD

Clinical and Experimental Optometry

Reviewer/Referee


Clinical Ophthalmology

Reviewers



Clinical Ophthalmic Oncology

Section Editor

Julian D. Perry, MD

Comprehensive Ophthalmology Update

Reviewer/Referee

Peter K. Kaiser, MD

Contemporary Ophthalmology

Editorial Board


Cornea

Editorial Board


Reviewers/Referees



Current Eye Research

Reviewers/Referees


Peter K. Kaiser, MD

Current Concepts in Retina (Dothen

Healthcare Press, Morristown, N.J.)

Editor-in-Chief

Peter K. Kaiser, MD

Developmental Neuropsychology

Reviewer


Documenta Ophthalmolgica

Editorial Board

Neal S. Peachey, PhD

Experimental Eye Research

Executive Editor, Editor-in-Chief

Joe G. Hollyfield, PhD

Section Editor


Editorial Board

Bela Anand-Apte, MBBS, PhD

John W. Crabb, PhD


Reviewer/Referee




Eye

Reviewer/Referee

Rishi P. Singh, MD


Investigative Ophthalmology

and Visual Science

Editorial Board


Reviewer/Referee



Journal of Cataract & Refractive Surgery

Reviewer


Journal of Glaucoma

Reviewer


Journal of Refractive Surgery

Editorial Board


Reviewer


Ophthalmic Genetics

Editor-in-Chief


Ophthalmology

Editor-in-Chief


Reviewer/Referee




Julian D. Perry, MD


Rishi P. Singh, MD


Optometry & Visual Science

Reviewer/Referee


Pediatric Perspectives

Editorial Board


Proceedings of the National

Academy of Science USA

Reviewer/Referee

John W. Crabb, PhD

23

24


L E A D E R S H I P R O L E S continued

Retina

Editorial Board

Peter K. Kaiser, MD

Reviewer/Referee

Peter K. Kaiser, MD




Rishi P. Singh, MD

Retina Case Reports

Editorial Advisory Board


Retinal Degeneration Symposia

(Springer Publishers)

Co-editor


Retinal Physician

Editorial Board

Peter K. Kaiser, MD

Retina Today

Editorial Board

Peter K. Kaiser, MD

Review of Endocrinology

Editorial Board; Reviewer/Referee

Peter K. Kaiser, MD

Review of Refractive Surgery

Editorial Board


Ryan’s Retina

Editor


Survey of Ophthalmology

Reviewer/Referee


Wiley Interdisciplinary Reviews:

Systems Biology & Medicine

Reviewer/Referee

William J. Dupps, Jr., MD

Xenotransplantation

Reviewer/Referee

William J. Dupps, Jr., MD

LE ADERSHIP ROLES

AT CONFERENCES

World Forum of Ophthalmological

Journal Editors

Co-Chair


2010 Gordon Conference

Conference co-organizer


2010 International Congress of

Eye Research

Cornea Section Organizer


ROLES IN PROFESSIONAL

SOCIETIES AND ORGANIZ ATIONS

American Academy of Ophthalmology

International Council Representative;

Executive Committee Member; Program

Committee Subcommittee Member;

Education Committee Chair


Pre-Academy Retina Subspecialty

Symposium, Planning Committee


Chairman, Self-Assessment Print

Subcommittee; Maintenance of

Certification Education Committee;

LEO Committee, SAC Liason; Breakfast

with the Experts Panel


Board of Trustees


American Association for Pediatric

Ophthalmology and Strabismus

Chair, Website Committee; Membership

and Credentials Committee


American Board of Ophthalmology

Director

David M. Meisler, MD

American Glaucoma Society

Research Committee Expert Panel


American Health Assistance Foundation

Chairman, Macular Degeneration

Review Panel



American Society of Ophthalmic Plastic

and Reconstructive Surgery

Fellowship

Julian D. Perry, MD

American Society of Retina Specialists

Board Member


Case Western University School

of Medicine

Chairman, Annual Fund of the CWRU

School of Medicine; Medical Alumni

Association Board

Allen S. Roth, MD

Cleveland Browns,

National Football League

Team Ophthalmologist

Peter K. Kaiser, MD

Cleveland Cavaliers,

National Basketball Association


Peter K. Kaiser, MD

Board of Directors, Assistant Medial

Director, Chairman of the Medical

Advisory Committee

Allen S. Roth, MD

25

26


L E A D E R S H I P R O L E S continued

Cleveland Indians,

Major League Baseball


Peter K. Kaiser, MD

Cleveland Ophthalmological Society

Bylaws Committee


Educational Committee


Cleveland Sight Center

Board of Trustees


The Eye Care Professional

Advisory Committee


Foundation Fighting Blindness

Scientific Advisory Board,

Cell Biology Committee


GANSU, INC. (Gaining a New

Sight for Unsighted in China)

President, Board of Directors


Heed Ophthalmic Foundation

Heed Award, 2008


The Helen Keller Eye

Research Foundation

Scientific Advisory Board and

Director, External Research


International Society of Refractive

Surgery of the American Academy

of Ophthalmology

Co-sponsorship Subcommittee Chair


Program Planning Committee


Knights Templar Eye Foundation, Inc.

Scientific Advisory Board


National Ophthalmic Genotyping

Network (eyeGENE)

Steering Committee


Pan American Association


Board of Directors


Pan American Society of

Ocular Inflammatory Diseases

President


Society of Heed

Fellows Foundation

Executive Secretary

Froncie A. Gutman, MD

South African Retinitis

Pigmentosa Foundation

Scientific Advisory Board


University of Oklahoma

Medical Sciences Center

COBRE External Advisory Committee,

Department of Ophthalmology


AWARDS & RECOGNITION

American Academy


Lans Distinguished Award

by the ISRS/AAO, 2008


Lifelong Education for the

Ophthalmologist Award, 2008


Best Poster, 2008


American Society of Cataract

and Refractive Surgery

Best Paper Award, Corneal

Crosslinking and Segments Session


American Society of Ophthalmic

Plastic & Reconstructive Surgery

Awards Committee

Julian D. Perry, MD

Association for Research

in Vision in Ophthalmology

Proctor Medal, May 2009


Gold Fellow 2009




Best Doctors in America, 2008




Andreas Marcotty, MD




Stephen E. Wilson, MD

Best Doctors in America:

Midwest Region


Best Doctors in U.S., 2008


Best Doctors in U.S., 2009

Andreas Marcotty, MD

Canadian Ophthalmological Society

Annual W. Bruce Jackson Lecture Award,

Canadian Cornea Society, 2009


Castle Connolly America’s

Top Doctors






Consumers’ Research Council

of America

America’s Top Ophthalmologists


Research to Prevent Blindness

Steinbach Award 2008, 2009

John W. Crabb, PhD

27


Education

HELPING PROFESSIONALS CONTINUE TO DEVELOP

T R A I N I N G T H E L E A D E R S O F T O M O R R O W

RESIDENCY/FELLOWSHIP PROGR AMS

Cleveland Clinic Cole Eye Institute is committed to offering one

of the best residency and fellowship programs in the United

States. These programs are highly competitive and produce

superbly trained clinical and academic ophthalmologists.

RESIDENCY PROGR AM

The Cole Eye Institute Residency Training Program’s mission

is to prepare participants to become leaders in patient care,

teaching and vision research. The program meets all the

requirements of the American Board of Ophthalmology and the

Accreditation Council for Graduate Medical Education (ACGME).

There are 12 residents in the three-year training program, with

four residents who match into the program annually. Residents

rotate among the Institute’s nine departments and a residentrun

clinic at MetroHealth Medical Center, while completing

their board requirements. They work under the direct supervision

of the staff during each rotation in the following areas:

• Cornea, external disease, anterior segment

• Glaucoma

• Neuro-ophthalmology/oncology

• Ophthalmic pathology

• Ophthalmic plastic, reconstructive and orbital surgery

• Pediatric ophthalmology and adult strabismus

• Refractive surgery

• Retina, vitreous, low vision

• Uveitis, ocular inflammatory disease and immunology

This curriculum provides a balanced exposure to all subspecialty

areas of ophthalmology, ensuring graduates the ability

to perform general ophthalmology with skill, knowledge and

confidence. Each resident works in a one-on-one relationship

with a staff physician to provide the best opportunity to study

disease processes and their medical and surgical management.

This arrangement also provides excellent supervision and

optimal continuity of patient care in the outpatient and

hospital settings.

CLEVELAND CLINIC | COLE EYE INSTITUTE | CLEVELANDCLINIC.ORG/OUSPECIAL | EDUCATION

Residents are expected to participate in clinical and basic

research activities utilizing the staff’s expertise. They complete

independent clinical research projects which involve reviewing

the literature, developing a hypothesis and designing and

executing the study. Activities are carefully supervised by an

experienced clinical investigator. Residents are expected to

submit and present their research at national meetings and

to write several papers for publication based on their research

activities. Each June, ophthalmology residents, fellows and

staff participate in the Annual Research, Residents and

Alumni Meeting, a scientific forum for the presentation

of research projects.

Residency Graduates, 6/09

Brian Lee, MD

Thu Pham, MD

Ying Qian, MD

Residents, 1st Year, 7/09

Baseer Ahmad, MD Theodore Pasquali, MD

Eric Ahn, MD Xiang Qi Werdich, MD, PhD

Residents, 2nd Year, 7/09

James Kim, MD, PhD Benjamin Nicholson, MD

Breno Lima, MD Reecha Sachdeva, MD

Residents, 3rd Year, 7/09

Jeffrey Goshe, MD Ahmad Tarabishy, MD

Christopher Hood, MD Mary Beth Turell, MD

29

30


T R A I N I N G T H E L E A D E R S O F T O M O R R O W continued

FELLOWSHIP PROGR AM

Cleveland Clinic Cole Eye Institute also offers high-quality

fellowship training opportunities in a variety of subspecialties.

These fellowships train the next generation of academic leaders

in the respective fields by combining an excellent academic

environment with mentorship support in a state-of-the-art

eye care facility.

Our fellowships include:

• 2-year vitreoretinal fellowship

(slots rotate — even years = 1, uneven years = 2)

• 1-year cornea, external disease and refractive surgery

fellowship (2 slots)

• 1-year glaucoma fellowship (1 slot)

• 1-year pediatric-ophthalmology fellowship (1 slot)

• 2-year oculoplastics fellowship (sponsored by ASOPRS) (1 slot)

For more information about Cole Eye Institute fellowship

programs, visit clevelandclinic.org/eyefellowships or

contact Jane Sardelle at sardelj@ccf.org.

Fellow Graduates, 6/09

Vitreoretinal Fellows

Hajir Dadgostar, MD

Mehran Taban, MD

Cornea, External Disease and Refractive Surgery Fellow

Andrew Esposito, MD

Ricardo Sepulveda, MD

Glaucoma Fellow

Samantha Chai, MD

Pediatric Ophthalmology Fellow

Michelle Ariss, MD

Fellows, 7/09

Vitreoretinal Fellows

Omar Ahmad, MD

Nathan Steinle, MD

Cornea, External Disease & Refractive Surgery

Hooman Harooni, MD

Ravindrah Shah, MD

G R A N D R O U N D S

Cole Eye Institute hosts Grand Rounds every Monday from 7

to 8 a.m. during the academic year (except holidays and major

meeting times). For the academic year 2009-2010, meetings

will begin in mid-September, and run through mid-June. The

meetings are designed for residents, fellows and staff physicians

of the Cole Eye Institute, as well as other comprehensive

and subspecialty ophthalmologists. We are pleased to offer

Category 1 continuing education credits for each meeting.

Evaluations are offered online following each meeting and

attendance certificates can be printed or saved for your

record-keeping purposes.

The Grand Rounds’ forum consists of two clinical cases

presented by Cole Eye Institute residents, followed by

extensive discussion. Cases selected for presentation

represent outstanding teaching examples and are either

difficult-to-manage cases, unusual presentations of common

disorders, rare conditions or cases that highlight state-of-theart

diagnosis or management. In addition, approximately

every six weeks, M&M cases are presented and discussed

by third-year residents with follow-up discussion.

The meetings are held the James P. Storer Conference Room

the first floor of the Cole Eye Institute and registration is not

required to attend. Park in the patient/visitor lot at E. 102nd

Street (facing the front of the Cole Eye Institute), or the patient/

visitors garage at E. 100th Street and Carnegie Avenue. Parking

tickets will be validated.

For questions, email Jane Sardelle at sardelj@ccf.org.


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D I S T I N G U I S H E D L E C T U R E S E R I E S

The Cleveland Clinic Cole Eye Institute is proud to present the

2009 Distinguished Lecture Series, which provides a forum for

renowned researchers in the visual sciences to present their

latest research findings. This series of lectures will feature

advances in many areas of ophthalmic research presented by

noted basic and clinical scientists from throughout the world.

Ample opportunity for questions and answers will be provided.

September 17, 2009

NEW INSIGHTS INTO THE MOLECUL AR

AND CELLUL AR REGUL ATION OF

CORNE AL IMMUNIT Y

Reza Dana, MD, MPH, MSc

Director of Cornea and Refractive Surgery Services

Massachusetts Eye & Ear Infirmary

Professor and Senior Scientist, Harvard Medical School

W. Clement Stone Scholar & Director of the Corneal Immunology

Lab Schepens Eye Research Institute

Director, Harvard-Vision Clinical Scientist Development Program

Boston

October 15, 2009

ROLE OF VEGF IN BLOOD VESSEL

GROW TH AND STABILIT Y IMPLICATIONS

FOR ANTI-ANGIOGENIC THER APIES

Patricia A. D’Amore, PhD

Senior Scientist

Ankeny Scholar of Retinal Molecular Biology

Professor, Harvard Medical School

The Schepens Eye Research Institute

Boston

Please join us for these insights into ophthalmic research

and the promises they hold for patient care. No registration

is required; call 216.444.5832 with any questions.

All programs will be held in the James P. Storer Conference

Center of the Cole Eye Institute from 7 to 8 a.m. Attendees

should park in the East 102nd Street parking lot (facing the

front of the Cole Eye Institute) or the visitor’s parking garage

at East 100th Street and Carnegie Avenue. We will validate

your parking ticket.

November 19, 2009

EMERGING CONCEPTS IN UVE AL MEL ANOMA

Hans E. Grossniklaus, MD, MBA

F. Phinizy Calhoun Jr. Professor of Ophthalmology

Director, L.F. Montgomery Pathology Laboratory

Vice-Chairman, Department of Ophthalmology

Emory Eye Center

Emory University

Atlanta, Ga.


P R O G R A M S I N O P H T H A L M I C E D U C AT I O N 2 0 0 9 -2 010

Physicians are invited to attend the following ophthalmic

continuing medical education courses at Cleveland Clinic’s

Cole Eye Institute. For more information, contact Jane Sardelle,

program coordinator, at 216.444.2010 or 800.223.2273, ext.

42010, or sardelj@ccf.org.

COMPREHENSIVE OPHTHALMOLOGY UPDATE

December 5, 2009

Location: Cole Eye Institute

UVEITIS UPDATE

March 6, 2010


NORTH COAST VITREORETINAL COURSE

May 22, 2010


ANNUAL RESEARCH, RESIDENTS & ALUMNI MEETING

June 19, 2010


33


Research

PURSUING ANSWERS

C L I N I C A L T R I A L S

The following studies are currently enrolling. All studies have

been approved by the Institutional Review Board.

AGE-RELATED MACULAR DEGENERATION

A Phase I Open-label, Dose Escalation Trial of REDD14NP

Delivered by a Single Intravitreal Injection to Patients with

Choroidal Neovascularization Secondary to Exudative

Age-related Macular Degeneration (QUARK)

Objective: This is an open-label, dose-escalation study in which

patents will receive a single intravitreal injection of REDD14NP.

The primary objective of the study is to determine the safety

and pharmacokinetics of REDD14NP when administered as

a single intravitreal injection.

Contact: Peter K. Kaiser, MD, 216.444.6702 or Lynn Bartko, RN,

216.444.7137

A Randomized, Double Masked, Active Controlled Phase III

Study of the Efficacy, Safety and Tolerability of Repeated

Doses of Intravitreal VEGF Trap in Subjects with Neovascular

Age-Related Macular Degeneration (VEGF Trap)

Objective: This study is a Phase III, double-masked, randomized,

study of the efficacy and safety of VEGF Trap-Eye in

patients with neovascular age-related macular degeneration.

Contact: Peter K. Kaiser, MD, 216.444.6702 or Laura Holody,

216.445.2264

CLEVELAND CLINIC | COLE EYE INSTITUTE | CLEVELANDCLINIC.ORG/OUSPECIAL | RESEARCH

RETINAL VEIN OCCLUSION

An Open-Label, Multicenter Extension Study To Evaluate

the Safety and Tolerability of Ranibizumab in Subjects with

Macular Edema Secondary to Retinal Vein Occlusion (RVO)

Who Have Completed a Genentech-sponsored Ranibizumab

Study (HORIZON 2)

Objective: This is an open-label, multicenter extension study

of intravitreally administered ranibizumab in subjects with

macular edema secondary to RVO who have completed the

six-month treatment and six-month observation phases (12

months total) of a Genentech-sponsored study (FVF4165g or

FVF4166g).

Contact: Rishi P. Singh, MD, 216.445.9497 or Gail Kolin, RN,

216.445.4086

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C L I N I C A L T R I A L S continued

DIABETIC RETINOPATHY

Vascular Remodeling and Effects of Angiogenic Inhibition in

Diabetic Retinopathy (NIH)

Objective: This study will test whether the pattern of the retinal

vasculature changes in patients with different levels of diabetic

retinopathy can be quantified using computerized image

analysis. In addition, the study will evaluate whether new

drugs to treat diabetic retinopathy will be able to reverse these

vascular changes.

Contact: Peter K. Kaiser, MD, 216.444.6702 or Ly Pung, RN,

216.445.6497

UVEITIS

A Prospective, Multicenter, Randomized, Double-Masked,

Safety, Tolerability and Efficacy Study of Four Iontophoretic

Doses of Dexamethasone Phosphate Ophthalmic Solution

in Patients with Non-Infectious Acute Anterior Segment

Uveitis (EYEGATE)

Objective: The purpose of this Phase II study is to define a safe

and effective dose of iontophoretic delivery of dexamethasone

phosphate ophthalmic solution using the EyeGate ® II Drug

Delivery System in patients with non-infectious acute anterior

segment uveitis.

Contact: Careen Lowder, MD, PhD, 216.444.3642 or Ly Pung, RN,

216.445.6497

An Open-Label, Multicenter, Phase II Trial of Adalimumab

(Humira ® ) in the Treatment of Refractory Non-infectious

Uveitis (HUMIRA)

Objective: This study will assess the safety and efficacy

of adalimumab, a humanized monoclonal antibody,

against TNF-α (Abbott) in the treatment of refractory,

vision-threatening, non-infectious uveitis.

Contact: Careen Lowder, MD, PhD, 216.444.3642 or Laura Holody,

216.445.2264

PEDIATRIC EYE DISEASE

Infant Aphakia Treatment Study (IATS)

Objective: The primary purpose of this study is to determine

whether infants with a unilateral congenital cataract are more

likely to develop better vision following cataract extraction

surgery if they undergo primary implantation of an intraocular

lens or if they are treated primarily with a contact lens. In

addition, the study will compare the occurrence of postoperative

complications and the degree of parental stress between

the two treatments.

Contact: Elias Traboulsi, MD, 216.444.4363 or Sue Crowe, RN,

216.445.3840

GENETICS

Studies of the Molecular Genetics of Eye Diseases (BRTT)

Objective: The objective of this project is to study the molecular

genetics of ophthalmic disorders through the compilation of a

collection of DNA, plasma and eye tissue samples from patients

and from families with a broad range of eye diseases and

malformations.

Contact: Elias Traboulsi, MD, 216.444.4363 or Patrice Nerone, RN,

216.445.9886

CORNEA /REFRACTIVE SURGERY

A Clinical Safety and Efficacy Comparison of Nevanac ® 0.1% to

Vehicle Following Cataract Surgery in Diabetic Retinopathy

Patients (NEVANAC)

Objective: The purpose of this study is to determine whether

Nepafenac is safe and effective for reducing the incidence

of macular edema following cataract surgery in diabetic

retinopathy patients.

Contact: Richard Gans, MD, 216.444.0848 or Gail Kolin, RN,

216.445.4086


IN FOLLOWUP

The following studies have completed patient enrollment

in the last year at Cole Eye Institute and are in

follow up:

• A 24-month Randomized, Double-masked, Controlled,

Multicenter, Phase IIIB study Assessing

Safety and Efficacy of Verteporfin (Visudyne ® )

Photodynamic Therapy Administered in Conjunction

with Ranibizumab (Lucentis ® ) versus Ranibizumab

(Lucentis ® ) Monotherapy in Patients with Subfoveal

Choroidal Neovascularization Secondary to Agerelated

Macular Degeneration (DENALI)

• A Phase III, Multicenter, Randomized,

Sham-Controlled Study of the Efficacy and

Safety of Ranibizumab Compared with Sham

in Subjects with Macular Edema Secondary to

Central Retinal Vein Occlusion (CRVO)

• A Phase III, Double-Masked, Multicenter, Randomized,

Sham-Controlled Study of the Efficacy and

Safety of Ranibizumab Injection in Subjects with

Clinically Significant Macular Edema with Center

Involvement Secondary to Diabetes Mellitus (DME)

• An 8-Week, Multicenter, Masked, Randomized Trial

to Assess the Safety and Efficacy of 700 µg and 350 µg

Dexamethasone Posterior Segment Drug Delivery

System Applicator System Compared with Sham

DEX PS DDS Applicator System in the Treatment of

Non-Infectious Ocular Inflammation of the Posterior

Segment in Patients with Intermediate Uveitis

(POSURDEX UVEITIS)

• Posterior Lamellar Endothelial Keratoplasty Study

(PLEK)

• US Clinical Study of the ACRYSOF Angle-Supported

Phakic IOL

• A 2-year, Multicenter, Randomized, Controlled,

Masked, Dose-finding Trial to Assess the Safety and

Efficacy of Multiple Intravitreal Injections of AGN

211745 in Patients with Subfoveal Choroidal

Neovascularization Secondary to Age-related

Macular Degeneration (SIRIUS)

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G R A N T S

GUND FOUNDATION SUPPORTS CHAIR FOR

CLE VEL AND CLINIC E YE RESE ARCH

Cleveland Clinic has received a $2 million gift from the Llura

and Gordon Gund Foundation to expand research into retinal

diseases that cause vision loss and blindness.

The gift establishes the Llura and Gordon Gund Endowed Chair

for Ophthalmology Research. Joe G. Hollyfield, PhD, will be the

inaugural chair holder. Dr. Hollyfield is director of research at

Cole Eye Institute, which has current research grant awards

totaling $22 million.

“Dr. Hollyfield has made extraordinary contributions to the field

of retinal disease research and Llura and I are pleased to support

continued study of these causes of vision loss,” says Mr. Gund.

Mr. Gund, a Cleveland native, is chairman of Gund Investment

Corporation and was past majority owner of the National

Basketball Association’s Cleveland Cavaliers. He was diagnosed

as a young adult with retinitis pigmentosa. Mr. Gund has

experienced blindness since 1970.

Dr. Hollyfield is known for his research of cell and developmental

biology of the retina in both normal and degenerative

tissues. He is currently Editor-in-Chief of the journal, Experimental

Eye Research, and serves on the scientific advisory board

of the Foundation Fighting Blindness, a national nonprofit

organization founded by a group including Llura and Gordon

Gund, and where Mr. Gund is board chairman.

“Joe leads a sophisticated research group which is at the

forefront of investigation of retinal disease. This gift will

provide resources to expand our inquiry into causes and

potential treatment options for eye conditions which cause

vision loss and blindness,” said Daniel F. Martin, MD,

Chairman of the Cole Eye Institute.

PRE VENT BLINDNESS OHIO

Prevent Blindness Ohio has awarded a fellowship grant to Rao

Fu, Cole Eye Institute, through its Young Investigators Student

Fellowship Award for Female Scholars in Vision Research. This

program encourages female scientists at the beginning of their

careers to pursue vision research that can contribute toward the

early detection and treatment discoveries that will be needed to

curb the growth of vision loss in Ohio. Fu is conducting research

that has the potential for significantly impacting an important,

but poorly understood aspect of photoreceptor biology relevant

to human retinal disease, including retinitis pigmentosa.

Results could ultimately lead to the discovery of new approaches

for the detection, prevention, and treatment of vision loss.

Cole Eye Institute Research Funding Sources

Industry

23%

Non-Profit

24%

State 3%

Federal

50%

Cleveland Clinic Cole Eye Institute had an aggregate annual grant

level of $22,298,900 in 2009*, with $12,444,277 coming from

Cole Eye Basic Research Funding

federal sources. As part of this funding, Cole Eye Institute

researchers received the institute’s first endowed chair for

ophthalmic research.

Title Source Sponsor ID Investigator

Role of TIMP-3 in

Ocular Neovascularization

Inhibition of VEGF Mediated

Angiogenesis by TIMP-3

Age-related Changes in

Epithelia Microvilli

Proteomic Studies of Age Related

Macular Degeneration

Federal NIH EY016490 Bela Anand-Apte, MBBS, PhD

Federal NIH CA106415 Bela Anand-Apte, MBBS, PhD

Federal NIH EY07153 Vera Bonilha, PhD

Federal NIH EY014239 John W. Crabb, PhD

Role of TULP1 in Photoreceptor Cells Federal NIH EY016072 Stephanie Hagstrom, PhD

Initiating Events in AMD:

An Animal Model for the Human

Corneal Epithelial Growth Factors

and Receptors

Can CD 133 Cells prevents hypoxia

driven retinal neovascularization in

a rodent model?

Analysis of Neural Retina

Transport Function

Study of Retinal

Degenerative Diseases

Federal NIH R56 EY014240 Joe G. Hollyfield, PhD

Federal NIH EY010056 Steven E. Wilson, MD

Federal

sub-award

Federal

sub-award

NIH EY018784 Bela Anand-Apte, MBBS, PhD

NIH EY012830 Neal S. Peachey, PhD

Non-Profit Foundation for

Fighting Blindness

Lew Wasserman Award Non-Profit Research to

Prevent Blindness

Identification of Biomarkers Non-Profit Ruth & Milton

Steinbach Foundation

RPB Unrestricted Grant Non-Profit Research to Prevent

Blindness

The Role of Complement Regulation in

Maintaining Outer Retinal Integrity

Stimulating Retina Development During

Phase I of Retinopathy of Prematurity

* through June 2009


Non-Profit American Health

Assistance Foundation

Non-Profit Knights Templar

Eye Foundation

CMM-0707-0407;

CMM-0707-0408;

CMM-0707-0409;

CMM-0707-0410

Joe G. Hollyfield, PhD;

John W. Crabb, PhD;

Stephanie A. Hagstrom, PhD;


Bela Anand-Apte, MBBS, PhD

John W. Crabb, PhD



Jonathan Sears, MD

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P U B L I C AT I O N S

Journal Publications

Ahuja Y, Kohl S, Traboulsi EI. CNGA3 mutations in two United

Arab Emirates families with achromatopsia. Mol Vis.

2008;14:1293-1297.

Ambrosio R, Jr., Tervo T, Wilson SE. LASIK-associated dry

eye and neurotrophic epitheliopathy: pathophysiology and

strategies for prevention and treatment. J Refract Surg. 2008

Apr;24(4):396-407.

Applegate RA, Krueger RR. Introduction to the proceedings of

the 9th International Congress of Wavefront and Presbyopic

Refractive Corrections. J Refract Surg. 2008 Nov;24(9):963-964.

Asbell PA, Colby KA, Deng S, McDonnell P, Meisler DM,

Raizman MB, Sheppard JD, Jr., Sahm DF. Ocular TRUST:

nationwide antimicrobial susceptibility patterns in ocular

isolates. Am J Ophthalmol. 2008 Jun;145(6):951-958.

Bollinger KE, Langston RHS. What can patients expect from

cataract surgery? Cleve Clin J Med. 2008 Mar;75(3):193-200.

Bollinger KE, Kattouf V, Arthur B, Weiss AH, Kivlin J, Kerr N,

West CE, Kipp M, Traboulsi EI. Hypermetropia and esotropia

in myotonic dystrophy. J AAPOS. 2008 Feb;12(1):69-71.

Callanan DG, Jaffe GJ, Martin DF, Pearson PA, Comstock TL.

Treatment of posterior uveitis with a fluocinolone acetonide

implant: three-year clinical trial results. Arch Ophthalmol.

2008 Sep;126(9):1191-1201.

Chappelow AV, Reid J, Parikh S, Traboulsi EI. Aicardi syndrome

in a genotypic male. Ophthalmic Genet. 2008 Dec;29(4):181-183.

Chappelow AV, Kaiser PK. Neovascular age-related macular

degeneration: potential therapies. Drugs. 2008;68(8):1029-1036.

Chappelow AV, Singh AD, Perez VL, Lichtin A, Pohlman B,

Macklis R. Bilateral panocular involvement with mantle-cell

lymphoma. J Clin Oncol. 2008 Mar 1;26(7):1167.

Charkoudian LD, Gower EW, Solomon SD, Schachat AP, Bressler

NM, Bressler SB. Vitamin usage patterns in the prevention of

advanced age-related macular degeneration. Ophthalmology.

2008 Jun;115(6):1032-1038.e4.

Cohen VML, Sweetenham J, Singh AD. Ocular adnexal

lymphoma: What is the evidence for an infectious aetiology?

Br J Ophthalmol. 2008 Apr;92(4):446-448.

Dadgostar H, Waheed N. The evolving role of vascular endothelial

growth factor inhibitors in the treatment of neovascular

age-related macular degeneration. Eye. 2008 Jun;22(6):761-767.

de Medeiros FW, Mohan RR, Suto C, Sinha S, Bonilha VL,

Chaurasia SS, Wilson SE. Haze development after photorefractive

keratectomy: mechanical vs ethanol epithelial removal in

rabbits. J Refract Surg. 2008 Nov;24(9):923-927.

Doyle V, Schachat AP. Increased transparency: making the journal

better for readers and for authors. Ophthalmology. 2008

Sep;115(9):1443-1444.

Dua HS, Singh AD. The British Journal of Ophthalmology.

At a glance. Br J Ophthalmol. 2008 Jul;92(7):869.

Dupps WJ, Jr., Qian Y, Meisler DM. Multivariate model of

refractive shift in Descemet-stripping automated endothelial

keratoplasty. J Cataract Refract Surg. 2008 Apr;34(4):578-584.

Fu EX, Kosmorsky GS, Traboulsi EI. Giant intracavernous

carotid aneurysm presenting as isolated sixth nerve palsy in

an infant. Br J Ophthalmol. 2008 Apr;92(4):576-577.

Fuller ML, Sweetenham J, Schoenfield L, Singh AD. Uveal

lymphoma: a variant of ocular adnexal lymphoma. Leuk

Lymphoma. 2008 Dec;49(12):2393-2397.

Galor A, Lowder CY, Kaiser PK, Perez VL, Sears JE. Surgical

drainage of chronic serous retinal detachment associated with

uveitis. Retina. 2008 Feb;28(2):282-288.


Gorovoy MS, Meisler DM, Dupps WJ, Jr. Late repeat Descemetstripping

automated endothelial keratoplasty. Cornea. 2008

Feb;27(2):238-240.

Grant LW, Anderson C, Macklis RM, Singh AD. Low dose

irradiation for diffuse choroidal hemangioma. Ophthalmic

Genet. 2008 Dec;29(4):186-188.

Gupta OP, Ho AC, Kaiser PK, Regillo CD, Chen S, Dyer DS, Dugel

PU, Gupta S, Pollack JS. Short-term outcomes of 23-gauge pars

plana vitrectomy. Am J Ophthalmol. 2008 Aug;146(2):193-197.

Heur M, Costin B, Crowe S, Grimm RA, Moran R, Svensson LG,

Traboulsi EI. The value of keratometry and central corneal

thickness measurements in the clinical diagnosis of marfan

syndrome. Am J Ophthalmol. 2008 Jun;145(6):997-1001.e1.

Iseli HP, Spoerl E, Wiedemann P, Krueger RR, Seiler T. Efficacy

and safety of blue-light scleral cross-linking. J Refract Surg.

2008 Sep;24(7):S752-S755.

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P U B L I C AT I O N S continued

Jeng BH, Marcotty A, Traboulsi EI. Descemet stripping automated

endothelial keratoplasty in a 2-year-old child. J AAPOS.

2008 Jun;12(3):317-318.

Jeng BH, Dupps WJ, Jr., Meisler DM, Schoenfield L. Epithelial

debridement for the treatment of epithelial basement membrane

abnormalities coincident with endothelial disorders.

Cornea. 2008 Dec;27(10):1207-1211.

Jeng BH, Galor A, Lee MS, Meisler DM, Hollyfield JG, Schoenfield

L, McMahon JT, Langston RHS. Amantadine-associated

corneal edema potentially irreversible even after cessation of

the medication. Ophthalmology. 2008 Sep;115(9):1540-1544.

Kaiser PK. Ranibizumab: The evidence of its therapeutic value in

neovascular age-related macular degeneration. Core Evidence.

2008;2(4):273-294.

Keeler R, Singh AD, Dua HS. Anatomical eye model.

Br J Ophthalmol. 2008 Sep;92(9):1179.

Keeler R, Singh A, Dua H. Focimeter. Br J Ophthalmol. 2008

May;92(5):593.

Kim SJ, Lo WR, Hubbard GB, III, Srivastava SK, Denny JP,

Martin DF, Yan J, Bergstrom CS, Cribbs BE, Schwent BJ,

Aaberg TM, Sr. Topical ketorolac in vitreoretinal surgery: a

prospective, randomized, placebo-controlled, double-masked

trial. Arch Ophthalmol. 2008 Sep;126(9):1203-1208.

Koenig SB, Meisler DM, Dupps WJ, Rubenstein JB, Kumar R.

External refinement of the donor lenticule position during

Descemet’s stripping and automated endothelial keratoplasty.

Ophthalmic Surg Lasers Imaging. 2008 Nov;39(6):522-523.

Kosmorsky GS, Dupps WJ, Jr., Drake RL. Nonuniform pressure

generation in the optic chiasm may explain bitemporal

hemianopsia. Ophthalmology. 2008 Mar;115(3):560-565.

Kovoor TA, Bahl D, Singh AD, Ufret-Vincenty R. Bilateral

isolated choroidal melanocytosis. Br J Ophthalmol. 2008

Jul;92(7):892, 1008.

Krueger RR, Ramos-Esteban JC, Kanellopoulos AJ. Staged

intrastromal delivery of riboflavin with UVA cross-linking in

advanced bullous keratopathy: laboratory investigation and

first clinical case. J Refract Surg. 2008 Sep;24(7):S730-S736.

Krueger RR, Trattler W, Yee R. Introduction to the proceedings of

the Sixth International Congress on Advanced Surface Ablation

& SBK. J Refract Surg. 2008 Jan;24(1):S55-S56.

Krueger RR. September consultation # 4. J Cataract Refract Surg.

2008 Sep;34(9):1430-1431.

Krueger RR, Mrochen M. Introduction to the proceedings of

the Third International Congress of Corneal Cross-Linking.

J Refract Surg. 2008 Sep;24(7):S713-S714.

Krueger RR, Rocha KM. Introduction to wavefront-optimized,

wavefront-guided, and topography-guided customized

ablation: fifth year in review. J Refract Surg. 2008

Apr;24(4):S417-S418.

Krueger RR, Thornton IL, Xu M, Bor Z, van den Berg TJTP.

Rainbow glare as an optical side effect of IntraLASIK.

Ophthalmology. 2008 Jul;115(7):1187-1195.e1.

Kutz WE, Wang LW, Dagoneau N, Odrcic KJ, Cormier-Daire V,

Traboulsi EI, Apte SS. Functional analysis of an ADAMTS10

signal peptide mutation in Weill-Marchesani syndrome

demonstrates a long-range effect on secretion of the full-length

enzyme. Hum Mutat. 2008 Dec;29(12):1425-1434.

Lee BJ, Jeng BH, Singh AD. OCT and ultrasound biomicroscopic

findings in iris arteriovenous malformation. Ophthalmic Surg

Lasers Imaging. 2008 Sep;39(5):426-428.

Lee BJ, Traboulsi EI. Update on the morning glory disc anomaly.

Ophthalmic Genet. 2008 Jun;29(2):47-52.

Lee MS, Kosmorsky GS, Cook JR, Barton JJS, Briemberg HR.

My, what asthenia you have. Surv Ophthalmol. 2008

Sep;53(5):506-511.

Lewis C, Traboulsi EI. Use of Tegaderm for postoperative eye

dressing in children. J AAPOS. 2008 Aug;12(4):420.

Li Y, Meisler DM, Tang M, Lu ATH, Thakrar V, Reiser BJ, Huang

D. Keratoconus diagnosis with optical coherence tomography

pachymetry mapping. Ophthalmology. 2008

Dec;115(12):2159-2166.

Liesegang TJ, Albert DM, Schachat AP. Not for your eyes:

information concealed through publication bias. Am J

Ophthalmol. 2008 Nov;146(5):638-640.


Liesegang TJ, Albert DM, Schachat AP. How to ensure

our readers’ trust: the proper attribution of authors and

contributors. Am J Ophthalmol. 2008 Sep;146(3):337-340.

Lin DTC, Holland SR, Rocha KM, Krueger RR. Method for

optimizing topography-guided ablation of highly aberrated eyes

with the ALLEGRETTO WAVE Excimer Laser. J Refract Surg.

2008 Apr;24(4):S439-S445.

Loddenkemper T, Friedman NR, Ruggieri PM, Marcotty A,

Sears J, Traboulsi EI. Pituitary stalk duplication in association

with moya moya disease and bilateral morning glory disc

anomaly - broadening the clinical spectrum of midline defects.

J Neurol. 2008 Jun;255(6):885-890.

Margolis R, Singh RP, Bhatnagar P, Kaiser PK. Intravitreal

triamcinolone as adjunctive treatment to laser panretinal

photocoagulation for concomitant proliferative diabetic

retinopathy and clinically significant macular edema.

Acta Ophthalmol Scand. 2008 Feb;86(1):105-110.

McKay TL, Gedeon DJ, Vickerman MB, Hylton AG, Ribita D, Olar

HH, Kaiser PK, Parsons-Wingerter P. Selective inhibition of

angiogenesis in small blood vessels and decrease in vessel

diameter throughout the vascular tree by triamcinolone

acetonide. Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1184-1190.

Mohan RR, Stapleton WM, Sinha S, Netto MV, Wilson SE. A

novel method for generating corneal haze in anterior stroma

of the mouse eye with the excimer laser. Exp Eye Res. 2008

Feb;86(2):235-240.

Nehemy MB, Zisman M, Marigo FA, Nehemy PG, Schachat AP.

Ultrasound biomicroscopy after vitrectomy in eyes with normal

intraocular pressure and in eyes with chronic hypotony. Eur J

Ophthalmol. 2008 Jul;18(4):614-618.

Netto MV, Barreto J, Jr., Santo R, Bechara S, Kara-Jose N, Wilson

SE. Synergistic effect of ethanol and mitomycin C on corneal

stroma. J Refract Surg. 2008 Jun;24(6):626-632.

Nolan WP, See JL, Aung T, Friedman DS, Chan YH, Smith SD,

Zheng C, Huang D, Foster PJ, Chew PTK. Changes in angle

configuration after phacoemulsification measured by anterior

segment optical coherence tomography. J Glaucoma. 2008

Sep;17(6):455-459.

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44



Otri AM, Singh AD, Dua HS. Cover illustration. Abu Bakr Razi.

Br J Ophthalmol. 2008 Oct;92(10):1324.

Perry JD. Periocular reflation creates better facial rejuvenating

effect. Ocular Surgery News. 2008 Apr 10;(Suppl):32-35.

Qian Y, Zakov ZN, Schoenfield L, Singh AD. Iris melanoma

arising in iris nevus in oculo(dermal) melanocytosis. Surv

Ophthalmol. 2008 Jul;53(4):411-415.

Ramos-Esteban JC, Bamba S, Krueger RR. Tracking difficulties

after femtosecond laser flap creation with the LADARVision

excimer laser system. J Refract Surg. 2008 Nov;24(9):953-956.

Renganathan K, Ebrahem Q, Vasanji A, Gu X, Lu L, Sears J,

Salomon RG, Anand-Apte B, Crabb JW. Carboxyethylpyrrole

adducts, age-related macular degeneration and neovascularization.

Adv Exp Med Biol. 2008;613:261-267.

Rocha KM, Ramos-Esteban JC, Qian Y, Herekar S, Krueger RR.

Comparative study of riboflavin-UVA cross-linking and

“flash-linking” using surface wave elastometry. J Refract Surg.

2008 Sep;24(7):S748-S751.

Sautter NB, Citardi MJ, Perry J, Batra PS. Paranasal sinus

mucoceles with skull-base and/or orbital erosion: Is the

endoscopic approach sufficient? Otolaryngol Head Neck Surg.

2008 Oct;139(4):570-574.

Sayanagi K, Sharma S, Kaiser PK. Spectral domain optical

coherence tomography and fundus autofluorescence findings

in pseudoxanthoma elasticum. Ophthalmic Surg Lasers

Imaging. 2008 Jul-Aug;39(4 Suppl):S108-S110.

Schachat AP. A new look at an old treatment for diabetic macular

edema. Ophthalmology. 2008 Sep;115(9):1445-1446.

Sears JE. Anti-vascular endothelial growth factor and retinopathy

of prematurity. Br J Ophthalmol. 2008 Nov;92(11):1437-1438.

Singh AD, Schachat AP, Diener-West M, Reynolds SM. Small

choroidal melanoma. Ophthalmology. 2008 Dec;115(12):2319.

Singh AD, Triozzi PL. Endoresection for choroidal melanoma:

palliative or curative intent? Br J Ophthalmol. 2008

Aug;92(8):1015-1016.

Singh AD, Kivela T, Seregard S, Robertson D, Bena JF. Primary

transpupillary thermotherapy of “small” choroidal melanoma:

is it safe? Br J Ophthalmol. 2008 Jun;92(6):727-728.

Singh RP, Bando H, Brasil OFM, Williams DR, Kaiser PK.

Evaluation of wound closure using different incision techniques

with 23-gauge and 25-gauge microincision vitrectomy systems.

Retina. 2008 Feb;28(2):242-248.

Stapleton WM, Chaurasia SS, Medeiros FW, Mohan RR, Sinha S,

Wilson SE. Topical interleukin-1 receptor antagonist inhibits

inflammatory cell infiltration into the cornea. Exp Eye Res.

2008 May;86(5):753-757.

Taban M, Taban M, Perry JD. Lower eyelid position after

transconjunctival lower blepharoplasty with versus without a

skin pinch. Ophthal Plast Reconstr Surg. 2008 Jan-Feb;24(1):7-9.

Taban M, Ventura AACM, Sharma S, Kaiser PK. Dynamic

evaluation of sutureless vitrectomy wounds: an optical

coherence tomography and histopathology study.

Ophthalmology. 2008 Dec;115(12):2221-2228.

Taban M, Taban M, Sears JE. Ocular findings following trauma

from paintball sports. Eye. 2008 Jul;22(7):930-934.

Taban M, Lowder CY, Hajj-Ali R, Singh AD. Anterior scleritis as

the presenting sign of metastatic lung cancer. Br J Ophthalmol.

2008 Jan;92(1):147.

Thornton I, Xu M, Krueger RR. Comparison of standard (0.02%)

and low dose (0.002%) mitomycin in the prevention of corneal

haze following surface ablation for myopia. J Refract Surg.

2008 Jan;24(1):S68-S76.

Traboulsi EI. Reply [Congenital cranial dysinnervation disorders/

syndrome]. J AAPOS. 2008 Aug;12(4):421.

Traboulsi EI, Ellison J, Sears J, Maumenee IH, Avallone J,

Mohney BG. Aniridia with preserved visual function: A report of

four cases with no mutations in PAX6. Am J Ophthalmol. 2008

Apr;145(4):760-764.

Traboulsi EI, Sarfarazi M. The use of microarray technology

in deciphering the cause of genetic eye diseases: LOXL1 and

exfoliation syndrome. Am J Ophthalmol. 2008

Mar;145(3):391-393.


Triozzi PL, Eng C, Singh AD. Targeted therapy for uveal

melanoma. Cancer Treat Rev. 2008 May;34(3):247-258.

Utz VM, Krueger RR. Management of irregular astigmatism

following rotationally disoriented free cap after LASIK. J Refract

Surg. 2008 Apr;24(4):383-391.

Vasconcelos-Santos DV, Nehemy PG, Schachat AP, Nehemy MB.

Secondary ocular hypertension after intravitreal injection of

4 mg of triamcinolone acetonide: incidence and risk factors.

Retina. 2008 Apr;28(4):573-580.

Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, Karkera J,

Mahurkar S, Lisch W, Dupps WJ, Jr., White PS, Winters RS,

Kim C, Rapuano CJ, Sutphin J, Reidy J, Hu FR, Lu DW,

Ebenezer N, Nickerson ML. Genetic analysis of 14 families with

Schnyder crystalline corneal dystrophy reveals clues to UBIAD1

protein function. Am J Med Genet A. 2008 Feb 1;146(3):271-283.

Wilkinson DA, Kolar M, Fleming PA, Singh AD. Dosimetric

comparison of 106Ru and 125I plaques for treatment of shallow

(

46



Book Chapters

AGE-REL ATED MACUL AR DEGENER ATION

Singh RP, Chung JY, Kaiser PK. Fundus autofluorescence in

age-related macular degeneration. In: Lim JI, ed. Age-related

macular degeneration. 2nd ed. New York, NY: Informa

Healthcare; 2008. Chapter 12. p. 191-202.

ALBERT & JAKOBIEC’S PRINCIPLES

AND PR ACTICE OF OPHTHALMOLOGY

Chalita MR, Krueger RR. Wavefront-guided excimer laser

surgery. In: Albert DM, ed. Albert & Jakobiec’s principles and

practice of ophthalmology. 3rd ed. Philadelphia, PA: Saunders/

Elsevier; 2008. Volume 1. Chapter 80. p. 1041-1049.

Do DV, Schachat AP. Leukemias. In: Albert DM, ed. Albert &

Jakobiec’s principles and practice of ophthalmology. 3rd ed.

Philadelphia, PA: Saunders/Elsevier; 2008. Volume 4. Chapter

358. p. 4949-4952.

Dupps WJ, Jr., Wilson SE. Biomechanics and wound healing

in refractive surgery. In: Albert DM, ed. Albert & Jakobiec’s

principles and practice of ophthalmology. 3rd ed. Philadelphia,

PA: Saunders/Elsevier; 2008. Volume 1. Chapter 72. p. 971-980.

Singh AD, Sisley K, Wackernagel W. Genetics of uveal melanoma.

In: Albert DM, ed. Albert & Jakobiec’s principles and

practice of ophthalmology. 3rd ed. Philadelphia, PA: Saunders/

Elsevier; 2008. Volume 4. Chapter 355. p. 4925-4934.

Traboulsi EI, Singh AD. The phakomatoses. In: Albert DM, ed.

Albert & Jakobiec’s principles and practice of ophthalmology.

3rd ed. Philadelphia, PA: Saunders/Elsevier; 2008. Volume 4.

Chapter 366. p. 5009-5024.

ANTERIOR SEGMENT OPTICAL

COHERENCE TOMOGR APHY

Wackernagel W, Rao NA, Steinert RF, Singh AD. Optical

coherence tomography for anterior segment tumors. In:

Steinert RF, Huang D, eds. Anterior segment optical coherence

tomography. Thorofare, NJ: SLACK; 2008. Chapter 12.

p. 127-136.

CORNE AL SURGERY: THEORY,

TECHNIQUE, AND TISSUE

Cox CA, Dupps WJ, Jr., Brent GJ, Meisler DM. Corneal and

scleral ruptures and lacerations. In: Brightbill FS, ed. Corneal

surgery: theory, technique, and tissue. 4th ed. [St. Louis, MO.]:

Mosby/Elsevier; 2009. Chapter 71. p. 617-626.

Dupps WJ, Jr. Principles of biomechanics in refractive surgery.

In: Brightbill FS, ed. Corneal surgery: theory, technique, and

tissue. 4th ed. [St. Louis, MO.]: Mosby/Elsevier; 2009. Chapter

81. p. 711-719.

CURRENT CLINICAL MEDICINE 2009

Chung JY, Singh RP. Preventive measures and screening for

ophthalmic problems. In: Carey WD, ed. Current clinical

medicine 2009. Philadelphia, PA: Saunders/Elsevier;

2009. p. 1321-1324.

DIABETIC RETINOPATHY

Margolis R, Kaiser PK. Diagnostic modalities in diabetic

retinopathy. In: Duh E, ed. Diabetic retinopathy. Totowa, NJ:

Humana Press; 2008. Chapter 4. p. 109-133.

IRREGUL AR ASTIGMATISM:

DIAGNOSIS AND TRE ATMENT

Jankov MR, II, Krueger RR. Corneal cross-linking with

riboflavin and ultraviolet irradiation in unstable corneas

with progressive irregular astigmatism. In: Wang M, Swartz

TS, eds. Irregular astigmatism: diagnosis and treatment.

Thorofare, NJ: SLACK; 2008. Chapter 15. p. 145-148.

MANAGEMENT OF COMPLICATIONS

IN REFR ACTIVE SURGERY

Ramos-Esteban JC, Wilson SE. Dry eye. In: Alio JL, Azar DT,

eds. Management of complications in refractive surgery.

Berlin: Springer; 2008. Chapter 5.1. p. 74-85.

MECHANISMS OF THE GL AUCOMAS: DISE ASE

PROCESSES AND THER APEUTIC MODALITIES

Bhattacharya SK, Crabb JW. Proteomic advances toward

understanding mechanisms of glaucoma pathology. In:

Tombran-Tink J, Barnstable CJ, Shields MB, eds. Mechanisms

of the glaucomas: disease processes and therapeutic modalities.

Totowa, NJ: Humana Press; 2008. Chapter 24. p. 443-458.


OCUL AR THER APEUTIC S:

E YE ON NEW DISCOVERIES

Wilson SE, Medeiros FW. Refractive surgery - Corneal opacity

(haze) after surface ablation. In: Yorio T, Clark AF, Wax MB,

eds. Ocular therapeutics: eye on new discoveries. Amsterdam;

Boston, MA: Academic; 2008. Chapter 7. p. 133-141.

REDOX BIOCHEMISTRY

Lou MF, Crabb JW. Oxidative stress in the eye: Age-related

cataract and retinal degeneration. In: Banerjee R, ed. Redox

biochemistry. Hoboken, NJ: Wiley-Interscience; 2008. Chapter

5.2. p. 194-204.

REFR ACTIVE SURGERY

Krueger RR. The LadarVision system. In: Roy FH, ed. Refractive

surgery. Philadelphia, PA: Saunders/Elsevier; 2008. Chapter 3.

p. 47-56.

Books

Anderson RE, LaVail MM, Hollyfield JG. Recent advances in

retinal degeneration. New York, NY: Springer; 2008. 423 p.

(Advances in Experimental Medicine and Biology; v.613).

47

48


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REFERR ALS

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© The Cleveland Clinic Foundation 2009

09-EYE-005

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