O ne of the nation’s most important clinical trials in exudative age-related macular degeneration — the Comparison of AMD Treatments Trials (CATT) — is led by Daniel F. Martin, MD, Chairman of Cleveland Clinic’s Cole Eye Institute. Now, a researcher at Cole Eye Institute has received a two-year, $900,000 National Eye Institute challenge grant for an innovative, first-of-its kind project aimed at studying the genetic makeup of the majority of the 1,208 CATT participants. AMD GENOTYPE MAY PREDICT RESPONSE CATT is designed to determine the relative efficacy of two drugs — ranibizumab (Lucentis®) and bevaci- zumab (Avastin®) — for the treatment of age-related macular degeneration. The work of Stephanie A. Hagstrom, PhD, will define the AMD genotype in CATT patients to reveal which genetic traits make a patient more likely to have a favorable response to each treatment, both of which block vascular endothelial growth factor (VEGF), an important driver of retinal angiogenesis. “We hope to correlate specific single nucleotide polymorphisms (SNPs) with a patient’s response to anti-VEGF therapy. It is possible that patients with the major AMD risk genotypes will not respond to treatment as well as patients who have other genetic variants,” Dr. Hagstrom says. LOOKING AHEAD TO PERSONALIZED MEDICINE “We hope the results from this pharmacogenetic study will allow ophthalmologists to offer personal- ized medicine based on a patient’s underlying genetic background,” she adds. CATT began enrolling patients with newly diagnosed, untreated neovascular AMD in February 2008. Patients were randomly assigned to one of four treatment arms: ranibizumab given monthly, bevacizumab given monthly, ranibizumab given PRN or bevacizumab given PRN. Genetics of AMD Being Studied by Researchers at Cole Eye Institute Cole Eye Institute SPRING 2011 Ophthalmology Update Continued on page 2 Stephanie A. Hagstrom, PhD Ocular Inflammation Can Signal Underlying Systemic Disease Page 6 AMD: Combination Therapy Is More Convenient, but Not Superior Page 3 Case Study: Cole Eye Special- ists Join Fetal Care Center Team Page 4 Research Seeks to Elucidate Causes of Acute Retinal Necrosis Page 8 Also Inside: Clinical Trials and Basic Research; Cole Eye CME, Distinguished Lecture Series & Grand Rounds
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O ne of the nation’s most important clinical
trials in exudative age-related macular
degeneration — the Comparison of AMD
Treatments Trials (CATT) — is led by Daniel F. Martin,
MD, Chairman of Cleveland Clinic’s Cole Eye Institute.
Now, a researcher at Cole Eye Institute has received a
two-year, $900,000 National Eye Institute challenge
grant for an innovative, first-of-its kind project aimed
at studying the genetic makeup of the majority of the
1,208 CATT participants.
AMD genotype MAy preDict response
CATT is designed to determine the relative efficacy
of two drugs — ranibizumab (Lucentis®) and bevaci-
zumab (Avastin®) — for the treatment of age-related
macular degeneration.
The work of Stephanie A. Hagstrom, PhD, will define
the AMD genotype in CATT patients to reveal which
genetic traits make a patient more likely to have a
favorable response to each treatment, both of which
block vascular endothelial growth factor (VEGF), an
important driver of retinal angiogenesis.
“We hope to correlate specific single nucleotide
polymorphisms (SNPs) with a patient’s response to
anti-VEGF therapy. It is possible that patients with
the major AMD risk genotypes will not respond to
treatment as well as patients who have other genetic
variants,” Dr. Hagstrom says.
Looking AheAD to personALizeD MeDicine
“We hope the results from this pharmacogenetic
study will allow ophthalmologists to offer personal-
ized medicine based on a patient’s underlying genetic
background,” she adds.
CATT began enrolling patients with newly diagnosed,
untreated neovascular AMD in February 2008. Patients
were randomly assigned to one of four treatment arms:
ranibizumab given monthly, bevacizumab given monthly,
ranibizumab given PRN or bevacizumab given PRN.
Genetics of AMD Being Studied by Researchers at Cole Eye Institute
Cole Eye Institute Spring 2011
Ophthalmology Update
Continued on page 2
Stephanie A. Hagstrom, phD
Ocular Inflammation Can Signal Underlying Systemic Disease
page 6
AMD: Combination Therapy Is More Convenient, but Not Superior
page 3
Case Study: Cole Eye Special-ists Join Fetal Care Center Team
page 4
Research Seeks to Elucidate Causes of Acute Retinal Necrosis
page 8
Also Inside: Clinical Trials and Basic Research; Cole Eye CME, Distinguished Lecture Series & Grand Rounds
2 ophthalmology Update | spring 2011
All patients are evaluated every four weeks at one
of the 44 participating clinical centers. The primary
outcomes measures are visual acuity at one year and
at two years.
At LeAst 35 snps to be genotypeD
Dr. Hagstrom’s study team began collecting samples
in late summer 2010. At least 35 SNPs will be
genotyped, including those that have previously been
shown to have the strongest associations with AMD.
Dr. Hagstrom expects to recruit the majority of CATT
participants because they are already committed to the
original trial.
“Patients will have several opportunities to join the
study because they are seen every month,” she says.
MeAsUring response by genotype
Genotype and clinical measures of response to
anti-VEGF therapy will be compared. The clinical
responses measured will be:
• Visual acuity
• Presence or absence of subretinal, intraretinal
or sub-retinal pigment epithelial (sub-RPE) f luid
as seen on optical coherence tomography
• Retinal thickness
• Lesion size as seen on f luorescein angiography
• Number of treatments deemed necessary by
the clinician for patients assigned to the PRN
treatment arms
Dr. Martin calls this genetic study a high-profile,
timely undertaking that effectively utilizes the work
already being done for CATT. “Dr. Hagstrom’s work
will generate valuable data that will help propel us
into a new era in the treatment of macular degenera-
tion,” he says.
Contact Dr. Stephanie Hagstrom or Dr. Daniel Martin
Joe G. Hollyfield, PhD John W. Crabb, phD Stephanie Hagstrom, phD neal S. peachey, phD
$2,090,018
Study of retinal Degenerative Disease otherMacula vision research Foundation
Joe G. Hollyfield, PhD $240,000
clevelandclinic.org/oUspring 11
Wolf Family Award other wolf Foundation Joe G. Hollyfield, PhD $100,000
rpB unrestricted grant otherresearch to prevent blindness
Daniel Martin, MD $200,000
Electrical Activity of the Mouse retinal pigment Epithelium
other neal S. peachey, phD $400,000
Electrophysiological Markers other neal S. peachey, phD $316,433
The role of Complement regulation in Maintaining Outer retinal integrity
otherAmerican health Assistance Foundation
neal S. peachey, phD $100,000
Title Source Sponsor iD investigator Amount
NEI Grant Focuses on Corneal HealingSteven E. Wilson, MD, cleveland clinic ophthalmologist, has been awarded a $2 million national
eye institute grant to study corneal epithelial growth factors and healing. Dr. wilson, Director of
corneal research at cole eye institute, says the study will focus on intracellular communication
within the cornea to elucidate the regulation of healing after injury, infection or surgery.
his other research interests include gene delivery to human cells using viral vectors, wound healing,
and cytokines and receptors in tissues in the eye, as well as research into the mechanisms of dry eye
and clinical research into corneal shape and corneal diseases.
Dr. wilson specializes in laser refractive procedures (LAsik/prk) and corneal surgery (penetrating keratoplasty and DsAek), and is
a leading expert in dry eye and ocular surface diseases. he is listed in Best Doctors in America (2004-2010) and has won numerous
awards. he is a former trustee and vice president of the Association for research in vision and ophthalmology (Arvo), the largest
vision research organization in the world, and is currently north American councilor for the international society for eye research.
retinal Disease
A phase ii Dose ranging Study of pazopanib to Treat neovascular Age-related Macular Degeneration (gSK AMD)
Objective: the purpose of this study is to determine the safety and efficacy of different dosage regimens of pazopanib eye drops for the treatment of neovascular age-related macular degeneration.
Contact: Andrew p. schachat, MD, 216.444.7963, or Laura holody, 216.445.3762
retinal Vein Occlusion Fluocinolone Acetonide intravitreal inserts for Vein Occlusion in retina (FAVOr)
Objective: this study will assess the safety and efficacy of fluocinolone acetonide intravitreal inserts in subjects with macular edema secondary to retinal vein occlusion.
Contact: peter k. kaiser, MD, 216.444.6702, or gail kolin, rn, 216.445.4086
Macular Edema incidence/Severity reduction with nevanac® (MiZAr)
Objective: the purpose of this study is to determine the safety and efficacy of Nevanac for the prevention of macular edema in patients with diabetic retinopathy within 90 days following cataract surgery.
Contact: rishi p. singh, MD, 216.445.9497, or gail kolin, rn, 216.445.4086
genetic Eye Disease
Corneal Shape and Biomechanics in the Diagnosis of Marfan Syndrome
Objective: this study will examine the corneal biomechanical properties of individuals with Marfan syndrome.
Contact: william j. Dupps jr., MD, phD, 216.444.8396, or Laura holody, 216.445.3762
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 i. traboulsi, MD, 216.444.4363, or emma Lessieur, 216.445.9886
Cornea and External Diseases
Donor preparation pressure and refractive Shift in Descemet Stripping Automated Endothelial Keratoplasty (DSAEK)
Objective: the purpose of this study is to determine if the infusion pressure used during DsAek (Descemet stripping automated endothelial keratoplasty) donor tissue preparation affects postoperative graft morphology, refractive outcome and graft endothelial cell count in the recipient.
Contact: william j. Dupps jr., MD, phD, 216.444.8396
Safety and Effectiveness of the VEgA uV-A System for Corneal Collagen Cross-Linking in Eyes with Keratoconus (X-Linking)
Objective: the purpose of this research study is to test the safety, tolerability and effectiveness of corneal collagen cross-linking (cxL) when used to treat keratoconus.
Contact: ronald r. krueger, MD, Mse, 216.444.8158, or Fadiah Al khawaldeh, 216.445.3641
Other studies
Safety Study of a Single iVT injection of Qpi-1007 in Chronic Optic nerve Atrophy and recent Onset nAiOn patients (nAiOn)
Objective: in this open-label, dose escalation, safety, tolerability and pharmacokinetic study, active study drug (Qpi-1007) will be given to all participating patients. this study will determine whether Qpi-1007 is safe when injected into the eye, and will reveal any side effects of the drug and how long it takes for the body to clear the drug.
Contact: rishi p. singh, MD, 216.445.9497, or Laura holody, 216.445.2264
in Follow-upthe following studies have completed enrollment and are in follow-up at cole eye institute:
A phase ii Multicenter, prospective, randomized, comparator controlled, Dose ranging study evaluating pF-04523655 versus ranibizumab in the treatment of subjects with choroidal neovascularization (Monet)
A Clinical Safety and Efficacy Comparison of nevanac® 0.1% to vehicle Following cataract surgery in Diabetic retinopathy patients (nevAnAc)
A randomized, Double-Masked, sham-controlled Phase III Study of the Efficacy, Safety and tolerability of repeated intravitreal Administra-tion of vegF trap-eye in subjects with Macular edema secondary to central retinal vein occlusion (vegF trap crvo)
An open-Label, Multicenter extension study to evaluate the safety and tolerability of ranibizumab in subjects with Macular edema secondary to retinal vein occlusion who have completed a genentech sponsored ranibi-zumab study (horizon 2)
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 Age-related Macular Degeneration (DenALi)
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 eight-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)
CLiniCAL TRIAlSAll studies have been approved by the Institutional Review Board. Highlighted studies are currently enrolling.
12 ophthalmology Update | spring 2011
clevelandclinic.org/oUspring 13
DISTINGUISHED lECTURE SEriES
March 17, 2011
Functionalizing Cell-Based Therapy
for Age-related Macular Degeneration
Marco A. zarbin, MD, phD
Alfonse A. cinotti, MD/Lions eye
research professor and chair,
institute of ophthalmology and
visual science,
new jersey Medical school,
University of Medicine & Dentistry
of new jersey
newark, n.j.
April 21, 2011
Age-related Macular Degeneration:
Any More genes Left to Find?
bernhard weber, phD
professor, institute of human genetics,
University of regensburg
regensburg, germany
May 19, 2011
The Biology of Latent infection
With Herpes Simplex Virus
todd p. Margolis, MD, phD
Foundation Director and Director, ralph
and sophie heintz research Laboratory,
Francis i. proctor Foundation
professor of ophthalmology,
University of california, san Francisco
san Francisco, calif.
June 16, 2011
Building a Focused research group:
glaucoma research at Devers Eye institute
George A. Cioffi, MD
chairman, Devers eye institute,
senior vice president and chief
Medical Officer, Legacy Health,
professor of ophthalmology,
oregon health & science University
portland, ore.
July 21, 2011
High-resolution imaging in patients
With inherited retinal Degenerations
jacque L. Duncan, MD
professor of clinical ophthalmology,
beckman vision center,
University of california, san Francisco,
school of Medicine
san Francisco, calif.
Sept. 15, 2011
DnA repair in retinal Degenerations
jeffrey h. boatright, phD
Associate professor of ophthalmology,
research (basic science) section,
emory University school of Medicine
Atlanta, ga.
Oct. 20, 2011
ironing Out the role of Oxidative Stress
in Age-related Macular Degeneration
joshua L. Dunaief, MD, phD
Assistant professor of ophthalmology,
F.M. kirby center for Molecular
ophthalmology,
scheie eye institute,
University of pennsylvania school of
Medicine
philadelphia, pa.
nov. 17, 2011
Emerging Human Adenoviruses:
A Systems Biology Approach to predicting
the next Eye pathogen
james chodosh, MD, Mph
Lecturer in ophthalmology,
harvard Medical school
Massachusetts Eye & Ear Infirmary
boston, Mass.
the Distinguished Lecture series is held
from 7 to 8 a.m. in the james p. storer
Conference Center on the first floor of
cleveland clinic’s cole eye institute. no
registration is required, and we will validate
your parking ticket. call Laura hogan at
216.444.5832 with any questions.
Cleveland Clinic’s Cole Eye Institute is proud to present the 2011 Distinguished lecture Series, which provides a forum for internationally renowned researchers in the visual sciences to present their latest findings on basic and clinical ophthalmic research. Ample opportunity for questions and answers is provided after lectures.
14 ophthalmology Update | spring 2011
CME OppORTUNITIES & GRAND ROUNDS
cole eye institute cMe Mark your calendars for continuing medical education symposia
hosted by cole eye institute. you’ll gain insights into state-of-the-art
diagnostic, medical and surgical techniques as well as the promise
that research holds for patients with ophthalmic conditions.
uveitis update
saturday, April 9, 2011
Activity Director: careen y. Lowder, MD, phD
north Coast retina Symposium ii
Friday-saturday, May 13-14, 2011
Activity Director: Daniel F. Martin, MD
Annual research, residents & Alumni Meeting
Friday, june 17, 2011
Activity Director: elias i. traboulsi, MD
An optical coherence tomography Update is tentatively scheduled
for july 2011.
cMe symposia are held in the james p. storer conference cen-
ter on the first floor of Cleveland Clinic’s Cole Eye Institute unless
otherwise indicated. For further details or updates and for parking
information, please contact jane sardelle at 216.444.2010 or
cole eye institute grand rounds ophthalmologists from other institutions are welcome to attend cole
eye institute grand rounds, held Mondays from 7 to 8 a.m. through-
out the academic year, except during holidays and major meetings.
each session features two cases that represent outstanding teaching
examples, followed by extensive discussion. cases may feature rare
or difficult-to-manage conditions, unusual presentations of common
disorders, and/or state-of-the-art diagnosis and management. three
to four M&M cases are presented each year.
category 1 continuing education credits are offered. grand rounds,
held in the james p. storer conference center at cole eye institute,
are videoconferenced weekly to cleveland clinic ophthalmology
(Lakeland eye) in Lorain, ohio, and monthly to Lv prasad institute
in hyderabad, india. no registration is required. For details and
parking vouchers, please contact jane sardelle at [email protected].
Ophthalmology Update, a publication of cleveland clinic’s cole eye institute, provides information for ophthalmologists about state-of-the-art diagnostic and management techniques and current research.
please direct any correspondence to:
steven e. wilson, MD cole eye institute / i32 the cleveland clinic Foundation 9500 euclid Ave. cleveland, oh 44195
phone 216.444.5887 Fax 216.445.8475
institute Chairman Daniel F. Martin, MD
Editor-in-Chief steven e. wilson, MD
Managing Editor cora Liderbach
Art Director Michael viars
Marketing Manager bill sattin, phD
Marketing Associate natalie weigl, rn
the cleveland clinic Foundation is an independent, not-for-profit, multispecialty academic medical center. It is dedicated to providing quality specialized care and includes an outpa-tient clinic, a hospital with more than 1,000 available beds, an education division and a research institute.
Ophthalmology Update is written for physicians and should be relied upon for medical education purposes only. it does not provide a complete overview of the topics covered and should not replace the independent judgment of a physician about the appropriateness or risks of a procedure for a given patient. physicians who wish to share this information with patients need to make them aware of any risks or potential complica-tions associated with any procedures.
pATIENT rEFErrALSto refer a patient to the cole eye institute, please call 216.444.2020 or 800.223.2273, ext 42020.
cole eye institute
the cleveland clinic Foundation
9500 euclid Avenue / Ac311
cleveland, oh 44195
Ophthalmology Update
physician resource guidereFerrALs
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the cleveland clinic cole eye institute vision Line is your direct link for prompt physician referrals to an ophthalmology subspecialist for consultation and appointments.
reFerring physiciAn center
For help with service-related issues, information about our clinical specialists and services, details about cMe opportunities, and more, contact the referring physician center at [email protected], or 216.448.0900 or 888.637.0568.
trAck yoUr pAtient’s cAre onLine
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reQUest MeDicAL recorDs
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oUtcoMes DAtA
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