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Focal Points
Taming The
ReSidency
leaRning cuRve
surgery
September 15, 2016 VOL. 41, NO. 15
Drug therapy
Reverse optic capture
When the posterior capsule tears
Why wait?
Considering option for decentered, single-piece IOL
as result of compromised posterior capsule support
a
b
with the continuous advances in ophthalmic techniques and technologies,
it can be challenging for even the most
experienced surgeons to keep up—let
alone residents. To that end, an educational website designed by ophthalmology residents for ophthalmology residents offers just the right amount of
information, according to its founders.
c
( See story on page 8 : Residency )
Special Report
Silicone oil
challenge moSTly
manageable
IN VIEW: a Vitreous incarceration in bimanual aspirating canula. b Three-month postoperative photo showing
well-centered IOL with reverse optic capture. c OCT imaging showing good clearance between anterior IOL
surface and posterior iris. (Images courtesy of Richard S. Hoffman, MD)
Visit us at Booth 2356 for AAO 2016
paR adisE Val l E y, a Z :: use of silicone oil for retinal tamponade can result in a range of complications. Most
By Lynda Charters;
Reviewed by Richard S. Hoffman, MD
of these events can be avoided with
careful attention to surgical technique
EugEnE, OR ::
or successfully treated if they occur,
All surgeons, no matter how experienced,
whereas those without any known preencounter tough cases that require creative approaches.
ventive strategies are very rare, said
Richard S. Hoffman, MD, described such a case
Derek Kunimoto, MD, JD. Reviewing the
with a 2+ nuclear sclerotic cataract that he removed
complications associated with silicone
using a standard bimanual technique, which prooil based on anatomic location, he said
EYLEA
is a registered
trademark
of Regeneron Pharmaceuticals,
Inc.
gressed routinely.
that silicone
oil in the
subconjunctival
A horizontal chopping technique was used to respace presents a cosmetic issue and
move the nucleus and the capsular bag was filled
can also lead to granuloma formation.
©2016,
Regeneron
Inc.,
with a cohesive viscoelastic (OVD). All rights reserved
Avoiding
siliconePharmaceuticals,
oil in the subconjuncti777 Old Saw Mill River Road, Tarrytown, NY 10591
The anterior capsulorhexis and posterior capsule
val space requires good scleral closure
were intact, explained Dr. Hoffman, clinical associwith small-gauge vitrectomy.
Science University, Eugene, OR. He then injected a
See our enclosed advertisement.
single-piece, hydrophobic acrylic IOL into the bag.
( See story on page 36 : Silicone oil )
ate professor of ophthalmology, Oregon Health and
iS The woRld a beTTeR Place becauSe oF youR PRacTice?
The haptics were covered with polymethylmethacrylate “mittens” to prevent them from sticking
to the optic.
During the centering of the IOL, a crease in the
posterior capsule was visible. Dr. Hoffman hypothesized it was a zonular dialysis with a wrinkled bag
that might resolve with gentle pushing on the IOL.
Repeated pushing did not reach the desired end.
Since the lens was centered, Dr. Hoffman started
to remove the OVD.
In doing so, the IOL began to shimmy and 06/2016
vitreUS-LEA-11943a
ous was visible in the aspirating cannula. The IOL
appeared slightly tilted and moved down toward
( Continues on page 28 : Reverse optic )
How visionary leadership sets the tone. PAGe 68
CUTTING-EDGE ADVANCEMENTS
CLINICAL DIAGNOSIS
OphthalmologyTimes.com
FOLLOW US ONLINE:
Focal Points
TAMING THE
RESIDENCY
LEARNING CURVE
SURGERY
September 15, 2016 VOL. 41, NO. 15
DRUG THERAPY
Reverse optic capture
When the posterior capsule tears
Considering option for decentered, single-piece IOL
as result of compromised posterior capsule support
A
B
WITH THE continuous advances in ophthalmic techniques and technologies,
it can be challenging for even the most
experienced surgeons to keep up—let
alone residents. To that end, an educational website designed by ophthalmology residents for ophthalmology residents offers just the right amount of
information, according to its founders.
C
( See story on page 8 : Residency )
Special Report
SILICONE OIL
CHALLENGE MOSTLY
MANAGEABLE
PAR ADISE VAL L E Y, A Z :: USE OF silicone oil for retinal tamponade can result in a range of complications. Most
of these events can be avoided with
careful attention to surgical technique
or successfully treated if they occur,
whereas those without any known preventive strategies are very rare, said
Derek Kunimoto, MD, JD. Reviewing the
complications associated with silicone
oil based on anatomic location, he said
that silicone oil in the subconjunctival
space presents a cosmetic issue and
can also lead to granuloma formation.
Avoiding silicone oil in the subconjunctival space requires good scleral closure
with small-gauge vitrectomy.
( See story on page 36 : Silicone oil )
IN VIEW: A Vitreous incarceration in bimanual aspirating canula. B Three-month postoperative photo showing
well-centered IOL with reverse optic capture. C OCT imaging showing good clearance between anterior IOL
surface and posterior iris. (Images courtesy of Richard S. Hoffman, MD)
By Lynda Charters;
Reviewed by Richard S. Hoffman, MD
EUGENE, OR ::
ALL SURGEONS, no matter how experienced,
encounter tough cases that require creative approaches.
Richard S. Hoffman, MD, described such a case
with a 2+ nuclear sclerotic cataract that he removed
using a standard bimanual technique, which progressed routinely.
A horizontal chopping technique was used to remove the nucleus and the capsular bag was filled
with a cohesive viscoelastic (OVD).
The anterior capsulorhexis and posterior capsule
were intact, explained Dr. Hoffman, clinical associate professor of ophthalmology, Oregon Health and
IS THE WORLD A BETTER PLACE BECAUSE OF YOUR PRACTICE?
Science University, Eugene, OR. He then injected a
single-piece, hydrophobic acrylic IOL into the bag.
The haptics were covered with polymethylmethacrylate “mittens” to prevent them from sticking
to the optic.
During the centering of the IOL, a crease in the
posterior capsule was visible. Dr. Hoffman hypothesized it was a zonular dialysis with a wrinkled bag
that might resolve with gentle pushing on the IOL.
Repeated pushing did not reach the desired end.
Since the lens was centered, Dr. Hoffman started
to remove the OVD.
In doing so, the IOL began to shimmy and vitreous was visible in the aspirating cannula. The IOL
appeared slightly tilted and moved down toward
( Continues on page 28 : Reverse optic )
How visionary leadership sets the tone. PAGE 68
BACITRACIN OPHTHALMIC OINTMENT USP
%GXMZIEKEMRWXXSSJMHIRXM¿IHOI]
gram-positive isolates from conjunctivitis and blepharitis
from in vitroWXYHMIW².ERYEV]1
In Vitro Susceptibility Data Provided Through the University of Pittsburgh Medical Center. In Vitro Data Should Not Be
Considered Representative of Clinical Efficacy1
Established therapeutic utility in blepharitis, conjunctivitis, and other superficial
ocular infections caused by Bacitracin-susceptible organisms
OExcellent
safety profile—low incidence
of adverse events2
OOintment
provides long-lasting ocular surface
contact time and greater bioavailability3
OAnti-infective
OFlexible
efficacy in a lubricating base2
dosing—1 to 3 times daily2
OTier
1 pharmacy benefit status—
on most insurance plans4
Indication
Bacitracin Ophthalmic Ointment is indicated for the treatment of superficial ocular infections involving the conjunctiva
and/or cornea caused by Bacitracin susceptible organisms.
Important Safety Information
This product should not be used in patients with a history of hypersensitivity to Bacitracin.
Bacitracin Ophthalmic Ointment should not be used in deep-seated ocular
infections or in those that are likely to become systemic.
There is a low incidence of allergenicity exhibited by Bacitracin.
If such reactions do occur, therapy should be discontinued.
Please see adjacent page for full prescribing information.
Logo is a trademark of Perrigo.
©2016 Perrigo Company plc
Printed in USA
0S4-PAD01-ver02
3/16
For a closer look, visit
www.perrigobacitracin.com
SEPTEMBER 15, 2016 :: Ophthalmology Times
contents
Bacitracin Ophthalmic
Ointment USP
Rx Only
STERILE
DESCRIPTION: Each gram of ointment contains 500 units
of Bacitracin in a low melting special base containing
White Petrolatum and Mineral Oil.
62
CLINICAL PHARMACOLOGY: The antibiotic, Bacitracin,
exerts a profound action against many gram-positive
pathogens, including the common Streptococci and
Staphylococci. It is also destructive for certain gramnegative organisms. It is ineffective against fungi.
INDICATIONS AND USAGE: For the treatment of
superficial ocular infections involving the conjunctiva
and/or cornea caused by Bacitracin susceptible organisms.
CONTRAINDICATIONS: This product should not be used
in patients with a history of hypersensitivity to Bacitracin.
PRECAUTIONS: Bacitracin ophthalmic ointment should
not be used in deep-seated ocular infections or in those
that are likely to become systemic. The prolonged use of
antibiotic containing preparations may result in
overgrowth of nonsusceptible organisms particularly fungi.
If new infections develop during treatment appropriate
antibiotic or chemotherapy should be instituted.
ADVERSE REACTIONS: Bacitracin has such a low
incidence of allergenicity that for all practical purposes
side reactions are practically non-existent. However, if
such reaction should occur, therapy should be discontinued.
To report SUSPECTED ADVERSE REACTIONS, contact
Perrigo at 1-866-634-9120 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
DOSAGE AND ADMINISTRATION: The ointment
should be applied directly into the conjunctival sac 1 to 3
times daily. In blepharitis all scales and crusts should be
carefully removed and the ointment then spread
uniformly over the lid margins. Patients should be
instructed to take appropriate measures to avoid gross
contamination of the ointment when applying the
ointment directly to the infected eye.
HOW SUPPLIED:
NDC 0574-4022-13 3 - 1 g sterile tamper evident tubes
with ophthalmic tip.
NDC 0574-4022-35 3.5 g (1/8 oz.) sterile tamper evident
tubes with ophthalmic tip.
50
30
Surgery
Special Report
18 CXL REMAINS AS TREATMENT
FOR KERATOCONUS, ECTASIA
34 FACE-DOWN POSITION NOT
NEEDED FOR MACULAR HOLES
Patient cohort reported improved
topography, visual acuity, satisfaction
Positioning may include any position in which
head is tilted forward, eyes look downward
Clinical Diagnosis
Practice Management
50 UPDATED CORNEAL
DYSTROPHY CLASSIFICATIONS
68 IS THE WORLD A BETTER PLACE
BECAUSE OF YOUR PRACTICE?
Updated categories aimed to offer more
precise diagnosis, treatment
These seven focal points will help communicate
your values, ideas with your team
Store at 20°-25°C (68°-77°F)
[see USP Controlled Room Temperature].
In This Issue
Manufactured For
4 EDITORIAL
71 MARKETPLACE
®
Minneapolis, MN 55427
0S400 RC J1 Rev 08-13 A
References: 1. Antibiotic susceptibility: conjunctivitis and blepharitis.
University of Pittsburgh Medical Center, Charles T. Campbell Eye
Microbiology Lab Web site. http://eyemicrobiology.upmc.com/
AntibioticSusceptibilities/Conjunctivitis.htm. Accessed March 21, 2016.
2. Bacitracin Ophthalmic Ointment [package insert]. Minneapolis, MN:
Perrigo Company; August 2013. 3. Hecht G. Ophthalmic preparations.
In: Gennaro AR, ed. Remington: the Science and Practice of Pharmacy.
20th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2000.
4. Data on file. Perrigo Company.
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SEPTEMBER 15, 2016 :: Ophthalmology Times
editorial
SEPTEMBER 15, 2016 ◾ VOL. 41, NO. 15
How to choose a subspecialty
Shub-ad knew her wise chairman would help her weigh options
By Peter J. McDonnell, MD
director of the Wilmer Eye Institute,
Johns Hopkins University School of
Medicine, Baltimore, and chief medical
editor of Ophthalmology Times.
He can be reached at 727 Maumenee Building
600 N. Wolfe St. Baltimore, MD 21287-9278
Phone: 443/287-1511 Fax: 443/287-1514
E-mail: [email protected]
SHUB-AD WALKED into the office of
her department chairman. It was the year 1745
B.C. and Shub-ad’s residency in ophthalmology
was almost complete. Always an excellent student, she had graduated in the top of her class
at Baghdad University and then at The Hammurabi School of Medicine, allowing her to secure a highly coveted residency slot in this
competitive specialty.
A great resident and conscientious physician, she had a tremendous fund of knowledge; cared for each patient like he or she was
a family member; was respected by the faculty,
nurses, and her fellow residents; and (most im-
rative crystals and framed certificates from his
numerous named lectureships, along with the
usual smattering of autographed photos of him
with various politicians and celebrities.
Shub-ad began with the standard greeting of
a resident to her chairman: “Greetings to Your
Excellency, whose tireless efforts alone make
all good things happen in this department but
goeth unrecognized by so many.”
“Arise, my child,” responded Pay-Dro, “and
let your chairman know how he may further
thy career.”
“Well, here’s the thing,” Shub-ad said. “I am
having trouble deciding on a specialty. Cataract
surgery restoreth sight to my patients quickly
and is most gratifying. But oculoplastic surgery
alloweth me to rid my patients of their ptosis
and wrinkles, giving them back their youthful
beauty. And it goeth without saying that injecting the miraculous anti-VEGF agents into the
vitreous cavity all day is a joy. I love it all. “So what subspecialty shall I select? Also,
there is the matter of repaying my student
loans. Tuition and room-and-board in Baghdad are not cheap these days. As my chairman,
I know thou art all-knowing and will not steer
me wrong.”
Pay-Dro smiled. He remembered pondering
these same issues as a
resident.
“Young Shub-ad,” he
replied, “you have great
surgical abilities and are
already an excellent cataract surgeon.
“Plus, our great King
Hammurabi, whose enemies tremble at the sound of his name, issued
his Code just 5 years ago providing professional
fee reimbursement of ten shekels for successful surgery. Ten shekels is nothing to sneeze at,
as we chairmen like to say, and such a fee will
allow you to quickly repay your loans and purchase fine luxury items like you see scattered
around my office, and perhaps even a nice convertible chariot from Germany.
“Just be sure to document all elements of the
history and examination on thy clay tablets to
comply with meaningful use rules. So the path
for you should be that of busy cataract surgeon.
Continues on page 6 : Subspecialty
‘If all my residents were like this
young woman,’ Pay-Dro thought to
himself, ‘being chairman would be
the easiest job in the world.’
portantly) had scored at the 90th percentile or
higher each year on her OKAP examinations.
Shub-ad loved ophthalmology, but was having
trouble deciding on her subspecialty. She knew
her wise chairman, Pay-Dro, would help her
think through the options.
Pay-Dro welcomed her warmly into his office. He liked Shub-ad very much.
“If all my residents were like this young
woman,” he thought to himself, “being chairman would be the easiest job in the world.” Befitting his exalted position of chairman,
Pay-Dro’s office was richly adorned with fine
carpets, golden statues, and various commemo-
CONTENT
Chief Medical Editor Peter J. McDonnell, MD
Group Content Director Mark L. Dlugoss
[email protected] 440/891-2703
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Anterior Segment Techniques Ernest W. Kornmehl, MD
coding.doc L. Neal Freeman, MD, MBA
Money Matters John J. Grande, Traudy F. Grande, and
John S. Grande, CFPs®
Neuro-Ophthalmology Andrew G. Lee, MD
Ophthalmic Heritage Norman B. Medow, MD
Tech Talk H. Jay Wisnicki, MD
Uveitis Update Emmett T. Cunningham Jr., MD, PhD, MPH
P U B L I S H I N G /A D V E R T I S I N G
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© 2016 Novartis 08/16 US-CYP-16-E-3239
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SEPTEMBER 15, 2016 :: Ophthalmology Times
letters
LETTING HAPPINESS FIND US
CyPass® Micro-Stent
IMPORTANT PRODUCT INFORMATION
CAUTION: FEDERAL (USA) LAW
RESTRICTS THIS DEVICE TO SALE BY OR
ON THE ORDER OF A PHYSICIAN.
INDICATION: The CyPass® Micro-Stent is
indicated for use in conjunction with cataract
surgery for the reduction of intraocular pressure
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open-angle glaucoma (POAG).
CONTRAINDICATIONS: Use of the CyPass Micro-Stent is contraindicated in the following circumstances or conditions: (1) in eyes with angle-closure
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WARNINGS: Gonioscopy should be performed prior
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with vascular disorders, pseudophakic eyes with
glaucoma, eyes with uveitic glaucoma, eyes with
pseudoexfoliative or pigmentary glaucoma, eyes
with other secondary open-angle glaucomas, eyes
that have undergone prior incisional glaucoma
surgery or cilioablative procedures, eyes with laser
trabeculoplasty performed ≤ 3 months prior to the
surgical screening visit, eyes with unmedicated IOP
less than 21 mmHg or greater than 33 mmHg, eyes
with medicated IOP greater than 25 mmHg, in the
setting of complicated cataract surgery with iatrogenic
injury to the anterior or posterior segment, and when
implantation is without concomitant cataract surgery
with IOL implantation for visually significant cataract.
The safety and effectiveness of use of more than a
single CyPass Micro-Stent has not been established.
ADVERSE EVENTS: In a randomized, multicenter
clinical trial comparing cataract surgery with the
CyPass Micro-Stent to cataract surgery alone,
the most common postoperative adverse events
included: BCVA loss of 10 or more letters at 3
months after surgery (8.8% for the CyPass Micro-Stent
vs. 15.3% for cataract surgery only); anterior chamber
cell and flare requiring steroid treatment 30 or more
days after surgery (8.6% vs. 3.8%); worsening of visual
field mean deviation by 2.5 or more decibels (6.7% vs.
9.9%); IOP increase of 10 or more mmHg 30 or more
days after surgery (4.3% vs. 2.3%); and corneal edema
30 or more days after surgery, or severe in nature
(3.5% vs. 1.5%).
ATTENTION: PLEASE REFER TO THE
INSTRUCTIONS FOR A COMPLETE LIST
OF CONTRAINDICATIONS, WARNINGS,
PRECAUTIONS, AND ADVERSE EVENTS.
© 2016 Novartis
08/16 US-CYP-16-E-3239
EVER SINCE I SAT WITH Arnall Patz, MD, at my interview for a Wilmer Residency, during that first year
of the SF Match in 1978, I have held the Wilmer Eye
Institute in very high regard. Dr. Patz made it very
clear that Wilmer was looking to train ophthalmologists who were invested in research and wanted to
chair departments across America.
I truly appreciated his candor and still am in awe
of his accomplishments.
As a student at Columbia University’s School of
Engineering and Applied Science, majoring in Chemical Engineering (bioengineering was not even a
major in 1971-1975) I felt my calling was private
practice, teaching, and living a life that I chose to
create on my own terms.
I matriculated at Columbia University’s College of
Physicians and Surgeons where my desire to pursue
a clinical practice in ophthalmology was nurtured.
Fred Jakobiec, MD, gave me a wonderful opportunity to do some important clinical research on pigmented lesions of the iris which occupied 4 months
of my fourth year at Columbia. That research experience, although superb, further confirmed my
desire to enter private practice upon completing
my residency.
I was especially touched by the recent editorial
by Peter J. McDonnell, MD, entitled, “Are you really happy?” (Ophthalmology Times, July 15, 2016).
SUBSPECIALTY
( Continued from page 4)
Plus, there is only the one downside.”
As already mentioned, Shub-ad was sharp
as a tack and nothing ever got past her.
“Downside? What downside?” she inquired.
THE DOW NSIDE
“Well, our great King Hammurabi, whose knowledge of health care policy exceeds that of all
other policy wonks, has included in his reimbursement formula the caveat that if the surgery
is unsuccessful and the patient loses his sight,
the surgeon shall have his/her hands cut off.”
“You’re kidding!” exclaimed Shub-ad, who
had grown rather fond of her hands.
“Not at all,” Pay-Dro responded. “Perhaps
you have noticed that almost all of your senior faculty have no hands. My 5,000th cataract surgery patient regrettably developed
postoperative endophthalmitis from a strain
of multiple drug-resistant Staphylococcus au-
I think happiness finds us more easily when we
are kind, generous, grateful, and compassionate
in our ways; with our families, our friends, and our
patients as well.
Being attached to a material world and competing for “more money and more rewards” makes it
much more difficult to allow happiness into our lives.
I presently spend 2 days a week in the Comprehensive Eye Clinic at New York Eye and Ear Infirmary, mentoring our great residents in the skills
of our profession and guiding them towards living
empowered lives.
There is much for them to learn over a nice dinner and a glass of wine about what it means to live
life fully and what it takes in one’s mind to set the
stage for that wonderful and “happy” life.
—Glenn R. Silbert, MD
Associate clinical professor of ophthalmology
The Carl Icahn School of Medicine at Mount Sinai
The Mount Sinai Health System
New York
Letters to the Editor may be submitted to
[email protected].
Letters may be edited for clarity and length.
reus and lost his vision. Statistically, a 1-in5,000 rate of infection is pretty darn good
and superior to what is published in the literature, but rules are rules, so my hands were
cut off. So what do you say?”
“I think neuro-ophthalmology seemeth
like a good option. It is a very intellectually
challenging field,” responded Shub-ad, as she
backed out of the office while being careful
to constantly bow toward her chairman. Q
References
1. Shub-ad is the name of a queen and priestess historically
documented to have lived in ancient Mesopotamia. http://www.womeninworldhistory.com/lesson2.html
2. The sixth Babylonian King, Hammurabi, issued his legal
system code around 1750 BC. https://en.wikipedia.org/
wiki/Code_of_Hammurabi
3. One shekel of silver equaled 180 grains or 5.5 grams of
silver. According to the Ishnuna Code of Law, a labourer
received the monthly wage of one shekel plus his food. http://www.ishtartv.com/en/viewarticle,35322.html
SEPTEMBER 15, 2016
2014 :: Ophthalmology Times
editorial advisory board
7
Official publication sponsor of
EDITORIAL ADVISORY BOARD
Chief Medical Editor
Peter J. McDonnell, MD
Wilmer Eye Institute
Johns Hopkins University
Baltimore, MD
Anne L. Coleman, MD
Joan Miller, MD
Jules Stein Eye Institute, UCLA
Los Angeles, CA
Massachusetts Eye & Ear Infirmary
Harvard University
Boston, MA
Ernest W. Kornmehl, MD
Harvard & Tufts Universities
Boston, MA
Associate Medical Editors
Robert K. Maloney, MD
Dimitri Azar, MD
Los Angeles, CA
University of Illinois, Chicago
Chicago, IL
Ashley Behrens, MD
Wilmer Eye Institute, Johns Hopkins University
Baltimore, MD
Elizabeth A. Davis, MD
Randall Olson, MD
University of Utah
Salt Lake City, UT
Ophthalmology Times’ vision is to be the leading content resource for ophthalmologists.
Robert Osher, MD
Through its multifaceted content channels, Ophthalmology Times will assist physicians
with the tools and knowledge necessary to provide advanced quality patient care in the
global world of medicine.
Kuldev Singh, MD
Jonathan H. Talamo, MD
Stanford University
Stanford, CA
Harvard University
Boston, MA
Joshua D. Stein, MD
Kazuo Tsubota, MD
University of Michigan
Ann Arbor, MI
Keio University School of Medicine
Tokyo, Japan
Robert N. Weinreb, MD
University of Minnesota,
Minneapolis, MN
Hamilton Glaucoma Center
University of California, San Diego
Uday Devgan, MD
Neuro-Ophthalmology
Jules Stein Eye Institute,UCLA
Los Angeles, CA
Andrew G. Lee, MD
Richard S. Hoffman, MD
Retina/Vitreous
Stanley Chang, MD
Columbia University
New York, NY
David Chow, MD
Blanton Eye Institute, Houston Methodist Hospital University of Toronto
Toronto, Canada
Houston, TX
Oregon Health & Science University
Portland, OR
Oculoplastics/
Reconstructive Surgery
Samuel Masket, MD
Jules Stein Eye Institute,UCLA
Los Angeles, CA
Robert Goldberg, MD
Bartly J. Mondino, MD
Jules Stein Eye Institute, UCLA
Los Angeles, CA
Jules Stein Eye Institute,UCLA
Los Angeles, CA
John T. LiVecchi, MD
Mark Packer, MD
Boulder, CO
St. Luke’s Cataract & Laser Institute
Tarpon Springs, FL
Michael Raizman, MD
Shannath L. Merbs, MD
Massachusetts Eye & Ear, Harvard University
Boston, MA
Ehsan “Ethan” Sadri, MD, FACS
Newport Beach, CA
Wilmer Eye Institute, Johns Hopkins University
Baltimore, MD
Pediatric Ophthalmology
Pravin U. Dugel, MD
Phoenix, AZ
Sharon Fekrat, MD
Duke University
Durham, NC
Julia Haller, MD
Wills Eye Institute, Thomas Jefferson University
Philadelphia, PA
Tarek S. Hassan, MD
Oakland University
Rochester, MI
Michael Ip, MD
Doheny Eye Institute
Los Angeles, CA
Michael Snyder, MD
Norman B. Medow, MD
Carmen A. Puliafito, MD
Cincinnati Eye Institute
Cincinnati, OH
Albert Einstein College of Medicine
Bronx, NY
Keck School of Medicine, USC
Los Angeles, CA
Walter J. Stark, MD
Jennifer Simpson, MD
Carl D. Regillo, MD
Wilmer Eye Institute, Johns Hopkins University
Baltimore, MD
University of California, Irvine
Irvine, CA
Wills Eye Institute, Thomas Jefferson University
Philadelphia, PA
Farrell “Toby” Tyson, MD
H. Jay Wisnicki, MD
Lawrence J. Singerman, MD
Cape Coral, FL
New York Eye & Ear Infirmary, Beth Israel Medical Case Western Reserve University
Center, Albert Einstein College of Medicine
Cleveland, OH
New York, NY
Glaucoma
Robert D. Fechtner, MD
University of Medicine & Dentistry of New Jersey
Newark, NJ
University of Toronto
Toronto, Canada
Richard K. Parrish II, MD
Uveitis
Practice Management
Joseph C. Noreika, MD
Medina, OH
Stanford University
Stanford, CA
Frank Weinstock, MD
Chief Medical EditorsEmeritus
Boca Raton, FL
Refractive Surgery
New York, NY
Peter S. Hersh, MD
Joel Schuman, MD
University of Medicine & Dentistry of New Jersey
Newark, NJ
yness redness sore tired ey
gritty pain irritation dry visio
sitivity foreign body sensa
edness Your LASIK drynes
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yness redness sore tired ey
rritation burning dry itching
sitivity foreign body sensa
y fatigue Don’t let irritation
ness post-op dry eye sore
tired talk over them. tired
n excess watering gritty sa
nsitivity foreign body sensa
ing burning gritty excess te
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New York University School of Medicine
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Miami,
FL
New York Eye & Ear Infirmary
NYU Langone Medical Center
New York, NY
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focal points
SEPTEMBER 15, 2016 :: Ophthalmology Times
Website serves as residency
educational resource
Content designed for ‘rapid learning,’ tailored to knowledge residents already have
By Stephanie Skernivitz; Reviewed by David Xu, MD
ith the continuous advances idency can expect to discover what Dr. Xu
in ophthalmic techniques and calls the “highest-yield information” needed
technologies, it can be chal- to begin evaluating patients and running a
lenging for even the most clinic. Such information might include basic
experienced surgeons to keep tips (how to use an indirect ophthalmoscope,
for example) to advanced material, including
up—let alone residents.
To that end, a new educational-based web- using ophthalmic ultrasound.
The site features what is called an EyeGuru
site (EyeGuru.org) designed by ophthalmology
residents for ophthalmology residents offers Deck, or an ability to acquire knowledge with
just the right amount of information, accord- the help of spaced-repetition flash cards.
So far, news about the site is
ing to its founder, David Xu,
traveling quickly via word of
MD, ophthalmology resident
mouth, e-mails to colleagues
at University of California, Los
of Dr. Xu and his team, and
Angeles (UCLA), and his colEyeGuru.org is
by the founders participating
leagues, Shawn Lin, MD, also
an educational
in interviews across the nation.
of UCLA, and Ben Lin, MD,
website designed
Already there are 4,000-plus
a UCLA medical student—all
by ophthalmology
page views a month, with 200
who founded the site earlier
residents for
registered members and 52%
this year. The website states
ophthalmology
return users. The site also curupfront, “You get no more and
residents. The website
rently holds a 12% sign-up rate.
no less information than exstates upfront, “You
“We’re already getting posiactly what’s needed.”
get no more and
tive
feedback from a lot of dif“With the help of some colno less information
ferent
hospitals from East Coast
leagues in residency, the reason
than exactly what’s
to
the
West Coast, from places
EyeGuru.org got started was to
needed.”
such as the Bascom Palmer Eye
find a new way for ophthalInstitute and Case Western Remology residents to access
and know how to use the latest generation of serve,” he said.
In determining the content to post on the
tools that have been recently developed,” Dr.
Xu said. “We want to bring the power of the site, Dr. Xu explained, “What residents need
Internet and a new generation of educational to know at each point in their career is well
known. It’s material that people would agree on.”
tools to them.”
And that’s exactly the type of content residents will find on the site.
HOW IT GOT STARTED
“We have detailed experience because we
EyeGuru.org was created by residents who realized the need for an efficient learning tool are so close to that point in time ourselves,” he
during the busy training years. Article content said. “We are trying to figure what we know
on the site is designed for “rapid learning” op- so that we can make things incredibly relevant
portunities for residents and is tailored to the for new residents.”
The site originally included a set of 12 arknowledge residents already have, according
ticles, which already have garnered positive
to the website.
“We did this because ophthalmology is so reviews from people who have returned to the
highly specialized. Residents are faced with a EyeGuru.org team with feedback, noting, “These
challenge,” Dr. Xu continued. “They are need- were just what we needed.”
Article topics address, for example, intering to tackle clinical, surgical, and basic science
preting optical coherence tomography (OCT)
material with steep learning curves.”
On the site, students who are new to res- and management of glaucoma.
W
TAKE-HOME
By residents,
for residents
The website’s mission aims to provide residents
with “Everything you wanted to know about
succeeding in ophthalmology in one easy source.”
W R I T T E N BY R E SIDE N T S . Highyield concepts are explained simply in 5-minute
tutorials to bring residents up to speed, according
to the website.
R ESIDENCY ESSENTIALS. Material
is provided about the most common conditions
residents must know for clinic (glaucoma, AMD,
and diabetic retinopathy, for example).
CLINICAL TECHNIQUES. Technique
guides answer common questions: Worried about
using the slit lamp? The indirect? Interpreting
OCTs? Fluorescein angiography?
“Some people we have heard from are from
our own program—new residents who say the
site is incredibly helpful,” Dr. Xu said. “They
can go back during clinic and look through
articles to help them manage cases.”
Going forward, the plan remains to continue to use the digital-based platform for residents, he said.
“While going to meetings and learning about
the website there can be helpful,” Dr. Xu said,
“we really want to make other residents aware
of us through e-mail, web forums, etc. Our vision is for every resident to use this content as
a key part of how they learn.”
COMPETITORS
What about competitor sites? Dr. Xu is quick
to note that other sites may have an educational focus but are not really viewed as
competitors.
Continues on page 11 : Residency
Down, Boy.
Help Tame Postoperative Ocular Inflammation
and Pain With LOTEMAX® GEL
Indication
LOTEMAX® GEL (loteprednol etabonate ophthalmic gel) 0.5% is indicated for the treatment of
post-operative inflammation and pain following ocular surgery.
Important Safety Information about LOTEMAX® GEL
2 ® GEL is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes
simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the
eye and fungal diseases of ocular structures.
2 )&#&%,*&&)+ &*+)& *$0)*,#+ %#,&$. +$+&+&'+ %)-+* %- *,#
, +0% #*&- * &%+ *')&,+ *,*&)0*&)#&%)*&,#$&% +&)
2 *&&)+ &*+)& *$0)*,#+ %'&*+) &)*,'*,#)+)+&)$+ &%
2 *&*+)& *+)+)+*,))0$0#0# %% %)*+ % %&#&)$+ &%%
occurrence of perforations in those with diseases causing corneal and scleral thinning. The initial prescription
and renewal of the medication order should be made by a physician only after examination of the patient with
the aid of magnification, and where appropriate, fluorescein staining.
2 )&#&%,*&&)+ &*+)& *$0*,'')**+&*+)*'&%*%+,* %)*+1)&*&%)0&,#)
infection. In acute purulent conditions, steroids may mask infection or enhance existing infection.
2 *&&)+ &*+)& $ + &% %++)+$%+&'+ %+*. + *+&)0&)'** $'#/)(, )*)+
,+ &%*&&,#)*+)& *$0')&#&%+&,)*%/)++*-) +0&$%0- )# %+ &%*&
the eye (including herpes simplex).
2 ,%# %+ &%*&+&)%)')+ ,#)#0')&%+&-#&'& % %+##0
. +#&%+)$#&#*+)& ''# + &%,%,* %-* &%$,*+&%* )
in any persistent corneal ulceration where a steroid has been used or is in use.
2 + %+**&,#%&+.)&%++#%**.%,* %® GEL.
2 $&*+&$$&%&,#)-)*),)+ &%*)'&)+.)%+) &)
chamber inflammation (5%), eye pain (2%) and foreign body sensation (2%).
Please see brief summary of Prescribing Information on adjacent page.
®/™ are trademarks of Bausch & Lomb Incorporated or its affiliates. © 2015 Bausch & Lomb Incorporated. All rights reserved. Printed in USA. US/LGX/15/0041(1)
BRIEF SUMMARY OF PRESCRIBING INFORMATION
This Brief Summary does not include all the information needed to
prescribe Lotemax Gel safely and effectively. See full prescribing
information for Lotemax Gel.
Lotemax
(loteprednol etabonate ophthalmic gel) 0.5%
Rx only
Initial Rx Approval: 1998
INDICATIONS AND USAGE
LOTEMAX is a corticosteroid indicated for the treatment of post-operative
inflammation and pain following ocular surgery.
DOSAGE AND ADMINISTRATION
Invert closed bottle and shake once to fill tip before instilling drops.
Apply one to two drops of LOTEMAX into the conjunctival sac of the affected
eye four times daily beginning the day after surgery and continuing
throughout the first 2 weeks of the post-operative period.
CONTRAINDICATIONS
LOTEMAX, as with other ophthalmic corticosteroids, is contraindicated in
most viral diseases of the cornea and conjunctiva including epithelial herpes
simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in
mycobacterial infection of the eye and fungal diseases of ocular structures.
WARNINGS AND PRECAUTIONS
Intraocular Pressure (IOP) Increase
Prolonged use of corticosteroids may result in glaucoma with damage to the
optic nerve, defects in visual acuity and fields of vision. Steroids should be
used with caution in the presence of glaucoma. If this product is used for 10
days or longer, intraocular pressure should be monitored.
Cataracts
Use of corticosteroids may result in posterior subcapsular cataract formation.
Delayed Healing
The use of steroids after cataract surgery may delay healing and increase the
incidence of bleb formation. In those diseases causing thinning of the cornea
or sclera, perforations have been known to occur with the use of topical
steroids. The initial prescription and renewal of the medication order should
be made by a physician only after examination of the patient with the aid
of magnification such as slit lamp biomicroscopy and, where appropriate,
fluorescein staining.
Bacterial Infections
Prolonged use of corticosteroids may suppress the host response and
thus increase the hazard of secondary ocular infections. In acute purulent
conditions of the eye, steroids may mask infection or enhance existing
infection.
Viral Infections
Employment of a corticosteroid medication in the treatment of patients with
a history of herpes simplex requires great caution. Use of ocular steroids may
prolong the course and may exacerbate the severity of many viral infections
of the eye (including herpes simplex).
Fungal Infections
Fungal infections of the cornea are particularly prone to develop
coincidentally with long-term local steroid application. Fungus invasion must
be considered in any persistent corneal ulceration where a steroid has been
used or is in use. Fungal cultures should be taken when appropriate.
Contact Lens Wear
Patients should not wear contact lenses during their course of therapy with
LOTEMAX.
ADVERSE REACTIONS
Adverse reactions associated with ophthalmic steroids include elevated
intraocular pressure, which may be associated with infrequent optic nerve
damage, visual acuity and field defects, posterior subcapsular cataract
formation, delayed wound healing and secondary ocular infection from
pathogens including herpes simplex, and perforation of the globe where
there is thinning of the cornea or sclera.
The most common adverse drug reactions reported were anterior chamber
inflammation (5%), eye pain (2%), and foreign body sensation (2%).
USE IN SPECIFIC POPULATIONS
Pregnancy
Teratogenic Effects: Pregnancy Category C.
Loteprednol etabonate has been shown to be embryotoxic (delayed
ossification) and teratogenic (increased incidence of meningocele, abnormal
left common carotid artery, and limb flexures) when administered orally
to rabbits during organogenesis at a dose of 3 mg/kg/day (35 times
the maximum daily clinical dose), a dose which caused no maternal
toxicity. The no-observed-effect-level (NOEL) for these effects was
0.5 mg/kg/day (6 times the maximum daily clinical dose). Oral treatment
of rats during organogenesis resulted in teratogenicity (absent innominate
artery at ≥5 mg/kg/day doses, and cleft palate and umbilical hernia
at ≥50 mg/kg/day) and embryotoxicity (increased post-implantation
losses at 100 mg/kg/day and decreased fetal body weight and skeletal
ossification with ≥50 mg/kg/day). Treatment of rats with 0.5 mg/kg/day
(6 times the maximum clinical dose) during organogenesis did not result
in any reproductive toxicity. Loteprednol etabonate was maternally toxic
(significantly reduced body weight gain during treatment) when administered
to pregnant rats during organogenesis at doses of ≥5 mg/kg/day.
Oral exposure of female rats to 50 mg/kg/day of loteprednol etabonate from
the start of the fetal period through the end of lactation, a maternally toxic
treatment regimen (significantly decreased body weight gain), gave rise to
decreased growth and survival, and retarded development in the offspring
during lactation; the NOEL for these effects was 5 mg/kg/day. Loteprednol
etabonate had no effect on the duration of gestation or parturition when
administered orally to pregnant rats at doses up to 50 mg/kg/day during the
fetal period.
There are no adequate and well controlled studies in pregnant women.
LOTEMAX should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether topical ophthalmic administration of corticosteroids
could result in sufficient systemic absorption to produce detectable quantities
in human milk. Systemic steroids appear in human milk and could suppress
growth, interfere with endogenous corticosteroid production, or cause other
untoward effects. Caution should be exercised when LOTEMAX is administered
to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
No overall differences in safety and effectiveness have been observed
between elderly and younger patients.
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term animal studies have not been conducted to evaluate the
carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was
not genotoxic in vitro in the Ames test, the mouse lymphoma tk assay, or in
a chromosome aberration test in human lymphocytes, or in vivo in the single
dose mouse micronucleus assay. Treatment of male and female rats with up
to 50 mg/kg/day and 25 mg/kg/day of loteprednol etabonate, respectively,
(600 and 300 times the maximum clinical dose, respectively) prior to and
during mating did not impair fertility in either gender.
PATIENT COUNSELING INFORMATION
Administration
Invert closed bottle and shake once to fill tip before instilling drops.
Risk of Contamination
Patients should be advised not to allow the dropper tip to touch any surface,
as this may contaminate the gel.
Contact Lens Wear
Patients should be advised not to wear contact lenses when using LOTEMAX.
Risk of Secondary Infection
If pain develops, redness, itching or inflammation becomes aggravated, the
patient should be advised to consult a physician.
Bausch & Lomb Incorporated
Tampa, Florida 33637 USA
US Patent No. 5,800,807
©Bausch & Lomb Incorporated
®/™ are trademarks of Bausch & Lomb Incorporated or its affiliates.
US/LGX/15/0042
Based on 9269100-9269200
Revised: 9/2012
SEPTEMBER 15, 2016 :: Ophthalmology Times
RESIDENCY
focal points
11
TAKE A TOUR OF EYEGURU.ORG
( Continued from page 8 )
“We mainly made our site as an educational resource, but we also made ours
different,” he said. “In one way, we use
spaced repetition as a format of learning.
Students can review information and get
it fed back to them at appropriate pace
for them, instead of the traditional textbook cramming.”
The website also offers a virtual clinic
where residents can learn from clinical
examples. Through the exam, residents
can learn from history and learn to manage in a digital fashion.
“Because we are web-based, residents
can use EyeGuru.org during downtime
allowing distributed learning to happen
whether they are at home, in clinic,
or on the road,” Dr. Xu said.
Currently, the site is social mediafriendly, with regular posts on Twitter, Facebook, and Google Plus.
“We are working with a millennial generation of ophthalmology practitioners,” Dr.
Xu said. “They need a new, efficient way
to learn in the complex medical landscape.”
‘Our vision is
for every resident
to use this content
as a key part
of how they learn.’
— David Xu, MD
As for future plans, Dr. Xu said he and
his colleagues are seeking faculty sponsors. They’re also working on supplying
personal impressions of clinical events via
video modality.
“It’s an important way to share information,” he said. “We can offer video demonstrations and educational material.”
Though the site primarily targets ophthalmology residents, “as ophthalmologists turn
Ophthalmolgy residents
will have access to
timely blog content
that touches upon
ophthalmic lasers,
intravitreal injection
doses, and more.
Clinical information
on the website includes
many tutorials, such as
an overview of four types
of hyperfluorescence
in fluorescein angiography.
(Images courtesy of David Xu, MD)
into young and mid-career ophthalmologists,
we will evolve, too, and generate video relevant to these guys,” Dr. Xu said. “Ophthalmologists strive to be lifelong learners. If we
want to ultimately create the most efficient
learning platform for ophthalmology residents, then it’s our goal to make more residents aware.” ■
12
MEETING PREVIEW
Special Report )
AAO 2016
INNOVATION RISING
TO OCCASION AT AAO 2016
120th annual meeting returns to Windy City with cutting-edge clinical education
By Beth Thomas Hertz
O
CHICAGO ::
The 2016 meeting
of the American
Academy of
Ophthalmology will
convene in Chicago
from Oct. 15 to 18.
Visit www.aao.org
for the latest updates.
Held in conjunction with the Asia-Pacific Academy of Ophthalmology (APAO), the annual meeting also includes eight subspecialty days over Oct. 14 and 15 (see “Innovation Abounds at Subspecialty Day” on Page 14).
In addition, the American Academy of Ophthalmic Executive (AAOE)’s Practice Management Program will convene from
Oct. 15 to 18.
With this year’s theme of “Innovate,” the annual meeting is
“the best place to learn about these innovations and connect with
the top innovators in our field,” said Jonathan B. Rubenstein, MD,
secretary for the AAO meeting. “We hope that attendees will be
inspired to formulate their own innovative ideas.
“As this is our 120th annual meeting, it’s exciting to think about
how much advancement has taken place over the years and how
innovation has dramatically improved outcomes for our patients,”
Dr. Rubenstein added. “Diseases that were once ‘one-way tickets’ to blindness are now treatable thanks to research presented
at AAO meetings.”
He added that the theme also relates to the host city of Chicago,
with a long history of being innovative.
AC A DEM Y PLUS COU R SE PA S S
New this year is the Academy Plus—a course
pass that offers unlimited access to more than
350 AAO and AAOE instruction courses.
There is no need to plan ahead or pre-select
courses. Attendees can float among all instruction courses at will. Individual tickets for AAO
and AAOE instruction courses are no longer
sold. However, seating capacities for course
rooms is limited and seating is available on a
first-come basis.
Attendees can buy the pass when registering for the annual meeting, or buy it onsite at
the conference. Attendees will not receive an
actual separate pass, but will get an “Academy
Plus” symbol on badges that provides their admission. The pass is non-transferable.
Academy Plus does not cover sessions that
require an individual ticket, including AAOE
Practice Management Master Classes, AAOE Coding Sessions, Breakfast with the Experts, Skills
Transfer labs, and Subspecialty Day meetings.
OPENING SESSION
The Opening Session will be held Sunday, Oct.
16, from 8:30 a.m. to 10 a.m. In addition to addresses from leaders of AAO and APAO, the
event will feature the annual Jackson Memorial Lecture.
This year’s lecture is being given by Douglas
D. Koch, MD, professor at the Baylor College
Continues on page 14 : AAO 2016
Getty Images/Swapan Jha
take-home
phthalmic professionals
looking for leading-edge
research and developments
need look no further than
this year’s meeting of the
American Academy of Ophthalmology (AAO) at Chicago’s McCormick Place
from Oct. 15 to 18.
THIS IS YOUR
OPENING.
Make a once-in-a-lifetime difference with the safe MIGS procedure
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INDICATION FOR USE. The iStent® Trabecular Micro-Bypass Stent (Models GTS100R and GTS100L) is indicated for use in conjunction with cataract surgery for the reduction of intraocular pressure (IOP) in adult patients with mild to moderate open-angle
glaucoma currently treated with ocular hypotensive medication. CONTRAINDICATIONS. The iStent® is contraindicated in eyes with primary or secondary angle closure glaucoma, including neovascular glaucoma, as well as in patients with retrobulbar
tumor, thyroid eye disease, Sturge-Weber Syndrome or any other type of condition that may cause elevated episcleral venous pressure. WARNINGS. Gonioscopy should be performed prior to surgery to exclude PAS, rubeosis, and other angle abnormalities
or conditions that would prohibit adequate visualization of the angle that could lead to improper placement of the stent and pose a hazard. The iStent ® is MR-Conditional meaning that the device is safe for use in a specified MR environment under specified
conditions, please see label for details. PRECAUTIONS. The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. The safety and effectiveness of the iStent ® has not been established as an alternative to the
primary treatment of glaucoma with medications, in children, in eyes with significant prior trauma, chronic inflammation, or an abnormal anterior segment, in pseudophakic patients with glaucoma, in patients with pseudoexfoliative glaucoma, pigmentary,
and uveitic glaucoma, in patients with unmedicated IOP less than 22 mmHg or greater than 36 mmHg after “washout” of medications, or in patients with prior glaucoma surgery of any type including argon laser trabeculoplasty, for implantation of more than
a single stent, after complications during cataract surgery, and when implantation has been without concomitant cataract surgery with IOL implantation for visually significant cataract. ADVERSE EVENTS. The most common post-operative adverse events
reported in the randomized pivotal trial included early post-operative corneal edema (8%), BCVA loss of * 1 line at or after the 3 month visit (7%), posterior capsular opacification (6%), stent obstruction (4%) early post-operative anterior chamber cells (3%),
and early post-operative corneal abrasion (3%). Please refer to Directions for Use for additional adverse event information. CAUTION: Federal law restricts this device to sale by, or on the order of, a physician. Please reference the Directions for Use labeling
for a complete list of contraindications, warnings, precautions, and adverse events.
GLKOS-14346 Professional Trade Ad-OSN.indd
©2016 Glaukos Corporation. Glaukos and iStent are registered trademarks of Glaukos Corporation. 400-0285-2016-US Rev. 0
8/9/16
4c
9.5" x 13"
OCULAR SURGERY NEWS
0
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14
SEPTEMBER 15, 2016 :: Ophthalmology Times
MEETING PREVIEW
AAO 2016
AAO 2016
INNOVATION ABOUNDS AT SUBSPECIALTY DAY
( Continued from page 12 )
FRIDAY
of Medicine Ophthalmology Department, on
the topic “Hiding in Plain Sight: The Enigmatic
Cornea and IOL Calculations.” The lecture will
address the current focus of improving IOL
calculations in cataract and refractive surgery
as well as shed light on new corneal imaging
technology and IOL calculation formulas that
are improving outcomes and promise more
progress, according to the AAO.
Also at the Opening Session, Matthew D.
Davis, MD, will receive the Laureate Recognition Award.
Dr. Davis is the emeritus director of the
Fundus Photograph Reading Center, Department of Ophthalmology and Visual Sciences,
University of Wisconsin-Madison. From 1972
to 1979, he chaired the Diabetic Retinopathy
Study, the first randomized, multicenter clinical
trial sponsored by the National Eye Institute.
The trial documented the value of photocoagulation in reducing the risk of visual loss from
diabetic retinopathy, then a leading cause of
blindness. To analyze the retinal photographs
collected in the trial, Dr. Davis established the
FPRC, which is an invaluable, international resource for researchers, according to the AAO. Other awards being presented at the Opening Session include:
> Guests of Honor: Stephen A. Kamenetzky,
MD, James A. Loreto, MD, and A. Raymond Pilkerton, MD, FACS
> Distinguished Service Award: Association of University Professors of
Ophthalmology
> Special Recognition Award: European
Board of Ophthalmology
> Outstanding Humanitarian Service
Award: Paul S. Bernstein, MD, PhD, and
Benjamin W. Roberts, MD
> Outstanding Advocate Award: Donald J.
Cinotti, MD
> International Blindness Prevention
Award: Van C. Lansingh, MD
> Straatsma Award for Excellence in Resident Education: Steven J. Gedde, MD
> Visionary Society Award: David E. I.
Pyott, CBE, MD(HON)
NAMED LECTURES
In addition to the Jackson Memorial lecture, the
AAO also many other named lectures planned:
Refractive Surgery Subspecialty Day 2016 – Friday,
“Pursuit of Perfection” is also the Annual Meeting of
the International Society of Refractive Surgery
Retina Subspecialty Day 2016 – Friday and
Saturday, “Winds of Innovations.” Being held in
conjunction with the American Society of Retina
Specialists, the Macula Society, the Retina Society,
and Club Jules Gonin
SATURDAY
Cornea Subspecialty Day 2016
“Advancements in Cornea and External Disease:
Essential Tools for Success in 2016.” Being held in
conjunction with The Cornea Society
Glaucoma Subspecialty Day 2016
“Innovations in Glaucoma Care: Evolution and
Revolution.” Being held in conjunction with the
American Glaucoma Society
>
>
>
SUNDAY:
> Marshall M. Parks Lecture: “Ocular Motor
Misbehavior in Children: Where Neuro-
>
Ophthalmology Meets Strabismus,” given
by Michael Brodsky, MD. Cosponsored
by the American Association of Pediatric
Ophthalmology and Strabismus
Castroviejo Lecture: “Surgical Treatment of
Presbyopia: The Journey from Corneal
Refractive Surgery to Smart Intraocular
Lenses,” given by Dimitri T. Azar, MD.
Cosponsored by the Cornea Society and
Sektion Kornea of the German Ophthalmological Society
Michael F. Marmor, MD, Lecture in Ophthalmology and the Arts: “The Alchemy of Color
in 19th Century Art,” given by Francesca
Casadio, PhD, A.W. Mellon Senior Conservation Scientist with The Art Institute of
Chicago
Ruedemann Lecture: “Past, Present, and Future,” given by James V. Strauss, BCO,
FASO. Cosponsored by the American Society of Ocularists
Wendell L. Hughes Lecture: “Advances in Military Ocular and Combat Casualty Care:
Ocular Oncology and Pathology Subspecialty
Day 2016 “Breezing Along in Ocular Oncology
and Pathology in the Windy City.” Being held in
conjunction with American Association of Ophthalmic
Oncologists and Pathologists
Oculofacial Plastic Surgery Subspecialty Day
2016 “Beauty and the Beast: From Aesthetics to
Advanced Orbital Disease.” Being held in conjunction
with the American Society of Ophthalmic Plastic and
Reconstructive Surgery
Pediatric Ophthalmology and Strabismus
Subspecialty Day 2016
“Decision 2016 - Cast Your Votes Wisely.” Being held
in conjunction with the American Association for
Pediatric Ophthalmology and Strabismus and the
American Academy of Pediatrics
Uveitis Subspecialty Day 2016
“To Bootcamp and Beyond.” Being held in
conjunction with the American Uveitis Society
>
>
>
>
Translating Lessons Learned In War To
Peacetime Practice,” given by Col. Robert A. Mazzoli, MD. Cosponsored by the
American Society of Ophthalmic Plastic
and Reconstructive Surgery
Whitney G. Sampson Lecture: “Myth Busting
in Refractive Surgery: Corneal Inlays for
Presbyopia, and More,” given by Julian D.
Stevens, MD. Cosponsored by the Contact
Lens Association of Ophthalmologists
Straatsma Lecture: “Career Choices in Ophthalmology,” given by Steven J. Gedde,
MD. Cosponsored by the Association for
University Professors of Ophthalmology
Jones/Smolin Lecture: “Trachoma, From
Control To Eradication,” given by Thomas
M. Lietman, MD. Cosponsored by the Ocular Microbiology and Immunology Group
Arnall Patz Lecture: “The Retina Specialist:
Do We Practice Evidence-Based Medicine?” given by Paul Sternberg, Jr., MD.
This lecture is new this year.
Continues on page 16 : Innovate
Getty Images/Ken Ilio
Special Report )
16
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
MEETING PREVIEW
AAO 2016
INNOVATE
( Continued from page 14 )
MONDAY:
TUESDAY:
> Zimmerman Lecture: “Changes in Diagnosis and Treatment of Orbital Tumors in
50 Years,” given by Zeynel A. Karcioglu,
MD. Cosponsored by the American Association of Ophthalmic Oncologists and
Pathologists
> William F. Hoyt Lecture: “Can A Unique Little Specialty Show Us Some Pervasive Issues With The Old And New Models Of
Healthcare Delivery?” given by Larry P.
Frohman, MD. Cosponsored by the North
American Neuro-Ophthalmology Society
SYMPOSIA
Here are several highlighted symposia that
may be of interest:
> Case-Based Corneal Conundrums: Review a variety of diagnostic and therapeutic dilemmas commonly encountered
by anterior segment specialists. Sunday,
10:30 a.m.to 12:30 p.m.
> Clinical Dilemmas in Neuro-Ophthalmology: Who to Admit and Why? Hear discussion of the considerations for urgent
hospital admission, imaging and treatment. Tuesday, 8:30 to 10 a.m.
VISIT
OPHTHALMOLOGY
TIMES
> Areas of Controversy Regarding Cataract Surgical Preferred Practices: Join
the debate on two hot topics: (1) Whether
intracameral antibiotic is a superior postoperative endophthalmitis prophylaxis
and (2) whether femtosecond laser-assisted cataract surgery results in superior outcomes at a reasonable cost. Audience members will listen to both sides
and then vote on which argument they
find the most persuasive. Monday, 12:15
to 1:30 p.m.
OTHER HIGHLIGHTS
With 250 instruction courses scheduled, the
AAO has identified these as among the hottest topics:
> Management of Malpositioned IOLs
> Corneal Inlays for Treatment of
Presbyopia
> iGlaucoma: The Latest Innovations in
Glaucoma Therapy
> Optical Coherence Tomography Angiography in Retinal Diseases
> Panel discussion: A panel discussion,
“Physician Payment under MACRA:
Choices for Ophthalmologists,” will be
moderated by Mike X. Repka, MD. The
panel will include George A. Williams, MD,
Cynthia Mattox, MD and David A. Glaser,
MD. Learn more about the Medicare Access
and CHIP Reauthorization Act, which will
affect up to 836,000 clinicians and allocate
more than $1.2 billion in payment bonuses
and penalties in its first year alone. > Skills Transfer Labs: A total of 57 will be
AT BOOTH
2473
>
>
>
>
offered this year, including these new ones:
Laser Retinopexy for Retinal Breaks:
Simulation Workshop Smartphone Fundus Photography
Advanced Suturing: Scleral and Iris Fixation of Posterior Chamber IOLs plus Intraocular Knot Tying Breakfast with the Experts: These roundtables are an opportunity to combine a
buffet breakfast with informative conversations. These will be held Sunday
through Tuesday from 7:30-8:30 a.m. Purchase tickets when you register for the
meeting for $30, or upon arrival in Chicago for $40. Seating is limited, so register
early for best selection.
N AV I G A T I N G I T A L L
Although the scope of the meeting may seem
large and intimidating, the ability to navigate
the meeting content and the location of exhibits and sessions is greatly enhanced by the use
of the Mobile Meeting Guide (http://www.aao.
org/annual-meeting/mobile-meeting-guide), Dr.
Rubenstein advised.
“This smartphone app has proven to be invaluable to me,” he said. “There is no other
ophthalmology meeting in the world that provides the wide breadth of content and the ability to meet and interact with local and international colleagues.
Dr. Rubenstein added, “I am really looking forward to this year’s meeting and I hope
to see my many friends and colleagues from
around the world there.” ■
Getty Images/MattFrankel
> Charles D. Kelman Lecture: Given Roger F.
Steinert, MD
> Parker Heath Lecture: “Assessing Late Stage
Physicians, The State of the Art,” given
by Stephen R. Permut, MD, JD
> Dr. Allan Jensen & Claire Jensen Lecture in
Professionalism and Ethics: “Ophthalmology Took a Stand!” given by Alfred Sommer, MD, MHS. Cosponsored by the Ethics
Committee
> Robert N. Shaffer Lecture: “Glaucoma Population Management,” given by George A. Cioffi, MD. Cosponsored by Prevent Blindness
> C. Stephen and Frances Foster Lecture on Uveitis
and Immunology: “Immunosuppression for
the Uveitides: Current Status and Future
Directions,” given by Douglas A. Jabs, MD,
MBA. This lecture also is new this year.
> Barraquer Lecture: “Keratoconus: Progressive Management of a Progressive Disease,” given by Alaa M. Eldanasoury, MD.
Cosponsored by the International Society
of Refractive Surgery
18
surgery
SePtember 15, 2016 :: Ophthalmology Times
CXL advances treatment
of keratoconus, ectasia
Patient cohort provides opportunity to consider other aspects of crosslinking outcomes
By Peter S. Hersh, MD, Special to Ophthalmology Times
e
T e aneck , n J ::
arlier this year, the corneal collagen crosslinking (CXL) procedure was approved by the FDA
for the treatment of progressive
keratoconus in patients >14 years
of age as well as for ectasia after
refractive surgery.
The treatment is designed to decrease the
progression of keratoconus, a disease typified
by distortion of the normal corneal optical
dome secondary to biomechanical structural
weakening. CXL aims to mitigate the progression of this distortion by strengthening the
corneal stroma.
Approval was granted to Avedro, using its
riboflavin products (Photrexa Viscous and Photrexa). The first comprises riboflavin 5’-phosphate 0.146% in solution containing 20% dextran and is used for riboflavin loading and during UV exposure, whereas the latter is riboflavin 5’-phosphate 0.146% without dextran and
is used for corneal swelling after the loading
phase in corneas which have an intraoperative thickness <400 um. The riboflavin drops
are used in conjunction with the Avedro KXL
System, which operates at 365 nm UVA at a
power of 3mW/cm 2.
The approved procedure is similar to the
method used internationally for many years:
1. The eye is prepped and draped in the usual
fashion and a lid speculum is placed.
2. A 9.0 mm removal of the central epithelium
is performed per the surgeon’s preference. Usually, either a spatula or 20% alcohol is used to
remove the epithelium.
3. With the lid speculum removed, riboflavin with
dextran (Photrexa Viscous) is applied topically
every 2 minutes for 30 minutes. The patient is
instructed to keep eyes closed between drops.
4. After 30 minutes, confirm adequate riboflavin uptake by slit lamp examination. Uptake is
confirmed by a homogeneous green fluorescence throughout the corneal stroma and by
the presence of a yellow/green flare in the anterior chamber. If uptake is not adequate, ad-
ditional riboflavin is administered until flare is
observed. (Figure 1)
5. UV administration should not be started in
corneas thinner than 400 microns. If the corneal thickness is less than 400 microns, instill
Photrexa drops (riboflavin without dextran) every
5 to 10 seconds until the corneal thickness increases to at least 400 microns. Photrexa is a
relatively hypotonic solution which swells the corneal stroma, the goal of which is to protect the
endothelium from damage by the riboflavin/UV
interaction. Typically, we apply the drops for two
minute intervals and then recheck pachymetry
until this 400 micron threshold is met.
6. Place the patient under the KXL System. Place
lid speculum and use the controller to center
the treatment in the x,y, and z planes over the
central cornea. Irradiate the eye for 30 minutes,
assuring that the patient maintains gaze and
the treatment is centered. During irradiation,
continue topical instillation of Photrexa Viscous
onto the eye every 2 minutes. (Figure 2)
Trial criTeria
FDA approvals of CXL for the two indications
were each based on the results of two randomized, controlled clinical trials sponsored by
Avedro. The primary efficacy criterion was a
difference in the change in maximum keratometry on corneal topography analysis between
treatment and sham control groups.
Maximum keratometry was chosen as a
quantitative descriptor of keratoconus severity. Change in maximum keratometry can be
thought of as an indicator for progression or
stability of keratoconus. For the multicenter
studies of progressive keratoconus, average
maximum keratometry improved by 1.6 D for
patients enrolled with keratoconus, compared
with average progression in control eyes. In
corneal ectasia, average maximum keratometry improved by about 0.7 D.
In our own patient cohort treated within
the U.S. multicenter trials we looked at a number of other aspects of crosslinking outcomes:
Corneal topography: In a 71 eye study, we
(Figure 1) Slit lamp photo
showing homogeneous
saturation of riboflavin
throughout cornea. (Images
courtesy of Peter S. Hersh, MD)
(Figure 2) The corneal collagen crosslinking
procedure.
(Figure 3) Topography improvement
1 year after crosslinking.
noted an improvement in corneal topography
indices using Scheimpflug imaging, including
the keratoconus index (KI), index of surface
Continues on page 20 : CXL
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solution prior to intraocular use.
OMIDRIA is contraindicated in patients with a known hypersensitivity to any of its ingredients.
Systemic exposure of phenylephrine may cause elevations in blood pressure.
Use OMIDRIA with caution in individuals who have previously exhibited sensitivities to
acetylsalicylic acid, phenylacetic acid derivatives, and other nonsteroidal anti-inflammatory drugs
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The most commonly reported adverse reactions at 2-24% are eye irritation, posterior
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20
SEPTEMBER 15, 2016 :: Ophthalmology Times
variance (ISV) and index of vertical asymmetry (IVA). The improvements observed in ISV indicate a
decrease of the curvature variation
compared to the mean curvature
of the cornea, and IVA, a measurement of the difference between the
superior and inferior curvature of
the cornea, is analogous to an improvement in the more commonly
used inferior-superior steepness.
Improvement in KI may indicate that there is an improvement
normalization of the keratoconic
topographic appearance postoperatively. The overall improvements
in corneal topography indices suggest, in general, that the cone is
flattening and that the post-CXL
cornea is becoming more optically
regular and symmetric. (Figure 3)
Higher- order aberrat ions
(HOAs): Corroborating our findings from corneal topography, we
analysed HOAs in 96 eyes undergoing crosslinking and found significant improvements in ocular
and anterior corneal HOAs 1 year
after CXL. We found that the average total anterior corneal HOAs,
total coma, third-order coma, and
vertical coma all improved after
crosslinking. Looking at total ocular HOAs, total coma, third-order
coma, trefoil, and spherical aberration all improved. (Figure 4)
Patient satisfaction: In an effort
to expand on the objective postoperative assessment of the crosslinking procedure and to further
elucidate the expected clinical response, self-reported patients’ optical symptoms and visual function
were analyzed in 107 cases. In our
study, patients generally noted subjective improvement in visual symptoms. Specifically, night driving,
difficulty reading, diplopia, glare,
halo, starbursts, and foreign body
sensation were all improved one
year after CXL. (Figure 5)
Postoperative timecourse and
corneal haze/demarcation line: It
is important for surgeons and patients alike to be aware of the time-
3.0
2.8 2.6*
2.0
2.6 2.4
1.0
1.0 0.9*
0.9 0.8*
0.0
Total HOA
Spherical
Aberration
Coma
Trefoil
(FIGURE 4) Changes in higher-order aberrations preoperatively to 1 year after
crosslinking. (All figures/images courtesy of Peter S. Hersh, MD)
3.5
Patient ratings (0–5)
( Continued from page 18 )
3.2
3.0
3.1
2.8
2.7
2.5
Preop
1 year
3.1
2.9
2.5
2.6
2.7
2.5
2.4
2.0
1.8 1.6
1.5
*
ng
rivi
D
ht
re*
Gla
Nig
lo*
Ha
*
*
rts
rbu
Sta
u
fic
Dif
ing
ad
re
lty
gn
rei
dy
*
ion
sat
sen
2.1 2.0
Dry
n
ess
2.5 2.6
2.4
1.6 1.6
in
Pa
ion
ia
ob
ph
to
ho
P
bo
in
ns
vis
tio
tua
c
Flu
Fo
(FIGURE 5) Changes in subjective vision surgery preoperatively to 1 year after
crosslinking.
62.5
Keratometry
CXL
Higher order aberrations
(RMS wavefront error in μm)
surgery
60.0
58.0
58.5
59.8
58.2
56.0
57.1
56.9
54.0
52.0
Baseline
1 month
3 months
6 months
1 year
(FIGURE 6) Timecourse of improvement in maximum keratometry after CXL.
Note worsening, on average, at 1 month.
course of healing and vision recovery after crosslinking. In general,
there is a worsening of vision and
steepening of the keratoconic cone
at 1 month postoperatively with
improvement thereafter. (Figure 6)
On examination, corneal haze
is generally noted after the CXL
procedure. It appears initially as
a dust-like change in the corneal
stroma and evolves over time to a
mid-stromal demarcation line, delineating the posterior extent of the
crosslinking reaction. (Figure 7)
We quantified the natural history of corneal haze over time
after crosslinking using Sheimp-
flug densitometry. Similar to the
timecourse of clinical outcomes
after crosslinking, there appears
to be an increase in haze, which
peaks at one month, and plateaus
between 1 and 3 months. Between
3 and 6 months the cornea begins
to clear, and continues to return toward baseline at 1 year. (Figure 8)
It remains unclear whether this
postoperative haze is an unwanted
side effect or rather a desired wound
healing affect demonstrating the efficacy of the crosslinking procedure.
We also looked at corneal thickness after CXL and found that mild
corneal thinning is a general con-
comitant of the early CXL postoperative course. Similar to the
timecourse of crosslinking associated corneal haze and crosslinking clinical outcomes, the cornea
appears to thin at 1 and 3 months,
and to re-thicken between 3 and
12 months. In our study, at 1 year,
corneas remained slightly thinner
than preoperative measurements.
Predictors of outcomes: The essential goal of collagen crosslinking
is to stabilize the progression of the
ectatic cornea. With regard to this
disease stabilization, crosslinking
certainly appears efficacious. In our
study, 98.1% of eyes showed <2 D
and 91.6% showed <1.0 D of topographic progression over one year
postoperatively. Although there was,
on average, 1.7 D flattening of the
cone, looking at individual eyes, the
maximum K value decreased by 2.00
D or more in 31% patients, remained
unchanged within 1 D in 65%, and
increased by 2 D or more in 4%.
To determine preoperative patient characteristics that may predict topography and visual acuity
outcomes of CXL, we performed
multiple regression and odds ratio
analysis on a cohort of 104 eyes. The
finding was that eyes with more
preoperative steepening tended to
have a greater improvement in topography; specifically, those with
maximum K >55 D were 5.4x more
likely to have topographic flattening >2 D after CXL compared with
eyes with flatter corneas.
With regard to eyes in which
corneal topography continued to
steepen, that is, those in which
the crosslinking procedure failed
to completely stabilize the disease,
there were no independent predictors of continued disease progression even at the more refined >1D
level; all eyes were equivalently
likely to be stabilized by the CXL
procedure. Specifically, in patients
with an initial maximum K >55
D, 40/44 (90%) eyes showed less
than 1 D of progression, one year
after CXL; similarly, in patients
with initial maximum K <55.0D,
55/60 (92%) eyes were stable.
Finally, preoperative cone location may play an important role
in the efficacy of the CXL. There
appears to be more topographic
21
SEPTEMBER 15, 2016 :: Ophthalmology Times
surgery
(FIGURE 7) Early general
haze evolves to
demarcation line after
crosslinking.
(FIGURE 8) Scheimpflug
densitometry showing
evolution of corneal haze,
peaking at one month,
plateauing at 3 months, and
improving to baseline at 6
and 12 months.
flattening in those eyes with centrally located cones. We found that
maximum keratometry flattened by
2.6 D in eyes with centrally located
cones, and by only 1 D and 0.05
D, in those eyes with paracentral
and peripheral cones, respectively.
With regard to corrected visual
acuity, we found, on average, an approximately 1-line improvement in
the cohort analyzed. When stratified by individual eyes, however, vision improved by 2 or more Snellen
lines in 21% and remained stable
within 1 line in 78%; 1 eye in our
patient cohort lost 2 Snellen lines.
In our analysis, the only independent predictor of a change in
postoperative best-corrected vision after CXL was preoperative
best corrected visual acuity. Those
eyes with worse preoperative best
corrected visual acuity were more
likely to experience an improvement of >2 Snellen lines. Specifically, eyes with a preoperative
Snellen visual acuity of 20/40 or
worse were 5.9 times more likely
to improve by two lines or more;
43% of eyes with best corrected
vision 20/40 or worse had on improvement of >2 lines compared
with only 11% of eyes who were
better than 20/40 preoperatively.
With regard to eyes which lost vision from the procedure, the most
salient indicator of an unwanted
outcome, there was no independent preoperative indicator; however, it is very important to advise
those patients with very good correctable vision before crosslinking
of the changes in vision that may
be experienced during the healing process. ■
References
1. Hersh PS, Greenstein SA, Fry KL.
Corneal cCollagen crosslinking for
keratoconus and Corneal ectasia:
One year results of a randomized
prospective Study. J Cat Refract Surg.
2011:37:149-160.
2. Greenstein SA, Fry KL, Bhatt J, Hersh
PS. Natural history of corneal haze after
collagen crosslinking for keratoconus
and corneal ectasia: A Scheimpflug and
biomicroscopic analysis. J Cat Refract
Surg. 2010:35:2105-2114.
3. Greenstein SA, Fry KL, Hersh PS.
Corneal topography indices after
corneal collagen crosslinking for
keratoconus and corneal ectasia:
one year results. J Cat Refract Surg.
2011:37:1282-1290
4. Greenstein SA, Fry KL, Hersh, MJ,
Hersh, PS. Higher-order aberrations
after corneal collagen crosslinking for
keratoconus and corneal ectasia. J Cat
Refract Surg. 2012;38:292-302.
5. Greenstein SA, Shah VP, Fry KL,
Hersh PS. Corneal thickness changes
after corneal collagen crosslinking
for keratoconus and corneal ectasia:
one year results. J Cat Refract Surg
2011:37:691-700.
6. Brooks NO, Greenstein SA, Fry KL,
Hersh, PS. Patient subjective visual
function after corneal collagen
crosslinking for keratoconus and
corneal ectasia. J Cat Refract Surg
2012;38:615-619.
7. Greenstein SA, Hersh PS.
Characteristics influencing outcomes
of corneal collagen crosslinking for
keratoconus and ectasia: Implications
for patient selection. J Cat Refract Surg.
2013;39:1133-1140.
8. Greenstein SA, Fry KL, Hersh, PS. Effect
of topographic cone location on outcomes
of corneal collagen cross-linking for
keratoconus and corneal Ectasia. J Cat
Refract Surg 2012; 28: 397-405.
PETER S. HERSH, MD, FACS
E: [email protected]
Dr. Hersh discloses he is medical monitor with Avedro Inc.,
Waltham MA.
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SEPTEMBER 15, 2016 :: Ophthalmology Times
surgery
Optimizing toric IOL outcomes
via techniques, technologies
Accuracy of results requires attention to multiple sources for residual astigmatism
By Cheryl Guttman Krader; Reviewed by Rudy M.M.A. Nuijts, MD, PhD
MA AS T RICH T, T HE NE T HERL ANDS ::
A LARGE MAJORITY of cataract surgery patients with a toric IOL implanted will
achieve spectacle independence for distance
vision, but a sizeable proportion are left with
significant residual astigmatism and find themselves needing glasses at least sometimes.
Understanding the sources of residual astigmatism allows surgeons to choose techniques
and technologies that will optimize outcomes
for toric IOL surgery, according to Rudy M.M.A.
Nuijts, MD, PhD.
“Results from a trial we conducted showed
that 70% of patients who underwent bilateral
toric IOL implantation could see 20/25 uncorrected at distance and 84% of patients were
spectacle independent for distance vision,” said
Dr. Nuijts, professor of ophthalmology, Maastricht University Medical Center, Maastricht,
The Netherlands.
However, 26% of patients had more than 1 D
of residual stigmatism and 54% were left with
at least 0.5 D of residual astigmatism. (Figure 1)
He reviewed factors affecting the astigmatic
outcome, including preoperative measurement
errors; surgically induced astigmatism (SIA);
calculation inaccuracies, including the effect
of posterior corneal astigmatism, and toric IOL
misalignment.
PR EOPER ATIVE ISSUES
Accuracy of preoperative measurements is critical, and different instruments can be used
for determining keratometry values. Dr. Nuijts noted that a study performed by his group
found there was not a large difference between
the measurements obtained when using several different instruments for autorefraction, a
manual keratometer, or the sim K value measured with a topographer or a Scheimpflug
tomographer (Pentacam, Oculus).
However, the equivalent K value measured
with the latter device was significantly lower
than the values obtained with the other devices. The explanation for the difference is that
the equivalent K incorporates astigmatism of
the posterior corneal surface, Dr. Nuijts said.
He noted that the influence of the posterior
cornea on total astigmatism has been described
RCT Toric versus Monofocal IOLs
100
99
Toric
Monofocal
80
Percentage of patients
22
74
60
40*
46
41
30
20
10
0
≤0.50
≤1.00
≤1.50
Refractive astigmatism
´ 26% of eyes still had >1.0 D of residual astigmatism
´ 54% of eyes still had >0.5 D of residual astigmatism
*p < 0.05
(FIGURE 1) Residual refractive astigmatism after toric IOL implantation.
(FIGURE 2) Influence of the posterior corneal surface showing 1.5 D of posterior corneal astigmatism.
(Images courtesy of Rudy M.M.A. Nuijts, MD, PhD)
by Douglas Koch, MD, and colleagues. Essentially, the posterior cornea acts as a minus
lens and is generally steep vertically, inducing
against-the-rule (ATR) corneal astigmatism
that compensates for some of the with-the-rule
astigmatism on the anterior corneal surface.
On a population basis, the magnitude of
posterior corneal astigmatism is about 0.3 D,
SEPTEMBER 15, 2016 :: Ophthalmology Times
surgery
and in about 10% of eyes, the value
PER IOPER ATIV E ISSUES
Misalignment of the toric IOL afexceeds 0.5 D.
Results from various studies show fects the astigmatic outcome as
that the accuracy of the astigmatic there is about a 3% loss of effioutcome with toric IOL implanta- cacy for every degree of misaligntion can be improved when the ment. For surgeons who manually
posterior corneal astigmatism is mark the eye, accuracy of toric IOL
factored into power calculations, alignment depends on the accuracy of the preoperative markings,
Dr. Nuijts said.
“Especially in cases with high including both the reference and
anterior corneal astigmatism, the in- axis alignment marks.
Dr. Nuijts said
fluence of the postethat he likes to use a
rior corneal surface
bubble marker, but
can be significant
noted that research
and has to be taken
Achieving spectacle
conducted by Oliver
into consideration
independence for
Findl, MD, comparwhen performing
distance vision after
ing marking at the
the toric IOL power
toric IOL implantation
slit lamp, a penducalculation,” said
depends on the
lar marker, bubble
Dr. Nuijts.
refractive outcome.
marker, and tonomHe presented a
Factors affecting
eter marker showed
case to illustrate
residual astigmatism
the most predictthis point (Figure
and studies
able outcomes were
2) and discussed
evaluating the use
achieved using the
resu lt s of one
of various surgical
pendular marker.
study investigattechniques and
Intraoperative
ing showing that
technologies relating
digital guidance
in eyes with ATR
to those factors are
techniques have
total corneal astigdiscussed.
been developed to
matism, the proporovercome the inaction of eyes left with
<0.45 D of refractive astigmatism curacies of manual marking.
However, there is still room for
decreased from 67% to 42% using
a method that accounted for pos- error when using this technology
because digital marking cannot
terior corneal astigmatism.
Another study comparing differ- eliminate human error from malent methods for measuring kera- positioning of the IOL relative to
tometry and different formulas for the intended meridian.
“A study we conducted found that
power calculations found that the
most accurate results were achieved even when using a digital markusing an optical low coherence re- ing system, there was still an averflectometry device and a calcu- age inaccuracy of 2.6° in this last
lation method that compensates step of toric IOL positioning,” Dr.
for the effect of posterior corneal Nuijts said.
In addition, there is still the poastigmatism (Barrett calculator).
SIA also influences the astigmatic tential for the toric IOL to rotate
outcome and needs to be factored postoperatively, although on averinto toric IOL power calculations. age, modern toric IOLs demonstrate
Dr. Nuijts noted that the amount of excellent postoperative stability. ■
SIA varies depending on incision
size, location, and level of preoperative astigmatism.
However, he pointed out that in
a study his group conducted evaluRUDY M.M.A. NUIJTS, MD, PHD
ating the effect of incision size on
E: [email protected]
SIA, the standard deviation of the
This article was adapted from Dr. Nuijts’ presentation during
average error was the same across
Refractive Surgery Subspecialty Day at the 2015 meeting
the different incision sizes (0.52 to
of the American Academy of Ophthalmology. Dr. Nuijts is
0.54 D), indicating there is still a
a consultant, lecturer, and or receives grant support from
problem with predictability of SIA.
companies that market toric IOLs. TAKE-HOME
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24
SEPTEMBER 15, 2016 :: Ophthalmology Times
surgery
Creating corneal inlay pockets
with femtosecond laser technology
Surgeons should be familiar with laser parameters, techniques to achieve best outcomes
By Fred Gebhart; Reviewed by Majid Moshirfar, MD
SALT L AK E CI T Y ::
CREATING A CORNEAL pocket for
One notable pearl for surgeons is to crea small-aperture corneal inlay (Kamra, Acu- ate a pocket that penetrates at least 40% of
Focus) in itself is not a difficult process. Using the cornea depth.
a femtosecond laser to create the proper pocket
“LASIK flaps today are around 100 to 120
in the correct position to allow precise place- μm,” he explained. “For a corneal inlay, a
ment for optimal vision correction requires pocket as deep as 225, 250, or even 300 μm
finesse and expertise.
is advantageous for placement. The deeper
“We have three different platforms that can you go, as long as you respect the stromal
create pockets for the inlay and they can all bed of 250 μm, the more you reduce the risk
do an excellent job in experienced hands,” of hyperopic shift, visual fluctuations, and
said Majid Moshirfar, MD.
dry eye symptoms in patients.”
“I personally use the Intralase iFS and the
Alcon FS200 to create pockets and I can’t find
PR ACTIC A L PE A R LS
a difference between them in performance,” Dr. Moshirfar offered five additional tips for
said Dr. Moshirfar, clinical professor of oph- successful corneal pocket creation and pinthalmology, University of Utah Moran Eye hole-aperture vision correction:
> Good patient selection
Center and medical research director, Hoopes
> Manage patient expectations
Vision, Salt Lake City.
> Proper centration
But the Intralase iFS, Alcon FS200, and
> Surgical microscope
Ziemer FEMTO LDV Z8 are not identical. The
> Decentered suction ring
iFS was the first femtosecond laser on the
U.S. market, Dr. Moshirfar said.
U.S. surgeons have more experience on
Patient selection is vital. Good surgical canthe iFS system than any other platform and didates are in good health, Dr. Moshirfar said,
have devoted more time and attention to with no underlying disease.
tweaking and calibrating its operational paGood surgical candidates also have a smallrameters, he noted.
angle kappa, the distance between the center of
“The limitation with this device is that it the pupil and the Purkinje reflex. The smaller
can only create a pocket along
the angle kappa, the more likely
the temporal aspect of the corthe patient is to see significant
nea,” he added. “That can be
vision improvement. Patients
A surgeon
a limitation when you have a
whose angle kappa is 500 μm or
with clinical
patient who could be better
larger are not good candidates
experience with
treated with an incision from
for Kamra vision correction.
three femtosecond
another direction.”
Patients should also have minlasers discusses
The FS200 and the Z8 have
imal refractive error before surthe practicalities
their own advantages and limigery and little to no astigmatism.
of creating ideal
tations. Both can create pockPatients with significant refracfemtosecond laser
ets at any angle.
tive error may need LASIK or
inlay pockets.
The Z8 creates wider pockets
PRK correction before the inlay
than the other two platforms,
pocket is created. Patients with
which gives more space for insignificant astigmatism must
strumentation and maneuvering while placing have it corrected before inlay surgery.
the inlay. Docking is very easy and the de“You have to talk with your patients about
vice gives the familiar feel of microkeratome. expectations,” Dr. Moshirfar continued. “PinThe FS200 is quick and easy to operate and hole-aperture technology can allow most paallows the operator to trace the path of the tients to attain good near vision, but it won’t
incision for more precise placement.
make everyone a J1. If you look at the FDA ap-
TAKE-HOME
proval study, more than 87% of patients were
20/40 or better for near vision and 31% were
20/20 or better for near vision at the end of
the 60 months study period. We cannot promise all patient that they will become 20/20 at
near after surgery.”
Proper centration of the inlay is also crucial. In an ideal world, the center of the pupil
would be coaxial with the four Purkinje images. In the real world, surgeons must assess
the eye preoperatively.
If distance from the center of the pupil and
the Purkinje reflex is less than 300 μm, Dr.
Moshirfar advised centering the device on the
Purkinje.
If the distance is more than 300 μm, he advised centering the device between the center
of the pupil and the Purkinje reflex. Patients
with a larger gap are not good candidates for
the device.
SURGICAL MICROSCOPE
Dr. Moshirfar also advised using a surgical
microscope for optimal device placement. Current femtosecond laser platforms lack a microscope, which has prompted many surgeons
to use the microscope on an excimer laser to
implant the device. A conventional surgical
microscope provides better visualization and
more precise movement when inserting and
placing the inlay.
The final tip is to decenter the suction ring
slightly in the direction of the incision. Decentering the ring to visualize a small bit of
conjunctiva makes it easier to open the incision closer to the limbus. The closer the incision is to the limbus, the lower the risk of
astigmatism and the less likely the pocket is
to interfere with any later surgery. ■
MAJID MOSHIRFAR, MD
P: 801/568-0200
This article was adapted from Dr. Moshirfar’s presentation at the 2016 meeting
of the American Society of Cataract and Refractive Surgery. He did not indicate any
proprietary interest in the subject matter.
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26
SEPTEMBER 15, 2016 :: Ophthalmology Times
surgery
Combination therapy targets pupil
maintenance, pain during surgery
Analysis finds positive results compared with placebo in two pooled phase III studies
By Vanessa Caceres; Reviewed by Thomas Walters, MD
Intraoperative Mean AUC
Change-from-Baseline in Pupil Diameter
p < 0.0001
p < 0.0001
p < 0.0001
Mean Area Under Curve (mm)
0.0
0.0
0.0
-0.5
-0.4
0.6
-0.7
-1.0
-0.9
-0.9
-1.5
-2.0
p < 0.0001
p < 0.0001
p < 0.0035
p < 0.0620
14.2
17.2
40
Less Pain
0.0
-0.0
Decrease in Pupil Size
0.5
0.1
p < 0.0001
p < 0.0053
1.0
Mean Area Under Curve (mm)
p < 0.0001
Postoperative Mean AUC Subject-Reported
Ocular Pain Measured by Visual Analog Scale
30
20
7.5
13.0
11.9
-0.9
10
5.3
3.5
5.1
4.9
4.8
0
≤ 10 min
> 10 min
> 12 min
> 15 min
> 20 min
≤ 10 min
> 10 min
> 12 min
> 15 min
> 20 min
n = 242 N = 249
n = 138 N = 130
n = 105 N = 94
n = 52 N = 43
n = 19 N = 11
n = 258 N = 261
n = 145 N = 142
n = 111 N = 103
n = 57 N = 48
n = 22 N = 15
Placebo
Phenylephrine/Ketorolac
Error bars depict standard deviation
Placebo
Phenylephrine/Ketorolac
Error bars depict standard deviation
(Figures courtesy of Thomas Walters, MD)
AUS T IN, T X ::
PATIENTS WHO RECEIVED the utes or less, longer than 10 minutes, longer
combination medication phenylephrine/ than 12 minutes, longer than 15 minutes, and
ketorolac (Omidria, Omeros Corp.) during cata- longer than 20 minutes. Researchers used the
ract surgery were better able to maintain their mean area under the curve analysis to measure
pupil diameter during surgery compared with intraoperative change from baseline in pupil
placebo, according to Thomas Walters, MD.
diameter (figure, above left) and postoperative
The investigation looked at the
subject-reported ocular pain as
pooled results from two phase
measured by a Visual Analog
III randomized, double-masked,
Scale (figure, above right).
The combination
placebo-controlled studies inAll procedures were recorded,
of phenylephrine and
cluding 808 subjects—403 reand changes in pupil diameter
ketorolac helped
ceived phenylephrine/ketorolac
were measured at 1-minute inmaintain pupil
and 405 received placebo, said
tervals from time of incision to
diameter and lowered
Dr. Walters, who is in private
wound closure (end of surgery).
postoperative pain
practice in Austin, TX.
A single masked central reader
compared with
The study objectives were to
made the measurements.
placebo in patients
measure maintenance of pupil
having cataract
diameter during cataract surBETTER PUPIL
surgery in two pooled
gery or refractive lens exchange
MAINTENANCE
phase III studies.
and postoperative ocular pain
Demographics and cataract charduring the first 10 to 12 hours
acteristics were similar between
after surgery.
the group receiving phenylephThe medication was administered in stan- rine/ketorolac and the placebo group. The group
dard irrigation solution during the procedure, receiving phenylephrine/ketorolac had better
and all subjects in both areas received standard pupil maintenance at all time points, and there
preoperative mydriatic and anesthetic agents. was less postoperative pain, he said.
Procedure times were categorized as 10 minAs for postoperative ocular pain, “it increased
TAKE-HOME
in the placebo group with increasing surgical duration, but was numerically similar in
the phenylephrine/ketorolac group,” Dr. Walters said.
The addition of phenylephrine/ketorolac to
the cataract surgeon’s armamentarium is important because of the risks associated with
pupil constriction, he said.
“You can get iris touch with the phaco probe,
which induces miosis and inflammation,” Dr.
Walters explained. “When you have reduced
visibility of the lens, it makes the procedure
more difficult for the surgeon and potentially
more complicated for the patient with iris trauma
and postop inflammation.”
Dr. Walters concluded that the medication
aids with ease of the procedure and quicker
visual recovery. ■
THOMAS WALTERS, MD
E: [email protected]
This article was adapted from Dr. Walters’ presentation at the 2016 meeting
of the American Society of Cataract and Refractive Surgery. Dr. Walters is a consultant
for Omeros Corp.
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ASTIGMATISM MANAGEMENT: A JOURNEY OF
O INNOVATION
ON
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Hilton Chicago – International Ballroom North†
Registration: 5:30 – 6:15 PM
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28
SEPTEMBER 15, 2016 :: Ophthalmology Times
surgery
REVERSE OPTIC
( Continued from page 1 )
what Dr. Hoffman described as an obvious
opening in the equator of the bag.
He noted that surgical options for a torn
posterior include:
> Leave the IOL in place and address it if it
subluxates further;
> Levitate the IOL into the ciliary sulcus (not
an option for a single-piece IOL);
> Levitate the IOL into the ciliary sulcus and
suture the haptics (also not a viable option);
> Use the capsulorhexis to capture the optic;
> Exchange the IOL for a three-piece IOL in
the sulcus
and kept the irrigator in the eye to maintain
the pressure and prevent vitreous from coming from around the lens.
“The reality was that with the optic captured
on the rhexis, even if the chamber did become
shallow, additional vitreous probably would
not have come forward,” Dr. Hoffman said.
He finished by hydrating the wounds, removing the infusing cannula, and injecting acetylcholine (Miochol-E, Bausch + Lomb) into the
anterior chamber. Three months postoperatively, the IOL remained centered. OCT showed
good clearance between the anterior surface
of the IOL and the posterior surface of the iris.
CONSIDER ATIONS
The Cataract Clinical Committee of the American Society of Cataract and Refractive Surgery
has emphasized that single-piece IOLs should
not be implanted into the ciliary sulcus without
fixation because of the risk of pigment disperDr. Hoffman opted to perform a reverse optic sion, glaucoma, uveitis, and recurrent vitreous
capture. He first injected an OVD in front of hemorrhages, Dr. Hoffman noted.
“However, it may be okay to put single-piece
the lens and more behind the lens to push the
vitreous back behind the capsule. He then used IOLs in the bag and perform reverse optic capture,” said Dr. Hoffman, recountthe same viscoelastic cannula to
ing a recent study of the proceprolapse the optic up in front of
dure performed in 16 eyes, with
the anterior rhexis, which proved
Reverse optic
12 of the fellow eyes serving as
to be successful.
capture may be
controls (Ophthalmic Surg La“At this point, the IOL was
a viable option
sers Imaging. 2012;43:480-488).
centered and stable,” he said.
for addressing a
The authors reported that paBecause vitreous was in the
decentered singletients achieved 20/25 or better
anterior chamber previously, Dr.
piece IOL as the result
vision in 94% of the eyes in
Hoffman removed the OVD using
of a compromised
which the reverse optic capa 23-gauge vitrector. A 20-gauge
posterior capsule or a
ture was performed compared
irrigating cannula was positioned
posterior capsular tear.
to 92% in the control eyes. In
through the left-hand incision.
both groups, 94% and 100%,
Hindsight suggested a 20-gauge
respectively, were within 1 D
vitrector would have prevented
fluid from egressing from the bimanual incision. of the intended correction. The IOLs in all eyes
After removing as much of the OVD as pos- that underwent reverse optic capture remained
sible, Dr. Hoffman removed the vitrector and centered, and no vision-threatening complicakept the irrigator in the eye. He injected tri- tions occurred after 19 months of follow-up.
The study concluded that reverse optic capamcinolone to identify any vitreous in the anterior chamber, and used the irrigator to wash ture of a single-piece acrylic IOL through an
anterior capsulorhexis merits consideration for
the triamcinolone out of the eye.
When no vitreous was seen in the anterior IOL placement in selected cases of insufficient
chamber, Dr. Hoffman hydrated the incision posterior capsule support. ■
SURGICAL CASE
VIDEO Following “high-speed” removal
of this routine 2+ nuclear sclerotic cataract, a
single-piece IOL is injected into the capsular bag
resulting in a “crease” in the posterior capsule.
During viscoelastic removal, it became apparent
the crease was a large opening in the posterior
capsule, which resulted in vitreous prolapsed and
aspiration into the aspirating bimanual cannula.
(Videos courtesy of Richard S. Hoffman, MD)
TAKE-HOME
VIDEO The IOL optic is prolapsed in
front of the capsulorhexis (reverse optic capture)
with an OVD cannula following by removal of the
OVD with a 23-gauge vitrector and a 20-gauge
irrigating cannula. Triamcinolone is injected
into the anterior chamber to check for vitreous
followed by stromal hydration of the wounds and
injection of miochol to constrict the pupil.
Go to OphthalmologyTimes.com/
ReverseOpticCapture
RICHARD S. HOFFMAN, MD
E: [email protected]
This article was adapted from Dr. Hoffman’s presentation at the 2015 meeting of
the American Academy of Ophthalmology. He has no financial interest in the subject
matter.
AAO, societies issue post-surgery, co-management guidance
THE AMERICAN Academy of Ophthalmology (AAO)—along with 60 other ophthalmic
societies—has issued new, more patient-centric
guidelines (http://bit.ly/2ccuiu6) for postoperative co-management of ophthalmic procedures.
A principal aim of the revision is to better
inform patients with full disclosure of compensation arrangements for the non-operating
practitioner and fees that practitioners may
charge beyond those that Medicare and other
third-party payors would cover, said the AAO
in a prepared statement.
The new guidelines call for written informed
consent and financial disclosure; reflect that
co-management goes beyond cataract surgery
to all ophthalmic surgery; and address the distinction between the legal and ethical aspects
of co-management. ■
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30
NEXT FRONTIER IN MANAGEMENT OF
Special Report )
RETINA DISEASE
ADVANCES CONTINUE TO PROGRESS IN THE AREAS OF PHARMACOLOGY, SURGERY, AND DIAGNOSIS
CASE 1: 29-year-old male
20/60
20/60
Macula is flat, foveal yellow spot
(FIGURE 1) This 29-year-old male had no relevant previous of family history but had blurry vision in both eyes for the past 4 days, seeing a yellow spot in the center.
The macula is flat and there is a small yellowish spot, which, in OCT, looks like a stop in the photoreceptor continuation in the ellipsoid and interdigitation area.
There is also some hyperreflective material from the retinal pigment epithelium toward the outer nuclear layer. (Images courtesy of Anat Loewenstein, MD, MHA)
SD-OCT ENHANCES
VISUALIZATION EARLIER
IN DISEASE PROCESS
Detailed imaging facilitates evaluation of foveal disorders
By Lynda Charters; Reviewed by Anat Loewenstein, MD, MHA
S
T EL AVIV, ISR AEL ::
take-home
Spectral-domain
optical coherence
tomography facilitates
detailed evaluation of
foveal disorders even
in the very earliest
disease stages.
pectral-domain optical coherence tomography (SD-OCT) has
become indispensable for visualizing the fovea and diagnosing
retinal diseases. Importantly,
detailed visualization facilitates
diagnosis during the early disease stages, according to Anat Loewenstein, MD, MHA.
SOL A R M ACU LOPAT H Y
The first case (Figure 1) illustrating the importance of high-detailed
imaging was that of a 29-year-old male, as described by Dr. Loewenstein. The patient’s past ocular medical and family histories
were not remarkable.
The patient reported blurry vision in both
eyes over the past 4 days with a yellow spot
centrally. He denied any recent exposure to
drugs, however, he had used cocaine and cannabis “crystal” 1 year previously.
SD-OCT examination showed a normal flat
macula with a small yellow spot. However,
there was a stop in the photoreceptor continuity in the ellipsoid and inter-digitation zones.
“A hyper-reflective material was seen emerging from the retinal pigment epithelium [RPE]
toward the outer nuclear layer,” said Dr. Loewenstein, professor of ophthalmology, deputy
dean of the medical school, Sackler Faculty
of Medicine, Tel Aviv University, Israel, and
chairman of ophthalmology, Tel Aviv Sourasky
Medical Center, Tel Aviv.
The patient later admitted to lying on the
beach exposed to sunlight for the entire day
when symptoms began. The diagnosis was
solar retinopathy, secondary to sun gazing.
During follow-up, SD-OCT showed the hyperreflective material was absorbed with abrupt
continuation of the photoreceptor layer in the
fovea and the external limiting membrane (ELM)
was preserved. This status was maintained at
2 and 4 months of follow-up.
“Solar retinopathy occurs mainly during celestial events—such as eclipses, religious rituals, and sunbathing—and in psychiatric patients,” Dr. Loewenstein said. “The light is of
Continues on page 33 : SD-OCT
INDICATIONS AND USAGE
IMPORTANT SAFETY INFORMATION (continued)
ZYLET® (loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic
suspension) is a topical anti-infective and corticosteroid combination
for steroid-responsive inflammatory ocular conditions for which a
corticosteroid is indicated and where superficial bacterial ocular
infection or a risk of bacterial ocular infection exists.
Ocular steroids are indicated in inflammatory conditions of the
palpebral and bulbar conjunctiva, cornea and anterior segment of the
globe such as allergic conjunctivitis, acne rosacea, superficial punctate
keratitis, herpes zoster keratitis, iritis, cyclitis, and where the inherent
risk of steroid use in certain infective conjunctivitides is accepted to
obtain a diminution in edema and inflammation. They are also indicated
in chronic anterior uveitis and corneal injury from chemical, radiation or
thermal burns, or penetration of foreign bodies.
The use of a combination drug with an anti-infective component is
indicated where the risk of superficial ocular infection is high or where
there is an expectation that potentially dangerous numbers of bacteria
will be present in the eye.
The particular anti-infective drug in this product (tobramycin) is active
against the following common bacterial eye pathogens: Staphylococci,
including S. aureus and S. epidermidis (coagulase-positive and coagulasenegative), including penicillin-resistant strains. Streptococci, including
some of the Group A-beta-hemolytic species, some nonhemolytic
species, and some Streptococcus pneumoniae, Pseudomonas aeruginosa,
Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus
mirabilis, Morganella morganii, most Proteus vulgaris strains, Haemophilus
influenzae, and H. aegyptius, Moraxella lacunata, Acinetobacter
calcoaceticus and some Neisseria species.
6-*'*)" 0. *!*-/$*./ -*$.(4- .0'/$)"'0*(2$/#
damage to the optic nerve, defects in visual acuity and fields of
vision. Steroids should be used with caution in the presence of
glaucoma. If this product is used for 10 days or longer, intraocular
pressure should be monitored.
6. *!*-/$*./ -*$.(4- .0'/$)+*./ -$*-.0+.0'-
cataract formation.
6# 0. *!./ -*$.!/ -/-/.0-" -4(4 '4# '$)")
increase the incidence of bleb formation. In those diseases causing
thinning of the cornea or sclera, perforations have been known to
occur with the use of topical steroids. The initial prescription and
renewal of the medication order should be made by a physician only
after examination of the patient with the aid of magnification such as
a slit lamp biomicroscopy and, where appropriate, fluorescein staining.
6-*'*)" 0. *!*-/$*./ -*$.(4.0++- ../# #*./- .+*). and thus increase the hazard of secondary ocular infections. In acute
purulent conditions, steroids may mask infection or enhance existing
infections. If signs and symptoms fail to improve after 2 days, the
patient should be re-evaluated.
6(+'*4( )/*!*-/$*./ -*$( $/$*)$)/# /- /( )/*!+/$ )/.
2$/##$./*-4*!# -+ ..$(+' 3- ,0$- ."- /0/$*). *!*0'-
steroids may prolong the course and exacerbate the severity of many
viral infections of the eye (including herpes simplex).
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must be considered in any persistent corneal ulceration where a steroid
has been used or is in use.
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and superficial punctate keratitis, increased intraocular pressure,
burning and stinging upon instillation.
Please see Brief Summary of Prescribing Information for ZYLET®
on adjacent page.
IMPORTANT SAFETY INFORMATION
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conjunctiva including epithelial herpes simplex keratitis (dendritic
keratitis), vaccinia, and varicella, and also in mycobacterial infection
of the eye and fungal diseases of ocular structures.
®/™ are trademarks of Bausch & Lomb Incorporated or its affiliates.
© 2015 Bausch & Lomb Incorporated. All rights reserved. Printed in USA. US/ZYL/15/0013
BRIEF SUMMARY OF PRESCRIBING INFORMATION
This Brief Summary does not include all the information needed to use Zylet safely
and effectively. See full prescribing information for Zylet.
Zylet®(loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension)
Initial U.S. Approval: 2004
DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing
Apply one or two drops of Zylet into the conjunctival sac of the affected eye every four to six
hours. During the initial 24 to 48 hours, the dosing may be increased, to every one to two hours.
Frequency should be decreased gradually as warranted by improvement in clinical signs. Care
should be taken not to discontinue therapy prematurely.
2.2 Prescription Guideline
Not more than 20 mL should be prescribed initially and the prescription should not be
refilled without further evaluation [see Warnings and Precautions (5.3)].
CONTRAINDICATIONS
4.1 Nonbacterial Etiology
Zylet, as with other steroid anti-infective ophthalmic combination drugs, is contraindicated
in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex
keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of
the eye and fungal diseases of ocular structures.
WARNINGS AND PRECAUTIONS
5.1 Intraocular Pressure (IOP) Increase
Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve,
defects in visual acuity and fields of vision. Steroids should be used with caution in the
presence of glaucoma.
If this product is used for 10 days or longer, intraocular pressure should be monitored.
5.2 Cataracts
Use of corticosteroids may result in posterior subcapsular cataract formation.
5.3 Delayed Healing
The use of steroids after cataract surgery may delay healing and increase the incidence
of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations
have been known to occur with the use of topical steroids. The initial prescription and
renewal of the medication order should be made by a physician only after examination
of the patient with the aid of magnification such as a slit lamp biomicroscopy and, where
appropriate, fluorescein staining.
5.4 Bacterial Infections
Prolonged use of corticosteroids may suppress the host response and thus increase the
hazard of secondary ocular infections. In acute purulent conditions of the eye, steroids may
mask infection or enhance existing infection. If signs and symptoms fail to improve after
2 days, the patient should be re-evaluated.
5.5 Viral Infections
Employment of a corticosteroid medication in the treatment of patients with a history of
herpes simplex requires great caution. Use of ocular steroids may prolong the course and
may exacerbate the severity of many viral infections of the eye (including herpes simplex).
5.6 Fungal Infections
Fungal infections of the cornea are particularly prone to develop coincidentally with longterm local steroid application. Fungus invasion must be considered in any persistent
corneal ulceration where a steroid has been used or is in use. Fungal cultures should be
taken when appropriate.
5.7 Aminoglycoside Hypersensitivity
Sensitivity to topically applied aminoglycosides may occur in some patients. If hypersensitivity
develops with this product, discontinue use and institute appropriate therapy.
ADVERSE REACTIONS
Adverse reactions have occurred with steroid/anti-infective combination drugs which can
be attributed to the steroid component, the anti-infective component, or the combination.
Zylet:
In a 42 day safety study comparing Zylet to placebo, ocular adverse reactions included injection
(approximately 20%) and superficial punctate keratitis (approximately 15%). Increased
intraocular pressure was reported in 10% (Zylet) and 4% (placebo) of subjects. Nine percent
(9%) of Zylet subjects reported burning and stinging upon instillation.
Ocular reactions reported with an incidence less than 4% include vision disorders,
discharge, itching, lacrimation disorder, photophobia, corneal deposits, ocular discomfort,
eyelid disorder, and other unspecified eye disorders.
The incidence of non-ocular reactions reported in approximately 14% of subjects was
headache; all other non-ocular reactions had an incidence of less than 5%.
Loteprednol etabonate ophthalmic suspension 0.2% - 0.5%:
Reactions associated with ophthalmic steroids include elevated intraocular pressure,
which may be associated with infrequent optic nerve damage, visual acuity and field
defects, posterior subcapsular cataract formation, delayed wound healing and secondary
ocular infection from pathogens including herpes simplex, and perforation of the globe
where there is thinning of the cornea or sclera.
In a summation of controlled, randomized studies of individuals treated for 28 days or
longer with loteprednol etabonate, the incidence of significant elevation of intraocular
pressure (≥10 mm Hg) was 2% (15/901) among patients receiving loteprednol etabonate,
7% (11/164) among patients receiving 1% prednisolone acetate and 0.5% (3/583) among
patients receiving placebo.
Tobramycin ophthalmic solution 0.3%:
The most frequent adverse reactions to topical tobramycin are hypersensitivity and
localized ocular toxicity, including lid itching and swelling and conjunctival erythema.
These reactions occur in less than 4% of patients. Similar reactions may occur with the
topical use of other aminoglycoside antibiotics.
Secondary Infection:
The development of secondary infection has occurred after use of combinations containing
steroids and antimicrobials. Fungal infections of the cornea are particularly prone to
develop coincidentally with long-term applications of steroids.
The possibility of fungal invasion must be considered in any persistent corneal ulceration
where steroid treatment has been used.
Secondary bacterial ocular infection following suppression of host responses also occurs.
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Teratogenic effects: Pregnancy Category C. Loteprednol etabonate has been shown to be
embryotoxic (delayed ossification) and teratogenic (increased incidence of meningocele,
abnormal left common carotid artery, and limb fixtures) when administered orally to
rabbits during organogenesis at a dose of 3 mg/kg/day (35 times the maximum daily
clinical dose), a dose which caused no maternal toxicity. The no-observed-effect-level
(NOEL) for these effects was 0.5 mg/kg/day (6 times the maximum daily clinical dose).
Oral treatment of rats during organogenesis resulted in teratogenicity (absent innominate
artery at ≥5 mg/kg/day doses, and cleft palate and umbilical hernia at ≥50 mg/kg/day)
and embryotoxicity (increased post-implantation losses at 100 mg/kg/day and decreased
fetal body weight and skeletal ossification with ≥50 mg/kg/day). Treatment of rats at
0.5 mg/kg/day (6 times the maximum daily clinical dose) during organogenesis did not
result in any reproductive toxicity. Loteprednol etabonate was maternally toxic (significantly
reduced body weight gain during treatment) when administered to pregnant rats during
organogenesis at doses of ≥5 mg/kg/day.
Oral exposure of female rats to 50 mg/kg/day of loteprednol etabonate from the start
of the fetal period through the end of lactation, a maternally toxic treatment regimen
(significantly decreased body weight gain), gave rise to decreased growth and survival
and retarded development in the offspring during lactation; the NOEL for these effects
was 5 mg/kg/day. Loteprednol etabonate had no effect on the duration of gestation or
parturition when administered orally to pregnant rats at doses up to 50 mg/kg/day during
the fetal period.
Reproductive studies have been performed in rats and rabbits with tobramycin at doses
up to 100 mg/kg/day parenterally and have revealed no evidence of impaired fertility or
harm to the fetus. There are no adequate and well controlled studies in pregnant women.
Zylet should be used during pregnancy only if the potential benefit justifies the potential
risk to the fetus.
8.3 Nursing Mothers
It is not known whether topical ophthalmic administration of corticosteroids could result in
sufficient systemic absorption to produce detectable quantities in human milk. Systemic
steroids that appear in human milk could suppress growth, interfere with endogenous
corticosteroid production, or cause other untoward effects. Caution should be exercised
when Zylet is administered to a nursing woman.
8.4 Pediatric Use
Two trials were conducted to evaluate the safety and efficacy of Zylet® (loteprednol
etabonate and tobramycin ophthalmic suspension) in pediatric subjects age zero to six
years; one was in subjects with lid inflammation and the other was in subjects with
blepharoconjunctivitis.
In the lid inflammation trial, Zylet with warm compresses did not demonstrate efficacy
compared to vehicle with warm compresses. Patients received warm compress lid
treatment plus Zylet or vehicle for 14 days. The majority of patients in both treatment
groups showed reduced lid inflammation.
In the blepharoconjunctivitis trial, Zylet did not demonstrate efficacy compared to vehicle,
loteprednol etabonate ophthalmic suspension, or tobramycin ophthalmic solution.
There was no difference between treatment groups in mean change from baseline
blepharoconjunctivitis score at Day 15.
There were no differences in safety assessments between the treatment groups in either trial.
8.5 Geriatric Use
No overall differences in safety and effectiveness have been observed between elderly
and younger patients.
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been conducted to evaluate the carcinogenic potential
of loteprednol etabonate or tobramycin.
Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma
TK assay, a chromosome aberration test in human lymphocytes, or in an in vivo mouse
micronucleus assay.
Oral treatment of male and female rats at 50 mg/kg/day and 25 mg/kg/day of loteprednol
etabonate, respectively, (500 and 250 times the maximum clinical dose, respectively) prior
to and during mating did not impair fertility in either gender. No impairment of fertility was
noted in studies of subcutaneous tobramycin in rats at 100 mg/kg/day (1700 times the
maximum daily clinical dose).
PATIENT COUNSELING INFORMATION
This product is sterile when packaged. Patients should be advised not to allow the dropper
tip to touch any surface, as this may contaminate the suspension. If pain develops,
redness, itching or inflammation becomes aggravated, the patient should be advised to
consult a physician. As with all ophthalmic preparations containing benzalkonium chloride,
patients should be advised not to wear soft contact lenses when using Zylet.
MANUFACTURER INFORMATION
BAUSCH & LOMB INCORPORATED
TAMPA, FLORIDA 33637 USA
©Bausch & Lomb Incorporated
Zylet is a registered trademark of Bausch & Lomb Incorporated.
Based on 9007705-9004405
Revised 08/2013
US/ZYL/15/0014
33
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
NEXT FRONTIER IN MANAGEMENT OF
RETINA DISEASE
CASE 2: 15-year-old boy
20/20
20/20
Macula is flat, foveal yellow spot
(FIGURE 2) This 15-year-old boy presented no relevant past of family history. He did admit to staring with one eye and then with the other at a laser pointer, following
which he experienced an acute decrease in vision. (Images courtesy of Anat Loewenstein, MD, MHA)
SD-OCT
( Continued from page 30 )
low power but exposure was usually for a long
duration. The light intensity is amplified by
the cornea and the lens by a factor of 10,000.
The pathophysiology includes both thermal
and photochemical damage. While recovery is
possible, permanent damage is a possibility.”
The importance of SD-OCT is underscored in
this case by the defects that were visible in the
ellipsoidal zone as well as the strong correlation between the disruption of the inner photoreceptor junction and the worsened vision.
L A S E R-I N DUC E D R ET I NOPAT H Y
A second case (Figure 2) was that of a 15-yearold boy who experienced an acute decrease
in vision in both eyes after staring at a laser
pointer. The patient’s medical and ocular histories and that of his family were unremarkable.
The macula was flat with a yellow spot in the
fovea. Similar to the first case report, SD-OCT
showed the contour of the fovea was normal
with a stop in the photoreceptors continuity in
the ellipsoid and interdigitation zones and the
presence of a hyperreflective material emerging
from the RPE toward the outer nuclear layer.
SD-OCT follow-up of this patient showed the
reabsorption of the hyperreflective material,
abrupt discontinuation of the photoreceptor
layer in the fovea, and preservation of the ELM.
“The size of the outer macular hole in the
right eye decreased between the examinations
at 2 weeks and 2 months,” Dr. Loewenstein said.
“Laser-induced retinopathy is caused by the
coherent, monochromatic, unidirectional, minimally divergent laser beam,” she said. “The exposure to the light is short, about 0.25 second,
as a result of the blink reflex. The light intensity
is intensified by the cornea and lens by a factor
of 10,000. The pathophysiology includes thermal
damage primarily in the RPE, and photochemical and mechanical plasma formation damage.”
The vast majority of patients (95%) with laser-induced retinopathy experience improvement; 32% have vision better than 20/40.
In this case, SD-OCT showed defects in the
ellipsoid zone, hyper-reflectivity at the retinal
surface, and retinal or intraretinal hemorrhages
and even neovascularization.
HYDROXYCHLOROQUINE
R ET I NOPAT H Y
Another case was a 29-year-old woman who
had been treated for 13 years with prednisone, azathioprine (Imuran, Aspen Australia),
and hydroxychloroquine for systemic lupus
erythemathosus.
The patient presented with the complaint
of a central visual defect.
Examination showed a paracentral scotoma
that developed between 2004 and 2013. This
was the consequence of retinal toxicity resulting from hydroxychloroquine.
“In this case, SD-OCT showed loss of the
perifoveal and macular ellipsoid zones, thinning of the outer nuclear layer, and sparing
OphthalmologyTimes.com
Online Exclusive
PLASMA KALLIKREIN
INHIBITOR SHOWING
PROMISE FOR DME
RESULTS FROM a phase I study of KVD001
for the treatment of central involved diabetic
macular edema show that this plasma kallikrein
inhibitor was well tolerated, according to
Jennifer Sun, MD.
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of the fovea with establishment of the ‘flying
saucer’ sign,” Dr. Loewenstein said.
“Hydroxychloroquine maculopathy is characterized by a bull’s eye appearance and a
dense central scotoma,” she said.
The drug was discontinued but the damage
was permanent.
Dr. Loewenstein summarized that SD-OCT has
dramatically enhanced the ability to diagnose
foveal disorders even during the stage when
they are not visible using other technologies. ■
ANAT LOEWENSTEIN, MD, MHA
E: [email protected]
Dr. Loewenstein in a consultant to Allergan, Alcon Laboratories, Bayer Healthcare, Notal
Vision, and Novartis. Michaela Goldstein, MD, and Dafna Goldenberg, MD, from Dr.
Loewenstein’s department participated in the care of the patients under discussion.
34
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
NEXT FRONTIER IN MANAGEMENT OF
RETINA DISEASE
Considering patient body posture
after macular hole surgery
Advice on positioning recognizes ‘face-down’ is a matter of degree
By Cheryl Guttman Krader; Reviewed by John S. Pollack, MD, and Ehab N. El Rayes, MD, PhD
IT IS THE RESPONSIBILITY of surgeons to provide patients the opportunity for
their best chance at success.
With that in mind, retina surgeons should
know that while macular hole surgery can
be effective without face-down positioning,
the highest success rates are
achieved with some form of
face-down positioning, said
John S. Pollack, MD.
“Patients can be counseled
that face-down positioning does
not require lying in the prone
Dr. Pollack
position, but only that the head
be tilted forward so that the eyes are looking
down, such as in a position used for reading
or texting,” said Dr. Pollack, assistant professor of ophthalmology, Rush University Medical Center, Chicago. “Armed with all of this
information, individuals can then decide for
themselves whether face-down positioning is
worth the effort.”
CONDITIONS FOR SUCCESS
Ehab N. El Rayes, MD, PhD, offered a somewhat
different perspective on the issue of face-down
positioning after macular hole surgery that is
based on his review of outcomes data, knowledge about
mechanisms of macular hole
closure and healing, and the
aim of obtaining patient consent for surgery and increasing
postoperative comfort.
Dr. El Rayes
However, he still advises patients about postoperative positioning, telling
them to avoid lying supine on their backs, but
that it is okay to sit or sleep on their side.
Dr. El Rayes said that vitrectomy with internal limiting membrane (ILM) peeling and
95% gas fill provides the conditions needed
for success—these techniques increase retinal
elasticity, keep the edges of the hole dry for at
least 7 days without supine positioning, and
trigger and support the process of retinal healing. Phacoemulsification is also performed to
avoid cataractous changes and maintain optical clarity.
“Then, surgeons speaking to elderly patients
are more likely to encourage their acceptance surgery with face-down positioning (includof the macular hole procedure by saying: ‘For 1 ing supine or reading position) that met the
week, you should stay sitting or sleep on your criteria of having at least 50 subjects and not
side opposite to the side of your surgery, but being reported either as a poster or in an onnot on your back’ than to say: ‘You have to line-only journal. Across those eight studies,
stay strictly in a face-down position,’” said Dr. the closure rate was consistently above 90%,
El Rayes, professor of ophthalmoland it ranged from 97.4% to 100%
ogy, retina department Institute of
in four of the studies.
Ophthalmology, Cairo, Egypt.
Pooling data from these “credLooking at the world’s literature,
ible” studies, Dr. Pollack said the
Dr. El Rayes identified 21 articles
average closure rate was 95% for
Retina surgeons
published in major peer-review jour- discuss the need for
surgeries with face-down positionnals reporting on 867 eyes that un- face-down positioning
ing and only 83% for no positioning.
derwent macular hole surgery with- after macular
out face-down positioning. The pri- hole surgery. The
SURGERY R EFINED
mary success rate ranged from 79% interpretation of what
In the 25-plus years since macular
to 98%, and was at least 90% for constitutes “facehole surgery was first performed,
hole closure without a face-down down” is key to their
the technique has been refined and
position in 16 of the 21 reports that messages.
its outcomes have improved thanks
included a total of 763 eyes.
to instrumentation, visualization,
Taking a more critical look at the literature, and imaging, Dr. El Rayes noted.
Dr. Pollack said that after excluding posters,
Advances have also contributed to better unarticles appearing in online only journals, and derstanding of the mechanisms of macular hole
studies with fewer than 50 subjects, only four closure that provides a foundation for understudies on macular hole surgery without face- standing why strict face-down positioning is
down positioning remain.
not necessary. Hole closure requires increasing
However, the data are credible in only two retinal elasticity and eliminating all forms of
of the four studies, and they represent the two surface traction, which is accomplished through
studies that report the lowest closure rates, 81% posterior vitreous detachment and ILM peeling.
and 87%, respectively.
In addition, retinal detergence is necessary
One of the two remaining studies reported and is created by injecting a gas bubble. Therea 96% closure rate. However, the authors also after, the tissue repair process begins, and acnote that 20% of patients used face-down po- cording to several published articles, healing can
sitioning for at least 30 hours.
happen within 1 to 2 days, Dr. El Rayes said.
In the fourth study, which was designed
“With intraoperative OCT we can see how
as a retrospective review of 102 consecutive efficiently we removed epiretinal traction and
cases, only 70% of the eyes were included in even begin to see the hole edges begin to flatthe final analysis, which raises concern about ten while the patient is still on the table,” he
selection bias, Dr. Pollack said.
said. “Postoperatively, OCT studies have shown
He noted, “The best paper of the four was a retinal changes such as healing, flattening, reprospective multicenter trial that included ILM sorption of cystic fluid, and approximation of
peeling with dye, gas selection based on hole the hole edges and closure within 1 to 2 days
size, and randomized patients to face-down or after surgery.”
no positioning. In that study, the closure rate
In addition, measurements of postsurgical
was 87% for the 72 eyes in the no positioning intraocular cytokines show they are at their
group and 97.4% for the 78 eyes assigned to highest levels on day 1 after surgery, and that
face-down positioning.”
seems to correspond to hole closure and the
Including the latter study, Dr. Pollack identi- reparative process, he said.
fied eight papers on outcomes of macular hole
Continues on page 35 : Macular hole
take-home
We’ll tell you how it works.
Your patients can see it for themselves.
| Without continuous microdosing |
IMPORTANT SAFETY INFORMATION
Indication
ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg is indicated for the treatment of diabetic
macular edema (DME) in patients who have been previously treated with a course of corticosteroids and
did not have a clinically significant rise in intraocular pressure.
Contraindications
• ILUVIEN is contraindicated in patients with active or suspected ocular or periocular infections including
most viral disease of the cornea and conjunctiva including active epithelial herpes simplex keratitis
(dendritic keratitis), vaccinia, varicella, mycobacterial infections and fungal diseases.
• ILUVIEN is contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8.
• ILUVIEN is contraindicated in patients with known hypersensitivity to any components of this product.
Warnings and Precautions
• Intravitreal injections, including those with ILUVIEN, have been associated with endophthalmitis, eye
inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored
following the intravitreal injection.
• Use of corticosteroids including ILUVIEN may produce posterior subcapsular cataracts, increased
intraocular pressure and glaucoma. Use of corticosteroids may enhance the establishment of
secondary ocular infections due to bacteria, fungi, or viruses. Corticosteroids are not recommended to
be used in patients with a history of ocular herpes simplex because of the potential for reactivation of
the viral infection.
• Patients in whom the posterior capsule of the lens is absent or has a tear are at risk of implant migration
into the anterior chamber.
Adverse Reactions
• In controlled studies, the most common adverse reactions reported were cataract development
(ILUVIEN 82%; sham 50%) and intraocular pressure elevation of ≥ 10 mm Hg (ILUVIEN 34%; sham 10%).
Please see Brief Summary of full Prescribing Information on reverse side of following page.
| With continuous microdosing |
CONTINUOUS MICRODOSINGTM Delivery for Continuous
Therapy in Patients With Diabetic Macular Edema (DME)
ILUVIEN® has been implanted in over
eyes worldwide.1
0.37 mm
diameter
5,000
ILUVIEN is a CONTINUOUS MICRODOSINGTM Delivery
System specifically engineered for the release of
fluocinolone acetonide (FAc) for the treatment of DME in
patients who have been previously treated with a course of
corticosteroids and did not have a clinically significant rise
in intraocular pressure.
In pivotal studies, ILUVIEN demonstrated a proven increase
in visual acuity through 24 months (primary endpoint) and
sustained up to 36 months.2-4
Engineered to deliver
FAc for 36 months
3.5 mm length
Adverse reactions in the ILUVIEN Phase 3 clinical trials were
consistent with other corticosteroid treatments.2
Learn more at ILUVIEN.com.
1. Data on file. Alimera Sciences, Inc. 2. Iluvien [package insert]. Alpharetta, GA: Alimera Sciences, Inc; 2014.
3. Campochiaro PA, Brown DM, Pearson A, et al. Long-term benefit of sustained delivery fluocinolone acetonide
vitreous inserts for diabetic macular edema. Ophthalmology. 2011;118(4):626-635.e2. 4. Campochiaro PA, Brown DM,
Pearson A, et al. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in
patients with diabetic macular edema. Ophthalmology. 2012;119(10):2125-2132.
Please see Brief Summary of full Prescribing Information on the following page.
CONTINUOUS MICRODOSING is a trademark of Alimera Sciences, Inc.
ILUVIEN is a registered trademark of Alimera Sciences, Inc.
Copyright © 2016 Alimera Sciences, Inc. All rights reserved.
1-844-445-8843. Printed in USA. US-ILV-MMM-0312. 6/16
BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION
Table 1 (continued)
®
ILUVIEN (fluocinolone acetonide intravitreal implant) 0.19 mg For
Intravitreal Injection
Adverse Reactions
INDICATIONS AND USAGE
ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg is indicated for the
treatment of diabetic macular edema in patients who have been previously treated
with a course of corticosteroids and did not have a clinically significant rise in
intraocular pressure.
CONTRAINDICATIONS
Ocular or Periocular Infections: ILUVIEN is contraindicated in patients with active
or suspected ocular or periocular infections including most viral disease of the
cornea and conjunctiva including active epithelial herpes simplex keratitis (dendritic
keratitis), vaccinia, varicella, mycobacterial infections and fungal diseases.
Glaucoma: ILUVIEN is contraindicated in patients with glaucoma, who have cup
to disc ratios of greater than 0.8.
Hypersensitivity: ILUVIEN is contraindicated in patients with known hypersensitivity
to any components of this product.
WARNINGS AND PRECAUTIONS
Intravitreal Injection-related Effects: Intravitreal injections, including those with
ILUVIEN, have been associated with endophthalmitis, eye inflammation, increased
intraocular pressure, and retinal detachments. Patients should be monitored
following the intravitreal injection.
Steroid-related Effects: Use of corticosteroids including ILUVIEN may produce
posterior subcapsular cataracts, increased intraocular pressure and glaucoma. Use
of corticosteroids may enhance the establishment of secondary ocular infections
due to bacteria, fungi, or viruses.
Corticosteroids are not recommended to be used in patients with a history of
ocular herpes simplex because of the potential for reactivation of the viral infection.
Risk of Implant Migration: Patients in whom the posterior capsule of the lens is
absent or has a tear are at risk of implant migration into the anterior chamber.
ILUVIEN (N=375)
n (%)
Sham (N=185)
n (%)
Non-ocular
Anemia
40 (11%)
10 (5%)
Headache
33 (9%)
11 (6%)
Renal failure
32 (9%)
10 (5%)
Pneumonia
28 (7%)
8 (4%)
1
Includes cataract, cataract nuclear, cataract subcapsular, cataract cortical
and cataract diabetic in patients who were phakic at baseline. Among these
patients, 80% of ILUVIEN subjects vs. 27% of sham-controlled subjects
underwent cataract surgery.
2
235 of the 375 ILUVIEN subjects were phakic at baseline; 121 of 185
sham-controlled subjects were phakic at baseline.
Increased Intraocular Pressure
Table 2: Summary of Elevated IOP-Related Adverse Reactions
Event
ILUVIEN (N=375) Sham (N=185)
n (%)
n (%)
Non-ocular
IOP elevation ≥ 10 mm Hg from baseline
127 (34%)
18 (10%)
IOP elevation ≥ 30 mm Hg
75 (20%)
8 (4%)
Any IOP-lowering medication
144 (38%)
26 (14%)
Any surgical intervention for elevated
intraocular pressure
18 (5%)
1 (1%)
Figure 1: Mean IOP during the study
ADVERSE REACTIONS
Clinical Studies Experience: Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a drug
cannot be directly compared to rates in the clinical trials of another drug and may
not reflect the rates observed in practice.
Adverse reactions associated with ophthalmic steroids including ILUVIEN include
cataract formation and subsequent cataract surgery, elevated intraocular pressure,
which may be associated with optic nerve damage, visual acuity and field defects,
secondary ocular infection from pathogens including herpes simplex, and
perforation of the globe where there is thinning of the cornea or sclera.
ILUVIEN was studied in two multicenter, randomized, sham-controlled, masked
trials in which patients with diabetic macular edema were treated with either
ILUVIEN (n=375) or sham (n=185). Table 1 summarizes safety data available when
the last subject completed the last 36-month follow up visit for the two primary
ILUVIEN trials. In these trials, subjects were eligible for retreatment no earlier than
12 months after study entry. Over the three-year follow up period, approximately
75% of the ILUVIEN treated subjects received only one ILUVIEN implant.
Table 1: Ocular Adverse Reactions Reported by ≥1% of Patients and
Non-ocular Adverse Reactions Reported by ≥5% of Patients
Cataract1
192/2352 (82%)
Myodesopsia
80 (21%)
17 (9%)
Eye pain
57 (15%)
25 (14%)
Conjunctival haemorrhage
50 (13%)
21 (11%)
Posterior capsule opacification
35 (9%)
6 (3%)
Eye irritation
30 (8%)
11 (6%)
Vitreous detachment
26 (7%)
12 (7%)
Cataracts and Cataract Surgery
At baseline, 235 of the 375 ILUVIEN subjects were phakic; 121 of 185
sham-controlled subjects were phakic. The incidence of cataract development in
patients who had a phakic study eye was higher in the ILUVIEN group (82%)
compared with sham (50%). The median time of cataract being reported as an
adverse event was approximately 12 months in the ILUVIEN group and 19 months
in the sham group. Among these patients, 80% of ILUVIEN subjects vs. 27% of
sham-controlled subjects underwent cataract surgery, generally within the first 18
months (Median Month 15 for both ILUVIEN group and for sham) of the studies.
Postmarketing Experience: The following reactions have been identified during
post-marketing use of ILUVIEN in clinical practice. Because they are reported
voluntarily, estimates of frequency cannot be made. The reactions, which have
been chosen for inclusion due to either their seriousness, frequency of reporting,
possible causal connection to ILUVIEN, or a combination of these factors, include
reports of drug administration error and reports of the drug being ineffective.
Conjunctivitis
14 (4%)
5 (3%)
USE IN SPECIFIC POPULATIONS
Corneal oedema
13 (4%)
3 (2%)
Pregnancy: Pregnancy Category C.
There are no adequate and well-controlled studies of ILUVIEN in pregnant women.
Animal reproduction studies have not been conducted with fluocinolone acetonide.
Corticosteroids have been shown to be teratogenic in laboratory animals when
administered systemically at relatively low dosage levels. ILUVIEN should be used
during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers: Systemically administered corticosteroids are present in human
milk and could suppress growth and interfere with endogenous corticosteroid
production. The systemic concentration of fluocinolone acetonide following
intravitreal treatment with ILUVIEN is low. It is not known whether intravitreal
treatment with ILUVIEN could result in sufficient systemic absorption to produce
detectable quantities in human milk. Exercise caution when ILUVIEN is
administered to a nursing woman.
Pediatric Use: Safety and effectiveness of ILUVIEN in pediatric patients have not
been established.
Geriatric Use: No overall differences in safety or effectiveness have been observed
between elderly and younger patients.
Adverse Reactions
ILUVIEN (N=375)
n (%)
Sham (N=185)
n (%)
Ocular
61/1212 (50%)
Foreign body sensation in eyes
12 (3%)
4 (2%)
Eye pruritus
10 (3%)
3 (2%)
Ocular hyperaemia
10 (3%)
3 (2%)
Optic atrophy
9 (2%)
2 (1%)
Ocular discomfort
8 (2%)
1 (1%)
Photophobia
7 (2%)
2 (1%)
Retinal exudates
7 (2%)
0 (0%)
Anterior chamber cell
6 (2%)
1 (1%)
Eye discharge
6 (2%)
1 (1%)
Manufactured for: Alimera Sciences, Inc. • 6120 Windward Parkway
Alpharetta, GA 30005 • Patented. • See: www.alimerasciences.com
All Rights Reserved; Issue Date December 2014;
ILUVIEN is a registered trademark of Alimera Sciences, Inc.
Copyright © 2016 Alimera Sciences, Inc. All rights reserved.
1-844-445-8843. Printed in USA. US-ILV-MMM-0312. 6/16
35
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
NEXT FRONTIER IN MANAGEMENT OF
RETINA DISEASE
Innovations bringing benefits
of 27-gauge vitrectomy to more eyes
Vitrectomy surgery with equipment, technology improving for greater efficiency, functionality
By Cheryl Guttman Krader; Reviewed by Yusuke Oshima, MD, PhD
TAK T SUK I, JAPAN ::
CONTINUED ADVANCES in vitrectomy machines and instrumentation have led
to progressive improvements in the efficiency
of 27-gauge vitrectomy and made ultra-smallgauge surgery suitable for the full spectrum
of vitreoretinal pathologies,
said Yusuke Oshima, MD, PhD.
Use of a three-dimensional
heads-up surgery platform
(Tr ueVision 3D Surgical,
TrueVision) that minimizes
phototoxicity risk provides yet
Dr. Oshima
another novel benefit and represents the next step toward achieving ultraminimally invasive vitrectomy surgery, added
Dr. Oshima, founder and director, Oshima Eye
Clinic, Taktsuki, Japan.
“In 2010, we [reported] our initial experience
with 27-gauge vitrectomy that showed very favorable results in a set of selected cases comprised mainly of eyes with macular disease and
simple vitreous hemorrhage,” he said.
Five years later, the introduction of an ultrahigh-speed cutter (Dutch Ophthalmic Research
Center International BV) that exerts less tractional force allowed expansion of 27-gauge vitrectomy to a broader range of eyes, including
those with challenging tractional detachments.
Most recently, a 27-gauge, twin-duty cycle
MACULAR HOLE
( Continued from page 34 )
Citing a theory on mechanisms of surgical
repair of macular hole developed by Mark Blumenkranz, MD, Dr. El Rayes said that removal
of vitreous releases traction and allows apposition of a foreign non-porous surface (i.e., gas
bubble or silicone) to the edges of the macular hole. Membrane peeling or ILM removal
stimulates an intrinsic retinal wound healing
response through gene activation, and these
events in concert stimulate the migration of
cutter with a double-port (TDC cutter, Dutch
Ophthalmic Research Center International BV)
has been developed to provide a very high duty
cycle regardless of the cutting rate and provides
even better cutting efficiency than a conventional 25-gauge cutter, he noted.
“Now, we are using the 3-D heads-up surgery system that provides a sufficiently bright
and clear fundus view on the display monitor with only 10% to 20% of the illumination
power that is used for viewing through the
surgical microscope,” he said.
The standardized 27-gauge vitrectomy procedures are performed with chandelier endoillumination and wide-angle viewing systems.
The small port of the 27-gauge vitreous cutter
with its position near to the top of the tip enables direct dissection of fibrotic neovascular
membranes because it is easy to insert into the
small space between the membrane and retina.
Using a bimanual technique for membrane
dissection in which the membrane is lifted
with a forceps in one hand, the 27-gauge cutter is used to sever the anchoring point before
cutting the membrane en bloc.
“The ease of insertion of the 27-gauge cutter under the membrane makes it easier to cut
the anchor point first without causing bleeding,” Dr. Oshima said.
He added he likes to peel the internal limiting
Mueller cells and associated retinal neurons
that fill in the defect.
Intrinsic photoreceptor paracrine and autocrine stimuli result in photoreceptor realignment
and synapse repair, resulting in restoration of
normal or near normal macular anatomy and
function. After complete fluid/gas exchange,
the gas bubble serves to isolate the retina from
vitreous fluid for the 5 to 7 days that it takes
for macular scab contraction to occur.
Dr. El Rayes explained that based on the Pascal principle of transmission of fluid pressure,
the gas bubble transmits pressure equally in
all directions and creates the necessary conditions to keep the hole edges dry.
27-GAUGE DIABETIC VITRECTOMY
VIDEO Watch 27-gauge diabetic
vitrectomy for fibrovascular membrane dissection.
(Video courtesy of Yusuke Oshima, MD, PhD)
Go to OphthalmologyTimes.com/27Gauge
membrane in eyes with diabetic tractional detachment because that step eliminates any scaffold for postoperative membrane proliferation.
After laser photocoagulation, the 27-gauge
procedure is easily concluded by simply removing the trocar cannula and the optical fiber. ■
YUSUKE OSHIMA, MD, PHD
E: [email protected]
This article was adapted from Dr. Oshima’s presentation during Retina Subspecialty
Day at the 2015 meeting of the American Academy of Ophthalmology. Dr. Oshima
receives lecture fees from Alcon Laboratories and is a consultant to Synergetics.
“The idea of first week face-down positioning is inconsistent with this principle,” Dr. El
Rayes said. “The gases used have a long enough
half-life to isolate the macula from the vitreous in all positions except face-up supine.” ■
JOHN S. POLLACK, MD
E: [email protected]
EHAB N. EL RAYES, MD, PHD
E: [email protected]
This article was adapted from presentations by Dr. Pollack and Dr. El Rayes during
Retina Subspecialty Day at the 2015 meeting of the American Academy of Ophthalmology. Dr. Pollack and Dr. El Rayes have no relevant financial interests to disclose.
36
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
NEXT FRONTIER IN MANAGEMENT OF
RETINA DISEASE
Managing silicone oil complications
in anterior, posterior segments
Many events can be avoided with attention to technique or successfully treated if they occur
By Cheryl Guttman Krader; Reviewed by Derek Kunimoto, MD, JD
PAR ADISE VAL L E Y, A Z::
USE OF SILICONE OIL (SO) for retinal tamponade can result in a range of complications. Fortunately, most of these events
can be avoided with careful attention to surgical technique or successfully treated if they
occur, while those without any known preventive strategies are very rare, said Derek
Kunimoto, MD, JD.
Treatment of silicone oil in the anterior chamber is performed by creating a paracentesis
through which the oil can drain passively.
“As long as there is posterior infusion, the
oil will follow itself out of the small opening
in the cornea,” Dr. Kunimoto said.
POSTERIOR SEGMENT
COMPLICATIONS
ANTERIOR SEGMENT
Although oil is supposed to be present in the
COMPLICATIONS
vitreous cavity, its presence does decrease aqueUsage of SO in the subconjunctival space pres- ous volume that can pose a problem in patients
ents a cosmetic issue and can lead to granuloma who are receiving ongoing intravitreal injecformation; avoiding it requires tions. Surgeons can either remove the SO or,
good scleral closure with the according to anecdotal reports, compensate
use of small-gauge vitrectomy, for the change by adjusting the dosage of the
said Dr. Kunimoto, managing intravitreal injection.
partner, Retinal Consultants of
Oil in the vitreous can also migrate into the
Arizona, and director, Scotts- subhyaloid space. This complication, which ocdale Eye Surgery Center, Scott- curs more commonly in pediatric cases, will
Dr. Kunimoto
sdale, AZ.
prevent complete oil fill and leave vitreoretinal
“SO in the subconjunctival space is becom- tractional forces in place that can predispose
ing more common because of the use of small- to recurrent retinal detachment.
gauge vitrectomy, but it can be avoided with
“Ensuring creation of a complete posterior
a good mattress suture and good apposition,” vitreous detachment during surgery will avoid
Dr. Kunimoto said.
SO getting into the subhyaloid space,” Dr. KunThe options for managing oil in the subcon- imoto said.
Another posterior segment comjunctival space include observation
plication is SO emulsification in a
if the cosmetic appearance is acthin layer over the retina. Treatment
ceptable to the patient and watching
of that situation requires silicone
for granuloma formation or surgioil exchange or removal.
cal intervention by performing a
Complications
“SO droplets can also become
simple conjunctival cutdown.
of silicone oil occur
embedded within the layers of the
“As long as the cutdown is in when it is inadvertently
retina, and there is no known way
the correct plane, the SO will come placed in anatomic
to avoid these intraretinal deposout nicely,” he said.
areas other than the
its,” Dr. Kunimoto said.
SO can also be present in the an- vitreous cavity. Derek
The oil can also penetrate or be
terior chamber, which can lead to Kunimoto, MD, JD,
inadvertently placed into the subsecondary open-angle glaucoma, discusses methods
retinal space where it will interfere
inaccurate IOP measurements, and for managing and
with retinal detachment repair. SO
in severe cases, corneal decompen- avoiding these issues.
in the subretinal space raises posation. Keeping the zonules intact
during vitrectomy will prevent SO from getting tential concern about retinal pigment epitheinto the anterior chamber. In the setting of an lium (RPE) or retina toxicity. Chronic presence
aphakic eye, placement of an anterior cham- of oil in the subretinal space can also lead to
ber IOL or anterior chamber maintaining su- retinal atrophy and large retinal cysts, and silitures is advised to provide a physical barrier cone oil can emulsify in the subretinal space.
“To avoid getting SO in the subretinal space,
against anterior migration.
take-home
SILICONE OIL REMOVAL
VIDEO Derek Kunimoto, MD, JD, shows
the proper removal of silicone oil from the anterior
chamber using small-gauge vitrectomy.
(Video courtesy of Derek Kunimoto, MD, JD)
Go to OphthalmologyTimes.com/SiliconeOil
surgeons should visually confirm that the cannula tip is not in the subretinal space,” Dr.
Kunimoto said.
In addition, surgeons should be cautious
about using SO in eyes with large retinal tears,
retinectomy greater than 3 clock hours, as well
as in those with retinal detachments associated
with optic nerve pits or macular holes, he said.
The oil can also be present in the sub-RPE
or choroidal space that will cause a choroidal
detachment, preventing retinal detachment repair. Potentially, silicone oil in the sub-RPE or
choroidal space might also be toxic to the RPE
or compromise choroidal vasculature.
Proper cannula selection and positioning is
the solution for avoiding these complications.
“Do not use a short cannula and make sure
the cannula tip is not in the choroidal space,”
Dr. Kunimoto said.
The approach to management of oil in the
sub-RPE or choroidal space is similar to the
treatment of choroidal hemorrhage or effusion. Surgeons should create a cutdown in the
sclera with vitreous cavity infusion and then
slightly gape open the sclerotomy to allow passive drainage of the oil. Increasing the infusion pressure will facilitate the passive egress
of SO. The choroidal detachment will then flatten, enabling repair of the retinal detachment.
Continues on page 37 : Silicone oil tips
37
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
NEXT FRONTIER IN MANAGEMENT OF
RETINA DISEASE
Anti-VEGF in high-risk populace drives
regression of diabetic retinopathy
Patients who benefited most from ranibizumab had highest risk of proliferative progression
By Lynda Charters; Reviewed by Charles C. Wykoff, MD
HOUS TON ::
INVESTIGATORS IN a follow-up RISE/
Ranibizumab also was found to significantly
RIDE analysis of patients who had the high- (p < 0.05) decrease worsening of retinal non-perest risk of progression to proliferative dia- fusion compared with sham treatment (Campobetic retinopathy (PDR) saw “robust” regres- chiaro et al. Ophthalmology. 2014;121:1783-1789).
sion of diabetic retinopathy (DR) in high percentages of patients treated with ranibizumab
R ANIBIZUMAB EFFECT
(Lucentis, Genentech) independent of baseline Investigators analyzed patients at high risk of
characteristics.
PDR progression—i.e., those who had moderWith the incidence rate of ately severe or severe NPDR/ETDRS DR seDR expected to nearly double verity, or levels 47/53 at baseline—and evalufrom 2010 to 2050, identification ated the effect of baseline characteristics and
of effective treatments is para- macular non-perfusion on patient outcomes.
mount, according to Charles C.
To assess DR, several stereoscopic seven-field
Wykoff, MD, who is in private color fundus photographs were obtained and
Dr. Wykoff
practice in Houston.
evaluated. To assess macular non-perfusion,
The Early Treatment Diabetic Retinopathy fluorescein angiograms were obtained at the
Study (ETDRS) Diabetic Retinopathy Severity same time points and analyzed by masked
Scale and other studies have demongraders to measure the area of
strated decreases in patients’ healththe macular non-perfusion.
related quality of life when the DR
The levels of DR at baseline
severity worsens beyond the 43 level,
were similar in the three treatwhich is then moderate non-proliferment groups—i.e., sham, 0.3-, and
About 75% of
ative diabetic retinopathy (NPDR).
0.5-mg ranibizumab. The most
patients in the RIDE/
“It is at this level that difficulty in RISE trials who had
ranibizumab benefits were in padriving begins to increase,” he said. the highest risk
tients with moderately severe or
Patients with DR and diabetic mac- of progression to
severe NPDR at baseline, he noted.
ular edema were randomly assigned proliferative diabetic
“Importantly, 75% of patients
sham injections or treatment with retinopathy benefited
treated with ranibizumab who
0.3- or 0.5-mg doses of ranibizumab. from ranibizumab with
had a DR level of 47/53 at baseTime to PDR was significantly de- “robust” regression of
line had a two-step or greater imlayed in the ranibizumab group.
provement in DR compared with
DR severity levels.
Both ranibizumab doses signifisham treatment by month 12,”
cantly (p < 0.001) improved DR levels based Dr. Wykoff said.
on the pooled RIDE/RISE data (Ip et al. OphPatients in the sham group with moderately
thalmology. 2015;122:367-374).
severe and severe NPDR at baseline were six
take-home
SILICONE OIL TIPS
( Continued from page 36 )
SO can also emulsify in the vitreous cavity, though the risk is lower with use of higher
centistoke oil (5000 versus 1000).
Management requires vitrectomy or SO
exchange.
Migration of SO into the optic nerve, optic
chiasm, and cerebral ventricles as well as unexplained central vision loss with a decrease
of visual acuity to the 20/200 level are other
complications that can occur with SO tamponade that have no known avoidance strategy.
Surgeons should be aware the risk for SO
times more likely to progress to PDR through
24 months, he said.
Baseline characteristics such as central foveal thickness (CFT), best-corrected visual acuity (BCVA), and duration of diabetes were not
predictive of two-step or greater improvements
in patients with a DR severity level of 47/53.
Investigators also found no predictive value
of subscale levels within DR severity levels 47
and 53 in predicting a two-step or greater improvement in DR severity at month 24 for patients with the highest-risk NPDR at baseline.
M ACUL A R NON-PER FUSION
Data indicated that macular non-perfusion at
baseline did not affect the two-step or greater
improvements in DR that occurred as the result of treatment with ranibizumab in patients
with a baseline DR level of 47/53.
The proportions of patients with macular
non-perfusion increased in the sham group and
remained stable in the ranibizumab groups.
In conclusion, ranibizumab led to robust improvements in DR severity scores in patients
with the highest risk of progression to PDR.
“Such disease-modifying effects of ranibizumab indicate a substantial role in DR management beyond simple mitigation of diabetic
macular edema,” Dr. Wykoff said. ■
CHARLES C. WYKOFF, MD
E: [email protected]
This article was adapted from Dr. Wykoff’s presentation at the 2016 meeting of the
Association for Research in Vision and Ophthalmology. Dr. Wykoff is a consultant to
Genentech.
migration into the central nervous system is
increased when optic nerve pits are present. ■
DEREK KUNIMOTO, MD, JD
E: [email protected]
This article was adapted from Dr. Kunimoto’s presentation during Retina Subspecialty
Day at the 2015 meeting of the American Academy of Ophthalmology. Dr. Kunimoto is
a consultant to Allergan, Bausch+ Lomb, DORC, Genentech, and Synergetics.
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40
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
NEXT FRONTIER IN MANAGEMENT OF
RETINA DISEASE
CATT follow-up explores long-term
outcomes with anti-VEGF in AMD
Mean visual acuity at 5 years points to unmet need; still, 50% of eyes were 20/40 or better
By Lynda Charters; Reviewed by Maureen Maguire, PhD
PHIL ADEL PHIA ::
THE COMPARISON OF Age-related
angiography, the images
Macular Degeneration Treatments Trials (CATT) showed that the mean
follow-up study found that the gains in visual size of the lesions was
acuity achieved at the end of the 2-year CATT 12.9 mm 2, which was a
study, a clinical trial of the anti-vascular en- mean of 4.8 mm 2 larger
dothelial growth factor (VEGF) drugs ranibi- than that at the 2-year visit.
zumab (Lucentis, Genentech) and bevacizumab The investigators observed
(Avastin, Genentech), were not sustained 3 geographic atrophy in 41%
years later.
of the eyes that could be
In the CATT clinical trial, patients were ran- graded and it was subfodomly assigned to either ranibizumab or beva- veal in 17% of those eyes.
cizumab and followed for 2 years after assignSpectral-domain optical
ment to one of three dosing regimens.
coherence tomography imIn this study, 3 years after the end of the ages were available for 555
CATT clinical trial, the investigators, led by eyes. Among them, fluid
Maureen Maguire, PhD, from the Department was seen in 83%, specifiof Ophthalmology, University of Pennsylvania, cally, intraretinal in 61%,
Philadelphia, and Daniel Martin, MD, from the subretinal in 38%, and subCole Eye Institute, Cleveland Clinic Founda- retinal pigment epithelial in 36%. The mean
tion, Cleveland, evaluated 647 patients who foveal thickness was 278 μm, which was lower
were recalled from the original CATT clinical by 182 μm from the baseline value and 20 μm
trial cohort to determine how the visual acuity below that from the 2-year evaluation, they relevels and anatomic outcomes survived over ported. The retina was less than 120 μm thick
time in the CATT follow-up study.
in 36% of eyes.
The CATT Research Group found
Interestingly, the patients who
that in these patients, who had an
had been randomly assigned to raaverage follow-up of 5.5 years, half
nibizumab for 2 years had a greater
of the eyes had a visual acuity of
decrease in visual acuity, i.e., -4
The Comparison of
20/40 or better, 20% had a visual Age-related Macular
letters, compared with those who
acuity of 20/200 or worse, and al- Degeneration Treatment
had been assigned to bevacizumab.
most 10% had 20/20. The authors Trial (CATT) follow-up
This difference reached significance
reported their findings in Ophthal- study found that the
(p = 0.008). The investigators did
mology (Maguire et al. Ophthalmol- initial gains in visual
not find significant differences in
ogy 2016;123:1751-1761).
visual acuity or morphologic outacuity achieved with
They reported “the mean change two anti-vascular
comes between the groups.
in visual acuity was -3 letters from endothelial growth
Dr. Maguire pointed out that in
baseline and -11 letters from 2 factor drugs were lower
the CATT Follow-up Study there
years.”
were multiple processes that caused
than those achieved at
These patients underwent ex- the end of the 2-year
the visual acuity decreases, but they
aminations for age-related macu- CATT study.
seemed to be associated with an
lar degeneration (AMD) a mean
increase in the numbers of patients
of 25.3 times after the end of the CATT study with abnormally thin retinas, that is, less than
and received a mean of 15.4 treatments. Re- 120 μm; a greater prevalence of geographic atgarding the treatments, more than half of the rophy, and an increase in the size of the lesions.
patients (60%) were treated with a drug other
The investigators noted, “The CATT Followthan the one to which they had been assigned up Study results provided the most complete
in the CATT study, according to Dr. Maguire. follow-up reported to date on the long-term outAmong 467 eyes that underwent fluorescein comes for the treatment of neovascular AMD
The investigators noted, ‘The
CATT Follow-up Study results
provided the most complete
follow-up reported to date on
the long-term outcomes for the
treatment of neovascular AMD
with anti-VEGF drugs.’
take-home
with anti-VEGF drugs. …Because very few patients continued to receive the originally assigned drug or dosing schedule between the
end of year 2 and the follow-up of approximately 5 years, the CATT Follow-up Study results provide information primarily on overall treatment outcomes with anti-VEGF drugs
and limited information on effects of different
drugs and dosing regimens. The mean visual
acuity at 5 years was 3 letters worse than baseline, highlighting an unmet need for further
therapeutic advances.”
They also considered that with 50% of the
patients having 20/40 or better visual acuity
and 10% having 20/20, these results are a great
step forward and would not have been possible
before the anti-VEGF drugs were developed. ■
MAUREEN MAGUIRE, PHD
E: [email protected]
Dr. Maguire has received financial support from Roche/Genentech for service on a
Data Safety and Monitoring Committee for Genentech.
DANIEL MARTIN, MD
E: [email protected]
Dr. Martin has no financial interest in this subject matter.
This article was adapted from a presentation by Dr. Maguire and Dr. Martin at the
2016 meeting of the Association for Research in Vision and Ophthalmology.
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42
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
NEXT FRONTIER IN MANAGEMENT OF
RETINA DISEASE
Protocol T: Anti-VEGF DME therapies
maintain impressive results at 2 years
Vision gains from baseline seen in all 3 groups with fewer injections, decreased visits, less laser
By Laird Harrison
Building the Ophthalmic Tech’s Community of Practice
modernmedicine.com/iTech
Resource Center for Technician Education
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CONTENT
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PAGE 11
Brought to you by
TWO-YEAR RESULTS from
a comparative effectiveness trial may
help clinicians faced with the difficult
choice among the three anti-vascular endothelial growth factor (VEGF)
drugs approved for diabetic macular
edema (DME).
Among eyes with worse baseline visual acuity, aflibercept (Eylea, Regeneron) had superior 2-year visual acuity
outcomes compared with bevacizumab
(Avastin, Genentech), but superiority of
aflibercept over ranibizumab (Lucentis, Genentech), noted at 1 year, was
no longer identified, researchers said.
“Vision gains from baseline at 2 years
were seen in all three groups with about
half the number of injections, slightly decreased frequency of visits, and decreased
amounts of laser in the second year,” said
John A. Wells, MD, Palmetto Retina Center,
Columbia, SC. Dr. Wells and colleagues
from the Diabetic Retinopathy Clinical Research Network (DRCR.net) published findings from the Protocol T trial in
Ophthalmology (http://bit.ly/2csX6yu).
ABOUT THE RESEARCH
The DRCR.net investigators enrolled
660 people with DME at 88 sites across
the United States. At baseline, the patients had a mean age of 61 years and
had type 1 or type 2 diabetes for a
mean of 17 years.
The investigators restricted the trial
to people with a visual acuity of 20/32
or worse. At enrollment, about half of
the participants had 20/32 to 20/40
vision, and the other half had 20/50
or worse vision.
The researchers randomly divided
the participants into thirds. One group
received 2.0 mg/0.05 mL of aflibercept, one received 1.25 mg/0.05 mL
of bevacizumab, and one received 0.3
mg/0.05 mL of ranibizumab.
Clinicians evaluated participants
every 4 weeks during the first year
and every 4 to 16 weeks during the
second year, depending on treatment
course. At each visit, they assessed the
study eyes for re-treatment with the
anti-VEGF agent based on visual and
‘Vision gains from baseline
at 2 years were seen in all three
groups with about half the number
of injections.’ — John A. Wells, MD
Separately, all three drugs have
shown impressive results in restoring or protecting vision in patients
with DME, but their prices are very
different. Based on Medicare allowable charges, the drugs at the doses
used in this study cost about $1,960 for
aflibercept, $1,200 for ranibizumab,
and about $70 for bevacizumab per
injection, according to the National
Eye Institute.
optical coherence tomography (OCT)
criteria. They administered intravitreal
injections of the study drugs until the
DME resolved or stabilized.
Additionally, they administered
focal/grid laser photocoagulation
treatment if DME persisted without
continual improvement after 6 months
of injections.
Participants did not know which
Continues on page 45 : Visual acuity
The
®
PROLENSA Effect
POWERED FOR
PENETRATION
Advanced Formulation to Facilitate
Corneal Penetration1-3
PROLENSA® delivers potency and
corneal penetration with QD dosing
at a low concentration1-3
INDICATIONS AND USAGE
PROLENSA® (bromfenac ophthalmic solution) 0.07% is a
nonsteroidal anti-infl ammatory drug (NSAID) indicated
for the treatment of postoperative infl ammation and
reduction of ocular pain in patients who have undergone
cataract surgery.
IMPORTANT SAFETY INFORMATION ABOUT PROLENSA®
9PROLENSA® contains sodium sulfite, a sulfite that may
cause allergic type reactions including anaphylactic
symptoms and life-threatening or less severe asthmatic
episodes in certain susceptible people. The overall
prevalence of sulfite sensitivity in the general population is
unknown and probably low. Sulfite sensitivity is seen more
frequently in asthmatic than in non-asthmatic people.
9All topical nonsteroidal anti-inflammatory drugs (NSAIDs),
including bromfenac, may slow or delay healing.
Concomitant use of topical NSAIDs and topical steroids
may increase the potential for healing problems.
9There is the potential for cross-sensitivity to acetylsalicylic
acid, phenylacetic acid derivatives, and other NSAIDs,
including bromfenac. Use with caution in patients who
have previously exhibited sensitivities to these drugs.
9There have been reports that ocularly applied NSAIDs
may cause increased bleeding of ocular tissues (including
hyphemas) in conjunction with ocular surgery. Use with
caution in patients with known bleeding tendencies or
who are receiving other medications which may prolong
bleeding time.
PROLENSA is a registered trademark of Bausch & Lomb Incorporated or its affiliates.
© Bausch & Lomb Incorporated. All rights reserved. Printed in USA. PRA.0188.USA.15
9Use of topical NSAIDs may result in keratitis.
Patients with evidence of corneal epithelial breakdown
should immediately discontinue use of topical NSAIDs,
including bromfenac, and should be closely monitored
for corneal health. Patients with complicated ocular
surgeries, corneal denervation, corneal epithelial
defects, diabetes mellitus, ocular surface diseases
(e.g., dry eye syndrome), rheumatoid arthritis, or repeat
ocular surgeries within a short period of time may be
at increased risk for corneal adverse events which may
become sight threatening. Topical NSAIDs should be used
with caution in these patients. Post-marketing experience
with topical NSAIDs suggests that use more than 24 hours
prior to surgery or use beyond 14 days post-surgery may
increase patient risk for the occurrence and severity of
corneal adverse events.
9PROLENSA® should not be instilled while wearing contact
lenses. The preservative in PROLENSA®, benzalkonium
chloride, may be absorbed by soft contact lenses.
Lenses may be reinserted after 10 minutes following
administration of PROLENSA®.
9The most commonly reported adverse reactions in 3%-8%
of patients were anterior chamber inflammation, foreign
body sensation, eye pain, photophobia, and blurred vision.
Please see brief summary of full Prescribing Information
for PROLENSA® on adjacent page.
References: 1. PROLENSA Prescribing Information, April 2013. 2. Data on file, Bausch & Lomb Incorporated.
3. Baklayan GA, Patterson HM, Song CK, Gow JA, McNamara TR. 24-hour evaluation of the ocular distribution of
(14)C-labeled bromfenac following topical instillation into the eyes of New Zealand white rabbits. J Ocul Pharmacol Ther.
2008;24(4):392-398.
PROLENSA® (bromfenac ophthalmic solution) 0.07%
Brief Summary
INDICATIONS AND USAGE
PROLENSA® (bromfenac ophthalmic solution) 0.07% is indicated for the
treatment of postoperative inflammation and reduction of ocular pain in
patients who have undergone cataract surgery.
PROLENSA® ophthalmic solution following cataract surgery include:
anterior chamber inflammation, foreign body sensation, eye pain,
photophobia and vision blurred. These reactions were reported in 3 to
8% of patients.
USE IN SPECIFIC POPULATIONS
Pregnancy
Treatment of rats at oral doses up to 0.9 mg/kg/day (systemic
exposure 90 times the systemic exposure predicted from the
recommended human ophthalmic dose [RHOD] assuming the human
systemic concentration is at the limit of quantification) and rabbits
at oral doses up to 7.5 mg/kg/day (150 times the predicted human
systemic exposure) produced no treatment-related malformations in
reproduction studies. However, embryo-fetal lethality and maternal
toxicity were produced in rats and rabbits at 0.9 mg/kg/day and
7.5 mg/kg/day, respectively. In rats, bromfenac treatment caused
delayed parturition at 0.3 mg/kg/day (30 times the predicted human
CONTRAINDICATIONS
exposure), and caused dystocia, increased neonatal mortality and
None
reduced postnatal growth at 0.9 mg/kg/day.
WARNINGS AND PRECAUTIONS
There are no adequate and well-controlled studies in pregnant women.
Sulfite Allergic Reactions
Because animal reproduction studies are not always predictive of
Contains sodium sulfite, a sulfite that may cause allergic-type reactions
human response, this drug should be used during pregnancy only if
including anaphylactic symptoms and life-threatening or less severe
the potential benefit justifies the potential risk to the fetus.
asthmatic episodes in certain susceptible people. The overall prevalence
Because of the known effects of prostaglandin biosynthesisof sulfite sensitivity in the general population is unknown and probably
inhibiting drugs on the fetal cardiovascular system (closure of ductus
low. Sulfite sensitivity is seen more frequently in asthmatic than in nonarteriosus), the use of PROLENSA® ophthalmic solution during late
asthmatic people.
pregnancy should be avoided.
Slow or Delayed Healing
Nursing Mothers
All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including
Caution should be exercised when PROLENSA is administered to a
bromfenac, may slow or delay healing. Topical corticosteroids are also
nursing woman.
known to slow or delay healing. Concomitant use of topical NSAIDs and Pediatric Use
topical steroids may increase the potential for healing problems.
Safety and efficacy in pediatric patients below the age of 18 have not
Potential for Cross-Sensitivity
been established.
There is the potential for cross-sensitivity to acetylsalicylic acid,
Geriatric Use
phenylacetic acid derivatives, and other NSAIDs, including bromfenac.
There is no evidence that the efficacy or safety profiles for
Therefore, caution should be used when treating individuals who have
PROLENSA differ in patients 70 years of age and older compared to
previously exhibited sensitivities to these drugs.
younger adult patients.
Increased Bleeding Time
NONCLINICAL TOXICOLOGY
With some NSAIDs, including bromfenac, there exists the potential for
Carcinogenesis, Mutagenesis and Impairment of Fertility
increased bleeding time due to interference with platelet aggregation.
Long-term carcinogenicity studies in rats and mice given oral
There have been reports that ocularly applied NSAIDs may cause
doses of bromfenac up to 0.6 mg/kg/day (systemic exposure 30
increased bleeding of ocular tissues (including hyphemas) in conjunction
times the systemic exposure predicted from the recommended
with ocular surgery.
human ophthalmic dose [RHOD] assuming the human systemic
It is recommended that PROLENSA® ophthalmic solution be used with
concentration is at the limit of quantification) and 5 mg/kg/day (340
caution in patients with known bleeding tendencies or who are receiving
times the predicted human systemic exposure), respectively, revealed
other medications which may prolong bleeding time.
no significant increases in tumor incidence.
Keratitis and Corneal Reactions
Bromfenac did not show mutagenic potential in various mutagenicity
Use of topical NSAIDs may result in keratitis. In some susceptible
studies, including the reverse mutation, chromosomal aberration, and
patients, continued use of topical NSAIDs may result in epithelial
micronucleus tests.
breakdown, corneal thinning, corneal erosion, corneal ulceration or
Bromfenac did not impair fertility when administered orally to male
corneal perforation. These events may be sight threatening. Patients with
and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day,
evidence of corneal epithelial breakdown should immediately discontinue
respectively (systemic exposure 90 and 30 times the predicted human
use of topical NSAIDs, including bromfenac, and should be closely
exposure, respectively).
monitored for corneal health.
Post-marketing experience with topical NSAIDs suggests that patients
with complicated ocular surgeries, corneal denervation, corneal epithelial PATIENT COUNSELING INFORMATION
defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), Slowed or Delayed Healing
Advise patients of the possibility that slow or delayed healing may
rheumatoid arthritis, or repeat ocular surgeries within a short period
occur while using NSAIDs.
of time may be at increased risk for corneal adverse events which may
become sight threatening. Topical NSAIDs should be used with caution Sterility of Dropper Tip
Advise patients to replace bottle cap after using and to not touch
in these patients.
dropper tip to any surface, as this may contaminate the contents.
Post-marketing experience with topical NSAIDs also suggests that use
Advise patients that a single bottle of PROLENSA® ophthalmic
more than 24 hours prior to surgery or use beyond 14 days post-surgery
solution, be used to treat only one eye.
may increase patient risk for the occurrence and severity of corneal
Concomitant Use of Contact Lenses
adverse events.
Advise patients to remove contact lenses prior to instillation of
Contact Lens Wear
PROLENSA. The preservative in PROLENSA, benzalkonium
PROLENSA should not be instilled while wearing contact lenses.
chloride, may be absorbed by soft contact lenses. Lenses may be
Remove contact lenses prior to instillation of PROLENSA. The
reinserted after 10 minutes following administration of PROLENSA.
preservative in PROLENSA, benzalkonium chloride may be absorbed by
Concomitant Topical Ocular Therapy
soft contact lenses. Lenses may be reinserted after 10 minutes following
If more than one topical ophthalmic medication is being used, the
administration of PROLENSA.
medicines should be administered at least 5 minutes apart
ADVERSE REACTIONS
Rx Only
Clinical Trial Experience
Manufactured by: Bausch & Lomb Incorporated, Tampa, FL 33637
Because clinical trials are conducted under widely varying conditions,
Under license from:
adverse reaction rates observed in the clinical trials of a drug cannot be
Senju Pharmaceuticals Co., Ltd.
directly compared to rates in the clinical trials of another drug and may
Osaka, Japan 541-0046
not reflect the rates observed in clinical practice.
Prolensa is a trademark of Bausch & Lomb Incorporated or its affiliates.
The most commonly reported adverse reactions following use of
© Bausch & Lomb Incorporated.
9317600
US/PRA/14/0024
DOSAGE AND ADMINISTRATION
Recommended Dosing
One drop of PROLENSA® ophthalmic solution should be applied to
the affected eye once daily beginning 1 day prior to cataract surgery,
continued on the day of surgery, and through the first 14 days of the
postoperative period.
Use with Other Topical Ophthalmic Medications
PROLENSA ophthalmic solution may be administered in conjunction
with other topical ophthalmic medications such as alpha-agonists, betablockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics.
Drops should be administered at least 5 minutes apart.
45
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
VISUAL ACUITY
( Continued from page 42 )
drug they were receiving until the
primary results were published in
February 2015. At that time, if the
investigators considered it to be warranted, the study participant could
switch anti-VEGF agents.
After 2 years, 201 patients (90%)
remained in the aflibercept group,
185 (85%) in the bevacizumab group,
and 218 (88%) in the ranibizumab
group. At that point, the aflibercept
group had received a median of 15
injections, the bevacizumab had received 16, and the ranibizumab group
had received 15.
Sixty-four percent of the bevacizumab group received laser treatment, compared with 41% of the aflibercept group and 52% of the ranibizumab group.
V ISUA L ACU I T Y EF F ECT S
On average, visual acuity improved
over the 2 years by 12.8 letters with
aflibercept, 10.0 with bevacizumab,
and 12.3 with ranibizumab. The difference was statistically significant
(p = 0.02) for aflibercept versus bevacizumab, but not for aflibercept
versus ranibizumab (p = 0.47) and
not for ranibizumab versus bevacizumab (p = 0.11).
Among patients with an initial visual acuity of 20/50 or worse, improvement was 18.1 letters with aflibercept, 13.3 with bevacizumab, and
16.1 with ranibizumab. Once again,
this difference was only statistically
significant for aflibercept versus bevacizumab (p = 0.02).
With visual acuity of 20/32 or 20/40,
mean improvement at 2 years was
7.8 letters for aflibercept, 6.8 for bevacizumab, and 8.6 for ranibizumab,
and none of these differences were
statistically significant.
These findings carried forward
many of the trends from the previous
year. At the 1-year follow-up, when
visual acuity was 20/32 to 20/40 at
the start of the trial, vision improved
on average almost 2 lines in all three
treatment groups.
At the end of the first year, for
NEXT FRONTIER IN MANAGEMENT OF
participants whose visual acuity was
20/50 or worse at the start of the
trial, aflibercept improved vision on
average almost 18.9 letters, bevacizumab 11.8 letters, and ranibizumab
14.2 letters, with a statistically significant difference between aflibercept and bevacizumab (p < 0.001)
as well as between aflibercept and
ranibizumab (p = 0.003), but not
between ranibizumab and bevacizumab (p = 0.21).
Averaging the results over the 2
years, aflibercept maintained its statistically significant superiority over
the other two drugs.
The mean change in central subfield thickness was greatest with aflibercept, with a drop of 172 μm by
the end of the second year. This was
better than the drop of 149 μm for
ranibizumab and 126 μm for bevacizumab, with the differences between aflibercept and bevacizumab
(p < 0.001) and ranibizumab (p =
0.08) statistically significant, but not
between ranibizumab and bevacizumab (p = 0.001).
Among patients with a baseline visual acuity of 20/50 or worse, bevacizumab reduced central subfield thickness by 185 μm, which was more than
ranibizumab’s 174 μm, though still
not as much as aflibercept’s 211 μm.
In patients with visual acuity of
20/32 to 20/40, on the other hand,
bevacizumab only reduced central
subfield thickness by 68 μm, versus
125 μm for ranibizumab and 133 μm
for aflibercept.
There were no statistically significant differences in the percentages of patients suffering adverse
events among the groups. Elevated
IOP was the most frequently reported
complication.
RETINA DISEASE
In eyes with better vision, he
prefers ranibizumab because it
is less expensive than aflibercept
and because in these patients, it
might reduce edema more than
bevacizumab. ■
JOHN A. WELLS, MD
P: 803/252-1953
This article was adapted from Dr. Wells’ presentation during the 2016 meeting of the American Society of Retina
Surgeons. Dr. Wells discloses grants and non-financial
support from Genentech and Regeneron during the
conduct of the study.
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WEIGHING OPTIONS
In his own practice, Dr. Wells said,
he still prefers aflibercept for patients
with the weakest vision.
“I would think clearly baseline vision is important. And if baseline vision were 20/50 or worse, I would
choose [aflibercept],” he said. “It’s
obviously more effective at 1 year,
and even though the difference with
ranibizumab is narrowed at the 2-year
endpoint, you want to give people
better vision as quickly as you can.”
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46
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
NEXT FRONTIER IN MANAGEMENT OF
RETINA DISEASE
Real-world study tracks clinical use
of dexamethasone implant for DME
Interim analysis from REINFORCE trial finds vision gains, no new safety concerns
By Vanessa Caceres; Reviewed by Howard F. Fine, MD, MHSc
NE W BRUNSWICK , N J ::
USE OF a dexamethasone intra-
take-home
‘Since this is a real-world study,
the majority of patients (93.6%)
had received prior treatment
for DME.’ — Howard F. Fine, MD, MHSc
Dexamethasone implant injection
Mean (SE) BCVA change from baseline (EDTRS letters)
tive or monotherapy in patients, all
vitreal implant (Ozurdex, Allergan) of whom had DME. Eighty-eight
was associated with 1- to 2-line vi- patients (93.6%) were previously
sion gains on average in patients treated prior to the first dexamethwith diabetic macular edema (DME) asone injection. The mean DME
in the phase IV REINFORCE study, duration was more than 1 year in
73 eyes (72.3%) and more than 2
said Howard F. Fine, MD, MHSc.
The steroid implant has been years in 51 eyes (50.5%). In 63 eyes
approved by the FDA for macular (62.4%), the injection was used as
edema secondary to retinal vein monotherapy.
The mean injection frequency
occlusion and noninfectious uveitis, noted Dr. Fine, clinical asso- was 1.5, and the mean re-injection
ciate professor, Rutgers Robert interval in patients receiving mulWood Johnson Medical School, tiple implants was 135.4 days, according to the study
New Brunswick, NJ.
abstract.
It also was approved
“The top-line study
for DME after positive
data are the mean peak
results from the phase
improvement from
III MEAD study.
A 6-month
baseline was 8.2 letThe prospective, analysis from the
ters following the first
multicenter, observa- REINFORCE study of
[injection] and 8.7 lettional registry REIN- the dexamethasone
ters following the secFORCE study—short intravitreal implant
ond injection,” Dr. Fine
for Real-World Assess- found an average of
said. The proportion of
ment of Dexametha- 1- to 2-line vision gains
3-line gainers at any
sone Intravitreal Im- and no new safety
follow-up visit was
plant in Diabetic Macu- concerns.
27.6%, and the re-inlar Edema—measured
real-world outcomes of the implant jection interval was 4.5 months
when used to treat DME, Dr. Fine on average.
“What was most impressive
said. The data he presented were
an interim analysis of the 1-year to me is that since this is a realstudy of 101 study eyes (94 pa- world study, the majority of patients
tients) that had completed at least (93.6%) had received prior treatment
for DME, particularly anti-vascular
6 months of follow-up.
The implant was used as adjunc- endothelial growth factor [VEGF]
8.7 ± 2.6
12
10
8.2 ± 1.3
8
6
4
2
n=98 eyes
n=35 eyes
1st
2nd
0
(FIGURE 1) Mean (±SE) peak improvement (from baseline) in BCVA after first
and second steroid implant injection. (Figure courtesy of Howard F. Fine, MD, MHSc)
injections and/or laser,” Dr. Fine
said. “Therefore, this study demonstrates a significant role for [the
steroid implant] in patients treated
for DME, such as incomplete antiVEGF responders and those who
cannot tolerate a high anti-VEGF
injection frequency.”
Patients’ central retinal thickness improved from baseline each
month over the first 6 months after
the first injection, with a mean
peak change of –122.5 μm from
baseline at month 2. IOP increased
in 7.2% of eyes; 8.2% had an IOP
greater than 25 mm Hg, and 1%
had an IOP greater than 35 mm Hg.
Dr. Fine and fellow investigators concluded that as either monotherapy or combination therapy,
patients receiving the dexametha-
sone intravitreal implant had improved best corrected visual acuity
and central retinal thickness, and
there were no new safety concerns.
The 1-year results from REINFORCE should be ready by the end
of 2016. Dr. Fine said he is particularly interested in data regarding
combination therapy of both antiVEGF and dexamethasone injections. ■
HOWARD F. FINE, MD, MHSC
E: [email protected]
This article was adapted from Dr. Fine’s presentation
at the 2016 meeting of the Association for Research
in Vision and Ophthalmology. Dr. Fine is a consultant
for Allergan.
As demonstrated in phase 3 clinical
trials in patients with Wet AMD,
Macular Edema following RVO, DME,
and DR in patients with DME
Choose EYLEA® (aflibercept)
Injection from the start
Learn about EYLEA at EYLEA.us/ot
INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
EYLEA® (aflibercept) Injection is indicated for the treatment
of patients with Neovascular (Wet) Age-related Macular
Degeneration (AMD), Macular Edema following Retinal Vein
Occlusion (RVO), Diabetic Macular Edema (DME), and Diabetic
Retinopathy (DR) in Patients with DME.
CONTRAINDICATIONS
EYLEA® (aflibercept) Injection is contraindicated in patients
with ocular or periocular infections, active intraocular
inflammation, or known hypersensitivity to aflibercept or
to any of the excipients in EYLEA.
WARNINGS AND PRECAUTIONS
Intravitreal injections, including those with EYLEA, have been
associated with endophthalmitis and retinal detachments.
Proper aseptic injection technique must always be used
when administering EYLEA. Patients should be instructed
to report any symptoms suggestive of endophthalmitis or
retinal detachment without delay and should be managed
appropriately. Intraocular inflammation has been reported
with the use of EYLEA.
Acute increases in intraocular pressure have been seen
within 60 minutes of intravitreal injection, including with
EYLEA. Sustained increases in intraocular pressure have also
been reported after repeated intravitreal dosing with VEGF
inhibitors. Intraocular pressure and the perfusion of the optic
nerve head should be monitored and managed appropriately.
There is a potential risk of arterial thromboembolic events
(ATEs) following intravitreal use of VEGF inhibitors, including
EYLEA. ATEs are defined as nonfatal stroke, nonfatal
myocardial infarction, or vascular death (including deaths of
unknown cause). The incidence of reported thromboembolic
events in wet AMD studies during the first year was 1.8%
(32 out of 1824) in the combined group of patients treated
with EYLEA. The incidence in the DME studies from baseline
to week 52 was 3.3% (19 out of 578) in the combined group
of patients treated with EYLEA compared with 2.8% (8 out
of 287) in the control group; from baseline to week 100,
the incidence was 6.4% (37 out of 578) in the combined
group of patients treated with EYLEA compared with 4.2%
(12 out of 287) in the control group. There were no reported
thromboembolic events in the patients treated with EYLEA in
the first six months of the RVO studies.
ADVERSE REACTIONS
Serious adverse reactions related to the injection procedure
have occurred in <0.1% of intravitreal injections with EYLEA
including endophthalmitis and retinal detachment.
The most common adverse reactions (≥5%) reported in
patients receiving EYLEA were conjunctival hemorrhage,
eye pain, cataract, vitreous floaters, intraocular pressure
increased, and vitreous detachment.
Please see brief summary of full Prescribing Information on the
following page.
EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc.
©2016, Regeneron Pharmaceuticals, Inc.,
777 Old Saw Mill River Road, Tarrytown, NY 10591
All rights reserved
06/2016
US-LEA-1648(1)
BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION
FOR COMPLETE DETAILS, SEE FULL PRESCRIBING INFORMATION.
1 INDICATIONS AND USAGE
EYLEA® (aflibercept) Injection is indicated for the treatment of patients
with Neovascular (Wet) Age-Related Macular Degeneration (AMD), Macular
Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema
(DME), and Diabetic Retinopathy (DR) in Patients with DME.
2 DOSAGE AND ADMINISTRATION
2.1 Important Injection Instructions. For ophthalmic intravitreal injection.
EYLEA must only be administered by a qualified physician.
2.2 Neovascular (Wet) Age-Related Macular Degeneration (AMD).
The recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters)
administered by intravitreal injection every 4 weeks (monthly) for the first
12 weeks (3 months), followed by 2 mg (0.05 mL) via intravitreal injection
once every 8 weeks (2 months). Although EYLEA may be dosed as frequently
as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated
in most patients when EYLEA was dosed every 4 weeks compared to every
8 weeks. Some patients may need every 4 week (monthly) dosing after the
"%./0āĂƬ3!!'/Ĩă)+*0$/ĩċ
2.3 Macular Edema Following Retinal Vein Occlusion (RVO). The
recommended dose for EYLEA is (0.05 mL or 50 microliters) administered
by intravitreal injection once every 4 weeks (monthly).
2.4 Diabetic Macular Edema (DME). The recommended dose for EYLEA
is (0.05 mL or 50 microliters) administered by intravitreal injection every
4 weeks (monthly) for the first 5 injections followed by 2 mg (0.05 mL)
via intravitreal injection once every 8 weeks (2 months). Although EYLEA
may be dosed as frequently as 2 mg every 4 weeks (monthly), additional
efficacy was not demonstrated in most patients when EYLEA was dosed
every 4 weeks compared to every 8 weeks. Some patients may need every
4 week (monthly) dosing after the first 20 weeks (5 months).
2.5 Diabetic Retinopathy (DR) in Patients with DME. The recommended
dose for EYLEA is 2 mg (0.05 mL or 50 microliters) administered by
intravitreal injection every 4 weeks (monthly) for the first 5 injections,
followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks
(2 months). Although EYLEA may be dosed as frequently as 2 mg every
4 weeks (monthly), additional efficacy was not demonstrated in most
patients when EYLEA was dosed every 4 weeks compared to every 8 weeks.
Some patients may need every 4 week (monthly) dosing after the first
ĂĀƬ3!!'/ĨĆ)+*0$/ĩċ
2.6 Preparation for Administration. EYLEA should be inspected
visually prior to administration. If particulates, cloudiness, or discoloration
are visible, the vial must not be used. Using aseptic technique, the intravitreal
injection should be performed with a 30-gauge x ½-inch injection needle.
For complete preparation for administration instructions, see full prescribing
information.
2.7 Injection Procedure. The intravitreal injection procedure should be
carried out under controlled aseptic conditions, which include surgical
hand disinfection and the use of sterile gloves, a sterile drape, and a sterile
eyelid speculum (or equivalent). Adequate anesthesia and a topical broad–
spectrum microbicide should be given prior to the injection.
Immediately following the intravitreal injection, patients should be monitored
for elevation in intraocular pressure. Appropriate monitoring may consist of a
check for perfusion of the optic nerve head or tonometry. If required, a sterile
paracentesis needle should be available.
Following intravitreal injection, patients should be instructed to report any
symptoms suggestive of endophthalmitis or retinal detachment (e.g., eye
pain, redness of the eye, photophobia, blurring of vision) without delay (see
Patient Counseling Information).
Each vial should only be used for the treatment of a single eye. If the
contralateral eye requires treatment, a new vial should be used and the sterile
field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles
should be changed before EYLEA is administered to the other eye.
After injection, any unused product must be discarded.
3 DOSAGE FORMS AND STRENGTHS
Single-use, glass vial designed to provide 0.05 mL of 40 mg/mL solution
(2 mg) for intravitreal injection.
4 CONTRAINDICATIONS
EYLEA is contraindicated in patients with
G $/A8->;><1>5;/A8->5:21/@5;:?
G /@5B15:@>-;/A8->5:28-99-@5;:
G :;C:4E<1>?1:?5@5B5@E@;-285.1>/1<@;>-:E;2@411D/5<51:@?5:,!
Hypersensitivity reactions may manifest as severe intraocular inflammation.
5 WARNINGS AND PRECAUTIONS
5.1 Endophthalmitis and Retinal Detachments. Intravitreal injections,
including those with EYLEA, have been associated with endophthalmitis
and retinal detachments (see Adverse Reactions). Proper aseptic injection
technique must always be used when administering EYLEA. Patients should
be instructed to report any symptoms suggestive of endophthalmitis or
retinal detachment without delay and should be managed appropriately (see
Dosage and Administration and Patient Counseling Information).
5.2 Increase in Intraocular Pressure. Acute increases in intraocular pressure
have been seen within 60 minutes of intravitreal injection, including with
EYLEA (see Adverse Reactions). Sustained increases in intraocular pressure
have also been reported after repeated intravitreal dosing with vascular
edothelial growth factor (VEGF) inhibitors. Intraocular pressure and the
perfusion of the optic nerve head should be monitored and managed
appropriately (see Dosage and Administration).
5.3 Thromboembolic Events. There is a potential risk of arterial
thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors,
including EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial
infarction, or vascular death (including deaths of unknown cause). The
incidence of reported thromboembolic events in wet AMD studies during the
first year was 1.8% (32 out of 1824) in the combined group of patients treated
with EYLEA. The incidence in the DME studies from baseline to week 52 was
3.3% (19 out of 578) in the combined group of patients treated with EYLEA
compared with 2.8% (8 out of 287) in the control group; from baseline to
week 100, the incidence was 6.4% (37 out of 578) in the combined group
of patients treated with EYLEA compared with 4.2% (12 out of 287) in the
control group. There were no reported thromboembolic events in the patients
treated with EYLEA in the first six months of the RVO studies.
6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in the
Warnings and Precautions section of the labeling:
Endophthalmitis and retinal detachments
Increased intraocular pressure
Thromboembolic events
6.1 Clinical Trials Experience. Because clinical trials are conducted under
widely varying conditions, adverse reaction rates observed in the clinical
trials of a drug cannot be directly compared to rates in other clinical trials of
the same or another drug and may not reflect the rates observed in practice.
A total of 2711 patients treated with EYLEA constituted the safety population
in seven phase 3 studies. Among those, 2110 patients were treated with
the recommended dose of 2 mg. Serious adverse reactions related to
the injection procedure have occurred in <0.1% of intravitreal injections
with EYLEA including endophthalmitis and retinal detachment. The most
common adverse reactions (*5%) reported in patients receiving EYLEA were
conjunctival hemorrhage, eye pain, cataract, vitreous floaters, intraocular
pressure increased, and vitreous detachment.
Neovascular (Wet) Age-Related Macular Degeneration (AMD). The data
described below reflect exposure to EYLEA in 1824 patients with wet AMD,
including 1223 patients treated with the 2-mg dose, in 2 double-masked,
active-controlled clinical studies (VIEW1 and VIEW2) for 12 months.
Table 1: Most Common Adverse Reactions (*1%) in Wet AMD Studies
Active Control
EYLEA
Adverse Reactions
(ranibizumab)
(N=1824)
(N=595)
Conjunctival hemorrhage
25%
28%
Eye pain
9%
9%
Cataract
7%
7%
Vitreous detachment
6%
6%
Vitreous floaters
6%
7%
Intraocular pressure increased
5%
7%
Ocular hyperemia
4%
8%
Corneal epithelium defect
4%
5%
Detachment of the retinal pigment
3%
3%
epithelium
Injection site pain
3%
3%
Foreign body sensation in eyes
3%
4%
Lacrimation increased
3%
1%
Vision blurred
2%
2%
Intraocular inflammation
2%
3%
Retinal pigment epithelium tear
2%
1%
Injection site hemorrhage
1%
2%
Eyelid edema
1%
2%
Corneal edema
1%
1%
Less common serious adverse reactions reported in <1% of the patients
treated with EYLEA were hypersensitivity, retinal detachment, retinal tear,
and endophthalmitis.
Macular Edema Following Retinal Vein Occlusion (RVO). The data described
below reflect 6 months exposure to EYLEA with a monthly 2 mg dose in 218
patients following CRVO in 2 clinical studies (COPERNICUS and GALILEO) and
91 patients following BRVO in one clinical study (VIBRANT).
Table 2: Most Common Adverse Reactions (*1%) in RVO Studies
Adverse Reactions
CRVO
BRVO
EYLEA Control EYLEA Control
(N=218) (N=142) (N=91) (N=92)
Eye pain
13%
5%
4%
5%
Conjunctival hemorrhage
12%
11%
20%
4%
Intraocular pressure increased
8%
6%
2%
0%
Corneal epithelium defect
5%
4%
2%
0%
Vitreous floaters
5%
1%
1%
0%
Ocular hyperemia
5%
3%
2%
2%
Foreign body sensation in eyes
3%
5%
3%
0%
Vitreous detachment
3%
4%
2%
0%
Lacrimation increased
3%
4%
3%
0%
Injection site pain
3%
1%
1%
0%
Vision blurred
1%
<1%
1%
1%
Intraocular inflammation
1%
1%
0%
0%
Cataract
<1%
1%
5%
0%
Eyelid edema
<1%
1%
1%
0%
Less common adverse reactions reported in <1% of the patients treated with
EYLEA in the CRVO studies were corneal edema, retinal tear, hypersensitivity,
and endophthalmitis.
Diabetic Macular Edema (DME). The data described below reflect
exposure to EYLEA in 578 patients with DME treated with the 2-mg dose in 2
double-masked, controlled clinical studies (VIVID and VISTA) from baseline
to week 52 and from baseline to week 100.
Table 3: Most Common Adverse Reactions (*1%) in DME Studies
Adverse Reactions
Baseline to Week 52 Baseline to Week 100
EYLEA
Control
EYLEA
Control
(N=578) (N=287) (N=578) (N=287)
Conjunctival hemorrhage
28%
17%
31%
21%
Eye pain
9%
6%
11%
9%
Cataract
8%
9%
19%
17%
Vitreous floaters
6%
3%
8%
6%
Corneal epithelium defect
5%
3%
7%
5%
Intraocular pressure increased
5%
3%
9%
5%
Ocular hyperemia
5%
6%
5%
6%
Vitreous detachment
3%
3%
8%
6%
Foreign body sensation in eyes
3%
3%
3%
3%
Lacrimation increased
3%
2%
4%
2%
Vision blurred
2%
2%
3%
4%
Intraocular inflammation
2%
<1%
3%
1%
Injection site pain
2%
<1%
2%
<1%
Eyelid edema
<1%
1%
2%
1%
Less common adverse reactions reported in <1% of the patients treated with
EYLEA were hypersensitivity, retinal detachment, retinal tear, corneal edema,
and injection site hemorrhage.
6.2 Immunogenicity. As with all therapeutic proteins, there is a potential for
an immune response in patients treated with EYLEA. The immunogenicity
of EYLEA was evaluated in serum samples. The immunogenicity data reflect
the percentage of patients whose test results were considered positive for
antibodies to EYLEA in immunoassays. The detection of an immune response
is highly dependent on the sensitivity and specificity of the assays used,
sample handling, timing of sample collection, concomitant medications,
and underlying disease. For these reasons, comparison of the incidence of
antibodies to EYLEA with the incidence of antibodies to other products may
be misleading.
In the wet AMD, RVO, and DME studies, the pre-treatment incidence of
immunoreactivity to EYLEA was approximately 1% to 3% across treatment
groups. After dosing with EYLEA for 24-100 weeks, antibodies to EYLEA were
detected in a similar percentage range of patients. There were no differences
in efficacy or safety between patients with or without immunoreactivity.
6.3 Postmarketing Experience. The following adverse reactions have been
identified during postapproval use of EYLEA. Because these reactions are
reported voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency or establish a causal relationship
to drug exposure.
G E<1>?1:?5@5B5@E5:/8A05:3>-?4<>A>5@A?-:0A>@5/->5--?C188-?5?;8-@10
cases of severe anaphylactic/anaphylactoid reactions.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy. Pregnancy Category C. Aflibercept produced embryo-fetal
toxicity when administered every three days during organogenesis to
pregnant rabbits at intravenous doses *3 mg per kg, or every six days at
subcutaneous doses *0.1 mg per kg. Adverse embryo-fetal effects included
increased incidences of postimplantation loss and fetal malformations,
including anasarca, umbilical hernia, diaphragmatic hernia, gastroschisis, cleft
palate, ectrodactyly, intestinal atresia, spina bifida, encephalomeningocele,
heart and major vessel defects, and skeletal malformations (fused vertebrae,
sternebrae, and ribs; supernumerary vertebral arches and ribs; and incomplete
ossification). The maternal No Observed Adverse Effect Level (NOAEL) in
these studies was 3 mg per kg. Aflibercept produced fetal malformations at
all doses assessed in rabbits and the fetal NOAEL was less than 0.1 mg per kg.
Administration of the lowest dose assessed in rabbits (0.1 mg per kg) resulted
in systemic exposure (AUC) that was approximately 10 times the systemic
exposure observed in humans after an intravitreal dose of 2 mg.
There are no adequate and well-controlled studies in pregnant women.
EYLEA should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus. Females of reproductive potential should use
effective contraception prior to the initial dose, during treatment, and for at
least 3 months after the last intravitreal injection of EYLEA.
8.3 Nursing Mothers. It is unknown whether aflibercept is excreted in human
milk. Because many drugs are excreted in human milk, a risk to the breastfed
child cannot be excluded. EYLEA is not recommended during breastfeeding.
A decision must be made whether to discontinue nursing or to discontinue
treatment with EYLEA, taking into account the importance of the drug to
the mother.
8.4 Pediatric Use. The safety and effectiveness of EYLEA in pediatric patients
have not been established.
8.5 Geriatric Use. In the clinical studies, approximately 76% (2049/2701)
of patients randomized to treatment with EYLEA were *65 years of age
and approximately 46% (1250/2701) were *75 years of age. No significant
differences in efficacy or safety were seen with increasing age in these
studies.
17 PATIENT COUNSELING INFORMATION
In the days following EYLEA administration, patients are at risk of developing
endophthalmitis or retinal detachment. If the eye becomes red, sensitive
to light, painful, or develops a change in vision, advise patients to seek
immediate care from an ophthalmologist (see Warnings and Precautions).
Patients may experience temporary visual disturbances after an intravitreal
injection with EYLEA and the associated eye examinations (see Adverse
Reactions). Advise patients not to drive or use machinery until visual function
has recovered sufficiently.
Manufactured by:
Regeneron Pharmaceuticals, Inc.
777 Old Saw Mill River Road
Tarrytown, NY 10591-6707
EYLEA is a registered trademark of
Regeneron Pharmaceuticals, Inc.
© 2016, Regeneron Pharmaceuticals, Inc.
All rights reserved.
Issue Date: June 2016
Initial U.S. Approval: 2011
June 2016
49
SEPTEMBER 15, 2016 :: Ophthalmology Times
Special Report )
NEXT FRONTIER IN MANAGEMENT OF
RETINA DISEASE
Retinal prosthesis system ranks high
in safety, performance endpoints
Follow-up at 5 years continues to show positive results for vision-restoring device
Lynda Charters; Reviewed by Lyndon da Cruz, MD, and Jessy D. Dorn, PhD
LONDON AND SY L MAR, CA ::
RECENTLY PUBLISHED results from
an ongoing 10-year clinical study of a retinal
prosthesis system (Argus II Retinal Prosthesis
System, Second Sight) showed the device has
continued to maintain a high safety profile as
of the 5-year time point in 30 patients with retinitis pigmentosa implanted with the device.
“[It] is the first retinal prostheses approved for
commercialization in the European Economic
Area that can help restore some visual function
in patients with retinitis pigmentosa, and the
only one to receive FDA approval in the United
States and Health Canada approval,” according
to Lyndon da Cruz, MD, consultant ophthalmic
surgeon, Department of Vitreoretinal Surgery,
Moorfields Eye Hospital, London, and lead author of the paper (da Cruz et al. Ophthalmology. 2016 Jul 19. pii: S0161-6420(16)30579-6.
doi: 10.1016/j.ophtha.2016.06.049. [Epub ahead
of print]).
Patients will continue to be followed for an
additional 5 years.
The prospective trial, conducted at 10 centers in the United States and Europe, enrolled
processing unit in their pocket or slung over
their shoulder, explained Jessy D. Dorn, PhD,
study co-author and senior director of Clinical and Scientific Research, Second Sight. The
processing unit converted the images into stimulation patterns sent
wirelessly to the electrode array.
patients, 24 serious adverse events occurred,
all of which were treatable and no patient required enucleation.
By 5 years, one additional adverse event,
a rhegmatogenous retinal detachment, occurred and was treated
successfully. In addition, two implants had failed due to the inability to maintain the radioSAFETY
The retinal prosthesis
frequency link between the antenIn measuring the primary safety
nae mounted on the glasses and
endpoint, investigators recorded system is providing
implanted in the eye, Dr. Dorn
the number, type, and the severity a safe option for
explained.
of serious or non-serious adverse restoration of some
events associated with the surgery visual function in
PERFORMANCE
or the device. Visual function, as- patients with severe
“Overall, the patients performed
sessed using three computer-based vision loss associated
better on computerized and realtests, was the secondary endpoint. with retinitis
life tests to evaluate their level of
All of the visual assessments were pigmentosa.
functional vision when they wore
performed with the device turned
on and off, with the latter relying only on re- the system compared to when the system was
sidual vision. Secondary endpoints included turned off,” Dr. da Cruz said.
For example, when patients were instructed
a number of “real world” tasks the patients
were asked to perform to determine the prac- to find a white square on a black background of
the computer screen, 81% scored significantly
ticality of the device.
At the 5-yea r better using the system, he explained, nottime point, 24 pa- ing about half of the patients did better while
tients still had the using the system for identifying the direction
prosthesis system in which a bar was moving across the screen.
“The device has gone on to be implanted
i m pl a n te d a n d
functioning. None in many patients; in many countries, it reof the 30 patients mains the only currently available treatment
were completely for profound vision loss resulting from [retinilost to follow-up, tis pigmentosa] and outer retinal dystrophy,”
and safety data the authors concluded. “The new long-term
could be obtained data from the original study continue to demfrom 27 patients at onstrate that this therapy remains an option
evaluation, as three for patients with [retinitis pigmentosa] and
devices were ex- may allow for stable and reliable restoration
planted due to re- of some basic visual function.” ■
current conjunctival erosions in two
patients and hypotLYNDON DA CRUZ, MD
ony and ptosis in
E: [email protected]
one patient, Dr. da
Dr. da Cruz did not indicate any proprietary interest in the subject matter.
Cruz reported.
At the 3-year time point, 18 (60%) of the 30
JESSY D. DORN, PHD
patients had no serious adverse event related
E: [email protected]
to surgery or the device. In the remaining 12
Dr. Dorn is a senior director of Clinical and Scientific Research at Second Sight.
‘The device has gone on to be
implanted in many patients; in
many countries, it remains the
only currently available treatment
for profound vision loss resulting
from [retinitis pigmentosa] and
outer retinal dystrophy.’
30 patients implanted with an electrode array
on the retinal surface of the worse eye.
Patients wore glasses on which a video camera had been mounted and carried a video
take-home
50
SeptemBer 15, 2016 :: Ophthalmology Times
clinical diagnosis
Updated classification gives
order to corneal dystrophy
Better diagnosis can help patients, physicians chart out best approach to treatment
By Laird Harrison; Reviewed by Jayne S. Weiss, MD
Ne w Orl e aNs ::
hat’s in a name? Would
lead to multiple opacities in adults. The condiSchnyder corneal dystrotion is autosomal dominant disease.
> A chromosome 10 dystrophy was eliminated
phy (SCD) cause as much
vision loss by any other
from the Thiel-Behnke category. Earlier reports
name? Perhaps, but it may
of a Thiel-Behnke dystrophy on chromosome
not be properly diagnosed,
10 were not substantiated by further research,
said Jayne S. Weiss, MD.
which confirmed that all Thiel-Behnke dystroToo often the condition has been referred
phies are on the TGFBI gene on chromosome
to as Schnyder crystalline corneal dystrophy,
5. The dystrophy resembles Thiel-Behnke and
leading clinicians to misdiagnose patients who
may belong in the ERED category.
> Congenital hereditary endothelial dystrophy 1
had no crystals in their corneas, said Dr. Weiss,
chairman, Department of Ophthalmology, Lou(CHED 1) was eliminated. The autosomal domiisiana State University, New Orleans.
nant condition that was being called CHED 1 was
That is only one example of many confusing
actually a different dystrophy called posterior
and misleading names of dystrophies which
polymorphous corneal dystrophy. Consequently,
inspired Dr. Weiss to lead an effort to properly
the autosomal recessive corneal dystrophy predifferentiate and name corneal dystrophies.
viously called CHED 2 is now named CHED.
“If we don’t know what we’re looking at,
how will we ever make any headway into sciThe new document builds on the work in
entific investigation for a better treatment or the original document, which replaced categoprevention?” she asked. “That, ultimately, as ries based on anatomy with categories based
a clinician scientist, was my goal for this.”
on genes.
In 2005, she organized the International Com“Two things that look the same, if they have
mittee for the Classification of Corneal Dystro- a different genetic origin, are probably not the
phies (IC3D), whose results were first published same,” Dr. Weiss said. “We may have some disin 2008. Between 2008 and 2012, new infor- eases on the same gene that may look very difmation about the dystrophies became avail- ferent, but if they’re on the same gene, maybe
able, for which Dr. Weiss also led the update. with different mutations, there could be more
The updated classification appears in Cornea similarity . . . than you might guess at first
under the title “IC3D classificaglance.”
tion of corneal dystrophies—
The researchers also found
edition 2,” and is most easily
exceptions to the commonly
An updated
accessed by selecting the pubused definition of corneal dysclassifcation of
lisher’s button in its Pubmed
trophy—an inherited, bilateral,
corneal dystrophies
listing (http://bit.ly/2c9WFMf).
slowly progressing corneal diswill help clinicians
The most important changes
ease without systemic associawith properly
in the update included:
tions. In some cases, the oppodifferentiating and
> A new anatomic category for
site can also be true, she said.
naming the disorders.
The document offers one-page
dystrophies that map to the
descriptions of each dystrophy,
TGFBI gene.
> Expansion of the epithelial
how it is inherited, genetic information, the age of onset, signs and symprecurrent erosion dystrophy (ERED) category.
toms, how rapidly it progresses, and photos.
Recent research has uncovered more subtypes
“There are levels of detail in the article that
of ERED, which often causes recurrent unexare certainly relevant to many physicians in
plained corneal erosions in children and can
w
Take-Home
magenta
cyan
yellow
black
Schnyder corneal
dystrophy
TOP Central subepithelial crystals are present.
BOTTOM Central panstromal corneal opacity,
peripheral arcus lipoides, and more subtle
midperipheral corneal haze are visible, though
no corneal crystals are present.
(Images courtesy of Jayne S. Weiss, MD)
terms of assisting them to make the diagnosis
and helping inform the patient what the prognosis is,” Dr. Weiss said.
Some corneal dystrophies cause few symptoms. Others can lead to opacification, but corneal transplants can usually restore good vision in these patients, she noted.
“One of my goals is for us to get to the next
level that we have gotten to in many other diseases, where we can intervene to prevent disease
progression and avoid visual loss,” she said.
In the meantime, better diagnosis can help
patients plan for the future, Dr. Weiss said.
Continues on page 52 : Corneal dystrophy
ES838947_OT091516_050.pgs 09.12.2016 22:37
ADV
Photo by: J. Bradley Randleman, MD
Extreme example of visual distortion from keratoconus.
Corneal Cross-linking can help improve vision.
YOUR VISION, OUR FOCUS
Corneal Cross Linking—the recent FDA approved treatment
to reverse corneal warpage and visual distortion from
keratoconus and complications of LASIK is now available
at the USC Roski Eye Institute.
Find out more at AAO, 2016
Therapeutic & Refractive Crosslinking Refractive Surgery by J. Bradley Randleman, MD
Monday, October 17, 2016 — 3:45-5:20PM, Grand Ballroom S100AB
For Referring Physicians: 323-442-eyes
or visit www.usceye.org
# "##
52
SEPTEMBER 15, 2016 :: Ophthalmology Times
clinical diagnosis
How pregnancy can affect Sjögren’s
ectopic lymphoid structures
Early detection of cell organization in lacrimal glands may enable disease interventions
By Nancy Groves; Reviewed by Austin K. Mircheff, PhD
LOS ANGEL ES ::
RESEARCH IN AN ANIMAL model
shows pregnancy can increase accumulation
and activation of cells and functions associated with ectopic lymphoid structures (ELS)
in Sjögren’s syndrome.
Further research on the mechanisms in ELS
development could lead to interventions preventing the onset of Sjögren’s syndrome, said
Austin K. Mircheff, PhD, Department of Physiology and Biophysics, Keck School of Medicine,
University of Southern California, Los Angeles.
Dr. Mircheff and colleagues are exploring
an approach to describe what happens during
pregnancy that could cause Sjögren’s syndrome.
“It’s not just a way of visualizing the precursors of a disease process, but also seeing
what the biological mechanisms and signaling interactions are between the various types
of cells that have to organize themselves into
rather complex structures,” Dr. Mircheff said.
CELLS ORGANIZING
Earlier research discovered a cluster of very
strongly correlating transcripts in the lacrimal
glands of rabbits that seemed to organize into a
network resembling an ELS, Dr. Mircheff noted.
The team hypothesized that pregnancy might
influence the development of the cellular network. Additional studies testing six pregnant
CORNEAL DYSTROPHY
( Continued from page 50 )
“When we see patients, they want to know
what do they have and what can they expect
as their life goes on,” she said. “Are they going
to need surgery? Is their vision going to be impaired? What are the chances of them giving
this to their progeny? Unless we really understand what we’re looking at, we can’t give the
disease the correct name and most importantly
we can’t really give the patient an accurate
idea about what they may face in the future.”
For example, Dr. Weiss, an authority on
rabbits and six virgin rabbits using q-RT-PCR
aimed to determine the abundances of 62 transcripts in each lacrimal gland. The researchers
used Pearson’s test to identify clusters of positively and negatively correlating transcripts.1
There were few statistically significant differences between the lacrimal glands of pregnant
and virgin rabbits for the network transcripts.
“There was a bigger range of variation among
the glands from the pregnant animals than the
glands from the virgin animals,” Dr. Mircheff
said, adding that the individual glands sorted
into two clusters: one with transcripts higher
than normal, and one where they were lower.
MOV ING TO SJÖGR EN’S ELS
Pregnancy affects the cells that form the network that eventually may become Sjögren’s ELS.
“They can either become more numerous
and more highly activated or less numerous
and less highly activated in pregnancy,” Dr.
Mircheff said. “The obvious inference . . . is
that the glands that become more active or
more prevalent are the ones that will go on to
develop Sjögren’s because this network will
continue developing of its own with time.”
Still, that inference may not entirely be correct.
“At the same time, we find evidence for negative crosstalk between that network and cells
Schnyder corneal dystrophy, had a young patient with this dystrophy who wanted to be a
pilot. She showed the patient a chart indicating how the patient’s vision would likely be
affected at each age. The patient decided to
become a pilot while understanding the career
might not last past the age of 30 or 40 years.
“Many times when I’m in a room with patients
I’ll open the IC3D article and show them where
they are,” Dr. Weiss said. “I find my patients
are always appreciative of the information.”
In another case, a patient with Schnyder was
considering laser treatment for corneal crystals.
She explained the treatment would not entirely
restore the patient’s vision because of coexistent corneal haze underneath the crystals.
or types of cells that express other proteins
involved in ELS,” he said. “That may prevent
all of the cells from coming together to form
those structures, and it may be in the glands
where the first cluster is poorly developed . . .
you may have reciprocal networks developing.”
The ability to detect the networks of cells organizing themselves, while they’re still precursors to the ELS, may enable possible interventions to prevent them from coalescing, he said.
It is significant the study involved rabbits
instead of mice, given persistent questions on
how closely immunological mechanisms in mice
or rats correspond to those in humans, he said.
“Histologically, and in some functional aspects, rabbit lacrimal glands are more similar to humans,” Dr. Mircheff said. “If we had
done this study with rodents, we may not have
seen anything like the results we’ve gotten.” ■
Reference
1. Mircheff et al. Potentially pathogenic immune cells
and networks in apparently healthy lacrimal cell
glands. Ocul Surf. 2015;13:47-81.
AUSTIN K. MIRCHEFF, PHD
P: 323/442-1242
E: [email protected]
This article was adapted from Dr. Mircheff and colleagues’ poster presentation at the
2015 meeting of the Association for Research in Vision and Ophthalmology.
A correct diagnosis might help uncover systemic conditions as well. Since families with
Schnyder often have elevated cholesterol levels
whether or not the eye is affected, clinicians
should advise these patients to have their systemic cholesterol levels checked, Dr. Weiss noted.
“No one wants a disease,” she said, “but
the unknown is often more frightening than
the known.” ■
JAYNE S. WEISS, MD
E: [email protected] This article was adapted from Dr. Weiss’ delivery of the Richard L. Lindstrom, MD,
Lecture during the 2016 meeting of the American Society of Cataract and Refractive
Surgery. She did not indicate any proprietary interest in the subject matter.
Corneal Hysteresis
is more associated
with visual field
progression than
CCT or IOP.
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References: 1. Medeiros FA, Meira-Freitas D, Lisboa R, Kuang TM, Zangwill LM, Weinreb RN. Corneal hysteresis as
a risk factor for glaucoma progression: a prospective longitudinal study. Ophthalmology. 2013 Aug;120(8):153340. 2. De Moraes CV, Hill V, Tello C, Liebmann JM, Ritch R. Lower corneal hysteresis is associated with more rapid
glaucomatous visual fi eld progression. J Glaucoma. 2012 Apr-May;21(4):209-13. 3. Aashish Anand, MD, Carlos
Gustavo De Moraes, MD, Christopher C Teng, MD, Celso Tello, MD, Jeffrey M Liebmann, MD Robert Ritch, MD. Lower
Corneal Hysteresis Predicts Laterality in Asymmetric Open Angle Glaucoma, IOVS Papers in Press. Published on
June 23, 2010 as Manuscript iovs.10-5580. CPT is registered trademark of the American Medical Association.
54
SEPTEMBER 15, 2016 :: Ophthalmology Times
clinical diagnosis
Using structure, function analysis
to track progression of glaucoma
Mapping best treatment requires consideration of individualized disease progression rates
By Laird Harrison
MEASURES OF STRUCTURE and
function change can help ophthalmologists
individualize treatment of glaucoma patients,
according to Robert Chang, MD.
Since glaucoma progresses faster in some
patients than others, optical coherence tomography (OCT) and visual field progression analysis can be more useful than IOP in guiding
treatment decisions, said Dr. Chang, assistant
professor of ophthalmology, Stanford University Medical Center, Stanford, CA.
“I use structure and function glaucoma progression analysis to really customize therapy
over a lifetime,” he said. “That’s my method
of precision medicine in treating glaucoma patients today.”
The concept of precision medicine has received growing attention in recent years, he
said, citing the Precision Medicine Initiative
presented by President Barack Obama in his
2015 State of the Union address. The initiative calls on health-care providers to take into
consideration genetic, lifestyle, and environmental factors to tailor treatments to patients.
“How are we going to apply precision medicine when we don’t have much genetic data
and we don’t know what the patient’s environmental effects are?” Dr. Chang asked. “Maybe
there aren’t any specifically for glaucoma.”
CONSIDER ATIONS
The answer to treating glaucoma starts with
preserving ganglion cells as long as the patient lives, Dr. Chang said. Clinicians must
consider the rate the disease is progressing
in each patient in order to choose a treatment
that strikes the right balance between probable efficacy and the risk of adverse reactions.
“We need something quantitative,” he said,
“not just looking at the nerve or asking them
how their vision is doing.”
OCT-guided progression analysis in early
stages of glaucoma and visual field progression analysis in later stages can provide the
data to monitor progression, he said.
OCT is highly repeatable, so clinicians can
compare a patient’s status to baseline measurements. Additionally, visual field index can be
calculated against the patient’s age.
“Everyone should know that there is no agerelated loss progression correction on these
OCT calculations,” Dr. Chang said. “On average, age-related loss is about 2 to 3 μm every
decade or 0.2 μm per year.”
In some patients, the disease may progress
very slowly, Dr. Chang said. He cited the Canadian Glaucoma Study (Arch Ophthalmol.
2010;128:1249-1255), in which 216 patients
were followed up at 4-month intervals with
perimetry and were monitored for progression.
The patients who reached an endpoint based
on total deviation analysis underwent 20%
or greater reduction in IOP. The researchers
found the median mean deviation rate in progressing patients prior to the first endpoint
was −0.35dB/y.
USEFUL INFOR MATION
Dr. Chang recalled a patient he had followed
for about 5 years who was “very noncompliant.” At baseline, the patient’s untreated IOP
was a maximum of 32 mm Hg. The patient
refused surgery, so Dr. Chang was “almost
just documenting the natural course of disease.” Interestingly, the patient’s right eye did
not progress as fast as the right, despite high
pressure in both.
The structural changes generally precede
the functional changes, but eventually if a
patient loses a certain amount of nerve fiber
layer, the patient will experience a visual field
defect, he said.
How can clinicians make use of this information? Dr. Chang pointed out more glaucoma
treatments that are available than in the past.
Ophthalmologists have to decide whether to
prescribe medications, perform conventional
surgery, or implant a minimally invasive glaucoma surgery device.
“While we have a lot of studies, major trials that give us the target range pressures, it
may not be the absolute value of the pressure
that you should reach for in every single patient,” Dr. Chang said. “Instead, start looking
at what their individualized rates of progressions are over time.”
Because glaucoma doesn’t change overnight, it might be worthwhile to “sacrifice a
PRECISION MEDICINE
VIDEO Watch as Dr. Chang discusses
portable technology options that help provide
better patient care. Go to OphthalmologyTimes.
com/PrecisionMedicine
few neurons” to avoid subjecting patients to a
treatment that may cause side effects, he said.
“What we’re really getting at here is their personalized rate of progression.”
He uses a grid to figure out what treatment
might work best, and to present it to the patient. On the left column is “high-efficacy,
but high side-effects” treatments, like filtering
surgery. On the right is “watchful waiting.”
In between are treatments with medium efficacy and medium risk. The faster the patient’s
disease is progressing, the farther the left the
patient belongs, and vice versa.
Dr. Chang still sets initial target pressures,
and he lowers the patient’s pressure if he thinks
the patient’s condition is deteriorating.
“That’s what I’m focusing on, using visual
fields maximally . . . to know if they are getting a little worse,” he said. “Therefore, I’m
going to think about all the new treatments
available.” ■
ROBERT CHANG, MD
E: [email protected]
This article was adapted from Dr. Chang’s presentation during the Glaucoma
Symposium CME at the 2016 Glaucoma 360 meeting. Dr. Chang disclosed that he does
research for Carl Zeiss Meditec.
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56
SEPTEMBER 15, 2016 :: Ophthalmology Times
clinical diagnosis
Coin-sized scanner may enable
early diagnosis of retinal diseases
Technology may also expand individuals who can be screened outside of hospitals, practices
By Nancy Groves; Reviewed by Prof. Wolfgang Drexler
VIENNA ::
A CONSORTIUM OF EUROPEAN
experts in academia and industry is collaboratElectrical
ing on an ambitious, 4-year project to shrink
Swept Interposer PIC
both the size and cost of optical coherence toMicrolens
Source
Array
mography (OCT) systems.
The OCTChip (ophthalmic OCT on a chip)
Reference
project aims to use photonic integrated cirArm
cuits to produce a coin-sized retinal scanner
that will improve the screening and diagnosis
of retinal diseases, such as age-related macular degeneration, diabetic retinopathy, and
ages conveyed to a reading center via a wireless
glaucoma.
Wolfgang Drexler, professor of medical phys- or Bluetooth connection using a cellphone or
ics, head of the Center for Medical Physics and tablet. This arrangement would also allow for
Biomedical Engineering, Medical University rapid feedback and open a pathway to quicker
of Vienna, is leading the project, which began diagnosis and treatment.
The research and development team is
at the start of 2016. Less than a year in, his
team has come up with preliminary designs also envisioning that an extremely compact OCT system could one day be on store
and ideas for packaging.
“I’m quite positive that in a year or so we’ll shelves as a consumer product for self-dihave the first prototype, and then in 2 or 3 agnosis of retinal or dermatologic diseases,
years we will go into clinical trials with an Prof. Drexler said.
The miniaturized OCT system would repreimproved prototype,” Prof. Drexler said.
sent a significant leap in OCT
Commercialization and mass
technology. OCT is now 25 years
production could be achieved
old and reigns as the gold stanby 2020, he noted.
By shrinking the
dard in the diagnosis of eye dis“It’s something that will revocore technology of
eases, as well as being used in
lutionize the biomedical or biooptical coherence
such specialties as cardiology
optical imaging world because
tomography to the
and gastroenterology.
it can be made very compact
size of a coin—and
But according to Prof. Drexand it is maintenance-free,”
reducing its cost—a
ler, despite steady improvement
Prof. Drexler added.
team of European
in OCT technology over the
The chip will be packaged in
scientists hopes
years, miniaturization has
a format that could be handto improve early
never been a priority as it has
held or maneuvered in front
diagnosis and
been in fields, such as conof a patient’s eyes, perhaps rescreening of retinal
sumer electronics, where tabsembling a larger laser pointer.
diseases.
lets and mobile phones have
This could broaden the specsupplanted desktop computers
trum of patients who could
for many users.
more readily undergo imagIn addition, the bulk and cost of current
ing, such as premature infants or elderly patients who have difficulty traveling to medi- OCT systems have limited their use to facilities and practitioners that could afford them
cal facilities.
and support the technology.
Prof. Drexler was already thinking about
R EMOTE USAGE
Such a compact tool scanner could also be eas- how to transfer the optical set-up of OCT to
ily transported to developing or remote areas of a chip a decade ago and began collaborating
the world where electricity is scarce, with im- with academic experts who were working on
TAKE-HOME
As a miniaturized imaging system, the core
component of the device targets the size of a
1-cent coin. (Image courtesy of Photonics21)
‘It’s something that
will revolutionize
the biomedical or
bio-optical imaging
world because it
can be made very
compact and it is
maintenance-free.’
— Prof. Wolfgang Drexler
photonic integrated circuits in telecommunications. One of the thornier problems they had
to solve was how to minimize optical losses
when transferring optical imaging technology
to a chip, since high optical losses are common in telecommunications.
Prof. Drexler subsequently initiated not
only the OCTChip project that he now heads
but another for dermatologic OCT on a chip,
which has now been commercialized for cancer diagnosis.
The novel approach the OCTChip team of
scientists and engineers is using to ensure suContinues on page 59 : Scanner
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58
SEPTEMBER 15, 2016 :: Ophthalmology Times
clinical diagnosis
Strategies may eliminate issues
impeding Tunisian pediatric care
Tactics include improving public/physician education, access to quality care, patient follow-up
By Cheryl Guttman Krader; Reviewed by Lamia El Fekih, MD
T UNIS, T UNISIA ::
DELAYED PATIENT presentation, compounded by problems relating to insufficient
resources and lack of follow-up, explain why
pediatric cataract remains an important cause
of visual impairment in Tunisia.
Thorough understanding of these existing challenges is providing a framework for
developing solutions, according to Lamia El
Fekih, MD.
“It is important that strategies for managing congenital cataract be developed and adopted according to regional conditions,” said
Dr. El Fekih, faculty of medicine, University
of Tunis-El Manar, Tunisia. “In Tunisia, we
are working together to eliminate surgical disequalities, and we have to focus on improving public and physician education, access
to good quality care, and patient follow-up.”
Dr. El Fekih suggested that maldistribution of services is the principal reason why
children with cataract do not receive the surgical care and follow-up they need for successful vision rehabilitation.
There are few centers in Tunisia where
pediatric ophthalmology and pediatric anesthesiology services are available, she noted.
Consequently, families are faced with the
need to travel long distances to procure care
for their child, and they may lack a means
of transportation.
In addition, there are multiple other factors limiting access to care.
For example, although surgery is available
at no charge for the poor in Tunisia, inability
to pay for other necessary services remains
an important barrier, considering the low socioeconomic level of the population in some
regions of the country.
HER EDITARY COMPONENT
“Moreover, congenital cataract in Tunisia appears to have a hereditary component,” Dr.
El Fekih said. “When a family has more than
one child needing treatment, the financial impact increases. In addition, these children with
congenital cataract often have other medical
and physical issues that can make it difficult
for families to bring them for care.”
Even if children undergo surgery, their visual prognosis depends on proper follow-up
care. In Tunisia, there is also a scarcity of
practitioners who can provide contact lenses
for aphakic refractive correction.
Furthermore, compliance with amblyopia
therapy among families in Tunisia is poor.
Dr. El Fekih noted that a review of a series
of children operated for congenital cataract at
her institution showed that about half of those
who needed occlusion therapy to prevent amblyopia did not receive it.
Children who develop amblyopia need low
vision training, but there are only two low vision centers in Tunisia, and even when physical access to these services is not an issue, a
financial obstacle can exist.
“Children may need more than one low vision device or there may be a need to replace
devices that get broken. Low vision aids, however, can be expensive,” Dr. El Fekih said.
Dr. El Fekih said that overcoming these challenges requires a multipronged approach. The
development of health education targeting
parents and health providers is imporBy 2020,
tant to raise awareness about pedithe hope is specialist
atric cataract and its management
centers
will be prepared
so more children are presented for
and
able
to
provide surgery
ophthalmic care.
and
effective
optical
Increasing parental knowledge
correction to all children
also leads to improved compliance
with congenital
said. “And, new trainees
with postoperative follow-up and amcataract.
are showing little interest
blyopia treatment protocols.
in specializing in pediatric
Focusing on education and other stratophthalmology.”
egies to increase patient access, Dr. El Fekih
She added that “by 2020, [the hope is] we
and others are working with the government
to strengthen programs for early detection for will have prepared equipped specialist centers
all causes of childhood blindness and to imple- and be able to provide surgery to all of our
children with congenital cataract along with
ment or improve referral systems.
In addition, they are mapping and identify- immediate and effective optical correction.” ■
ing tertiary eye care centers that have facilities for pediatric patients. They also are trying to encourage young ophthalmologists to
train in pediatrics.
“Although there are about 600 ophthalmologists in Tunisia serving our country’s popLAMIA EL FEKIH, MD
ulation of about 12 million people, there are
E: [email protected]
few pediatric ophthalmologists,” Dr. El Fekih
Dr. El Fekih has no relevant financial interests to disclose.
Tunisia has a population of
about 12 million people.
There are about
600 ophthalmologists.
But few specialize in
pediatric ophthalmology.
ALGERIA
TUNISIA
LIBYA
SEPTEMBER 15, 2016 :: Ophthalmology Times
clinical diagnosis
SCANNER
( Continued from page 56 )
perior optical quality while shrinking the core
OCT technology is the use of photonic integrated
circuits.
“By using photonic integrated circuits we
can combine planar optical waveguides, and
we also use microelectronics packaged on these
chips so that it’s extremely compact and low
cost and hopefully even higher performing
than recent commercial OCT systems,” Prof.
Drexler said.
Participants in the OCTChip project include
the Medical University of Vienna, which is coordinating the effort, University College Cork
in Ireland, the Austrian Institute of Technology, the Fraunhofer Network in Germany, Carl
Zeiss Meditec, Austrian sensor firm AMS, and
the Swiss company Exalos AG. ■
59
PROF. WOLFGANG DREXLER
E: [email protected]
Prof. Drexler is a consultant for Carl Zeiss Meditec as well as Exalos regarding
OCTChip and the topic it covers.
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He added that the use of integrated optics and
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OCTChip is funded by the Photonics Public Private Partnership (Photonics PPP); the
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60
SEPTEMBER 15, 2016 :: Ophthalmology Times
clinical diagnosis
Mild corticosteroids may safely
reduce Sjögren’s inflammation
Pilot study also helps investigators refine technique for tear analysis
By Nancy Groves; Reviewed by Ranjini Kottaiyan, OD, MBA
ROCHES T ER, N Y ::
A MILD TOPICAL corticosteroid could be
effective in treating the symptoms of Sjögren’s
syndrome by reducing the inflammatory tear
cytokines and the rate of evaporation, suggest
findings from a small pilot study.
Ocular surface metrology performed with
tools—such as wavefront sensing and thermal
imaging—appear to be effective in analyzing
the effects of treatment, said Ranjini Kottaiyan, OD, MBA, lead researcher, Ocular Surface
Laboratory, Flaum Eye Institute, University of
Rochester, Rochester, NY.
Corticosteroids have been used to treat dry
eye symptoms of Sjögren’s syndrome. However,
the risk of adverse effects, such as increased
IOP and cataract formation after prolonged use,
has prompted interest in a lower-strength steroid, such as loteprednol etabonate ophthalmic
suspension 0.5% (Lotemax, Bausch + Lomb).
Loteprednol was administered QID for 2
weeks in this study, which enrolled 10 subjects (20 eyes) with Sjögren’s syndrome.
All measurements were taken in a controlled-environmental chamber, a 12- × 12-foot room in which the
temperature, humidity, and airflow could be controlled precisely. (Image courtesy of Ranjini Kottaiyan, OD, MBA)
parameters,” Dr. Kottaiyan added. “We comCYTOKINES
pared the objective measures to the presence
HARD TO DETECT
According to Dr. Kottaiyan, it appears all cy- of inflammatory mediators in the eye after
treatment.”
tokines are not easily detectAt baseline, Dr. Kottaiyan
able in all patients. For examand colleagues recorded clinical
ple, IL-17 was detected in 13%
A mild topical
characteristics, such as Schirmof patients in one study. TNFa
corticosteroid may be
er’s test results, tear break-up
was detected in only 2% of paeffective in treating
time, entrance and exit IOP, ostients in one study and 12% in
the symptoms of
molarity, and corneal staining.
another (LaFrance et al., Curr
Sjögren’s disease
They also used a customEye Res. 2008;33:525-544. doi:
without causing
built Shack-Hartmann wave10.1080/02713680802190085;
the adverse effects
front sensor, which measured
Enriquez-de-Salamanca et al.,
associated with
visual quality changes caused
Mol Vis. 2010;16:862-873.).
higher-dose steroids.
by aberrations in tear film dy“The goal of the study was
Findings from a pilot
namics, and a thermal camera
to evaluate tear cytokines bestudy also suggest
(Thermovision A40, FLIR Sysfore and after a treatment regithat ocular surface
tems) to assess ocular surface
men, and we chose people with
metrology is useful in
temperature.
Sjögren’s syndrome because they
evaluating the effects
All measurements were taken
have inflammatory mediators in
of the steroid.
in a controlled-environmental
their eyes,” Dr. Kottaiyan said.
chamber, a 12- × 12-foot room in
“The unique thing about this
which the temperature, humidstudy is that we utilized our ocular metrology in conjunction with tear analy- ity, and airflow could be controlled precisely.
The subjects were asked to present for 3
sis to noninvasively and objectively study tear
TAKE-HOME
weekly visits. After baseline measurements
were taken at the first visit, loteprednol was
administered, and then measurements were
taken again 30 minutes later with the wavefront sensor and thermal imaging to evaluate
the drug’s short-term effect. Tears were collected by two techniques, with and without
a saline wash.
“We found that with the saline wash, the
data was highly variable, and did not show
trends across the sampling time points,” Dr.
Kottaiyan said. “So we published data just from
native tear collection.”
TESTING CONDITIONS
The subjects were then directed to use the steroid QID for the remainder of the study. At the
first and second visits, patients were tested in
nominal environmental conditions in which
the temperature was about 75° F and relative
humidity 45%.
In the final visit, the subjects were tested as
soon as they arrived and again after spending
30 minutes under stressed environmental conditions (temperature 80° F, relative humidity 20%).
SEPTEMBER 15, 2016 :: Ophthalmology Times
clinical diagnosis
Changes in visual quality and ocular surface temperature were observed
throughout the study. During the first
visit, testing of the short-term effect
showed that 30 minutes after instillation of the steroid, the visual quality worsened and the average ocular
surface temperature increased.
This trend was not significant but
was indicative of reduced surface evaporation, Dr. Kottaiyan said. However,
long-term effects were more apparent.
“The ocular surface temperature
significantly increased at 2 weeks after
treatment (p = 0.02),” Dr. Kottaiyan
said. “This shows that this is a good
way to objectively measure how the
ocular surface responds.”
NORMAL, STRESSED
CONDITIONS
The researchers also compared the subjects based on their responses under
normal and stressed environmental
conditions.
“In the stressed environment, we
found that the ocular surface temperature increases but visual quality decreases,” Dr. Kottaiyan said.
The study also included Luminex
analysis of tear cytokines. Only 6 of 9
tear samples collected could be evaluated due to low tear-volume collection.
“We chose people with severe form
of dry eye, so it was very challenging
to collect tears from them,” Dr. Kottaiyan said.
The results showed that at least 6
cytokines were elevated in the study
population before treatment, and all of
them were reduced after loteprednol
treatment at 2 weeks. In at least 3 of
the 9 patients, all 6 of the cytokines
were reduced, while concentrations
of some, but not all cytokines, were
lower in other subjects.
This analysis could be considered a
pilot study that will help researchers
refine the technique for tear analysis.
The ocular surface metrology, using
the wavefront sensing, thermal imaging, combined cytokine analysis, is
equally important, Dr. Kottaiyan said.
“We can extend this technique to
a bigger study where we can study
cytokines in other types of dry eye
patients and perform ocular surface
metrology to study dry eye in other
Mark S. Humayun, MD, PhD,
elected as new president of ASRS
CHICAGO ::
MARK S. HUMAYUN, MD,
PhD, who recently received the National Medal of Technology and Innovation—the nation's highest honor for
technological achievement—has been
elected president of the American Society of Retina Specialists (ASRS) for
a 2-year term through August 2018.
Dr. Humayun is co-director of the
University of Southern California (USC)
Roski Eye Institute, director of the USC
Institute for Biomedical Therapeutics,
and is a professor with joint appointments in both USC’s Keck School of
Medicine and Viterbi School of Engineering. He is the only ophthalmologist
to be elected as a member of both U.S.
National Academies of Medicine and
Engineering, according to a prepared
statement. Over the years, he has served
in numerous ASRS leadership roles.
In his more than 25 years of research,
Dr. Humayun has secured over 100 patents and co-invented the Argus Series
retinal implants, the world’s first artificial retinal prostheses, manufactured
by Second Sight Medical Products. The
Argus technology, which has been in
commercial use in Europe since 2011,
gained FDA approval in the United
States in 2013 and is successfully restoring useful vision to patients who
suffer from certain blinding diseases,
such as retina pigmentosa.
ASRS is the largest retinal organization in the world, representing nearly
3,000 members across the United States,
District of Columbia, Puerto Rico, and
59 countries. ■
To read more about the latest
Argus 5-year safety results,
go to Page 49.
treatments to see how the disease progresses,” Dr. Kottaiyan
added. “We observed that thermal imaging and wavefrontsensing techniques were very
effective.” ■
RANJINI KOTTAIYAN, OD, MBA
E: Ranjini_Kottaiyan@
URMC.Rochester.edu
This article was adapted from Dr. Kottaiyan’s poster
presentation at the 2015 meeting of the Association for
Research in Vision and Ophthalmology. The researchers
received grant support from Bausch + Lomb and
Research to Prevent Blindness.
61
62
drug therapy
SEPTEMBER 15, 2016 :: Ophthalmology Times
Exploring oral anti-VEGF/PDGF
inhibitor for AMD therapy
Oral administration makes agent suitable for treating patients with bilateral disease
By Cheryl Guttman Krader; Reviewed by Nauman Chaudhry, MD
NE W LONDON, C T ::
phase II study investigating oral
X-82 (Tyrogenex) in patients with
Baseline
Month 1
Month 2
exudative age-related macular
degeneration (AMD) requiring
frequent anti-vascular endothelial growth factor (VEGF) therapy is under way after positive
results were achieved in a phase I study, said
Nauman Chaudhry, MD.
(FIGURE 1) The central subslice of SD-OCT images are shown for a naïve patient in the X-82 phase Ib study.
The main objective of the phase I study was
From left: at baseline, after 1 month of treatment, and after 2 months of treatment. Over the 2 months,
to evaluate the safety of X-82 and any dose-limvisual acuity had improved from 70 letters to 84 letters. (Images courtesy of Nauman Chaudhry, MD)
iting toxicity. The open-label,
ascending, repeat-dose study
enrolled 35 patients with exuPHASE I TRIAL
Of the 10 patients who did not complete 6
dative AMD. Six regimens were The phase I study enrolled 35 patients who months of treatment, 6 were withdrawn for
evaluated with doses ranging were treated for up to 6 months with one of six adverse event-related reasons, including transfrom 50 mg every other day regimens: 50 mg every other day, 50 mg daily, aminase elevations (n = 2), leg cramps (n =
to 300 mg daily.
100 mg every other day, 100 mg daily, 200 mg 2), and gastrointestinal symptoms (diarrhea
Dr. Chaudhry
Initially, only patients with daily, or 300 mg daily. Patients returned every or nausea/mild anorexia, n = 2).
heavily treated refractory disease were enrolled 4 weeks for assessment of BCVA and central
(patients unable to achieve a dry macula despite foveal thickness (CFT) measured by spectral
E X PA N DI NG R E SE A RCH
frequent anti-VEGF injections), but treatment- domain OCT. Patients were eligible for anti- The phase II study is a randomized, doublenaïve patients were eligible for participation VEGF rescue therapy if they had a 5-letter de- masked, comparative dose (50, 100, and 200
as the study progressed.
crease in BCVA or ≥50-μm increase in CFT.
mg daily) and placebo-controlled study. It is
During treatment lasting up
Twenty-five of the 35 enrolled enrolling previously treated patients who have
to 6 months, no dose-limiting
patients completed 6 months demonstrated the ability to achieve a reductoxicity was identified for X-82,
of treatment. BCVA was main- tion in CFT in response to anti-VEGF injection.
An oral anti-VEGF/
and the investigational agent
tained or improved in most paPatients must have wet AMD and received
PDGF inhibitor had
showed evidence of biological
tients and was improved in the at least two prior anti-VEGF injections at inno dose-limiting
activity based on functional and
majority of patients who com- tervals of not greater than 6 weeks. They will
toxicity and improved
anatomic endpoints.
pleted the study. Mean CFT was be followed monthly and be eligible to receive
visual acuity and OCT
Dr. Chaudhry, principal invesalso significantly reduced in pa- injections as needed.
findings in patients
tigator for the X-82 AMD studies
tients who completed the study,
The primary endpoint of the study is change
with exudative
and clinical assistant professor
with some patients achieving in visual acuity in X-82 patients compared with
age-related macular
of ophthalmology, Yale Univercomplete resolution of fluid.
placebo at 1 year. Secondary endpoints include
degeneration in a
sity, New Haven, CT, noted the
Of the 25 patients who com- number of anti-VEGF injections received durphase I study.
investigational tyrosine kinase
pleted the 6 months of treat- ing the first year of the study and anatomical
inhibitor has features that make
ment, 15 (60%) did not require changes on SD-OCT imaging. ■
it attractive for treating wet AMD.
any rescue anti-VEGF injections.
“X-82 blocks kinase activity associated with
“The proportion of patients in each dose coall receptor subtypes of VEGF and also platelet- hort who did not require any rescue injections
NAUMAN CHAUDHRY MD
derived growth factor (PDGF), which is impor- increased as the dose of X-82 increased,” said
E: [email protected]
tant because anti-VEGF effects are enhanced Dr. Chaudhry, who also is in private practice,
This article was adapted from Dr. Chaudhry’s presentation during Retina Subspecialty
by anti-PGDF activity,” he said. “Its oral route New London, CT. “None of the patients in the
Day at the 2015 meeting of the American Academy of Ophthalmology. He is principal
of administration makes X-82 suitable for treat- 300-mg daily dose group who completed the
investigator for the Tyrogenex AMD studies but has no other relevant financial interest
ing patients with bilateral disease.”
study required anti-VEGF injections.”
in the material.
A
TAKE-HOME
SEPTEMBER 15, 2016 :: Ophthalmology Times
drug therapy
Sustained-release implant is viable
alternative to anti-VEGFs for DME
Fluocinolone acetonide implant showed positive results for DME refractory to other treatments
By Lynda Charters; Reviewed by Usha Chakravarthy, MBBS
BEL FAS T, NOR T HERN IREL AND ::
ANALYSIS OF REAL-WORLD
interim data from patients treated with
fluocinolone acetonide intravitreal implant (Iluvien, Alimera Sciences), a sustained-release intravitreal implant and
the subject of a safety
trial in Europe, showed
that most patients with
chronic diabetic macular edema (DME) who
received the therapy
did not require mediDr. Chakravarthy
cation to reduce IOP.
Importantly, a substantial percentage of patients experienced sustained
gains in visual acuity over the course
of the study following one injection.
The implant, which contains 190
milligrams of the drug, was used in
patients with DME in the Iluvien Registry Safety Study (IRISS). At least twothirds of the patients had undergone
previous injections of anti-vascular endothelial growth factor (VEGF) agents
and a course of corticosteroids. The
implant releases fluocinolone acetone
over a period of 36 months.
The medication fills an important gap
in this patient population, according
to Usha Chakravarthy, MBBS, clinical
professor, School of Medicine, Dentistry and Biomedical Sciences, Centre
for Public Health, Queen’s University
of Belfast, Belfast, Northern Ireland,
and principal investigator of the IRISS.
In patients with DME refractory to
anti-VEGF medication, patients were
switched to the steroid implant when
it had been determined that their vision was decreasing and the macular
appearance was worsening.
“Following the switch, there were
improvements in visual acuity and
retinal morphology in the majority
of patients,” she said. “This finding
indicated that [the implant] is an important addition to our therapeutic
armamentarium.”
The IRISS is a 5-year post-authorization registry study required for
all markets in which the product is
sold: currently, the United Kingdom
(26 study sites), Germany (10 study
sites), and Portugal (1 study site). The
study examined the incidence of IOP
increases and their management after
patients were treated and evaluated
the status of their visual acuity.
The interim data available from 328
eyes of 292 patients had a mean age of
61.7 years and a mean IOP of 15.4 mm
Hg, Dr. Chakravarthy noted.
I O P E L E VA T I O N S
A ND M A NAGEMEN T
Fifty-four (18.4%) patients required
treatment to lower the IOP and two
(0.6%) patients needed surgery to control the IOP, she said.
More than three-quarters of the eyes
treated (77.4%, n = 255 eyes) did not
need additional treatments during the
period of the study. Of those who did
require additional therapies, laser was
applied in 5.2%, intravitreal injection
of an anti-VEGF drug in 16.8%, steroids in 4.0%, and an implant retreatment in 0.3%.
V ISUA L ACUIT Y EFFECTS
The mean change in visual acuity at
month 6 after implantation was a gain
of about 5 letters (from 50.9 to 55.7
letters), which was sustained up to 18
months after implantation of the device, Dr. Chakravarthy said. After this
time point, the mean gain in visual
acuity diminished, which was most
likely explained by the small number
of patients in this cohort who were followed for 21 months or longer, heavily
affecting the mean by loss of visual
acuity in three patients, according to
the study investigators.
At month 6, 15.9% of patients gained
Continues on page 64 : DME implant
63
64
SEPTEMBER 15, 2016 :: Ophthalmology Times
drug therapy
DME IMPLANT
( Continued from page 63 )
ment of Diabetic Retinopathy Study provements in a significant proportion of patients, some of whom were
(ETDRS) letters.
After implantation, the distribution able to resume driving. The vision imchanged with more patients having a vi- proved in 58% of patients 6 months
after implantation and
sual acuity between 69
61% at 1 year.
and 100 ETDRS letters.
The safety profile of
Most of the patients
A real-world
the drug was positive,
in this study had latesafety study of
with 81.6% of patients
stage DME. However,
fluocinolone
not requiring any meddespite this, 3 months
acetonide intravitreal
ications to control the
after implantation, 58%
implant in patients
IOP. The patients will
of patients had a gain in
with chronic DME
continue to be followed
visual acuity that was
(328 eyes from 292
for 3 more years.
sustained to month 21
patients) showed that
Another study, the
(57%) with a peak of
81.6% of patients did
ongoing MediSOFT
74% at month 15.
not require initiation
audit, is a post hoc
The percentage of
of IOP-lowering
chart review of elecpatients achieving the
therapy during the
tronic medical records
needed 6/12 (20/40)
study and 60% of
data systems used in 13
acuity for driving level
patients included in
study centers. Interim
vision increased from a
this registry study
data were extracted in
baseline of 18% to 34%
gained vision after
February 2016.
at M 12 representing a
injection that was
“The introduction of
16% rate of improvesustained over the
[the implant] has been
ment, the investigators
study period.
an important addition
reported.
to our therapeutic arThe results of the
mamentarium and in
interim analysis indicated the patients with long-term DME particular for managing DME that is
benefitted from the implant in a way persistent or insufficiently responsive
they did not from previous treatment to anti-VEGF therapies,” Dr. Chakrawith anti-VEGF drugs, other steroids, varthy concluded. ■
and laser application.
The results of the use of the device,
which was considered a last-line therUSHA CHAKRAVARTHY, MBBS
apy to be used in an attempt to save
E: [email protected]
or maintain vision in these patients,
Dr. Chakravarthy has no proprietary interest in any aspect of this
resulted in useful visual acuity imreport.
TAKE-HOME
15 letters of vision or more and
20.8% of patients gained 15 letters or more at month 12, the
investigators reported. Most patients had a visual acuity between 34 and 68 Early Treat-
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to a prepared statement.
RST-001 is a gene therapy application of optogenetics, a therapeutic
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RetroSense’s Investigational New
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to the company. ■
SEPTEMBER 15, 2016 :: Ophthalmology Times
technology
Handheld device offers early
screening of amblyopia
With high degree of accuracy, device can be used to screen nonverbal children in seconds
By Fred Gebhart; Reviewed by David G. Hunter, MD, PhD
BOS TON ::
here’s a new tool on the market for
amblyopia and strabismus screening of even very young children:
the Pediatric Vision Scanner (PVS),
which received FDA clearance this
year. The device offers pediatricians, school nurses, and other
health-care providers a screening method that
not only is easy to use, but also more reliable
than manual examination or photoscreening,
said co-developer David G. Hunter, MD, PhD.
Scanning with the handheld device is completed in 2.5 seconds, and independent clinical trials show that the accuracy is about 95%,
exceeding that of existing screening products,
said Dr. Hunter, who serves as ophthalmologist-in-chief at Boston Children’s Hospital and
co-founded the medical device start-up, REBIScan, in 2009 to commercialize the product
and other ocular scanning technology.
T
‘We want to get these
kids when they’re
preschoolers because
that’s when it’s easier
to treat the amblyopia.’
— David G. Hunter, MD, PhD
Developing the scanner and getting it into
the hands of users has taken more than 20
years. The effort to secure investor funding
and mass produce the device is an ongoing
challenge, Dr. Hunter said, but attaining FDA
marketing clearance was a crucial step.
The FDA approved the device via the de
novo pathway, meaning that there is no other
device with the same indication.
The portable, handheld device will reduce false referrals to eye-care professionals while improving
detection of disease and bringing children to care earlier, according to REBIScan.
“Even today, most pediatric practices use
manual methods of screening kids for vision
problems,” Dr. Hunter said. “That is, they
have them hold a cover over one eye and try
to read an eye chart across the room. While
that works okay for kids who are already in
school, it doesn’t work so well for preschoolers, and it doesn’t work at all for kids who
can’t yet read or talk.
“As a result, there are lots of kids who don’t get
any kind of efficient eye screening until school
age,” he said. “The problem is, we want to get
these kids when they’re preschoolers because
that’s when it’s easier to treat the amblyopia.”
Over the years, a number of photoscreeners or refractors have been developed to look
for amblyopia by checking for refractive error.
“The problem with those is that risk factors
aren’t the same as disease,” Dr. Hunter said.
“Only a small fraction of kids who have risk
factors for amblyopia actually need to have any
kind of treatment,” he said. “You end up referring a lot of kids who will never need treatment, and that’s not going to be an effective
screening program.”
Instead, Dr. Hunter and colleagues, including his mentor, David L. Guyton, MD, currently Zanvyl Krieger professor of pediatric
ophthalmology, Wilmer Eye Institute, Johns
Hopkins University School of Medicine, Baltimore, wanted to screen for strabismus since
most patients who have amblyopia also have
this companion condition.
Continues on page 66 : Screening
65
66
SEPTEMBER 15, 2016 :: Ophthalmology Times
technology
SCREENING
( Continued from page 65 )
Their idea was to scan the retina with
polarized light, examine the pattern of nerve
fibers emanating from the fovea, and use this
as a means of detecting fixation.
In the early 1990s, they built a scanner that
could reliably identify fixation of the eye, although the first model could only scan one
eye at a time.
The next steps were to condense the device to handheld dimensions, and then to
combine two scanners so both eyes could be
analyzed simultaneously. After many years
of refinement, the result was the recently approved product.
The current device works even better than
the developers hoped, Dr. Hunter said. “We
thought we were going to have to have two
steps: One, look for strabismus; and two, look
for risk factors. But it turns out that we were
able to completely dispense with the whole
risk factor piece because the [device] not only
detects strabismus but it detects amblyopia
as well.”
This feature will allow the device to be used
by eye-care professionals for early diagnosis
of amblyopia in preverbal children.
Interpreting results
is simple: If two lights
on top of the scanner
both turn green, then
child’s eyes are normal.
The portable, handheld device uses retinal birefringence scanning to detect amblyopia and strabismus
when they develop. (Images courtesy of David G. Hunter, MD, PhD)
TAKE-HOME
be more cost-effective in public
CLINICAL TRIALS
health campaigns than sending
Studies have tested the device
A new handheld
squads of nurses to schools,
on children as young as 2 years,
pediatric vision
clinics, or other sites to conthough outside of that formal
scanner can detect
duct vision screenings by more
setting it has been used to screen
amblyopia and
conventional methods.
infants. As long as a child can
strabismus with
Because the device is small,
sit still and look at the smiley>90% accuracy. The
easy to use, and accurate, it
face target inside the machine
device can be used
would be ideal for remote areas
for a few seconds, he or she can
to screen children
once a durable, battery-powered
be tested, Dr. Hunter explained.
too young to read
version is available, he said.
Interpreting results is simor recognize letters
Potentially, Dr. Hunter noted,
ple: If two lights on top of the
as well as those of
thousands of children could
scanner both turn green, then
school age since the
be scanned in a day by a team
child’s eyes are normal. Howonly requirements
using several scanners, and the
ever, a child’s eyes will change
are to sit still for
small percentage with apparent
during development, so annual
a few seconds and
problems—not just strabismus
screenings are recommended.
look at a smileyand amblyopia but cataracts,
“If the day could ever come
face target in the
tumors, and retinal abnormalwhere every pediatrician is
machine.
ities—could then be referred
scanning every child at the
for further evaluation. ■
well-child visit starting at age
2 with this device, considering
its accuracy, then we could eliminate severe
vision loss from amblyopia,” he said.
DAVID G. HUNTER, MD, PHD
This is a problem in both developed and
E: [email protected]
developing countries. Using the device would
Dr. Hunter is co-developer of the device.
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practice management
68
September 15, 2016 :: Ophthalmology Times
Is the world a better place
because of your practice?
Visionary leaders have ability to communicate values, ideas in way that connects
Let's Chat By donna suter
W
hen Martin Luther King
said, “I have a dream,”
he had a vision for people, not a program. Visionary leaders have
the ability to communicate values and ideas in
a way that connects. In your practice, they
bring certainty into the uncertain world of
reimbursement rates and rapid change.
What is your capacity to bring vision and
direction into times of uncertainty? If there
is one thing that sets a practice apart, it is
the leadership ability of the owner/physician/administrator. Any one of these positions may be where a truly visionary leader
is found. Why do people reluctantly comply
with one leader, while passionately following another to the end of the earth?
The answer lies in the focus of the individual. He or she has an uncanny ability to
infuse every employee with a clearly articulated vision of where the practice is going.
A visionary is a leader that sets the tone in
the workplace and insists that patients be
treated with respect, excellence, and has
revenue-generating ideas for the future.
Offices that have an “I can” attitude when
it comes to excellence in patient care and
collaborative teamwork are often ran by
leaders with vision. On a daily basis, the
emphasis is on quick, pleasant patient interactions and fast, accurate treatment.
The cultures of today’s practices are so diverse. How does a leader even know which
model to pick? And then it’s a question of
how to communicate it day after day to employees and eye-care practitioners alike.
Despite all of the images, signals, forecasts, alternatives, and hypothetical possibilities they must consider, the best leaders are
able to formulate a comprehensive goal based
on a myriad of influencing factors, and then
achieve it in a manner that supports the earning power and net worth of the practice.
Leadership can be developed. Sure, natural leaders excel quicker, but leadership can
magenta
cyan
yellow
black
and should be developed (or recruited) by
all practice owners.
Improve your leadership abilities by developing vision at these seven “focal points.”
1. For esight
This is the ability to judge how a leader's visions or goals will fit into his or her practice’s evolving mission and environment. A
positive process is dependent to a great extent on the quality of the leader’s dialogue
with his or her team. Employees must be
able to raise issues that may be sensitive
and to give and receive feedback.
Everyone in the practice should be clear
on the goals of the practice. Take time to
discuss department goals and individual tactics that support the practice’s overall goal.
2. hindsight
Leaders take their practice’s history and traditions into consideration, so their goals and
visions won’t contradict their practice culture. On one level, this means collecting the
data and producing metrics but not being so
busy crunching the numbers that employees
feel neglected.
The ongoing shortage of qualified workers means an ever-growing need to retain
the good ones. According to countless workforce polls, people connect and commit
themselves to a practice when they feel respected. They stay when they are fulfilling
their skills and when they find meaning in
their workday community.
A leader with clear hindsight knows the
importance of giving employee feedback. He
or she is a leader that allows the harsh cold
light of facts to illuminate performance and
highlight training needs.
3 . A wor ldv iew
This is essential when analyzing and interpreting new developments and trends. Look
outward so you can make the best decisions possible. A worldview means knowing which services will next be impacted
by third-party payers as well as the demographics of your community.
What is changing? Are you changing with
it? What are you doing about the changes
that you see? A visionary has a plan for the
worst possible outcomes.
How is your understanding of not just
marketing but advertising and public relations? Because it is new, there is a lot of
chatter about online marketing. Yes, controlling your online image is important, but so
is the impact the practice has on the community in which you practice.
4. insight
How good are you at looking within the
practice and using your insight to identify
internal conflict and facilitate communication and resolution? Dynamic practices encourage everyone to share what they learn
in the course of performing their jobs. This
often means visionaries listen more than
they talk at staff meetings.
One must be silent to truly listen. This
means silencing your thoughts, questions,
and preconceived notions to understand
what the other person is trying to say. Listening, almost by itself, can eliminate misunderstanding and give you greater insight.
5. depth perception
Leaders know how to keep things in perspective. They must view the entire picture
and see things in appropriate detail. Describing all the details for effectively managing your patient flow would fill several large
books. On a scale of 1 to 10, everything isn’t
a 10. The practice will not go broke if you
insist that all lanes are equipped with the
same instrumentation and drops. The doctor
isn’t going to die if the patient isn’t worked
up properly. The lead tech should not be
able to bully you into giving her a raise.
Make expectations about communication,
problem-solving, and conflict resolution part
of your new-employee orientation program.
Continues on page 70 : Visionary leader
ES839170_OT091516_068.pgs 09.13.2016 02:40
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70
SEPTEMBER 15, 2016 :: Ophthalmology Times
practice management
VISIONARY LEADER
( Continued from page 68 )
Depth perception also means seeing a
ringing phone and a complaining patient as
an opportunity rather than an annoyance.
Train and empower everyone with patient
contact to resolve conflict before it escalates.
And the ringing phone? The phone tree
should not be an excuse not to answer the
phone. Everyone with patient phone contact
should know how to schedule appointments.
6. PERIPHER AL VISION
Visionaries leaders must keep a watchful
eye on their competitors and stakeholders.
Be an active member in at least one professional organization and one local civic organization or charity.
When was the last time you paid someone
to mystery shop your competition? Reimburse a friend for an eye exam and complete
pair of eyewear from the private practice
that your former patients seem to prefer. The
insights you gain point the way toward staff
training and process improvement.
Stakeholders are there to help you. A conference is the perfect opportunity to build
stronger relationships. Spend at least a day
in the exhibit hall. Reach out to vendors to
schedule a time to view new products.
what you see. Does it increase your resolve to
improve your practice or are you depressed?
Proceed as if success is inevitable. Believe
in yourself and let other people see your
self-confidence. What needs your focused
attention? It could be financial, adverse
work hours, patient mix, or toxic internal
politics. Break the issues down to their component parts. Work with the doctors and senior staff to come up with an action plan
that puts you back on track. In just a matter
of months, you’ll enjoy the view! ■
7. R E V I S I O N
Leaders must be able to open-mindedly review and revise their goals, opinions, attitudes, and direction so they can act and
react in the most effective, efficient manner
possible.
How is your vision? Do you see clearly at
all seven focal points? Now that you are really looking at your practice, you may not like
To read more blogs from Donna and
others, visit OphthalmologyTimes.com/
Blogs.
DONNA SUTER
P: 423/400-3727
Donna Suter is president of Suter Consulting Group.
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Micro Medical Devices Inc.
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www.micromedinc.com
61
Omeros Corp.
www.omeros.com
19
Perrigo Pharmaceuticals
866/634-9120
www.perrigo.com
7
45
Rumex
727/535-9600
www.rumex.net
63
Shire Ophthalmic
800/828-2088
www.shire-eyes.com
38-39
P:
CV2, 3
Sun Pharmaceutical Industries Inc.
800/818-4555
www.sunpharma.com
25
TearLab Corp.
855/832-7522
www.tearlab.com
15
TTI Medical
800/322-7373
www.ttimedical.com
64
USC Roski Eye Institute
323/745-2223
www.usceye.org
51
P:
CVTIP,
47A-48A*
914/345-7400
www.regeneron.com
P:
Reichert Ophthalmic Instrument
888/849-8955
www.reichert.com
53
Retina World Congress
303/395-1782
www.retinaworldcongress.org
67
P:
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Rhein Medical
P: 727/209-2244
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P:
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800/931-2230
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SEPTEMBER 15, 2016 :: Ophthalmology Times
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IN DISPENSABLE
73
( In Brief )
Wearable technology
USC, VSP TAKES DIGITAL
HEALTH TO EYEGLASSES
Making rebates
work for patients,
practice
In age of online retailing, strategy can boost compliance
with contact lens wear, improve clinical care
Getty Images/Peathegee Inc.; Video courtesy of USC CBC
By Charissa D. Young, OD
evenue lost from patients
not purchasing their contact lenses at the practice
also relates to revenue lost
from missed annual exams.
In a study of 151 college
students,1 23% reported
having ordered contact lenses online rather
than purchasing from their eyecare professional (ECP).
Of those surveyed who exclusively bought
contact lenses online, 24% admitted to not
having regular annual eye exams (the survey was conducted in a state with contact
lens prescriptions limited to 1 year), and
the same number of people acknowledged
ordering contact lenses online with an expired prescription.
Using manufacturer rebates to promote
in-office purchases not only helps patients’
R
bottom line, but also (most importantly)
their long-term eye health.
In a review of major contact lens manufacturer rebates, I found patient savings as
high as $130 for an annual supply. Offsetting the sticker shock of a contact lens supply
order by informing patients of rebates can
encourage them not only to support business
but also can foster lens wear compliance.
A 2013 study showed patients who purchased contact lenses from their ECP returned for annual eye examinations sooner
than those who did not by almost 2 months
(466 versus 522 days).2 Unsurprisingly, those
who did not buy contact lenses from their
ECP not only took longer to return for annual appointments, but also were less compliant following the manufacturer’s recommended replacement frequency.
Continues on page 74 : Compliance
LOS ANGEL ES :: THE UNIVERSITY of Southern California (USC) Center for Body Computing (CBC) has teamed with VSP Global’s innovation lab, The Shop, and the USC Roski Eye
Institute to take wearable health to the eyes.
A pilot study, which kicked off last month at
USC, will assess users’ engagement with and
feedback of the smartphone app synched to
the embedded sensor in a prototype optical
frame (Level, The Shop).
The study of USC employee daily eyeglass
wearers has participants tracking steps, calories burned, distance traveled, and activity
time. Biometrics are tracked by technology
embedded in the temple of the frame—including an accelerometer, a magnetometer and a
gyroscope—and synched wirelessly via Bluetooth to an accompanying smartphone app.
USC Roski Eye Institute is the optometric
care partner in the study having its ophthalmologists and optometrists at its USC clinics
on the school’s main campus and health sciences campus perform the eye exams and ensure accurate prescriptions for the participants.
“We’re thrilled to be partnering with [VSP] to
maximize the wearable sensor in eyeglasses
by engaging wearers in improved health fueled
by philanthropic endeavors,” said Leslie Saxon,
MD, founder and executive director, USC Center for Body Computing.
“Offering our patients digital health tools
and wearable technology in our eye clinics is
the wave of the future,” said Rohit Varma, MD,
MPH, interim dean, USC Keck School of Medicine, and director, USC Roski Eye Institute. “As
one of the key medical partners in the USC
CBC’s Virtual Care Clinic, we’re proud to be at
the forefront of digital health innovation.” ■
VIDEO For more about the pilot study,
go to OphthalmologyTimes.com/SensorGlasses
74
SEPTEMBER 15, 2016 :: Ophthalmology Times
indispensable
COMPLIANCE
( Continued from page 73 )
Some 75% of subjects reported wearing contact
lenses every day, but only 43% purchased the suggested annual supply. If ECPs can provide a seamless transition from exam chair to order at the same
visit, it truly is in patients’ best interest.
BR EAK OUT R EBATE SHEETS
Rebate tear sheets overview the discount based
on boxes bought as well as a time-sensitive offer
code. Patients typically need to register the code
on the manufacturer’s website with their information and mail the manufacturer the original
eye exam receipt, original contact lens purchase
receipt, and original UPC codes from the contact
lens boxes once they’ve received them. Patients
usually receive rebates in the form of a prepaid
gift card within 60 days of receipt of materials.
In an age of competing with online contact lens
retailers, rebates can make a practice shine by
highlighting personalized service. I’ve worked
at a private practice that addressed, stamped,
and included in the envelope a copy of the contact lens purchase receipt for patients as an amenity they hadn’t experienced at any other office.
Free shipping regardless of order amount should
always be available. Also offer free replacements,
within reason, for any ripped or defective lenses.
At checkout, staff should lead with annual
supply information to support the ECP’s recommendation and will be backed up with the best
rebates, which usually are for annual supplies.
I recommend having staff explain how unilateral pricing policies work or offer to pricematch competitors if patients are wary to order
at checkout, which gives patients little reason to
spend their dollars for contact lenses outside the
practice. And speaking of competition, most rebates cannot be used at big box stores. Save patients an extra trip with in-practice purchases.
MISSED OPPORTUNITY
If you are not offering manufacturer rebates for
contact lens orders, why not? Rebates support patients purchasing annual lens supplies from their
ECP, and we know patients who not only purchase their lenses (as well as an annual supply)
from the practice see their ECPs more regularly
and are at less risk of overwear and associated
side effects. Let’s end the noncompliance cycle
and break out the rebate sheets. ■
EDITOR’S NOTE: The full text of this
article originally appeared in sister
publication, Optometry Times.
OptometryTimes.com/Rebates
References
1. Fogel J, Zidile C. Contact lenses purchased over the
Internet place individuals potentially at risk for harmful
eye care practices. Optometry. 2008;79:23-35.
2. Dumbleton K, Richter D, Bergenske P, Jones
LW. Compliance with lens replacement and the
interval between eye examinations. Optom Vis Sci.
2013;90:351-358.
CHARISSA D. YOUNG, OD, is interested in dry eye and
specialty contact lenses. As the current anterior segment fellow at
Specialty Eyecare Group, Seattle, she is involved in active research,
particularly in the areas of meibomian gland dysfunction and
ocular surface inflammation. She can be reached [email protected]
of time may be at increased risk for corneal adverse
events which may become sight threatening. Topical
NSAIDs should be used with caution in these patients.
Post marketing experience with topical NSAIDs also
suggests that use more than 1 day prior to surgery or
use beyond 14 days post-surgery may increase patient
risk and severity of corneal adverse events.
Nursing Mothers
ILEVRO® Suspension is excreted in the milk of lactating
rats. It is not known whether this drug is excreted
in human milk. Because many drugs are excreted in
human milk, caution should be exercised when ILEVRO®
Suspension is administered to a nursing woman.
Pediatric Use
Contact Lens Wear
ILEVRO® Suspension should not be administered while
using contact lenses.
BRIEF SUMMARY OF PRESCRIBING INFORMATION
INDICATIONS AND USAGE
ILEVRO® (nepafenac ophthalmic suspension) 0.3% is
associated with cataract surgery.
DOSAGE AND ADMINISTRATION
Recommended Dosing
One drop of ILEVRO® Suspension should be applied to
to cataract surgery, continued on the day of surgery
period. An additional drop should be administered 30
to 120 minutes prior to surgery.
Use with Other Topical Ophthalmic Medications
ILEVRO® Suspension may be administered in
conjunction with other topical ophthalmic
medications such as beta-blockers, carbonic
anhydrase inhibitors, alpha-agonists, cycloplegics,
and mydriatics. If more than one topical ophthalmic
medication is being used, the medicines must be
administered at least 5 minutes apart.
CONTRAINDICATIONS
ILEVRO® Suspension is contraindicated in patients with
previously demonstrated hypersensitivity to any of the
ingredients in the formula or to other NSAIDs.
WARNINGS AND PRECAUTIONS
Increased Bleeding Time
including ILEVRO® Suspension, there exists the
potential for increased bleeding time due to
interference with thrombocyte aggregation. There
have been reports that ocularly applied nonsteroidal
of ocular tissues (including hyphemas) in conjunction
with ocular surgery. It is recommended that ILEVRO®
Suspension be used with caution in patients with
known bleeding tendencies or who are receiving other
medications which may prolong bleeding time.
Delayed Healing
including ILEVRO® Suspension, may slow or delay
healing. Topical corticosteroids are also known to slow
or delay healing. Concomitant use of topical NSAIDs
and topical steroids may increase the potential for
healing problems.
Use of topical NSAIDs may result in keratitis. In
some susceptible patients, continued use of topical
NSAIDs may result in epithelial breakdown, corneal
thinning, corneal erosion, corneal ulceration or corneal
perforation. These events may be sight threatening.
Patients with evidence of corneal epithelial breakdown
should immediately discontinue use of topical
NSAIDs including ILEVRO® Suspension and should be
closely monitored for corneal health. Post marketing
experience with topical NSAIDs suggests that patients
with complicated ocular surgeries, corneal denervation,
corneal epithelial defects, diabetes mellitus, ocular
surface diseases (e.g., dry eye syndrome), rheumatoid
arthritis, or repeat ocular surgeries within a short period
ADVERSE REACTIONS
Because clinical studies are conducted under widely
varying conditions, adverse reaction rates observed
in the clinical studies of a drug cannot be directly
compared to the rates in the clinical studies of another
Serious and Otherwise Important Adverse Reactions
The following adverse reactions are discussed in greater
detail in other sections of labeling:
>
94)45Time (Warnings and Precautions)
>+=4,5(Warnings and Precautions)
Ocular Adverse Reactions
The most frequently reported ocular adverse reactions
following cataract surgery were capsular opacity,
decreased visual acuity, foreign body sensation,
increased intraocular pressure, and sticky sensation.
These reactions occurred in approximately 5 to 10%
of patients.
Other ocular adverse reactions occurring at an
incidence of approximately 1 to 5% included
conjunctival edema, corneal edema, dry eye, lid
margin crusting, ocular discomfort, ocular hyperemia,
ocular pain, ocular pruritus, photophobia, tearing and
vitreous detachment.
Some of these reactions may be the consequence of the
cataract surgical procedure.
Non-Ocular Adverse Reactions
Non-ocular adverse reactions reported at an incidence
of 1 to 4% included headache, hypertension, nausea/
vomiting, and sinusitis.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C: Reproduction studies
performed with nepafenac in rabbits and rats at oral
doses up to 10 mg/kg/day have revealed no evidence of
teratogenicity due to nepafenac, despite the induction
of maternal toxicity. At this dose, the animal plasma
exposure to nepafenac and amfenac was approximately
70 and 630 times human plasma exposure at the
recommended human topical ophthalmic dose for
rats and 20 and 180 times human plasma exposure
for rabbits, respectively. In rats, maternally toxic doses
≥10 mg/kg were associated with dystocia, increased
postimplantation loss, reduced fetal weights and
growth, and reduced fetal survival.
Nepafenac has been shown to cross the placental
barrier in rats. There are no adequate and wellcontrolled studies in pregnant women. Because animal
reproduction studies are not always predictive of
human response, ILEVRO® Suspension should be used
pediatric patients below the age of 10 years have not
been established.
Geriatric Use
been observed between elderly and younger patients.
NONCLINICAL TOXICOLOGY Carcinogenesis,
Mutagenesis, Impairment of Fertility
Nepafenac has not been evaluated in long-term
carcinogenicity studies. Increased chromosomal
aberrations were observed in Chinese hamster ovary
cells exposed JOWJUSP to nepafenac suspension.
Nepafenac was not mutagenic in the Ames assay or
in the mouse lymphoma forward mutation assay. Oral
doses up to 5,000 mg/kg did not result in an increase
in the formation of micronucleated polychromatic
erythrocytes JOWJWP in the mouse micronucleus assay
in the bone marrow of mice. Nepafenac did not
impair fertility when administered orally to male and
female rats at 3 mg/kg.
PATIENT COUNSELING INFORMATION
Slow or Delayed Healing
Patients should be informed of the possibility that slow
or delayed healing may occur while using nonsteroidal
Avoiding Contamination of the Product
Patients should be instructed to avoid allowing the
tip of the dispensing container to contact the eye or
surrounding structures because this could cause the tip
to become contaminated by common bacteria known
to cause ocular infections. Serious damage to the eye
and subsequent loss of vision may result from using
contaminated solutions.
Use of the same bottle for both eyes is not
recommended with topical eye drops that are used in
association with surgery.
Contact Lens Wear
ILEVRO® Suspension should not be administered while
wearing contact lens.
Intercurrent Ocular Conditions
Patients should be advised that if they develop an
intercurrent ocular condition (e.g., trauma, or infection)
or have ocular surgery, they should immediately seek
their physician’s advice concerning the continued use
of the multi-dose container.
Concomitant Topical Ocular Therapy
If more than one topical ophthalmic medication is
being used, the medicines must be administered at
least 5 minutes apart.
Shake Well Before Use
Patients should be instructed to shake well before
each use.
Released: February 2014
the potential risk to the fetus.
U.S. Patent Nos. 5,475,034; 6,403,609; and 7,169,767.
©2016 Novartis 2/16 US-ILV-16-E-0334
biosynthesis inhibiting drugs on the fetal cardiovascular
system (closure of the ductus arteriosus), the use of
ILEVRO® Suspension during late pregnancy should
be avoided.
WHEN TREATING INFLAMMATION AND PAIN
IN YOUR CATARACT SURGERY PATIENTS
#
POTENCY, PRECISELY
WHERE YOU NEED IT
1
Prescribed
Branded
Ophthalmic
NSAID1
ILEVRO® Suspension offers proven efficacy,
once-daily postoperative dosing, and
affordable access for your patients2-4
INFLAMMATION
C O M P L E T E LY
CLEARED IN
O C U L A R PA I N
C O M P L E T E LY
R E S O LV E D I N
2 OUT OF 3
>80%
PATIENTS AT
OF PATIENTS AT
2,3 †
3†‡
DAY14
*
• ILEVRO® Suspension should be applied to
the affected eye one-time-daily beginning
1 day prior to cataract surgery, continued
on the day of surgery and through the first
2 weeks of the postoperative period. An
additional drop should be administered
30 to 120 minutes prior to surgery3
POSTOPERATIVE • Use of ILEVRO® Suspension more than 1
day prior to surgery or use beyond 14 days
D O S I N G post-surgery may increase patient risk and
R E G I M E N3 severity of corneal adverse events3
1x
DAILY
DAY 14
B R O A D
COVERAG E 4
ELIGIBLE COMMERCIAL
PAT I E N T S M AY PAY
AS LITTLE AS
$35
OUT OF POCKET§
To learn more about treating postoperative inflammation and
pain with ILEVRO® Suspension, visit myalcon.com/ilevro
INDICATIONS AND USAGE
ILEVRO® (nepafenac ophthalmic suspension) 0.3% is a nonsteroidal,
anti-inflammatory prodrug indicated for the treatment of pain and
inflammation associated with cataract surgery.
Dosage and Administration
One drop of ILEVRO® Suspension should be applied to the affected
eye one-time-daily beginning 1 day prior to cataract surgery,
continued on the day of surgery and through the first 2 weeks of
the postoperative period. An additional drop should be administered
30 to 120 minutes prior to surgery.
IMPORTANT SAFETY INFORMATION
Contraindications
ILEVRO® Suspension is contraindicated in patients with previously
demonstrated hypersensitivity to any of the ingredients in the
formula or to other NSAIDs.
Warnings and Precautions
• Increased Bleeding Time – With some nonsteroidal antiinflammatory drugs including ILEVRO® Suspension there exists
the potential for increased bleeding time. Ocularly applied
nonsteroidal anti-inflammatory drugs may cause increased
bleeding of ocular tissues (including hyphema) in conjunction
with ocular surgery.
• Delayed Healing – Topical nonsteroidal anti-inflammatory drugs
(NSAIDs) including ILEVRO® Suspension may slow or delay
healing. Concomitant use of topical NSAIDs and topical steroids
may increase the potential for healing problems.
• Corneal Effects – Use of topical NSAIDs may result in keratitis.
In some patients, continued use of topical NSAIDs may result
in epithelial breakdown, corneal thinning, corneal erosion,
corneal ulceration or corneal perforation. These events may be
sight threatening. Patients with evidence of corneal epithelial
breakdown should immediately discontinue use.
Patients with complicated ocular surgeries, corneal denervation,
corneal epithelial defects, diabetes mellitus, ocular surface
© 2016 Novartis 04/16 US-ILV-16-E-0586
diseases (e.g., dry eye syndrome), rheumatoid arthritis, or
repeat ocular surgeries within a short period of time may be at
increased risk for corneal adverse events which may become
sight threatening. Topical NSAIDs should be used with caution
in these patients.
Use more than 1 day prior to surgery or use beyond 14 days
post-surgery may increase patient risk and severity of corneal
adverse events.
• Contact Lens Wear – ILEVRO® Suspension should not be
administered while using contact lenses.
Adverse Reactions
The most frequently reported ocular adverse reactions following
cataract surgery occurring in approximately 5 to 10% of patients
were capsular opacity, decreased visual acuity, foreign body
sensation, increased intraocular pressure, and sticky sensation.
For additional information about ILEVRO® Suspension, please refer
to the brief summary of prescribing information on adjacent page.
*With ILEVRO® Suspension versus 24% to 32% with vehicle; P<0.05.3
Results from 2 randomized, multicenter, controlled, double-masked trials of adult patients
undergoing cataract extraction. In Study 1, patients were randomized to receive either ILEVRO®
Suspension (n=851), NEVANAC® Suspension (n=845), ILEVRO® Suspension vehicle (n=211), or
NEVANAC® Suspension vehicle (n=213). In Study 2, patients were randomized to receive either
ILEVRO® Suspension (n=540) or ILEVRO® Suspension vehicle (n=268).2,3
‡
84% to 86% with ILEVRO® Suspension versus 38% to 46% with vehicle; P<0.05.3
§
This offer is not valid for patients who are enrolled in Medicare Part D, Medicaid, Medigap,
VA, DOD, Tricare, or any other government-run or government-sponsored health care
program with a pharmacy benefit. Additional eligibility terms apply. See copay savings
material for specific details.
†
References: 1. IMS Health Xponent, January 2015-December 2015. Accessed December 2015.
2. Data on file. 3. Ilevro [package insert]. Fort Worth, TX: Alcon Laboratories, Inc; 2014. 4. Fingertip
Formulary, October 2015 (estimate derived from information used under license from Fingertip
Formulary, LLC, which expressly reserves all rights, including rights of copying, distribution and
republication).
®
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INDICATIONS FOR USEdŚĞdE/^^LJŵĨŽŶLJdžƚĞŶĚĞĚZĂŶŐĞŽĨsŝƐŝŽŶ/K>DŽĚĞůyZϬϬŝƐŝŶĚŝĐĂƚĞĚĨŽƌƉƌŝŵĂƌLJŝŵƉůĂŶƚĂƟŽŶĨŽƌƚŚĞǀŝƐƵĂůĐŽƌƌĞĐƟŽŶŽĨ
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ŝŶũĞĐƟŽŶƐĨŽƌĐLJƐƚŽŝĚŵĂĐƵůĂƌĞĚĞŵĂĂŶĚĞŶĚŽƉŚƚŚĂůŵŝƟƐϮĞLJĞƐϬϳйAEŽůĞŶƐ"ƌĞůĂƚĞĚĂĚǀĞƌƐĞĞǀĞŶƚƐŽĐĐƵƌƌĞĚĚƵƌŝŶŐƚŚĞƚƌŝĂůATTENTION Reference
ƚŚĞŝƌĞĐƟŽŶƐĨŽƌhƐĞĨŽƌĂĐŽŵƉůĞƚĞůŝƐƟŶŐŽĨ/ŶĚŝĐĂƟŽŶƐĂŶĚ/ŵƉŽƌƚĂŶƚ^ĂĨĞƚLJ/ŶĨŽƌŵĂƟŽŶ
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ΞϮϬϭϲďďŽƩDĞĚŝĐĂůKƉƟĐƐ/ŶĐOǁǁǁďďŽƩDĞĚŝĐĂůKƉƟĐƐĐŽŵOWWϮϬϭϲdϭϭϰϲ