Download Take second look at - ModernMedicine.com

CUTTING-EDGE ADVANCEMENTS
CLINICAL DIAGNOSIS
OphthalmologyTimes.com
FOLLOW US ONLINE:
Drug Therapy
RETINAL GENE
THERAPY ENTERING
CLINICAL REALITY
SURGERY
April 15, 2015 VOL. 40, NO. 7
DRUG THERAPY
Take second look at
Endophthalmitis
Surgeons’ ability to reduce its rate, understand
risk factors grows as population at risk expands
IN VIEW:
Hypoyon in the eye
of a patient with
acute bacterial
endophthalmitis
complicating
cataract extraction.
ALACHUA, FL :: MANY DISEASES have
a genetic aspect whereby a mutated
gene is passed down from generation
to generation. Mutated genes may encode abnormal proteins or disable the
production of a protein completely, either of which can cause disease. Gene
therapy introduces a functional copy of
the gene into a patient’s own cells. By
correcting the underlying genetic defect that causes disease, gene therapy
can potentially provide lifelong clinical
benefits after a single administration,
according to Jeffrey D. Chulay, MD.
(Image courtesy of
Peter J. McDonnell, MD)
( See story on page 23 : Gene therapy )
Clinical Diagnosis
WHY CONTRAST
SENSITIVITY IS MORE
THAN VISION METRIC
CONTRAST sensitivity is a more valuable metric than many ophthalmologists
realize, with applications in preoperative and postoperative management of
corneal and refractive surgery patients
and routine screening of patients’ quality of vision. Contrast sensitivity has
perhaps been underused in ophthalmology practices despite the wealth
of data on its application in various
procedures, according to Gregory J.
Pamel, MD, and Prof. Dan Reinstein,
MD, FRCSC.
( See story on page 56 : Contrast )
By Stephanie Skernivitz;
Reviewed by Oliver D. Schein, MD, MPH
by 2020 and almost triple by 2030,” he said. “You’ll
be busy—you may not be paid for it, but you will
be busy taking care of patients with cataracts.”
BALT IMORE ::
IN THE UNITED STATES, the moderately
rare condition endophthalmitis impacts 1 case per
1,100 cataract surgeries.
The question may surface: Why should physicians care with a rate that is so low?
“For one, the population at risk is expanding,”
explained Oliver D. Schein, MD, MPH, Grossman
Professor of Ophthalmology, vice chairman for quality and safety, Wilmer Eye Institute, Johns Hopkins
University School of Medicine, Baltimore.
With several risk factors—though many are not
modifiable—there are strategies to counter the risk
factors that really make a difference, Dr. Schein said.
“If you apply the current cataract surgical rate
to the projected age distribution of our population,
the number of cataract surgeries will at least double
WHAT HAS CHANGED?
The disease itself has not changed in any way, but
ophthalmologists’ ability to reduce its rate and understand its risk factors has grown substantially,
Dr. Schein noted.
He addressed acute endophthalmitis that occurs
within the first week or so of cataract surgery. Virtually all (95% plus), according to Dr. Schein, are
gram positive.
“We either let these organisms in during surgery or
they get in [during] the first 12 to 24 hours,” he said.
The rate of the condition has varied according
to results of various studies in Europe and the
United States, including trials from Denmark and
the Netherlands.
( Continues on page 34 : Second look )
CUTTING-EDGE ADVANCEMENTS
CLINICAL DIAGNOSIS
OphthalmologyTimes.com
FOLLOW US ONLINE:
Drug Therapy
RETINAL GENE
THERAPY ENTERING
CLINICAL REALITY
SURGERY
April 15, 2015 VOL. 40, NO. 7
DRUG THERAPY
Take second look at
Endophthalmitis
Surgeons’ ability to reduce its rate, understand
risk factors grows as population at risk expands
IN VIEW:
Hypoyon in the eye
of a patient with
acute bacterial
endophthalmitis
complicating
cataract extraction.
ALACHUA, FL :: MANY DISEASES have
a genetic aspect whereby a mutated
gene is passed down from generation
to generation. Mutated genes may encode abnormal proteins or disable the
production of a protein completely, either of which can cause disease. Gene
therapy introduces a functional copy of
the gene into a patient’s own cells. By
correcting the underlying genetic defect that causes disease, gene therapy
can potentially provide lifelong clinical
benefits after a single administration,
according to Jeffrey D. Chulay, MD.
(Image courtesy of
Peter J. McDonnell, MD)
( See story on page 23 : Gene therapy )
Clinical Diagnosis
WHY CONTRAST
SENSITIVITY IS MORE
THAN VISION METRIC
CONTRAST sensitivity is a more valuable metric than many ophthalmologists
realize, with applications in preoperative and postoperative management of
corneal and refractive surgery patients
and routine screening of patients’ quality of vision. Contrast sensitivity has
perhaps been underused in ophthalmology practices despite the wealth
of data on its application in various
procedures, according to Gregory J.
Pamel, MD, and Prof. Dan Reinstein,
MD, FRCSC.
( See story on page 56 : Contrast )
By Stephanie Skernivitz;
Reviewed by Oliver D. Schein, MD, MPH
by 2020 and almost triple by 2030,” he said. “You’ll
be busy—you may not be paid for it, but you will
be busy taking care of patients with cataracts.”
BALT IMORE ::
IN THE UNITED STATES, the moderately
rare condition endophthalmitis impacts 1 case per
1,100 cataract surgeries.
The question may surface: Why should physicians care with a rate that is so low?
“For one, the population at risk is expanding,”
explained Oliver D. Schein, MD, MPH, Grossman
Professor of Ophthalmology, vice chairman for quality and safety, Wilmer Eye Institute, Johns Hopkins
University School of Medicine, Baltimore.
With several risk factors—though many are not
modifiable—there are strategies to counter the risk
factors that really make a difference, Dr. Schein said.
“If you apply the current cataract surgical rate
to the projected age distribution of our population,
the number of cataract surgeries will at least double
WHAT HAS CHANGED?
The disease itself has not changed in any way, but
ophthalmologists’ ability to reduce its rate and understand its risk factors has grown substantially,
Dr. Schein noted.
He addressed acute endophthalmitis that occurs
within the first week or so of cataract surgery. Virtually all (95% plus), according to Dr. Schein, are
gram positive.
“We either let these organisms in during surgery or
they get in [during] the first 12 to 24 hours,” he said.
The rate of the condition has varied according
to results of various studies in Europe and the
United States, including trials from Denmark and
the Netherlands.
( Continues on page 34 : Second look )
FDA APPROVED
IS THE TIME TO PREVENT INTRAOPERATIVE MIOSIS
AND REDUCE POSTOPERATIVE OCULAR PAIN
OMIDRIA™ (phenylephrine and ketorolac injection) 1% / 0.3%
is the first and only FDA-approved treatment that both1:
Preemptively inhibits intraoperative miosis
Decreases postoperative ocular pain for 10 to 12 hours
Easy to integrate into routine operating procedures
Add preoperatively to irrigation solution
One 4-mL single-patient-use vial to 500 mL1
Can be added to irrigation solution in the surgical suite
No other preparation required
INDICATIONS AND USAGE
OMIDRIA is added to ophthalmic irrigation solution used during
cataract surgery or intraocular lens replacement and is indicated
for maintaining pupil size by preventing intraoperative miosis and
reducing postoperative ocular pain.
OMIDRIA™ IS NOW AVAILABLE TO ORDER
NDC#: 62225-600-04
Unit quantity: One (1) carton contains four (4) single-patient-use vials
OMIDRIA is reimbursed by CMS
For ordering information or for live reimbursement support for OMIDRIA,
contact 1-844-OMEROS1 (1-844-663-7671), or visit www.omidria.com.
IMPORTANT SAFETY INFORMATION
OMIDRIA must be added to irrigation 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 non-steroidal
anti-inflammatories (NSAIDs), or have a past medical history of asthma.
The most commonly reported adverse reactions at 2-24% are eye irritation,
posterior capsule opacification, increased intraocular pressure, and anterior
chamber inflammation.
Use of OMIDRIA in children has not been established.
Please see the Full Prescribing Information for OMIDRIA
at www.omidria.com/prescribinginformation.
You are encouraged to report Suspected Adverse Reactions to
the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Reference: 1. OMIDRIA [package insert]. Seattle, WA: Omeros Corporation; 2014.
Omeros® and the Omeros logo® are registered trademarks, and Omidria™ and the Omidria logo™
are trademarks, of Omeros Corporation. © Omeros Corporation 2015, all rights reserved. 2015-062
4
APRIL 15, 2015
contents
8
62
36
52
Meeting Preview
Clinical Diagnosis
Practice Management
8 ARVO 2015 MAKING
POWERFUL CONNECTIONS
58 YIN-YANG OF OPIOID GROWTH
REGULATORY SYSTEM
78 MOVING EHR BEYOND
CLINICAL PRACTICE
New Saturday session focuses on vision,
traumatic brain injury in veterans and
athletes
In Every Issue
6 EDITORIAL
What’s Trending
See what the ophthalmic community is
reading on OphthalmologyTimes.com
1
In defense of Sen. Rand Paul
http://bit.ly/1GNrpfv
2 A cautionary surgical tale
http://bit.ly/186lEKD
Gene therapy link shows promise
for epithelial wound healing, corneal
sensitivity, dry eye
66 FOCAL POINT
Digital App
Vendors cater to needs of ASC
with software that increases efficiency,
quality of care, profits
75 MARKETPLACE
Video
Introducing the
Ophthalmology Times
app for iPad and
iPhone. Download
it for free today at
OphthalmologyTimes.
com/OTapp.
3 When a doctor is at the center
of a political scandal
http://bit.ly/1C4BEuT
4 Managing the dissatisfied
multifocal IOL patient
http://bit.ly/18y0wNP
eReport
Sign up for
Ophthalmology
Times’ weekly
eReport at http://
bit.ly/XjksXX.
To watch a phacotrabeculectomy surgical
video, go to http://bit.ly/1rOQAED
(Video courtesy of Ronald L. Fellman, MD)
Facebook
Like Ophthalmology Times at
Facebook.com/OphthalmologyTimes
CATARACT
SURGERY
SO POWERFUL
IT CAN EVEN
HELP YOU
SEE THE
FUTURE
Visit Us
At Booth #
2622
LENS EXTRACTION
CATALYS® PRECISION LASER SYSTEM & WHITESTAR SIGNATURE® SYSTEM
It’s tough to make capital investments in the middle of a technology evolution. How do you choose the
platform that prepares you for the future of cataract surgery? Consider this: the CATALYS® Precision
Laser System offers precise incisions and complete cataract segmentation and softening.1 The
WHITESTAR SIGNATURE® Phacoemulsification System provides switch-on-the-fly transition
between peristaltic and venturi pump modalities, for true low-energy lens extraction.2 Let the future
come; you’ll be ready.
Plan your future in lens extraction at
ExtractTheFuture.com
INDICATIONS AND IMPORTANT SAFETY INFORMATION for the CATALYS® Precision Laser System and WHITESTAR SIGNATURE® System
Reference the labeling for a complete listing of Indications and Important Safety Information.
CAUTION: Federal law restricts these devices to sale by or on order of a physician.
CATALYS® Precision Laser System
INDICATIONS: The CATALYS® System is indicated for use in patients undergoing cataract surgery for removal of the crystalline lens. Intended uses in cataract surgery include anterior
capsulotomy, phacofragmentation, and the creation of single-plane and multi-plane arc cuts/incisions in the cornea, each of which may be performed either individually or
consecutively during the same procedure. CONTRAINDICATIONS: Should not be used in patients with corneal ring and/or inlay implants, severe corneal opacities, corneal
abnormalities, significant corneal edema or diminished aqueous clarity that obscures OCT imaging of the anterior lens capsule, patients younger than 22 years of age, descemetocele
with impending corneal rupture, and any contraindications to cataract surgery. ADVERSE EFFECTS: Complications include mild Petechiae and subconjunctival hemorrhage due to
vacuum pressure of the LIQUID OPTICS Interface suction ring. Potential complications and adverse events include those generally associated with the performance of capsulotomy and
lens fragmentation, or creation of a partial-thickness or full-thickness cut or incision of the cornea. CAUTION: Should be used
only by qualified physicians who have extensive knowledge of the use of this device and have been trained and certified by
Abbott Medical Optics/OptiMedica.
WHITESTAR SIGNATURE® System
INDICATIONS: The WHITESTAR SIGNATURE® System incorporating FUSION® Fluidics is a modular ophthalmic microsurgical
system that facilitates anterior segment (cataract) ophthalmic surgery. The modular design allows the users to configure the
system to meet their surgical requirements. WARNINGS: Risks and complications of cataract surgery may include broken
ocular capsule or corneal burn. This device is only to be used by a trained licensed physician.
1. Conrad-Hengerer et al. J Cat Refract Surg. 2012; Conrad-Hengerer et al, JCRS 2012; 38(11): 1888-94.
2. Fabian E et al. New Phaco Fluidics Control: Case to Prevent Surge. Presented at ESCRS, Sept 2006, London, U.K.
WHITESTAR SIGNATURE, CATALYS, LIQUID OPTICS and FUSION are trademarks owned by or licensed
to Abbott Laboratories, its subsidiaries or affiliates.
© 2015 Abbott Medical Optics Inc. www.AbbottMedicalOptics.com PP2015CT0141
6
APRIL 15, 2015 :: Ophthalmology Times
editorial
APRIL 15, 2015 ◾ VOL. 40, NO. 7
CONTENT
Ronald McDonald for Surgeon General
Building ‘golden arches’ in the fight against antibiotic-fed animals
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]
ONCE AGAIN, IT WAS A CHILLY
winter in the Mid-Atlantic and Northeastern
regions of our fair land. And once again, I ask
myself why all ophthalmologists haven’t moved
to Southern California or southern Florida (as
opposed to only 95% of them).
As I write this, two of my family members
are on antibiotics for sinusitis and other sequelae from the waning cold and flu season.
Within 24 hours of starting their medicines,
their symptoms were noticeably improved. Fortunately, no resistant organisms here.
Antibiotic-resistant “super bugs,” however,
are frequently mentioned in the lay press. The
Centers for Disease Control and Prevention
says that at least 2 million people become infected each year in the United States, and at
least 23,000 die as the direct result of these infections. Many more die from other conditions
complicated by an antibiotic-resistant infection.1 Although other countries have the same
problem, the magnitude is substantially greater
in the United States.
Antibiotic resistance may relate to overuse of
antibiotics by physicians in patients with viral
illnesses. The major culprit is thought by many
to be use of these drugs in farming. Staggering
amounts are used not as treatment of infected
animals, but as prophylaxis in feed and drinking water to encourage faster growth of larger
animals.
For every antibiotic prescription written for a
human being in our country, the rough equivalent of a dump truck full of antimicrobials is
being used on our farms. In most other countries of the world, antibiotic usage in healthy
animals is either discouraged and limited or
specifically banned. Many experts cite this as
the key reason why patients in those nations
experience fewer infections with super bugs.
Recently, McDonald’s announced it would
stop purchasing chickens treated with antibiotics commonly used in humans. Because this
purveyor of fast food buys an estimated 3%
to 4% of all chicken produced in the United
States, the decision is expected to put pressure
on the industry overall to remove these drugs
from the diets of their fowl.
“This is a landmark announcement in the
fight to keep life-saving antibiotics working
for us and our children,” said Jonathan Kaplan, director of the Natural Resources Defense
Council.2
SOLID PL A N OF ACTION
Time will prove whether this decision has a
measurable beneficial impact on public health
on the United States. If it does, I think we are
led to only one reasonable plan of action.
In a room full of physicians, I asked each if
he or she could name the Surgeon General of
the United States. All respondents said they
did not know the name; one asked whether we
even have a surgeon general now.
“Who is the last surgeon general whose
name you can remember?” I asked.
One physician in the room thought of C. Everett Koop, MD, whereas another could recall the
name of Jocelyn Elders, MD.
My concern is this person is intended to be
“the leading spokesperson on matters of public
health in the federal government of the United
States.” Yet, very few physicians in the United
States know whether we have one—or can even
name the person, let alone articulate what he or
she has done to improve public health.
Hence, my proposal: If this ban on antibiotic-fed chicken results in fewer infections and
deaths from resistant organisms, I nominate
Ronald McDonald (no relation) for Surgeon
General. Q
Chief Medical Editor Peter J. McDonnell, MD
Group Content Director Mark L. Dlugoss
[email protected] 440/891-2703
Content Channel Director Sheryl Stevenson
[email protected] 440/891-2625
Content Specialist Rose Schneider
[email protected] 440/891-2707
Group Art Director Robert McGarr
Art Director Nicole Davis-Slocum
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
The Glaucoma Angle Malik Y. Kahook, MD
Uveitis Update Emmett T. Cunningham Jr., MD, PhD, MPH
What’s New at the AAO John Gallagher
P U B L I S H I N G /A DV E R T I S I N G
Executive Vice President Georgiann DeCenzo
[email protected] 440/891-2778
VP, Group Publisher Ken Sylvia
[email protected] 732/346-3017
Group Publisher Leonardo Avila
[email protected] 302/239-5665
Associate Publisher Erin Schlussel
[email protected] 215/962-5399
National Account Manager Cherie Pearson
[email protected] 609/636-0172
Account Manager, Classified/Display Advertising Karen Gerome
[email protected] 440/891-2670
Account Manager, Recruitment Advertising Joanna Shippoli
[email protected] 440/891-2615
Business Director, eMedia Don Berman
[email protected] 212/951-6745
Special Projects Director Meg Benson
[email protected] 732/346-3039
Director of Marketing & Research Services Gail Kaye
Sales Support Hannah Curis
Reprints 877-652-5295 ext. 121 / [email protected]
Outside US, UK, direct dial: 281-419-5725. Ext. 121
List Account Executive Renée Schuster
[email protected] 440/891-2613
Permissions/International Licensing Maureen Cannon
[email protected] 440/891-2742
PRODUCTION
Senior Production Manager Karen Lenzen
AUDIENCE DEV ELOPMEN T
Corporate Director Joy Puzzo
Director Christine Shappell
Manager Tammy Sundbom-Otterson
UBM Advanstar
Chief Executive Officer:
Joe Loggia
Executive Vice-President,
Life Sciences:
Tom Ehardt
Executive Vice-President:
Georgiann DeCenzo
Executive Vice-President:
Chris DeMoulin
Executive Vice-President,
Business Systems:
Rebecca Evangelou
Executive Vice-President,
Human Resources:
Julie Molleston
Executive Vice-President,
Strategy & Business Development:
Mike Alic
Sr Vice-President:
Tracy Harris
Vice-President, General Manager
Pharm/Science Group:
Dave Esola
Vice-President, Legal:
Michael Bernstein
Vice-President, Media Operations:
Francis Heid
Vice-President,
Treasurer & Controller:
Adele Hartwick
UBM Americas
Chief Executive Officer:
Sally Shankland
Chief Operating Officer:
Brian Field
Chief Financial Officer:
Margaret Kohler
UBM plc
Chief Executive Officer:
Tim Cobbold
Group Operations Director:
Andrew Crow
Chief Financial Officer:
Robert Gray
Chairman:
Dame Helen Alexander
UBM Advanstar provides certain customer contact data (such as customers’ names,
References
1. www.cdc.gov/drugresistance/threat-report-2013
2. McDonald’s to ban chicken treated with human antibiotics.
USA Today. March 5, 2015.
addresses, phone numbers, and e-mail addresses) to third parties who wish to promote
relevant products, services, and other opportunities that may be of interest to you. If you
do not want UBM Advanstar to make your contact information available to third parties for
marketing purposes, simply call toll-free 866-529-2922 between the hours of 7:30 a.m.
and 5 p.m. CST and a customer service representative will assist you in removing your name
from UBM Advanstar’s lists. Outside the U.S., please phone 218-740-6477.
Ophthalmology Times does not verify any claims or other information appearing in any
of the advertisements contained in the publication, and cannot take responsibility for any
losses or other damages incurred by readers in reliance of such content.
Ophthalmology Times cannot be held responsible for the safekeeping or return of
unsolicited articles, manuscripts, photographs, illustrations or other materials.
Ophthalmology Times is a member of the Association of Independent Clinical
Publications Inc.
Library Access Libraries offer online access to current and back issues of Ophthalmology
Times through the EBSCO host databases.
To subscribe, call toll-free 888-527-7008. Outside the U.S. call 218-740-6477.
PRINTED IN
U.S.A.
APRIL 15, 2015
2014 :: Ophthalmology Times
7
editorial advisory board
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
University of Minnesota,
Minneapolis, MN
Uday Devgan, 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.
Joel Schuman, MD
Peter S. Hersh, MD
University of Pittsburgh Medical Center
Pittsburgh, PA
University of Medicine & Dentistry of New Jersey
Newark, NJ
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
Jules Stein Eye Institute,UCLA
Los Angeles, CA
Hamilton Glaucoma Center
University of California, San Diego
Richard S. Hoffman, MD
Neuro-Ophthalmology
Oregon Health & Science University
Portland, OR
Andrew G. Lee, MD
Samuel Masket, MD
Methodist Hospital, Texas Medical Center
Houston, TX
Jules Stein Eye Institute,UCLA
Los Angeles, CA
Oculoplastics/
Reconstructive Surgery
Bartly J. Mondino, MD
Jules Stein Eye Institute,UCLA
Los Angeles, CA
Robert Goldberg, MD
Mark Packer, MD
Bowie, MD
Jules Stein Eye Institute, UCLA
Los Angeles, CA
Michael Raizman, MD
John T. LiVecchi, MD
Massachusetts Eye & Ear, Harvard University
Boston, MA
Ehsan “Ethan” Sadri, MD, FACS
Newport Beach, CA
St. Luke’s Cataract & Laser Institute
Tarpon Springs, FL
Shannath L. Merbs, MD
Wilmer Eye Institute, Johns Hopkins University
Baltimore, MD
Michael Snyder, MD
Cincinnati Eye Institute
Cincinnati, OH
Pediatric Ophthalmology
Retina/Vitreous
Stanley Chang, MD
Columbia University
New York, NY
David Chow, MD
Pravin U. Dugel, MD
Phoenix, AZ
Sharon Fekrat, MD
Duke University
Durham, NC
Wills Eye Institute, Thomas Jefferson University
Philadelphia, PA
Farrell “Toby” Tyson, MD
Jennifer Simpson, MD
Carl D. Regillo, MD
Cape Coral, FL
University of California, Irvine
Irvine, CA
Wills Eye Institute, Thomas Jefferson University
Philadelphia, PA
H. Jay Wisnicki, MD
Lawrence J. Singerman, MD
University of Toronto
Toronto, Canada
Malik Kahook, MD
University of Colorado,Denver
Denver, CO
Richard K. Parrish II, MD
New York Eye & Ear Infirmary, Beth Israel Medical Case Western Reserve University
Center, Albert Einstein College of Medicine
Cleveland, OH
New York, NY
Practice Management
Joseph C. Noreika, MD
Medina, OH
Uveitis
Emmett T. Cunningham Jr., MD, PhD
Stanford University
Stanford, CA
Frank Weinstock, MD
Chief Medical EditorsEmeritus
Boca Raton, FL
Refractive Surgery
Bascom Palmer Eye Institute, University of Miami
Jack M. Dodick, MD
Miami, FL
William Culbertson, MD
New York University School of Medicine
Bascom
Palmer
Eye
Institute,
University
of
Miami
New York, NY (1976–1996)
Robert Ritch, MD
Miami,
FL
New York Eye & Ear Infirmary
David R. Guyer, MD
New York, NY
New York, NY (1996–2004)
Ophthalmology Times Industry Council
John Bee
Bob Gibson
Chris Thatcher
Rhein Medical Inc.
President and CEO
Topcon Medical Systems Inc.
Vice President of Marketing
Alastair Douglas
Aziz Mottiwala
Reichert Technologies
Division Vice President and Reichert Business
Unit Manager
Alcon Laboratories Inc.
Director of U.S. Commercial Support
Allergan
Vice President of Marketing, U.S. Eye Care
to
Subscription Services Advertising
24950 Country Club Blvd.,
Toll-Free: 888/527-7008 or
218/740-6477
Suite 200
North Olmsted, OH 44070-5351 FAX: 218/740-6417
440/243-8100
FAX: 440/756-5227
485 Route 1 South
Building F, Suite 210,
Iselin, NJ 08830-3009
732/596-0276
FAX: 732/596-0003
n
de
l
Fo
Di
n
-E
Do
m
Fe
4
14
10
8-
The Folden Femto Dissector Is A Single Instrument Designed For Smooth
Opening Of All Femtosecond Laser – Created Corneal Incisions During
Cataract Surgery. The Double-Ended Instrument Measures 0.7mm At
One End, And 1.2mm At The Other.
The Polished, Semi-Blunted Leading Tip Allows For “Scoring” Of The
Epithelium And Provides Easy, Glided Entry Into The Femtosecond Laser
– Created Corneal Incision. The Unique Sharp Edge Design Cleanly
Separates Residual Tissue Bridges And Stromal Adhesions That Provide
Resistance To Entry Using Standard Instruments.
s
#LEAR#ORNEAL)NCISIONS##)34HEMM%ND0ROVIDES%ASY
%NTRY)NTO3TANDARD3MALL)NCISIONS!S7ELL!S3UBMM
-ICRO)NCISIONS 4HE MM %ND 0ROVIDES !MPLE #LEARANCE
&OR%NTRY)NTO4HE0ARACENTESIS
s ! R C U A T E ) N C I S I O N S ! ) 3 ! R C U A T E ) N C I S I O N S & O R
!STIGMATISM!RE/PENED1UICKLY!ND#LEANLY$OWN4O4HEIR
"ASE 7ITHOUT 2ISK /F 0ERFORATION 4HE 0OLISHED 3EMI
"LUNTED ,EADING 4IP 'LIDES 3MOOTHLY !LONG 4HE "ASE /F
4HE!RCUATE)NCISION7HILE4HE3HARP%DGE0ROVIDES3MOOTH
/PENING /F 3TROMAL 4ISSUE "RIDGES !ND -AINTAINS #LEAN
%PITHELIAL %DGES &EWER 3URFACE !BRASIONS 2ESULT )N
,ESS &OREIGN "ODY 3ENSATION !ND )MPROVED 0ATIENT #OMFORT
0OSTOPERATIVELY
0LEASE7ATCH4HE6IDEO/R#ONTACT
&OR-ORE)NFORMATION
How to Contact Ophthalmology Times
Editorial
c
se
le
ub
University of Wisconsin
Madison, WI
Keck School of Medicine, USC
Los Angeles, CA
Neeru Gupta, MD
d
de
Michael Ip, MD
Albert Einstein College of Medicine
Bronx, NY
1.
s
Oakland University
Rochester, MI
Wilmer Eye Institute, Johns Hopkins University
Baltimore, MD
&
m
.7
0
r,
m
to
Tarek S. Hassan, MD
Carmen A. Puliafito, MD
University of Medicine & Dentistry of New Jersey
Newark, NJ
m
2m
Julia Haller, MD
Norman B. Medow, MD
Glaucoma
The Folden* Femto
Double-Ended Dissector
University of Toronto
Toronto, Canada
Walter J. Stark, MD
Robert D. Fechtner, MD
Ophthalmology Times is a physician-driven media brand that presents cutting-edge
advancements and analysis from around the world in surgery, drug therapy, technology, and
clinical diagnosis to elevate the delivery of progressive eye health from physician to patient.
Randall Olson, MD
University of Cincinnati
Cincinnati, OH
Anterior Segment/Cataract
Cornea/External Disease
Ophthalmology Times Mission Statement
#OME3EE5S!T!3#23"OOTH.O
Production
131 W. First St.
Duluth, MN 55802-2065
800/346-0085
FAX: 218/740-7223,
218/740-6576
3360 Scherer Drive, Suite B, St. Petersburg, FL 33716
s4ELs&AX
%MAIL)NFO 2HEIN-EDICALCOMs7EBSITEWWW2HEIN-EDICALCOM
$EVELOPED)N#OORDINATION7ITH$AVID&OLDEN-$
1360 Rev.A
,AMENTATION-ICHELANGELO
ACBF
8
APRIL 15, 2015 :: Ophthalmology Times
meeting preview
ARVO 2015: Making powerful
connections in research
New Saturday session focuses on vision, traumatic brain injury in veterans and athletes
ARVO View By Katrina Norfleet
TAKE-HOME
More than 11,000 clinicians and
researchers will gather in Denver to
learn more about leading eye and
vision research at the 2015 meeting of
the Association for Research in Vision
and Ophthalmology.
ARVO
at the Colorado
Convention Center
in Denver from
May 3-7
DENVER ::
he Association for Research in Vision and Ophthalmology (ARVO) is
weeks away from hosting its 2015
annual meeting in Denver—where
more than 11,000 attendees from
more than 75 countries are expected
to gather May 3 to 7 under the theme,
“Powerful Connections: Vision Research and
Online Networking.”
Starting with a Sunday keynote address by
Gary Shapiro, president and CEO of Consumer
Electronics Association, ARVO will explore how
online networking is changing the way clinicians communicate, collaborate, and conduct
research. Attendees will discover and discuss
the increasing importance of these networks
in exchanging ideas, promoting scientific discourse, sharing discoveries, building global
collaborations, and advancing careers.
T
NEW THIS YEAR:
A SAT UR DAY SESSION
athletes and combat veterans, and
> Experimental models of impact and blast neurotrauma: implications for ophthalmology and
vision research
This session, free and open to the public,
will address the interface between traumatic
brain injury (TBI) and visual function. Learn
about the research that is uncovering important similarities between military blast TBIrelated visual dysfunction and ocular pathology resulting from sports-related head injuries.
Following an introduction by Rep. Diana
DeGette (D-CO), four of the field’s most prominent researchers will discuss:
> Retinal pathology in chronic traumatic
Vision and Traumatic Brain Injury in
Veterans and Athletes
> Visual sensory impairments and progression
Saturday, May 2, 10 a.m. to noon
following mild TBI,
encephalopathy,
Plus, attendees will hear from a panel
of blinded veterans affected by TBI and visual disorders.
A R V O /A L C O N K E Y N O T E S E R I E S
Ninja Innovation – Where Technology
is Taking Us
Sunday, May 3, Noon to 1:15 p.m.
Shapiro—head of the largest technology trade
association in the United States—will share with
attendees the next trends in technology and
their implications for health, lifestyle, privacy,
and safety. Shapiro will also describe coming
changes in display technology. Attendees also
should learn how these changes might affect
your practice.
Continues on page 10 : ARVO
photos courtesy Scott Dressel-Martin and VISIT DENVER
NEED CME UNITS?
ARVO is accredited by the Accreditation Council for Continuing Medical Education (ACCME)
to provide continuing medical education for
physicians. Physicians can choose from more
than 130 CME-approved activities. The maximum amount of credit attendees can earn is
31.25 AMA PRA Category 1 Credits. To view
the complete ARVO 2015 CME program, visit
arvo.org/cme.
> Afferent visual function in veterans with TBI,
> TBI and chronic traumatic encephalopathy in
LET’S KEEP SOMETHING
STRAIGHT ABOUT AREDS2
Only PreserVision® AREDS 2 Formula
contains the exact ingredient dosages
recommended by the National Eye Institute†
based on the evidence from the AREDS2 study.1,2*
Get patient samples and education
materials at 1-844-BL-VITES.
†
For patients with moderate to advanced age-related macular degeneration.
*This statement has not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any disease.
PreserVision. Exactly.
References: 1. Yong JJ, Scott IU, and Greenberg PB. Ocular nutritional supplements. Ophthalmology.
2014:1-5. 2. Chew EY, Clemens TE, SanGiovanni JP, et al. Lutein and zeaxanthin and omega-3 fatty
acids for age-related macular degeneration. JAMA. 2013;309(19):1-11.
PreserVision is a trademark of Bausch & Lomb Incorporated or its affiliates. AREDS2 is a
registered trademark of the United States Department of Health and Human Services (HHS).
©2015 Bausch & Lomb Incorporated. PREV-56994 US/PV2/15/0006a
SEE BETTER. LIVE BETTER.
10
APRIL 15, 2015 :: Ophthalmology Times
meeting preview
ARVO
( Continued from page 8 )
vascular mechanisms involving the vasculatures of the retina, hyaloid and choroid, and
six associated diseases in order to expand and
broaden the understanding of neurovascular
interactions in the posterior eye.
Champalimaud Vision Award Lecture
Joan Miller, MD, FARVO and Napoleone Ferrara, MD
Tuesday, May 5, 5:45 p.m. to 7 p.m.
Thursday, May 7, 1:55 p.m. to 3:15 p.m.
Dr. Miller and Dr. Ferrara—two of the
seven ARVO members named as the recipients of the 2014 Antonio Champalimaud Vision Award—will present on their pioneering
work to treat age-related macular degeneration
and diabetic retinopathy. Dr. Miller will present on the topic, “VEGF: From Discovery to
Therapy.” Dr. Ferrara’s presentation is titled,
“Discovery of VEGF-A, a Key Regulator of Intraocular Neovascularization.”
The 2014 Champalimaud recipients are:
> NAPOLEONE FERRARA, MD — University of
Ian Crozier, MD, an infectious disease specialist, was living in Uganda where he was
teaching physicians and providing care for
patients with HIV/AIDS, when the Ebola outbreak began in West Africa. He signed on with
the World Health Organization and arrived
in Kenema, Sierra Leone to help in the fight
against the outbreak in August 2014. Within
a few weeks, he himself contracted the disease and was evacuated to Emory University
Hospital in critical condition.
Dr. Crozier and a team of ophthalmology
and infectious disease physicians from Emory
University and the Centers for Disease Control
and Prevention will share their perspectives
into Crozier's evacuation, treatment, recovery
and subsequent vision-threatening condition,
as each of them dealt with the uncertainty and
long-term implications of this virus. Moderated by ARVO president William Mieler, the
panel and discussion will include:
> Update and Challenges in the Management
of the Ebola Outbreak in West Africa — Tim
Uyeki, MD, Centers for Disease Control and Prevention, Atlanta.
> Hospital Course and Infection Control in the
Emory Serious Communicable Diseases Unit
— Jay B. Varkey, MD, Division of Infectious Disease, Department of Internal Medicine, Atlanta.
> Ophthalmic Course and Management of Panuveitis Due to Ebola Virus Disease — Steven
Yeh, MD, Department of Ophthalmology, Emory
Eye Center, Atlanta.
> Diagnostic and Treatment Uncertainty in a
Novel, Sight-Threatening Disease — Jessica G.
Shantha, MD, Department of Ophthalmology,
Emory Eye Center, Atlanta.
> Perspectives on Ebola Virus Disease: Both
Sides of the Curtain — Ian Crozier, MD, Infectious Diseases Institute, Mulago Hospital Complex, Kampala, Uganda
BASIC CLINICAL LECTURE
Neurovascular Interactions in
Diseases of the Eye
California, San Diego School of Medicine and
Moores Cancer Center
> JOAN WHITTEN MILLER, MD, FARVO —
Massachusetts Eye and Ear Infirmary in
Boston
> EVANGELOS S. GRAGOUDAS, MD,
FARVO — Massachusetts Eye and Ear Infirmary in Boston
> PATRICIA A. D'AMORE, PHD, MBA,
FARVO — Massachusetts Eye and Ear
Infirmary
> ANTHONY P. ADAMIS, MD, FARVO —
Genentech; also affiliated with HMS Ophthalmology and Massachusetts Eye and Ear
Infirmary
> GEORGE L. KING, MD, FARVO — Joslin Diabetes Center
> LLOYD PAUL AIELLO, MD, PhD, FARVO —
Massachusetts Eye and Ear Infirmary and
Joslin Diabetes Center in Boston
ST U DE N T/T R A I N E E EV E N T S
ARVO Education Course
Strategies for Effective Grant Writing
Saturday, May 2, 8:30 a.m. to 4 p.m.
Led by an international faculty, including
experts in grantsmanship, this full-day course
will focus on grant-targeting strategies, planning, writing impactful proposal, and responding to reviews. The course will be interactive,
with time dedicated throughout the day to address questions from participants. The training
will focus on strategies that apply to any grantmaking organization, including NIH, private
foundations, and non-U.S. funding agencies.
These popular sessions offer informal discussions over pizza lunch on Sunday or breakfast on Wednesday on a wide range of topics. Experienced colleagues provide personal
guidance, insight, and skills to help students
and trainees advance their career. Topics
focus on professional development in academic clinical medicine and clinician-scientists careers.
Career Forum
Monday, May 5, 1 p.m. to 2:30 p.m.
Small-group roundtable discussions will
focus on helping students, fellows and residents prepare for their next career move. Attendees should bring their lunch.
Clinician-Scientist Forum:
How to Become a Successful
Clinician-Scientist
Wednesday, May 6, 1 p.m. to 2:30 p.m.
Clinician-scientists at various stages in their
career will share their experiences with attendees. Plus, an extramural representative from the National Eye Institute will be
available to discuss funding mechanisms for
clinician-scientists.
GET R E A DY F OR A RVO 2 016
It’s not too early to start planning for the ARVO
2016 annual meeting in Seattle, May 1 to 5.
The Washington State Convention Center
is conveniently located in Seattle’s downtown
center, within walking distance from hotels
and only blocks away from the popular Pike
Place Market.
To learn more about ARVO 2016 registration, hotel, program, or social events, visit
arvo.org/am. Q
Sunday, May 3, 5:15 p.m. to 7:15 p.m.
This symposium will address an NEI Audacious Goal, “Neural Connections in the Eye and
Visual System.” Experts will highlight neuro-
Pizza and Breakfast with an expert
Sunday, May 3, 1:30 p.m. to 3 p.m.
Wednesday, May 6, 7 a.m. to 8:30 a.m.
KATRINA NORFLEET is assistant director of communications,
Association for Research in Vision and Ophthalmology. Readers may
contact Norfleet at 240/221-2924 or [email protected].
photo courtesy VISIT DENVER
Ebola and the Eye: A Story of Discovery and Uncertainty
Important Safety
Information
with known hypersensitivity to any
Contraindications
components of this product.
sILUVIEN is contraindicated in patients
Warnings and Precautions
with active or suspected ocular or
periocular infections including most
s)NTRAVITREALINJECTIONSHAVEBEEN
viral disease of the cornea and
associated with endophthalmitis, eye
conjunctiva including active epithelial
inflammation, increased intraocular
herpes simplex keratitis (dendritic
pressure, and retinal detachments.
keratitis), vaccinia, varicella, mycobacterial
Patients should be monitored following
infections and fungal diseases.
the intravitreal injection.
sILUVIEN is contraindicated in patients
sUse of corticosteroids may produce
with glaucoma, who have cup to disc
posterior subcapsular cataracts,
ratios of greater than 0.8.
increased intraocular pressure,
glaucoma, and may enhance the
sILUVIEN is contraindicated in patients
Please see brief summary of full Prescribing Information on following page.
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.
Make the move to ILUVIEN and provide sustained,
submicrogram levels of fluocinolone acetonide (FAc)
for 36 months from a single intravitreal implant.1
Primary month-24
endpoint met.
Significantly more
patients treated with
ILUVIEN achieved
≥15-letter
improvement
from baseline.1
The most common
adverse reactions
reported were cataract
development (ILUVIEN
82%; sham 50%)
and intraocular
pressure elevation of
>10 mmHg (ILUVIEN
34%; sham 10%).1
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.
s0ATIENTSINWHOMTHEposterior capsule of the lens
is absent or has a tear are at risk of implant
migration into the anterior chamber.
Adverse Reactions
sThe most common adverse reactions reported
were cataract development (ILUVIEN 82%; sham
50%) and intraocular pressure elevation of >10
mmHg (ILUVIEN 34%; sham 10%).
Nonbioerodable,
implant designed
to deliver
submicrogram
levels of steroid.1
Learn more at ILUVIEN.com
1.ILUVIEN® [package insert]. Alpharetta, GA: Alimera Sciences, Inc.; 2014.
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.
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.
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
Adverse Reactions
ILUVIEN (N=375)
n (%)
Sham (N=185)
n (%)
Ocular
Cataract1
192/2352 (82%)
61/1212 (50%)
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%)
Conjunctivitis
14 (4%)
5 (3%)
Corneal oedema
13 (4%)
3 (2%)
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%)
US-ILV-MMM-0034-02 02/15
Non-ocular
Anemia
Headache
Renal failure
Pneumonia
40 (11%)
33 (9%)
32 (9%)
28 (7%)
Sham (N=185)
n (%)
10 (5%)
11 (6%)
10 (5%)
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)
n (%)
Non-ocular
IOP elevation ≥ 10 mm Hg from baseline
IOP elevation ≥ 30 mm Hg
Any IOP-lowering medication
Any surgical intervention for elevated
intraocular pressure
Sham (N=185)
n (%)
127 (34%)
75 (20%)
144 (38%)
18 (10%)
8 (4%)
26 (14%)
18 (5%)
1 (1%)
25
Mean Intraocular Pressure (mm Hg)
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.
ILUVIEN (N=375)
n (%)
20
15
10
5
0
0
6
12
18
Month
ILUVIEN (N=375)
24
30
36
Sham (N=185)
Figure 1: Mean IOP during the study
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 postmarketing 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.
USE IN SPECIFIC POPULATIONS
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.
Manufactured for:
"MJNFSB4DJFODFT*ODt8JOEXBSE1BSLXBZ
"MQIBSFUUB("t1BUFOUFE4FFXXXBMJNFSBTDJFODFTDPN
All Rights Reserved; Issue Date September 2014;
ILUVIEN is a registered trademark of Alimera Sciences, Inc.
APRIL 15, 2015 :: Ophthalmology Times
surgery
Strategies for handling complex
pterygium surgery, complications
Spotlighting aggressive pterygia, recurrent pterygia, symblepharon, corneal scars, scleral melts
Gloves Off with Gulani By Arun C. Gulani, MD
TAKE-HOME
In this second of a two-part series on
pterygia and pinguecula surgery with
cosmetic expectations, Arun C. Gulani,
MD, addresses the complex pterygia and
complications.
RECURRENT PTERYGIUM
Day 1 Postop
JACKSONVIL L E, F L ::
ith a worldwide referral base for complex
pterygia and pinguecula complication cases,
I have condensed my
observations and approach over the past
two decades to share in this column.
Personally I have seen less than 1% recurrence rate over 14 years with my technique
despite doing very complex pterygia. Additionally, I have had a case of muscle adhesion and a case of pupil abnormality (probably ischemia) in aggressive bitemporal
cases.
My approach always as emphasized in
the first part of this column (http://bit.
ly/1NGKqiJ) is to make sure patients understand the seriousness of this surgery and
that complications can happen.
Once again, I must first emphasize that
the mindset associated with treating recurrent pterygia and associated complications
is the same as when dealing with the virgin
pterygial surgery.
Surgeons should not adopt the notion
that the previous surgeon did a bad job or
that they are now trying to help a patient
and therefore aim for a mediocre outcome.
Rather, the mindset should be the same as
when treating the primary pterygium with
the expectation of achieving outstanding
cosmetic outcomes on the next postoperative day that will remain stable in the future. Every step should not only correct the
problem but also enhance the appearance of
the eye and possibly improve vision.
W
Day 2 Postop
(FIGURE 1) Recurrent pterygium excision, next the appearance. (Photos courtesy of Arun C. Gulani, MD)
VIDEO Learn more about the technique.
Go to http://bit.ly/1JlOZ1i (Videos courtesy of Arun C. Gulani, MD)
More Video
http://bit.ly/1yanO8N
http://bit.ly/1afWECd
http://bit.ly/1DfmAJw
http://bit.ly/1yRWsz5
http://bit.ly/1yanQ0x
When correcting recurrences and complications arising in pterygia/pinguecula surgery, I have suggested three facets that surgeons must consider: the recurrence and
or complications of the lesion itself; the associated conditions such as fornix shortening, corneal and conjunctival scarring,
symblepharon, and ischemia or scleral
melts; and the predisposing factor for such a
recurrence/complication.
Regardless of the expertise of the surgeon
who performed the initial surgery, complications can develop that require devising a
treatment plan with realistic expectations
for the patient but without lowering our
own desire to achieve excellence.
I always presume and reiterate to patients that their initial surgeon did the best
they could to remove the lesion; the goals of
the second surgeon now are to pick up the
baton and take it to the end zone by beautiContinues on page 12 : Strategies
11
12
APRIL 15, 2015 :: Ophthalmology Times
surgery
(FIGURE 2) Aggressive, recurrent pterygium with next day and long
term outcome
(FIGURE 3) Residual Salzmann nodules in aggressive recurrent
pteygium surgery, corrected by PROKERA application
Self Resolving Scleral Melt In an elderly patient
resolved with lubrication over time
Scleral Melt
(FIGURE 4) Residual corneal scars the following recurrent pterygium
surgery can undergo laser Corneoplastique to emmetropic vision
STRATEGIES
( Continued from page 11 )
fying the eye, correcting the comorbidity of
associated problems, and enhancing vision.
RESECTING
RECURRENT LESIONS
To perform minimal dissection, the goal is to
identify the bare sclera by careful and gentle
cut down through the recurrent scar tissue.
The first surgeon has usually done a nice
job of preparing a clear/bare sclera. Once
that plane is reached the most difficult
part is over. In most cases now the rest of
the scariform tissue lifts off like a “plate of
armor” from the underlying sclera.
Following this approach there is minimal
bleeding. Bleeding usually occurs when sur-
Scleral Melt
One Month
Scleral Melt
Six Months
(FIGURE 5) Self-resolving scleral thinning
geons chase the scar tissue from different
approaches and cut into it causing multiple
planes with a messy and distorted anatomy
that further complicates the surgical steps.
In most recurrent cases referred to me,
the original pterygium was removed only
partially. The surgical steps described
in Part 1 of this column can now be followed. These include mitomycin C application and application of Tisseel Glue (Baxter International) along with amniotic graft
reconstruction.
FOCUSING ON
A S SOCI AT ED PAT HOLOGY
After the mass of the pterygium is removed, the surgeon should consider the
anatomy and methods to improve the ocular appearance and address the associated
comorbidities.
One such adjustment is forming the forni-
ces. This is done by redeepening and relieving the conjunctival scarring and symblepharon, clearing the corneal area using a number 64 blade without cutting in a smooth
rapid fashion, and then applying an amniotic graft to reconstruct the fornix by deepening it and arranging the conjunctiva in
an elaborate fashion such that it is cosmetically hidden under the lids but is functionally viable.
As described in part 1 of this column, the
amniotic membrane can be used to cover
the sclera. This can also be multilayered to
strengthen the thin sclera. The membrane is
attached using Tisseel Glue. The area of the
corneal scar is smoothed and application of
the amniotic membrane can be extended beyond the limbus onto the cornea for better
healing. In many of these cases, I use ProKera (Bio-Tissue) or AmbioDisk (IOP OphContinues on page 14 : Appearance
SYMPTOMATIC VITREOMACULAR
ADHESION (VMA)
SYMPTOMATIC VMA MAY LEAD TO VISUAL IMPAIRMENT FOR YOUR PATIENTS1-3
IDENTIFY
REFER
Recognize metamorphopsia as a key sign of symptomatic VMA
and utilize OCT scans to confirm vitreomacular traction.
Because symptomatic VMA is a progressive condition that may lead
to a loss of vision, your partnering retina specialist can determine
if treatment is necessary.1-3
THE STEPS YOU TAKE TODAY MAY MAKE A DIFFERENCE
FOR YOUR PATIENTS TOMORROW
© 2014 ThromboGenics, Inc. All rights reserved. ThromboGenics, Inc., 101 Wood Avenue South, Suite 610, Iselin, NJ 08830 – USA. THROMBOGENICS and the THROMBOGENICS logo are trademarks or registered trademarks of
ThromboGenics NV. 9/14 OCRVMA0220
References: 1. Sonmez K, Capone A, Trese M, et al. Vitreomacular traction syndrome: impact of anatomical configuration on anatomical and visual outcomes. Retina. 2008;28:1207-1214. 2. Hikichi T, Yoshida A,
Trempe CL. Course of vitreomacular traction syndrome. Am J Ophthalmol. 1995;119(1):55-56. 3. Stalmans P, Lescrauwaet B, Blot K. A retrospective cohort study in patients with diseases of the vitreomacular interface (ReCoVit).
Poster presented at: The Association for Research in Vision and Ophthalmology (ARVO) 2014 Annual Meeting; May 4-8, 2014; Orlando, Florida.
14
APRIL 15, 2015 :: Ophthalmology Times
surgery
APPEARANCE
( Continued from page 12 )
thalmics) on the day after the surgery.
Sclera melts are another possible complication of pterygium surgery; some of these
are self-resolving while others require a tis-
Lateral Recurrent Pterygium
sue intervention such as lamellar cornea,
conjunctival, or Tenon’s pedicles, and amniotic graft reconstruction. In severe cases, I
also use Tutoplast (Tutogen Medical GmbH)
with amniotic graft combination to further
reconstruct and strengthen the sclera.
The Tenon’s pedicle can be used to supply vascularity to a usually ischemic sclera
and the lamellar cornea can be used in
cases with superficial scleral thinning and
glued in place for a cosmetically appealing
endpoint.
Granulomas also can occur in some case
and can resolve spontaneously with steroids
or gentle cautery excision.
In extensive and deeper scleral involvement, I also have used Tutoplast and tried
Continues on page 17 : Scleral
Day One Post op with
Tenons Reinforcement
Scleral Melt
Scleral Melt
with Lateral Calcification
Day One Post op with Tenons
Reinforcement—High Mag
(FIGURE 6) Tenon’s pedicle reinforcement for areas of scleral
thinning in aggressive lateral recurrent pterygium
2.5 years post Rec Pterygium surgery
Scleral Melt
1 Day Postop
Day 1 Post-op
2 Months Post-op
1 Week Postop
1 Month Post-op
6 Months Post-op
2.5 years post Rec Pterygium surgery
2 Years Postop
6 Years Postop
1 Month Postop
4 Years Postop
8 Years Postop
(FIGURE 9, 10 & 11) Glued Tutoplast used for scleral melt
(FIGURE 7 & 8) Lamellar corneal graft used in scleral thinning to
retain cosmetic appearance and ocular integrity.
ALREX :
®
TREATS THE ITCH
AND MORE.
SHORT-TERM TREATMENT FOR
THE FULL SPECTRUM OF SAC*
SIGNS AND SYMPTOMS1-3
*Seasonal allergic conjunctivitis.
INDICATION
ALREX® (loteprednol etabonate ophthalmic suspension) is indicated for the temporary relief of the signs and
symptoms of seasonal allergic conjunctivitis.
IMPORTANT SAFETY INFORMATION
ALREX® 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
the ocular structures. ALREX® is also contraindicated in individuals with known or suspected hypersensitivity to any of
the ingredients of this preparation and to other corticosteroids.
Prolonged use of ALREX® is associated with several warnings and precautions, including glaucoma with optic nerve damage,
defects in visual acuity, cataract formation, secondary ocular infections, and exacerbation or prolongation of viral ocular
infections (including herpes simplex).
If this product is used for 10 days or longer, intraocular pressure should be monitored. The initial prescription
and renewal of the medication order beyond 14 days should be made by a physician only after reexamination of
the patient with the aid of magnification. Fungal infections of the cornea may develop with prolonged use
of corticosteroids.
Ocular adverse reactions occurring in 5-15% of patients treated with loteprednol etabonate ophthalmic suspension
(0.2%-0.5%) in clinical studies included abnormal vision/blurring, burning on instillation, chemosis, discharge, dry eyes,
epiphora, foreign body sensation, itching, infection, and photophobia.
Please see brief summary of full Prescribing Information on the following page.
References: 1. ALREX [package insert]. Tampa, FL: Bausch & Lomb Incorporated; 2013. 2. Dell SJ, Lowry GM, Northcutt JA,
Howes J, Novack GD, Hart K. A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate
in patients with seasonal allergic conjunctivitis. J Allergy Clin Immunol. 1998;102(2):251-255. 3. Shulman DG, Lothringer LL,
Rubin JM, et al. A randomized, double-masked, placebo-controlled parallel study of loteprednol etabonate 0.2% in patients with
seasonal allergic conjunctivitis. Ophthalmology. 1999;106(2):362-369.
ALREX is a trademark of Bausch & Lomb Incorporated or its affiliates.
©Bausch & Lomb Incorporated. US/ALX/15/0001
BRIEF SUMMARY OF PRESCRIBING INFORMATION
This Brief Summary does not include all the information needed to use
Alrex® (loteprednol etabonate ophthalmic suspension 0.2%) safely and
effectively. See full prescribing information for Alrex.
Alrex
®
loteprednol etabonate
ophthalmic suspension 0.2%
Sterile Ophthalmic Suspension
Rx only
INDICATIONS AND USAGE
ALREX Ophthalmic Suspension is indicated for the temporary relief of the
signs and symptoms of seasonal allergic conjunctivitis.
CONTRAINDICATIONS
ALREX, 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.
ALREX is also contraindicated in individuals with known or suspected
hypersensitivity to any of the ingredients of this preparation and to other
corticosteroids.
WARNINGS
Prolonged use of corticosteroids may result in glaucoma with damage to
the optic nerve, defects in visual acuity and fields of vision, and in posterior
subcapsular cataract formation. Steroids should be used with caution in the
presence of glaucoma.
Prolonged use of corticosteroids may suppress the host response and thus
increase the hazard of secondary ocular infections. In those diseases causing
thinning of the cornea or sclera, perforations have been known to occur with
the use of topical steroids. In acute purulent conditions of the eye, steroids
may mask infection or enhance existing infection.
Use of ocular steroids may prolong the course and may exacerbate the
severity of many viral infections of the eye (including herpes simplex).
Employment of a corticosteroid medication in the treatment of patients with
a history of herpes simplex requires great caution.
PRECAUTIONS
General: For ophthalmic use only. The initial prescription and renewal of the
medication order beyond 14 days 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.
If signs and symptoms fail to improve after two days, the patient should be
re-evaluated.
If this product is used for 10 days or longer, intraocular pressure should be
monitored.
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.
Information for Patients: 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 redness or itching becomes aggravated,
the patient should be advised to consult a physician.
Patients should be advised not to wear a contact lens if their eye is red.
ALREX should not be used to treat contact lens related irritation. The
preservative in ALREX, benzalkonium chloride, may be absorbed by soft
contact lenses. Patients who wear soft contact lenses and whose eyes are
not red, should be instructed to wait at least ten minutes after instilling
ALREX before they insert their contact lenses.
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, (1500
and 750 times the maximum clinical dose, respectively) prior to and during
mating did not impair fertility in either gender.
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 (85 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 (15 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 postimplantation 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 (15 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.
ALREX Ophthalmic Suspension 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 ALREX is administered to a nursing woman.
Pediatric Use: Safety and effectiveness in pediatric patients have not been
established.
ADVERSE REACTIONS
Reactions associated with ophthalmic steroids include elevated intraocular
pressure, which may be associated with optic nerve damage, visual acuity
and field defects, posterior subcapsular cataract formation, secondary ocular
infection from pathogens including herpes simplex, and perforation of the
globe where there is thinning of the cornea or sclera.
Ocular adverse reactions occurring in 5-15% of patients treated with
loteprednol etabonate ophthalmic suspension (0.2% - 0.5%) in clinical
studies included abnormal vision/blurring, burning on instillation, chemosis,
discharge, dry eyes, epiphora, foreign body sensation, itching, injection,
and photophobia. Other ocular adverse reactions occurring in less than 5%
of patients include conjunctivitis, corneal abnormalities, eyelid erythema,
keratoconjunctivitis, ocular irritation/pain/discomfort, papillae, and uveitis.
Some of these events were similar to the underlying ocular disease being
studied.
Non-ocular adverse reactions occurred in less than 15% of patients. These
include headache, rhinitis and pharyngitis.
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. Among the smaller group of patients who were
studied with ALREX, the incidence of clinically significant increases in IOP
(≥10 mm Hg) was 1% (1/133) with ALREX and 1% (1/135) with placebo.
DOSAGE AND ADMINISTRATION
SHAKE VIGOROUSLY BEFORE USING.
One drop instilled into the affected eye(s) four times daily.
Revised: August 2013.
Bausch & Lomb Incorporated, Tampa, Florida 33637
©Bausch & Lomb Incorporated
Alrex® is a registered trademark of Bausch & Lomb Incorporated
Based on 9007904-9005504
US/ALX/15/0005
Issued: 02/2015
APRIL 15, 2015 :: Ophthalmology Times
surgery
(FIGURE 12) Correcting the “Eye Brightening” surgery with amniotic
graft reconstruction to cosmetic outcomes
SCLERAL
( Continued from page 14 )
to always keep it the least bulky as possible.
While these are salvage cases, the extraocular movement and appearance should be
preserved as best as possible.
These cases can look cosmetically appealing the next day after surgery and remain that way for years to come. An anchor
suture can be used if needed. Clearing and
strengthening are the main objectives, although cosmesis and vision are the primary
desires.
Corneal scars can be easily addressed
using Laser Corneoplastique principles as
explained in previous columns (Decoding
Corneal Scars) and the patients can achieve
emmetropia.
PR EDISPOSING
COMORBIDITIES
If predisposing conditions such as rheumatoid arthritis, Sjögrens syndrome, dry eye,
or collagen vascular diseases are present,
we must involve the patient’s physician for a
systemic workup and management.
In addition, every attempt at surgery
raises the chances of a recurrence so we
must strive to do it right the first time following the principles of the Iceberg concept.
This minimalistic approach results in
surprisingly good results for these patients
with its elegant arrangement of tissue. The
cosmetic outcomes, high functionality, and
improved vision are the final goals of this
17
(FIGURE 13) Staged surgery using amniotic graft for aggressive
recurrent pterygium with laminar fill of amniotic graft on the cornea
followed by Multifocal lens implant for cataract and Laser ASA in
Corneoplastique mode to emmetropia and cosmetic appearance.
surgery regardless of the preoperative appearance. Therefore, recurrent pterygia can
be addressed in the same fashion but with
a slightly different approach and the same
mindset as the initial surgeries.
Importantly, numerous patients of mine
who have undergone complex pterygial surgery and complication correction have also
undergone subsequent laser vision surgery
and premium cataract surgery with excellent visual outcomes.
A C AV E A T
Given the unique nature of my practice with
a large number of patients referred for cosmetic outcomes, their expectations need to
be addressed because doing a mediocre job
on a case in which the pterygium/pinguecula was primary and small but with a resultant scar is less tolerable and more agonizing than a recurrence in a complex pterygium case.
This is very similar to present-day premium cataract surgery where patients with
20/60 vision and easily extractable cataracts
expect perfection as opposed to patients
with 20/400 vision even if the latter may
have a mature, hard, and complex cataracts.
This is the price we must pay for our desire to excel for our patients by undertaking
this level of commitment as long as the patients are educated about the fact that complications can occur.
Mastering the art of pterygium and pinguecula surgery to treat emerging cases
as well as complications and side effects
empowers the surgeon to become a fullspectrum ocular surface surgeon who re-
lentlessly follows the goals of raising the
bar on ocular surface surgery to cosmetic
outcomes along with enhancing vision
simultaneously.
In an upcoming “Gloves Off with Gulani”
column, I look forward to discussing “Designer Cataract Surgery: Beyond Premium
Technology; The Time Is Now.” ■
References
1. Gulani AC. Sutureless amniotic surgery for pterygium:
cosmetic outcomes for ocular surface surgery.
Techniques in Ophthalmology. 2008;6:41-4.
2. Gulani AC. No-stitch pterygium surgery: next day
cosmetic outcomes. Video Journal of Ophthalmology.
2009.
3. Gulani AC. Corneoplastique. Video Journal of Cataract
and Refractive Surgery. 2006;22:3.
4. Gulani A, Gulani A. pterygium surgery: raising ocular
surface surgery to cosmetic outcomes. Mastering
corneal surgery: recent advances and current
techniques. Thorofare, NJ: SLACK Incorporated.
2015;25:269-276.
5. Gulani AC. Gulani Iceberg Technique. Cataract &
Refractive Surgery Today Europe. 2014;9:48-49.
6. Gulani, AC. A cornea-friendly pterygium procedure.
Rev Ophthalmol. 2012;52-56.
7. Gulani AC. Shaping the future and reshaping the past:
the art of vision surgery. Chapter 98. In: Copeland
and Afshari’s Principles and Practice of Cornea. New
Delhi, India: Jaypee Brothers Medical Publishers
2013;2: 1252-1273.
8. Gulani AC. Corneoplastique. Ind J Ophthalmol.
2014;62:3-11.
9. Gulani, AC. Competencies in oculoplastics: anatomy,
trauma, involutions, and exam preparation. New
Retina MD. 2013;1-2.
ARUN C. GULANI, MD, is founding director and chief surgeon
of the Gulani Vision Institute, Jacksonville, FL. Dr. Gulani has no
financial interests to declare.
18
APRIL 15, 2015 :: Ophthalmology Times
surgery
Presbyopic-correcting devices
poised for growing patient sector
Potential for excellent near vision independent of lens replacement closer to reality
Focus on Refractive Surgery By Ehsan “Ethan” Sadri, MD, FACS
BE ACH, CA ::
“typical” patient who comes
in for cataract surgery has extremely high expectations regarding the visual outcomes
at all visual distances and is
not willing to settle for less.
Because of the large number of patients who will need cataract surgery, the pool of patients willing to spend
money on the most advanced technologies
to provide the highest level of vision is expanding exponentially.
With this potential market, many companies are designing presbyopia-correcting
devices, and the attention they are getting
is just the tip of the iceberg. In excess of
100,000 inlays have been implanted worldwide. The devices are currently approved in
51 countries in Europe, the Asia-Pacific, the
Middle East, North and South America, and
India. But this is just the beginning.
Product milestones in this area include
development of the:
> Kamra corneal inlay (Acufocus),
> Raindrop Near Vision Corneal Inlay (ReVi-
A
sion Optics),
> PresbyLens (in the United States)/the PresbyVue+ (in Europe)—both from ReVision
Optics,
> Flexivue Microlens (Presbia), and
> the corneal onlay, which is still in the experimental stages.
The devices that are further along in
the testing process are highlighted in this
article.
K A MR A COR NE A L INL AY
This inlay—which is on the verge of approval by the FDA—is made of polyvinyledene fluoride and carbon nanoparticles
and is highly biocompatible. The device improves near vision by extending the depth
of focus. A typical patient with presbyopia
may have only 0.25 D of depth of focus. Following implantation of the Kamra inlay, that
can increase to in excess of 2.5 D.
The central aperture is a hole in the inlay
Investigators have reported a small dethat has no power. The inlay is designed
crease in the photopic and mesopic contrast
to provide an unobstructed pathway for fosensitivity, but the values are within the
cused light to reach the retina. Advantages
normal range 2 years postoperatively.
are its small size with a diameter of 3.8
However, at the end of the day compared
mm, a 1.6-mm aperture, and
with the benefits provided
a thickness of only 5 μm.
by the inlay the reduction in
The device has 8,400 holes
contrast is considered minor.
ranging in size from 5 to 11
Patients also reported
Because of the
μm, which provide its high
a low incidence of visual
large number of
permeability.
symptoms 2 years after surpatients who will
Two surgical procedures
gery that included glare,
need cataract
can be used to implant the
halos, and night-vision probsurgery, many
Kamra inlay, i.e., in a pocket
lems. In line with these posicompanies are
or a dual interface. The fortive results, patients reported
designing presbyopiamer approach, which can be
significantly increased readcorrecting devices.
used with emmetropic presing speed and reading abilbyopes, involves creation of
ity and decreased distance at
a pocket about 200 to 250 μm deep in the
which they could read.
stroma into which the inlay is placed.
The increased reading ability at J2 after
The latter surgery is good for patients
implantation was sustained out to 5 years
with ametropic presbyopia and presbyopia
postoperatively.
who had undergone a LASIK procedure or
Another benefit of the technology is that
were to undergo a LASIK-Kamra procedure.
the procedure is reversible and does not reWith the combination procedure, LASIK is
strict future refractive options.
performed under a 100-μm flap. With the
Cataracts and lens opacities can be seen
other approach, a minimum of 1 month
easily through a dilated pupil with the imafter LASIK, a pocket is created 100 μm
plant in place. When a patient with a Kamra
under the LASIK interface and the inlay is
inlay develops a cataract, there are several
inserted.
options— namely, performance of phacoThe mean near uncorrected visual acuemulsification and implantation of a monoity that is achieved is quite good at J2 12
focal IOL with the inlay in place, removal of
months postoperatively. Importantly, at
the inlay after implantation of a monofocal
the same time point the uncorrected disIOL, and removal of the inlay followed by
tance visual acuity remains stable at about
implantation of a posterior chamber IOL.
20/30. Patients with the inlay implanted in
While this was the first and most extena pocket had no change in the mean dissively used of the inlays, it still is not aptance stereoacuity scores between preoperproved in the United States.
atively and 6 months after implantation of
the inlay.
R AINDROP NEAR VISION
At 2 years post-implantation, the ease of
COR NE A L INL AY
performing distance visual tasks remained
This corneal inlay is constructed from a perstable after implantation of the inlay using a
meable hydrogel with the same refractive
pocket procedure. Patients rated the ease of
index as that of the cornea. The device is 2
performing near visual tasks with both eyes
mm in diameter and the central thickness
without wearing glasses as 7 on the ranking
is 32 μm. This inlay affects the patient’s acscale, with 1 indicating “not easy at all” and
commodative power by causing the central
7 “very easy.”
radius of corneal curvature over the implant
TAKE-HOME
Bio
ics
han
ec
M
BioM
ate
ri
al
NO MATTER THE CASE,
THE ACRYSOF® PLATFORM
PROVIDES AN OPTION
FOR ACHIEVING
PATIENT SATISFACTION
Bonnie An Henderson, MD
Ophthalmic Consultants of Boston
BioOptics
Patients have their concerns before cataract surgery.
These concerns can vary as much as the patients
themselves. AcrySof® IOLs deliver top quality vision
to address the visual goals of my patients.
This supplement presents actual case studies. Individual results may vary.
Advancing
CATARACT SURGERY
CASE 1
PROFESSIONAL DRIVER. GLARE SUFFERER. APPREHENSIVE.
Patient Study
63-year-old male
Bilateral cataracts
Works two jobs as a van and bus driver; regularly works morning
and late night shifts
&RPSODLQVRILQFUHDVLQJGLɝ
FXOW\GULYLQJGXHWRJODUH
Concerned about improving visual quality to maintain work
No additional ocular concerns (ie, glaucoma, retina)
Clinical Assessment
Preoperative VA (OD): 20/40
Preoperative VA (OS): 20/40
Preoperative MRx (OD): +3.00 –1.25 X 85
Preoperative MRx (OS): +2.50 –1.00 X 105
Recommendations
“This patient was primarily concerned about his ability to
keep driving for work once he received his IOLs, since he
alternates between daytime and nighttime shifts. Following
a thorough conversation about his visual goals, he selected
the monofocal lens, particularly since he wanted to achieve
the clearest possible distance vision for his nighttime driving.
I recommended an AcrySof®Ζ2/ZLWKDEOXHOLJKWOWHULQJ
chromophore in order to give him excellent vision with
minimal glare. He is quite happy with his results and is truly
grateful he achieved such outstanding visual quality following
surgery.”
– Bonnie An Henderson, MD
AcrySof® IQ Aspheric IOL (SN60WF 19.0)
Results
Postoperative uncorrected vision: 20/20 (OD), 20/25 (OS)
3DWLHQWLVVDWLVHGZLWK
Overall visual quality
Visual acuity
Newfound comfort with both daytime and nighttime driving
6LJQLFDQWJODUHUHGXFWLRQ
Driving vision during photopic/scotopic/mesopic conditions
This is an actual case study; the photograph is an actor portrayal.
ARTIST. RETIRED. PRIORITIZES COLOR VISION.
CASE 2
Patient Study
76-year-old female
Unilateral cataract (OD)
Retired graphics design artist; works part time as
freelance artist
ΖQFUHDVLQJGLɝ
FXOW\VHHLQJSDLQWLQJVFOHDUO\
Extremely worried about color perception loss; does not
want vision options to compromise color perception
No additional ocular concerns (ie, glaucoma, retina)
Clinical Assessment
Preoperative VA (OD): 20/50
Preoperative MRx (OD): +3.00 –1.25 X 107
Recommendations
AcrySof® IQ Aspheric IOL (SN60WF 21.5)
Results
Postoperative uncorrected vision: 20/20 (OD)
3DWLHQWLVVDWLVHGZLWK
Overall visual quality
Overall color contrast vision across photopic/scotopic/
mesopic conditions
Visual acuity, particularly near vision quality
This is an actual case study; the photograph is an actor portrayal.
“This patient felt her world ‘was becoming a faded canvas’ and was
absolutely adamant about her need to preserve and improve her
RYHUDOOFRORUYLVLRQ%HFDXVHVKHVSHFLFDOO\ZDQWHGWRPDLQWDLQ
perfect color perception, I thought she would be a great candidate
for the AcrySof®Ζ4OHQVVLQFHWKHEOXHOLJKWOWHULQJ\HOORZ
chromophore would cut down on her glare while mimicking the
natural crystalline lens.
Following surgery, she was completely thrilled with her vision. She
recalled previously how she was increasingly missing details in her
work. Since the surgery, she feels her improved vision now fully
supports her talent, and that the details in her work are now much
more apparent.
When I saw her recently, she burst into tears of gratitude over her
outcome, and she shared her prior fears that she would have to
give up painting altogether. She even brought me a painting as a
thank you gift! An incredibly gratifying case for me personally.”
– Bonnie An Henderson, MD
CASE 3
PHYSICIAN. NIGHT SHIFT. SLEEP CONCERNS.
Patient Study
70-year-old male
Bilateral cataracts
Works as an obstetrician/gynecologist
Frequently works long, late night shifts at a local hospital
1RWHGLQFUHDVLQJGLɝ
FXOW\PDQDJLQJKLVJODUH
Does not desire an advanced technology IOL
Reports some sleep issues; concerned that his IOL will impact
his sleep and driving habits
No additional ocular concerns (ie, glaucoma, retina)
Clinical Assessment
“As a physician who works late at night, maintaining sleep
quality was as precious to this patient as improving his
visual quality. He noted that since he often works day–night
GRXEOHVKLIWVLWLVGLɝ
FXOWIRUKLPWRURXWLQHO\UHJXODWHKLV
VOHHSȂZDNHF\FOHKHVSHFLFDOO\GLGQRWZDQWKLVΖ2/WR
interfere with this challenge. Based on his stated vision
goals and concerns, I recommended the AcrySof® IQ lens.
Following surgery, he was incredibly pleased with his visual
outcome. He also reported his overall sleep quality actually
LPSURYHGZLWKOHVVGLɝ
FXOW\IDOOLQJDVOHHSDQGUHJXODWLQJ
his sleep–wake cycle. This isn’t typical and it is important
to note that no controlled clinical studies have shown
DSRVLWLYHHHFWRQVOHHSTXDOLW\+RZHYHUDWOHDVWRQH
UHSRUWHGVWXG\KDVIRXQGQRQHJDWLYHHHFWRQVOHHS1“
– Bonnie An Henderson, MD
Preoperative VA (OD): 20/200
Preoperative MRx (OD): –11.00 –1.25 X 095
Recommendations
AcrySof® IQ Aspheric IOL (SN60WF 14.0)
Results
Postoperative uncorrected vision: 20/20 (OD)
3DWLHQWLVVDWLVHGZLWK
Overall visual quality and acuity
Improved vision for driving and reading
Reduction in glare
Overall sleep quality
This is an actual case study; the photograph is an actor portrayal.
DENTAL HYGIENIST. ASTIGMATIC. DRIVING CHALLENGES.
CASE 4
Patient Study
62-year-old female
Bilateral cataracts with bilateral astigmatism
Works as a dental hygienist; requires daily driving
Complains of poor vision interfering with ability to read
VWUHHWVLJQVDQGQHSULQW
Seeks spectacle independence
No additional ocular concerns (ie, glaucoma, retina)
Reports no sleep issues
Clinical Assessment
Preoperative VA (OD): 20/40
Preoperative VA (OS): 20/200
Preoperative MRx (OD): +0.75 –3.25 X 001
Preoperative MRx (OS): +0.25 –2.50 X 116
Recommendations
AcrySof® IQ Toric IOL (SN6AT7 21.0)
Results
Postoperative uncorrected vision: 20/20 (OU)
3DWLHQWLVVDWLVHGZLWK
Overall visual quality and clarity
Astigmatism correction
Spectacle independence for distance vision
Photopic/scotopic/mesopic contrast sensitivity
Vision for driving
This is an actual case study; the photograph is an actor portrayal.
“This patient was primarily concerned with maintaining her visual
FODULW\SDUWLFXODUO\IRUGULYLQJDQGUHDGLQJQHSULQWDWZRUN
and home. During her examination and our conversation about
treatment options, she did not realize that she could actually
correct the astigmatism that she had been living with her entire
life.
After surgery, she was over the moon with her visual outcome–
she was so happy that she could simply get out of bed every day
and immediately begin enjoying her new vision. She uses simple
reading glasses now instead of expensive corrective lenses, and
she feels the long-term cost savings associated with spectacle
independence far outweighs the one-time cost of her AcrySof® IQ
Toric IOL.”
– Bonnie An Henderson, MD
IMPORTANT PRODUCT INFORMATION
ACRYSOF® IQ IOL
CAUTION:
Federal (USA) law restricts this device to the sale by or on the order of a physician.
INDICATIONS:
The AcrySof® IQ posterior chamber intraocular lens is intended for the replacement of the human lens to achieve visual correction
of aphakia in adult patients following cataract surgery. This lens is intended for placement in the capsular bag.
WARNING/PRECAUTION:
&DUHIXOSUHRSHUDWLYHHYDOXDWLRQDQGVRXQGFOLQLFDOMXGJPHQWVKRXOGEHXVHGE\WKHVXUJHRQWRGHFLGHWKHULVNEHQHWUDWLREHIRUH
implanting a lens in a patient with any of the conditions described in the Directions for Use labeling. Caution should be used prior
to lens encapsulation to avoid lens decentrations or dislocations.
6WXGLHVKDYHVKRZQWKDWFRORUYLVLRQGLVFULPLQDWLRQLVQRWDGYHUVHO\DHFWHGLQLQGLYLGXDOVZLWKWKH$FU\6RI® Natural IOL and
QRUPDOFRORUYLVLRQ7KHHHFWRQYLVLRQRIWKH$FU\6RI® Natural IOL in subjects with hereditary color vision defects and acquired
color vision defects secondary to ocular disease (e.g., glaucoma, diabetic retinopathy, chronic uveitis, and other retinal or optic
nerve diseases) has not been studied. Do not resterilize; do not store over 45°C; use only sterile irrigating solutions such as BSS®
or BSS PLUS® Sterile Intraocular Irrigating Solutions.
ATTENTION:
Reference the Directions for Use labeling for a complete listing of indications, warnings and precautions.
ACRYSOF® IQ TORIC IOL
CAUTION:
Federal (USA) law restricts this device to the sale by or on the order of a physician.
INDICATIONS:
The AcrySof® IQ Toric posterior chamber intraocular lenses are intended for primary implantation in the capsular bag of the eye
for visual correction of aphakia and pre-existing corneal astigmatism secondary to removal of a cataractous lens in adult patients
with or without presbyopia, who desire improved uncorrected distance vision, reduction of residual refractive cylinder and
increased spectacle independence for distance vision.
WARNING/PRECAUTION:
&DUHIXOSUHRSHUDWLYHHYDOXDWLRQDQGVRXQGFOLQLFDOMXGJPHQWVKRXOGEHXVHGE\WKHVXUJHRQWRGHFLGHWKHULVNEHQHWUDWLR
before implanting a lens in a patient with any of the conditions described in the Directions for Use labeling. Toric IOLs should
not be implanted if the posterior capsule is ruptured, if the zonules are damaged, or if a primary posterior capsulotomy is
planned. Rotation can reduce astigmatic correction; if necessary lens repositioning should occur as early as possible prior to lens
encapsulation. All viscoelastics should be removed from both the anterior and posterior sides of the lens; residual viscoelastics
may allow the lens to rotate.
Optical theory suggests that high astigmatic patients (i.e. > 2.5 D) may experience spatial distortions. Possible toric IOL related
factors may include residual cylindrical error or axis misalignments. Prior to surgery, physicians should provide prospective
patients with a copy of the Patient Information Brochure available from Alcon for this product informing them of possible risks
DQGEHQHWVDVVRFLDWHGZLWKWKH$FU\6RI® IQ Toric Cylinder Power IOLs.
6WXGLHVKDYHVKRZQWKDWFRORUYLVLRQGLVFULPLQDWLRQLVQRWDGYHUVHO\DHFWHGLQLQGLYLGXDOVZLWKWKH$FU\6RI® Natural IOL and
QRUPDOFRORUYLVLRQ7KHHHFWRQYLVLRQRIWKH$FU\6RI® Natural IOL in subjects with hereditary color vision defects and acquired
color vision defects secondary to ocular disease (e.g., glaucoma, diabetic retinopathy, chronic uveitis, and other retinal or optic
nerve diseases) has not been studied. Do not resterilize; do not store over 45° C; use only sterile irrigating solutions such as BSS®
or BSS PLUS® Sterile Intraocular Irrigating Solutions.
ATTENTION:
Reference the Directions for Use labeling for a complete listing of indications, warnings and precautions.
REFERENCES:
/DQGHUV-$7DPEO\Q'3HUULDP'(HFWRIDEOXHOLJKWEORFNLQJLQWUDRFXODUOHQVRQWKHTXDOLW\RIVOHHS
J Cataract Refract Surg. 35(1):83–88.
©2015 Novartis 03/15 ACR14039MS
APRIL 15, 2015 :: Ophthalmology Times
surgery
to increase in the non-dominant eye. The
inlay is implanted under a corneal flap created by a femtosecond laser.
Study of this inlay is still in its infancy:
> A small study of the inlay was undertaken by Jose Guell, MD, and associates
in which 38 patients aged 45 to 56 years
who received the implant in their nondominant eye. Most of the subjects did
not need glasses to perform intermediate
tasks, such as when reading a computer
screen. All had 20/25 or better distance vision in both eyes. In this study, the only adverse effect was the need for repositioning
of one inlay.
> Another study (Chayet et al. J Cataract Refract Surg. 2013;39:1713-1721) of 16 patients with hyperopia found that as early as
1 day after implantation, the uncorrected
near visual acuity significantly improved
in the implanted eyes compared with
preoperatively.
The uncorrected distance visual acuity
also improved significantly and remained
stable out to the 12-month visit.
FLEXIVUE MICROLENS
This device is made of a hydrophilic polymer (hydroxyethylmethacrylate and meth-
ylmethacrylate), is 3 mm in diameter, and
only 20 μm thick at the edges. The microlens is designed to change the refractive
power in the center of the cornea to facilitate near visual function. The device is implanted using an injector roughly 300 μm
deep into a corneal pocket created using a
femtosecond laser.
In a study of 47 patients with emmetropia, Limnopoulou et al. (J Refract Surg.
2013; 29:12-28) reported that 1 year after implantation of the microlens, the mean uncorrected near vision had improved significantly compared with preoperatively.
The mean uncorrected distance vision decreased significantly following implantation
in the eye that received the implant, but the
binocular distance vision did not change
substantially.
COR NE A L ONL AYS
The synthetic corneal onlay differs from inlays because it is implanted in a pocket in
the outer corneal tissue rather than under a
flap.
The procedure—which is adjustable and
reversible—is minimally invasive to the
central optical zone. The epithelium in the
central cornea is debrided and the lenticule
is placed on the exposed stroma where the
pocket maintains the position of the onlay.
This pocket then holds the onlay in place
19
until the disturbed epithelial cells grow
back to cover the device.
The device is comprised of a genetically
engineered material resembling collagen.
Currently, the microlens has not been
tested in humans, only experimentally. In
a study in which the device was implanted
in cats, the investigators found that the
epithelium began to regrow as soon as 1
to 2 days after implantation and after 5
to 11 days full epithelialization had taken
place (Evans et al. Invest Ophthalmol Vis
Sci. 2002;43:3196-3201). This onlay has
been on hold because of other competing
technologies.
The future of presbyopic correcting inlays is very strong. The promise of having
excellent near vision independent of lens
replacement is soon to be a reality.
In addition, the competing technologies
will allow the best results as choices for surgeons for their patients. ■
EHSAN “ETHAN” SADRI, MD, FACS
E: [email protected]
Dr. Sadri is in private practice in Newport Beach, CA. Dr. Sadri is
a consultant for AcuFocus.
Making the move to MIGS in practice
By Cheryl Guttman Krader
BOS TON ::
WHEN WEIGHING the decision to adopt
minimally invasive glaucoma surgery (MIGS)
into their practice, several advantages may support surgeons’ rationale, according to Richard
A. Lewis, MD.
“MIGS, defined as a minimally invasive procedure performed through an ab interno incision, is changing how we manage glaucoma,”
said Dr. Lewis, a glaucoma specialist in private practice, Sacramento, CA.
“We know that glaucoma is a spectrum
of disease and that one procedure will not
be effective for each different type. Thus,
there is a need for different approaches to
manage the range of conditions glaucoma
represents, and MIGS is the first effort to be
more specific.”
Explaining the advantages of MIGS, Dr.
Lewis said it fits with an evolving truism
for all glaucoma surgery in that it strives
for greater safety. Compared with filtering
and tube surgery, MIGS causes less tissue
trauma, has fewer complications, and allows for earlier intervention while not precluding the opportunity for other types of
glaucoma surgery.
Another major advantage of MIGS is that it
focuses on the target tissue that is the root of
the problem in Schlemms canal. In addition,
it coincides with the concept that glaucoma
is a surgical disease.
“The simplicity of treating glaucoma with
surgery and the benefit of having a surgical
cure as an alternative to a lifetime of medical
treatment with its issues of compliance, cost,
and side effects cannot be denied. If we had a
surgical procedure that was safe and simple,
I don’t believe anyone would opt not to use
it,” Dr. Lewis said.
“Up until the present, the safety element
has been the missing factor in an acceptable
surgical solution.”
In order to understand the procedure and
develop skills, Dr. Lewis said surgeons need
to read about it, take training courses, consult with experienced colleagues, and practice. He recommended watching videos of
their own procedures and those performed
by other surgeons, learning from differences in technique and their colleagues’ approaches for managing complications. In addition, he emphasized making education an
ongoing process. ■
20
APRIL 15, 2015 :: Ophthalmology Times
surgery
Transepithelial surface ablation
Clinical experience in myopic eyes with or without astigmatism
By Dr Amir Hamid, FRCOphth, CertLRS, Dr Sajjad Mughal, FRCS, CertLRS and Arif Sokwala, BSc;
Special from Ophthalmology Times Europe
TAKE-HOME
PRK has been an established method
for laser vision correction for nearly
30 years, however, its popularity has
reduced somewhat due to the advent
of LASIK. With a recent renewed
interest in surface ablation techniques
some modifications have been made
to alleviate disadvantages of the
procedure. In this article, the authors
highlight their clinical experience of
TESA in myopic eyes with or without
astigmatism.
P
hotorefractive keratectomy has
been an established method for
laser vision correction for nearly
30 years.1,2 Its popularity amongst
both patients and surgeons has
reduced since the advent of laser-assisted in situ keratomile-
usis (LASIK).
However, there has been a renewed interest
in surface ablation as a method for correcting refractive errors due to the advantages of
maintaining corneal biomechanical strength
and elimination of flap-related complications
and optimization of the methods for epithelial removal.
The disadvantages of surface ablations have
traditionally been postoperative pain, delayed
epithelial healing and stromal haze. Modifications to PRK have been introduced to alleviate
these issues. The key area that has been addressed in this respect is that of epithelial removal prior to excimer laser ablation. Ethanol
has commonly been used as an alternative to
mechanical debridement with preservation of
the epithelial flap. An even more recent development is Transepithelial PRK (t-PRK) where
epithelial removal is performed via laser phototherapeutic keratectomy (PTK) either through
a two step or single step process.
E P I T H E L I A L R E M OVA L
W ITH SUR FACE A BL ATION
(T W O S T E P V S S I N G L E S T E P)
T-PRK (2 STEP METHOD)
Several studies have looked at the results of
2-step surgery using older generation broad
beam laser systems in comparison to ethanol assisted PRK.3-5 The results of two studies4.5 demonstrated better outcomes but in one
there were overcorrections.3 In these studies
the epithelium was ablated using a broad beam
(even) PTK profile. A PTK treatment was initially performed to ablate the epithelium followed by a PRK procedure for correction of
refractive error.
TRANSEPITHELIAL SURFACE ABLATION (TESA)
(1 STEP METHOD)
The Schwind Amaris excimer laser (Schwind
eye-tech-solutions, Kleinostheim, Germany)
achieves epithelial and stromal ablation in a
single uninterrupted step that consists of uniform precise epithelial removal followed by
stromal ablation.
TESA differs from the earlier two-step methods by using a customized epithelial profile
derived from population based high frequency
digital ultrasonography. These studies demonstrated that the corneal epithelium is thicker in
the periphery.6 This customized profile ablates
55 um centrally and 65 um peripherally for a
typical 8 mm total ablation zone. There is a
further compensation for differential ablation
between epithelium and stroma. Furthermore,
TESA will also compensate for the phenomena
of ‘epithelial masking’ in areas of stromal irregularity to achieve smoother ablations.
V ISUA L OUTCOMES
O F S I N G L E S T E P T- P R K / T E S A
Fadlallah et al.7 found the visual outcomes
comparable between single step t-PRK and a
conventional alcohol-assisted PRK group. The
postoperative mean sphere and mean astigmatism in the single step t-PRK group was -0.21
± 0.61 and +0.43 ± 0.62 respectively. There
was significantly less postoperative pain and
rapid complete epithelial healing in the single
step t-PRK group. Uncorrected distance visual
acuity (UDVA) was not significantly different
between the two groups at 3 months. Postoperative corneal haze can also occur after
PRK and their study found at postoperative
3 months, 10% of eyes in the single step t-PRK
group had grade 1 haze compared to 26% in
the alcohol-assisted PRK group.
Aslanides et al.8 found both single step t-PRK
and the alcohol-assisted PRK groups to have
safe outcomes. Their primary finding was that
in the single step t-PRK group, patients had less
early postoperative pain and photophobia on
the third postoperative day with rapid epithelialization. Patients in this group also had better vision by 3 Snellen lines on this day. Corneal haze was significantly less at 1, 3 and 6
months (0.2 versus 0.43) but by year 1 there
was no haze present in both groups. At postoperative 1-month, there was no significant
difference in the unaided Snellen visual acuity
(0.94 versus 0.97). Similarly, Fadlallah et al.7
also found no significant difference in visual
acuity between the 2 groups at the 1 month
and 3 month postoperative periods.
Luger et al.9 found that between the single
step t-PRK group and an alcohol-assisted PRK,
the postoperative mean spherical equivalent
(SE) 1 year after surgery was +0.07 D ± 0.23
and +0.01 D ± 0.27 respectively and 97% of
eyes in both groups achieved an UDVA of 0.1
logMAR or better.
T E S A : OU R R E SU LT S
We recently presented our unpublished clinical
results at the 15th International Schwind Users
Meeting 2014 in Vancouver, Canada,9 and at
the XXXII Congress of the ESCRS 2014 in London.10 In our retrospective analysis of patients
treated in our Optimax Laser Eye Clinics in
UK by five surgeons, 399 eyes underwent single-step laser epithelial removal and stromal
ablation using the transepithelial PRK nomogram of the Amaris laser’s ORK-CAM software
(Schwind eye-tech-solutions).
All eyes underwent ablation with an Aberration-Free algorithm with the Schwind Amaris at a repetition rate of 750 Hz pulse with
1050 Hz eye tracking. The laser ablation was
centred on the pupillary axis. The intended refractive aim for all eyes was emmetropia and
there were no retreatments included. Adjunct
mitomycin C was not used in any patient.
The preoperative manifest SE was –3.88 ±
1.47 D (range: –1.25 to –8.00 D). At 1 month the
Continues on page 22 : Ablation
22
APRIL 15, 2015 :: Ophthalmology Times
surgery
ABLATION
( Continued from page 20 )
postoperative manifest SE was reduced to –0.20 ± 0.53 D (range:
–4.88 to 1.88) and at 3 months it
was –0.17 ± 0.18 D (range: 0.88
to –1.25 D). The manifest SE was
within 0.50 D and 1.00 D of emmetropia in 89% and 99% of eyes,
respectively. At 3 months, the preoperative manifest sphere was reduced from –3.58 ± 1.44 D (range:
–0.50 to –7.75 D) to –0.05 ± 0.33 D
(range: +1.25 to –1.00 D) and the
preoperative manifest astigmatism was reduced from –0.60 ±
0.53 (range: 0 to –3.50 D) to –0.25
± 0.25 D (range: 0 to –1.75 D).
UDVA of 20/25, 20/20 and 20/16
or better was achieved in 20%,
45% and 24% of 399 eyes, respectively. A gain of 1 or more lines
was observed in 25% of eyes.
Postoperative corneal haze of ≥1.5
was observed in 2% of eyes only.
TESA IN SUMMARY
TESA is effective at producing
very safe and predictable visual
outcomes for mild to moderate
simple myopia or compound myopic astigmatism. We have also
been able to demonstrate refractive stability and safety (clinically significant corneal haze is
uncommon).
The role of the corneal epithelium as a smoothing agent in relation to any underlying stromal
topographical irregularity allows
transmission of the smoothness
of the aspheric ablation profile
to the underlying stroma. This
yields more predictable refractive results and less induction
of clinically significant corneal
aberrations.
When t-PRK/TESA is used
instead of ethanol assisted PRK
there is the theoretical benefits
of reduced postoperative dry eye,
chronic ocular surface disease
and recurrent corneal erosions.
This is due to the reduced levels
of keratocyte apoptosis and hence
reduced generation of proinflam-
matory mediators.11,12 This may
also explain the lower levels of
postoperative pain reported and
more rapid epithelial healing.8
TESA represents an effective
new method of surface ablation
which is safe, predictable, stable
and effective. Intraoperatively it
is a very easy experience for a patient to undergo as it is painless,
no touch technique (bladeless). ■
References
1. J. Marshall et al., Lasers
Ophthalmol., 1986;21–48.
2. S.L. Trokel, R. Srinivasan and
B. Braren, Am. J. Ophthalmol.,
1983;96(6):710–715.
3. H.K. Lee et al., Am. J. Ophthalmol.,
2005;139:56–63.
4. F. Ghadhfan, A. Al-Rajhi and M.D.
Wagoner, J. Cataract Refract.
Surg., 2007;33:2041–2048.
5. L. Buzzonetti et al., J. Refract.
Surg., 2009;25:S122–S124.
6. D.Z. Reinstein et al., J. Refract.
Surg., 2008;24:571–581.
7. A. Fadlallah et al., J. Cataract
Refract. Surg.,
2011;37:1852–1857
8. I.M. Aslanides et al., Clin.
Ophhalmol., 2012;67:973–980
9. http://www.eye-tech-solutions.
com/en/home/information-centre/
events/ (S. Mughal et al.)
10. http://www.escrs.org/london2014/
programme/free-papers-details.
asp?id=21925 (S. Mughal et al.)
11. W.-J. Kim, S. Shah and S.E. Wilson,
J. Refract. Surg., 1998;14:526–
533.
12. J.Y. Oh, J.M. Yu and J.H. Ko,
Invest. Ophthalmol. Vis. Sci.,
2013;54(6):3852–3856.
DR AMIR HAMID, FRCOPHTH, CERTLRS
E: [email protected]
Dr. Hamid is Consultant Ophthalmic Surgeon and Medical
Director at Optimax and Ultralase, London, UK.
DR SAJJAD MUGHAL, FRCS, CERTLRS
Dr. Mughal is a Corneal Laser Surgeon at Optimax and
Ultralase, Birmingham, UK.
ARIF SOKWALA, BSC
Sokwala is Head Optometrist at Optimax and Ultralase,
Leicester, UK.
The authors have no financial interests to disclose.
APRIL 15, 2015 :: Ophthalmology Times
drug therapy
Retinal gene therapy moving
closer to clinical reality
Developments have potentially lifelong benefits after single therapeutic administration
By Jeffrey D. Chulay, MD, Special to Ophthalmology Times
AL ACHUA, F L ::
enes encode proteins that perform an array of functions.
Many diseases have a genetic
aspect whereby a mutated gene
is passed down from generation to generation. Mutated
genes may encode abnormal
proteins or disable the production of a protein
completely, either of which can cause disease.
Gene therapy introduces a functional copy
of the gene into a patient’s own cells. By correcting the underlying genetic defect that
causes disease, gene therapy can potentially
provide lifelong clinical benefits after a single
administration.
G
A DENO -AS SOCI AT ED V IRUSE S
Gene therapy uses viral vectors to deliver genes
into cells affected by disease. Viral vectors have
been optimized for this purpose by removing
pathogenic elements and severely impairing
the viruses’ ability to replicate.
Adeno-associated virus (AAV) vectors are
well suited for treating retinal diseases. AAV is
a small, simple, non-enveloped virus with only
two native genes, making the virus straightforward to work with from a vector-engineering standpoint. AAV vectors can carry gene
sequences up to 4,000 base pairs in length.1
More than 90% of human genes have coding
sequences less than 3,000 base pairs in length.
AAV vectors have been used in more than
100 human clinical trials with no serious adverse events traced to the use of AAV as the
gene delivery vector and are considered to be
the safest viral vector for use in human gene
therapy. AAV has never been linked to human
disease and elicits only a mild immune response.
AAV vectors have no viral genes remaining,
virtually eliminating the possibility that any
viral genes will cause an adverse event.1
AAV vectors can now be produced at a commercial scale in compliance with current Good
Manufacturing Practice for use in clinical trials and future marketed products. As many
as 2.4 x 1014 vector copies per liter have been
(FIGURE 1) X-linked retinoschisis (XLRS) is an inherited retinal disease associated with splitting of the
retinal layers and caused by mutations in the RS1 gene, which encodes the retinoschisin protein
produced, with batches up to 100 liters, using
the latest advances in large-scale viral vector
production technology.2
Studies have confirmed that the purification
process eliminates all but a trace amount of
the raw materials used during manufacture,
in many cases below assay detection levels.3
GENE THER APIES
FOR RETINAL DISEASES
Leber congenital amaurosis (LCA) is an inherited, early-onset retinal degenerative disease caused by mutations in any one of 16
genes. One form is caused by mutations in
the RPE65 gene. The safety of AAV vector expressing RPE65 is supported by multiple phase
I clinical trials.4-6
The safety and efficacy of RPE65 gene therapy for LCA continues to be evaluated in ongoing clinical trials including a phase III study.
Wet age-related macular degeneration (AMD)
is a major cause of visual impairment in older
adults that is associated with neovascularization and macular edema. Current standard of
care is intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors that
must be administered monthly or bimonthly.
An emerging wet AMD gene therapy approach
uses an AAV vector to deliver the sFLT01 gene
into retinal cells. The sFLT01 gene is an engineered version of the VEGF receptor that binds
and inhibits VEGF ligand.7
The safety and tolerability of sFLT01 gene
therapy for wet AMD is under investigation
in an active phase I trial. Other AMD gene
therapy programs include an active phase I/
II trial evaluating the safety of an AAV vector expressing the naturally occurring VEGF
decoy receptor sFlt-1, and an active phase I
trial evaluating the safety of a lentiviral vector
expressing the anti-angiogenic proteins endostatin and angiostatin.
Choroideremia is an inherited X-linked degenerative disease of the retina and choroid
caused by mutations in the CHM gene. An ongoing phase I/II clinical trial reported promising 6-month findings with an AAV vector expressing the CHM gene.8Recruitment for a second phase I/II trial has recently commenced.
X-linked retinoschisis (XLRS) is an inherited retinal disease associated with splitting
of the retinal layers and caused by mutations
in the RS1 gene, which encodes the retinoschisin protein (Figure 1).
Two phase I/II trials are planned to evaluate safety and tolerability of AAV vectors expressing RS1 (Figure 2 on Page 24).
One trial is currently recruiting and the
other is scheduled to start recruitment in the
first half of 2015.
Stargardt disease is an inherited retinal dysContinues on page 24 : Gene therapy
23
24
APRIL 15, 2015 :: Ophthalmology Times
drug therapy
GENE THERAPY
Preclinical evaluations of gene
therapy for color vision deficiencies, including BCM, are ongoing.
( Continued from page 23 )
trophy characterized by photoreceptor degeneration in the macula. Most cases are caused
by mutations in the ABCA4 gene.9Patients are
currently being enrolled in a phase I/II trial
that will evaluate the safety and tolerability of
a lentiviral vector expressing the ABCA4 gene.
Usher syndrome type 1 is an inherited disease associated with congenital deafness and
early-onset photoreceptor loss. About half of
Usher type 1 cases are caused by mutations in
the MYO7A gene (type 1B). Patients are currently being enrolled in a phase I/II trial that
will evaluate the safety and tolerability of a
lentiviral vector expressing the MYO7A gene.
Leber hereditary optic neuropathy (LHON)
is a maternally inherited disorder characterized by loss of retinal ganglion cells and optic
nerve atrophy. Nearly all cases are caused by
mutations in any one of three mitochondrial
genes (ND1, ND4, and ND6). About half of
LHON cases are caused by the same mutation
in the ND4 gene.10,11
Recruitment is ongoing for two phase I trials that will evaluate the safety and tolerability of AAV vectors expressing the ND4 gene.
Achromatopsia is an inherited retinal disease
characterized by lack of cone photoreceptor
function. The most common causes are mutations in the CNGA3 and CNGB3 genes. A preclinical study in dog models of achromatopsia
with CNGB3 mutations showed restoration of
cone function and improved ability to navigate
mazes under bright light conditions after treatment with AAV vector expressing CNGB3.12
Clinical gene therapy programs to develop
treatments for CNGB3 and CNGA3 mutations
are under way.
Retinitis pigmentosa is an inherited retinal
dystrophy associated with progressive vision
loss. In the United States about 10 to 15% of
retinitis pigmentosa cases are X-linked (XLRP)
and three-fourths of these cases are caused by
mutations in the RPGR gene. Studies in dog
models of XLRP with RPGR mutations showed
delayed disease progression after treatment
with AAV vector expressing RPGR.13Preclinical
evaluation is ongoing.
Blue cone monochromacy (BCM) is an inherited color vision deficiency characterized
by lack of functional long-wavelength (L) and
medium-wavelength (M) cone photoreceptors.
BCM is caused by mutations in an area of the
X chromosome that regulates expression of
the L and M opsin genes.14
FUTURE OUTLOOK
The once theoretical promise of gene
therapy is evolving into clinical reality. Gene therapy can provide transformative disease-modifying effects
by correcting the underlying defect
that causes disease, potentially with
lifelong clinical benefits after a single administration.
An additional advancement in the
treatment of retinal degeneration is
an approach that delivers a lightsensitive protein to neurons in the
retina. One such light-sensitive protein is channelrhodopsin 2. When
channelrhodopsin 2 is inserted into
a neuron and the neuron is stimulated by light, the neuron is activated and can transmit a signal to
(FIGURE 2) Two phase I/II trials are planned to evaluate safety
and tolerability of AAV vectors expressing RS1.
the visual cortex.
(Figures courtesy of Mark Pennesi)
This technique, called optogenetics, is being applied to the design of
therapeutic genes that can be exchimeric molecules delivered by AAV vectors for
pressed by AAV vectors for the treatment of
inhibition of retinal neovascularization. Gene Ther.
2009;16:10-16.
advanced retinal degeneration.15
8. MacLaren RE, Groppe M, Barnard AR, et al. Retinal
The current status of preclinical and clinigene therapy in patients with choroideremia: initial
cal evaluation supports continued investment
findings from a phase 1/2 clinical trial. Lancet.
in the development of AAV-based gene thera2014;383:1129-1137.
pies for retinal diseases, with ongoing research
9. Testa F, Melillo P, Di Iorio V, et al. Macular function
and morphologic features in juvenile stargardt
bringing these treatments closer to the clinic.
References
1. Le Bec C and Douar AM. Gene therapy progress
and prospects–vectorology: design and production
of expression cassettes in AAV vectors. Gene Ther.
2006;13:805-813.
2. Thomas DL, Wang L, Niamke J, et al. Scalable
recombinant adeno-associated virus production using
recombinant herpes simplex virus type 1 coinfection
of suspension-adapted mammalian cells. Hum Gene
Ther. 2009;20:861-870.
3. Ye GJ, Scotti MM, Thomas DL, Wang L, Knop DR and
Chulay JD. Herpes Simplex Virus Clearance During
Purification of a Recombinant Adeno-Associated
Virus Serotype 1 Vector. Hum Gene Ther Clin Dev.
2014;25:212-217.
4. Bainbridge JW, Smith AJ, Barker SS, et al. Effect of
gene therapy on visual function in Leber's congenital
amaurosis. N Engl J Med. 2008;358:2231-2239.
5. Jacobson SG, Cideciyan AV, Ratnakaram R, et
al. Gene therapy for leber congenital amaurosis
caused by RPE65 mutations: safety and efficacy in
15 children and adults followed up to 3 years. Arch
Ophthalmol. 2012;130:9-24.
6. Testa F, Maguire AM, Rossi S, et al. Three-year
follow-up after unilateral subretinal delivery of adenoassociated virus in patients with Leber congenital
Amaurosis type 2. Ophthalmology. 2013;120:12831291.
7. Pechan P, Rubin H, Lukason M, et al. Novel anti-VEGF
10.
11.
12.
13.
14.
15.
disease: longitudinal study. Ophthalmology.
2014;121:2399-2405.
Gueven N and Faldu D. Therapeutic strategies for
Leber's hereditary optic neuropathy: A current
update. Intractable Rare Dis Res. 2013;2:130-135.
Lam BL, Feuer WJ, Abukhalil F, Porciatti V, Hauswirth
WW and Guy J. Leber hereditary optic neuropathy
gene therapy clinical trial recruitment: year 1. Arch
Ophthalmol. 2010;128:1129-1135.
Komaromy AM, Alexander JJ, Rowlan JS, et al.
Gene therapy rescues cone function in congenital
achromatopsia. Hum Mol Genet. 2010;19:2581-2593.
Beltran WA, Cideciyan AV, Lewin AS, et al. Gene
therapy rescues photoreceptor blindness in dogs
and paves the way for treating human X-linked
retinitis pigmentosa. Proc Natl Acad Sci U S A.
2012;109:2132-2137.
Gardner JC, Michaelides M, Holder GE, et al. Blue
cone monochromacy: causative mutations and
associated phenotypes. Mol Vis. 2009;15:876-884.
Busskamp V, Picaud S, Sahel JA and Roska B.
Optogenetic therapy for retinitis pigmentosa. Gene
Ther. 2012;19:169-175.
JEFFREY D. CHULAY, MD, is vice president and chief medical officer at Applied
Genetic Technologies Corp. (AGTC).
The Cataract
Refractive Suite
BY ALCON
Advancing
CATARACT SURGERY
1
Talk to your Alcon representative to experience superior visualization today.
© 2015 Novartis 3/15 LUX15008JAD
$OFRQGDWDRQOH
26
APRIL 15, 2015 :: Ophthalmology Times
drug therapy
Observations may provide evidence
of systemic effect of anti-VEGF therapy
About one-half of patients had significant reduction in DME of more than 50 μm in fellow eye
By Lynda Charters; Reviewed by Lawrence J. Singerman, MD, FACS
SAN TA BARBAR A, CA ::
flibercept (Eylea, Regeneron)
administered intravitreally may
be associated with systemic effects based on an observable
reaction in the fellow eyes of
patients with diabetic macular
edema (DME), according to Robert L. Avery, MD.
The reduction in DME in the fellow eyes exceeded 50 μm in almost half of the patients,
a reduction that exceeds a routine variation.
The serum levels of three major intravitreally
administered, anti-vascular endothelial growth
factor (VEGF) drugs—ranibizumab (Lucentis, Genentech); bevacizumab (Avastin, Genentech); aflibercept—differ when measured
1 and 3 months after monthly injections. Bevacizumab was found to have the highest serum
level followed by aflibercept and ranibizumab.
“There was about a 70-fold difference in the
area under the curve with bevacizumab compared with ranibizumab regarding systemic
exposure,” said Dr. Avery, who is in private
practice in Santa Barbara, CA.
Differences of opinion exist regarding the
relevance of this finding, with some believing
that the intravitreal doses of the drugs are too
small to have a systemic effect, the good safety
profiles of the drugs negate concern, and no
fellow-eye effect has been observed.
A
FELLOW-EYE EFFECTS
However, fellow-eye effects have occurred. About
a decade previously, when bevacizumab was
used to treat proliferative vitreoretinopathy,
the new vessels on the disc in the fellow eye
stopped leaking about a week after treatment,
Dr. Avery noted. The leakage resumed 2 weeks
after treatment.
“This caused me to consider that if this is
a real effect, the doses must be much higher
than needed to cause regression of the new
vessels on the disc,” he said, and undertook
an inverse dose response curve study.
With 1/100 of the usual intravitreal dose, the
new vessels on the disc stopped leaking. He also
achieved the same effect with 1/200 of the dose.
Dr. Avery and colleagues performed a retro“A reason that a fellow-eye effect is not seen
is that the pharmacokinetics of the drug var- spective review of patients with bilateral DME.
In this study, one eye of each patient was treated
ies,” he said.
The Harbor Study reported a wide range in with 2.0 mg of aflibercept. The fellow eye had
the levels of ranibizumab at a concentration been untreated for 3 months before the start of
measured 1 month after the last injection. At the study. Investigators determined that significant effects would be a 50-μm
the time point because of the
decrease in the retinal thickness
high therapeutic level of the drug
and at least a 10% decrease in
still in patients, VEGF could be
Intravitreal
the maximal thickness seen on
inhibited.
aflibercept may be
optical coherence tomography.
Another reason that the felassociated with
The study included 25 eyes,
low-eye effect may have been
systemic effects
12 eyes of which had a signifioverlooked is that investigators
based on an
cant decrease in retinal thickare not evaluating the patients
observable reaction
ness exceeding 50 μm and 3 eyes
at the 1-week time point after
in the fellow eyes of
had an increase in the retinal
treatment when the drug levels
patients with diabetic
thickness.
are highest.
macular edema.
Compared with 19 control paHowever, a number of case
tients with DME, “not nearly the
reports have described, for exsame reduction in retinal thickample, regression of edema in
the fellow eye of a patient with uveitic cystoid ness was seen and there clearly is variability in
macular edema after ranibizumab, regressed these patients with diabetes,” Dr. Avery said.
He reported that the mean change in retinal
neovascularization of a disc in the fellow eye
after treatment, and regressed scarring in the thickness in the fellow-eye patients was 43 μm
compared with 6 μm in the control group, a
fellow eye after ranibizumab injection.
The effects of bevacizumab treatment in significant difference.
Dr. Avery demonstrated the variable effects
the fellow eye also have been reported in pain patients, with subtle fellow-eye changes aptients treated for retinopathy of prematurity.
The Comparison of AMD Treatment Trial parent as early as 1 day after treatment.
“The meaning of decreased circulating VEGF
(Ophthalmology. 2013;120:2035-2041) also hinted
at an effect of treatment in the fellow eye, ac- levels related to systemic serious adverse efcording to Dr. Avery, in that the fellow eyes fects after injection of anti-VEGF drugs is conwithout choroidal neovascularization (CNV) troversial,” he said.
“In our small study of aflibercept, about half
had a nonsignificant reduction in the incidence
of CNV when treated with bevacizumab com- the patients had a significant reduction in DME
of more than 50 μm in the fellow eye, which
pared with ranibizumab.
A mouse model also showed an effect of is beyond what is typically considered to be a
injecting bevacizumab in the fellow eye that routine variation,” Dr. Avery said. “These obwas greater than the fellow-eye effect with servations may provide evidence that there is
a systemic effect associated with intravitreal
ranibizumab.
aflibercept.” ■
VA R I A B L E E F F E C T S
Regarding DME, a large study of the felloweye effects by Bakbak and colleagues (Retina.
ROBERT L. AVERY, MD
2009;29:20-26) showed a significant decrease
E: [email protected]
in DME with bevacizumab, but not ranibiThis article was adapted from Dr. Avery’s presentation at the 2014 meeting of the
zumab, which agreed with the pharmacokiAmerican Academy of Ophthalmology. Dr. Avery is a consultant to and shareholder in
netics of the drugs, Dr. Avery noted.
Genentech and Regeneron Pharmaceuticals.
TAKE-HOME
ZYLET® (LOTEPREDNOL ETABONATE 0.5% AND TOBRAMYCIN 0.3% OPHTHALMIC SUSPENSION) TECHNICAL PAPER
1
Blepharitis Management: A Clinical Approach
John R. Favetta, MD
Blepharitis refers to a variety of eyelid conditions with multiple,
often concomitant, etiologies. Characterized by eyelid inflammation,
bacterial overgrowth or infection—or the risk of infection—is also
frequently present in blepharitis. As definitions and sub-categories of
blepharitis have changed over the years, clear-cut estimates of prevalence have
been challenging to obtain; but blepharitis is very frequently seen in ophthalmology
practices. Left untreated, the presence of blepharitis may affect the risk of infection
following ocular surgery and can limit the success of contact lens wear. A detailed
history and careful attention to the lids, lashes, and meibomian glands during the
slit lamp examination will aid in blepharitis detection and diagnosis. At a minimum,
treatment includes eyelid hygiene; and acute presentations may benefit from
combined antiinflammatory/antiinfective therapy. Combination agents can be
particularly useful in the treatment of blepharitis.
Blepharitis is a catchall term encompassing the many, often overlapping, inflammatory and infectious conditions
of the eyelids. Without a single, etiology-based definition, it has not been
possible to gain a good idea of the prevalence of blepharitis. But the conditions
that comprise blepharitis are among the
most common encountered in a comprehensive ophthalmology practice.1 Indeed,
nearly a third of the patients I see—from
young adults to seniors—present with
signs and/or symptoms of blepharitis.
It is often useful to distinguish types
of blepharitis based on anatomical location. Thus, we have anterior blepharitis,
which affects the area around the lashes
and follicles, and posterior blepharitis,
which affects the meibomian glands and
proximate tissues. In either form, multiple causative factors and disease processes may be involved; and anterior and posterior blepharitis often coexist.
Comorbidities, including chalazion
and hordeolum, conjunctivitis, keratopathy (from superficial punctate keratitis
to peripheral ulceration), and dry eye
disease may be present with blepharitis.2
Blepharitis affects a broad swath of
our patients: we see it in younger patients, who may have associated seborrheic dermatitis or acne rosacea; we see it
in contact lens wearers, and in candidates
for refractive, cataract, or other ocular
surgeries; and we see it in patients who
Sponsored by Bausch + Lomb
come in simply because they are bothered
by its symptoms. I consider it imperative
to treat even mild blepharitis, as treatment can reduce the risk of infection and
inflammation, and—of particular importance to me as a surgeon—help ensure
success for surgical candidates.
PATHOGENESIS
Anterior blepharitis is often associated with excessive bacterial growth on the
lid margins. The microbes involved are
typically the same species that normally reside there, including Staphylococcus
epidermidis and Staphylococcus aureus.2
While questions remain about the role(s)
of bacteria in blepharitis, it appears that
toxic exoenzymes produced by the colonizing species—particularly S. epidermidis—irritate the eyelids and ocular surface, causing the release of inflammatory
mediators.1
In some cases, altered meibomian
gland secretions may be an initiating factor, offering a supportive environment for
bacterial proliferation.3 But bacteria can
INDICATIONS AND USAGE
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 coagulase-negative), 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.
IMPORTANT RISK INFORMATION
ZYLET 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.
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 sued for 10
days or longer, intraocular pressure should be monitored.
Use of corticosteroids may result in posterior subcapsular cataract formation.
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.
Prolonged use of corticosteroids may suppress the host response 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.
Employment of 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 exacerbate the severity of many viral infections of
the eye (including herpes simplex).
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.
ADVERSE REACTIONS
Most common adverse reactions reported in patients were injection and superficial punctate keratitis, increased
intraocular pressure, burning and stinging upon instillation.
Please see the full prescribing information for ZYLET® on pages 3 and 4.
ZYLET® (LOTEPREDNOL ETABONATE 0.5% AND TOBRAMYCIN 0.3% OPHTHALMIC SUSPENSION) TECHNICAL PAPER
2
also alter ocular surface lipids. For example, lipolytic staphylococcal enzymes
break down the wax and sterol esters in
the tear film; and the release of irritating
breakdown products, including free fatty acids, as well as the resulting tear film
instability, contribute to inflammation of
the lid margin and conjunctiva.2
A number of potential non-microbial
factors (eg, age and hormonal changes,
medication use) can contribute to the
changes in meibum quality and the ductal keratinization that underlies posterior blepharitis.3 Obstructive meibomian
gland dysfunction (MGD) may not be
inflammatory in its early stages, but the
tear film changes (instability and hyperosmolarity), ocular surface irritation, increased ductal pressure, and bacterial involvement all contribute to inflammation
and frank posterior blepharitis.3
blepharitis may report discomfort and
significantly reduced wearing time.
A close look at the lids forms a key
part of the examination. Patients with
anterior blepharitis often have reddened,
swollen lids, telangiectasia, and debris or
collarettes along the lashes. In addition,
the tear meniscus may be foamy, a result
of bacterial lipases causing breakdown of
the meibomian lipids. In posterior blepharitis, we often see plugged, pouting meibomian glands that yield turbid, viscous
meibum—or no meibum at all. Diagnostic
gland expression is helpful in evaluating
and grading a patient’s underlying MGD.
Again, because either anterior or posterior blepharitis can affect the ocular
surface, corneal and conjunctival staining
with lissamine green, rose bengal, or fluorescein can help identify tissue changes
indicative of blepharoconjunctivitis or
blepharokeratoconjunctivitis.
DIAGNOSIS
In blepharitis diagnosis, history is paramount. Questioning patients about their
ocular symptoms throughout the day can
be very revealing: when patients describe
stickiness and burning upon waking,
with improvement through the day and a
worsening in the evening, I know to look
closely for signs of posterior blepharitis
on my examination.
Patients with anterior blepharitis report a gamut of symptoms. Some patients
have red and swollen lids; others complain of irritation and burning. Contact
lens wearers with anterior or posterior
TREATMENT
Eyelid hygiene is a mainstay of my
treatment regimen for virtually every
stage and subtype of blepharitis. Cleaning the crust, keratinized tissue, and bacteria and bacterial byproducts off the lid
margin removes some contributors to the
condition. I recommend any of several
commercially available lid cleansing pads
for my patients, giving a brief demonstration of their use in the office.
For patients with posterior blepharitis, especially, I also add a hot compress
and massage step to follow the cleans-
CASE STUDY: PREOPERATIVE BLEPHARITIS
A 65-year-old male patient presented to our clinic complaining of decreased vision, which upon
examination was attributable to cataract. The patient was motivated to undergo surgery, but
because the examination also revealed significant lid swelling, telangiectasia, and inspissated
meibomian glands, I opted to delay the operation in order to address his blepharitis.
I explained to the patient that treating his inflamed and possibly infected eyelids was
important prior to undergoing ocular surgery. I believe that we have the best chance for a
good surgical result when the lids and ocular surface are healthy at the outset.
In addition to a routine of eyelid hygiene and warm compresses, I prescribed ZYLET® four
times a day for 2 weeks. When the patient returned, his IOP was normal and the redness
and edema of his lid margins had greatly decreased. In my opinion, the patient responded to
ZYLET® therapy.
At this point, I felt comfortable scheduling the patient for surgery—but I did make clear to
him that blepharitis is a chronic condition; and that while his blepharitis was under control at
the moment, he would need to continue regular eyelid hygiene and warm compresses, and
to return to our office in the event of a significant flare-up.
Sponsored by Bausch + Lomb
ing scrub; an omega-3 fatty acid dietary
supplement may also be part of the regimen.4,5 Lid hygiene may be performed
once or twice a day; in cases where I add
a topical pharmaceutical agent, I tell patients to instill their final dose of drug after performing their bedtime lid cleaning
and warm compresses.
Because blepharitis is often chronic
and recurring, I emphasize to patients
that even after we bring their acute condition under control, continued eyelid
hygiene and warm compresses will help
them maintain a healthy ocular surface.
PHARMACOLOGIC INTERVENTION
Lid hygiene alone is often insufficient
to bring the coexisting and mutually-reinforcing inflammatory and infectious
aspects of blepharitis under control. Topical corticosteroids, powerful inhibitors
of inflammation, can be extremely useful for treating the acutely inflammed lid
margin and ocular surface. The risks associated with corticosteroid use—particularly increased intraocular pressure (IOP)
and cataractogenesis—are important
considerations when selecting an agent
and determining the duration of therapy.
In many cases, the presence of bacterial overgrowth and the risk of superficial
ocular infection also warrant the use of
an antibiotic in treating blepharitis.6 A
combination antibiotic/steroid agent is
therefore well suited to address both the
inflammatory and the potentially infectious components of this condition.
My agent of choice for treating blepharitis is ZYLET® (loteprednol etabonate
and tobramycin ophthalmic suspension
0.5%/0.3%). The steroid component, loteprednol etabonate 0.5%, is one key reason I favor ZYLET® in the treatment of
blepharitis.
Loteprednol etabonate combines antiinflammatory potency with an established safety profile.6,7 The loteprednol
etabonate molecule contains an ester
group in place of a ketone at the C-20
position. In the eye, the drug undergoes
predictable hydrolysis into inactive metabolites, which is thought to contribute
to its safety profile.6,7
Tobramycin, the antibiotic in ZYLET®,
is broadly effective against common ocular pathogens, including the staphylococci often implicated in blepharitis.6,8
Please see Important Risk Information on page 1 and the full prescribing information for ZYLET® on pages 3 and 4.
ZYLET® (LOTEPREDNOL ETABONATE 0.5% AND TOBRAMYCIN 0.3% OPHTHALMIC SUSPENSION) TECHNICAL PAPER
I typically prescribe ZYLET® QID for
10 to 14 days, depending on severity. To
this I add eyelid hygiene and, where applicable, warm compresses and omega-3
supplements. I bring patients back within
about 10 days to evaluate sign and symptom resolution and to check IOP. When I
prescribe ZYLET® for blepharitis, I emphasize to patients that it is intended as shortterm therapy only, and that long-term
continuation of eyelid hygiene should
help reduce the likelihood of recurrence.
CONCLUSION
Paying close attention to the lid margins
can be beneficial for patients and practitioners. Neither a pristine surgical outcome
nor successful contact lens wear is likely
without a healthy ocular surface. Indeed, I
have postponed surgeries for patients who
present with significant blepharitis. To help
get the acute inflammation and bacterial
overgrowth of blepharitis under control,
treatment with ZYLET® can be important.
John R. Favetta, MD, practices in North
Arlington, NJ.
Please see Important Risk Information on page 1
and the full prescribing information for ZYLET® on
this page and the next.
REFERENCES
1. Lemp MA, Nichols KK. Blepharitis in the Unites
States 2009: A survey-based perspective on
prevalence and treatment. Ocul Surf. 2009;7(2)
Suppl:A1-A22.
2. Jackson WB. Blepharitis: current strategies for
diagnosis and management. Can J Ophthalmol.
2008;43:170-9.
3. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis
Sci. 2011;52(4):1922-9.
4. Macsai MS. The role of omega-3 dietary supplementation in blepharitis and meibomian gland
dysfunction (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:336-56.
5. Olenik A, Jimenez-Alfaro I, Alejandre-Alba
N, Mahillo-Fernandez I. A randomized, double-masked study to evaluate the effect of omega-3
fatty acids supplementation in meibomian gland
dysfunction. Clin Interv Aging. 2013;8:1133-8.
6. Comstock TL, Holland EJ. Loteprednol and tobramycin in combination: a review of their impact on
current treatment regimens. Expert Opin Pharmacother. 2010;11(5):843-50.
7. Chen M, Gong L, Sun X, et al. A multicenter,
randomized, parallel-group, clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of
Chinese patients with blepharokeratoconjunctivitis. Curr Med Res Opin. 2012;28(3):385-94.
8. Zylet (loteprednol etabonate and tobramycin ophthalmic suspension 0.5%/0.3%) prescribing information. Tampa, FL: Bausch & Lomb, Inc; 2013.
Sponsored by Bausch + Lomb
®
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to
use ZYLET® (loteprednol etabonate and tobramycin ophthalmic
suspension) safely and effectively. See full prescribing information for ZYLET (loteprednol etabonate and tobramycin ophthalmic
suspension, 0.5%/0.3%).
Zylet (loteprednol etabonate and tobramycin ophthalmic suspension)
0.5%/0.3%
Initial U.S. Approval: 2004
- - - -- - - -- - - -- - - -- INDICATIONS AND USAGE - - - -- - - -- - - -- - - -Zylet is a topical anti-infective and steroid combination for steroidresponsive inflammatory ocular conditions for which a corticosteroid
is indicated and where superficial bacterial ocular infection or a risk
of bacterial ocular infection exists. (1)
- - - -- - - -- - - -- - DOSAGE AND ADMINISTRATION- -- - - -- - - -- - - -Apply one or two drops of Zylet into the conjunctival sac of the
affected eye every four to six hours. (2.1)
- - - -- - - -- - - -- - DOSAGE FORMS AND STRENGTHS -- - - -- - - -- - - -Zylet contains 5 mg/mL loteprednol etabonate and 3 mg/mL
tobramycin. (3)
- - - -- - - -- - - -- - - -- - CONTRAINDICATIONS -- - - -- - - -- - - -- - - -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. (4.1)
- - - -- - - -- - - -- - -WARNINGS AND PRECAUTIONS - -- - - -- - - -- - - -D7=;*8,>5*;9;.<<>;. !!;85870.-><.8/,8;=2,8<=.;82-<6*B
result in glaucoma with damage to the optic nerve, defects in visual
*,>2=B*7-/2.5-<8/?2<287/=12<9;8->,=2<><.-/8;
-*B<8;
5870.; !<18>5-+.6872=8;.-
D*=*;*,=<%<.8/,8;=2,8<=.;82-<6*B;.<>5=2798<=.;28;<>+,*9<>5*;
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
".,866.7-.-8<270
!;.<,;29=287>2-.527.
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
87+*,=.;2*5=28580B
5 WARNINGS AND PRECAUTIONS
7=;*8,>5*;!;.<<>;. !7,;.*<.
*=*;*,=<
.5*B.-.*5270
*,=.;2*57/.,=287<
&2;*57/.,=287<
>70*57/.,=287<
627805B,8<2-.B9.;<.7<2=2?2=B
3
cataract formation. (5.2)
D.5*B.-1.*5270F$1.><.8/<=.;82-<*/=.;,*=*;*,=<>;0.;B6*B
-.5*B1.*5270*7-27,;.*<.=1.27,2-.7,.8/+5.+/8;6*=2877=18<.
diseases causing thinning of the cornea or sclera, perforations have
+..7478@7=88,,>;@2=1=1.><.8/=892,*5<=.;82-<$1.272=2*5
prescription and renewal of the medication order should be made
by a physician only after examination of the patient with the aid
of a magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. (5.3)
D*,=.;2*527/.,=287<F!;85870.-><.8/,8;=2,8<=.;82-<6*B<>99;.<<
the host response and thus increase the hazard of secondary ocular
27/.,=2877*,>=.9>;>5.7=,87-2=287<<=.;82-<6*B6*<427/.,=287
8;.71*7,..A2<=27027/.,=287/<207<*7-<B69=86</*25=8269;8?.
after 2 days, the patient should be re-evaluated. (5.4)
D&2;*527/.,=287<F6958B6.7=8/*,8;=2,8<=.;82-6.-2,*=28727=1.
treatment of patients with a history of herpes simplex requires great
,*>=287%<.8/8,>5*;<=.;82-<6*B9;85870=1.,8>;<.*7-6*B
exacerbate the severity of many viral infections of the eye (including herpes simplex). (5.5)
D>70*527/.,=287<F>70*527/.,=287<8/=1.,8;7.**;.9*;=2,>5*;5B
prone to develop coincidentally with long-term local steroid applica=287>70><27?*<2876><=+.,87<2-.;.-27*7B9.;<2<=.7=,8;7.*5
ulceration where a steroid has been used or is in use. (5.6)
- - - -- - - -- - - -- - - -- - ADVERSE REACTIONS- -- - - -- - - -- - - -- - - -Most common adverse reactions reported in patients were injection
and superficial punctate keratitis, increased intraocular pressure, burning and stinging upon instillation. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb
at 1-800-323-0000 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch
See 17 for PATIENT COUNSELING INFORMATION
Revised: 08/2013
6 ADVERSE REACTIONS
8 USE IN SPECIFIC POPULATIONS
!;.07*7,B
8.3 Nursing Mothers
!.-2*=;2,%<.
.;2*=;2,%<.
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
!1*;6*,8427.=2,<
13 NONCLINICAL TOXICOLOGY
*;,2780.7.<2<>=*0.7.<2<69*2;6.7=8/.;=252=B
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information
are not listed
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
Zylet® 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.
,>5*;<=.;82-<*;.27-2,*=.-2727/5*66*=8;B,87-2=287<8/=1.9*59.+;*5*7-+>5+*;,873>7,=2?*,8;7.**7-*7=.;28;<.06.7=8/=1.058+.
such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, and where the inherent risk
8/<=.;82-><.27,.;=*2727/.,=2?.,873>7,=2?2=2-.<2<*,,.9=.-=88+=*27*-2627>=28727.-.6**7-27/5*66*=287$1.B*;.*5<827-2,*=.-27
chronic anterior uveitis and corneal injury from chemical, radiation or thermal burns, or penetration of foreign bodies.
$1.><.8/*,86+27*=287-;>0@2=1*7*7=227/.,=2?.,86987.7=2<27-2,*=.-@1.;.=1.;2<48/<>9.;/2,2*58,>5*;27/.,=2872<12018;@1.;.
there is an expectation that potentially dangerous numbers of bacteria will be present in the eye.
$1.9*;=2,>5*;*7=227/.,=2?.-;>027=12<9;8->,==8+;*6B,272<*,=2?.*0*27<==1./8558@270,86687+*,=.;2*5.B.9*=180.7<
Staphylococci, including S. aureus and S. epidermidis (coagulase-positive and coagulase-negative), including penicillin-resistant strains.
#=;.9=8,8,,227,5>-270<86.8/=1.;8>9+.=*1.685B=2,<9.,2.<<86.7871.685B=2,<9.,2.<*7-<86.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.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing
995B87.8;=@8-;89<8/'B5.=27=8=1.,873>7,=2?*5<*,8/=1.*//.,=.-.B..?.;B/8>;=8<2A18>;<>;270=1.272=2*5=818>;<=1.
-8<2706*B+.27,;.*<.-=8.?.;B87.=8=@818>;<;.:>.7,B<18>5-+.-.,;.*<.-0;*->*55B*<@*;;*7=.-+B269;8?.6.7=27,5272,*5<207<
*;.<18>5-+.=*4.778==8-2<,87=27>.=1.;*9B9;.6*=>;.5B
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)].
3 DOSAGE FORMS AND STRENGTHS
Zylet (loteprednol etabonate and tobramycin ophthalmic suspension) 0.5%/0.3% contains 5 mg/mL loteprednol etabonate and 3 mg/mL
tobramycin.
4 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.
5 WARNINGS AND PRECAUTIONS
5.1 Intraocular Pressure (IOP) Increase
!;85870.-><.8/,8;=2,8<=.;82-<6*B;.<>5=2705*>,86*@2=1-*6*0.=8=1.89=2,7.;?.-./.,=<27?2<>*5*,>2=B*7-/2.5-<8/?2<287#=.;82-<
should be used with caution in the presence of glaucoma.
/=12<9;8->,=2<><.-/8;
-*B<8;5870.;27=;*8,>5*;9;.<<>;.<18>5-+.6872=8;.-
5.2 Cataracts
%<.8/,8;=2,8<=.;82-<6*B;.<>5=2798<=.;28;<>+,*9<>5*;,*=*;*,=/8;6*=287
/™ are trademarks of Bausch & Lomb Incorporated or its affiliates. All other product/brand names are trademarks of their respective owners.
©2014 Bausch & Lomb Incorporated
US/ZYL/14/0002
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 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.
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.
6 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.
8 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 noobserved-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.
Sponsored by Bausch + Lomb
C24H31ClO7
Mol. Wt. 466.96
C18H37N5O9 Mol. Wt. 467.52
Chemical Name:
O-3-Amino-3-deoxy-α-D-glucopyranosyl-(1¤ 4)-O- [2,6-diamino2,3,6-trideoxy-α-D-ribo-hexopyranosyl- (1¤ 6)] -2-deoxystreptamine
Each mL contains: Actives: Loteprednol Etabonate 5 mg (0.5%) and Tobramycin 3 mg (0.3%). Inactives: Edetate Disodium, Glycerin, Povidone,
Purified Water, Tyloxapol, and Benzalkonium Chloride 0.01% (preservative). Sulfuric Acid and/or Sodium Hydroxide may be added to adjust the
pH to 5.7-5.9. The suspension is essentially isotonic with a tonicity of 260 to 320 mOsm/kg.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema,
fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation. There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However,
corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that
these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release
of their common precursor arachidonic acid.
Arachidonic acid is released from membrane phospholipids by phospholipase A2. Corticosteroids are capable of producing a rise in intraocular pressure.
Loteprednol etabonate is structurally similar to other corticosteroids. However, the number 20 position ketone group is absent.
The anti-infective component in the combination (tobramycin) is included to provide action against susceptible organisms. In vitro studies have
demonstrated that tobramycin is active against susceptible strains of the following microorganisms:
Staphylococci, including S. aureus and S. epidermidis (coagulase-positive and coagulase-negative), including penicillin-resistant strains.
Streptococci, including some of the Group A-beta-hemolytic species, some nonhemolytic species, and some Streptococcuspneumoniae. 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.
12.3 Pharmacokinetics
In a controlled clinical study of ocular penetration, the levels of loteprednol etabonate in the aqueous humor were found to be comparable
between Lotemax and Zylet treatment groups.
Results from a bioavailability study in normal volunteers established that plasma levels of loteprednol etabonate and Δ1 cortienic acid etabonate (PJ 91), its primary, inactive metabolite, were below the limit of quantitation (1 ng/mL) at all sampling times.
The results were obtained following the ocular administration of one drop in each eye of 0.5% loteprednol etabonate ophthalmic suspension
8 times daily for 2 days or 4 times daily for 42 days. This study suggests that limited (<1 ng/mL) systemic absorption occurs with 0.5%
loteprednol etabonate.
13 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).
16 HOW SUPPLIED/STORAGE AND HANDLING
Zylet (loteprednol etabonate and tobramycin ophthalmic suspension) is supplied in a white low density polyethylene plastic bottle with a
white controlled drop tip and a white polypropylene cap in the following sizes:
5 mL (NDC 24208-358-05) in a 7.5 mL bottle
10 mL (NDC 24208-358-10) in a 10 mL bottle
USE ONLY IF IMPRINTED NECKBAND IS INTACT.
Storage: Store upright at 15º-25º C (59º-77º F).
PROTECT FROM FREEZING
17 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.
9007705 (FOLDED)
9004405 (FLAT)
Tobramycin:
Chemical name: chloromethyl 17α-[(ethoxycarbonyl)oxy]11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate
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.
11 DESCRIPTION
Zylet (loteprednol etabonate and tobramycin ophthalmic suspension) is a sterile, multiple dose topical anti-inflammatory corticosteroid and
anti-infective combination for ophthalmic use. Both loteprednol etabonate and tobramycin are white to off-white powders. The chemical
structures of loteprednol etabonate and tobramycin are shown below.
Loteprednol etabonate:
4
ZYLET® (LOTEPREDNOL ETABONATE 0.5% AND TOBRAMYCIN 0.3% OPHTHALMIC SUSPENSION) TECHNICAL PAPER
Please see Important Risk Information for ZYLET® on page 1.
APRIL 15, 2015 :: Ophthalmology Times
technology
Capsule retractor improves
challenge of weak zonules
Design mimics artificial zonules to help achieve sufficient capsular bag stabilization
By Luigi Fontana, MD, PhD, Special to Ophthalmology Times
TAKE-HOME
Capsule Retractor Placement
Weak zonules are known to add
intraoperative complications and
affect every step of the cataract
procedure. Luigi Fontana, MD, PhD,
describes how capsule retractors have
helped him tackle this issue in his
cataract practice.
REGGIO EMIL IA, I TALY ::
onular weakness on occasion can
be well foreseen before surgery,
but most usually has been known
to occur unexpectedly.
Surgeons typically try to stabilize the capsular bag by inserting a capsular tension ring to
reinforce the weak part of the capsular bag
in the presence of focal zonular dialysis or
weakness.
Tension rings can be somewhat difficult to
insert in these patients, however, and they
Z
Place through a 0.8 mm or larger
paracentesis.
If needed slip the working end
under the capsulorhexis.
Move the silicone stopper
forward and into place.
Capsule Retractor Removal
MANAGING ZONULAR WEAKNESS
Move the silicone stopper back
and then the entire MST Capsule
Retractor centrally to disengage.
VIDEO Go to http://bit.ly/1JkPTLA
(Videos courtesy of Luigi Fontana, MD, PhD)
More Video
http://bit.ly/1Fy6472
http://bit.ly/1DgbPqd
Remove the silicone stopper.
have often proved inefficient in successfully
stabilizing the zonular capsular complex.
Typically, iris hooks have
been used to support the capsular bag when there have
been cases of focal or diffusely loose zonules. However, as the hooked ends are
short and flexible, these commonly used iris retractors may Dr. Fontana
tend to slip off the anterior capsular edge during phacoemulsification and provide little or
no support to the equator of the capsular bag.
Furthermore, because iris hooks also have
Remove from the main incision
using forceps and cutting the tail
end off if necessary.
sharp ends, this may pose a risk in causing
damage by tearing the anterior capsule.
A new and useful capsule retractor (MST
Capsule Retractor, MicroSurgical Technology)
has allowed for easier and safer management
of weak zonules during cataract surgery. The
shape and elongation of the hooks provide a
broader area of contact that gently supports
the peripheral capsular bag equator, as well
as the capsulorhexis edge.
This allows the retractors to mimic and act
as artificial zonules that help the surgeon to
achieve sufficient stabilization throughout the
Continues on page 31 : Retractor
27
OZURDEX
®
(dexamethasone intravitreal implant) 0.7 mg
Brief Summary—Please see the OZURDEX® package insert for full
Prescribing Information.
INDICATIONS AND USAGE
Retinal Vein Occlusion: OZURDEX® (dexamethasone intravitreal implant) is a
corticosteroid indicated for the treatment of macular edema following branch retinal
vein occlusion (BRVO) or central retinal vein occlusion (CRVO).
Posterior Segment Uveitis: OZURDEX® is indicated for the treatment of non-infectious
uveitis affecting the posterior segment of the eye.
Diabetic Macular Edema
OZURDEX® is indicated for the treatment of diabetic macular edema.
CONTRAINDICATIONS
Ocular or Periocular Infections: OZURDEX® (dexamethasone intravitreal implant)
is contraindicated in patients with active or suspected ocular or periocular infections
including most viral diseases of the cornea and conjunctiva, including active epithelial
herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial
infections, and fungal diseases.
Glaucoma: OZURDEX® is contraindicated in patients with glaucoma, who have cup
to disc ratios of greater than 0.8.
Torn or Ruptured Posterior Lens Capsule: OZURDEX® is contraindicated in patients
whose posterior lens capsule is torn or ruptured because of the risk of migration
into the anterior chamber. Laser posterior capsulotomy in pseudophakic patients
is not a contraindication for OZURDEX® use.
Hypersensitivity: OZURDEX® is contraindicated in patients with known
hypersensitivity to any components of this product [see Adverse Reactions].
WARNINGS AND PRECAUTIONS
Intravitreal Injection-related Effects: Intravitreal injections, including those with
OZURDEX®, have been associated with endophthalmitis, eye inflammation, increased
intraocular pressure, and retinal detachments.
Patients should be monitored regularly following the injection [see Patient
Counseling Information].
Steroid-related Effects: Use of corticosteroids including OZURDEX® may produce
posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and
may enhance the establishment of secondary ocular infections due to bacteria,
fungi, or viruses [see Adverse Reactions].
Corticosteroids should be used cautiously in patients with a history of ocular herpes
simplex because of the potential for reactivation of the viral infection.
ADVERSE REACTIONS
Clinical Studies Experience: 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 rates in the clinical studies of another drug and
may not reflect the rates observed in practice.
Adverse reactions associated with ophthalmic steroids including OZURDEX® include
elevated intraocular pressure, which may be associated with optic nerve damage,
visual acuity and field defects, posterior subcapsular cataract formation, secondary
ocular infection from pathogens including herpes simplex, and perforation of the
globe where there is thinning of the cornea or sclera.
Retinal Vein Occlusion and Posterior Segment Uveitis
The following information is based on the combined clinical trial results from
3 initial, randomized, 6-month, sham-controlled studies (2 for retinal vein occlusion
and 1 for posterior segment uveitis):
Adverse Reactions Reported by Greater than 2% of Patients
MedDRA Term
Intraocular pressure increased
Conjunctival hemorrhage
Eye pain
Conjunctival hyperemia
Ocular hypertension
Cataract
Vitreous detachment
Headache
OZURDEX®
N=497 (%)
125 (25%)
108 (22%)
40 (8%)
33 (7%)
23 (5%)
24 (5%)
12 (2%)
19 (4%)
Sham
N=498 (%)
10 (2%)
79 (16%)
26 (5%)
27 (5%)
3 (1%)
10 (2%)
8 (2%)
12 (2%)
Increased IOP with OZURDEX® peaked at approximately week 8. During the initial
treatment period, 1% (3/421) of the patients who received OZURDEX® required
surgical procedures for management of elevated IOP.
Following a second injection of OZURDEX® (dexamethasone intravitreal implant)
in cases where a second injection was indicated, the overall incidence of cataracts
was higher after 1 year.
Diabetic Macular Edema
The following information is based on the combined clinical trial results from 2
randomized, 3-year, sham-controlled studies in patients with diabetic macular
edema. Discontinuation rates due to the adverse reactions listed in the table below
were 3% in the OZURDEX® group and 1% in the Sham group. The most common
ocular (study eye) and non-ocular adverse reactions are as follows:
Ocular Adverse Reactions Reported by ≥ 1% of Patients and Non-ocular
Adverse Reactions Reported by ≥ 5% of Patients
MedDRA Term
Ocular
Cataract1
Conjunctival hemorrhage
Visual acuity reduced
Conjunctivitis
Vitreous floaters
Conjunctival edema
Dry eye
Vitreous detachment
Vitreous opacities
Retinal aneurysm
Foreign body sensation
Corneal erosion
Keratitis
Anterior Chamber
Inflammation
Retinal tear
Eyelid ptosis
Non-ocular
Hypertension
Bronchitis
OZURDEX®
N=324 (%)
Sham
N=328 (%)
166/2432 (68%)
73 (23%)
28 (9%)
19 (6%)
16 (5%)
15 (5%)
15 (5%)
14 (4%)
11 (3%)
10 (3%)
7 (2%)
7 (2%)
6 (2%)
6 (2%)
49/230 (21%)
44 (13%)
13 (4%)
8 (2%)
6 (2%)
4 (1%)
7 (2%)
8 (2%)
3 (1%)
5 (2%)
4 (1%)
3 (1%)
3 (1%)
0 (0%)
5 (2%)
5 (2%)
2 (1%)
2 (1%)
41 (13%)
15 (5%)
21 (6%)
8 (2%)
Includes cataract, cataract nuclear, cataract subcapsular, lenticular opacities in
patients who were phakic at baseline. Among these patients, 61% of OZURDEX®
subjects vs. 8% of sham-controlled subjects underwent cataract surgery.
2
243 of the 324 OZURDEX® subjects were phakic at baseline; 230 of 328
sham-controlled subjects were phakic at baseline.
Increased Intraocular Pressure
Summary of Elevated IOP Related Adverse Reactions
1
Treatment: N (%)
IOP
OZURDEX®
N=324
Sham
N=328
IOP elevation ≥10 mm Hg
from Baseline at any visit
≥30 mm Hg IOP at any visit
91 (28%)
13 (4%)
50 (15%)
5 (2%)
Any IOP lowering medication
136 (42%)
32 (10%)
Any surgical intervention for
elevated IOP*
4 (1.2%)
1 (0.3%)
* OZURDEX®: 1 surgical trabeculectomy for steroid-induced IOP increase, 1 surgical
trabeculectomy for iris neovascularization,1 laser iridotomy, 1 surgical iridectomy
Sham: 1 laser iridotomy
Cataracts and Cataract Surgery
At baseline, 243 of the 324 OZURDEX® subjects were phakic; 230 of 328
sham-controlled subjects were phakic. The incidence of cataract development in
patients who had a phakic study eye was higher in the OZURDEX® group (68%)
compared with Sham (21%). The median time of cataract being reported as an
adverse event was approximately 15 months in the OZURDEX® group and 12
months in the Sham group. Among these patients, 61% of OZURDEX® subjects
vs. 8% of sham-controlled subjects underwent cataract surgery, generally between
Month 18 and Month 39 (Median Month 21 for OZURDEX® group and 20 for
Sham) of the studies.
APRIL 15, 2015 :: Ophthalmology Times
technology
RETRACTOR
( Continued from page 27 )
The MST Capsule Retractor allows
for safe and easier management
of weak zonules during surgery.
(Images courtesy of MicroSurgical Technology)
entire bag during phacoemulsification and cortical cleanup. This
minimizes any hindering during
cortical lens material aspiration.
This has not been the case when
using capsular tension rings. The
retractors allow the surgeon to get
the required support vitally needed
in the anterior-posterior direction
and not trap the cortex.
The capsule retractors also have
a smooth looped tip that reduces
the risk of puncturing the equatorial capsule or tearing the anterior capsule edge. In addition, a
silicone button slides to allow for
precise adjustment and monitoring of the degree of required tension during every procedure from
patient to patient.
REDUCED
COMPLICATIONS
The instrument can also reduce
the number of complications occurring in patients presenting with
zonular weakness, such as vitreous loss and lens fragment dislocation in the vitreous. This is typically because the surgeon is able
to pull the capsule and distribute
gentle force in the equator, achieve
a broader area of contact with the
capsulorhexis margin, and also easily direct and control the tension.
Managing zonular weakness has
been improved with the thought
of knowing that there are minimal or no intraoperative complications. As every surgeon will lament, complications in patients with
The retractor
can also
reduce the
number of
complications
occurring
in patients
with zonular
weakness.
zonular weakness during cataract
surgery prolongs operating time
and further increases the risk of
re-operation. Capsular retractors have helped to control and
possibly reduce the risk of complication and, therefore, reduce
operating room time with these
complicated cases. As an example to illustrate how
convenient and easy the retractors
have made patient management,
a recent case presented with posttraumatic cataract and 120° zonular
weakness with iris dialysis. With
use of the retractors, it was possible
to successfully and simultaneously
pull the iris remnants aside and
stabilize the capsular bag.
In this otherwise-difficult case,
the capsule retractors allowed safe
and easy emulsification of the hard
cataract and preservation of the
capsular bag, as well as the implantation of a capsular tension ring
and an IOL in the capsular bag.
The use of the capsular retractors have made the approach much
more proficient and adept in tackling complicated anterior segment
surgery cases and managing zonular weakness with ease. ■
LUIGI FONTANA, MD, PHD
E: [email protected]
Dr. Fontana is director of the ophthalmology department of
the hospital Santa Maria Nuova IRCCS, Reggio Emilia, Italy.
Dr. Fontana has no financial disclosure with MicroSurgical
Technology (MST).
The increase in mean IOP was seen with each treatment cycle, and the mean
IOP generally returned to baseline between treatment cycles (at the end of the
6 month period).
USE IN SPECIFIC POPULATIONS
Pregnancy Category C
Risk Summary
There are no adequate and well-controlled studies with OZURDEX® in pregnant
women. Animal reproduction studies using topical ocular administration of
dexamethasone were conducted in mice and rabbits. Cleft palate and embryofetal
death in mice and malformations of the intestines and kidneys in rabbits were
observed. OZURDEX® should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
Animal Data
Topical ocular administration of 0.15% dexamethasone (0.375 mg/kg/day) on
gestational days 10 to 13 produced embryofetal lethality and a high incidence of
cleft palate in mice. A dose of 0.375 mg/kg/day in the mouse is approximately
3 times an OZURDEX® injection in humans (0.7 mg dexamethasone) on a mg/m2
basis. In rabbits, topical ocular administration of 0.1% dexamethasone throughout
organogenesis (0.13 mg/kg/day, on gestational day 6 followed by 0.20 mg/kg/
day on gestational days 7-18) produced intestinal anomalies, intestinal aplasia,
gastroschisis and hypoplastic kidneys. A dose of 0.13 mg/kg/day in the rabbit is
approximately 4 times an OZURDEX® injection in humans (0.7 mg dexamethasone)
on a mg/m2 basis.
Nursing Mothers: Systemically administered corticosteroids are present in human
milk and can suppress growth and interfere with endogenous corticosteroid
production. The systemic concentration of dexamethasone following intravitreal
treatment with OZURDEX® is low. It is not known whether intravitreal treatment
with OZURDEX® could result in sufficient systemic absorption to produce detectable
quantities in human milk. Exercise caution when OZURDEX® is administered to
a nursing woman.
Pediatric Use: Safety and effectiveness of OZURDEX® in pediatric patients have not
been established.
Geriatric Use: No overall differences in safety or effectiveness have been observed
between elderly and younger patients.
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
No adequate studies in animals have been conducted to determine whether
OZURDEX® (dexamethasone intravitreal implant) has the potential for carcinogenesis.
Although no adequate studies have been conducted to determine the mutagenic
potential of OZURDEX®, dexamethasone has been shown to have no mutagenic
effects in bacterial and mammalian cells in vitro or in the in vivo mouse micronucleus
test. Adequate fertility studies have not been conducted in animals.
PATIENT COUNSELING INFORMATION
Steroid-related Effects
Advise patients that a cataract may occur after repeated treatment with OZURDEX®.
If this occurs, advise patients that their vision will decrease, and they will need an
operation to remove the cataract and restore their vision.
Advise patients that they may develop increased intraocular pressure with OZURDEX®
treatment, and the increased IOP will need to be managed with eye drops, and,
rarely, with surgery.
Intravitreal Injection-related Effects
Advise patients that in the days following intravitreal injection of OZURDEX®, patients
are at risk for potential complications including in particular, but not limited to, the
development of endophthalmitis or elevated intraocular pressure.
When to Seek Physician Advice
Advise patients that if the eye becomes red, sensitive to light, painful, or develops
a change in vision, they should seek immediate care from an ophthalmologist.
Driving and Using Machines
Inform patients that they may experience temporary visual blurring after receiving
an intravitreal injection. Advise patients not to drive or use machines until this
has been resolved.
©2014 Allergan, Inc., Irvine, CA 92612, U.S.A. ® marks owned by Allergan, Inc.
Patented. See: www.allergan.com/products/patent_notices
Made in Ireland.
Based on 72212US18
Re-order: APC02BN14
Rx only
32
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
ADVANCES CONTINUE TO PROGRESS FOR REDUCING RISK AND INCIDENCE OF INFECTION
(FIGURE 1) No
prospective
study has ever
been conducted
to prove that
topical antibiotics
lowers the risk of
endophthalmitis.
(Photo courtesy of Francis
S. Mah, MD)
INTRACAMERAL
ANTIBIOTICS STILL
RAISING CONCERNS
Topical drugs widely used despite the lack of direct
evidence proving their efficacy
By Cheryl Guttman Krader; Reviewed by Francis S. Mah, MD
A
L A JOL L A, CA ::
take-home
Accumulating
evidence shows
intracameral
antibiotics
decrease the risk
of endophthalmitis
after cataract surgery,
but questions and
concerns remain.
ntibiotic prophylaxis for cataract surgery remains a controversial topic, despite convincing data showing the efficacy
of intracameral antibiotic use
for reducing the risk of postoperative endophthalmitis, said Francis S. Mah, MD.
“The low rate of postoperative infection and the potential for
many different variables to affect the risk make it difficult to conduct an appropriate large-scale clinical trial,” said Dr. Mah, director, corneal and external disease, and co-director, refractive
surgery, Scripps Clinic, La Jolla, CA.
The prospective study undertaken by the European Society of
Cataract and Refractive Surgeons (ESCRS) provides the best evidence available, and subsequently, the efficacy of intracameral
antibiotic prophylaxis has been demonstrated in other prospective studies, Dr. Mah said.
“However, there are still concerns about
that approach and questions about the optimal technique,” he said.
Reviewing the outcomes of the ESCRS study,
members of the Infectious Disease Task Force
of the American Society of Cataract and Refractive Surgery (ASCRS) concluded that intracameral antibiotic use may be a paradigm shift for
endophthalmitis prophylaxis. However, continued research was needed to examine the
optimal drug, dose, and method of delivery,
as well as the short- and long-term effects.
In addition, widespread adoption would depend on access to a product that would be safe
and simple to use with minimal risk of dilution errors and contamination, Dr. Mah said.
SINGLE-USE CEFUROXIME
In 2012, single-use cefuroxime for intracameral
use became commercially available in some
countries in Europe. This product represents a
step forward as it significantly reduces safety
concerns associated with extemporaneous
preparation.
However, it does not completely eliminate
the potential for dilution errors and contamination, and there have been reports of anaphylaxis associated with its use.
“The risk of an allergic reaction is much
lower with cefuroxime compared with penicillin, but it still exists,” Dr. Mah said.
Interestingly, in a survey of ESCRS members
published in 2014, only 74% of respondents were
always or usually using an intracameral antibiotic in cataract surgery, despite the fact that
it is recommended by the ESCRS and various
European national ophthalmology societies.
“Many of the respondents still questioned
the scientific merit or need for intracameral
antibiotic use, but concern over risks associated with compounding the dose was also
common,” Dr. Mah said.
No prospective study has ever been conducted
to provide direct proof that topical antibiotic
use decreases the risk of endophthalmitis. In
the ESCRS study, perioperative use of topical
levofloxacin was associated with a decreased
rate of endophthalmitis, but the benefit did
not achieve statistical significance.
Dr. Mah said use of topical antibiotics for
endophthalmitis prophylaxis is supported by
surrogate evidence derived from microbiology studies demonstrating reduced bacteria
Continues on page 35 : Raising concerns
Visit us at AAO Booth 1207
The Quintessential
Proven therapeutic utility in blepharitis, conjunctivitis, and other
superficial ocular infections
Profound bactericidal effect against gram-positive pathogens1
O
Excellent, continued resistance profile—maintains susceptibility,2,3 even against
methicillin-resistant Staphylococcus aureus 4
OOintment provides long-lasting ocular surface contact time and greater bioavailability5
OAnti-infective efficacy in a lubricating base6
OUnsurpassed safety profile—low incidence of adverse events6
OConvenient dosing—1 to 3 times daily6
OTier 1 pharmacy benefit status—on most insurance plans7
O
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
The low incidence of allergenicity exhibited by Bacitracin means
that adverse events are practically non-existent. If such reactions
do occur, therapy should be discontinued.
Bacitracin Ophthalmic Ointment should not be used in deep-seated
ocular infections or in those that are likely to become systemic.
This product should not be used in patients with a history
of hypersensitivity to Bacitracin.
Please see adjacent page for full prescribing information.
References: 1. Kempe CH. The use of antibacterial agents: summary of round table discussion. Pediatrics. 1955;15(2):221-230.
2. Kowalski RP. Is antibiotic resistance a problem in the treatment of ophthalmic infections? Expert Rev Ophthalmol.
2013;8(2):119-126. 3. Recchia FM, Busbee BG, Pearlman RB, Carvalho-Recchia CA, Ho AC. Changing trends in the microbiologic
aspects of postcataract endophthalmitis. Arch Ophthalmol. 2005;123(3):341-346. 4. Freidlin J, Acharya N, Lietman TM, Cevallos
V, Whitcher JP, Margolis TP. Spectrum of eye disease caused by methicillin-resistant Staphylococcus aureus. Am J Ophthalmol.
2007;144(2):313-315. 5. Hecht G. Ophthalmic preparations. In: Gennaro AR, ed. Remington: the Science and Practice of
Pharmacy. 20th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2000. 6. Bacitracin Ophthalmic Ointment [package insert].
Minneapolis, MN: Perrigo Company; August 2013. 7. Data on file. Perrigo Company.
Logo is a trademark of Perrigo.
©2014 Perrigo Company
Printed in USA
4022-05-01-JA
01/14
www.perrigobacitracin.com
APRIL 15, 2015 :: Ophthalmology Times
Bacitracin Ophthalmic
Ointment USP
Special Report )
OCULAR INFECTION CONTROL
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.
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 gram-negative 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.
Store at 20°-25°C (68°-77°F)
[see USP Controlled Room Temperature].
Manufactured For
®
Minneapolis, MN 55427
0S400 RC J1 Rev 08-13 A
EFFECTIVE CONCEPTS IN
SECOND LOOK
dence whatsoever that one antibiotic is better
than another,” he said.
( Continued from page 1 )
WHAT ABOUT
SURGICAL TECHNIQUE?
Evidence based on results of a randomized trial
from Japan and two case-control studies from
the United States all found a three-fold excessive risk of corneal versus scleral incisions.
“I interpret this in a simplistic manner that
wound is important whether doing corneal or
scleral incisions,” Dr. Schein said. “Blood is a
good adhesive, and it has antibacterial properties.”
Sweden has a unique approach to endophthalmitis. In reviewing national data in Sweden
with the same methodology over a decade or
so, there is evidence that its rate of endophthalmitis has progressively declined and then leveled out at about 0.02%, he noted.
Beginning in the late 1990s, Sweden started
using intracameral cefuroxime and published
a series of case-control studies. Lack of use of
cefuroxime intracamerally became the dominant
risk factor for endophthalmitis, even greater
than vitreous access or older age.
“In Sweden, they don’t use preoperative topical
antibiotics as a rule, and they don’t use topical antibiotics postoperatively,” Dr. Schein said. “They
use cefuroxime intraoperatively almost entirely.
“So, with all this evidence, why are we not
doing it in United States?” he asked.
For one, he noted that the United States does
not yet have ready access to safe, available, and
predictable intracameral antibiotic.
“If you put the wrong antibiotic in or use
the wrong concentration, you can blind a patient,” he said. “Because endophthalmitis is a
known risk, as a surgeon you hate to be the
person responsible for a catastrophe when trying to prevent it.”
U.S. regulatory barriers also add a layer of
obstacles. The FDA has gone on record that to
approve a drug’s intracameral use requires one,
if not two, randomized clinical trials. It would
take many millions of dollars to prove again
what has been quite well substantiated, he noted.
“Finally, despite the enormous costs to Medicare and patients of perioperative topical antibiotics, there is not a good mechanism for
facilities to be reimbursed the cost of delivering antibiotics on the day of surgery—even if
those drugs were sufficiently long lasting in
effect to substitute for eye drops currently used
postoperatively,” Dr. Schein said. ■
Dr. Schein shared data on incidence taken
from the U.S. National Medicare Database and
explained that rates in the late 1990s were as
high as about 1 in 700. Most recent reliable
U.S. estimates put the rate at about 1 in 1,100
cases per year.
“Interestingly, higher-volume surgeons have
lower rates,” he said. “Data can’t tell you why
that’s true. I expect it’s because they have less
of the known major risk factors, such as vitreous loss.”
The same results are found in Canada—
about 1 in 700. Again, risk factors are similar
whether in the United States, Canada, or elsewhere—older age, vitrectomy, higher-volume
surgeons with less risk of disease.
“What do we know from these national studies? Vitreous access, older age, men more than
women, and lower surgical volume are all chief
risk factors.
R ATE R EDUCTION
Dr. Schein sifted through pre-, intra-, and postoperative opportunities for reducing the rate.
“Preoperatively, it’s essentially standard in
the United States to use topical antibiotics on
the day of surgery—ones that were all approved
for conjunctivitis, though there is no indication
for preoperative use and little evidence of any
benefit in reducing endophthalmitis,” he said.
Evidence supports the standard use of povidone-iodine in preparing the ocular surface.
What is not confirmed is whether povidoneiodine works better than other antiseptics, for
example, 0.05% chlorhexidine, he said.
Dr. Schein is working on a national study
which represents a huge series of endophthalmitis from around the country—about 92%
gram positive. Of those, 90% were staph and
10% were streptococcus, along with a few cases
of gram negatives, he noted.
“If you did believe that using topical antibiotics before surgery was important, and you’re
wanting to kill the bugs that are most frequent,
you could do what Bascom Palmer Eye Institute did in 2005 when they asked the question:
‘If you took our cases of endophthalmitis and
wanted to kill the bugs preoperatively, which
were the most effective antibiotics, and what
did they cost?’” Dr. Schein said.
Gentamycin fared much better than the more
current antibiotics primarily because “it’s a
good staph drug. But evidence that adding an
antibiotic to a preoperative regimen is beneficial is very minimal,” he said. “There is no evi-
OLIVER D. SCHEIN, MD, MPH
E: [email protected]
This article was adapted from Dr. Schein’s presentation during Wilmer Eye Institute’s
27th Annual Current Concepts in Ophthalmology meeting in 2014. He did not indicate
any financial interest relevant to the subject matter.
35
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
RAISING CONCERNS
( Continued from page 32 )
counts in cultures grown from conjunctiva and
aqueous humor specimens. In addition, there
are data from retrospective studies showing
benefit.
Despite the lack of definitive evidence demonstrating its efficacy, topical antibiotics are
widely used for endophthalmitis prophylaxis,
especially in the United States. Findings from
a member survey conducted by the ASCRS
Cataract Committee in 2007 showed 88% of
respondents were using a topical anti biotic
preoperatively and 98% used a topical antibiotic postoperatively. U.S. surgeons accounted
for about three-fourths of survey participants.
The advanced-generation fluoroquinolones
have become the most commonly used antibiotics
for topical endophthalmitis prophylaxis due to
their broader spectrum of antimicrobial activity
and superior ocular penetration characteristics
compared with earlier-generation fluoroquinolones and other alternatives. Dr. Mah noted that
regimens vary among surgeons.
However, based on pharmacokinetics and
pharmacodynamics data, there are recommendations to initiate treatment 1 to 3 days prior
to surgery or to increase the frequency of dosing immediately prior to surgery in order to increase the concentration of antibiotic in the anterior chamber.
Certain strategies for reducing risk of postoperative endophthalmitis are well accepted as
standard of care. They include the need to preoperatively identify and treat periocular conditions
that have been associated with an increased risk
of endophthalmitis—e.g., conjunctivitis, blepharitis, and dry eye.
Meticulous lid draping is also mandatory, recognizing that lid flora are the predominant patho-
Correction
An error occurred in a recent article (“Compounded combination drops safe, effective
for postLASIK management,” Ophthalmology
Times, March 15, 2015, Page 26). The second paragraph under the heading “Patient
series” should be replaced with this text:
The typical dosage for the “less drops” technique was q.i.d. for 1 week then b.i.d. for
one additional week. With that said, some
patients only required 1 week of drops at
the q.i.d. level, whereas others had the additional week of b.i.d. drops. Ophthalmolgens in cases of postoperative endophthalmitis,
ogy Times regrets the error.
and preoperative antisepsis with povidone-iodine
OCULAR INFECTION CONTROL
should always be performed.
“The povidone-iodine prep should include not only use of the 10% scrub on the
lids and lashes but also placing a drop of
the 5% solution in the conjunctival cul de
sac for a minimum 5-minute contact time,”
Dr. Mah said. ■
FRANCIS S. MAH, MD
E: [email protected]
This article was adapted from Dr. Mah’s presentation during Cornea Subspecialty
Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. Mah is a
consultant to Alcon Laboratories, Allergan, Bausch + Lomb/Valeant, Ocular Therapeutix,
and PolyActiva.
Building the Ophthalmic Tech’s Community of Practice
modernmedicine.com/iTech
Resource Center for Technician Education
WEB EXCLUSIVE CONTENT
Related Articles | Continuing Education | Clinical Tools & Tips
iTech provides educational presentations and information
for ophthalmic and optometric technicians, helping them
work effectively with their doctors to enhance the practice.
1
AND
SUPPLE
TO
MENT
GI N G
MANA A
R ET I N N TS
PATIE
d on
time an
at any
t one
y. Abou
any da
gical
my sur
third of unschedare
is cones
It
.
cas
ing
encies
is excit
ound.
emerg after
ina
ab
d
ret
ule
ies
of
rm
rtunit
The field
t I perfo
g. Oppo t options we
tha
ening
gin
an
ch
the ev
reasatmen
tinually
clinic in
the tre
ever inc
ds.
s more, tients are for
l and
weeken
What’
or on
pa
y schoo
at
er our
pathy
tometr
uld
se I tre
retino
an
can off
s in op
Becau
le, I wo
betic
tient as
en I wa
cular ho
pa
ive dia
Wh
be
.
ma
ery
a
ing
ev
could
en the Proliferat
diagnose t nothing
ual, ev
the
t
ivid
would
tha
s
tha
ind
patient
chance fellow
ter varie
was a
tell the
encoun nt to
his
re
in
the
tie
ses.
and
happen lly surgically
done
l disea
from pa rprisingly,
could
retina
cessfu
thing
re are
tient. Su a variety of
same
I can suc les.
I see, the
lks pa
se
t, now
ho
will
is quite
patients es of disea
m all wa
, and
eye. Bu ny macular
there
all the
s been
ople fro span the
come,
egori
ma
Out of
oval ha time to
I see pe
on cat
jor
repair
tients
act rem for some e and a ma ic
comm
office,
My pa
Catar
who are four most
In my
es.
s
car
ag
.
hthalm
remain
orn
all
unter
likely rstone of eye most op
e newb
ndand of
t I enco
ne
matur
ue for
at-gra
of life
tha
cor
en
a
pre
gre
rev
care
of
on
t from
way to
Retinal
the eye
thy
source .
gamu
st comm
all the
rks in
rly 100s.
ces
ssing
retinopa
ys old
ow
the mo
practi ne who wo least a pa
their ea d here in Ha
only da
Diabetic eye disease is . All of us kn
at
Anyo
o are in
An
have
s
wh
es.
ter
ns.
itie
ts
w
uld
tic
un
rac
ho
nic
all
portio
paren
Diabe
I enco
field shoanding of the surgery
of eth
ect
mic pro
ns affect
n that
,
g pot
tes
also aff
underst develop the
conditio ve a meltin
conditio tes is of epide
Diabe
cts
se can
ha
be
ersity
erican
catara oves them, e, and the
more
al disea
waii we
that dia
tin
the div
the Am
. Retin
affects
that rem rative rou hnology of
ng to
ups. So me.
ented
diabetes1 dly, many
pe
repres
Accordi
mic gro
posto evolving tec Ls).
Sa
(ADA),
sting to
d;
y
paioecono
cans.
iation
ses (IO
rapidl
gnose
ry intere
of my
all soc
Ameri
Assoc
ar len
dia
ve
n
ity
is
cul
un
a
llio
ers
she
tin
nts
are
intrao
n 25 mi
the div
he or
betes
cific Re
in patie
s me,
ion to
nk tha nts with dia
y at Pa
dit
A
see
da
thi
ad
l
AD
nt
e
In
patie
would
patie
typica
se. Th
e4
se, my
g. One
time the tic eye disea
gery
a on Pag
tient ba ever changin and set sur
by the
be
See Retin
ek.
ys
for
ere dia
Care is
clinic da day every we y has sev
e
r da
have set
the sam 24 hours pe
that I
t were
in
call
days tha se I am on
called
be
cau
, I can
But be
r week
days pe
and 7
rk
By Ma
foy
E. Ta
MD
a, OD,
:
E
INSID
ct
ney
nt’s jour
ract patie
The cata
Catara
Brought to you by
ue 2 |
e 2 | iss
volum
er 2013
Summ
PAGE 10
2013
06.07.
00:09
&
A
36
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
Systematic approach key for treating
pediatric atopic keratoconjunctivitis
Starting patients on calcineurin inhibitors beneficial to reducing conjunctival inflammation
By Lynda Charters; Reviewed by Stephen Pflugfelder, MD
HOUS TON ::
WHEN FACED with challenging pediatric
to treat bacteria, topical calcineurin inhibitor
(tacrolimus or cyclosporine), or referral of the
patient to a cornea specialist.
cases of atopic keratoconjunctivitis, a treatment
strategy based on disease severity may be the
most beneficial, said Stephen Pflugfelder, MD.
CALCINEURIN INHIBITOR
“It is fine to start treatment with antihista- Dr. Pflugfelder opted for treatment with a topimines and mast cell stabilizers and then pre- cal calcineurin inhibitor to treat the patient’s
scribe topical corticosteroids, with dose adjust- atopic keratoconjunctivitis. In this condition, T
ments based on disease sever- helper 1 (Th1) and Th2 cells contribute to the
ity,” said Dr. Pflugfelder, pro- goblet cell and mucus hyperplasia, subepithelial
fessor of ophthalmology, Baylor fibrosis, and eosinophil and mast cell recruitCollege of Medicine, Houston. ment that amplify disease severity and contrib“However, children cannot be ute to corneal epithelial disease. Tacrolimus
treated with high-dose topical and cyclosporine reportedly improve the signs
steroids over the long term.”
and symptoms of atopic keratoconjunctivitis.
Dr. Pflugfelder shared some
“Calcineurin inhibitors prevent calcineurin
Dr. Pflugfelder
clinical pearls for treating a pa- phosphatase activity on the nuclear factor of actient with persistent ocular redness and eye- tivated T cells, which is important for translocalid swelling. In one case, an 11-year-old boy tion of the nucleus and a cause of T-cell producpresented with a history of ocular redness of tion of a variety of factors that can amplify the
several years duration, tearing, and itching. severity of atopic disease,” Dr. Pflugfelder said.
Most recently, the boy complained of diffi“These drugs limit T-cell activation in the
culty seeing the board at school. His mother cytokines that the cells produce,” he added.
reported eyelid swelling.
Such cases require aggressive anti-inflamThe patient was healthy with the exception matory therapy to treat the severe conjunctival
of asthma that was controlled. Treatment of inflammation that contributes to the corneal
the redness with olopatadine drops (Patanol, epithelial disease that reduces visual acuity,
Alcon Laboratories) resulted in minimal ben- he emphasized.
efit. Symptom improvement did occur with
The treatment plan for this patient included
prednisolone acetate.
olopatadine instillation once daily to reduce the
Bilateral best-corrected visual acuity was conjunctival edema and itching, prednisolone
20/50. Examination showed mild
acetate 1% drops four times daily
swelling of the upper eyelids and
for 2 weeks, and then twice daily
edematous inferior puncta. Tears
for 2 weeks, and preservative-free
overflowed from the inferior tear
tacrolimus 0.03% ointment twice
meniscus. The eyelids had a veldaily first applied on the eyelid
Pediatric
vet papillary reaction and thick- patients with atopic
margin and later instilled into the
ened inferior and superior palpe- keratoconjunctivitis
inferior fornix if the patient does
bral conjunctiva. A vortex pattern affecting the eyes may
not complain of burning or irritaof fluorescein staining was seen best be treated with
tion. The last treatment is an offfrom the superior limbus to the topical calcineurin
label use of tacrolimus.
central cornea in both eyes.
The patient had marked improveinhibitors to decrease
While no dermatitis was pres- the conjunctival
ment by 1 month after the start
ent on the child’s head and face, inflammation.
of treatment in the conjunctival
dermatitis was present in the aninflammation and corneal epithetecubital fossa on both arms.
lial disease. The dose of prednisolone acetate
Possible treatment considerations were ar- was decreased to once daily for 1 month and
tificial tears, moxifloxacin 0.5% (Vigamox, the tacrolimus was stopped. Cyclosporine A
Alcon Laboratories) drops three times daily 0.05% (Restasis, Allergan) was started twice
take-home
(FIGURE 1) TOP A patient with atopic
keratoconjunctivitis before tacrolimus therapy.
BOTTOM A patient with atopic
keratoconjunctivitis after tacrolimus therapy was
started. (Photos courtesy of Stephen Pflugfelder, MD)
daily with the instruction to continue it indefinitely. This is an off-label indication for
cyclosporine A.
Before tacrolimus therapy was started, a great
deal of limbal and conjunctival inflammation
was present. One month later, the limbal inflammation had decreased.
“It is not unusual to observe at least a 50% decrease in the superior tarsal edema and inflammation that can minimize the frictional force exerted by the upper eyelid on the cornea, which, in
this case, was likely contributing to the corneal
epithelial disease,” Dr. Pflugfelder said.
Among the noteworthy points in this care are:
> Atopic dermatitis is a cause of substantial ocular morbidity, with eyelid involvement in 20%
to 43% of patients;
> Atopic keratoconjunctivitis is a chronic, po-
37
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
tentially blinding condition, the diagnosis of which
can be overlooked in patients with mild eczema or
when it affects skin other than that on the eyelid;
> Corneal involvement occurs frequently, ranging
from punctate epithelial erosion to epithelial defects, epithelial filaments, and stem cell dysfunction; and
> Corneal scarring and neovascularization from
chronic conjunctival inflammation and corneal
trauma can cause loss of vision.
OCULAR INFECTION CONTROL
“Starting patients on topical calcineurin inhibitors can be extremely valuable because of
the steroid-sparing effects and for decreasing the
conjunctival inflammation,” Dr. Pflugfelder said.
“In severe cases with corneal epithelial defects
that do not heal and potentially blinding inflammation, systemic calcineurin inhibitors or pulse
oral corticosteroids can be used.” ■
STEPHEN PFLUGFELDER, MD
E: [email protected]
This article was adapted from Dr. Pflugfelder’s presentation during
Pediatric Subspecialty Day at the 2014 meeting of the American Academy of
Ophthalmology. Dr. Pflugfelder did not indicate any proprietary interest in
the subject matter.
New
CDC: Ocular
syphilis
advisory
Double-X Speculums
parallel retraction. less pressure. better docking.
AT L AN TA ::
THE CENTERS for Disease Control and
Prevention (CDC) has issued a clinical advisory
on ocular syphilis.
At least 15 cases of ocular syphilis from California and Washington have been reported to
the CDC since December 2014, and at least five
other states have suspected cases under investigation. The majority of cases have been among
HIV-infected MSM, and a few cases have occurred among HIV-uninfected persons including heterosexual men and women. Several of
the cases have resulted in significant sequelae
including blindness.
Neurosyphilis can occur during any stage of
syphilis including primary and secondary syphilis. Ocular syphilis, a clinical manifestation of
neurosyphilis, can involve almost any eye structure, but posterior uveitis and panuveitis are the
most common.
Additional manifestations may include anterior uveitis, optic neuropathy, retinal vasculitis
and interstitial keratitis. Ocular syphilis may lead
to decreased visual acuity including permanent
blindness. While previous research supports evidence of neuropathogenic strains of syphilis, it
remains unknown if some Treponema pallidum
strains have a greater likelihood of causing ocular infections.
To receive advice from CDC regarding clinical
management of ocular syphilis, or assistance with
shipment of clinical samples for molecular typing, physicians may contact Robyn Neblett Fanfair, MD, MPH at 404/639-6044 or [email protected].
Updates to this clinical advisory will be posted
on the “Syphilis: Treatment and Care” section of
the CDC website (http://1.usa.gov/1NRHMGY). ■
patent pending
K1-5691 K-Wire, 15mm
K1-5696
K1-5695 V-Wire, 15mm
Katena introduces a new family of
speculums that feature the patented
“Double - X” mechanism. Their unique action
opens the lids in a parallel motion for minimal
K1-5696 Chu, 17mm
external pressure on the globe. In addition, the mechanism is
GHVLJQHGWRPRYHDZD\IURPWKHVXUJLFDOÀHOGDVWKHEODGHVRSHQ
IRUXQREVWUXFWHGDFFHVVWRWKHVXUJLFDOÀHOG
K1-5697 Chu, 13mm
Ideal for cataract, refractive, glaucoma and corneal procedures.
Key Features:
1
Unique “Double - X” mechanism retracts
blades in a parallel motion for even
tension along the lid.
2
As the lids are retracted the mechanism
moves out of the way for unobstructed access.
3
Ball tips eliminate discomfort for
patients with excess lid tissue.
2
1
3
®
Watch it!
973-989-1600
r 800-225-1195 r www.katena.com
38
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
Proper case management required
to address pediatric herpes simplex
Acyclovir is effective in children, but dosage needs adjustment to maintain suppressive levels
By Lynda Charters; Reviewed by Kathryn Colby, MD, PhD
BOS TON ::
PEDIATRIC HERPES SIMPLEX
virus is an important disease in children, a
high percentage of whom have stromal disease.
The disease is associated with a high risk of
recurrence and a risk of induced astigmatism
from corneal scarring and reduced vision, said
Kathryn Colby, MD, PhD.
“[Treatment with] oral acyclovir is safe, although not FDA-approved for use in children,”
said Dr. Colby, associate professor of ophthalmology, Harvard Medical School, Boston, and
director, Pediatric Cornea Service, Boston Children’s Hospital.
“The dose of acyclovir must be adjusted with
growth in children,” she added.
STR ATEGY FOR
CASE M A NAGEMEN T
Dr. Colby recounted the case of a 4-year-old
girl from Bermuda with recurrent red eye in
the right eye only since 8 months of age. She
had been treated multiple times with topical
antibiotics and steroids, but the disease continued to recur. Previous diagnoses included
staphylococcal marginal disease, limbal ver-
Next, Dr. Colby measured the corneal sensa- risk of recurrence, a 75% risk of stromal distion, which was decreased in the affected eye. ease, and a 30% rate of misdiagnosis.”
The working diagnosis was recurrent herDr. Colby added that 80% of children with
pes simplex keratitis. The clinical findings herpes simplex keratitis develop scarring,
and history did not support the
mostly in the central cornea. Howpreviously entertained diagnoses
ever, the induced irregular astiglisted above.
matism accompanying bouts of
The patient was started on a
stromal keratitis is an even more
treatment of oral acyclovir, which,
clinically relevant factor in these
Pediatric herpes
in children, is an off-label use of
patients.
this medication. Taken into con- simplex virus should be
Twenty-five percent of children
sideration were the patient’s his- part of the differential
have more than 2 D of astigmatory of recurrent unilateral disease, diagnosis when a
tism, most of which is irregular.
decreased corneal sensation, and patient has unilateral
Visual acuity is less than 20/40 in
recurrent disease in
anterior stromal footprints.
about 25% of children and 60%
“Her mother noted an almost the anterior segment.
of children have reduced corneal
immediate improvement,” Dr.
sensation.
Colby said. However, another ophthalmoloAcyclovir is well tolerated by pediatric pagist stopped the acyclovir treatment because tients, but Dr. Colby advised that ophthalmoloof the improved clinical picture. Symptoms gists be aware of lactose intolerance. The drug
recurred almost immediately.
has a wide therapeutic and safety index.
Dr. Colby restarted the acyclovir treatment
and also began low-dose prednisolone acetate
PROPER DOSAGE
0.12% to help with the corneal vasculariza- Dr. Colby prescribes 100 mg of acyclovir twice
tion and azithromycin applied to the eyelashes daily as prophylaxis for very young infants,
for blepharitis.
200 mg twice daily for toddlers, 300 mg twice
daily for children older than toddlers, and 400
mg twice daily for older children. When a child
presents with acute infectious herpes simplex
virus, she prescribes the same number of milligrams three-times daily based on age and
— Kathryn Colby, MD, PhD
weight.
“When treating children with topical steroids, tapering of the drugs should be done
“The neovascularization regressed over sev- slowly, over a long period,” Dr. Colby said.
eral months with no recurrences,” Dr. Colby “Management of amblyopia is key.
said.
“Always consider pediatric herpes simplex
Once the child’s symptoms were stable, virus when a patient has unilateral recurrent
Dr. Colby was able to taper the topical ste- disease in the anterior segment, with awareness
roid therapy. The child completed a 1-year of the protean manifestations of this virus,”
course of a prophylactic dose of acyclovir and she concluded. ■
symptoms remained “quiet” without further
recurrences.
“Herpes simplex virus is a very important
KATHRYN COLBY, MD, PHD
common disease in children,” she said. “The
E: [email protected]
end result of stromal herpes simplex virus is
This article was adapted from Dr. Colby’s presentation during Pediatric Subspecialty
a scarred vascularized cornea. We know that
Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. Colby has no
pediatric herpes simplex keratitis has an 80%
financial interest in any aspect of this report.
take-home
‘The end result of stromal herpes simplex virus is a
scarred vascularized cornea.’
nal keratoconjunctivitis, and phlyctenular
keratoconjunctivitis.
Dr. Colby first considered the relevant historical patient information, such as familial
corneal disease, systemic allergies or atopy, and
duration and frequency of episodes. The child
had no history of systemic allergic disease.
Examination showed extensive corneal neovascularization and swelling at the inferior
limbus in the affected eye. Peripheral anterior
stromal footprints and mild blepharitis were
seen, but no giant papillary conjunctivitis or
limbal follicles were noted on clinical exam.
The contralateral eye was normal.
NOW APPROVED
ANTICIPATED RETAIL
AVAILABILITY MARCH 10
From Alcon, committed to providing new treatment options for patients.
Olopatadine is licensed from Kyowa Hakko Kirin Co., Ltd. Japan
©2015 Novartis
01/15
PAZ15017JAD
40
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
DALK explored as early approach
to refractory Acanthamoeba keratitis
Procedure should be done by experienced surgeons with low rates of conversion to PK
By Lynda Charters; Reviewed by Enrica Sarnicola, MD
SIENA, I TALY ::
DEEP ANTERIOR LAMELLAR keratoplasty (DALK) should be considered as an
early approach for treating refractory acanthamoeba keratitis with substantial corneal
ulceration, said Enrica Sarnicola, MD.
“DALK is a safe procedure with good, longterm graft survival; that is, 99% after 10 years
has been reported in the literature,” said Dr.
Sarnicola, a resident in ophthalmology, Siena
University, Italy. “The procedure has a low
rejection rate with a low risk of secondary
complications.”
Dr. Sarnicola and colleagues conducted a
retrospective, noncomparative study of 12 eyes
of 11 consecutive patients who had been diagnosed previously with Acanthamoeba keratitis. All patients had been followed for 2 years.
In these patients, the investigators performed
a DALK procedure in 9 eyes with a post-infective stromal scar and in 3 eyes with active
infection.
All 3 eyes with active infection were refractory to medical therapy. DALK, as a therapeutic
approach, was performed from 30 to 60 days
from the time of symptom onset.
All patients had extensive ulcers in the optical zone that exceeded 150 μm, but less than
300 μm in depth, according to Dr. Sarnicola.
The DALK technique they performed included
either a cannula big-bubble technique or manual
dissection. The DALK diameter was as large as
possible; that is, 8.5 mm in 8 eyes and 9 mm
in 4 eyes. Interrupted sutures were placed. A
histologic examination was performed after
the lamellar tissue was removed.
3 DRUGS USED
Patients used three drugs preoperatively and
postoperatively: the antiseptic drug chlorhexidine gluconate, a DNA synthesis inhibitor propamidine isethionate, and a protein synthesis
inhibitor neomycin sulfate.
Postoperatively, the drugs were instilled
4 times daily for 1 month. Propamidine isethionate was instilled 4 times daily for other
2 months.
“Most importantly, Descemet’s membrane
did not rupture in any eye,” Dr. Sarnicola said. mitis developed, which required vitrectomy.
Visual recovery was very good, she pointed One month later, a fungal keratitis infection
out. Best spectacle-corrected visual acuities required a second penetrating keratoplasty.
ranged from 14/20 to 20/20 (average, 17/20). However, the graft was rejected, and a retNone of the infections recurred and no com- inal detachment developed in addition to
plications, such as secondary cataract or glau- secondary glaucoma, limbal deficiency, and
perforation. Ultimately, the eye was enuclecoma, developed.
“The histopathologic evaluation confirmed ated, Dr. Sarnicola said.
In another case, a 15-year-old
our diagnoses with cysts in the
girl who wore contact lenses was
stromal specimens,” she said.
diagnosed late with biopsy-conThe peripheral margin was free
firmed acanthamoeba keratitis.
of infection in all cases. The deep
She was treated with targeted
margin was free of infection in
Therapeutic deep
therapy that included topical
eight cases, but not so in four anterior lamellar
polyhexamethylene biguanide,
cases. Dr. Sarnicola speculated keratoplasty performed
hexamidine, and chlorhexidine.
that these four cases were all des- early should be
However, despite treatment the
cemetic DALK (dDALK).
considered in cases
lesion enlarged, and intense pan“We believe this is the reason of acanthamoeba
nus and deep stromal vascularwhy the surgery was still radi- keratitis refractory to
ization developed. The vision decal,” she said.
medical therapy with
DALK seems to be a very good substantial optical zone creased to counting fingers.
Therapeutic DALK was perprocedure in eyes with active and ulceration.
formed early using the big-bubquiescent acanthamoeba infection,
she said. However, she noted the importance ble technique. A 9-mm graft was applied
of a larger study to confirm the success rate centered on the infection.
“One year postoperatively, the visual rewith the procedure and to determine any
covery was good at 20/30,” Dr. Sarnicola
possible late complications.
said. “The acanthamoeba keratitis did not
recur. The endothelial cell count is good
CASE REPORTS
Dr. Sarnicola recounted the case of a 61-year-old and stable.”
In acanthamoeba infections, an early DALK
man with acanthamoeba keratitis who was
misdiagnosed as bacterial. Delayed antiamoe- procedure must be considered in cases of
bic therapy was unable to prevent and avoid acanthamoeba keratitis refractory to mediinfection progression and corneal melting, cal therapy with substantial optical zone
ulceration, she noted.
so therapeutic keratoplasty was indicated.
“The only caveat is that the procedure
“Usually, surgeons prefer to perform keratoplasty when the infection is controlled, should be performed by highly experienced
because with penetrating keratoplasty, open- surgeons with low rates of conversion to pening of the anterior chamber can allow intra- etrating keratoplasty,” Dr. Sarnicola said. ■
ocular spread of infection,” she said.
“In addition, using a graft with a large diameter in the presence of inflammation in
the eye carries a very high risk of rejection
and graft failure,” she said. “Therefore, deENRICA SARNICOLA, MD
laying the surgery is the last option.”
E: [email protected]
By the time the surgery was performed,
This article was adapted from Dr. Sarnicola’s presentation at the 2014 meting of the
the full corneal thickness had become inAmerican Academy of Ophthalmology. Dr. Sarnicola has no financial interest in any
fected. Five days postoperatively, endopthalaspect of this report.
take-home
As Demonstrated in 2 Pivotal, Phase 3 Trials in
Patients With DME Evaluating Mean Change in
BCVA* at 52 Weeks vs Baseline1
EYLEA® (aflibercept) Injection Offers Extended
Dosing in DME—2-mg Every 8 Weeks
Following 5 Initial Monthly Doses1
Initial Dosing
Follow-Up Dosing
5 Initial 2-mg Injections Monthly
(Every 4 Weeks)
2-mg Every 2 Months
(Every 8 Weeks)
Although EYLEA may be dosed as frequently as
2 mg every 4 weeks (monthly), additional efficacy
was not demonstrated when EYLEA was dosed
every 4 weeks compared to every 8 weeks.
*BCVA = best-corrected visual acuity, as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letters.
IMPORTANT SAFETY INFORMATION FOR
EYLEA® (aflibercept) INJECTION
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.
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 use of intravitreal VEGF inhibitors, including EYLEA, 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 during the first year
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.
There were no reported thromboembolic events in the patients
treated with EYLEA in the first six months of the RVO studies.
Serious adverse reactions related to the injection procedure have
occurred in <0.1% of intravitreal injections with EYLEA including
endophthalmitis and retinal detachment.
*'/156%1//10#&8'45'4'#%6+105j¢Ik4'2146'&+02#6+'065
receiving EYLEA were conjunctival hemorrhage, eye pain, cataract,
vitreous floaters, intraocular pressure increased, and vitreous
detachment.
IMPORTANT PRESCRIBING INFORMATION FOR
EYLEA® (aflibercept) INJECTION
EYLEA® (aflibercept) Injection is indicated for the treatment of
patients with
Neovascular (Wet) Age-related Macular Degeneration (AMD): The
recommended dose is 2 mg administered by intravitreal injection
every 4 weeks (monthly) for the first 12 weeks (3 months), followed
by 2 mg 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 when EYLEA was dosed every
4 weeks compared to every 8 weeks.
Macular Edema following Retinal Vein Occlusion (RVO): The
recommended dose is 2 mg administered by intravitreal injection
every 4 weeks (monthly).
Diabetic Macular Edema (DME): The recommended dose is 2 mg
administered by intravitreal injection every 4 weeks (monthly) for the
first 5 injections, followed by 2 mg 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 when EYLEA was
dosed every 4 weeks compared to every 8 weeks.
For more information, visit www.EYLEA.com.
Reference: 1. EYLEA® (aflibercept) Injection full U.S. Prescribing Information.
Regeneron Pharmaceuticals, Inc. October 2014.
Please see brief summary of full Prescribing Information on the following page.
EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc.
© 2015, Regeneron Pharmaceuticals, Inc.
777 Old Saw Mill River Road, Tarrytown, NY 10591
All rights reserved
1/2015
LEA-0685
43
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
Latest option for fungal keratitis draws
interest; new study prefers to differ
MUTT I confirms that while voriconazole may work in some cases, it is not recommended
By Nancy Groves; Reviewed by Namperumalsamy Venkatesh Prajna, MBBS
azole had captured their imagination worldwide,” Dr. Prajna said. “Sixty-eight percent of
Trial I (MUTT I), visual acuity and perfora- the ophthalmologists would prefer voriconazole
tion outcomes were significantly better in pa- if the choice was given to them.”
These findings set the stage for the MUTT
tients with fungal keratitis who were randomly
I trial comparing the efficacy of
assigned to treatment with natanatamycin, the gold standard,
mycin (Natacyn, Alcon Laboratoand the newer alternative, voriries) than to voriconazole (Vfend,
conazole, in patients with fungal
Pfizer), said principal investigator
corneal ulcers. MUTT I, sponsored
Namperumalsamy Venkatesh PraNatamycin was
by the National Eye Institute, was
jna, MBBS.
superior to voriconazole
Patients randomly assigned to in a randomized clinical a double-masked, randomized trial
in which more than 300 patients
voriconazole were more likely to trial for outcome
from three centers in South India
perforate and to require therapeutic measures, such as
were enrolled.
penetrating keratoplasty, said Dr. visual acuity and
Patients with corneal ulcers who
Prajna, chief, Department of Medi- perforations.
were smear positive for fungus
cal Education, Aravind Eye Care
were screened and then randomly assigned
System, Madurai, Tamil Nadu, India.
However, the differences in efficacy in this to receive either natamycin (5%) or voriconstudy were primarily attributable to the high azole (1%), Dr. Prajna noted.
Study participants remained at the treatnumber of cases caused by Fusarium, about
ment centers for at least a week to ensure that
50% of the positive cultures.
“It’s a well-known fact that different bacteria the drugs were administered on schedule.
have different susceptibility patterns. But for Masking was conducted to the extent posfungus, it was always antifungals,” Dr. Prajna sible (the drugs were dispensed in similar
said. “We never realized that there could be bottles), although natamycin could be identified by its tendency to precipitate.
a differential sensitivity to different drugs.”
The primary endpoint was best-corrected
visual acuity (BVCA) at 3 months compared
NO R ECOMMENDATION
In this study, Fusarium responded much bet- with baseline. Secondary endpoints included
ter to natamycin than to voriconazole. In light treatment failure as evidenced by perforations,
of these results—where differential antifun- size of infiltrate, scarring post-treatment comgal susceptibility has been clearly established pared to pre-treatment, and time to resolution
and in light of the fact that culture is not per- of epithelial defect.
After screening, 323 patients were enrolled
formed for all patients with fungal keratitis—
voriconazole as monotherapy for filamentous in the study. Of the 323 ulcers, 256 (79%)
fungal keratitis is not recommended, Dr. Pra- had positive cultures; 128 (50%) were Fusarium, 54 (21%) were Aspergillus species,
jna noted.
For almost 50 years, natamycin was the 20 (8%) were Curvularia, and 54 (21%) were
only drug available for treating fungal kerati- other species.
Patients had significantly poor visual acuity
tis. However, isolated case reports and small
cases on the efficacy of voriconazole began with a median Snellen visual acuity of 20/90.
to appear within the past decade. A survey, The median scar size was 3.2 mm, and 35%
whose results were published in Cornea in of hypopyon were more than 1 mm.
2009, revealed that the majority of cornea
OLDER TR EATMENT OPTION
specialists preferred voriconazole for topiThe results—which were inconsistent with the
cal treatment.
“The results were very clear that voricon- preference of corneal specialists worldwide—
MADUR AI, TAMIL NADU, INDIA ::
IN THE MYCOTIC ULCER Treatment
take-home
showed better efficacy for the older treatment
than the newer option.
“At 3 months, very clearly natamycin-treated
cases had significantly better BCVA than voriconazole-treated cases (95% CI, p = 0.006),”
Dr. Prajna said.
In the entire study population, 52 perforations were reported, with almost twice as
many in the voriconazole group (34 versus
18, p = 0.009).
SU B GR OU P A N A LY S I S
A subgroup analysis showed that patients positive for Fusarium healed significantly more
rapidly with natamycin than voriconazole (p
= 0.005), while there was no significant difference in healing time with non-Fusarium
cases.
The investigators also explored an association between in vitro susceptibility to antifungal medication and clinical outcomes.
“We found out that voriconazole was not
a great drug for Fusarium,” Dr. Prajna said.
A. flavus had the highest minimum inhibitory concentration (MIC) 50 and MIC 90 among
natamycin-treated organisms, and Fusarium
species had the highest MIC 50 and MIC 90
among voriconazole-treated organisms.
“When we correlated MIC with the final
visual outcome, we found that decreased susceptibility to natamycin correlated with increased odds of perforation, while susceptibility to voriconazole was not clearly associated with measured outcomes,” he added.
Limitations to the study included enrollment exclusively of patients in South India,
exclusion of contact lens wearers, comparison
only of monotherapies, and the predominance
of Fusarium cases, the organism most prevalent in fungal keratitis cases in South India. ■
NAMPERUMALSAMY VENKATESH PRAJNA, MBBS
P: 91(452)4356-100
E: [email protected]
This article was adapted from Dr. Prajna’s presentation during Cornea Subspecialty Day
at the 2014 meeting of the American Academy of Ophthalmology. Dr. Prajna reported
no financial interests or relationships.
44
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
Early intervention considered key
in diagnosis and treatment of scleritis
Steroids, followed by cytotoxic immunosuppressives have shown efficacy in treating disease
By Vanessa Caceres; Reviewed by Vincent de Luise, MD, FACS
NE W HAVEN, C T ::
SCLERITIS REQUIRES AN EARLY
and accurate diagnosis to help patients recover
from this potentially sight- and life-threatening disease, said Vincent de Luise, MD, FACS.
“We need to confront these cases confidently,
diagnose them accurately, and provide prompt,
correct intervention,” said Dr. de Luise, assistant clinical professor of ophthalmology, Yale
University School of Medicine, New Haven, CT.
Scleritis is a painful, progressive disease
characterized by inflammation and edema in
In the photo at left, a patient presents with anterior scleritis; at right, a patient with diffuse episcleritis.
the sclera and deep episclera. Corneal and exPain is a distinguishing factor between scleritis and episcleritis. If there is pain, physicians may consider
ternal disease specialists are more likely than
scleritis. If it’s just itching, they may consider episcleritis. (Photos courtesy of Vincent de Luise, MD, FACS)
general ophthalmologists to see scleritis regularly. Scleritis is more common in females. In
50% of cases, it is idiopathic.
“In the other 50%, there is an underlying ally blanch with episcleritis but not scleritis.
with caution as they have the risks of scleral
systemic disease,” Dr. de Luise said.
Ocular sequelae for scleritis include cata- melt and perforation.
The underlying disease could be an immune- ract, glaucoma, uveitis, and peripheral ulcerOral tumor necrosis factor inhibitors (TNFmediated systemic disease, and the
ative keratitis.
alpha inhibitors) and other biologics have also
strongest association is with vasLaboratory testing can help shown efficacy in patients with scleritis but
culitis. Associated diseases include
identify the type of scleritis, Dr. should be prescribed in collaboration with a
rheumatoid arthritis, Wegener’s
de Luise said.
rheumatologist, as they have serious systemic
granulomatosis, polyarteritis noDepending
on
the
history,
testing
side effects, Dr. de Luise said.
Scleritis can indicate
dosa, and herpes zoster.
should
include
rheumatoid
factor,
Of the biologics, infliximab, adalimumab,
serious systemic
In a quarter of the cases where disease and requires
anti-nuclear antibodies, human leu- daclizumab, rituximab, and etanercept have
there is underlying disease, the eye prompt diagnosis and
kocyte antigen, anti-neutrophilic been used in the management of recalcitrant
is the presenting sign.
cycloplasmic antibodies, and tests cases of scleritis, with variable degrees of
treatment. Episcleritis
“In these cases, the eye is the also has certain
for tuberculosis, Lyme disease, sar- effectiveness.
barometer, and the initial sign of treatment pearls.
coidosis, and gout. Imaging tests
For necrotizing scleritis, IV corticosteroids
a potentially lethal disease,” Dr.
include CXR, B-scan, sinus films, and IV methylprednisolone should be considde Luise said.
and CT or MRI tests.
ered, Dr. de Luise advised.
Scleritis is almost always anterior, and it
If there is impending scleral perforation, Dr.
is classified as diffuse, nodular, necrotizing
de Luise said tectonic scleral patch graft surTR EATMENT STR ATEGIES
with inflammation, or necrotizing without in- To treat scleritis, Dr. de Luise has found oral gery is the recommended initial management
flammation. Posterior scleritis is rare and can nonsteroidal anti-inflammatory drugs (NSAIDs) as the diagnosis is being pursued and oral
mimic a choroidal tumor.
to be of little value, and he advised moving treatment begun.
immediately to oral steroids followed by oral
MAKING THE DISTINCTION
EPISCLER ITIS IDEN TIFICATION,
cytotoxic immunosuppressives, assuming no
Pain is a distinguishing factor between scleri- systemic contraindications.
TR EATMENT
tis and episcleritis, Dr. de Luise said.
Methotrexate, azathioprine, and cyclophos- In contrasting the presentation of scleritis with
“If there is pain, consider scleritis; if it’s just phamide, are cytotoxic immunosuppressives that of episcleritis, Dr. de Luise said the latter
itching, consider episcleritis,” he said.
that have shown efficacy in scleritis, Dr. de is a self-limited disease of the episclera.
In an examination under natural light, pa- Luise said.
“In episcleritis, the inflammation is supertients with scleritis will present with a bluMycophenolate mofetil and cyclosporine ficial, and the sclera is minimally engorged,
ish-red discoloration in the area with scleritis. have also been employed.
if at all,” he said.
Using neosynephrine 2.5%, vessels will usuDr. de Luise said to use periocular steroids
Continues on page 46 : Scleritis
take-home
INCREDIBLE
RED REFLEX.
(SO GOOD, THE OTHER COLORS ARE JEALOUS.)
Red Reflex is crucial to the success of your cataract procedure. It’s equally crucial
to know that Haag-Streit has engineered outstanding technology for illuminating
the anterior segment, even in low light. C.RED features a revolutionary LED light
which provides brilliant red reflex with outstanding stability, and only one cornea
reflection. Learn more at HSmicroscopes.com/OPH
80O.787.5426
HSmicroscopes.com/OPH
© 2015 Haag-Streit USA. All Rights Reserved.
46
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
Tacrolimus viable option for treating
vernal keratoconjunctivitis patients
Small study finds low dose of macrolide antibiotic to be effective, safe, with few side effects
By Vanessa Caceres; Reviewed by Samir Shoughy, MD, FRCS (Glasg.)
RI YADH, SAUDI AR ABIA ::
A LOW DOSE OF TOPICAL tacro-
helper cell-mediated B-cell proliferation, and
cytokine formation.
limus was a safe and effective treatment for
vernal keratoconjunctivitis (VKC) in a recent
OUTCOMES FROM SMALL SER IES
study, said Samir Shoughy, MD, FRCS (Glasg.). Dr. Shoughy shared results from a study of 62
Vernal keratoconjunctivitis is a leading cause patients with refractory VKC. Patients—who
of outpatient ophthalmic morbidity, said Dr. ranged in age from 5 to 47 years old (mean
Shoughy, The Eye Center and The Eye Founda- age, 18 years)—had symptoms and signs of
tion for Research in Ophthalmology, Riyadh, VKC even though they had used conventional
Saudi Arabia.
medications. VKC was diagnosed by itching,
“If not properly treated, it can lead to scar- redness, foreign body sensation, and discharge.
ring, microbial keratitis, limbal tisResearchers excluded patients
sue hyperplasia, amblyopia, and
with known hypersensitivity to tadry eye syndrome,” he said.
crolimus, infectious eye disease,
VKC is more common in dry
those who were pregnant, and those
and hot climates and in children
on systemic therapy for other alTacrolimus 0.01%
or young adults with an atopic back- was effective for the
lergic diseases.
ground. More males than females treatment of vernal
Clinical symptoms were graded
have VKC.
as
normal (0), mild (1+), moderate
keratoconjunctivitis
Typical treatment for VKC in- in a study with 62
(2+), or severe (3+). Researchers
cludes antihistamines, mast cell patients.
assessed patients before tacrolimus
stabilizers, vasoconstrictors, cortreatment began and at one month
ticosteroids, and immunomodulaafter treatment.
tors, Dr. Shoughy said.
Tacrolimus eye drops were reconstituted at
“Corticosteroids are an important line of Dr. Shoughy’s center in a sterile environment
treatment but are associated with complica- by adding balanced salt solution to the contions like increased IOP and cataract forma- tents of a tacrolimus capsule, to achieve a dose
tion,” he said. “We are in need of more safe of 0.01%. Patients used the solution twice a
and effective drugs.”
day for a month.
Tacrolimus is a macrolide antibiotic that is
Itching improved in 82% of patients, red10 to 100 times more potent than cyclospo- ness improved in 75%, discharge reduced in
rine, he explained.
84%, and foreign body sensation reduced in
The drug suppresses T-cell activation, T 77%. All percentages were based on the actual
take-home
SCLERITIS
( Continued from page 44 )
Patients usually have a history of allergy.
Episcleritis can be divided into two types: simple (diffuse) and nodular. Although episcleritis is usually idiopathic, it may be associated with trauma, gout, atopy, rheumatoid arthritis, lupus, or inflammatory bowel disease.
There is rarely an anterior chamber reaction
in episcleritis.
There is also a related form, called pingueculitis, where the episcleritis manifests as an
inflamed pinguecula, he said.
Treatment for mild episcleritis includes sunglasses and artificial tears. If the patient has
itching, the specialist can recommend topical
anti-allergics. For discomfort, Dr. de Luise advised the use of topical NSAIDS. In recalcitrant
number of patients experiencing a symptom,
not the full study group.
The improved signs included conjunctival
hyperemia, limbal infiltrates, Trantas dots, and
superficial punctate keratitis. Papillary hypertrophy also improved but to a lesser degree
compared with the other signs.
Five percent (three patients) experienced side
effects from the treatment. Two felt a burning
sensation, and one felt irritation.
When asked why such a low percentage of
patients had side effects compared with others’
use of tacrolimus, Dr. Shoughy said it was likely
because the study dose was particularly low.
“We use one-tenth of the concentration used
in most trials,” he said.
Dr. Shoughy also reported that a maintenance
dose of 0.01% could be used by patients. He
and study researchers have prescribed this dose
safely for once daily or once every other day.
He also said that he uses tacrolimus as a
first-line therapy, without the use of steroids.
After one week of therapy, he typically sees
70% to 80% of the needed response in patients, and itching usually resolves in 2 to 3
days after patients begin to use it. ■
SAMIR SHOUGHY, MD, FRCS (GLASG.)
E: [email protected]
This article was adapted from Dr. Shoughy’s presentation at the 2014 meeting of the
American Academy of Ophthalmology. Dr. Shoughy did not indicate any proprietary
interest in the subject matter.
cases, oral NSAIDs such as indomethacin 75
mg to 100 mg orally per day, and/or topical
pulsed corticosteroids, can be used. ■
VINCENT DE LUISE, MD, FACS
E: [email protected]
This article was adapted from Dr. de Luise’s presentation during Cornea Subspecialty
Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. de Luise did
not indicate any proprietary interest in the subject matter.
47
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
Infectious scleritis exists in many forms
Treatments and causes can vary widely; diagnosis crucial part of managing disease
By Vanessa Caceres; Reviewed by Ana Luisa Höfling-Lima, MD, MBA
roids and systemic antivirals.
“The drug of choice is acyclovir for three
in only 5% to 10% of scleritis patients, but it to eight weeks,” she said. “If the patient has
can have poor visual outcomes, said Ana Luisa had previous treatment with immunotherapy, this can worsen their inflammation.”
Höfling-Lima, MD, MBA.
Inflammation may last 5 months to more
“Since it’s uncommon, there is usually a
late diagnosis,” said Dr. Höfling-Lima, head than 2 years.
Bacterial scleritis includes
professor, Ophthalmology Department at Escola Paulista de Medicina – UNIFESP, São Pseudomonas aeruginosa, MyPaulo, Brazil. “The visual outcome can be cobacterium chelonae, Mycobacpoor because of aggressive infection and dif- teriumabsessus, and Mycobacficulty in penetration of drugs in the scleral teriumtuberculosis. Bacterial
scleritis has been seen after
tissue.”
It is crucial to evaluate if the tests for infec- pterygium surgery. It can sometious scleritis are negative before proceeding times have a delayed occurwith treatment for rheumatological disease rence after surgery or trauma
as in most situations, high doses of steroids and could be caused by a dormant organism,
or immunosuppressors will be prescribed, Dr. Höfling-Lima said.
“We have to pay attention to that possibilshe said.
Infectious scleritis can be caused by bacte- ity,” she said.
In her home country of Brazil, Dr. Höflingria, virus, fungi and protozoan, and the infections can be endogenous or exogenous. Cases Lima and fellow ophthalmologists have seen
are often traced back to trauma, immunosup- Pseudomonas scleritis caused by trauma caused
pression, conjunctiva or pterygium surgery, by sugar cane leaves. They treated these cases
or geographic-specific systemic diseases that with topical and systemic amikacin.
Treatment for Pseudomonas scleritis can
include syphillis, tuberculosis, toxoplasmotypically include intravenous ceftazidime
sis, and leprosy.
Patients will present with redness, pain, lac- and aminoglycosides, which may be more
rimation, intraocular inflammation, scleral ne- effective with single-intravenous agents
when used in addition to topicrosis anterior chamber reaction
cal antibiotics.
with anterior and posterior involve“These may obviate the need
ment, scleral abscesses, and tissue
for adjunctive surgical procedures,
damage beyond obvious clinical
such as cryotherapy, surgical exfindings.
Consider infectious
tirpation, or conjunctival recesscleritis if a patient with
sion,” she said.
TR ACK ING DISE ASE
Topical ceftazidime 5% and forUltrasound biomicroscopy, opti- scleritis tests negative
tified aminoglycosides 1.4% also
cal coherence tomography, scleral for rheumatological
may be useful, safe, and effective
scrapings when possible, poly- disease.
therapy for pseudomonal keratimerase chain reaction used with
tissue specimens from the scleral biopsy, and tis, she added.
Another possibility in infectious scleritis,
immunofluorescence are all useful in helping to diagnose and track infectious scleri- although it is not that common, is Nocardia
scleritis, Dr. Höfling-Lima said. Signs of this
tis, Dr. Höfling-Lima said.
Also, “new CT technology has become a tool include scleritis with multiple nodules that
for us not for diagnosis but to follow patients do not respond to fluoroquinolones.
Mycotic scleritis can also occur and often
with necrotizing scleritis,” she said.
Dr. Höfling-Lima outlined several forms of progresses quickly despite treatment. This
infectious scleritis and how to treat it. For ex- can turn quickly into cataracts, serious retample, she said that herpes scleritis is hard inal or choroidal detachments, and endoto diagnose and requires both systemic ste- phthalmitis, Dr. Höfling-Lima said. How-
SÃO PAULO, BR A ZIL ::
INFECTIOUS SCLERITIS OCCURS
ever, prognosis is often poor because of late
diagnosis, poor penetration of antifungal
drugs into the avascular sclera, and the ability of organisms to remain in the avascular
scleral tissue without inciting an inflammatory response.
‘New CT technology has
become a tool . . . to follow
patients with necrotizing
scleritis.’ — Ana Luisa Höfling-Lima, MD, MBA
take-home
Dr. Höfling-Lima addressed Acanthamoeba
scleritis, noting that 14% of Acanthamoeba keratitis cases have associated scleritis that can
be anterior, diffuse, or nodular necrotizing.
Causes include scleral invasion by Acanthamoeba and immune-mediated response to dead
and dying ameba. Treatment in these cases
can include systemic treatment with miltefosine or voriconazole as well as cryotherapy.
Sometimes, enucleation is required.
If a patient presents with M. tuberculosis
scleritis, it is secondary to a primary spot,
such as on the lung.
However, it can also be seen without systemic symptoms, Dr. Höfling-Lima said.
Diagnosis is made with a PPD test, a chest
X-ray, and a smear of the scleral lesion. The
most common treatment is systemic steroids
as well as a fixed combination with rifampcin, isoniazid, and pyrazinamide.
For Mycobacterium other than tuberculosis
scleritis, treatments are commonly clarithroymycin 500 mg every 12 hours and amikacin 7.5
mg/kg three times a day for 3 weeks.
Yet another infectious possibility is toxopolasmosis, Dr. Höfling-Lima said. ■
ANA LUISA HÖFLING-LIMA, MD, MBA
E: [email protected]
This article was adapted from Dr. Höfling-Lima’s presentation at the 2014 meeting of
the American Academy of Ophthalmology. She did not indicate any proprietary interest
in the subject matter.
ADVANCEMENT
NEVER STOPS.
Please see adjacent page for Important Product Information.
k1RYDUWLV25$-$'&
Lens power, sphere, cylinder
and axis recommendation
3URYHQWRVLJQLFDQWO\LQFUHDVH
accuracy of lens power selection and decrease prediction
error in prior myopic LASIK
patients1
Improved astigmatic outcomes
by accounting for posterior
corneal contribution2
™
ORA System, now featuring new
VerifEye+ Technology
™
IMAGE
PLAN
GUIDE
VALIDATE
NOW WITH REAL-TIME DATA VALIDATION IN YOUR OCULAR
The ORA™ System with new VerifEye+™ Technology empowers decision
PDNLQJLQWKH25ZLWKLQWUDRSHUDWLYHGDWDYHULFDWLRQ:KHQFRPSDUHGWR
Verion
conventional (preoperative) calculation of cylinder power and axis, surgeons
™
IMAGE GUIDED SYSTEM
ORA System
™
using the ORA™ System with VerifEye+™ Technology have reduced the number
WITH VERIFEYE+™
RISDWLHQWVZKRIDOORXWVLGHWKHLQWHQGHGDVWLJPDWLFWDUJHWE\DOPRVW*,2
Talk to your Alcon rep to learn more.
ORA System
™
WITH VERIFEYE+™
Advancing
CATARACT SURGERY
50
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
Preop focus on patient best offense
against postoperative infection
Identifying specific risk factors more effective approach rather than reacting to organisms
By Lynda Charters; Reviewed by Terrence P. O’Brien, MD
MIAMI ::
THE OCULAR ISOLATES
that are most likely to be recovered in the United States from
infections related to ophthalmic
surgeries are predominantly grampositive bacterial
organisms, especially coagulasepositive and coagulase-negative
Dr. O’Brien
staphylococci.
These organisms are linked in
upward of 95% of post-cataract in-
fections with gram negative and
fungal organisms being much less
commonly implicated.
“This trend to recovery of grampositive organisms, while not new,
is continuing, and studies over the
past few years have documented
the preponderance,” said Terrence
P. O’Brien, MD, professor of ophthalmology, University of Miami,
and co-director, Ocular Microbiology Laboratory, Bascom Palmer
Eye Institute, Miami.
The most recent laboratory research has reinforced that no sin-
trast to that enjoyed four decades
gle antibiotic agent is universally
ago,” he said.
effective for eradicating these bacOphthalmic surgeons recogteria and suggests that a combinize the eye’s precarious and
nation of antibacterial agents may
vulnerable situation because of
be more effective.
its unique structure and the easy
However, turning one’s attenaccess through which organisms
tion on the host, i.e., the patient,
can gain entry during ophthalmic
and identifying specific risk facsurgery.
tors may be a more effective ap“Because bacteria can be sequesproach for beating these culprits
tered in a relatively closed environof infection rather than reacting to
ment, this a unique risk factor for
the organisms—given their abilall ophthalmic procedures, includity to rapidly evolve and become
ing cataract and glaucoma surgerresistant to prevention as well as
ies, LASIK, and even
treatment.
injections into the vitAn alarming trend
reous cavity for retinal
that has surfaced over
disorders,” Dr. O’Brien
the past several years
said.
is the evolving resisPostoperative
“Ocular surgeons
tance seen among infections with ocular
must gain an underocular pathogens to surgeries may be
standing of those risk
commonly used an- reduced substantially
factors and use stratetibiotics, especially by effectively treating
gies to improve or ref luoroqu i nolones, active ocular disease
duce the likelihood of
as well as other fre- in advance before the
patients contracting inquently prescribed an- patient enters the
fection,” he added.
tibiotics. Among the operating room.
These strategies inpredominantly recovclude adopting universal precautions
ered, gram-positive organisms, reto prevent infection and special atduced susceptibility to the comtention that is unique to the eye. One
monly used antibiotics is being
important step is to treat patients
observed, he noted.
who may have chronic external ocular infections, such as blepharitis
FEW DRUGS DEV ELOPED
and blepharoconjunctivitis, before
Another unfortunate trend comthey undergo an ocular surgery, he
pounds this problem, according
noted.
to Dr. O’Brien. Fewer new drugs
“Many studies have found that
are being investigated by fewer
these external ocular infections
companies because of the dauntare the sources of the organism’s
ing costs of research and developaccess at the time of an ocular
ment (R&D), he observed.
surgery,” Dr. O’Brien said. “Pre“Compared with the golden age
treatment is a recognized approach
of R&D of antibiotics in the 1970s
that prevents patients from going
when multiple new agents were
into surgery with an active exterintroduced every year, now the
nal ocular disease.”
situation for drug development …
Having said this, Dr. O’Brien
to treat systemic, as well as ocualso noted there is controversy surlar infections, is in marked con-
take-home
ORA™ SYSTEM IMPORTANT PRODUCT INFORMATION
CAUTION: Federal (USA) law restricts this device to sale by, or on the order of, a
physician. INTENDED USE: The ORA™ System uses wavefront aberrometry data in the
measurement and analysis of the refractive power of the eye (i.e. sphere, cylinder, and
axis measurements) to support cataract surgical procedures. CONTRAINDICATIONS:
The ORA™ System is contraindicated for patients: who have progressive retinal pathology
such as diabetic retinopathy, macular degeneration, or any other pathology that the
SK\VLFLDQGHHPVZRXOGLQWHUIHUHZLWKSDWLHQW[DWLRQZKRKDYHFRUQHDOSDWKRORJ\VXFK
as Fuchs’, EBMD, keratoconus, advanced pterygium impairing the cornea, or any other
SDWKRORJ\ WKDW WKH SK\VLFLDQ GHHPV ZRXOG LQWHUIHUH ZLWK WKH PHDVXUHPHQW SURFHVV
whose preoperative regimen includes residual viscous substances left on the corneal
VXUIDFH VXFK DV OLGRFDLQH JHO RU YLVFRHODVWLFV ZLWK YLVXDOO\ VLJQLFDQW PHGLD RSDFLW\
VXFKDVSURPLQHQWRDWHUVRUDVWHURLGK\DORVLVZKDWZLOOHLWKHUOLPLWRUSURKLELWWKH
PHDVXUHPHQW SURFHVV RU ZKR KDYH UHFHLYHG UHWUR RU SHULEXOEDU EORFN RU DQ\ RWKHU
WUHDWPHQWWKDWLPSDLUVWKHLUDELOLW\WRYLVXDOL]HWKH[DWLRQOLJKWΖQDGGLWLRQXWLOL]DWLRQ
of iris hooks during an ORA™ System image capture is contraindicated, because the use
of iris hooks will yield inaccurate measurements. WARNINGS AND PRECAUTIONS:
6LJQLFDQW FHQWUDO FRUQHDO LUUHJXODULWLHV UHVXOWLQJ LQ KLJKHU RUGHU DEHUUDWLRQV PLJKW
yield inaccurate refractive measurements. Post refractive keratectomy eyes might yield
LQDFFXUDWHUHIUDFWLYHPHDVXUHPHQW7KHVDIHW\DQGHHFWLYHQHVVRIXVLQJWKHGDWDIURP
the ORA™ System have not been established for determining treatments involving higher
order aberrations of the eye such as coma and spherical aberrations. The ORA ™ System
LVLQWHQGHGIRUXVHE\TXDOLHGKHDOWKSHUVRQQHORQO\ΖPSURSHUXVHRIWKLVGHYLFHPD\
result in exposure to dangerous voltage or hazardous laser-like radiation exposure.
Do not operate the ORA™6\VWHPLQWKHSUHVHQFHRIDPPDEOHDQHVWKHWLFVRUYRODWLOH
solvents such as alcohol or benzene, or in locations that present an explosion hazard.
ATTENTION: Refer to the ORA™ System Operator’s Manual for a complete description
of proper use and maintenance of the ORA™ System, as well as a complete list of
contraindications, warnings and precautions.
Advancing
CATARACT SURGERY
© 2015 Novartis
3/15 ORA15009JAD-C
51
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
(FIGURE 1) Postoperative pseudophakic endophthalmitis
due to culture-proven Staphylococcus aureus with intense
hypopyon.
rounding the use of antibiotics before, during, and following cataract surgeries regarding their effectiveness and the most optimal
route of administration.
“Topical antibiotics, which have been the
mainstay of ophthalmic care, have not been
shown conclusively to universally lower the
risk of infection during ocular surgery,” he
said. “There is a rationale for their use, but no
large-scale multicenter study that definitively
proves their effectiveness has been completed.”
To date, two steps have been shown to reduce
infections, especially during cataract surgeries:
> Topical antiseptic (povidone iodine) during
patient preparation for surgery, and
> Intracameral injection of antibiotic.
While the latter was proven beneficial in
a large European study, questions remained
about which antibiotic was preferred for delivery and the manner in which the drug should
be made and delivered. In the United States,
no such commercial drugs are yet approved
for intracameral use in a prophylactic fashion.
With the goal of reducing ocular infections associated with surgery, Dr. O’Brien noted a trend
away from the use of nondisposable instruments.
This is the result of investigations into development of toxic anterior segment syndrome (TASS)
after cataract surgery because of incomplete processing and handling of the instruments.
In the same way, surgeons have recognized
that small-gauge cannulas are hard to clean
and material can be retained in the absence of
proper cleaning and sterilization. Cataract surgeons are using more IOLs that are preloaded
and injected, which eliminates excessive handling and lowers the risk of contamination.
OCULAR INFECTION CONTROL
(FIGURE 2) Preoperative prospective cataract surgery patient with active anterior blepharitis.
Cultures from the lid margins grew heavy methicillin-resistant Staphylococcus epidermidis. (Images
courtesy of Terrence P. O’Brien, MD)
“Alternatives to conventional antibiotics—such
as antimicrobial peptides, antisense agents, or
natural killers, like hypochlorous acid, present
in human neutrophils—may have an increasing role in both treatment and prevention of
infection,” Dr. O’Brien predicted.
These alternatives are attractive because of
their novel mechanisms of action and resistance
to the development of resistance, he noted.
New drug delivery systems are being considered to transport and distribute available
antibiotics and thereby extend their usefulness.
“Some strategies are afoot to use drug delivery, especially nanotechnology, that may
enhance the penetration and potency of the
existing compounds so that higher concentrations can be achieved in the target tissues and
even greater contact time to facilitate greater
drug activity,” Dr. O’Brien explained.
T H E A R MOR ST U DY
The ongoing Antibiotic Resistance Monitoring in
Ocular MicroRganisms (ARMOR) study of bacterial resistance underscores the importance of
concern about this growing resistance problem.
Dr. O’Brien commends surveillance efforts,
such as the ARMOR Study and other such large
undertakings, to maintain awareness of the
evolving trends in organisms that cause ocular infections and in the antimicrobial susceptibility patterns.
“These surveillance strategies are essential
for a better understanding of the enemy, as well
as the rational choices of optimal agents for
treatment and prevention of infection,” he said.
The ARMOR Study has been an important
tool for monitoring trends in resistance to antibiotics, especially fluoroquinolones, he noted.
The latest data collected over the previous
few years have reinforced the concern about
growing microbial resistance to available drugs.
Resistance is growing among the commonly
seen organisms to the most commonly administered ocular antibiotics.
“These data suggested that in some instances
a single agent may be insufficient, but rather
a combination of more than one agent may be
preferred for treating an active infection or for
prophylaxis,” Dr. O’Brien said.
The latest data from the ARMOR study are
expected to be presented at the 2015 annual
meeting of the Association for Research in Vision and Ophthalmology in Denver.
A KEY STR ATEGY
Dr. O’Brien emphasized the importance of heightened preoperative awareness about the patients
who may be at unique risk of developing an
infection by focusing attention on the hosts
first, and not reacting later to the organisms.
“The latter approach over the years has shown
that the bugs tend to win because they are
clever and have evolved over time,” he said.
“They have devised increasingly cunning strategies to evade our efforts to eliminate them.
Extra endeavors exerted preoperatively aimed
to protect the patient during the window of
vulnerability can eliminate problems postoperatively in these altered hosts.”
Focusing on the host may help uncover newer
strategies to protect patients who are uniquely
at risk of infection, he said. ■
TERRENCE P. O’BRIEN, MD
E: [email protected]
Dr. O’Brien is an ad hoc non-salaried consultant for Alcon Laboratories, Allergan,
Bausch + Lomb, Santen Pharmaceuticals, Senju, and Shire.
52
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
Postop topical antibiotic minimizes
infection rate after blepharoplasty
Surgeons should always consider possible presence of community-acquired MRSA
By Cheryl Guttman Krader; Reviewed by Mark A. Alford, MD
FOR T WOR T H, T X ::
SURGICAL SITE INFECTIONS after
blepharoplasty surgery are uncommon whether
or not patients receive antibiotic prophylaxis.
However, postoperative use of a topical antibiotic ointment significantly reduces the risk,
according to a prospective, observational, cohort study undertaken by Mark A. Alford, MD.
The findings of the study should also alert
surgeons to suspect methicillin-resistant Staphylococcus aureus (MRSA) as the
causative pathogen if infection
occurs, said Dr. Alford, the oculoplastic surgeon in private practice, Fort Worth, TX, who conducted the single-surgeon study.
Dr. Alford was motivated to
Dr. Alford
conduct the study recognizing
that while antibiotic ointment is widely used
by oculoplastic surgeons to reduce the risk of
infection after blepharoplasty, there is very little scientific evidence to support the practice.
POTENTIAL CONCERNS
Moreover, there are potential concerns as antibiotic use may lead to contact sensitivity reactions, promote bacterial resistance, and increased cost.
To evaluate its benefits and risks, Dr. Alford
conducted an IRB-approved study comparing
two similar consecutive groups of patients undergoing upper lid blepharoplasty.
The first cohort included 384 patients operated on from November 2011 to April 2013,
who were instructed to use bacitracin ointment
twice daily for 7 days, beginning immediately
after the surgery.
The second cohort comprised 158 patients
operated on from April to December 2013, who
used a sterile ocular lubricant ointment (Refresh P.M., Allergan) with the same application regimen.
Patients were excluded if they had a history
of allergy to bacitracin or had used any antibiotic within the week before surgery. They
were all operated on with the same technique,
which involved a full sterile prep and running
suture closure with 6-0 silk.
One patient using antibiotic ointment developed a surgical site infection (0.26%), which did not culture
positive for MRSA. In the control
group, there were 10 patients with
a surgical site infection (6.3%). Nine
of the patients had a bilateral event
and all were positive for communityacquired MRSA (CA-MRSA).
All of the infections were managed by suture removal and treatment
with an oral antibiotic chosen based
on culture and sensitivity testing.
All of the infections cleared, but all
patients with a CA-MRSA infection
were left with hypertrophic scars.
Photos of a patient in the study who underwent blepharoplasty
“I stopped enrolling patients in the
surgery. Later, the eye became infected. (Photos courtesy of Mark A.
second cohort earlier than planned
Alford, MD)
because the between-group difference in infection rate was statistiIn addition, all personnel who came into
cally significant,” said Dr. Alford.
“The hypertrophic scarring that developed contact with the patients in the operating room
in patients with the CA-MRSA is improving, were negative for MRSA colonization. Only 1
but they are all finding the scarring is cos- patient who developed an MRSA infection was
a health-care worker. None had a previous
metically significant.”
Among the patients who used bacitracin, Staphylococcal infection or smoked.
“The finding that all of the infections were
14 (3.6%) developed an allergic reaction characterized by bilateral erythema, edema, and caused by CA-MRSA is really not unexpected,
itching. Cultures were done in all cases and considering it is a virulent pathogen that has
were negative, and the reactions resolved after become epidemic in the United States,” Dr.
Alford said.
discontinuation of the antibiotic.
“We believe the surgical wounds became
“The rate of allergic reactions to bacitracin ointment in this study is lower than what contaminated by exposure to a community
has been previously reported,” Dr. Alford said. source or self-inoculation from a colonized
nasal cavity,” he said.
Dr. Alford also emphasized that he was not
CONSISTENT APPEAR ANCE
Dr. Alford noted that the CA-MRSA infections promoting the use of bacitracin ointment to
were characterized by the presence of signifi- prevent infection after blepharoplasty.
“Any antibiotic ointment that provides good
cant erythema, purulent material, and elevation along the suture line along with areas of coverage against gram-positive organisms might
tissue necrosis at the site of the sutures and have similar effects,” he said. ■
only minimal edema.
Concerning the possible source of the pathogens, Dr. Alford noted the cultured organisms
MARK A. ALFORD, MD
represented various strains and subtypes of
E: [email protected]
MRSA. He said that the infection rates were low
This article was adapted from Dr. Alford’s presentation at the 2014 meeting of the
(<0.2%) over the past 2 years at both surgery
American Academy of Ophthalmology. Dr. Alford has no relevant financial interests to
centers where the procedures were performed.
disclose.
46TH ANNUAL
DOHENY DAYS CONFERENCE
JUNE 19-20, 2015
GUEST SPEAKERS
The Irvine Memorial Lecturer
Julia A. Haller, MD
Ophthalmologist-in-Chief,
Wills Eye Hospital
Professor and Chair,
Thomas Jeīerson University
Philadelphia, Pennsylvania
The Doheny Memorial Lecturer
Simmons Lessell, MD
Professor of Ophthalmology,
Harvard Medical School
DOHENY SOCIETY OF SCHOLARS
2015 HONOREES
Donald S. Minckler, MD
Young Hee Yoon, MD
Director Ophthalmic Pathology,
University of California at Irvine
Professor of Ophthalmology,
Asan Medical Center
University of Ulsan
Seoul, South Korea
THE ANNUAL DOHENY DAYS CONFERENCE HOSTS DOZENS OF PRESENTERS REPRESENTING A WIDE RANGE OF OPHTHALMIC
SPECIALTIES AIMED AT DISSEMINATING STATE-OF-THE-ART RESEARCH FINDINGS TO IMPROVE CLINICIANS’ ABILITY TO
BETTER DIAGNOSE AND MANAGE PATIENTS WITH OCULAR DISEASE.
Please contact: Sandra Espinoza, CME Coordinator
323-442-6427 l [email protected]
54
APRIL 15, 2015 :: Ophthalmology Times
Special Report )
EFFECTIVE CONCEPTS IN
OCULAR INFECTION CONTROL
Analysis confirms previous conclusion
with intracameral antibiotic use
Kaiser Permanente Northern California study again shows benefit for postop endophthalmitis
By Cheryl Guttman Krader; Reviewed by Neal H. Shorstein, MD
two-thirds of intracameral antibiotic use and
moxifloxacin was used in almost all of the reexpanded patient cohort corroborates the ben- maining cases. Overall, intracameral antibiotic was injected in 39.5% of study eyes and
efit of intracameral antibiotic use.
“We can conclude that intracameral antibi- was almost always used together with a topiotic injections are effective in reducing endo- cal antibiotic.
The analysis excluded eyes that had planned
phthalmitis risk,” said Neal H. Shorstein, MD,
ophthalmologist and associate chief of quality, complex surgery, cases that were performed
Kaiser Permanente, Walnut Creek, CA, and by a retina specialist or oculoplastic surgeon,
and cases with combined glaucoma or corlead author of the original study.
“However, due to the low incidence of this nea surgery.
Cases of endophthalmitis occurring within
infection and because of the effectiveness of
intracameral treatment, no definite conclusion 90 days of surgery were identified from diagcan be drawn to differentiate between cefu- nostic codes in Kaiser Permanente’s Healthroxime and moxifloxacin,” Dr. Shorstein said Connect electronic health record. To validate
“Given the very high concentration of agent in the diagnosis, pertinent information from all
the anterior chamber achieved with intracam- of those cases was thoroughly reviewed by a
eral injection, there may be little difference trained medical abstractor and research ophthalmologist using defined criteria. A total of
between them.”
In 2013, ophthalmologists from Kaiser Per- 113 validated cases of endophthalmitis were
manente Northern California published the identified.
Risk of endophthalmitis was analyzed by lofirst United States study demonstrating the efficacy of intracameral antibiotic injection for gistic regression analysis that was conditioned
on the surgeon to account for techreducing the rate of postoperative
nique and unmeasured factors reendophthalmitis [J Cataract Refract
lated to the surgeon and adjusted
Surg. 2013;39:8-14].
for age, year of surgery, ocular and
The study analyzed data from
systemic comorbidities, posterior
16,264 eyes operated on between
An updated analysis
capsule rupture, and topical anti2007 and 2011, including 12, 609 from cataract surgeons
biotic use. Using eyes treated with
that received intracameral injection at Kaiser Permanente
topical antibiotic only as the refprimarily with cefuroxime (84%), Northern California
erence group, the results showed
and found adoption of intracam- again shows the
that the combination of topical and
eral antibiotic use was associated benefit of intracameral
intracameral antibiotic use signifiwith a 22-fold decline in the rate antibiotic use for
cantly reduced the risk of postoperaof clinical endophthalmitis.
reducing the rate
tive endophthalmitis by almost half
The updated analysis included of postoperative
(adjusted odds ratio = 0.55; 95%
data for 129,077 procedures per- endophthalmitis.
confidence interval 0.32 to 0.93).
formed by 99 community-based
The intracameral only group had a simisurgeons in 20 surgical centers over the years
lar adjusted odds ratio of infection (0.47), al2005 to 2012.
Use of intracameral antibiotic for endophthal- though the confidence interval overlapped 1.
mitis prophylaxis began in late 2007 with in- Patients with no record of pharmacy dispensjection of cefuroxime 1 to 2 mg into the an- ing of a topical antibiotic were over 3 times as
terior chamber. The intracameral technique likely to develop endophthalmitis compared
was increasingly adopted over time, and at with the reference group (adjusted odds ratio
many centers, moxifloxacin 100 mcg was the = 3.10; 95% confidence interval 1.64 to 5.84).
“Intracameral antibiotic injection eliminates
preferred antibiotic.
In the series, cefuroxime accounted for about the added risk that occurs with failure of pharWAL NU T CREEK , CA ::
AN UPDATED ANALYSIS based on an
take-home
MAKING THE INJECTION
VIDEO Watch as intracameral antibiotic
(0.1 mL) is injected. Go to http://bit.ly/1IGSSx1
(Video courtesy of Neal H. Shorstein, MD)
macy dispensing or improper administration
of topical drops,” Dr. Shorstein said.
In the analysis comparing intracameral antibiotic effectiveness, the risk of endophthalmitis
was higher when moxifloxacin was used compared with cefuroxime (adjusted odds ratio =
1.3). However, the difference between groups
was not statistically significant.
“When intracameral antibiotic use was introduced at Kaiser Permanente Northern California, the endophthalmitis rate decreased dramatically and it has continued to fall over time.
“As a paradoxical effect of the increasing adoption of intracameral injection, the plummeting
incidence of endophthalmitis makes statistical
conclusion of the comparative effectiveness of
this already rare complication even more difficult,” Dr. Shorstein commented.
In 2013, intracameral antibiotic was used
in 79% of cataract surgery cases, he noted.
Among about 25,000 injected eyes, the rate of
endophthalmitis was just 1 in 12,000. ■
NEAL H. SHORSTEIN, MD
E: [email protected]
This article was adapted from a presentation at the 2014 meeting of the American
Academy of Ophthalmology. Dr. Shorstein has no relevant financial interests to
disclose.
56
APRIL 15, 2015 :: Ophthalmology Times
clinical diagnosis
Contrast sensitivity reaches
beyond measure of vision
Valuable screening tool for pre- and postop management, IOLs, CXL, diagnostic aid
By Nancy Groves; Reviewed by Gregory J. Pamel, MD, and Prof. Dan Reinstein, MD, FRCSC
ontrast sensitivity provides an
objective measurement of quality of vision to complement the
standard routine measurement
of visual acuity, or quantity of
vision, and is a useful metric in
routine care as well as preoperative and postoperative patient management.
Routine contrast sensitivity testing gives the
ophthalmologist, and particularly the refractive surgeon, another string to their bow and
provides a more complete understanding of
the patient’s visual function.
C
BASELINE MEASUREMENT
For both corneal and intraocular refractive
surgery applications, it is important to measure contrast sensitivity routinely to provide
a baseline measurement so that a comparison
is always possible postoperatively, said Prof.
Dan Reinstein, MD, FRCSC, medical director,
London Vision Clinic, London.
Preoperatively, contrast sensitivity can aid
the physician to pick up signs of deteriorating vision earlier than visual acuity testing.
For example, patients with early cataract
might be diagnosed earlier by a drop in contrast
sensitivity before the visual acuity is affected.
This could help a surgeon decide whether
corneal or intraocular refractive surgery might
be best for the patient, said Prof. Reinstein,
who is also adjunct professor of ophthalmology, Department of Ophthalmology, Columbia University Medical Center, New York, and
professor associé, Centre Hospitalier National
D’Ophthalmologie, Paris.
Postoperatively, contrast sensitivity is used
to assess the quality of vision.
In cases of patients complaining of poor vision, a postoperative contrast sensitivity measurement can be compared to the baseline measurement to evaluate the change in the quality
of vision. This information can then be used
along with topography and wavefront data to
make a diagnosis of the cause of a drop in
quality of vision.
The surgeon can then consider the differ-
ent options available to treat the patient, Prof.
In this example, contrast sensitivity is a useReinstein said.
ful measurement to assess the impact of aberFor corneal surgery, in the past, older-generation rations on visual quality.
Similarly, with new laser surgery platexcimer lasers have been shown to reduce contrast
forms—such as topographysensitivity. However, modern exguided LASIK—clinicians use
cimer lasers have been shown to
contrast sensitivity to show pamaintain or even slightly increase
Contrast sensitivity
tients that their quality of vicontrast sensitivity.
is a more valuable
sion has improved because treat“For example, we have previmetric than many
ment was customized to their
ously reported no reduction in
ophthalmologists
needs, and corneal aberrations
contrast sensitivity at 3, 6, 12,
realize, with
were reduced to improve qualor 18 cpd for myopic and hyperapplications in
ity of vision.
opic LASIK with the Carl Zeiss
preoperative and
Meditec MEL80 excimer laser,”
postoperative
Prof. Reinstein said.
W E A LT H OF DATA
management of
“In comparison, a statistically
Contrast sensitivity has perhaps
corneal and refractive
significant decrease in contrast
been underused in ophthalmolsurgery patients and
sensitivity has been reported
ogy practices despite the wealth
routine screening of
after multifocal IOL surgery,” he
of data on its application in varipatients’ quality of
added. “Studies such as these
ous procedures.
vision. help to educate ophthalmolo“In intraocular optics, any
gists on the changes in vision
time you attempt to expand the
that might be expected for difrange of vision with a multifoferent refractive procedures.”
cal IOL, you’re going to lose some contrast sensitivity,” said Gregory J. Pamel, MD, a LASIK
D I A G N O S I S O F C O M P L I C A T I O N S and vision correction surgery specialist in New
Finally, contrast sensitivity is a useful mea- York and clinical assistant professor of ophsurement to consider as part of the diagnosis thalmology at New York University School of
of optical complications following refractive Medicine. “That’s been well documented in
surgery. Contrast sensitivity has been shown the literature.”
to be correlated with wavefront measurements.
He added that when a patient is dissatisfied
For example, in a previous study, Prof. Re- following a multifocal lens implant despite exinstein and colleagues compared contrast sen- cellent visual acuity on the Snellen chart, ophsitivity between 2 groups of patients: a repair thalmologists already understand that vision
group of eyes selected for wavefront-guided re- has been impacted by the procedure and don’t
pair because of debilitating night vision distur- need contrast sensitivity testing to prove it.
bances following primary myopic LASIK, and a
Consequently, they may not consider it neccontrol group matched for spherical equivalent essary as a routine component of postoperatreated but with no night vision complaints.
tive patient management.
In the control group, there was an increase
Another reason why contrast sensitivity testin spherical aberration but no change in con- ing has had a limited postoperative role is that
trast sensitivity. In the wavefront-guided re- it is challenging to determine when it might
pair group, there was a reduction of spheri- be worthwhile.
cal aberration by 27%, and although spheri“We’ve all had patients who can see very
cal aberration was still much higher than that well postoperatively, seeing 20/20 at distance
of the normal group, contrast sensitivity re- and J1 up close with a multifocal lens who are
turned to normal.
unhappy, and there are those who don’t nec-
TAKE-HOME
APRIL 15, 2015 :: Ophthalmology Times
clinical diagnosis
essarily see 20/20 at distance and don’t necessarily read 20/20 at near after a multifocal
lens implant who are very happy,” Dr. Pamel
said. “Contrast sensitivity doesn’t always differentiate those patients.”
The explanation may lie in part with the
neuroadaptivity of the brain and how well it
is allowing patients to see to their level of satisfaction. However, contrast sensitivity testing may still play a role by a circuitous route.
“We know that contrast sensitivity improves
in the first 6 months after implantation of a
multifocal lens as a result of neuroadaptation,”
Dr. Pamel said. “So if a patient is not happy at
1 month we could take their contrast sensitivity
and check it again at 6 months to show them
that it has improved. That may be a way to
continue to educate the patient after surgery.”
Contrast sensitivity may be even more valuable as advancements continue in the technology of multifocal lenses, Dr. Pamel said.
Soon, surgeons may perform comparative
studies of older versus newer lens technologies and use the contrast sensitivity results
to show future cataract patients the dramatically better real-world results they are likely
to have with the improved lenses.
HELPFUL IN ENHANCEMENTS
Contrast sensitivity could also be helpful when
performing enhancements on patients who may
have had laser surgery 10 or more years ago
with earlier versions of technology and are experiencing problems, such as glare and halos
or poor night vision. Often, these patients have
gone to a number of physicians who have corrected their vision in a darkened exam room
to see the 20/20 or 20/25 line, yet they are still
unhappy with their vision and its impact on
their quality of life.
“This really is a function of their loss of
contrast sensitivity, and the laser technology
that is out there now can improve upon that
dramatically,” Dr. Pamel said. “Contrast sensitivity would be very beneficial in explaining
to the patient why they’re not seeing well.”
Yet another aspect of vision correction in
which contrast sensitivity could be helpful is
corneal collagen crosslinking (CXL) for keratoconus. Sometimes patients subjectively report improved vision after this procedure despite modest gains in visual acuity, and this
may be due to enhanced contrast sensitivity.
Dr. Pamel and colleagues are performing a
study on contrast sensitivity before and after
CXL to determine if they can better understand
potential benefits and apply this knowledge
to future cases.
Contrast sensitivity testing has been part
of the clinical trial process for presbyopic cor-
neal inlays. Results have shown that contrast
sensitivity does not change significantly after
corneal inlays have been implanted.
Contrast sensitivity testing will be important
for physicians to perform both preoperatively
and postoperatively to demonstrate to patients
that their visual quality has not changed, Dr.
Pamel suggested. ■
57
GREGORY J. PAMEL, MD
E: [email protected]
Dr. Pamel has no financial interests in any of the products mentioned in this article.
PROF. DAN REINSTEIN, MD, FRCSC
E: [email protected]
Dr. Reinstein is a consultant for Carl Zeiss Meditec.
Finding the right angle
can be challenging !
Sign up for the Pentacam® educational
events at www.pentacamseminar.com
Finding the correct orientation of a Toric IOL implant is
not an easy task ! The OCULUS Pentacam® can help:
9
9
9
9
Topography of anterior and posterior corneal surface
Total #orneal 2efractive 0ower
Evaluation of corneal optical densitometry
Support for selection, orientation and calculation of Toric IOLs
Visit the OCULUS Booth #1845 at the ASCRS 2015 in San Diego
www.oculususa.com
+ (* #0-"2*2020 "-+4Tel: 888-519-5375
58
APRIL 15, 2015 :: Ophthalmology Times
clinical diagnosis
Yin-yang of OGRS has implications
for diabetic ocular complications
Gene therapy link shows promise for epithelial wound healing, corneal sensitivity, dry eye
By Nancy Groves; Reviewed by Joseph W. Sassani, MD, MHA
HERSHE Y, PA ::
he opioid growth regulatory system
(OGRS) is inadequately recognized
for its implications in the pathobiology and treatment of the complications of diabetes, said Joseph W.
Sassani, MD.
The OGRS appears to be disordered in diabetic animals, added Dr. Sassani, professor of ophthalmology and pathology, Penn State University’s Hershey Medical
Center (HMC), Hershey, PA.
Studies have shown, however, that function
can be restored to normalize corneal epithelial wound healing, corneal sensitivity, and
tear production in models of both type 1 and
type 2 diabetes through treatment with naltrexone, the pharmacologic antagonist of naturally occurring opioid growth factor (OGF,
[MET5]-Enkephalin).
Dr. Sassani described OGF and naltrexone
as the “yin and yang” of the OGRS, whose
main components are OGF and its specific receptor, OGFr.
OGF is a naturally occurring opioid that suppresses cell division when bound to OGFr. It
is tonically produced, and its level in tissue is
usually neither maximized nor minimized. As
a result of this characteristic, manipulation of
the OGRS can decrease or increase cell division.
T
regulates cell division, while cell division could be accelerated by decreasing the interaction of OGF with
its receptor, either by decreasing the
production of OGF or its receptor or
by utilizing a blocking agent, like
naltrexone, to directly block OGFOGFr interaction, Dr. Sassani said.
TWO DECADES
OF RESEARCH
Over past 25 years, the research
team—including Ian S. Zagon, PhD,
and Patricia J. McLaughlin, PhD, of
the HMC Department of Neural and
Behavioral Science—has delineated
Ian Zagon, PhD (left), and Patricia McLaughlin, PhD, were
the role of the OGF-OGFr system in
part of the research team that linked the OGF-OGFr system to
the homeostasis and healing of ocdiabetic ocular complications. (Photo courtesy of Joseph Sassani, MD)
ular tissues and demonstrated its
role in the pathobiology of diabetic
ocular complications.
The researchers initially demonwhile antisense diminished the expression and
strated that the OGRS modulates outgrowth of accelerated wound healing.
the corneal epithelium in organ culture, then
Next, a series of studies showed that naldemonstrated the ability of OGF treatment to trexone accelerated re-epithelialization, while
suppress DNA synthesis in the cornea of the OGF suppressed epithelial wound healing. The
living rat and that of naltrexone to increase it. results also showed that naltrexone increased
Building on these findings, the researchers DNA synthesis and OGF decreased the process.
conducted a series of investigations determining
Connecting these laboratory findings to pathat treatment with either systemic or topical tient care, Dr. Sassani explained that keratopathy and neuropathy are common complications of this disease, and both type 1 and
type 2 diabetes are associated with delayed
corneal epithelial wound healing, abnormal
corneal sensitivity, and dry eye.
‘These yin-and-yang characteristics
make it uniquely suitable for therapeutic
manipulation.’ — Joseph W. Sassani, MD
“These ‘yin-and-yang’ characteristics make
it uniquely suitable for therapeutic manipulation,” Dr. Sassani said.
The OGF-OGFr axis can be manipulated in
several ways to regulate cell division. OGF is a
negative or inhibitory growth factor, while naltrexone, which blocks OGFr, stimulates growth.
The addition of exogenous OGF or an increase in the number of its receptors down-
naltrexone resulted in an increased rate of rat
corneal epithelial wound healing. Treatment
with topical naltrexone also led to more rapid
healing in rabbit corneas.
The team also studied regulation of wound
healing by using a gene gun to deliver sense
and antisense OGFr cDNA into corneal epithelial cells in rat eyes. Sense caused overexpression of OGFr and delayed wound healing,
LINK WITH DIABETES
The link between endogenous opioids and
diabetes is that elevated levels of OGF have
been found in the plasma of diabetic humans,
as well as in genetically obese diabetic mice,
and both OGF and OGFr have been found in
the epithelium of diabetic animals.
“We postulated that abnormalities of opioid
regulation could contribute to the complications
of diabetes and that blockade of the OGRS by
naltrexone might reverse or ameliorate these
complications,” Dr. Sassani said.
APRIL 15, 2015 :: Ophthalmology Times
clinical diagnosis
‘We postulated that abnormalities of opioid regulation could
contribute to the complications
of diabetes . . .’ — Jospeh W. Sassani, MD
eye and compiled data that support
Summarizing a series of studies,
the concept of OGRS modulation
he explained that in diabetic aniof tear production even in nondiamals, topical naltrexone restores
betic rats. Naltrexone treatment of
corneal epithelial wound healing
diabetic dry eye has restored tear
to levels comparable to systemiproduction to normal levels for up
cally or topically insulin-treated
to 3 days following discontinuation
animals without apparent epitheof the naltrexone therapy in type
lial toxicity.
1 or type 2 diabetic rats.
He also referred to results indiProposing broader implicacating that combined insulin and
tions for the OGRS, Dr. Sassani
naltrexone were no more effective
suggested that it
than either one used
is important in the
independently.
pathobiology of di“The possibilResearch supports
abetic ocular surity exists that inthe hypothesis that
face disease and
sulin and naltrexmanipulation of
that blockade of
one have their efthe opioid growth
the OGFr may have
fect through simiregulatory system can
systemic implicalar mechanisms in
restore function and
tions for OGRS and
diabetic animals or
normalize corneal
diabetes.
that each has the
epithelial wound
Dr. Sassani and
potential to maxhealing, corneal
h i s c ol lea g ue s
imize epit helial
sensitivity, and tear
have e x tende d
wound healing in
production in models
their research to
these animals, leavof both type 1 and
non-ocular diaing no opportunity
type 2 diabetes.
betic complicafor further increase
tions, such as deby the complemenlayed skin wound healing. A 2011
tary modality,” Dr. Sassani said.
study showed that topical treat“Insulin has no effect on wound
ment with naltrexone facilitates
healing in normal animals, and
closure of full-thickness wounds
naltrexone has no impact on blood
in diabetic rats.
glucose levels in diabetic animals,”
Further research suggests that
he added.
naltrexone accelerates wound cloData from various studies also
sure in part by stimulating the
suggest that the route of adminisexpression of angiogenic factors
tration could be a factor and that
within healing tissue in diabetic
systemic insulin may be unable to
animals.
reach the tear film in a concentra“Obviously, there is the potential
tion equivalent to that of topical
for a significant impact on faciliadministration.
tating the initial closure of such
wounds,” Dr. Sassani said.
BROADER
He also observed that naltrexone
IMPLICATIONS
has a more pervasive impact on the
Turning to diabetic corneal neuoverall process of wound healing beropathy, Dr. Sassani noted that sevyond wound closure. For example,
eral studies suggest that it can be
research showed that diminished
reversible with naltrexone therapy.
collagen formation and maturation
The team has also studied dry
in healing granulation tissue were
restored to normal by topical treatment with the opioid antagonist.
In another study, inadequate
healing at 60 days after wounding
in type 1 diabetic rats, reflected
in reduced tensile strength, was
reversed by naltrexone. ■
59
JOSEPH W. SASSANI, MD, MHA
P: 717/531-5690
E: [email protected]
This article was adapted from Dr. Sassani’s presentation of
the Zimmerman Lecture at the 2014 meeting of the American
Academy of Ophthalmology. Dr. Sassani has patent interests
through Pennsylvania State University in the clinical applications of opioid growth regulatory system.
icare-usa.com
888.422.7313
TAKE-HOME
VISIT ASCRS #752!
ICARE REBOUND TONOMETER
ACCURATE AND EASY
IOP MEASUREMENTS
DR. MING WANG, MD, PHD,
DIRECTOR, WANG VISION INSTITUTE,
NASHVILLE TN
“Icare has been a unique device for our cataract
and LASIK clinic in that it not only gives us a
reliable IOP reading, but also and even more
importantly it does not cause any corneal
epithelium damage at all and can be used safely
even right after a LASIK procedure.”
60
APRIL 15, 2015 :: Ophthalmology Times
clinical diagnosis
Palinopsia: Peeking behind doors
of visual perception, visual memory
Pathological afterimages split into two categories: hallucinatory, illusory palinopsia
The Neuro-Connection By David Gersztenkorn, MD, MS, and Andrew G. Lee, MD
THE PATIENT with palinopsia may be
particularly challenging, because of the strange
and sometimes bizarre descriptions that are
reminiscent of what might be heard on a psychiatric ward.
In addition, the physical exam and workup are usually negative. Illusory or hallucinatory visual symptoms can cause patients
considerable mental distress, and these challenging encounters often result in a referral to
neuro-ophthalmology.
In this article, we discuss the clinical considerations for a general ophthalmologist seeing a patient with palinopsia (Greek: opsia for
“seeing”, palin for “again”).
Palinoptic afterimages are pathological and
should be distinguished from physiological afterimages, common and benign phenomena that
occur after viewing a bright stimulus, such as
seeing stars after a retinal exam.
Palinopsia thus describes a heterogeneous
group of pathological symptoms, which we
split into two categories: hallucinatory palinopsia and illusory palinopsia.1Each group
has similarities in symptom description, etiology, mechanism, prognosis, and treatment.
A palinoptic scene consists of a short, stereotyped action sequence that continuously replays for several minutes (e.g., a patient views a
person throwing a ball and then sees the same
scene repeated many times). The palinoptic
image or scene may occur immediately following the stimulus or may be delayed.
Hallucinatory palinopsia can also refer to
seeing an object or physical feature which is
superimposed onto other objects or people in
the same context for a few minutes (Figure B).
For example, a patient sees a man with a
beard and then observes the same beard on
every subsequent person viewed. Another example might be seeing a person wearing distinctive shoes and then the same footwear is
observed on every other person. Hallucinatory palinoptic afterimages are a dysfunction
of visual memory and are caused by seizures
or cortical lesions, such as neoplasms, infarctions, and abscesses.
ILLUSORY PA LI NOPSI A
A visual illusion is the altered perception of a
real external stimulus, such as seeing distortions in shape, size, or color. Illusory palinopsia is similar to a visual illusion in that there
is a dysfunction in the original perception of
H A LLUCI NAT ORY PA LI NOPSI A
A visual hallucination is the creation of an a stimulus, and the afterimages are unformed
image or scene where none exists and can and indistinct.
For example, when viewing a light or other
be simple/unformed (e.g., lights, colors, lines,
bright stimulus—such as a comgeometric designs) or complex/
puter screen and shifting visual
formed (e.g., objects, animals,
focus—a prolonged, indiscrete
people, scenes). Hallucinatory
afterimage remains for several
palinopsia is similar to a comPalinopsia can
minutes in the same location in
plex hallucination but describes
be broadly defined
the visual field. These illusory
the persistence or recurrence
as the persistence
palinoptic afterimages are difof a previously seen, formed,
or recurrence of
ferentiated from physiological
high-resolution image or scene
an image after the
afterimages based on the after(Figure A).
stimulus has been
image intensity and duration.
For example, after seeing a
removed. Formed,
Illusory palinopsia may also
cat, an almost identical copy of
high-resolution
refer
to an object or light in mothe cat may remain fixed in the
afterimages are
tion
leaving
a comet-like tail in
field of view. The hallucinatory
typically more
its
wake
(Figure
C).
afterimage usually is transitory
alarming to patients
The
visual
trails
may be disand of short duration (e.g., lastthan unformed,
continuous,
such
as
in a film
ing seconds to minutes) but may
blurred afterimages.
reel, or may be blurred together,
persist for hours.
TAKE-HOME
A
B
C
Various examples of hallucinatory palinopsia
(Figures A and B) and illusory palinopsia
(Figure C). (Images courtesy of Kelli Gross)
such as in a long-exposure photograph. These
movement-induced afterimages persist for several seconds before fading and are usually identical in color and shape to the original object
or light, but may be vague or less intense. Illusory palinopsia occurs in migraineurs, after
concussions, after hallucinogen use, and as a
prescription drug side effect (e.g., trazodone,
clomiphene, oral contraceptives, topiramate).
ILLUSORY VERSUS
HALLUCINATORY
Illusory palinopsia is due to an abnormality in
the original perception of a stimulus, whereas
hallucinatory palinopsia is due to an abnormality after a stimulus has been encoded in
APRIL 15, 2015 :: Ophthalmology Times
clinical diagnosis
visual memory. External conditions—such as stimulus intensity,
background contrast, fixation time,
and movement—typically affect
the generation and severity of illusory palinopsia but not hallucinatory palinopsia.
Illusory palinopsia occurs immediately after seeing the original
stimulus in the same location in
the visual field, while hallucinatory palinopsia may appear anywhere in the visual field and can
be delayed in time. Illusory palinopsia occurs continuously or predictably, such as in the morning or
during light adaptation. However,
hallucinatory palinopsia is unpredictable. Visual field deficits are
often present with hallucinatory
palinopsia, but not with illusory
palinopsia.
Illusory palinopsia may be
caused by diffuse neuronal pathology, such as global alterations in
neurotransmitter receptors, while
hallucinatory palinopsia is typically
caused by focal cortical pathology.
The clinical characteristics that
separate illusory from hallucinatory palinopsia also help differentiate and assess risk in visual illusions and hallucinations. Complex
visual hallucinations are usually
more worrisome to patients than
simple visual hallucinations or visual illusions.2
CLINICAL ENCOUNTER
The examiner should obtain the
details of the palinopsia to determine if it is hallucinatory or illusory. A full neuro-ophthalmologic
exam including automated visual
fields should then be performed.
Hallucinatory palinopsia, usually
caused by a cortical lesion or seizure, can be the presenting symptom of a serious neurological disease and typically resolves after
treating the underlying disturbance.
A patient reporting even one such
episode should probably be offered
an MRI and a possible referral to
neurology or neuro-ophthalmology.
In contrast, illusory palinopsia
is more common and usually less
worrisome. Patients often have multiple types of illusory palinopsia,
along with visual illusions and
simple hallucinations like visual
snow, Alice in Wonderland Syndrome, and entoptic phenomena.
These illusory symptoms are generally benign and long standing, but
are often refractory to treatment.
Diagnosing the etiology of illusory palinopsia is based on clinical history, with the physical exam
and work-up usually being noncontributory. Illusory palinopsia
can be attributed to prescription
drugs, head trauma, migrainous
neuronal dysfunction, hallucinogen ingestion, or symptoms may
be idiopathic. There is occasional
treatment success with pharmaceuticals that reduce cortical excitability, such as gabapentin. Sunglasses or tinted lenses or filters
may improve symptoms.
Many patients with illusory palinopsia have played referral pinball between neurologists and ophthalmologists and have already received extensive work-ups. Due to
the subjective nature of the symptoms and the absence of physical
findings, clinicians are sometimes
dismissive or mention non-organic
disease.
There is considerable evidence in
the literature confirming the symptom legitimacy, so validating and
explaining the patient’s symptoms
can help ease anxiety and should
be of primary concern. Illusory
palinopsia is presumably due to a
modified neural excitability state
causing dysfunction in light and
DAVID GERSZTENKORN, MD, MS, is an ophthalmology resident affiliated with the Department of
Ophthalmology, Houston Methodist Hospital, Houston, and the Department of Ophthalmology, UTMB, Galveston, TX. He
did not indicate any proprietary interest in the subject matter.
ANDREW G. LEE, MD, is editor of “The Neuro-Connection” column. Dr. Lee is chairman, Department of Ophthalmology, Houston Methodist Hospital, Houston; adjunct professor of ophthalmology, Baylor College of Medicine, Houston; professor
of ophthalmology, neurology, and neurosurgery, Weill Cornell Medical College, Houston; clinical professor of ophthalmology,
The University of Texas Medical Branch, Galveston, TX and The UT MD Anderson Cancer Center; and adjunct professor of
ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, IA and the University of Buffalo, SUNY, Buffalo, NY.
motion processing mechanisms,
thus there is an exaggeration of
normal phenomena, such as physiological afterimages from bright
lights and trails behind quicklymoving objects.
For more information on palinopsia, refer to the review article.1 ■
References
1. Gersztenkorn D, Lee AG. Palinopsia
revamped: A systematic review of the
literature. Surv Ophthalmol. 2014.
2. Teeple RC, Caplan JP, Stern TA.
Visual hallucinations: differential
diagnosis and treatment. Prim
Care Companion J Clin Psychiatry.
2009;11:26-32.
61
62
APRIL 15, 2015 :: Ophthalmology Times
clinical diagnosis
Treatment of TBI, concussions an
underutilized focus in ophthalmology
Visual performance training can improve rehabilitation course, generate more patient visits
By Barry L. Seiller, MD, MBA, Special to Ophthalmology Times
The severity or number of
AS ONE OF THE FEW
visual problems does not apophthalmologists who specialpear to relate to the severity
izes in the evaluation and trainof the brain injury. While
ing of visual skills and how
moderate-to-severe brain
those skills impact athletics,
injury can understandably
academics, and rehabilitation,
cause significant problems, it
I am surprised by how many
is now postulated that even
of my colleagues are unfamilminor brain injuries can disiar with this area of the visual
rupt the overall speed, efsystem.
ficiency, and integration of
While the area of visual permental and central nervous
formance is given little expofunction.
sure during residency trainThese symptoms frequently
ing, it has an impact on many
do not correlate with the
functions of patients’ everyamount of pathology and
day lives.
are not found on radiologic
I became interested in this
imaging. There may be sefield in the 1990s through an
vere cognitive and behavioral
optometrist who received an
impairments causing headeducation in the field of viaches, dizziness, photophosual performance as part of
Patient measures his vision skills on the Vizual Edge Performance Trainer, a Web-based
bia, delay in return to play
his training. Visual perforvisual performance program that allows reproducible results that are portable and to
or work, inability to drive,
mance services can generwhich users can gain easy access to the technology. (Photo courtesy of Barry Seiler, MD)
emotional instability, and
ate more patient visits, and
memory difficulties. Sympdepending on the business
toms may be a combination
model, the ophthalmologist
or optometrist can charge “out of pocket” military environments, the topic of TBI—par- of organic and psychological factors.
The impact of visual deficits may be furticularly concussions—has recently received a
for the services.
great deal of media exposure and has created ther complicated by the injured person not
being aware of a change in vision. Without
high visibility in the athletic arena.
VISUAL FUNCTION AR EAS
As mentioned in the Physical Medicine & appreciation for the deficit, the injured person
Four main areas of visual function include: vithereby fails to compensate for
sual acuity, visual field, oculomotor control, Rehabilitation textbook chapthe deficit.
ter, which I authored, patients
and central visual processing.
Also, because visual percepOne of the parts of the visual system—the may experience a variety of
tion is a subjective experience,
visual-motor portion—comprises such com- visual impairments after TBI
Though given little
the person may have difficulty
ponents as tracking, convergence/divergence, or post-concussion syndrome,
attention during
articulating his or her difficulties
visual recognition/memory, and depth percep- which can result in both overt
residency training,
and relating them to impairtion. While interrelated, these components can and insidious symptoms.
the area of visual
ment in vision.
Impairment of ocular motor
be isolated, are measurable, and in many inperformance should
Conversely, the patient may
control is one of the most frestances are trainable.
become the standard
also have developed a comStudents with reading issues may be born quently associated with TBI. It
of care in patients
pensatory strategy as a result
with reduced visual skills; athletes may want is estimated that between 40%
with traumatic brain
of the impairment that interto enhance their existing visual skills to im- and 75% of patients with TBI
injury, explains Barry
feres with his or her ability
prove athletic performance; and civilians and/ experience some reduction of
L. Seiller, MD, MBA.
to compensate in other areas
or athletes with traumatic brain injury (TBI) oculomotor control. A dysfuncof visual functioning and that
tion in this area can lead to a
would like to restore them.
Although there have always been large num- spectrum of issues affecting athletic play and may confuse both the person and the rehabilitation team.
bers of head injuries in both the civilian and daily activities.
TAKE-HOME
63
APRIL 15, 2015 :: Ophthalmology Times
clinical diagnosis
However, if the visual impairment
can be correctly and promptly diagnosed and provided appropriate
therapeutic intervention, the patient's rehabilitation course may
be improved and the medical outcome enhanced.
In order for survivors of acquired
brain injury to benefit during the acute
phase of trauma, there may be a variety of disciplines available to them
in the inpatient or outpatient setting.
Most concussion programs do not include an ophthalmologist and only
some include an optometrist.
Unfortunately, for those patients in
the subacute or chronic phase of concussions, the rehabilitation team has
less to offer, while the patient/athlete
frustratingly is waiting for the symptoms to dissipate and return to work
or play. The patients, usually athletes,
are frequently in the chronic phase
and have continued symptoms years
after the initial event. Although they
have seen numerous physicians, only
rarely will these physicians have considered a compromised visual system
as the basis of the dysfunctionality.
Now the landscape is changing for
these patients.
VISION
PERFORMANCE
PROGR AMS
In 1989, I founded the Visual Fitness
Institute to investigate and implement
vision performance programs for athletes and head injuries. Up until recently, there were a multitude of visual
devices that existed that attempted
to measure the most important visual skills. A vast majority of these
devices were produced by a variety
of clinicians, but most had no credible basis especially for researchers
looking to examine the validity of
this field.
As a result of the work performed
at Visual Fitness, the Vizual Edge Performance Trainer (VEPT) was developed to address the issues inherent
in these previous devices. This Webbased visual performance program
allows for consistently reproducible
results that are portable and to which
users can gain easy, economical access to the technology.
The commercially available program reliably collects metrics that are
used to measure the most important
visual skills and create a database of
scores for each user. The system offers valuable information to athletes,
coaches, researchers, and now rehabilitation staff.
The program can be used by oneself or by a coach or trainer. On the
clinical side, it allows for a comparison of one user’s skills to another
and also a method to monitor training progress.
Researchers have utilized the program for a variety of investigational
studies in multiple sports. This has
also lent new credibility to visual
performance testing and vision training that now can be correlated to
performance on-court, field, or ice.
Many high school, collegiate, Olympic, and professional athletes take advantage of the technology for athletic
enhancement.
Just as access to athletes has grown,
so has the use of the program in determining the visual effects of a concussion and its remediation. The program
can help determine affected visual
skills and a method to rehabilitate
them either at home on their own
computer or in an office setting.
This includes a number of eye-care
professionals’ offices, facilities, and
hospitals in the United States and Canada. Utilizing the program can help
to determine dysfunctions, such as
convergence insufficiency, which is
one of the most common problems
post-trauma and the most overlooked.
Athletes are also being visually
tested pre-injury similar to the popular ImPACT program that tests cognitive function for similar purposes.
We will continue to educate the
eye-care practitioner in this seldomconsidered area of the visual system. However, given the frequency
of visual symptomatology that results
from mild-to-moderate brain injury,
the epidemic of concussions, readily
available new technology such as the
VEPT, ophthalmologists or optometrists should be integrated either as a
member of an interdisciplinary concussion team or as a value-added service in the practice.
The visual performance program
provides a new depth of understanding that should become the standard
of care in patients with TBI. ■
BARRY L. SEILLER, MD, MBA is the developer and owner of the Vizual
Edge Performance Trainer and lead consultant of visual performance research
in the newly opened Sport Performance Research Lab at Texas A&M University
Corpus Christi.
Digital Acuity Suite
We Provide Complete
All In One Systems or Software
Only to Add to Your Current
Windows EHR System
ALREADY HAVE ACUITY PRO?
Version 9 adds many features. Check our homepage
for a history of new features since Version 7.
'
#"! #"&esting
'""#"
' "
"
'
o Cr" #!"%#!
'" !
No Annual FTech Support FForced Upgrades
DAVID HETTLER, O.D.
The best things about Acuity Pro are never changing a
bulb, and unlimitied flexibility with letters, pictures, and
videos. Once you have this system, you will never go
back to a projector.
AcuityPr.$.,7
[email protected]
Like Us on Facebook
W
CELEBRATING OUR 15TH ANNIVERSARY
In 50 States, Over 20 Countries, And
On Board The International Space Station!
64
APRIL 15, 2015 :: Ophthalmology Times
clinical diagnosis
Invisible portions of Bruch's
membrane influence rim estimates
An examination of why current methods are inaccurate and what should change
By Felicity Thomas, Ophthalmology Times Europe; Reviewed by Balwantray C. Chauhan, PhD, and Claude Burgoyne, MD
SINCE THE INTRODUCTION of the
ophthalmoscope by Helmholtz in 1851,1 the
health of the neuroretinal rim has been determined through the appearance of the optic disc.
“In its essence, we, as clinicians, try to identify the disc margin and the rim margin, and
then conceptualize that the disc margin is a
true outer boundary of the neural tissues, as
is the rim margin,” said Claude Burgoyne, MD,
Devers Eye Institute, Portland, OR, at the Heidelberg Engineering-sponsored symposium
which took place during the EGS congress in
Nice, France.
Technological advancements in spectraldomain optical coherence tomography (SDOCT) have allowed clinicians to better visualize optic nerve head (ONH) anatomy and
have led clinicians to question the accuracy of
current methods used to estimate the health
of the neuroretinal rim.
“I want to highlight the fact,” Dr. Burgoyne
continued, “that there’s absolutely no agreement among us on what the disc margin is in
any given eye or what it should be.”
To address this uncertainty, Dr. Burgoyne
and Balwantray Chauhan, PhD, Department
of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, explained how recent SD-OCT-detected anatomy
challenge current concepts of the clinical disc
margin and neuroretinal rim quantification.2
INVISIBLE ANATOMY
Three and a half years ago, Drs. Burgoyne
and Chauhan discovered there are portions of
Bruch’s membrane anatomy that are clinically
invisible. Working in their respective labs, they
co-localized stereo optic disc photographs to
SD-OCT data to precisely identify optic disc
anatomy that corresponds to features seen with
direct ophthalmoscopy, slit lamp biomicroscopy, or optic disc photography.3,4
“So, for every one of the patients we examined, we had a clinical disc margin and
we had SD-OCT-detected, Bruch’s Membrane
Opening (BMO) that we could co-localize,”
Dr. Burgoyne continued. “However, in most
of the 40 eyes we looked at, there was at least
some portion in which there was a
mismatch between OCT anatomy
and the clinical disc margin. This
led us to believe that OCT imaging
was seeing things that the clinician couldn’t see.”5
“What we are seeing currently
today as a disc margin does not
correspond to a fixed anatomic
structure,” explained Dr. Chauhan. “So, if this is the basis with
which we make our neuroretinal
rim measurements, then we don’t
actually have a solid foundation to
make those measurements, simply because it isn’t a consistent
structure and the problem is that
it varies in individual eyes and
between eyes. So, we can’t really
predict in which eyes and where a
mismatch will occur as it is present in all eyes.”
“BMO is a border, not the only
(FIGURE 1) Identification of individual fovea to BMO centre
one, but it is a border that we can
(FoBMO) axis enables measurements to be placed according
see quite well today with SD-OCT,”
to individual anatomy of the eye. As opposed to a horizontal
reference plane, the analysis and classification according
he continued.
to individual anatomy of the eye is adjusted to take the
Furthermore, Drs. Burgoyne
FoBMO axis into account. (Figure adapted from ref. 10: L. He et al.,
and Chauhan pointed out that
‘Anatomic vs. Acquired Image Frame Discordance in Spectral Domain Optical
the current clinical assessment
Coherence Tomography Minimum Rim Measurements’, PLoS One, 2014;9:e92225.
of the neuroretinal rim is made
doi:10.1371/journal.pone.0092225.)
along a two-dimensional plane of
the perceived optic disc margin.
that can be done within each individual BThey showed examples of how,
in a single eye, the orientation of the rim tis- scan and it can be done in all 24 or 48 radial
sue varies around the ONH. Axons may exit B-scans so that a continuous measurement of
the eye parallel or perpendicular to the visual BMO-minimum rim area can be estimated.”
Although this measurement has previously
axis, causing potentially significant errors in
assessment of the neuroretinal rim width to been proposed,6–8 Drs. Burgoyne’s and Chaube made if the measurement plane is fixed. han’s work has shown that the BMO-minimum
Drs. Burgoyne and Chauhan suggested that rim width (BMO-MRW) parameter significantly
this potential error can be omitted if the neu- enhances the ability to detect glaucoma comroretinal rim width is assessed using the most pared with current analyses.9
geometrically accurate measurement, repreDrs. Burgoyne and Chauhan highlighted that
sented by the minimum distance from BMO there are additional geometric errors arising
to the internal limiting membrane.
from current assumptions to consider.
“In other words,” explained Dr. Burgoyne,
“Currently, we assume that when a patient
“it’s a minimum measurement, the smallest places their head into the imaging device, rethickness that’s present at that location. And, gionalization works according to a fixed-image
65
APRIL 15, 2015 :: Ophthalmology Times
clinical diagnosis
frame, so everyone’s superior temporal sector
refers to the same anatomical location,” Dr.
Chauhan said. “Of course, this is not the case.”
NOV E L S OF T WA R E
Based on the findings of Drs. Burgoyne and Chauhan, Heidelberg Engineering has developed software to enable the identification, in real time, of
the BMO, the fovea, the varying trajectory of the
rim around the ONH, and to adjust measurements
according to the path of retinal nerve fibre layer
bundles relative to the axis between the fovea and
the ONH. (Editor’s Note: The software is available in Canada and Europe and is pending FDA
clearance in the United States.)
To determine whether rim parameters based
on BMO, measured using SD-OCT, are better
identifiers of glaucomatous discs, Drs. Burgoyne and Chauhan performed a case controlled
study.9 They found that BMO-MRW measurements not only offered an anatomically accurate border of the rim from which to measure
but also accounted for the variances in trajectory relative to the point of measurement. As
such, it was deemed that BMO-MRW may be
used as a new structural marker for the detection and risk profiling of glaucoma. To overcome these flaws, an independent normative
database was collected from a different set of
glaucoma subjects.
CONCLUSIONS
“SD-OCT should not mimic what the clinician
does. We should not expect new technologies to
fit into our clinical mold, otherwise science will
never progress,” Dr. Chauhan said. “Rim measurements should be made in an anatomically
and geometrically accurate manner and this,
in our view today, should be done from BMO
and perpendicular to the orientation of BMO.
“With any technology, any advances that
you make do not mean that a clinical examination isn’t necessary. The clinical examination is still the core of what you do or what
you should do."
References
1. H. von Helmholtz, Beschreibung eines Augenspiegels
zur Untersuchung der Netzhaut am lebenden Auge.
Berlin: A Förstner’sche Verlagsbuchhandlung; 1851.
2. B.C. Chauhan and C.F. Burgoyne, Am J Ophthalmol.
2013:156:218–227 e212.
3. A.S. Reis et al., Ophthalmology. 2012;119:738–747.
4. A.S. Reis et al., Invest Ophthalmol Vis Sci.
2012;53:1852–1860.
5. http://ophthalmology.medicine.dal.ca/research/onh.html
6. T.C. Chen, Trans Am Ophthalmol Soc. 2009;107:
254–281.
7. B. Povazay et al., J Biomed Opt. 2007;12:041204.
8. N.G. Strouthidis et al., Invest Ophthalmol Vis Sci.
2011;52:1206–1219.
BALWANTRAY C. CHAUHAN, PHD is Mathers Professor and research
director, Department of Ophthalmology and Visual Sciences, Dalhousie University,
Halifax, Nova Scotia, Canada. Dr. Chauhan has received research and travel support
and is a consultant for Heidelberg Engineering, and has received travel support and is
a consultant for Allergan.
CLAUDE BURGOYNE, MD is senior scientist and Van Buskirk Chair for
Ophthalmic Research; director, Optic Nerve Head Research Laboratory; Devers Eye
Institute, Portland, OR. Dr. Burgoyne has received research support, instruments
occasional travel support and is a consultant to Heidelberg Engineering, and has
received instruments from Reichert.
N I D E K I N N O VAT I O N !
NIDEK
RS-3000
ADVANCE
OCT
NIDEK
AFC-330
FUNDUS
CAMERA
Over 90% of the time we are getting excellent quality photo images
which enables us to show optic nerve defects directly to patients.
It’s like an epiphany when patients can see for themselves. This cuts
down on second opinions. The quality transforms the whole patient conversation.
– Dr. Thomas Jennings, Key-Whitman Eye Center, Dallas, Texas
The RS-3000 Advance provides outstanding anatomic detail, superb ergonomics and enhanced office efficiency. I can
visualize vital structures in the cornea, angle, choroid and retina with minimal effort. Because the software is well
designed, I can show patients their images from the privacy of the exam room...even when the RS-3000 Advance is
being used by another practitioner. No other device has this functionality. It is a breath of fresh air.
– Dr. James S. Lewis, Elkins Park, Pennsylvania
The NIDEK RS-3000 Advance OCT unit makes for increased efficiency when it comes to doing OCT scans.
Patients are easily positioned for an OCT scan and technicians are able to quickly perform the scan with minimal
instruction to the patient during the scan. The results of the scan are immediately available for viewing in the exam
room by the physician and the patient on any available workstation. The software for analyzing the scan is easy to
use and the images are clear and easy to present to the patient. The RS-3000 Advance is a winner for physicians,
technicians, and most importantly, the patients.
– Dr. Darrell Genstler, Genstler Eye Center, Albany, Oregon
NIDEK Inc.
47651 Westinghouse Drive
Fremont, California 94539-7474 USA
T$*$.'-,$
5ax: 1-510-226-5750
usa.nidek.com
CONTACT NIDEK TO
SCHEDULE A DEMO TODAY.
Visit our website to
download our brochures.
Caution: U.S. Federal Law restricts this device to sale, distribution, and use by or on the order of a physician or other licensed eye care practitioner.
Specifications may vary depending on circumstances in each country. Specifications and design are subject to change without notice.
March 10, 2015
15-0023
66
APRIL 15, 2015 :: Ophthalmology Times
focal points
Antique book collection brings
ophthalmic history to life
Seminal works on medicine, diagnostic instruments featured in Museum of Vision display
Our Ophthalmic Heritage By Norman B. Medow, MD, FACS
SAN F R ANCISCO ::
hilanthropy and
the collecting and
preservation of important books have
not been relegated
to the pages of history thanks
to a “lasting monument to early
pioneers of ocular science.”
The Museum of Vision of
the Foundation of the American Academy of Ophthalmology
(AAO) has received a donation of
the Spencer E. Sherman Collection
of Antique Ophthalmology Books.
More than 130 rare books and catalogs represent the lifelong collection of Dr. Sherman, a New York ophthalmologist and one of the founders of the museum
and early chairman of its board of directors.
The collection is important for the
breadth of ophthalmology subjects covered,
as well as the history it spans (16th through
19th centuries). Seminal works in glaucoma,
cataract, cornea, embryology, refraction,
and ophthalmic history are featured.
P
SIGNIFICANT TEXTS
Two important books in the history of ophthalmology are included in this collection.
One book, entitled “Ophthalmodouleia:
Das ist Augendienst” (“In the service of the
Eyes”), was written by Georg Bartisch in
1583. Bartisch is considered by many to be
the father of modern ophthalmology. This
book is considered to be the first on ophthalmic medicine and comprehensive surgery written in the vernacular.
The folio edition book was published with
92 pages of woodcuts—one of the first books
to have such woodprints—and described
all of the surgery and medicine related to
the eyes known at this period. Some of the
woodcuts are in overlay and are mobile.
The book’s popularity remained so strong
that a second edition—with the woodcuts
The title pages of two seminal texts in ophthalmic
history are reflective of the period in which they were
written. (Images courtesy of Norman B. Medow, MD, FACS)
reflecting the clothing of the period—was
published in 1686. The title page is classical for the great books of the period, such as
“De Humani Corporis Fabrica,” published in
1543 by Andreas Vesalius.
The second book—“Beschreibung eines
Augenspiegels zur Untersuchung der netzhaut in Lebenden Auge” (“Description of
an ophthalmoscope for examination of the
retina in a living eye”)—written by Hermann Helmholtz in 1851 is equally as important. It describes what is arguably considered to be one of the two most important
portable clinical diagnostic instruments in
all of medicine—the ophthalmoscope. (The
other instrument being the stethoscope first
described in 1816.)
The discovery was made because Helmholtz wanted to aid his physiology class in
understanding the eye. He used his wife to
develop the ophthalmoscope and thereby
she was the first person whose fundus of
the eye was seen in the living eye.
The ophthalmoscope’s discovery revolu-
tionized eye care, and within a
short period all of the leading
eye-care practitioners in the
world had one. Helmholtz sent
one of his instruments to Bowman in London, Von Graefe in
Berlin, and Donders in Holland.
Their descriptions of the fundus led to the publishing of a
number of atlases of the retina—
two of which are present in the
Sherman collection: “Atlas of
Ophthalmoscopy” by Otto Haab
published in 1898, and the “Atlas
of the Ophthalmoscopy” by Liebreich published in 1870.
Also included in the collection
is Volume I of the transactions
of the American Ophthalmological Society,
as well as classic textbooks of the period by
Scarpa, Beer, Fuchs, and Desmarres.
Knowledge of what instruments were
present and used at any period is gained by
looking at instrument manufacturers’ catalogs of the time. The Sherman collection has
a large number of these catalogues—most
importantly, by those of the following companies: Queen, Maw, American Optical, and
Mueller, as well as others.
This collection will be on display on a rotating basis in specially designed cabinets
at the AAO’s Museum of Vision in San Francisco (http://bit.ly/19SqQTA).
There is something special about holding a book in your hands that is 200 years
old and first described an important historical event or invention—the content of which
can be found on the Internet, but it is not
the same! Q
NORMAN B. MEDOW, FACS, is director, pediatric
ophthalmology and strabismus, Montefiore Hospital Medical Center,
and professor of ophthalmology and pediatrics, Albert Einstein
College of Medicine, Bronx, NY. He did not indicate a financial interest
in the subject matter.
IN DISPENSABLE
( In Brief )
Patient Education
Low Vision
Rehabilitation
Services
OT
Low Vision
Evaluation
and
Supervision
OD/MD
FROM STAFF REPORTS
Bright color scheme
CRVT
CLVT
COMS
Support
Services
/FVSPr(FSJBUSJDT
$PNNVOJUZSFTPVSDFT
4VQQPSUHSPVQT
$PVOTFMJOH
5SBOTQPSUBUJPOTFSWJDFT
"HJOHTFSWJDFT
Disease
Diagnosis,
Management
and Ongoing
Eye Care
Marketing to
the low vision
patient
Specialized techniques and tips target how, why, where
low vision aids can help individual needs
Figure courtesy of Dan Roberts, MME
By Rose Schneider, Content Specialist, Ophthalmology Times
atients with low vision can come in many forms—a young
child just starting school, a teenager who lives and breathes
the Internet, or a senior citizen who prefers reading the newspaper than watching television.
Each of these patients requires specific needs
to fit his or her lifestyle. But how do eye-care
professionals ensure these patients receive
the proper knowledge and devices to aid their low vision?
“The information is the same, but the approaches (must)
come from different places,” said Dan Roberts, MME, editor-in-chief of “Living Well with Low Vision” (http://lowvi- Roberts
sion.preventblindness.org). The online resource is an educational program
launched by Prevent Blindness.
Continues on page 68 : Low vision
P
67
OKIA LAUNCHES HAPPY
FRAMES COLLECTION
HONG KONG :: OKIA RECENTLY LAUNCHED
its latest line of optical and sunglasses frames
called Happy Frames, full of bright colors and
fun patterns.
Each style in the collection is named after
a different cocktail—including Tequila Sunrise, Apple Martini, and Mojito—and features
bright color contrasts, dots, animal prints, or
houndstooth patterns, and glitter.
According
to Okia, all
of the styles
in the Happy
Frames line feature its HDA Technology, which showcases colors and
textures in high definition, and its CSB technique, which combines acetate with shining
materials and allows random or controlled patterns with a non-delaminated effect.
June product launch
MARCOLIN + MARCEL
LAUNCH SUNWEAR LINE
V IL L A NOVA , I TALY :: MARCOLIN RECENTLY
launched a new sunwear line with Marcel Burlon County of Milan.
Each of the three new styles feature premium materials, original patterns, and handmade details. The line will be available in
June 2015.
Madre Tierra Leather is an acetate frame
with a square-shaped silhouette covered with
matte black leather and finished with handstitched details and metal inserts.
Madre Tierra Pixel is a square-shaped black
acetate frame with a white-gradient, pixel
texture on the internal side of the temples.
This style also features a shiny metal clipon with gold lenses.
Madre Tierra All Black is a square-shaped
black acetate frame with a metallic clip-on
and gold lenses.
This style also features metal details, including the County of Milan’s logo, on the temples
and front. ■
68
APRIL 15, 2015 :: Ophthalmology Times
indispensable
ate e-mail and phone-based guidance), and
make sure they get what they came for (e.g.,
immediate news reports, plus a large library
of audiovisual and printed information pro( Continued from page 67)
duced in layman’s terms and backed by trusted
professionals), he explained.
“We challenge children and teens to develop
This approach works best for teenage pagood health habits that will become natural
tients and those who recognize they have a
to them,” Roberts said. “We challenge young
need and have already begun looking for help,
adults to take care of themselves for the sake
according to Roberts.
of their children and their personal future.
“In the early days of the InAnd we challenge senior adults
ternet, we had to depend solely
to do everything they can to
upon the media and professional
maintain their quality of life
Subject matter
referrals,” he continued. “Now,
as they age.”
experts weigh in on
the majority of people begin
Furthermore, because of these
marketing techniques
their search on the Web, so we
differences, it is a necessity to
to reach every
make sure we are visible by
utilize specialized marketing
generation of patients
not only staying high in the
approaches to figure out how,
with low vision.
search engine ratings, but by
why, and where a low vision aid
partnering and linking with
is needed for each patient, acother highly-recognizable orcording to Terri Griffin, product
ganizations and maintaining a presence at
manager for School Health, Hanover Park, IL.
local and national conferences.”
“Marketing to all ages is important to help
But what about elderly patients—a signifipeople maintain their independence and abilicant portion of the population—who may not
ties to work, study, read, do hobbies, and more,”
utilize the Internet? Roberts recommended
Griffin said.
staying in touch via live support groups and
state affiliates, and encouraging eye-care proMAR K ETING TO INDIV IDUA L
fessionals to inform their patients further about
Needs that vary by age can be age-related vilow vision aid—an important aspect of consion impairment versus physical- or diseasetinued care from diagnosis through rehabilirelated impairment, she explained.
tation and personal support.
“The focus (then) is more about individual
Using a similar approach to reach young
ability and willingness to use or learn a level
patients with low vision has proven successof technology that will best suit their needs,
ful over the years, Roberts said.
based on their impairment and the activities
These techniques include programs in schools
they do,” Griffin said.
and libraries, and educational materials and
The changing needs of patients as they age
lesson plans for teachers.
is a highly important factor to address contin“To target different groups, advertise in pubually throughout their lives.
lications or websites that appeal to them and
“Vision impairment can change over time
tailor the message to their lifestyles or interalong with tasks, goals, and technology,” she
ests,” Griffin advised. “For example, heavy
said. “Whether an individual has used low
computer users may be more interested in
vision aids for years, for a short time, or is
screen magnifier/reader software, while peoconsidering them (for the first time), the indiple who are active may be interested in lightvidual should periodically re-evaluate the low
weight, portable devices, and people who enjoy
vision aids he or she needs or uses.”
reading may want a device that can magnify
Having the ability to connect with patients
full pages.
is key to the conversation that leads to inves“Use images or models that represent the
tigating which low vision aids are best for
group you are directing the message,” she
each individual
continued.
Whichever method physicians decide to go
MARKETING TO GENER ATION
about connecting with patients with low vi“After trying virtually every marketing tool
sion, Griffin stressed remembering that each
available over the past 20 years, the method
person is unique and requires specific needs
that works best for me is to remain visible,
and solutions.
reachable, and content-rich,” Roberts said.
“(This is) critical to getting the best outCompare it with a church: construct a tall
come from aids and technology,” she said.
steeple so people know you’re there (e.g., large
To do so, Griffin offered several tips to help
Internet presence), greet newcomers warmly
understand each patient’s individual needs:
at the front door (e.g., personal and immedi-
LOW VISION
TAKE-HOME
Tailoring techniques
to specific
audience needs
Dan Roberts, MME, suggests possible techniques
that either may flourish or fail when marketing
to patients with low vision:
SUCCESSFUL TECHNIQUES
W I T H CHILDR EN: Programs in schools
and libraries, educational materials and lesson
plans for teachers
U N SUC C E S SF U L T ECH N IQU E S
W ITH CHILDR EN: Flyer distribution
SUCCESSFUL TECHNIQUES WITH
YOU NG A DULT S: Websites, newsletters,
kiosks, social media, Internet support groups,
telephone help line
U N SUC C E S SF U L T ECH N IQU E S
W I T H Y O U N G A DU LT S : Information
provided to clinics for distribution, broadcast
media, e-mail broadcasts
SUCCESSFUL TECHNIQUES WITH
SENIOR A DULT S: Websites, newsletters,
telephone help line, telephone support groups,
live support groups, presentations to community
groups, retirement centers, churches, libraries,
Internet support groups (listservs and message
boards), direct mail
U N SUC C E S SF U L T ECH N IQU E S
W I T H S E N IOR A DU LT S : Information
provided to clinics for distribution, broadcast
media, e-mail broadcasts
> Investigate the type of vision impairment and
degree of loss.
> Find out how and where the patient will use
the product (e.g., work, school, hobbies, near
or far magnification, etc.).
> Ask the patient about his or her ability to
handle and operate a device.
> Discover the goals/budget of the patient.
“There are dozens of different low vision
aids to help improve the lives of people with
low vision,” Griffin said. “Each aid has its
own advantages and limitations. To get the
most from a low vision aid, it’s important to
see and understand what that device can and
cannot do (for the patient).”
By considering these factors, patients will
not only be paired with the appropriate aid
for their low vision, but will continue to be
informed through the best channel they understand. ■
APRIL 15, 2015 :: Ophthalmology Times
indispensable
69
Post-closing issues deserve attention
to avoid optical buyer’s remorse
Take notice of details of creating positive customer experience at all steps of retail sale
Dispensing Solutions By Arthur De Gennaro
JUST BECAUSE a shopper becomes a
buyer (makes a purchase) does not mean
the sale is over. A lot of things can happen
after the optical shopper agrees to become a
buyer. Let’s look at some post-closing issues.
All of us have purchased something and
almost immediately questioned the decision. This is known as “buyer’s remorse.” In
some cases, the buyer is so convinced the
decision was a bad one that he or she will
call to cancel the order or the eyeglasses are
returned for a refund.
Customers who are completely convinced
that their purchase decision was a good one
will not return it. How can you limit the
number of customers who cancel or return
their purchase? The answer is to deliver a
customer experience that is outstanding.
Some retail consultants would use the word
“legendary.”
Creating such a customer experience is
hard work. It requires scrutinizing and reengineering all of the elements that make
up the customer experience. This is one
additional reason for following all of the
steps in the selling process and doing them
as expertly as possible.
At the moment customers question their
purchase, what you said and did during
the sales presentation will play over in
their mind. That is the moment of truth for
your work, not the fact that the customers
said, “yes.”
If the customers received exceptional,
knowledgeable, personalized service that
resulted in them getting just what they were
looking for, they are more likely not to return the purchase. This suggests that you
should be considering what you can do to
create and consistently deliver such a legendary experience.
REASSUR ANCE
We humans are often insecure. We derive
much of our self-image from the positive reinforcement we receive from those around
us. The more we trust a person, the more
valuable the reinforcement. This is why re-
inforcing the buyer’s decision to make the
purchase is a productive selling technique.
Simply reiterating the benefits of the
frame, lenses, and add-ons allows the buyer
mentally to double check those decisions.
If the customer questions the decision later
the double check should help minimize buyer’s remorse, because the buyer has already
made this mental review with you.
POSITIVE PROGR AMMING
When customers pick up their new eyeglasses the last thing many opticians say is,
“If you have any problems with your new
eyeglasses or if they need adjusting please
feel free to come back to see me.”
This is negative programming. Essentially, the optician is telling the customer
that he or she could potentially have problems with their new eyeglasses. This programs the customer to be on the lookout for
problems. Although you are probably trying
to express your willingness to be available
and help, I doubt this is the outcome for
which you are looking.
A better way is to program the customer
positively. Instead of talking about potential problems, ask, “Would you be willing
to do me a favor? I know you will get a lot
of compliments on your new eyeglasses.
Would you be willing to stop by or call to
let me know how you are enjoying your new
eyeglasses?”
In this instance the customer will be programmed to watch for compliments—compliments he or she will surely get. Each time
a compliment is received, the purchasing
decision will be reinforced and the customer
will be reassured that the decision was a
good one.
BUILDING YOUR BUSINESS
Businesses are built one transaction and one
customer at a time. Each successful transaction fosters another, and each enthusiastic customer tells his or her friends, which
builds the business overall and over time.
Successful opticians know this; so does
7 Steps
of a Retail Sale
1. OPENING
http://bit.ly/1CCzqzY
2. INTERVIEW
http://bit.ly/1Iw7Upf
3. DEMONSTRATION
http://bit.ly/1ESb1tK
4. TRIAL CLOSE
http://bit.ly/1CCzuQ4
5. OVERCOMING OBJECTIONS
http://bit.ly/1AsAntC
6. CLOSING
http://bit.ly/1yKmm7W
7. MAINTAINING AN ONGOING
RELATIONSHIP
every successful businessperson I know.
Every successful transaction is a chance to
build your business.
When customers have had an extremely
positive experience they are likely to tell
others. Programming customers to refer you
to other potential customers will encourage
them to do so.
Doing so is as easy as asking. Saying
something as simple as, “Mr. Arthur, I have
enjoyed working with you. If you have enjoyed working with me, I would appreciate it you would mention me to any of your
friends or family who you feel I can help at
this time.”
Handing the customer a few of your business cards will give him or her something to
pass along.
Notice I did not say “… if you have enjoyed working with us.” That is because the
customer did not do business with your dispensary; he or she did business with you
and you are a unique commodity. If customers want your superior level of customer serContinues on page 70 : Post-closing
70
APRIL 15, 2015 :: Ophthalmology Times
indispensable
POST-CLOSING
( Continued from page 69 )
vice they must get it from you. In essence,
you are your dispensary’s “secret weapon.”
As basic as it may seem, this simple technique of asking for referrals can dramatically increase a dispensary’s business. It
goes without saying that the more skillful
the optician, the more likely it is that he or
she will build a significant personal clientele. As a sometimes recruiter I can attest to
the fact that some opticians have loyal customers who follow them from job to job.
That is a wonderful asset for whatever practice for which they work.
ORDER FULFILLMENT
From an operations standpoint, what happens after the sale is known as order fulfillment. In other words, your optical dispensary must have the eyeglasses fabricated
and deliver them to the customer on time,
as promised.
There is a long list of things that can go
wrong with this process—too long to review here. Since the customer has already
made a purchase, suffice it to say that this
is your game to lose at this point. All of the
hard work you did to gain the buyer’s trust
can be ruined by having flawed logistical
processes in place or by just not following
through.
Remember, “The devil is in the details.” A
buyer can quickly go from excitement about
a purchase to distress when the order is not
ready on time or if the new eyeglasses are
flawed in any way.
PROCESS M A NAGEMEN T
If you have not done so lately, I suggest you
create a map of your order fulfillment processes. This begins with order entry into
your dispensary’s management system and
ends with the finished eyeglasses being delivered to the patient, on time, after passing
rigorous, quality-assurance testing. One pro-
cess I recommend is to check the status of
each job each day. Be sure you are getting
updates from your laboratory every day.
Billing errors are irksome to customers.
Not filing their managed vision care claim
or filing it incorrectly signals to the customer a certain lack of attention to details. I
cannot think of a practice that would want
that reputation connected to its brand and
image.
CONCLUSION
We have come to the end of this series on
the selling process. It is my sincere hope
that you have found these articles helpful
and that they will contribute in some way
to your continued success. I look forward to
your comments. ■
ARTHUR DE GENNARO is president of Arthur De Gennaro
& Associates LLC, an ophthalmic practice management firm that
specializes in optical dispensary issues. De Gennaro is the author
of the book The Dispensing Ophthalmologist. He can be reached at
803/359-7887, [email protected], or through the company’s Web site, www.
adegennaro.com. He maintains a blog at www.adgablog.wordpress.com.
LensFerry offers alternative
to online contact lens retail
By Colleen McCarthy
PL E ASAN TON, CA ::
A NEW CONTACT lens delivery service offers convenience to
patients and financial benefits for
eye-care professionals (ECPs)—while
offering an alternative to other online contact lens retailers.
LensFerry allows patients to order
contact lenses via a mobile device,
tablet, or computer for direct shipment to their homes. The contact
lenses are sold at ECPs’ specified
prices, and the prescribing practice
receives the sales revenue.
“With the marketplace going
mobile, we want to make it very
easy for the consumer to make a
purchase from the storefront,” said
Jeremy Godsil, general manager of
WebSystems3.
WebSystem3 is CooperVision’s
cloud-based software to automate
office communications and improve
practice productivity. LensFerry is
able to work in conjunction with
WebSystem3.
Patients can purchase their lenses
in several ways:
> A monthly plan to purchase a
year’s supply of lenses—ideally,
increasing compliance.
> By enrolling in LensFerry, the company can contact patients via text
or e-mail when it’s time to purchase
new lenses. Lenses are shipped directly to patients.
> When patients are ready to order
lenses, they are able to contact LensFerry via text with a specified number. The company will respond with
the product and pricing, and patients confirm the order by replying “yes” via text.
A nationwide rollout is planned for
later this year. LensFerry will be
open to both ophthalmologists and
optometrists. ■
APRIL 15, 2015 :: Ophthalmology Times
practice management
The revenue cycle decision
Should practice billing be handled in-house or contracted through external vendors?
By Susan Kreimer
ven the most experienced phy- tion of insourcing or outsourcing collections
sicians and practice managers from a scale and internal capability perspecface a daunting dilemma on the tive,” said Jim Lazarus, managing director of
financial front: Should they han- strategy and innovation in revenue cycle soludle billing and collections inter- tions at The Advisory Board Co., a healthcare
nally or hand over these tasks consulting firm in Washington, DC.
For a practice with 15 or fewer physicians,
to an external vendor?
There are strategies that physicians can use internal billing is usually a more cost-effective
to evaluate potential vendors and make the approach. It may be prudent to hire a capable
person to focus on billing, but
best decision for their practice.
to serve also as a “jack of all
In these challenging times for
trades,” overseeing medical rephysician practices, the busiA cost analysis
cords and providing other office
ness side of medicine requires
is essential to
support, Lazarus said.
navigating reimbursement dedetermining whether
If a practice consists of 15
clines and rising costs while
to outsource revenue
to 30 physicians, the decision
conforming to the Affordable
cycle management
to outsource depends on the
Care Act and transitioning to
services.
market and the staff’s experithe International Classification
ence with billing and collecof Diseases-10th revision (ICDA company with
tions. The existence of multiple
10) code set. And while deliverstate-of-the-art
office sites doesn’t necessarily
ing high-quality care remains
technology offers
tip the scales in favor of exterphysicians’ top priority, sound
greater security
nal billing, according to Lazarevenue cycle management noneassurance for
rus. Once a practice exceeds 30
theless dovetails closely with
protecting patient
physicians, however, the numthe success of their practices.
information in
ber of locations factors into the
About 35% of respondents—
compliance with the
decision, along with the billing
mainly acute-care hospitals and
Health Insurance
staff’s expertise.
clinics/physician practices—to
Portability and
“Vendors bring advantages,”
a 2014 survey by the American
Accountability Act
Lazarus said. “They have the
Health Information Management
(HIPAA).
ability to field operations that leAssociation/eHealth Initiative
verage technology and dedication
believe ICD-10 will have a negative effect on their revenue; 18% are uncer- of functions.” For example, one employee may
tain of its impact; and 27% haven’t conducted answer billing inquiries from patients, while another may enter data from insurance companies.
financial impact assessments.
Selecting a reputable vendor is critical. A
Many physicians ponder whether to seek outside expertise for revenue cycle management. company with state-of-the-art technology offers
An estimated 95% of independent physicians greater assurance for protecting patient informaperceive outsourcing these services and tech- tion in compliance with the Health Insurance
nology processes as the most sensible solu- Portability and Accountability Act (HIPAA).
The vendor should offer a business associate
tion, according to the Black Book Report 2015,
a healthcare market research entity. Of those agreement—a formal arrangement in the healthpractices, 64% are contemplating a combination care industry for anyone dealing with highly
of new software and outsourcing help to im- sensitive patient data. “If the vendor doesn’t
prove their revenue cycle management systems. insist on a business associate agreement, you
Before making these decisions, a practice should walk away immediately,” Lazarus said.
While it’s important for a billing company’s
must weigh the pros and cons carefully. There
are multiple aspects to consider, such as the size coders to safeguard personal health informaof the practice and the capabilities of its staff. tion, they should also feel comfortable reading
“Physicians really need to approach the ques- medical terminology in patients’ charts. There
E
TAKE-HOME
Keep the revenue
cycle in mind
KEEP THE FOLLOWING POINTS IN MIND
WHEN EVALUATING YOUR PRACTICE’S
REVENUE CYCLE AND ACCOUNTS RECEIVABLE (A/R) PROCESSES:
WHERE’S PAYMENT? Some payers take longer to pay claims than the average number of days
in A/R. For example, if your practice’s average
number of days in A/R is 49.94, but Medicaid
claims average 75 days, this should be addressed.
CONSIDER ACCOUNTS IN COLLECTION
Accounts sent to a collection agency are written
off of current receivables, and the revenue may
not be accounted for in the calculation of days
in A/R. Be sure to calculate days in A/R with
and without the inclusion of collection revenue.
BUILD A PAYMENT PLANS ACCOUNT Payment plans that extend the time patients have to
pay accounts can result in an increase in days in
A/R. Consider creating a separate account that
includes all patients on payment plans and determine whether your practice should or should
not include this “payer” in the calculation of
days in A/R.
FACTOR IN OLDER CLAIMS Good overall
days in A/R can also mask elevated amounts in
older receivables, so it is important to use the
“A/R greater than 120 days” benchmark.
may be additional security concerns if a company uses coders in a different country, where
HIPAA rules don’t apply, said Margo J. Williams,
MHA, CMPE, a senior associate in practice management for the American College of Physicians.
Employee turnover is another consideration,
with a billing company missing out on some of
its revenue collections as balls are dropped between employees departing and new employees
coming on board. Questions to ask: “What kind
of turnover does the billing company have? Are
they doing your specialty, or do they know other
specialties better?,” Williams said.
Continues on page 72 : Revenue cycle
71
72
APRIL 15, 2015 :: Ophthalmology Times
practice management
REVENUE CYCLE
( Continued from page 71 )
In Williams' experience, a practice maintains greater control over internal billing. From
knowing the nuances of different insurance
carriers to being familiar with the region and
patients’ records, “all steps of the billing process are there in your office,” she said. “Collection rates will be better. You’re on top of it,
and you have more at stake.” However, Williams acknowledged that “not everybody has
the ability or knowledge to do it themselves.”
It is possible to outsource all or only part of
revenue cycle management. Many physician practices decide to use the influence of the third party’s name in outsourcing bad debt collections.
QUESTION BECOMES WHEN
“The question becomes: when does the physician practice send the patient account to a
third-party collection outsourcer?” asked Tom
Gavinski, a member of the board of directors
at ACA International, the Association of Credit
and Collection Professionals and vice president
of healthcare market and industry initiatives
at I.C. System Inc. in St. Paul, MN, a debt collection agency. “That depends on when they
want to use the outsourcer’s services.”
Those services can be tailored to begin anywhere between one and 150 days after a payment is past due. For payments up to 90 days
past due, services can be outsourced to collections as a self-pay account in the name of the
physician practice. Accounts that are 90 or more
days past due are usually sent to an outsourcer
as a third-party bad debt account, said Gavinski.
PE R F OR M A C O ST A N A LY S I S
A cost analysis is essential to determine whether
to outsource. The practice may choose to enlist the advice of an independent consultant
to evaluate the pros and cons of each scenario
and to assist in decision making, Gavinski said.
Any in-depth analysis should include a future forecast that accounts for increases in employee wages and benefit packages. This would
compare the current costs of billing internally
with the costs of employing an outside vendor.
In addition to staffing, the tally should quantify the current costs that would be eliminated
with an outside vendor, identifying them as
a percentage of total expenses and comparing that to the costs of using the vendor, according to Jeff Akers, CPA, vice president of
financial management at McKesson Business
Performance Services, Reading, MA.
Evaluating RCM Vendors:
10 Questions to Ask
WHAT IS THE COST AND WHAT DO I GET FOR
THAT PRICE?
The cost of revenue cycle management (RCM) services can
vary significantly depending on the size and complexity
of services. Some charge monthly fees while others
charge a percentage of the total amount collected. Two
vendors may charge similar rates, but what is included
in that price can vary.
It’s important for the vendor to spell out everything
included in its fees, and be transparent about the services
it charges extra to provide.
WHAT ARE THE PERFORMANCE GUARANTEES?
The potential vendor should explain how it will solve the
problems the practice identified during its discovery
phase and its success rate with previous clients. Some
vendor proposals may include incentives for exceeding
set goals, or penalties if goals are not met.
WHAT TECHNOLOGY WILL THE VENDOR
PROVIDE AND HOW WILL IT INTERFACE
WITH EXISTING SYSTEMS?
RCM companies have economies of scale that allow
them to offer a practice technology it would otherwise
be unable to afford or maintain. But it should be clear
from the outset what technology the vendor will supply
and what will be expected from the practice, and how
the vendor-supplied technology will interface with
existing technology.
WHERE ARE THE CALL CENTER EMPLOYEES
LOCATED?
A growing number of RCM companies employ people
abroad, a fact that they should disclose. Practices
should find out what the call center hours will be, the
employees’ language skills, and their knowledge of
local laws and regulations.
HOW LONG IS THE CONTRACT?
A practice may want to outsource RCM for only a short
time to get through a growth or transition period. If
short-term contracts aren’t an option, the practice may
lose money if it decides to terminate early.
For example, current expenses may amount
to 10% of the total cost, whereas outsourcing
expenditures typically run in the 5% to 8%
range. “While the immediate cost seems to
be reduced, the real key is the 5-year impact,
as the 10% likely will creep up over time due
to raises, benefits and increased expenses,”
Akers said. Even with sound management,
operational oversight also takes away from a
physician’s focus on direct patient care.
Physician groups that choose an in-house
solution should anticipate future costs to maintain their systems of practice management and
WHAT ARE THE TERMINATION CLAUSES?
Find out how the practice can get out of the contract
if the vendor doesn’t hold up its end of the contract
or what penalties, if any, will apply if the practice opts
out of the contract early.
ARE EMPLOYEES CERTIFIED AND FAMILIAR
WITH INDUSTRY BEST PRACTICES?
The Healthcare Financial Management Association,
the American Association of Healthcare Administrative
Management, and others set industry best practices
vendors should know. These organizations also certify RCM
professionals, ensuring that clients have knowledgeable
representatives working on their behalf.
WHAT SECURITY MECHANISMS ARE IN PLACE
TO DEAL WITH SENSITIVE PROTECTED HEALTH
INFORMATION?
As a business associate to the practice, the RCM company
should be able to provide potential clients with risk
assessments and explain what measures they take to
remain compliant with the Health Insurance Portability
and Accountability Act (HIPAA).
WHAT REPORTING IS PROVIDED?
The most effective way for a practice to assess its vendor’s
performance is through reporting. Reports should be
provided regularly that include, at minimum, an analysis
of accounts receivable, the percentage of accounts in
receivable for 60 days, 90 days or 120 days, and a
breakdown of payers and providers with accounts in
each category. In addition, the reports should provide
a breakdown of the who and why of denials, and the lag
time between date of service and when bills are sent out.
WHERE TO AND HOW OFTEN IS MONEY
TRANSFERRED?
Some RCM vendors first collect on behalf of their clients,
then send a check once a month, or send the money to
a lock box. Others post the collections in real-time via
direct deposit. The way the RCM vendor handles this
could affect a practice’s ability to meet its financial
obligations.
electronic health records. Akers estimates that
in general, a practice can expect a 6% to 10%
improvement in its revenues from outsourcing its billing.
As changes take place in billing and coding, “the need for a vendor who has its finger
on the pulse of healthcare reform is critical
to ensure there are no missed opportunities,”
Akers said. “The risk of compliance issues can
be devastating to a practice. Having an outside
vendor with extremely high compliance policies and protocols in place will help mitigate
risks to your practice.” ■
APRIL 15, 2015 :: Ophthalmology Times
practice management
How to prevent payer denials
Physician’s roadmap must include best practices to reduce and reverse unpaid claims
By Debra Beaulieu-Volk
ou may be thinking you’re doing
everything possible to submit clean,
accurate claims to payers—yet denials persist. And if it seems that
every day insurers are sending
back different types of denials,
you’re probably right.
"That’s the way it is,” said Elizabeth Woodcock, MBA, FACMPE, CPC, a healthcare consultant and author with Woodcock and Associates, Atlanta. “No matter how hard you
try to make everything perfect, denials still
happen. But you have to recognize that the
insurance companies have an economic incentive to deny claims, so you’re never going
to get it down to zero.”
That’s the bad news. The good news, however, is that with a strong parallel strategy of
denial prevention and follow-up, you can significantly reduce your denial rate and ensure
that almost all denied claims get paid.
to analyze the reasons claims are rejected in ported by Medicare rules. Those types of denithe first place only perpetuates the problem. als we like to be able to build them back into
“Denials are your treasure
our contracting efforts, but it’s
chest for performance improveexceedingly difficult to call those
ment,” Woodcock said. “This
out and have them addressed
Review all denials
is your guide to really make a
specifically in our contract.”
within 72 hours and
difference.”
Another complicating factake action on them
For example, by reviewing
tor in this process is lack of
within seven days.
your explanations of benefits
consistency in the terminology
Leverage your
you might learn that you’ve
payers use to describe their
team’s insights and
been submitting procedure
reasons for denial.
expertise, and take
codes that are inconsistent
“So getting them translated,
advantage of claimswith diagnosis codes, indicross-referenced, and put into
scrubbing systems
cating that you need to work
actionable information for those
that help you catch
on coding. Or you may find a
three sections is very difficult
errors.
pattern of missing or inaccuand manual,” he added.
rate demographic information,
This process is cumbersome
indicating possible problems
for large systems like Tenet and
with your front-desk registration procedures. small practices alike, but is too important to
overlook, Woodcock said. “Even though it’s
frustrating, we’re in a battle, and this battle
3. DIVIDE AND CONQUER
But to really put this information to work, you is fought every single day,” she said. “If we
1. F OL L OW U P PR OM P T LY
need to organize it. For Brett Waress, MHA, give up, we’re going to give up money as well.”
To maximize reimbursements, review all de- FACMPE, chief operating officer at Tenet Florida
4. SET PRIORITIES
nials within 72 hours and act on them within Physician Services, Boca Raton, the first phase
seven days, Woodcock said. Gone are the of that process is dividing denials into those Addressing denials is far less daunting, howdays billing staff can simply reprint a denied the practice understands and those it does not. ever, if you prioritize well.
“Don’t try to fix demographics, coding, and
claim and send it back to the payer with a
“There are denials for reasons that are
rubber stamp that says “appeal,” she added. specified by insurance companies that we so forth in a month,” said Owen Dahl, MBA,
“Insurance companies would laugh at you.” can understand, such as maybe we didn’t get FACHE, principal of Owen Dahl Consulting in
But by correcting claims, such as by add- the middle initial or get the patient registra- The Woodlands, Texas. “Focus on your biging requested information, and sending them tion right," Waress said. "Those are denials gest impact point first."
Once the first item is resolved, move down
back to payers quickly, Woodcock said that we know how to handle.”
at least 80% of them eventually will get paid.
Denials in this group then go through an- to the next-biggest problem.
“It’s hard to chase more than one rabbit
other (but not the last) round of sorting so
at a time,” Waress added. Where to begin
is a matter of preference.
“You either pick the high-dollar, high effort or the low-dollar, low effort,” he said.
Either way, prioritization is extremely helpful for a practice of any size.
—Elizabeth Woodcock, MBA, FACMPE, CPC
Y
TAKE-HOME
‘Denials are your treasure chest for performance
improvement. This is your guide to really make a difference.’
2. OPEN YOUR TR EASUR E CHEST
The key to long-term, revenue-cycle improvement, however, is learning from and correcting recurrent mistakes. Your most valuable
resource in this quest is the denial report,
Woodcock said.
It can be tempting simply to correct denied claims and send them back, but failing
they are addressed by the correct department:
front office; billing office; or clinical staff,
including physicians, notes Waress.
“But there’s a whole other category of denials for reasons that we may not understand
or appreciate," Waress explained. "It may be
a denial for bundling of services in a surgical
procedure that is payer-specific and not sup-
5 . R A L LY (D ON ’ T PU N I S H)
YOUR TEAM
Another common mistake is for a practice manager to attempt to come up with the solutions
to identified problems alone, Dahl said.
“Talk and brainstorm with your staff and
identify what the real source of the problem
is,” he said.
Continues on page 74 : Denials
73
74
APRIL 15, 2015 :: Ophthalmology Times
practice management
DENIALS
Common reasons for claim denials
( Continued from page 73 )
This approach not only eases the burden on
managers, it also enhances buy-in among
employees to follow through with the solutions they helped create.
Keep in mind, too, that firing an employee
who may be responsible for a discovered mistake may not be a productive move.
“Eighty-five percent of the time an employee
is involved in an error, a system causes the
error, not the employee,” Dahl said.
And such systems aren’t necessarily ITrelated, but may have to do with inadequate
training, poor tools, or too many tasks being
assigned to employees, which winds up compromising their performance.
“Look at this as a teachable or fixable
moment,” Dahl said. “Don’t make the mistake of perpetuating the problem by firing
one person and hiring a new one.”
6. OPTIMIZE TECHNOLOGY
In addition to leveraging your team’s insights
and expertise, take advantage of claimsscrubbing systems that help you catch errors before you submit them.
“The clearinghouse world has gotten much
better and more sophisticated," Dahl said.
"There are tools available that practices may
not be fully aware of or taking advantage of.”
Some basic versions of these tools may be
bundled into general practice management
software that practices already use, Dahl
said, adding the caveat that practices might
need to spend some time to understand the
technology and how it works.
“People need to look at both what’s in
their practice management system (PMS)
package and what’s in their claims management package from the clearinghouse, and
then the compatibility of the two,” Dahl outlined. “Do I fix a claim in the scrubber or
the PMS and how do I make sure that data
is being recorded properly?”
Furthermore, practices should determine
whether their PMS allows them to build in
their own edits on top of the basic pre-loaded
rules. “You might say it’s kind of a pain
to put in all those edits, all those rules,"
Woodcock added. "But remember, if I can
prevent five, six, 15, or 25 errors from happening by building the rule each and every
time, it’s definitely going to be worth the 30
to 45 minutes I spend researching and inputting that rule.”
DUPLICATE CLAIMS
PROBLEM WITH MODIFIERS
A duplicate claim was submitted when a practice has
not received reimbursement.
The claim form is missing a modifier or modifiers, or
the modifier(s) are invalid for the procedure code.
TYPOS
CODING MIX UP
Errors or typos were made while collecting pertinent
information from the patient or during the data entry
process for a claim.
There is a coding or data error with mismatched totals
or codes that are mutually exclusive.
OUTDATED CODES
DEDUCTIBLE
The service will not be reimbursed because the patient
has not yet met their insurance plan’s deductible.
The claim includes outdated current procedural
terminology codes, or it lists deleted or truncated
diagnosis codes.
HEALTH PLAN BENEFITS EXCEEDED
SERVICE NOT COVERED
The patient has exceeded his or her health plan’s benefit
for the provided service.
A particular service is not covered under the health
plan’s benefits.
INSUFFICIENT INFORMATION
LACK OF MEDICAL NECESSITY
The claim is deficient in certain information. It may be
missing a prior authorization or the effective period
of time within which the service must be provided for
reimbursement to occur.
The health plan could deny a claim if it appears that
a service was not medically necessary, or if there is
a mismatch between the actual diagnosis and the
service performed.
SITE OF SERVICE PROBLEM
OUT OF NETWORK
An inconsistent site of service is marked on the claim
form, such as an inpatient procedure billed in an
outpatient setting.
When the physician is not an in-network provider for
the patient, the payer may reimburse a lesser amount
if the patient has out-of-network benefits.
7. F I N D A S U PP O R T S Y S T E M
Despite the influx of technology into claims
processing in recent years, interpersonal relationships with payers still matter.
“Payers are getting more sophisticated and
doing more things electronically just like we
are," Dahl said, "but there’s still no substitute for the fact that I’ve known Mary from
insurance company X for all these years and
she always tries her best to help me.
"How you communicate with Mary could
change to e-mail, instant messaging, or texting, but I still recommend you contact Mary
verbally on occasion just to say, 'hi.'”
Woodcock agreed, noting that such relationships may help give your practice a voice at the
payer if you find that a claims-scrubbing rule
built into the insurer’s system isn’t accurate.
“So that relationship may recognize that
they’re working for a company just like us,"
Woodcock said. "Sometimes humans make
mistakes in what they input and we need humans to correct them.”
Unfortunately, when Waress experienced
just such a problem with a payer incorrectly
denying claims, he was unable to reach payer
employees empowered to resolve the error.
“Even if they agree with and are sympathetic to your problem, people can’t always
affect systemic changes in insurance algorithms,” he said.
As a result, his practice ultimately had to
undertake a formal dispute process involving
the state medical society and department of
insurance, which took 18 months to complete.
Because the denials were found to violate the
group’s contract as well as department of insurance rules, Waress was successful in obtaining a settlement from the payer that included
penalties and interest.
“The department of insurance of the state I
was in, particularly their health insurance division, was instrumental in helping us get the
attention of payers and getting them to change
the way they denied or paid claims,” he added.
For situations that require less extreme efforts,
professional organizations, such as the Medical
Group Management Association and state medical societies, can often help practices get in touch
with other offices tackling the same challenges.
“The important thing to remember is that
you’re not alone,” Waress said. ■
75
APRIL 15, 2015 :: Ophthalmology Times
marketplace
For Products & Services advertising information, contact: Karen Gerome BUFYUt'BYt&NBJMLHFSPNF!BEWBOTUBSDPN
For Recruitment advertising information, contact: Joanna Shippoli BUFYUt'BYt&NBJMKTIJQQPMJ!BEWBOTUBSDPN
PRODUCTS & SERVICES
BILLING SERVICES
PRACTICE SHARING
PM Medical Billing
& Consulting
PRACTICE SHARING OPPORTUNITY
Exclusive Ophthalmology Billers
Expert Ophthalmology Billers
Excellent Ophthalmology Billers
Triple E = Everything gets Paid
Concentrating on one Specialty makes the difference.
We are a Nationwide Ophthalmology Billing Service.
We have been in business over twenty years. Our staff
consists of billers who are certified Ophthalmic Techs,
Ophthalmic assistants, and fundus photographers who
are dual certified ophthalmic coders and billers. This
combination of clinical backgrounds in ophthalmology
with the certified coding degree is the ideal combination
of expertise that you need to dramatically increase your
revenue. We will get you paid on every procedure every
single time. No more bundling, downcoding or denials…
Primary, Secondary, Tertiary and Patient Billing
Relentless and meticulous follow up.
t Experts in Forensic Billing. Specializing in
old AR cleanup
t Credentialing and Re credentialing our Specialty.
We have a separate Credentialing Department who
has cultivated years of contacts to expedite the
process as well as getting providers on plans that
are technically closed.
t We can offer you our own Practice Management
software at no cost to you or we can VPN into your
system if that is what you prefer.
t Totally Hippa compliant. We are certified Hippa and
have invested in the most secure Hippa connection
that Google and Cisco use.
t Monthly custom reports provided.
We presently work on all of the following Practice
Management systems :
NextGen, MD Office, Centricity, Medisoft, Office Mate,
MD Intellus, Medware, Medcomp, Management Plus,
ADS, Revolution EHR, EyeMd EMR, Next Tec, Open
Practice Solutions, Cerner Works and more….
All of our clients were paid the PQRI and E-prescribe
bonuses and we are ready for the ICD-10 change
Our staff has years of Attendance at AAO and ASCRS
and attends all ongoing Ophthalmology billing and
Practice Management continuing education classes.
We are always knowledgeable and prepared for all
government and commercial changes.
On staff MBA consultants
Call today to schedule a free on site consultation.
We will travel to you anytime to evaluate your AR and show
you how we can dramatically increase your Revenue.
Call toll free at 1-888-PM-BILLING (1-888-762-4554)
Email: JOGP!QNCJMMFSDPNtWeb: www.pmbiller.com
24 hours: 516-830-1500
Our Prestigious National Ophthalmology Clients
reference list will be provided at your request
Near Pomona/LA County.
MARKETPLACE
ADVERTISING
Looking for Ophthalmologist
Call Karen Gerome
to share existing space
to place your Marketplace ad
with optometrist.
Please call
(909) 621-3952
at 800-225-4569, ext. 2670
[email protected]
Content Licensing for
Every Marketing Strategy
Marketing solutions fit for:
Outdoor | Direct Mail | Print Advertising
Tradeshow/POP Displays | Social Media
Radio & TV
Leverage branded content from Opthalmology Times to
create a more powerful and sophisticated statement
about your product, service, or company in your
next marketing campaign. Contact Wright’s Media
to find out more about how we can customize your
acknowledgements and recognitions to enhance your
marketing strategies.
For information, call Wright’s Media
at 877.652.5295 or visit our website
at www.wrightsmedia.com
PM (Practice Management) Billing will keep an EYE on
your Billing so you can keep an EYE on your patients.
76
APRIL 15, 2015 :: Ophthalmology Times
marketplace
For Products & Services advertising information, contact: Karen Gerome BUFYUt'BYt&NBJMLHFSPNF!BEWBOTUBSDPN
For Recruitment advertising information, contact: Joanna Shippoli BUFYUt'BYt&NBJMKTIJQQPMJ!BEWBOTUBSDPN
CAREERS
FELLOWSHIP
LOUISIANA
OCULOPLASTIC FELLOWSHIP
One year fellowship offered
by Dr. Roger E. Bassin of the
Bassin Center for Plastic Surgery.
Learn about face lift, lazerlift,
blepharoplasty, brow lift, cheek
lift, laser resurfacing, fat transfer
and body liposuction as well as
basic oculoplastic surgery.
Please submit resumes to:
[email protected]
ADVERTISE
NOW!
Combine
Ophthalmology Times
Marketplace
print advertising
with our
online offerings
to open up
unlimited potential.
9,;05(
Ochsner Health System in New Orleans seeks a board certified, fellowship
trained Vitreoretinal Subspecialist to join its established practice. The
Department of Ophthalmology serves as a referral center for the region.
This clinic surgical-based position includes teaching responsibilities in the
Department Ophthalmology. Through our training program affiliations, this
position also includes faculty appointments at Louisiana State University
School of Medicine and The University of Queensland Medical School
in Brisbane, Australia. Clinical research is encouraged. Salary is highly
competitive and commensurate with experience.
Ochsner Health System is southeast Louisiana’s largest non-profit, academic,
multi-specialty, healthcare delivery system. Driven by a mission to Serve,
Heal, Lead, Educate and Innovate, coordinated clinical and hospital patient
care is provided across the region by Ochsner’s 13 owned, managed and
affiliated hospitals and more than 50 health centers. Ochsner is the only
Louisiana hospital recognized by 2014-15 U.S. News & World Report as a
“Best Hospital” across nine specialty categories. Ochsner employs more than
15,000 employees, over 900 physicians in over 90 medical specialties and
subspecialties and conducts over 750 clinical research studies. Please visit
us at www.ochsner.org.
Ochsner Health System and The University of Queensland Medical School
in Brisbane, Australia began a unique, joint partnership in 2009 by opening
the University of Queensland School of Medicine Clinical School at Ochsner,
providing U.S. medical students with an unprecedented educational
experience.
New Orleans is one of the most exciting and vibrant cities in America.
Amenities include multiple universities, academic centers, professional
sports teams, world-class dining, cultural interests, renowned live
entertainment and music.
Please e-mail your CV to:
[email protected], Ref# ARETNO3
or call (800) 488-2240
Ochsner is an equal opportunity employer and all qualified applicants
will receive consideration for employment without regard to race, color,
religion, sex, national origin, sexual orientation, disability status, protected
veteran status, or any other characteristic protected by law.
RECRUITMENT ADVERTISING
WORKS!
Call Joanna Shippoli to place your Recruitment ad at
FYUtKTIJQQPMJ!BEWBOTUBSDPN
77
APRIL 15, 2015 :: Ophthalmology Times
marketplace
For Products & Services advertising information, contact: Karen Gerome BUFYUt'BYt&NBJMLHFSPNF!BEWBOTUBSDPN
For Recruitment advertising information, contact: Joanna Shippoli BUFYUt'BYt&NBJMKTIJQQPMJ!BEWBOTUBSDPN
CAREERS
LOUISIANA
6*<3673(:;0*:65*636.0:;
Ochsner Health System in New Orleans is seeking a Board Certified
Ophthalmologist with fellowship training in Oculoplastics and
experience in Ocular Oncology. This position includes medical student
and ophthalmology resident teaching responsibilities in the Department
of Ophthalmology. Through our training program affiliations, this position
also includes faculty appointments at Louisiana State University School of
Medicine and The University of Queensland Medical School in Brisbane,
Australia. Clinical research is encouraged.
Ochsner Health System is southeast Louisiana’s largest non-profit, academic,
multi-specialty, healthcare delivery system. Driven by a mission to Serve,
Heal, Lead, Educate and Innovate, coordinated clinical and hospital patient
care is provided across the region by Ochsner’s 13 owned, managed and
affiliated hospitals and more than 50 health centers. Ochsner is the only
Louisiana hospital recognized by 2014-15 U.S. News & World Report as a
“Best Hospital” across nine specialty categories. Ochsner employs more than
15,000 employees, over 900 physicians in over 90 medical specialties and
subspecialties and conducts over 750 clinical research studies. Please visit
us at www.ochsner.org.
Ochsner Health System and The University of Queensland Medical School
in Brisbane, Australia began a unique, joint partnership in 2009 by opening
The University of Queensland School of Medicine Clinical School at Ochsner,
providing U.S. medical students with an unprecedented educational
experience.
RECRUITMENT
ADVERTISING
Can Work For You!
Reach highly-targeted,
market-specific business
professionals, industry
New Orleans is one of the most exciting and vibrant cities in America.
Amenities include multiple universities, academic centers, professional
sports teams, world-class dining, cultural interests, renowned live
entertainment and music.
experts and prospects by
Please e-mail your CV to:
[email protected], Ref# AOCU13
or call (800) 488-2240
placing your ad here!
Ochsner is an equal opportunity employer and all qualified applicants
will receive consideration for employment without regard to race, color,
religion, sex, national origin, sexual orientation, disability status, protected
veteran status, or any other characteristic protected by law.
CONNECT
with qualified leads and career professionals
Post a job today
Joanna Shippoli
ZZZPRGHUQPHGLFLQHFRPSK\VLFLDQFDUHHUV
RECRUITMENT MARKETING ADVISOR
(800) 225-4569, ext. 2615
[email protected]
78
APRIL 15, 2015 :: Ophthalmology Times
practice management
Moving EHR beyond clinical practice
Vendors cater to needs of ASC with software that increases efficiency, quality of care, profits
By William L. Watson and Lizbeth Alicea
odern health-care facilities
like ambulatory surgery
centers (ASCs) are a primary source for surgical
procedures by providing
same-day care. Prior to
the advent of ASCs, surgery was performed in hospitals and required
that patients waited weeks for an appointment
and spent days in the hospital.
As a result, electronic health record (EHR)
vendors are beginning to cater to the unique
needs of ASCs with the advent of software that
increases efficiency, quality of care, and profits. Tomoka Eye Associates recently incorporated an EHR that is ideally suited for an ASC
environment. Some of the lessons learned are
shared in this article.
According to the American Society of Ophthalmic Administrators’ technician benchmarking study (http://bit.ly/1ajPHk0), EHR increases
efficiency. In the operating room, surgeons are
able to chart quickly, as well as capture images from surgical monitors during the procedure, integrating all components into the
patient’s file.
Compartmentalizing communication between staff and employees also plays a role
in increasing efficiency.
For example, users can access test results
through an EHR chart, rather than relying on
a staff member to make a physical transfer
of a paper chart to the surgery center for the
M
an electronic chart at the same time. All data
are stored in one place, which makes access
easier logistically compared with paper.
MITIGATE RISKS
EHR for ASCs not only eliminates the need for
paper charts and streamlines workflow, but
it also lowers the risk of errors by standardizing processes.
For example, it ensures that a patient’s record is complete and has undergone proper
review by the necessary physicians prior to
the patient’s discharge. EHR in an ASC also
mitigates risks by reducing legal exposure and
improving compliance with the Health Insurance Portability and Accountability Act.
Staff can easily access any data requested
during accreditation or surveys by Centers for
Medicare and Medicaid Services, as well as
provide documented proof for compliance issues when needed.
Additionally, it is possible to incorporate a
mobile computer that can travel from bedside
to bedside to ensure privacy for each patient—
although extreme care is still given to what
information is displayed on the screen when
patients are present.
PAT I E N T, PH Y S IC I A N
SATISFACTION
In the combined practice-ASC, both physicians
and staff have experienced increased satisfaction with use of an EHR.
For e x a mple,
physicians can access patient records
from any location
in real time, which
eliminates the need
for them to travel to
the ASC to fill a prescription or to carry
files home in order
to manage a patient
case remotely.
EHR in an ASC
also reduce costs
associated with paper-related administrative duties, such as buying paper, printing copies, and storing and retrieving paper charts.
Streamlining an EHR from a
clinic to an ASC allows data
to become easily available
on both ends with less room
for error or lost data.
day, then retrieve the record and file it back
with the clinic.
As a result, more than one person can read
Tips for ASC-EHR
Implementation
CHOOSE A V EN DOR that provides
exceptional support and whose representatives
are reliable and accessible.
SELECT A N ASC-EHR TEMPL ATE
that is easily customizable.
TA K E T IME . There are no meaningful
use requirements to meet for ASCs.
ST R AT E GIC A L LY S E L E C T K E Y
INDIV IDUALS for the install team. A nurse
manager, business manager, and IT specialist
are ideal. Keep the group small to streamline the
decision-making and implementation processes.
TR AIN THE PHYSICIANS FIRST as
champions of the system. Ensure that physicians
do not speak negatively about the system in
front of staff.
However, this also translates into reallocating staff responsibilities that are spent on
time-consuming tasks associated with managing paper charts. Physician and staff reap
the benefits of spending time on more rewarding tasks.
INCORPOR ATE AN
EHR INTO AN ASC
Streamlining an EHR from a clinic to an ASC
allows data to become easily available on both
ends with less room for error or lost data. When
the decision was made to implement EHR into
the ASC, ManagementPlus’ eye-care-specific
EHR had already been implemented into the
clinic. Therefore, there was complete comfort
with the software.
Prior to purchasing the EHR, peers who
were utilizing the software were shadowed
to witness how the vendor engaged with its
clients as partners. It was kept in mind that
the purchase also included the people behind
the company, because it is a given that software is often in a constant state of change.
79
APRIL 15, 2015 :: Ophthalmology Times
practice management
business managers from the ASC to customManagementPlus worked alongside as a partize every template to fit the needs of the ASC.
ner to help create an ASC-EHR that now serves
Clinics that have already
as a model for the vendor.
invested in EHR will find that
Involvement at this level was
transition to an ASC will benan important component for sucefit both the clinic and the ASC
cessful implementation. Because
Implementing
alike, and will continue to foster
there was no time frame manelectronic health
efficiency and increase patient
dated by meeting meaningful
records into an
and staff satisfaction.
use requirements, the practice
ambulatory surgery
Fortunately, there is EHR softwas able to take the time needed
center fosters
ware designed to fit the unique
to customize the software with
efficiency and
needs of many types of ophthalthe EHR specialist.
increases patient and
mic specialties and health-care
In addition, weekly meetings
staff satisfaction.
organizations.
were held with the nurse and
EHR software designed specifically for ASCs
can conform to the needs of an ASC without
adding complexity to its protocols. ■
TAKE-HOME
WILLIAM L. WATSON is chief executive officer, Tomoka Eye
Associates, Ormond Beach, FL. He may be reached at 386/672-4448
or [email protected].
LIZBETH ALICEA is IT Manager, Tomoka Eye Associates, Ormond
Beach, FL. She may be reached at 386/672-4244 or lizbetha@
tomokaeye.com.
Advertiser Index
Advertiser
Abbott Medical Optics
Page
Advertiser
Page
5
Haag Streit
45
www.amo-inc.com
P: 513/658-0574
www.haag-streit-usa.com
AcuityPro Vision Science Software
Alcon Laboratories Inc.
Perrigo Specialty Pharmaceuticals
ICare USA
59
P: 866/634-9120
www.perrigo.com
37
Regeneron Pharmaceuticals
www.icare-usa.com
18A-D, 25, 39, 48-50,
81-82, CV3, CV4
P: 800/862-5266
www.alcon.com
Omeros
Katena Products Inc.
Page
CV2, 3
www.omeros.com
63
P: 877/228-4890
www.AcuityPro.com
Advertiser
P: 973/989-1600
F: 973/989-8175
www.katena.com
33-34
41A*-42A*
P: 914/345-7400
www.regeneron.com
Rhein Medical
Alimera Sciences
CVTIP, 10A–D*
www.iluvien.com
Allergan Inc.
Maine Society of Eye Physicians
70
P: 207/445-2260
www.maineeyemds.com
21-22, 28-31
P: 714/246-4500 or
800/433-8871 (Customer Service)
F: 714/246-4971
www.allergan.com
Rumex
Micro Medical Devices
61
P: 866/730-0663
www.micromedinc.com
Nidek Inc.
9, 15-16, 26A–D
P: 800/227-1427 or
800/323-0000 (Customer Service)
www.bausch.com
53
www.doheny.org
OPHTHALMOLOGY TIMES (Print ISSN 0193-032X, Digital ISSN 2150-7333) is published
semimonthly except for one issue in Jan, May, Aug and Dec (20 issues yearly) by UBM
Advanstar, 131 W First Street, Duluth, MN 55802-2065. Subscription rates: $200 for one
year in the United States & Possessions, Canada and Mexico; all other countries $263 for
one year. Pricing includes air-expedited service. Single copies (prepaid only): $13 in the
United States & Possessions, Canada and Mexico; $20 all other countries. Back issues,
if available are $25 in the U.S. $ Possessions; $30 in Canada and Mexico; $35 in all other
countries. Include $6.50 per order plus $2 per additional copy for U.S. postage and handling.
65
P: 800/223-9044
www.usa.nidek.com
Oculus Inc.
Doheny Eye Institute
55
www.rumex.net
ThromboGenics
Bausch + Lomb
7
P: 800/637-4346
www.rheinmedical.com
13
P: 732/590-2900
www.thrombogenics.com
This index is provided as an additional service.
The publisher does not assume any liability for errors
or omissions.
57
*Indicates a demographic advertisement.
P: 425/670-9977
F: 425/670-0742
www.oculususa.com
If shipping outside the U.S., include an additional $10 per order plus $5 per additional
copy. Periodicals postage paid at Duluth, MN 55806 and additional mailing offices.
POSTMASTER: Please send address changes to OPHTHALMOLOGY TIMES, P.O. Box 6009,
Duluth, MN 55806-6009. Canadian G.S.T. number: R-124213133RT001, Publications Mail
Agreement Number 40612608. Return undeliverable Canadian addresses to: IMEX Global
Solutions, PO Box 25542 London, ON N6C 6B2 CANADA. Printed in the U.S.A.
©2015 Advanstar Communications Inc. All rights reserved. No part of this publication
may be reproduced or transmitted in any form or by any means, electronic or mechanical
including by photocopy, recording, or information storage and retrieval without permission
in writing from the publisher. Authorization to photocopy items for internal/educational or
personal use, or the internal/educational or personal use of specific clients is granted by
Advanstar Communications Inc. for libraries and other users registered with the Copyright
Clearance Center, 222 Rosewood Dr. Danvers, MA 01923, 978-750-8400 fax 978-6468700 or visit http://www.copyright.com online. For uses beyond those listed above, please
direct your written request to Permission Dept. fax 440-756-5255 or email: mcannon@
advanstar.com.
80
APRIL 15, 2015 :: Ophthalmology Times
practice management
Unchecked supply chain process can
degrade a product's safety, efficacy
Refrigeration, system of checks and balances implemented by phenylephrine manufacturer
By Paul S. Koch, MD, Special to Ophthalmology Times
inition of room temperature is general storage
henylephrine hydrochloride solu- between 68° F and 78° F, but also allowing for
tion has traditionally been used temporary excursions as low as 59° F and as
as a topical agent to dilate the pu- high as 86° F.”
pils. While physicians have had
many choices between branded
and generic solutions, many do
not realize that they had likely
been using a non-FDA-approved solution.
The first of these phenylephrine hydrochloride ophthalmic solutions to undergo the FDA’s
rigorous approval process belongs to Paragon
BioTeck Inc., Portland, OR.
Physicians may also be unaware that phenylephrine hydrochloride is a drug that can oxidize and degrade in ophthalmic solutions when
exposed to light and higher temperatures.1-3
The article went on to explain that experts
This degradation process can often be visibly suggest that storing medications over 86° F—a
observed, as the solution may become discol- fairly typical summer temperature in many
areas of the country—can have a significant
ored turning dark yellow or brown.4
Even in light-controlled packaging, certain phys- effect on their potency.
For example, when stored at temperatures
ical and chemical degradation can occur, which
has been reported to result in decreased potency.5-8 over 98° F, lorazepam and diazepam decrease
To combat this degradation, it has been sug- in potency by 75% and 25% respectively. Ingested that minimizing light exposure and higher sulin and thyroid hormones are widely pubtemperature conditions may be important in lished as being sensitive to heat, and can lose
optimizing efficacy and performance of this effectiveness in higher temperatures. Concentrated epinephrine can lose potency by 64%
commonly used drug.
During a busy day at the clinic, it may not when exposed to cyclical heating (repetitive
be practical or efficient to return a bottle of heating and cooling).
While this may be of less concern in an
drops that is used on virtually every patient
office setting, what about the
to the refrigerator.
multiple warehouses that a prodHowever, maintaining labeled
uct touches prior to the clinic?
storage conditions when the botPhysicians may
Or, even worse, how about the
tle is out of use at the end of the
know how a product is
back of a delivery truck in July?
day may be more important than
stored once it reaches
previously understood. If this
their offices, but there
SYSTEM OF CHECKS
is true for the limited amount
is no way of knowing
AND BALANCES
of time that a drug, such as
the supply chain
Phenylephrine is just one examphenylephrine hydrochloride,
storage conditions
ple of one drug that has been
is stored in an office setting,
during manufacture
shown to degrade and oxidize
then it certainly should be a
and transit.
under higher temperatures. So
consideration throughout the
for this drug, maintaining refrigentire supply chain.
erated storage conditions whenIn a recent online article
(http://bit.ly/1DAWrFC) Amy Peak, director ever possible—for example, in transition and
of drug information services for Butler Uni- transport and in the office—may be key.
Leaving the solution unrefrigerated for an undeterversity, Indianapolis, states: “The technical defWARWICK , RI ::
P
mined amount of time in unmonitored climate and
temperature conditions through the supply chain
may be cause for physician and patient concern.
Paragon BioTeck is one company that has
‘Certain physical and chemical
degradation can occur, which
has been reported to result in
decreased potency.’ — Paul S. Koch, MD
TAKE-HOME
a system of checks and balances in place for
proper storage procedures that are implemented
through distribution. These standards of transport are upheld to ensure the stability of the
phenylephrine hydrochloride, as any sort of
oxidation or degradation of the product may
lead to the drug becoming less stable over time.
DEGR ADATION AND POTENCY
If degradation occurs and the phenylephrine
hydrochloride becomes less active, physicians
may experience difficulty with dilation.
In response, this may lead to increased chair
time for physicians and their staff, and the use
of more drops than the recommended dosage
in order to obtain the desired result. Using any
product above recommended dosage can contribute to adverse events and should be avoided.
For companies with drug products that are
historically stored at room temperature, this
means that throughout manufacture and the
supply chain, little attention may be paid to
maintain optimum temperatures and storage
conditions. With the significant distances products like phenylephrine often travel to reach a
practice, it is possible they have sat in a truck
on a hot tarmac with unregulated temperatures or have gone through a variety of environmental climate and temperature changes.
Physicians may know how a product is stored
once it reaches their offices, but there is no way
Continues on page 82 : Supply chain
DUOVISC® OVD BRIEF STATEMENT
DESCRIPTION: DUOVISC®9LVFRHODVWLF6\VWHPLVGHVLJQHGWRJLYHWZR9LVFRHODVWLFPDWHULDOVZLWKGLHUHQWSK\VLFRFKHPLFDOSURSHUWLHVWKDWFDQEHXVHG
GLHUHQWO\ DQGRU VHTXHQWLDOO\ WR SHUIRUP VSHFLF WDVNV GXULQJ D FDWDUDFW SURFHGXUH '829Ζ6&® 9LVFRHODVWLF 6\VWHP FRQVLVWV RI 9Ζ6&2$7® 2SKWKDOPLF
9LVFRVXUJLFDO'HYLFHDQG3529Ζ6&®2SKWKDOPLF9LVFRVXUJLFDO'HYLFH
CAUTION:)HGHUDO86$ODZUHVWULFWVWKLVGHYLFHWRVDOHE\RURQWKHRUGHURIDSK\VLFLDQ
DESCRIPTION:9Ζ6&2$7®6RGLXP&KRQGURLWLQ6XOIDWHȂ6RGLXP+\DOXURQDWH2SKWKDOPLF9LVFRVXUJLFDO'HYLFH
INDICATIONS:9Ζ6&2$7®29'LVLQGLFDWHGIRUXVHDVDQRSKWKDOPLFVXUJLFDODLGLQDQWHULRUVHJPHQWSURFHGXUHVLQFOXGLQJFDWDUDFWH[WUDFWLRQDQGLQWUDRFXODU
OHQVΖ2/LPSODQWDWLRQ9Ζ6&2$7®29'PDLQWDLQVDGHHSDQWHULRUFKDPEHUGXULQJDQWHULRUVHJPHQWVXUJHULHVHQKDQFHVYLVXDOL]DWLRQGXULQJWKHVXUJLFDO
SURFHGXUHDQGSURWHFWVWKHFRUQHDOHQGRWKHOLXPDQGRWKHURFXODUWLVVXHV7KHYLVFRHODVWLFLW\RIWKHVROXWLRQPDLQWDLQVWKHQRUPDOSRVLWLRQRIWKHYLWUHRXVIDFH
DQGSUHYHQWVIRUPDWLRQRIDDWFKDPEHUGXULQJVXUJHU\
WARNINGS: )DLOXUHWRIROORZDVVHPEO\LQVWUXFWLRQVRUXVHRIDQDOWHUQDWHFDQQXODPD\UHVXOWLQFDQQXODGHWDFKPHQWDQGSRWHQWLDOSDWLHQWLQMXU\
PRECAUTIONS: 3UHFDXWLRQV DUH OLPLWHG WR WKRVH QRUPDOO\ DVVRFLDWHG ZLWK WKH VXUJLFDO SURFHGXUH EHLQJ SHUIRUPHG $OWKRXJK VRGLXP K\DOXURQDWH DQG
VRGLXPFKRQGURLWLQVXOIDWHDUHKLJKO\SXULHGELRORJLFDOSRO\PHUVWKHSK\VLFLDQVKRXOGEHDZDUHRIWKHSRWHQWLDODOOHUJLFULVNVLQKHUHQWLQWKHXVHRIDQ\
ELRORJLFDOPDWHULDO
ADVERSE REACTIONS:9Ζ6&2$7®29'KDVEHHQH[WUHPHO\ZHOOWROHUDWHGLQKXPDQDQGDQLPDOVWXGLHV$WUDQVLHQWULVHLQLQWUDRFXODUSUHVVXUHLQWKHHDUO\
SRVWRSHUDWLYHSHULRGPD\EHH[SHFWHGGXHWRWKHSUHVHQFHRIVRGLXPK\DOXURQDWHZKLFKKDVEHHQVKRZQWRHHFWVXFKDULVHΖWLVWKHUHIRUHUHFRPPHQGHG
WKDW9Ζ6&2$7®29'EHUHPRYHGIURPWKHDQWHULRUFKDPEHUE\WKRURXJKLUULJDWLRQDQGRUDVSLUDWLRQDWWKHHQGRIVXUJHU\WRPLQLPL]HSRVWRSHUDWLYHΖ23
LQFUHDVHV'RQRWRYHUOODQWHULRUFKDPEHU
ATTENTION: 3OHDVHUHIHUWRWKHGLUHFWLRQVIRUXVHIRUDFRPSOHWHOLVWLQJRILQGLFDWLRQVZDUQLQJVDQGSUHFDXWLRQV
DESCRIPTION: 3529Ζ6&®6RGLXP+\DOXURQDWH2SKWKDOPLF9LVFRVXUJLFDO'HYLFH
INDICATIONS:3529Ζ6&®29'LVLQGLFDWHGIRUXVHDVDQRSKWKDOPLFVXUJLFDODLGLQWKHDQWHULRUVHJPHQWGXULQJFDWDUDFWH[WUDFWLRQDQGLQWUDRFXODUOHQVΖ2/
LPSODQWDWLRQ2SKWKDOPLFYLVFRHODVWLFVVHUYHWRPDLQWDLQDGHHSDQWHULRUFKDPEHUGXULQJDQWHULRUVHJPHQWVXUJHU\DOORZLQJUHGXFHGWUDXPDWRWKHFRUQHDO
HQGRWKHOLXPDQGVXUURXQGLQJRFXODUWLVVXHV7KH\KHOSSXVKEDFNWKHYLWUHRXVIDFHDQGSUHYHQWIRUPDWLRQRIDDWFKDPEHUGXULQJVXUJHU\
PRECAUTIONS: 3RVWRSHUDWLYHLQFUHDVHVLQLQWUDRFXODUSUHVVXUHKDYHEHHQUHSRUWHGZLWKVRGLXPK\DOXURQDWHSURGXFWV7KHΖ23VKRXOGEHFDUHIXOO\PRQLWRUHG
DQGDSSURSULDWHWKHUDS\LQVWLWXWHGLIVLJQLFDQWLQFUHDVHVVKRXOGRFFXUΖWLVUHFRPPHQGHGWKDW3529Ζ6&®29'EHUHPRYHGE\LUULJDWLRQDQGRUDVSLUDWLRQDW
WKHFORVHRIVXUJHU\'RQRWRYHUOODQWHULRUFKDPEHU$OWKRXJKVRGLXPK\DOXURQDWHLVDKLJKO\SXULHGELRORJLFDOSRO\PHUWKHSK\VLFLDQVKRXOGEHDZDUHRIWKH
SRWHQWLDODOOHUJLFULVNVLQKHUHQWLQWKHXVHRIDQ\ELRORJLFDOPDWHULDOFDUHVKRXOGEHXVHGLQSDWLHQWVZLWKK\SHUVHQVLWLYLW\WRDQ\FRPSRQHQWVLQWKLVPDWHULDO
&DQQXODDVVHPEO\LQVWUXFWLRQVVKRXOGEHIROORZHGWRSUHYHQWSDWLHQWLQMXU\
ADVERSE REACTIONS:3RVWRSHUDWLYHLQDPPDWRU\UHDFWLRQVVXFKDVK\SRS\RQDQGLULWLVKDYHEHHQUHSRUWHGZLWKWKHXVHRIRSKWKDOPLFYLVFRHODVWLFVDV
ZHOODVLQFLGHQWVRIFRUQHDOHGHPDFRUQHDOGHFRPSHQVDWLRQDQGDWUDQVLHQWULVHLQLQWUDRFXODUSUHVVXUHΖWLVWKHUHIRUHUHFRPPHQGHGWKDW3529Ζ6&® OVD
EHUHPRYHGIURPWKHDQWHULRUFKDPEHUE\WKRURXJKLUULJDWLRQDQGRUDVSLUDWLRQDWWKHHQGRIVXUJHU\WRPLQLPL]HSRVWRSHUDWLYHΖ23LQFUHDVHV'RQRWRYHUOO
DQWHULRUFKDPEHU
ATTENTION:3OHDVHUHIHUWRWKHGLUHFWLRQVIRUXVHIRUDFRPSOHWHOLVWLQJRILQGLFDWLRQVZDUQLQJVDQGSUHFDXWLRQV
ACRYSOF® IQ TORIC INTRAOCULAR LENSES IMPORTANT PRODUCT INFORMATION
CAUTION:)HGHUDO86$ODZUHVWULFWVWKLVGHYLFHWRWKHVDOHE\RURQWKHRUGHURIDSK\VLFLDQ
INDICATIONS:7KH$FU\6RI®Ζ47RULFSRVWHULRUFKDPEHULQWUDRFXODUOHQVHVDUHLQWHQGHGIRUSULPDU\LPSODQWDWLRQLQWKHFDSVXODUEDJRIWKHH\HIRUYLVXDOFRUUHFWLRQRI
DSKDNLDDQGSUHH[LVWLQJFRUQHDODVWLJPDWLVPVHFRQGDU\WRUHPRYDORIDFDWDUDFWRXVOHQVLQDGXOWSDWLHQWVZLWKRUZLWKRXWSUHVE\RSLDZKRGHVLUHLPSURYHGXQFRUUHFWHG
GLVWDQFHYLVLRQUHGXFWLRQRIUHVLGXDOUHIUDFWLYHF\OLQGHUDQGLQFUHDVHGVSHFWDFOHLQGHSHQGHQFHIRUGLVWDQFHYLVLRQ
WARNINGS/PRECAUTIONS:&DUHIXOSUHRSHUDWLYHHYDOXDWLRQDQGVRXQGFOLQLFDOMXGJPHQWVKRXOGEHXVHGE\WKHVXUJHRQWRGHFLGHWKHULVNEHQHWUDWLREHIRUH
LPSODQWLQJDOHQVLQDSDWLHQWZLWKDQ\RIWKHFRQGLWLRQVGHVFULEHGLQWKH'LUHFWLRQVIRU8VHODEHOLQJ7RULFΖ2/VVKRXOGQRWEHLPSODQWHGLIWKHSRVWHULRUFDSVXOHLV
UXSWXUHGLIWKH]RQXOHVDUHGDPDJHGRULIDSULPDU\SRVWHULRUFDSVXORWRP\LVSODQQHG5RWDWLRQFDQUHGXFHDVWLJPDWLFFRUUHFWLRQLIQHFHVVDU\OHQVUHSRVLWLRQLQJVKRXOG
RFFXUDVHDUO\DVSRVVLEOHSULRUWROHQVHQFDSVXODWLRQ$OOYLVFRHODVWLFVVKRXOGEHUHPRYHGIURPERWKWKHDQWHULRUDQGSRVWHULRUVLGHVRIWKHOHQVUHVLGXDOYLVFRHODVWLFV
PD\DOORZWKHOHQVWRURWDWH
2SWLFDOWKHRU\VXJJHVWVWKDWKLJKDVWLJPDWLFSDWLHQWVLH!'PD\H[SHULHQFHVSDWLDOGLVWRUWLRQV3RVVLEOHWRULFΖ2/UHODWHGIDFWRUVPD\LQFOXGHUHVLGXDOF\OLQGULFDO
HUURURUD[LVPLVDOLJQPHQWV3ULRUWRVXUJHU\SK\VLFLDQVVKRXOGSURYLGHSURVSHFWLYHSDWLHQWVZLWKDFRS\RIWKH3DWLHQWΖQIRUPDWLRQ%URFKXUHDYDLODEOHIURP$OFRQIRUWKLV
SURGXFWLQIRUPLQJWKHPRISRVVLEOHULVNVDQGEHQHWVDVVRFLDWHGZLWKWKH$FU\6RI®Ζ47RULF&\OLQGHU3RZHUΖ2/V
6WXGLHVKDYHVKRZQWKDWFRORUYLVLRQGLVFULPLQDWLRQLVQRWDGYHUVHO\DHFWHGLQLQGLYLGXDOVZLWKWKH$FU\6RI®1DWXUDOΖ2/DQGQRUPDOFRORUYLVLRQ7KHHHFWRQYLVLRQ
RIWKH$FU\6RI®1DWXUDOΖ2/LQVXEMHFWVZLWKKHUHGLWDU\FRORUYLVLRQGHIHFWVDQGDFTXLUHGFRORUYLVLRQGHIHFWVVHFRQGDU\WRRFXODUGLVHDVHHJJODXFRPDGLDEHWLF
UHWLQRSDWK\FKURQLFXYHLWLVDQGRWKHUUHWLQDORURSWLFQHUYHGLVHDVHVKDVQRWEHHQVWXGLHG'RQRWUHVWHULOL]HGRQRWVWRUHRYHUr&XVHRQO\VWHULOHLUULJDWLQJVROXWLRQV
VXFKDV%66®RU%663/86®6WHULOHΖQWUDRFXODUΖUULJDWLQJ6ROXWLRQV
ATTENTION:5HIHUHQFHWKH'LUHFWLRQVIRU8VHODEHOLQJIRUDFRPSOHWHOLVWLQJRILQGLFDWLRQVZDUQLQJVDQGSUHFDXWLRQV
Advancing
CATARACT SURGERY
© 2015 Novartis 2/15 CRS15003JAD-A
82
APRIL 15, 2015 :: Ophthalmology Times
practice management
SUPPLY CHAIN
( Continued from page 80 )
of knowing the storage conditions
during manufacture and transit.
When products like phenylephrine are proven to perform with
higher efficacy under refrigeration,
it stands to reason that they should
be maintained in cold storage from
start to finish. The increased safety
and efficacy of a properly stored
product far outweighs the minimal,
one-time inconvenience of installing a mini-fridge in the office. ■
References
1. “Sterile Drug Products: Formulation,
Packaging, Manufacturing and
Quality.” Michael J. Akers p. 100.
2. “Remington: The Science and Practice
of Pharmacy.” Ed. David B. Troy, Paul
Beringer p. 1030.
3. US 20090047343 A1
4. “Photochemical Hydroxylation of
Phenylephrine to Epinephrine
CAUTION: Federal (USA) law
restricts this device to the
sale by or on the order of a
physician.
INDICATIONS: The AcrySof®
IQ posterior chamber
intraocular lens is intended
for the replacement of the
human lens to achieve visual
correction of aphakia in adult
patients following cataract
surgery. This lens is intended
for placement in the capsular
bag.
WARNING/PRECAUTION:
Careful preoperative
evaluation and sound clinical
judgment should be used
by the surgeon to decide
the risk/benefit ratio before
implanting a lens in a patient
with any of the conditions
described in the Directions
for Use labeling. Caution
should be used prior to lens
encapsulation to avoid lens
decentrations or dislocations.
(Adrenaline).” Journal of Pharmaceutical
and Biomedical Analysis, Vol. 6, No. 5,
pps. 511-514 1988.
5. Douša M, Gibala P, Havlícek J, et
al. Drug-excipient compatibility
testing-Identification and
characterization of degradation
products of phenylephrine in several
pharmaceutical formulations
against the common cold. Journal
of Pharmaceutical and Biomedical
Analysis. 2011;55:949-956.
6. Luduena FP, Snyder AL, Lands AM.
Effect of ultra-violet irradiation of
phenylephrine. J Pharm Pharmacol.
1963;15:538–543.
7. Al Taji RAAA, Stanford JB, Sugden JK.
Some aspects of the photolysis of
aqueous solutions of phenylephrine
hydrochloride. Pharm Acta Helv.
1982;57:56–60.
8. El-Shibini HAM, Daabis NA, Motawi
MM. The Stability of Phenylephrine:
Part I The Rate of Degradation of
the Amino Group., 19 (1969) pgs.
676–678.
PAUL S. KOCH, MD
E: [email protected]
Dr. Koch is founder and medical director of Koch Eye
Associates.
Studies have shown that
color vision discrimination
is not adversely affected in
individuals with the AcrySof®
Natural IOL and normal color
vision. The effect on vision
of the AcrySof® Natural IOL
in subjects with hereditary
color vision defects and
acquired color vision defects
secondary to ocular disease
(e.g., glaucoma, diabetic
retinopathy, chronic uveitis,
and other retinal or optic
nerve diseases) has not been
studied. Do not resterilize;
do not store over 45° C; use
only sterile irrigating solutions
such as BSS® or BSS PLUS®
Sterile Intraocular Irrigating
Solutions.
ATTENTION: Reference the
Directions for Use labeling
for a complete listing of
indications, warnings and
precautions.
© 2013 Novartis
2/13
NIQ14041JAD
From quantity to
quality: Meeting
new demands of
value-based care
WITH MEDICARE and
commercial insurers increasingly
tying physicians’ reimbursement
to their ability to report on—and
meet—outcome measurements,
the question logically arises, is it
working? Is the growing emphasis on quality and value having
an impact on patient health, and/
or healthcare spending?
The short answer is, it’s too
soon to tell. Still, intriguing—
if scattered—evidence is beginning to emerge that it might be.
For example:
> Medicare spending for 2014
was projected to be about $1,200
less per beneficiary than had been
forecast in 2010, the year the Affordable Care Act was passed, according to a Kaiser Family Foundation study. The slowdown in
spending is partially attributable
to “reductions in provider payment updates and Medicare Advantage payments” as well as cuts
resulting from the 2013 budget
sequester, the authors say, while
adding that “providers may be
tightening their belts and looking
to deliver care more efficiently
in response to financial incentives included in the ACA, and it
is possible that these changes
are having a bigger effect than
expected.”
> The National Council of Quality
Assurance found improvements
in 46% of the 139 Healthcare
Effectiveness Data and Information Set performance measures
it tracked over the previous three
to five years, performance declines in 8%, and mixed results
or no trend in 46%.
> Medicare’s evaluation of the
first year of its Comprehensive
Primary Care (CPC) initiative con-
cluded that “CPC appears to have
reduce total monthly Medicare
Part A and B expenditures per
beneficiary . . . by $14, or 2%.
The reductions appear to be due
to the favorable . . . impacts on
hospitalizations and emergency
department visits (total and outpatient.)” The evaluation also found
a 4% reduction in unplanned 30day hospital readmissions, a decline it calls “sizable but not quite
statistically significant.”
> The national 30-day, all-cause
hospital readmission rate average for Medicare fee-for-service
beneficiaries fell from 19% in
the 2007-2011 period to 18.4%
in 2012, according to a 2013
study in Medicare & Medicaid
Research Review. The re-admission rate fell below 18% for the
first part of 2013.
“I’m a contract negotiator, and
from my perspective I can tell you
payers wouldn’t be investing (in
quality initiatives) if they hadn’t
already seen the outcome and the
return on investment,” said Doral
Jacobsen, MBA, FACMPE, senior
manager with DHG healthcare.
“Pieces of this are working, though
it varies by market and practice.”
Nitin Damle, MD, FACP, a member of the American College of
Physicians Board of Regents, is
more cautious.
“We feel a more value-based approach to practicing medicine is
important, so moving away from
pure fee-for-service to a more valuebased reimbursement system is
the direction we want to move in.
We’re not sure yet if we are moving the needle in terms of whether
patients overall are getting a higher
quality of care,” Dr. Damle said. ■
Visual Performance.
AcrySof ® IQ – The monofocal IOL proven
to deliver excellent visual performance.
Give your patients more time to react with
the performance of AcrySof ® IQ IOL.
CONFIDENCE
Simulated image
For important product information, please see adjacent page.
© 2014 Novartis 7/14 NIQ14041JAD
YOUR SPECIALTY. ALCON TECHNOLOGIES.
The Cataract Refractive Suite by Alcon.
AcrySof IQ
®
IOL FAMILY
Visit MyAlcon.com to see how you can take your
cataract refractive outcomes a step further.
Advancing
CATARACT SURGERY
See adjacent page for important product information.
© 2015 Novartis 2/15 CRS15003JAD-A
See product instructions for use for indications, warnings, precautions and adverse events for all referenced devices.
Caution: Federal law restricts all referenced devices to sale by or on the order of a physician.