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RETINA
TIMES
The Official Publication of the American Society of Retina Specialists
Fall 2012
Issue 46
46
RETINA
TIMES
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Retina Times (ISSN 2164-4411) is published 5 times a year
by the American Society of Retina Specialists (ASRS)
as a service to its membership.
The mission of the publication is to strive to be the definitive
information source for ASRS members on Society news,
meeting plans, socioeconomic topics, international news, and
other relevant information on issues, instruments, and study
updates for the practicing retinal specialist.
Articles published herein are reviewed by the editor-in-chief
and managing editor for editorial content only. The accuracy
of information contained is the responsibility of the individual
author. Letters and other unsolicited material are assumed to be
intended for publication and are subject to rejection or editing.
All articles which appear in Retina Times are intended for
informational purposes only and should not be relied on by
any reader for any other purpose. The opinions and positions
expressed in Retina Times articles are solely those of
the authors and do not represent the opinions or positions
of the American Society of Retina Specialists Board of
Directors, members, employees, or Retina Times editorial
staff and volunteers.
Funding for Retina Times is provided by advertisements
contained within.
Organizational Staff
J. Michael Jumper, MD
Editor-in-Chief
San Francisco, CA
[email protected]
Susan Raef, MSMC
Managing Editor
Chicago, IL
[email protected]
phone: 312-578-8760
www.asrs.org
© 2012 American Society of Retina Specialists.
All rights reserved. No part of this publication may be reproduced or
transmitted, in any form, without the prior written permission of the
American Society of Retina Specialists.
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Dr. Jumper – COVALENT MEDICAL, INC: Equity Owner, Stock; Dutch
Ophthalmics USA: Speaker, Honoraria.
Ms. Blim – None. Ms. Raef – None. Ms. Schedler – None. Ms. Zallman – None.
Oonagh Petrizzi
Proofreader
Stamford, CT
Stacy Kiff
Annual Meeting Section Editor
Chicago, IL
John T. Thompson, MD
ASRS President
Baltimore, MD
William T. Koch, COA, COE, CPC
Coding Pitfalls Section Editor
St. Louis, MO
Gaurav K. Shah, MD
ASRS Communications Committee Chair
St. Louis, MO
Mathew W. MacCumber, MD, PhD
ASRS-AAO Councilor Representative
Chicago, IL
Jill F. Blim, MS
ASRS Executive Vice President
Chicago, IL
Charles W. Mango, MD
E-Retina Section Editor
New York, NY
Section Editors
Michael M. Altaweel, MD
Literature Roundup Section Co-Editor
Madison, WI
Carl C. Awh, MD
Fellows’ Forum Section Editor
Nashville, TN
Zélia M. Corrêa, MD, PhD
Ocular Oncology Section Co-Editor
Cincinnati, OH
Pravin U. Dugel, MD
Research & Development Section Editor
Phoenix, AZ
Nicholas E. Engelbrecht, MD
Pediatric Retina Section Co-Editor
St. Louis, MO
Philip J. Ferrone, MD
Site Selection Section Editor
Great Neck, NY
Mitchell S. Fineman, MD
Block Time Section Co-Editor
Philadelphia, PA
Brett T. Foxman, MD
Film Festival Section Editor
Northfield, NJ
Ms. Petrizzi – None.
Dr. Thompson – GENENTECH: Investigator, Grants; REGENERON
K. Bailey Freund, MD
X-Files Section Editor
New York, NY
PHARMACEUTICALS, INC: Investigator, Grants; PFIZER, INC:
Investigator, Grants.
Dr. Shah – ALCON LABORATORIES, INC: Consultant, Equipment
(department or practice); ALLERGAN, INC: Consultant, Equjpment
(department or practice); QLT, INC: Consultant, Equipment (department
or practice); DORC: Consultant, Equipment (department or practice).
Sunir J. Garg, MD
Block Time Section Co-Editor
Philadelphia, PA
Omesh Gupta, MD, MBA
Retina Education Section Co-Editor
Philadelphia, PA
Larry Halperin, MD
Retinomics Section Editor
Ft. Lauderdale, FL
On the Cover
Intraretinal neovascularization associated with
macular fibrosis in Coats disease, courtesy
J. Michael Jumper, MD.
G. Baker Hubbard, III, MD
Pediatric Retina Section Co-Editor
Atlanta, GA
J. Michael Jumper, MD
PAT Survey Section Editor
San Francisco, CA
Marcus H. Colyer, MD, MAJ, MC, USA
Retina in the Military Section Co-Editor
Bethesda, MD
Chicago, IL 60606
Suber S. Huang, MD, MBA
President, Foundation of the ASRS
Cleveland, OH
Ana Schedler
Graphic Designer
Toby Zallman
Production Artist
Schedler Brennan Design + Consulting
Chicago, IL
Jerald A. Bovino, MD
Jerry’s Wisdom Section Editor
Aspen, CO
20 North Wacker Drive, Suite 2030
Jeffrey S. Heier, MD
Clinical Trials: Future Pathways Section Editor
Boston, MA
J. William Harbour, MD
Ocular Oncology Section Co-Editor
Miami, FL
Tarek S. Hassan, MD
Road Test Section Editor
Royal Oak, MI
Peter K. Kaiser, MD
ASRS-AAO Councilor Representative
Cleveland, OH
John R. Minarcik Jr, MD, CDR, MC, USN
Retina in the Military Section Co-Editor
Fairfax, VA
Robert A. Mittra, MD
PAT Survey Section Co-Editor
Minneapolis, MN
Prithvi Mruthyunjaya, MD
Retina Education Section Co-Editor
Durham, NC
Joel Pearlman, MD, PhD
Retina Genetics Section Co-Editor
Sacramento, CA
Dante J. Pieramici, MD
What’s News Section Editor
Santa Barbara, CA
P. Kumar Rao, MD
Uveitis Section Editor
St. Louis, MO
Carl D. Regillo, MD
KOL Corner Section Editor
Philadelphia, PA
David Rhee, MD
Road Test Section Editor
Philadelphia, PA
William L. Rich III, MD
AAO Medical Director of Health Policy
Falls Church, VA
SriniVas R. Sadda, MD
Ocular Imaging Section Editor
Los Angeles, CA
Michael A. Samuel, MD
In the Spotlight Section Editor
Pasadena, CA
Reginald J. Sanders, MD
Practice Management Meeting Section Editor
Chevy Chase, MD
Chirag P. Shah, MD, MPH
Clinical Trials: Future Pathways Section Co-Editor
Boston, MA
Marc J. Spirn, MD
KOL Corner Section Co-Editor
Philadelphia, PA
Asheesh Tewari, MD
Literature Roundup Section Co-Editor
Detroit, MI
Trexler M. Topping, MD
Tea Leaves Section Editor
Boston, MA
Kang Zhang, MD, PhD
Retina Genetics Section Co-Editor
San Diego, CA
CONTENTS >>
Photo courtesy J. Michael Jumper, MD
Color photograph corresponding to the angiographic image on the cover.
The macular fibrosis is associated with an intraretinal vascular anastamosis and neovascularization.
7 FROM THE PRESIDENT
ASRS Version 3.0: Moving the
Vision Forward
20 INTERNATIONAL CORNER
Bringing the International Retina
Community Together
8 FOUNDATION UPDATE
Foundation Seeks Volunteers in 4 Key Areas
22 RETINOMICS
9 FROM THE EDITOR’S DESK
A Special Thanks to Our Active-Duty
Military Retina Specialists
10 FILM FESTIVAL
Film Festival Honors Winners from
5 Countries
44 RETINA PRACTICE PEARLS
The Patient Protection and
Affordable Care Act: 2010-2012—
a Curmudgeon’s Report Card
46 BLOCK TIME
How Has the Retina Subspecialty Changed
Since Vitrectomy?
The ACA Opens the Door to Health
Coverage for Millions
50 JERRY’S WISDOM
Everybody Is Sellin’ Somethin’
26 ASRS SYMPOSIUM
Clinical Trials ‘Unplugged’—
Part 1: Applying AMD Trial Results
to Clinical Practice
ASRS 30TH Anniversary
42 THE KOL CORNER
Wet AMD: The Changing Landscape
51 TEA LEAVES
Concierge Retina—That’s What We
Already Provide!
12 ASRS 30th ANNUAL MEETING
HIGHLIGHTS
ASRS Celebrates 30th Anniversary
at Annual Meeting
33 RETINA IN THE MILITARY
Serving in Afghanistan: 3 Deployed Retina
Specialists Share Their Stories
53 LITERATURE ROUNDUP
38 POINT/COUNTERPOINT NEW
56 X-FILES SOLUTION
16 CLINICAL TRIALS:
FUTURE PATHWAYS
Understanding Time-to-Event Analysis
Counterpoint: Most Primary Retinal
Detachments Can Be Repaired With
a Vitrectomy
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Point: Scleral Buckling Has a Continuing
Role in Repairing Retinal Detachment
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52 THE ASRS X-FILES
57 ADVERTISER INDEX
FROM THE PRESIDENT >>
John T. Thompson, MD
President, ASRS
ASRS Version 3.0: Moving the Vision Forward
I am honored to serve you as I begin my term as the 18th president of the ASRS, and
I look forward to helping the Society advocate on behalf of retina specialists. As you know,
we just celebrated our 30th annual meeting in Las Vegas—an outstanding event with
record attendance of nearly 1000 retina specialists. (For a recap of the meeting, including
photos, please see page 12.)
This year’s gala dinner and Umbo Lounge
at the Haze Nightclub were as memorable
as the 1999 Rome meeting gala, which
featured chariots, Roman centurians, and
attendees wearing togas. (The togas were
Kirk Packo’s idea.)
The field of retina has changed substantially
since the first ASRS meeting in 1983. Being a
retina specialist 30 years ago meant spending
about half of your time in the OR and seeing
some patients in the office for preop/postop
visits and laser treatments. Vitreous surgery
was relatively new, and the early Vitreous
Society meetings were devoted mostly to
sharing surgical techniques and insights
about new indications for vitrectomy.
The recent advent of anti-VEGF agents for
choroidal neovascularization, venous occlusive
disease, and diabetic macular edema has been
the most transformative change in retina since
the development of vitreous surgery. All of our
practices are adapting to the new paradigm where
most of our time is spent in the office seeing
more patients and less time is spent in the OR.
I have titled my first column “ASRS Version
3.0” to highlight where our Society has come
from and what we hope to accomplish in the
next few years.
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The first few Vitreous Society meetings were
organized by founders Jerry Bovino, Roy
Levit, and Allen Verne with an emphasis on
collegiality and informality. In the mid-1980s,
the idea of a retina meeting where any retina
specialist could attend was a novel one—predating the AAO Retina Subspecialty Day—
and the organization grew from 3 founders
and 44 charter members as word spread
within the retina community.
Our Society’s first 2 administrators, Dee
Smith (Roy’s secretary) and Jerry Lewis (Allen’s
office manager), were focused primarily
on admitting new members, processing dues,
and organizing the annual meetings. The
2 accomplished much, even though Jerry
worked out of her home and the membership
records were kept on file cards. The Vitreous
Society was granted ACCME accreditation
during Jerry Lewis’ tenure, and it was under
her leadership that a club became a society
with 1400 members.
The first Vitreous Society meeting I attended
was in 1992 at the Ritz-Carlton, Laguna
Niguel in Dana Point, California, an idyllic
cliff-side resort overlooking the Pacific
Ocean. I brought my family to another
Vitreous Society meeting at the Ritz-Carlton
in Aspen, Colorado during the summer of
1994 and realized this group knew how to
ensure a great time for my family as well
as me. (The meeting itself was pretty good,
too.) One afternoon, all attendees went
whitewater rafting on the Colorado River
and we enjoyed dumping buckets of water
on nearby members’ rafts.
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Cordie Miller became our executive director
after the 2000 Annual Meeting in Cancun,
Mexico, and opened the first Vitreous Society
office in Chico, California. She helped the
Vitreous Society to evolve into the American
Society of Retina Specialists by moving
many Society activities online and managing
an organization that became larger and
more complex.
By 2002, the scope of ASRS had increased
to include The Vitreous Society Times (now
Retina Times) published 4 times a year, in
addition to a much larger annual meeting
and ancillary conferences such as the practice
management and masters meetings.
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David Williams, president from 2008 to 2010,
recognized that the ASRS infrastructure
was limiting the Society and needed to
change if we wished to implement many of
our members’ great ideas. He assembled a
committee of leaders and future leaders early
in his presidency. Their mission: to develop
a strategic plan to take advantage of our
increasing size and influence.
‘Today, I am assuming
the presidency of
an organization
with substantially
improved capacity
for managing change.’
A multiyear plan was formulated to move
ASRS forward. This required a major
improvement in the capabilities of ASRS that
was made possible when Jill Blim was hired as
our executive vice president in 2010.
The ASRS headquarters moved to Chicago
and the organization quickly outgrew its office
space. Suber Huang implemented many new
initiatives during his presidency, including
integrating the Foundation with ASRS and
overseeing development of an enhanced
ASRS website, new educational initiatives,
redesigned ASRS/Foundation logos, and the
Retina Image Bank.
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FROM THE PRESIDENT >>
Today, I am assuming the presidency of an
organization with substantially improved
capacity for managing change. I visited the
new, larger ASRS office this summer and can
assure you that Jill has assembled a talented
staff to improve the Society’s ability to expand
existing programs and initiate new ones.
ASRS has grown from 1 full-time employee
in the summer of 2010 to 7 today. Chicago
is a great place to find experienced people
to staff medical organizations, as many have
headquarters in this area.
The fiscal conservatives among you will
question how we can afford such growth.
ASRS used to subcontract many services to
external vendors, but now most of those
functions have been moved in-house. The
new ASRS employees also help with many
other important activities throughout the
year, further increasing the Society’s ability
to work for you.
outstanding Executive Committee consisting
of Tarek Hassan, Mark Humayun, John
Pollack, Tim Murray, and Carl Awh.
Suber Huang has completed his term as
president, but he is not leaving us. He has
agreed to serve as president of the Foundation
of the ASRS and will be expanding the role
of the Foundation in physician and patient
education as well as in philanthropic work.
Educating our members will require more
than just gathering at an annual meeting.
We plan to produce more online educational
content and will promptly apprise you of
the latest developments in the treatment of
retinal diseases. We’ve had great meetings in
the past and will organize even better ones in
the future.
The changing needs of our members will
require ASRS to take a more active role in
protecting retina specialists and patients in
a rapidly changing health care environment.
Our new Retinal Advocacy and Federal Affairs
Committee (RAFA) will increase our efforts
in the socioeconomic arena with federal and
state government, as well as with insurers
who try to regulate the practice of medicine
Staff support is especially important with the
Society’s increasing reliance on work
by committees, as we are fortunate to have
many talented members who have offered
their skill and time. I will be working with an
through reimbursements. I wish to safeguard
the power of patients to make medical
decisions based on the best advice from
their physicians.
The vitreoretinal specialty was virtually
unknown by the Centers for Medicare &
Medicaid Services and private insurers in
the past; however, the advent of expensive
pharmaceuticals has increased their desire to
understand the growing costs of retina care
and ultimately to manage them. We are also
working more closely with our members
around the world with a new International
Affairs Committee to understand how
ASRS can help them and how international
members can enhance our Society.
I certainly don’t know what ASRS will look
like in 10 years for its 40th anniversary, but I
will work diligently to help move it forward.
Please email me at [email protected] if you
have ideas that will help me to serve you better
as your president.
Financial Disclosures
:h$J^ecfied – GENENTECH: Investigator, Grants;
REGENERON PHARMACEUTICALS, INC: Investigator,
Grants; PFIZER, INC: Investigator, Grants
FOUNDATION UPDATE >>
Foundation Seeks Volunteers
in 4 Key Areas
As I write my first column as President of the
Foundation of the American Society of Retina
Specialists (FASRS), I am reminded of the
many positive changes the Foundation has
recently undergone. We have a new name and
a new branding that exemplify our synergy
with the ASRS. We have a new mission as
the official fundraising arm of the ASRS—to
support the Society in improving the quality
of life for all people with retinal diseases.
Our new governance structure overlaps with
the ASRS board and will assist the Foundation
in achieving its mission to secure funds to
support the ASRS’s high-priority initiatives.
The Foundation’s strategic plan clearly defines
its overall strategy and goals, which include
attracting new donors in 4 key areas: corporate,
member, patient, and Foundation. Our next step
is to build our leadership team to assist us in
achieving these goals. We are now actively recruiting members for the following committees:
8 | retina times |
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Suber S. Huang, MD, MBA
President, Foundation of the
American Society of Retina Specialists
sThe Corporate Fundraising Committee
will increase the number and type of corporate
donors as well as the level of contributions.
sThe Member Fundraising Committee
will establish a culture of philanthropy and
will increase the number of contributions
and the level of annual contributions.
sThe Patient Fundraising Committee
will develop a grateful-patient strategy
that relies on member involvement and
commitment.
sThe Foundation Fundraising Committee
will maximize Foundation opportunities
that mesh with ASRS programs.
Each committee is integral to the Foundation’s
success; together, they will work to grow
FASRS into the charitable arm of the ASRS.
The committees will educate the public on our
specialty, identify new revenue streams, and
build a solid infrastructure for ASRS projects.
Our Foundation is at an advantage because
we are focused on things that matter most to
donors. We are guided by a well-defined list
of projects, so contributors will know exactly
where their support dollars are going.
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The Foundation is looking for leadership
volunteers at all levels—no donation of time
is too small. If you would like to become
involved, please contact ASRS Foundation
Director Robyn Lira at 312-477-8866 or
[email protected] for more information.
Thank you for contributing to the Foundation’s
continued success.
Financial Disclosures
:h$>kWd] – SEQUENOM: Advisory Board, Honoraria;
SECOND SIGHT: Consultant, Honoraria; NOTAL VISION:
Consultant, Honoraria; BAUSCH+LOMB: Advisory Board,
Honoraria; ALCON: Speaker, Honoraria
FROM THE EDITOR’S DESK >>
J. Michael Jumper, MD
Editor-in-Chief
A Special Thanks to Our Active-Duty
Military Retina Specialists
All ASRS members know that retina specialists almost always become
involved with any case of globe trauma. What you may not know is that
ocular trauma accounts for approximately 13% of all injuries due to
modern armed conflict.
Considering that there have been nearly 50,000 injuries to American
soldiers engaged in Operation Enduring Freedom in Afghanistan
(2001-present) and Operation Iraqi Freedom (2003-2008), military
retina specialists have been very busy. The stories of 3 recently deployed
military retina specialists are featured on page 33. Their experiences
have been remarkable.
I joined the United States Air Force as a retina specialist in 1998, during
the same month that the US Embassies in Kenya and Tanzania were
attacked, leaving 258 dead and 5000 injured. A small fraction of those
with eye injuries were evacuated to US military hospitals. The mean
time to initial evaluation by an ophthalmologist was 4 days; the time
to initial globe rupture repair was 5 days; and the time to intraocular
foreign body (IOFB) removal was 9 days.
When on duty at their military medical center in the United States,
these vitreoretinal surgeons are incredibly busy with the most complex
trauma repairs on soldiers evacuated from the battlefield. There have
been many important publications over the past decade describing
injury patterns, surgical techniques, and outcomes of the many eye
injuries during this time. One such publication (co-authored by our
‘Our current military ophthalmologists
have risen to the challenges brought
on by the horrible epidemic of ocular
trauma resulting from the wars in
Iraq and Afghanistan.’
I, along with others, worked to decrease the time to definitive ophthalmic surgery by developing a rapidly deployable, self-contained surgical
unit. A year later, as a part of a humanitarian mission and joint military
exercise, I was performing vitreous surgery in a small village in Cameroon using equipment we checked onto a commercial airliner. This was
pre-9/11. Imagine checking an argon laser as your carry-on today!
‘[O]cular trauma accounts for
approximately 13% of all injuries due
to modern armed conflict.’
Of course, September 11, 2001 changed everything. The residents I
worked with in San Antonio, Texas at Wilford Hall Medical Center and
Brooke Army Medical Center became part of the first wave of ophthalmologists to be deployed to Iraq and Afghanistan. Now, 11 years
later, many advances have allowed injured soldiers to receive definitive
care sooner. In the case of the conflicts in Iraq and Afghanistan,
ophthalmologists have become an important part of the trauma teams
at the hospitals in theater.
The 3 retina specialists featured in the story on page 33—Maj Darrell
Baskin, MD, USAF; Capt Steve O’Connell, MD, USN; and LCDR Bryan
Propes, MD, USN—represent the latest of the vitreoretinal surgeons
who have served in the United States military since the “war on terror”
began in 2001. When overseas, these retina specialists are called on to
be comprehensive ophthalmologists in the greatest sense of the word.
For the local civilians, allied soldiers, and adversaries with an eye
problem, if they can’t do it, it won’t get done.
Maj Mike Jumper, MD, USAF, performing vitrectomy and
lensectomy in Garoua, Cameroon in 1998.
Retina in the Military Section Editor, Marcus Colyer) relates the experience at Walter Reed Army Medical Center during the height of the
conflict in Iraq from 2003-2006. They treated 523 eyes in 387 soldiers,
198 of which were open-globe injuries.
Our current military ophthalmologists have risen to the challenges
brought on by the horrible epidemic of ocular trauma resulting
from the wars in Iraq and Afghanistan. I am proud to have worked
with some of them. I think I can speak for the ASRS when I offer my
gratitude and appreciation for their efforts.
Financial Disclosures
:h$@kcf[h – COVALENT MEDICAL, INC: Equity Owner, Stock; Dutch Ophthalmics USA:
Speaker, Honoraria.
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FILM FESTIVAL >>
Brett T. Foxman MD
Chair, ASRS Film Festival
Film Festival Honors Winners
from 5 Countries
The 14th Annual ASRS Film Festival featured 37 outstanding films from Society members around
the globe, with topics ranging from vitrectomy to vitreous humor. If you missed the 30th ASRS
Annual Meeting in Las Vegas, you can view the films at http://meeting.asrs.org/Film-Festival/Films.
We sincerely thank the 45 judges who spent many
hours watching, reviewing, and grading the films
for the 9 Rhett Buckler Awards presented at the
Annual Meeting’s gala dinner. After the meeting,
we also presented the new Doctors’ Choice Award
based on voting from ASRS members.
Use of Perfluoron for Large-Volume
Vitreous Biopsy—Or, How We Learned
From Aesop’s Crow
Pauline T. Merrill, MD (Oak Park, Illinois);
Renaud Duval, MD, FRCSC (Chicago, Illinois);
Kirk H. Packo, MD, FACS (Chicago, Illinois)
If you would like to be a judge for next year’s
Film Festival, please email chayal.patel@asrs.
org. It’s not too early to start thinking of ideas
for the 2013 Annual Film Festival in Toronto.
Surgical Management of Myopic Traction
Maculopathy (Myopic Foveoschisis)
Sung Pyo Park, MD, PhD; Gregory Chang,
BA; Gonzalo A. Sepulveda Moreno, MD;
and Stanley Chang, MD (all of New York,
New York)
(&'(H^[jj8kYab[h7mWhZM_dd[hi
A New Technique for Safe, Atraumatic
Removal of Intraocular Foreign Bodies
Jeffrey L. Olson, MD; and Douglas L.
MacKenzie, MD (both of Aurora, Colorado)
BEST OF SHOW
Post-Traumatic Aniridia: Artificial Iris
Combined With IOL Implantation
Cesare Forlini, MD (Ravenna, Italy)
“Vitreoschisis”—Live!
Malhar Soni, DO, MS, DNB, FRCS
(London, England)
Scleral-fixated IOL Using a 25-Gauge Needle
Scleral Tunnel
Phoebe Lin, MD, PhD; and Sharon Fekrat, MD,
FACS (both of Durham, North Carolina)
The True Nature of OCTs
Gilles Desroches, MD, FRCSC
(Ottawa, Canada)
Sutureless Scleral Fixation of a
Dislocated Three-Piece Intraocular Lens
Jonathan L. Prenner, MD (Lawrenceville, New
The winning films earned the coveted Rhett Buckler
Award, an impressive 8-pound, 24-carat-gold-plated
statuette custom-sculpted by RS Owens & Company,
manufacturer of the famous Oscar.
Jersey); Harold M. Wheatley, MD (Edison,
New Jersey); and Leonard Feiner, MD, PhD
(Teaneck, New Jersey)
OutVITing the Humor: The Art of
PVD Induction
Manish Nagpal, MD, FRCS; Navneet Mehrotra,
DNB; and Siddharth Bhardwaj, MS (all of
Ahmedabad, Gujarat, India)
DOCTORS’ CHOICE AWARD
Endoscopic Vitrectomy in Pediatric Vitreoretinal Diseases: Improving Visualization
and Outcomes
S. Chien Wong, MBBS, FRCSEd(ophth),
MRCOphth (Los Angeles, California)
Financial Disclosures:
Film Festival winners Gilles Desroches, MD, FRCSC; Jeffrey L. Olson, MD; Pauline T. Merrill, MD; Renaud Duval, MD, FRCSC;
Manish Nagpal, MD, FRCS; Cesare Forlini, MD; Sung Pyo Park, MD, PhD; and Film Festival Chair Brett T. Foxman, MD.
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Dr. Foxman – GENENTECH: Investigator, Other Financial
Benefit; REGENERON PHARMACEUTICALS, INC: Investigator, Other Financial Benefit.
ASRS 30TH Anniversary
HIGHLIGHTS >>
@e^dJ$J^ecfied"C:
ASRS Scientific Program Chair
IjWYoA_\\
ASRS Director of Education
ASRS Celebrates 30th
Anniversary at Annual Meeting
On August 25-29, nearly 1000 retina specialists from around the world
gathered at the Aria Resort in Las Vegas for the 2012 Annual Scientific
Meeting. The 30th anniversary conference presented 149 scientific
papers, 155 posters, 23 instructional courses, 37 films, and a full array
of social events.
Incoming ASRS President John Thompson, MD, and his wife, Mary Ann;
Pyron Award winner Daniel Martin, MD, and his wife, Pam; outgoing President
Suber Huang, MD, MBA; Gloria Sternberg; Emily Chew, MD; and keynote speaker
Paul Sternberg, MD.
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Retina Case Conference
The ASRS 30th Annual Meeting opened on
Saturday afternoon with uveitis, glaucoma,
and neuro-ophthalmology subspecialty
reviews. Narsing Rao, MD, noted infectious
uveitis entities not to miss: treponema
pallidum (syphilis), tuberculosis,
toxoplasmosis, and herpetic infection, as
well as masquerade syndromes such as
primary intraocular lymphoma.
Rohit Varma, MD, MPH, pointed out that a
diagnosis of chronic open-angle glaucoma
is determined by optic nerve damage and
glaucomatous visual fields, not by IOP level.
Anthony Arnold, MD, gave an entertaining
review of specific neuro-ophthalmic
conditions, including optic neuritis,
nonarteritic anterior ischemic optic
neuropathy, arteritic AION, “Viagra blindness,” and optic nerve sheath meningioma.
Drs. Carl Awh, William Mieler, and Richard
Spaide moderated the Retina Case
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ASRS President John Thompson, MD, (right) congratulates Harry Flynn Jr, MD,
co-author of the winning AMD poster, “Management of Submacular Hemorrhage
Secondary to Neovascular Age-Related Macular Degeneration With Anti-Vascular
Endothelial Growth Factor Monotherapy.” The Foundation grant was awarded
to poster author Gary Shienbaum, MD; other co-authors included Carlos A de A
Garcia-Filho, MD; and Philip J. Rosenfeld, MD, PhD.
Conference, featuring 26 clinical presentations. Saturday night concluded with a
welcome reception at the Aria Resort.
Suber Huang, MD, MBA, presented the
Founders Award to David Parke II, MD, for
excellence in vitreoretinal medicine.
IkdZWo0Iocfei_W"WmWhZiY[h[cedo
Sunday’s activities started at 6:00 AM with
the Foundation’s 6th Annual 5K Indoor/
Outdoor Run/Walk for Retina. Nearly 60
runners and walkers participated in the
fundraising event.
John Kitchens, MD, head of the Young
Physicians Section, presented the Crystal
Apple Award to Dean Eliott, MD. Outgoing
Foundation President Mark Hammer, MD,
presented the Foundation Report, and
Retina Image Bank Curator Suber Huang,
MD, MBA, presented the Retina Image
Bank Report. The Foundation grant was
awarded to Gary Shienbaum, MD, for the
best AMD poster.
The scientific symposia began Sunday
morning after opening remarks by
Program Chair and incoming President
John Thompson, MD. In the AMD I
Symposium, presenters Zohar Yehoshua,
MD, MHA, and Philip Rosenfeld, MD, PhD,
noted that COMPLETE study results show
systemic complement inhibition with
eculizumab anti-C5 antibody does not slow
the progression of dry AMD nor reduce
drusen volume.
At Sunday’s awards ceremony, John
Thompson, MD, presented Daniel Martin,
MD, the Pyron Award for his outstanding
contributions to knowledge about
vitreoretinal disease. Outgoing President
The morning concluded with a presentation of the 2012 ASRS Preferences and
Trends (PAT) Survey by Survey Editor
J. Michael Jumper, MD. Results showed
that 67% of US and Canadian respondents
follow a treat-and-extend protocol in
managing wet AMD, whereas International
members see patients monthly and treat
as needed. Complete PAT Survey results—
as well as multi-year trending data—are
available at www.asrs.org/asrs-community/
pat-survey.
Nearly 60 early risers participated in the Foundation’s 6th Annual Indoor/Outdoor Run/Walk for Retina, held at the Aria Resort and Crystals at CityCenter Las Vegas.
RETINAWS panelists. Front row: Alay Banker, MD; Ehab El-Rayes, MD, PhD;
moderator Kourous Rezaei, MD; José Garcia Arumi, MD. Back row: Mathew
MacCumber, MD, PhD; George Williams, MD; Homayoun Tabandeh, MD; ASRS
Past-President Kirk Packo, MD.
Women in Retina Case Conference organizers Alice Lyon, MD; Jennifer Lim, MD;
and Pauline Merrill, MD.
Sunday afternoon began with the Macular
Surgery I Symposium. Presenter Emmanuel
Chang, MD, PhD, reported on his retrospective study of all patients who underwent
bilateral macular hole surgery between
1985 and 2011. He reported an incidence of
bilateral macular holes of 3.1%, with a 3:1
female-to-male ratio. The study concluded
that the outcomes of bilateral macular
holes are excellent with the indocyanine
green-assisted ILM peeling technique.
that telemedicine screening is effective
at identifying patients who need
further examinations.
Afternoon sessions also included the
Imaging Symposium, Retinal Vascular
Symposium, and the Women in Retina
(WinR) Case Conference.
The AMD II Symposium presented
rapid-fire papers on initial experiences
with aflibercept. Presenter Allen Ho, MD,
reported on the 96-week results of the
VIEW 1 and VIEW 2 studies; 2457 patients
were randomized to ranibizumab 0.5 mg
q4 weeks, aflibercept 0.5 mg q4 weeks,
aflibercept 2.0 mg q4 weeks, or aflibercept
2.0 mg q8 weeks. In the second year,
patients were treated PRN with a minimum
of quarterly aflibercept injections. There
was a similar treatment effect in all 4 treatment arms, with a faster fluid resolution in
the 2.0 mg aflibercept arms.
Monday: Scientific sessions, social events
Monday morning began with the Diabetic
Retinopathy I Symposium. Ingrid ZimmerGaller, MD, reported on a study in which
she and her colleagues imaged 1151 patients
with a remote non-mydriatic camera to test
the feasibility of a telemedicine screening
program. They found that 25% had diabetic
retinopathy and 41% had non-diabetic
retinopathy ocular findings, suggesting
Monday’s symposia also included Ocular
Oncology and Retinal Surgery I. The
evening concluded with social events
including the wine and cheese reception,
new member/International Delegate
reception, Young Physicians Section
dinner, and the Fellows-in-Training
Section dinner.
In the Socioeconomic Sessions, Wiley
Chambers, MD, who has worked for the
FDA for 25 years, gave an overview of the
FDA drug approval process. He noted that
the biggest reason that a pharmaceutical
product is not approved by the FDA is that
no one submitted an application.
Tuesday: Instructional courses, gala dinner
Tuesday morning began with symposia on
Trauma/Pharmacology, Inflammation, and
Infections. Harry Flynn Jr, MD, reported
that after studying the recent endophthalmitis outbreak following intravitreal
injections in South Florida, the CDC and
the Florida Health Department studies
confirmed Streptococcus mitis/oralis
contamination of the bevacizumab as the
most likely source of the outbreak.
At the AMD III Symposium, Tarek Hassan,
MD, presented the results of a patient
questionnaire showing that retina
surgeons and industry representatives
underestimate patients willingness’
|
Issue 46
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Volume 30, Number 4
|
Fall 2012
| retina times | 13
HIGHLIGHTS >>
At the third annual “Unplugged” Symposium, physicians and investigators discussed the real-world implications of clinical trial results. Panelists included (l-r): Peter
Kaiser, MD, Jeffrey Heier, MD, Jay Duker, MD, David Boyer, MD, and moderator Pravin Dugel, MD. In foreground: Panelist William Mieler, MD.
Allen Verne, MD, and Jerry Bovino, MD, 2 of the Society’s founders, offer a toast
to the ASRS’s 30th anniversary at the gala dinner.
Incoming President John Thompson, MD, enjoys the welcome reception with
ASRS co-founder Roy Levit, MD, and ASRS Board Member and Retina Times
Tea Leaves Section Editor Trexler Topping, MD.
to continue intravitreal injections indefinitely to maintain their vision.
š Challenge the Masters, moderated by
Calvin Mein, MD
The Retinal Surgery II Symposium featured
Timothy Murray, MD, MBA, describing how
MIVS 23-gauge pars plana vitrectomy
can effectively manage complex retinal
detachments in eyes having undergone
125-iodine brachytherapy for uveal
melanoma. Nearly half (48%) achieved
a visual outcome of 20/40 or better.
š Anterior Segment Surgery for the
Vitreoretinal Surgeon: Discussion and
Wetlab, led by Carl Awh, MD
š Vitreous Manipulation with
Ocriplasmin, by Michael Trese, MD
š Pneumatic Retinopexy: Pearls and
Pitfalls, by Emmanouil Mavrikakis, MD, PhD
Sophie Bakri, MD, organized the Special
Interest Group luncheons featuring casual
roundtable discussions on a variety of
conditions, treatments, and procedures.
š RETINAWS: When the Going Gets
Tough, the Tough Get Going:
Challenging Cases in Vitreoretinal
Surgery, by Kourous Rezaei, MD
Tuesday afternoon featured 23 instructional courses, a few of which included:
š High-Stakes Vitrectomy: Vitreoretinal
Surgery in Inflamed Eyes, by
Thomas Albini, MD
š The Third Annual ASRS Research and
Development Committee Symposium:
Clinical Trials “Unplugged”—Real,
Practical Questions and Answers,
led by Pravin Dugel, MD (see page 26)
Tuesday evening concluded with the 30th
anniversary gala dinner and Umbo Lounge,
featuring opening remarks by ASRS founders
Jerry Bovino, MD, and Allen Verne, MD. Brett
Foxman presented this year’s Film Festival
winners (see page 10), and the celebration
š Newer Advances in Vitreo-Retina
Surgeries: Tools and Techniques, by
S. Natarajan, MD
14 | retina times |
Fall 2012
|
Volume 30, Number 4
|
Issue 46
|
continued at the Aria’s Haze Nightclub
with performances by dancers, aerialists,
and magicians.
Wednesday: Symposia, wrap-up
In the Macular Surgery II/Anterior Segment
Surgery Symposium, Maziar Lalezary, MD,
reported baseline findings on the
Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study. PROVE is a
5-year longitudinal analysis of eyes undergoing unilateral pars plana vitrectomy (PPV) to
evaluate long-term outcomes compared with
the non-vitrectomized fellow eye. Patients
undergoing routine PPV for epiretinal
membrane, macular hole, or vitreous opacity
may have unidentified risks for glaucoma at
baseline, specifically narrow angles, found in
13%, and abnormal visual fields, found in 18%.
The AMD IV Symposium featured Christine
Gonzales, MD, reporting on a Phase I study
targeting tissue factor with a single dose of
intravitreal hI-con1 for wet AMD. In the study,
just one injection demonstrated safety and
biologic activity—regression of choroidal
neovascularization, reduced OCT thickness,
The wet lab provided hands-on instruction.
Cesare Forlini, MD, of Ravenna, Italy, winner of the ASRS Film Festival’s Best of
Show Award, enjoys the festivities with Carl Awh, MD; Dr. Forlini’s daughter-inlaw Caterina Benatti, MD; his son Matteo Forlini, MD; and Philip Ferrone, MD.
Dean Eliott, MD, winner of the Crystal Apple Award, and John Kitchens, MD,
ASRS Board member and head of the Young Physicians Section.
Reginald Sanders, MD; Adrienne Scott, MD; and William Rich III, MD attend the
wine and cheese reception in the exhibit hall.
and improved vision. HI-con1 is a novel
agent that binds tissue factor, leading to
natural killer cell destruction of abnormal
vascular endothelial cells.
reporting that initial experience shows oral
rifampin was found to have an apparent
therapeutic effect on patients with central
serous chorioretinopathy.
In the Pediatric Retina Symposium,
Audina Berrocal, MD, FACS, demonstrated
the importance of digital fluorescein
angiography-guided laser treatment for
various pediatric retinal diseases including
Coats and FEVR. She noted that wide-field
angiography is especially good at detecting areas of capillary dropout.
Following the Wednesday morning symposia, John Thompson, MD, concluded the
meeting just before noon.
The Diabetic Retinopathy II Symposium
featured Elliott Sohn, MD, presenting the
outcomes of pars plana vitrectomy for
tractional retinal detachment secondary
to proliferative diabetic retinopathy. The
10-year data on 240 eyes of 203 patients
showed that 12% of patients had a
combined traction/rhegmatogenous retinal
detachment; 6.3% required reoperation,
and 1.3% required enucleation.
The Instrumentation/Pharmacology
Symposium featured Zac Ravage, MD,
MD; Jeremiah Brown Jr, MD, MS; Mina Chung,
MD; Pouya N. Dayani, MD; Nicholas E. Engelbrecht, MD; Mitchell J. Goff, MD; Judy E. Kim,
MD; Tamer H. Mahmoud, MD, PhD; Andrew A.
Moshfeghi, MD, MBA; Prithvi Mruthyunjaya,
MD; Joel Pearlman, MD, PhD; Polly A. Quiram,
MD, PhD; Chirag P. Shah, MD, MPH; Michael A.
Singer, MD; Asheesh Tewari, MD; and Robert
W. Wong, MD.
7jj[dZ[[ihWj[j^[c[[j_d]^_]^bo
Evaluations by more than 400
attendees showed:
FbWdjeWjj[dZ(&')7ddkWbC[[j_d]
in Toronto
Mark your calendar for the 31st Annual
Meeting, August 24-28, 2013, at the Sheraton
Centre Toronto. The ASRS Annual Scientific
Meeting has earned its place as the premiere
educational event for retina specialists.
Beginning in January 2013, online registration and abstract submission will be available
at www.asrs.org/annual-meeting. Questions?
Contact ASRS Director of Education
Stacy Kiff at [email protected].
š //mekbZh[Yecc[dZj^[c[[j_d]
to their colleagues.
š /-iW_Zj^[c[[j_d]^[bf[Z_dYh[Wi[
confidence in their ability to do their job.
š /'m_bbcWa[Y^Wd][i_dfhWYj_Y[WiW
result of the knowledge or skills gained
through the meeting.
If[Y_Wbj^Wdaijeekhf^oi_Y_Wdh[fehj[hi
Retina Times thanks the physician reporting
team who gathered the news for the daily
email updates at the Las Vegas meeting:
Thomas M. Aaberg Jr, MD; Kevin J. Blinder,
Financial Disclosures:
Dr. Thompson – GENENTECH: Investigator, Grants; REGENERON PHARMACEUTICALS, INC: Investigator, Grants; PFIZER
INC: Investigator, Grants.
Ms. Kiff – None.
|
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|
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|
Fall 2012
| retina times | 15
CLINICAL TRIALS: FUTURE PATHWAYS >>
Desmond E.
Thompson, PhD
DES Enterprises
New Hope, Pennsylvania
Chirag P. Shah, MD, MPH
Jeffrey S. Heier, MD
Section Co-Editor
Section Editor
Understanding Time-to-Event Analysis
s#ANMULTIPLECAUSESOFTHEEVENTBETAKEN
into account?
s(OWDOPARTICULARCIRCUMSTANCESOR
characteristics increase or decrease the odds
of being event-free?
Time-to-event analysis is often used in
medical, epidemiological, and sales research.
Survival analysis—or more generally, timeto-event analysis—is of interest when the data
represent the time to a defined event.
While well-established in oncology and
cardiology, time-to-event analysis has not been
widely applied to ophthalmology research,
possibly because the data are usually collected
intermittently rather than continuously, and
because of the awkwardness of interpreting
treatment effect in survival terms. However,
this method is an interesting approach for
analyzing time to elevated IOP, absence of fluid,
gain of 15 or more letters, or loss of 5 letters.
Is it correct to infer that the treatments
were equally effective without knowing
when the events occurred? Figure 1 shows that
INTREATMENTGROUP!THEEVENTSOCCURRED
at 30 days (2 patients), 60 days (1 patient),
and 90 days (2 patients). One patient discontinued the study at day 50. In treatment
group B, the events occurred at 300 days
(1 patient), 330 days (2 patients), and at
360 days (2 patients). One patient discontinued
the study on day 60. The total time at risk
INGROUP!XXXX
360x4 = 1790 days at risk.
Time-to-event analysis attempts to answer
questions such as:
s7HATFRACTIONOFAPOPULATIONWILLBEEVENT
free past a certain time?
s!TWHATRATEWILLTHOSEWHOAREEVENTFREE
at a given time experience the event in
the future?
The event rate equals the total number of
events divided by the total time at risk, or
5/1790 (0.0028 events per day or 2.8 events
per 1000 days at risk). The total time at risk
INTREATMENTGROUP"XX
XXXDAYSATRISK
The event rate is 5/3180 (0.0016 events per
day or 1.6 events per 1000 days at risk). Thus,
the ratio of the rates is 2.8/1.6 = 1.75. The
simple interpretation would be that patients
INTREATMENTGROUP!WERETIMESMORE
likely to gain 10 or more letters than patients
in treatment group B.
Kaplan-Meier curves
šM_bbWbmWoijh[dZkfmWhZÆWij^[
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_dY_Z[dY[ik]][iji
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:_WX[j[i9edjhebWdZ9ecfb_YWj_edi
Jh_Wb:99J"m^[h[j^[h[mWiWd
[Whbomehi[d_d]e\h[j_defWj^o_dj^[
]hekfjh[Wj[Zm_j^_dj[di_l[j^[hWfo
šI^emZWjWYedi_ij[djm_j^WYedijWdj
h[bWj_l[h_iaeh^WpWhZ_dceij
YWi[iÆjhWdibWj_d]_djeWkd_\ehcbo
_dYh[Wi_d]i[fWhWj_edX[jm[[dj^[
AWfbWd#C[_[hYkhl[i
Fall 2012
|
Volume 30, Number 4
|
Issue 46
The following hypothetical example illustrates
some key concepts in time-to-event analysis.
)NITPATIENTSWITHWET!-$ARERANDOMLY
ASSIGNEDTOTREATMENTGROUPS!PATIENTS
and B (10 patients) and will be followed
for 360 days. The outcome of interest is the
incidence of gaining 10 or more letters on the
%4$23SCALEDURINGTHESTUDY
!SSUMETHATTHETREATMENTGROUPSARE
balanced at baseline as to outcome-influencing
characteristics. In each treatment group,
there were 5 events. Thus, the proportion
experiencing the event is 50% in each group
and the relative risk = 50%/50% or 1.
Time-to-event analysis can address the
clinically relevant question of who improves
sooner (eg, gain of 15 or more letters) or
who gets worse earlier (eg, loss of 5 or
more letters). Such analysis uses data from
all time-points to define the likelihood of
getting better or worsening throughout the
entire assessment period. These data can then
be used to quantify and test the difference
between 2 or more therapies.
16 | retina times |
Interpreting rates vs proportions
)TCANBESEENTHATALLTHEEVENTSINGROUP!
occurred earlier in the study than those in
|
group B. When the data are viewed
with regard to time-to-event, it is clear that
there is a substantial treatment advantage not
revealed by the initial analysis based
on proportions.
Perhaps the simplest way to evaluate time-toevent analysis is to examine the ratio of the
rates. This is often called the hazard ratio or
the relative risk.!RATIOOFMEANSTHEREISNO
DIFFERENCEBETWEENTHETREATMENTGROUPS!
RATIOOFGREATERTHANOFTREATMENT!TREATment B (and all members of the confidence
interval are >1) supports the hypothesis that
THERATEINGROUP!ISGREATERTHANTHATIN
GROUP"!RATIOSUPPORTSTHEHYPOTHESIS
THATTHERATEINGROUP!ISLESSTHANTHERATEIN
group B. If the confidence interval of the ratio
contains 1, one cannot rule out equality of the
rates in the 2 treatment groups.
Understanding KaplanMeier curves
The usual method of analyzing binary data
is to compute the simple proportion of
those with the event of interest at the end
of the study and compare these proportions
BETWEENTHEORMORETREATMENTGROUPS!S
noted earlier, this method ignores the time
at which the events occur and can lead to
erroneous conclusions.
There is a method that uses proportions,
yet takes into account the time of event and
the fact that not all patients can complete
THESTUDY!TEACHVISITDURINGACLINICALTRIAL
patients are assessed for the presence or
absence of the event. For example, did the
patient gain 10 or more letters? The cumulative incidence of the event is computed using
a special method called the product-limit
formula. The resulting curves provide Kaplan-EIERESTIMATES4HESTEPSINTHECURVESOCCUR
only when there is an event at the visit.
+APLAN-EIERMETHODOLOGYATTEMPTSTOESTImate the cumulative incidence at each point
during the follow-up period. These curves are
a simple means to visualize the cumulative
incidence of an event, enabling one to see if
there is evidence of an early effect and—more
important—to estimate the difference in the
effect between groups.
Kaplan-Meier curves are presented in 2 ways:
1. A downward-trending plot displays the
proportion of patients free of the event (see
Figure 2A on page 18). This proportion will,
of course, decline over time.
2. An upward-trending plot shows the cumulative proportion of patients experiencing the
event by time (see Figure 2B on page 18).
‘The Kaplan-Meier
method computes the
expected proportion
having an event at
the end of the study.
This is not exactly the
same as the observed
proportion …’
other in a statistically meaningful manner.
The method most often used for this purpose
is the log-rank test, based on comparing the
observed data with the expected data.
Three steps to evaluate time-toevent analysis
If the log-rank test identifies a significant
difference between the curves, methods are
needed to quantify it. The Cox proportional
hazard model is widely used to calculate the
relative hazard (ratio of rates). The difference
between the curves can be reported with a
statistic called the hazard ratio, with confidence intervals to show its precision and a test
of significance to determine the likelihood
that any difference is due to chance.
2. A test of whether the curves are
different
š J^[be]#hWdaj[ijfheXWXboj^[
most widely used
š J[ijcWa[il[ho\[mWiikcfj_edi
about the data
1. A figure
š KikWbboAWfbWd#C[_[hYkhl[i
š I[fWhWj[fbej\eh[WY^]hekf
3. The means to quantify the risk reduction
š 9enfhefehj_edWb^WpWhZceZ[b
normally used
š Jhis procedure requires
some assumptions
M^o_iY[dieh_d]ki[Z5
In principle, both curves contain the same
information, but the visual perceptions of
treatment group comparisons can be quite
different.1 There is no statistical advantage of
one representation over the other—it can be
viewed as the cup being half-full or half-empty.
An essential feature of the Kaplan-Meier
methodology is that the 2 curves are generated
independent of each other. Means are needed
to establish whether the time-to-event data
represented in these curves differ from each
Patients not followed long enough for the
event to occur have their event times censored
at the last follow-up. One reason for censoring
is that patients cannot be followed forever.
At some point, the study must end and not
all people will have experienced the event.
Another common cause is that people are lost
to follow-up during a study—whether due to
death, relocation, an adverse drug reaction, or
simply a wish to discontinue participation.
can take that into account. In evaluating the
difference between curves, it is assumed that
the censoring pattern is random and the same
in both treatment groups.
Each step in a Kaplan-Meier curve provides
evidence of the time the patient experienced
the event. There are no steps to recognize
the time of a censored observation. In some
reports, the times of the censored observations
are indicated on the Kaplan-Meier curves. In
others, the number at risk and the cumulative
number of events are provided at the bottom
of the graph.
These are examples of random censoring,
when follow-up ends for reasons not under
the investigator’s control. However, in
time-to-event analysis, censored observations
contribute to the total number at risk up to
the time that they ceased to be followed. One
advantage: the length of time an individual
is followed does not have to be equal for
everyone. All observations can have different
amounts of follow-up time, and the analysis
This information enables the reader to
determine whether the number at risk toward
the end of the follow-up period is large
enough to make meaningful comparisons
between the treatment groups. In essence,
it can question whether the extreme right
of the Kaplan-Meier curves should have
influence in the overall conclusion. The
concept of time at risk means that all available
follow-up is put to good use; this reduces
the bias that can creep into analyses if only
data at the end of a study are used to assess
the treatment effect.
>emje9ecfkj[J_c[WjH_iaWdZj^[HWj[e\Wd;l[dj
Group
A
36
72
108
144
180
216
252
288
324
The summary table that provides the rate of
events and the relative hazard (or risk) has
not been frequently used in ophthalmology.
Rates when expressed as the number of events
per unit of time at risk can be very flexible.
In epidemiology, the rate is expressed as
events per 100,000 patient years at risk. In
clinical trials, smaller numbers are used. as the
number of events is low. It is strongly recommended that summary statistics be included
in a table or on the curve. This should include
the rates, the relative risk, and the 95%
confidence interval.
360
Time in Days
Group
B
FIGURE 1
Rates can be large if the number of events
is large, or if the time at risk is small—
Redfern JS, Thompson D. The risks and hazards of interpreting and reporting health study measures: a simple, practical
overview. AMWA Journal. 2011;26(3):111-116.
|
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Fall 2012
| retina times | 17
CLINICAL TRIALS: FUTURE PATHWAYS >>
particularly when assessing early effects of
a treatment in one group compared with
late effects in the control group. The number
of events may be the same in both groups,
but the time to event—and hence the time
at risk—is the key that differentiates the
treatment groups.
Kaplan Meier Survival Estimate, by Era,
Va = 20/200 or Worse (n = 58)
Proportion Free of Event
1.00
In addition to describing the treatment
difference for selected baseline characteristics,
time-to-event analysis can be very useful in
visualizing the role of treatment factors.
Interpretation of Kaplan-Meier curves comes
with experience. An important point of
interest is the time point at which the curves
appear to begin to separate. There is no
statistical test to determine that point; it is
mainly a descriptive measure.
FIGURE 2A
Cumulative Incidence of a Sustained Change
in Retinopathy in Patients With IDDM Receiving
Intensive or Conventional Therapy
Percentage of Patients
60
Dr. Shah – ALCON: Grant Support; ALIMERA SCIENCES:
Grant Support; ALLERGAN, INC: Grant Support;
GENENTECH: Grant Support; GENZYME: Grant Support;
GLAXOSMITHKLINE: Grant Support; MOLECULAR PARTNERS:
Grant Support; NEOVISTA: Grant Support; PALOMA
PHARMACEUTICALS, INC: Grant Support; REGENERON
PHARMACEUTICALS, INC: Grant Support.
50
Conventional
40
30
P<0.001
20
Intensive
10
0
Dr. Heier – ACUCELA INC: Consultant, Consulting
Fees; ALLERGAN, INC: Consultant, Consulting Fees;
BAUSCH+LOMB: Consultant, Consulting Fees; BAYER
HEALTHCARE: Consultant, Consulting Fees; ENDO OPTIKS
INC: Consultant, Consulting Fees; FORSIGHT LABS, LLC:
Consultant, Consulting Fees; FOVEA PHARMACEUTICALS
SA: Consultant, Consulting Fees; GENENTECH: Consultant,
Consulting Fees; GENZYME: Consultant, Consulting Fees;
HEIDELBERG ENGINEERING: Consultant, Consulting
Fees ; KATO PHARMACEUTICALS: Consultant, Consulting
Fees; NEOVISTA, INC: Consultant, Consulting Fees;
NOTAL VISION: Consultant, Consulting Fees; ORAYA
THERAPEUTICS, INC: Consultant, Consulting Fees; PALOMA
PHARMACEUTICALS, INC: Consultant, Consulting Fees;
QLT OPHTHALMICS: Consultant, Consulting Fees; QUARK
PHARMACEUTICALS, INC: Consultant, Consulting Fees;
REGENERON PHARMACEUTICALS, INC: Consultant,
Consulting Fees; SEQUENOM: Consultant, Consulting Fees.
Dr. Thompson – REGENERON PHARMACEUTICALS, INC:
Consultant, Other Financial Benefit.
Issue 46
6
Tibbetts MD, Shah CP, Young LH, Duker JS, Maguire JI, Morley MG. Treatment of acute retinal necrosis. Ophthalmol.
2010;117(4):818-824.
Financial Disclosures
|
4
Acyclovir-only
Newer antivirals
1.Pocock SJ, Clayton TC, Altman DG. Survival plots of
time-to-event outcomes in clinical trials: goodpractice and
pitfalls. Lancet. 2002;359(9318):1686-1689.
Volume 30, Number 4
2
Analysis time (years)
Reference
|
0.25
0
The use of time-to-event analysis in
ophthalmology is increasing and represents a
modern way of looking at data. Such analysis
provides valuable information on the patient
experience during the follow-up period.
Ignoring the temporal information, which is
not provided when simple proportions are
used, can lead to less-than-optimal use of the
information collected during the study. This
loss of information can potentially lead to
erroneous conclusions.
Fall 2012
0.50
0.00
One cannot determine from Kaplan-Meier
analysis the point at which the drug begins to
be effective; Kaplan-Meier analyses were not
intended for that purpose. It is not appropriate
to ask at what point the differences between
the curves become significant, although it is
sometimes useful to speculate on the shape
of the curve.
18 | retina times |
0.75
|
0
1
2
3
4
5
6
7
8
9
Year of Study
Number
at Risk
Conventional
348
324
128
79
Intensive
354
335
136
93
FIGURE 2B
The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the
development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med.
1993;(329)14:977-986.
INTERNATIONAL CORNER >>
Kourous A. Rezaei, MD
Chair, International Affairs Committee
Bringing the International
Retina Community Together
ASRS has members in 55 nations. Beginning with this issue of Retina Times, the International
Corner will profile retina societies from countries around the world. We encourage you
to visit their websites, find out more about their conferences, and become involved in the
international retina community.
Brazilian Retina
WdZL_jh[eki
IeY_[jo
®
The Brazilian Retina
and Vitreous Society
(SBRV), headquartered in São
Paulo, Brazil, was
founded in 1977 and
has grown to 920
members. SBRV’s
goal is to promote educational and professional
interaction among retina and vitreous specialists
by sponsoring meetings and offering support
for collaborative scientific research.
7hWX7\h_YWdIeY_[joe\
Retina Specialists
Each quarter, the Society publishes
The Brazilian Retina and Vitreous Society Journal,
which will soon be indexed.
The idea to form the Arab African Society of
Retina Specialists (AASRS) originated in 2004
at the first Cairo Retina Meeting. AASRS’s aim
is to promote collaboration and continuing
education between retina specialists in the
Arab world and Africa, as well as with their
scientific colleagues around the world.
FbWdjeWjj[dZj^[(&')
I8HL7ddkWbC[[j_d]
The 5th Cairo Retina Meeting will be held in
January 2014 at the Cairo Marriott Hotel and
Omar Khayyam Casino in Cairo, Egypt.
For information, visit www.crmaasrs.com.
|
Volume )&, Number *
|
Issue *,
International Delegates Attend
ASRS Annual Meeting
Many of the more than 20 international
delegates nominated by their countries’
retina societies attended the ASRS 30th
Annual Meeting in Las Vegas. Their
response was most enthusiastic:
“Best retina meeting I have
ever attended.”
“Great meeting, meeting old friends
and making new ones ...”
“This is my first time at ASRS ... I hope
I could bring more retina specialists
to ASRS.”
Financial Disclosures
SBRV invites ASRS members to participate in
the 38th Annual Meeting, to be held in Belo
Horizonte, Minas Gerais, Brazil on April 11-13,
2013 at the Minas Centro Convention Center.
77IHI?dl_j[ioekjej^[+j^9W_he
H[j_dWC[[j_d]
Fall 2012
For information and registration, visit
www.retina2013.com.br.
“ASRS was outstanding as usual ... It
was a unique experience to meet many
colleagues from different countries ....”
In 2010 at the third Cairo Retina Meeting,
the AASRS was launched with Egypt as its
headquarters. The Cairo Retina Meeting, now
held every 2 years, became the official meeting
of the AASRS in 2012. The AASRS and the
European School for Advanced Studies in
Ophthalmology organized the 2012 meeting
with 24 invited guest speakers, attracting
more than 600 participants from 24 countries.
AASRS now has 412 members representing
18 nations.
20 | retina times |
The meeting will feature leading experts from
Europe, the US, and Latin America.
|
Dr. Rezaei – ALCON LABORATORIES, INC: Other, Grants,
Honoraria; GENENTECH: Other, Grants, Honoraria; BMC
OPHTHALMOLOGY: Consultant, Honoraria; ALIMERA
SCIENCES: Advisory Board, Honoraria; THROMBOGENICS:
Advisory Board, Honoraria; REGENERON PHARMACEUTICALS, INC: Other, Grants.
RETINOMICS >>
William L. Rich III, MD, FACS
President, Northern Virginia
Ophthalmology Associates
Falls Church, Virginia
Medical Director of Health Policy
American Academy of Ophthalmology
Larry Halperin, MD
Section Editor
Retina Group of Florida
Boca Raton and
Fort Lauderdale, Florida
The Patient Protection and Affordable Care Act:
2010-2012—A Curmudgeon’s Report Card
The Affordable Care Act, or “Obamacare”, will affect all of us, our practices, and our patients,
for years to come. The US Supreme Court legitimized certain aspects of the Act; thus, presidential
politics aside, healthcare reform is upon us.
Following are perspectives from Bill Rich, a hero of our
profession, and from Chris Fisher, the health care advisor
to Florida Democratic Representative Ted Deutch.
Please contact me with comments at [email protected].
—Larry Halperin
In 1915, Theodore Roosevelt first proposed compulsory health insurance. It failed to pass. FDR, Truman, and Kennedy also pursued this
unsuccessfully. Finally, President Johnson proposed limited programs
to cover the elderly, poor, and disabled. Medicaid and Medicare were
enacted in 1965. However, the number of uninsured continues to
expand annually and costs have exceeded predictions.
What led to the passage of President Obama’s historic Patient
Protection and Affordable Care Act (ACA)?
sMILLIONUNINSUREDACCORDINGTOTHE53#ENSUS"UREAU
s(EALTHCARESPENDINGONAMETEORICRISE
s.OCOMPARATIVEEFFECTIVENESSRESEARCHONGROWINGTECHNOLOGYTHE
major cause of increased utilization of services
s0ERCEIVEDPOORQUALITY
The ACA is complex, comprehensive, and evolving legislation. However,
the administration’s implementation plans can be evaluated.
J^[kd_dikh[Z
The ACA has taken a moderate approach to the uninsured; it is not
the “socialistic” insurance plan favored by liberal Democrats, where
government is the single payer as in Canada and Great Britain. The
ACA more closely models the approach developed by the conservative
Heritage Foundation. Consider the Dutch system, where benefits are
defined; there are individual and employer mandates to purchase
insurance from competing private insurance firms. Patients can select
a plan to meet their needs. Sound familiar? Massachusetts? The ACA?
The ACA individual mandate was reaffirmed by the recent Supreme Court
decision. Competing plans offered in state exchanges will be available to
patients in 2014 for those whose employer declined to offer insurance
or who qualify for government subsidies to purchase insurance.
Federal subsidies are provided for the working poor—both individuals
and small firms. For those at less than 133% of the poverty level, expansion of state Medicaid is available. The Supreme Court also ruled that
states that decline to expand their Medicaid rolls will not lose federal
contributions for existing Medicaid programs. However, hospitals and
care providers would be left bearing the burden of uncompensated care.
These providers are aggressively lobbying Republican governors to take
the federal money.
‘The cost of insurance will far
outweigh the small tax/penalty
for not obtaining coverage.’
Hurdles include the complexity and cost of implementing state insurance
exchanges, as well as the definition of the minimum benefit package.
Expanded Medicaid and state insurance exchanges are slated to start in
2014—a short time line.
The strength of the ACA is that it could:
s%XPANDCOVERAGETOANADDITIONALMILLION!MERICANSWITHAMODEL
that has worked in other countries
s"UILDONOURSYSTEMOFPRIVATEINSURANCE
s%XPANDOURCURRENTPUBLICPROGRAMS
s)NTRODUCETYPICALLY!MERICANPRINCIPLESOFCOMPETITIONINTHEPRIVATESECTOR
s!VOIDASINGLEPAYERSYSTEMSUPPORTEDONLYBYPROGRESSIVE$EMOCRATS
The individual mandate is a prerequisite for 2 popular ACA reforms:
“guaranteed issue” and “community rating.” A major weakness is the
low “tax” for noncompliance with the individual mandate.
The cost of insurance will far outweigh the small tax/penalty for not
obtaining coverage. Some economists predict that up to 30% of eligible
patients may elect to pay the tax. This would negatively affect the risk
pool and increase the costs for those purchasing insurance. For political
reasons, the ACA fails to make insurance available to the more than
7 million undocumented workers, leaving an uncompensated burden
for hospitals and physicians.
Scorecard: Design: A / ?cfb[c[djWj_ed: Incomplete, but
the model has proved successful in the Netherlands and Germany.
Republicans might try to limit the implementation, but will not
be able to repeal the legislation. Even if the Republicans did
overturn the ACA, they would still face the same problems that
led to its passage.
Continued on page 24
22 | retina times |
Fall 2012
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RETINOMICS >>
Chris Fisher
Legislative Assistant to
Congressman Ted Deutch (D-FL-19)
The ACA Opens the Door to Health Coverage
for Millions
The Patient Protection and Affordable Care Act (ACA) makes access to
quality, affordable health insurance part of the American experience.
For the tens of millions of uninsured and underinsured Americans,
this law represents the only path to comprehensive coverage and access
to the health care system. Ophthalmologists know that comprehensive
coverage and access to primary care can stem the tide of preventable
vision loss if, for example, patients with early macular degeneration can
talk to their doctors about recent vision changes.
Overhauling the nation’s health care system and reforming a broken
insurance market faced peculiar headwinds. Despite the poor comparative
scores of the US health care system, most Americans are satisfied with
their coverage. Fear of the unknown, distrust of a president committed
to extending coverage to the working poor, or even a sincere belief
that American health care outperforms the world in critical metrics
left policymakers with severely limited options.
Asking taxpayers to further subsidize a health care system that spends
almost twice as much per capita as the rest of the world—without
better outcomes—would have surely been unsustainable. The popular
private insurance market reforms alone would have caused premiums
to skyrocket, leading to a complete market collapse. Provisions like
bans on pre-existing conditions, rescissions, and coverage limits were
designed by insurance companies for actuarial soundness in the absence
of a regulated marketplace with coverage mandates.
‘For the tens of millions of uninsured
and underinsured Americans, [the
ACA] represents the only path to
comprehensive coverage and access
to the health care system.’
Health care reformers were left with the unenviable task of restraining
costs and mandating coverage, while navigating the waters of politically
powerful health care interests. Fortunately, all stakeholders agreed on
the dual premise: the system is broken, and this may be the last chance
to repair it.
The Affordable Care Act will extend Medicaid to all adults up to 133% of
the poverty level and will make private insurance affordable for families
up to 400% of the poverty level. It will create state-based exchanges
where insurance companies, bound by new federal pro-patient regulations,
can compete for customers. The ACA will use Medicare’s market influence to accelerate delivery-side reforms, provide performance incentives,
and curb excessive billing.
The recent Supreme Court case considered whether the federal government could:
s-ANDATETHEPURCHASEOFPRIVATEHEALTHINSURANCE
s#OMPELSTATESTOEXPANDTHEIR-EDICAIDROLLSBYUSINGEXISTING
Medicaid funding as leverage
The government argued that because all Americans participate in the
health care system, the mandate was simply regulating how care was
financed. The law’s supporters were concerned that a conservative court
would not only strike the mandate, but be unwilling to sever the provision,
striking down insurance reforms and affordability credits as well.
‘The ACA will use Medicare’s market
influence to accelerate deliveryside reforms, provide performance
incentives, and curb excessive billing.’
In the end, a slight majority found that the mandate could survive as
a tax, but that the federal government could not compel the expansion
of Medicaid. This reversal of widely used federal power may preclude
Medicaid coverage for millions of working poor Americans in states
that choose to opt out of federal health care dollars.
The ACA’s success in improving the nation’s health and health care
finances depends almost exclusively on absolute implementation. The
numerous, interdependent provisions of this public-private health
partnership will function most efficiently in states that aggressively take
ownership of the health of their populace.
Any successful efforts to repeal or sabotage the ACA will necessarily
take place prior to successful implementation. Once the promise of
health care has been delivered to millions of Americans and adequately
financed, it will become exceedingly difficult to undo. We have seen
“Obamacare” become characterized positively by those already affected:
newly insured young adults, seniors in the donut hole, and small
businesses that can now afford to cover their workers.
While those in health care and politics know that the ACA will mean
expanded coverage and consumer-friendly reforms, most Americans
remain focused on keeping their current situations from getting worse.
When it yields better access to more cost-effective insurance instead
of death panels and government takeovers, the ACA will join Social
Security and Medicare in the minds of middle-class families as an
historic American achievement.
Financial Disclosures
Ch$<_i^[h – None.
|
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|
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|
Fall 2012
| retina times | 23
RETINOMICS >> Continued from page 22
Costs
Exploding health care costs have been a monumental problem for our
society for decades. Past attempts to curb costs have all failed: Nixon’s
price controls, the Health Planning Act, managed care and managed
competition, a resource-based physician fee schedule, and prospective
payment of hospitals.
The financing problems that stimulated passage of the ACA include:
s0ROJECTEDBANKRUPTCYOF-EDICARE0ART!IN
s$OUBLINGOFPATIENT0ART"PREMIUMSINYEARS
s/UTOFPOCKETCOSTSFORAFAMILYOFWEREINRISINGTO
IN
s!DOUBLINGOFEMPLOYERHEALTHCAREPREMIUMSINYEARS
s(EALTHCARECOSTSˆTHELEADINGCAUSEOFDECREASESINDISPOSABLEHOUSEhold income, leading to economic stagnation over the last decade
The ACA is based on a belief that moving from fee-for-service to
paying providers based on quality and efficiency will lead to decreased
expenditures—a more than problematic assumption.
The Obama administration has claimed that passage of the ACA has
already led to “bending the cost curve.” Ridiculous. Health care spending
growth began to moderate in 2005, well before the recession, and has
continued to the present day. Physician revenue growth has been lower
than any other sector of health care spending, probably a result of flat
public payments and more cost-sharing for private patients. The ACA
had no impact.
‘The ACA is based on a belief
that moving from fee-for-service
to paying providers based on
quality and efficiency will lead to
decreased expenditures—a more
than problematic assumption.’
The ACA mandated the formation of the Center for Medicare and
Medicaid Innovation (CMMI) within the Centers for Medicare &
-EDICAID3ERVICES#-3WITHABUDGETOFBILLIONTODEVELOPNEW
value-based payment methodologies and innovative care delivery
models. CMMI has recruited many bright staffers with a primary care
and master of public health (MPH) orientation who have had little
or no experience leading physicians, administering care delivery, or
understanding how to change physician behavior.
Because these staffers have eschewed cooperation with long-time CMS
administrators, their policies have been top-down, focused on primary
care, insular, and unresponsive to specialty care input.
telemedicine program to improve renal dialysis patient adherence and
education, creating only 3 new jobs, and affecting patients who already
congregate in a delivery site 3 times a week? Enough said.
Most CMMI payment models are no more promising.
Accountable Care Organizations
Elliot Fisher, MD, Dartmouth Institute for Health Policy, and Glenn
Hackbarth, JD, chair of MedPac, hypothesized a new model for
integrating care to improve quality and decrease costs: an accountable
care organization (ACO). An ACO is an organization, virtual or real,
that provides care for a particular population while achieving specified
quality objectives and containing costs. An ACO emphasizes integration
of care and shared savings.
There are 2 types of ACOs:
s!SHAREDSAVINGSMODELDEVELOPEDAROUNDHOSPITALSYSTEMSORLARGE
medical groups like California independent physician associations (IPAs)
s!0IONEER!#/-ODELFORMEDBYLARGEINTEGRATEDSYSTEMSLIKE+AISER
or Geisinger
Market share consolidation by hospitals and large IPAs will lead to little
change for Medicare, but will very likely drive up overall health care
spending. The Pioneer ACOs will probably be successful, but their small
number will result in little impact on federal Medicare expenditures.
The ACO concept is based on the CMS Group Demonstration Project,
in which 10 large medical groups agreed to be measured on quality
and costs over 5 years. Those who achieved savings and met quality
goals would get a bonus. Many achieved targets on measures of simple
quality process measures.
Three received no bonus at all. Only 2 received a bonus in all 5 years. ACO
DEVELOPMENTCOSTSSTARTAROUNDMILLION4HEDEMOCOVEREDLIVES
-EDICARESAVEDMILLIONOVERYEARSORPERBENElCIARY0EANUTS
Bundling of services
Most of the new payment models being considered by Congress entail
large penalties for physicians not involved in one of the new value-based
payment models. CMMI elected to develop its initial bundled payment
initiatives around a high-cost hospital episode of care—eg, a major joint
replacement. However, disputes over allocation of revenue and costs
among hospitals, surgeons, anesthesia, radiology services, short-stay
nursing facilities, and rehabilitation services have been problematic.
‘Market share consolidation by
hospitals and large IPAs will lead to
little change for Medicare, but will
very likely drive up overall health
care spending.’
Examples of CMMI initiatives:
sPartnership for Patients: !BILLIONDOLLARINITIATIVETOIMPROVEPATIENT
safety in hospitals and develop new care models post-discharge. Result: A
proliferation of consulting contracts with no evidence of efficacy.
sChallenge grants: 7ELLMEANINGBILLIONTOPDOWNAPPROACHTO
improving care, lowering costs, and creating jobs through 3-year grants.
!GRANTOFMILLIONTO'EORGE7ASHINGTON5NIVERSITYWOULDFUNDA
24 | retina times |
Fall 2012
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CMMI declined to develop bundling for outpatient chronic disease treatment provided by a single specialty, even though this would have been easier
to develop and would have saved money and improved outcomes. Wet
AMD and diabetic macular edema, 2 clinical entities with huge costs and
wide variation in resource use, would have been successful bundling efforts.
Continued on page 36
ASRS SYMPOSIUM >>
Pravin U. Dugel, MD
ASRS Research and Therapeutics Committee Chair
Phoenix, Arizona
ASRS Research and Therapeutics Symposium:
Clinical Trials ‘Unplugged’
Part 1: Applying AMD Trial Results to Clinical Practice
The third annual ASRS Research and Therapeutics “Unplugged” Symposium, moderated by
Pravin Dugel, MD, focused on the real-world applications of key clinical trial results. Practicing
retina specialists and leading researchers engaged in a spirited discussion, seeking to understand
differences between clinical trial findings and what is done in everyday practice.
Pravin Dugel opened the discussion by presenting 2009 Medicare
utilization data: In the first year after neovascular AMD diagnosis, the
number of anti-VEGF injections per patient averaged between 5.8 for
ranibizumab and 4.5 for bevacizumab.
Robert L. Avery, MD
J. Michael Jumper, MD
California Retina Consultants
Santa Barbara, California
West Coast Retina
San Francisco, California
ANTI-VEGF USE IN NV AMD
12
David S. Boyer, MD
Peter K. Kaiser, MD
Retina-Vitreous Associates
Medical Group
Los Angeles, California
Cole Eye Institute
Cleveland, Ohio
Average
number =
9
6
3
2006
2007
2008
ANCHOR (2006)
Ranibizumab
Jay S. Duker, MD
William F. Mieler, MD
New England Eye Center
Boston, Massachusetts
University of Illinois, Chicago
Chicago, Illinois
0
2009
MARINA (2006)
12
Average
number =
9
6
3
Harry W. Flynn Jr, MD
Timothy G. Murray, MD, MBA
Bascom Palmer Eye Institute
University of Miami
Miller School of Medicine
Miami, Florida
Murray Ocular Oncology and Retina
Miami, Florida
2006
2007
ANCHOR (2006)
Bevacizumab
2008
0
2009
MARINA (2006)
FIGURE 1*
Yet, according to randomized controlled trials (ANCHOR and MARINA),
patients should receive 11 to 12 injections in that first year. The Medicare
data showed similar discrepancies from other clinical trials:
Jeffrey S. Heier, MD
Michael A. Singer, MD
Ophthalmic Consultants of Boston
Boston, Massachusetts
Medical Center Ophthalmology
Associates
San Antonio, Texas
s !NTI6%'&USEINBRANCHVEINOCCLUSION"6/WAS
INJECTIONSCOMPAREDTO"2!6/AT
s &ORCENTRALVEINOCCLUSION#6/ANTI6%'&USEWAS
compared with CRUISE at 8.8
s $IABETICMACULAREDEMA$-%USEOFANTI6%'&WAS
compared with DRCR.net Protocol I at 9 injections
26 | retina times |
Fall 2012
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Volume 30, Number 4
|
Issue 46
|
ANTIVEGF USE IN BVO
ANTI-VEGF
9
Average
number =
7
5
2
2006
2007
2008
BRAVO (2011)
0
2009
Bevacizumab
ANTI-VEGF
ANTIVEGF USE IN CVO
9
Average
number =
7
5
2
2006
2007
2008
CR I (2011)
‘I don’t see my patients every month
when I’m treating and extending, and
I don’t think it’s a disservice. I think
it may be better to treat them before
they recur every time instead of after
—Robert Avery, MD
they recur.’
Monthly follow-ups, however, are not always practical. “When you can
find the interval where they don’t recur, I feel it’s not unsafe to extend
a few weeks beyond the monthly visit,” said Robert Avery. “I don’t see
my patients every month when I’m treating and extending, and I don’t
think it’s a disservice. I think it may be better to treat them before they
recur every time instead of after they recur.”
Michael Jumper added that “in some ways, it is emotionally easier on
the patient to say, ‘You’re going to get an injection every time you come.
We’re hoping that you get to the point where you are coming in every 6
weeks and then every 8 or 10 weeks.’”
0
2009
Bevacizumab
ANTI-VEGF
ANTIVEGF USE IN DME
9
Average
number =
Practical considerations weigh into the decision to treat on a monthly
basis or individualize treatment. If the latter, what treatment strategy
does one employ? While treat and extend has not yet been proven effective in a randomized clinical trial, most panelists felt it was a reasonable
strategy. Jeffrey Heier stated that the “best data show that you either
treat monthly or, at a minimum, any non-monthly regimen mandates
monthly follow-up.”
7
Peter Kaiser noted that it is easy to become lulled into complacency in
our own practice patterns as we do not critically look at our visual acuity results, anatomic outcomes, and number of injections in the same
way as in a randomized clinical trial.
He recommended periodically looking at your results to ensure you are
achieving similar visual results as the clinical trials.
“Now I’m interested in hearing about what we’re treating,” said Pravin
Dugel. “We’ll start with the case studies.
5
2
2006
2007
2008
0
2009
RCRne4 I (Ran'e) a3e2) (2011)
Bevacizumab
FIGURE 2*
AMD Case #1: Persistent fluid
Pravin Dugel presented a case from his practice, a 65-year-old monocular woman who is an occasional smoker. “She lives alone, so her 20/40
vision is important to her,” he noted. “I started treating this patient in
2005 with Macugen and continued to treat her with Lucentis. She did
well with both; actually, the OCT improved nicely.”
The clinical trial data show a direct correlation between the treatment
“If you had spectral-domain OCT available early on, you would have
frequency and visual acuity, approximating a one-to-one relationship for said there’s fluid there,” Peter Kaiser observed.
AMD, DME, and vein occlusion.
When asked to explain why patients received significantly fewer injections in practice than in clinical trials, the panelists offered a number of
‘[O]ur patients don’t live in
patient-centric explanations and identified data deficiencies. Jay Duker
—Jay S. Duker, MD
pointed out that “our patients don’t live in clinical trials,” and, as William clinical trials.’
Mieler noted, some patients would not be eligible for many reasons
including presenting vision, disease characteristics, and comorbidities.
“For nonfinancial reasons, the patient wanted Avastin,” Dr. Dugel
added. “Recall that at that time, we thought Avastin lasted longer,
* Slater D, Yeh WS, Chia YJ, Kowalski JW. Real-world utilization of intravitreal
because it is a larger molecule—and now she loves Avastin. She does
anti-vascular endothelial growth factor (anti-VEGF) agents in common retinal
diseases. Poster presented at: Academy of Managed Care Pharmacy
not want to switch.”
Educational Conference; October 19-21, 2011; Atlanta, GA.
|
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Fall 2012
| retina times | 27
ASRS SYMPOSIUM >>
AMD Case #1—
Presented by Pravin Dugel, MD
By 2011, after continued Avastin treatment, the fluid appeared to have
increased, but the patient’s vision remained 20/40.
Jay Duker commented, “Maybe this is no longer VEGF-mediated
disease; perhaps those are cysts over the fibrotic scar and they’re never
going to go away.”
“You can figure that out that very easily,” said Peter Kaiser. “Do an
injection; bring her back in a week. If it’s VEGF-responsive, you’ll
see an effect at one week. If not, I would have to think about doing
something else and obtain indocyanine green (ICG) imaging to see
if there’s any other pathology, especially a masquerade syndrome. If
it’s truly choroidal neovascularization (CNV) or polypoidal choroidal
vasculopathy, I’d probably add verteporfin photodynamic therapy
(PDT) to see if I can dry the macula better.”
9/27/05 MACUGEN
‘[The] best data show that you
either treat [with anti-VEGF agents]
monthly or, at a minimum, any nonmonthly regimen mandates monthly
—Jeffrey S. Heier, MD
follow-up.’
Jeffrey Heier commented that to determine whether a patient is VEGFresponsive, he would follow a similar protocol, but double the dose and
bring the patient back at 2 weeks. “I want to know if she is anti-VEGF
responsive,” he explained.
2/16/06 LUCENTIS
“It’s been a number of years now,” said Pravin Dugel. “This is starting
in 2005. She’s perfectly happy with her vision. The fluid may be a little
bit more there. She’s still 20/40. Is it wrong to just keep going? Is this
treatment failure?”
“She’s reading and driving,” said Jay Duker. “You haven’t failed, no.”
Peter Kaiser said that even though the patient is happy, he would consider switching her to Eylea for 2 reasons. “At the minimum, I’m hoping
that I can get the Q2 month dosing of Eylea maybe even a longer
interval. My reasoning is that normally I do not switch someone who is
happy to another medication, but since she’s monocular, I would want
to limit the number of injections as much as possible,” he explained.
5/14/07 AVASTIN
‘[W]e like to get patients as dry as
possible, but I’m not convinced that
in every case we have to do that.
[If the patient is happy], I can live
with a little bit of fluid there.’
—William F. Mieler, MD
William Mieler recommended a slightly different approach. “I agree
that we like to get patients as dry as possible, but I’m not convinced
that in every case we have to do that. This patient has been very stable;
vision is 20/40 and she’s happy. I’d be pretty happy. I can live with a
little bit of fluid there.”
8/24/11 AVASTIN
FIGURE 3
28 | retina times |
Fall 2012
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Volume 30, Number 4
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|
AMD Case #2—
Presented by Robert Avery, MD
Baseline
Baseline
20/200
20/200
Avastin #1
Month 1
Month 1
20/70
20/70
Avastin #2
Month5 5
Month
20/60-1
20/60-1
Avastin #6
Avastin #1
Avastin #2
Avastin #6
10/26/11
Month 80
20/30
20/30
Lucentis #65
Lucentis
#65
Month
1/4/1283
20/60
20/60
Lucentis
#67
Lucentis #67
8/15/12
Month 90
20/30
20/30
Eylea
#7#7
Eylea
FIGURE 4
Jeffrey Heier said the patient seems to be one of a group that may have
a higher VEGF load. “They respond to the Eylea; but then if I try to
extend them out at all, I can’t,” he said.
“Although to date there’s no well-performed clinical study to show that
switching someone from Avastin to Eylea is any more beneficial than
continuing the anti-VEGF they’re on,” said Peter Kaiser, “there have
been numerous anecdotal reports suggesting that we have a possibility
of improving outcomes in this patient by switching. If this were a
2-eyed patient, you could take the risk and say, ‘Okay, we’ll skip this
shot and we’ll see you in a month and see if the fluid increases and your
vision drops.’ But getting that vision back once it drops is much harder
than preventing it from dropping in the first place. We can’t make a
mistake in this patient.”
After a discussion of the pharmacokinetic issues of anti-angiogenesis
agents, Pravin Dugel asked, “Would you be worried about safety issues
with long-term Avastin use in a patient like this?”
“I’m not particularly worried if the patient is not at a high risk for
stroke,” said Robert Avery. “The people I worry about are those who
have had previous strokes or arrhythmias, or who are at high risk for
stroke. I look at the safety data in the VIEW 1, VIEW 2, CATT, and
IVAN, and I don’t see much stroke risk in the average person. A
meta-analysis in the October 2012 Retina seems to imply that if you are
at high risk for stroke, your risk with these drugs may be higher.”1
AMD Case #2: Early Avastin patient
Robert Avery presented a case of a patient with 20/200 vision from neovascular AMD in his better eye. “We began Avastin therapy on him in
2005,” he explained. “He did well and came back to about 20/60 vision
after 6 injections, but still had persistent fluid and pigment epithelial
detachment (PED). After a year of Avastin, we changed him to Lucentis,
and he stayed in the 20/60 range with monthly treatment. He still had
PED and some fluid at the edge of it.”
After 65 monthly Lucentis injections, the patient was back to 20/40,
with a small amount of persistent fluid. He started to lose a bit of
vision in 2012, so he was switched to Eylea. “I hoped this would last
longer and dry the fluid out,” Dr. Avery explained. The intraretinal fluid
decreased and his vision slowly came back to 20/30 after 6 or 7 Eylea
injections.
“This is indicative of what I see—a slight improvement in some
patients with Eylea, just as I saw with Lucentis over Avastin for a few
patients,” Dr. Avery added. “But what’s going to happen in the future? Is
the patient going to continue to dry up and develop atrophy? Should I
have chased this fluid?”
“In a lot of cases, the location of the fluid is what matters,” noted Peter
Kaiser. “The beginning images of this case showed a lot of the fluid was
intraretinal or subretinal. Now it’s almost all sub-RPE.”
Michael Singer queried the panel and the audience on whether they
had extended patients on Eylea who previously had been nonresponsive to Lucentis. “When the patients have dried out, have you been able
to extend them to 2 months?” he asked. No one raised their hand.
“This has been my experience as well,” said Dr. Singer. “I have been able
to extend treatment-naïve patients, but have not been able to extend
patients whose lesions have been resistant to treatment such as PEDs.”
“I think we’re biased,” said Michael Jumper. “In our practice, the only
people we treat with Eylea are those who have persistent fluid on
another drug. When reimbursement issues allow for patients to start
out on Eylea, we might have the sort of treatment-naïve patients who
are more like those in the VIEW studies.”
AMD Case #3: Bilateral choroidal vascularization
Jay Duker presented the case of an elderly woman, still quite sharp, who
recently noticed a rather sudden vision decrease in her left eye. “She’s
20/50 right eye, 20/400 left. Her fluorescein clearly shows bilateral
choroidal vascularization, and in the right eye, it’s extrafoveal.”
Dr. Duker noted that the patient was treatment-naïve and asked
whether the panel was comfortable treating her bilaterally on the
first visit.
William Mieler commented, “I have no trouble treating bilaterally, but
usually at the first visit I’ll treat just one eye so the patient understands
the process. You hate to induce a problem bilaterally on day one.”
‘In a lot of cases, the location of the
fluid is what matters.’—Peter K. Kaiser, MD
Others commented that they would inject both eyes the first time,
which is what Dr. Duker did after discussion with the patient.
Peter Kaiser offered a caveat: “I assume all of you are saying you would
treat bilaterally with Lucentis the first time, because if you’re going to
use Avastin … Whenever I use bilateral Avastin, I always use different
lots of the compounded medication.”
“Excellent point,” Dr. Duker responded, adding, “And you always record
that in your document chart.”
Harry Flynn asked, “Does it matter if it’s the same
compounding pharmacy?”
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ASRS SYMPOSIUM >>
This question prompted a discussion surrounding Avastin safety.
“At the Cole Eye Institute, our Avastin is compounded by our own
Cleveland Clinic pharmacy,” Peter Kaiser explained. “They send
samples of each lot to the microbiology lab to test for contamination
before the lot can be used. It’s done in the same place, so that you could
argue that it’s an issue if there’s a systemic problem, but at least I’m
using 2 different lots.”
AMD Case #3—
Presented by Jay Duker, MD
Right eye
Baseline
“I use Avastin from 2 different compounding pharamacies to minimize
the risk,” David Boyer commented.
VA = 20/50
Month 12, Lucentis #12
“We at the University of Miami take 1 out of every 10 syringes,
culture it, and quarantine it for 2 weeks,” said Harry Flynn. “Once it’s
culture-negative, we release the other 9.” He added that none of the
approximately 60,000 syringes at Bascom Palmer have tested culture
positive.
Dr. Duker presented a slide showing the patient’s eyes after one
ranibizumab injection in both eyes. “She didn’t want an off-label
medication,” he noted. “She had a little less fluid in both eyes and
improvement in her vision. We treated her again and went to 3
monthly injections. The right eye showed just a trace subretinal fluid;
the left eye still showed subretinal fluid.
“At that point we started to talk about the maintenance phase,” Dr.
Duker added, “with the idea that you treat monthly until dry or until
you get no further improvement in the fluid or vision and then go into
maintenance. The patient had several options, and after I discussed
them with her, she said, ‘I want continued monthly injections in both
eyes,’ so that’s what we did.”
Dr. Duker presented a slide showing the patient after a year of treatment. “The right eye 20/50, initially 20/30. I think we’d all agree she’s
doing just fine with monthly injections,” he said. “And after a year, the
left eye is visually doing great. She perceives no difference between the
vision in her 2 eyes, but she still has subretinal fluid in the PED in her
left eye.
“I think this illustrates what we’ve been talking about—that sometimes
a little bit of subretinal fluid in the PED doesn’t preclude good vision,”
Dr. Duker continued. “And I don’t believe that holding off treatment in
a PRN fashion puts this kind of patient at higher risk for a hemorrhage.
The worst hemorrhages I’ve gotten in the last couple years have been
within a month of treatment.”
“Here again, the location of the fluid is important,” said Pravin Dugel.
The panelists agreed they would be willing to do bilateral same-day
injections on those patients.
‘We at the University of Miami take
1 out of every 10 syringes, culture it,
and quarantine it for 2 weeks. Once
it’s culture-negative, we release the
—Harry W. Flynn Jr, MD
other 9.’
VA = 20/30
Month 24, Lucentis #22
VA = 20/30
Left eye
Baseline
Month 12, Lucentis #12
Month 24, Lucentis #21
and Eylea #1
VA = 20/400
VA = 20/30
VA = 20/30
FIGURE 5
Do AREDS supplements help
bilateral wet-AMD patients?
PAT Survey Editor Michael Jumper posed a question referring to past
years’ survey responses: If patients with bilateral wet AMD are being
maintained and their condition is controlled, should they continue taking AREDS vitamins even though there’s no proof that it’s worthwhile
for advanced AMD patients?
“We know CATT data about atrophy being a potential problem,” Dr.
Jumper explained. “Do you consider keeping patients with bilateral wet
AMD on AREDS vitamins?
“We get asked that all the time, don’t we?” Jay Duker commented—and
other panelists and audience members concurred.
“My response is that continuing AREDS supplements is essentially
locking the barn door when the cow’s out, but it’s only costing $20 or
$30 a month,” said Dr. Duker. “I tell patients, ‘If you want to keep doing
it, fine. I don’t think it’s helping you.’”
Lack of data on switching anti-VEGF agents
Pravin Dugel noted the lack of clinical data on patients who switched
from one anti-VEGF agent to another. “I remember meetings where
case reports were presented of patients switching from Lucentis to
Avastin and improving vision. There were also accounts of the reverse
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with similar results. Now we have reports of patients switching from
Avastin or Lucentis to Eylea who have improved.
“We must be appropriately skeptical of all these case reports and must
not fall in the trap of extrapolating their results,” Dr. Dugel cautioned.
“There is no credible scientific data whatsoever that switching patients
from one anti-VEGF drug to another is of any benefit.”
‘I use Avastin from 2 different
compounding pharmacies to
minimize the risk.’ —David S. Boyer, MD
If fluid increases, it might have done so if the patient had stayed with
the previous anti-VEGF agent as well. “In those studies, it’s important
to ask how many injections were done before the switch,” Dr. Dugel
advised. “Ultimately, you’ll see in most reports that there may not have
been an optimal injection frequency prior to declaring failure; the
patients were often in a treat-and-extend phase. Then they switched
anti-VEGF agents, went into a monthly injection regimen, and did
better. This improvement may have occurred had the same monthly
frequency been adopted with the original anti-VEGF agent. We must
not draw unwarranted conclusions without head-to-head data—and
we do not have this.”
Jeffrey Heier asked, “Are you saying that we should be careful and not
switch them?”
Dr. Dugel answered, “No. What I’m saying is that we should
understand and admit where we have data and where we don’t. There’s
no reason not to switch if you feel that’s a proper thing to do—but
we must be honest and admit that this is not based on any level-one
scientific evidence.
“It is not that we cannot act without level-one scientific evidence; we
can, and often do so,” Dr. Dugel concluded. “Rather, if we chose to do
that, we must be truthful and transparent about our dearth of scientific
knowledge to our patients, to our colleagues, and to ourselves.”
Reference
1. Bressler NM, Boyer DS, Williams DF, et al. Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials. Retina. 2012;32(9):18211828. doi:10.1097/IAE.0b013e31825db6ba
Financial Disclosures
Dr. Dugel – ABBOTT LABORATORIES: Consultant, Honoraria; ALCON LABORATORIES, INC:
Consultant, Honoraria; ALLERGAN, INC: Consultant, Honoraria; ARCTICDX: Consultant,
Honoraria, Stockholder, Stock; GENENTECH: Consultant, Honoraria; MACUSIGHT INC: Consultant, Honoraria, Stockholder, Stock; NEOVISTA, INC: Consultant, Honoraria, Stockholder,
Stock; ORA: Consultant, Honoraria; THROMBOGENICS: Consultant, Honoraria; REGENERON
PHARMACEUTICALS, INC: Consultant, Honoraria; OPHTHOTECH CORP: Consultant,
Stockholder, Honoraria; ALIMERA SCIENCES: Consultant, Honoraria; Bausch+Lomb: [ed:
Please specify relationship, eg, consultant] Honoraria; LUX BIOSCIENCES, INC: Consultant,
Honoraria; ACUCELA, INC: Consultant, Honoraria; NEUROTECH INC: Consultant, Stock; QLT
INC: Consultant, Honoraria; NOVARTIS PHARMACEUTICALS CORPORATION: Consultant,
Honoraria; TOPCON MEDICAL SYSTEMS: Consultant, Honoraria; HEIDELBERG ENGINEERING: Consultant, Honoraria; DIGISIGHT: Consultant, Stock..
Dr. Avery – ALCON LABORATORIES, INC: Consultant, Investigator, Speaker, Grants,
Honoraria; ALLERGAN, INC: Consultant, Investigator, Grants, Honoraria; GENENTECH:
Consultant, Investigator, Speaker, Grants, Honoraria; NOVARTIS PHARMACEUTICALS
CORPORATION: Consultant, Stockholder, Honoraria, Stock; NOTAL VISION: Consultant,
Honoraria; OPHTHOTECH CORPORATION: Consultant, Honoraria; REPLENISH, INC: Advisory
Board, Consultant, Stockholder, Intellectual Property Rights, Royalty, Stock; REGENERON
PHARMACEUTICALS, INC: Consultant, Stockholder, Honoraria; Stock; ALEXION PHARMACEUTICALS: Stockholder, Stock; QLT INC: Consultant, Honoraria; I-TECH JV DEVELOPMENT
COMPANY, LLC: Stockholder, Stock.
Dr. Boyer – ALCON LABORATORIES, INC: Advisory Board, Consultant, Investigator,
Speaker, Grants, Honoraria; ALLERGAN, INC: Advisory Board, Consultant, Investigator,
Speaker, Grants, Honoraria; ALLEGRO OPHTHALMICS: Advisory Board, Stockholder,
Honoraria; GENENTECH: Consultant, Investigator, Speaker, Grants, Honoraria; REGENERON
PHARMACEUTICALS, INC: Consultant, Investigator, Grants, Honoraria; iCo THERAPEUTICS
INC: Consultant, Investigator, No Compensation Received; GLAXOSMITHKLINE: Consultant,
Honoraria; NOVARTIS PHARMACEUTICALS CORPORATION: Consultant, Investigator, Grants,
Honoraria; BAYER HEALTHCARE: Consultant, Honoraria; QUARK PHARMACEUTICALS, INC:
Investigator, Grants.
Dr. Duker – HEMERA BIOSCIENCES INC: Founder, Stock; OPHTHOTECH CORPORATION:
Consultant, Stock; EYENETRA: Consultant, Stock; PALOMA PHARMACEUTICALS:
Advisory Board, No Compensation Received; EMC/SERONO, INC: Consultant, Honoraria;
GENENTECH: Consultant, Honoraria; ALCON LABORATORIES, INC: Consultant, Honoraria;
REGENERON PHARMACEUTICALS, INC: Consultant, Honoraria; THROMBOGENICS:
Consultant, Honoraria; CARL ZEISS MEDITEC: Other, Equipment (Department or Practice);
TOPCON MEDICAL SYSTEMS, INC: Other, Equipment (Department or Practice); OPTOVUE:
Other, Equipment (Department or Practice); NEOVISTA, INC: Advisory Board, Honoraria;
NOVARTIS PHARMACEUTICALS CORPORATION: Consultant, Honoraria; QLT INC: Consultant, Honoraria.
‘There is no credible scientific data
whatsoever that switching patients
from one anti-VEGF drug to another
is of any benefit.’ —Pravin U. Dugel, MD
Dr. Flynn – ALIMERA SCIENCES: Consultant, Honoraria; PFIZER, INC: Consultant, Honoraria;
SANTEN: Consultant, Honoraria.
“This highlights the danger of cross-trial comparisons and unwarranted extrapolations,” Dr. Dugel explained. “We must recognize the
nature of disease itself, as well as the level of credibility of studies. The
disease is variable and is influenced by intrinsic and extrinsic factors.
For instance, the baseline neovascular lesion size will have a direct
and profound impact on the vision outcome. Cross-trial comparisons
cannot be done because such biases cannot be controlled. However, in
a properly randomized and powered clinical trial, such biases can be
negated, or at least minimized.
Dr. Jumper – COVALENT MEDICAL, INC: Equity Owner, Stock; Dutch Ophthalmics USA:
Speaker, Honoraria.
“Finally, we must subject untested recommendations to the appropriate
scientific rigor,” Dr. Dugel added. “Remember that there is no level-one
data to recommend a particular anti-VEGF agent or to switch to a
particular anti-VEGF agent based on efficacy. None of the 3 anti-VEGF
drugs have been proven to be superior.
Dr. Heier – Dr. Heier – ACUCELA INC: Consultant, Consulting Fees; ALLERGAN, INC: Consultant, Consulting Fees; BAUSCH+LOMB: Consultant, Consulting Fees; BAYER HEALTHCARE:
Consultant, Consulting Fees; ENDO OPTIKS INC: Consultant, Consulting Fees; FORSIGHT
LABS, LLC: Consultant, Consulting Fees; FOVEA PHARMACEUTICALS SA: Consultant,
Consulting Fees; GENENTECH: Consultant, Consulting Fees; GENZYME: Consultant, Consulting Fees; HEIDELBERG ENGINEERING: Consultant, Consulting Fees ; KATO PHARMACEUTICALS: Consultant, Consulting Fees; NEOVISTA, INC: Consultant, Consulting Fees; NOTAL
VISION: Consultant, Consulting Fees; ORAYA THERAPEUTICS, INC: Consultant, Consulting
Fees; PALOMA PHARMACEUTICALS, INC: Consultant, Consulting Fees; QLT OPHTHALMICS:
Consultant, Consulting Fees; QUARK PHARMACEUTICALS, INC: Consultant, Consulting
Fees; REGENERON PHARMACEUTICALS, INC: Consultant, Consulting Fees; SEQUENOM:
Consultant, Consulting Fees.
Dr. Kaiser – ALCON LABORATORIES, INC: Consultant, Honoraria; NOVARTIS PHARMACEUTICALS CORPORATION: Consultant, Grants, Honoraria; REGENERON PHARMACEUTICALS,
INC: Consultant, Grants, Honoraria; BAYER HEALTHCARE: Consultant, Honoraria; SKS
OCULAR, LLC: Stockholder, Stock; ARCTICDX: Consultant, Stock Options; ALIMERA
SCIENCES: Consultant, Honoraria; OPHTHOTECH CORPORATION: Consultant, Honoraria;
ORAYA THERAPEUTICS, INC: Consultant, Honoraria.
Dr. Mieler – GENENTECH: Consultant, Honoraria; ALCON LABORATORIES, INC: Consultant,
Honoraria; ALLERGAN, INC: Consultant, Honoraria; QLT INC/NOVARTIS PHARMACEUTICALS CORPORATION: Consultant, Honoraria; ALIMERA SCIENCES: Consultant, Honoraria.
Dr. Murray – ALCON LABORATORIES, INC: Consultant, Honoraria; THROMBOGENICS:
Consultant, Honoraria.
Dr. Singer – GENENTECH: Investigator, Speaker, Grants, Honoraria; ALLERGAN, INC:
Advisory Board, Consultant, Investigator, Speaker, Grants, Honoraria; DRCR.NET: Investigator, Other, Grants, No Compensation Received; NEOVISTA, INC: Investigator, Other, Grants,
No Compensation Received; ISTA PHARMACEUTICALS: Investigator, Grants; OPTOS
PLC: Investigator, Equipment (Department or Practice), No Compensation Received;
REGENERON PHARMACEUTICALS, INC: Speaker, Investigator, Grants; SANTEN: Consultant,
Consulting Fees.
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RETINA IN THE MILITARY >>
Marcus H. Colyer, MD,
MAJ, MC, USA
John R. Minarcik Jr, MD,
CDR, MC, USN
Section Co-Editor
Section Co-Editor
Serving in Afghanistan:
3 Deployed Retina Specialists Share Their Stories
After a decade of combat in Southeast Asia, the US military continues to see a steady stream of
eye injuries, from corneal abrasions to complex globe and oculoplastics injuries. In recent years,
ophthalmology care has evolved in Afghanistan; and with rising combat activity, there has been
a commensurate increase in the number of deployed ophthalmologists.
Most deployed ophthalmologists
are not retina-trained, but there have
been several military retina specialists
in the recent past. We asked 3 of our
recently deployed retina specialist
brethren—Darrell Baskin (Craig Joint
Theater Hospital, Bagram Air Base,
2010), Bryan Propes (Kandahar
Airfield, 2011), and Steve O’Connell
(Kandahar Airfield, 2012) to comment
on their experiences.
Maj Darrell Baskin,
MD, USAF
I took over the reins from a
close friend and fellow ophthalmologist in August 2010; as
Chris Kurz, MD, detailed and demonstrated my
new responsibilities, I quickly realized my vastly
expanded scope of practice. We ran a 24/7 clinic
for our US military servicemen and women to
field any ocular complaints, and we could airevacuate any who required an escalation in care.
Nearly every single active-duty person who
received a globe repair or enucleation by my
hands was evacuated before I rounded on the
first postoperative day. I also took care of many
International Security Assistance Force coalition
troops and even some members of the media.
For the rest of my patients, though, air
evacuation was not an option. During my
time in particular, we accepted civilian
patients from the host nation, Afghan
National Army and police, and even hostile
forces. For these patients, I was the only eye
doctor they might ever encounter. If I could
not or would not fix their ocular problem,
there weren’t any other options.
Tuesdays and Thursdays were particularly
difficult, as my clinic was populated with local
Afghans with a broad range of ailments, from
acid burns to ocular prosthesis fittings. The
range of conditions could easily have covered
half of the topics in The Wills Eye Manual.
Given the complexity of the wounds, I was
grateful for the coaching I received from our
deployed oculoplastic surgeon, Daniel Elizondo,
MD, the first ophthalmologist in Kandahar,
for many oculoplastics procedures beyond my
comfort zone. I was particularly appreciative of
his help when I had to perform my first and only
dermis fat graft for an infected and extruding
polymethylmethacrylate orbital implant.
Typical deplaning at Bagram
But my retina training did not completely
wither on the vine during my deployment.
Gary Lane, MD, one of the best retina
surgeons I know, coordinated the transport
‘The range of conditions
[treated] could easily have
covered half of the topics
in The Wills Eye Manual.’
—Maj Darrell Baskin,
MD, USAF
Dr. Baskin’s first scleral buckle procedure in Afghanistan
of an Alcon Accurus system to Afghanistan.
With 2 weeks remaining in my 3-month
deployment, I was able to perform 7 vitrectomies.
Most cases were for retained lens material
associated with open-globe injuries in the
local Afghan population. Thanks to Gary, we
performed the first posterior vitrectomy in the
history of deployed US warfare.
I am grateful for the experience and the
opportunity to serve, but I was terribly
relieved to come home 2 weeks before my
beautiful wife was due with our fourth child.
An enucleation specimen; much of the sclera could not
be located in the orbit.
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RETINA IN THE MILITARY >>
Capt Steve O’Connell,
MD, USN
Greetings from the other
side of the world and thanks
to all who have supported
me in the Kandahar Airfield (KAF) NATO
Role 3 Multinational Medical Unit mission.
It’s a privilege to be given this responsibility
and of course a daunting challenge. I’m the
fourth ophthalmologist to attend here as we
wind down our Afghanistan involvement.
At the moment, there seems to be as much
military action as ever.
Dr. Propes at Kandahar “Role 3” Hospital
Dr. Propes teaching an Afghani doctor
The concept is One Deep. There’s only one
neurosurgeon, one oral surgeon, and one
ophthalmologist in southern Afghanistan.
Like a modern day Noah’s Ark, there are pairs
or multiples of other specialties and nonphysicians. There are usually about 5 surgeons
(vascular, plastic, general, trauma) and
5 orthopedic surgeons (spine, trauma, foot,
hand, general), but only one ophthalmologist.
There’s plenty of nonsurgical ophthalmology
here, eg, patients whose vision is not only
blurry, but their eyes are red and/or they
hurt. An unbelievable variety of foreign
bodies seem to make their way into the
eye. Other diagnoses are those typical of
any general ophthalmology practice: syphilis,
chlamydia, multiple sclerosis causing internuclear ophthalmoplegia, cataract, thalamic
infarct producing a skew deviation, herpes
simplex virus, epidemic keratoconjunctivitis,
anesthetic abuse, new-onset Harada’s disease,
bacterial keratitis, pituitary tumor producing
a bitemporal field deficit, chalazia, reactive
arthritis/iritis—the list goes on.
We have 2 or 3 additional general surgeons,
orthopedic surgeons, and anesthesiologists
from Australia and Belgium for the next
couple of months. The plastic and maxillofacial
surgeons can do facial skin and bones, but
no one does globes except the ophthalmologist.
What this means is careful planning for
6 to 7 months.
The nature of the typical injury is shocking
and shockingly predictable. Most injuries
involve a local national army or police
member engaged in hazardous duty without
eye protection. Many times, defusing a bomb
is performed by someone wearing only light
clothing and no eye protection, even though
it has been given to them.
Trauma is inherently unpredictable. No one
knows when there will be multiple casualties,
so we must always be prepared, whether going
to the gym, meals, the exchange, etc. Within
2 weeks of my arrival, I had 7 open globes in
36 hours. As I sit here writing this on a Sunday
afternoon, I’ve already been to the hospital
3 times to see patients with a migraine and
a trailer hitch to the orbit, and a sailor with
shrapnel to the cornea who took his eye
protection off for just a few moments.
On my way back to the barracks, I saw the
ER crew gearing up and passed one of the
2 radiologists on his way in to review
essentially whole-body CT scans on every
trauma patient. I make sure the pager
is nearby at all times with a good battery.
I know it will sound off shortly.
Dr. Propes at the surgical microscope
There used to be an Army optometrist
stationed here. Apparently this position was
simply terminated, even though there was
no commensurate reduction in personnel or
need. The duties that used to be performed
by the optometrist have now fallen to the
ophthalmologist by default. There are roughly
30,000 personnel on KAF, and numerous
forward operating bases that rely on KAF
for routine eye care services.
Entrance to the Kandahar OR
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Often, someone will walk in saying they can
no longer see well enough to drive a convoy
vehicle, fly their jet, or aim their weapon
with their current spectacles. Performing a
refraction is a simple but essential task to
ensure our forces have good acuity for the
mission. Lives depend on good vision.
‘Lives depend on
good vision.’
—Capt Steve O’Connell,
MD, USN
The force of the blast rips off limbs, macerates
facial skin, and propels dirt deep into the
tissues. It’s as if they’ve been tattooed with
dirt. Brown ooze will continue to exit burned
skin for days. The cornea is usually extremely
edematous. Defects are not lacerations as
much as they are punch-type wounds with
missing tissue—difficult to close with suture
material alone.
Fortunately, there is a little time to treat a
ruptured globe. Unlike a chemical burn or a
retro-bulbar hemorrhage that needs and gets
immediate attention, a ruptured globe can
sometimes wait hours while life-saving
procedures (transfusions, chest tubes,
amputations) are carried out.
The typical sequence is the notification that
multiple Afghan National Army or coalition
personnel have been involved in an improvised
RETINA IN THE MILITARY >>
explosive device (IED) explosion and
multiple eye injuries have been sustained.
The duty general surgeon will act as traffic
cop, orchestrating the use of ER and OR
resources to prioritize and accomplish all of
the required procedures. Three rooms and a
minor procedure room are available.
When a room is open, an excellent, but
ever-changing cadre of nursing and corps
staff helps you accomplish your globe closure,
enucleation, lid laceration, etc. Rarely, you’ll
be asked to give up the room before you’re
done if suddenly there’s a double or a triple
amputation coming in. When possible, you
may bring your patient back in. Life, limbs,
and eyesight are given the highest priority.
LCDR Bryan Propes,
MD, USN
Every day you see young
people—our fighting soldiers,
sailors, and marines—
children, enemy combatants, and innocent
civilians—all horribly injured. Not an
individual with a wounded leg or extremity,
or an eye wound or abdominal wound, but
someone with all of the above, and bilateral
open globes and a facial degloving injury
with a fractured mandible and a Le Fort
type III all at the same time.
And not just that person, but 3 or 4 just like
him, all arriving at the same time, all needing
multiple surgical procedures. As soon as those
patients are triaged, 3 or 4 more are just as
likely to come in; sometimes before you get
through the first batch, more will arrive. Mostly
they come in stable, or at least with tourniquets
on and not exsanguinating. At least once or
twice a week, someone comes in and requires
immediate life-saving surgery and undergoes
massive transfusion—20-30 units of PRBCs.
They live, almost always, but they often lack
extremities and other vital pelvic organs.
The ethical obligation to train an ophthalmologist has never been more apparent than
in Afghanistan. In the entire country, there
are only about 40 or so ophthalmologists
practicing. There are a few frustrations
practicing ophthalmology here, most having
to do with practicing on the local population.
First, you must work to do everything during
a single surgery with as little follow-up as
possible. This requires performing slightly
different surgeries than you ordinarily would.
Your patients are unlikely to ever again see
a properly trained surgeon, and are even
unlikely to follow up with you.
trained to save sight. It’s what we do. It’s
why we are here. There are some obvious
reasons—there’s only one of me and I’ll need
to sleep sometime, there is a finite supply
of drugs, equipment, etc, and these must
be judiciously used to ensure proper treatment
of patients who meet the medical rules
of engagement.
Regardless, I find it very difficult to turn away
a patient who needs to be treated. I took an
oath; there is a moral obligation to treat a
suffering patient, and seeing a patient could
help the wider goal of winning the hearts and
minds of the Afghan people. So it was for my
first couple of months here that I would agree
to see essentially anyone who asked to be seen.
Dr. O’Connell preparing for a Sunday drive
‘The ethical
obligation to train
an ophthalmologist
has never been more
apparent than in
Afghanistan.’
—LCDR Bryan Propes,
MD, USN
A medevac helicopter lands at Kandahar
Halfway through my deployment, I met a
senior Naval officer. One of his responsibilities
is the state of Afghanistan health care after
we leave, and he was giving a presentation
at a mini-meeting set up by our command.
During his talk, he explained that by seeing
patients who don’t meet the medical rules
of engagement, we are putting the local
doctors out of business. Thus, when we leave,
there will be no one to take care of the local
population. Quite a simple concept, really,
but one that I had completely overlooked.
Now, I require any local national who was not
involved in conflict-related injury to obtain
a referral from a local ophthalmologist.
Typical American muscle car in Afghanistan
Disclaimer: The views expressed in this presentation are those of the authors and do not reflect
the official policy of the Department of the
Army, Navy, Air Force, Department of Defense,
or US government.
Financial Disclosures
Dr. Colyer – None.
Dr. Minarcik – None.
Dr. Baskin – None.
Dr. O’Connell – None.
Dr. Propes – None.
Dr. O’Connell at Kandahar Airfield
Secondly, you must refuse to see some local
national patients. This kills me, as we are
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Fall 2012
| retina times | 35
RETINOMICS >> Continued from page 24
Some CMMI initiatives were brilliantly conceived and have great
promise, such as the Comprehensive Primary Care Initiative headed
by Richard Baron, MD, MACP. This initiative will coordinate public
and private insurer funding of comprehensive medical homes not
constrained by the top-down NCQA criteria.
‘[I]mplementation of the ACA follows
a disturbing pattern of overreliance
on MPH public policy mavens rather
than listening to concerned and
cooperative physicians.’
CMMI has failed to meet the lofty triple-aim goals of former CMS
Administrator Donald Berwick, MD: improved health, better experience
of care, and lower costs.
When these new models fail in 2015-2017, we will face a financing
crisis and physician payments will be targeted, despite the fact that
expenditures on physician services have lagged behind all other sectors
of health care spending growth since 2005.
Scorecard: Design: D / ?cfb[c[djWj_ed: D
9ecfWhWj_l[[\\[Yj_l[d[iih[i[WhY^9;H
True evidence-based CER benefits all except providers or developers of
marginal technologies who gain market share via marketing strategies
rather than demonstrated value. The promise of CER is exemplified by
the CATT trial.
The ACA established the Patient Centered Outcomes Research Institute
0#/2)WITHABUDGETOFBILLIONTOMEETTHISNEED(OWEVERTHE
design by Congress emphasized “patient centeredness” rather than true
CER. As a result, the initial PCORI grants financed studies to measure
“patient centeredness” rather than patient-centered outcomes research.
The PCORI policies have proven a great benefit to industry that doesn’t
really want CER, and a great disservice to patients suffering from
diseases where there are treatment controversies.
The flawed PCORI approach is the fault of the congressional design.
The Foundation for Informed Decision Making is a successful
entity that educates patients and their families on treatment options
independent of the professional providing the service when there are
competing approaches. Wouldn’t it have made more sense to fund
needed CER and utilize an extant patient-centered educational tool
rather than funding measurement of “patient centeredness”?
GkWb_jo
The ACA has mandated National Quality Forum-endorsed measurement
in ACOs, bundled payments, and all their new payment initiatives. Few
measures address eye care because of the ACA and CMMI singular
emphasis on primary care and public health, and because there are no
payment models that invite meaningful ophthalmic participation.
Scorecard: Design: B+ / ?cfb[c[djWj_ed: B+
As a physician in a large ophthalmic group in a suburban Northern Virginia
county with the highest per-capita household education and income in the
United States, I was depressed by the 35% uninsured status of obstetrical
patients in our large referral hospital. Three pediatric ophthalmologists in my
group have an even higher number of uninsured patients. Many of us have
been infuriated by the disjointed care received by an elderly, frail parent that
resulted in medical errors and needless hospital admissions.
We are all frustrated by the disruptive commercial insurance policies
on coverage limits, exclusions for pre-existing conditions, and administrative hassles. (Under the ACA, there is relief in 2014.) For these
reasons, I strongly supported passage of health care reform legislation.
However, implementation of the ACA follows a disturbing pattern of
over-reliance on MPH public policy mavens rather than listening to
concerned and cooperative physicians.
The strength of the ACA lies in the expansion of health care coverage.
However, the weak individual mandate and state decisions not to
expand Medicaid may result in less than half the projected patients
attaining coverage. More important, the new payment models will not
lead to lower costs and will result in a funding crisis within 5 years.
‘The strength of the ACA lies in the
expansion of health care coverage.
However, the weak individual mandate
and state decisions not to expand
Medicaid may result in less than half the
projected patients attaining coverage.’
The failure to achieve the ACA cost savings envisioned by Congress is
due to hubris, an overemphasis on primary care, and the revenge of the
Harvard MPHers. Stay tuned. Change will be forthcoming to address
these deficiencies in the ACA.
Financial Disclosures
Scorecard: Design: D / ?cfb[c[djWj_ed: B- PCORI staff
:h$H_Y^ – None.
are limited by the legislative language
Dr. Halperin – ALIMERA SCIENCES: Consultant, Honoraria.
36 | retina times |
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POINT/COUNTERPOINT >>
Robert A. Mittra, MD
Edwin H. Ryan Jr, MD
VitreoRetinal Surgery, PA
Minneapolis/St. Paul, Minnesota
VitreoRetinal Surgery, PA
Minneapolis/St. Paul, Minnesota
Point: Scleral Buckling Has a Continuing Role
in Repairing Retinal Detachment
Scleral buckling (SB) with an episcleral exoplant was popularized
by Charles Schepens, MD, and others in the 1950s as a means to repair
rhegmatogenous retinal detachment (RRD), and was successful for
a variety of cases.1,2 After the introduction of pars plana vitrectomy
(PPV) in the early 1970s by Robert Machemer, MD,3 this technique
began to be employed for RRD repair, especially in complex cases,4,5
post-trauma,6,7 and when proliferative vitreoretinopathy was present.8-10
‘While some cases can be managed
successfully with PPV, a significant
subset of patients will benefit from
SB surgery, either alone or in
conjunction with PPV.’
The use of PPV has expanded greatly in recent years with advances in
instrumentation and the widespread availability of wide-angle viewing
systems. Some have suggested that PPV alone should be employed for
nearly all RRDs. While some cases can be managed successfully with
PPV, a significant subset of patients will benefit from SB surgery, either
alone or in conjunction with PPV.
All RRDs are not created equal
The underlying problem with suggesting that PPV or SB alone is
superior is that RRD is not a homogenous condition that can be treated
similarly in all cases. While this may be possible with most cataract
cases, as any clinician can attest, a wide variety of presentations of RRD
and several key factors can affect the choice of the required procedure
to ensure the highest success rate.
These factors include, but are not limited to the:
s0ATIENTSAGE
s3TATUSOFTHEVITREOUS
s0RESENCEORABSENCEOFLATTICEDEGENERATION
s3TATUSOFTHELENS
s0RESENCEOFHYPOTONYANDCHOROIDALSPROLIFERATIVEVITREORETINOPATHY
and/or significant vitreous hemorrhage
Patient systemic factors such as use of anticoagulant medications can
also be a mitigating factor. Following are some clinical scenarios where
SB might be superior to PPV, and other situations where adding SB to
PPV can increase the success rate.
Clinical settings where scleral buckling alone
is superior
Young phakic patients with a limited retinal detachment, particularly
with holes in lattice and an inferior location, are ideal for scleral
38 | retina times |
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buckling. In these patients, the vitreous is typically not detached, and
segmental or encircling scleral buckling is almost invariably successful
in repairing these detachments with minimal refractive change.11-13
A middle-aged person, typically a phakic myope, who presents with a
posterior vitreous detachment and one or more retinal tears with a subtotal acute retinal detachment, can also be repaired with scleral buckling
alone. The reported single-surgery success rate if the macula is attached
was 97%,14 with an overall success rate of 99% in a second series.15
Retinal detachment due to dialysis is most commonly seen in young
people, and usually the vitreous remains attached centrally. This
detachment is usually amenable to treatment with a segmental
sponge or silicone element with or without encircling buckle, with
a greater than 90% likelihood of stable reattachment noted with
one operation.11,16
Scleral buckling as an adjunct to vitrectomy
PPV is beneficial for repair of pseudophakic retinal detachment,
particularly when the breaks are small, anteriorly located, and problematic to find and treat using indirect ophthalmoscopy. During PPV,
especially with wide-field viewing, these peripheral breaks are often
easily identified.17 PPV alone can be sufficient for the repair of RRD in
APSEUDOPHAKICSETTINGASLONGASTHEPATIENTSVITREOUSISSEPARATEDOR
can be separated far into the periphery.
The issue of vitreous separation arises repeatedly when discussing
whether scleral buckling is necessary in repair of retinal detachment,
as the status of the vitreous is by far the most important variable to
consider. Young patients generally have vitreous that is attached or only
partially separated. When these patients develop RRD, removal of core
vitreous is relatively straightforward. However, separation of the posterior hyaloid and other areas of adherent vitreous in the periphery of
an eye that has very mobile retina can be technically intricate, especially
when concurrent lattice degeneration is present.18
‘The underlying problem with
suggesting that PPV or SB alone
is superior is that RRD is not
a homogenous condition that can
be treated similarly in all cases.’
These eyes have an elevated risk of recurrent detachment, either from
new breaks resulting from contraction of the residual vitreous or from
proliferative vitreoretinopathy (PVR) with residual vitreous serving as
a scaffolding for fibrous proliferation.19 While most pseudophakes with
Continued on page 40
Manfred von Fricken, MD
Retina Group of Washington
Fairfax and Tysons Corner, Virginia
Counterpoint: Most Primary Retinal Detachments
Can Be Repaired With a Vitrectomy
Leo Tolstoy wrote, “Happy families are all alike; every unhappy family
is unhappy in its own way.” Similarly, all successful retinal detachment
repairs resemble one another, but all unsuccessful surgical procedures
are memorable and imperfect in their own way. There is no consensus
among vitreoretinal surgeons on the optimal management of primary
rhegmatogenous retinal detachment (RRD), although a recent
evaluation of peer-reviewed literature suggests that scleral buckling
and primary pars plana vitrectomy (PPV) may yield comparable
success rates.1
Historically, retinal detachment repair has evolved from ignipuncture
to diathermy and dissected scleral beds; from polyethylene tubes to
large encircling elements and bands, segmental and circumferential
sponges, in-office pneumatic retinopexy, and PPVs—with or without
scleral buckles.2-6 We can choose from a wide variety of procedures and
techniques, all of which have merit, precedent, and support in
the literature.
Primary vitrectomy alone for RRD repair has also evolved and gained
support.7-14 Most literature on retinal detachment repair is retrospective. Efforts have been made to perform prospective comparisons
of primary buckles and vitrectomy, although patient selection and
surgeon bias can materially affect these reports.15-18
‘The primary vitrectomy became
the preferred procedure for
many surgeons in the early 1990s
when wide-angle viewing systems
were developed …’
More than 30 years ago, scleral buckle surgery involved hospital stays,
often for several days, bed rest with bilateral patching, positioning,
and pain management. The advent of primary vitrectomy has allowed
this surgery to be done as an outpatient procedure; and the evolution
of minimally invasive small-gauge vitrectomy with 25- and 23-gauge
instrumentation has lessened trauma and significantly reduced patient
discomfort without creating refractive or myopic shifts.
The primary vitrectomy became the preferred procedure for many
surgeons in the early 1990s when wide-angle viewing systems were developed, allowing visualization of the peripheral retina for the first time
without using the indirect ophthalmoscope or a mirrored contact lens.
FWj_[dji[b[Yj_ed07a[o\WYjeh
The scleral buckle is emphatically not obsolete and remains the
procedure of choice in specific settings. It is the preferred procedure
in young patients with an RRD in the absence of a vitreous detachment,
regardless of the RRD’s size or location. These are eyes with chronic
RRD and RPE changes with subretinal bands and subretinal demarcation lines. There is often associated moderate or high myopia and
lattice degeneration with atrophic holes.
‘Older patients with some
pre-existing nuclear sclerosis or
existing cataract and very high
myopes who may need future
cataract surgery are encouraged
to have primary vitrectomy ...’
Management consists of external drainage of usually proteinaceous
subretinal fluid and cryopexy and/or laser to the breaks. The minimal
scleral buckle needed is used to support the breaks, usually a circumferential segmental sponge, but occasionally a #41 encircling band or radial
sponge element. This approach also works for idiopathic or traumatic
inferotemporal dialyses. Likewise, a buckle can be used for select PVR
cases and for some recurrent RRDs, especially with inferior disease or in
patients unable to position postoperatively for gas tamponade.
Some RRDs can be repaired in-office with pneumatic retinopexy,
although patient selection is important. In my practice, all aphakic or
pseudophakic patients presenting with RRD are treated with primary
vitrectomy, and most other retinal detachments are preferentially
approached with PPV, my technique since the early 1990s with the
advent of wide-angle viewing systems.
Since 2005, almost all primary RRDs have been done with small-gauge
instruments, mostly 25-gauge, and occasionally 23-gauge. Phakic eyes
undergoing vitrectomy are faced with the almost certain progression
of nuclear sclerosis; this must be disclosed and discussed with the
patient when obtaining consent and may result in the patient choosing
a primary scleral buckle.
Older patients with some pre-existing nuclear sclerosis or existing
cataract and very high myopes who may need future cataract surgery
are encouraged to have primary vitrectomy, as are patients with:
s0OSTERIORBREAKSASSOCIATEDWITHLATTICEDEGENERATION
s$ENSEVITREOUSHEMORRHAGE
s7AGNER3TICKLERDISEASE
s/THERVITREORETINOPATHIESSUCHASCICATRICIALRETINOPATHYOF
prematurity (ROP)
s#OMBINEDTRACTION22$S
s#OMPLEXRETINOSCHISIS22$
Continued on page 41
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POINT/COUNTERPOINT >>
Drs. Mittra and Ryan, continued from page 38
RRD are older, younger pseudophakes with RRD (patients
younger than 55-60 years old) often have peripheral vitreous
still adherent during PPV when excision is attempted. In these cases, a
scleral buckle encircling the globe is often quite helpful in reducing the
risk of recurrent detachment from either new breaks in the periphery
or PVR arising from areas of residual vitreous attachment.
There are several other RRD repair scenarios in which an SB should be
considered to supplement PPV. One example is eyes with significant
PVR on presentation.20 Support in the inferior quadrants with a buckle
can sometimes prevent recurrent RD.21
Other indications for adding an SB to PPV revolve around the issue of
visualization (especially of the periphery) during vitrectomy. Eyes with
dense peripheral vitreous hemorrhage, phakic patients with marked
cortical spoking, and pseudophakic eyes with peripheral capsular opacification will all have areas of peripheral vitreous that may be difficult to
safely remove. These eyes can benefit from an SB to support the remaining
vitreous should it contract and/or form anterior fibrous proliferation.
Why is scleral buckling falling out of favor?
Significant skill and practice are needed to place a scleral buckle in the
correct location with the desired indentation to support the retinal
breaks and to drain subretinal fluid without complications. Scleral
buckling is very different from microscope-based ophthalmic surgery,
and there appears to be a significant learning curve associated with it.22
Those who train surgeons find that microscope-based surgery is
easier to monitor than indirect ophthalmoscopy, and many fellowship
programs correspondingly allow their trainees to do only a small
number of these cases on their own. Surgeons end up getting trained
predominantly with vitrectomy for RRD and often find themselves
uncomfortable unless the retina is completely flat at the end of the case.
‘Scleral buckling is very different
from microscope-based ophthalmic
surgery, and there appears to be a
significant learning curve associated
with it.’
There are several situations in which scleral buckling is superior to PPV
and others in which it is helpful as an adjunct to PPV. Scleral buckling
still has a role in retinal detachment repair, and it remains an important
skill for retinal surgeons.
References
1. Custodis E. Treatment of retinal detachment by circumscribed diathermal coagulation
and by scleral depression in the area of tear caused by imbedding of a plastic implant
[in German]. Klin Monatsblatter Augenheilkd Augenarztl Fortbild. 1956;129(4):476-495.
2. Schepens CL, Okamura ID, Brockhurst RJ. The scleral buckling procedures. 1. Surgical
techniques and management. Arch Ophthalmol. 1957;58(6):797-811.
3. Machemer R, Buettner H, Norton EW, Parel JM. Vitrectomy: a pars plana approach. Trans
Am Acad Ophthalmol Otolaryngol. 1971;75(4):813-820.
4. Machemer R, Allen AW. Retinal tears 180 degrees and greater. Management with
vitrectomy and intravitreal gas. Arch Ophthalmol. 1976;94(8):1340-1346.
5. Michels RG. Vitrectomy techniques in retinal reattachment surgery. Ophthalmol.
1979;86(4):556-585.
6. Hutton WL, Snyder WB, Vaiser A. Vitrectomy in the treatment of ocular perforating
injuries. Am J Ophthalmol. 1976; 81(6):733-739.
7. Peyman GA, Huamonte FU, Rose M. Management of traumatic retinal detachment with
pars plana vitrectomy, scleral buckling, and gas injection. Acta Ophthalmol (Copenh).
1975; 53(5):731-737.
8. Michels RG. Surgery of retinal detachment with proliferative vitreoretinopathy. Retina.
1984;4(2):63-83.
9. Hanneken AM, Michels RG. Vitrectomy and scleral buckling methods for proliferative
vitreoretinopathy. Ophthalmol. 1988;95(7):865-869.
10. de Bustros S, Michels RG. Surgical treatment of retinal detachments complicated by
proliferative vitreoretinopathy. Am J Ophthalmol. 1984;98(6):694-699.
11. Häring G, Wiechens B. Long-term results after scleral buckling surgery in uncomplicated juvenile retinal detachment without proliferative vitreoretinopathy. Retina.
1998;18(6):501-505.
12. Lincoff H, Kreissig I. Extraocular repeat surgery of retinal detachment. A minimal
approach. Ophthalmol. 1996;103(10):1586-1592.
13. Tillery WV, Lucier AC. Round atrophic holes in lattice degeneration--an important cause
of phakic retinal detachment. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol.
1976;81(3 Pt 1):509-518.
14. Wilkinson CP. Visual results following scleral buckling for retinal detachments sparing
the macula. Retina. 1981;1(2):113-116.
15. Tani P, Robertson DM, Langworthy A. Rhegmatogenous retinal detachment without
macular involvement treated with scleral buckling. Am J Ophthalmol. 1980;90(4):
503-508.
16. Stoffelns BM, Richard G. Is Buckle Surgery Still the State of the Art for Retinal Detachments Due to Retinal Dialysis? J Pediatr Ophthalmol Strabismus. 2010;47(5):281-287.
doi:10.3928/01913913-20091019-10.
17. Campo RV, Sipperley JO, Sneed SR, et al. Pars plana vitrectomy without scleral buckle
for pseudophakic retinal detachments. Ophthalmol. 1999;106(9):1811-1815.
18. Michels RG, Wilkinson CP, Rice TA. Retinal Detachment. St. Louis, MO: Mosby; 1990:16
A failure of vitrectomy for retinal reattachment may not be apparent to
the surgeon for many weeks, whereas a failed scleral buckling operation
is apparent often within days. Those with a cynical view as to why
physicians make choices between procedures would point out that
because vitrectomy reimburses more than SB and can take less time
(and SB is not reimbursed at all when combined with PPV), many are
apt to forego placement of a buckle despite any potential benefit.23
‘Scleral buckling still has a role in
retinal detachment repair, and it
remains an important skill for
retinal surgeons.’
40 | retina times |
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19. Michels RG, Wilkinson CP, Rice TA. Retinal Detachment. St. Louis, MO: Mosby; 1990:1068.
20. Wickham L, Connor M, Aylward GW. Vitrectomy and gas for inferior break retinal
detachments: are the results comparable to vitrectomy, gas, and scleral buckle?
Br J Ophthalmol. 2004;88(11):1376-1379.
21. Alexander P, Ang A, Poulson A, Snead MP. Scleral buckling combined with vitrectomy
for the management of rhegmatogenous retinal detachment associated with inferior
retinal breaks. Eye (Lond). 2008;22(2):200-203.
22. Sagong M, Chang W. Learning curve of the scleral buckling operation: lessons from the
first 97 cases. Ophthalmologica. 2010;224(1):22-29.
23. Ryan EH Jr, Mittra RA. Scleral buckling versus vitrectomy, the continued role for scleral
buckling in the vitrectomy era. Arch Ophthalmol. 2010;128(9):1202-1205
Financial Disclosures
Dr. Mittra – None.
Dr. Ryan – ALCON LABORATORIES, INC: Consultant, Intellectual Property Rights.
Dr. von Fricken, continued from page 39
Patients who present with RRD associated with giant tears
are managed with primary lens-sparing PPV and no scleral
buckle. The anterior vitreous is carefully shaved where it is attached to
the anterior retinal flap, followed by a perfluorocarbon-1000 CS silicone
oil exchange. Not doing a fluid-air exchange reduces retinal slippage and
minimizes the surface area of exposed RPE. This may reduce the severe
PVR historically associated with giant tears.
The silicone oil is removed after several months unless there is proliferation of membranes or PVR in which case the membranes are removed
under silicone oil. Giant tears should be thought of as staged procedures.
Determining a surgical technique
Using a routine encircling element such as a #240 band or #41 band
when performing a small-gauge PPV for RRD is more invasive than
necessary, especially in sutureless surgery. A limbal conjunctival
peritomy may affect future filtering surgery, a point made emphatically
by a glaucoma surgery colleague. An encircling band in a primary
PPV creates an unneeded safety net and may imply to the patient that
“everything that can be done has been done.” However, the original
intent of encircling elements was to create a new ora serrata, preventing
the posterior movement or guttering of subretinal fluid over the
encircling element.
‘Primary vitrectomy for the repair
of retinal detachment is an elegant
and highly effective procedure.’
Vitreous traction is best reduced by carefully shaving or excising the
vitreous base with external scleral depression. This scleral depression can
be done by the surgeon with chandelier illumination, or bimanually with
a skilled assistant depressing 360°. This removes traction from flap tears
and allows careful shaving and debulking of the vitreous base using a
mostly closed port duty cycle and low infusion pressure, even in areas of
detached retina, with minimal risk for forming iatrogenic breaks.
Eyes with very posterior lattice degeneration have the vitreous
debulked over the areas of lattice degeneration, as further anterior
vitreous separation is not physically possible. Using diluted triamcinolone acetonide to identify and better visualize the vitreous base
is advocated by some. Clearly, in the absence of an encircling element
or scleral buckle, it is crucial to perform a meticulous peripheral
vitrectomy and to ensure that all breaks are identified and treated.
A benefit of primary PPV is that the surgeon can remove all vitreous
opacities, deal with opacified lens capsules, and address macular
puckers. It is possible to peel epiretinal membrane (ERM) and inner
limiting membrane (ILM) in cases where there is substantial macular
distortion from puckers or mild PVR involving the macula. Fluid-fluid
exchange followed by fluid-air exchange removes viscous subretinal
fluid. It is rare to have chronic and persistent submacular fluid in
vitrectomized eyes, which can occur in macula-off RRDs repaired with
a scleral buckle.
Subretinal fluid is removed with a soft-tip extrusion cannula through
a small internal retinotomy or through existing breaks. Some surgeons
effectively use perfluorocarbon (PFO) liquids in primary RRD, while
others tend to reserve PFO in cases of giant retinal tears or select
diabetic and PVR cases. The retinotomy and all breaks are treated with
endolaser or indirect ophthalmoscopic laser photocoagulation. Gas
tamponade is usually 20% SF6 and slightly expansile SF6 for inferior
RRDs. C3F8 is probably not necessary in primary RRDs.
Postoperative positioning and compliance are crucial for the success
of primary PPV, and the importance of patient education can’t be
overemphasized. There is a role for scleral buckle in patients who have
physical disability and are unable to position, although primarily with
inferior retinal detachments. In macula-off RRDs, the patients remain
supine in the recovery room or are positioned with the temporal retina
in a down or dependent position to avoid creating a macular fold.
All patients leave the operating room with a wristband identifying the
intraocular gas bubble.
‘We are all products of our training,
but we must continue to evolve and
mature as surgeons and apply new
surgical developments.’
Our retinal community has been fortunate to have had input from
extremely talented and innovative surgeons and the commitment of
manufacturers. This has led to the development of vastly improved
vitrectomy platforms, more rigid small-gauge cutters with improved
fluidics, superior endoilluminators, and wide-angle viewing systems.
Primary vitrectomy for the repair of retinal detachment is an elegant
and highly effective procedure. While there will always be a role for the
scleral buckle in select cases, my preference is to approach RRD with
vitrectomy alone, except in the cases described above. Arguably, this
remains a complex and controversial topic, and there is no real “right”
or “wrong” way to fix a detached retina.
All surgical approaches should be driven by what is in that patient’s
best interest and what best fits the particular circumstances of the
patient. The 2012 ASRS Preferences and Trends (PAT) survey shows
trends toward more vitrectomies or vitrectomies with scleral buckle
and fewer primary scleral buckles.19 I look forward to future surveys
and believe that vitrectomy will continue to be embraced and widely
adopted.
We are all products of our training, but we must continue to evolve
and mature as surgeons and apply new surgical developments. The
principle of surgical evolution has always been to make procedures less
invasive, safer, and with quicker recovery and good outcomes.
References
1. Schwartz SG, Flynn HW. Primary retinal detachment: scleral buckle or pars plana
vitrectomy? Curr Opin Ophthalmol. 2006;17(3):245-250.
2. Gonin J. The treatment of detached retina by sealing the retinal tears. Arch Ophthalmol.
1930;4(5):621-625.
3. Custodis E. Bedeutet die plombenaufnahung auf die sclera einen fortschritt in der
operatven behandlung der netzhautablosung. Ber Dtsch Ophthalmol Ges. 1953;58:102.
4. Schepens CL. Scleral buckling procedures. Trans Am Acad Ophthalmol Otolaryngol.
1958;(62)2:206-218.
5. Schepens CL. Symposium: Present Status of Retinal Detachment Surgery. Scleral Buckling with Circling Element. Trans Am Acad Ophthalmol Otolaryngol. 1964;68:959-979.
Continued on page 55
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Fall 2012
| retina times | 41
THE KOL CORNER >>
Marc J. Spirn, MD
Carl D. Regillo, MD
Section Co-Editor
Section Editor
Wet AMD: The Changing Landscape
Since 2005, when intravitreal bevacizumab was first recognized as a treatment for neovascular
age-related macular degeneration (AMD), patient outcomes have been greatly enhanced. Visual
acuity gains with bevacizumab and ranibizumab were typically far better than with thermal laser,
photodynamic therapy (PDT), and pegaptanib.
Yet after several years and hundreds of
thousands of patients treated, several
questions remained:
J^_i?iik[ÊiA[oEf_d_edB[WZ[hi
David Boyer, MD
s7ERERANIBIZUMABAND
bevacizumab equivalent?
s(OWOFTENSHOULDPATIENTSBETREATED
and/or followed?
s7HATISTHEBESTWAYTOTREAT
suboptimal responders?
s7HATWOULDBETHENEXTBLOCKBUSTER
pharmacotherapy for neovascular AMD?
Omesh P. Gupta,
MD, MBA
Retina-Vitreous Associates
Medical Group
Los Angeles, California
Mid Atlantic Retina
Philadelphia, Pennsylvania
In the last year, new light has been shed
on several of these questions. The CATT
trial showed that with possible small-scale
differences, bevacizumab and ranibizumab
are largely equivalent. Aflibercept, which
inhibits placental growth factor in addition to
VEGF-A, was introduced in November 2011
with much fanfare. So now, instead of 2 highly
effective treatment options, we have 3.
David M. Brown, MD
Retina Consultants of Houston
Houston, Texas
Fall 2012
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I would use a treat-and-extend protocol. If
there is continued fluid on OCT, I would
switch to ranibizumab or aflibercept to dry
the OCT and continue to treat until dry. If an
RPE detachment were also present, I would
probably favor aflibercept.
Omesh Gupta: This patient would be
treated as most patients in my practice, with
anti-VEGF agents. I would initially treat
monthly until there are no signs of exudation.
Treatment regimen is a continually evolving
issue, and is often tailored to individual
needs. Patients with a very active lesion, a
fellow eye with a disciform scar, or monocular
vision for any other reason are treated much
more aggressively.
As the HARBOR trial comparing high-dose
(2.0 mg) to standard-dose Lucentis (0.5mg)
(Genentech, South San Francisco, CA), comes
to a close and with the drug pipeline full of
exciting new therapies, the treatment choices
for neovascular AMD will likely become even
more complex and effective. In this environment, we sought several key opinion leaders to
discuss how they are treating wet AMD.
Patients with minimally active lesions
or a pigment epithelial detachment as the
only remaining sign of exudation are
treated less aggressively. In these patients,
the treatment interval might be gradually
extended or, in some cases, intravitreal
injections might be stopped until signs of
exudation recur.
An 86-year-old woman presents
with new-onset, predominantly
classic, subfoveal neovascular
AMD and visual acuity of 20/100
in her right eye. What treatment
and regimen would you use for
this patient?
David Brown: My preferred treatment
would be induction with either Eylea
(Regeneron Pharmaceuticals, Tarrytown, NY)
or Lucentis for 3 months. If dry at 3 months,
we would discuss the option of very close
observation—particularly if the other eye is
relatively good, as 20% of patients are lucky
enough to dry out with induction and not
require ongoing injections.
David Boyer: I would start with an
anti-VEGF agent. If there is any doubt on
insurance status, I would use bevacizumab
and obtain co-pay assistance forms to be filled
out. I would see the patient in one month and
42 | retina times |
retreat. If she is dry or has had a significant
improvement in OCT, I would continue the
bevacizumab and schedule the next visit
4-5 weeks later.
If there is any fluid at 3 months, I would
continue monthly therapy until dry. Should
the fluid ever recur with close observation, I
would use a treat-and-extend regimen—never
extending more than 2 weeks at a time.
I’m more conservative on the extension in
monocular patients, typically not going more
than 6 weeks.
For a patient with a Medicare Advantage Plan
(HMO) that discourages Eylea or Lucentis use,
I would typically recommend Avastin (Genentech, South San Francisco, CA) monthly for
3 months with very cautious extension, as the
CATT 2-year data imply that very few patients
dry up on monthly Avastin, and PRN Avastin
therapy is detrimental.
After 6 monthly intravitreal
bevacizumab injections, a
67-year-old man with neovascular AMD has decreased, but
persistent, subretinal fluid on
OCT and visual acuity of
20/70. Do you change your
treatment regimen?
David Boyer: I assume the patient has
received monthly injections of bevacizumab.
At this point, I would switch the drug to
ranibizumab or aflibercept and have the
patient return in 10 days. If the OCT shows a
response, I would reevaluate 4 weeks after the
last injection and continue monthly injections
with the hope of eventually extending the
treatment intervals.
If there has been no response on the OCT
at 10 days, I would have to assume this
is a non-VEGF-related disease such as
polypoidal and would re-image the
patient with indocyanine green (ICG),
autofluorescence and intravenous fluorescein
angiography (IVFA), though aflibercept
may work on polypoidal disease.
Omesh Gupta: With other very good
options available, my threshold to consider
other treatments is very low. I may not change
treatment in every case in which there is
persistent subretinal fluid at 6 months of
monotherapy. At this time, I would consider
switching to intravitreal ranibizumab.
While bevacizumab and ranibizumab are
similar, differences in response have been well
described. In time, as aflibercept eventually
is covered by more insurance carriers, it will
become a more compelling option. I would
also consider using photodynamic therapy in
combination therapy.
David Brown: I would prefer to switch the
patient to Eylea or Lucentis if the insurance
coverage allows it. If this is not an option, I
would continue monthly therapy, as many
of these patients with subretinal fluid (SRF)
maintain VA. I would also make sure the
patient doesn’t have a thickened choroid—
indicative of central serous retinopathy
(CSR)—or polyps on ICG angiography. If
either CSR or idiopathic polypoidal choroidopathy (IPC) is suspected, I would treat
with concomitant photodynamic therapy.
reported a significantly greater number
of bevacizumab patients suffered serious
systemic adverse events.
David Brown: As CATT 2-year data show
that Avastin is not as durable as Lucentis,
I treat more aggressively (more injections)
in patients who are on Avastin. I am also
more reticent to use Avastin in patients with
systemic heart disease or CVA, given the
anti-VEGF systemic suppression shown in
IVAN. The anti-VEGF suppression seen with
intravitreal use shown in IVAN was recently
added to the European Avastin warning label.
How have the CATT and IVAN
trials affected your prescribing
of bevacizumab and ranibizumab? Have they altered your
daily practice? If so, how?
David Boyer: The CATT trial made me
realize that a PRN treatment of ranibizumab
can result in good vision, but the patient
needs to be followed monthly. I also felt
better that I was not compromising vision
by using bevacizumab.
A 72-year-old man with
new-onset neovascular AMD and
decreased visual acuity asks to
be treated with aflibercept. You
agree and begin treatment. After
the third injection, despite a
significant improvement in
subretinal fluid, mild subretinal
fluid persists. You inject him
again. When would you ask
the patient to return for repeat
evaluation? Under what circumstances would you extend your
treatment interval?
Because I tend to treat and extend, I would
probably favor ranibizumab due to its
superior drying effect. The CATT and IVAN
trials did not allay my concern for systemic
safety, though the biologic mechanism for the
increase signal is not apparent.
Omesh Gupta: While a significant amount
of information can still be extracted from
these data sets, the 2-year results of the CATT
study have changed my practice patterns.
This study demonstrated that monthly dosing
produced slightly more vision gain than an
as-needed regimen. Treating patients with
individualized protocol, such as treat and
extend, has become a popular approach in
my practice.
David Boyer: I treat until dry, so I would
see the patient in 4 weeks. I have found that
there are patients who have persistence of
subretinal fluid despite monthly injections.
Though the studies showed injections of
aflibercept given every 2 months (after
3 loading doses) yielded the same visual
results as ranibizumab or aflibercept given
monthly, I treat until dry if possible. I extend
my interval only when the OCT is dry. If it has
taken a long time to dry the patient out,
I proceed very slowly.
While I still attempt to individualize care
based on a number of factors, I tend to
be a bit more conservative with extending
follow-up. In fact, in some “high-risk” patients
as described above, I may recommend
monthly dosing.
However, in the CATT study, the final visual
results were also similar in all treatment
groups, regardless of dosing frequency. As
more data are obtained, my treatment
regimen will also evolve.
Omesh Gupta: While there are a lot of
factors to consider, I would still continue with
Eylea. After 3 monthly injections, it has been
proposed that Eylea be dosed every 2 months.
For all patients I treat with Eylea, I always
discuss this unique treatment protocol before
initiating treatment. At this point, similar
efficacy was demonstrated with every2-month dosing compared with monthly
dosing. Again, I would continue with Eylea q2
month dosing.
We must be careful in interpreting results
regarding systemic adverse events (SAEs).
The CATT and IVAN studies were neither
designed nor powered to evaluate SAEs.
In the CATT trial, more events occurred
in the patient group that received fewer
injections, which is not the typical doseresponse relationship.
If the subretinal improvement and/or visual
acuity do not continue to improve with
subsequent injections, I would consider
bevacizumab, ranibizumab, or photodynamic
therapy. I would also discuss surgical options
for patients with a concurrent epiretinal
membrane or vitreomacular traction.
The IVAN trial observed more arteriothromboembolic events or heart failure
with ranibizumab than with bevacizumab.
On the other hand, the CATT study
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Fall 2012
| retina times | 43
THE KOL CORNER >>
Omesh Gupta: Photodynamic therapy
is the only option I still use—typically in
patients in whom I want to limit the injection
burden. There are a couple of scenarios where
PDT has worked really well.
David Brown: I would treat monthly
until dry. In my experience, approximately
30%-40% of Eylea patients need dosing more
frequently than q8 weeks. If all intraretinal
fluid is gone but SRF persists, I really look
at the EDI-OCT and ICG. If the patient
has evidence of a thickened choroid (CSR),
hyperpermeability (CSR) or polyps (IPC),
I recommend concomitant PDT therapy.
One patient was receiving monthly dosing and
the treatment interval could not be extended
without an exudative recurrence. She lived a
significant distance from our nearest office
and was inquiring about other options. After
one round of half-fluence PDT, I was able to
stabilize her treatment interval at 2-3 months.
I may also use PDT in patients who refuse
injections or are “high-risk.”
Are there instances when you
consider therapies other than
bevacizumab, ranibizumab,
and aflibercept when treating
neovascular AMD, such as
pegaptanib, focal choroidal laser,
or PDT?
David Brown: As mentioned, masquerade
syndromes of CSR and IPC should be considered, particularly in patients with persistent
fluid despite monthly therapy; if present, they
should be treated with PDT. However, I would
caution against using PDT if the choroid is
atrophic as determined by EDI-OCT, as PDT
causes choroidal hypoperfusion, which may
lead to decreased VA in these eyes.
David Boyer: I still use PDT with
anti-VEGF in patients with extrafoveal
choroidal neovascularization (CNV) or
growing peripapillary CNV lesions. I also
treat patients with PDT and anti-VEGF for
reactivation of previously quiescent scars
that begin to activate on the margin (usually
in the better eye of the patient) with fluid
and/or hemorrhage.
I occasionally recommend Macular
Photocoagulation Study (MPS)-style laser
for extrafoveal and peripapillary lesions
if the lesions require ongoing monthly
injections. If the patient is undergoing
chemotherapy for colon cancer, I sometimes
suggest that the oncologist consider systemic
Avastin or Zaltrap (Sanofi-Aventis US, LLC,
Bridgewater, NJ; and Regeneron Pharma-
I rarely use focal choroidal laser, but would if
the lesion were extrafoveal and well demarcated (mostly non-AMD patients). I have not
used the LEVEL trial results very much and
can think of only 1 or 2 patients I converted
to Macugen (Eyetech, Inc, Cedar Knolls, NJ)
after a stroke when I discussed the potential
risks of an additional stroke.
ceuticals, Inc, Tarrytown, NY) as part
of the regimen, as this will control the
AMD process without the need for ongoing
intravitreal injections.
Financial Disclosures
Dr. Regillo – GENENTECH: Consultant, Investigator, Speaker,
Grants, Honoraria; REGENERON PHARMACEUTICALS,
INC: Consultant, Investigator, Speaker, Grants, Honoraria;
GLAXOSMITHKLINE: Consultant, Investigator, Grants,
Honoraria; OPHTHOTECH CORPORATION: Investigator,
Grants; NEOVISTA, INC: Investigator, Grants; SECOND
SIGHT: Investigator, Grants; ACT: Investigator, Grants; AMO:
Advisory Board, Consultant, Honoraria; ALCON LABORATORIES, INC: Consultant, Investigator, Grants, Honoraria;
ALLERGAN, INC: Consultant, Investigator, Grants, Honoraria.
Dr. Spirn – None.
:h$8eo[h – ALCON LABORATORIES, INC: Advisory Board,
Consultant, Investigator, Speaker, Grants, Honoraria;
ALLERGAN, INC: Advisory Board, Consultant, Investigator,
Speaker, Grants, Honoraria; ALLEGRO OPHTHALMICS:
Advisory Board, Stockholder, Honoraria; GENENTECH:
Consultant, Investigator, Speaker, Grants, Honoraria;
REGENERON PHARMACEUTICALS, INC: Consultant,
Investigator, Grants, Honoraria; iCo THERAPEUTICS INC:
Consultant, Investigator, No Compensation Received;
GLAXOSMITHKLINE: Consultant, Honoraria; NOVARTIS
PHARMACEUTICALS CORPORATION: Consultant, Investigator,
Grants, Honoraria; BAYER HEALTHCARE: Consultant,
Honoraria; QUARK PHARMACEUTICALS, INC:
Investigator, Grants.
:h$=kfjW – None.
Dr. Brown – GENENTECH/ROCHE: Advisory Board,
Consultant, Investigator, Grants, Honoraria; REGENERON
PHARMACEUTICALS, INC: Advisory Board, Consultant,
Investigator, Grants, Honoraria; ALLERGAN, INC: Advisory
Board, Consultant, Investigator, Grants, Honoraria; ALCON
LABORATORIES, INC: Advisory Board, Consultant,
Investigator, Grants, Honoraria.
RETINA PRACTICE PEARLS >>
‘Follow the 5-year plan: At
‘Gratitude is a memory of
the end of 5 years in your
the heart.’’
—Credited to Jean Baptiste Massieu (1772-1846),
practice, you and your spouse
pioneering deaf educator
Submitted by Suber Huang, MD, MBA
or significant other should vote
on whether to stay or leave. One
vote to leave means you both
‘The things you do for yourself
leave and find a new practice
are gone when you are gone,
location. I have shared this
advice with all of my fellows over but the things you do for others
remain as your legacy.’
the last 25 years, and Judy and
—Credited to Kalu Kalu, Professor of Political Science,
I both firmly believe in it.’
Auburn University Montgomery
Submitted by Suber Huang, MD, MBA
—Submitted by Trexler Topping, MD;
credited to his wife, Judy
44 | retina times |
Fall 2012
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‘Learn and be accountable for
your mistakes. Try not to make
the same mistake twice.’
—Submitted by Paul E. Tornambe, MD
Send us your Retina Practice Pearls
Have a Retina Practice Pearl to share? Please
send it to [email protected], noting
whether the quote is your own; if it is, we
will give you full attribution. If the quote is
attributable to someone else, please specify
the originator. We will credit the source and
acknowledge you for submitting the quote.
BLOCK TIME >>
Sunir J. Garg, MD
Mitchell S. Fineman, MD
Section Co-Editor
Section Co-Editor
PA R T 2
How Has the Retina Subspecialty Changed
Since Vitrectomy?
In the 30th Anniversary Retina Times, Block Time asked 6 veteran retina educators how the
retina subspecialty has progressed from its inception in the 1960s and 1970s. Part 2 of this series
explores the evolution in treatment of diabetic patients, as well as how vitrectomy has changed
the practice of retina.
Thomas Aaberg Sr,
MD, MSPH
Jay Federman, MD
Professor of
Ophthalmology
Wills Eye Institute
Philadelphia, Pennsylvania
Former Chair, Department
of Ophthalmology
Emory University
Atlanta, Georgia
What happened to diabetic patients
in the pre-vitrectomy era?
allowed us to manage the most severe
complications of diabetic retinopathy.
Lov Sarin: They often did poorly. Prior
to vitrectomy, we had contact lens laser, but
pars plana vitrectomy (PPV) was a boon for
diabetic patients. Panretinal photocoagulation
(PRP) became accepted around the time we
started using vitrectomy routinely, so both
technologies developed together.
Jay Federman: Xenon arc photocoagulation (Meyer Schwickerath, MD) and then
laser photocoagulation (Frank L’Esperance,
MD) led the way both in Europe and the
US to cause regression of the proliferative
component. But even then, traction RDs could
be managed only with large buckles and 360°
scleral resections and infoldings.
Thomas Aaberg Sr: We were using PRP
and focal ablative laser for neovascularization
elsewhere (NVE), but little was done for
diabetic cystoid macular edema until after
the ETDRS trial was completed.
Gary Abrams, MD
Lov Sarin, MD
Professor of Ophthalmology
Former Chair
Kresge Eye Institute
Wayne State University
Detroit, Michigan
Professor of Ophthalmology
Wills Eye Institute
Philadelphia, Pennsylvania
William Benson, MD
William Tasman, MD
Former Director
The Retina Service
Wills Eye Institute
Philadelphia,
Pennsylvania
Professor and Emeritus
Chairman
Wills Eye Institute
and Jefferson
Medical College
Philadelphia, Pennsylvania
‘In the pre-vitrectomy
era, if the PRP didn’t
contain the proliferative
retinopathy, diabetic
patients would get
horrible traction RDs or
a vitreous hemorrhage
and go blind.’
—William Benson, MD
Gary Abrams: If a traction retinal detachment (TRD) wouldn’t settle with a scleral
buckle (SB) or scleral shortening procedure,
there was really nothing to do. In the early
1970s, PRP was introduced only shortly before
vitrectomy; both of these major advances
46 | retina times |
Fall 2012
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William Tasman: What happened before
vitrectomy? There were diabetic traction
detachments, some of which we did cure,
miraculously enough, with scleral buckles.
Before scleral buckling, diabetic retinopathy
was treated with all kinds of witchcraft. For
example, some patients were put on rhubarb
to treat their vitreous hemorrhages. Vitrectomy was a real blessing—one of the major
advances of the 20th century.
William Benson: In the pre-vitrectomy
era, if the PRP didn’t contain the proliferative
retinopathy, diabetic patients would get
horrible traction RDs or a vitreous hemorrhage and go blind.
When vitrectomy was introduced, did
retina specialists think it was a major
advance, or simply another fad?
Lov Sarin: Until Robert Machemer invented a
closed system to remove vitreous, a lot of people
thought you should never touch the vitreous, so
all we had were buckles. Can you imagine how
difficult it is to find a hole in a bullous RD even
with the indirect ophthalmoscope? PPV made
life easier and less stressful for these types of
cases, and also had a better success rate.
Thomas Aaberg Sr: Some thought it was
heresy to interfere with the anatomic structure
of the vitreous, although “open-sky” vitrectomy
through the limbus had been used for several
years and localized vitreous “bands” had been
severed (in part) with pars plana insertion
of scissors or forceps. However, the advent of
closed-eye mechanical pars plana vitrectomy
made believers of most retina specialists.
Jay Federman: Most felt vitrectomy was a
major advance, as it was the most efficient way
to manage nonclearing vitreous hemorrhage,
but that it was a very aggressive procedure
fraught with potential complications and
performed by only a few retina specialists.
Gary Abrams: At first I don’t think
everybody realized the importance of the
advance. Robert Machemer said that Ron
Michaels was the first fellow at Miami to
truly grasp the importance of the procedure
and to make vitrectomy his main fellowship
objective. I think Robert had been doing
vitrectomies for about 3 years by the time Ron
started his fellowship.
‘Until Robert Machemer
invented a closed
system to remove
vitreous, a lot of
people thought you
should never touch
the vitreous, so all we
had were buckles.’
—Lov Sarin, MD
I was a first-year resident in the fall of 1973 with
Tom Aaberg in Milwaukee. Interestingly, the
fellow let me scrub on all of the vitrectomies
during my 2-month retina rotation because he
wanted to scrub on all the scleral buckles. I think
that is a comment on the attitude at that time.
William Tasman: It was obvious to me that
vitrectomy was a major advance, and we got
in on this very early because Dr. Machemer
was generous enough to spread his knowledge
around the world. There was a real learning
curve when you started to do vitrectomy,
which can be true for any operation.
William Benson: I think most people
recognized that vitrectomy was a great thing.
Initially when people started doing vitrectomies,
some ophthalmologists thought, “So what? You
of long-acting gases (Stanley Chang), and
perfluorocarbon liquids (Stanley Chang,
separately and simultaneously Gholam
Peyman), and more creative instrumentation,
the debate of scleral buckle vs vitrectomy or
combined procedures became more prominent
in the early 2000s. Although some of us
used vitrectomy a little earlier for non-PVR
detachments, I think this is relatively new
thinking in the past decade.
operate and remove the blood, but they will just
bleed again,” and people didn’t initially realize
that once you took the traction off the neovascularization it often regressed. Some of the patients
did re-bleed, but many did not.
When did vitrectomy become a
regular surgical option for RD repair?
Lov Sarin: Initially, PPV was used for cases
with proliferative vitreoretinopathy (PVR).
There was a movement toward vitrectomy
because it was easier to find the breaks,
especially in bullous RD. PPV also reduced
how often we used cryo, which was starting to
be recognized as a contributor to PVR. Once
people realized they could find breaks during
vitrectomy, it began to be used even more for
routine RD repairs.
‘PPV was used for PVR
repair in the early to
mid-1970s, but success
rates were poor until
the intraocular argon
laser was developed in
the early 1980s …’
With buckles, we had to find all the holes, and
in many cases, there could be holes anteriorly,
posteriorly, etc—and all had to be identified
and supported. During PPV, all we had to do
was remove the gel and do 360° laser. PPV
increased success and made life less stressful.
—Thomas Aaberg Sr, MD
Thomas Aaberg Sr: PPV was used for
PVR repair in the early to mid-1970s, but
success rates were poor until the intraocular
argon laser was developed in the early 1980s,
as xenon photocoagulation could not be readily employed in an air-filled eye.
Gary Abrams: For the first 15 years,
vitrectomy was used only for complex retinal
detachments and never for primary, uncomplicated detachments. Rich Escoffery and the group
in St. Louis presented their series of primary
detachments managed with vitrectomy without
an SB at the Vail Vitrectomy Meeting, and the
paper was published in the American Journal
of Ophthalmology in 1985.1 The presentation
and paper were not well-received initially, and
vitrectomy for primary retinal detachment did
not become common until the mid-1990s.
Jay Federman: When I completed my
retinal fellowship at the Retina Service of
the Wills Eye Hospital in 1971, all the retina
surgeons only resected scleral beds, creating
buckles, and used diathermy with scleral/
transchoroidal drainage. The attendings were all
scleral buckle-trained and vitrectomy did not
exist. In 1972, I started to do vitrectomy at Wills,
mainly for nonclearing vitreous hemorrhage,
traction RDs, recurrent RDs with PVR, retained
lens material and vitreous incarceration after
cataract surgery, and endophthalmitis.
The report by Bartz-Schmidt, et al in the British
Journal of Ophthalmology in 19962 that showed
excellent results in pseudophakic RDs was
important; vitrectomy gradually became the
most common technique for pseudophakic
detachments after that. From 1997 to 2007,
according to the Medicare database, vitrectomy
with or without SB increased 72%, while SB
without vitrectomy decreased by 69%.3
For complicated RDs, the vitrectomy was
usually combined with a buckling procedure
with a silicone plate, band, or sponge and cryo.
We did not have the laser delivery systems
of today, so if a posterior lesion needed
treatment, we used external transscleral cryo;
if you could not reach the posterior problem,
you used internal cryo. This was a challenge.
William Tasman: Vitrectomy became a
regular part of retinal detachment repair in the
1980s. There were other techniques that came
along in the interim, like pneumoretinopexy,
which is obviously still done. But vitrectomy
matured and was more and more accepted.
Today it seems to be the most popular
procedure—even for primary detachments.
In the late 1970s and 1980s as the viewing
systems, instruments, and techniques
improved, we began to find more uses where
vitrectomy was beneficial, such as for giant
tears and macular puckers. In the 1980s and
1990s as more retina specialists were trained
in vitrectomy, and with the development
William Benson: I stopped doing surgery
in 2000, but we were still doing primary
buckles. The real breakthrough was pneumatic
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BLOCK TIME >>
long-acting gas, silicone oil, retinectomy
techniques, and perfluorcarbon liquids. We
started doing vitrectomy for giant tears early,
but we couldn’t unfold them with the patient
in a supine position.
retinopexy. At first, I was afraid that putting
gas into the vitreous would increase the
incidence of PVR, and then you wouldn’t
be able to fix the detachment with a buckle.
But when I saw the results of a collaborative
trial indicating that even if pneumatic failed,
you still would be able to fix the RDs at the
accustomed rate, I became somebody who
really enjoyed doing pneumatics.
‘The introduction
of perfluorocarbon
liquids took giant-tear
management out of
the medical center and
into the community.’
In the early days, which cases
underwent vitrectomy?
Lov Sarin: Ninety percent of the cases were
vitreous hemorrhage (VH) due to diabetes.
We did some complicated PVR detachments as
well. However, some people got a little carried
away with vitrectomy and spent 90 minutes
fixing an RD with PPV, when a number of
those cases could be fixed in 10 minutes with
a buckle.
—Gary Abrams, MD
We used a Stryker table modified to make
the patient prone following vitrectomy, then
unfolded the giant tear with a prone fluid-air
exchange (with the surgeon on the floor,
looking up at the prone patient). It was very
difficult and fraught with potential complications and failure.
Jay Federman: As mentioned, nonclearing
vitreous hemorrhage, traction RD, and PVR
RD followed. The development of intraocular
lenses (IOLs) and phacoemulsification was just
in its infancy and most cataract procedures
were open-sky; vitrectomy proved most effective
in managing many complications resulting
from these anterior segment procedures.
Vitrectomy was also performed very early for
endophthalmitis.
I remember when Kim Frumar from Sydney,
Australia, who had trained with Peter Leaver
at Moorfields Eye Hospital in the United
Kingdom, came through Milwaukee in 1984;
he drew me a diagram on a dinner napkin on
how to manage a giant tear with silicone oil
with the patient in a supine position. On
July 4, 1984, I repaired a 270° giant tear with
the technique on a young woman and never
did another prone fluid-air exchange for a
giant tear again.
‘For complicated RDs
[in the early 1970s],
the vitrectomy was
usually combined with a
buckling procedure with
a silicone plate, band,
or sponge and cryo.’
It was really exhilarating to be able to let go of
that terrible technique. Many of us used fluidsilicone oil exchange to unfold giant tears until
perfluorocarbon liquids were introduced. It
was a good technique that few people outside
of a few major centers did, so I got to do a
lot of giant tears in the mid to late 1980s. The
introduction of perfluorocarbon liquids took
giant-tear management out of the medical
center and into the community. —Jay Federman, MD
Thomas Aaberg Sr: I began doing
closed-eye pars plana mechanical vitrectomy
in 1970, and the vast majority of the early
series that I, as well as others, reported were
for eyes with vitreous opacification, most
commonly hemorrhage.
William Tasman: The first cases were
diabetic vitreous hemorrhages, especially the
long-standing ones that had so-called yellow
ochre membranes. These lent themselves
beautifully to vitrectomy, as these were
patients who might not have been able to see
for years, and then you took this opacification
out of the vitreous cavity and their sight was
restored. It was not one of the more difficult
vitrectomies—in fact, it wasn’t difficult at
all because most of the time the vitreous
Gary Abrams: Diabetic vitreous hemorrhage
was the most common indication. Trauma
was also an early indication. We operated
on complex detachments even early in the
vitrectomy era, but the success rate was not
good until advances of air pump, endolaser,
48 | retina times |
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was detached, and all you had to do was get
through the yellow ochre membranes so you
could identify the retina, and then just eat up
the vitreous.
Following that, of course, vitrectomy
expanded into difficult retinal detachments—
those with PVR—and I think it was helpful in
traumatic cases, especially perforating injuries
where the missile might have gone in and out
of the eye. It became helpful there because we
could reach exit sites in the posterior pole that
were inaccessible prior to vitrectomy. Giant
tears were also important; we found we could
do much better with a vitrectomy than we
had with all of the earlier procedures.
William Benson: Diabetic hemorrhages
and giant tears are the 2 I can think of right
now. I was there when Machemer unrolled
the retina—he took a needle, unrolled the
retina, and the giant tear rolled over. That was
a miracle.
How has training of your fellows
changed since the 1970s?
Lov Sarin: Certain aspects have been the
same throughout. Some of the fellows were
exceptionally talented. The fellowship went
from 1 to 2 years, which was a big change.
At one point, we had 6 or 7 fellows per year.
We got a lot of complaints about how many
specialists we as a retina community were
training, so we went to 2 or 3 for a 1-year
fellowship. Then our volume and the amount
to learn became so great that the fellowship
went to 2 years.
Thomas Aaberg Sr: Retina fellows now
get great experience with office intravitreal
injections, OCT and real-time ultrasonography,
photocoagulation, and vitrectomy, but their
training in scleral buckling is often deficient.
Gary Abrams: Until the 1990s, most
fellowships lasted only 1 year and that was
plenty of time to learn what was necessary to
do vitrectomy and repair retinal detachments
with scleral buckles. However, as vitrectomy
became more complex and we were doing
more technically challenging procedures, it
was apparent that clinical fellowships should
be 2 years.
My approach to fellowship training has not
changed much over the years. I firmly believe
that fellows learn best by doing, so I have
always allowed fellows to do what they can
safely do. I closely supervise them and let
them continue until I detect that they are
not making progress or are struggling with
technique. At that point, I usually take over,
but try to let them back in at some later
point in the case so they will feel a sense of
accomplishment at the end of the case.
With each new advance, we usually get the
fellows involved relatively early with the
process. Be it use of perfluorcarbon liquids,
membrane peeling, retinectomy, or internal
limiting membrane peeling, once we as teachers became comfortable with a technique,
we allowed the fellow to begin doing it. We
are doing different techniques than many
years ago, but I don’t think the approach to
training has changed much. Fellows now
have the opportunity for early training with
computerized surgical simulators, but it is still
a specialty that requires direct apprenticeship
with great surgeons to gain skill.
‘The first [vitrectomy]
cases were diabetic
vitreous hemorrhages,
especially the longstanding ones that had
so-called yellow ochre
membranes.’
—William Tasman, MD
Jay Federman: The fellowship has
evolved with time, mostly as the technology
improved. Vitrectomy machines improved
with the development of full-function units,
smaller-diameter instruments resulted in
smaller incisions, viewing systems improved,
infusion fluids have been made safer, operating
time is much shorter. Other improvements
include use of silicone oil and long-acting
gases, vitreous and membrane stains, more
varied disposable instruments, and improved
viewing systems.
day—it was difficult. The fellows also had to
show up to make rounds on the people in the
hospital for 4 days post-op. They had to make
rounds on them every day before surgery. Now
with surgery centers, 4 cases can be done by
10:00 AM. Fellows used to work a lot longer
hours; the current fellows that I see are going
home some days at 1:00 or 2:00 PM.
William Tasman: The big change was
switching from buckles to vitrectomy. Over
the last 10-15 years, training of fellows has
accentuated vitrectomy. Fellows today don’t
have to know how to do an old-time scleral
buckle—and their idea of a buckle compared
with mine can be very different. Sometimes a
buckle is referred to as just a band around the
eye, and I think that’s pretty common today.
Of course, buckles were much more involved
when they were the procedure of choice.
References
1. Escoffery RF,Olk RJ,Grand MG,Boniuk I (1985) Vitrectomy
withoutscleral buckling for primary rhegmatogenous
retinal detachment.Am J Ophthalmol 99:275–281Escoffery
RF,Olk RJ,Grand MG,Boniuk I (1985) Vitrectomy withoutscleral buckling for primary rhegmatogenous retinal
detachment.Am J Ophthalmol 99:275–2811. Escoffery RF,
Olk RJ, Grand MG, Boniuk I. Vitrectomy without scleral
buckling for primary rhegmatogenous retinal detachment.
Am J Ophthalmol. 1985;99(3):275-281.
2. Bartz-Schmidt KU, Kirchhof B, Heimann K. Br J Ophthalmol.
1996;80:4 346-349. doi:10.1136/bjo.80.4.346.
The emphasis now is on vitrectomy training,
and rightly so. I think the surgical results
speak for themselves and that the training
changes as the field evolves. Fellows have
moved to operating with the microscope
rather than simply operating on the outside
of the eye. The fellows become proficient in
vitrectomy, learn how to peel membranes, and
do not have to use a buckle as the primary
method of attack in many cases.
3. Ramulu PY, Do DV, Corcoran KJ, Corcoran SL, Robin AL.
Use of retinal procedures in Medicare beneficiaries from
1997 to 2007. Arch Ophthalmol. 2010;128(10):1335-1340.
William Benson: Training fellows changed
because as new techniques were developed, we
added them to their training. I remember Lov
Sarin telling me that doing 4 cases was a really
busy day. Part of the problem we had was with
general anesthesia and the turnover time was
long and it was hard to do more than 4 cases.
Sometimes you’d do 5 or 6, but you really had
to press to get it done.
:h$7WX[h]ÅNone.
Financial Disclosures
:h$=Wh]ÅMD INTELLISYS: Stockholder, No Compensation
Received; GENENTECH: Investigator, Grants; REGENERON
PHARMACEUTICALS, IN C: Investigator, Grants; LUX
BIOSCIENCES: Investigator, Grants; EYE GATE: Investigator,
No Compensation Received; ALLERGAN, INC: Speaker,
Honoraria; QLT INC: Consultant, Honoraria.
:h$<_d[cWd—THROMBOGENICS: Consultant, Grants;
PHYSICIAN RECOMMENDED NUTRICEUTICALS: Consultant,
Honoraria.
:h$7XhWciÅALCON RESEARCH INSTITUTE: Advisory
Board, Honoraria.
:h$8[diedÅ NATIONAL EYE INSTITUTE: Investigator,
Grants; GENENTECH: Investigator, Grants; ALCON LABORATORIES, INC: Investigator, Grants; LUX BIOSCIENCES:
Investigator, Grants; JOHNSON & JOHNSON: Investigator,
Grants; GLAXOSMITHKLINE: Investigator, Grants.
:h$<[Z[hcWdÅOMTI (telemedicine software company):
Director/Principal, No Compensation; ESCALON MEDICAL
CORP: Director, Stock Options; RETINA IMPLANT AG:
Consultant.
Dr. Sarin – None.
:h$JWicWdÅNone.
After the fellows had finished the day in the
OR at 5:00 or 6:00 PM, they had to work up the
patients who had been admitted for the next
The American Society of Retina Specialists gratefully acknowledges the following
Corporate Members who have committed generous support to the Society for 2012.
Emerald Corporate Member
Genentech
Platinum Corporate Member
Alcon Laboratories, Inc.
Allergan, Inc.
Silver Corporate Members
Bronze Corporate Members
Bausch + Lomb
Carl Zeiss Meditec
Insight Instruments, Inc.
QLT, Inc.
DORC International BV/
Dutch Ophthalmic USA
Santen Pharmaceutical Co, Ltd.
IRIDEX Corporation
ThromboGenics
PanOptica, Inc.
Regeneron Pharmaceuticals, Inc.
Synergetics™ USA, Inc.
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Fall 2012
| retina times | 49
JERRY’S WISDOM >>
Jerald A. Bovino, MD
Section Editor
Everybody Is Sellin’ Somethin’
you until he had the back of your head pinned
firmly against the wall. To make the situation
even more desperate, he had the world’s worst
case of bad breath. If the Iranians could put
that breath in centrifuges and weaponize it,
they would have no need to build an atomic
bomb. The Western world would just surrender
after one whiff. Just a sniff of concentrated
neurosurgeon breath, and all American women
would be wearing burkas.
The hospital dinner was running late and the
doctors were furious. Hospital dinners seem
anachronistic in this age of outpatient surgery.
However, those of you who started out with me
in the early Pleistocene era will remember when
we were forced to attend hospital staff dinners
each month to keep our surgical privileges.
‘They ran to Johnny and
started taunting him:
“Your mom’s a whore!”’
The neurosurgeon proceeded to tell us in great
detail how he was raised in an affluent family
in New Jersey horse country. As a boy, he spent
his summer vacations at the beach in Atlantic
City, which was actually quite fashionable and
even chic back in the late 1940s and early 1950s.
Of course, that all changed as the honky-tonk
of the boardwalk took over and evolved into
the messy vitality of the casino era, but Atlantic
City, especially before air conditioning, was a
playground of the rich.
On this particular night, the executives droned
on about the waves of HMOs and PPOs that
were washing across the medical landscape.
They told us that we would have to discount
this or that and work harder and be happy
being a member of the hospital team. In return,
the doctors were all lamenting the undesirable
and unwanted commercialization of medicine.
“Why can’t they just let us be doctors and
practice medicine?” we wondered. “Why does
medicine have to be like a Turkish bazaar?”
The clock was pushing 11:00 PM as the neurosurgeon reminisced about playing on the beach
with 10 or 12 other privileged boys from his
elite private school. However, there was one boy
who joined the group who simply did not fit
into the affluent mold. It was clear that Johnny
was from the wrong side of the tracks, but he
was ebullient and athletic and a great ballplayer,
and they all became fast summer friends.
As we digested the last of our overcooked
chicken and prepared to dash for the exits, one
of the neurosurgeons invited himself to the
podium, grabbed the mike, and started telling
a seemingly irrelevant and out-of-place story
about his boyhood. “Has he lost his mind?” we
thought. “Shut the guy up so we can get home!”
One day toward the end of the summer, one of
the horse-country-boys’ parents told her son
the most horrifying thing that he could possibly
imagine. It seems that Johnny’s mother was
“working” the boardwalk. The boys were stunned.
They ran to Johnny and started taunting him:
“Your mom’s a whore! Your mom’s a whore!”
This particular neurosurgeon was even more
peculiar than most in his specialty. That says
a lot! The doctor wore tweedy bespoke British
suits, shoes that didn’t match, and striped Ivy
League ties that were always wrinkled.
He was a tall man with rigid posture, but he
had a high-pitched, squeaky voice that made
it sound like he had just been sucking on
a helium balloon. He was one of those guys
who always had Phi Beta Kappa and AOA keys
and fobs hanging from a gold chain attached
to the middle buttonhole on his vest, and he
fondled them excessively as he talked.
Another idiosyncrasy was that he had
absolutely no understanding of the concept
of personal space. The neurosurgeon was brilliant beyond compare, but if he stopped you
in the hallway, he would keep inching toward
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rich kids just made Johnny cry because of my
line of work,” she told the boys. “I am going
to tell you something now and I want you to
remember it your entire life.”
As the boys cowered and held their breath, she
said “Everybody is sellin’ somethin’!”
We are a lot more fortunate than the young
lady in the yellow sun dress. You and I have
been able to get a sound education, a medical
degree, specialized training in an ophthalmology
residency, and a great fellowship in retina
surgery. We can be proud of our profession
and our accomplishments and the wonderful
things we do every day to help patients.
However, just like Johnny’s mother, to be
successful, you will be “sellin’ somethin’” your
entire life. It might be convincing your chairman
that you are a great researcher. Maybe it’s
trying to get your paper published in the AJO.
It could be demonstrating to a patient that you
are a compassionate physician. It can happen
when you get up to give a lecture to your peers
about a new instrument or procedure or
drug at the ASRS meeting.
‘[Johnny’s mom] told
the boys, “I am going
to tell you something
now and I want you to
remember it your
entire life … “Everybody
is sellin’ somethin’!”’
Johnny was embarrassed, started crying
uncontrollably, and dashed out of sight.
Fifteen minutes later, Johnny’s mom, a pretty
woman in her early 30s, walked toward the
group. Terrified, the boys ducked under the
boardwalk to hide, but she quickly stuck
her head beneath the timbers. She was wearing
a bright yellow sundress with big white flowers
and the young boys’ eyes were as wide as
saucers as she started to talk.
We serve our patients as part of a noble
profession, but never lose sight of the fact that
almost everyone in our field is promoting
something. Sometimes they are simply
promoting themselves. It’s neither good nor
bad—but it’s important to evaluate every
lecture, every new drug, and every new device
through the prism of this knowledge.
She spoke in slow, measured tones. “I understand that you are only 10 years old, but you
Financial Disclosures
:h$8el_de– EYE SCIENCE OCULAR VITAMIN COMPANY:
Board of Directors, No Compensation Received.
>> >>
BREAKING
TEA
LEAVES
NEWS
Trexler M. Topping, MD
Section Editor
Concierge Retina—That’s What We Already Provide!
Those of us who are deeply involved with health policy feel that we will experience a 15%
income drop in the next 5 to 10 years due to the inevitable juggernaut of health care reform.
Not surprisingly, all branches of medicine are contemplating how to maintain income.
The internists and primary care physicians
are selling concierge medicine, a process by
WHICHAPATIENTPAYSTOAYEAR
to ensure access to the doctor, usually by
phone or email. Patients are normally
also permitted an appointment within 24
hours. Can we do this in ophthalmology—
specifically in retina practices?
In concierge medicine, your retainer covers
services that are typically not covered, such as
refractions, corneal topography, etc. However,
virtually all that we as retina specialists do is
already covered by Medicare and insurance
companies—so what “extra” can we sell to be
concierge retina specialists?
‘[V]irtually all that we
as retina specialists
do is already covered
by Medicare and
insurance companies—
so what “extra” can
we sell to be concierge
retina specialists?’
Well, we can assure patients that we, or our
staff, will speak with them on the phone
whenever they call. We can see patients right
away if they call with new flashes, floaters, or
a field defect—and if AMD patients have new
distortion in the fellow eye, they can come
right in for evaluation and possible immediate
treatment with the best modalities known
to mankind.
As retina specialists, we will enhance both our
practice efficiency and delivery paradigms
to give personalized, patient-centered care
in less time. We won’t bellyache about low
reimbursement levels as many internists do,
but will creatively develop improved systems
of patient management and care delivery.
But wait a minute—that is exactly the current
standard of care in American retina practices!
Like it or not, we already provide a concierge level
of retina medicine at no premium. In a sense, we
give Mercedes-Benz care at Yugo prices.
Meanwhile, our surgical approaches, techniques,
and instrumentation have improved to the
extent that our surgery works better, takes less
time, and has better outcomes with much less
patient morbidity. In the world of free enterprise,
this would merit increases in physician income.
However, in the real world of medicine, these
improvements across the board result in
decreasing payment for you, the physician.
(Thank you, RVS Update Committee!)
‘Like it or not, we already
provide a concierge
level of retina medicine
at no premium.’
Thinking out of the box has distinguished us
vitreoretinal specialists from the beginning.
Didn’t they say the vitreous was inviolate 50
years ago? We did not listen then, and we will
not listen now.
So how can we retina specialists cope with the
forthcoming changes? We have an increasing
patient population, we have more therapies
that will improve the health of Americans, and
yet we face decreasing reimbursement. Retina
specialists accept these challenges in stride.
And we will do what we have always done.
We retina specialists will gather in small or
large groups and solve the delivery problem.
We will develop best-practice solutions, and
will share the approaches with each other at
our local meetings and at ASRS. As a group
who already provides a concierge level of
retina care, that is how we will succeed in
the face of the significant health care funding
obstacle ahead.
We will address the issues, see where care is
required—looking at the increasing number
of graying Americans like me—and see
where new treatment modalities are leading
toward changes in practice needs. For
example, just as the advent of anti-VEGF
therapy for AMD caused changes, we will
see similar changes caused by adding diabetic
retinopathy to the conditions responding to
anti-VEGF injections.
Contact Trexler Topping at tmtopping@
eyeboston.com.
Financial Disclosures
Dr. Topping – OPHTHALMIC MUTUAL INSURANCE
COMPANY: Board of Directors, Honoraria; NATIONAL EYE
INSTITUTE: Contract Research, Grants.
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Fall 2012
| retina times | 51
THE ASRS X-FILES >>
K. Bailey Freund, MD
Jerome Giovinazzo
Sarah Mrejen, MD
Section Editor
Case History: A 21-year-old male with no medical or family history experienced the sudden
onset of a central scotoma in his left eye 3 days prior to presentation. On examination, his
best-corrected visual acuity was 20/20 in the right eye and 20/200 in the left eye. The anterior
segment examination of both eyes was normal. Color photographs showing the funduscopic
findings and spectral-domain optical coherence tomography (SD-OCT) of both eyes at
presentation are shown in Figure 1.
Two weeks later, the patient returned after being
seen in the emergency room for acute abdominal
pain. His best-corrected visual acuity was 20/20 in
the right eye and 20/70 in the left eye. Color photographs and SD-OCT of both eyes at follow-up
are shown in Figure 2. The next day, the patient
developed a partial left hemiparesis and began
slurring his words while in his internist’s office.
What is your diagnosis?
See discussion on page 56
‘[T]he patient returned
after being seen in the
emergency room for
acute abdominal pain.’
Figure 1: Color photographs and SD-OCT of both eyes
at presentation
Color photograph of the right eye (A) shows an area
of intraretinal hemorrhage and nerve fiber layer
whitening along the superotemporal arcades, with
slight obscuration of vessels at the nasal margin of
the optic nerve. Color photograph of the left eye (B)
shows a sub-internal limiting membrane hemorrhage
overlying the fovea, some obscuration of the disc
margins, a few intraretinal hemorrhages at the superior
and inferior poles of the optic disc, a small cotton-wool
spot superiorly in the macular region, and moderate
congestion of the venous system. SD-OCT horizontal
scan of the right fovea (C) is normal. SD-OCT vertical
scan through the left fovea (D) shows a sub-internal
limiting membrane hemorrhage overlying the fovea with
a fluid-erythrocyte separation.
Figure 2: Color photograph montages and SD-OCT scans
of both eyes at 2-week follow-up
Color montage photograph of the right eye (A) shows 3
Roth’s spots in the superior and temporal mid-periphery
of the fundus. Color montage photograph of the left
eye (B) shows a foveolar hemorrhage, more intraretinal
hemorrhages and cotton-wool spots, and more
pronounced optic disc edema compared with initial
presentation (Figure 1).
SD-OCT scan through a Roth’s spot (C) shows a hyperreflective lesion at the level of the superficial and inner
retina with underlying subretinal fluid and overlying
numerous hyper-reflective dots in the vitreous. SD-OCT
vertical scan through the left foveal hemorrhage (D)
shows an intraretinal isoreflective lesion that contains
numerous hyper-reflective dots.
52 | retina times |
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LITERATURE ROUNDUP >>
Michael M. Altaweel, MD
Amol Kulkarni, MD
Asheesh Tewari, MD
Section Co-Editor
7(#O[WhFheif[Yj_l[HWdZec_p[Z9edjhebb[Z
Jh_Wbe\?djhWl_jh[Wb8[lWY_pkcWXehBWi[h
J^[hWfo8EBJ_dj^[CWdW][c[dje\:_WX[j_Y
CWYkbWh;Z[cW0(*#Cedj^:WjW0H[fehj)
[published online ahead of print April 9, 2012]
Rajendram R, Fraser-Bell S, Kaines A, et al. Arch
Ophthalmol. 2012;130(8):972-979. doi:10.1001/
archophthalmol.2012.393.
The Early Treatment Diabetic Retinopathy Study (ETDRS) showed
that macular laser photocoagulation decreased the risk of vision loss
of 15 letters due to clinically significant macular edema (CSME) by
50% compared with eyes that did not receive treatment. However,
there is a subset of patients unresponsive to this therapy. Intravitreal
injections with bevacizumab have been demonstrated to be safe and
effective for treating persistent diabetic macular edema (DME)
despite laser treatment.
The Bevacizumab or Laser Therapy (BOLT) in the Management of
Diabetic Macular Edema study is a prospective, randomized controlled
trial evaluating the role of intravitreal bevacizumab and modified
ETDRS macular laser therapy (MLT) in patients with persistent DME.
The study consisted of 80 patients with center-involved DME who had
previously received focal laser and had visual acuity of 20/40 to 20/320.
Patients were randomly assigned to a bevacizumab arm receiving
injections every 6 weeks for the first 3 months and every 6 weeks as
needed thereafter, and a laser arm receiving as-needed macular laser
every 4 months. At 2 years, the bevacizumab arm gained a median
of 9 ETDRS letters vs 2.5 letters for laser group. Forty-nine percent
of patients treated with bevacizumab gained 10 or more letters as
compared with 7% in the laser group. The median number of treatments
over 24 months was 13 for bevacizumab and 4 for laser. A mean of
4 injections were required in the second year.
Application to Practice: Persistent center-involving macular
edema despite previous laser photocoagulation is a common clinical
dilemma faced by practitioners. The BOLT trial specifically focused on
this subgroup with persistent DME; results support the longer term
use of bevacizumab. This trial reconfirms that the benefits of laser
photocoagulation may not be fully realized until at least the second
year of follow-up.
;\\[Yje\9ecX_dWj_edJ^[hWfoM_j^8[lWY_pkcWX
WdZ:[nWc[j^Wied[?djhWl_jh[Wb?cfbWdj_d
FWj_[djiM_j^H[j_dWbL[_dEYYbki_ed
Singer MA, Bell DJ, Woods P, et al. Retina.
2012;32(7):1289-1294. doi:10.1097/IAE.0b013e318242b838.
Retinal vein occlusions (RVOs) cause macular edema (ME), which can
be treated with laser photocoagulation and/or intravitreal pharmacotherapy. The intravitreal medications available include triamcinolone,
dexamethasone intravitreal implant (Ozurdex; Allergan, Inc, Irvine,
CA), and ranibizumab (Lucentis; Genentech, Inc, South San Francisco,
CA), as described in the SCORE, OZURDEX GENEVA, and BRAVO/
Section Co-Editor
CRUISE studies respectively. Bevacizumab has also been shown to be
efficacious in the treatment of ME secondary to RVO.
This prospective, interventional case series consisted of 34 eyes of
33 patients with ME associated with RVO who were injected with
bevacizumab, followed by dexamethasone intravitreal implant
injection 2 weeks later. These patients were reexamined monthly
and retreated with bevacizumab when ME recurred during the
6-month study period.
The primary outcome measure was the time to reinjection based on
OCT and vision criteria. Thirty-five percent of patients had central
RVO (CRVO) and 65% had branch RVO (BRVO); 82% (28 of 34)
needed at least 1 more injection before month 6, while 18% (6 of 34)
did not need an additional injection of bevacizumab. Ninety-seven
percent of patients gained vision during the study, and mean visual
acuity improved from initially 11 letters to a maximum of 25 letters
during the study period. OCT showed macular thickness decreased
with the combination treatment, and the effect continued an average of
126 days from the initial bevacizumab treatment.
Eighteen percent (6 of 34) of patients had an IOP of 23 mmHg or
greater. Five of these 6 subjects were controlled with drops alone, while
one required an additional selective laser trabeculoplasty. This study
demonstrates efficacy and the duration of effect using a combination
of bevacizumab and dexamethasone vs dexamethasone alone. The
combination is synergistic, increasing visual acuity and prolonging the
time between injections, compared with either medication alone.
Application to Practice: Various treatment options are available
for treatment of macular edema associated with RVO. This study demonstrates that the combination of a vascular endothelial growth factor
inhibitor and a dexamethasone implant may be a valuable option for
RVO treatment. The study design is applicable to many patients with
persistent ME secondary to RVO in the typical ophthalmology practice.
H_ia\ehH[j_dWb:[jWY^c[dj7\j[h
F^WYe[ckbi_ÓYWj_ed07M^eb[#FefkbWj_ed
IjkZoe\9WjWhWYjIkh][hoEkjYec[i
Clark A, Morlet N, Ng JQ, Preen DB, Semmens JB.
Arch Ophthalmol. 2012;130(7):882-888. doi:10.1001/
archophthalmol.2012.164.
There is 1% overall incidence of retinal detachment (RD) following
cataract surgery. The risks include patient factors (younger age, male
sex, and long axial length), surgical factors (operative technique,
vitreous loss, and posterior capsule rupture), and postoperative factors
(Nd:YAG laser posterior capsulotomy). There has been a significant
reduction in incidence of RD subsequent to adoption of phacoemulsification compared with intracapsular cataract extraction.
The long-term risk for RD after phacoemulsification was studied in
the entire Western Australia (WA) population using validated linked
health administrative data from January 1989 to December 2001.
Kaplan-Meier analysis was used to calculate a cumulative incidence
(CI) of RD as a percentage of cataract procedures. Cox proportional
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Fall 2012
| retina times | 53
LITERATURE ROUNDUP >>
hazards regression modeling was used to calculate hazard ratios (HRs),
which were 95% CIs for each risk factor examined.
There were 237 RD cases following 65,055 phacoemulsification
procedures, with a 10-year cumulative incidence of 0.68%. Significant
risk factors were year of surgery (hazard ratio, 0.43; 95% CI, 0.28-0.66
[1999-2001 compared with 1989-1993] for each 5-year period after
1985), age younger than 60 years, male gender, and anterior vitrectomy.
Hospital location, patient rural or remote locality, hospital cataract
surgery volume, failed intraocular lens insertion, length of stay, and
patient insurance status were not significantly associated with RD.
The axial length and need for Nd:YAG laser posterior capsulotomy in
the RD cases were not examined. Thus, risk for RD after phacoemulsification has almost halved for each 5-year period since its adoption
in the mid-1980s. Younger patient age and male gender significantly
increased risk for RD. Phacoemulsification requiring anterior
vitrectomy vastly increased risk for RD.
Application to Practice: Pseudophakic RD is a rare, sight-threatening
complication following phacoemulsification cataract surgery. Complicated
cataract surgical procedures necessitating anterior vitrectomy carry
significantly increased risk for RD. The study emphasizes the important
risk factors for subsequent RD. A thorough knowledge of these risk
factors is important for physicians to guide preoperative counseling
and postoperative review with patients.
;d^WdY[Z:[fj^?cW]_d]Efj_YWb9e^[h[dY[
Jece]hWf^oe\IcWbb9^ehe_ZWbC[bWdecW0
9ecfWh_iedM_j^9^ehe_ZWbD[lki
Shields CL, Kaliki S, Rojanaporn D, Ferenczy SR, Shields
JA. Arch Ophthalmol. 2012;130(7):850-856. doi:10.1001/
archophthalmol.2012.1135.
The clinical differentiation of small choroidal melanoma from benign
choroidal nevus can be challenging, especially when lesion thickness is
3 mm or less. The various ophthalmoscopically visible factors include
greater tumor thickness, the presence of subretinal fluid, overlying
lipofuscin, tumor margin near the optic disc, and the absence of drusen
and halo.
OCT can be used for detection of subretinal fluid; however, little
detail is apparent within the tumor or surrounding choroid. Recent
improvements in enhanced depth imaging spectral-domain OCT
(EDI-SD-OCT) allow for better imaging of choroidal detail.
The retrospective comparative analysis consisted of 37 eyes with
small choroidal melanoma and 51 eyes with choroidal nevi imaged
using EDI-SD-OCT. The mean tumor thickness was 1025 μm by
EDI-SD-OCT, compared with 2300 μm by ultrasonography. The
choroidal features included optical shadowing and thinning of
overlying choriocapillaris. There was subretinal fluid in 92%, and
subretinal lipofuscin deposition in 95%.
In comparison with similar-sized choroidal nevus, the statistically
significant EDI-SD-OCT features for small choroidal melanoma
include intraretinal edema (P = .003), shaggy photoreceptors or loss
of photoreceptors (P = .005), loss of external limiting membrane
(P = .008), loss of inner segment-outer segment junction (P = .02),
irregularity of inner plexiform layer (P = .04), and irregularity of
ganglion cell layer (P = .04) (t test and x2 test).
The term shaggy photoreceptors describes the irregular, elongated, and
presumed swollen photoreceptors from fresh subretinal fluid. Shaggy
54 | retina times |
Fall 2012
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Volume )&, Number *
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photoreceptors were found overlying small choroidal melanoma in
18 eyes (49%), but were not observed overlying choroidal nevus
(P < .001). Thus, EDI-SD-OCT provides in vivo quantification of
tumor dimensions and cross-sectional detail of the tumor and
surrounding choroidal tissues that previously were not depicted.
Application to Practice: EDI-SD-OCT is an exciting technology
for imaging small choroidal lesions. It shows numerous changes in
the overlying retina, especially shaggy photoreceptors, which can help
differentiate small choroidal melanoma from similar-sized choroidal
nevus. EDI-SD-OCT imaging is ideal only for smaller choroidal tumors
(< 3 mm), particularly those located in the macula.
Ijhea[HWj[i7\j[h?djheZkYj_ede\LWiYkbWh
;dZej^[b_Wb=hemj^<WYjeh?d^_X_jehi\ehCWYkbWh
:[][d[hWj_ed07J_c[I[h_[i7dWboi_i
[published online ahead of print June 19, 2012]
Campbell RJ, Bell CM, Paterson JM, et al. Ophthalmol.
2012;119(8):1604-1608.
AMD treatment has been revolutionized by intravitreal anti-VEGF
medications. Ranibizumab and bevacizumab are the commonly used
drugs and have comparable efficacy. Intravenous administration of
bevacizumab in patients with cancer has been associated with an
increased risk of stroke, and a meta-analysis has suggested an increased
risk of stroke among patients with AMD receiving ranibizumab.
The population-based, time series analysis was used to assess stroke
rates among patients on therapy with bevacizumab and ranibizumab
for AMD. The encrypted, linked health care databases in Ontario,
Canada were used to select all patients aged 66 years or older with
physician-diagnosed AMD in the previous 5 years between 2002 and
2010 (N = 116,388). A secondary analysis evaluated patients who had
undergone photodynamic therapy (PDT) within the preceding year
(N = 10,059).
A segmented regression analysis was used to evaluate changes in the
rate of hospitalization for ischemic stroke associated with bevacizumab
and ranibizumab therapy. The stroke rate was compared across
3 mutually exclusive periods: the period before the availability of
bevacizumab or ranibizumab, the period of bevacizumab-dominant
AMD therapy, and the period of ranibizumab-dominant AMD therapy.
Neither the trend nor the level of the stroke time series changed with
bevacizumab or ranibizumab therapy.
Similar results were observed in the analysis restricted to patients with
recent PDT and in analyses stratified on age, sex, history of stroke, and
history of diabetes. The present study was limited to strokes requiring
hospitalization, and does not take into account milder vascular events
not requiring hospitalization. Thus, use of intravitreal bevacizumab
and ranibizumab for AMD is not associated with a change in the rate
of hospitalization for stroke among Ontario seniors.
Application to Practice: The study results agree with the
Comparisons of Age-Related Macular Degeneration Treatments
(CATT) Trials regarding the safety of anti-VEGF agents. Stroke rates
were not different in patients on bevacizumab and ranibizumab
therapy. These results will assist clinicians as they balance the comparative
efficacy, safety, and cost of these 2 closely related treatments.
Incidence of Endophthalmitis and Use of
Antibiotic Prophylaxis After Intravitreal Injections
[published online ahead of print April 4, 2012]
Cheung CS, Wong AW, Lui A, Kertes PJ, Devenyi RG,
Lam WC. Ophthalmol. 2012;119(8):1609-1614.
Intravitreal injections of VEGF inhibitors and triamcinolone acetonide
are rapidly becoming the mainstay in treating various retinal diseases.
A rare but sight-threatening complication of this procedure is endophthalmitis. The reported rates of endophthalmitis after intravitreal
injections are low (0.019% to 1.4%). The preferred prophylactic
method to minimize risk of endophthalmitis involves preparation of
the injection site with topical povidone-iodine. There is conflicting
evidence on the effectiveness of topical antibiotic prophylaxis in
preventing endophthalmitis after intravitreal injections.
The retrospective, comparative case series studied the incidence of
endophthalmitis in association with different antibiotic prophylaxis
strategies after intravitreal injections of anti-VEGF and triamcinolone
acetonide. Three strategies of topical antibiotic prophylaxis were
used by the treating physicians: antibiotics given for 5 days after each
injection; antibiotics given immediately after each injection; and no
antibiotics given.
A total of 15,895 intravitreal injections (9453 ranibizumab, 5386
bevacizumab, 935 triamcinolone acetonide, 121 pegaptanib sodium)
were reviewed for 2465 patients between January 5, 2005, and
August 31, 2010.
Nine eyes of 9 patients with suspected endophthalmitis after injection
were identified. Three of the 9 cases had culture-positive results. The
overall incidence of endophthalmitis per injection was 5 in 8259 for
patients who were given antibiotics for 5 days after injection, 2 in 2370
for those who received antibiotics immediately after each injection,
and 2 in 5266 who received no antibiotics.
However, if considering culture-proven endophthalmitis alone,
the use of topical antibiotics given immediately or for 5 days after
injection showed lower rates of endophthalmitis compared with those
without postinjection antibiotics. The incidence of endophthalmitis
per injection was 2 in 935 for triamcinolone acetonide, 3 in 9453 for
ranibizumab, and 4 in 5386 for bevacizumab.
Thus, the overall rate of intravitreal injection-related endophthalmitis
is greater with the use of topical antibiotics, given immediately or for
5 days after the injection, compared with no antibiotics.
Application to Practice: These findings recommend no topical
antibiotic use after intravitreal injection, and they raise concern about
a higher rate of endophthalmitis after administration of topical
antibiotics. However, because the study is retrospective, with a small
sample of patients, the conclusions may be the result of a random
sampling error.
Financial Disclosures
Dr. Altaweel – NATIONAL EYE INSTITUTE: Investigator, Grants; GLAXOSMITHKLINE:
Investigator, Grants; PFIZER, INC: Investigator, Grants; REGENERON PHARMACEUTICALS,
INC: Investigator, Grants.
Dr. Tewari – SYNERGETICS USA: Consultant, Honoraria.
Dr. Kulkarni – None.
POINT/COUNTERPOINT >>
Dr. von Fricken, continued from page 41
6. Lincoff HA, Baras I, McLean J. Modifications to the Custodis Procedure for Retinal
Detachment. Arch Ophthalmol. 1965;73(2):160-163.
7. Fujii GY, De Juan E, Jr., Humayun MS, et al. A new 25-gauge instrument
system for transconjunctival sutureless vitrectomy surgery. Ophthalmol.
2002;109(10):1807-1812; discussion 1813.
8. Escoffery RF, Olk RJ, Grand MG, Boniuk I. Vitrectomy without scleral buckling for
primary rhegmatogenous retinal detachment. Am J Ophthalmol. 1985; 99(3): 275-281.
9. Campo RV, Sipperley JO, Sneed SR, et al. Pars plana vitrectomy without scleral buckle for
pseudophakic retinal detachments. Ophthalmol. 1999; 106(9):1811-1815; discussion 1816.
10. Speicher MA, Fu AD, Martin JP, von Fricken MA. Primary vitrectomy alone for repair of
retinal detachments following cataract surgery. Retina. 2000;20(5):459-464.
11. von Fricken MA, Kunjukunju N, Weber C, Ko G. 25-Gauge sutureless vitrectomy versus
20-gauge vitrectomy for the repair of primary rhegmatogenous retinal detachment.
Retina. 2009;29(4):444-450.
12. Weichel ED, Martidis A, Fineman MS, et al. Pars plana vitrectomy versus combined pars
plana vitrectomy-scleral buckle for primary repair of pseudophakic retinal detachment.
Ophthalmol. 2006;113(11):2033-2040.
13. Martínez-Castillo V, Boixadera A, Verdugo A, García-Arumí J. Pars plana vitrectomy
alone for the management of inferior breaks in pseudophakic retinal detachment
without facedown position. Ophthalmol. 2005;112(7):1222-1226.
14. Colyer MH, Barazi MK, von Fricken MA. Retrospective comparison of 25-gauge transconjunctival sutureless vitrectomy to 20-gauge vitrectomy for the repair of pseudophakic
primary inferior rhegmatogenous retinal detachment. Retina. 2010;30(10):1678-1684.
15. Brazitikos PD, Androudi S, Christen WG, Stangos NT. Primary pars plana vitrectomy
versus scleral buckle surgery for the treatment of pseudophakic retinal detachment:
a randomized clinical trial. Retina. 2005;25(8):957-964.
16. Ahmadieh H, Moradian S, Faghihi H, et al. Anatomic and visual outcomes of scleral
buckling versus primary vitrectomy in pseudophakic and aphakic retinal detachment: six-month follow-up results of a single operation—report no. 1. Ophthalmol.
2005;112(8):1421-1429.
17. Heiman H, Bartz-Schmidt KU, Bornfeld N, et al. Scleral buckling versus primary vitrectomy
in rhegmatogenous retinal detachment: a prospective randomized multicenter clinical
study. Ophthalmol. 2007;114(12):2142-2154.
18. Koriyama M, Nishimura T, Matsubara T, Taomoto M, Takahashi K, Matsumura M.
Prospective study comparing the effectiveness of scleral buckling to vitreous surgery
for rhegmatogenous retinal detachment. Jpn J Ophthalmol. 2007;51(5):360-367.
19. Jumper JM, Mittra RA, eds. ASRS 2012 Preferences and Trends Membership Survey.
Chicago, IL. American Society of Retina Specialists. 2012.
Financial Disclosures
Dr. von Fricken – None.
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Fall 2012
| retina times | 55
X-FILES SOLUTION >> Continued from page 52
Case History: Discussion
At initial presentation (Figure 1, page 52), the
right color photograph (B) shows an area of
intraretinal hemorrhage and nerve fiber layer
whitening along the superotemporal arcades.
There is slight obscuration of vessels at the nasal
margin of the optic nerve. The photograph of
the left eye (A) shows a sub-internal limiting
membrane hemorrhage overlying the fovea.
There is some obscuration of the disc margins
with a few intraretinal hemorrhages at the
superior and inferior poles of the optic disc
and a small cotton-wool spot superiorly in the
macular region. There is moderate congestion of
the venous system with some mild tortuosity.
that time are shown in Figures 3 (right eye)
and 4 (left eye).
dots in the vitreous and a complete resolution of
the subretinal fluid.
The color photograph of the right eye (Figure 3)
shows a near-complete resolution of the Roth’s
spots. The SD-OCT horizontal scan through one
Roth’s spot shows a major decrease in the size of
the hyper-reflective lesion that seems to be located
at the level of the retinal nerve fiber layer, with a
near-complete resolution of the hyper-reflective
In the left eye (Figure 4), the color photograph
shows the complete resolution of the subinternal limiting membrane hemorrhage,
intraretinal hemorrhages, and cotton-wool
spots. The SD-OCT scan through the fovea
shows the resolution of the sub-internal limiting
membrane hemorrhage with consequent focal
SD-OCT vertical scan through the left fovea
shows a sub-internal limiting membrane
hemorrhage overlying the fovea with a fluiderythrocyte separation. The SD-OCT horizontal
scan of the right fovea is normal. The patient’s
visual symptoms appeared to be related to a
sub-internal limiting membrane hemorrhage
overlying the left fovea. Blood pressure at that
time was normal. The patient was referred to his
internist to rule out hematologic abnormalities
causing hyperviscosity or vasculitic entities with
associated retinal vascular changes. A medical
work-up revealed blood on urinalysis, an elevated
C-reactive protein (CRP) at 10.1 mg/l, an elevated
erythrocyte sedimentation rate (ESR) at 66 mm
per hour, a normal white blood cell count
and platelets. The complete blood count (CBC)
showed low hemoglobin and hematocrit.
When the patient returned for 2-week follow-up,
the left color photograph (A—Figure 2, page
52) showed more intraretinal hemorrhages
and cotton-wool spots and more pronounced
optic disc edema. The right color photograph
(B) showed multiple intraretinal hemorrhages
centered by a white spot characteristic of Roth’s
spots. The SD-OCT scan through a Roth’s spot
showed a hyper-reflective lesion at the level of
the superficial and inner retina with underlying
subretinal fluid and overlying numerous
hyper-reflective dots in the vitreous. At that
time, the patient was immediately referred back
to the internist for a complete work-up and had
symptoms suggestive of a stroke in his office.
Figure 3: Color photographs and SD-OCT scans of the right eye at second (2 weeks) and last (6 weeks) follow-up examinations
Color photograph at last follow-up (B) shows near-complete resolution of Roth’s spots compared with previous
examination (A). SD-OCT horizontal scan through one Roth’s spot at last follow-up (D) shows a decrease in the size of
the hyper-reflective lesion that seems to be now located at the level of the retinal nerve fiber layer, a near-complete
resolution of the hyper-reflective dots in the vitreous, and a complete resolution of the subretinal fluid as compared
with previous examination (C).
He was medically evaluated and subsequently
diagnosed with infectious endocarditis related
to a congenital bicuspid aortic valve. Cultures
from his recent emergency room visit grew
Streptococcus viridans. He underwent an aortic
valve replacement after 4 weeks of intravenous
antibiotics and had a full recovery from the
stroke. Four weeks later, the best-corrected
visual acuity recovered to 20/20 in both eyes.
His color photographs and SD-OCT scans at
56 | retina times |
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Volume 30, Number 4
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Issue 46
Figure 4: Color photographs and SD-OCT scans of the left eye at second (2 weeks) and last (6 weeks) follow-up examinations
Color photographs at last follow-up (B) shows resolution of intraretinal hemorrhages, cotton-wool spots, and optic disc edema
compared with previous examination (A). SD-OCT vertical foveal scan at last follow-up (D) shows resolution of the intraretinal
isoreflective lesion with consequent thinning of the inner nuclear layer compared with previous examination (C).
|
X-FILES SOLUTION >>
inner retinal thinning. Roth first described
seeing white retinal lesions and separate oval
hemorrhages in patients with sepsis in 1872.
In 1878, Litten, a French ophthalmologist,
described oval hemorrhages with pale centers
in patients with endocarditis and named these
spots “Roth’s spots.” Roth’s spots are nonspecific and there have been conflicting reports
in the literature concerning their composition.
of disease is high, immediate tests should be
ordered. Blood cultures should be obtained
prior to antibiotic therapy. A CBC with a
differential, ESR, CRP, urinalysis, and an electrocardiogram (ECG) also should be included
in the work-up, and an echocardiogram should
be obtained. Once the tests have returned,
the modified Duke criteria should be used to
establish the possibility of endocarditis.9
Roth originally hypothesized that the white centers
may contain bacteria but may also be composed
of collections of sterile white blood cells.1
To the best of our knowledge, this is the
first time a Roth’s spot has been evaluated
with high-resolution SD-OCT imaging. Past
histological studies have shown that the white
centers surrounded by hemorrhages are
fibrin-platelet aggregates or thrombi.10 Subacute
bacterial endocarditis is thought to produce
septic thrombi which can embolize to distant
locations. One of the organs affected is the eye.
The white center has also been hypothesized to
be composed of fibrin thrombus at the site of
the capillary rupture.2 These lesions can be seen
in patients with leukemia,3 subacute bacterial
endocarditis,4 severe anemia, hypertensive states,
rheumatologic disorders, trauma, and HIV.5
Our patient initially presented with a subinternal limiting membrane hemorrhage
directly overlying the fovea in the left eye and
a few intraretinal hemorrhages, cotton-wool
spots, and mild optic disc edema in both eyes.
Sub-internal limiting membrane hemorrhages
can occur in a variety of settings including
increased venous pressure from a Valsalva
maneuver, ocular trauma, and various retinal
vascular diseases. Preretinal hemorrhages have
been reported to be the presenting sign for
subacute bacterial endocarditis.6-7 Li and Kapusta
argued that the hemorrhage may be concealing
retinal findings more consistent with subacute
bacterial endocarditis, such as Roth’s spots.7
We suggest that patients presenting with a
sub-internal limiting membrane hemorrhage
associated with other retinal vascular and
optic nerve abnormalities be questioned
regarding other manifestations of subacute
bacterial endocarditis such as splinter hemorrhages, petechiae, clubbing, Janeway lesions,
Osler’s nodes, and cardiac murmurs.
Patients with a cardiac history are more
likely to have infectious endocarditis than
those without.8 When the clinical likelihood
the lesion. We believe these SD-OCT findings
show that the Roth’s spots in subacute bacterial
endocarditis are more likely to represent
inflammatory lesions than cotton-wool spots
surrounded by hemorrhage. These images may
support Roth’s and Litten’s original theory that
Roth’s spots represent septic emboli.
References
1. Gass JD. Inflammatory Diseases of the Retina and
Choroid. In: Gass JD, ed. Stereoscopic Atlas of Macular
Diseases. 4th ed. St Louis, MO: Mosby; 1997:601-603.
2. Duane TD, Osher RH, Green WR. White centered hemorrhages: their significance. Ophthalmol. 1980;87(1):66-69.
3. Kapadia RK, Steeves JH. Roth spots in chronic myelogenous leukemia. CMAJ. 2011;183(18):E1352. doi:10.1503/
cmaj.100561.
4. Falcone PM, Larrison WI. Roth spots seen on ophthalmoscopy: diseases with which they may be associated.
Conn Med. 1995;59(5):271-273.
Another presumptive cause of Roth’s spots proposed in more recent literature is a generalized
thrombocytopenia from increased intravascular
coagulation; this can lead to increased capillary
bleeding in the retina.11 Compared with the
typical high-resolution OCT imaging of
cotton-wool spots, the OCT scan through the
Roth’s spot in our patient showed additional
findings: numerous hyper-reflective dots in the
vitreous adjacent to the lesion and subretinal
fluid underlying the lesion. These hyperreflective dots were seen focally in the vitreous
directly overlying the lesion.
5. Vose MJ, Charles SJ. Roth’s spots: an unusual presentation of HIV. Postgrad Med J. 2003;79(928):108-109.
doi:10.1136/pmj.79.928.108.
6. Kim JE, Han DP. Premacular hemorrhage as a sign of
subacute bacterial endocarditis. Am J Ophthalmol.
1995;120(2):250-251.
7. Li G, Kapusta MA. Preretinal hemorrhages as the
presenting sign of subacute bacterial endocarditis.
Can J Ophthalmol. 2004;39(1):80-82.
8. Silverman ME, Upshaw CB Jr. Extracardiac manifestations of infective endocarditis and their historical
descriptions. Am J Cardiol. 2007;100(12):1802-1807.
doi:10.1016/j.amjcard.2007.07.034.
9. Moreillon P, Que YA. Infective endocarditis.
Lancet. 2004;363(9403):139-149. doi:10.1016/
S0140-6736(03)15266-X.
10. von Barsewisch B, ed. Perinatal Retinal Haemorrhages.
Berlin, NY: Springer-Verlag; 1979.
Based on their distribution, size, shape, and
decrease in number over time (Figure 3), these
hyper-reflective dots in the vitreous likely
represent inflammatory cells. We hypothesize
that these hyper-reflective dots may represent
a “shedding” of inflammatory cells from the
Roth’s spot lesion into the vitreous. There was
also subretinal fluid below the Roth’s spot that
resolved over time (Figure 3).
11. Ling R, James B. White-centred retinal haemorrhages
(Roth spots). Postgrad Med J. 1998;74(876):581-582.
doi:10.1136/pgmj.74.876.581.
Financial Disclosures
Dr. Freund – GENENTECH: Advisory Board, Investigator,
Honoraria; REGENERON PHARMACEUTICALS, INC: Advisory Board, Consultant, Honoraria; QLT, INC: Consultant,
Honoraria; ALIMERA SCIENCES: Advisory Board, Honoraria;
DIGISIGHT: Advisory Board, Honoraria.
Dr. Mrejen – None.
We hypothesize that this subretinal detachment
underlying the lesion likely indicates a
transient inflammatory reaction adjacent to
Mr. Giovinazzo – None.
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