retina

retinatimes
A VOICE FOR GREATER VISION
The Official Publication of
the American Society of Retina Specialists
Fall 2005 Issue 14
14
ASRS 23RD ANNUAL MEETING HIGHLIGHTS

INTRAVITREAL AVASTIN

4TH ANNUAL RETINAL RESEARCH REPORT

RNA INTERFERENCE TECHNOLOGIES

RISK MANAGEMENT: ROP

retina
retinatimes
Fall 2005 Issue 14 Organizational Staff Todd R. Klesert, MD, PhD
Volume 23, No. 3 KOL Corner Section Editor
The Retina Times is published quarterly by Tom S. Chang, MD
the American Society of Retina Specialists Editor-in-Chief Roy Levit, MD
(ASRS), Chico, California, as a service to the Foundation Chairman
membership. Steve Lenier
Managing Editor Mark Levitan, MD
The mission of the publication is to strive to State Carrier Network Director
be the definitive information source for ASRS Lida Asatryan
members on Society news, meeting plans, Assistant Managing Editor Klaus Lucke, MD
socioeconomic topics, international news, EVRS News Section Editor
and other relevant information on issues,
Cordie L. Miller
instruments and study updates for the Mathew MacCumber, MD, PhD
ASRS Managing Director
practicing retinal specialist. Articles published Classifieds Section Editor
herein are reviewed by the editor-in-chief and
Eugene de Juan, Jr., MD
managing editor for editorial content only.
ASRS President G. Philip Matthews, MD, PhD
The accuracy of information contained is the
Practice Management Meeting
responsibility of the individual author. Letters
John S. Pollack, MD Section Editor
and other unsolicited material are assumed to
Communications Committee Chairperson
be intended for publication and are subject to
John S. Pollack, MD
rejection or editing.
Section Editors PAT Survey Section Editor
All articles which appear in The Retina Times
are intended for informational purposes only Arthur W. Allen, Jr., MD Ethan Priel
and should not be relied upon by any reader for Risk Management Section Editor OPS/ASRS Liaison
any other purpose. The opinions and positions
expressed in The Retina Times articles are solely Carl C. Awh, MD Hugo Quiroz-Mercado, MD
those of the authors and do not represent the Fellows Forum Section Editor International News Section Editor
opinions or positions of the ASRS Board, its
members, or The Retina Times editorial staff. Karen Baranick William L. Rich, III, MD
Annual Meeting Section Editor AAO Medical Director of Health Policy
American Society of Retina Specialists Section Editor
PMB #A Abdhish R. Bhavsar, MD
2485 Notre Dame Blvd., Suite 370 Film Festival Section Editor Michael A. Samuel, MD
Chico, CA 95928 In the Spotlight Section Editor
phone: (530) 566-9181 Antonio Capone, Jr., MD
fax: (530) 566-9192 AAO/Federal Affairs Liaison Ingrid U. Scott, MD, MPH
e-mail: cordie@retinaspecialists.org Tips and Techniques Section Editor
David R. Chow, MD
About the Cover: Retsumer Reports Section Co-Editor Jay M. Stewart, MD
Posterior synechiae of iris to lens. In the Pipeline Section Editor
Photographer: Doheny Imaging Department Suzanne Demming, MD
Retinal World Section Editor Trexler M. Topping, MD
Coding Tip of the Quarter
Calvin A. Grant, MD
X-Files Section Editor Allen Z. Verne, MD
The Retina Times would like to thank
Site Selection Section Editor
Novartis Ophthalmics,
Alcon Laboratories, Scott G. Foxman, MD
and Practice Management Section Editor Creative Staff
Bausch & Lomb
for providing Tarek S. Hassan, MD Tun Min Soe
Unrestricted Educational Grants. Retsumer Reports Section Editor Art Director
Their generosity assists in MADLab, Doheny Eye Institute
enabling ongoing enhancements
to this publication. Nancy M. Holekamp, MD
Medical Ethics Section Editor John Tom
Designer
Mark S. Humayun, MD, PhD
R&D Committee Section Editor

Judy E. Kim, MD
JCAHPO News Section Editor

© 2005 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.
Implantable Miniature Telescope (IMT™). Dr. John Irvine’s patient.
Photographer: Doheny Imaging Department.

We want to publish your images too. If you have an interesting

image you want us to consider for publication in the Retina Times
(or possibly on the cover!) contact Steve Lenier, Managing Editor, at
steve@stevelenier.com.
>> CONTENTS

18 8 10

6 36 52
FROM THE EDITOR’S DESK IN THE PIPELINE CODING TIP
Are we Surgeons or Oncologists? Researchers Eye RNA The Time Has Come
Interference Technologies
7 57
FROM THE INSIDE 37 FOUNDATION UPDATE
Creative Design Rationale for TIPS AND TECHNIQUES
the Retina Times Pneumatic Retinopexy 57
Misconceptions JCAHPO NEWS
8
EVRS NEWS 39 59
European Sleepless Nights PRACTICE MANAGEMENT AAO LIAISON REPORT
in Sweden The Retina Practice
Business Process 59
10 PRACTICE MANAGEMENT
ASRS 23RD ANNUAL 43 MEETING
MEETING HIGHLIGHTS RETINAL RISK MANAGEMENT
Retinopathy of Prematurity: 59
15 Creating a Safety Net ADVERTISER INDEX
THE 7TH ANNUAL ASRS
FILM FESTIVAL 47 60
UNCLE RICH FELLOWS’ FORUM
18 Competitive Acquisition
THE KOL CORNER Program 60
So you want to try THE RETINAL WORLD
Intravitreal Avastin 49 Upcoming Meetings
MEDICAL ETHICS
23 Physicians as Investment
4TH ANNUAL RETINAL Consultants: Risky Business
RESEARCH REPORT
50
THE ASRS X-FILES

51
CARRIER NETWORK
Billing Macugen–
and what else?

4 retina times
E
>> FROM THE EDITOR’S DESK

Tom Chang, MD
Editor-in-Chief

Are we SURGEONS or ONCOLOGISTS?

After the roll-out of the FOCUS, PRONTO and MARINA data at the ASRS
meeting in Montreal I found myself sitting in a room filled with intense
excitement and almost a sense of relief. To quote the president of the ASRS,
Dr. Eugene de Juan, “ it was like being present when penicillin was introduced
to medicine”. This may very well represent the turning point for us at which
time we, as a collective specialty, finally realized that our field has officially
entered a new era of pharmacotherapy.
I have often heard the statement that retina specialists are undergoing a metamorphosis into oncologists. This is based
on the acute and sub-acute nature of the disease progression but also (to no lesser extent) to the financial issues of pass-
through pharmaceutical purchases. Although I believe that our field is becoming more like that of oncology, there are
some fundamental differences about us that may pose problems in this transition. Here are a few of my observations:
1) Retina specialists are first and foremost surgeons. Although a small minority of retina specialists identify themselves
as exclusively focusing their practice on medical retina, all of us began initially as ophthalmologists and have learned a
surgical mindset primarily.
For example, most of us rank our first experience with cataract surgery or peeling an epiretinal membrane as among
the most memorable moments in our lives (at least among the things we can talk about in mixed company!). As a surgical
field, we identify problems rather abruptly as fixable or not and have great creativity for new treatment exploration for the
latter category of problems. The impressive results from the Lucentis trials are expected to make significant advances in
our ability to treat our patients with neovascular AMD. It is important to begin to think of solutions to diseases like AMD
as more complex than one that can be resolved in a binary explanation of success or failure. Moreover, it is important for
us not to lose sight of the fact that Macugen and Visudyne have been (and will continue to be) valuable contributions to
treatment armamentarium.
Our experience with Macugen and Visudyne highlight an important difference between retina specialists and
oncologists. Any “medical” specialty would have wholeheartedly embraced a 20% difference in the ability to avoid a
primary outcome measure (i.e. 3 lines vision loss) and would have likely seen it as a breakthrough. I encourage you all to
talk to your internal medicine colleagues and explore this difference. The problem is that we, as ophthalmologists and as
retina specialists, are traditionally accustomed to a 95% macular hole closure success or retinal reattachment success rate.
Sure, we embrace treatments with less overt or slower success (i.e. laser for DME) but these therapies have not required
such a dramatic shift in our treatment patterns or mindsets and have not been seen as invasive/risky to our patients.
As we move forward in this time of significant change, it is helpful to continually remind ourselves not only about the
significance of these incremental changes but also that we will need to learn to think differently.
2) As a fellowship program director I find myself wondering how much we will have to overcome in our training
programs if we are going to embrace this transformation to becoming oncologists.
The most frequently asked question by applicants revolves around the surgical experience of the fellowship they are
applying to. In my experience, applicants seem largely uninterested in the number of medical retina specialists in our
program or in the research that is underway in treatments for AMD. An interesting aside is that the PRONTO data was
presented by Dr. Anne Fung who, despite being a fellow at the time, was trusted to present this important information
and did so in a highly professional manner. I believe that this is as much a testament to Dr. Fung’s accomplishments in her
research as it is to her program director’s focus on the importance of their medical retina fellowship. Will future fellow
applicants consider opportunities such as this to be as significant as the number of membrane peeling cases they perform?
If we are all truly going to become more like oncologists, why do we still have such an emphasis on the surgical aspects of
our field even from the early days of our education? Certainly I understand the anxiety about completely mastering the
techniques of vitreo-retinal surgery. Will we as a group have the same anxiety about being on the cutting edge of medical
treatments for AMD? It is entirely possible that, like oncology, we may increase the divide between medical and surgical
retina. Fortunately, our specialty is uniquely suited to be able to offer comprehensive care for our patients.
It is incumbant upon all of us to consider our surgical biases and mindset as we move forward into our brave new
world. One final note is that up until a few years ago, retina specialists looked a lot more like the oncologist generation of
the past, when the only answer was ...” sorry,...nothing I can do...”. The modern oncologist is different and operates at the
frontiers of bioscience.....the same is true for the retina specialists of today.

Tom Chang, MD
Editor-in-Chief
tomschang@hotmail.com

6 retina times
>> FROM THE INSIDE

Tun Min Soe

Art Director, MADLab
Doheny Eye Institute

CREATIVE DESIGN RATIONALE

FOR THE RETINA TIMES
The task of re-designing the Retina Times has been a
real challenge for us here at the MADLab. To take an
already established and successful formula and bring to
it a new and fresh perspective was no easy task.
From an open brief, we determined two initial
objectives. One, the design and presentation of the
magazine needed to be brought up to date, offering
improved readability in a modern and consistent
style. Two, there was a plan underway to bolster the
editorial content, to give readers greater depth and more
coverage on issues that are of most interest to them. We
needed to find a way to present this increased content in
a manner that makes sense, and creates an environment
of comfort for the reader. Both of these objectives were
to be accomplished with a tight budget, and while
staying on schedule.
Our first task was to establish a strong graphic
identity. A successful application of a strong identity
brings brand recognition and builds familiarity and
trust amongst the general readership and advertisers.
Part of the new graphic identity development
included the redesign of the main masthead. After
many rounds of concept reviews where different
opinions were canvassed–including those of ASRS
members–the final design was chosen for its flexibility
and expressive character. As you will see in future issues
of this magazine, the unique color combinations in the
masthead will change, giving each new issue freshness
and life. The restrained Perpetua font and use of its
lower serif case promotes a quiet approachability while
the impression of overlapping type effect gives it a
subtle transparency.
Next was to develop and deploy an integrated
contemporary design system to carry the content inside
of the new magazine. Consistency and better readability
were our prime goals here. We continued with the new
masthead aesthetics such as in the use of colors and
fonts, and employed balanced white space within a
tight grid structure to lay out the content, giving it an
open, fresh appeal. Where we can, and when available,
images such as photographs, diagrams, and other
graphical elements are given maximum exposure and
focus, especially within the main feature stories. We also
examined the physical charcteristics of the magazine.
The paper weight and the matt texture we settled on
were chosen for their look and tactile feel as well as for
durability.
Our first two issues are by no means the end of
the story, and you will see more changes over the next
issues as the new design system grows and matures. We
will maintain and build on our first steps, and we very
much welcome input and comments from readers on
improvement ideas for this magazine.

retina times 7
>> EVRS NEWS

Giampaolo Gini, MD Klaus Lucke, MD

European Sleepless Nights Section Editor

in Sweden
THE ANNUAL MEETING IN ÖREBRO
As the date of the EVRS meeting in Sweden approached, many of us wondered if the success which had
characterized the previous meeting in Istanbul could be matched. After all, Örebro is not particularly easy to
reach and does not convey to one’s mind immediate images of exotic and sophisticated tourist attractions.
So, it was with some surprise that, as we started counting, we found an unexpected number of members
quietly flocking into this delightful nordic town. We probably were not the only ones to be surprised.
Örebro’s tiny airport, reminiscent of what flying was all about before today’s colossal airports were built, had
probably rarely seen such intense traffic. Over 400 people attended the meeting, turning up from as far away
as Saudi Arabia and Korea, and representing 48 nations.
Örebro itself proved to be a pleasant surprise. Quaint, relaxed and exhibiting extremely friendly hospitality,
it made everyone feel at ease. In stark contrast to Istanbul there was not much sightseeing to be done, but simple and enjoyable social events with
plenty of time to catch up with old friends, share experiences and discuss future plans. Being so far north in the middle of June the sun in this place
hardly ever sets, making for extremely long days–an unusual experience especially for the many participants from countries further south. In fact
one member was made to wonder aloud how Swedish people ever manage to sleep.

THE MACULA IN FOCUS FUTURE CHALLENGES

The scientific program was concerned The General Assembly found the Society in good financial
with all that could be said on the shape and ready to meet future challenges. Among
macula. The importance of correctly these is an “International Fellowship Program” whereby
planning and executing diagnostic young surgeons can complete their training by travelling
procedures was stressed through a and spending some time with masters in the field. The
variety of papers and posters. enrolling phase is open and generating great interest.
The use of an assortment of The Assembly of Country Delegates elected Francesco
therapeutic agents such as intravitreal Boscia of Italy as their new chairman. Claude Boscher,
triamcinolone, r-TPA and the new who stepped down from that position, would like to
anti-angiogenetic drugs was thoroughly devote more time to representing EVRS with national and
examined. The discussion on these European authorities.
Lively discussions–a hallmark of EVRS meetings
issues was particularly lively and Cannes, the next major event, will take place in
focused on very practical clinical issues. shed new light on the possible nature of September 2006. This will be a joint meeting with the
Not surprisingly for a society such as macular hole formation. Conventional American Society of Retina Specialists and promises to be
ours, the surgical part drew the greatest and 25 gauge surgery in macular a memorable event for all.
attention. The surgical treatment of pathology was, understandably, another Thus, EVRS has begun to prove its extremely versatile
epiretinal membranes and macular hot topic. The results associated with nature and to display the wealth of different cultures
edema was revised and different macular translocation were discussed Europe has to offer. Perhaps EVRS has gone even a step
techniques were compared in detail. and relatively new techniques such as further, showing its truly
Histology, both conventional and RPE transplantation were presented. global reach, as professionals
associated with electron microscopy, Peep Algvere of Stockholm, who from many parts of the world
was presented with this year’s Relja gather under its insignia
Zivojnovic Award for his outstanding with the common goal of
contributions to the field of vitreoretinal excellence in patient care.
surgery, highlighted this session with a Keep posted on the website
keynote lecture on “The Challenge of and....see you in Cannes!
Retinal Transplantation”.
Following EVRS tradition, ADDITIONAL INFORMATION:
discussion on all the topics was quite The EVRS board of directors:
open and frank. Those involved, both Didier Ducournau, Nantes (President)
email: ddd@club-internet.fr
speakers and moderators, did their best Klaus Lucke, Bremen (Vice-President)
to leave the audience with the clearest email: K.Lucke@retina.to
Peep Algvere (left) being awarded the 2005 Relja Athanasios Nikolakopoulos, Thessaloniki (Secretary)
Zivojnovic prize by the President of this year’s possible “take home message” on each
email: nikolako@spark.net.gr
meeting, Sven Crafoord specific issue. Jerzy Nawrocki, Lodz (Treasurer)
email: J_Nawrocki@mail.e.pl
Frank Koch, Frankfurt
“TRUE TO LIFE” SURGERY email: 106063.536@compuserve.com
This year the “live surgery” session was substituted with a “true to life” one. Giampaolo Gini, Prato
Operations were videotaped in the surgeon’s own operating theater after prior email: giampaolo.gini@tiscali.it
Francesco Boscia, Bari (Chairman, Assembly of Country Delegates)
submission of the case. Cheating by case selection was impossible. Although this email: francescoboscia@hotmail.com
method lacks the emotional impact that live surgery has, “true to life” demonstrated Ferenc Kuhn, Birmingham Alabama (representative of the ASRS)
that it allowed a more inquisitive approach to each case, a more compact email: Fkuhn@mindspring.com
presentation, and an opportunity for wider discussion, and was generally felt to be Sven Crafoord, Örebrö (Meeting Host 2005)
email: Sven.Crafoord@orebroll.se
more ethical towards the patient. It may very well be that members may require Mario Facino, Genoa (Head, Young EVRS)
both of these forms to co-exist and complement each other in the future. email: mafacino@tin.it

The EVRS can be reached via its website: www.EVRS.org

8 retina times
M O N
T R E
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0 0 5
>> ASRS 23RD ANNUAL MEETING HIGHLIGHTS

Julia A. Haller, MD Karen Baranick

ASRS Scientific Program Meeting Planner
Committee Chairman Medical Conference Planners, Inc.

The ASRS 23rd Annual
Meeting was an unparalleled
success, setting records
for attendance, scientific
presentations, and “buzz”.
Over 600 ASRS members and
guests from 25 countries,
joined by enthusiastic family members and
360 representatives from 35 companies,
created the ideal mix for an outstanding
scientific and social program. The meeting
consisted of more than 130 papers, 80
posters, four instructional courses, panel
discussions, and special evening celebrations
and side trips.
SATURDAY
The meeting opened Saturday afternoon with
the Fluorescein Angiography & Surgical Case
Conference, moderated by Bill Mieler & Neil
Bressler. The “Bill and Neil Show” was well
attended and the interesting cases stimulated
plenty of discussion. The Welcome Reception
& Dinner that followed, presented by the
ASRS in partnership with Bausch & Lomb,
featured strolling musicians and stations with
themed “Taste of Montreal” dining selections.
SUNDAY
ASRS President Gene de Juan & Program
Chair Julia Haller officially opened the 23rd
Annual Meeting on Sunday morning. The
leadoff session featured cutting edge talks
on new devices, instruments and surgical
techniques (25 gauge vitrectomy remaining
a hot topic), followed by an “illuminating”
panel discussion deftly managed by Carl
Awh and his team of experts on vitrectomy
lighting options. Next we enjoyed a series
of provocative presentations on diabetic
retinopathy and venous occlusive disease.
The annual Young Physicians Section
Lunch Meeting, co-chaired by Sundeep Dev
and Ingrid Scott, honored Bill Mieler with the
Crystal Apple Award for excellence in teaching
and mentorship. Bill’s “Life in Addition to
Ophthalmology” presentation was a highlight
of the meeting, which also included an
informative, interactive discussion featuring
an electronic audience response system. The
YPS festivities were supported by Eyetech
Pharmaceuticals/Pfizer Ophthalmics, Inc.
The afternoon continued with a scientific
session on Pharmacology (“Drugs and
Bugs”), followed by a special Distinguished
Recognition Award ceremony honoring Bill
Rich for his Herculean labors on our behalf
over many years. Bill delivered a thoughtful
and provocative lecture entitled “The Tragedy
of the Commons and the ASRS’ Frontier.”
The first full day of the meeting concluded
its scientific portion with a special symposium,
“Managing the Risks of Intravitreous
Injections” adeptly organized by Harry Flynn
and featuring a panel of opinionated expert
discussants.
As the cooler air of the evening swept
over Montreal (the weather was the hottest
recorded in 30 years!), attendees dispersed
to restaurants and other attractions of their
choice, with a large group choosing the
delightful musical review and dinner at the
Cabaret du Casino de Montréal.
MONDAY
The annual Breakfast with the Masters,
orchestrated by David Boyer and supported by
Genentech, Inc., kicked off Monday morning
with record attendance. The table discussion
was so animated that it was difficult to clear
the room and move attendees into the session
hall.
Once seated in the main hall, attendees
were treated to a very special awards
presentation ceremony. Mark Blumenkranz
received the Retina Research Foundation’s
Gertrude D. Pyron Award for Outstanding
Achievement in Retina Research and presented
his captivating lecture “Clinical Research
and Vitreoretinal Practice: The Impact of
Rapid Technology Change and Quantitative
Modeling in the Decision-making Process.”
Steve Ryan was then recognized with the
ASRS Founders Award. This annual award
honors the society’s founders Jerry Bovino,
Roy Levit, and Allen Verne for their vision of
an open society which promotes the collegial
exchange of ideas between retina surgeons,
and is presented to individuals who have made

ASRS VOICES

“The young physicians section once again proved to be a great forum for younger retina
specialists to interact and share experiences. The audience response system provided real-time
useful information on difficult treatment controversies. Dr. Mieler’s distinguished lecture on Life
Beyond Ophthalmology is one everyone would benefit from.”
—Sundeep Dev, MD
Minneapolis, MN “As always, the ASRS meeting had its pulse on the cutting edge topics
affecting the daily practices of retina specialists. Most importantly, the
latest data on treatments such as investigational treatments for AMD,
intravitreal steroids for diabetic edema and venous occlusive diseases, and
advances in surgical techniques and instrumentation were emphasized.
This meeting provides an invaluable service to all retina surgeons.”
“Flawless performance. Congratulations to the entire ASRS Annual —Jeffrey S. Heier, MD
Meeting Organizing Committee and Medical Conference Planners, Boston, MA
Inc. This meeting had an extra bit of excitement–media and analyst
coverage of the announcement of Lucentis data.”
—Brett T. Foxman, MD
Northfield, NJ

12 retina times
major contributions to the advancement of
vitreoretinal surgery, treatment, research,
surgical instrumentation, and patient care.
Steve gave a thought-provoking lecture
on “Genetic Predisposition to Macular
Degeneration.”
David Parke then updated us on the AAO
and Vitreoretinal Issues–2005.
The morning’s scientific session entitled
Treatment of AMD 2005 was perhaps the
“hottest ticket” of the week. An estimated
crowd of over 800 packed the room to capacity
and more as investigators reported study
results, culminating in Joan Miller’s discussion
of the Phase 3 results from the Genentech
study of ranibizumab for the treatment
of minimally classic and occult choroidal
neovascularization in AMD.
Monday night’s Evening at the Montréal
Museum of Fine Arts, hosted by the ASRS
in partnership with Genentech, Inc., was a
lively affair as guests enjoyed the galleries of
14th to 19th century European Art as well
as delicious food, signature beverages, and
collegial discussion of the day’s presentations
and adventures.
TUESDAY
The topic of Age-Related Macular
Degeneration remained in the forefront as
Tuesday morning began, kicking off with
cutting edge reports by Emily Chew and Eric
Postel on the association of Complement
H-related genetic mutations with AMD, and
continuing with other studies looking at
risk factors, imaging and treatment. A nice
overview of the exciting but increasingly
complicated management issues confronting
all of us who treat patients with AMD was
then provided by a team of lucid discussants,
expertly organized and moderated by Phil
Rosenfeld.
The next session took participants first into
new developments and uses for ocular imaging
and then on to the field of pediatric retina.
Lunchtime’s optional Malpractice
Protection Seminar seemed headed for
disaster when the guest speaker’s plane was
delayed–but not to worry: our own George
Williams, David Parke, Bill Rich and Trex
Topping came to the rescue with polished
expertise until the featured guest arrived for
the wrap-up.
Optional instructional courses filled the
afternoon for those choosing to take them.
The topics this year included Retinal Coding,
Molson with the Masters, Advances and
Controversies in Vitreoretinal Surgery, and
Intraocular Tumors.
Tuesday evening the lecture hall was
transformed into a magical candelabra-
bedecked and elegant ballroom for the Gala
Dinner, featuring the Film Festival Awards,
and some amazing dance moves from retinal
specialists who should know better (do not
attempt these at home)–all to the tunes of
La Gioventu Orchestra. The dance floor was
packed until the end of the evening.....with a
number of “postparties” continuing into the
wee hours for many!
WEDNESDAY
Wednesday morning an intrepid crew of post-
Gala attendees were treated to a compelling
leadoff session entitled Macula 2005–Beyond
AMD. The meeting concluded with a strong
session on Retinal Detachment and Trauma.
PAT SURVEY & RESEARCH REPORT
The Seventh Annual PAT Survey Committee
had its comprehensive display with often
surprising responses to multiple issues
regarding vitreoretinal medicine, techniques,
and controversies. Also providing attendees
with an impressive poster display was the
Research & Development Committee that
posted its annual report of ongoing trials.
Thanks to the PAT Survey Editors Rob Mittra
and John Pollack and their committee as well
as the R & D Committee, chaired by Mark
Humayun, for all of their efforts and hard
work.
THE 7TH ANNUAL ASRS FILM FESTIVAL
This year, 44 films were entered in the Annual
Film Festival, making it one of the biggest to
date. The winners of the Rhett Buckler and
Dr. Vitrector Awards can be found in Abdhish
Bhavsar’s article in this issue of The Retina

“The meeting was perhaps the most exciting retina meeting that I have attended yet; the
presence of so many analysts on Monday, for better or worse, created a huge buzz. And, as
usual, the attention to detail by the organizers and meeting planners was impressive!”
—Colin A. McCannel, MD
Rochester, MN

“This ASRS meeting was special, even by ASRS standards. A wonderful mix of science,
practical take-home messages, and great friendships. Montreal was a wonderful,
cosmopolitan venue for a meeting, and Cannes in ‘06 should be even better.”
—David W. Parke II, MD
Oklahoma City, OK
“I really enjoy the ASRS meeting as an opportunity to hear about
everything that’s going on in the world of vitreoretinal diseases
and meet up with my mentors and colleagues who I trained with
over the years, particularly my previous fellows and residents.”
—Philip J. Rosenfeld, MD, PhD
“This meeting has been terrific. Once again outstanding scientific content, Miami, FL
terrific location, and seamless meeting production have led to the ASRS Annual
Meeting reputation as the one meeting not to be missed by retina specialists”.
—John S. Pollack, MD
Joliet, IL

retina times 13
 >> ASRS 23RD ANNUAL MEETING HIGHLIGHTS

Times. Congratulations to all winners, many of attend! Please visit www.retinaspecialists.org Laserex
Leica Microsystems
whom represent our outstanding international for up-to-date annual meeting information. Lumenis
contingency. Mediflex Surgical Products
Direct meeting questions to MedOne Surgical Inc.
Nidek
SPECIAL ACKNOWLEDGEMENT karen.baranick@medconfs.com or Ophthalmic Imaging Systems
The ASRS would like to recognize and thank petra.dwyer@medconfs.com Ophthalmic Technologies, Inc.
John Focosi of Advanced Media Systems for Optos North America
doing a simply superlative, flawless job with Priority Healthcare
CORPORATE SUPPORT Quantel Medical, Inc.
the technical direction of the 23rd Annual Retinal Physician
The American Society of Retina Specialists wishes to once
Meeting. In addition, great meeting photos again extend its gratitude to the corporate supporters who Theragenics Corporation
taken by Kevin Caldwell Photography are have demonstrated a commitment to the advancement of VisionCare Ophthalmic Technologies, Inc.
our profession through their generous support of the 23rd Volk Optical, Inc./Keeler Instruments, Inc.
up for viewing at www.retinaspecialists.org.
Annual Meeting. Their interest and contributions have been
Finally, enough thanks simply can not be critical to the success of this meeting. SPECIAL THANKS TO THE FOLLOWING COMPANIES
given to Karen Baranick, Petra Dwyer, FOR THEIR ADDITIONAL SUPPORT...
Carrie Jacobowitz and their team of super- PLATINUM PARTNERS
Genentech, Inc.
Alcon Laboratories, Inc.
competent, unflappable, ever-charming Allergan The Evening at the Museum of Fine Arts
planners at Medical Conference Planners, Inc. Bausch & Lomb Breakfast with the Masters
The Meeting Bags
who manage to put the innumerable pieces of Carl Zeiss Meditec
Scientific Poster Display
Eyetech Pharmaceuticals/Pfizer Ophthalmics
this ever-more-complicated meeting puzzle Two Refreshment Breaks
Genentech, Inc.
together year after year–and it just keeps
Novartis Ophthalmics
getting better! GOLD PARTNERS
Insight Instruments Inc. The Gala Dinner Banquet
Iridex
MARK YOUR CALENDAR Novartis Ophthalmics Bausch & Lomb
“Cannes Retina Festival” OccuLogix, Inc. The Welcome Reception & Dinner
The 24th Annual ASRS Meeting & Synergetics, Inc
Topcon Medical Systems Alcon Laboratories, Inc.
The 6th Annual EVRS Meeting The 7th Annual Film Festival
Palais des Festivals et des Congrés SILVER PARTNERS
American Academy of Ophthalmology Eyetech Pharmaceuticals/Pfizer Ophthlamics
Cannes, France Young Physicians Section Meeting
American Retina Foundation
September 9-13, 2006 Compulink Hotel Key Cards
DORC International,bv/Dutch Ophthalmic, USA
Allergan
A “Call for Papers and Meeting Registration” Health Care Intranet Technologies, Inc.
One Refreshment Break
Heidelberg Engineering
brochure will be mailed to all members in Innovative Imaging, Inc.
January 2006. We hope you are planning to Labtician Ophthalmics, Inc.

“The 2005 ASRS Annual Meeting in Montréal was another great success, with an excellent scientific program and a
typically elegant and fun series of social gatherings. It was gratifying to see the increasing national influence of the
ASRS reflected in the prominent press and financial analyst interest that was so apparent at this year’s meeting.
Congratulations and “thanks for all the hard work” to Dr. Julia Haller as Program Chairperson, Karen Baranick and her
talented and hardworking crew at Medical Conference Planners, Inc. and Cordie Miller for a job well done!”
—David F. Williams, MD, MBA
Minneapolis, MN

”The meeting struck a healthy balance among well-presented papers, small-group

sessions, and lively social gatherings; this allowed for formal presentation of cutting-
edge research as well as intimate discussions with colleagues.”
—Franco M. Recchia, MD
Nashville, TN

“The Montreal meeting offered some truly interesting information on the management of
wet ARMD asking as many ethical as scientific questions. Interacting with colleagues to
get their take on the new information added tremendously to the value of the meeting.”
—Mark Michels, MD
Palm Beach Gardens, FL
14 retina times
>> FILM FESTIVAL
THE 7TH ANNUAL ASRS FILM FESTIVAL–
ASRS 23RD ANNUAL MEETING IN MONTREAL
The 7th Annual ASRS Film Festival was an outstanding
success! There were 44 films submitted this year and all
of them were well done.
We owe sincere appreciation to Mark Forchette
and Alcon for their support
of the ASRS Film Festival
for the past, the present and
the future. I also want to
personally thank Kirk Packo
and Paul Tornambe. They have
influenced me greatly in my decisions of how to proceed
through the task of completing this year’s Festival.
The 2005 ASRS Film Festival Judges and I saw every single second of
every single movie and worked very hard on this year’s film festival.
We owe a debt of gratitude to the judges of this year’s Film Festival in
Montreal, all of whom went above and beyond the call of duty with the
many hours that it took to review and judge the films this year:
JUDGES
Edgar Thomas (Los Angeles, CA), Lead Judge
Mark Balles (South Portland, ME)
Anurag Gupta (Los Angeles, CA)
Richard Johnston (Minneapolis, MN)
Hugo Quiroz-Mercado (Mexico City, Mexico)
WINNERS OF THE RHETT BUCKLER AWARD:
“BEST OF SHOW”
1. Managing Dry Macular Folds after Vitreoretinal
Surgery
Carlos Mateo, MD (Barcelona, SPAIN)
Borja Corcostegui, MD
2. Condiments in Vitreoretinal Surgery: A Bad Day in
the Kitchen!
J. Fernando Arevalo, MD, FACS (Caracas, VENEZUELA)
Reinaldo A. Garcia, MD
3. Primary PVR in Buphthalmos
Gaetano R. Barile, MD (New York, NY)
Avi Grinblat
Michael Turano
4. Heavy Silicones in Severe Vitreoretinal Diseases
Cesare Forlini, MD (Ravenna, ITALY)
Paolo Rossini, MD
5. Origin of Subretinal Fluid in Optic Disc Pit
Maculopathy: ß-2 Transferrin Analysis
Ronald C. Gentile, MD (New York, NY)
Alfonso Ponce, MD
Abdhish R. Bhavsar, MD
Chair, ASRS Film Festival
6. The Use of New Surgical Strategies in Dealing with
Ocular Trauma
Giampaolo Gini, MD (Prato, ITALY)
Vincent S. Reppucci, MD (New York, NY)
7. Vitrectomy for Dummies
Virgilio Morales-Canton, MD (Mexico City, MEXICO)
8. The Use of Different Illumination/Observation
Systems for Peripheral Vitrectomy
Jerzy Nawrocki, MD (Lodz, POLAND)
Zofia Nawrocka, MD
Janusz Michalewski, MD
Zofia Michalewska
9. A New Microscope with Wide Angle Viewing System
without Endoillumination
Murat Oncel, MD (Istanbul, TURKEY)
10. Modified Technique for Improving Trypan Blue
(TB) Staining of Epiretinal Membranes (ERM)
Stanislao Rizzo, MD (Lucca, ITALY)
Michele Palla, MD (Pisa, ITALY)
Federica Genovesi-Ebert, MD, PhD
DR. VITRECTOR AWARD
The new Dr. Vitrector Award, for innovative film
technique and vitreous humor, as inspired by the
original Dr. Vitrector films, was given to three film
producers this year.
DR. VITRECTOR AWARD JUDGE:
Abdhish R. Bhavsar, MD
WINNERS OF THE NEW DR. VITRECTOR AWARD:
1. Origin of Subretinal Fluid in Optic Disc Pit
Maculopathy: ß-2 Transferrin Analysis
Ronald C. Gentile, MD (New York, NY)
Alfonso Ponce, MD
2. 25-Gauge Vitrectomy for Vitreoretinal Diseases
Fabio Patelli, MD (Rome, ITALY)
Paolo Radice, MD
Giulio Zumbo, MD
Giuseppe Fasolino, MD
3. Mission Possible: Iridocyclectomy for Ciliary Body
Leiomyoma
Michael A. Samuel, MD (Los Angeles, CA)
Jennifer I. Lim, MD
retina times 15
>> FILM FESTIVAL

FILM CRITIQUE
In upcoming issues of The Retina Times, Garee Thomas and I will be reviewing other films that were winners of either the Rhett Buckler award,
granted by the film festival judges, or the Dr. Vitrector Award that was granted by me. In this issue, we will discuss three films:

“BEST OF SHOW”
1. Managing Dry Macular Folds after Vitreoretinal Surgery

2. Condiments in Vitreoretinal Surgery: A Bad Day in the Kitchen!

3. Origin of Subretinal Fluid in Optic Disc Pit Maculopathy:

ß-2 Transferrin Analysis

Abdhish R. Bhavsar, MD Edgar L. Thomas, MD

1. Managing Dry Macular Folds after Vitreoretinal Surgery

Carlos Mateo, MD (Barcelona, SPAIN)
Borja Corcostegui, MD
Drs. Mateo and Corcostegui have done a great job of overlaying the Drs. Mateo and Corcostegui have outdone the “weather man!” This
narrator, Dr. Mateo, on a moving background of the retina. This beautiful synthesis of video, overlay and graphics presentation of
gives us a 3-D view of the macular fold and the contour as if we were a complicated macular fold is a unique way of explaining it to the
looking at a fault line in the desert. This is a superb maneuver to help clinician in a way that is the state of the art in videography. The
us understand the pathology. The animations, graphics and video authors (producers may be a better video term), did an outstanding
in the film are also outstanding. I have learned a great deal about job of this presentation and deserve the major accolade.
managing dry macular folds from the techniques utilized in limited
macular translocation. I am certain that after you view the video, you
will find the same to be true. A wonderful video and certainly the Best
of Show for this year’s film festival!

2. Condiments in Vitreoretinal Surgery: A Bad Day in the Kitchen!

J. Fernando Arevalo, MD, FACS (Caracas, VENEZUELA)
Reinaldo A. Garcia, MD
Drs. Arevalo and Garcia have allowed us to see into the world of What a bad day! We so often depend on our assistants to use the
complications in an environment where complications can happen. utmost care in performing complicated tasks that we feel are just “so
They have redefined the meaning of exquisite film editing of retina easy!” Drs. Arevalo and Garcia share a catastrophic complication of
surgical video. The entire film is clear with good surgical footage and ICG injection. It’s really not related to the toxicity of the dye, but the
clear lighting. They have elucidated a series of maneuvers to avoid mere shearing forces of liquid under pressure in an air filled eye. In an
the severe complications of a high pressure jet stream creating retinal eye with fluid, this would probably not have occurred. They deserve
trauma. The toxicity of the ICG may only have been incidental to credit for sharing this problem with us, demonstrating it with great
the subretinal injection and retinal tear. The narration is succinct candor and helping us avoid a similar circumstance in the future. This
and clear. Follow their instructions and hold your breath during the type of presentation benefits all of us doing complicated vitreoretinal
injection! An excellent film! surgery. Congratulations.

3. Origin of Subretinal Fluid in Optic Disc Pit Maculopathy: ß-2 Transferrin Analysis
Ronald C. Gentile, MD (New York, NY)
Alfonso Ponce, MD
Drs. Gentile and Ponce have added a new meaning to the theme Drs. Gentile and Ponce have done what the “video” should do. I have
for the Pink Panther. The entire movie is set the music from the always had a pet peeve about presenters reading their slides or doing
Pink Panther. The lack of a voice-over during any of the video voice-overs when the text is on the screen. No other video in the
demonstrates the fact we learn 90% from the our visual input. The program had nary a word spoken (except for the Dr. Vitrector teaser
graphics and morphing are outstanding. This film is totally deserving for Cannes 2006!). I can tell you I got a great deal of knowledge from
of the Dr. Vitrector award for innovation and humor in the spirit of this video and it confirms my belief in the origin of sub-retinal fluid
the original Dr. Vitrector films. In addition, this film was awarded the in optic pits. This was a scholarly presentation with a very specific
Rhett Buckler Award as well by the team of judges. This was the only marker for CSF and it wasn’t found. Congratulations on one of the
film this year to have the privilege of winning both the Rhett Buckler best!
Award and the Dr. Vitrector Award!

Stay tuned for the next issue and additional critiques of the winners from the 7th Annual ASRS Film Festival!

16 retina times
>> THE KOL CORNER

Todd R. Klesert, MD, PhD

KOL Corner Section Editor

So You Want to Try

Intravitreal
Avastin®

Editor’s Note. The term Key Opinion Leader (KOL) is used frequently degeneration and refractory macular edema secondary to venous
by pharmaceutical companies to refer to individuals in the field who are occlusive disease. Better yet, the per-treatment cost of Avastin® works
felt to be thought leaders. In this time of rapidly evolving treatments and out to be only a fraction of other currently available FDA-approved
decision paradigms, controversies will likely arise. We have created this therapies, such as Visudyne® and Macugen®. So, what is the catch?
new column as a forum to allow members of our society to provide their Avastin® was developed and is marketed as an intravenous treatment for
thoughts regarding important new and potentially controversial issues metastatic colorectal cancer, and is FDA approved for that indication
that present to our specialty. only. Intravitreal injection of Avastin® is therefore an off-label use of the
We will try to engage, whenever possible, the most noted experts in medication, employing an altered route of administration.
the field for each issue. However, in my many discussions and e-mails
with ASRS members in the past 6 months, I must say that I have learned
much from every member. Specifically, it is our belief that although
certain individuals are leaned on more frequently to provide opinions
on controversial or new topics, the opinions of all retina specialists are
important. In future articles, we will try to rotate our KOL list to include
individuals from the entire spectrum of our specialty.

The retina community is currently abuzz with talk of promising

new therapies for the treatment of macular degeneration and
refractory macular edema. The recent announcement by Genentech
of preliminary phase III clinical trial results for their forthcoming
anti-VEGF drug Lucentis® (ranibizumab) has raised expectations of
what will be available for treatment of patients with these debilitating
conditions in the future. FDA approval and commercial availability of
Lucentis®, however, may still be more than a year away.
Avastin® (bevacizumab) is a close relative of Lucentis®, also
developed by Genentech, which is already commercially available.
Illustrates intravenous Avastin (bevacizumab) molecules inhibiting the action of VEGF
Early evidence (both published1-3 and anecdotal) suggests that it may (vascular endothelial growth factor) in a subfoveal CNV (choroidal neovascular vessels)
be as effective as Lucentis® in treating exudative age-related macular condition.

18 retina times
 This raises many important ethical, medical-legal, and practical
questions that anyone contemplating the use of intravitreal Avastin®
should carefully consider before proceeding. As guidance, the
editorial office of the Times has collected individual opinions of
several leaders within our society and has sought clarification from
some of our pertinent regulatory bodies to provide guidance to our
membership. These are the express opinions of those interviewed and
are NOT an endorsement from the ASRS or the Times.
THIS MONTH’S OPINION LEADERS:
Kirk Packo (K.P.), MD is a vitreoretinal specialist
with Illinois Retina Associates, chair of the
Rush-Presbyterian Medical Center Dept. of
Ophthalmology (Chicago, IL), and past President
of the American Society of Retina Specialists.
George Williams (G.W.), MD is a vitreoretinal
specialist with Associated Retinal Consultants,
chair of the William Beaumont Hospital Dept. of
Ophthalmology (Royal Oak, MI), past President of
the American Society of Retina Specialists, and a
committee member for OMIC.
Bob Avery (B.A.), MD is a vitreoretinal specialist in
private practice with California Retina Consultants
(Santa Barbara, CA), and has been a principal
investigator in 8 clinical trials investigating new
retinal treatments. He and his associates were the
first to implement off-label intravitreal Avastin® for
patient care on the West Coast.
Tom Chang (T.C.), MD is Editor-in-Chief of
Retina Times and a faculty member of the Doheny
Retina Institute, University of Southern California
(Los Angeles, CA).
Anne Menke (A.M.), RN, PhD, is Risk Manager of
Ophthalmic Mutual Insurance Company (OMIC).
Her articles on ophthalmic risk management
have appeared in the OMIC Digest, Retina Times,
EyeNet, and Techniques, and she is a regular speaker
at state, national, and sub-specialty ophthalmology
conferences.
Wiley Chambers (W.C.), MD is Deputy Division Director of the
Division of Anti-Infective and Ophthalmology Products in the
Center for Drug Evaluation and Research at the Food and Drug
Administration.
What are the medical-legal risks of using intravitreal Avastin®
off-label?
K.P.: Medical-legal considerations only take place if there is a failure
to deliver the standard of care and harm is caused. The definition
of standard of care changes from geographic location to geographic
location. One can argue that the community can be described as the
“vitreoretinal community of practioners”. This seems to have been the
case for intravitreal Kenalog®, for which the off-label use was embraced
whole-heartedly by the retina community without clinical trials.
I think the term “off-label” has an inappropriately negative
connotation. The FDA is not explicitly against the off-label use of
medications, as long as those uses are generally accepted by the
community of medical practicioners. The FDA understands that
requiring approval for all uses of any given medication would
completely bog down the drug approval process.
B.A.: We retina specialists frequently use other drugs off-label as well.
For instance, intravitreal antibiotics for endophthalmitis, TPA for
hemorrhagic AMD, pre- and post-operative antibiotics, and C3F8 for
cases other than pneumatic retinopexy are all off-label uses.
A.M.: Once a device or medication is approved by the FDA,
physicians may use it “off-label” for other purposes as part of the
practice of medicine if 1) they are well-informed about the product,
2) they base its use on firm scientific method and sound medical
evidence, and 3) they maintain records of its use and effects. When
medications are first used “off-label” for a new indication, there are
often few if any adequate studies of the safety, efficacy, and long-term
risks of its use. The physician must therefore exercise care in selecting
patients, be familiar with the information that the manufacturer
includes in the FDA-approved “label” detailing the indications,
risks, and benefits that were determined during clinical trials, and
monitor the patient for ongoing need, efficacy, and safety. In addition,
ophthalmologists would be well advised to inform patients of the
medication’s “off-label” status during the consent discussion, and
keep a file of articles and other materials that support the decision to
use the drug in question.
G.W.: At the end of the day, with medical-legal matters, the only
“standard of care” issues that will be of importance will be those
which a jury will decide.
Avastin® contains a “black box” warning in the package insert,
indicating a risk of serious and potentially fatal adverse side
effects, including GI hemorrhage, GI perforation/wound healing
complications and pulmonary hemorrhage. Increased risk of
arterial thromboembolic events, hypertension, proteinuria, and
congestive heart failure were also observed in the clinical trials.
Does the “black box” status of Avastin® change the medical-legal
equation?
K.P.: Glaucoma specialists have used mitomycin off-label for
trabeculectomies for some time. This is a drug with teratogenic as
well as other potentially serious systemic effects.
G.W.: These potential complications need to be discussed with
patients before consideration of use, but keep in mind that the drug
is being injected at a dose several hundred times lower than the dose
given intravenously to cancer patients. The safety profile should
arguably be considerably lower at these concentrations.
T.C.: It should be noted that the FDA clinical trials for Avastin® were
conducted on patients with metastatic GI and lung malignancies. The
“black box” warnings for Avastin® [potentially fatal GI hemorrhage,
pulmonary hemorrhage, GI perforation, and a doubling of the
thromboembolic risk] are almost certainly a unique reflection of
this patient population. The documented fatal GI and pulmonary
hemorrhages likely developed secondary to tumor contraction or
necrosis (i.e. a positive treatment effect). Similarly, the well-known
association between cancer and coagulation abnormalities was
probably a significant factor contributing to the increased risk of
arterial thromboembolic events in patients treated with Avastin®. It
should also be remembered that these patients received high-dose
retina times 19
>> THE KOL CORNER
systemic treatment every two weeks for months and months, and
were concurrently treated with other chemotherapeutic agents. On
the whole, AMD patients are a significantly healthier population.
A.M.: Whether these complications will occur with lower dose,
intravitreal administration in patients who do not have cancer
is precisely what, in part, clinical trials will determine. For now,
ophthalmologists should proceed with caution, since patients
likely to need Avastin® may also have cardiovascular conditions
and hypertension. First, physicians should carefully screen patients
for medical conditions that might increase the likelihood of these
complications. Next, they should give patients information about
the known risks of the drug when used intravenously for colorectal
cancer patients, and explain that while the decreased dosage
and regional administration of the medication may decrease the
likelihood of these risks, neither the safety, efficacy, or long-term
risks of intravitreal Avastin® for ocular conditions has been proven.
Patients should also be told that whenever a medication is used
in a large number of patients, a small number of coincidental
life-threatening problems may occur that have no relationship to
the treatment. Ophthalmologists should consider getting medical
clearance for patients with pertinent medical comorbidities. Before,
during, and after administration, patients should be monitored for
adverse events. At the time of discharge, patients should be given
written contact information detailing eye symptoms that should be
immediately reported to the ophthalmologist or, if they experience
symptoms of life-threatening conditions affecting organs other than
the eye, the primary care physician.
Do you have any absolute medical contraindications for intravitreal
Avastin®?
B.A.: In Phil Rosenfeld’s study of intravenous Avastin®, a mild
elevation in blood pressure in some patients treated with systemic
Avastin® was observed. However, our group has not seen a significant
elevation in blood pressure or other adverse systemic effects in those
patients treated with intravitreal Avastin®. Nevertheless, I would feel
uncomfortable treating someone with a recent myocardial infarction,
unstable angina, or a recent stroke until more safety data is obtained
and published. So far, the intravitreal drug seems to be very well
tolerated. We have treated over 75 patients and we have yet to see
uveitis.
What must be included in the documentation of informed consent?
Is a special procedure-specific consent form required for off-label use
of Avastin®?
G.W.: It is important for us to remember that informed consent
is a process and not a form. The consent form is simply a vehicle
to document that process. Any informed consent with patients for
intravitreal Avastin® must include disclosure that the patient is being
offered off-label use and that there are no definitive trials showing
efficacy. In addition, detailed discussion of all other potential
treatment options (i.e. Macugen®, PDT) must be documented.
T.C.: It will be important to demonstrate/document a clear
justification for the use of this off-label application, for example, if
a patient has been shown to be a treatment failure to Macugen® or
PDT. We need to keep in mind that these are treatments that have
demonstrated efficacy in randomized clinical trials.
G.W.: I would be reluctant to deny someone an approved therapy
without detailed explanation of the reasons why in the informed
consent.
A.M.: Ophthalmologists should carefully document the decision-
20 retina times
making process that led to using Avastin®, and write a note in the
medical record about the consent discussion, including the disclosure
of the drug’s off-label status and any complications for which the
patient has an increased risk. Except for truly minor procedures with
little risk, it is always prudent to use a procedure-specific consent
form (a sample form for intravitreal Avastin® will be posted soon on
the OMIC website). Patients should be offered a copy to read at home
and encouraged to contact the physician with any questions.
How do you bill for intravitreal Avastin® injections? Do you get paid?
G.W.: The payment for the injection should be automatic since
intravitreal injection of therapeutic agents is covered by CPT code
67028. Any discussion on payments for the drug itself will require
discussion with individual local carriers.
K.P.: Yes, the national carrier decision on reimbursing the injection
was demonstrated with Kenalog®. For the drug coverage, it is likely
that the local carriers will need to see more published data.
How do you mix and aliquot Avastin® for intravitreal injection?
B.A.: Avastin® is available in 100 mg and 400 mg vials. We use the 100
mg vial, which contains 4 cc of a 25 mg/cc concentration of the drug.
We have a compounding pharmacy divide this into 0.1 cc aliquots.
We inject 0.05 cc, for a delivered dose of 1.25 mg.
W.C.: Although FDA does not regulate the practice of medicine, were
this product to be used under an IND in a clinical trial, FDA would
expect adequate information would be presented to insure that use
of the product as outlined above would in fact provide adequate
protection against the administration of non-sterile product into
the eye. The ophthalmic use of an unpreserved product in multiple
patients is contrary to the Code of Federal Regulations concerning
ophthalmic products (21 CFR 200.50).
B.A.: I am surprised to learn of this regulation. We were simply
following the exact protocol of a major teaching hospital. I know
other universities would aliquot TPA in the past, and many university
and private practices use a single unpreserved vial of Botox® on
multiple patients. In fact, Medicare has given guidance with respect to
how to bill for one vial of Botox® used in multiple Medicare patients.
Nevertheless, even if this code does apply to injected medicines, a
100 mg vial of Avastin® is still significantly cheaper than a vial of
Macugen® or Visudyne®, and the effects are quite striking. As Phil
Rosenfeld showed in his published case reports, we too are seeing
some remarkable early responses. Eight of our first 21 injected eyes
had complete resolution of retinal thickening at 4 weeks.
A.M.: The medication comes in preservative-free vials intended
for use on a single cancer patient at a much larger dose. Using
one Avastin® vial for multiple patients with ophthalmic problems
raises a number of patient safety and professional liability issues.
OMIC obtained a formal legal opinion from an outside attorney
about whether federal regulations (i.e., 21 CFR 200.50) prohibit
ophthalmologists from treating more than one patient with a single
unpreserved vial. The regulations pertain to the manufacture and
packaging of ophthalmic drugs, and nothing, according to the
attorney, specifically addresses the use of an unpreserved product
in multiple patients. As a risk management measure, therefore, and
to respect the intent of the regulations even if they do not appear to
pertain to how the drug is used, physicians should take certain steps.
First, to ensure safe administration, ask a compounding pharmacy
to prepare the medication for ophthalmic use, confirm the dose
and sterility, identify a syringe suitable for this protein, and provide
storage and “beyond-use” instructions, and the lot number of the vial.
Second, to reduce the risk to their patients and themselves,
ophthalmologists would be well-advised to “credential” the
compounding pharmacy to which they send the prescription for
intravitreal Avastin®. Recent legislation should make that
quality assurance step a little easier. In response to concerns
about contamination and potency, a new federal standard
for preadministration manipulation of compounded sterile
preparations (CSP) was established, effective January 2004,
and codified in USP Chapter 797. The standard addresses
compounding, transportation, and storage of CSPs and is
enforceable by the FDA, state boards of pharmacy, boards
of health, and other regulatory agencies (e.g., JCAHO).4
Physicians should ask the compounding pharmacy
for assurance that it is licensed/registered in the
state in which it is dispensing and is complying
with USP Chapter 797. In addition to providing
ophthalmologists with a CSP upon receipt
of a prescription for an individual patient,
“pharmacists may compound drugs in very
limited quantities prior to receiving a
valid prescription based on a history
of receiving valid prescriptions that
have been generated solely within
an established pharmacist/
patient/prescriber relationship,
and provided that they maintain
the prescriptions on file for all
such products compounded at the
pharmacy (as required by State law).”5 Ophthalmologists should
be wary of obtaining CSP from pharmacies that advertise their
ability to compound specific drug products such as Avastin®, since
advertisements of that type are contrary to the “Good Compounding
Practices” and ethical standards of the National Association of State
Boards of Pharmacies.5
Do you need an IRB approval and/or IND application to perform a
retrospective study on patients on an off-label basis (i.e. no formal
“research” consent, IRB submission, or protocol)?
W.C.: Avastin is an approved biologic agent, approved for use in a
®
different patient population by a different route of administration.
As such, the intravitreal use of Avastin® in a study requires an
Investigational New Drug exemption (IND). The regulations do not
provide an exception for any type of study. A retrospective study is
still a study and the regulations would call for an IND. While the use
in an individual patient may be considered the practice of medicine
in a case where the physician clearly believes that this treatment is in
the patient’s best interest, physicians should check with their local
IRBs concerning the need for local IRB approval.
A.M.: From a common sense point of view, there does not appear
to be any additional risk to the patient during a retrospective
review, especially if it is conducted under the auspices of an IRB.
And ophthalmologists engaged in studies of ophthalmic devices
rely upon their IRBs to determine when an IDE (investigational
device exemption) is required. However, any study of a drug would
require an IND, and IRBs do not have the authority to waive the IND
requirement. A quick review of the difference between the practice of
medicine and research, and between ophthalmic drugs and devices,
may help ophthalmologists understand the reasoning behind the FDA
regulation, and provide guidance on when to apply for an IND. The
two most important points to consider are the intent of the physician
and the risk to the patient. The FDA Information Sheet, “’Off-Label’
and Investigational Use of Marketed Drugs, Biologics, and Medical
Devices,”6 differentiates between off-label use of approved (marketed)
drugs as part of the practice of medicine and investigational use.
When the intent is to practice medicine, that is, to treat an individual
patient, no IND, IDE, or review by an IRB is required. If the intent is
to “develop information about the product’s safety or efficacy,”6
the use would be considered investigational, and in the case
of a drug, an IND application would be required unless six
conditions are met (I will discuss only three). The first two
address the intent of the investigational use. Studies whose
purpose is to submit information to the FDA in support
of a new indication for the drug or any other significant
change in the labeling, or to support a significant change
in the advertising of the product would require an IND.
The third condition that, if it were met, would allow a
study of a drug to proceed without an IND, requires
that use “not involve a route of administration
or dosage level, use in a subject population, or
other factor that significantly increases the
risks (or decreases the acceptability of the
risks) associated with the use of the drug
product.”6 According to information
obtained from representatives of the
FDA, this condition never applies
to ophthalmic drugs, because
of the potential toxic effect
on the eye of active and inert
ingredients. The take-away
message for ophthalmologists
who plan to publish the results of
their clinical experience with off-label medications is to apply for an
IND and submit their proposed study to their IRB.
References
1. Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings
after intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular
degeneration. Ophthalmic Surg Lasers Imaging 2005;36:331-335.
2. Rosenfeld PJ, Fung AE, Puliafito CA. Optical coherence tomography findings after
intravitreal injection of bevacizumab (Avastin) for macular edema from central retinal vein
occlusion. Ophthalmic Surg Lasers Imaging 2005;36:336-339.
3. Michels S, Rosenfeld PJ, et al. Systemic bevacizumab (Avastin) therapy for neovascular
age-related macular degeneration: twelve-week results of an uncontrolled open-label clinical
study. Ophthalmology 2005;112:1035-1047.
4. “An Update on USP Chapter 797: The New National Standard for Sterile Preparation,”
Lawrence A. Trissel, B.S., FASHP, www.ashpadvantage.com/monograph/797, accessed 25
August 2005.
5. “Good Compounding Practices Applicable to State Licensed Pharmacies,” National
Academy of Boards of Pharmacies, www.nabp.net/law/modelact/appendixc.asp, accessed
25 August 2005. See also “Guidance for FDA Staff and Industry. Compliance Policy Guides
Manual. Chapter 4, Subchapter 460. Section 200 Pharmacy Compounding.” May 2002.
6. Guidance for Institutional Review Boards and Clinical Investigators: “Off-Label” and
Investigational Use of Marketed Drugs, Biologics, and Medical Devices. U.S. Food and Drug
Administration. 1998 Update, www.fda.gov/oc/ohrt/irbs/offlabel.html, accessed 8/16/05.
7. Feinsod M, Chambers WA. Trials and tribulations: a primer on successfully navigating the
waters of the Food and Drug Administration. Ophthalmology 2004;111:1801-1806.
8. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress.
Endocrine Reviews 2004;25:581-611.
Useful online resources
Searchable, full-text copies of Title 21 of the Code of Federal Regulations, which
encompasses the Food and Drug Act, are available at www.fda.gov. Section 21 CFR 312
covers the laws and requirements pertaining to investigational new drug (IND) applications.
Section 21 CFR 50 covers the protection of human subjects, which includes informed
consent requirements. Section 21 CFR 56 covers institutional review requirements (IRBs).
Finally, section 21 CFR 200.50 covers issues specific to ophthalmic drugs and products.
Useful resources concerning medical-legal matters in ophthalmology, including procedure-
specific consent forms, can be found at www.omic.com.
retina times 21
4TH
ANNUAL
RETINAL
RESEARCH
REPORT

2005
>> RETINAL RESEARCH REPORT
CLINICAL
TRIALS
The ASRS Research & Development
Committee is committed to maintaining an
updated forum for members of the Society
to have ready access to ongoing clinical
trials in vitreoretinal diseases.
The R&D Committee has implemented
a Web-based access platform for
rapid entry of new study information to
enable wide dissemination of ongoing
clinical research. The R&D Committee is
devising a Web-based library of surgical
instruments and devices focused toward
comparative review by members of the
Society.
This fourth annual Retinal Research
Report provides a current list of ongoing
clinical trials.
The information in these tables has been
collected from publicly available sources
and is by no means inclusive of all clinical
trials.The ASRS does not support or en-
dorse this information, nor does the ASRS
attest to its correctness and validity. This
information has been provided as a service
to its members to further its mission and
nonprofit purposes.
RESEARCH & DEVELOPMENT
COMMITTEE:
Mark S. Humayun, MD
Chairperson
Eugene de Juan, Jr., MD
Sharon Fekrat, MD
Peter K. Kaiser, MD
SriniVas Sadda, MD
24 retina times
DIABETES MELLITUS
• B7A-MC-MBCM: Protein Kinase C Beta
Inhibitor-Diabetic Retinopathy Study 2
(PKC-DRS2) A Phase 3 Clinical Trial
• Diabetic Macular Edema Vitrectomy
Study (DMEVS)
• Phase 2 Study to Evaluate the Safety and
Efficacy of an Intravitreal Fluocinolone
Acetonide (0.5 or 2mg) Implant in Patients
with Diabetic Macular Edema (DME)
• Epidemiology of Diabetes Intervention
and Complications (EDIC)
• A Multicenter, Randomized, Masked,
Controlled Study to Evaluate the Safety
and Efficacy of Retisert, an Intravitreal
Fluocinolone Acetonide Implant, in the
Treatment of Patients with Diabetic
Macular Edema, FAME 4
• A Phase 2 Randomized, Open Label,
Multicenter, Controlled Trial to Assess the
Safety and Efficacy of Dexamethasone
Segment Drug Delivery System (DEX
PS DDS) in the Treatment of Persistent
Macular Edema
• Vitrase of Vitreous Hemorrhage Study
(VVHS)
• MBBK/MBBM
• Pegaptanib Sodium Injection (Macugen)
• Reduction in the Occurrence of Center-
threatening DME
• Intravitreal Triamcinolone Acetonide and
Laser Photocoagulation for DME
• Laser Photocoagulation for DME
OCULAR MELANOMA
• Collaborative Ocular Melanoma Study
(COMS)
BRVO
• Intravitreal Steroid Injection Study Trials
(ISIS)
• European Arteriovenous Sheatotomy
Trial (EAST)
• Surgical Decompression of Branch Vein
Occlusion
• The Standard Care vs. COrticosteroid
for REtinal Vein Occlusion (SCORE) Study:
to Compare the Efficacy and Safety of
Intravitreal Injection(s) of Triamcinolone
Acetonide with Standard Care to Treat
Macular Edema: 1 for CRVO and 1 for
BRVO
UVEITIS
• Randomized trial of Acetazolamide
for Uveitis-Associated Cystoid Macular
Edema (CME)
• A Multicenter, Randomized, Double
Masked, Controlled Study to Evaluate the
Safety and Efficacy of an Fluocinolone
Acetonide (0.5 or 2.0 mg) implant in
Patients with Non-Infectious Uveitis
Affecting the Posterior Segment of the Eye
• Pilot Study of a Sustained Release
Cyclosporine-A Implant
for Uveitis
• Longitudinal Study of Ocular
Complications of AIDS (LSOCA)
• CMV Retinitis and Viral Drug Resistance
(CRVR)
ROP
• Cryotherapy for Retinopathy of
Prematurity (CRYO-ROP) - Outcome
Study of Cryotherapy for Retinopathy of
Prematurity
AMD • Women’s Health Initiative Sight
Examination Study (WHI-SE)
• Submacular Surgery Trials (SST)
• Randomized Trial of Beta-Carotene and
Macular Degeneration
• Anecortave Acetate in Age-Related
Macular Degeneration
• Age-Related Eye Disease Study
• A Phase I, Open Labeled, Randomized
• Transpupillary Thermotherapy for
Study of the Safety, Tolerability, and
Choroidal Neovascularization Clinical Trial
Pharmacokinetics of Escalating Multiple-
(TTT4CNV)
Dose Intravitreal Injections of Rhufab
V2 in Subjects with Neovascular AMD
• Dry Age-Related Macular Degeneration
(FVF2425G Study)
(AMD) Trial
• A Phase III, Multicenter, Randomized,
• Complications of Age-Related Macular
Double-Masked, Sham Injection-
Degeneration Prevention Trial (CAPT)
Controlled Study of the Efficacy and Safety
of Rhufab V2 (Ranibizumab) in Subjects
• Photodynamic Therapy (VISUDYNE)
with Minimally Classic or Occult Classic
in Minimally Classic Subretinal
Subfoveal Neovascular AMD (FVF2598G
Neovascularization (VIM) Study
Study - MARINA)
• Submacular Surgery Trials (SST)
• Indocyanine Green (ICG) Risk Factors for
Choroidal Neovascularization
• Randomized Trials of Vitamin
Supplements and Eye Disease
• Prophylactic Diode Laser Photo
Coagulation for the Prevention of
• Anecortave Acetate Risk Reduction Trial
Choroidal Neovascularization in Age-
(AART)
Related Macular Degeneration (PTAMD)
• SIRNA 0401
• Visudyne with Altered (Delayed) Light in
Occult CNV Study (VALIO)
• Visudyne with Intravitreal Triamcinolone
Acetonide (VisTA) Trial
• Multicenter Investigation of
Rheopheresis for Age-Related Macular
• Preservative-free Triamcinolone
Degeneration (MIRA-1)
Acetonide (PFTA)
• An Evaluation of Efficacy and Safety
• Combretastatin A-4 Phosphate (CA4P) in
of Posterior Juxtascleral Injections of
Patients with Neovascular AMD (FBO-206)
Anecortave Acetate 15mg Versus Visudyne
in Patients with Subfoveal Exudative
• ANCHOR
Age-Related Macular Degeneration
(AMD) Eligible for Initial Treatment with
• MARINA
Photodynamic Therapy (PDT) Using
Visudyne
• Evaluation of Safety and Efficacy of
Anecortave Acetate vs. Placebo in Patients
• A Phase II Multi Center Trial to Establish
with Subfoveal CNV due to Exudative AMD
the Safety and Pharmacokinetic Profile
of Intravitreal Anti-VEGF Pegylated
(C-02-29)
Aptamer (Eye001) in Age-Related Macular
• Evaluation and Tolerability of 4-dose
Degeneration Undergoing Photodynamic
Levels of Cand5 Administered by Single
Therapy
Intravitreal Injection in Patients with Wet
AMD
• A phase II/III Randomized, Double
Masked, Controlled, Dose Ranging Multi
• PIER
Center Comparative Trial , in Parallel
Groups, to Establish the Safety and
• The Effect of Pegaptanib Sodium
Efficacy of Intravitreal Injections of
on Foveal Thickening in Patients with
Eye001 (Anti-VEGF Pegylated Aptamer)
Exudative Subfoveal AMD
Given Every 6 Wks to 54 Wks, in Patients
with Exudative Age-Related Macular
• Squalamine
Degeneration (AMD)
• Noncomparative Protocol for Use of
• Lutetium Taxaphyrin (LuTex/Optrin) in
Intravitreous Macugen Injections in
Age-Related Macular Degeneration (Phase
Patients with AMD
I Studies)
• PrONTO
• A Phase I/II, Multicenter, Dose
Escalation, Controlled Study of the Safety,
• Safety and Efficacy of AG-013958
Tolerability, Pharmacokinetics and Activity
in subjects with subfoveal choroidal
of Multiple Dose Intravitreal Injections of
neovascularization associated with age-
Rhufab V2 in Subjects with Neovascular
related macular degeneration
AMD (FVF2128G Study)
• A Randomized, Placebo Controlled,
• TheraSight Ocular Brachytherapy System
for Treatment of AMD
Double Masked, Multi Center Phase III
Study of the Effect of Visudyne Therapy
• AdGVPEDF.11D in Neovascular Age-
in Occult with No Classic Subfoveal
Related Macular Degeneration (Wet AMD).
Choroidal Neovascularization (CNV)
Secondary to Age-Related Macular
• Interval Dose Evaluation of Anecortave
Degeneration (VIO)
Acetate (IDEAA) I
• Photodynamic Therapy (Visudyne) Early
• Interval Dose Evaluation of Anecortave
Re-Treatment for Subfoveal Choroidal
Acetate (IDEAA) II
Neovascularization (VER) Study
• Denufosol Tetrasodium (INS37217
• A Phase III, Multicenter, Randomized,
Ophthalmic), P2Y2 Receptor Agonist for
Double-Masked, Active Treatment-
Intravitreal Injection
Controlled Study of the Efficacy and Safety
of Rhufab V2 (Ranibizumab) Compared
• Genetics and Clinical Characteristics of
with Verteporfin (Visudyne) Photodynamic
Bardet-Biedl Syndrome
Therapy in Subjects with Predominantly
Classic Subfoveal Neovascular AMD
• Cell Transplantation to Replace Retinal
(FVF2587G Study - Anchor)
Cells and RPE in Retinal Dystrophies
• Limited Macular Translocation Study
• Optical Coherence Tomography Study of
Retinal Thickness
• A Phase II, Randomized, Double Masked,
Placebo Controlled Study of the Matrix
• Phase I Trial for Wet Age-Related
Metalloproteinase Inhibitor AG3340
Macular Degeneration with VEGF Trap
in Patients with Subfoveal Choroidal
Neovascularization Associated with Age-
Related Macular Degeneration
DIABETES MELLITUS
Study
B7A-MC-MBCM: Protein Kinase C Beta
Inhibitor-Diabetic Retinopathy Study 2
(PKC-DRS2) a Phase 3 Clinical Trial
Sponsor
Eli Lilly Co.
Study Purpose
To determine whether an inhibitor of the
beta-isoform Protein Kinase C (PKC), relative
to placebo, will inhibit visual loss or the
development of PDR
Study Design
• Phase 3, multicenter, parallel, randomized,
double masked, placebo controlled study
• Subjects with Type I or II diabetes, ETDRS
retinopathy severity of 47A-53E in at least
one eye will receive a once a day tablet
(either the investigational drug or placebo)
with a meal
Eligibility/Exclusion
• Subjects 18 years of age and older
• Type I or II DM with HbA1C of < 13.0% at
time of screening and enrollment
• History of PRP for DR, uncontrolled HTN,
unstable angina
Results
Pending
Study
Diabetic Macular Edema Vitrectomy Study
(DMEVS)
Sponsor
Juvenile Diabetes Research Foundation and
Rush Medical College
Study Purpose
• To investigate whether the use of vitrectomy
can preserve or improve visual acuity in
individuals with diffuse diabetic macular
edema compared to standard laser therapy.
• To determine whether optical coherence
tomography (OCT) has value in the evaluation
of this disorder
Study Design
Randomized, prospective clinical trial
Number of Patients Enrolled
Not available
Follow Up
6 months
Eligibility/Exclusion
Entry criteria include:
• Best-corrected ETDRS visual acuity 20/40-
20/800
• Foveal avascular zone less than 1000
microns
• No benefit from previous medical or laser
treatments within previous 3 months
• Stable systemic health
Results
Pending
Study
Phase II Study to Evaluate the Safety and
Efficacy of an Intravitreal Fluocinolone
Acetonide (0.5 or 2mg) Implant in Patients
with Diabetic Macular Edema (DME)
Sponsor
Bausch & Lomb, Inc.
Study Purpose
• To evaluate the safety and efficacy of
intravitreal fluocinolone implant in the
management of patients with Diabetic
Macular Edema (DME)
• To compare the safety and efficacy of
two doses of fluocinolone (0.8 or 2.0 mg)
delivered by an intraocular/intravitreal implant
in patients with macular edema
Study Design
• Eligible patients include those with diabetic
macular edema that have had previous
treatment with laser photocoagulation and
have persistent retinal thickening involving
the center of the macula
• Patients are randomized to pars plana
insertion of either the 0.5 or 2mg fluocinolone
implant
• Patients are followed for clinical response
with monitoring of ETDRS visual acuity,
implant and eye receiving Retisert in
conjunction with a PPV to control eyes
Participating Centers
Not available
intraocular pressure, color photography and receiving a placebo implant in conjunction Number of Patients
fluorescein angiography with PPV Not available
Eligibility/Exclusion Number of Patients Enrolled Participating Centers
Eligibility: Up to 180 pts Not available
• Diabetic Macular Edema in the study eye Follow Up Results
• Pregnant lactating females 4 years
Pending
• DME must involve fixation and be at least
Eligibility/Exclusion
one disc area in size
• Patients 18 yrs and older with diffuse DME
• Males and non-pregnant females must be involving fixation
at least 18 years of age • DME should be at least one disc area in size Study
Exclusion:
• Allergy to fluocinolone or any component of Participating Centers MBBK/MBBM
the delivery system 25 centers Sponsor
• Visual acuity of >20 and <68 letters by Results Eli Lilly Co.
ETDRS in the study eye Pending Study Purpose
• Presence of history of uncontrolled ocular The objective is to test the hypothesis that
pressure (IOP) while on steroid therapy the oral administration of the study drug will
resulting in loss of vision inhibit the action of Protein Kinase C and
• IOP >25 mm Hg requiring 2 types of anti- Study prevent or delay the development of macular
glaucoma medication to lower to <25 mm A Phase 2 Randomized, Open Label, edema and proliferative diabetic retinopathy
HG. Multicenter, Controlled Trial to Assess the in diabetics with mild to moderately severe
• The study eye must have received at least Safety and Efficacy of Dexamethasone Diabetic Retinopathy
one macular laser treatment >3 months prior Segment Drug Delivery System (DEX Study Design
to entry into the study PS DDS) in the Treatment of Persistent Prospective, randomized, placebo controlled,
Results Macular Edema double masked study
Pending Sponsor Eligibility/Exclusion
Oculex Pharmaceuticals, Incl. 601 W. • 18 yrs or older
California Ave, Sunnyvale, CA 94086 • Type I or II diabetes
Status • Visual acuity of 20/100 or better in the eye
Study Not available under study and have moderately severe
Epidemiology of Diabetes Intervention and Diabetic Retinopathy or have visual acuity or
Patient Accrual Date
Complications (EDIC) 20/32 or better in the eye under study and
Pending
Sponsor have swelling of the macular region of the eye
Study Center
National Institute of Health Results
Not available
Study Purpose Pending
Study Chairman
• Overall goal of this study is to help Cynthia Selfridge, RN; Oculex Pharm
determine factors that are associated with the
development of kidney, large blood vessel, Study Purpose
To compare the effectiveness of DEX PS DDS
eye and nerve complications in diabetes. Study
• A new study indicates that despite to observation in the treatment of persistent Pegaptanib Sodium Injection (Macugen)
macular edema
increased hyperglycemia, a reduction in Sponsor
the risk of progressive retinopathy and Study Design Eyetech Pharmaceuticals and Pfizer Inc.
Randomized, open label, multi center, and
nephropathy persists for at least 4 years in Status
patients with Type I diabetes who manage controlled study
No longer enrolling patients. Study
their condition through intensive therapy Number of Patients Enrolled completion expected Q1 2005
• This research was part of the Multicenter 160 pts
Diabetes Control and Complications Trial Study Purpose
Follow Up Compare the safety and efficacy of
(DCCT) and the Epidemiology of Diabetes 6 months
Interventions and Complications Research pegaptanib with placebo in patients with
Eligibility/Exclusion DME
Group (EDIC)
• Persistent macular edema due to: Study Design
Study Design • Diabetic Retinopathy (DR)
• EDIC is an observational study to compare Phase 2, multicenter, randomized, placebo-
• Branch Retinal Vein Occlusion (BRVO) control, double-masked. Patients received
the long term effects of intensive or • Irvine-Gass Syndrome
conventional therapy provided during the varying doses (0.3 mg, 1 mg, 3 mg) of drug
• Uveitis or sham injection every 6 weeks for at least
DCCT on the development of more advanced
Participating Centers 12 weeks and then at the discretion of the
retinal and renal complications of diabetes
Not available investigators
• The study compared the effects of two
treatment regimens- standard therapy and Results Eligibility/Exclusion
intensive control- on the complications of Pending Eligibility for thermal laser therapy for DME
diabetes Number of Patients
• Patients were randomly assigned to each 169
treatment group Participating Centers
Eligibility/Exclusion Study 41
• Patients with Type I diabetes Vitrase of Vitreous Hemorrhage Study
Results
• Patients with Type I DM for at least 1 year (VVHS)
Pending
but no longer than 15 years Sponsor
• Required to have either no DR or early Advanced Corneal Systems
NPDR Study Purpose
Results • To evaluate the safety and efficacy of an Study
Pending injection of Vitrase for intravitreal injection for Reduction in the Occurrence of Center-
facilitating the clearance of severe vitreous threatening DME
hemorrhage
Sponsor
Study Design
Eli Lilly and Company
Study • The Vitrase study is a prospective,
randomized, parallel, double-masked study Status
A Multicenter, Randomized, Masked,
Recruiting
Controlled Study to Evaluate the Safety Eligibility/Exclusion
and Efficacy of Retisert, an Intravitreal • Patients with severe vitreous hemorrhage Study Purpose
Determine whether ruboxistaurin can slow the
Fluocinolone Acetonide Implant, in the of a minimum of 1 month’s duration due
Treatment of Patients with Diabetic to diabetic retinopathy or bleeding of any progression of DME
Macular Edema, FAME 4 etiology except those listed in the subject Study Design
Sponsor exclusion criteria, randomized by computer Randomization 1:1, ruboxistaurin/ placebo
Control Delivery Systems, Inc. into four study groups Eligibility/Exclusion
• Subject is 18 years of age or older, Inclusion Criteria: Macular edema: if >= 1/6
Status
severe vitreous hemorrhage that obscures DA up to < 1DA, location must be >500 mm
Actively enrolling
visualization of the fundus on indirect 3000 mm from center of macula or if >=1
Patient Accrual Date ophthalmoscopy that was DA location must be >1500 mm 3000 mm
TBA • A: red reflex with no retinal detail visible from center of macula, ETDRS retinopathy
Study Center posterior to the equator or level of >=20 and 47D in the study eye, best
Control Delivery Systems, Inc; 313 Pleasant • B: no red reflex is visible refracted visual acuity in the study eye of
Street, Watertown, MA 02472 • Severe vitreous hemorrhage as defined 20/32 or better
above Exclusion Criteria: H/o any focal, grid, or
Study Chairman
Not available that has been present > 1 month by scatter laser for DME in the study eye; retinal
history or exam artery/vein occlusions, macular degeneration,
Study Purpose
To evaluate the safety and efficacy of Retisert • Best corrected visual acuity is worse than chorioretinal scars; any intraocular surgery,
in the management of patients with Diabetic 20/200 at the time of the screening visit including YAG laser, within the previous 6
Macular Edema (DME) months; preretinal or vitreous hemorrhage
(currently); treatment for DME with any
Study Design therapy, including intravitreal or sub-
Trial comparing eyes receiving a Retisert
retina times 25
>> RETINAL RESEARCH REPORT
Tenon’s steroid, in the previous 6 months;
h/o vitrectomy; poorly controlled DM (HA1c
>11%), hypertension greater than 170
systolic; chronic renal failure on dialysis; s/p
renal transplant or creatinine >4.0; treatment
with or planned treatment with topical or oral
carbonic anhydrase inhibitors; participation in
previous Lilly ruboxistaurin study
Participating Centers
Not available
Number of Patients
Not available
Participating Centers
Not available
Results
Pending
Study
Intravitreal Triamcinolone Acetonide and
Laser Photocoagulation for DME
Sponsor
Diabetic Retinopathy Clinical Research
Network
Status
Recruiting
Study Purpose
Determine whether intravitreal triamcinolone
at doses of 1 mg or 4 mg provides greater
benefit, with an acceptable safety profile,
than macular laser in the treatment of DME
Study Design
One eye eligible: randomization, 1:1:1, laser/1
mg triamcinolone/4 mg triamcinolone. Both
eyes eligible: 1 eye randomized to laser, the
other to 1 mg or 4 mg of triamcinolone
Eligibility/Exclusion
Age >=18 years, study eye with best
corrected E-ETDRS acuity >24 letters (20/320
or better) and <68 letters (worse than 20/40),
study eye with center-involved DME present
on clinical exam and on OCT, mean retinal
thickness on 2 OCT measurements >250
microns in the central subfield, fellow eye
either eligible or has acuity >19 letters (20/
400 or better) has not been previously treated
with intravitreal corticosteroids
Number of Patients
795
Participating Centers
1 by the ophthalmic surgeon
Results
Pending
Study
Laser Photocoagulation for DME
Sponsor
Diabetic Retinopathy Clinical Research
Network (DRCR.net) and National Eye
Institute
Status
Recruiting
Study Center
Joslin Diabetes Center. Beetham Eye
Institute, 1 Joslin Place, Boston, MA 02215
Study Chairman
Lloyd P. Aiello, MD, PhD
Study Purpose
Compare standard laser treatment with
mild, macular-grid treatment that is milder
in intensity, but more extensive in number of
laser burns
Study Design
Pilot Study. One eye eligible: randomization,
1:1, standard/mild macular grid. Both
eyes eligible: 1 eye randomized to 1 of the
treatments, the other eye randomized to the
other treatment
Eligibility/Exclusion
Age >=18 years, study eye with best
corrected E-ETDRS acuity >19 letters (20/400
or better), definite retinal thickening due to
diabetic macular edema
Number of Patients
Approximately 200 patients
Participating Centers
71
Results
pending
26 retina times
OCULAR MELANOMA
Study
Collaborative Ocular Melanoma Study
(COMS)
Sponsor
National Eye Institute (NEI)
Status
Ongoing
Patient Accrual Date
Pre-enucleation radiation completed 12/15/
94; radioactive plaque completed 8/1/98
Study Centers
Scheie Eye Inst. at U of Penn and Wilmer Eye
Inst. ; 550 N. Broadway, Suite 700; Baltimore,
MD 21205; 410-955-1966
Study Chairman
Stuart Fine, MD; Scheie Eye Institute / 215-
662-8657
Study Purpose
• To evaluate therapeutic interventions for
patients who have choroidal melanoma, the
most common primary eye cancer affecting
adults, and to assess the potential life
preserving as well as sight-preserving role of
radiation therapy
• To determine which of two standard
treatments, removal of the eye or
brachytherapy, is more likely to prolong
survival of eligible patients with medium sized
choroidal melanoma
• To determine whether preoperative radiation
prolongs life for patients whose eyes with
large choroidal melanoma are enucleated.
Study Design
• The COMS is a set of long term,
multicenter, randomized controlled trials. In
the trial for patients with tumors of medium
size, enucleation and irradiation with an
iodine-125 episcleral plaque are compared on
the basis of length of remaining life
• All randomized patients will be followed for
5-15 years or until death
• For patients randomly assigned to
enucleation, the eye was removed following a
standard procedure
• For patients assigned to plaque radiation,
the margins of the tumor were located and
the dimensions of the tumor were measured
• A gold plaque with a plastic seed carrier
that contained the proper dosage and
configuration of radioactive iodine seeds was
sutured to the outside (sclera) of the eye over
the base of the tumor
• This procedure made possible the delivery
of a high does of radiation to a very localized
area (85 Gy [TG-43] to the tumor apex)
• The plaque typically was removed from the
eye after three to seven days.
Number of Patients Enrolled
1317
Follow Up
Patient f/u ongoing in the trial of radioactive
plaque
Eligibility/Exclusion
• Men and women eligible for the study had
to be age 21 or older, have primary choroidal
melanoma in only one eye, and have no
evidence of metastatic disease.
• Accurate estimation of tumor thickness by
echography also was required
Participating Centers
40
Results
• Nonrandomized Small Tumor Pilot Study:
the treatment and mortality results of the
COMS Nonrandomized Small Tumor Pilot
Study were reported in 1997. From 12/86
to 8/89, 204 patients with small choroidal
melanoma, defined as 1.0 to 3.0 mm in apical
height and at least 5.0mm in basal diameter,
were enrolled in a prospective follow up
study. The median length of f/u was 92
months. 8% of patients were treated at the
time study enrollment and an additional 33%
were treated during f/u. Based on 27 deaths,
the Kaplan-Meier estimate of 5 year all cause
mortality was 6.0% (95% confidence interval,
2.7% - 9.3%) and 8-year all cause mortality
was 14.9% (95% confidence interval, 9.6%-
20.2%). Mortality findings and analysis of
predictors of growth have been published
(COMS reports no. 4 and 6)
• Randomized Trial of Pre-Enucleation
Radiation for Large Choroidal Melanoma:
initial mortality findings published in 1998
(COMS report no. 10) showed that patients
with large choroidal melanoma had similar
survival rates regardless of whether they were
treated with radiation prior to removal of the
eye or had their eye removed without prior
radiation therapy
• 5-year survival rates were approx. 60%
in both treatment arms. The COMS large
tumor trial found neither benefit nor harm
from treating ocular melanoma patients with
radiation before removal of the eye. However,
patients who had pre-enucleation radiation
had fewer local complications (COMS report
no. 11).
• Randomized Trial of I-125 Brachytherapy
for medium choroidal melanoma: initial
mortality findings published in 2001 (COMS
report no. 18) showed that survival rates for
radiation therapy (I-125 brachytherapy) and
enucleation (removal of eye) are about the
same. The 5-year survival rate of patients
who were treated with either radiation therapy
or eye removal was 82%, considerably better
than the 70% 5-year survival rate that had
been projected when the study was designed
in 1985. Compared to immediate loss of
vision when the eye is removed, eyes treated
with radiation steadily lost vision gradually,
with 63% having visual acuity of 20/200 or
worse by 3 years after treatment (COMS
report no. 16)
BRVO
Study
Intravitreal Steroid Injection Study Trials
(ISIS)
Sponsor
Illinois Retina Associates, S.C
Study Purpose
• Series of five separate prospective FDA and
IRB approved studies designed to determine
if there is a possible role for intravitreal steroid
injections in the management of refractory
macular edema secondary to DME, BRVO,
CRVO, JRT and post-op CME
Study Design
This is a pilot study. Subjects are randomized
to either 2mg or 4mg dose of intravitreal
Kenalog® injection
Number of Patients Enrolled
30 per treatment group
Eligibility/Exclusion
• Persistent macular edema due to
• Diabetic Retinopathy (DR)
• Branch Retinal Vein Occlusion (BRVO)
• Central Retinal Vein Occlusion (CRVO)
• Irvine-Gass Syndrome
Results
DME arm of study has completed enrollment.
Results are pending. Remaining arms are still
enrolling.
Study
European Arteriovenous Sheatotomy Trial
(EAST)
Sponsor
Not available
Study Purpose
• To compair the efficacy of surgical arterio-
venous decompression with the natural cause
in patients with BRVO
Study Design
• A prospective, randomized multicenter trial,
including 216 patients (108 receive vitrectomy
AV-decompression no ILM-peeling; 108
observation). If the hematocrit is >40% an
optional isovolemic hemodilution may be
optional performed.
Eligibility/Exclusion
Patients with BRVO, onset < 3 months,
ETDRS VA< 20/50, no previous treatment
Results
Pending
Study
Surgical Decompression of Branch Vein
Occlusion
Sponsor
Not available
Study Purpose
• To evaluate vitreous surgery as treatment
for BRVO
Study Design
• A prospective, non-randomized trial.
Eligibility/Exclusion
Not available
Results
Pending
Study
The Standard Care vs. COrticosteroid for
REtinal Vein Occlusion (SCORE) Study:
to Compare the Efficacy and Safety of
Intravitreal Injection(s) of Triamcinolone
Acetonide with Standard Care to Treat
Macular Edema: 1 for CRVO and 1 for
BRVO
Sponsor
National Eye Institute, National Institutes of
Health, Department of Health and Human
Services
Status
Enrollment began in October 2004
Study Purpose
To compare the effectiveness and safety of
standard care to intravitreal injection(s) of
triamcinolone for treating macular edema
(swelling of the central part of the retina)
associated with CRVO and BRVO
Study Design
Multicenter, randomized, phase 3 trial. Eligible
patients within each of these 2 disease
entities are randomized in a 1:1:1 ratio to
1 of 3 groups: standard care, intravitreal
injection(s) of 4 mg of triamcinolone
acetonide, or intravitreal injection(s) of 1 mg
of triamcinolone acetonide. Enrolled patients
are followed for 3 years. The preparation of
triamcinolone acetonide used in the study is
specially made for injection into the eye and
does not contain any preservatives
Eligibility/Exclusion
Participants with macular edema associated
with CRVO and BRVO who are 18 years
of age or older and are willing to provide
consent. Detailed Inclusion/Exclusion Criteria
are available on the SCORE Web site at http:
//spitfire.emmes.com/study/score/.
Number of Patients
1260 total; 630 with CRVO and 630 with
BRVO
Participating Centers
27
Results
Pending
UVEITIS
Study
Randomized Trial of Acetazolamide for
Uveitis-Associated Cystoid Macular
Edema (CME)
Sponsor
NEI/NIH
Study Purpose
To test the efficacy of acetazolamide for
the treatment of Uveitis Associated Cystoid
Macular Edema (CME)
Study Design
• This is a double masked randomized
crossover trial designed to test the efficacy
of acetazolamide compared with a placebo
for the treatment of uveitis associated cystoid
macular edema
• Randomized adult patients received either
oral acetazolamide socium 500 mg or a
matched placebo every 12 hours for the first
4 weeks of the study
• Children 8 years of age or older received a
lesser dose based on body weight. Following
a 4 week period, during which no medication
was given, patients then received a 4 week
course of the opposite medication
• Primary end points included reduction
of Cystoid Macular Edema (graded on
fluorescein angiography) and improvement
in visual acuity (measured on standardized
ETDRS charts)
• Acuity was also assessed as a secondary
outcome variable.
• Adverse effects of the acetazolamide
therapy were monitored by clinical and
laboratory technicians
Eligibility/Exclusion
Eligibility:
• Males and females 7 years of age and older,
weighing at least 35kg were eligible for the
study
• Patients had to have at best a corrected
visual acuity of 20/40 or worse in one eye
with Cystoid Macular Edema demonstrable
on FA
• Patients were allowed to receive systemic
therapy for their uveitis
Exclusion:
• Current use of acetazolamide as part of a
therapeutic regimen
• A history of hypersensitivity reactions to
acetazolamide, sulfonamide, or angiography
dye
• Unclear ocular media that would obscure
FA
• Macular subretinal neovascularization or a
macular hole
• Inability to take acetazolamide for medical
reasons
Results
Thirty-seven patients completed the trial
and were available for analysis. Seventeen
patients (46 percent) were randomized to
receive acetazolamide and 20 (54 percent) to
receive placebo during course A. Visual acuity
data were available for all 37 patients for all
visits. Fluorescein angiography data were
available for 145 of the 148 study visits (98
percent). Acetazolamide therapy resulted in
0.5 disc area (25 percent) decrease in cystoid
macular edema over that of placebo (p =
0.01; estimated treatment effect = -0.5 disc
areas, 95 percent confidence interval [-0.9,
-0.1]). In contrast, there was no statistically
significant effect of acetazolamide on visual
acuity (p = 0.61; estimated treatment effect
= 0.6 letters, 95 percent confidence interval
[-2, 3]). Possible adverse drug reactions were
reported by 34 of the 37 (92 percent) during
acetazolamide therapy. In contrast, at least
one adverse drug reaction was reported
in only 5 of 37 patients (14 percent) during
placebo therapy.
Acetazolamide therapy results in a
statistically significant but small decrease
in cystoid macular edema in patients with
chronic uveitis but does not improve visual
acuity. Since acetazolamide is associated
with a number of adverse effects, patients
should be closely monitored and the drug
discontinued if no therapeutic benefit is
documented.
Study
A Multicenter, Randomized, Double
Masked, Controlled Study to Evaluate
the Safety and Efficacy of a Fluocinolone
Acetonide (0.5 or 2.0 mg) Implant in
Patients with Non-Infectious Uveitis
Affecting the Posterior Segment of the Eye
Sponsor
Bausch & Lomb, Inc.
Study Purpose
To evaluate the safety and efficacy of an
intravitreal Fluocinolone Acetonide (0.5 or 2.0
mg) implant in patients with non-infectious
uveitis affecting the posterior segment of
the eye
Study Design
A 3 year, multi-center, randomized, double-
masked, controlled, safety and efficacy study
comparing 2 does levels of Fluocinolone
Acetonide (0.5 or 2.0mg) in intravitreal
implants
Eligibility/Exclusion
Patients with non-infectious uveitis affecting
the posterior segment of the eye will be
enrolled
Results
The U.S. Food and Drug Administration has
approved the single-indication orphan drug
Retisert™ (fluocinolone acetonide intravitreal
implant), 0.59 mg, for the treatment of chronic
non-infectious uveitis affecting the posterior
segment of the eye, a sight-threatening
inflammatory disease that primarily afflicts
people between the ages 20 and 50, during
their prime working years.
FDA approval of the single-indication orphan
drug was based on 34-week results from
two three-year randomized, double-masked,
multicenter clinical studies demonstrating
that in eyes with Retisert there was:
• a statistically significant decrease in the
recurrence of uveitis from approximately
40% to 54% for the 34-week period pre-
implantation to approximately 7% to 14% for
the 34-week period post-implantation;
• a statistically significant decrease in the
use of adjunctive therapy including systemic
corticosteroid and/or immunosuppressive
therapy from approximately 47% to 63% at
the time of implantation to approximately 5%
to 10% at 34 weeks post-implantation, and
for patients needing periocular corticosteroid
injections from approximately 50% to 65%
for the 34 week period pre-implantation to
approximately 3% to 6% for the 34 week
period post-implantation;
• statistically significant improvement of three
or more lines of visual acuity in approximately
19% to 21% of study eyes at 34 weeks post-
implantation.
The most common adverse events include
cataract progression, which is managed
by standard cataract surgery; increased
intraocular pressure, which is managed with
the use of IOP-lowering eye drops or filtering
surgery; and procedural complications and
eye pain.
Study
Longitudinal Study of Ocular
Complications of AIDS (LSOCA)
Sponsor
National Eye Institute
Status
Recruiting
Patient Accrual Date
Contact chairman’s office
Study Center
Curtis Meinert, PhD; Dept. of Epidemiology,
School of Hygiene & Public Health; JHU, 615
N. Wolf Street, #5010; Baltimore, MD 410-
955-8198
Study Chairman
Douglas Jabs, MD, MD/ 410-955-1966
Study Purpose
• CMV retinitis and other ocular
complications of AIDS
• To determine the effect of highly active anti-
retroviral therapy (HAART)-induced immune
status on the risk of developing CMV retinitis
and other ocular complications of AIDS
• To determine the characteristics (clinical,
virologic, hematologic, and biochemical) of a
population at high risk for CMV retinitis and
other ocular complications of AIDS
• To evaluate the effects of treatments for
CMV retinitis and other ocular complications
on visual function, quality of life, and survival.
Study Design
• The longitudinal study of ocular
complications of AIDS (LSOCA) is
prospective observational study of patients
with AIDS
• Patients with prior diagnosis of AIDS
according to the 1993 CDC criteria with or
without ocular complications will be enrolled
over a 4 year period
• Approx. 2000 patients will be enrolled in
the study. enrollments of patients with CMV
retinitis at baseline will be between 300 and
600 patients
• Follow up visits for patients with ocular
complications at baseline or diagnosed
during follow up will be every 3 months
• Follow up data will include eye
examinations, fundus photographs, visual
function testing, medical history, hematology,
and serum chemistry, and collection of
plasma and blood cells for banking
• Analysis of banked specimens will include
HIV RNA levels and CMV DNA levels
Number of Patients Enrolled
Ongoing
Follow Up
Not available
Eligibility/Exclusion
Males and females age 13 years and older
with diagnosis of AIDS will be eligible.
Participating Centers
19
Results
Pending
Study
CMV Retinitis and Viral Drug Resistance
(CRVR)
Sponsor
National Institute of Health
Study Purpose
• To determine the incidence and prevalence
of CMV drug resistance in patients with AIDS
and CMV retinitis
• To determine risk factors for the
development of resistance, clinical correlates
of viral drug resistance, phenotype-genotype
correlation, ocular blood CMV correlations
and determination of blood PCR and CMV
viral load resistance correlations
Study Design
Prospective, cohort clinical trial
Eligibility/Exclusion
• Inclusion: newly diagnosed CMV retinitis not
previously treated, confirmed HIV diagnosis
• Exclusion: treatment of extraocular CMV
within the past 28 days, subjects under 18
years of age
Results
Pending
Study
A Pilot Study of a Sustained Release
Cyclosporine-A Implant for Uveitis
Sponsor
National Eye Institute 98-EI-0110
Study Purpose
Cyclosporine is a medication that is useful
for treating patients with inflammation in the
eye (uveitis)
Study Design
Patients with active uveitis and poor vision
in one eye will receive a surgically place
cyclosproine implant that will release the
medication into the eye
Eligibility/Exclusion
Not available
Results
Pending
ROP
Study
Cryotherapy for Retinopathy of
Prematurity (CRYO-ROP) - Outcome
Study of Cryotherapy for Retinopathy of
Prematurity
Sponsor
National Eye Institute
Status
Ongoing. Comments: The 15-year
examination period has ended, and study
centers are closed. Currently, data from this
final study examination are being analyzed
to determine if the benefits of cryotherapy
are sustained in adolescence, when late
structural complications and loss of visual
acuity have been reported to occur. A
comparison will be made between treated
and untreated eyes for many conditions,
such as late retinal detachment, macular
degeneration, and vision failure. This
information will be used for evaluating
the overall outcome for these teenagers.
A manuscript reporting the results of this
examination is in process.
Patient Accrual Date
No longer recruiting. Comments:
Recruitment, which began in January 1986,
was stopped January 22, 1988.
Study Center
Robert J. Hardy, PhD, Principal Investigator
School of Public Health
University of Texas-Houston Health Science
Center
Coordinating Center for Clinical Trials
1200 Herman Pressler Street, E827
Houston, TX 77030
Study Chairman
Earl A. Palmer, MD, Chairman
Casey Eye Institute
Oregon Health & Science University
3375 S.W. Terwilliger Boulevard
Portland, OR 97239-4197
Study Purpose
• To determine the safety and efficacy of
trans-scleral cryotherapy of the peripheral
retina in certain low birth-weight infants with
retinopathy of prematurity (ROP) for reducing
blindness from ROP.
• To determine the long-term outcome for
eyes that had severe (“threshold”) ROP, both
with and without cryotherapy.
Study Design
The randomized, controlled, single-blind,
multicenter trial of cryotherapy for ROP
enrolled more than 4,000 premature infants
who weighed no more than 1,250 grams
at birth. The eyes of the infants enrolled in
the study were examined at predetermined
intervals while the subjects were still in
the intensive care nursery. After the pupils
were dilated with eye drops, the eyes were
examined by an ophthalmologist using
a binocular indirect ophthalmoscope to
visualize the developing retina. The natural
history of the condition of each infant’s retina
was recorded. When examination disclosed
the severe form of ROP (threshold ROP) in
both eyes, and the parents gave informed
consent, one of the infant’s eyes was
randomly selected to receive cryotherapy.
Outcome of the therapy was assessed
at 3 months and 12 months following
randomization by an extensive examination
that included photography of the interior
of both the treated and the control eyes.
The 12-month exam also measured visual
function with preferential-looking techniques.
Neither the trained photograph readers who
evaluated the pictures from both eyes nor the
specially trained vision testers knew which
eyes had received cryotherapy. Additional
assessments of visual acuity and retinal
status have been made approximately each
year through age 10, with a final examination
at age 15 for patients in the randomized trial
of cryotherapy who did not have bilateral total
retinal detachment and blindness.
Number of Patients Enrolled
4099
Follow-up
15 years
Eligibility/Exclusion
Premature infants of either gender who were
eligible for the natural history study had
weighed less than 1,251 grams at birth and
had survived the first 28 days of life. They
had no major ocular or systemic congenital
anomalies. Infants who met these criteria and
also had a threshold level of ROP (defined as
stage 3+ of the International Classification
of Retinopathy of Prematurity occupying five
or more contiguous or eight cumulative 30°
sectors [clock hours] of stage 3 ROP in zone
I or II in the presence of plus disease) could
be referred for examination to determine
eligibility for entry to the cryotherapy trial.
Participating Centers
23
Results
The Cryotherapy for Retinopathy of
Prematurity Cooperative Group reported
preliminary results in 1988. This study
registered 9,751 infants with birth weights
less than 1,251 grams at 23 study centers.
Of these infants, 4,099 were systematically
examined. The defined threshold severity of
ROP developed in 291 infants.
Cryotherapy was performed in half the
eligible eyes of the 291 infants. Twelve
months after randomization, the results of
masked grading of fundus photographs of
the posterior pole indicated an unfavorable
outcome in 25.7 percent of the eyes that had
received cryotherapy and in 47.4 percent of
the control eyes. Masked Teller Acuity Card
assessment of grating acuity indicated an
unfavorable functional outcome in 35 percent
of the treated eyes, compared with 56.3
percent of the control eyes. These results
indicate that cryotherapy reduces the risk of
unfavorable retinal and functional outcome
from threshold ROP.
retina times 27
>> RETINAL RESEARCH REPORT
Although the surgery was stressful, no
major complications occurred during or
following treatment. Physicians’ diagnoses
and the unbiased photograph gradings
were statistically similar. These data support
the efficacy of cryotherapy in reducing by
approximately one-half the risk of unfavorable
retinal outcome from threshold ROP.
Results at 31⁄2 years and 51⁄2 years following
randomization continue to support the long-
term efficacy and safety of cryotherapy in
the treatment of severe ROP. However, the
51⁄2-year data suggested that cryotherapy
could reduce the chance of normal vision
in some cases. Findings from the 10-year
examination showed fewer unfavorable
outcomes for both visual acuity and structure
in treated vs untreated eyes. The examination
at age 10 included measurement of contrast
sensitivity and visual fields. Results of
contrast sensitivity testing demonstrated
no evidence of adverse treatment effects
in eyes that received cryotherapy. The
findings for visual field testing with Goldmann
Perimetry showed a visual field area that was
24 percent to 26 percent larger in treated
eyes versus untreated eyes, when blind
eyes were included and assigned a score
of 0. When blind eyes were excluded, visual
field area was 5 percent smaller for treated
eyes than for untreated eyes, indicating that
cryotherapy slightly reduces the visual field
area in eyes with severe ROP. This small
reduction in visual field area in treated eyes
is minor when compared with the much
greater risk that an eye will be blind without
treatment. However, this and any other
possible adverse side effects are important
considerations in determining whether to treat
milder cases of ROP that have a relatively
good prognosis for vision without treatment.
Cryotherapy is now recommended for
both eyes whenever stage 3+ retinopathy
of prematurity involves the posterior retina
(zone I) of both eyes and for both eyes (in
most patients) in cases of threshold ROP in
zone II. There are, as yet, insufficient data to
mandate cryotherapy in any method different
from the one used in this trial, or to apply it to
patients with less severe disease. Following
the publication of the positive results of
this study in 1988, the U.S. pattern of care
changed rapidly to embrace these guidelines
as standard practice.
Laser therapy has been shown to have similar
value to cryotherapy. Currently the risk data
from the CRYO-ROP study are being used
to test the value of ealier interventions in
selected high risk eyes, in the Early Treatment
for ROP study (ETROP).
AMD
Study
Submacular Surgery Trials (SST)
Sponsor
NEI
Study Purpose
• To determine whether surgical removal of
subfoveal choroidal neovascularization (CNV)
and associated hemorrhage in patients with
Age-Related Macular Degeneration (AMD),
the Ocular Histoplasmosis Syndrome (OHS),
or idiopathic CNV stabilizes or improves
vision more often than observation.
• To determine how surgical removal
compared to observation of subfoveal
CNV due to AMD, OHS, or idiopathic
causes changes the patient’s perception of
health- and vision-related “quality of life,” as
measured by telephone interview using the
Medical Outcomes Survey Short Form-36
(MOS SF-36) instrument, the Hospital Anxiety
and Depression Scale, and the National Eye
Institute Visual Function Questionnaire (NEI
VFQ-25).
• To determine whether randomized trials
of surgery are warranted for patients with
subfoveal CNV associated with Age-Related
Macular Degeneration not suitable for laser
treatment.
Study Design
• Vision data collected at baseline include a
protocol refraction, best-corrected logMAR
visual acuity (ETDRS charts), contrast
threshold (Pelli-Robson charts), and reading
28 retina times
speed (enlarged text). Other baseline data
recorded include stereoscopic color fundus
photographs, fluorescein angiograms, and
lens photographs, as well as health- and
vision-related quality of life interview data (by
telephone).
• Eligible patients who gave signed,
informed consent were randomly assigned
to surgery (within 8 days of randomization)
or observation. Patients, assigned to
surgery, are seen one month post-surgery
for an examination and photographs. All
participants are examined at 3, 6, 12, 24, 36,
and 48 months after randomization to collect
vision data (collected in a masked fashion at
24 and 48 months after randomization) and to
repeat photography. Quality of life telephone
interviews are repeated at 6, 12, 24, 36, and
48 months after randomization.
• The primary outcome is improvement in
visual acuity from baseline to the two-year
examination or retention of baseline visual
acuity through the two-year examination.
Secondary outcomes include change in
quality of life from baseline to the 2- and
4-year examinations, change in visual acuity
over 4 years, large losses of visual acuity,
and adverse ocular outcomes (e.g., those
requiring additional treatment such as
cataract, retinal detachment, or recurrent
CNV).
Eligibility/Exclusion
• Group B: Patients with evidence of large
hemorrhages from subfoveal neovascular
AMD lesions, visual acuity (SST protocol)
of 20/100 to light perception, with the
area of hemorrhage larger than the area of
fluorescein angiographically visible CNV, with
any visible CNV < 9 MPS disc areas, and
ability to return for 4 years of follow up may
be eligible for the Group B (Blood) protocol.
• Group N: Patients with new CNV (no
prior laser) due to AMD, visual acuity (SST
protocol) of 20/100 to 20/800, fluorescein
angiographic evidence of subfoveal CNV
lesion which is < 9 MPS disc areas, and
ability to return for 4 years of follow up
may be eligible for the Group N (New CNV)
protocol.
• Group H: Patients with evidence of CNV
due to OHS or idiopathic cause, visual acuity
(SST protocol) 20/50 to 20/800, fluorescein
angiographic evidence of subfoveal CNV
lesion (new or recurrent) which is < 9 MPS
disc areas, and ability to return for 4 years of
follow up may be eligible for inclusion in the
Group H (Histoplasmosis/Idiopathic CNV)
protocol.
• Exclusion criteria include other ocular
diseases compromising vision, history of
submacular surgery in the study eye, history
of subfoveal laser photocoagulation that
extends under the foveal avascular zone,
recent intraocular surgery, or previous
investigational therapy for CNV.
Results
Of 454 patients enrolled, 228 study eyes
were assigned to observation and 226 to
surgery. The percentages of eyes that had
successful outcomes were similar in the 2
arms: 44% assigned to observation and
41% assigned to surgery. Median VA losses
from baseline to the 24-month examination
were 2.1 lines (10.5 letters) in the observation
arm and 2.0 lines (10 letters) in the surgery
arm. Median VA declined from 20/100 at
baseline to 20/400 at 24 months in both
arms. No subgroup of patients was identified
in which submacular surgery led to better VA
outcomes. In the surgery arm, 55 (39%) of
142 initially phakic eyes had cataract surgery
by the 24-month examination, compared
with 6 (5%) of 133 eyes in the observation
arm. Rhegmatogenous retinal detachment
occurred in 12 surgery eyes (5%) and 1
observation eye. Submacular surgery, as
performed in this clinical trial, did not improve
or preserve VA for 24 months in more eyes
than observation and is not recommended for
patients with similar lesions.
Of 454 patients enrolled, 228 were assigned
to observation and 226 to surgery. At
baseline, median overall NEI-VFQ scores
were 67 in the observation group and 69 in
the surgery group; by 2 years, the observation
group had lost a median of 3 points (95%
confidence interval [CI]: −6 to −2), and the
surgery group gained a median of 1 point (CI:
−1 to 3). The largest difference was observed
for the mental health subscale,
where the observation group lost a median of
5 points (CI: −5 to 0), and the surgery group
gained a median of 5 points (CI: 0–10) by 2
years. Treatment differences in median 2-year
changes in NEI-VFQ scores favored surgery
by up to 10 points for unilateral cases and up
to 8 points for bilateral cases. No treatment
difference in 2-year change was observed
for the SF-36 physical component summary;
2-year change in the mental component
summary favored surgery by 2 points. Few
patients (2%–4%) had HADS definite anxiety
or depression at baseline or at 24 months.
Although HRQOL outcomes were better
in the submacular surgery arm than in the
observation arm, surgery (per protocol) is
not recommended because VA outcomes
(reported elsewhere) were similar in the
treatment arms.
Study
Anecortave Acetate in Age-Related
Macular Degeneration
Sponsor
Alcon Research; South Freeway Drive; Ft.
Worth, TX 817-615-2583
Study Purpose
This study is an evaluation of the safety
and duration of efficacy of Anecortave
Acetate sterile suspension (30mg, 15mg,
or 3mg) versus placebo after a single
(subtenon) injection for the inhibition of
neovascularization in patients with exudative
Age-Related Macular Degeneration following
laser treatment of extrafoveal or juxtafoveal
neovascular membranes.
Study Design
Dose duration study
Eligibility/Exclusion
• AMD with lesion 12 disc areas or less and
50% or more of the total lesion with choroidal
neovascularization (CNV), and either the
classic component is 50% or more of the
total CNV or the classic component of the
CNV is > 0.75 DA in total size
• Visual Acuity:
• ETDRS vision in the study eye = Log
MAR~0.0
0.9 (20/20-20/160)
• ETDRS vision in the non study eye =
Log MAR
1.6 (20/800) or better
Results
Outcomes following anecortave acetate
injection were compared with outcomes
without anecortave acetate treatment. 73
percent of patients treated with anecortave
acetate 15 mg had stable or improved vision
from baseline to 24 months after treatment,
significantly more than the 47 percent of
patients in the placebo group who did not
receive anecortave acetate (p=0.035).
Patients treated with anecortave acetate 15
mg had no increase in growth of the classic
component of the subfoveal choroidal
neovascular membrane (CNV) between
months 12 and 24, and the total lesion size
remained stable over this period. Additionally,
at 24 months, in the sub-group of patients
with the more aggressive, predominantly
classic CNV lesions, no patients treated
with anecortave acetate 15 mg had severe
vision loss (> 6 lines loss) compared to a 23
percent rate in the placebo group, (p=0.023).
The U.S. Food and Drug Administration
(FDA) issued an approvable letter for its New
Drug Application (NDA) for Retaane(R) 15
mg (anecortave acetate suspension) in May,
2005.
Study
Indocyanine Green (ICG) Risk Factors for
Choroidal Neovascularization
Sponsor
Macula Society; Scheie Eye Institute,
Philadelphia, PA
Study Purpose
• To determine risk factors of ICG for CNV
Study Design
Not available
Eligibility/Exclusion
Not available
Results
Pending
Study
Lutetium Taxaphyrin (LuTex/Optrin) in
Age-Related Macular Degeneration (Phase
I Studies)
Sponsor
Alcon Research; South Freeway Drive; Ft.
Worth, TX 817-615-2583
Study Purpose
• To evaluate the safety and efficacy of
Lutetium texaphyrin combined with light
laser treatment for the occlusion of abnormal
vessels and membranes in people with AMD
and CNV (CNV-abnormal growth of new
blood vessels) for whom traditional heat laser
therapy is not an option, or who have refused
the recommended heat laser therapy
Study Design
• Multicenter, dose ranging, prospective, non
randomized clinical study
• Patients with AMD will be entered and
evaluated in 2 phase I and IB studies
• The first trial involves a dose and light
ranging study to evaluate the utility of
lutetium taxaphyrin as an imaging and
photodynamic therapy agent in choroidal
neovascularization
• Second study will evaluate lutetium
taxaphyrin as an imaging agent alone,
with subsequent therapy with standard
thermal photocoagulation or verteporfin
photodynamic therapy
Eligibility/Exclusion
Not available
Results
Pending
Study
A Phase I, Open-Labeled, Randomized
Study of the Safety, Tolerability, and
Pharmacokinetics of Escalating Multiple-
dose Intravitreal Injections of RhuFab
V2 in Subjects with Neovascular AMD
(FVF2425G Study)
Sponsor
Genentech, Inc. 888-662-6728
Study Purpose
• To investigate the safety and tolerability
of recombinant humanized anti-VEGF
monoclonal antibody fragment (RhuFab
V2) administered as multiple, intravitreal
injections up to a final dose of 2mg
Study Design
• This phase I, multicenter, randomized
trial enrolled 30 patients into three dosing
regimens.
• All patients were treated for a total of 16
weeks and followed through 20 weeks.
• Group 1 received escalating doses from
300µg to 1.0mg every 2 weeks over 6 weeks
followed by 1.0mg of RhuFab V2 every 4
weeks.
• Group 2 received escalating doses from
300µg to 2.0mg every 2 weeks over 14 weeks
followed by a final 2mg dose at week 16.
• Group 3 received escalating doses from
300µg to 2mg every 4 weeks over 16 weeks.
• All patients underwent ETDRS visual acuity
testing, ophthalmological examination, and
adverse event assessment at each study
visit, with fundus photography, fluorescein
angiography, OCT, and pharmacokinetic
evaluations at selected visits.
Eligibility/Exclusion
• Inclusion: active subfoveal CNV, visual
acuity in the study eye of 20/40 to 20/400 and
better or equal to 20/800 in the fellow eye,
age >50 years old;
• Exclusion: more than 3 prior treatments with
Visudyne in the study eye within 12 months,
lesions larger
Participating Centers
Multicenter
Results
• Twenty-one of the 30 patients were enrolled
at the Bascom Palmer Eye Institute; Group1
(n=5), Group 2 (n=8), and Group 3 (n=8).
• The types of subfoveal CNV lesions
enrolled included occult CNV with no
classic CNV (n=6), minimally classic CNV
(n=6), predominantly classic CNV (n=2),
predominantly classic CNV after PDT (n=4),
and CNV with RPE tears (n=3).
• Intravitreal injections as frequent as every 2
weeks were well tolerated by the patients.
• The most frequent adverse event was mild
inflammation.
• Significant intraocular inflammation was
not observed when RhuFab was escalated
from an initial dose of 300µg to doses as
high as 2mg. At week 20 (Day 140), 19 of the
21 patients (90%) had stable (± 4 letters) or
improved (> 5 letters) vision with 11 patients
(52%) gaining at least 3 lines (15 letters).
• Stable and improved visual acuity
correlated well with decreased fluorescein
angiographic leakage and decreased retinal
thickness measured by OCT.
Study
A Phase III, Multicenter, Randomized,
Double-Masked, Sham Injection-
Controlled Study of the Efficacy and Safety
of rhuFab V2 (Ranibizumab) in Subjects
with Minimally Classic or Occult Classic
Subfoveal Neovascular AMD (FVF2598G
Study - MARINA)
Sponsor
Genentech, Inc. 888-662-6728
Status
Actively enrolling
Study Center
Genentech, Inc., 1 DNA way, South San
Francisco, CA 94080-4990
Study Chairman
Robert Y. Kim, MD, Genentech
Study Purpose
• To investigate the efficacy, safety, and
tolerability of monthly intravitreal injections of
rhuFab V2 in preventing visual loss
Study Design
• Phase III, multicenter, randomized pivotal
study.
• 1:1:1 Randomization: Sham injection: 300
micrograms rhuFab V2: 500 micrograms
RhuFab V2 by 24 monthly intravitreal
injections
• All patients to receive ETDRS visual acuity
testing, ophthalmological examination,
and adverse event assessment at each
study visit, with fundus photography,
fluorescein angiography, OCT, visual function
questionnaires and health surveys, and
pharmacokinetic evaluations at selected
visits.
Number of Patients Enrolled
Fully enrolled. 716
Follow Up
Ongoing
Eligibility/Exclusion
• Inclusion: active primary or recurrent
subfoveal CNV lesions due to AMD with
occult or minimally classic CNV, CNV must be
50% of lesion GLD , total lesion < 12 MPS
DA; visual acuity in the study eye of 20/40
to 20/320
• Exclusion: prior PDT, TTT, XRT, or other
experimental CNV treatment. Previous
intravitreal drug delivery. Prior vitrectomy,
submacular surgery, or other surgical
intervention for AMD. Subfoveal atrophy
or fibrosis. Other cause of CNV. RPE tear.
Selected subfoveal hemorrhage ( 1 Disk area
or 50% of lesion)
Participating Centers
Multicenter (100 sites)
Results
Pending
Study
Visudyne With Altered (Delayed) Light in
Occult CNV Study (VALIO)
Sponsor
QLT Inc/Novartis Ophthalmics, Inc
Study Purpose
• To determine the potential of delaying
light application to 30 minutes after
initiation of infusion to improve outcomes
of photodynamic therapy with verteporfin
(Visudyne®, Novartis AG) in AMD patients
with occult with no classic CNV
Study Design
• AMD patients (>50 years of age) with
subfoveal CNV were randomized 1:1 to
receive verteporfin therapy with delayed
light or verteporfin therapy with standard
light application (15 minutes after initiation
of infusion)
• Patients were followed for at least 6 months
after initial treatment. Inclusion criteria
comprised a lesion composition that was
occult with no classic CNV, in which <50%
of the lesion area was CNV and in which
the greatest linear dimension of the lesion
was <5400 microns on the retina, presumed
recent disease progression, and baseline
best-corrected visual acuity (approximate
Snellen equivalent) 20/50-20/200.
• Verteporfin therapy was administered at
baseline, with the option of an additional
treatment at month 3, 6, and 9 if there was
evidence of fluorescein leakage from CNV
• Best-corrected visual acuity, color
fundus photography, and fluorescein and
Indocyanine Green (ICG) angiography were
assessed at scheduled follow up visits
through month 6
• Potential treatment benefit was assessed
based on angiographic outcomes and visual
acuity change from baseline
• Safety was assessed by evaluating
adverse events, visual acuity, color
fundus photographs, fluorescein and ICG
angiograms
Eligibility/Exclusion
Inclusion:
• Subfoveal CNV, occult CNV with no classic
CNV
• Vision 20/40-20/200
• Recent progression of disease
Exclusion:
• Lesions larger than 9MPS DA
• Cataract surgery within previous 3 months
Results
• Most baseline characteristics did not
appear different between the two treatment
groups (median age 78, 42% men, median
total lesion size 8.59 mm [approximately 4.85
MPS DA]
• The baseline median visual acuity score
was higher in the standard light application
group (58 letters vs. 52 letters [approximate
Snellen equivalent 20/64-2 vs. 20/100+2] as
measured by ETDRS criteria).
• Angiographic and vision outcomes and
safety results through 12 months showed no
statistically significant difference.
Study
Prophylactic Diode Laser Photo
Coagulation for the Prevention of
Choroidal Neovascularization in Age-
Related Macular Degeneration (PTAMD)
Sponsor
University of Pittsburgh
Status
Active
Patient Accrual Date
3rd year of recruitment
Study Center
University of Pittsburg
Study Chairman
Thomas Friberg, MD; U of Pittsburg;
Pittsburg, PA 412-647-7212
Study Purpose
• To determine whether a specific laser
treatment will prevent individuals who have
the less severe dry macular degeneration
from progressing to the more severe wet form
of macular degeneration
Study Design
• Bilateral Dry AMD patients with both eyes
eligible will have one eye randomized to laser
treatment and the fellow eye assigned to
observation
• Unilateral patients with only one eye eligible
will have the eligible eye randomized to either
laser treatment or observation
• Laser treatment consists of a grid of 48
subthreshold (ophthalmoscopically invisible)
diode laser spots placed around the macula
Number of Patients Enrolled
150
Follow Up
5 yrs
Eligibility/Exclusion
• Inclusion: males and females, 50 yrs or
older, able to understand and give written
informed consent before treatment, vision
20/60 or better with at least 5 Drusen in each
eye or 5 large Drusen in one eye with an
event occurring in the other eye, no major
health problems
• Exclusion: worse vision than 20/60, event
or drusen, size/amounts, inhibiting health
factors
Participating Centers
13
Results
Pending
Study
Multicenter Investigation of Rheopheresis
for Age-Related Macular Degeneration
(MIRA-1)
Sponsor
OccuLogix; 2575 Ulmerton Road, suite 210;
Clearwater, FL 33762; 727-561-4181
Status
Ongoing
Patient Accrual Date
Not available
Study Center
OccuLogix, Inc.
Study Chairman
Not available
Study Purpose
This study is designed to determine if the
removal of LDL cholesterol and other harmful
substances from the blood will improve vision
in people with Dry AMD
Study Design
• At entry, patients undergo a complete
ocular and physical examination, including a
series of baseline blood tests
• Patients will be randomly assigned to
one of two study treatment groups: the
Rheopheresis treatment group (120 patients)
or placebo treatment group (60 patients)
• The design is single masked with a 2:
1 chance of being in the apheresis group.
Patients undergo 8 treatments over a period
of 2 1/2-months
• Patients in the Rheopheresis treatment
group will have their blood pumped through
the filter system being investigated
• Patients in the placebo treatment group will
not have blood filtered. At each visit, patients’
vital signs will be recorded, and blood
samples obtained pre- and post- treatment
• Between the 4th and 5th treatments, two
weeks after the 8th treatment, and at 6, 9,
and 12 months, patients will receive the same
blood tests and examinations performed at
entry
Number of Patients Enrolled
Approx. 200.
Follow Up
• In either of these groups, patients will
undergo 8 treatments over a period of about
2-1/2 months
• Patients in the Rheopheresis treatment
group will have their blood pumped through
the filter system being investigated
• Patients in the placebo treatment group will
not have their blood filtered
• At each visit, patients’ vital signs will be
recorded, and they will be asked to give
blood samples for complete testing prior to
and immediately after each treatment, which
takes about 3 hours to complete
• Between the 4th and 5th treatments and
two weeks after the 8th treatment, patients
will come back to the clinic for a visit where
they will receive many of the same tests taken
at the initial qualifying visit
• There will be three more evaluations at
approx. 6 months, 9 months, and 12 months
• At those evaluations, the patients’ blood will
be tested and another complete set of ocular
examinations will be performed
Eligibility/Exclusion
Not available
Participating Centers
Not available
Results
Pending
Study
An Evaluation Of Efficacy And Safety
of Posterior Juxtascleral Injections of
Anecortave Acetate 15mg Versus Visudyne
in Patients with Subfoveal Exudative
Age- Related Macular Degeneration
(AMD) Eligible for Initial Treatment with
Photodynamic Therapy (PDT) Using
Visudyne
Sponsor
Alcon Research; South Freeway Drive; Ft.
Worth, TX 817-615-2583
Study Purpose
To demonstrate that Anecortave Acetate is
non-inferior after 12 months of treatment to
PDT with Visudyne in patients eligible for
initial PDT treatment
Study Design
• Patients randomized to the Anecortave
Acetate treatment group will also receive
at the same visit and prior to the posterior
juxtascleral inject a sham PDT treatment
• Patients randomized to PDT with Visudyne
will also receive at the same visit following the
PDT treatment a sham posterior juxtascleral
injection
Eligibility/Exclusion
Eligibility:
• Lesion area less than or equal to 5400
microns in GLD; 50% or more of the total
lesion is CNV; the classic component of the
total CNV must be at least 50% of the total
lesion
Exclusion:
• Ophthalmic disease in the study eye that
would compromise visual acuity
• Previous PDT treatment, previous laser
photocoagulation is allowed if performed 30
days before enrollment
• Patient has scleral buckle in the study eye
• Patient is on anticoagulant therapy, with the
exception of aspirin and anti-platelet therapy
Results
There was no statistical difference between
the anecortave acetate treatment and the
PDT treatment outcomes regarding the
primary endpoint of loss of fewer than 3 lines
of visual acuity. Forty-five percent of the
patients in the anecortave acetate group had
less than a 3-line loss of visual acuity, and
49% of patients had less than a 3-line loss of
visual acuity in the PDT group. The statistical
endpoint, however, was not reached
regarding non-inferiority of anecortave
acetate compared with PDT. Both groups had
approximately the same number of adverse
ocular and systemic events.
Study
A Phase II Multicenter Trial to Establish
the Safety and Pharmacokinetic Profile
of Intravitreal Anti-VEGF Pegylated
Aptamer (EYE001) in Age-Related Macular
Degeneration Undergoing Photodynamic
Therapy
Sponsor
Eyetech Pharmaceuticals, Inc.; 666 Fifth
Avenue;
35th floor; New York, NY 10103; 212-582-
8376
Study Purpose
• The primary objective of this study will be
to evaluate the safety of 3 repeat doses of
EYEO01 administered after photodynamic
therapy.
• Secondary objectives include the evaluation
of the pharmacokinetic profile, preliminary
efficacy, and patient’s immune response to
EYEO01 when given as intravitreal injections
(3mg/eye) once every 28 days for 3 doses in
patients with the neovascular form of AMD.
Study Design
• This is a multi-center, open-label, repeat
dose phase 18 study of 3mg/eye of EYEO01
following PDT, inpatients with choroidal
subfoveal neovascular AMD with a visual
acuity worse than 20/100 in the study eye or
equal to 20/400 in the fellow eye.
• If 3 or more patients experience Dose-
Limiting Toxicity (DLTs), the dose will be
reduced to 2mg and 1 mg, if necessary in a
further 10 patients.
• Patient accrual into the trial is expected to
be completed within 2 to 3 months. Four to
10 sites in the U.S. will provide 1 to 8 patients
per site.
Eligibility/Exclusion
• Age-Related Macular Degeneration with
subfoveal sub-retinal neovascularization.
• Visual acuity less than or equal to 20/80.
Results
• 87.5% of patients who received the anti-
VEGF drug alone showed stable or improved
vision 3 months after treatment.
• Vision improved by 3 or more lines in 25%
of eyes that received this drug alone.
• However when combined with
photodynamic therapy, many more eyes
(60% ) gained 3 or more lines of vision.
This study has reported short term (3 month)
results, which look encouraging. Further
clinical trials are necessary to demonstrate
the efficacy and long-term safety of anti-
VEGF therapy for wet macular degeneration.
No definitive conclusions regarding the
retina times 29
>> RETINAL RESEARCH REPORT
efficacy of the drug can be deduced from this
study because of the absence of a control
group, small sample size, and short follow-up
period. Phase II/III trials using this drug are
presently underway to evaluate this potential
treatment in more than a 1000 patients in
more than 100 centers worldwide.
Study
A Phase II/III Randomized, Double
Masked, Controlled, Dose Ranging Multi
Center Comparative Trial , in Parallel
Groups, to Establish the Safety and
Efficacy of Intravitreal Injections of
EYE001 (Anti-VEGF Pegylated Aptamer)
Given Every 6 wks to 54 wks, in Patients
with Exudative Age-Related Macular
Degeneration (AMD)
Sponsor
Eyetech Pharmaceuticals, Inc.; 666 Fifth
Avenue;
35th floor; New York, NY 10103; 212-582-
8376
Status
Ongoing
Patient Accrual Date
TBA
Study Center
Eyetech Pharmaceuticals, Inc.
Study Chairman
Not available
Study Purpose
To establish a safe and effective dose of
EYEOO1. Patients will be randomized to
intravitreal injections of either EYEO01 or
placebo every 6 weeks
Study Design
The study is a randomized, double-masked,
controlled, dose-ranging, multi-center
comparative trial
Number of Patients Enrolled
540
Follow Up
54 weeks
Eligibility/Exclusion
Not available
Participating Centers
Not available
Results
Pending
Study
A Phase I/II, Multicenter, Dose Escalation,
Controlled Study of the Safety, Tolerability,
Pharmacokinetics and Activity of Multiple
Dose Intravitreal Injections of rhuFab V2 in
Subjects with Neovascular AMD (FVF2128g
study)
Sponsor
Genentech, Inc. 888-662-6728
Study Purpose
• To investigate the safety and tolerability
of recombinant humanized anti-VEGF
monoclonal antibody fragment (RhuFab
V2) administered as multiple, intravitreal
injections
Study Design
• Phase I/II multi-center. Dose excalation
controlled study
Eligibility/Exclusion
• Inclusion: active subfoveal CNV, visual
acuity in the study eye of 20/40 to 20/400 and
better or equal to 20/800 in the fellow eye,
age >50 years old;
• Exclusion: more than 3 prior treatments
with Visudyne in the study eye within 12
months, lesions larger than 9MPS disc areas,
cataract surgery within the previous 30 days,
current or recent use of oral or parental
anticoagulants or anti-platelets other than
aspiring, ticlopididne, clopidogrel and/or
nosteroidal anti-inflammatory agents
Results
Pending
Study
A Randomized, Placebo Controlled,
Double Masked, Multi Center Phase III
Study of the Effect of Visudyne Therapy
30 retina times
in Occult with No Classic Subfoveal
Choroidal Neovascularization (CNV)
Secondary to Age-Related Macular
Degeneration (VIO)
Sponsor
QLT Inc/Novartis Ophthalmics, Inc
Study Purpose
To demonstrate that Visudyne therapy in
patients who have occult with no classic
subfoveal CNV lesions will, with an
acceptable safety profile significantly reduce
the risk of vision loss compared with placebo
Study Design
• A randomized, placebo-controlled, double-
masked, multi-center, Phase III study
• Patients stratified by study center and
randomized to Visudyne therapy or placebo
in a 2:1 ratio
Eligibility/Exclusion
Eligible:
• Must have occult with no classic subfoveal
CNV secondary to AMD BCVA between 73
and 34 letters (approx. Snellen equivalent of
20/40 to 20/200)
• GLD of entire lesions must no exceed 5400
microns
• Must not have a CNV lesions size that is
>4 MPS disc areas, associated with a BCVA
of >65 letters (approx. Snellen Equivalent of
20/50 or better)
• Presumed recent progression of occult
CNV within the preceding 3 months before
randomization to treatment
Exclusion:
• Any additional ocular disease that may
compromise visual acuity in the study eye.
• No previous PDT, m or other local treatment
in study eye
Results
Pending
Study
Photodynamic Therapy (Visudyne) Early
Re-Treatment For Subfoveal Choroidal
Neovascularization (VER) Study
Sponsor
QLT Inc/Novartis Ophthalmics, Inc.
Study Purpose
To determine whether early retreatment
with Visudyne therapy in patients with
predominantly classic subfoveal choroidal
neovascularization secondary to AMD will
reduce the risk of vision loss
Study Design
Multi-center, randomized, parallel group,
double-masked, controlled phase III, 2 year
study using standard treatment and an
experimental retreatment schedule (as often
as every 1.5 months retreatment interval
during the first 6 months)
Eligibility/Exclusion
Eligible:
• Subfoveal, predominantly classic CNV (area
of classic> 50% area of entire lesion) I GLD
not to exceed 5400 microns BCVA between
20/40 and 20/200
Exclusion:
• Any additional ocular disease that may
compromise visual acuity in the study eye
• No previous PDT, or other local treatment
in study eye
Results
Results from the Phase III early retreatment
(VER) study with Visudyne showed that the
early retreatment regimen did not result in a
significant improvement in vision outcomes
over the standard retreatment regimen every
3 months. The data did reconfirm the vision
benefits and safety shown in the original
TAP or Treatment in Age-related macular
degeneration with Photodynamic therapy
study.
Study
A Phase III, Multicenter, Randomized,
Double-Masked, Active Treatment-
Controlled Study of the Efficacy and Safety
of rhuFab V2 (Ranibizumab) Compared
with Verteporfin (Visudyne) Photodynamic
Therapy in Subjects with Predominantly
Classic Subfoveal Neovascular AMD
(FVF2587G Study - ANCHOR)
Sponsor
Genentech, Inc. 888-662-6728
Status
Actively Enrolling
Study Center
Genentech, Inc., 1 DNA way,
South San Francisco, CA 94080-4990
Study Chairman
Robert Y. Kim, MD, Genentech, Inc.
Study Purpose
• To investigate the efficacy, safety, and
tolerability of monthly intravitreal injections of
rhuFab V2 compared with verteporfin PDT
Study Design
• Phase III, multicenter, randomized pivotal
study.
• 1:1:1 Randomization : Sham injection: 300
micrograms rhuFab V2: 500 micrograms
rhuFab V2 by 24 monthly intravitreal
injections
• Sham injection group to receive PDT, and
rhuFab injection groups to receive sham PDT
q3 months.
• All patients to receive ETDRS visual acuity
testing, ophthalmological examination,
and adverse event assessment at each
study visit, with fundus photography,
fluorescein angiography, OCT, visual function
questionnaires and health surveys, and
pharmacokinetic evaluations at selected visits
Number of Patients Enrolled
TBA. Target enrollment = 426
Follow Up
Ongoing
Eligibility/Exclusion
• Inclusion: primary or recurrent subfoveal
CNV lesions due to AMD eligible for PDT with
Verteporfin, >50% classic CNV, lesion GLD
<5400 microns; visual acuity in the study eye
of 20/40 to 20/320, age >50 years old
• Exclusion: prior PDT, TTT, XRT, or other
experimental CNV treatment. Previous
intravitreal drug delivery. Prior vitrectomy.
Subfoveal atrophy or fibrosis. Other cause
of CNV. RPE tear. Selected subfoveal
hemorrhage (1 disk area or 50% of lesion)
Participating Centers
Multicenter (100 sites)
Results
Pending
Study
Limited Macular Translocation Study
Sponsor
Pilot study - self funded
Study Purpose
To determine whether translocation plus
standard laser is better than PDT or
observation alone
Study Design
Randomized, prospective, multi center study.
Patients randomized:
• Translocation versus PDT -100 patients
• Translocation versus observation - 100
patients.
• Vision <20/40 to >20/800.
• Subfoveal, choroidal neovascularization
(classic, occult, both)
• CNV secondary to Age-Related Macular
Degeneration
• Inferior border of lesion 1000um or less
from foveal center
• Ages greater than 49 years.
• > Light perception vision in fellow eye.
Results
Pending
Study
A Phase II, Multicenter, Randomized,
Double-Masked, Placebo Controlled
Study of the Matrix Metalloproteinase
Inhibitor AG3340 in Patients with Subfoveal
Choroidal Neovascularization Associated
with Age- Related Macular Degeneration
Sponsor
Agouron Pharmaceuticals, Inc.
Study Purpose
• This phase II clinical trial will assess the
safety and efficacy of AG3340 (prinomastat)
in approx. 200 patients aged 50 years and
older affected with the neovascular form of
Age-Related Macular Degeneration (AMD)
• To determine the optimal dose and regimen
to use in subsequent phase III trials.
Study Design
A phase II, randomized, double-masked,
placebo-controlled, multicenter study.
Eligibility/Exclusion
• Patients age 50 years and older with new
or recurrent choroidal neovascular lesions
associated with AMD, subfoveal, or mostly
classic.
• Visual acuity score by ETDRS chart> 39
(Snellen equivalent of 20/160).
• Patients must not have other serious ocular
diseases or conditions present.
• Patients must not currently be using
systemic steroids or other drugs which may
affect the macula.
• No unstable or severe concurrent medical
conditions or active uncontrolled infections
present.
Results
Pending
Study
Women’s Health Initiative Sight
Examination Study (WHI-SE)
Sponsor
University of Michigan
Status
Recruitment ended
Patient Accrual Date
5/2000-12/2001
Study Center
Women’s Health Initiative Sight Examination
Coordination Center; 611 Church St, Ann
Arbor, MI 48104; 734-615-8190
Study Chairman
Dr. Mary Haan; University of Michigan, 734-
615-8190
Study Purpose
• To evaluate whether exogenous estrogen
use through hormone replacement therapy
can prevent incident cases of AMD, or slow
the progression of this disease in women
who already have AMD. To evaluate if
exogenous estrogen reduces the risk of late
forms of age related maculopathy, including
geographic atrophy, retinal pigment epithelial
detachments and choroidal neovascular
membranes
Study Design
• The WHI-SE study is an 8 year project
and will involve 19 clinical centers across
the country to obtain eye exams on approx.
5,000 women who are 65 years of age
and older enrolled in the Women’s Health
Initiative’s main clinical trial of hormone
replacement therapy
• The participants in this study are a
component of the larger clinical trial funded
by NIH, the Women’s Health Initiative
Number of Patients Enrolled
4688 people participated in a baseline
examination done between 1998 - 2002
Follow Up
• The cohort may be reexamined if new
funding is received.
• The cohort is being reexamined (10 year
follow-up), with approx. 3,000 participants
expected to be seen
• The 10-year examinations conclude on May
31, 2000
Eligibility/Exclusion
• Only women who were enrolled in the WH1
were eligible to participate in WHI-SE.
• Women in the study received Premarin or
Prempro, forms of estrogen, or a placebo
sugar pill.
• In addition, women asked to:
• Undergo a vision exam when enrolling
in WHI-SE and again in 3-4 years to check
visual acuity and to photograph the retina
(require dilation)
• Complete two questionnaires on vision,
history of eye disease and medication use
• Complete brief questionnaire on vision
each year between the two eye exams
• Have blood collected for studies on the
effect of diet and cardiovascular disease
on macular degeneration
Participating Centers
15-20
Results
Currently pending funding to do follow-up
exams.
Study
Photodynamic Therapy (Visudyne)
in Minimally Classic Subretinal
Neovascularization (VIM) Study
Sponsor
QLT Inc/Novartis Ophthalmics, Inc
Study Purpose
• To compare potential treatment benefit and
safety of verteporfin (Visudyne, Novartis AG)
therapy and placebo for minimally classic
subfoveal CNV due to AMD using a standard
light dose and one delivered with reduced
fluence rate
Study Design
• Patients (>50 years of age) with minimally
classic lesions of <6 MPS disc areas (DA) (1
MPS DA=2.54mm2) in this double-masked
study were randomized (1:1:1) to one of three
treatment groups:
• (1) Verteporfin therapy with reduced light
fluence rate (300 mW/cm2) for 83 seconds
(25 J/cm2);
• (2) Verteporfin therapy with standard light
fluence rate (600 mW/cm2) for 83 seconds
(50 J/cm2);
• (3) Placebo; half with reduced and half
with standard light fluence rate
• Fluorescein and ICG angiography and
best-corrected visual acuity were assessed
1 week after treatment in 10 patients from
each group.
• All patients were assessed at 6 weeks, 3
months, and 6 months after initial visit
• Changes in total area of the lesion and
individual components were assessed
through month 3 and change in visual acuity
from baseline was assessed at all visits
• Safety was evaluated by adverse events,
visual acuity, fluorescein angiograms, and
color fundus photographs
Eligibility/Exclusion
• Minimally Classic CNV lesions secondary
to AMD
• Baseline VA between 20/40 and 20/200
• Lesion size up to 4 DA
Results
• At baseline, main demographic variables
did not appear different among treatment
groups: overall, mean age 78, 64% women,
mean study eye visual acuity (approximate
Snellen equivalent) 20/100-1
• At baseline, for the reduced fluorescence,
standard fluorescence, and placebo groups,
respectively
• Mean total lesion area was 3.65, 3.91, 3.25
MPS DA
• Mean area of occult CNV 3.28, 3.36, 2.89
MPS DA; and classic CNV 0.26, 0.41, 0.29
MPS DA
• Six-month vision and fluorescein
angiographic outcomes will be reported
Results
Pending
Study
Age-Related Eye Disease Study
Sponsor
Eye 92-EI-0250
Study Purpose
• To assess the clinical course, prognosis,
and risk factors of Age-Related Macular
Degeneration (AMD) and cataract
• To evaluate, in randomized clinical trials,
the effects of pharmacologic doses of (1)
antioxidants and zinc on the progression of
AMD and (2) antioxidants on the development
and progression of lens opacities
Study Design
• The Age-Related Eye Disease Study
(AREDS) is a major research program
to improve our understanding of the
predisposing factors, clinical course, and
prognostic factors of AMD and cataract.
• Eligible patients are randomized to
treatment with placebo, antioxidants, zinc, or
antioxidants plus zinc, and are followed for a
minimum of 5 years
Eligibility/Exclusion
• Men and women between the ages of 55
and 80 years whose macular status ranges
from no evidence of AMD in either eye to
relatively severe disease with vision loss in
one eye but good vision in the fellow eye
(20/30 or better) are eligible for the study
provided that their ocular media are clear
enough to allow good fundus photography
Results
• AREDS researchers found that people at
high risk of developing advanced stages of
AMD lowered their risk by about 25 percent
when treated with a high-dose combination of
vitamin C, vitamin E, beta-carotene, and zinc
• In the same high risk group -- which
includes people with intermediate AMD, or
advanced AMD in one eye but not the other
eye -- the nutrients reduced the risk of vision
loss caused by advanced AMD by about 19
percent
• For those study participants who had either
no AMD or early AMD, the supplements did
not provide an apparent benefit.
• In the cataract portion of the study,
researchers discovered that the same
nutrients had no significant effect on the
development or progression of age-related
cataract
Results
Pending
Study
Randomized Trial of Beta-Carotene and
Macular Degeneration
Sponsor
NEI
Status
Ongoing; randomized treatment complete;
collection of medical reports for reported
cases of AMD is continuing
Patient Accrual Date
Recruitment for the Physicians Health Study
began in 4/82 and was completed in 12/84.
The randomized trial of beta-carotene and
macular degeneration began evaluating from
that study in 1990
Study Center
Charles Hennekens, MD; Brigham & Women’s
Hospital; 900 Commonwealth Ave, E;
Brookline, MA 02215; 617-732-4965
Study Chairman
William Christen, MD / 617-278-0795
Study Purpose
• To determine whether 50mg of beta
carotene taken every other day reduces
the risk of developing Age-Related Macular
Degeneration (AMD) among male US
physicians who were aged 40-84 in 1982
• To investigate the possible relationship
of AMD with other antioxidants including
selenium and vitamins A, C, and E
• To identify potential risk factors for
development of AMDM
• Possible risk factors include height,
systemic hypertension, cardiovascular
disease, blood cholesterol, cigarette smoking,
iris and skin color, sunlight exposure, body
mass index, diabetes, and alcohol intake
Study Design
• It is an ongoing, randomized placebo-
controlled trial of aspirin in the prevention of
cardiovascular mortality and of beta-carotene
in the prevention of cancer
• Following randomization, each of the
22,071 patients enrolled was assigned to
one of four groups to take either aspirin or its
placebo and beta-carotene or its placebo
• Follow up questionnaires are sent 6 and
12 months after randomization and every 21
months thereafter
Number of Patients Enrolled
22,071
Follow Up
More than 12 years
Eligibility/Exclusion
• The study population consists of 22,071
male US physicians who were aged 40-84
years in 1982.
• The subjects have no history of myocardial
infarction, cancer, kidney disease, renal
disease, or any other contraindication to the
use of aspirin or beta-carotene. Including
regular use of corticosteroids
Participating Centers
For information call the chairman’s office
Results
532 cases of ARM confirmed (261 in beta-
carotene grp & 271 in placebo). Results
suggest that 12 years of beta-carotene
supplementation has no appreciable effect
on ARM during the treatment period. (ARVO
2004 program #2111)
Study
Transpupillary Thermotherapy for
Choroidal Neovascularization Clinical Trial
(TTT4CNV)
Sponsor
Iridex, Inc.; 1212 Terra Bella Avenue;
Mountain View, CA 94043; 650-962-8840
Study Purpose
• To determine whether TTT is a safe and
effective treatment for occult subfoveal
choroidal neovascularization in AMD
Study Design
• Prospective randomized multicentered
clinical trial. 112 patients are observed,
224 treated with TTT Outcome variable:
best corrected visual acuity pre and post
treatment, exudation measured by stereo
fundus photos and FA
Eligibility/Exclusion
• Inclusion: AMD, 50 yrs or older, visual
acuity: 20/50 - 20/400 ETDRS, occult CNVM
• Exclusion: prior retinal laser/surgery, ocular
surgery within 3 months, medication toxic to
retina, lens or optic nerve, glaucoma
• Angiographic eligibility: total lesions
<3000mm (2DD) in diameter, CNV underlying
or surrounding center of macula, occult CNV
is required: late leakage or fibrovascular
PED, subretinal fluid or exudate is required;
if present, classic CNV if <10% of the lesion;
if present, serous PED must be <25% of the
lesion; if present, subretinal hemorrhage must
be <50% of the lesion; if present, subretinal
fibrosis <25% of the lesion, cannot have
chorioretinal anastomosis, cannot have
geographic atrophy >0.5 DA within 500mm of
the foveal center
Results
Results confirmed that a subgroup of
patients, who were enrolled into the study
with baseline visual acuity of 20/100 or
worse, benefited from TTT treatment. Within
the TTT4CNV Clinical Trial, about 41% of
the patients enrolled had baseline vision of
20/100 or worse. (Baseline vision means
that was the vision the patient had when
he/she entered the study). Specifically, at
12 months following treatment 23% of TTT
treated eyes in this subgroup improved vision
by one or more lines and 14% of TTT treated
eyes improved vision by three or more lines.
None of the eyes in the placebo treated
control group showed any improvement of
vision. After 18 months, the patients in this
subgroup who did lose vision (as one would
expect over time), did better than the placebo
treated eyes. Specifically, TTT treated eyes
on average lost 2 lines of visual acuity while
placebo treated eyes lost 4 lines. These
findings were statistically significant.
Results
Pending
Study
Dry Age-Related Macular Degeneration
(AMD) Trial
Sponsor
Apheresis Technologies, Inc.
Study Purpose
To determine whether patients with Dry AMD
experience improvement in their vision after
apheresis treatments
Study Design
• Multi-center study, enrolling a total of 180
patients to be randomized into 2 groups: 120
in the treatment group and 60 in the placebo
control group
• Patients will receive 8 treatments (actual or
placebo) and the results between the groups
will be compared during follow up visits
• The treatments are provided at no cost to
qualifying patients
• The quality of life questionnaires VFQ-25
and AMD will be utilized to determine how
much the patients’ life is affected by their
visual problems
Eligibility/Exclusion
• Between the ages of 50 and 85 years of age
and weigh greater than 110 lbs.
• Have some vision loss in at least one eye
due to macular degeneration, with no other
major eye diseases.
• Patient must be in reasonably good health
with a visual acuity between 20/32 and 20/
125 and have more than 10 large soft drusen.
Results
Pending
Study
Complications of Age-Related Macular
Degeneration Prevention Trial (CAPT)
Sponsor
National Eye Institute/NIH
Status
Recruitment Completed
Patient Accrual Date
5/1/99.
Study Center
Maureen Maguire, PhD; Director CAPT
Coordinating Center; 3535 Market Street,
Suite 700; Philadelphia, PA 19104. 215-615-
1531
Study Chairman
Stuart Fine, MD; Scheie Eye Institute / 215-
662-8142
Study Purpose
• To determine whether application of low
intensity laser treatment of eyes with drusen
in the macula can prevent later complications
of Age-Related Macular Degeneration and
thereby preserve visual function
Study Design
• The CAPT is a multi-center, prospective,
randomized clinical trial designed to assess
the safety and effectiveness of low intensity
laser treatment in preventing vision loss
among patients with large drusen in both
eyes
• Eligible patients will have one eye randomly
assigned to laser treatment performed by
CAPT-certified ophthalmologists. The other
eye is not treated. Both eyes are observed
carefully for any changes for a period of five
years
• The effectiveness of the treatment will be
assessed using the following criteria:
• Change in visual acuity (primary
outcome measure of the study), incidence
of complications of AMD such as
neovascularization, serous detachment of
the pigment epithelium and geographic
atrophy, changes in contrast threshold
and critical print size for reading
• QOL assessments for patients, using
the VFQ 25 will be conducted at the time
of enrollment and at 5 years
Number of Patients Enrolled
1052
Follow Up
Minimum of 5 years
Eligibility/Exclusion
• Patients eligible for CAPT can be either
male or female and meet the following
criteria:
• Age at least 50 years old, vision in each
eye must measure 20/40 or better,
• At least 10 large Drusen in each eye,
available for follow-up exams for 5 years
after enrollment
Participating Centers
22 centers
Results
Pending
Study
Randomized Trials of Vitamin Supplements
and Eye Disease
Sponsor
National Eye Institute
Status
Ongoing. Comments: Both studies ongoing.
Patient Accrual Date
No longer recruiting. Comments: Women’s
Health Study: Recruitment began in
November 1992 and was completed in July
1995. Women’s Antioxidant Cardiovascular
Study: Recruitment began in August 1993
and was completed in October 1996.
Study Center
Julie E. Buring Sc.D.
Charles H. Hennekens, M.D.
Brigham and Women’s Hospital
900 Commonwealth Avenue East
Boston, MA 02215-1204
Study Chairman
William G. Christen, Ph.D.
Brigham and Women’s Hospital
900 Commonwealth Avenue East
Boston, MA 02215-1204
retina times 31
>> RETINAL RESEARCH REPORT
Study Purpose
• To determine whether vitamin E
supplementation reduces the risk of cataract
and age-related macular degeneration (AMD)
in women.
• To determine whether vitamin C
supplementation reduces the risk of cataract
and AMD in women.
• To determine whether beta-carotene
supplementation reduces the risk of cataract
and AMD in women.
• To determine whether alternate day, low-
dose aspirin reduces the risk of cataract and
AMD in women.
• To identify potential risk factors for cataract
and AMD including cigarette smoking, alcohol
intake, blood pressure, blood cholesterol,
cardiovascular disease, height, body mass
index, and diabetes.
Study Design
These randomized, double-masked, placebo-
controlled trials will test the hypotheses that
supplementation with antioxidant vitamins
and with low-dose aspirin reduces the
risk of age-related cataract and AMD. The
study populations are the Women’s Health
Study (WHS) and the Women’s Antioxidant
Cardiovascular Study (WACS). The WHS is
a randomized, double-masked, placebo-
controlled trial using a 2x2 factorial design
to test low-dose aspirin (100 mg on alternate
days) and vitamin E (600 IU on alternate days)
in the primary prevention of cardiovascular
disease (CVD) and cancer. It is being
conducted among 39,876 apparently healthy
female health professionals age 45 years and
older. The WACS is a randomized, double-
masked, placebo-controlled secondary
prevention trial using a 2x2x2x2 factorial
design to test antioxidant vitamins (vitamins
E [600 IU on alternate days] and C [500 mg
daily], beta carotene [50 mg on alternate
days]), and a combination of folate (800 mg
daily), vitamin B6 (25 mg daily), and vitamin
B12 (1 mg daily) among women who are at
high risk for CVD morbidity and mortality. It is
being conducted among 8,171 female health
professionals, ages 40 years or older, who
either have preexisting CVD or have at least
three coronary risk factors and therefore are
at high risk for the development of CVD.
Number of Patients Enrolled
Women’s Health Study: 39,876
Women’s Antioxidant Cardiovascular Study:
8,171
Follow Up
Not available
Eligibility/Exclusion
Women’s Health Study:
A participant must have met all of the
following criteria:
(a) female;
(b) aged 45 years or older;
(c) postmenopausal or with no intention of
becoming pregnant;
(d) no reported personal history of
cardiovascular disease, cancer (other than
non-melanoma skin cancer), gout, peptic
ulcer, chronic renal or liver disease, or other
serious illness precluding participation;
(e) no reported history of serious side effects
to the study treatments;
(f) not currently taking aspirin, aspirin
containing medication, or nonsteroidal anti-
inflammatory drugs (NSAIDs) more than 1 day
per week or, if so doing, willing to forego use
of these medications;
(g) not currently taking individual supplements
of vitamin E or beta carotene more than 1 day
per week;
(h) not currently taking anticoagulants or
corticosteroids.
Women’s Antioxidant Cardiovascular Study:
Potentially eligible female health professionals
for WACS were identified from the pool
of respondents to the Women’s Health
Study initial mailing and must have met the
following criteria:
(a) female;
(b) date of birth before January 1, 1955;
(c) a reported history of myocardial infarction
(MI), stroke (CVA), angina pectoris (AP),
coronary artery bypass grafting (CABG),
percutaneous transluminal angioplasty
(PCTA), transient ischemic attack (TIA),
carotid endarterectomy (CEA), or peripheral
artery surgery (PAS);
(d) no history of cancer (except non-
melanoma skin cancer) within the past 10
years and no active liver disease or cirrhosis;
(e) pregnancy physiologically impossible due
32 retina times
to menopause (natural or surgical) or tubal
ligation, or the participant does not intend to
become pregnant in the future as indicated
on the initial WHS questionnaire;
(f) no current use of a vitamin K-depleting
anticoagulant agent (e.g., Coumadin).
Individuals taking aspirin or other NSAIDs
were not excluded.
Participating Centers
Not available
Results
Pending
Study
Anecortave Acetate Risk Reduction Trial
(AART)
Sponsor
Alcon Research, Ltd.
Status
Enrollment is ongoing
Study Purpose
Demonstrate that anecortave acetate (15 mg
or 30 mg) is safe and effective in arresting the
progression of nonexudative AMD in patients
who are at risk for progressing to exudative
AMD
Study Design
Phase 3, double-masked, randomized,
parallel group, no-treatment (sham
administration), safety/efficacy study
Eligibility/Exclusion
Patients at least 50 years of age, any race
and either sex, with a clinical diagnosis of
exudative AMD in the nonstudy eye, and at
least 5 or more intermediate (>63 microns)
or larger soft drusen within 3000 microns of
the foveal center and/or confluent drusen
within 3000 microns of the foveal center, and
hyperpigmentation within 3000 microns of the
foveal center in the study eye.
Results
Pending
Study
SIRNA 0401
Sponsor
Sirna Therapeutics, Inc., Boulder, CO
Status
Enrolling patients
Study Purpose
Assess the safety and tolerability of Sirna-
027; assess the presence of Sirna-027 in
plasma; determine the range of doses for the
phase 2 clinical trial; and assess biological
and anatomical changes in the retina.
Study Design
Phase 1, open-label, dose-escalation -4 to 6
dose cohorts, 1 intravitreal injection
Number of Patients
12¬-30
Participating Centers
4
Eligibility/Exclusion
50 years of age or older; subfoveal to AMD,
classic and/or occult; no other causes of
CNV; total lesion size 12 MPS disc area;
subretinal hemorrhage < 50% of lesion;
subfoveal scaring < 50% of lesion; lesion
thickness 250 m ; inter occular pressure
25 mm Hg; visual acuity 20/100 to 20/800
ETDRS; fellow eye visual acuity not worse
than 20/800 ETDRS
Results
Pending
Study
Visudyne with Intravitreal Triamcinolone
Acetonide (VisTA) Trial
Sponsor
LuEsther T. Mertz Retinal Research Center
Status
Recruiting
Study Purpose
Evaluate the effect of photodynamic therapy
in conjunction with intravitreous triamcinolone
acetonide in subjects with occult or minimally
classic subfoveal CNV secondary to AMD
Study Design
Randomization 1:1:1, PDT and 0 mg
of triamcinolone/PDT and 1 mg of
triamcinolone/PDT and 4 mg of triamcinolone
Eligibility/Exclusion
Inclusion Criteria: 50 years or older, occult or
minimally classic subfoveal CNV, presence
of blood associated with the lesion, vision
loss or growth of lesion objectively recorded
within preceding 3 months, baseline VA score
between 20/40¬-20/400, lesion 5400 microns
Exclusion Criteria: Predominantly classic
CNV, additional eye disease, CNV not
involving geometric center of FAZ, inability
to be photographed; fluorescein allergy;
photophobia; lens opacities expected to
progress during study; previous treatment
for CNV, other than confluent laser
photocoagulation (eg, PDT, submacular
surgery, radiotherapy, macular grid);
participation in another clinical trial; IOP
>21 mm Hg on or off meds; prior treatment
with another antiangiogenic compound
within 6 months of screening; inability to
comply with all study-related procedures;
concomitant therapy with systemic or
topical corticosteroids or NSAIDS (chronic
concomitant therapy is defined as multiple
doses taken daily for 3 or more consecutive
days at any time during the course of the
12-month study); a low dose of ASA (up to
100 mg PO qd) taken for prophylaxis of MI
and/or stroke is permitted during the study;
concomitant coumadin therapy
Number of Patients to be Enrolled
120
Results
Pending
Study
Preservative-free Triamcinolone Acetonide
(PFTA)
Sponsor
QLT Inc., National Eye Institute
Status
Enrolling patients
Study Purpose
Investigate the long-term safety and potential
efficacy of PFTA in patients with wet AMD (all
types) undergoing Visudyne therapy
Study Design
Phase 3, randomized, prospective
Number of Patients
300
Eligibility/Exclusion
Inclusion Criteria: Age greater than or equal
to 50 years; in the study eye, diagnosis of
AMD defined by the presence of drusen
larger than 63 micro m; visual acuity of 20/40
- 20/200 (73-34 letter score) as measured
on an ETDRS chart; in the study eye, the
presence of choroidal neovascularization
under the fovea
Exclusion Criteria: Choroidal
neovascularization, in the study eye,
associated with other ocular diseases such
as pathologic myopia, ocular histoplasmosis
or posterior uveitis, etc.; presence of
geographic atrophy under the fovea in
the study eye; the presence of a chorio-
retinal anastomosis; presence of fibrosis,
hemorrhage, pigment epithelial detachments,
and other hypofluorescent lesions obscuring
greater than 50% of the CNV lesion
Results
Pending
Study
Combretastatin A-4 Phosphate (CA4P) in
Patients with Neovascular AMD (FBO-206)
Sponsor
OXiGENE
Status
Enrolling patients
Study Purpose
Assess the safety and tolerability of
combretastatin administered intravenously in
patients with all forms of neovascular AMD
(classic and occult)
Study Design
Phase 1/2, open label, safety and tolerability
study. The study cycle consists of a prestudy
evaluation period (2¬4 weeks), a 22-day
treatment period, and an 8-week post-
treatment evaluation period
Number of Patients
15¬-20
Participating Centers
1
Eligibility/Exclusion
Age 50 or older, study eye BCVA of 20/40
or less, fellow eye better or equal to 20/800
ETDRS, no history of previous subfoveal
thermal laser therapy
Study
ANCHOR
Sponsor
Genentech
Status
Ongoing
Study Purpose
Evaluate the safety and efficacy of
ranibizumab (Lucentis) compared with
verteporfin photodynamic therapy in
preventing vision loss associated with AMD
Study Design
Phase 3, randomized, double-blind, active
control, parallel assignment. Three treatment
arms: PDT and sham injection, sham PDT
and Lucentis dose A, sham PDT and Lucentis
dose B
Eligibility/Exclusion
50 or older; predominantly classic; subfoveal
CNV due to AMD; study eye BCVA equal to
or worse than 20/40, but no worse than 20/
320; lesion eligible for PDT per labeling; no
prior laser treatment involving the center of
the fovea; no prior PDT; no prior experimental
treatments for AMD
Number of Patients
426
Participating Centers
100
Study
Evaluation of Safety and Efficacy of
Anecortave Acetate vs. Placebo in Patients
with Subfoveal CNV due to Exudative AMD
(C-02-29)
Sponsor
Alcon Research, Ltd.
Status
Enrollment is ongoing in South America
Study Purpose
Demonstrate that anecortave acetate 15
mg is superior to placebo in maintenance of
visual acuity
Study Design
Phase 3, double-masked, randomized,
parallel group, placebo-control, safety and
efficacy study
Inclusion/Exclusion Criteria
Patients at least 50 years of age, any race
and either sex with minimally classic and
occult exudative AMD with subfoveal
choroidal neovascularization
Results
Pending
Study
Evaluation and Tolerability of 4-dose
Levels of Cand5 Administered by Single
Intravitreal Injection in Patients with Wet
AMD
Sponsor
Acuity Pharmaceuticals
Status
Recruiting
Study Purpose
Evaluate 4-dose levels of the small RNA
interference therapeutic agent Cand5 in
subjects with exudative AMD
Study Design
Open label study. One intravitreal injection;
4-dose levels
Eligibility/Exclusion
Inclusion Criteria: Male or female patients 50
years of age or older; subfoveal CNV, classic
or occult; total lesion size <12 total disc
areas, of which at least 50% is active CNV;
subretinal hemorrhage (if any)-no more than
50% of the lesion; minimally classic or occult
lesion must have hemorrhage and/or lipid
and or documented loss of 3 or more lines of
vision during the previous 3 months; vision
20/50 to 20/320, with better acuity in the
fellow eye; IOP 22 mm Hg
Exclusion Criteria: Concomitant ocular
disease, 3 or more prior PDT treatments,
thermal laser within the previous 2
weeks, subfoveal scarring or atrophy, h/o
abdominal aortic aneurysm, stroke within
previous 12 months, diabetes or use of oral
hypoglycemics or insulin, h/o peripheral
vascular disease, allergy to fluorescein
Number of Patients
12
Participating Centers
2 Sponsor
Study
PIER
Sponsor
Genentech
Study Purpose
Evaluate safety and efficacy of Lucentis in
patients with wet AMD
Study Design
Lucentis phase 3b, randomized, double-
masked, sham injection-controlled trial.
Patients will be assigned to 1 of the following
treatment arms: Lucentis dose A, Lucentis
dose B, sham injection
Eligibility/Exclusion
Inclusion Criteria: Men and women age
50 and older; active primary or recurrent
wet AMD involving the center of the fovea
(“subfoveal”); best corrected visual acuity of
equal to or worse than 20/40, but no worse
than 20/320 in the study eye; classic or occult
forms of CNV due to AMD and not another
cause
Exclusion Criteria: Previous verteporfin
photodynamic therapy, external
beam radiation therapy, transpupillary
thermotherapy or intravitreal drug delivery
in the study eye, participation in any clinical
trial involving antiangiogenic drugs (ie,
ranibizumab, pegaptanib, anecortave acetate,
protein kinase C inhibitors, etc.) or any other
clinical trial within the last month
Number of patients
180
Participating Centers
3
Study
The Effect of Pegaptanib Sodium on
Foveal Thickening in Patients with
Exudative Subfoveal AMD
Sponsor
Eyetech Pharmaceuticals
Status
Recruiting
Study Purpose
Compare the safety of Macugen with that of
sham treatment and to assess Macugen’s
effect on foveal thickening
Study Design
Phase 2 prospective, randomized,
double-masked, sham-controlled, dose-
ranging, multicenter trial. First 3 injections:
randomization, 1:1:1, 0.3 mg/1 mg/sham;
subjects in sham treatment group
subsequently rerandomized to 0.3 mg or
1 mg
Eligibility/Exclusion
Inclusion Criteria: CNV with total lesion size
of 12 DA or less of which at least 50% is
active CNV; subretinal hemorrhage not more
than 50% of total lesion size; no subfoveal
scarring, atrophy, fibrosis, or blood over
fovea; no more than 25% of the total lesion
made up of scarring or atrophy, for minimally
classic or occult lesions: >=3 line vision loss
during the previous 12 week and/or subretinal
hemorrhage (not more than 50% of the total
lesion size); VA approximately 20/40-20/320
in study eye and 20/800 or better in fellow
eye; foveal thickness on OCT >=300 mm;
classic CVN for which PDT can be deferred
for 54 weeks
Exclusion Criteria: Previous subfoveal thermal
laser or PDT laser; intraocular surgery,
including extrafoveal/juxtafoveal laser within
the previous 3 months; h/o PPV or SB;
pigment epithelial tears or rips; any other
conditions that may be causing CNV, diabetic
retinopathy; h/o stroke within 12 months of
study entry; h/o peripheral vascular disease
or severe cardiac disease; significant
hematologic, renal, or hepatic disease
Results
Pending
Study
Squalamine
Genaera Corporation
Status
Enrolling patients
Study Purpose
Evaluate the safety and efficacy of
intravenously administered squalamine as a
first-line therapy for wet AMD
Study Design
Phase 2, randomized, double-masked,
controlled study; 2 dose levels once weekly
for 4 weeks, followed by maintenance doses
once every 4 weeks through week 48. At the
end of therapy, each patient will be followed
for an additional year
Number of Patients
100
Participating Centers
Multicenter
Study
Noncomparative Protocol for Use of
Intravitreous Macugen Injections in
Patients with AMD
Sponsor
Eyetech Pharmaceuticals
Status
Recruiting
Study Purpose
Provide Macugen to patients who have
subfoveal CNV secondary to AMD and who
are unable to participate in any other clinical
studies of Macugen for AMD, until such time
as the patient’s lesion is considered to have
resolved or stabilized or Macugen becomes
commercially available
Study Design
Open label study, 0.3 mg intravitreous
injection every 6 weeks
Eligibility/Exclusion
Inclusion Criteria: CNV with total lesion size of
12 DA or less of which at least 50% is active
CNV; subretinal hemorrhage not more than
50% of the total lesion size; no subfoveal
scarring, atrophy, or fibrosis; no more than
25% of the total lesion is scarring or atrophy;
VA approximately 20/40-20/320 in the study
eye; no fellow eye requirement; IOP 23
Exclusion Criteria: Eligibility for PDT with
Visudyne (including patients for whom
prior PDTs have been deemed ineffective);
eligibility for any other Macugen trials,
presence of other causes of CNV - myopia
> 8 diopters, ocular histoplasmosis, angioid
streaks, choroidal rupture, multifocal
choroiditis; h/o severe cardiac disease;
MI within previous 6 months; ventricular
tachyarrhythmias requiring ongoing
treatment; unstable angina; stroke within
previous 12 months; acute ocular or
periocular infection; serious allergy to FA
Participating Centers
Not available
Results
Pending
Study
PrONTO
Sponsor
Bascom Palmer Eye Institute and Genentech,
Inc
Status
Recruiting
Study Purpose
Determine how quickly the central retinal
thickness decreases following ranibizumab
(Lucentis) therapy using OCT and then, after
3 monthly doses determine the durability
of the treatment response with intermittent
therapy offered only if needed based on OCT
findings
Study Design
Prospective, open-label, uncontrolled, clinical
study
Eligibility/Inclusion
Neovascular AMD; subfoveal CNV; all lesion
types; recent disease progression, central
retinal thickness at least 300 microns;
multiple visits required--6 visits each month
for the first 3 months, then visits once a
month thereafter for a total of 2 years
Results
Pending
Study
Safety and Efficacy of AG-013958 in
subjects with subfoveal choroidal
neovascularization associated with age-
related macular degeneration
Sponsor
Pfizer
Status
Recruiting
Study Purpose
Assess the safety, efficacy, and
pharmacokinetics of the investigational drug
AG-013958 in subjects with exudative AMD
Study Design
Phase 1/2, randomized, masked, single and
multiple-dose, single and multiple-dose,
sequential dose-escalation
Eligibility/Exclusion
Inclusion Criteria: AMD, minimally classic
& occult-classic eligible in stage 2 of study
(after first 46 pts), no subfoveal fibrosis;
total lesion fibrosis or scar <25% total area;
hemorrhage <50% of total lesion area, total
lesion area 9 DA; ETDRS best corrected
score of approximately 20/40-20/230; fellow
eye VA >=24 letters (20/320 or better); normal
ECG or nonsignificant changes
Exclusion Criteria: Prior PDT >3 months
before entry; serous pigment epithelial
detachment without surrounding
neovascularization; diabetic retinopathy,
glaucoma, or other serious ocular diseases or
conditions; prior subfoveal photocoagulation
of the macula; prior intravitreal, sub-Tenon’s,
or systemic therapy for AMD; prior TTT
(transpupillary thermotherapy) or intravitreal
steroids in study eye or likely to undergo
these procedures within 6 months of entry;
cataract surgery within previous 12 months;
intraocular surgery within previous 3 months;
prior vitrectomy or submacular surgery; prior
scleral buckling, myopia >= 6 diopters; sitting
BP >159/99 mm Hg on 2 out of 3 evaluations;
stroke within the previous 12 months; h/o
severe cardiac disease; peripheral vascular
disease; unstable angina; MI within 6 months;
ventricular tachycardia requiring treatment;
inability to stop anticoagulants 4 days prior to
injection (ASA okay to continue); participation
in any clinical trials within the previous 60
days; use of systemic steroids currently or
within the previous 30 days
Results
Pending
Study
TheraSight Ocular Brachytherapy System
for Treatment of AMD
Sponsor
Theragenics Corporation
Status
Enrolling
Study Purpose
Investigate the safety, feasibility, and
tolerability of the TheraSight Brachytherapy
System for treatment of wet AMD
Study Design
A multicenter, randomized study of 3 doses
of radiation (assigned 1:1:1) delivered by
the TheraSight Brachytherapy System in
participants with CNV secondary to AMD
Eligibility/Exclusion
Inclusion Criteria: Age 50 years or older;
active primary or recurrent subfoveal CNV
secondary to AMD with minimally classic
or occult lesion; where an active lesion
is defined, lesion < 6 mm greatest linear
dimension (GLD); submacular blood must
comprise less than 75% of the total lesion;
subretinal fibrosis must comprise less
than 25% of the total lesion; study eye
best-corrected vision of 20/100 or poorer
measured on an ETDRS chart (<48 letters
correct); fellow eye best-corrected vision that
is at least 1 line better on an ETDRS chart
than the best-corrected vision of the study
eye; HbA1c <6%, signed informed consent
Exclusion Criteria: Prior AMD therapy
treatment; presence of other eye diseases
that could compromise visual acuity
in the study eye; CNV due to other
causes; hypertensive retinopathy, major
cardiovascular or cerebrovascular event
within the last year; inability to complete
follow-up; allergy to fluorescein dye; previous
radiation to the study eye; pregnancy at time
of surgical procedure
Number of Patients
30
Results
Pending
Study
AdGVPEDF.11D in Neovascular Age-
Related Macular Degeneration (Wet AMD).
Sponsor
GenVec, Inc.
Status
Part 1 is complete; Part 2 is Enrolling Patients
Study Purpose
To assess the safety, tolerability and feasibility
of single direct intravitreal injection of
AdPEDF, identify an appropriate dose range
for Phase II testing of AdPEDF and assess
the biologic activity of AdPEDF.
Study Design
Phase I, open-label, dose-escalating study
of a single intravitreal administration of
AdPEDF. Part 1 of the study is complete;
AdPEDF (at eight ascending dose levels) was
administered to twenty-eight (28) patients
with severe wet AMD and was generally
well-tolerated at all dose levels, with no dose-
limiting toxicities, endophthalmitis, retinal or
vitreous detachment, cataracts or glaucoma.
Part 2 will treat twenty (20) additional patients
with less advanced (moderate to severe) wet
AMD at two of the highest doses tested in
part 1.
Eligibility/Exclusion
Inclusion Criteria: Patients of at least 50 years
in age, with moderate to severe wet AMD
(best corrected vision of 20/40 to 20/320 in
the most impaired eye), active leakage or
CNV with lesion diameter less than or equal
to 5400 microns and no significant subretinal
fluid, who are not candidates for, or who
have refused treatment with, subfoveal laser
photocoagulation or PDT.
Exclusion Criteria: Significant retinal disease
other than neovascular AMD; Significant non-
retinal disease; Cataract or other significant
media opacity; Other causes of choroidal
neovascularization such as pathologic
myopia (>8 diopters), ocular histoplasmosis
or angioid streaks; Evidence of inflammation
(grade 1 or higher) in the anterior and/or
posterior chambers; Cataract surgery or
submacular surgery within 3 months; Prior
ocular treatment with radiation; Known allergy
to fluorescein; Liver enzymes > 2 x ULN (ALT,
AST, bilirubin); Clinical evidence of active
infection of any type, including adenovirus,
hepatitis A, B, or C virus or HIV virus; Other
treatment for AMD in the study eye within
the last twelve weeks prior to Day 1; Other
experimental medications within the last four
weeks prior to Day 1; Abnormal prothrombin
or partial thromboplastin time (>1.5 X ULN) or
anticoagulant therapy that cannot be withheld
for treatment; Prior or current glaucoma or
any atrophic change in the fovea.
Number of Patients
Up to 48
Participating Centers
7
retina times 33
>> RETINAL RESEARCH REPORT
Study
Interval Dose Evaluation of Anecortave
Acetate (IDEAA)
Sponsor
Alcon
Status
Recruiting
Study Purpose
Compare anecortave acetate 15 mg
administered every 3 months vs. anecortave
acetate 15 mg administered every 6 months
vs. anecortave acetate 30 mg administered
every 6 months in patients with exudative
AMD
Study Design
Prospective, randomized 1:1:1
Eligibility/Exclusion
Inclusion Criteria: Clinical diagnosis of
exudative AMD and a primary or recurrent
(after laser photocoagulation) subfoveal CNV
lesion, lesion area 12 disc areas (30.5 mm)
of any lesion type (predominantly classic,
minimally classic, or occult.), choroidal
neovascularization (CNV) >=50% of the total
lesion (defined as angiographic evidence of
neovascularization, associated contiguous
areas of serous elevation of the RPE, elevated
blocked fluorescence, and/or late staining),
evidence of recent disease progression for
occult lesions (defined as having experienced
a loss of at least 1 line of vision or change in
lesion size of more than 1 disc area [2.54 mm]
or the appearance of new blood in the lesion
within the past 3 months)
Snellen equivalent of 20/40 to 20/200 visual
acuity in the study eye (no vision criteria for
the non-study eye).
Exclusion Criteria: Amblyopia, uncontrolled
glaucoma with an IOP > 30 mmHg, ischemic
optic neuropathy, PDR, clinically relevant
NPDR, clinically relevant diabetic macular
edema, significant active uveitis ,clinical signs
of myopic retinopathy, or refraction of >-8.00
diopters in the patient’s current Rx, more than
1 PDT treatment in the study eye, extrafoveal
or juxtafoveal thermal laser treatment less
than 30 days prior to enrollment, more than
2 Macugen injections in the study eye, more
than one Triamcinolone treatment in the study
eye, previous treatment with anecortave
acetate in the study eye, intraocular surgery
in the study eye within 60 days prior to
enrollment., scleral buckle in the study eye
Any previous systemic anti-angiogenic
therapy for AMD, radiation treatment in the
study eye, scleral thinning, any unstable
medical condition that would preclude ability
to keep study visits, coumadin therapy that
cannot be interrupted for a 5-day period
Results
Pending
Study
Interval Dose Evaluation of Anecortave
Acetate (IDEAA)
Sponsor
Alcon
Status
Recruiting
Study Purpose
To evaluate the safety and efficacy of 2 doses
of dexamethasone vs. sham treatment with
the dexamethasone posterior segment drug
delivery system applicator in patients with
macular edema following central retinal vein
occlusion or branch retinal vein occlusion
Study Design
Phase 3, prospective; first 6 months
randomized, additional 6 months open label if
patient is eligible
Eligibility/Exclusion
Inclusion Criteria: Macular edema due to
branch vein occlusion (duration of 3-12
months) or central retinal vein occlusion
(duration of 3-9 months), patient unlikely to
be adversely affected by not being treated
for 6 months, BCVA20/50 to 20/200, retinal
thickness >= 300 by OCT
Exclusion Criteria: Minimum age, 18 years,
any ocular condition that would prevent
a 15-letter improvement in visual acuity,
epiretinal membrane as the primary cause
of the macular edema, history of elevated
intraocular pressure in response to steroid
treatment, history of glaucoma or optic
nerve change consistent with glaucoma,
34 retina times
ocular HTN requiring more than one Study
medication, aphakia or presence of ACIOL, Genetics and Clinical Characteristics of Study
active retinal neovascularization, diabetic Bardet-Biedl Syndrome Optical Coherence Tomography Study of
retinopathy, rubeosis, active or previous CNV, Purpose Retinal Thickness
active ocular infection, active or inactive The purpose of this study is to increase Sponsor
toxoplasmosis, scleral thinning, intraocular knowledge about the genetics and clinical National Eye Institute (NEI)
surgery including cataract surgery or laser characteristics of Bardet-Biedl syndrome.
of any type within 90 days prior to baseline Status
Eligibility Currently Recruiting Patients
examination, history of central serous Enrollment includes adult and pediatric
retinopathy, history of pars plana vitrectomy, Patient Accrual Date
patients and close family members.The
anticipated need for ocular surgery during Ongoing
researchers will include in the study patients
the 12-month study period, previous who present with four primary features OR Study Center
treatment with intravitreal steroid or any three primary features and two secondary National Eye Institute (NEI), 9000 Rockville
intravitreal injectable drug, periocular steroid features: Pike, Bethesda, Maryland 20892
treatment within 6 months prior to baseline, Primary features Study Chairman
systemic steroid treatment within 1 month 1) rod-cone dystrophy Not available
prior to baseline, dexamethasone treatment 2) polydactyly Study Purpose
within 1 month prior to baseline, treatment 3) obesity
with topical ophthalmic steroids or topical This study, conducted at the NIH Clinical
4) learning disabilities
NSAIDS, warfarin or heparin therapy within 1 Center and the University of Wisconsin
5) hypogonadism in males
month prior to baseline, allergy to fluorescein University, will compare measurements
6) renal anomalies
or iodine, uncontrolled systemic disease, obtained using older and newer models
female patients who are pregnant, planning of a machine called an optical coherence
Secondary features
on becoming pregnant, or nursing tomography (OCT) scanner.
1) speech disorder/delay
Results Study Design
2) strabismus, cataracts, astigmatism Observational, prospective, randomized
Pending 3) developmental delay
clinical trial.
4) poly-uria/dipsia (nephrogenic diabetes
insipidus) Number of Patients
5) ataxia, poor coordination, imbalance Expected Total Enrollment: 120
Study 6) spasticity Follow Up
Denufosol Tetrasodium (INS37217 7) diabetes mellitus 3 months
Ophthalmic), P2Y2 Receptor Agonist for 8) dental crowding/hypodontia Eligibility/Exclusion
Intravitreal Injection 9) left ventricular hypertrophy/congenital Inclusion Criteria:
heart disease 1. Patient must understand and sign the
Sponsor
Inspire Pharmaceuticals 10) hepatic fibrosis informed consent.
A durable power of attorney (DPA) will be 2. Patient must be at least 18 years of age.
Status
obtained for all cognitively impaired adults. 3. Pupillary dilation to at least 6 mm must be
Enrolling patients
Results possible.
Study Purpose 4. Ocular media must be sufficiently clear to
Pending
Compare the safety and efficacy of INS37217 allow for quality images.
Ophthalmic to placebo as a first-line therapy Exclusion Criteria:
in patients with rhegmatogenous retinal 1. Any condition such as corneal opacifiation
detachment that precludes adequate slit lamp
Study
Study Design examination and photography of the fundus.
Cell Transplantation to Replace Retinal
Phase 2, double-masked, randomized, Participating Centers
Cells and RPE in Retinal Dystrophies
placebo-controlled, parallel-dose. Patients Not available
will be given a single intravitreal injection Sponsors
of drug or placebo and allows for up to 2 University of Louisville Department of Results
additional consecutive daily injections for Ophthalmology and Visual Sciences Pending
patients who show signs of improvement Vitreoretinal Research Foundation
following the previous injection Status
Enrolling patients for a Phase II clinical trail.
Eligibility/Exclusion
Inclusion Criteria: Rhegmatogenous retinal Patient Accrual Date
Study
detachment (RRD) in only 1 eye; >=18 years Ongoing
Phase I Trial for Wet Age-Related Macular
of age; no more than 3 separate breaks; Study Center
Degeneration with VEGF Trap
all breaks must be clustered together and Retina Vitreous Resource Center
Sponsor
confined within an area that is no more than 3 Audubon Plaza Drive, Suite 240
Regeneron/Aventis
2 clock hours in extent on the fundus; total Louisville, KY 40217
area of all open breaks in the detached part Study Chairman Status
of the retina is no greater than 1 clock hour Norman D. Radtke, MD Currently recruiting patients
in extent; retinal detachment is large enough
Study Purpose Patient Accrual Date
that it cannot be immediately repaired with Ongoing
laser or cryo (eg, accumulated subretinal The aim of this clinical trial is to test the
safety of transplanting human fetal neural Study Center
fluid extends at least 3 disk diameters from
retinal tissue and retinal pigment epithelium Wilmer Eye Institute at Johns Hopkins
the edges of the break); macula on¬VA
into the eyes of human patients with age- Hospital (Baltimore, Maryland)
20/50 or better in both eyes, macula off¬VA
20/50 nonstudy eye, plus history prior to related macular degeneration or retinitis Study Chairman
this detachment of reading capability in the pigmentosa. Not available
study eye Study Design Study Purpose
Exclusion Criteria: Nonrhegmatogenous Ten patients with AMD, five with dry and five To determine the safety of the VEGF Trap
(tractional or exudative); atrophic RPE or with wet age-related macular degeneration, and obtain a preliminary assessment of the
choroid; choroidal detachment; demarcation and a vision of 20/400 or worse in one eye potential effect of the VEGF Trap on visual
lines; coexisting pathology; > 0.8 cup/disc will be selected for the study and will undergo acuity.
ratio; prior RD repair (surgical or nonsurgical); an operation to implant fetal neural retina
Study Design
intravitreal corticosteroid treatment within with RPE under the retina. Two complete This is a Phase I randomized, placebo-
the previous 3 months; symptoms consistent examinations will be performed at least
controlled, dose-escalating study. Based on
with RRD for >14 days prior to screening if 30 days apart to confirm the visual acuity, safety and visual outcome measurements
macula-on or h/o loss of reading vision in and only one eye will be subject to surgery.
in the initial study period, subjects may be
the study eye for more than 6 days prior to Postoperatively, the patients will be evaluated allowed to continue treatment with VEGF Trap
screening if macula-off; if macula-off and at one week, one month, three months, six in a one-year, open-label safety extension
enrolled in study subject must be able to months, nine months, twelve months, and study.
receive study drug injections (possibly up twenty-four months for follow-up(F/U).
Number of Patients
to 3) and be repaired or rescued all by the Number of Patients Enrolled
Not available
10th day of the detachment. If enrolled in the Not available
study, subject must not be macula-off for Follow Up
Follow-up 1-2 years
>10 days; ongoing treatment with Diamox 2 years
or Trusopt (dorzolamide); known sensitivity Eligibility/Exclusion
to P2Y2 Eligibility/Exclusion Subjects must be 50 years or older, currently
To participate a person must be at least 21 have wet AMD in at least one eye and be in
Number of Patients years of age, have no diabetes or glaucoma, general good health.
160 and have vision of 20/200 or worse in one
Participating Centers eye. The transplant is in that one eye only. Participating Centers
25 4
Pregnancy rules out eligibility.
Results
Results Participating Centers
Expected Mid-2005 1 Pending
Results
Pending
>> IN THE PIPELINE
Researchers Eye RNA
Interference Technologies
Editor’s Note:
The rapid expansion of technology in the field of therapeutics for Retinal diseases has been paralleled with an increase in the mainstream awareness of
these treatments through the internet, the evening news, etc. In this Editor’s opinion, there are few places to get summary discussions on new technologies
above and beyond that of abstracts printed of papers presented at major meetings. This section of the Times will be a recurring item and will highlight
emerging technologies. It is not meant to be comprehensive but more of a brief report of the potential benefits and a description of why attention is being
drawn to it. With the demonstration of the efficacy of Lucentis in treating AMD by blocking VEGF activity, other methods of reducing the effects of this
pathogenic molecule are soon to follow. Dr. Jay Stewart has reviewed the topic of siRNA and highlights some of the salient features of this new technology.
As a retina specialist, you may be fielding
questions from your patients about RNA
interference (RNAi), or small interfering RNA
(siRNA), technologies. They may have heard
some of the buzz about RNAi applications
in the treatment of age-related macular
degeneration to prevent vision loss.
One goal of research in the treatment
of neovascular AMD is to find ways to
lower vascular endothelial growth factor
(VEGF) levels. VEGF is known to be a major
culprit in the process of neovascularization.
Currently, the focus is on molecules that bind
and inactivate VEGF, such as aptamers and
antibodies, but some researchers believe that
an attractive alternate approach lies in trying
to shut down VEGF production at the source.
It is believed that RNAi technologies, with
their ability to silence the message of a gene,
could potentially shut down VEGF production
rather than block existing VEGF molecules.
Is one approach better than the other? How
effective is RNAi in treating neovascular
AMD?
Answers to these questions continue to
develop, because the technology is still in
its infancy. However, there is widespread
optimism about its efficacy, and it is being
studied for treatments in cancer, asthma,
hepatitis, diabetes, Huntington’s disease and
other afflictions. Most of the research is in
proof-of-concept or pre-clinical stages, with
RNAi research in AMD further along than for
most conditions.
Figure 1. RNA silencing depends upon double-stranded
RNA sequences (shown here interacting with a plant viral
protein). This figure reprinted with permission from Dr.
Keqiong Ye, Memorial Sloan-Kettering Cancer Center,
New York.
36 retina times
RNAi was introduced to the retina
literature by Michael Tolentino, MD, and
colleagues from Scheie Eye Institute and
Acuity Pharmaceuticals. In their study,
reported in Retina, a single intravitreal
injection of siRNA molecules directed
against VEGF production was performed in
monkeys. During 5 weeks of follow up, the
injections were found to reduce leakage in a
laser-induced CNV model. Importantly, no
inflammation or toxic effects of the treatment
were identified.
According to Dr. Tolentino and colleagues,
siRNA may be 100 to 1,000 times more potent
than protein antagonists such as aptamers
and antibodies, which could allow for lower
and less-frequent dosing. This is because it
intervenes earlier in the VEGF production
process, preventing the production of multiple
VEGF protein molecules every time it disables
a single VEGF mRNA molecule–and each
siRNA molecule can inactivate multiple
mRNA molecules, further amplifying the
effect. By contrast, protein antagonists must
bind the VEGF molecules in a one-to-one
ratio. Tolentino, who is now in private practice
with the Center for Retina and Macular
Disease in Lakeland and Winter Haven,
FL, said, “It’s like anything else–if you can
prevent something from being produced, it’s
better than dealing with it once it has been
produced.”
Safety is another positive aspect of the
technology. “They are made from RNA, which
is similar to the product that makes aptamers,
and we know from the Macugen data that
aptamers are very safe in the eyes, and RNA
is safe in the eyes,” Tolentino said. “They are
inert molecules that are well-tolerated in the
human body.”
How it Works
In order to understand how one might
“turn off ” the production of VEGF or any
other protein, it is important to recall basic
principles of molecular biology. Genes are
encoded in DNA, which resides in the cell
nucleus. The first step toward the making
of a protein is transcription of the gene into
messenger RNA (mRNA). After the mRNA
moves from the nucleus to the cytoplasm, it
Jay M. Stewart, MD
Section Editor
encounters the ribosome. The ribosome allows
the genetic message to be translated into a
chain of amino acids, which comprise the
newly formed protein, in this case VEGF.
Figure 2. After delivery into the cell, siRNA molecules
activate RISC, a protein complex that disrupts messenger
RNA and thereby prevents translation of the gene into
a protein. In this example, the targeted mRNA sequence
encodes the gene for VEGF.
It is clear from this sequence of events
that mRNA plays a key role as a “middleman”
between the gene encoded in DNA and the
final protein product. With this in mind,
researchers have been looking at ways to stop
the action of mRNA.
Recent insights from plant biology have
provided a possible answer to this challenge.
Within the past decade, researchers have come
to recognize that introduction of specific short
double-stranded RNA sequences (siRNA)
into cells can induce the degradation of the
targeted mRNA molecules. In plants, this
has evolved as a natural defense mechanism
against viruses. The strategy, also known
as “gene silencing,” inactivates (mRNA)
molecules inside cells by interacting with a
protein known as the RNA-induced silencing
complex, which cleaves mRNA molecules
that are homologous to the short (a.k.a.
small) interfering RNA (siRNA) sequence.
Investigators have shown that similar antiviral
defenses exist in Drosophila fruit flies, proving
the existence of the RNAi mechanisms in
animals. Further studies have shown that
the replication of viruses such as respiratory
syncytial virus (RSV) and HIV-1 can be
successfully inhibited in vitro using siRNA.
RNAi Strategies for Retinal Disease
It is this process that shows promise in eye
disease. Researchers believe that they can
target the mRNA that is required for VEGF
production by using siRNA sequences
that are tailored to the VEGF gene. It is
hoped that when delivered locally to the
eye, siRNA will shut down the production
of VEGF, preventing the development of
ocular neovascularization and vision loss in
neovascular AMD, diabetic retinopathy, and
other conditions.
Approaches to the use of siRNA technology
vary among those involved in its research
and development related to retinal disease.
One approach uses a synthetic polymer
(nanoparticles) to protect the RNA from
serum degradation and excretion, while
another[JS1] uses native RNA, and yet
another[JS2] uses chemically modified RNA.
The Future of RNAi in Ophthalmology
Retinal specialists can expect to hear more
about clinical trials for RNAi treatments of
eye disease in the near future. Currently a
number of companies are spearheading the
effort to get RNAi ready for the clinics. Acuity
Pharmaceuticals’ siRNA product that targets
VEGF production is in phase 1 trials for AMD
and diabetic retinopathy and is expected to
enter phase 2 by the end of this year. Acuity
also recently signed a deal giving it the rights
to the ophthalmic technologies of Intradigm
Pharmaceuticals, another company developing
siRNA products that had been working on
a treatment to block production of VEGF
and its receptors. Alnylam Pharmaceuticals,
which has partnered with Merck for
commercialization of its ophthalmic products,
uses siRNA to target VEGF production and
expects to enter phase 1 trials in the near
future. Sirna Therapeutics is in phase 1 trials
with its RNAi treatment, an siRNA therapy
blocking production of VEGF receptor-1.
According to Sirna, the rationale for targeting
VEGF receptor-1 rather than VEGF itself is
that it allows effective inhibition of pathologic
angiogenesis without affecting normal
VEGF pathways: the literature suggests that
VEGF receptor-1, which binds both VEGF
and placental growth factor, is important in
pathologic processes, whereas VEGF receptor-
2, which binds only VEGF, has more of a role
in normal pathways. Sirna is in phase 1 trials
and expects results by the end of the year,
with a phase 2 trial scheduled to begin soon
thereafter.
There is still considerable debate over
whether blocking VEGF pathways with
treatments such as RNAi can be more effective
than rendering existing VEGF ineffective with
treatments such as aptamers. As clinical trials
progress, the Retina Times will continue to
report progress on the developing technology
of RNAi and its application to treating diseases
of the back of the eye.

>> TIPS AND TECHNIQUES

Pneumatic Retinopexy
Paul E. Tornambe, M.D. Ingrid U. Scott, MD, MPH
Section Editor

Misconceptions
I advocate pneumatic retinopexy for retinal detachment repair because 2. Retrobulbar anesthesia is required if cryopexy is needed.
it results in the best and quickest visual outcome and restores the eye I never use retrobulbar anesthesia. Subconjunctival anesthesia works
to its predetachment state better than any other procedure. I have given very well. Try it–you’ll like it.
many lectures on pneumatic retinopexy and the following are the most
common misconceptions about pneumatic retinopexy voiced by the 3. Laser is preferable to cryopexy.
audience. I am frequently told by audience members that my results The pneumatic trial showed no benefit of laser over cryopexy with
following pneumatic retinopexy are better than theirs. The following regard to ERM formation, PVR, or attachment rates. I prefer focal
misconceptions may be the reasons why: cryopexy to the retinal breaks prior to gas injection if the breaks are not
highly elevated (i.e., would require heavy cryopexy) or if the pathology
1. Pneumatic retinopexy is only for young, educated people with no is not very posterior. Cryopexy is advised for breaks in the horizontal
skeletal abnormalities. meridian which may reopen when the patient ceases positioning to
In my experience, more than 90% of patients who present with a retinal come to your office the next day for laser treatment. Retinal breaks are
detachment are able to comply hard to find once the retina attaches and can be missed or inadequately
with instructions and may treated with laser once the retina is attached. Be generous with cryopexy
undergo pneumatic retinopexy. about the break(s), and extend the cryopexy to the ora, for it is the only
The secret is informing the force counteracting vitreous traction in the region of the break.
patient and the family what
is expected beforehand, and 4. Five percent povidone-iodine is used to prep the eye.
educating them regarding the There was a single infection reported in the pneumatic retinopexy
operation and why positioning clinical trial, and that case was done in an outpatient OR with a full
is so important. The Escalon prep and drape. The nurse prepped the eye with diluted povidone-
pneumo level (which costs about $ iodine. I strongly advise 10% Betadine. It is irritating to the cornea
5) attached to the eye patch makes but I have had no cases of endophthalmitis (and I perform an anterior
positioning almost fool-proof. The chamber paracentesis in every case in addition to gas injection).
patient is your co-surgeon! Antibiotic drops given just prior to the procedure makes no sense since
antibiotics take hours to days to work. I do use an antibiotic/steroid
The is the Tornambe Pneumo Level sold by Escalon (picture taken from their web site).
Unfortunately I have no financial interest in this product. The level sticks to the eye
drop for five days after surgery. I also give a subconjunctival gentamicin
patch, there is an air bubble in the level and the patient is instructed to ‘put the bubble’ on (20 mg) injection at the end of each case, but that may be more for the
a certain clock hour. This device helps greatly with positioning. surgeon’s peace of mind than the patient’s eye.

retina times 37
>> TIPS AND TECHNIQUES
5. One should perform an anterior chamber paracentesis after
injecting gas only if the central retinal artery is compromised.
Although an anterior chamber paracentesis is usually not necessary if
a small volume (0.25-0.3cc) of C3F8 gas is used, for most cases C3F8
is “overkill” and should not be used. I routinely perform a paracentesis
before gas injection because 0.5cc or more of 100% SF6 gas is usually
injected. I use a plungerless TB syringe and a #27 needle and try to
stay over iris. The needle is slowly ‘twisted’ with gentle pressure so it
enters the anterior chamber without a ‘jumping’ motion which could
strike the lens. I never use a knife. Usually 0.2-0.3mls of aqueous
can be removed passively and in some cases 0.4-0.6mls (probably
liquid vitreous exiting around the zonules) may be removed in this
manner. A small amount of vitreous in the anterior chamber is not
a contraindication to paracentesis. If the paracentesis is performed
slowly, and if the #27 or #30 needle is directed away from the vitreous,
incarceration of the vitreous can be avoided. If vitreous is incarcerated,
YAG laser lysis of the vitreous membrane a week or two later will
restore the pupil shape and relieve vitreous traction. A paracentesis
prior to gas injection avoids a temporary high spike in IOP and is very
kind to the optic nerve. The most important point to document in your
record at the end of the procedure is not the IOP, or the status of the
central retinal artery; it is light perception.
6. C3F8 gas is used so one can inject a small gas volume and not
perform a paracentesis.
Patients with ‘no life’ should have a C3F8 injection. An eight week
gas bubble drives most patients crazy and is usually unnecessary. The
gas bubble is your friend when the retina is detached and becomes
your enemy after the retina attaches. All the bubble can do after the
retina attaches is irritate the vitreous and exert traction in other areas
of the retina, especially when the patient becomes more mobile. One
should use the shortest acting gas bubble which gets the job done. I use
C3F8 in about 5% of all cases. C3F8 should be reserved for large eyes,
with large and/or posterior breaks. The purpose of the bubble is to
isolate the break from liquid vitreous long enough for a chorioretinal
adhesion to form to counteract vitreous traction. Three to five days of
tamponade is usually enough (16 hours per day). It is not necessary for
patients to position themselves during sleep although I suggest that for
the first 24 hours they position as much as tolerated. 0.5cc of 100% SF6
is usually adequate to treat the majority of retinal detachments. When
more than 0.25cc of gas is injected a paracentesis is advised. Therefore,
I always perform a paracentesis before I inject 0.5cc of SF6. I use SF6
ninety-five percent of the time.
7. How can I avoid subretinal and anterior hyaloidal gas?
Most complications of pneumatic retinopexy are avoidable. I have had
only a few complications in approximately 500 cases. If one injects
away from the break in an area where the bubble will not rise in the
direction of the tear, subretinal gas is rare. Never inject inferiorly,
which allows fish egg gas bubbles to rise into the region of the break.
Always penetrate the eye deeply to be sure the needle has penetrated the
anterior hyaloid to avoid gas in the space of Petit (sausage sign). A small
gas bubble beneath the retina absorbs more quickly than a bubble in
the vitreous cavity and, so long as the vitreous bubble is large enough
to close/isolate the edges of the break, the retina will attach. Larger
amounts of subretinal gas require vitrectomy.
8. The gas bubble must cover all breaks simultaneously.
Sequential positioning works well to close separated breaks in the
superior quadrants. Close the break which detaches the macula first. It
is not necessary to pump in a very large gas bubble to try to cover all
the breaks simultaneously. Such a large bubble may create new breaks.
9. I don’t use PR because it is associated with new breaks.
Although an open break is the primary cause for failure, I believe the
majority of breaks are missed breaks and not new breaks. The better
38 retina times
you examine the retina preoperatively, the fewer “new” breaks you will
discover postoperatively. If you cannot examine the peripheral retina
well for any reason, don’t perform pneumatic retinopexy.
10. I perform PR in phakic eyes but don’t perform it in pseudophakic
eyes because the success rate is lower, perhaps in the 70% range.
Sandy Grizzard states “the phakic status of the eye is not a
consideration when I evaluate an eye for RD repair”, and I agree with
this statement. The most important parameter is the ability to examine
the entire retina. Many papers have reported that the success rate in
pseudophakic eyes with retinal detachments is lower than in phakic
eyes across the board, regardless of the procedure used to repair the
detachment. Many papers have also shown that a failed pneumatic
does not disadvantage the eye to ultimate attachment or vision return.
For argument’s sake, let’s assume the single operation success rate
for pseudophakic detachments treated with pneumatic retinopexy
is 70%, and for scleral buckle is 90%. If there are ten patients with a
pseudophakic retinal detachment, seven of the ten will be cured with a
single pneumatic and nine will be cured with a single buckle. Therefore
a surgeon selecting scleral buckling exclusively is willing to expose nine
patients to an OR procedure so that perhaps two will be saved a second
operation. If a failed pneumatic doesn’t disadvantage the eye, why not
try pneumatic retinopexy first?
11. How can I increase the overall success rate?
The best way to improve your batting average is to select the correct
patient and identify all pathology. Once pneumatic retinopexy is
selected, and especially for pseudophakic eyes, 360 retinopexy between
the insertion of the vitreous base and ora will improve the success
rate by 5-10%. Data from the pneumatic retinopexy trial revealed that
most new/missed breaks were noted within three clock hours of the
initial break. Therefore, treating these areas prophylactically should
prevent redetachment if a break develops within the treated area. If
360 retinopexy is considered, it should be staged. Treat the recognized
elevated break(s) with focal cryopexy, and treat attached retina with
light laser, avoiding the edge of the detachment by one clock hour so
that if fluid is displaced by the bubble, it will not detach freshly treated
areas of laser burns and possibly result in new break formation. The
steamroller technique can be used in such instances to “debulk” the
subretinal fluid load. Once the retina attaches, complete the laser
treatment. Never laser elevated retina.
12. For a particular patient, is there a way to “guesstimate” success?
We all like to give our patients “odds” for success before surgery so they
have realistic expectations. I reviewed over 300 of my cases and came up
with the following formula: a phakic one quadrant retinal detachment
with one superior break (3 to 9) carries a 97% success rate. If the eye
is pseudophakic subtract 10%; if there are multiple breaks (broader
vitreous traction) subtract 10%; if there is more than a quadrant
detached (more likely you’ll miss a small break) subtract 10%; if you
perform 360 retinopexy add 5-10%. Thus, a pseudophakic patient with
a total retinal detachment and several retinal breaks has a 67% chance
of attachment with one pneumatic procedure if 360 retinopexy is not
performed; with 360 retinopexy it increases to about 75%.
No matter how ‘simple’ the procedure, one cannot separate the
surgeon from the surgery. The secret of pneumatic retinopexy is case
selection, which means identifying all pathology before the gas bubble
is injected. I believe most failed cases are due to missed breaks. Some
breaks are very difficult or impossible to see. Don’t beat yourself up
over a failed pneumatic, no harm is done and if it works, the patient
has dodged a big bullet! Check out the ASRS online journal for my AOS
thesis which goes into the subject in much greater detail.
>> PRACTICE MANAGEMENT

Ron Rosenberg, PA.-C, MPH Scott G. Foxman, MD

Section Editor

The Retina Practice Business Process

About the Author

Ron Rosenberg, PA-C, MPH, began his healthcare career as a U.S. Navy Hospital Corpsman in 1965. After discharge from the Navy he
entered the Physician Assistant training program at the Dartmouth College Medical School, and graduated as one of the first Physician
Assistants in the United States in 1972. Over the next ten years he practiced in a variety of clinical settings, including rural primary care,
academic cardiology and family practice, and urban urgent care.
While on the clinical staff of the University of Utah College of Medicine, Ron completed his Masters in Public Health degree, with a
concentration in Health Services Research. In 1982 Ron left clinical practice and moved to the business side of medicine, first in developing
and delivering health risk-appraisals and health promotion programs, and then in developing and marketing market analysis reports
using data files from the Healthcare Finance Administration (HCFA). In 1986, Ron began consulting in the management of medical
practices, and was a partner in Consulting Concepts, Inc. (CCI), a practice management consulting firm. CCI evolved into a specialty firm,
concentrating in advising medical school faculty practices on reimbursement, compliance with HCFA’s teaching physician guidelines,
business office operations, and managed care. In 1992, Ron left CCI and founded the Practice Management Resource Group (PMRG), a
consulting firm providing practice management services to physicians’ practices of all specialties and organizational structure (i.e., private,
academic, and institutional practices). PMRG has successfully completed various engagements, including reimbursement enhancement,
practice financial performance assessments, practice valuations, managed care strategic planning and marketing, alliance formation,
practice mergers, and managed care (capitation) contracting.
Ron has written book chapters on “practice financial policies and fee schedules” and “physician compensation in managed care”, and
articles on physician alliance development. He also co-authored a book for the American Academy of Ophthalmology on capitation for
medical-surgical eyecare. Ron Rosenberg brings his blend of clinical background and practice management experience to all of PMRG’s
engagements. PMRG’s success is based on the premise that in the currently evolving managed care environment, that blend of clinical and
business skill is required for the success of any practice.

Any practice has a “business process”, the purpose of which is to transform clinical activity into
CLINICAL SERVICE
practice income.
There are two aspects of the process of transforming clinical activity into practice
income. The first is the content of the business process itself–the steps taken to have that
CHARGE CAPTURE
transformation (clinical service into income) occur. The second aspect is the monitoring of the
business process–the key “registers” (measurements) that a practice can use to determine the
effectiveness of that business process.
CODING
Are there differences in the business process of a Retina practice from that of General
Ophthalmology or other specialties? Yes, by virtue of the number of diagnostic and therapeutic
services done in a typical Retina office, and by the multiple components of some Retina
surgical cases. While these differences must be accommodated, the basic structure of the Retina FEES

Practice’s business process is substantially the same as for other specialties.

The following is a very brief overview of each of the steps listed in the figure shown to the
right. This overview is not meant to provide a detailed, step-by-step guide in implementing CLAIMS SUBMISSION
the process. Rather, it is simply a guide for each physician to compare to their own business
process, and to allow you to assess whether you have an understanding of how your practice
accomplishes each of these steps. RECEIVABLES MANAGEMENT

CHARGE-CAPTURE
The Step – Charge-capture is the identification of each billable clinical service and “capturing” MANAGEMENT REPORTING
it as a charge in the billing computer system.

The Register – First, charge volumes can be compared to independent sources of data, such as PRACTICE OVERHEAD
operating/procedure room logs, appointment schedules, and supply volumes. Second, regular
These are the steps included in the
(weekly) physician review of charge-volumes for low-volume services (specialty procedures) business process after the provision of the
can be compared to the physician’s anecdotal recollection of services he or she provided. clinical services.

retina times 39
 This is a component of the business process that, along with
CPT coding, is somewhat more complex for Retina than for General
Ophthalmology. There is more office “testing” (e.g., FAs, Photos,
OCT/HRT, etc.), office procedures, and surgeries with multiple
components. These require vigilance in capturing all services as
they are provided, as well as processes to allow retrospective audits
to measure charge-capture effectiveness.
CODING
The Step – Each service is described by a procedure code (CPT),
and the justification for providing the service is made with a
diagnosis code (ICD-9).
The Register – Coding “patterns” should be regularly reviewed to
assess accuracy and to identify “over-coding” and “under-coding.”
This includes CPT codes for both Evaluation and Management
(E&M) and procedural services.
There is often a blurred boundary between charge-capture and
coding. For example, is the inclusion of all component procedures
in a multi-part surgery a function of coding or of charge-capture? It
may well be that the answer is immaterial. What is important is that
all of the components are accurately and appropriately captured
and described. Another coding pattern to be closely monitored is
the distribution of the “Levels of Service” for the Evaluation and
Management services.
FEES
The Step – The practice should have a fee schedule that is rational–
that is, there is a relationship between the fees for various services
that follows the relationship between the allowable payments
for those same services from the major insurers. This prevents
overpriced and underpriced services, and allows for the calculation
and monitoring of the practice’s collection target.
An example would be a fee schedule calculated as a multiple
of the local Medicare Fee Schedule. Since many of the insurance
carriers base their allowable payments on that same Medicare
Fee Schedule, a fairly constant relationship is created between the
practice’s fees and the allowable payments. If the practice set its fees
at two times the Medicare Fee Schedule, the maximum collection
ratio for Medicare services would be 50% (100% ÷ 200% = 50%). If
a local insurance plan paid at 150% of the Medicare Fee Schedule,
the maximum collection for those services would be 75% (150% ÷
200% = 75%).
The Register – A fee schedule evaluation and re-calculation should
be done at least annually.
CLAIMS SUBMISSION
The Step – Claims for services should be entered into the billing
computer system and transmitted to the insurers accurately and in a
timely manner.
The Register – A “lag” report can be developed showing the average
time between date-of-service, date of charge-entry, and date of
claim submission. Additionally, a “Denials Log” can be kept to
identify patterns of rejected claims so errors can be corrected (and
prevented).
40 retina times
RECEIVABLES MANAGEMENT
The Step – This is the most crucial part of the process because it
is the source of more lost practice income than any other part of
the business process. Receivables management is the process of
receiving payments and posting those payments into the computer
system. It is a system for knowing the level of payment expected
for each charge, the time frame in which the payment should be
received, and actions needing to be taken when the payment is not
the expected amount and/or not received within the expected
time frame.
The Registers – There are several important registers to monitor
receivables management (and by extension, financial performance
of the practice). In order to accurately monitor receivables
management, a competent, properly set-up practice management
computer system is required. The key registers it should include are:
• Collection target calculation – Given the practice’s fees, payor
allowable payment levels, and payor-mix, what are the expected
collections for a set of charges?
• Collection performance – What are the totals received and how do
those totals compare to the target?
• Revenue flow – How quickly are payments received?
• Accounts Receivable (AR) – This is an analysis of outstanding
claims. While the collection performance report shows what
HAS happened, the AR analysis is a report of what HAS NOT yet
happened. It is a valuable report for following up on individual
unpaid claims as well as patterns of late or missing payments from
insurance plans.
MANAGEMENT REPORTING
The Step – The reports required to measure the registers described
in each piece of the business process.
The reports most valuable to monitor can be broken down into
two categories. These are Operational Reports (e.g., charge-capture,
collection performance, etc.) and Productivity Reports.
The operational reports measure the effectiveness of the business
process, while the productivity reports are used to measure the
practice’s service volumes, and source of patients. This productivity
information is used for charting the practice’s strategic direction.
PRACTICE OVERHEAD
The Step – A measure of the non-physician practice expenses, by
category.
The Register – The practice’s Income Statement, showing cost
by category, and displayed as monthly and year-to-date totals,
comparison to year-to-date totals for the same periods in previous
years, and the year-to-date totals expressed as a percentage of
practice income. That percentage of income represented by non-
physician cost is the practice’s “overhead rate”.
SUMMARY
This set of steps will provide the practice’s owners and managers
with an accurate picture of their business process, and expected
financial performance. If that performance is below the calculated
target level, this monitoring system will show the areas where
improvement is needed, and the steps required to bring the
performance back into the expected range. At the same time, data
will be generated to show the growth and direction of the practice,
allowing for effective strategic management.
>> RETINAL RISK MANAGEMENT
Retinopathy of Prematurity:
Creating a Safety Net
Due to space restrictions, the tables and letters referred to in the
article are not included here. You can access the complete text of
“Retinopathy of Prematurity: Creating A Safety Net” in the “Risk
Management Recommendations” section of the OMIC website
(www.omic.com); articles are in alphabetical order.
DISCLAIMER: Recommendations presented here should not be
considered inclusive of all proper methods of care or exclusive of
other methods of care reasonably directed to obtain the same results.
The ultimate judgment regarding the propriety of any specific
procedure or treatment must be made by the ophthalmologist in light
of the individual circumstances presented by the patient.
This information is intended solely to provide risk management
recommendations. It is not intended to constitute legal advice and
should not be relied upon as a source for legal advice. If legal advice is
desired or needed, an attorney should be consulted.
Screening and treating premature infants for retinopathy of
prematurity (ROP) is an important aspect of pediatric ophthalmic
care that provides a valuable service to not only the individual
patient but also to society as a whole. Although claims against
ophthalmologists for mismanagement of ROP are relatively
infrequent, indemnity payments for these claims can be high due
to the young age of the plaintiffs and the significant loss of vision
that can result even with treatment. Concerned about their liability
exposure, numerous screening and treating ophthalmologists called
OMIC to request sample protocols to help standardize care at the
hospitals where they care for ROP patients.
The goal of the risk management recommendations offered here is
to promote patient safety and minimize the liability exposures related
to ROP care. They were developed after a detailed analysis of OMIC
ROP cases and of data from the Physician Insurer’s Association of
America (PIAA), Jury Verdict Reports, and IDEX (an expert witness
database), as well as a Failure Mode and Effects Analysis (FMEA),
designed to identify vulnerable points in the care process. They have
been reviewed by a number of pediatric ophthalmologists and retina
specialists, risk managers, and attorneys.
These suggested practices are designed to complement the clinical
recommendations found in published studies and summarized in
“Screening Examination of Premature Infants for Retinopathy of
Prematurity,” the Joint Statement issued by the Ophthalmology
Division of the American Academy of Pediatrics (AAP), the American
Academy of Pediatric Ophthalmology and Strabismus (AAPOS), and
the American Academy of Ophthalmology (AAO), and published in
Pediatrics 2001; 108:809-811. The Joint Statement has recently been
revised, and approved by the Boards of AAO and AAPOS. As soon
as it is approved by the AAP Board, it will be published in Pediatrics.
Information given here is from the 2001 version (referred to as “Joint
Statement”) or other articles.
Risk management recommendations do not establish a standard
of care, but rather, serve as suggestions on how the healthcare team–
the ophthalmologist, neonatologist/pediatrician, NICU (Neonatal
Intensive Care Unit) nurses, hospital, and parents–can create a
safety net for these at-risk infants. They also serve to both reduce
the likelihood of a professional liability lawsuit and improve the
defensibility of care if it is ever questioned.
Anne M. Menke, RN, PhD Arthur W. Allen, MD
OMIC Risk Manager Section Editor
This document assigns responsibility for each task in the ROP
care process (see Table 1), based upon the fact that the neonatologist
is the primary care physician, whereas the screening and treating
ophthalmologist serve as consultants, while the baby is in the
hospital. Accordingly, while the baby remains in the hospital, we
have assigned the neonatologist and NICU nurses the principle role
for coordinating and tracking appointments with consultants and
for communicating with the baby’s parents. At critical junctures
in the ROP care process, however, the entire team needs to be
involved. These points are the ongoing education of the parents and
coordinating transfer of care to ophthalmologists at another hospital
or in an outpatient practice. Once the baby has been discharged, the
ophthalmologist is responsible for tracking outpatient ophthalmic
care (this assumes that the ophthalmologist has been notified of the
discharge/transfer, and has agreed to treat the baby).
We want to acknowledge that during the hospital-care phase,
you as the ophthalmologist will not be able to implement all of
these recommendations without the cooperation of the hospital,
neonatologist/pediatrician, NICU nurses, and parents (by “parents,”
we mean whoever has current custody of the baby and is responsible
for making medical decisions on the baby’s behalf).
You can, however, act as a patient advocate, and use these
recommendations as the starting point for constructive dialogue.
OMIC’s Risk Manager can be an important source of information
and support for policyholders engaged in these discussions.
Conduct a risk analysis of your current process of care
by identifying any steps in the following sequence for which
responsibility has not been assigned, or when care is not being
provided according to current clinical guidelines (e.g., the “Joint
Statement”).
RISK MANAGEMENT RECOMMENDATIONS FOR HOSPITAL-BASED
ROP CARE
1. The neonatologist can use Table 3 to determine which babies
need screening, and Table 4 to determine the timing of the first eye
examination.
2. SAFETY NET: Hospital ROP Tracking System. Most medical
malpractice lawsuits related to ROP occur when the baby is “lost to
follow up,” either in the hospital or after discharge or transfer. To
prevent this, the hospital needs to develop and maintain a hospital
ROP tracking system. Ideally, one highly-educated and trained
person is designated as the ROP coordinator, and back-up is available
when this person is on vacation. (For simplicity’s sake, we have
assigned this function to the NICU. Some hospitals appoint the NICU
nurse responsible for discharge planning). Information to be tracked
includes: name, date of birth, weight, gestational age, parent’s name
and phone number, hospital account number, date of visit, findings,
and date of next follow-up visit. When the neonatologist identifies a
baby for screening, the NICU enters the baby into the system. After
the ophthalmologist hasconducted the initial examination, he or
she determines when the baby should be seen again, and documents
the follow-up interval. The screening or treating ophthalmologist
writes an order indicating the follow up interval. The NICU updates
the tracking system each time the baby is evaluated or treated,
noting the current condition and follow up interval, and evaluates
retina times 43
>> RETINAL RISK MANAGEMENT
the tracking system at least once a week to ensure that all follow-
up appointments are scheduled and kept. The NICU immediately
notifies the neonatologist of any missed, cancelled, or rescheduled
ROP appointments while the baby is in the hospital.
The NICU tracks the baby until one of these conditions is met:
1) the screening ophthalmologist verifies that both eyes have met
the conclusion-of-acute-phase-ROP-screening criteria, 2) the
treating ophthalmologist verifies that treatment and necessary
follow-up examinations are completed, 3) an ophthalmologist at the
hospital to which the baby is transferred accepts responsibility for
further ophthalmic care and an initial appointment is scheduled,
or 4) an outpatient ophthalmologist accepts responsibility and an
initial outpatient appointment is scheduled. The hospital’s role
in tracking is complete when all of these conditions have been
met: 1) the ophthalmologist who will be providing care has been
notified of the discharge/transfer and has agreed to treat the baby, 2)
a ROP appointment is scheduled at the second hospital or with an
outpatient ophthalmologist, 3) the baby’s pertinent medical records
have been sent, and 4) the parents/guardian’s contact information has
been sent.
3. The ophthalmologist should have sufficient knowledge and
expertise to enable accurate identification of the location and
sequential retinal changes of ROP after pupillary dilation using
binocular indirect ophthalmoscopy (Joint Statement).
4. The ophthalmologist should include an ROP consult note in the
infant’s hospital chart, and use the International Classification of
Retinopathy of Prematurity (ICROP) to classify, diagram, and record
the retinal findings at the time of the examination or treatment
(Table 2). Some ophthalmologists now also categorize pre-threshold
ROP as Type 1 and Type 2. See Table 7.
5. Table 5 is helpful in determining the follow up interval during the
screening phase. The screening ophthalmologist should write follow-
up orders in the hospital chart, and the NICU should update the
tracking system and schedule the follow-up appointment.
6. The screening ophthalmologist should screen until both eyes have
met the conclusion-of-acute-phase-ROP screening criteria
(Table 6) or until the treating ophthalmologist has verified that
treatment and all follow-up examinations are completed. One
examination is sufficient only if it unequivocally shows the retina to
be fully vascularized in each eye.
7. Table 7 provides guidance on when to initiate treatment and
explains how to further categorize pre-threshold ROP as Type 1
and Type 2 ROP. The screening ophthalmologist should notify the
neonatologist and document the recommendation to begin treatment
in the hospital record. Depending upon the protocol at the hospital,
either the screening ophthalmologist or the neonatologist should
write an order for the NICU to both update the tracking system
and schedule an appointment with a treating ophthalmologist. The
screening ophthalmologist conducts and documents a transfer-of-
care discussion with the treating ophthalmologist, conveying the
urgency of the referral, and ensures that the second doctor has access
to, or copies of, the patient’s previous history and eye examinations.
8. SAFETY NET: Parent Education. All members of the team need
to help educate the parents about ROP, the need for careful follow
up until both of the baby’s eyes have either met the conclusion-of-
acute-screening criteria or treatment and follow-up examinations
are completed during the acute phase, the consequences of
missing screening or treatment appointments, and the need for
long-term ophthalmic care. Verify the parents’ understanding of
the information, and carefully document all educational efforts.
The neonatologist should inform the parents when the baby needs
screening evaluations, and when treatment is recommended. The
neonatal nurse should educate the parents before and after screening
44 retina times
and treatment, and prior to transfer or discharge. The screening and
treating ophthalmologists should complete the attached document,
“Parents: Read This About Your Premature Baby’s Eyes,” each time
an infant is first screened/treated for ROP, and whenever the infant’s
ROP status changes. The NICU should ask the parents to sign this
document and place it in the hospital record, as well as give the
parents a copy to take home. If the hospital is unwilling to give the
parents the document and/or ask them to sign it, the ophthalmologist
can mail it to the parents.
9. SAFETY NET: Transfer/Discharge. This is the most vulnerable
point in the ROP care process, so all members of the team need
to be involved in discharge/transfer planning to ensure proper
ophthalmic follow up. No baby should be transferred/discharged
until an initial appointment has been made with the new screening
or treating ophthalmologist and all pertinent records and current
contact information for the baby’s parents/guardian are sent.
The neonatologist informs the neonatal nurse and the screening
or treating ophthalmologist of a planned discharge or transfer,
in order to allow the ophthalmologist to assess the baby from an
ophthalmic perspective, and determine current follow-up needs.
The ophthalmologist conveys the recommendations orally to the
neonatologist, and writes a final ophthalmic consult note, unless a
screening examination or treatment took place and was documented
very recently. The neonatologist speaks with the pediatrician at the
other hospital, or the baby’s outpatient pediatrician, and includes
the ophthalmic care needs in the discharge/transfer orders. The
neonatologist and pediatrician together ensure that a new screening
or treating ophthalmologist has been found to assume the ophthalmic
care (with recommendations, if possible, from the screening or
treating ophthalmologist). Experience shows that parents cannot
be relied upon to schedule this care. Cultural, language, and health
literacy issues, as well as difficulties inherent in assuming the care
of premature infants, often interfere with the accurate transmission
of key information, and place these babies at great risk. To protect
the infant, the NICU nurse talks with a nurse at the nursery at the
new hospital, or with the ophthalmologist’s office staff, to schedule
the initial ophthalmic appointment and provide all necessary
information. If the current ophthalmologist will continue to see the
baby after transfer or discharge, he or she also notifies office staff
to expect a call from the NICU, and instructs staff to enter the baby
in the office ROP tracking system. If the NICU is unwilling to help
coordinate the initial 2nd hospital or outpatient visit, and you as the
ophthalmologist are asked to see the baby, ensure that the appropriate
records, including recent contact information for the parents, are sent
to you.
10. To ensure the standardization, reliability, and effectiveness of ROP
care, the ophthalmologist, neonatologist, and hospital need to have a
written agreement or protocol (see sample protocol).
RISK MANAGEMENT RECOMMENDATIONS FOR OUTPATIENT ROP
CARE
1. The ophthalmologist should have sufficient knowledge and
expertise to enable accurate identification of the location and
sequential retinal changes of ROP after pupillary dilation using
binocular indirect ophthalmoscopy (Joint Statement).
2. SAFETY NET: Coordinate transfer of care to the outpatient setting.
This is the most vulnerable point in the ROP care process, so all
members of the team need to be involved in discharge planning
to ensure proper ophthalmic follow up. Conduct and document
a transfer-of-care discussion with the current screening or treating
ophthalmologist. Instruct your staff to speak to the NICU nurse
to determine the discharge date, schedule the initial outpatient
appointment, and obtain all relevant medical records and current
contact information for the parents. Instruct staff to enter the baby
into the ROP tracking system.
3. SAFETY NET: Telephone Screening of Ophthalmic Problems. If
the NICU in your hospital is unwilling to speak with your office to
coordinate the transfer of care, ensure that staff members who answer
phones are trained in telephone screening and know how to identify
babies who need ROP care. Some babies have been lost to follow up
because the parents did not identify the need for ROP care, and the
staff member who scheduled the appointment did not ask if the baby
was premature or had been seen in the hospital. Other parents have
changed the name of the baby since the baby was seen in the hospital,
so the practice did not recognize the infant as one who had already
been seen when the parents scheduled the appointment. If the baby is
identified as premature, staff should be directed to ask the gestational
age in weeks, and the date of birth, so postmenstrual age can be
calculated (see Table 4). Also see OMIC’s “Telephone Screening of
Ophthalmic Problems” guidelines for forms and general telephone
screening recommendations (available in the Risk Management
Recommendations section at www.omic.com).
4. SAFETY NET: Office ROP Tracking System. Most medical
malpractice lawsuits related to ROP occur when the baby is “lost to
follow up.” To prevent this, the practice must create and maintain
a ROP tracking system. When the initial outpatient appointment is
scheduled, the baby is entered into the system. Each time the baby
is evaluated or treated, the ophthalmologist indicates the follow up
interval, and the office schedules the follow-up appointment before
the parents leave the office. The tracking system is then updated
to note the current condition and follow up interval. The tracking
system is evaluated at least once a week to ensure that all follow-
up appointments are scheduled and kept. The ophthalmologist is
notified immediately of any missed, cancelled, or rescheduled ROP
appointments (see Follow Up, below). The baby is tracked until
one of these conditions is met: 1) the screening ophthalmologist
verifies that both eyes have met the conclusion-of-acute-phase-ROP-
screening criteria (Table 6), 2) the treating ophthalmologist has
verified that treatment and follow-up examinations are completed,
or 3) care is transferred to another ophthalmologist. If care is
transferred to another ophthalmologist, the office’s role in tracking
is complete when all of these tasks have been accomplished: 1) a
ROP appointment is scheduled at the other ophthalmologist’s office,
2) the baby’s medical records have been sent, and 3) the parents’
contact information has been sent.
5. Use the International Classification of Retinopathy of Prematurity
(ICROP) to classify, diagram, and record the retinal findings at the
time of the examination or treatment (Table 2). Table 7 explains how
to differentiate between Type 1 and Type 2 ROP.
6. Use Table 5 to determine and note the follow up interval. Instruct
your staff to schedule the next appointment before the parents leave
the office, and to update the tracking system. Do not rely upon the
parents to schedule the follow-up appointments. Cultural, language,
and health literacy issues, as well as difficulties inherent in assuming
care of premature infants, often interfere with the parents’ ability to
understand ROP and can place the infant at great risk.
7. SAFETY NET: Parent Education. Enlist appropriate members
of your staff to help educate the parents about ROP, the need
for careful follow up until both of the baby’s eyes have met the
conclusion-of-acute-ROP-screening criteria or treatment and
follow-up examinations are completed, the consequences of
missing screening or treatment appointments, and the need for
long-term ophthalmic care. Verify the parents’ understanding of the
information, and carefully document all educational efforts. Fill out
the attached document, “Parents: Read This About Your Premature
Baby’s Eyes,” each time an infant is first screened or treated for ROP,
and whenever the infant’s ROP status changes. Ask parents to read
and sign the form, put the form in the chart, and give them a copy to
take home (see sample letter).
8. Screen until both eyes have met the conclusion-of-acute-phase-
ROP-screening criteria (Table 6). One examination is sufficient only
if it unequivocally shows the retina to be fully vascularized in each
eye.
9. See Table 7 for when to initiate treatment.
10. Carefully document in the infant’s medical record your referral
of any ROP patient to another physician (e.g., for treatment), and
include the physician’s contact information. In addition, conduct and
document all transfer of care discussions and forward to the second
doctor documentation noting the indication and urgency of the
referral, along with a copy of a record of the patient’s previous history
and eye exams.
11. SAFETY NET: Follow up on all changes in appointments. To
ensure that missed appointments are noticed, instruct your staff to
schedule the next appointment before the parents leave the office,
and to update the tracking system. Do not rely upon the parents to
schedule the follow-up appointments. Instruct your staff to review
appointments on a daily basis, and to notify you immediately of any
change in ROP appointments, including no-shows and cancelled or
rescheduled appointments. Instruct staff on the type and urgency of
follow-up needed (e.g., “Need to see baby tomorrow at the latest, call
parents immediately”). The follow up should be tailored to the level
of risk to the infant’s vision. Implement your ROP follow-up protocol
for all of these schedule changes and document all follow-up efforts.
Recommended follow-up efforts: 1) Instruct staff member to call
same day of changed appointment. 2) Send “missed appointment”
letter, with a copy to the baby’s pediatrician, if staff member doesn’t
speak to parent, or parent is unwilling/unable to bring infant at
designated interval. Letter should explain the urgency of the needed
care and consequences of noncompliance (see sample “Missed
ROP Appointment” letter). For further instructions, see OMIC
“Noncompliance” guidelines (available in the Risk Management
Recommendations section at www.omic.com). If the infant is at high
risk for vision loss, send by regular and certified mail. 3) Notify the
baby’s pediatrician of noncompliance by phone, and by faxing a copy
of the letter to the parents, and document the discussion. 4) Consider
contacting your state’s Child Protective Services office for extremely
high risk infants who may meet treatment criteria at the time of
the missed examination, or for treated infants with a suboptimal
treatment response.
OMIC policyholders who have additional questions or concerns
about ROP are invited to call Anne M. Menke, R.N., Ph.D., OMIC
Risk Manager, at (800) 562-6642, extension 651.
ELEMENTS OF A SAMPLE PROTOCOL/AGREEMENT
FOR HANDLING ROP CARE IN THE HOSPITAL
To ensure the standardization, reliability, and effectiveness of ROP
care, the ophthalmologist, neonatologist, and hospital need to have a
written agreement or protocol that addresses:
• Task assignments (see Table 1 for a summary)
• The guidelines used to identify at-risk infants
º The recently revised AAP/AAO/AAPOS Joint Statement, when
available, provides an excellent summary of current research and
recommendations
• Identifying infants to be screened
º Responsibility: neonatologist
º See Table 3 for infants needing ROP screening examination
• Dilating protocol: that clarifies drugs, dosages, RN administration
retina times 45
>> RETINAL RISK MANAGEMENT
• Talking to the parents about screening the baby for ROP
º Responsibility:
• Neonatologist
• NICU nurse
• Scheduling the initial eye examination with the screening
ophthalmologist
º Responsibility:
• Neonatologist to order initial examination
• NICU to schedule and administer drops per dilating protocol
º Based upon the infant’s postmenstrual age (gestational age plus
chronologic age)
º See Table 4 for timing of initial examination
• Entering the baby into the ROP tracking system. Track infant
until 1) screening ophthalmologist verifies that both eyes have
met conclusion-of-acute-ROP-screening criteria, 2) the treating
ophthalmologist verifies that treatment and follow-up examinations
are completed, or 3) NICU has scheduled initial appointment with
screening or treating ophthalmologist at other hospital or in office
º Responsibility: NICU
º The tracking system must be updated for each new baby, and
after each screening or treating appointment
• How the ROP examinations and treatments will be documented
º Responsibility: screening and treating ophthalmologists
º Use ICROP
º See Table 2 for ICROP system. See Table 7 for how to
classify pre-threshold ROP as Type 1 or Type 2 ROP.
• Determining follow up interval after screening
º Responsibility: Screening ophthalmologist by writing order in
chart
º See Table 5 for timing of follow-up examinations
• Informing the parents of the results of the screening evaluation,
follow up interval, consequences of no follow up
º Responsibility:
• Neonatologist and NICU nurse talk to parents
• Screening ophthalmologist completes letter for NICU to give
to parent
• See sample letter
• The need to screen after pupillary dilation using binocular indirect
ophthalmoscopy until both eyes have met the conclusion-of-acute-
screening criteria
º One examination is sufficient only if it unequivocally shows the
retina to be fully vascularized in each eye
º See Table 6 for conclusion-of-acute-phase-ROP screening
criteria
• Scheduling follow-up screening appointments in the hospital
º Responsibility: NICU based upon order of screening
ophthalmologist
• Deciding when treatment for ROP is needed
º Responsibility: Screening ophthalmologist
º See Table 7 for when to initiate treatment
• Informing the neonatologist about need for ROP treatment
º Responsibility: Screening ophthalmologist (talk and progress
note)
• Informing the parents about the proposed ROP treatment
º Responsibility:
• Neonatologist (talk to parents)
• NICU nurse (talk to parents)
• Screening ophthalmologist (by phone and by completing
letter that NICU gives to parents)
• Finding an ophthalmologist to treat the ROP
º Responsibility: Neonatologist or screening ophthalmologist by
written order, depending upon protocol
• Conducting and documenting a transfer-of-care discussion with the
treating ophthalmologist
46 retina times
r
º Responsibility: Screening ophthalmologist
• Scheduling the treatment appointment with the treating
ophthalmologist
º Responsibility: NICU based upon written order from
neonatologist or screening ophthalmologist
• Obtaining informed consent for the ROP treatment
º Responsibility: Treating ophthalmologist
• Use procedure-specific consent form that clarifies that even
with treatment, some babies still develop retinal detachments
and blindness, and that long-term follow up is required
• Informing parents of results of treatment, need for follow up, and
consequences of no follow up
º Responsibility:
• Treating ophthalmologist (by letter given to parents by
NICU)
• Neonatologist (talk to parents)
• NICU nurse (talk to parents)
• Following the infant after treatment
º Responsibility: Treating ophthalmologist by written order
• Scheduling follow-up treatment appointments in the hospital
º Responsibility: NICU based upon written order from treating
ophthalmologist
• Determining that the baby is ready for transfer/discharge
º Responsibility: Neonatologist
• Notifying the screening or treatment ophthalmologist that the infant
is ready for transfer/discharge
º Responsibility: Neonatologist
• Writing an ophthalmic consultant note prior to discharge/
transfer that summarizes ROP status and screening/treatment
recommendations
º Responsibility: Screening or treating ophthalmologist, depending
upon who is currently providing ROP care
• If the ophthalmologist has evaluated or treated the baby very
recently, no further note may be needed
• Writing discharge/transfer orders that address ROP if the infant is
transferred/discharged before the screening ophthalmologist verifies
that the retina has met conclusion-of-acute-phase-ROP-screening
criteria or the treating ophthalmologist verifies that treatment and
follow-up examinations are completed
º Responsibility: Neonatologist
• Conducting and documenting a pre-transfer discussion with the
pediatrician who will be assuming role of primary care provider
after transfer/discharge
º Responsibility: Neonatologist
• Finding a screening or treating ophthalmologist at the other hospital
or in an office prior to transfer/discharge
º Responsibility: Neonatologist and pediatrician, with
recommendations when possible from the screening or treating
ophthalmologist
• Conducting and documenting a pre-transfer/discharge discussion
with the parents regarding the infant’s ROP status, follow up
interval, and consequences of no follow up
º Responsibility:
• Neonatologist (talk to parents)
• NICU nurse (talk to parents)
• Current screening or treating ophthalmologist (phone and
letter, which the NICU gives to parents)
• Scheduling the initial follow-up appointment after transfer/
discharge with the screening or treating ophthalmologist
º Responsibility: NICU
• Conducting and documenting a transfer-of-care discussion with the
new ophthalmologist
º Responsibility: Current ophthalmologist
 c
>> UNCLE RICH
r
Competitive Acquisition Program
h
Dear Uncle Rich:
What is the story on our ability to buy retinal
drugs in 2006? There have been so many
changes in the past couple years in Medicare
payment for drugs given in the office for
ARMD: 95% of AWP (Average Wholesale
Price), 85% of AWP, ASP (Average Sales
Price) + 6%, etc., etc. This has been very
disruptive to my practice and has resulted in
large monetary losses because of our inability
to collect co-payments for these expensive
drugs! I am tired of acting as a billing agent
for the pharmaceutical industry!! Is there any
relief in sight?
Overwhelmed in Oneida
Dear Overwhelmed:
Relief is in sight. As part of the Medicare
Prescription Drug, Improvement and
Modernization Act of 2003 (a.k.a. MMA),
Congress mandated that CMS establish a
competitive acquisition program (CAP) for
Part B drugs and biologicals administered in
physicians’ offices. An initial proposal from
i
CMS was going to limit the CAP program to
2-3 regions in the country and only deal with
oncology. With ASP+6% payment, there was
huge frustration in the retinal community
with billing complexity and the financial
risks being borne by retinologists. The AAO,
working with George Williams and Reggie
Sanders of the ASRS, strongly advised CMS
to make the initial program national in
scope and to include retinal drugs. In a final
rule published this summer in the Federal
Register, CMS agreed with our comments. As
a result, in 2006 retinal docs may participate
in CAP to obtain drugs like Visudyne from
national vendors or continue to buy drugs
directly from the manufacturer at ASP+6.
How is CAP going to operate?
When a patient comes in and is determined
to need the use of a retinal drug, the doctor
will fax an order to the vendor. The vendor
must supply the drug to the physician’s
office within two business days for a routine
service and one day for an emergency. The
physician’s office must store the drug until
it is administered but it does not have to
have separate physical storage from other
pharmaceuticals. If state law permits and the
drug is unused and unopened, the doctor
may retain the drug and administer it to
another patient after a new order is sent to
the vendor. The retina doc must submit a
claim to CMS for the drug administration
service (67028 for intravitreal injections or
67221 for PDT) within 14 days of treatment.
CMS will not pay the vendor for the drug
unless they have received documentation
from the doctor that the service was provided
in the office.
When a patient is seen in consultation in
the office and it is deemed necessary to treat
that same day, the retina doc may dispense
the drug from inventory if:
1) the drugs are required immediately,
2) the doc could not have known the drugs
were needed prior to the visit,
3) the vendor could not have delivered the
drugs in a timely manner, and
4) the drugs were administered on the same
day as the consultation.
The office must add a new modifier to the
administration code if the drug is delivered
as an emergency. If the doc has signed a CAP
agreement and the emergency falls within
these guidelines, a drug may not be delivered
under direct purchase from the manufacturer
under ASP.
Once the vendor receives verification
from CMS that you have administered the
drug, they will proceed to bill Medicare and
the patient/Medigap plan for the 20% co-pay.
The vendor takes on all the financial liability
of billing and collections.
Advantages:
The physician is out of the drug business!
You are no longer the middleman and
have no more financial liability. There may
be some retinal practices with a superb
record of collecting all co-pays and they
may want to forgo the CAP program and
continue to purchase the drugs from the
manufacturer at the ASP+6% price. However,
informal surveys of retina specialists
William L. Rich, III, MD
AAO Medical Director
of Health Policy
showed an overwhelming preference for the
establishment of a CAP program. Our ability
to get CMS to change its original plans and
include retinal drugs is a major victory for
the profession.
As of this date the CAP program
will include verteporfrin (Visudyne),
triamcinolone, bevacizumab (Avastin), and
the IV solutions for Visudyne. Macugen did
not have the minimum sales volume when
the list of covered drugs was first published
but the AAO and Eyetech approached CMS
and we feel confident it will be included for
2006. Lucentis will not have approval in time
for inclusion in 2006.
Disadvantages:
The AAO has expressed concern about the
billing of wastage under the CAP program.
We hope to have this issue clarified by the
time physicians decide on their participation.
If you do elect to participate, you are locked
into the chosen CAP vendor for one full year.
Your staff should educate your patients that
shortly after the delivery of the service they
will be billed for the drug from the vendor.
You will be responsible for verifying that the
planned use of the drug is consistent with
any relevant carrier coverage policies but this
doesn’t preclude the use off label. If a patient
fails to pay the vendor or requested financial
assistance within 45 days from the postmark
date of the vendor’s bill, the vendor may
decline to ship more drug to the physician
for that beneficiary.
Participation:
Retinalogists will be asked to sign a CAP
participation agreement and select a vendor.
In summary, there is some hope of sanity
on the horizon after four years of chaos
dealing with the acquisition of retinal drugs
administered in the office. You will be
notified of the specifics of CAP participation
later this year in the AAO Washington Report
and on the ASRS Message Board. Good luck.
Hang in there.
retina times 47
>> MEDICAL ETHICS
Physicians as Investment Consultants:
Risky Business
As noted in the last issue, we had planned to bring you the “AAO Rules
of Ethics” in this issue. It was decided instead to run the following
article, due to its particular importance and timeliness. Part 2 of “Your
Code of Ethics” will appear in a future issue.
Great strides in ophthalmology research are making headlines–but
that is not necessarily good news. Reported in the Seattle Times on
August 7, 2005 in an article entitled, “Drug Researchers Leak Secrets
to Wall Street”: 1
“Recently, Citigroup Smith Barney penetrated a major study
to see how an experimental drug fared against a just-approved
drug for treating macular degeneration, an incurable eye
disease and the leading cause of blindness in the elderly.
The brokerage talked to 26 eye doctors, but they weren’t just
any doctors. Twenty of the 26 had researched the experimental
drug; 23 of the 26 had researched the other one, meaning that
more than half had worked on both. The doctors were able to
give Smith Barney valuable comparative information.
Nearly all agreed that the drug still being studied, a product
called Lucentis from biotech powerhouse Genentech, would
prove vastly superior to the drug that recently had gone on the
market, Macugen, made by Eyetech, a smaller company.
But the doctors were more explicit than that. Based on its
survey, Smith Barney predicted remarkable results: 97 percent
of patients on Lucentis would have stable or improved vision,
as measured by how many lines of an eye chart they could
read. Smith Barney summarized those findings in a report to
select customers May 5.
As it turned out, the numbers were almost exactly on the
money. On May 23, not long after Smith Barney’s report,
Genentech announced results from its Lucentis study: 95
percent of patients had stable or improved vision–just as
predicted by the doctors Smith Barney talked to.
The announcement battered Eyetech’s stock, which lost
nearly half of its value in a day. Any hedge fund or other
investor who had acted on Smith Barney’s research by betting
against Eyetech would have made better than a 40 percent
return in just three weeks.”
Nancy M. Holekamp, MD
Section Editor
The ethical issue at hand is respect for confidentiality agreements.
The 20 or 23 doctors involved in the clinical research on Lucentis
and Macugen had undoubtedly signed confidentiality agreements
with the respective pharmaceutical companies. In general, such
documents will include something like the following:
“Except as otherwise expressly provided in this agreement,
university (including investigator) shall keep the information
confidential and shall not disclose to others either the
information or any result of the discussions or evaluations.”2
Was there an unethical breach of confidentiality? We may never
know. But what would entice intelligent researchers to divulge
confidential information, even if unintentionally? The answer:
physicians may get paid $200 - $1000 per hour to talk to investment
firms. This is yet another financial conflict of interest for our
profession.
And ophthalmologists are not alone. A June 1, 2005 article in
JAMA3 estimates that 10% of the 700,000 U.S. physicians receive
payment from investment firms for their opinion. A “matchmaker”
company, Gerson Lehrman boasts contractual agreements between
over 60,000 physicians and roughly 50 investment firms. The
Seattle Times article uncovered 26 instances where doctors leaked
important details of ongoing clinical research to investment firms.
In 24 of those 26 cases the firms then issued reports to select
investment clients with advice to buy or sell a stock.
Physicians serving as consultants to analysts for investment
companies may be risky business. If it leads to divulging material
information prior to public release, such ethical breaches of
confidentiality agreements may be illegal. In the words of renowned
ethicist Arthur Caplan, director for the Center of Bioethics at the
University of Pennsylvania, “If this isn’t insider trading, I don’t
know what is.” In response to the Seattle Times article, the American
Association of Medical Colleges is urging its members to be aware
that such communications may be governed by federal securities
law and is recommending that agreements prohibiting disclosure
of clinical trial information to third parties be scrupulously
honored. Senator Charles E. Grassley, chairman of the Finance
Committee, has called on the Justice Department as well as the
S.E.C. to investigate the issue of payment for drug trial results.
Genentech said it was too early to decide if it will take action against
retina times 49
>> MEDICAL ETHICS

the 20 doctors who reportedly discussed clinical trial results with References:
1. “Drug Researchers Leak Secrets to Wall Street”
Citigroup Smith Barney. Seattle Times
August 7, 2005
An editorial for the New York Times on August 17, 2005 suggests a By Luke Timmerman and David Heath
http://seattletimes.nwsource.com/html/businesstechnology/drugsecrets1.html
solution:4
2. “Doctors’ Links With Investors Raise Concerns”
New York Times
“The best antidote would be a pledge of abstinence backed by August 16, 2005
the ethical guidelines of medical societies. Any doctor who has By Stephanie Saul and Jenny Anderson
inside information about clinical trials or the F.D.A.’s thinking http://www.nytimes.com/2005/08/16/business/16research.html
should not do consulting work for investment firms.” 3. Topol EJ, Blumenthal D., Physicians and the Investment Industry,
JAMA.2005;293:2654-2657
So, when the next investment banking firm calls and offers $400 http://jama.ama-assn.org/cgi/content/full/293/21/2654
to discuss a clinical researcher’s impression of the latest treatments 4. Editorial: “When Doctors Advise Investors”
for macular degeneration, he or she may want to think about it and New York Times
August 17, 2005
consider their prior contractual obligations. Editorial

X-
http://www.nytimes.com/2005/08/17/opinion/17wed2.html

Editor’s Note:
The issue of providing consulting information to investment firms is a new but rapidly growing area in our field. We at the Times plan to have
a specific “KOL Corner” article on this matter in our next issue. This will hope to specifically address the potential ethical issues that may be
breached but also will give individuals like Gerson Lehrman an opportunity at balanced reporting.

>> THE ASRS X-FILES

All readers are cordially invited to submit a

Calvin A. Grant, MD
case for discussion and publication in the next Section Editor
X-files section. Please submit your entry to
vitreoretinalsurgeon@gmail.com.

CASE: WF

History of Present Illness: WF is a

twelve-year-old male who presents with
blurred vision in his right eye. The family
denies prodromal symptoms including
upper respiratory infection or other review
of symptom abnormalities.

Visual acuity: 20/400 pinholed to 20/100

right eye and 20/30 left eye.
Pupils: No afferent papillary defect
Slit Lamp Exam: Unremarkable both eyes
Dilated Funduscopic exam: Vascular
constriction (greater than the appropriate
age) both eyes, macula with RPE atrophy
and hyperplasia, both eyes, OD>OS

FILES
Fluorescein angiography demonstrated
window defects consistent with RPE
atrophy and macular edema of the right eye.

OK Scully...
What is your diagnosis?
What would you do?

THE DISCUSSION IS ON PAGE 52

50 retina times
>> CARRIER NETWORK
Billing Macugen–
and what else?
CMS reimbursement for Macugen has been relatively uneventful
compared to our previous history with Visudyne. Billing
Medicare for the drug itself and the injection (CPT 67028) is not
controversial; however, that is not all we do in following macular
degeneration. Four areas of potential increased reimbursement
need to be discussed; increased treatment frequency, diagnostic
testing, combination treatment and same day examination.
The study protocol for intraocular Macugen was treatment every
6 weeks. Medicare Carriers will reimburse for treatments according
to “standard of care”. One issue that might trigger a review for
medically unnecessary would be an injection that occurs in less
than 6 weeks, or an increase in the total number of injections in
a year, exceeding 9. The Medicare Carriers Cahaba, Noridian and
Trailblazer have issued coding and billing guidance stating that they
don’t expect subsequent injections to be less than 6 weeks apart.
The Macugen studies did not use fluorescein angiograms
or OCT to determine the need for each subsequent treatment.
There are presently no medical coverage policies that prohibit
angiography. In fact, First Coast Services of Florida and
Connecticut allow for the potential use of an angiogram prior to
each treatment. The rationalization is that this may be needed to
monitor disease progression. Empire of New York has a draft policy
that prohibits non-angiogram testing for follow-up injections. This
is only a draft and is not ready to be enforced.
Currently, there are no written national or Carrier policies
prohibiting Medicare reimbursement for Macugen combined
with other intraocular injections. This is more than just a
reimbursement issue; it is a standard of care question. Medicare has
a blanket prohibition against medically unnecessary services so the
responsibility to defend combination use rests with the physician.
Empire of New York has proposed a draft policy specifically stating
that they won’t pay for combination Macugen (pegaptanib sodium
injection) and Visudyne (verteporfin) treatments.
Billing Medicare for an exam on the same day as a Macugen
treatment may be open to interpretation. Intravitreal injections
(CPT 67028) are defined as minor surgery; with no post-operative
period. The relative value units for this minor surgery include the
pre-operative and post-operative work done on that same day as
treatment. If the purpose of the examination is only to determine
Mark Levitan, MD
Director, Carrier Network
the need for the procedure then the same day evaluation is included
in the payment. CMS will pay for this same day evaluation only
when you and the carrier consider it a “significant and separate
identifiable service” and you attach modifier 25 to the exam. Be
careful to realize that even if you have been reimbursed that doesn’t
mean you were paid appropriately. Your carrier can always ask for
the money back if an audit determines you were paid incorrectly.
The Office of Inspector General has listed the inappropriate use of
modifier 25 as a target for investigation.
Several carriers have ruled on this problem with written policies.
The initial evaluation requiring intraocular Macugen and resulting
in same day treatment allows for a reimbursable exam. Subsequent
exam/treatments are a different story. Cigna has written that,
“review of previous treatment’s effectiveness is not a separate
service.” Empire of New York writes “evaluation of the effect of a
prior injection is not considered a separate identifiable service.”
The Medicare Carrier for Kansas, Nebraska and northwest Missouri
has a written policy on macular degeneration and photodynamic
therapy; “if a problem distinct from macular degeneration and OPT
is addressed then modifier 25 should be attached.” However, this
scenario is not the typical “one time” surgery that CPT originally
described. A significant and separate evaluation may be necessary
considering the progressive nature of macular degeneration. After
all, study protocols only answer a specific question and are not
meant to be a substitute for the practice of medicine.
The point is that your local CMS Carrier may be the limiting
factor for reimbursement. There is no Carrier written policy that
limits reimbursement when following the explicit guidelines
outlined in the Macugen label. Your changes to this protocol may be
“reasonable and necessary” if the carrier’s policy has no additional
limitations and they agree to your definition and assumptions for
the specific patient being treated. Macugen therapy is still relatively
new to the CMS bureaucracy; Empire of New York is the only
carrier to suggest such specific restrictions but more could follow.
Their draft policy can be implemented only after a public comment
period. Now is the time to be vigilant checking your own Carrier’s
website and join the political process. Speak out when you see draft
policies that are not allowing you the discretion to decide what is in
your patient’s best interest.
retina times 51
>> CODING TIP
The Time Has Come
This may seem like an unlikely topic, but it is one that has much
to do with how we as ophthalmologists are paid. The RBRVS
(Resource Based Relative Value System) pays us on the basis of
several factors–the physician work, the practice expense, and the
practice liability (malpractice insurance) risk. The practice expense
is based on the specific practice expense items related to the
particular code (use of an exam lane, cost of ophthalmic tech, cost
of the laser, etc.) and is also based on the overall practice expense
of ophthalmology. Based on the SMS survey of practice expense
in many specialties of medicine and surgery previously performed
by the AMA, the practice expense for ophthalmology is one of the
highest in medicine and surgery, running at about $140 per hour.
Each code we bill for Medicare patients is associated with a
physician time (the time the doctor expends in supplying the
service, e.g. 92014 Comprehensive eye, established patient, is 39
minutes, and 67107 Scleral buckle is 298 minutes for all surgery
and post-op visits). Thus CMS (Center for Medicare and Medicaid
Services) can take all codes submitted by ophthalmologists on
Medicare patients for a year, and add up all of the minutes eye
MDs have spent with Medicare patients. CMS then multiplies
the number of hours eye MDs spent with Medicare patients
and multiplies that by the ophthalmology practice expense per
hour (about $140) and that number represents the value of the
ophthalmology practice expense pool. Then this expense pool is
used to pay the practice expense portion of all the codes performed
by ophthalmologists.
Why is such an arcane bit of information of value to a retina
specialist? Well, the Five Year Review is currently underway. This is
a congressionally mandated process where CMS reviews a number
of codes to see if there has been a significant change in the value
of services in the last five years. A number of ophthalmology
codes have been submitted including vitrectomy with membrane
peeling, panretinal laser photocoagulation, fluorescein angiography,
extended ophthalmoscopy, and, significantly–cataract surgery. Why
do I include cataract? Well, cataract may be the most important of
the lot to all of us.
Currently cataract surgery is credited with 50 minutes of
intraservice time (skin to skin time). By the time you read this,
the data will all be in, but if the intraservice time for a phaco is
reduced say to 30 minutes, then with almost 2 million Medicare
cataracts performed in a year, there would be 20 min X 2 million,
67,000 fewer hours @ $140/hr less spent on Medicare patients.
That one little change would mean almost $100 million less in
the ophthalmology practice expense pool. This decline would be
spread over all of the eye codes, meaning about $5,000 less to each
ophthalmologist solely based on the impact of potential reduction
of time of cataract surgery on our practice expense pool.
The whole process of code valuation and reimbursement is
complex and often not apparent on the surface. Over the last fifteen
years of working with coding and reimbursement, I have learned
unfortunately that we are not paid fairly. I have labored to try to
prevent wholesale cuts in our reimbursements, and have tried to
52 retina times
Trexler M. Topping, MD
Section Editor
help strategize how to avoid specific cuts. Guys and gals, there is no
free lunch out there. We are not going to get special treatment and
be paid better than others. I personally feel there is little doubt that
physicians are greatly underpaid. Because of the SGR (sustainable
growth rate formula which is used to calculate the conversion factor
which CMS employs to calculate reimbursement for each code and
to penalize us for increased utilization) we are currently scheduled
to suffer a 1.5% reimbursement cut beginning in January of 2006.
This is in the face of our costs going up all the time with more
expensive equipment and supplies, higher rent, and of course we all
gave our staffs 3% or greater raises last year.
Patients mostly feel doctors are overpaid (they look at the billed
charges on the EOB, but usually fail to look at the amount Medicare
or the insurance company actually pays.) Whenever I deal with a
disgruntled patient, or more frequently a corporate CEO who is
dealing with selecting health insurance for his company, or when
dealing with legislators or with patients working in the media, I
give them a three minute course in health care finance. I point out
that our ‘charges’ are irrelevant. We get paid virtually the same by
Medicare and private insurance. Those without insurance seldom
pay, and rarely pay above Medicare allowable. Thus physician
fees are controlled. I then say if they need to go to the hospital for
surgery, the hospital reimbursement is set by DRGs. There is a zone
of medical expense which is truly ‘free trade’, the sector including
drugs and expendable supplies (pacemakers, stents, catheters,
devices). I then point out the average Medicare patient spends
more out of pocket for their medications than for all physician and
hospital services combined. I then urge them to speak to or write to
their Congressmen about this.
In summary, cuts are likely to come partially based on some
diminution of the ophthalmology practice expense pool, and
further losses are predicted for next year based on a declining
Conversion Factor. The system is unfair to all physicians, and I am
afraid the only hope will come through legislation. My friends,
the onus is on you. Your future and your well being as a physician
depend on it. Talk or write to your congressmen and ask your
patients to contact them also.
X-FILES DISCUSSION
(continued from page 50)
The patient presents in an interesting manner. The CME and the
vascular constriction make the possibility of a primary retinal
degeneration a possibility. Other entities have to be entertained
including AZOOR as well as other post-inflammatory entities.
The patient was given Diamox 250mg sequels P.O. BID with the
vision increasing to the 20/30 range. I believe other entities such as
Stargardt’s disease are less likely given the presentation of edema.
Input from all would be welcome regarding this fascinating case.
>> FOUNDATION UPDATE

Roy Levit, MD
American Retina
American Retina Foundation Update Foundation Chairman

One of the Foundation’s major efforts includes the goal of fostering the
Macular Degeneration Research Fellow Award
exchange of information between retinal specialists, their patients and
Beginning in 2006, the Foundation will award a fellow $2,000 for the
other health care specialists. With this goal in mind, the Foundation invites
best macular degeneration poster at the ASRS Annual Meeting. More
opportunities for future projects that involve a relationship between
information about this award will be available soon.
the physician, patient and retina specialist, including patient awareness
campaigns and other educational initiatives.
This year’s silent auction raised $23,575 Kenneth Moffat, MD, Nashville, TN
AMD Patient Education Project for the Foundation. The ARF gratefully Millennium Leather Roller Compu-Brief
The Foundation recently received an educational grant from Alcon acknowledges and thanks all ASRS donated by OccuLogix
members for their participation, as well as
Laboratories to fund an AMD campaign focused on the importance of the companies who donated the items up Pablo Munoz Rodriguez,
ocular vitamin therapy for patients with moderate to severe risk of AMD. for bid. The winners, items, and companies Guadalajara, Mexico
In October 2005, a select test market of ophthalmologists in Phoenix, AZ who donated are listed below: Bausch & Lomb Millennium™
and Tampa, FL will receive AMD Patient Education Photocoagulating Green Laser
Kits that contain a DVD, brochure, recipe cards, SILENT AUCTION WINNERS Synergetics 09.05 Low Mass Pick Forceps
Umberto Albanese, MD, Snyder, NY and 10.01 Vertical Scissors
Amsler grid, and a coupon for vitamins. A four Laserex Laser Elbow Pads, five sets
month local PR campaign will coincide with the kit Jeffrey S. Taylor, MD, Raleigh, NC
distribution, followed by a survey and follow-up Sheldon P. Braverman MD, AAO Ophthalmic Coding Coach 2005
calls to recipients for feedback. Kits will be revised San Antonio, TX
based on the feedback received and then sent out Volk Disposable Chalam Direct View® Tanu Thomas, MD, Chicago, IL
Steryl® Flat SSV Vit Lens, one box Cutter & Buck leather wine tote donated by
nationally, at which time ASRS members will also
Priority Healthcare
receive kits. John Carver, MD, Provo, UT
Labtician Wong Buckling Forceps Paul Weishaar, MD, Wichita, KS
Pediatric Training CD-ROM Two night stay at the Hotel del Coronado,
In addition to the AMD patient kit campaign, Lenin Gomez, MD, Guadalajara, Mexico Coronado, CA
The Foundation has also recently become a AAO Basic and Clinical Science Course
Section #12: Retina and Vitreous CONTRIBUTING COMPANIES
joint sponsor for a pediatric eye CD that will be Alcon Laboratories, Inc.
distributed to pediatricians. This interactive video disc describes common Roy Levit, MD, New York, NY American Academy of Ophthalmology
pediatric eye diseases and eye examination techniques for infants and Two night stay in a Junior Suite at the Bausch & Lomb
toddlers and will be released later in the year. Our focus in this project has Fairmont Queen Elizabeth Hotel, Montreal, Compass Management & Consulting, Inc.
to do with the early recognition of retinoblastoma. Quebec Fairmont Queen Elizabeth Hotel
Gulden Ophthalmics
Sanjay Logani, MD, Northridge, CA Hotel del Coronado
Foundation Activities at the ASRS Annual Meeting Volk Digital Wide Field Diagnostic Labtician
Each year, the ASRS selects one fellow to receive The Fellow Travel Grant, Ophthalmic Lens Laserex
funded by the ARF. Kartik Patel, MD, from Houston, TX was awarded this OccuLogix
year’s Travel Grant at the meeting. G. Matthews, MD, Ft. Worth, TX Park West Gallery
Alcon Greishaber DSP Instruments, Priority Healthcare
three boxes Synergetics, Inc.
Congratulations to Joseph L. Wilhelm, MD, from East Lansing, MI, Volk Optical, Inc.
for winning a laptop. ASRS meeting attendees who donated $10 to the
Foundation or bid on an auction item received a Scratch and Win card for
the chance to win a Dell Inspiron laptop computer.

>> JCAHPO NEWS

Judy E. Kim, MD
Section Editor
Awesome Educational Opportunities Await Your Staff in Chicago
“Chicago, Chicago... my home town!” sang Frank Sinatra. Chicago IS actually my home town. In October, your staff members will sing the same
tune, when they attend the Annual JCAHPO (Joint Commission on Allied Health Personnel in Ophthalmology) Educational Meeting which will
be held in conjunction with the American Academy of Ophthalmology Annual Meeting in Chicago. Various educational opportunities to learn
more about our exciting and fast changing subspecialty of retina will be offered for your technicians, nurses, photographers, and anyone else you
can afford to send. Planned retina courses during the meeting include an update on age-related macular degeneration (including presentations on
PDT, Macugen, and AREDS), diabetic retinopathy, a work-up of retina patients, and technologies for vitreoretinal surgery. Various photography
courses will be available as well. Once again the Retina Subspecialty session will be held for a half day of concentrated retina topics given by a
fantastic line-up of speakers. The topics include OCT, intravitreal steroid injections, uveitis, vitreoretinal surgeries and management of macular
edema and AMD.
In addition to these courses on Retina and Vitreous, the JCAHPO meeting will have courses covering all subspecialties. Make sure that your staff
members attend the Tech Bowl. This is a game-show-like event to review various ophthalmic topics, terms, and definitions. Everyone who attends
has the option to put his or her name in for a chance to play Ophthalmic Jeopardy and possibly win a prize. The full day package includes all four
days of lectures and a 4-day AAO Exhibit Hall Pass. An Economy package and a 1-day package are also available. For additional information on the
meeting, please go to www.jcahpo.org/ACE2005/ace2005home.htm or call JCAHPO at 651-731-2944.
See you in Chicago!

“It is never too late to be what you might have been”

—George Eliot

retina times 57
>> AAO LIAISON REPORT

Antonio Capone, Jr., MD

AAO/Federal Affairs Liason

ASRS selected by AAO as Outstanding Coalition Partner prophylaxis provided in the preoperative period for intraocular surgery.
The Academy announced the selection of the American Society of The Academy will submit at least two or three measures for review
Retina Specialists as an Outstanding Coalition Partner at the Partners by the AMA Physician Consortium for Performance Improvement
in Advocacy Reception, held in conjunction with the 2005 Mid-Year and the National Quality Forum. Review will involve more complex
Forum last April. This honor was bestowed in recognition of the ASRS’ evidence-based measures, and is likely to be a rigorous process
contribution as a society to the Surgical Scope Fund. requiring considerable time and effort for measurement definition,
development and approval. AAO Liaison representatives from all three
Optometric Scope of Practice and You vitreoretinal subspecialties will be consulted in this process.
You may be wondering why our Society’s contribution to this
fund is important. You likely are not alone, as many vitreoretinal Practicing Ophthalmologists Curriculum (POC)
specialists have considered themselves to be above the optometrist- In the past two years, the Knowledge Base Panels (now known as the
ophthalmologist fray. Practicing Ophthalmologists Curriculum (POC) Panels) have worked
The Surgical Scope Fund provides monies to aid the AAO as it to prioritize topics according to clinical relevancy, develop outlines
strives to address optometric scope of practice initiatives–whereby on Most Relevant topics, and come to agreement on the appropriate
optometry gains the privilege of practicing ophthalmology by content that should be included, incorporating input from our society
legislation versus education and training. and other reviewers (ABO and AAO Self-Assessment Committee).
Though you may be aware of initiatives in the area of general/ The Chair of the Retina/Vitreous Panel is Travis Meredith, M.D. The
comprehensive ophthalmology, you may not be aware that optometric POC will serve as knowledge base for ophthalmologic credentialing
scope of practice has the specialty of vitreoretinal diseases and surgery examinations.
in its sights. There is an optometric retina society–the ORS Version 1.0 of the Practicing Ophthalmologists’ Curriculum will
(http://optometricretinasociety.org/). In Oklahoma, for example, be launched on the Academy’s website in October 2005. A MOC
optometrists are moving to add Macugen to their injectable privilege Review Course is planned for July 2006 to review the curriculum
list, not to mention attacks in other states. Look for more on this in for MOC candidates. In addition, the revision of the Practicing
upcoming issues of The Retina Times. Ophthalmologists’ Curriculum, to be known as Version 2.0, will occur
by January 2006. All of the existing information will be reviewed for
Pay For Performance (P4P) currency, and new information will be added as appropriate.
Relief has finally been proposed for problems with the Medicare There will be a rotation of 2-3 members off of each panel at the end
fee schedule. As is true in politics, something has been requested in of this year, in order to maintain continuity and to bring new members
return. That “something” is in the form of what is known as the Pay for into the process as we begin working on Version 2.0. There will be an
Performance initiative–P4P for short. emphasis on including time-limited certificate holders among the new
Congressional leaders are developing legislation that would tie a members rotating on to the panels.
Medicare physician fee fix to moving forward with the physician Pay for
Performance program under Medicare–whereby policymakers develop
a system to reward physicians for performance based on recognized
quality measures under Medicare. This very likely will move forward. >> PRACTICE
CMS recently announced the success of their current hospital P4P
program in improving quality of care with over 98 percent of hospitals
MANAGEMENT
voluntarily participating. MEETING
The AAO has asked for a P4P liaison from each society. The
vitreoretinal community is well served in this area, with representatives
from the ASRS, Retina Society and Macula Society. There is also superb G. Philip Matthews
Section Editor
representation at higher levels in the administrative process, including
Trex Topping, MD, and George Williams, MD, as well as Bill Rich, MD
(See Dr. Rich’s article in the Summer 2005 issue of Retina Times.)
Next year’s ASRS practice management seminar will take place in
The Starter Set of Ophthalmology Performance Measures includes the Spring, 2006 in Orlando, Florida. Comprehensive retinal coding
8 preliminary measures, based on input from all the societies. They will comprise the Saturday session and for Sunday, various practice
include: management issues will be presented. Look for more details on the
1. Counseling on importance of blood sugar control and monitoring of ASRS website (www.retinaspecialists.org) in October. Hope to see
HgAlc in patients with diabetes mellitus. all of you there.
2. Counseling on the use of antioxidants in patients with intermediate
age-related macular degeneration (AMD), or advanced AMD in one
eye, based on data from the Age-Related Eye Disease Study.
3. Central corneal thickness measurement in a patient who is a primary ADVERTISER INDEX
open angle suspect, or measurement was already recorded in their
medical record. Alcon Laboratories, Inc. 1
4. Counseling and education about medication adherence for the Alcon Laboratories, Inc. 58
patient with glaucoma. Alcon/Grieshaber 61
5. Documentation of optic nerve appearance (by stereo photography, Bausch & Lomb 53
optic nerve head analysis or drawing) for a patient with glaucoma or Dutch Ophthalmic, USA 48
glaucoma suspect. Eyetech / Pfizer Ophthalmics 54
6. Consideration of causes of visual impairment other than cataract in Genentech 35
the prognosis presented to the patient candidate for cataract surgery.
Insight Instruments, Inc back cover
7. Questioning the patient about his/her visual function (includes a
review of the patient’s self-assessment of visual status and visual needs; Labtician Ophthalmics, Inc. 17
for a candidate for cataract surgery, this would include questions about MedOne 22
difficulties reading, difficulties in driving, and other activities of daily Novartis 41
living). Ophthalmic Imaging Systems 5
8. A 5% solution of povidone-iodine for the purpose of infection Quantel Medical 9

retina times 59
>> FELLOWS’
FORUM
Retina Fellows’ Forum
January 27-29, 2006
Westin Chicago River North
Chicago, IL
Course Directors:
Carl C. Awh, MD,
Tarek S. Hassan, MD,
David R. Chow, MD
The American Society of Retina
Specialists is pleased to announce
its support of the Sixth Retina
Fellows’ Forum, an all-expenses-
paid meeting for eligible North
American vitreoretinal fellows
in their final year of training.
During this intensive day-and-
a-half of education, invited
speakers will present topics
of universal interest to the
beginning retinal specialist.
The goals of the Fellows’
Forum are to provide a review of
current vitreoretinal treatments,
to allow fellows to meet and
interact with their peers, to
encourage research, and to
introduce fellows to industry. All
fellows in attendance will receive
a number of valuable gifts, as
well as a chance to receive the
American Retina Foundation’s
Travel Grant. In addition, the
winner of the Bausch & Lomb
Fellows’ Research Award will be
announced. This award includes
free registration and travel
support for the winning fellow
to present his or her paper at the
Annual Meeting of the American
Society of Retina Specialists.
The ASRS thanks Bausch
& Lomb Surgical as the major
corporate sponsor of the Retina
Fellows’ Forum and applauds
their support of retinal fellows’
education.
For further meeting information
please contact Karen Baranick
at (914) 722-0664 or by email at
karen.baranick@medconfs.com.
60 retina times
>> THE RETINAL WORLD
Upcoming Meetings for the Retinal Specialist
ASRS members and organizations that are January 15-20
planning a meeting, course or similar event Retina 2006
of interest to retinal specialists are invited Held in conjunction with
to list the event in the “The Retinal World.” Hawaiian Eye 2006
Meeting listings are free and published on Maui, HI
a space-available basis as a service to ASRS Grand Wailea Resort & Spa
members. Listings will be listed and linked Contact: Registration Manager at SLACK
at the ASRS Website: Incorporated
www.retinaspecialists.org. Phone: (877) 307-5225 (US/CN only),
(856) 848-1000
Send meeting information including E-mail: meetingregistration@slackinc.com.
sponsor, course director, contact name,
phone, fax, and e-mail/website to: January 27-29
American Society of Retina Specialists, 6th Annual Retinal Fellows’ Forum
PMB #A, 2485 Notre Dame Blvd., Chicago, IL
Suite 370, Chico, CA 95928; Westin River North
fax to 530-566-9192; or e-mail to Program Chairmen: Carl C. Awh, MD,
newsletter@retinaspecialists.org. Tarek S. Hassan, MD, David R. Chow, MD
Contact: Karen Baranick
Medical Conference Planners, Inc.
2005 Phone: (914) 722-0664
Fax: (914) 722-0465
October 1 E-mail: karen.baranick@medconfs.com
2005 Washington Retina Symposium Web: www.medconfs.com
Washington, DC
The St. Regis Hotel February 9-12
Course Directors: Mohammed K. Barazi, The 25th Annual Squaw Valley
MD, Daniel M. Berinstein, MD, Michael H. Retinal Symposium
Osman, MD Olympic Valley (Lake Tahoe), CA
Contact: Mohammed K. Barazi, MD The Resort at Squaw Creek
Phone: (703) 421-0931 Course Directors: Rob Wendel, M.D., Reece
Fax: (703) 421-7206 Landers, M.D.
E-mail: mkbarazi@yahoo.com Contact: Laura Wendel
Tel: (916) 483-6299
October 14-15 Fax (916) 483-6297
Retina 2005: Changing Concepts and E-mail: squawvalleyretina@comcast.net
Controversies Web: www.squawvalleyretina.com
(AAO Retina Subspecialty Day)
Chicago, IL February 17-18
McCormick Place Twentieth Annual Sarasota Vitreo-
Phone: (415) 561-8500 Retinal Update Course
Fax: (415) 561-8535 Sarasota, FL
E-mail: meetings@aao.org Ritz-Carlton Hotel
Web: www.aao.org/aao/annual_meeting/ Contact: Sherrie Colangelo
subspecialty/retina.cfm Phone: (941) 921-5335
Fax: (941) 921-1741
October 15-18 E-mail: srqretina@aol.com.
2005 American Academy of
Ophthalmology Annual Meeting Feb. 19-24
Chicago, IL XXX International Congress of
Phone: (415) 561-8500 Ophthalmology
Fax: (415) 561-8535 Held in conjunction with
E-mail: meetings@aao.org XVI Panamerican Congress of
Web: www.aao.org Ophthalmology
XXXIV Brazilian Congress of
October 30-31 Ophthalmology
Workshop with International Faculty: The World Congress Of The 150,000
Retinal and Vitreous Surgery Ophthalmologists
Hangzhou, China São Paulo - Brazil
Sponsor: University of Tuebingen, Prof. E-mail: info@ophthalmology2006.com.br
Ingrid Kreissig Web: www.ophthalmology2006.com.br
Contact: Jing Wang
Phone: +86-571-8721-4083 March 5-10
Fax: +86-571-8721-4128 34th Annual Aspen Retinal
E-mail: zyec@mail.hz.zj.cn Detachment Society Meeting
Web: www.kreissig.uni-hd.de Snowmass (Aspen), CO
Snowmass Conference Center at The
November 19 Silvertree Hotel
Advanced Retinal Therapy Program Chairman: Donald J. D’Amico, MD
Vienna, Austria Contact: Karen Baranick
Hotel Intercontinental Medical Conference Planners, Inc.
Sponsor: Alcon Laboratories Phone: (914) 722-0664
Course Directors: Ursula Schmidt-Erfurth, Fax: (914) 722-0465
MD E-mail: karen.baranick@medconfs.com
Christoph Scholda, MD Web: www.medconfs.com
Contact: Andrea Hiermann
Phone: +43 1 5966970 17 March 25
Fax: +43 1 5966970 11 Rush Retina Update: New Drugs &
E-mail: andrea.hiermann@alconlabs.com Devices for Retinal Diseases
Website: www.artvienna.at.tt Chicago, IL
Contact: Jennifer Cruz, Education
2006 Coordinator at Rush University Medical
Phone: (312) 563-2302
January 14-16 E-mail: jcruz@rsh.net
10th Annual American Uveitis Society
Winter Symposium March 30-April 2
Vail, CO 6th International Symposium on
Vail Marriott Mountain Resort & Spa Ocular Pharmacolgy and Therapeutics
Program Chairman: Russell N. Van Gelder, (ISOPT)
MD, PhD Berlin, Germany
Contact: Karen Baranick, Medical Contact: Secretariat
Conference Planners, Inc. Kenes Building
Phone: (914) 722-0664 Airport City 70151, P.O.Box 56
Fax: (914) 722-0465 Ben-Gurion Airport 70100, Israel
E-mail: karen.baranick@medconfs.com Tel: +972 3 9727510
Web: www.medconfs.com Fax: +972 3 9727555
E-mail: isopt@kenes.com
Web: http://www.kenes.com/isopt/
Suzanne Demming, MD
Section Editor
April 22-23
Frankfurt Retina Meeting 2006
Städtische Kliniken Frankfurt am Main-
Höchst
Gotenstraße 6 - 8, D-65929 Frankfurt am
Main
Program Chairman: Claus Eckardt, MD
Contact: Anne-Marie Ebert, Augenklinik
Phone: ++49 (0)69 3106-2972
Fax: ++49 (0)69 3087938
E-mail: C.Eckardt@em.uni-frankfurt.de
Web: www.eckardt-frankfurt.de
April 24
Retinal and Vitreous Surgery
Ekaterinburg, Russia
Scientific Contact: Ingrid Kreissig
Local Organ.: Oleg Shilovskikh
Phone: + 7 343 2406292
Fax: + 7 343 2403370
E-mail: ingrid.kreissig@augen.ma.uni-
heidelberg.de
E-mail: ecmntk@eyeclinic.ru
April 30 - May 4
2006 ARVO Annual Meeting
Greater Fort Lauderdale/Broward County
Convention Center
Fort Lauderdale, FL
Contact: Ellyn Terry, Director of Meetings
and Education
Phone: (240) 221-2935
E-mail: eterry@arvo.org
Web: www.arvo.org
May 31 - June 3
Retinal Physician Symposium 2006
Current Concepts in Retinal Medicine
Atlantis Paradise Island, Bahamas
Phone: (800) 549-3656
Web: www.RPS2006.com
May 20
New Developments in Retina: Trials,
Drugs and New Techniques
Cleveland, OH
Contact: Jane Sardelle at Cole Eye Institute,
Cleveland Clinic Foundation
Phone: (216) 444-2010
E-mail: sardelj@ccf.org
June 24-25
Retinal and Vitreous Surgery
Qingdao, China
Scientific Contact: Ingrid Kreissig
Local Organ.: Xiaoguang Dong
Phone: 0086-532-8587-6483
Fax: 0086-532-8589-1110
E-mail: ingrid.kreissig@augen.ma.uni-
heidelberg.de
E-mail: seih@public.qd.sd.cn
June 29-July 1
VII International Symposium on Ocular
Trauma
Rome, Italy
Contact: Francesca Galil
E-mail: forlini.org@virgilio.it
Web: www.forlinicesare.com/
September 9-13
24th Annual Meeting of the ASRS
6th Annual Meeting of the EVRS
Cannes, France
Web: www.retinaspecialists.org
www.evrs.org
November 11-14
2006 American Academy of
Ophthalmology Annual Meeting
Las Vegas, NV
Phone: (415) 561-8500
Fax: (415) 561-8535
E-mail: meetings@aao.org
Web: www.aao.org
2007
December 1-5
25th Annual Meeting of the
American Society of Retina Specialists
Maui, HI
Web: www.retinaspecialists.org