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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
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>> 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 on new devices, instruments and surgical As the cooler air of the evening swept
Meeting was an unparalleled techniques (25 gauge vitrectomy remaining over Montreal (the weather was the hottest
success, setting records a hot topic), followed by an “illuminating” recorded in 30 years!), attendees dispersed
for attendance, scientific panel discussion deftly managed by Carl to restaurants and other attractions of their
presentations, and “buzz”. Awh and his team of experts on vitrectomy choice, with a large group choosing the
Over 600 ASRS members and lighting options. Next we enjoyed a series delightful musical review and dinner at the
guests from 25 countries, of provocative presentations on diabetic Cabaret du Casino de Montréal.
joined by enthusiastic family members and retinopathy and venous occlusive disease.
360 representatives from 35 companies, The annual Young Physicians Section MONDAY
created the ideal mix for an outstanding Lunch Meeting, co-chaired by Sundeep Dev The annual Breakfast with the Masters,
scientific and social program. The meeting and Ingrid Scott, honored Bill Mieler with the orchestrated by David Boyer and supported by
consisted of more than 130 papers, 80 Crystal Apple Award for excellence in teaching Genentech, Inc., kicked off Monday morning
posters, four instructional courses, panel and mentorship. Bill’s “Life in Addition to with record attendance. The table discussion
discussions, and special evening celebrations Ophthalmology” presentation was a highlight was so animated that it was difficult to clear
and side trips. of the meeting, which also included an the room and move attendees into the session
informative, interactive discussion featuring hall.
SATURDAY an electronic audience response system. The Once seated in the main hall, attendees
The meeting opened Saturday afternoon with YPS festivities were supported by Eyetech were treated to a very special awards
the Fluorescein Angiography & Surgical Case Pharmaceuticals/Pfizer Ophthalmics, Inc. presentation ceremony. Mark Blumenkranz
Conference, moderated by Bill Mieler & Neil The afternoon continued with a scientific received the Retina Research Foundation’s
Bressler. The “Bill and Neil Show” was well session on Pharmacology (“Drugs and Gertrude D. Pyron Award for Outstanding
attended and the interesting cases stimulated Bugs”), followed by a special Distinguished Achievement in Retina Research and presented
plenty of discussion. The Welcome Reception Recognition Award ceremony honoring Bill his captivating lecture “Clinical Research
& Dinner that followed, presented by the Rich for his Herculean labors on our behalf and Vitreoretinal Practice: The Impact of
ASRS in partnership with Bausch & Lomb, over many years. Bill delivered a thoughtful Rapid Technology Change and Quantitative
featured strolling musicians and stations with and provocative lecture entitled “The Tragedy Modeling in the Decision-making Process.”
themed “Taste of Montreal” dining selections. of the Commons and the ASRS’ Frontier.” Steve Ryan was then recognized with the
The first full day of the meeting concluded ASRS Founders Award. This annual award
SUNDAY its scientific portion with a special symposium, honors the society’s founders Jerry Bovino,
ASRS President Gene de Juan & Program “Managing the Risks of Intravitreous Roy Levit, and Allen Verne for their vision of
Chair Julia Haller officially opened the 23rd Injections” adeptly organized by Harry Flynn an open society which promotes the collegial
Annual Meeting on Sunday morning. The and featuring a panel of opinionated expert exchange of ideas between retina surgeons,
leadoff session featured cutting edge talks discussants. 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 H-related genetic mutations with AMD, and La Gioventu Orchestra. The dance floor was
vitreoretinal surgery, treatment, research, continuing with other studies looking at packed until the end of the evening.....with a
surgical instrumentation, and patient care. risk factors, imaging and treatment. A nice number of “postparties” continuing into the
Steve gave a thought-provoking lecture overview of the exciting but increasingly wee hours for many!
on “Genetic Predisposition to Macular complicated management issues confronting
Degeneration.” all of us who treat patients with AMD was WEDNESDAY
David Parke then updated us on the AAO then provided by a team of lucid discussants, Wednesday morning an intrepid crew of post-
and Vitreoretinal Issues–2005. expertly organized and moderated by Phil Gala attendees were treated to a compelling
The morning’s scientific session entitled Rosenfeld. leadoff session entitled Macula 2005–Beyond
Treatment of AMD 2005 was perhaps the The next session took participants first into AMD. The meeting concluded with a strong
“hottest ticket” of the week. An estimated new developments and uses for ocular imaging session on Retinal Detachment and Trauma.
crowd of over 800 packed the room to capacity and then on to the field of pediatric retina.
and more as investigators reported study Lunchtime’s optional Malpractice PAT SURVEY & RESEARCH REPORT
results, culminating in Joan Miller’s discussion Protection Seminar seemed headed for The Seventh Annual PAT Survey Committee
of the Phase 3 results from the Genentech disaster when the guest speaker’s plane was had its comprehensive display with often
study of ranibizumab for the treatment delayed–but not to worry: our own George surprising responses to multiple issues
of minimally classic and occult choroidal Williams, David Parke, Bill Rich and Trex regarding vitreoretinal medicine, techniques,
neovascularization in AMD. Topping came to the rescue with polished and controversies. Also providing attendees
Monday night’s Evening at the Montréal expertise until the featured guest arrived for with an impressive poster display was the
Museum of Fine Arts, hosted by the ASRS the wrap-up. Research & Development Committee that
in partnership with Genentech, Inc., was a Optional instructional courses filled the posted its annual report of ongoing trials.
lively affair as guests enjoyed the galleries of afternoon for those choosing to take them. Thanks to the PAT Survey Editors Rob Mittra
14th to 19th century European Art as well The topics this year included Retinal Coding, and John Pollack and their committee as well
as delicious food, signature beverages, and Molson with the Masters, Advances and as the R & D Committee, chaired by Mark
collegial discussion of the day’s presentations Controversies in Vitreoretinal Surgery, and Humayun, for all of their efforts and hard
and adventures. Intraocular Tumors. work.
Tuesday evening the lecture hall was
TUESDAY transformed into a magical candelabra- THE 7TH ANNUAL ASRS FILM FESTIVAL
The topic of Age-Related Macular bedecked and elegant ballroom for the Gala This year, 44 films were entered in the Annual
Degeneration remained in the forefront as Dinner, featuring the Film Festival Awards, Film Festival, making it one of the biggest to
Tuesday morning began, kicking off with and some amazing dance moves from retinal date. The winners of the Rhett Buckler and
cutting edge reports by Emily Chew and Eric specialists who should know better (do not Dr. Vitrector Awards can be found in Abdhish
Postel on the association of Complement attempt these at home)–all to the tunes of 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

Abdhish R. Bhavsar, MD
Chair, ASRS Film Festival
THE 7TH ANNUAL ASRS FILM FESTIVAL–
ASRS 23RD ANNUAL MEETING IN MONTREAL

The 7th Annual ASRS Film Festival was an outstanding 6. The Use of New Surgical Strategies in Dealing with
success! There were 44 films submitted this year and all Ocular Trauma
of them were well done. Giampaolo Gini, MD (Prato, ITALY)
We owe sincere appreciation to Mark Forchette Vincent S. Reppucci, MD (New York, NY)
and Alcon for their support
of the ASRS Film Festival 7. Vitrectomy for Dummies
for the past, the present and Virgilio Morales-Canton, MD (Mexico City, MEXICO)
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 8. The Use of Different Illumination/Observation
through the task of completing this year’s Festival. Systems for Peripheral Vitrectomy
The 2005 ASRS Film Festival Judges and I saw every single second of Jerzy Nawrocki, MD (Lodz, POLAND)
every single movie and worked very hard on this year’s film festival. Zofia Nawrocka, MD
We owe a debt of gratitude to the judges of this year’s Film Festival in Janusz Michalewski, MD
Montreal, all of whom went above and beyond the call of duty with the Zofia Michalewska
many hours that it took to review and judge the films this year:
9. A New Microscope with Wide Angle Viewing System
JUDGES without Endoillumination
Edgar Thomas (Los Angeles, CA), Lead Judge Murat Oncel, MD (Istanbul, TURKEY)
Mark Balles (South Portland, ME)
Anurag Gupta (Los Angeles, CA)
Richard Johnston (Minneapolis, MN) 10. Modified Technique for Improving Trypan Blue
Hugo Quiroz-Mercado (Mexico City, Mexico) (TB) Staining of Epiretinal Membranes (ERM)
Stanislao Rizzo, MD (Lucca, ITALY)
WINNERS OF THE RHETT BUCKLER AWARD: Michele Palla, MD (Pisa, ITALY)
Federica Genovesi-Ebert, MD, PhD
“BEST OF SHOW”
1. Managing Dry Macular Folds after Vitreoretinal
Surgery
Carlos Mateo, MD (Barcelona, SPAIN) DR. VITRECTOR AWARD
Borja Corcostegui, MD The new Dr. Vitrector Award, for innovative film
technique and vitreous humor, as inspired by the
2. Condiments in Vitreoretinal Surgery: A Bad Day in original Dr. Vitrector films, was given to three film
the Kitchen! producers this year.
J. Fernando Arevalo, MD, FACS (Caracas, VENEZUELA)
Reinaldo A. Garcia, MD DR. VITRECTOR AWARD JUDGE:
Abdhish R. Bhavsar, MD
3. Primary PVR in Buphthalmos
Gaetano R. Barile, MD (New York, NY) WINNERS OF THE NEW DR. VITRECTOR AWARD:
Avi Grinblat
Michael Turano 1. Origin of Subretinal Fluid in Optic Disc Pit
Maculopathy: ß-2 Transferrin Analysis
4. Heavy Silicones in Severe Vitreoretinal Diseases Ronald C. Gentile, MD (New York, NY)
Cesare Forlini, MD (Ravenna, ITALY) Alfonso Ponce, MD
Paolo Rossini, MD
2. 25-Gauge Vitrectomy for Vitreoretinal Diseases
Fabio Patelli, MD (Rome, ITALY)
5. Origin of Subretinal Fluid in Optic Disc Pit Paolo Radice, MD
Maculopathy: ß-2 Transferrin Analysis Giulio Zumbo, MD
Ronald C. Gentile, MD (New York, NY) Giuseppe Fasolino, MD
Alfonso Ponce, 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 I think the term “off-label” has an inappropriately negative
questions that anyone contemplating the use of intravitreal Avastin® connotation. The FDA is not explicitly against the off-label use of
should carefully consider before proceeding. As guidance, the medications, as long as those uses are generally accepted by the
editorial office of the Times has collected individual opinions of community of medical practicioners. The FDA understands that
several leaders within our society and has sought clarification from requiring approval for all uses of any given medication would
some of our pertinent regulatory bodies to provide guidance to our completely bog down the drug approval process.
membership. These are the express opinions of those interviewed and
are NOT an endorsement from the ASRS or the Times. B.A.: We retina specialists frequently use other drugs off-label as well.
For instance, intravitreal antibiotics for endophthalmitis, TPA for
THIS MONTH’S OPINION LEADERS: hemorrhagic AMD, pre- and post-operative antibiotics, and C3F8 for
cases other than pneumatic retinopexy are all off-label uses.
Kirk Packo (K.P.), MD is a vitreoretinal specialist
with Illinois Retina Associates, chair of the A.M.: Once a device or medication is approved by the FDA,
Rush-Presbyterian Medical Center Dept. of physicians may use it “off-label” for other purposes as part of the
Ophthalmology (Chicago, IL), and past President practice of medicine if 1) they are well-informed about the product,
of the American Society of Retina Specialists. 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
George Williams (G.W.), MD is a vitreoretinal often few if any adequate studies of the safety, efficacy, and long-term
specialist with Associated Retinal Consultants, risks of its use. The physician must therefore exercise care in selecting
chair of the William Beaumont Hospital Dept. of patients, be familiar with the information that the manufacturer
Ophthalmology (Royal Oak, MI), past President of includes in the FDA-approved “label” detailing the indications,
the American Society of Retina Specialists, and a risks, and benefits that were determined during clinical trials, and
committee member for OMIC. monitor the patient for ongoing need, efficacy, and safety. In addition,
ophthalmologists would be well advised to inform patients of the
Bob Avery (B.A.), MD is a vitreoretinal specialist in medication’s “off-label” status during the consent discussion, and
private practice with California Retina Consultants keep a file of articles and other materials that support the decision to
(Santa Barbara, CA), and has been a principal use the drug in question.
investigator in 8 clinical trials investigating new
retinal treatments. He and his associates were the G.W.: At the end of the day, with medical-legal matters, the only
first to implement off-label intravitreal Avastin® for “standard of care” issues that will be of importance will be those
patient care on the West Coast. which a jury will decide.

Tom Chang (T.C.), MD is Editor-in-Chief of Avastin® contains a “black box” warning in the package insert,
Retina Times and a faculty member of the Doheny indicating a risk of serious and potentially fatal adverse side
Retina Institute, University of Southern California effects, including GI hemorrhage, GI perforation/wound healing
(Los Angeles, CA). 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
Anne Menke (A.M.), RN, PhD, is Risk Manager of equation?
Ophthalmic Mutual Insurance Company (OMIC).
Her articles on ophthalmic risk management K.P.: Glaucoma specialists have used mitomycin off-label for
have appeared in the OMIC Digest, Retina Times, trabeculectomies for some time. This is a drug with teratogenic as
EyeNet, and Techniques, and she is a regular speaker well as other potentially serious systemic effects.
at state, national, and sub-specialty ophthalmology
conferences. G.W.: These potential complications need to be discussed with
patients before consideration of use, but keep in mind that the drug
Wiley Chambers (W.C.), MD is Deputy Division Director of the is being injected at a dose several hundred times lower than the dose
Division of Anti-Infective and Ophthalmology Products in the given intravenously to cancer patients. The safety profile should
Center for Drug Evaluation and Research at the Food and Drug arguably be considerably lower at these concentrations.
Administration.
T.C.: It should be noted that the FDA clinical trials for Avastin® were
conducted on patients with metastatic GI and lung malignancies. The
What are the medical-legal risks of using intravitreal Avastin® “black box” warnings for Avastin® [potentially fatal GI hemorrhage,
off-label? pulmonary hemorrhage, GI perforation, and a doubling of the
thromboembolic risk] are almost certainly a unique reflection of
K.P.: Medical-legal considerations only take place if there is a failure this patient population. The documented fatal GI and pulmonary
to deliver the standard of care and harm is caused. The definition hemorrhages likely developed secondary to tumor contraction or
of standard of care changes from geographic location to geographic necrosis (i.e. a positive treatment effect). Similarly, the well-known
location. One can argue that the community can be described as the association between cancer and coagulation abnormalities was
“vitreoretinal community of practioners”. This seems to have been the probably a significant factor contributing to the increased risk of
case for intravitreal Kenalog®, for which the off-label use was embraced arterial thromboembolic events in patients treated with Avastin®. It
whole-heartedly by the retina community without clinical trials. 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 making process that led to using Avastin®, and write a note in the
were concurrently treated with other chemotherapeutic agents. On medical record about the consent discussion, including the disclosure
the whole, AMD patients are a significantly healthier population. of the drug’s off-label status and any complications for which the
patient has an increased risk. Except for truly minor procedures with
A.M.: Whether these complications will occur with lower dose, little risk, it is always prudent to use a procedure-specific consent
intravitreal administration in patients who do not have cancer form (a sample form for intravitreal Avastin® will be posted soon on
is precisely what, in part, clinical trials will determine. For now, the OMIC website). Patients should be offered a copy to read at home
ophthalmologists should proceed with caution, since patients and encouraged to contact the physician with any questions.
likely to need Avastin® may also have cardiovascular conditions
and hypertension. First, physicians should carefully screen patients How do you bill for intravitreal Avastin® injections? Do you get paid?
for medical conditions that might increase the likelihood of these
complications. Next, they should give patients information about G.W.: The payment for the injection should be automatic since
the known risks of the drug when used intravenously for colorectal intravitreal injection of therapeutic agents is covered by CPT code
cancer patients, and explain that while the decreased dosage 67028. Any discussion on payments for the drug itself will require
and regional administration of the medication may decrease the discussion with individual local carriers.
likelihood of these risks, neither the safety, efficacy, or long-term
risks of intravitreal Avastin® for ocular conditions has been proven. K.P.: Yes, the national carrier decision on reimbursing the injection
Patients should also be told that whenever a medication is used was demonstrated with Kenalog®. For the drug coverage, it is likely
in a large number of patients, a small number of coincidental that the local carriers will need to see more published data.
life-threatening problems may occur that have no relationship to
the treatment. Ophthalmologists should consider getting medical How do you mix and aliquot Avastin® for intravitreal injection?
clearance for patients with pertinent medical comorbidities. Before,
during, and after administration, patients should be monitored for B.A.: Avastin® is available in 100 mg and 400 mg vials. We use the 100
adverse events. At the time of discharge, patients should be given mg vial, which contains 4 cc of a 25 mg/cc concentration of the drug.
written contact information detailing eye symptoms that should be We have a compounding pharmacy divide this into 0.1 cc aliquots.
immediately reported to the ophthalmologist or, if they experience We inject 0.05 cc, for a delivered dose of 1.25 mg.
symptoms of life-threatening conditions affecting organs other than
the eye, the primary care physician. 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
Do you have any absolute medical contraindications for intravitreal expect adequate information would be presented to insure that use
Avastin®? of the product as outlined above would in fact provide adequate
protection against the administration of non-sterile product into
B.A.: In Phil Rosenfeld’s study of intravenous Avastin®, a mild the eye. The ophthalmic use of an unpreserved product in multiple
elevation in blood pressure in some patients treated with systemic patients is contrary to the Code of Federal Regulations concerning
Avastin® was observed. However, our group has not seen a significant ophthalmic products (21 CFR 200.50).
elevation in blood pressure or other adverse systemic effects in those
patients treated with intravitreal Avastin®. Nevertheless, I would feel B.A.: I am surprised to learn of this regulation. We were simply
uncomfortable treating someone with a recent myocardial infarction, following the exact protocol of a major teaching hospital. I know
unstable angina, or a recent stroke until more safety data is obtained other universities would aliquot TPA in the past, and many university
and published. So far, the intravitreal drug seems to be very well and private practices use a single unpreserved vial of Botox® on
tolerated. We have treated over 75 patients and we have yet to see multiple patients. In fact, Medicare has given guidance with respect to
uveitis. how to bill for one vial of Botox® used in multiple Medicare patients.
Nevertheless, even if this code does apply to injected medicines, a
What must be included in the documentation of informed consent? 100 mg vial of Avastin® is still significantly cheaper than a vial of
Is a special procedure-specific consent form required for off-label use Macugen® or Visudyne®, and the effects are quite striking. As Phil
of Avastin®? Rosenfeld showed in his published case reports, we too are seeing
some remarkable early responses. Eight of our first 21 injected eyes
G.W.: It is important for us to remember that informed consent had complete resolution of retinal thickening at 4 weeks.
is a process and not a form. The consent form is simply a vehicle
to document that process. Any informed consent with patients for A.M.: The medication comes in preservative-free vials intended
intravitreal Avastin® must include disclosure that the patient is being for use on a single cancer patient at a much larger dose. Using
offered off-label use and that there are no definitive trials showing one Avastin® vial for multiple patients with ophthalmic problems
efficacy. In addition, detailed discussion of all other potential raises a number of patient safety and professional liability issues.
treatment options (i.e. Macugen®, PDT) must be documented. OMIC obtained a formal legal opinion from an outside attorney
about whether federal regulations (i.e., 21 CFR 200.50) prohibit
T.C.: It will be important to demonstrate/document a clear ophthalmologists from treating more than one patient with a single
justification for the use of this off-label application, for example, if unpreserved vial. The regulations pertain to the manufacture and
a patient has been shown to be a treatment failure to Macugen® or packaging of ophthalmic drugs, and nothing, according to the
PDT. We need to keep in mind that these are treatments that have attorney, specifically addresses the use of an unpreserved product
demonstrated efficacy in randomized clinical trials. in multiple patients. As a risk management measure, therefore, and
to respect the intent of the regulations even if they do not appear to
G.W.: I would be reluctant to deny someone an approved therapy pertain to how the drug is used, physicians should take certain steps.
without detailed explanation of the reasons why in the informed First, to ensure safe administration, ask a compounding pharmacy
consent. to prepare the medication for ophthalmic use, confirm the dose
A.M.: Ophthalmologists should carefully document the decision- and sterility, identify a syringe suitable for this protein, and provide

20 retina times
storage and “beyond-use” instructions, and the lot number of the vial. Devices,”6 differentiates between off-label use of approved (marketed)
Second, to reduce the risk to their patients and themselves, drugs as part of the practice of medicine and investigational use.
ophthalmologists would be well-advised to “credential” the When the intent is to practice medicine, that is, to treat an individual
compounding pharmacy to which they send the prescription for patient, no IND, IDE, or review by an IRB is required. If the intent is
intravitreal Avastin®. Recent legislation should make that to “develop information about the product’s safety or efficacy,”6
quality assurance step a little easier. In response to concerns the use would be considered investigational, and in the case
about contamination and potency, a new federal standard of a drug, an IND application would be required unless six
for preadministration manipulation of compounded sterile conditions are met (I will discuss only three). The first two
preparations (CSP) was established, effective January 2004, address the intent of the investigational use. Studies whose
and codified in USP Chapter 797. The standard addresses purpose is to submit information to the FDA in support
compounding, transportation, and storage of CSPs and is of a new indication for the drug or any other significant
enforceable by the FDA, state boards of pharmacy, boards change in the labeling, or to support a significant change
of health, and other regulatory agencies (e.g., JCAHO).4 in the advertising of the product would require an IND.
Physicians should ask the compounding pharmacy The third condition that, if it were met, would allow a
for assurance that it is licensed/registered in the study of a drug to proceed without an IND, requires
state in which it is dispensing and is complying that use “not involve a route of administration
with USP Chapter 797. In addition to providing or dosage level, use in a subject population, or
ophthalmologists with a CSP upon receipt other factor that significantly increases the
of a prescription for an individual patient, risks (or decreases the acceptability of the
“pharmacists may compound drugs in very risks) associated with the use of the drug
limited quantities prior to receiving a product.”6 According to information
valid prescription based on a history obtained from representatives of the
of receiving valid prescriptions that FDA, this condition never applies
have been generated solely within to ophthalmic drugs, because
an established pharmacist/ of the potential toxic effect
patient/prescriber relationship, on the eye of active and inert
and provided that they maintain ingredients. The take-away
the prescriptions on file for all message for ophthalmologists
such products compounded at the who plan to publish the results of
pharmacy (as required by State law).”5 Ophthalmologists should their clinical experience with off-label medications is to apply for an
be wary of obtaining CSP from pharmacies that advertise their IND and submit their proposed study to their IRB.
ability to compound specific drug products such as Avastin®, since
advertisements of that type are contrary to the “Good Compounding References
1. Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings
Practices” and ethical standards of the National Association of State after intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular
Boards of Pharmacies.5 degeneration. Ophthalmic Surg Lasers Imaging 2005;36:331-335.

2. Rosenfeld PJ, Fung AE, Puliafito CA. Optical coherence tomography findings after
Do you need an IRB approval and/or IND application to perform a intravitreal injection of bevacizumab (Avastin) for macular edema from central retinal vein
retrospective study on patients on an off-label basis (i.e. no formal occlusion. Ophthalmic Surg Lasers Imaging 2005;36:336-339.
“research” consent, IRB submission, or protocol)?
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
W.C.: Avastin is an approved biologic agent, approved for use in a
®
study. Ophthalmology 2005;112:1035-1047.
different patient population by a different route of administration.
4. “An Update on USP Chapter 797: The New National Standard for Sterile Preparation,”
As such, the intravitreal use of Avastin® in a study requires an Lawrence A. Trissel, B.S., FASHP, www.ashpadvantage.com/monograph/797, accessed 25
Investigational New Drug exemption (IND). The regulations do not August 2005.
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 5. “Good Compounding Practices Applicable to State Licensed Pharmacies,” National
Academy of Boards of Pharmacies, www.nabp.net/law/modelact/appendixc.asp, accessed
in an individual patient may be considered the practice of medicine 25 August 2005. See also “Guidance for FDA Staff and Industry. Compliance Policy Guides
in a case where the physician clearly believes that this treatment is in Manual. Chapter 4, Subchapter 460. Section 200 Pharmacy Compounding.” May 2002.
the patient’s best interest, physicians should check with their local
6. Guidance for Institutional Review Boards and Clinical Investigators: “Off-Label” and
IRBs concerning the need for local IRB approval. 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.
A.M.: From a common sense point of view, there does not appear
7. Feinsod M, Chambers WA. Trials and tribulations: a primer on successfully navigating the
to be any additional risk to the patient during a retrospective waters of the Food and Drug Administration. Ophthalmology 2004;111:1801-1806.
review, especially if it is conducted under the auspices of an IRB.
And ophthalmologists engaged in studies of ophthalmic devices 8. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress.
rely upon their IRBs to determine when an IDE (investigational Endocrine Reviews 2004;25:581-611.
device exemption) is required. However, any study of a drug would Useful online resources
require an IND, and IRBs do not have the authority to waive the IND Searchable, full-text copies of Title 21 of the Code of Federal Regulations, which
requirement. A quick review of the difference between the practice of 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.
medicine and research, and between ophthalmic drugs and devices, Section 21 CFR 50 covers the protection of human subjects, which includes informed
may help ophthalmologists understand the reasoning behind the FDA consent requirements. Section 21 CFR 56 covers institutional review requirements (IRBs).
regulation, and provide guidance on when to apply for an IND. The Finally, section 21 CFR 200.50 covers issues specific to ophthalmic drugs and products.
two most important points to consider are the intent of the physician
Useful resources concerning medical-legal matters in ophthalmology, including procedure-
and the risk to the patient. The FDA Information Sheet, “’Off-Label’ specific consent forms, can be found at www.omic.com.
and Investigational Use of Marketed Drugs, Biologics, and Medical

retina times 21
4TH
ANNUAL
RETINAL
RESEARCH
REPORT

2005
>> RETINAL RESEARCH REPORT

CLINICAL DIABETES MELLITUS AMD • Women’s Health Initiative Sight


Examination Study (WHI-SE)
• B7A-MC-MBCM: Protein Kinase C Beta • Submacular Surgery Trials (SST)
• Randomized Trial of Beta-Carotene and

TRIALS
Inhibitor-Diabetic Retinopathy Study 2
Macular Degeneration
(PKC-DRS2) A Phase 3 Clinical Trial • Anecortave Acetate in Age-Related
Macular Degeneration
• Age-Related Eye Disease Study
• Diabetic Macular Edema Vitrectomy
Study (DMEVS) • A Phase I, Open Labeled, Randomized
• Transpupillary Thermotherapy for
Study of the Safety, Tolerability, and
Choroidal Neovascularization Clinical Trial
The ASRS Research & Development • Phase 2 Study to Evaluate the Safety and Pharmacokinetics of Escalating Multiple-
(TTT4CNV)
Committee is committed to maintaining an Efficacy of an Intravitreal Fluocinolone Dose Intravitreal Injections of Rhufab
updated forum for members of the Society Acetonide (0.5 or 2mg) Implant in Patients V2 in Subjects with Neovascular AMD
• Dry Age-Related Macular Degeneration
to have ready access to ongoing clinical with Diabetic Macular Edema (DME) (FVF2425G Study)
(AMD) Trial
trials in vitreoretinal diseases.
The R&D Committee has implemented • Epidemiology of Diabetes Intervention • A Phase III, Multicenter, Randomized,
• Complications of Age-Related Macular
a Web-based access platform for and Complications (EDIC) Double-Masked, Sham Injection-
Degeneration Prevention Trial (CAPT)
rapid entry of new study information to Controlled Study of the Efficacy and Safety
enable wide dissemination of ongoing • A Multicenter, Randomized, Masked, of Rhufab V2 (Ranibizumab) in Subjects
• Photodynamic Therapy (VISUDYNE)
clinical research. The R&D Committee is Controlled Study to Evaluate the Safety with Minimally Classic or Occult Classic
in Minimally Classic Subretinal
devising a Web-based library of surgical and Efficacy of Retisert, an Intravitreal Subfoveal Neovascular AMD (FVF2598G
Neovascularization (VIM) Study
instruments and devices focused toward Fluocinolone Acetonide Implant, in the Study - MARINA)
comparative review by members of the Treatment of Patients with Diabetic
• Submacular Surgery Trials (SST)
Society. Macular Edema, FAME 4 • Indocyanine Green (ICG) Risk Factors for
This fourth annual Retinal Research Choroidal Neovascularization
• Randomized Trials of Vitamin
Report provides a current list of ongoing • A Phase 2 Randomized, Open Label,
Supplements and Eye Disease
clinical trials. Multicenter, Controlled Trial to Assess the • Prophylactic Diode Laser Photo
Safety and Efficacy of Dexamethasone Coagulation for the Prevention of
• Anecortave Acetate Risk Reduction Trial
The information in these tables has been Segment Drug Delivery System (DEX Choroidal Neovascularization in Age-
(AART)
collected from publicly available sources PS DDS) in the Treatment of Persistent Related Macular Degeneration (PTAMD)
and is by no means inclusive of all clinical Macular Edema
• SIRNA 0401
trials.The ASRS does not support or en- • Visudyne with Altered (Delayed) Light in
dorse this information, nor does the ASRS • Vitrase of Vitreous Hemorrhage Study Occult CNV Study (VALIO)
• Visudyne with Intravitreal Triamcinolone
attest to its correctness and validity. This (VVHS)
Acetonide (VisTA) Trial
information has been provided as a service • Multicenter Investigation of
to its members to further its mission and • MBBK/MBBM Rheopheresis for Age-Related Macular
• Preservative-free Triamcinolone
nonprofit purposes. Degeneration (MIRA-1)
Acetonide (PFTA)
• Pegaptanib Sodium Injection (Macugen)
• An Evaluation of Efficacy and Safety
• Combretastatin A-4 Phosphate (CA4P) in
RESEARCH & DEVELOPMENT • Reduction in the Occurrence of Center- of Posterior Juxtascleral Injections of
Patients with Neovascular AMD (FBO-206)
COMMITTEE: threatening DME Anecortave Acetate 15mg Versus Visudyne
in Patients with Subfoveal Exudative
• ANCHOR
Mark S. Humayun, MD • Intravitreal Triamcinolone Acetonide and Age-Related Macular Degeneration
Chairperson Laser Photocoagulation for DME (AMD) Eligible for Initial Treatment with
• MARINA
Photodynamic Therapy (PDT) Using
Eugene de Juan, Jr., MD • Laser Photocoagulation for DME Visudyne
• Evaluation of Safety and Efficacy of
Anecortave Acetate vs. Placebo in Patients
Sharon Fekrat, MD • A Phase II Multi Center Trial to Establish
with Subfoveal CNV due to Exudative AMD
OCULAR MELANOMA the Safety and Pharmacokinetic Profile
of Intravitreal Anti-VEGF Pegylated
(C-02-29)
Peter K. Kaiser, MD
Aptamer (Eye001) in Age-Related Macular
• Collaborative Ocular Melanoma Study • Evaluation and Tolerability of 4-dose
SriniVas Sadda, MD Degeneration Undergoing Photodynamic
(COMS) Levels of Cand5 Administered by Single
Therapy
Intravitreal Injection in Patients with Wet
AMD
BRVO • A phase II/III Randomized, Double
Masked, Controlled, Dose Ranging Multi
• PIER
Center Comparative Trial , in Parallel
• Intravitreal Steroid Injection Study Trials Groups, to Establish the Safety and
(ISIS) • The Effect of Pegaptanib Sodium
Efficacy of Intravitreal Injections of
on Foveal Thickening in Patients with
Eye001 (Anti-VEGF Pegylated Aptamer)
• European Arteriovenous Sheatotomy Exudative Subfoveal AMD
Given Every 6 Wks to 54 Wks, in Patients
Trial (EAST) with Exudative Age-Related Macular
• Squalamine
Degeneration (AMD)
• Surgical Decompression of Branch Vein
Occlusion • Noncomparative Protocol for Use of
• Lutetium Taxaphyrin (LuTex/Optrin) in
Intravitreous Macugen Injections in
Age-Related Macular Degeneration (Phase
• The Standard Care vs. COrticosteroid Patients with AMD
I Studies)
for REtinal Vein Occlusion (SCORE) Study:
to Compare the Efficacy and Safety of • PrONTO
• A Phase I/II, Multicenter, Dose
Intravitreal Injection(s) of Triamcinolone Escalation, Controlled Study of the Safety,
Acetonide with Standard Care to Treat • Safety and Efficacy of AG-013958
Tolerability, Pharmacokinetics and Activity
Macular Edema: 1 for CRVO and 1 for in subjects with subfoveal choroidal
of Multiple Dose Intravitreal Injections of
BRVO neovascularization associated with age-
Rhufab V2 in Subjects with Neovascular
related macular degeneration
AMD (FVF2128G Study)
UVEITIS • A Randomized, Placebo Controlled,
• TheraSight Ocular Brachytherapy System
for Treatment of AMD
Double Masked, Multi Center Phase III
• Randomized trial of Acetazolamide Study of the Effect of Visudyne Therapy
for Uveitis-Associated Cystoid Macular • AdGVPEDF.11D in Neovascular Age-
in Occult with No Classic Subfoveal
Edema (CME) Related Macular Degeneration (Wet AMD).
Choroidal Neovascularization (CNV)
Secondary to Age-Related Macular
• A Multicenter, Randomized, Double • Interval Dose Evaluation of Anecortave
Degeneration (VIO)
Masked, Controlled Study to Evaluate the Acetate (IDEAA) I
Safety and Efficacy of an Fluocinolone • Photodynamic Therapy (Visudyne) Early
Acetonide (0.5 or 2.0 mg) implant in • Interval Dose Evaluation of Anecortave
Re-Treatment for Subfoveal Choroidal
Patients with Non-Infectious Uveitis Acetate (IDEAA) II
Neovascularization (VER) Study
Affecting the Posterior Segment of the Eye
• Denufosol Tetrasodium (INS37217
• A Phase III, Multicenter, Randomized,
• Pilot Study of a Sustained Release Ophthalmic), P2Y2 Receptor Agonist for
Double-Masked, Active Treatment-
Cyclosporine-A Implant Intravitreal Injection
Controlled Study of the Efficacy and Safety
for Uveitis of Rhufab V2 (Ranibizumab) Compared
• Genetics and Clinical Characteristics of
with Verteporfin (Visudyne) Photodynamic
• Longitudinal Study of Ocular Bardet-Biedl Syndrome
Therapy in Subjects with Predominantly
Complications of AIDS (LSOCA) Classic Subfoveal Neovascular AMD
• Cell Transplantation to Replace Retinal
(FVF2587G Study - Anchor)
• CMV Retinitis and Viral Drug Resistance Cells and RPE in Retinal Dystrophies
(CRVR) • Limited Macular Translocation Study
• Optical Coherence Tomography Study of
Retinal Thickness
ROP • A Phase II, Randomized, Double Masked,
Placebo Controlled Study of the Matrix
• Phase I Trial for Wet Age-Related
Metalloproteinase Inhibitor AG3340
• Cryotherapy for Retinopathy of Macular Degeneration with VEGF Trap
in Patients with Subfoveal Choroidal
Prematurity (CRYO-ROP) - Outcome Neovascularization Associated with Age-
Study of Cryotherapy for Retinopathy of Related Macular Degeneration
Prematurity

24 retina times
DIABETES MELLITUS • 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
Study
Eligibility: Up to 180 pts Not available
B7A-MC-MBCM: Protein Kinase C Beta
• Diabetic Macular Edema in the study eye Follow Up Results
Inhibitor-Diabetic Retinopathy Study 2
• Pregnant lactating females 4 years
(PKC-DRS2) a Phase 3 Clinical Trial Pending
• DME must involve fixation and be at least
Sponsor Eligibility/Exclusion
one disc area in size
Eli Lilly Co. • Patients 18 yrs and older with diffuse DME
• Males and non-pregnant females must be involving fixation
Study Purpose at least 18 years of age • DME should be at least one disc area in size Study
To determine whether an inhibitor of the Exclusion:
beta-isoform Protein Kinase C (PKC), relative • Allergy to fluocinolone or any component of Participating Centers MBBK/MBBM
to placebo, will inhibit visual loss or the the delivery system 25 centers Sponsor
development of PDR • Visual acuity of >20 and <68 letters by Results Eli Lilly Co.
Study Design ETDRS in the study eye Pending Study Purpose
• Phase 3, multicenter, parallel, randomized, • Presence of history of uncontrolled ocular The objective is to test the hypothesis that
double masked, placebo controlled study pressure (IOP) while on steroid therapy the oral administration of the study drug will
• Subjects with Type I or II diabetes, ETDRS resulting in loss of vision inhibit the action of Protein Kinase C and
retinopathy severity of 47A-53E in at least • IOP >25 mm Hg requiring 2 types of anti- Study prevent or delay the development of macular
one eye will receive a once a day tablet glaucoma medication to lower to <25 mm A Phase 2 Randomized, Open Label, edema and proliferative diabetic retinopathy
(either the investigational drug or placebo) HG. Multicenter, Controlled Trial to Assess the in diabetics with mild to moderately severe
with a meal • The study eye must have received at least Safety and Efficacy of Dexamethasone Diabetic Retinopathy
Eligibility/Exclusion one macular laser treatment >3 months prior Segment Drug Delivery System (DEX Study Design
• Subjects 18 years of age and older to entry into the study PS DDS) in the Treatment of Persistent Prospective, randomized, placebo controlled,
• Type I or II DM with HbA1C of < 13.0% at Results Macular Edema double masked study
time of screening and enrollment Pending Sponsor Eligibility/Exclusion
• History of PRP for DR, uncontrolled HTN, Oculex Pharmaceuticals, Incl. 601 W. • 18 yrs or older
unstable angina California Ave, Sunnyvale, CA 94086 • Type I or II diabetes
Results Status • Visual acuity of 20/100 or better in the eye
Pending 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
Study National Institute of Health Results
Not available
Diabetic Macular Edema Vitrectomy Study Study Purpose Pending
Study Chairman
(DMEVS) • Overall goal of this study is to help Cynthia Selfridge, RN; Oculex Pharm
Sponsor determine factors that are associated with the
development of kidney, large blood vessel, Study Purpose
Juvenile Diabetes Research Foundation and To compare the effectiveness of DEX PS DDS
Rush Medical College eye and nerve complications in diabetes. Study
• A new study indicates that despite to observation in the treatment of persistent Pegaptanib Sodium Injection (Macugen)
Study Purpose macular edema
• To investigate whether the use of vitrectomy increased hyperglycemia, a reduction in Sponsor
the risk of progressive retinopathy and Study Design Eyetech Pharmaceuticals and Pfizer Inc.
can preserve or improve visual acuity in Randomized, open label, multi center, and
individuals with diffuse diabetic macular nephropathy persists for at least 4 years in Status
patients with Type I diabetes who manage controlled study
edema compared to standard laser therapy. No longer enrolling patients. Study
• To determine whether optical coherence their condition through intensive therapy Number of Patients Enrolled completion expected Q1 2005
tomography (OCT) has value in the evaluation • This research was part of the Multicenter 160 pts
Diabetes Control and Complications Trial Study Purpose
of this disorder Follow Up Compare the safety and efficacy of
(DCCT) and the Epidemiology of Diabetes 6 months
Study Design Interventions and Complications Research pegaptanib with placebo in patients with
Randomized, prospective clinical trial Eligibility/Exclusion DME
Group (EDIC)
Number of Patients Enrolled • Persistent macular edema due to: Study Design
Study Design • Diabetic Retinopathy (DR)
Not available • EDIC is an observational study to compare Phase 2, multicenter, randomized, placebo-
• Branch Retinal Vein Occlusion (BRVO) control, double-masked. Patients received
Follow Up the long term effects of intensive or • Irvine-Gass Syndrome
6 months 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
Eligibility/Exclusion DCCT on the development of more advanced
Participating Centers 12 weeks and then at the discretion of the
Entry criteria include: retinal and renal complications of diabetes
Not available investigators
• Best-corrected ETDRS visual acuity 20/40- • The study compared the effects of two
20/800 treatment regimens- standard therapy and Results Eligibility/Exclusion
• Foveal avascular zone less than 1000 intensive control- on the complications of Pending Eligibility for thermal laser therapy for DME
microns diabetes Number of Patients
• No benefit from previous medical or laser • Patients were randomly assigned to each 169
treatments within previous 3 months treatment group Participating Centers
• Stable systemic health Eligibility/Exclusion Study 41
Results • Patients with Type I diabetes Vitrase of Vitreous Hemorrhage Study
Results
Pending • 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
Study Results • To evaluate the safety and efficacy of an Study
Phase II Study to Evaluate the Safety and Pending injection of Vitrase for intravitreal injection for Reduction in the Occurrence of Center-
Efficacy of an Intravitreal Fluocinolone facilitating the clearance of severe vitreous threatening DME
Acetonide (0.5 or 2mg) Implant in Patients hemorrhage
Sponsor
with Diabetic Macular Edema (DME) Study Design
Eli Lilly and Company
Sponsor Study • The Vitrase study is a prospective,
randomized, parallel, double-masked study Status
Bausch & Lomb, Inc. A Multicenter, Randomized, Masked,
Recruiting
Study Purpose Controlled Study to Evaluate the Safety Eligibility/Exclusion
and Efficacy of Retisert, an Intravitreal • Patients with severe vitreous hemorrhage Study Purpose
• To evaluate the safety and efficacy of Determine whether ruboxistaurin can slow the
intravitreal fluocinolone implant in 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
management of patients with Diabetic
Macular Edema (DME) Macular Edema, FAME 4 etiology except those listed in the subject Study Design
• To compare the safety and efficacy of Sponsor exclusion criteria, randomized by computer Randomization 1:1, ruboxistaurin/ placebo
two doses of fluocinolone (0.8 or 2.0 mg) Control Delivery Systems, Inc. into four study groups Eligibility/Exclusion
delivered by an intraocular/intravitreal implant • Subject is 18 years of age or older, Inclusion Criteria: Macular edema: if >= 1/6
Status
in patients with macular edema 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
Study Design Patient Accrual Date ophthalmoscopy that was DA location must be >1500 mm 3000 mm
• Eligible patients include those with diabetic TBA • A: red reflex with no retinal detail visible from center of macula, ETDRS retinopathy
macular edema that have had previous Study Center posterior to the equator or level of >=20 and 47D in the study eye, best
treatment with laser photocoagulation and Control Delivery Systems, Inc; 313 Pleasant • B: no red reflex is visible refracted visual acuity in the study eye of
have persistent retinal thickening involving Street, Watertown, MA 02472 • Severe vitreous hemorrhage as defined 20/32 or better
the center of the macula above Exclusion Criteria: H/o any focal, grid, or
• Patients are randomized to pars plana Study Chairman
Not available that has been present > 1 month by scatter laser for DME in the study eye; retinal
insertion of either the 0.5 or 2mg fluocinolone history or exam artery/vein occlusions, macular degeneration,
implant 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
OCULAR MELANOMA • Randomized Trial of Pre-Enucleation
Radiation for Large Choroidal Melanoma:
Study
Surgical Decompression of Branch Vein
>11%), hypertension greater than 170 initial mortality findings published in 1998 Occlusion
systolic; chronic renal failure on dialysis; s/p (COMS report no. 10) showed that patients Sponsor
renal transplant or creatinine >4.0; treatment with large choroidal melanoma had similar Not available
with or planned treatment with topical or oral Study survival rates regardless of whether they were
Collaborative Ocular Melanoma Study Study Purpose
carbonic anhydrase inhibitors; participation in treated with radiation prior to removal of the • To evaluate vitreous surgery as treatment
previous Lilly ruboxistaurin study (COMS) eye or had their eye removed without prior for BRVO
Participating Centers Sponsor radiation therapy Study Design
Not available National Eye Institute (NEI) • 5-year survival rates were approx. 60% • A prospective, non-randomized trial.
Status in both treatment arms. The COMS large
Number of Patients Eligibility/Exclusion
Ongoing tumor trial found neither benefit nor harm
Not available Not available
Patient Accrual Date from treating ocular melanoma patients with
Participating Centers radiation before removal of the eye. However, Results
Not available Pre-enucleation radiation completed 12/15/
patients who had pre-enucleation radiation Pending
Results 94; radioactive plaque completed 8/1/98
had fewer local complications (COMS report
Pending Study Centers no. 11).
Scheie Eye Inst. at U of Penn and Wilmer Eye • Randomized Trial of I-125 Brachytherapy
Inst. ; 550 N. Broadway, Suite 700; Baltimore, for medium choroidal melanoma: initial Study
MD 21205; 410-955-1966 mortality findings published in 2001 (COMS The Standard Care vs. COrticosteroid for
Study Study Chairman report no. 18) showed that survival rates for REtinal Vein Occlusion (SCORE) Study:
Intravitreal Triamcinolone Acetonide and Stuart Fine, MD; Scheie Eye Institute / 215- radiation therapy (I-125 brachytherapy) and to Compare the Efficacy and Safety of
Laser Photocoagulation for DME 662-8657 enucleation (removal of eye) are about the Intravitreal Injection(s) of Triamcinolone
Sponsor Study Purpose same. The 5-year survival rate of patients Acetonide with Standard Care to Treat
Diabetic Retinopathy Clinical Research • To evaluate therapeutic interventions for who were treated with either radiation therapy Macular Edema: 1 for CRVO and 1 for
Network patients who have choroidal melanoma, the or eye removal was 82%, considerably better BRVO
most common primary eye cancer affecting than the 70% 5-year survival rate that had Sponsor
Status been projected when the study was designed
adults, and to assess the potential life National Eye Institute, National Institutes of
Recruiting in 1985. Compared to immediate loss of
preserving as well as sight-preserving role of Health, Department of Health and Human
Study Purpose radiation therapy vision when the eye is removed, eyes treated Services
Determine whether intravitreal triamcinolone • To determine which of two standard with radiation steadily lost vision gradually,
at doses of 1 mg or 4 mg provides greater with 63% having visual acuity of 20/200 or Status
treatments, removal of the eye or
benefit, with an acceptable safety profile, worse by 3 years after treatment (COMS Enrollment began in October 2004
brachytherapy, is more likely to prolong
than macular laser in the treatment of DME survival of eligible patients with medium sized report no. 16) Study Purpose
Study Design choroidal melanoma To compare the effectiveness and safety of
One eye eligible: randomization, 1:1:1, laser/1 • To determine whether preoperative radiation standard care to intravitreal injection(s) of
mg triamcinolone/4 mg triamcinolone. Both prolongs life for patients whose eyes with triamcinolone for treating macular edema
eyes eligible: 1 eye randomized to laser, the large choroidal melanoma are enucleated. BRVO (swelling of the central part of the retina)
associated with CRVO and BRVO
other to 1 mg or 4 mg of triamcinolone Study Design
Eligibility/Exclusion • The COMS is a set of long term, Study Design
Age >=18 years, study eye with best multicenter, randomized controlled trials. In Multicenter, randomized, phase 3 trial. Eligible
corrected E-ETDRS acuity >24 letters (20/320 the trial for patients with tumors of medium Study patients within each of these 2 disease
or better) and <68 letters (worse than 20/40), size, enucleation and irradiation with an Intravitreal Steroid Injection Study Trials entities are randomized in a 1:1:1 ratio to
study eye with center-involved DME present iodine-125 episcleral plaque are compared on (ISIS) 1 of 3 groups: standard care, intravitreal
on clinical exam and on OCT, mean retinal the basis of length of remaining life injection(s) of 4 mg of triamcinolone
thickness on 2 OCT measurements >250 Sponsor acetonide, or intravitreal injection(s) of 1 mg
• All randomized patients will be followed for Illinois Retina Associates, S.C
microns in the central subfield, fellow eye 5-15 years or until death of triamcinolone acetonide. Enrolled patients
either eligible or has acuity >19 letters (20/ • For patients randomly assigned to Study Purpose are followed for 3 years. The preparation of
400 or better) has not been previously treated enucleation, the eye was removed following a • Series of five separate prospective FDA and triamcinolone acetonide used in the study is
with intravitreal corticosteroids standard procedure IRB approved studies designed to determine specially made for injection into the eye and
Number of Patients • For patients assigned to plaque radiation, if there is a possible role for intravitreal steroid does not contain any preservatives
795 the margins of the tumor were located and injections in the management of refractory Eligibility/Exclusion
the dimensions of the tumor were measured macular edema secondary to DME, BRVO, Participants with macular edema associated
Participating Centers CRVO, JRT and post-op CME
1 by the ophthalmic surgeon with CRVO and BRVO who are 18 years
• A gold plaque with a plastic seed carrier Study Design of age or older and are willing to provide
Results This is a pilot study. Subjects are randomized
that contained the proper dosage and consent. Detailed Inclusion/Exclusion Criteria
Pending to either 2mg or 4mg dose of intravitreal
configuration of radioactive iodine seeds was are available on the SCORE Web site at http:
sutured to the outside (sclera) of the eye over Kenalog® injection //spitfire.emmes.com/study/score/.
the base of the tumor Number of Patients Enrolled Number of Patients
• This procedure made possible the delivery 30 per treatment group 1260 total; 630 with CRVO and 630 with
Study of a high does of radiation to a very localized Eligibility/Exclusion BRVO
Laser Photocoagulation for DME area (85 Gy [TG-43] to the tumor apex) • Persistent macular edema due to Participating Centers
Sponsor • The plaque typically was removed from the • Diabetic Retinopathy (DR) 27
Diabetic Retinopathy Clinical Research eye after three to seven days. • Branch Retinal Vein Occlusion (BRVO)
Network (DRCR.net) and National Eye • Central Retinal Vein Occlusion (CRVO) Results
Number of Patients Enrolled Pending
Institute 1317 • Irvine-Gass Syndrome
Status Follow Up Results
Recruiting Patient f/u ongoing in the trial of radioactive DME arm of study has completed enrollment.
Study Center
Joslin Diabetes Center. Beetham Eye
plaque
Eligibility/Exclusion
Results are pending. Remaining arms are still
enrolling. UVEITIS
Institute, 1 Joslin Place, Boston, MA 02215 • Men and women eligible for the study had
Study Chairman to be age 21 or older, have primary choroidal
Lloyd P. Aiello, MD, PhD melanoma in only one eye, and have no
evidence of metastatic disease. Study Study
Study Purpose Randomized Trial of Acetazolamide for
Compare standard laser treatment with • Accurate estimation of tumor thickness by European Arteriovenous Sheatotomy Trial
echography also was required (EAST) Uveitis-Associated Cystoid Macular
mild, macular-grid treatment that is milder Edema (CME)
in intensity, but more extensive in number of Participating Centers Sponsor
40 Not available Sponsor
laser burns
NEI/NIH
Study Design Results Study Purpose
• Nonrandomized Small Tumor Pilot Study: • To compair the efficacy of surgical arterio- Study Purpose
Pilot Study. One eye eligible: randomization,
the treatment and mortality results of the venous decompression with the natural cause To test the efficacy of acetazolamide for
1:1, standard/mild macular grid. Both
COMS Nonrandomized Small Tumor Pilot in patients with BRVO the treatment of Uveitis Associated Cystoid
eyes eligible: 1 eye randomized to 1 of the
Study were reported in 1997. From 12/86 Macular Edema (CME)
treatments, the other eye randomized to the Study Design
to 8/89, 204 patients with small choroidal Study Design
other treatment • A prospective, randomized multicenter trial,
melanoma, defined as 1.0 to 3.0 mm in apical • This is a double masked randomized
Eligibility/Exclusion including 216 patients (108 receive vitrectomy crossover trial designed to test the efficacy
Age >=18 years, study eye with best height and at least 5.0mm in basal diameter, AV-decompression no ILM-peeling; 108
were enrolled in a prospective follow up of acetazolamide compared with a placebo
corrected E-ETDRS acuity >19 letters (20/400 observation). If the hematocrit is >40% an for the treatment of uveitis associated cystoid
or better), definite retinal thickening due to study. The median length of f/u was 92 optional isovolemic hemodilution may be
months. 8% of patients were treated at the macular edema
diabetic macular edema optional performed. • Randomized adult patients received either
time study enrollment and an additional 33%
Number of Patients Eligibility/Exclusion oral acetazolamide socium 500 mg or a
were treated during f/u. Based on 27 deaths,
Approximately 200 patients Patients with BRVO, onset < 3 months, matched placebo every 12 hours for the first
the Kaplan-Meier estimate of 5 year all cause
Participating Centers ETDRS VA< 20/50, no previous treatment 4 weeks of the study
mortality was 6.0% (95% confidence interval,
71 2.7% - 9.3%) and 8-year all cause mortality Results • Children 8 years of age or older received a
Results was 14.9% (95% confidence interval, 9.6%- Pending lesser dose based on body weight. Following
pending 20.2%). Mortality findings and analysis of a 4 week period, during which no medication
predictors of growth have been published was given, patients then received a 4 week
(COMS reports no. 4 and 6) course of the opposite medication
• Primary end points included reduction
of Cystoid Macular Edema (graded on
fluorescein angiography) and improvement

26 retina times
in visual acuity (measured on standardized segment of the eye, a sight-threatening Eligibility/Exclusion Study Chairman
ETDRS charts) inflammatory disease that primarily afflicts Males and females age 13 years and older Earl A. Palmer, MD, Chairman
• Acuity was also assessed as a secondary people between the ages 20 and 50, during with diagnosis of AIDS will be eligible. Casey Eye Institute
outcome variable. their prime working years. Participating Centers Oregon Health & Science University
• Adverse effects of the acetazolamide 19 3375 S.W. Terwilliger Boulevard
therapy were monitored by clinical and FDA approval of the single-indication orphan Portland, OR 97239-4197
Results
laboratory technicians drug was based on 34-week results from Pending Study Purpose
Eligibility/Exclusion two three-year randomized, double-masked, • To determine the safety and efficacy of
Eligibility: multicenter clinical studies demonstrating trans-scleral cryotherapy of the peripheral
• Males and females 7 years of age and older, that in eyes with Retisert there was: retina in certain low birth-weight infants with
weighing at least 35kg were eligible for the • a statistically significant decrease in the retinopathy of prematurity (ROP) for reducing
recurrence of uveitis from approximately Study
study blindness from ROP.
40% to 54% for the 34-week period pre- CMV Retinitis and Viral Drug Resistance
• Patients had to have at best a corrected • To determine the long-term outcome for
implantation to approximately 7% to 14% for (CRVR)
visual acuity of 20/40 or worse in one eye eyes that had severe (“threshold”) ROP, both
with Cystoid Macular Edema demonstrable the 34-week period post-implantation; Sponsor with and without cryotherapy.
on FA • a statistically significant decrease in the National Institute of Health
Study Design
• Patients were allowed to receive systemic use of adjunctive therapy including systemic Study Purpose The randomized, controlled, single-blind,
therapy for their uveitis corticosteroid and/or immunosuppressive • To determine the incidence and prevalence multicenter trial of cryotherapy for ROP
Exclusion: therapy from approximately 47% to 63% at of CMV drug resistance in patients with AIDS enrolled more than 4,000 premature infants
• Current use of acetazolamide as part of a the time of implantation to approximately 5% and CMV retinitis who weighed no more than 1,250 grams
therapeutic regimen to 10% at 34 weeks post-implantation, and • To determine risk factors for the at birth. The eyes of the infants enrolled in
• A history of hypersensitivity reactions to for patients needing periocular corticosteroid development of resistance, clinical correlates the study were examined at predetermined
acetazolamide, sulfonamide, or angiography injections from approximately 50% to 65% of viral drug resistance, phenotype-genotype intervals while the subjects were still in
dye for the 34 week period pre-implantation to correlation, ocular blood CMV correlations the intensive care nursery. After the pupils
• Unclear ocular media that would obscure approximately 3% to 6% for the 34 week and determination of blood PCR and CMV were dilated with eye drops, the eyes were
FA period post-implantation; viral load resistance correlations examined by an ophthalmologist using
• Macular subretinal neovascularization or a • statistically significant improvement of three Study Design a binocular indirect ophthalmoscope to
macular hole or more lines of visual acuity in approximately Prospective, cohort clinical trial visualize the developing retina. The natural
• Inability to take acetazolamide for medical 19% to 21% of study eyes at 34 weeks post- history of the condition of each infant’s retina
implantation. Eligibility/Exclusion
reasons • Inclusion: newly diagnosed CMV retinitis not was recorded. When examination disclosed
Results previously treated, confirmed HIV diagnosis the severe form of ROP (threshold ROP) in
The most common adverse events include both eyes, and the parents gave informed
Thirty-seven patients completed the trial • Exclusion: treatment of extraocular CMV
cataract progression, which is managed consent, one of the infant’s eyes was
and were available for analysis. Seventeen within the past 28 days, subjects under 18
by standard cataract surgery; increased randomly selected to receive cryotherapy.
patients (46 percent) were randomized to years of age
intraocular pressure, which is managed with
receive acetazolamide and 20 (54 percent) to Results
the use of IOP-lowering eye drops or filtering Outcome of the therapy was assessed
receive placebo during course A. Visual acuity Pending
surgery; and procedural complications and at 3 months and 12 months following
data were available for all 37 patients for all
eye pain. randomization by an extensive examination
visits. Fluorescein angiography data were
available for 145 of the 148 study visits (98 that included photography of the interior
percent). Acetazolamide therapy resulted in of both the treated and the control eyes.
0.5 disc area (25 percent) decrease in cystoid Study The 12-month exam also measured visual
macular edema over that of placebo (p = Study A Pilot Study of a Sustained Release function with preferential-looking techniques.
0.01; estimated treatment effect = -0.5 disc Longitudinal Study of Ocular Cyclosporine-A Implant for Uveitis Neither the trained photograph readers who
areas, 95 percent confidence interval [-0.9, Complications of AIDS (LSOCA) Sponsor evaluated the pictures from both eyes nor the
-0.1]). In contrast, there was no statistically Sponsor National Eye Institute 98-EI-0110 specially trained vision testers knew which
significant effect of acetazolamide on visual National Eye Institute Study Purpose eyes had received cryotherapy. Additional
acuity (p = 0.61; estimated treatment effect Status Cyclosporine is a medication that is useful assessments of visual acuity and retinal
= 0.6 letters, 95 percent confidence interval Recruiting for treating patients with inflammation in the status have been made approximately each
[-2, 3]). Possible adverse drug reactions were eye (uveitis) year through age 10, with a final examination
Patient Accrual Date
reported by 34 of the 37 (92 percent) during Study Design at age 15 for patients in the randomized trial
Contact chairman’s office
acetazolamide therapy. In contrast, at least Patients with active uveitis and poor vision of cryotherapy who did not have bilateral total
one adverse drug reaction was reported Study Center retinal detachment and blindness.
Curtis Meinert, PhD; Dept. of Epidemiology, in one eye will receive a surgically place
in only 5 of 37 patients (14 percent) during cyclosproine implant that will release the Number of Patients Enrolled
placebo therapy. School of Hygiene & Public Health; JHU, 615
medication into the eye 4099
N. Wolf Street, #5010; Baltimore, MD 410-
955-8198 Eligibility/Exclusion Follow-up
Acetazolamide therapy results in a 15 years
Study Chairman Not available
statistically significant but small decrease
in cystoid macular edema in patients with Douglas Jabs, MD, MD/ 410-955-1966 Results Eligibility/Exclusion
chronic uveitis but does not improve visual Pending Premature infants of either gender who were
Study Purpose
acuity. Since acetazolamide is associated eligible for the natural history study had
• CMV retinitis and other ocular
with a number of adverse effects, patients weighed less than 1,251 grams at birth and
complications of AIDS
should be closely monitored and the drug had survived the first 28 days of life. They
• To determine the effect of highly active anti-
discontinued if no therapeutic benefit is retroviral therapy (HAART)-induced immune ROP had no major ocular or systemic congenital
anomalies. Infants who met these criteria and
documented. status on the risk of developing CMV retinitis
also had a threshold level of ROP (defined as
and other ocular complications of AIDS
stage 3+ of the International Classification
• To determine the characteristics (clinical,
of Retinopathy of Prematurity occupying five
virologic, hematologic, and biochemical) of a Study or more contiguous or eight cumulative 30°
Study population at high risk for CMV retinitis and Cryotherapy for Retinopathy of sectors [clock hours] of stage 3 ROP in zone
A Multicenter, Randomized, Double other ocular complications of AIDS Prematurity (CRYO-ROP) - Outcome I or II in the presence of plus disease) could
Masked, Controlled Study to Evaluate • To evaluate the effects of treatments for Study of Cryotherapy for Retinopathy of be referred for examination to determine
the Safety and Efficacy of a Fluocinolone CMV retinitis and other ocular complications Prematurity eligibility for entry to the cryotherapy trial.
Acetonide (0.5 or 2.0 mg) Implant in on visual function, quality of life, and survival. Sponsor
Patients with Non-Infectious Uveitis Participating Centers
Study Design National Eye Institute
Affecting the Posterior Segment of the Eye 23
• The longitudinal study of ocular Status
Sponsor complications of AIDS (LSOCA) is Results
Ongoing. Comments: The 15-year
Bausch & Lomb, Inc. prospective observational study of patients The Cryotherapy for Retinopathy of
examination period has ended, and study
with AIDS Prematurity Cooperative Group reported
Study Purpose centers are closed. Currently, data from this preliminary results in 1988. This study
To evaluate the safety and efficacy of an • Patients with prior diagnosis of AIDS final study examination are being analyzed
according to the 1993 CDC criteria with or registered 9,751 infants with birth weights
intravitreal Fluocinolone Acetonide (0.5 or 2.0 to determine if the benefits of cryotherapy
without ocular complications will be enrolled less than 1,251 grams at 23 study centers.
mg) implant in patients with non-infectious are sustained in adolescence, when late
over a 4 year period Of these infants, 4,099 were systematically
uveitis affecting the posterior segment of structural complications and loss of visual
• Approx. 2000 patients will be enrolled in examined. The defined threshold severity of
the eye acuity have been reported to occur. A
the study. enrollments of patients with CMV ROP developed in 291 infants.
Study Design comparison will be made between treated
retinitis at baseline will be between 300 and and untreated eyes for many conditions,
A 3 year, multi-center, randomized, double- Cryotherapy was performed in half the
600 patients such as late retinal detachment, macular
masked, controlled, safety and efficacy study eligible eyes of the 291 infants. Twelve
• Follow up visits for patients with ocular degeneration, and vision failure. This
comparing 2 does levels of Fluocinolone months after randomization, the results of
complications at baseline or diagnosed information will be used for evaluating
Acetonide (0.5 or 2.0mg) in intravitreal masked grading of fundus photographs of
during follow up will be every 3 months the overall outcome for these teenagers.
implants the posterior pole indicated an unfavorable
• Follow up data will include eye A manuscript reporting the results of this
Eligibility/Exclusion examinations, fundus photographs, visual outcome in 25.7 percent of the eyes that had
examination is in process.
Patients with non-infectious uveitis affecting function testing, medical history, hematology, received cryotherapy and in 47.4 percent of
the posterior segment of the eye will be Patient Accrual Date the control eyes. Masked Teller Acuity Card
and serum chemistry, and collection of
enrolled No longer recruiting. Comments: assessment of grating acuity indicated an
plasma and blood cells for banking
Recruitment, which began in January 1986, unfavorable functional outcome in 35 percent
Results • Analysis of banked specimens will include
was stopped January 22, 1988. of the treated eyes, compared with 56.3
The U.S. Food and Drug Administration has HIV RNA levels and CMV DNA levels
approved the single-indication orphan drug Study Center percent of the control eyes. These results
Number of Patients Enrolled
Retisert™ (fluocinolone acetonide intravitreal Robert J. Hardy, PhD, Principal Investigator indicate that cryotherapy reduces the risk of
Ongoing
implant), 0.59 mg, for the treatment of chronic School of Public Health unfavorable retinal and functional outcome
Follow Up University of Texas-Houston Health Science from threshold ROP.
non-infectious uveitis affecting the posterior Not available Center
Coordinating Center for Clinical Trials
1200 Herman Pressler Street, E827
Houston, TX 77030

retina times 27
>> RETINAL RESEARCH REPORT

Although the surgery was stressful, no speed (enlarged text). Other baseline data where the observation group lost a median of Study
major complications occurred during or recorded include stereoscopic color fundus 5 points (CI: −5 to 0), and the surgery group Lutetium Taxaphyrin (LuTex/Optrin) in
following treatment. Physicians’ diagnoses photographs, fluorescein angiograms, and gained a median of 5 points (CI: 0–10) by 2 Age-Related Macular Degeneration (Phase
and the unbiased photograph gradings lens photographs, as well as health- and years. Treatment differences in median 2-year I Studies)
were statistically similar. These data support vision-related quality of life interview data (by changes in NEI-VFQ scores favored surgery Sponsor
the efficacy of cryotherapy in reducing by telephone). by up to 10 points for unilateral cases and up Alcon Research; South Freeway Drive; Ft.
approximately one-half the risk of unfavorable • Eligible patients who gave signed, to 8 points for bilateral cases. No treatment Worth, TX 817-615-2583
retinal outcome from threshold ROP. informed consent were randomly assigned difference in 2-year change was observed Study Purpose
to surgery (within 8 days of randomization) for the SF-36 physical component summary; • To evaluate the safety and efficacy of
Results at 31⁄2 years and 51⁄2 years following or observation. Patients, assigned to 2-year change in the mental component Lutetium texaphyrin combined with light
randomization continue to support the long- surgery, are seen one month post-surgery summary favored surgery by 2 points. Few laser treatment for the occlusion of abnormal
term efficacy and safety of cryotherapy in for an examination and photographs. All patients (2%–4%) had HADS definite anxiety vessels and membranes in people with AMD
the treatment of severe ROP. However, the participants are examined at 3, 6, 12, 24, 36, or depression at baseline or at 24 months. and CNV (CNV-abnormal growth of new
51⁄2-year data suggested that cryotherapy and 48 months after randomization to collect Although HRQOL outcomes were better blood vessels) for whom traditional heat laser
could reduce the chance of normal vision vision data (collected in a masked fashion at in the submacular surgery arm than in the therapy is not an option, or who have refused
in some cases. Findings from the 10-year 24 and 48 months after randomization) and to observation arm, surgery (per protocol) is the recommended heat laser therapy
examination showed fewer unfavorable repeat photography. Quality of life telephone not recommended because VA outcomes
outcomes for both visual acuity and structure interviews are repeated at 6, 12, 24, 36, and (reported elsewhere) were similar in the Study Design
in treated vs untreated eyes. The examination 48 months after randomization. treatment arms. • Multicenter, dose ranging, prospective, non
at age 10 included measurement of contrast • The primary outcome is improvement in randomized clinical study
sensitivity and visual fields. Results of visual acuity from baseline to the two-year • Patients with AMD will be entered and
contrast sensitivity testing demonstrated examination or retention of baseline visual evaluated in 2 phase I and IB studies
no evidence of adverse treatment effects acuity through the two-year examination. • The first trial involves a dose and light
Study ranging study to evaluate the utility of
in eyes that received cryotherapy. The Secondary outcomes include change in Anecortave Acetate in Age-Related
findings for visual field testing with Goldmann quality of life from baseline to the 2- and lutetium taxaphyrin as an imaging and
Macular Degeneration photodynamic therapy agent in choroidal
Perimetry showed a visual field area that was 4-year examinations, change in visual acuity Sponsor neovascularization
24 percent to 26 percent larger in treated over 4 years, large losses of visual acuity, Alcon Research; South Freeway Drive; Ft. • Second study will evaluate lutetium
eyes versus untreated eyes, when blind and adverse ocular outcomes (e.g., those Worth, TX 817-615-2583 taxaphyrin as an imaging agent alone,
eyes were included and assigned a score requiring additional treatment such as
of 0. When blind eyes were excluded, visual cataract, retinal detachment, or recurrent Study Purpose with subsequent therapy with standard
field area was 5 percent smaller for treated CNV). This study is an evaluation of the safety thermal photocoagulation or verteporfin
eyes than for untreated eyes, indicating that and duration of efficacy of Anecortave photodynamic therapy
Eligibility/Exclusion
cryotherapy slightly reduces the visual field Acetate sterile suspension (30mg, 15mg, Eligibility/Exclusion
• Group B: Patients with evidence of large
area in eyes with severe ROP. This small or 3mg) versus placebo after a single Not available
hemorrhages from subfoveal neovascular
reduction in visual field area in treated eyes (subtenon) injection for the inhibition of Results
AMD lesions, visual acuity (SST protocol)
is minor when compared with the much neovascularization in patients with exudative Pending
of 20/100 to light perception, with the
greater risk that an eye will be blind without Age-Related Macular Degeneration following
area of hemorrhage larger than the area of
treatment. However, this and any other laser treatment of extrafoveal or juxtafoveal
fluorescein angiographically visible CNV, with
possible adverse side effects are important neovascular membranes.
any visible CNV < 9 MPS disc areas, and
considerations in determining whether to treat ability to return for 4 years of follow up may Study Design Study
milder cases of ROP that have a relatively be eligible for the Group B (Blood) protocol. Dose duration study A Phase I, Open-Labeled, Randomized
good prognosis for vision without treatment. • Group N: Patients with new CNV (no Eligibility/Exclusion Study of the Safety, Tolerability, and
prior laser) due to AMD, visual acuity (SST • AMD with lesion 12 disc areas or less and Pharmacokinetics of Escalating Multiple-
Cryotherapy is now recommended for protocol) of 20/100 to 20/800, fluorescein 50% or more of the total lesion with choroidal dose Intravitreal Injections of RhuFab
both eyes whenever stage 3+ retinopathy angiographic evidence of subfoveal CNV neovascularization (CNV), and either the V2 in Subjects with Neovascular AMD
of prematurity involves the posterior retina lesion which is < 9 MPS disc areas, and classic component is 50% or more of the (FVF2425G Study)
(zone I) of both eyes and for both eyes (in ability to return for 4 years of follow up total CNV or the classic component of the
most patients) in cases of threshold ROP in Sponsor
may be eligible for the Group N (New CNV) CNV is > 0.75 DA in total size Genentech, Inc. 888-662-6728
zone II. There are, as yet, insufficient data to protocol. • Visual Acuity:
mandate cryotherapy in any method different • Group H: Patients with evidence of CNV • ETDRS vision in the study eye = Log Study Purpose
from the one used in this trial, or to apply it to due to OHS or idiopathic cause, visual acuity MAR~0.0 • To investigate the safety and tolerability
patients with less severe disease. Following (SST protocol) 20/50 to 20/800, fluorescein 0.9 (20/20-20/160) of recombinant humanized anti-VEGF
the publication of the positive results of angiographic evidence of subfoveal CNV • ETDRS vision in the non study eye = monoclonal antibody fragment (RhuFab
this study in 1988, the U.S. pattern of care lesion (new or recurrent) which is < 9 MPS Log MAR V2) administered as multiple, intravitreal
changed rapidly to embrace these guidelines disc areas, and ability to return for 4 years of 1.6 (20/800) or better injections up to a final dose of 2mg
as standard practice. follow up may be eligible for inclusion in the Study Design
Results • This phase I, multicenter, randomized
Group H (Histoplasmosis/Idiopathic CNV) Outcomes following anecortave acetate
Laser therapy has been shown to have similar protocol. trial enrolled 30 patients into three dosing
injection were compared with outcomes regimens.
value to cryotherapy. Currently the risk data • Exclusion criteria include other ocular without anecortave acetate treatment. 73
from the CRYO-ROP study are being used diseases compromising vision, history of • All patients were treated for a total of 16
percent of patients treated with anecortave weeks and followed through 20 weeks.
to test the value of ealier interventions in submacular surgery in the study eye, history acetate 15 mg had stable or improved vision
selected high risk eyes, in the Early Treatment of subfoveal laser photocoagulation that • Group 1 received escalating doses from
from baseline to 24 months after treatment, 300µg to 1.0mg every 2 weeks over 6 weeks
for ROP study (ETROP). extends under the foveal avascular zone, significantly more than the 47 percent of
recent intraocular surgery, or previous followed by 1.0mg of RhuFab V2 every 4
patients in the placebo group who did not weeks.
investigational therapy for CNV. receive anecortave acetate (p=0.035). • Group 2 received escalating doses from
Results
AMD Of 454 patients enrolled, 228 study eyes Patients treated with anecortave acetate 15
300µg to 2.0mg every 2 weeks over 14 weeks
followed by a final 2mg dose at week 16.
were assigned to observation and 226 to mg had no increase in growth of the classic • Group 3 received escalating doses from
surgery. The percentages of eyes that had component of the subfoveal choroidal 300µg to 2mg every 4 weeks over 16 weeks.
successful outcomes were similar in the 2 neovascular membrane (CNV) between • All patients underwent ETDRS visual acuity
Study arms: 44% assigned to observation and months 12 and 24, and the total lesion size testing, ophthalmological examination, and
Submacular Surgery Trials (SST) 41% assigned to surgery. Median VA losses remained stable over this period. Additionally, adverse event assessment at each study
Sponsor from baseline to the 24-month examination at 24 months, in the sub-group of patients visit, with fundus photography, fluorescein
NEI were 2.1 lines (10.5 letters) in the observation with the more aggressive, predominantly angiography, OCT, and pharmacokinetic
arm and 2.0 lines (10 letters) in the surgery classic CNV lesions, no patients treated evaluations at selected visits.
Study Purpose
arm. Median VA declined from 20/100 at with anecortave acetate 15 mg had severe
• To determine whether surgical removal of Eligibility/Exclusion
baseline to 20/400 at 24 months in both vision loss (> 6 lines loss) compared to a 23
subfoveal choroidal neovascularization (CNV) • Inclusion: active subfoveal CNV, visual
arms. No subgroup of patients was identified percent rate in the placebo group, (p=0.023).
and associated hemorrhage in patients with acuity in the study eye of 20/40 to 20/400 and
in which submacular surgery led to better VA The U.S. Food and Drug Administration
Age-Related Macular Degeneration (AMD), better or equal to 20/800 in the fellow eye,
outcomes. In the surgery arm, 55 (39%) of (FDA) issued an approvable letter for its New
the Ocular Histoplasmosis Syndrome (OHS), age >50 years old;
142 initially phakic eyes had cataract surgery Drug Application (NDA) for Retaane(R) 15
or idiopathic CNV stabilizes or improves • Exclusion: more than 3 prior treatments with
by the 24-month examination, compared mg (anecortave acetate suspension) in May,
vision more often than observation. Visudyne in the study eye within 12 months,
with 6 (5%) of 133 eyes in the observation 2005.
• To determine how surgical removal lesions larger
arm. Rhegmatogenous retinal detachment
compared to observation of subfoveal Participating Centers
occurred in 12 surgery eyes (5%) and 1
CNV due to AMD, OHS, or idiopathic Multicenter
observation eye. Submacular surgery, as
causes changes the patient’s perception of Results
performed in this clinical trial, did not improve Study
health- and vision-related “quality of life,” as • Twenty-one of the 30 patients were enrolled
or preserve VA for 24 months in more eyes Indocyanine Green (ICG) Risk Factors for
measured by telephone interview using the at the Bascom Palmer Eye Institute; Group1
than observation and is not recommended for Choroidal Neovascularization
Medical Outcomes Survey Short Form-36 (n=5), Group 2 (n=8), and Group 3 (n=8).
patients with similar lesions. Sponsor
(MOS SF-36) instrument, the Hospital Anxiety • The types of subfoveal CNV lesions
and Depression Scale, and the National Eye Macula Society; Scheie Eye Institute, enrolled included occult CNV with no
Of 454 patients enrolled, 228 were assigned Philadelphia, PA
Institute Visual Function Questionnaire (NEI classic CNV (n=6), minimally classic CNV
to observation and 226 to surgery. At
VFQ-25). Study Purpose (n=6), predominantly classic CNV (n=2),
baseline, median overall NEI-VFQ scores
• To determine whether randomized trials • To determine risk factors of ICG for CNV predominantly classic CNV after PDT (n=4),
were 67 in the observation group and 69 in
of surgery are warranted for patients with Study Design and CNV with RPE tears (n=3).
the surgery group; by 2 years, the observation
subfoveal CNV associated with Age-Related Not available • Intravitreal injections as frequent as every 2
group had lost a median of 3 points (95%
Macular Degeneration not suitable for laser weeks were well tolerated by the patients.
confidence interval [CI]: −6 to −2), and the Eligibility/Exclusion
treatment. • The most frequent adverse event was mild
surgery group gained a median of 1 point (CI: Not available
Study Design −1 to 3). The largest difference was observed inflammation.
• Vision data collected at baseline include a Results
for the mental health subscale, • Significant intraocular inflammation was
protocol refraction, best-corrected logMAR Pending
not observed when RhuFab was escalated
visual acuity (ETDRS charts), contrast from an initial dose of 300µg to doses as
threshold (Pelli-Robson charts), and reading

28 retina times
high as 2mg. At week 20 (Day 140), 19 of the recent disease progression, and baseline Study at the same visit and prior to the posterior
21 patients (90%) had stable (± 4 letters) or best-corrected visual acuity (approximate Multicenter Investigation of Rheopheresis juxtascleral inject a sham PDT treatment
improved (> 5 letters) vision with 11 patients Snellen equivalent) 20/50-20/200. for Age-Related Macular Degeneration • Patients randomized to PDT with Visudyne
(52%) gaining at least 3 lines (15 letters). • Verteporfin therapy was administered at (MIRA-1) will also receive at the same visit following the
• Stable and improved visual acuity baseline, with the option of an additional Sponsor PDT treatment a sham posterior juxtascleral
correlated well with decreased fluorescein treatment at month 3, 6, and 9 if there was OccuLogix; 2575 Ulmerton Road, suite 210; injection
angiographic leakage and decreased retinal evidence of fluorescein leakage from CNV Clearwater, FL 33762; 727-561-4181 Eligibility/Exclusion
thickness measured by OCT. • Best-corrected visual acuity, color Status Eligibility:
fundus photography, and fluorescein and Ongoing • Lesion area less than or equal to 5400
Indocyanine Green (ICG) angiography were microns in GLD; 50% or more of the total
assessed at scheduled follow up visits Patient Accrual Date
Not available lesion is CNV; the classic component of the
Study through month 6 total CNV must be at least 50% of the total
A Phase III, Multicenter, Randomized, • Potential treatment benefit was assessed Study Center lesion
Double-Masked, Sham Injection- based on angiographic outcomes and visual OccuLogix, Inc. Exclusion:
Controlled Study of the Efficacy and Safety acuity change from baseline Study Chairman • Ophthalmic disease in the study eye that
of rhuFab V2 (Ranibizumab) in Subjects • Safety was assessed by evaluating Not available would compromise visual acuity
with Minimally Classic or Occult Classic adverse events, visual acuity, color Study Purpose • Previous PDT treatment, previous laser
Subfoveal Neovascular AMD (FVF2598G fundus photographs, fluorescein and ICG This study is designed to determine if the photocoagulation is allowed if performed 30
Study - MARINA) angiograms removal of LDL cholesterol and other harmful days before enrollment
Sponsor Eligibility/Exclusion substances from the blood will improve vision • Patient has scleral buckle in the study eye
Genentech, Inc. 888-662-6728 Inclusion: in people with Dry AMD • Patient is on anticoagulant therapy, with the
• Subfoveal CNV, occult CNV with no classic Study Design exception of aspirin and anti-platelet therapy
Status
CNV • At entry, patients undergo a complete Results
Actively enrolling
• Vision 20/40-20/200 ocular and physical examination, including a There was no statistical difference between
Study Center • Recent progression of disease series of baseline blood tests the anecortave acetate treatment and the
Genentech, Inc., 1 DNA way, South San Exclusion: • Patients will be randomly assigned to PDT treatment outcomes regarding the
Francisco, CA 94080-4990 • Lesions larger than 9MPS DA one of two study treatment groups: the primary endpoint of loss of fewer than 3 lines
Study Chairman • Cataract surgery within previous 3 months Rheopheresis treatment group (120 patients) of visual acuity. Forty-five percent of the
Robert Y. Kim, MD, Genentech Results or placebo treatment group (60 patients) patients in the anecortave acetate group had
Study Purpose • Most baseline characteristics did not • The design is single masked with a 2: less than a 3-line loss of visual acuity, and
• To investigate the efficacy, safety, and appear different between the two treatment 1 chance of being in the apheresis group. 49% of patients had less than a 3-line loss of
tolerability of monthly intravitreal injections of groups (median age 78, 42% men, median Patients undergo 8 treatments over a period visual acuity in the PDT group. The statistical
rhuFab V2 in preventing visual loss total lesion size 8.59 mm [approximately 4.85 of 2 1/2-months endpoint, however, was not reached
Study Design MPS DA] • Patients in the Rheopheresis treatment regarding non-inferiority of anecortave
• Phase III, multicenter, randomized pivotal • The baseline median visual acuity score group will have their blood pumped through acetate compared with PDT. Both groups had
study. was higher in the standard light application the filter system being investigated approximately the same number of adverse
• 1:1:1 Randomization: Sham injection: 300 group (58 letters vs. 52 letters [approximate • Patients in the placebo treatment group will ocular and systemic events.
micrograms rhuFab V2: 500 micrograms Snellen equivalent 20/64-2 vs. 20/100+2] as not have blood filtered. At each visit, patients’
RhuFab V2 by 24 monthly intravitreal measured by ETDRS criteria). vital signs will be recorded, and blood
injections • Angiographic and vision outcomes and samples obtained pre- and post- treatment
• All patients to receive ETDRS visual acuity safety results through 12 months showed no • Between the 4th and 5th treatments, two Study
testing, ophthalmological examination, statistically significant difference. weeks after the 8th treatment, and at 6, 9, A Phase II Multicenter Trial to Establish
and adverse event assessment at each and 12 months, patients will receive the same the Safety and Pharmacokinetic Profile
study visit, with fundus photography, blood tests and examinations performed at of Intravitreal Anti-VEGF Pegylated
fluorescein angiography, OCT, visual function entry Aptamer (EYE001) in Age-Related Macular
questionnaires and health surveys, and Study Number of Patients Enrolled Degeneration Undergoing Photodynamic
pharmacokinetic evaluations at selected Prophylactic Diode Laser Photo Approx. 200. Therapy
visits. Coagulation for the Prevention of Follow Up Sponsor
Number of Patients Enrolled Choroidal Neovascularization in Age- • In either of these groups, patients will Eyetech Pharmaceuticals, Inc.; 666 Fifth
Fully enrolled. 716 Related Macular Degeneration (PTAMD) undergo 8 treatments over a period of about Avenue;
Follow Up Sponsor 2-1/2 months 35th floor; New York, NY 10103; 212-582-
Ongoing University of Pittsburgh • Patients in the Rheopheresis treatment 8376
Eligibility/Exclusion Status group will have their blood pumped through Study Purpose
• Inclusion: active primary or recurrent Active the filter system being investigated • The primary objective of this study will be
subfoveal CNV lesions due to AMD with • Patients in the placebo treatment group will to evaluate the safety of 3 repeat doses of
Patient Accrual Date not have their blood filtered
occult or minimally classic CNV, CNV must be 3rd year of recruitment EYEO01 administered after photodynamic
50% of lesion GLD , total lesion < 12 MPS • At each visit, patients’ vital signs will be therapy.
Study Center recorded, and they will be asked to give
DA; visual acuity in the study eye of 20/40 • Secondary objectives include the evaluation
University of Pittsburg blood samples for complete testing prior to
to 20/320 of the pharmacokinetic profile, preliminary
• Exclusion: prior PDT, TTT, XRT, or other Study Chairman and immediately after each treatment, which efficacy, and patient’s immune response to
experimental CNV treatment. Previous Thomas Friberg, MD; U of Pittsburg; takes about 3 hours to complete EYEO01 when given as intravitreal injections
intravitreal drug delivery. Prior vitrectomy, Pittsburg, PA 412-647-7212 • Between the 4th and 5th treatments and (3mg/eye) once every 28 days for 3 doses in
submacular surgery, or other surgical Study Purpose two weeks after the 8th treatment, patients patients with the neovascular form of AMD.
intervention for AMD. Subfoveal atrophy • To determine whether a specific laser will come back to the clinic for a visit where Study Design
or fibrosis. Other cause of CNV. RPE tear. treatment will prevent individuals who have they will receive many of the same tests taken • This is a multi-center, open-label, repeat
Selected subfoveal hemorrhage ( 1 Disk area the less severe dry macular degeneration at the initial qualifying visit dose phase 18 study of 3mg/eye of EYEO01
or 50% of lesion) from progressing to the more severe wet form • There will be three more evaluations at following PDT, inpatients with choroidal
of macular degeneration approx. 6 months, 9 months, and 12 months subfoveal neovascular AMD with a visual
Participating Centers
Study Design • At those evaluations, the patients’ blood will acuity worse than 20/100 in the study eye or
Multicenter (100 sites)
• Bilateral Dry AMD patients with both eyes be tested and another complete set of ocular equal to 20/400 in the fellow eye.
Results examinations will be performed
eligible will have one eye randomized to laser • If 3 or more patients experience Dose-
Pending
treatment and the fellow eye assigned to Eligibility/Exclusion Limiting Toxicity (DLTs), the dose will be
observation Not available reduced to 2mg and 1 mg, if necessary in a
• Unilateral patients with only one eye eligible Participating Centers further 10 patients.
will have the eligible eye randomized to either Not available • Patient accrual into the trial is expected to
Study laser treatment or observation be completed within 2 to 3 months. Four to
Visudyne With Altered (Delayed) Light in Results
• Laser treatment consists of a grid of 48 Pending 10 sites in the U.S. will provide 1 to 8 patients
Occult CNV Study (VALIO) subthreshold (ophthalmoscopically invisible) per site.
Sponsor diode laser spots placed around the macula
QLT Inc/Novartis Ophthalmics, Inc Eligibility/Exclusion
Number of Patients Enrolled • Age-Related Macular Degeneration with
Study Purpose
150 Study subfoveal sub-retinal neovascularization.
• To determine the potential of delaying
light application to 30 minutes after Follow Up An Evaluation Of Efficacy And Safety • Visual acuity less than or equal to 20/80.
initiation of infusion to improve outcomes 5 yrs of Posterior Juxtascleral Injections of Results
of photodynamic therapy with verteporfin Eligibility/Exclusion Anecortave Acetate 15mg Versus Visudyne • 87.5% of patients who received the anti-
(Visudyne®, Novartis AG) in AMD patients • Inclusion: males and females, 50 yrs or in Patients with Subfoveal Exudative VEGF drug alone showed stable or improved
with occult with no classic CNV older, able to understand and give written Age- Related Macular Degeneration vision 3 months after treatment.
Study Design informed consent before treatment, vision (AMD) Eligible for Initial Treatment with • Vision improved by 3 or more lines in 25%
• AMD patients (>50 years of age) with 20/60 or better with at least 5 Drusen in each Photodynamic Therapy (PDT) Using of eyes that received this drug alone.
subfoveal CNV were randomized 1:1 to eye or 5 large Drusen in one eye with an Visudyne • However when combined with
receive verteporfin therapy with delayed event occurring in the other eye, no major Sponsor photodynamic therapy, many more eyes
light or verteporfin therapy with standard health problems Alcon Research; South Freeway Drive; Ft. (60% ) gained 3 or more lines of vision.
light application (15 minutes after initiation • Exclusion: worse vision than 20/60, event Worth, TX 817-615-2583
of infusion) or drusen, size/amounts, inhibiting health This study has reported short term (3 month)
Study Purpose results, which look encouraging. Further
• Patients were followed for at least 6 months factors To demonstrate that Anecortave Acetate is
after initial treatment. Inclusion criteria Participating Centers clinical trials are necessary to demonstrate
non-inferior after 12 months of treatment to the efficacy and long-term safety of anti-
comprised a lesion composition that was 13 PDT with Visudyne in patients eligible for
occult with no classic CNV, in which <50% VEGF therapy for wet macular degeneration.
Results initial PDT treatment No definitive conclusions regarding the
of the lesion area was CNV and in which Study Design
Pending
the greatest linear dimension of the lesion • Patients randomized to the Anecortave
was <5400 microns on the retina, presumed Acetate treatment group will also receive

retina times 29
>> RETINAL RESEARCH REPORT

efficacy of the drug can be deduced from this in Occult with No Classic Subfoveal Study Center or recurrent choroidal neovascular lesions
study because of the absence of a control Choroidal Neovascularization (CNV) Genentech, Inc., 1 DNA way, associated with AMD, subfoveal, or mostly
group, small sample size, and short follow-up Secondary to Age-Related Macular South San Francisco, CA 94080-4990 classic.
period. Phase II/III trials using this drug are Degeneration (VIO) Study Chairman • Visual acuity score by ETDRS chart> 39
presently underway to evaluate this potential Sponsor Robert Y. Kim, MD, Genentech, Inc. (Snellen equivalent of 20/160).
treatment in more than a 1000 patients in QLT Inc/Novartis Ophthalmics, Inc Study Purpose • Patients must not have other serious ocular
more than 100 centers worldwide. Study Purpose • To investigate the efficacy, safety, and diseases or conditions present.
To demonstrate that Visudyne therapy in tolerability of monthly intravitreal injections of • Patients must not currently be using
patients who have occult with no classic rhuFab V2 compared with verteporfin PDT systemic steroids or other drugs which may
subfoveal CNV lesions will, with an Study Design affect the macula.
Study acceptable safety profile significantly reduce • Phase III, multicenter, randomized pivotal • No unstable or severe concurrent medical
A Phase II/III Randomized, Double the risk of vision loss compared with placebo study. conditions or active uncontrolled infections
Masked, Controlled, Dose Ranging Multi Study Design • 1:1:1 Randomization : Sham injection: 300 present.
Center Comparative Trial , in Parallel • A randomized, placebo-controlled, double- micrograms rhuFab V2: 500 micrograms Results
Groups, to Establish the Safety and masked, multi-center, Phase III study rhuFab V2 by 24 monthly intravitreal Pending
Efficacy of Intravitreal Injections of • Patients stratified by study center and injections
EYE001 (Anti-VEGF Pegylated Aptamer) randomized to Visudyne therapy or placebo • Sham injection group to receive PDT, and
Given Every 6 wks to 54 wks, in Patients in a 2:1 ratio rhuFab injection groups to receive sham PDT
with Exudative Age-Related Macular Eligibility/Exclusion q3 months. Study
Degeneration (AMD) Eligible: • All patients to receive ETDRS visual acuity Women’s Health Initiative Sight
Sponsor • Must have occult with no classic subfoveal testing, ophthalmological examination, Examination Study (WHI-SE)
Eyetech Pharmaceuticals, Inc.; 666 Fifth CNV secondary to AMD BCVA between 73 and adverse event assessment at each Sponsor
Avenue; and 34 letters (approx. Snellen equivalent of study visit, with fundus photography, University of Michigan
35th floor; New York, NY 10103; 212-582- 20/40 to 20/200) fluorescein angiography, OCT, visual function
Status
8376 • GLD of entire lesions must no exceed 5400 questionnaires and health surveys, and
Recruitment ended
Status microns pharmacokinetic evaluations at selected visits
Patient Accrual Date
Ongoing • Must not have a CNV lesions size that is Number of Patients Enrolled
5/2000-12/2001
Patient Accrual Date >4 MPS disc areas, associated with a BCVA TBA. Target enrollment = 426
of >65 letters (approx. Snellen Equivalent of Study Center
TBA Follow Up
20/50 or better) Women’s Health Initiative Sight Examination
Study Center Ongoing
• Presumed recent progression of occult Coordination Center; 611 Church St, Ann
Eyetech Pharmaceuticals, Inc. Eligibility/Exclusion Arbor, MI 48104; 734-615-8190
CNV within the preceding 3 months before
Study Chairman • Inclusion: primary or recurrent subfoveal
randomization to treatment Study Chairman
Not available CNV lesions due to AMD eligible for PDT with
Exclusion: Dr. Mary Haan; University of Michigan, 734-
Verteporfin, >50% classic CNV, lesion GLD
Study Purpose • Any additional ocular disease that may 615-8190
<5400 microns; visual acuity in the study eye
To establish a safe and effective dose of compromise visual acuity in the study eye. Study Purpose
of 20/40 to 20/320, age >50 years old
EYEOO1. Patients will be randomized to • No previous PDT, m or other local treatment • To evaluate whether exogenous estrogen
• Exclusion: prior PDT, TTT, XRT, or other
intravitreal injections of either EYEO01 or in study eye use through hormone replacement therapy
experimental CNV treatment. Previous
placebo every 6 weeks Results can prevent incident cases of AMD, or slow
intravitreal drug delivery. Prior vitrectomy.
Study Design Pending Subfoveal atrophy or fibrosis. Other cause the progression of this disease in women
The study is a randomized, double-masked, of CNV. RPE tear. Selected subfoveal who already have AMD. To evaluate if
controlled, dose-ranging, multi-center hemorrhage (1 disk area or 50% of lesion) exogenous estrogen reduces the risk of late
comparative trial forms of age related maculopathy, including
Participating Centers
Number of Patients Enrolled Study geographic atrophy, retinal pigment epithelial
Multicenter (100 sites)
540 Photodynamic Therapy (Visudyne) Early detachments and choroidal neovascular
Results membranes
Follow Up Re-Treatment For Subfoveal Choroidal Pending
54 weeks Neovascularization (VER) Study Study Design
Sponsor • The WHI-SE study is an 8 year project
Eligibility/Exclusion
QLT Inc/Novartis Ophthalmics, Inc. and will involve 19 clinical centers across
Not available
the country to obtain eye exams on approx.
Participating Centers Study Purpose Study 5,000 women who are 65 years of age
Not available To determine whether early retreatment Limited Macular Translocation Study and older enrolled in the Women’s Health
Results with Visudyne therapy in patients with Sponsor Initiative’s main clinical trial of hormone
Pending predominantly classic subfoveal choroidal Pilot study - self funded replacement therapy
neovascularization secondary to AMD will
Study Purpose • The participants in this study are a
reduce the risk of vision loss
To determine whether translocation plus component of the larger clinical trial funded
Study Design by NIH, the Women’s Health Initiative
standard laser is better than PDT or
Study Multi-center, randomized, parallel group, observation alone Number of Patients Enrolled
A Phase I/II, Multicenter, Dose Escalation, double-masked, controlled phase III, 2 year
Study Design 4688 people participated in a baseline
Controlled Study of the Safety, Tolerability, study using standard treatment and an
Randomized, prospective, multi center study. examination done between 1998 - 2002
Pharmacokinetics and Activity of Multiple experimental retreatment schedule (as often
as every 1.5 months retreatment interval Patients randomized: Follow Up
Dose Intravitreal Injections of rhuFab V2 in • Translocation versus PDT -100 patients • The cohort may be reexamined if new
Subjects with Neovascular AMD (FVF2128g during the first 6 months)
• Translocation versus observation - 100 funding is received.
study) Eligibility/Exclusion patients. • The cohort is being reexamined (10 year
Sponsor Eligible: • Vision <20/40 to >20/800. follow-up), with approx. 3,000 participants
Genentech, Inc. 888-662-6728 • Subfoveal, predominantly classic CNV (area • Subfoveal, choroidal neovascularization expected to be seen
of classic> 50% area of entire lesion) I GLD
Study Purpose (classic, occult, both) • The 10-year examinations conclude on May
not to exceed 5400 microns BCVA between
• To investigate the safety and tolerability • CNV secondary to Age-Related Macular 31, 2000
20/40 and 20/200
of recombinant humanized anti-VEGF Degeneration Eligibility/Exclusion
Exclusion:
monoclonal antibody fragment (RhuFab • Inferior border of lesion 1000um or less • Only women who were enrolled in the WH1
• Any additional ocular disease that may
V2) administered as multiple, intravitreal from foveal center were eligible to participate in WHI-SE.
compromise visual acuity in the study eye
injections • Ages greater than 49 years. • Women in the study received Premarin or
• No previous PDT, or other local treatment
Study Design • > Light perception vision in fellow eye. Prempro, forms of estrogen, or a placebo
in study eye
• Phase I/II multi-center. Dose excalation Results sugar pill.
Results • In addition, women asked to:
controlled study Pending
Results from the Phase III early retreatment • Undergo a vision exam when enrolling
Eligibility/Exclusion (VER) study with Visudyne showed that the in WHI-SE and again in 3-4 years to check
• Inclusion: active subfoveal CNV, visual early retreatment regimen did not result in a visual acuity and to photograph the retina
acuity in the study eye of 20/40 to 20/400 and significant improvement in vision outcomes (require dilation)
better or equal to 20/800 in the fellow eye, over the standard retreatment regimen every Study
A Phase II, Multicenter, Randomized, • Complete two questionnaires on vision,
age >50 years old; 3 months. The data did reconfirm the vision history of eye disease and medication use
• Exclusion: more than 3 prior treatments benefits and safety shown in the original Double-Masked, Placebo Controlled
Study of the Matrix Metalloproteinase • Complete brief questionnaire on vision
with Visudyne in the study eye within 12 TAP or Treatment in Age-related macular each year between the two eye exams
months, lesions larger than 9MPS disc areas, degeneration with Photodynamic therapy Inhibitor AG3340 in Patients with Subfoveal
Choroidal Neovascularization Associated • Have blood collected for studies on the
cataract surgery within the previous 30 days, study. effect of diet and cardiovascular disease
current or recent use of oral or parental with Age- Related Macular Degeneration
on macular degeneration
anticoagulants or anti-platelets other than Sponsor
aspiring, ticlopididne, clopidogrel and/or Agouron Pharmaceuticals, Inc. Participating Centers
nosteroidal anti-inflammatory agents 15-20
Study Study Purpose
Results • This phase II clinical trial will assess the Results
A Phase III, Multicenter, Randomized,
Pending safety and efficacy of AG3340 (prinomastat) Currently pending funding to do follow-up
Double-Masked, Active Treatment-
in approx. 200 patients aged 50 years and exams.
Controlled Study of the Efficacy and Safety
of rhuFab V2 (Ranibizumab) Compared older affected with the neovascular form of
with Verteporfin (Visudyne) Photodynamic Age-Related Macular Degeneration (AMD)
Study Therapy in Subjects with Predominantly • To determine the optimal dose and regimen
A Randomized, Placebo Controlled, Classic Subfoveal Neovascular AMD to use in subsequent phase III trials.
Double Masked, Multi Center Phase III (FVF2587G Study - ANCHOR) Study Design
Study of the Effect of Visudyne Therapy Sponsor A phase II, randomized, double-masked,
Genentech, Inc. 888-662-6728 placebo-controlled, multicenter study.
Status Eligibility/Exclusion
Actively Enrolling • Patients age 50 years and older with new

30 retina times
Study (20/30 or better) are eligible for the study Study Study
Photodynamic Therapy (Visudyne) provided that their ocular media are clear Transpupillary Thermotherapy for Complications of Age-Related Macular
in Minimally Classic Subretinal enough to allow good fundus photography Choroidal Neovascularization Clinical Trial Degeneration Prevention Trial (CAPT)
Neovascularization (VIM) Study Results (TTT4CNV) Sponsor
Sponsor • AREDS researchers found that people at Sponsor National Eye Institute/NIH
QLT Inc/Novartis Ophthalmics, Inc high risk of developing advanced stages of Iridex, Inc.; 1212 Terra Bella Avenue; Status
Study Purpose AMD lowered their risk by about 25 percent Mountain View, CA 94043; 650-962-8840 Recruitment Completed
• To compare potential treatment benefit and when treated with a high-dose combination of Study Purpose Patient Accrual Date
safety of verteporfin (Visudyne, Novartis AG) vitamin C, vitamin E, beta-carotene, and zinc • To determine whether TTT is a safe and 5/1/99.
therapy and placebo for minimally classic • In the same high risk group -- which effective treatment for occult subfoveal
subfoveal CNV due to AMD using a standard includes people with intermediate AMD, or Study Center
choroidal neovascularization in AMD
light dose and one delivered with reduced advanced AMD in one eye but not the other Maureen Maguire, PhD; Director CAPT
Study Design
fluence rate eye -- the nutrients reduced the risk of vision Coordinating Center; 3535 Market Street,
• Prospective randomized multicentered
loss caused by advanced AMD by about 19 Suite 700; Philadelphia, PA 19104. 215-615-
Study Design clinical trial. 112 patients are observed,
percent 1531
• Patients (>50 years of age) with minimally 224 treated with TTT Outcome variable:
classic lesions of <6 MPS disc areas (DA) (1 • For those study participants who had either best corrected visual acuity pre and post Study Chairman
MPS DA=2.54mm2) in this double-masked no AMD or early AMD, the supplements did treatment, exudation measured by stereo Stuart Fine, MD; Scheie Eye Institute / 215-
study were randomized (1:1:1) to one of three not provide an apparent benefit. fundus photos and FA 662-8142
treatment groups: • In the cataract portion of the study, Eligibility/Exclusion Study Purpose
• (1) Verteporfin therapy with reduced light researchers discovered that the same • Inclusion: AMD, 50 yrs or older, visual • To determine whether application of low
fluence rate (300 mW/cm2) for 83 seconds nutrients had no significant effect on the acuity: 20/50 - 20/400 ETDRS, occult CNVM intensity laser treatment of eyes with drusen
(25 J/cm2); development or progression of age-related • Exclusion: prior retinal laser/surgery, ocular in the macula can prevent later complications
• (2) Verteporfin therapy with standard light cataract surgery within 3 months, medication toxic to of Age-Related Macular Degeneration and
fluence rate (600 mW/cm2) for 83 seconds Results retina, lens or optic nerve, glaucoma thereby preserve visual function
(50 J/cm2); Pending • Angiographic eligibility: total lesions Study Design
• (3) Placebo; half with reduced and half <3000mm (2DD) in diameter, CNV underlying • The CAPT is a multi-center, prospective,
with standard light fluence rate or surrounding center of macula, occult CNV randomized clinical trial designed to assess
• Fluorescein and ICG angiography and is required: late leakage or fibrovascular the safety and effectiveness of low intensity
best-corrected visual acuity were assessed Study PED, subretinal fluid or exudate is required; laser treatment in preventing vision loss
1 week after treatment in 10 patients from Randomized Trial of Beta-Carotene and if present, classic CNV if <10% of the lesion; among patients with large drusen in both
each group. Macular Degeneration if present, serous PED must be <25% of the eyes
• All patients were assessed at 6 weeks, 3 lesion; if present, subretinal hemorrhage must • Eligible patients will have one eye randomly
Sponsor
months, and 6 months after initial visit be <50% of the lesion; if present, subretinal assigned to laser treatment performed by
NEI
• Changes in total area of the lesion and fibrosis <25% of the lesion, cannot have CAPT-certified ophthalmologists. The other
individual components were assessed Status eye is not treated. Both eyes are observed
chorioretinal anastomosis, cannot have
through month 3 and change in visual acuity Ongoing; randomized treatment complete; carefully for any changes for a period of five
geographic atrophy >0.5 DA within 500mm of
from baseline was assessed at all visits collection of medical reports for reported years
the foveal center
• Safety was evaluated by adverse events, cases of AMD is continuing • The effectiveness of the treatment will be
Results
visual acuity, fluorescein angiograms, and Patient Accrual Date assessed using the following criteria:
Results confirmed that a subgroup of
color fundus photographs Recruitment for the Physicians Health Study • Change in visual acuity (primary
patients, who were enrolled into the study
Eligibility/Exclusion began in 4/82 and was completed in 12/84. outcome measure of the study), incidence
with baseline visual acuity of 20/100 or
• Minimally Classic CNV lesions secondary The randomized trial of beta-carotene and of complications of AMD such as
worse, benefited from TTT treatment. Within
to AMD macular degeneration began evaluating from neovascularization, serous detachment of
the TTT4CNV Clinical Trial, about 41% of
• Baseline VA between 20/40 and 20/200 that study in 1990 the pigment epithelium and geographic
the patients enrolled had baseline vision of
• Lesion size up to 4 DA Study Center 20/100 or worse. (Baseline vision means atrophy, changes in contrast threshold
Results Charles Hennekens, MD; Brigham & Women’s that was the vision the patient had when and critical print size for reading
• At baseline, main demographic variables Hospital; 900 Commonwealth Ave, E; he/she entered the study). Specifically, at • QOL assessments for patients, using
did not appear different among treatment Brookline, MA 02215; 617-732-4965 12 months following treatment 23% of TTT the VFQ 25 will be conducted at the time
groups: overall, mean age 78, 64% women, Study Chairman treated eyes in this subgroup improved vision of enrollment and at 5 years
mean study eye visual acuity (approximate William Christen, MD / 617-278-0795 by one or more lines and 14% of TTT treated Number of Patients Enrolled
Snellen equivalent) 20/100-1 Study Purpose eyes improved vision by three or more lines. 1052
• At baseline, for the reduced fluorescence, • To determine whether 50mg of beta None of the eyes in the placebo treated Follow Up
standard fluorescence, and placebo groups, carotene taken every other day reduces control group showed any improvement of Minimum of 5 years
respectively the risk of developing Age-Related Macular vision. After 18 months, the patients in this Eligibility/Exclusion
• Mean total lesion area was 3.65, 3.91, 3.25 Degeneration (AMD) among male US subgroup who did lose vision (as one would • Patients eligible for CAPT can be either
MPS DA physicians who were aged 40-84 in 1982 expect over time), did better than the placebo male or female and meet the following
• Mean area of occult CNV 3.28, 3.36, 2.89 • To investigate the possible relationship treated eyes. Specifically, TTT treated eyes criteria:
MPS DA; and classic CNV 0.26, 0.41, 0.29 of AMD with other antioxidants including on average lost 2 lines of visual acuity while • Age at least 50 years old, vision in each
MPS DA selenium and vitamins A, C, and E placebo treated eyes lost 4 lines. These eye must measure 20/40 or better,
• Six-month vision and fluorescein • To identify potential risk factors for findings were statistically significant. • At least 10 large Drusen in each eye,
angiographic outcomes will be reported development of AMDM Results available for follow-up exams for 5 years
Results • Possible risk factors include height, Pending after enrollment
Pending systemic hypertension, cardiovascular
disease, blood cholesterol, cigarette smoking, Participating Centers
iris and skin color, sunlight exposure, body 22 centers
mass index, diabetes, and alcohol intake Results
Study Pending
Study Study Design Dry Age-Related Macular Degeneration
Age-Related Eye Disease Study • It is an ongoing, randomized placebo- (AMD) Trial
controlled trial of aspirin in the prevention of
Sponsor Sponsor
cardiovascular mortality and of beta-carotene
Eye 92-EI-0250 Apheresis Technologies, Inc. Study
in the prevention of cancer
Study Purpose • Following randomization, each of the Study Purpose Randomized Trials of Vitamin Supplements
• To assess the clinical course, prognosis, 22,071 patients enrolled was assigned to To determine whether patients with Dry AMD and Eye Disease
and risk factors of Age-Related Macular one of four groups to take either aspirin or its experience improvement in their vision after Sponsor
Degeneration (AMD) and cataract placebo and beta-carotene or its placebo apheresis treatments National Eye Institute
• To evaluate, in randomized clinical trials, • Follow up questionnaires are sent 6 and Study Design
the effects of pharmacologic doses of (1) Status
12 months after randomization and every 21 • Multi-center study, enrolling a total of 180 Ongoing. Comments: Both studies ongoing.
antioxidants and zinc on the progression of months thereafter patients to be randomized into 2 groups: 120
AMD and (2) antioxidants on the development in the treatment group and 60 in the placebo Patient Accrual Date
Number of Patients Enrolled No longer recruiting. Comments: Women’s
and progression of lens opacities control group
22,071 Health Study: Recruitment began in
Study Design • Patients will receive 8 treatments (actual or
Follow Up November 1992 and was completed in July
• The Age-Related Eye Disease Study placebo) and the results between the groups
More than 12 years 1995. Women’s Antioxidant Cardiovascular
(AREDS) is a major research program will be compared during follow up visits
to improve our understanding of the Eligibility/Exclusion • The treatments are provided at no cost to Study: Recruitment began in August 1993
predisposing factors, clinical course, and • The study population consists of 22,071 qualifying patients and was completed in October 1996.
prognostic factors of AMD and cataract. male US physicians who were aged 40-84 • The quality of life questionnaires VFQ-25 Study Center
• Eligible patients are randomized to years in 1982. and AMD will be utilized to determine how Julie E. Buring Sc.D.
treatment with placebo, antioxidants, zinc, or • The subjects have no history of myocardial much the patients’ life is affected by their Charles H. Hennekens, M.D.
antioxidants plus zinc, and are followed for a infarction, cancer, kidney disease, renal visual problems Brigham and Women’s Hospital
minimum of 5 years disease, or any other contraindication to the 900 Commonwealth Avenue East
Eligibility/Exclusion
use of aspirin or beta-carotene. Including Boston, MA 02215-1204
Eligibility/Exclusion • Between the ages of 50 and 85 years of age
regular use of corticosteroids Study Chairman
• Men and women between the ages of 55 and weigh greater than 110 lbs.
and 80 years whose macular status ranges Participating Centers • Have some vision loss in at least one eye William G. Christen, Ph.D.
from no evidence of AMD in either eye to For information call the chairman’s office due to macular degeneration, with no other Brigham and Women’s Hospital
relatively severe disease with vision loss in Results major eye diseases. 900 Commonwealth Avenue East
one eye but good vision in the fellow eye 532 cases of ARM confirmed (261 in beta- • Patient must be in reasonably good health Boston, MA 02215-1204
carotene grp & 271 in placebo). Results with a visual acuity between 20/32 and 20/
suggest that 12 years of beta-carotene 125 and have more than 10 large soft drusen.
supplementation has no appreciable effect Results
on ARM during the treatment period. (ARVO Pending
2004 program #2111)

retina times 31
>> RETINAL RESEARCH REPORT

Study Purpose to menopause (natural or surgical) or tubal Study Design Number of Patients
• To determine whether vitamin E ligation, or the participant does not intend to Randomization 1:1:1, PDT and 0 mg 15¬-20
supplementation reduces the risk of cataract become pregnant in the future as indicated of triamcinolone/PDT and 1 mg of Participating Centers
and age-related macular degeneration (AMD) on the initial WHS questionnaire; triamcinolone/PDT and 4 mg of triamcinolone 1
in women. (f) no current use of a vitamin K-depleting Eligibility/Exclusion Eligibility/Exclusion
• To determine whether vitamin C anticoagulant agent (e.g., Coumadin). Inclusion Criteria: 50 years or older, occult or Age 50 or older, study eye BCVA of 20/40
supplementation reduces the risk of cataract Individuals taking aspirin or other NSAIDs minimally classic subfoveal CNV, presence or less, fellow eye better or equal to 20/800
and AMD in women. were not excluded. of blood associated with the lesion, vision ETDRS, no history of previous subfoveal
• To determine whether beta-carotene Participating Centers loss or growth of lesion objectively recorded thermal laser therapy
supplementation reduces the risk of cataract Not available within preceding 3 months, baseline VA score
and AMD in women. between 20/40¬-20/400, lesion 5400 microns
Results
• To determine whether alternate day, low- Exclusion Criteria: Predominantly classic
Pending
dose aspirin reduces the risk of cataract and CNV, additional eye disease, CNV not
AMD in women. Study
involving geometric center of FAZ, inability
• To identify potential risk factors for cataract ANCHOR
to be photographed; fluorescein allergy;
and AMD including cigarette smoking, alcohol photophobia; lens opacities expected to Sponsor
intake, blood pressure, blood cholesterol, progress during study; previous treatment Genentech
Study
cardiovascular disease, height, body mass Anecortave Acetate Risk Reduction Trial for CNV, other than confluent laser Status
index, and diabetes. (AART) photocoagulation (eg, PDT, submacular Ongoing
Study Design Sponsor surgery, radiotherapy, macular grid); Study Purpose
These randomized, double-masked, placebo- Alcon Research, Ltd. participation in another clinical trial; IOP Evaluate the safety and efficacy of
controlled trials will test the hypotheses that >21 mm Hg on or off meds; prior treatment ranibizumab (Lucentis) compared with
supplementation with antioxidant vitamins Status with another antiangiogenic compound verteporfin photodynamic therapy in
and with low-dose aspirin reduces the Enrollment is ongoing within 6 months of screening; inability to preventing vision loss associated with AMD
risk of age-related cataract and AMD. The Study Purpose comply with all study-related procedures; Study Design
study populations are the Women’s Health Demonstrate that anecortave acetate (15 mg concomitant therapy with systemic or Phase 3, randomized, double-blind, active
Study (WHS) and the Women’s Antioxidant or 30 mg) is safe and effective in arresting the topical corticosteroids or NSAIDS (chronic control, parallel assignment. Three treatment
Cardiovascular Study (WACS). The WHS is progression of nonexudative AMD in patients concomitant therapy is defined as multiple arms: PDT and sham injection, sham PDT
a randomized, double-masked, placebo- who are at risk for progressing to exudative doses taken daily for 3 or more consecutive and Lucentis dose A, sham PDT and Lucentis
controlled trial using a 2x2 factorial design AMD days at any time during the course of the dose B
to test low-dose aspirin (100 mg on alternate Study Design 12-month study); a low dose of ASA (up to
days) and vitamin E (600 IU on alternate days) 100 mg PO qd) taken for prophylaxis of MI Eligibility/Exclusion
Phase 3, double-masked, randomized,
in the primary prevention of cardiovascular and/or stroke is permitted during the study; 50 or older; predominantly classic; subfoveal
parallel group, no-treatment (sham
disease (CVD) and cancer. It is being concomitant coumadin therapy CNV due to AMD; study eye BCVA equal to
administration), safety/efficacy study
conducted among 39,876 apparently healthy or worse than 20/40, but no worse than 20/
Eligibility/Exclusion Number of Patients to be Enrolled 320; lesion eligible for PDT per labeling; no
female health professionals age 45 years and Patients at least 50 years of age, any race 120
older. The WACS is a randomized, double- prior laser treatment involving the center of
and either sex, with a clinical diagnosis of Results the fovea; no prior PDT; no prior experimental
masked, placebo-controlled secondary exudative AMD in the nonstudy eye, and at Pending treatments for AMD
prevention trial using a 2x2x2x2 factorial least 5 or more intermediate (>63 microns)
design to test antioxidant vitamins (vitamins Number of Patients
or larger soft drusen within 3000 microns of
E [600 IU on alternate days] and C [500 mg 426
the foveal center and/or confluent drusen
daily], beta carotene [50 mg on alternate within 3000 microns of the foveal center, and Participating Centers
days]), and a combination of folate (800 mg Study 100
hyperpigmentation within 3000 microns of the Preservative-free Triamcinolone Acetonide
daily), vitamin B6 (25 mg daily), and vitamin foveal center in the study eye.
B12 (1 mg daily) among women who are at (PFTA)
high risk for CVD morbidity and mortality. It is Results Sponsor
being conducted among 8,171 female health Pending QLT Inc., National Eye Institute Study
professionals, ages 40 years or older, who Status Evaluation of Safety and Efficacy of
either have preexisting CVD or have at least Enrolling patients Anecortave Acetate vs. Placebo in Patients
three coronary risk factors and therefore are Study Purpose with Subfoveal CNV due to Exudative AMD
at high risk for the development of CVD. Study
Investigate the long-term safety and potential (C-02-29)
Number of Patients Enrolled SIRNA 0401
efficacy of PFTA in patients with wet AMD (all Sponsor
Women’s Health Study: 39,876 Sponsor types) undergoing Visudyne therapy Alcon Research, Ltd.
Women’s Antioxidant Cardiovascular Study: Sirna Therapeutics, Inc., Boulder, CO
Study Design Status
8,171 Status Phase 3, randomized, prospective Enrollment is ongoing in South America
Follow Up Enrolling patients
Number of Patients Study Purpose
Not available Study Purpose 300 Demonstrate that anecortave acetate 15
Eligibility/Exclusion Assess the safety and tolerability of Sirna-
Eligibility/Exclusion mg is superior to placebo in maintenance of
Women’s Health Study: 027; assess the presence of Sirna-027 in
Inclusion Criteria: Age greater than or equal visual acuity
A participant must have met all of the plasma; determine the range of doses for the
phase 2 clinical trial; and assess biological to 50 years; in the study eye, diagnosis of Study Design
following criteria: AMD defined by the presence of drusen
and anatomical changes in the retina. Phase 3, double-masked, randomized,
(a) female; larger than 63 micro m; visual acuity of 20/40 parallel group, placebo-control, safety and
(b) aged 45 years or older; Study Design - 20/200 (73-34 letter score) as measured efficacy study
(c) postmenopausal or with no intention of Phase 1, open-label, dose-escalation -4 to 6 on an ETDRS chart; in the study eye, the
becoming pregnant; dose cohorts, 1 intravitreal injection Inclusion/Exclusion Criteria
presence of choroidal neovascularization Patients at least 50 years of age, any race
(d) no reported personal history of Number of Patients under the fovea
cardiovascular disease, cancer (other than and either sex with minimally classic and
12¬-30 Exclusion Criteria: Choroidal
non-melanoma skin cancer), gout, peptic occult exudative AMD with subfoveal
Participating Centers neovascularization, in the study eye, choroidal neovascularization
ulcer, chronic renal or liver disease, or other associated with other ocular diseases such
4
serious illness precluding participation; as pathologic myopia, ocular histoplasmosis Results
(e) no reported history of serious side effects Eligibility/Exclusion Pending
50 years of age or older; subfoveal to AMD, or posterior uveitis, etc.; presence of
to the study treatments; geographic atrophy under the fovea in
(f) not currently taking aspirin, aspirin classic and/or occult; no other causes of
CNV; total lesion size 12 MPS disc area; the study eye; the presence of a chorio-
containing medication, or nonsteroidal anti- retinal anastomosis; presence of fibrosis,
inflammatory drugs (NSAIDs) more than 1 day subretinal hemorrhage < 50% of lesion;
hemorrhage, pigment epithelial detachments, Study
per week or, if so doing, willing to forego use subfoveal scaring < 50% of lesion; lesion
and other hypofluorescent lesions obscuring Evaluation and Tolerability of 4-dose
of these medications; thickness 250 m ; inter occular pressure
greater than 50% of the CNV lesion Levels of Cand5 Administered by Single
(g) not currently taking individual supplements 25 mm Hg; visual acuity 20/100 to 20/800
Results Intravitreal Injection in Patients with Wet
of vitamin E or beta carotene more than 1 day ETDRS; fellow eye visual acuity not worse
Pending AMD
per week; than 20/800 ETDRS
Sponsor
(h) not currently taking anticoagulants or Results
Acuity Pharmaceuticals
corticosteroids. Pending
Status
Women’s Antioxidant Cardiovascular Study: Study Recruiting
Potentially eligible female health professionals Combretastatin A-4 Phosphate (CA4P) in Study Purpose
for WACS were identified from the pool Study Patients with Neovascular AMD (FBO-206) Evaluate 4-dose levels of the small RNA
of respondents to the Women’s Health Visudyne with Intravitreal Triamcinolone Sponsor interference therapeutic agent Cand5 in
Study initial mailing and must have met the Acetonide (VisTA) Trial OXiGENE subjects with exudative AMD
following criteria: Sponsor Status Study Design
(a) female; LuEsther T. Mertz Retinal Research Center Enrolling patients Open label study. One intravitreal injection;
(b) date of birth before January 1, 1955; 4-dose levels
Status Study Purpose
(c) a reported history of myocardial infarction Eligibility/Exclusion
Recruiting Assess the safety and tolerability of
(MI), stroke (CVA), angina pectoris (AP), Inclusion Criteria: Male or female patients 50
Study Purpose combretastatin administered intravenously in
coronary artery bypass grafting (CABG), years of age or older; subfoveal CNV, classic
Evaluate the effect of photodynamic therapy patients with all forms of neovascular AMD
percutaneous transluminal angioplasty or occult; total lesion size <12 total disc
in conjunction with intravitreous triamcinolone (classic and occult)
(PCTA), transient ischemic attack (TIA), areas, of which at least 50% is active CNV;
carotid endarterectomy (CEA), or peripheral acetonide in subjects with occult or minimally Study Design
Phase 1/2, open label, safety and tolerability subretinal hemorrhage (if any)-no more than
artery surgery (PAS); classic subfoveal CNV secondary to AMD
study. The study cycle consists of a prestudy 50% of the lesion; minimally classic or occult
(d) no history of cancer (except non- lesion must have hemorrhage and/or lipid
melanoma skin cancer) within the past 10 evaluation period (2¬4 weeks), a 22-day
treatment period, and an 8-week post- and or documented loss of 3 or more lines of
years and no active liver disease or cirrhosis; vision during the previous 3 months; vision
(e) pregnancy physiologically impossible due treatment evaluation period
20/50 to 20/320, with better acuity in the
fellow eye; IOP 22 mm Hg

32 retina times
Exclusion Criteria: Concomitant ocular retinopathy; h/o stroke within 12 months of Study Design Eligibility/Exclusion
disease, 3 or more prior PDT treatments, study entry; h/o peripheral vascular disease Prospective, open-label, uncontrolled, clinical Inclusion Criteria: Age 50 years or older;
thermal laser within the previous 2 or severe cardiac disease; significant study active primary or recurrent subfoveal CNV
weeks, subfoveal scarring or atrophy, h/o hematologic, renal, or hepatic disease Eligibility/Inclusion secondary to AMD with minimally classic
abdominal aortic aneurysm, stroke within Results Neovascular AMD; subfoveal CNV; all lesion or occult lesion; where an active lesion
previous 12 months, diabetes or use of oral Pending types; recent disease progression, central is defined, lesion < 6 mm greatest linear
hypoglycemics or insulin, h/o peripheral retinal thickness at least 300 microns; dimension (GLD); submacular blood must
vascular disease, allergy to fluorescein multiple visits required--6 visits each month comprise less than 75% of the total lesion;
Number of Patients for the first 3 months, then visits once a subretinal fibrosis must comprise less
12 month thereafter for a total of 2 years than 25% of the total lesion; study eye
Study
best-corrected vision of 20/100 or poorer
Participating Centers Squalamine Results
measured on an ETDRS chart (<48 letters
2 Sponsor Pending
correct); fellow eye best-corrected vision that
Genaera Corporation is at least 1 line better on an ETDRS chart
Status than the best-corrected vision of the study
Enrolling patients eye; HbA1c <6%, signed informed consent
Study Study Exclusion Criteria: Prior AMD therapy
Study Purpose
PIER Safety and Efficacy of AG-013958 in treatment; presence of other eye diseases
Evaluate the safety and efficacy of
Sponsor subjects with subfoveal choroidal that could compromise visual acuity
intravenously administered squalamine as a
Genentech neovascularization associated with age- in the study eye; CNV due to other
first-line therapy for wet AMD
related macular degeneration causes; hypertensive retinopathy, major
Study Purpose Study Design
Evaluate safety and efficacy of Lucentis in Sponsor cardiovascular or cerebrovascular event
Phase 2, randomized, double-masked,
patients with wet AMD Pfizer within the last year; inability to complete
controlled study; 2 dose levels once weekly
Study Design for 4 weeks, followed by maintenance doses Status follow-up; allergy to fluorescein dye; previous
Lucentis phase 3b, randomized, double- once every 4 weeks through week 48. At the Recruiting radiation to the study eye; pregnancy at time
masked, sham injection-controlled trial. end of therapy, each patient will be followed Study Purpose of surgical procedure
Patients will be assigned to 1 of the following for an additional year Assess the safety, efficacy, and Number of Patients
treatment arms: Lucentis dose A, Lucentis Number of Patients pharmacokinetics of the investigational drug 30
dose B, sham injection 100 AG-013958 in subjects with exudative AMD Results
Eligibility/Exclusion Participating Centers Study Design Pending
Inclusion Criteria: Men and women age Multicenter Phase 1/2, randomized, masked, single and
50 and older; active primary or recurrent multiple-dose, single and multiple-dose,
wet AMD involving the center of the fovea sequential dose-escalation
(“subfoveal”); best corrected visual acuity of Eligibility/Exclusion Study
equal to or worse than 20/40, but no worse Inclusion Criteria: AMD, minimally classic AdGVPEDF.11D in Neovascular Age-
Study
than 20/320 in the study eye; classic or occult & occult-classic eligible in stage 2 of study Related Macular Degeneration (Wet AMD).
Noncomparative Protocol for Use of
forms of CNV due to AMD and not another (after first 46 pts), no subfoveal fibrosis; Sponsor
Intravitreous Macugen Injections in
cause total lesion fibrosis or scar <25% total area; GenVec, Inc.
Patients with AMD
Exclusion Criteria: Previous verteporfin hemorrhage <50% of total lesion area, total
Sponsor Status
photodynamic therapy, external lesion area 9 DA; ETDRS best corrected
Eyetech Pharmaceuticals Part 1 is complete; Part 2 is Enrolling Patients
beam radiation therapy, transpupillary score of approximately 20/40-20/230; fellow
thermotherapy or intravitreal drug delivery Status Study Purpose
eye VA >=24 letters (20/320 or better); normal
in the study eye, participation in any clinical Recruiting To assess the safety, tolerability and feasibility
ECG or nonsignificant changes
trial involving antiangiogenic drugs (ie, Study Purpose of single direct intravitreal injection of
Exclusion Criteria: Prior PDT >3 months
ranibizumab, pegaptanib, anecortave acetate, Provide Macugen to patients who have AdPEDF, identify an appropriate dose range
before entry; serous pigment epithelial
protein kinase C inhibitors, etc.) or any other subfoveal CNV secondary to AMD and who for Phase II testing of AdPEDF and assess
detachment without surrounding
clinical trial within the last month are unable to participate in any other clinical the biologic activity of AdPEDF.
neovascularization; diabetic retinopathy,
Number of patients studies of Macugen for AMD, until such time glaucoma, or other serious ocular diseases or Study Design
180 as the patient’s lesion is considered to have conditions; prior subfoveal photocoagulation Phase I, open-label, dose-escalating study
resolved or stabilized or Macugen becomes of the macula; prior intravitreal, sub-Tenon’s, of a single intravitreal administration of
Participating Centers
commercially available or systemic therapy for AMD; prior TTT AdPEDF. Part 1 of the study is complete;
3
Study Design (transpupillary thermotherapy) or intravitreal AdPEDF (at eight ascending dose levels) was
Open label study, 0.3 mg intravitreous steroids in study eye or likely to undergo administered to twenty-eight (28) patients
injection every 6 weeks these procedures within 6 months of entry; with severe wet AMD and was generally
cataract surgery within previous 12 months; well-tolerated at all dose levels, with no dose-
Study Eligibility/Exclusion limiting toxicities, endophthalmitis, retinal or
Inclusion Criteria: CNV with total lesion size of intraocular surgery within previous 3 months;
The Effect of Pegaptanib Sodium on vitreous detachment, cataracts or glaucoma.
12 DA or less of which at least 50% is active prior vitrectomy or submacular surgery; prior
Foveal Thickening in Patients with Part 2 will treat twenty (20) additional patients
CNV; subretinal hemorrhage not more than scleral buckling, myopia >= 6 diopters; sitting
Exudative Subfoveal AMD with less advanced (moderate to severe) wet
50% of the total lesion size; no subfoveal BP >159/99 mm Hg on 2 out of 3 evaluations;
Sponsor stroke within the previous 12 months; h/o AMD at two of the highest doses tested in
Eyetech Pharmaceuticals scarring, atrophy, or fibrosis; no more than part 1.
25% of the total lesion is scarring or atrophy; severe cardiac disease; peripheral vascular
Status disease; unstable angina; MI within 6 months; Eligibility/Exclusion
VA approximately 20/40-20/320 in the study
Recruiting ventricular tachycardia requiring treatment; Inclusion Criteria: Patients of at least 50 years
eye; no fellow eye requirement; IOP 23
Study Purpose Exclusion Criteria: Eligibility for PDT with inability to stop anticoagulants 4 days prior to in age, with moderate to severe wet AMD
Compare the safety of Macugen with that of Visudyne (including patients for whom injection (ASA okay to continue); participation (best corrected vision of 20/40 to 20/320 in
sham treatment and to assess Macugen’s prior PDTs have been deemed ineffective); in any clinical trials within the previous 60 the most impaired eye), active leakage or
effect on foveal thickening eligibility for any other Macugen trials, days; use of systemic steroids currently or CNV with lesion diameter less than or equal
Study Design presence of other causes of CNV - myopia within the previous 30 days to 5400 microns and no significant subretinal
Phase 2 prospective, randomized, > 8 diopters, ocular histoplasmosis, angioid Results fluid, who are not candidates for, or who
double-masked, sham-controlled, dose- streaks, choroidal rupture, multifocal Pending have refused treatment with, subfoveal laser
ranging, multicenter trial. First 3 injections: choroiditis; h/o severe cardiac disease; photocoagulation or PDT.
randomization, 1:1:1, 0.3 mg/1 mg/sham; MI within previous 6 months; ventricular Exclusion Criteria: Significant retinal disease
subjects in sham treatment group tachyarrhythmias requiring ongoing other than neovascular AMD; Significant non-
subsequently rerandomized to 0.3 mg or treatment; unstable angina; stroke within retinal disease; Cataract or other significant
Study
1 mg previous 12 months; acute ocular or media opacity; Other causes of choroidal
TheraSight Ocular Brachytherapy System
periocular infection; serious allergy to FA neovascularization such as pathologic
Eligibility/Exclusion for Treatment of AMD
myopia (>8 diopters), ocular histoplasmosis
Inclusion Criteria: CNV with total lesion size Participating Centers Sponsor or angioid streaks; Evidence of inflammation
of 12 DA or less of which at least 50% is Not available Theragenics Corporation (grade 1 or higher) in the anterior and/or
active CNV; subretinal hemorrhage not more Results Status posterior chambers; Cataract surgery or
than 50% of total lesion size; no subfoveal Pending Enrolling submacular surgery within 3 months; Prior
scarring, atrophy, fibrosis, or blood over ocular treatment with radiation; Known allergy
Study Purpose
fovea; no more than 25% of the total lesion to fluorescein; Liver enzymes > 2 x ULN (ALT,
Investigate the safety, feasibility, and
made up of scarring or atrophy, for minimally AST, bilirubin); Clinical evidence of active
tolerability of the TheraSight Brachytherapy
classic or occult lesions: >=3 line vision loss infection of any type, including adenovirus,
Study System for treatment of wet AMD
during the previous 12 week and/or subretinal hepatitis A, B, or C virus or HIV virus; Other
PrONTO Study Design
hemorrhage (not more than 50% of the total treatment for AMD in the study eye within
lesion size); VA approximately 20/40-20/320 Sponsor A multicenter, randomized study of 3 doses
Bascom Palmer Eye Institute and Genentech, of radiation (assigned 1:1:1) delivered by the last twelve weeks prior to Day 1; Other
in study eye and 20/800 or better in fellow experimental medications within the last four
eye; foveal thickness on OCT >=300 mm; Inc the TheraSight Brachytherapy System in
participants with CNV secondary to AMD weeks prior to Day 1; Abnormal prothrombin
classic CVN for which PDT can be deferred Status or partial thromboplastin time (>1.5 X ULN) or
for 54 weeks Recruiting anticoagulant therapy that cannot be withheld
Exclusion Criteria: Previous subfoveal thermal Study Purpose for treatment; Prior or current glaucoma or
laser or PDT laser; intraocular surgery, Determine how quickly the central retinal any atrophic change in the fovea.
including extrafoveal/juxtafoveal laser within thickness decreases following ranibizumab
the previous 3 months; h/o PPV or SB; Number of Patients
(Lucentis) therapy using OCT and then, after Up to 48
pigment epithelial tears or rips; any other 3 monthly doses determine the durability
conditions that may be causing CNV, diabetic of the treatment response with intermittent Participating Centers
therapy offered only if needed based on OCT 7
findings

retina times 33
>> RETINAL RESEARCH REPORT

Study ocular HTN requiring more than one Study


Interval Dose Evaluation of Anecortave medication, aphakia or presence of ACIOL, Genetics and Clinical Characteristics of Study
Acetate (IDEAA) active retinal neovascularization, diabetic Bardet-Biedl Syndrome Optical Coherence Tomography Study of
Sponsor retinopathy, rubeosis, active or previous CNV, Purpose Retinal Thickness
Alcon active ocular infection, active or inactive The purpose of this study is to increase Sponsor
Status toxoplasmosis, scleral thinning, intraocular knowledge about the genetics and clinical National Eye Institute (NEI)
Recruiting surgery including cataract surgery or laser characteristics of Bardet-Biedl syndrome.
of any type within 90 days prior to baseline Status
Study Purpose Eligibility Currently Recruiting Patients
examination, history of central serous Enrollment includes adult and pediatric
Compare anecortave acetate 15 mg retinopathy, history of pars plana vitrectomy, Patient Accrual Date
administered every 3 months vs. anecortave patients and close family members.The
anticipated need for ocular surgery during Ongoing
acetate 15 mg administered every 6 months researchers will include in the study patients
the 12-month study period, previous who present with four primary features OR Study Center
vs. anecortave acetate 30 mg administered treatment with intravitreal steroid or any three primary features and two secondary National Eye Institute (NEI), 9000 Rockville
every 6 months in patients with exudative intravitreal injectable drug, periocular steroid features: Pike, Bethesda, Maryland 20892
AMD treatment within 6 months prior to baseline, Primary features Study Chairman
Study Design systemic steroid treatment within 1 month 1) rod-cone dystrophy Not available
Prospective, randomized 1:1:1 prior to baseline, dexamethasone treatment 2) polydactyly Study Purpose
Eligibility/Exclusion within 1 month prior to baseline, treatment 3) obesity
with topical ophthalmic steroids or topical This study, conducted at the NIH Clinical
Inclusion Criteria: Clinical diagnosis of 4) learning disabilities
NSAIDS, warfarin or heparin therapy within 1 Center and the University of Wisconsin
exudative AMD and a primary or recurrent 5) hypogonadism in males
month prior to baseline, allergy to fluorescein University, will compare measurements
(after laser photocoagulation) subfoveal CNV 6) renal anomalies
or iodine, uncontrolled systemic disease, obtained using older and newer models
lesion, lesion area 12 disc areas (30.5 mm)
female patients who are pregnant, planning of a machine called an optical coherence
of any lesion type (predominantly classic, Secondary features
on becoming pregnant, or nursing tomography (OCT) scanner.
minimally classic, or occult.), choroidal 1) speech disorder/delay
neovascularization (CNV) >=50% of the total Results Study Design
2) strabismus, cataracts, astigmatism Observational, prospective, randomized
lesion (defined as angiographic evidence of Pending 3) developmental delay
neovascularization, associated contiguous clinical trial.
4) poly-uria/dipsia (nephrogenic diabetes
areas of serous elevation of the RPE, elevated insipidus) Number of Patients
blocked fluorescence, and/or late staining), 5) ataxia, poor coordination, imbalance Expected Total Enrollment: 120
evidence of recent disease progression for Study 6) spasticity Follow Up
occult lesions (defined as having experienced Denufosol Tetrasodium (INS37217 7) diabetes mellitus 3 months
a loss of at least 1 line of vision or change in Ophthalmic), P2Y2 Receptor Agonist for 8) dental crowding/hypodontia Eligibility/Exclusion
lesion size of more than 1 disc area [2.54 mm] Intravitreal Injection 9) left ventricular hypertrophy/congenital Inclusion Criteria:
or the appearance of new blood in the lesion heart disease 1. Patient must understand and sign the
within the past 3 months) Sponsor
Inspire Pharmaceuticals 10) hepatic fibrosis informed consent.
Snellen equivalent of 20/40 to 20/200 visual A durable power of attorney (DPA) will be 2. Patient must be at least 18 years of age.
acuity in the study eye (no vision criteria for Status
obtained for all cognitively impaired adults. 3. Pupillary dilation to at least 6 mm must be
the non-study eye). Enrolling patients
Results possible.
Exclusion Criteria: Amblyopia, uncontrolled Study Purpose 4. Ocular media must be sufficiently clear to
Pending
glaucoma with an IOP > 30 mmHg, ischemic Compare the safety and efficacy of INS37217 allow for quality images.
optic neuropathy, PDR, clinically relevant Ophthalmic to placebo as a first-line therapy Exclusion Criteria:
NPDR, clinically relevant diabetic macular in patients with rhegmatogenous retinal 1. Any condition such as corneal opacifiation
edema, significant active uveitis ,clinical signs detachment that precludes adequate slit lamp
of myopic retinopathy, or refraction of >-8.00 Study
Study Design examination and photography of the fundus.
diopters in the patient’s current Rx, more than Cell Transplantation to Replace Retinal
Phase 2, double-masked, randomized, Participating Centers
1 PDT treatment in the study eye, extrafoveal Cells and RPE in Retinal Dystrophies
placebo-controlled, parallel-dose. Patients Not available
or juxtafoveal thermal laser treatment less will be given a single intravitreal injection Sponsors
than 30 days prior to enrollment, more than of drug or placebo and allows for up to 2 University of Louisville Department of Results
2 Macugen injections in the study eye, more additional consecutive daily injections for Ophthalmology and Visual Sciences Pending
than one Triamcinolone treatment in the study patients who show signs of improvement Vitreoretinal Research Foundation
eye, previous treatment with anecortave following the previous injection Status
acetate in the study eye, intraocular surgery Enrolling patients for a Phase II clinical trail.
Eligibility/Exclusion
in the study eye within 60 days prior to
Inclusion Criteria: Rhegmatogenous retinal Patient Accrual Date
enrollment., scleral buckle in the study eye Study
detachment (RRD) in only 1 eye; >=18 years Ongoing
Any previous systemic anti-angiogenic Phase I Trial for Wet Age-Related Macular
of age; no more than 3 separate breaks; Study Center
therapy for AMD, radiation treatment in the Degeneration with VEGF Trap
all breaks must be clustered together and Retina Vitreous Resource Center
study eye, scleral thinning, any unstable Sponsor
confined within an area that is no more than 3 Audubon Plaza Drive, Suite 240
medical condition that would preclude ability Regeneron/Aventis
2 clock hours in extent on the fundus; total Louisville, KY 40217
to keep study visits, coumadin therapy that
area of all open breaks in the detached part Study Chairman Status
cannot be interrupted for a 5-day period
of the retina is no greater than 1 clock hour Norman D. Radtke, MD Currently recruiting patients
Results in extent; retinal detachment is large enough
Pending 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
Study into the eyes of human patients with age- Hospital (Baltimore, Maryland)
20/50 or better in both eyes, macula off¬VA
Interval Dose Evaluation of Anecortave 20/50 nonstudy eye, plus history prior to related macular degeneration or retinitis Study Chairman
Acetate (IDEAA) this detachment of reading capability in the pigmentosa. Not available
Sponsor study eye Study Design Study Purpose
Alcon 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
Status
choroid; choroidal detachment; demarcation and a vision of 20/400 or worse in one eye potential effect of the VEGF Trap on visual
Recruiting
lines; coexisting pathology; > 0.8 cup/disc will be selected for the study and will undergo acuity.
Study Purpose ratio; prior RD repair (surgical or nonsurgical); an operation to implant fetal neural retina
To evaluate the safety and efficacy of 2 doses Study Design
intravitreal corticosteroid treatment within with RPE under the retina. Two complete This is a Phase I randomized, placebo-
of dexamethasone vs. sham treatment with the previous 3 months; symptoms consistent examinations will be performed at least
the dexamethasone posterior segment drug 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
delivery system applicator in patients with macula-on or h/o loss of reading vision in and only one eye will be subject to surgery.
macular edema following central retinal vein 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
occlusion or branch retinal vein occlusion screening if macula-off; if macula-off and at one week, one month, three months, six in a one-year, open-label safety extension
Study Design enrolled in study subject must be able to months, nine months, twelve months, and study.
Phase 3, prospective; first 6 months receive study drug injections (possibly up twenty-four months for follow-up(F/U).
randomized, additional 6 months open label if Number of Patients
to 3) and be repaired or rescued all by the Number of Patients Enrolled
patient is eligible Not available
10th day of the detachment. If enrolled in the Not available
Eligibility/Exclusion study, subject must not be macula-off for Follow Up
Follow-up 1-2 years
Inclusion Criteria: Macular edema due to >10 days; ongoing treatment with Diamox 2 years
branch vein occlusion (duration of 3-12 or Trusopt (dorzolamide); known sensitivity Eligibility/Exclusion
to P2Y2 Eligibility/Exclusion Subjects must be 50 years or older, currently
months) or central retinal vein occlusion To participate a person must be at least 21 have wet AMD in at least one eye and be in
(duration of 3-9 months), patient unlikely to Number of Patients years of age, have no diabetes or glaucoma, general good health.
be adversely affected by not being treated 160 and have vision of 20/200 or worse in one
for 6 months, BCVA20/50 to 20/200, retinal Participating Centers eye. The transplant is in that one eye only. Participating Centers
thickness >= 300 by OCT 25 4
Pregnancy rules out eligibility.
Exclusion Criteria: Minimum age, 18 years, Results
any ocular condition that would prevent Results Participating Centers
Expected Mid-2005 1 Pending
a 15-letter improvement in visual acuity,
epiretinal membrane as the primary cause Results
of the macular edema, history of elevated Pending
intraocular pressure in response to steroid
treatment, history of glaucoma or optic
nerve change consistent with glaucoma,

34 retina times
>> IN THE PIPELINE

Jay M. Stewart, MD
Section Editor

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 RNAi was introduced to the retina encounters the ribosome. The ribosome allows
questions from your patients about RNA literature by Michael Tolentino, MD, and the genetic message to be translated into a
interference (RNAi), or small interfering RNA colleagues from Scheie Eye Institute and chain of amino acids, which comprise the
(siRNA), technologies. They may have heard Acuity Pharmaceuticals. In their study, newly formed protein, in this case VEGF.
some of the buzz about RNAi applications reported in Retina, a single intravitreal
in the treatment of age-related macular injection of siRNA molecules directed
degeneration to prevent vision loss. against VEGF production was performed in
One goal of research in the treatment monkeys. During 5 weeks of follow up, the
of neovascular AMD is to find ways to injections were found to reduce leakage in a
lower vascular endothelial growth factor laser-induced CNV model. Importantly, no
(VEGF) levels. VEGF is known to be a major inflammation or toxic effects of the treatment
culprit in the process of neovascularization. were identified.
Currently, the focus is on molecules that bind According to Dr. Tolentino and colleagues,
and inactivate VEGF, such as aptamers and siRNA may be 100 to 1,000 times more potent
antibodies, but some researchers believe that than protein antagonists such as aptamers
an attractive alternate approach lies in trying and antibodies, which could allow for lower
to shut down VEGF production at the source. and less-frequent dosing. This is because it
It is believed that RNAi technologies, with intervenes earlier in the VEGF production Figure 2. After delivery into the cell, siRNA molecules
their ability to silence the message of a gene, process, preventing the production of multiple activate RISC, a protein complex that disrupts messenger
could potentially shut down VEGF production VEGF protein molecules every time it disables RNA and thereby prevents translation of the gene into
rather than block existing VEGF molecules. a single VEGF mRNA molecule–and each a protein. In this example, the targeted mRNA sequence
Is one approach better than the other? How siRNA molecule can inactivate multiple encodes the gene for VEGF.
effective is RNAi in treating neovascular mRNA molecules, further amplifying the
AMD? effect. By contrast, protein antagonists must It is clear from this sequence of events
Answers to these questions continue to bind the VEGF molecules in a one-to-one that mRNA plays a key role as a “middleman”
develop, because the technology is still in ratio. Tolentino, who is now in private practice between the gene encoded in DNA and the
its infancy. However, there is widespread with the Center for Retina and Macular final protein product. With this in mind,
optimism about its efficacy, and it is being Disease in Lakeland and Winter Haven, researchers have been looking at ways to stop
studied for treatments in cancer, asthma, FL, said, “It’s like anything else–if you can the action of mRNA.
hepatitis, diabetes, Huntington’s disease and prevent something from being produced, it’s Recent insights from plant biology have
other afflictions. Most of the research is in better than dealing with it once it has been provided a possible answer to this challenge.
proof-of-concept or pre-clinical stages, with produced.” Within the past decade, researchers have come
RNAi research in AMD further along than for Safety is another positive aspect of the to recognize that introduction of specific short
most conditions. technology. “They are made from RNA, which double-stranded RNA sequences (siRNA)
is similar to the product that makes aptamers, into cells can induce the degradation of the
and we know from the Macugen data that targeted mRNA molecules. In plants, this
aptamers are very safe in the eyes, and RNA has evolved as a natural defense mechanism
is safe in the eyes,” Tolentino said. “They are against viruses. The strategy, also known
inert molecules that are well-tolerated in the as “gene silencing,” inactivates (mRNA)
human body.” molecules inside cells by interacting with a
protein known as the RNA-induced silencing
How it Works complex, which cleaves mRNA molecules
In order to understand how one might that are homologous to the short (a.k.a.
“turn off ” the production of VEGF or any small) interfering RNA (siRNA) sequence.
other protein, it is important to recall basic Investigators have shown that similar antiviral
principles of molecular biology. Genes are defenses exist in Drosophila fruit flies, proving
encoded in DNA, which resides in the cell the existence of the RNAi mechanisms in
Figure 1. RNA silencing depends upon double-stranded nucleus. The first step toward the making animals. Further studies have shown that
RNA sequences (shown here interacting with a plant viral
protein). This figure reprinted with permission from Dr. of a protein is transcription of the gene into the replication of viruses such as respiratory
Keqiong Ye, Memorial Sloan-Kettering Cancer Center, messenger RNA (mRNA). After the mRNA syncytial virus (RSV) and HIV-1 can be
New York. moves from the nucleus to the cytoplasm, it successfully inhibited in vitro using siRNA.

36 retina times
RNAi Strategies for Retinal Disease about clinical trials for RNAi treatments of that it allows effective inhibition of pathologic
It is this process that shows promise in eye eye disease in the near future. Currently a angiogenesis without affecting normal
disease. Researchers believe that they can number of companies are spearheading the VEGF pathways: the literature suggests that
target the mRNA that is required for VEGF effort to get RNAi ready for the clinics. Acuity VEGF receptor-1, which binds both VEGF
production by using siRNA sequences Pharmaceuticals’ siRNA product that targets and placental growth factor, is important in
that are tailored to the VEGF gene. It is VEGF production is in phase 1 trials for AMD pathologic processes, whereas VEGF receptor-
hoped that when delivered locally to the and diabetic retinopathy and is expected to 2, which binds only VEGF, has more of a role
eye, siRNA will shut down the production enter phase 2 by the end of this year. Acuity in normal pathways. Sirna is in phase 1 trials
of VEGF, preventing the development of also recently signed a deal giving it the rights and expects results by the end of the year,
ocular neovascularization and vision loss in to the ophthalmic technologies of Intradigm with a phase 2 trial scheduled to begin soon
neovascular AMD, diabetic retinopathy, and Pharmaceuticals, another company developing thereafter.
other conditions. siRNA products that had been working on There is still considerable debate over
Approaches to the use of siRNA technology a treatment to block production of VEGF whether blocking VEGF pathways with
vary among those involved in its research and its receptors. Alnylam Pharmaceuticals, treatments such as RNAi can be more effective
and development related to retinal disease. which has partnered with Merck for than rendering existing VEGF ineffective with
One approach uses a synthetic polymer commercialization of its ophthalmic products, treatments such as aptamers. As clinical trials
(nanoparticles) to protect the RNA from uses siRNA to target VEGF production and progress, the Retina Times will continue to
serum degradation and excretion, while expects to enter phase 1 trials in the near report progress on the developing technology
another[JS1] uses native RNA, and yet future. Sirna Therapeutics is in phase 1 trials of RNAi and its application to treating diseases
another[JS2] uses chemically modified RNA. with its RNAi treatment, an siRNA therapy of the back of the eye.
blocking production of VEGF receptor-1.
The Future of RNAi in Ophthalmology According to Sirna, the rationale for targeting
Retinal specialists can expect to hear more VEGF receptor-1 rather than VEGF itself is

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

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
>> 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 RECEIVABLES MANAGEMENT
CPT coding, is somewhat more complex for Retina than for General The Step – This is the most crucial part of the process because it
Ophthalmology. There is more office “testing” (e.g., FAs, Photos, is the source of more lost practice income than any other part of
OCT/HRT, etc.), office procedures, and surgeries with multiple the business process. Receivables management is the process of
components. These require vigilance in capturing all services as receiving payments and posting those payments into the computer
they are provided, as well as processes to allow retrospective audits system. It is a system for knowing the level of payment expected
to measure charge-capture effectiveness. for each charge, the time frame in which the payment should be
received, and actions needing to be taken when the payment is not
CODING the expected amount and/or not received within the expected
The Step – Each service is described by a procedure code (CPT), time frame.
and the justification for providing the service is made with a
diagnosis code (ICD-9). The Registers – There are several important registers to monitor
receivables management (and by extension, financial performance
The Register – Coding “patterns” should be regularly reviewed to of the practice). In order to accurately monitor receivables
assess accuracy and to identify “over-coding” and “under-coding.” management, a competent, properly set-up practice management
This includes CPT codes for both Evaluation and Management computer system is required. The key registers it should include are:
(E&M) and procedural services. • Collection target calculation – Given the practice’s fees, payor
There is often a blurred boundary between charge-capture and allowable payment levels, and payor-mix, what are the expected
coding. For example, is the inclusion of all component procedures collections for a set of charges?
in a multi-part surgery a function of coding or of charge-capture? It • Collection performance – What are the totals received and how do
may well be that the answer is immaterial. What is important is that those totals compare to the target?
all of the components are accurately and appropriately captured • Revenue flow – How quickly are payments received?
and described. Another coding pattern to be closely monitored is • Accounts Receivable (AR) – This is an analysis of outstanding
the distribution of the “Levels of Service” for the Evaluation and claims. While the collection performance report shows what
Management services. HAS happened, the AR analysis is a report of what HAS NOT yet
happened. It is a valuable report for following up on individual
FEES unpaid claims as well as patterns of late or missing payments from
The Step – The practice should have a fee schedule that is rational– insurance plans.
that is, there is a relationship between the fees for various services
that follows the relationship between the allowable payments MANAGEMENT REPORTING
for those same services from the major insurers. This prevents The Step – The reports required to measure the registers described
overpriced and underpriced services, and allows for the calculation in each piece of the business process.
and monitoring of the practice’s collection target. The reports most valuable to monitor can be broken down into
An example would be a fee schedule calculated as a multiple two categories. These are Operational Reports (e.g., charge-capture,
of the local Medicare Fee Schedule. Since many of the insurance collection performance, etc.) and Productivity Reports.
carriers base their allowable payments on that same Medicare The operational reports measure the effectiveness of the business
Fee Schedule, a fairly constant relationship is created between the process, while the productivity reports are used to measure the
practice’s fees and the allowable payments. If the practice set its fees practice’s service volumes, and source of patients. This productivity
at two times the Medicare Fee Schedule, the maximum collection information is used for charting the practice’s strategic direction.
ratio for Medicare services would be 50% (100% ÷ 200% = 50%). If
a local insurance plan paid at 150% of the Medicare Fee Schedule, PRACTICE OVERHEAD
the maximum collection for those services would be 75% (150% ÷ The Step – A measure of the non-physician practice expenses, by
200% = 75%). category.

The Register – A fee schedule evaluation and re-calculation should The Register – The practice’s Income Statement, showing cost
be done at least annually. by category, and displayed as monthly and year-to-date totals,
comparison to year-to-date totals for the same periods in previous
CLAIMS SUBMISSION years, and the year-to-date totals expressed as a percentage of
The Step – Claims for services should be entered into the billing practice income. That percentage of income represented by non-
computer system and transmitted to the insurers accurately and in a physician cost is the practice’s “overhead rate”.
timely manner.
SUMMARY
The Register – A “lag” report can be developed showing the average This set of steps will provide the practice’s owners and managers
time between date-of-service, date of charge-entry, and date of with an accurate picture of their business process, and expected
claim submission. Additionally, a “Denials Log” can be kept to financial performance. If that performance is below the calculated
identify patterns of rejected claims so errors can be corrected (and target level, this monitoring system will show the areas where
prevented). 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.

40 retina times
>> RETINAL RISK MANAGEMENT

Anne M. Menke, RN, PhD Arthur W. Allen, MD


OMIC Risk Manager Section Editor

Retinopathy of Prematurity:
Creating a Safety Net
Due to space restrictions, the tables and letters referred to in the This document assigns responsibility for each task in the ROP
article are not included here. You can access the complete text of care process (see Table 1), based upon the fact that the neonatologist
“Retinopathy of Prematurity: Creating A Safety Net” in the “Risk is the primary care physician, whereas the screening and treating
Management Recommendations” section of the OMIC website ophthalmologist serve as consultants, while the baby is in the
(www.omic.com); articles are in alphabetical order. hospital. Accordingly, while the baby remains in the hospital, we
have assigned the neonatologist and NICU nurses the principle role
DISCLAIMER: Recommendations presented here should not be for coordinating and tracking appointments with consultants and
considered inclusive of all proper methods of care or exclusive of for communicating with the baby’s parents. At critical junctures
other methods of care reasonably directed to obtain the same results. in the ROP care process, however, the entire team needs to be
The ultimate judgment regarding the propriety of any specific involved. These points are the ongoing education of the parents and
procedure or treatment must be made by the ophthalmologist in light coordinating transfer of care to ophthalmologists at another hospital
of the individual circumstances presented by the patient. or in an outpatient practice. Once the baby has been discharged, the
This information is intended solely to provide risk management ophthalmologist is responsible for tracking outpatient ophthalmic
recommendations. It is not intended to constitute legal advice and care (this assumes that the ophthalmologist has been notified of the
should not be relied upon as a source for legal advice. If legal advice is discharge/transfer, and has agreed to treat the baby).
desired or needed, an attorney should be consulted. We want to acknowledge that during the hospital-care phase,
you as the ophthalmologist will not be able to implement all of
Screening and treating premature infants for retinopathy of these recommendations without the cooperation of the hospital,
prematurity (ROP) is an important aspect of pediatric ophthalmic neonatologist/pediatrician, NICU nurses, and parents (by “parents,”
care that provides a valuable service to not only the individual we mean whoever has current custody of the baby and is responsible
patient but also to society as a whole. Although claims against for making medical decisions on the baby’s behalf).
ophthalmologists for mismanagement of ROP are relatively You can, however, act as a patient advocate, and use these
infrequent, indemnity payments for these claims can be high due recommendations as the starting point for constructive dialogue.
to the young age of the plaintiffs and the significant loss of vision OMIC’s Risk Manager can be an important source of information
that can result even with treatment. Concerned about their liability and support for policyholders engaged in these discussions.
exposure, numerous screening and treating ophthalmologists called Conduct a risk analysis of your current process of care
OMIC to request sample protocols to help standardize care at the by identifying any steps in the following sequence for which
hospitals where they care for ROP patients. responsibility has not been assigned, or when care is not being
The goal of the risk management recommendations offered here is provided according to current clinical guidelines (e.g., the “Joint
to promote patient safety and minimize the liability exposures related Statement”).
to ROP care. They were developed after a detailed analysis of OMIC
ROP cases and of data from the Physician Insurer’s Association of RISK MANAGEMENT RECOMMENDATIONS FOR HOSPITAL-BASED
America (PIAA), Jury Verdict Reports, and IDEX (an expert witness ROP CARE
database), as well as a Failure Mode and Effects Analysis (FMEA),
designed to identify vulnerable points in the care process. They have 1. The neonatologist can use Table 3 to determine which babies
been reviewed by a number of pediatric ophthalmologists and retina need screening, and Table 4 to determine the timing of the first eye
specialists, risk managers, and attorneys. examination.
These suggested practices are designed to complement the clinical 2. SAFETY NET: Hospital ROP Tracking System. Most medical
recommendations found in published studies and summarized in malpractice lawsuits related to ROP occur when the baby is “lost to
“Screening Examination of Premature Infants for Retinopathy of follow up,” either in the hospital or after discharge or transfer. To
Prematurity,” the Joint Statement issued by the Ophthalmology prevent this, the hospital needs to develop and maintain a hospital
Division of the American Academy of Pediatrics (AAP), the American ROP tracking system. Ideally, one highly-educated and trained
Academy of Pediatric Ophthalmology and Strabismus (AAPOS), and person is designated as the ROP coordinator, and back-up is available
the American Academy of Ophthalmology (AAO), and published in when this person is on vacation. (For simplicity’s sake, we have
Pediatrics 2001; 108:809-811. The Joint Statement has recently been assigned this function to the NICU. Some hospitals appoint the NICU
revised, and approved by the Boards of AAO and AAPOS. As soon nurse responsible for discharge planning). Information to be tracked
as it is approved by the AAP Board, it will be published in Pediatrics. includes: name, date of birth, weight, gestational age, parent’s name
Information given here is from the 2001 version (referred to as “Joint and phone number, hospital account number, date of visit, findings,
Statement”) or other articles. and date of next follow-up visit. When the neonatologist identifies a
Risk management recommendations do not establish a standard baby for screening, the NICU enters the baby into the system. After
of care, but rather, serve as suggestions on how the healthcare team– the ophthalmologist hasconducted the initial examination, he or
the ophthalmologist, neonatologist/pediatrician, NICU (Neonatal she determines when the baby should be seen again, and documents
Intensive Care Unit) nurses, hospital, and parents–can create a the follow-up interval. The screening or treating ophthalmologist
safety net for these at-risk infants. They also serve to both reduce writes an order indicating the follow up interval. The NICU updates
the likelihood of a professional liability lawsuit and improve the the tracking system each time the baby is evaluated or treated,
defensibility of care if it is ever questioned. 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- and treatment, and prior to transfer or discharge. The screening and
up appointments are scheduled and kept. The NICU immediately treating ophthalmologists should complete the attached document,
notifies the neonatologist of any missed, cancelled, or rescheduled “Parents: Read This About Your Premature Baby’s Eyes,” each time
ROP appointments while the baby is in the hospital. an infant is first screened/treated for ROP, and whenever the infant’s
The NICU tracks the baby until one of these conditions is met: ROP status changes. The NICU should ask the parents to sign this
1) the screening ophthalmologist verifies that both eyes have met document and place it in the hospital record, as well as give the
the conclusion-of-acute-phase-ROP-screening criteria, 2) the parents a copy to take home. If the hospital is unwilling to give the
treating ophthalmologist verifies that treatment and necessary parents the document and/or ask them to sign it, the ophthalmologist
follow-up examinations are completed, 3) an ophthalmologist at the can mail it to the parents.
hospital to which the baby is transferred accepts responsibility for 9. SAFETY NET: Transfer/Discharge. This is the most vulnerable
further ophthalmic care and an initial appointment is scheduled, point in the ROP care process, so all members of the team need
or 4) an outpatient ophthalmologist accepts responsibility and an to be involved in discharge/transfer planning to ensure proper
initial outpatient appointment is scheduled. The hospital’s role ophthalmic follow up. No baby should be transferred/discharged
in tracking is complete when all of these conditions have been until an initial appointment has been made with the new screening
met: 1) the ophthalmologist who will be providing care has been or treating ophthalmologist and all pertinent records and current
notified of the discharge/transfer and has agreed to treat the baby, 2) contact information for the baby’s parents/guardian are sent.
a ROP appointment is scheduled at the second hospital or with an The neonatologist informs the neonatal nurse and the screening
outpatient ophthalmologist, 3) the baby’s pertinent medical records or treating ophthalmologist of a planned discharge or transfer,
have been sent, and 4) the parents/guardian’s contact information has in order to allow the ophthalmologist to assess the baby from an
been sent. ophthalmic perspective, and determine current follow-up needs.
3. The ophthalmologist should have sufficient knowledge and The ophthalmologist conveys the recommendations orally to the
expertise to enable accurate identification of the location and neonatologist, and writes a final ophthalmic consult note, unless a
sequential retinal changes of ROP after pupillary dilation using screening examination or treatment took place and was documented
binocular indirect ophthalmoscopy (Joint Statement). very recently. The neonatologist speaks with the pediatrician at the
4. The ophthalmologist should include an ROP consult note in the other hospital, or the baby’s outpatient pediatrician, and includes
infant’s hospital chart, and use the International Classification of the ophthalmic care needs in the discharge/transfer orders. The
Retinopathy of Prematurity (ICROP) to classify, diagram, and record neonatologist and pediatrician together ensure that a new screening
the retinal findings at the time of the examination or treatment or treating ophthalmologist has been found to assume the ophthalmic
(Table 2). Some ophthalmologists now also categorize pre-threshold care (with recommendations, if possible, from the screening or
ROP as Type 1 and Type 2. See Table 7. treating ophthalmologist). Experience shows that parents cannot
5. Table 5 is helpful in determining the follow up interval during the be relied upon to schedule this care. Cultural, language, and health
screening phase. The screening ophthalmologist should write follow- literacy issues, as well as difficulties inherent in assuming the care
up orders in the hospital chart, and the NICU should update the of premature infants, often interfere with the accurate transmission
tracking system and schedule the follow-up appointment. of key information, and place these babies at great risk. To protect
6. The screening ophthalmologist should screen until both eyes have the infant, the NICU nurse talks with a nurse at the nursery at the
met the conclusion-of-acute-phase-ROP screening criteria new hospital, or with the ophthalmologist’s office staff, to schedule
(Table 6) or until the treating ophthalmologist has verified that the initial ophthalmic appointment and provide all necessary
treatment and all follow-up examinations are completed. One information. If the current ophthalmologist will continue to see the
examination is sufficient only if it unequivocally shows the retina to baby after transfer or discharge, he or she also notifies office staff
be fully vascularized in each eye. to expect a call from the NICU, and instructs staff to enter the baby
7. Table 7 provides guidance on when to initiate treatment and in the office ROP tracking system. If the NICU is unwilling to help
explains how to further categorize pre-threshold ROP as Type 1 coordinate the initial 2nd hospital or outpatient visit, and you as the
and Type 2 ROP. The screening ophthalmologist should notify the ophthalmologist are asked to see the baby, ensure that the appropriate
neonatologist and document the recommendation to begin treatment records, including recent contact information for the parents, are sent
in the hospital record. Depending upon the protocol at the hospital, to you.
either the screening ophthalmologist or the neonatologist should 10. To ensure the standardization, reliability, and effectiveness of ROP
write an order for the NICU to both update the tracking system care, the ophthalmologist, neonatologist, and hospital need to have a
and schedule an appointment with a treating ophthalmologist. The written agreement or protocol (see sample protocol).
screening ophthalmologist conducts and documents a transfer-of-
care discussion with the treating ophthalmologist, conveying the RISK MANAGEMENT RECOMMENDATIONS FOR OUTPATIENT ROP
urgency of the referral, and ensures that the second doctor has access CARE
to, or copies of, the patient’s previous history and eye examinations.
8. SAFETY NET: Parent Education. All members of the team need 1. The ophthalmologist should have sufficient knowledge and
to help educate the parents about ROP, the need for careful follow expertise to enable accurate identification of the location and
up until both of the baby’s eyes have either met the conclusion-of- sequential retinal changes of ROP after pupillary dilation using
acute-screening criteria or treatment and follow-up examinations binocular indirect ophthalmoscopy (Joint Statement).
are completed during the acute phase, the consequences of 2. SAFETY NET: Coordinate transfer of care to the outpatient setting.
missing screening or treatment appointments, and the need for This is the most vulnerable point in the ROP care process, so all
long-term ophthalmic care. Verify the parents’ understanding of members of the team need to be involved in discharge planning
the information, and carefully document all educational efforts. to ensure proper ophthalmic follow up. Conduct and document
The neonatologist should inform the parents when the baby needs a transfer-of-care discussion with the current screening or treating
screening evaluations, and when treatment is recommended. The ophthalmologist. Instruct your staff to speak to the NICU nurse
neonatal nurse should educate the parents before and after screening to determine the discharge date, schedule the initial outpatient

44 retina times
appointment, and obtain all relevant medical records and current Baby’s Eyes,” each time an infant is first screened or treated for ROP,
contact information for the parents. Instruct staff to enter the baby and whenever the infant’s ROP status changes. Ask parents to read
into the ROP tracking system. and sign the form, put the form in the chart, and give them a copy to
3. SAFETY NET: Telephone Screening of Ophthalmic Problems. If take home (see sample letter).
the NICU in your hospital is unwilling to speak with your office to 8. Screen until both eyes have met the conclusion-of-acute-phase-
coordinate the transfer of care, ensure that staff members who answer ROP-screening criteria (Table 6). One examination is sufficient only
phones are trained in telephone screening and know how to identify if it unequivocally shows the retina to be fully vascularized in each
babies who need ROP care. Some babies have been lost to follow up eye.
because the parents did not identify the need for ROP care, and the 9. See Table 7 for when to initiate treatment.
staff member who scheduled the appointment did not ask if the baby 10. Carefully document in the infant’s medical record your referral
was premature or had been seen in the hospital. Other parents have of any ROP patient to another physician (e.g., for treatment), and
changed the name of the baby since the baby was seen in the hospital, include the physician’s contact information. In addition, conduct and
so the practice did not recognize the infant as one who had already document all transfer of care discussions and forward to the second
been seen when the parents scheduled the appointment. If the baby is doctor documentation noting the indication and urgency of the
identified as premature, staff should be directed to ask the gestational referral, along with a copy of a record of the patient’s previous history
age in weeks, and the date of birth, so postmenstrual age can be and eye exams.
calculated (see Table 4). Also see OMIC’s “Telephone Screening of 11. SAFETY NET: Follow up on all changes in appointments. To
Ophthalmic Problems” guidelines for forms and general telephone ensure that missed appointments are noticed, instruct your staff to
screening recommendations (available in the Risk Management schedule the next appointment before the parents leave the office,
Recommendations section at www.omic.com). and to update the tracking system. Do not rely upon the parents to
4. SAFETY NET: Office ROP Tracking System. Most medical schedule the follow-up appointments. Instruct your staff to review
malpractice lawsuits related to ROP occur when the baby is “lost to appointments on a daily basis, and to notify you immediately of any
follow up.” To prevent this, the practice must create and maintain change in ROP appointments, including no-shows and cancelled or
a ROP tracking system. When the initial outpatient appointment is rescheduled appointments. Instruct staff on the type and urgency of
scheduled, the baby is entered into the system. Each time the baby follow-up needed (e.g., “Need to see baby tomorrow at the latest, call
is evaluated or treated, the ophthalmologist indicates the follow up parents immediately”). The follow up should be tailored to the level
interval, and the office schedules the follow-up appointment before of risk to the infant’s vision. Implement your ROP follow-up protocol
the parents leave the office. The tracking system is then updated for all of these schedule changes and document all follow-up efforts.
to note the current condition and follow up interval. The tracking Recommended follow-up efforts: 1) Instruct staff member to call
system is evaluated at least once a week to ensure that all follow- same day of changed appointment. 2) Send “missed appointment”
up appointments are scheduled and kept. The ophthalmologist is letter, with a copy to the baby’s pediatrician, if staff member doesn’t
notified immediately of any missed, cancelled, or rescheduled ROP speak to parent, or parent is unwilling/unable to bring infant at
appointments (see Follow Up, below). The baby is tracked until designated interval. Letter should explain the urgency of the needed
one of these conditions is met: 1) the screening ophthalmologist care and consequences of noncompliance (see sample “Missed
verifies that both eyes have met the conclusion-of-acute-phase-ROP- ROP Appointment” letter). For further instructions, see OMIC
screening criteria (Table 6), 2) the treating ophthalmologist has “Noncompliance” guidelines (available in the Risk Management
verified that treatment and follow-up examinations are completed, Recommendations section at www.omic.com). If the infant is at high
or 3) care is transferred to another ophthalmologist. If care is risk for vision loss, send by regular and certified mail. 3) Notify the
transferred to another ophthalmologist, the office’s role in tracking baby’s pediatrician of noncompliance by phone, and by faxing a copy
is complete when all of these tasks have been accomplished: 1) a of the letter to the parents, and document the discussion. 4) Consider
ROP appointment is scheduled at the other ophthalmologist’s office, contacting your state’s Child Protective Services office for extremely
2) the baby’s medical records have been sent, and 3) the parents’ high risk infants who may meet treatment criteria at the time of
contact information has been sent. the missed examination, or for treated infants with a suboptimal
5. Use the International Classification of Retinopathy of Prematurity treatment response.
(ICROP) to classify, diagram, and record the retinal findings at the OMIC policyholders who have additional questions or concerns
time of the examination or treatment (Table 2). Table 7 explains how about ROP are invited to call Anne M. Menke, R.N., Ph.D., OMIC
to differentiate between Type 1 and Type 2 ROP. Risk Manager, at (800) 562-6642, extension 651.
6. Use Table 5 to determine and note the follow up interval. Instruct
your staff to schedule the next appointment before the parents leave ELEMENTS OF A SAMPLE PROTOCOL/AGREEMENT
the office, and to update the tracking system. Do not rely upon the FOR HANDLING ROP CARE IN THE HOSPITAL
parents to schedule the follow-up appointments. Cultural, language,
and health literacy issues, as well as difficulties inherent in assuming To ensure the standardization, reliability, and effectiveness of ROP
care of premature infants, often interfere with the parents’ ability to care, the ophthalmologist, neonatologist, and hospital need to have a
understand ROP and can place the infant at great risk. written agreement or protocol that addresses:
7. SAFETY NET: Parent Education. Enlist appropriate members • Task assignments (see Table 1 for a summary)
of your staff to help educate the parents about ROP, the need • The guidelines used to identify at-risk infants
for careful follow up until both of the baby’s eyes have met the º The recently revised AAP/AAO/AAPOS Joint Statement, when
conclusion-of-acute-ROP-screening criteria or treatment and available, provides an excellent summary of current research and
follow-up examinations are completed, the consequences of recommendations
missing screening or treatment appointments, and the need for • Identifying infants to be screened
long-term ophthalmic care. Verify the parents’ understanding of the º Responsibility: neonatologist
information, and carefully document all educational efforts. Fill out º See Table 3 for infants needing ROP screening examination
the attached document, “Parents: Read This About Your Premature • Dilating protocol: that clarifies drugs, dosages, RN administration

retina times 45
>> RETINAL RISK MANAGEMENT

r
• Talking to the parents about screening the baby for ROP º Responsibility: Screening ophthalmologist
º Responsibility: • Scheduling the treatment appointment with the treating
• Neonatologist ophthalmologist
• NICU nurse º Responsibility: NICU based upon written order from
• Scheduling the initial eye examination with the screening neonatologist or screening ophthalmologist
ophthalmologist • Obtaining informed consent for the ROP treatment
º Responsibility: º Responsibility: Treating ophthalmologist
• Neonatologist to order initial examination • Use procedure-specific consent form that clarifies that even
• NICU to schedule and administer drops per dilating protocol with treatment, some babies still develop retinal detachments
º Based upon the infant’s postmenstrual age (gestational age plus and blindness, and that long-term follow up is required
chronologic age) • Informing parents of results of treatment, need for follow up, and
º See Table 4 for timing of initial examination consequences of no follow up
• Entering the baby into the ROP tracking system. Track infant º Responsibility:
until 1) screening ophthalmologist verifies that both eyes have • Treating ophthalmologist (by letter given to parents by
met conclusion-of-acute-ROP-screening criteria, 2) the treating NICU)
ophthalmologist verifies that treatment and follow-up examinations • Neonatologist (talk to parents)
are completed, or 3) NICU has scheduled initial appointment with • NICU nurse (talk to parents)
screening or treating ophthalmologist at other hospital or in office • Following the infant after treatment
º Responsibility: NICU º Responsibility: Treating ophthalmologist by written order
º The tracking system must be updated for each new baby, and • Scheduling follow-up treatment appointments in the hospital
after each screening or treating appointment º Responsibility: NICU based upon written order from treating
• How the ROP examinations and treatments will be documented ophthalmologist
º Responsibility: screening and treating ophthalmologists • Determining that the baby is ready for transfer/discharge
º Use ICROP º Responsibility: Neonatologist
º See Table 2 for ICROP system. See Table 7 for how to • Notifying the screening or treatment ophthalmologist that the infant
classify pre-threshold ROP as Type 1 or Type 2 ROP. is ready for transfer/discharge
• Determining follow up interval after screening º Responsibility: Neonatologist
º Responsibility: Screening ophthalmologist by writing order in • Writing an ophthalmic consultant note prior to discharge/
chart transfer that summarizes ROP status and screening/treatment
º See Table 5 for timing of follow-up examinations recommendations
• Informing the parents of the results of the screening evaluation, º Responsibility: Screening or treating ophthalmologist, depending
follow up interval, consequences of no follow up upon who is currently providing ROP care
º Responsibility: • If the ophthalmologist has evaluated or treated the baby very
• Neonatologist and NICU nurse talk to parents recently, no further note may be needed
• Screening ophthalmologist completes letter for NICU to give • Writing discharge/transfer orders that address ROP if the infant is
to parent transferred/discharged before the screening ophthalmologist verifies
• See sample letter that the retina has met conclusion-of-acute-phase-ROP-screening
• The need to screen after pupillary dilation using binocular indirect criteria or the treating ophthalmologist verifies that treatment and
ophthalmoscopy until both eyes have met the conclusion-of-acute- follow-up examinations are completed
screening criteria º Responsibility: Neonatologist
º One examination is sufficient only if it unequivocally shows the • Conducting and documenting a pre-transfer discussion with the
retina to be fully vascularized in each eye pediatrician who will be assuming role of primary care provider
º See Table 6 for conclusion-of-acute-phase-ROP screening after transfer/discharge
criteria º Responsibility: Neonatologist
• Scheduling follow-up screening appointments in the hospital • Finding a screening or treating ophthalmologist at the other hospital
º Responsibility: NICU based upon order of screening or in an office prior to transfer/discharge
ophthalmologist º Responsibility: Neonatologist and pediatrician, with
• Deciding when treatment for ROP is needed recommendations when possible from the screening or treating
º Responsibility: Screening ophthalmologist ophthalmologist
º See Table 7 for when to initiate treatment • Conducting and documenting a pre-transfer/discharge discussion
• Informing the neonatologist about need for ROP treatment with the parents regarding the infant’s ROP status, follow up
º Responsibility: Screening ophthalmologist (talk and progress interval, and consequences of no follow up
note) º Responsibility:
• Informing the parents about the proposed ROP treatment • Neonatologist (talk to parents)
º Responsibility: • NICU nurse (talk to parents)
• Neonatologist (talk to parents) • Current screening or treating ophthalmologist (phone and
• NICU nurse (talk to parents) letter, which the NICU gives to parents)
• Screening ophthalmologist (by phone and by completing • Scheduling the initial follow-up appointment after transfer/
letter that NICU gives to parents) discharge with the screening or treating ophthalmologist
• Finding an ophthalmologist to treat the ROP º Responsibility: NICU
º Responsibility: Neonatologist or screening ophthalmologist by • Conducting and documenting a transfer-of-care discussion with the
written order, depending upon protocol new ophthalmologist
• Conducting and documenting a transfer-of-care discussion with the º Responsibility: Current ophthalmologist
treating ophthalmologist
46 retina times
c
>> UNCLE RICH

William L. Rich, III, MD

r
AAO Medical Director
of Health Policy

Competitive Acquisition Program

h
Dear Uncle Rich: it is administered but it does not have to showed an overwhelming preference for the
What is the story on our ability to buy retinal have separate physical storage from other establishment of a CAP program. Our ability
drugs in 2006? There have been so many pharmaceuticals. If state law permits and the to get CMS to change its original plans and
changes in the past couple years in Medicare drug is unused and unopened, the doctor include retinal drugs is a major victory for
payment for drugs given in the office for may retain the drug and administer it to the profession.
ARMD: 95% of AWP (Average Wholesale another patient after a new order is sent to As of this date the CAP program
Price), 85% of AWP, ASP (Average Sales the vendor. The retina doc must submit a will include verteporfrin (Visudyne),
Price) + 6%, etc., etc. This has been very claim to CMS for the drug administration triamcinolone, bevacizumab (Avastin), and
disruptive to my practice and has resulted in service (67028 for intravitreal injections or the IV solutions for Visudyne. Macugen did
large monetary losses because of our inability 67221 for PDT) within 14 days of treatment. not have the minimum sales volume when
to collect co-payments for these expensive CMS will not pay the vendor for the drug the list of covered drugs was first published
drugs! I am tired of acting as a billing agent unless they have received documentation but the AAO and Eyetech approached CMS
for the pharmaceutical industry!! Is there any from the doctor that the service was provided and we feel confident it will be included for
relief in sight? in the office. 2006. Lucentis will not have approval in time
Overwhelmed in Oneida When a patient is seen in consultation in for inclusion in 2006.
the office and it is deemed necessary to treat
Dear Overwhelmed: that same day, the retina doc may dispense Disadvantages:
Relief is in sight. As part of the Medicare the drug from inventory if: The AAO has expressed concern about the
Prescription Drug, Improvement and 1) the drugs are required immediately, billing of wastage under the CAP program.
Modernization Act of 2003 (a.k.a. MMA), 2) the doc could not have known the drugs We hope to have this issue clarified by the
Congress mandated that CMS establish a were needed prior to the visit, time physicians decide on their participation.
competitive acquisition program (CAP) for 3) the vendor could not have delivered the If you do elect to participate, you are locked
Part B drugs and biologicals administered in drugs in a timely manner, and into the chosen CAP vendor for one full year.
physicians’ offices. An initial proposal from 4) the drugs were administered on the same Your staff should educate your patients that

i
CMS was going to limit the CAP program to day as the consultation. shortly after the delivery of the service they
2-3 regions in the country and only deal with The office must add a new modifier to the will be billed for the drug from the vendor.
oncology. With ASP+6% payment, there was administration code if the drug is delivered You will be responsible for verifying that the
huge frustration in the retinal community as an emergency. If the doc has signed a CAP planned use of the drug is consistent with
with billing complexity and the financial agreement and the emergency falls within any relevant carrier coverage policies but this
risks being borne by retinologists. The AAO, these guidelines, a drug may not be delivered doesn’t preclude the use off label. If a patient
working with George Williams and Reggie under direct purchase from the manufacturer fails to pay the vendor or requested financial
Sanders of the ASRS, strongly advised CMS under ASP. assistance within 45 days from the postmark
to make the initial program national in Once the vendor receives verification date of the vendor’s bill, the vendor may
scope and to include retinal drugs. In a final from CMS that you have administered the decline to ship more drug to the physician
rule published this summer in the Federal drug, they will proceed to bill Medicare and for that beneficiary.
Register, CMS agreed with our comments. As the patient/Medigap plan for the 20% co-pay.
a result, in 2006 retinal docs may participate The vendor takes on all the financial liability Participation:
in CAP to obtain drugs like Visudyne from of billing and collections. Retinalogists will be asked to sign a CAP
national vendors or continue to buy drugs participation agreement and select a vendor.
directly from the manufacturer at ASP+6. Advantages:
The physician is out of the drug business! In summary, there is some hope of sanity
How is CAP going to operate? You are no longer the middleman and on the horizon after four years of chaos
When a patient comes in and is determined have no more financial liability. There may dealing with the acquisition of retinal drugs
to need the use of a retinal drug, the doctor be some retinal practices with a superb administered in the office. You will be
will fax an order to the vendor. The vendor record of collecting all co-pays and they notified of the specifics of CAP participation
must supply the drug to the physician’s may want to forgo the CAP program and later this year in the AAO Washington Report
office within two business days for a routine continue to purchase the drugs from the and on the ASRS Message Board. Good luck.
service and one day for an emergency. The manufacturer at the ASP+6% price. However, Hang in there.
physician’s office must store the drug until informal surveys of retina specialists

retina times 47
>> MEDICAL ETHICS

Nancy M. Holekamp, MD
Section Editor

Physicians as Investment Consultants:


Risky Business
As noted in the last issue, we had planned to bring you the “AAO Rules The ethical issue at hand is respect for confidentiality agreements.
of Ethics” in this issue. It was decided instead to run the following The 20 or 23 doctors involved in the clinical research on Lucentis
article, due to its particular importance and timeliness. Part 2 of “Your and Macugen had undoubtedly signed confidentiality agreements
Code of Ethics” will appear in a future issue. with the respective pharmaceutical companies. In general, such
documents will include something like the following:

“Except as otherwise expressly provided in this agreement,


Great strides in ophthalmology research are making headlines–but university (including investigator) shall keep the information
that is not necessarily good news. Reported in the Seattle Times on confidential and shall not disclose to others either the
August 7, 2005 in an article entitled, “Drug Researchers Leak Secrets information or any result of the discussions or evaluations.”2
to Wall Street”: 1
Was there an unethical breach of confidentiality? We may never
“Recently, Citigroup Smith Barney penetrated a major study know. But what would entice intelligent researchers to divulge
to see how an experimental drug fared against a just-approved confidential information, even if unintentionally? The answer:
drug for treating macular degeneration, an incurable eye physicians may get paid $200 - $1000 per hour to talk to investment
disease and the leading cause of blindness in the elderly. firms. This is yet another financial conflict of interest for our
The brokerage talked to 26 eye doctors, but they weren’t just profession.
any doctors. Twenty of the 26 had researched the experimental And ophthalmologists are not alone. A June 1, 2005 article in
drug; 23 of the 26 had researched the other one, meaning that JAMA3 estimates that 10% of the 700,000 U.S. physicians receive
more than half had worked on both. The doctors were able to payment from investment firms for their opinion. A “matchmaker”
give Smith Barney valuable comparative information. company, Gerson Lehrman boasts contractual agreements between
Nearly all agreed that the drug still being studied, a product over 60,000 physicians and roughly 50 investment firms. The
called Lucentis from biotech powerhouse Genentech, would Seattle Times article uncovered 26 instances where doctors leaked
prove vastly superior to the drug that recently had gone on the important details of ongoing clinical research to investment firms.
market, Macugen, made by Eyetech, a smaller company. In 24 of those 26 cases the firms then issued reports to select
But the doctors were more explicit than that. Based on its investment clients with advice to buy or sell a stock.
survey, Smith Barney predicted remarkable results: 97 percent Physicians serving as consultants to analysts for investment
of patients on Lucentis would have stable or improved vision, companies may be risky business. If it leads to divulging material
as measured by how many lines of an eye chart they could information prior to public release, such ethical breaches of
read. Smith Barney summarized those findings in a report to confidentiality agreements may be illegal. In the words of renowned
select customers May 5. ethicist Arthur Caplan, director for the Center of Bioethics at the
As it turned out, the numbers were almost exactly on the University of Pennsylvania, “If this isn’t insider trading, I don’t
money. On May 23, not long after Smith Barney’s report, know what is.” In response to the Seattle Times article, the American
Genentech announced results from its Lucentis study: 95 Association of Medical Colleges is urging its members to be aware
percent of patients had stable or improved vision–just as that such communications may be governed by federal securities
predicted by the doctors Smith Barney talked to. law and is recommending that agreements prohibiting disclosure
The announcement battered Eyetech’s stock, which lost of clinical trial information to third parties be scrupulously
nearly half of its value in a day. Any hedge fund or other honored. Senator Charles E. Grassley, chairman of the Finance
investor who had acted on Smith Barney’s research by betting Committee, has called on the Justice Department as well as the
against Eyetech would have made better than a 40 percent S.E.C. to investigate the issue of payment for drug trial results.
return in just three weeks.” 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

Mark Levitan, MD
Director, Carrier Network

Billing Macugen–
and what else?

CMS reimbursement for Macugen has been relatively uneventful the need for the procedure then the same day evaluation is included
compared to our previous history with Visudyne. Billing in the payment. CMS will pay for this same day evaluation only
Medicare for the drug itself and the injection (CPT 67028) is not when you and the carrier consider it a “significant and separate
controversial; however, that is not all we do in following macular identifiable service” and you attach modifier 25 to the exam. Be
degeneration. Four areas of potential increased reimbursement careful to realize that even if you have been reimbursed that doesn’t
need to be discussed; increased treatment frequency, diagnostic mean you were paid appropriately. Your carrier can always ask for
testing, combination treatment and same day examination. the money back if an audit determines you were paid incorrectly.
The study protocol for intraocular Macugen was treatment every The Office of Inspector General has listed the inappropriate use of
6 weeks. Medicare Carriers will reimburse for treatments according modifier 25 as a target for investigation.
to “standard of care”. One issue that might trigger a review for Several carriers have ruled on this problem with written policies.
medically unnecessary would be an injection that occurs in less The initial evaluation requiring intraocular Macugen and resulting
than 6 weeks, or an increase in the total number of injections in in same day treatment allows for a reimbursable exam. Subsequent
a year, exceeding 9. The Medicare Carriers Cahaba, Noridian and exam/treatments are a different story. Cigna has written that,
Trailblazer have issued coding and billing guidance stating that they “review of previous treatment’s effectiveness is not a separate
don’t expect subsequent injections to be less than 6 weeks apart. service.” Empire of New York writes “evaluation of the effect of a
The Macugen studies did not use fluorescein angiograms prior injection is not considered a separate identifiable service.”
or OCT to determine the need for each subsequent treatment. The Medicare Carrier for Kansas, Nebraska and northwest Missouri
There are presently no medical coverage policies that prohibit has a written policy on macular degeneration and photodynamic
angiography. In fact, First Coast Services of Florida and therapy; “if a problem distinct from macular degeneration and OPT
Connecticut allow for the potential use of an angiogram prior to is addressed then modifier 25 should be attached.” However, this
each treatment. The rationalization is that this may be needed to scenario is not the typical “one time” surgery that CPT originally
monitor disease progression. Empire of New York has a draft policy described. A significant and separate evaluation may be necessary
that prohibits non-angiogram testing for follow-up injections. This considering the progressive nature of macular degeneration. After
is only a draft and is not ready to be enforced. all, study protocols only answer a specific question and are not
Currently, there are no written national or Carrier policies meant to be a substitute for the practice of medicine.
prohibiting Medicare reimbursement for Macugen combined The point is that your local CMS Carrier may be the limiting
with other intraocular injections. This is more than just a factor for reimbursement. There is no Carrier written policy that
reimbursement issue; it is a standard of care question. Medicare has limits reimbursement when following the explicit guidelines
a blanket prohibition against medically unnecessary services so the outlined in the Macugen label. Your changes to this protocol may be
responsibility to defend combination use rests with the physician. “reasonable and necessary” if the carrier’s policy has no additional
Empire of New York has proposed a draft policy specifically stating limitations and they agree to your definition and assumptions for
that they won’t pay for combination Macugen (pegaptanib sodium the specific patient being treated. Macugen therapy is still relatively
injection) and Visudyne (verteporfin) treatments. new to the CMS bureaucracy; Empire of New York is the only
Billing Medicare for an exam on the same day as a Macugen carrier to suggest such specific restrictions but more could follow.
treatment may be open to interpretation. Intravitreal injections Their draft policy can be implemented only after a public comment
(CPT 67028) are defined as minor surgery; with no post-operative period. Now is the time to be vigilant checking your own Carrier’s
period. The relative value units for this minor surgery include the website and join the political process. Speak out when you see draft
pre-operative and post-operative work done on that same day as policies that are not allowing you the discretion to decide what is in
treatment. If the purpose of the examination is only to determine your patient’s best interest.

retina times 51
>> CODING TIP

Trexler M. Topping, MD
Section Editor

The Time Has Come


This may seem like an unlikely topic, but it is one that has much help strategize how to avoid specific cuts. Guys and gals, there is no
to do with how we as ophthalmologists are paid. The RBRVS free lunch out there. We are not going to get special treatment and
(Resource Based Relative Value System) pays us on the basis of be paid better than others. I personally feel there is little doubt that
several factors–the physician work, the practice expense, and the physicians are greatly underpaid. Because of the SGR (sustainable
practice liability (malpractice insurance) risk. The practice expense growth rate formula which is used to calculate the conversion factor
is based on the specific practice expense items related to the which CMS employs to calculate reimbursement for each code and
particular code (use of an exam lane, cost of ophthalmic tech, cost to penalize us for increased utilization) we are currently scheduled
of the laser, etc.) and is also based on the overall practice expense to suffer a 1.5% reimbursement cut beginning in January of 2006.
of ophthalmology. Based on the SMS survey of practice expense This is in the face of our costs going up all the time with more
in many specialties of medicine and surgery previously performed expensive equipment and supplies, higher rent, and of course we all
by the AMA, the practice expense for ophthalmology is one of the gave our staffs 3% or greater raises last year.
highest in medicine and surgery, running at about $140 per hour. Patients mostly feel doctors are overpaid (they look at the billed
Each code we bill for Medicare patients is associated with a charges on the EOB, but usually fail to look at the amount Medicare
physician time (the time the doctor expends in supplying the or the insurance company actually pays.) Whenever I deal with a
service, e.g. 92014 Comprehensive eye, established patient, is 39 disgruntled patient, or more frequently a corporate CEO who is
minutes, and 67107 Scleral buckle is 298 minutes for all surgery dealing with selecting health insurance for his company, or when
and post-op visits). Thus CMS (Center for Medicare and Medicaid dealing with legislators or with patients working in the media, I
Services) can take all codes submitted by ophthalmologists on give them a three minute course in health care finance. I point out
Medicare patients for a year, and add up all of the minutes eye that our ‘charges’ are irrelevant. We get paid virtually the same by
MDs have spent with Medicare patients. CMS then multiplies Medicare and private insurance. Those without insurance seldom
the number of hours eye MDs spent with Medicare patients pay, and rarely pay above Medicare allowable. Thus physician
and multiplies that by the ophthalmology practice expense per fees are controlled. I then say if they need to go to the hospital for
hour (about $140) and that number represents the value of the surgery, the hospital reimbursement is set by DRGs. There is a zone
ophthalmology practice expense pool. Then this expense pool is of medical expense which is truly ‘free trade’, the sector including
used to pay the practice expense portion of all the codes performed drugs and expendable supplies (pacemakers, stents, catheters,
by ophthalmologists. devices). I then point out the average Medicare patient spends
Why is such an arcane bit of information of value to a retina more out of pocket for their medications than for all physician and
specialist? Well, the Five Year Review is currently underway. This is hospital services combined. I then urge them to speak to or write to
a congressionally mandated process where CMS reviews a number their Congressmen about this.
of codes to see if there has been a significant change in the value In summary, cuts are likely to come partially based on some
of services in the last five years. A number of ophthalmology diminution of the ophthalmology practice expense pool, and
codes have been submitted including vitrectomy with membrane further losses are predicted for next year based on a declining
peeling, panretinal laser photocoagulation, fluorescein angiography, Conversion Factor. The system is unfair to all physicians, and I am
extended ophthalmoscopy, and, significantly–cataract surgery. Why afraid the only hope will come through legislation. My friends,
do I include cataract? Well, cataract may be the most important of the onus is on you. Your future and your well being as a physician
the lot to all of us. depend on it. Talk or write to your congressmen and ask your
Currently cataract surgery is credited with 50 minutes of patients to contact them also.
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. X-FILES DISCUSSION
That one little change would mean almost $100 million less in (continued from page 50)
the ophthalmology practice expense pool. This decline would be
spread over all of the eye codes, meaning about $5,000 less to each The patient presents in an interesting manner. The CME and the
ophthalmologist solely based on the impact of potential reduction vascular constriction make the possibility of a primary retinal
of time of cataract surgery on our practice expense pool. degeneration a possibility. Other entities have to be entertained
The whole process of code valuation and reimbursement is including AZOOR as well as other post-inflammatory entities.
complex and often not apparent on the surface. Over the last fifteen The patient was given Diamox 250mg sequels P.O. BID with the
years of working with coding and reimbursement, I have learned vision increasing to the 20/30 range. I believe other entities such as
unfortunately that we are not paid fairly. I have labored to try to Stargardt’s disease are less likely given the presentation of edema.
prevent wholesale cuts in our reimbursements, and have tried to Input from all would be welcome regarding this fascinating case.

52 retina times
>> 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’ >> THE RETINAL WORLD
FORUM

Suzanne Demming, MD
Section Editor

Upcoming Meetings for the Retinal Specialist


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