10.1.1.124.9261[1]

ASRS 23RD ANNUAL MEETING HIGHLIGHTS

INTRAVITREAL AVASTIN

4TH ANNUAL RETINAL RESEARCH REPORT

RNA INTERFERENCE TECHNOLOGIES

RISK MANAGEMENT: ROP

14retinaretinatimesA VOICE FOR GREATER VISIONThe Official Publication ofthe American Society of Retina SpecialistsFall 2005 Issue 14

Organizational Staff

Tom S. Chang, MDEditor-in-Chief

Steve LenierManaging Editor

Lida AsatryanAssistant Managing Editor

Cordie L. MillerASRS Managing Director

Eugene de Juan, Jr., MDASRS President

John S. Pollack, MDCommunications Committee Chairperson

Section Editors

Arthur W. Allen, Jr., MDRisk Management Section Editor

Carl C. Awh, MDFellows Forum Section Editor

Karen BaranickAnnual Meeting Section Editor

Abdhish R. Bhavsar, MDFilm Festival Section Editor

Antonio Capone, Jr., MDAAO/Federal Affairs Liaison

David R. Chow, MDRetsumer Reports Section Co-Editor

Suzanne Demming, MDRetinal World Section Editor

Calvin A. Grant, MDX-Files Section Editor

Scott G. Foxman, MDPractice Management Section Editor

Tarek S. Hassan, MDRetsumer Reports Section Editor

Nancy M. Holekamp, MDMedical Ethics Section Editor

Mark S. Humayun, MD, PhDR&D Committee Section Editor

Judy E. Kim, MDJCAHPO News Section Editor

Todd R. Klesert, MD, PhDKOL Corner Section Editor

Roy Levit, MDFoundation Chairman

Mark Levitan, MDState Carrier Network Director

Klaus Lucke, MDEVRS News Section Editor

Mathew MacCumber, MD, PhDClassifieds Section Editor

G. Philip Matthews, MD, PhDPractice Management MeetingSection Editor

John S. Pollack, MDPAT Survey Section Editor

Ethan PrielOPS/ASRS Liaison

Hugo Quiroz-Mercado, MDInternational News Section Editor

William L. Rich, III, MDAAO Medical Director of Health Policy Section Editor

Michael A. Samuel, MDIn the Spotlight Section Editor

Ingrid U. Scott, MD, MPHTips and Techniques Section Editor

Jay M. Stewart, MDIn the Pipeline Section Editor

Trexler M. Topping, MDCoding Tip of the Quarter

Allen Z. Verne, MDSite Selection Section Editor

Creative Staff

Tun Min SoeArt DirectorMADLab, Doheny Eye Institute

John TomDesigner

Fall 2005 Issue 14Volume 23, No. 3The Retina Times is published quarterly by the American Society of Retina Specialists (ASRS), Chico, California, as a service to the membership.

The mission of the publication is to strive to be the definitive information source for ASRS members on Society news, meeting plans, socioeconomic topics, international news, and other relevant information on issues, instruments and study updates for the practicing retinal specialist. Articles published herein are reviewed by the editor-in-chief and managing editor for editorial content only. The accuracy of information contained is the responsibility of the individual author. Letters and other unsolicited material are assumed to be intended for publication and are subject to rejection or editing.

All articles which appear in The Retina Times are intended for informational purposes only and should not be relied upon by any reader for any other purpose. The opinions and positions expressed in The Retina Times articles are solely those of the authors and do not represent the opinions or positions of the ASRS Board, its members, or The Retina Times editorial staff.

American Society of Retina SpecialistsPMB #A2485 Notre Dame Blvd., Suite 370Chico, CA 95928phone: (530) 566-9181fax: (530) 566-9192e-mail: [email protected]

About the Cover:Posterior synechiae of iris to lens. Photographer: Doheny Imaging Department

© 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.

retinaretinatimes

The Retina Times would like to thank Novartis Ophthalmics,

Alcon Laboratories,and

Bausch & Lomb for providing

Unrestricted Educational Grants. Their generosity assists in

enabling ongoing enhancements to this publication.

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 [email protected].

6FROM THE EDITOR’S DESKAre we Surgeons or Oncologists?

7FROM THE INSIDECreative Design Rationale forthe Retina Times

8EVRS NEWSEuropean Sleepless Nights in Sweden

10ASRS 23RD ANNUAL MEETING HIGHLIGHTS

15THE 7TH ANNUAL ASRSFILM FESTIVAL 18THE KOL CORNERSo you want to try Intravitreal Avastin

234TH ANNUAL RETINALRESEARCH REPORT

36IN THE PIPELINEResearchers Eye RNA Interference Technologies

37TIPS AND TECHNIQUESPneumatic Retinopexy Misconceptions

39PRACTICE MANAGEMENTThe Retina Practice Business Process

43RETINAL RISK MANAGEMENTRetinopathy of Prematurity:Creating a Safety Net

47UNCLE RICHCompetitive Acquisition Program

49MEDICAL ETHICSPhysicians as Investment Consultants: Risky Business

50THE ASRS X-FILES

51CARRIER NETWORKBilling Macugen– and what else?

52CODING TIPThe Time Has Come

57FOUNDATION UPDATE

57JCAHPO NEWS

59AAO LIAISON REPORT

59PRACTICE MANAGEMENT MEETING

59ADVERTISER INDEX

60FELLOWS’ FORUM

60THE RETINAL WORLDUpcoming Meetings

>> CONTENTS

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EAre 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 [email protected]

Tom Chang, MDEditor-in-Chief

>> FROM THE EDITOR’S DESK

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ECREATIVE 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.

>> FROM THE INSIDE

retina times 7

Tun Min SoeArt Director, MADLabDoheny Eye Institute

THE MACULA IN FOCUSThe scientific program was concerned with all that could be said on the macula. The importance of correctly planning and executing diagnostic procedures was stressed through a variety of papers and posters. The use of an assortment of therapeutic agents such as intravitreal triamcinolone, r-TPA and the new anti-angiogenetic drugs was thoroughly examined. The discussion on these issues was particularly lively and focused on very practical clinical issues. Not surprisingly for a society such as ours, the surgical part drew the greatest attention. The surgical treatment of epiretinal membranes and macular edema was revised and different techniques were compared in detail. Histology, both conventional and associated with electron microscopy,

shed new light on the possible nature of macular hole formation. Conventional and 25 gauge surgery in macular pathology was, understandably, another hot topic. The results associated with macular translocation were discussed and relatively new techniques such as RPE transplantation were presented. Peep Algvere of Stockholm, who was presented with this year’s Relja Zivojnovic Award for his outstanding contributions to the field of vitreoretinal surgery, highlighted this session with a keynote lecture on “The Challenge of Retinal Transplantation”. Following EVRS tradition, discussion on all the topics was quite open and frank. Those involved, both speakers and moderators, did their best to leave the audience with the clearest possible “take home message” on each specific issue.

European Sleepless Nights in Sweden

>> EVRS NEWS

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Klaus Lucke, MDSection Editor

Giampaolo Gini, MD

THE ANNUAL MEETING IN ÖREBROAs 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.

Lively discussions–a hallmark of EVRS meetings

“TRUE TO LIFE” SURGERYThis year the “live surgery” session was substituted with a “true to life” one. Operations were videotaped in the surgeon’s own operating theater after prior submission of the case. Cheating by case selection was impossible. Although this method lacks the emotional impact that live surgery has, “true to life” demonstrated that it allowed a more inquisitive approach to each case, a more compact presentation, and an opportunity for wider discussion, and was generally felt to be more ethical towards the patient. It may very well be that members may require both of these forms to co-exist and complement each other in the future.

FUTURE CHALLENGESThe General Assembly found the Society in good financial shape and ready to meet future challenges. Among these is an “International Fellowship Program” whereby young surgeons can complete their training by travelling and spending some time with masters in the field. The enrolling phase is open and generating great interest. The Assembly of Country Delegates elected Francesco Boscia of Italy as their new chairman. Claude Boscher, who stepped down from that position, would like to devote more time to representing EVRS with national and European authorities. Cannes, the next major event, will take place in September 2006. This will be a joint meeting with the American Society of Retina Specialists and promises to be a memorable event for all. Thus, EVRS has begun to prove its extremely versatile nature and to display the wealth of different cultures Europe has to offer. Perhaps EVRS has gone even a step

further, showing its truly global reach, as professionals from many parts of the world gather under its insignia with the common goal of excellence in patient care.Keep posted on the website and....see you in Cannes!

ADDITIONAL INFORMATION:The EVRS board of directors:Didier Ducournau, Nantes (President) email: [email protected] Lucke, Bremen (Vice-President)email: [email protected] Nikolakopoulos, Thessaloniki (Secretary) email: [email protected] Nawrocki, Lodz (Treasurer)email: [email protected] Koch, Frankfurtemail: [email protected] Gini, Prato email: [email protected] Boscia, Bari (Chairman, Assembly of Country Delegates)email: [email protected] Kuhn, Birmingham Alabama (representative of the ASRS)email: [email protected] Crafoord, Örebrö (Meeting Host 2005) email: [email protected] Facino, Genoa (Head, Young EVRS) email: [email protected]

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

Peep Algvere (left) being awarded the 2005 Relja Zivojnovic prize by the President of this year’s meeting, Sven Crafoord

M O NT R EA L 20 0 5

Julia A. Haller, MDASRS Scientific ProgramCommittee Chairman

Karen BaranickMeeting PlannerMedical Conference Planners, Inc.

The ASRS 23rd Annual Meeting was an unparalleled success, setting records for attendance, scientific presentations, and “buzz”. Over 600 ASRS members and guests from 25 countries,

joined by enthusiastic family members and 360 representatives from 35 companies, created the ideal mix for an outstanding scientific and social program. The meeting consisted of more than 130 papers, 80 posters, four instructional courses, panel discussions, and special evening celebrations and side trips.

SATURDAYThe meeting opened Saturday afternoon with the Fluorescein Angiography & Surgical Case Conference, moderated by Bill Mieler & Neil Bressler. The “Bill and Neil Show” was well attended and the interesting cases stimulated plenty of discussion. The Welcome Reception & Dinner that followed, presented by the ASRS in partnership with Bausch & Lomb, featured strolling musicians and stations with themed “Taste of Montreal” dining selections.

SUNDAYASRS President Gene de Juan & Program Chair Julia Haller officially opened the 23rd Annual Meeting on Sunday morning. The leadoff session featured cutting edge talks

on new devices, instruments and surgical techniques (25 gauge vitrectomy remaining a hot topic), followed by an “illuminating” panel discussion deftly managed by Carl Awh and his team of experts on vitrectomy lighting options. Next we enjoyed a series of provocative presentations on diabetic retinopathy and venous occlusive disease. The annual Young Physicians Section Lunch Meeting, co-chaired by Sundeep Dev and Ingrid Scott, honored Bill Mieler with the Crystal Apple Award for excellence in teaching and mentorship. Bill’s “Life in Addition to Ophthalmology” presentation was a highlight of the meeting, which also included an informative, interactive discussion featuring an electronic audience response system. The YPS festivities were supported by Eyetech Pharmaceuticals/Pfizer Ophthalmics, Inc. The afternoon continued with a scientific session on Pharmacology (“Drugs and Bugs”), followed by a special Distinguished Recognition Award ceremony honoring Bill Rich for his Herculean labors on our behalf over many years. Bill delivered a thoughtful and provocative lecture entitled “The Tragedy of the Commons and the ASRS’ Frontier.” The first full day of the meeting concluded its scientific portion with a special symposium, “Managing the Risks of Intravitreous Injections” adeptly organized by Harry Flynn and featuring a panel of opinionated expert discussants.

As the cooler air of the evening swept over Montreal (the weather was the hottest recorded in 30 years!), attendees dispersed to restaurants and other attractions of their choice, with a large group choosing the delightful musical review and dinner at the Cabaret du Casino de Montréal.

MONDAYThe annual Breakfast with the Masters, orchestrated by David Boyer and supported by Genentech, Inc., kicked off Monday morning with record attendance. The table discussion was so animated that it was difficult to clear the room and move attendees into the session hall. Once seated in the main hall, attendees were treated to a very special awards presentation ceremony. Mark Blumenkranz received the Retina Research Foundation’s Gertrude D. Pyron Award for Outstanding Achievement in Retina Research and presented his captivating lecture “Clinical Research and Vitreoretinal Practice: The Impact of Rapid Technology Change and Quantitative Modeling in the Decision-making Process.” Steve Ryan was then recognized with the ASRS Founders Award. This annual award honors the society’s founders Jerry Bovino, Roy Levit, and Allen Verne for their vision of an open society which promotes the collegial exchange of ideas between retina surgeons, and is presented to individuals who have made

“ 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

“ Flawless performance. Congratulations to the entire ASRS Annual Meeting Organizing Committee and Medical Conference Planners, 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

“ 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.”— Jeffrey S. Heier, MD

Boston, MA

>> ASRS 23RD ANNUAL MEETING HIGHLIGHTS

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ASRS VOICES

major contributions to the advancement of vitreoretinal surgery, treatment, research, surgical instrumentation, and patient care. Steve gave a thought-provoking lecture on “Genetic Predisposition to Macular Degeneration.” David Parke then updated us on the AAO and Vitreoretinal Issues–2005. The morning’s scientific session entitled Treatment of AMD 2005 was perhaps the “hottest ticket” of the week. An estimated crowd of over 800 packed the room to capacity and more as investigators reported study results, culminating in Joan Miller’s discussion of the Phase 3 results from the Genentech study of ranibizumab for the treatment of minimally classic and occult choroidal neovascularization in AMD. Monday night’s Evening at the Montréal Museum of Fine Arts, hosted by the ASRS in partnership with Genentech, Inc., was a lively affair as guests enjoyed the galleries of 14th to 19th century European Art as well as delicious food, signature beverages, and collegial discussion of the day’s presentations and adventures.

TUESDAYThe topic of Age-Related Macular Degeneration remained in the forefront as Tuesday morning began, kicking off with cutting edge reports by Emily Chew and Eric Postel on the association of Complement

H-related genetic mutations with AMD, and continuing with other studies looking at risk factors, imaging and treatment. A nice overview of the exciting but increasingly complicated management issues confronting all of us who treat patients with AMD was then provided by a team of lucid discussants, expertly organized and moderated by Phil Rosenfeld. The next session took participants first into new developments and uses for ocular imaging and then on to the field of pediatric retina. Lunchtime’s optional Malpractice Protection Seminar seemed headed for disaster when the guest speaker’s plane was delayed–but not to worry: our own George Williams, David Parke, Bill Rich and Trex Topping came to the rescue with polished expertise until the featured guest arrived for the wrap-up. Optional instructional courses filled the afternoon for those choosing to take them. The topics this year included Retinal Coding, Molson with the Masters, Advances and Controversies in Vitreoretinal Surgery, and Intraocular Tumors. Tuesday evening the lecture hall was transformed into a magical candelabra-bedecked and elegant ballroom for the Gala Dinner, featuring the Film Festival Awards, and some amazing dance moves from retinal specialists who should know better (do not attempt these at home)–all to the tunes of

La Gioventu Orchestra. The dance floor was packed until the end of the evening.....with a number of “postparties” continuing into the wee hours for many!

WEDNESDAYWednesday morning an intrepid crew of post-Gala attendees were treated to a compelling leadoff session entitled Macula 2005–Beyond AMD. The meeting concluded with a strong session on Retinal Detachment and Trauma. PAT SURVEY & RESEARCH REPORTThe Seventh Annual PAT Survey Committee had its comprehensive display with often surprising responses to multiple issues regarding vitreoretinal medicine, techniques, and controversies. Also providing attendees with an impressive poster display was the Research & Development Committee that posted its annual report of ongoing trials. Thanks to the PAT Survey Editors Rob Mittra and John Pollack and their committee as well as the R & D Committee, chaired by Mark Humayun, for all of their efforts and hard work.

THE 7TH ANNUAL ASRS FILM FESTIVALThis year, 44 films were entered in the Annual Film Festival, making it one of the biggest to date. The winners of the Rhett Buckler and Dr. Vitrector Awards can be found in Abdhish Bhavsar’s article in this issue of The Retina

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

Rochester, MN

“ This meeting has been terrific. Once again outstanding scientific content, 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

“ 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

Miami, FL

retina times 13

Times. Congratulations to all winners, many of whom represent our outstanding international contingency.

SPECIAL ACKNOWLEDGEMENTThe ASRS would like to recognize and thank John Focosi of Advanced Media Systems for doing a simply superlative, flawless job with the technical direction of the 23rd Annual Meeting. In addition, great meeting photos taken by Kevin Caldwell Photography are up for viewing at www.retinaspecialists.org. Finally, enough thanks simply can not be given to Karen Baranick, Petra Dwyer, Carrie Jacobowitz and their team of super-competent, unflappable, ever-charming planners at Medical Conference Planners, Inc. who manage to put the innumerable pieces of this ever-more-complicated meeting puzzle together year after year–and it just keeps getting better!

MARK YOUR CALENDAR“Cannes Retina Festival” The 24th Annual ASRS Meeting & The 6th Annual EVRS Meeting Palais des Festivals et des Congrés Cannes, France September 9-13, 2006

A “Call for Papers and Meeting Registration” brochure will be mailed to all members in January 2006. We hope you are planning to

attend! Please visit www.retinaspecialists.org for up-to-date annual meeting information.

Direct meeting questions to [email protected] or [email protected]

CORPORATE SUPPORT The American Society of Retina Specialists wishes to once again extend its gratitude to the corporate supporters who have demonstrated a commitment to the advancement of our profession through their generous support of the 23rd Annual Meeting. Their interest and contributions have been critical to the success of this meeting.

PLATINUM PARTNERSAlcon Laboratories, Inc.AllerganBausch & LombCarl Zeiss MeditecEyetech Pharmaceuticals/Pfizer OphthalmicsGenentech, Inc.

GOLD PARTNERSInsight Instruments Inc.IridexNovartis OphthalmicsOccuLogix, Inc.Synergetics, IncTopcon Medical Systems

SILVER PARTNERSAmerican Academy of OphthalmologyAmerican Retina FoundationCompulinkDORC International,bv/Dutch Ophthalmic, USAHealth Care Intranet Technologies, Inc.Heidelberg EngineeringInnovative Imaging, Inc.Labtician Ophthalmics, Inc.

LaserexLeica MicrosystemsLumenisMediflex Surgical ProductsMedOne Surgical Inc.NidekOphthalmic Imaging SystemsOphthalmic Technologies, Inc.Optos North AmericaPriority HealthcareQuantel Medical, Inc.Retinal PhysicianTheragenics Corporation VisionCare Ophthalmic Technologies, Inc.Volk Optical, Inc./Keeler Instruments, Inc.

SPECIAL THANKS TO THE FOLLOWING COMPANIES FOR THEIR ADDITIONAL SUPPORT...

Genentech, Inc.The Evening at the Museum of Fine ArtsBreakfast with the MastersThe Meeting BagsScientific Poster DisplayTwo Refreshment Breaks

Novartis OphthalmicsThe Gala Dinner Banquet

Bausch & LombThe Welcome Reception & Dinner

Alcon Laboratories, Inc.The 7th Annual Film Festival

Eyetech Pharmaceuticals/Pfizer OphthlamicsYoung Physicians Section MeetingHotel Key Cards

AllerganOne Refreshment Break

“ 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 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

” 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

>> ASRS 23RD ANNUAL MEETING HIGHLIGHTS

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The 7th Annual ASRS Film Festival was an outstanding success! There were 44 films submitted this year and all of them were well done. We owe sincere appreciation to Mark Forchette and Alcon for their support of the ASRS Film Festival for the past, the present and the future. I also want to personally thank Kirk Packo and Paul Tornambe. They have influenced me greatly in my decisions of how to proceed through the task of completing this year’s Festival.

The 2005 ASRS Film Festival Judges and I saw every single second of every single movie and worked very hard on this year’s film festival. We owe a debt of gratitude to the judges of this year’s Film Festival in Montreal, all of whom went above and beyond the call of duty with the many hours that it took to review and judge the films this year:

JUDGESEdgar Thomas (Los Angeles, CA), Lead JudgeMark Balles (South Portland, ME) Anurag Gupta (Los Angeles, CA)Richard Johnston (Minneapolis, MN)Hugo Quiroz-Mercado (Mexico City, Mexico)

WINNERS OF THE RHETT BUCKLER AWARD:

“BEST OF SHOW”1. Managing Dry Macular Folds after Vitreoretinal SurgeryCarlos Mateo, MD (Barcelona, SPAIN)Borja Corcostegui, MD

2. Condiments in Vitreoretinal Surgery: A Bad Day in the Kitchen! J. Fernando Arevalo, MD, FACS (Caracas, VENEZUELA) Reinaldo A. Garcia, MD

3. Primary PVR in BuphthalmosGaetano R. Barile, MD (New York, NY) Avi Grinblat Michael Turano

4. Heavy Silicones in Severe Vitreoretinal DiseasesCesare Forlini, MD (Ravenna, ITALY)Paolo Rossini, MD

5. Origin of Subretinal Fluid in Optic Disc Pit Maculopathy: ß-2 Transferrin AnalysisRonald C. Gentile, MD (New York, NY) Alfonso Ponce, MD

6. The Use of New Surgical Strategies in Dealing with Ocular TraumaGiampaolo Gini, MD (Prato, ITALY)Vincent S. Reppucci, MD (New York, NY)

7. Vitrectomy for DummiesVirgilio Morales-Canton, MD (Mexico City, MEXICO)

8. The Use of Different Illumination/Observation Systems for Peripheral VitrectomyJerzy Nawrocki, MD (Lodz, POLAND) Zofia Nawrocka, MDJanusz Michalewski, MDZofia Michalewska

9. A New Microscope with Wide Angle Viewing System without EndoilluminationMurat Oncel, MD (Istanbul, TURKEY)

10. Modified Technique for Improving Trypan Blue (TB) Staining of Epiretinal Membranes (ERM)Stanislao Rizzo, MD (Lucca, ITALY)Michele Palla, MD (Pisa, ITALY)Federica Genovesi-Ebert, MD, PhD

DR. VITRECTOR AWARDThe new Dr. Vitrector Award, for innovative film technique and vitreous humor, as inspired by the original Dr. Vitrector films, was given to three film producers this year.

DR. VITRECTOR AWARD JUDGE:Abdhish R. Bhavsar, MD

WINNERS OF THE NEW DR. VITRECTOR AWARD:

1. Origin of Subretinal Fluid in Optic Disc Pit Maculopathy: ß-2 Transferrin AnalysisRonald C. Gentile, MD (New York, NY)Alfonso Ponce, MD

2. 25-Gauge Vitrectomy for Vitreoretinal DiseasesFabio Patelli, MD (Rome, ITALY)Paolo Radice, MDGiulio Zumbo, MDGiuseppe Fasolino, MD

3. Mission Possible: Iridocyclectomy for Ciliary Body LeiomyomaMichael A. Samuel, MD (Los Angeles, CA)Jennifer I. Lim, MD

Abdhish R. Bhavsar, MDChair, ASRS Film Festival

>> FILM FESTIVAL

THE 7TH ANNUAL ASRS FILM FESTIVAL–ASRS 23RD ANNUAL MEETING IN MONTREAL

retina times 15

>> FILM FESTIVAL

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FILM CRITIQUE

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

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

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 narrator, Dr. Mateo, on a moving background of the retina. This gives us a 3-D view of the macular fold and the contour as if we were looking at a fault line in the desert. This is a superb maneuver to help us understand the pathology. The animations, graphics and video in the film are also outstanding. I have learned a great deal about 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!

Drs. Mateo and Corcostegui have outdone the “weather man!” This beautiful synthesis of video, overlay and graphics presentation of a complicated macular fold is a unique way of explaining it to the clinician in a way that is the state of the art in videography. The authors (producers may be a better video term), did an outstanding job of this presentation and deserve the major accolade.

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 complications in an environment where complications can happen. They have redefined the meaning of exquisite film editing of retina surgical video. The entire film is clear with good surgical footage and clear lighting. They have elucidated a series of maneuvers to avoid the severe complications of a high pressure jet stream creating retinal trauma. The toxicity of the ICG may only have been incidental to the subretinal injection and retinal tear. The narration is succinct and clear. Follow their instructions and hold your breath during the injection! An excellent film!

What a bad day! We so often depend on our assistants to use the utmost care in performing complicated tasks that we feel are just “so easy!” Drs. Arevalo and Garcia share a catastrophic complication of ICG injection. It’s really not related to the toxicity of the dye, but the mere shearing forces of liquid under pressure in an air filled eye. In an eye with fluid, this would probably not have occurred. They deserve credit for sharing this problem with us, demonstrating it with great candor and helping us avoid a similar circumstance in the future. This type of presentation benefits all of us doing complicated vitreoretinal surgery. Congratulations.

3. Origin of Subretinal Fluid in Optic Disc Pit Maculopathy: ß-2 Transferrin AnalysisRonald C. Gentile, MD (New York, NY)

Alfonso Ponce, MD

Drs. Gentile and Ponce have added a new meaning to the theme for the Pink Panther. The entire movie is set the music from the Pink Panther. The lack of a voice-over during any of the video demonstrates the fact we learn 90% from the our visual input. The graphics and morphing are outstanding. This film is totally deserving of the Dr. Vitrector award for innovation and humor in the spirit of the original Dr. Vitrector films. In addition, this film was awarded the Rhett Buckler Award as well by the team of judges. This was the only film this year to have the privilege of winning both the Rhett Buckler Award and the Dr. Vitrector Award!

Drs. Gentile and Ponce have done what the “video” should do. I have always had a pet peeve about presenters reading their slides or doing voice-overs when the text is on the screen. No other video in the program had nary a word spoken (except for the Dr. Vitrector teaser for Cannes 2006!). I can tell you I got a great deal of knowledge from this video and it confirms my belief in the origin of sub-retinal fluid in optic pits. This was a scholarly presentation with a very specific marker for CSF and it wasn’t found. Congratulations on one of the best!

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

Editor’s Note. The term Key Opinion Leader (KOL) is used frequently by pharmaceutical companies to refer to individuals in the field who are felt to be thought leaders. In this time of rapidly evolving treatments and decision paradigms, controversies will likely arise. We have created this new column as a forum to allow members of our society to provide their thoughts regarding important new and potentially controversial issues that present to our specialty. We will try to engage, whenever possible, the most noted experts in 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. Early evidence (both published1-3 and anecdotal) suggests that it may be as effective as Lucentis® in treating exudative age-related macular

degeneration and refractory macular edema secondary to venous occlusive disease. Better yet, the per-treatment cost of Avastin® works out to be only a fraction of other currently available FDA-approved therapies, such as Visudyne® and Macugen®. So, what is the catch? Avastin® was developed and is marketed as an intravenous treatment for metastatic colorectal cancer, and is FDA approved for that indication only. Intravitreal injection of Avastin® is therefore an off-label use of the medication, employing an altered route of administration.

>> THE KOL CORNER

So You Want to Try

Intravitreal Avastin®

Todd R. Klesert, MD, PhDKOL Corner Section Editor

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Illustrates intravenous Avastin (bevacizumab) molecules inhibiting the action of VEGF (vascular endothelial growth factor) in a subfoveal CNV (choroidal neovascular vessels) condition.

This raises many important ethical, medical-legal, and practical questions that anyone contemplating the use of intravitreal Avastin® should carefully consider before proceeding. As guidance, the editorial office of the Times has collected individual opinions of several leaders within our society and has sought clarification from some of our pertinent regulatory bodies to provide guidance to our membership. These are the express opinions of those interviewed and are NOT an endorsement from the ASRS or the Times.

THIS MONTH’S OPINION LEADERS:

Kirk Packo (K.P.), MD is a vitreoretinal specialist with Illinois Retina Associates, chair of the Rush-Presbyterian Medical Center Dept. of Ophthalmology (Chicago, IL), and past President of the American Society of Retina Specialists.

George Williams (G.W.), MD is a vitreoretinal specialist with Associated Retinal Consultants, chair of the William Beaumont Hospital Dept. of Ophthalmology (Royal Oak, MI), past President of the American Society of Retina Specialists, and a committee member for OMIC.

Bob Avery (B.A.), MD is a vitreoretinal specialist in private practice with California Retina Consultants (Santa Barbara, CA), and has been a principal investigator in 8 clinical trials investigating new retinal treatments. He and his associates were the first to implement off-label intravitreal Avastin® for patient care on the West Coast.

Tom Chang (T.C.), MD is Editor-in-Chief of Retina Times and a faculty member of the Doheny Retina Institute, University of Southern California (Los Angeles, CA).

Anne Menke (A.M.), RN, PhD, is Risk Manager of Ophthalmic Mutual Insurance Company (OMIC). Her articles on ophthalmic risk management have appeared in the OMIC Digest, Retina Times, EyeNet, and Techniques, and she is a regular speaker at state, national, and sub-specialty ophthalmology conferences.

Wiley Chambers (W.C.), MD is Deputy Division Director of the Division of Anti-Infective and Ophthalmology Products in the Center for Drug Evaluation and Research at the Food and Drug Administration.

What are the medical-legal risks of using intravitreal Avastin® off-label?

K.P.: Medical-legal considerations only take place if there is a failure to deliver the standard of care and harm is caused. The definition of standard of care changes from geographic location to geographic location. One can argue that the community can be described as the “vitreoretinal community of practioners”. This seems to have been the case for intravitreal Kenalog®, for which the off-label use was embraced whole-heartedly by the retina community without clinical trials.

I think the term “off-label” has an inappropriately negative connotation. The FDA is not explicitly against the off-label use of medications, as long as those uses are generally accepted by the community of medical practicioners. The FDA understands that requiring approval for all uses of any given medication would completely bog down the drug approval process.

B.A.: We retina specialists frequently use other drugs off-label as well. For instance, intravitreal antibiotics for endophthalmitis, TPA for hemorrhagic AMD, pre- and post-operative antibiotics, and C3F8 for cases other than pneumatic retinopexy are all off-label uses.

A.M.: Once a device or medication is approved by the FDA, physicians may use it “off-label” for other purposes as part of the practice of medicine if 1) they are well-informed about the product, 2) they base its use on firm scientific method and sound medical evidence, and 3) they maintain records of its use and effects. When medications are first used “off-label” for a new indication, there are often few if any adequate studies of the safety, efficacy, and long-term risks of its use. The physician must therefore exercise care in selecting patients, be familiar with the information that the manufacturer includes in the FDA-approved “label” detailing the indications, risks, and benefits that were determined during clinical trials, and monitor the patient for ongoing need, efficacy, and safety. In addition, ophthalmologists would be well advised to inform patients of the medication’s “off-label” status during the consent discussion, and keep a file of articles and other materials that support the decision to use the drug in question.

G.W.: At the end of the day, with medical-legal matters, the only “standard of care” issues that will be of importance will be those which a jury will decide.

Avastin® contains a “black box” warning in the package insert, indicating a risk of serious and potentially fatal adverse side effects, including GI hemorrhage, GI perforation/wound healing complications and pulmonary hemorrhage. Increased risk of arterial thromboembolic events, hypertension, proteinuria, and congestive heart failure were also observed in the clinical trials. Does the “black box” status of Avastin® change the medical-legal equation?

K.P.: Glaucoma specialists have used mitomycin off-label for trabeculectomies for some time. This is a drug with teratogenic as well as other potentially serious systemic effects.

G.W.: These potential complications need to be discussed with patients before consideration of use, but keep in mind that the drug is being injected at a dose several hundred times lower than the dose given intravenously to cancer patients. The safety profile should arguably be considerably lower at these concentrations.

T.C.: It should be noted that the FDA clinical trials for Avastin® were conducted on patients with metastatic GI and lung malignancies. The “black box” warnings for Avastin® [potentially fatal GI hemorrhage, pulmonary hemorrhage, GI perforation, and a doubling of the thromboembolic risk] are almost certainly a unique reflection of this patient population. The documented fatal GI and pulmonary hemorrhages likely developed secondary to tumor contraction or necrosis (i.e. a positive treatment effect). Similarly, the well-known association between cancer and coagulation abnormalities was probably a significant factor contributing to the increased risk of arterial thromboembolic events in patients treated with Avastin®. It should also be remembered that these patients received high-dose

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>> THE KOL CORNER

systemic treatment every two weeks for months and months, and were concurrently treated with other chemotherapeutic agents. On the whole, AMD patients are a significantly healthier population.

A.M.: Whether these complications will occur with lower dose, intravitreal administration in patients who do not have cancer is precisely what, in part, clinical trials will determine. For now, ophthalmologists should proceed with caution, since patients likely to need Avastin® may also have cardiovascular conditions and hypertension. First, physicians should carefully screen patients for medical conditions that might increase the likelihood of these complications. Next, they should give patients information about the known risks of the drug when used intravenously for colorectal cancer patients, and explain that while the decreased dosage and regional administration of the medication may decrease the likelihood of these risks, neither the safety, efficacy, or long-term risks of intravitreal Avastin® for ocular conditions has been proven. Patients should also be told that whenever a medication is used in a large number of patients, a small number of coincidental life-threatening problems may occur that have no relationship to the treatment. Ophthalmologists should consider getting medical clearance for patients with pertinent medical comorbidities. Before, during, and after administration, patients should be monitored for adverse events. At the time of discharge, patients should be given written contact information detailing eye symptoms that should be immediately reported to the ophthalmologist or, if they experience symptoms of life-threatening conditions affecting organs other than the eye, the primary care physician.

Do you have any absolute medical contraindications for intravitreal Avastin®?

B.A.: In Phil Rosenfeld’s study of intravenous Avastin®, a mild elevation in blood pressure in some patients treated with systemic Avastin® was observed. However, our group has not seen a significant elevation in blood pressure or other adverse systemic effects in those patients treated with intravitreal Avastin®. Nevertheless, I would feel uncomfortable treating someone with a recent myocardial infarction, unstable angina, or a recent stroke until more safety data is obtained and published. So far, the intravitreal drug seems to be very well tolerated. We have treated over 75 patients and we have yet to see uveitis.

What must be included in the documentation of informed consent? Is a special procedure-specific consent form required for off-label use of Avastin®?

G.W.: It is important for us to remember that informed consent is a process and not a form. The consent form is simply a vehicle to document that process. Any informed consent with patients for intravitreal Avastin® must include disclosure that the patient is being offered off-label use and that there are no definitive trials showing efficacy. In addition, detailed discussion of all other potential treatment options (i.e. Macugen®, PDT) must be documented.

T.C.: It will be important to demonstrate/document a clear justification for the use of this off-label application, for example, if a patient has been shown to be a treatment failure to Macugen® or PDT. We need to keep in mind that these are treatments that have demonstrated efficacy in randomized clinical trials.

G.W.: I would be reluctant to deny someone an approved therapy without detailed explanation of the reasons why in the informed consent.A.M.: Ophthalmologists should carefully document the decision-

making process that led to using Avastin®, and write a note in the medical record about the consent discussion, including the disclosure of the drug’s off-label status and any complications for which the patient has an increased risk. Except for truly minor procedures with little risk, it is always prudent to use a procedure-specific consent form (a sample form for intravitreal Avastin® will be posted soon on the OMIC website). Patients should be offered a copy to read at home and encouraged to contact the physician with any questions.

How do you bill for intravitreal Avastin® injections? Do you get paid?

G.W.: The payment for the injection should be automatic since intravitreal injection of therapeutic agents is covered by CPT code 67028. Any discussion on payments for the drug itself will require discussion with individual local carriers.

K.P.: Yes, the national carrier decision on reimbursing the injection was demonstrated with Kenalog®. For the drug coverage, it is likely that the local carriers will need to see more published data.

How do you mix and aliquot Avastin® for intravitreal injection?

B.A.: Avastin® is available in 100 mg and 400 mg vials. We use the 100 mg vial, which contains 4 cc of a 25 mg/cc concentration of the drug. We have a compounding pharmacy divide this into 0.1 cc aliquots. We inject 0.05 cc, for a delivered dose of 1.25 mg.

W.C.: Although FDA does not regulate the practice of medicine, were this product to be used under an IND in a clinical trial, FDA would expect adequate information would be presented to insure that use of the product as outlined above would in fact provide adequate protection against the administration of non-sterile product into the eye. The ophthalmic use of an unpreserved product in multiple patients is contrary to the Code of Federal Regulations concerning ophthalmic products (21 CFR 200.50).

B.A.: I am surprised to learn of this regulation. We were simply following the exact protocol of a major teaching hospital. I know other universities would aliquot TPA in the past, and many university and private practices use a single unpreserved vial of Botox® on multiple patients. In fact, Medicare has given guidance with respect to how to bill for one vial of Botox® used in multiple Medicare patients. Nevertheless, even if this code does apply to injected medicines, a 100 mg vial of Avastin® is still significantly cheaper than a vial of Macugen® or Visudyne®, and the effects are quite striking. As Phil Rosenfeld showed in his published case reports, we too are seeing some remarkable early responses. Eight of our first 21 injected eyes had complete resolution of retinal thickening at 4 weeks.

A.M.: The medication comes in preservative-free vials intended for use on a single cancer patient at a much larger dose. Using one Avastin® vial for multiple patients with ophthalmic problems raises a number of patient safety and professional liability issues. OMIC obtained a formal legal opinion from an outside attorney about whether federal regulations (i.e., 21 CFR 200.50) prohibit ophthalmologists from treating more than one patient with a single unpreserved vial. The regulations pertain to the manufacture and packaging of ophthalmic drugs, and nothing, according to the attorney, specifically addresses the use of an unpreserved product in multiple patients. As a risk management measure, therefore, and to respect the intent of the regulations even if they do not appear to pertain to how the drug is used, physicians should take certain steps. First, to ensure safe administration, ask a compounding pharmacy to prepare the medication for ophthalmic use, confirm the dose and sterility, identify a syringe suitable for this protein, and provide

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storage and “beyond-use” instructions, and the lot number of the vial. Second, to reduce the risk to their patients and themselves, ophthalmologists would be well-advised to “credential” the compounding pharmacy to which they send the prescription for intravitreal Avastin®. Recent legislation should make that quality assurance step a little easier. In response to concerns about contamination and potency, a new federal standard for preadministration manipulation of compounded sterile preparations (CSP) was established, effective January 2004, and codified in USP Chapter 797. The standard addresses compounding, transportation, and storage of CSPs and is enforceable by the FDA, state boards of pharmacy, boards of health, and other regulatory agencies (e.g., JCAHO).4 Physicians should ask the compounding pharmacy for assurance that it is licensed/registered in the state in which it is dispensing and is complying with USP Chapter 797. In addition to providing ophthalmologists with a CSP upon receipt of a prescription for an individual patient, “pharmacists may compound drugs in very limited quantities prior to receiving a valid prescription based on a history of receiving valid prescriptions that have been generated solely within an established pharmacist/patient/prescriber relationship, and provided that they maintain the prescriptions on file for all such products compounded at the pharmacy (as required by State law).”5 Ophthalmologists should be wary of obtaining CSP from pharmacies that advertise their ability to compound specific drug products such as Avastin®, since advertisements of that type are contrary to the “Good Compounding Practices” and ethical standards of the National Association of State Boards of Pharmacies.5

Do you need an IRB approval and/or IND application to perform a retrospective study on patients on an off-label basis (i.e. no formal “research” consent, IRB submission, or protocol)?

W.C.: Avastin® is an approved biologic agent, approved for use in a different patient population by a different route of administration. As such, the intravitreal use of Avastin® in a study requires an Investigational New Drug exemption (IND). The regulations do not provide an exception for any type of study. A retrospective study is still a study and the regulations would call for an IND. While the use in an individual patient may be considered the practice of medicine in a case where the physician clearly believes that this treatment is in the patient’s best interest, physicians should check with their local IRBs concerning the need for local IRB approval.

A.M.: From a common sense point of view, there does not appear to be any additional risk to the patient during a retrospective review, especially if it is conducted under the auspices of an IRB. And ophthalmologists engaged in studies of ophthalmic devices rely upon their IRBs to determine when an IDE (investigational device exemption) is required. However, any study of a drug would require an IND, and IRBs do not have the authority to waive the IND requirement. A quick review of the difference between the practice of medicine and research, and between ophthalmic drugs and devices, may help ophthalmologists understand the reasoning behind the FDA regulation, and provide guidance on when to apply for an IND. The two most important points to consider are the intent of the physician and the risk to the patient. The FDA Information Sheet, “’Off-Label’ and Investigational Use of Marketed Drugs, Biologics, and Medical

Devices,”6 differentiates between off-label use of approved (marketed) drugs as part of the practice of medicine and investigational use. When the intent is to practice medicine, that is, to treat an individual patient, no IND, IDE, or review by an IRB is required. If the intent is

to “develop information about the product’s safety or efficacy,”6 the use would be considered investigational, and in the case of a drug, an IND application would be required unless six conditions are met (I will discuss only three). The first two address the intent of the investigational use. Studies whose purpose is to submit information to the FDA in support of a new indication for the drug or any other significant

change in the labeling, or to support a significant change in the advertising of the product would require an IND.

The third condition that, if it were met, would allow a study of a drug to proceed without an IND, requires

that use “not involve a route of administration or dosage level, use in a subject population, or

other factor that significantly increases the risks (or decreases the acceptability of the

risks) associated with the use of the drug product.”6 According to information

obtained from representatives of the FDA, this condition never applies

to ophthalmic drugs, because of the potential toxic effect on the eye of active and inert ingredients. The take-away message for ophthalmologists

who plan to publish the results of their clinical experience with off-label medications is to apply for an IND and submit their proposed study to their IRB.

References1. Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging 2005;36:331-335.

2. Rosenfeld PJ, Fung AE, Puliafito CA. Optical coherence tomography findings after intravitreal injection of bevacizumab (Avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg Lasers Imaging 2005;36:336-339.

3. Michels S, Rosenfeld PJ, et al. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration: twelve-week results of an uncontrolled open-label clinical study. Ophthalmology 2005;112:1035-1047.

4. “An Update on USP Chapter 797: The New National Standard for Sterile Preparation,” Lawrence A. Trissel, B.S., FASHP, www.ashpadvantage.com/monograph/797, accessed 25 August 2005.

5. “Good Compounding Practices Applicable to State Licensed Pharmacies,” National Academy of Boards of Pharmacies, www.nabp.net/law/modelact/appendixc.asp, accessed 25 August 2005. See also “Guidance for FDA Staff and Industry. Compliance Policy Guides Manual. Chapter 4, Subchapter 460. Section 200 Pharmacy Compounding.” May 2002.

6. Guidance for Institutional Review Boards and Clinical Investigators: “Off-Label” and Investigational Use of Marketed Drugs, Biologics, and Medical Devices. U.S. Food and Drug Administration. 1998 Update, www.fda.gov/oc/ohrt/irbs/offlabel.html, accessed 8/16/05.

7. Feinsod M, Chambers WA. Trials and tribulations: a primer on successfully navigating the waters of the Food and Drug Administration. Ophthalmology 2004;111:1801-1806.

8. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocrine Reviews 2004;25:581-611.

Useful online resourcesSearchable, full-text copies of Title 21 of the Code of Federal Regulations, which encompasses the Food and Drug Act, are available at www.fda.gov. Section 21 CFR 312 covers the laws and requirements pertaining to investigational new drug (IND) applications. Section 21 CFR 50 covers the protection of human subjects, which includes informed consent requirements. Section 21 CFR 56 covers institutional review requirements (IRBs). Finally, section 21 CFR 200.50 covers issues specific to ophthalmic drugs and products.

Useful resources concerning medical-legal matters in ophthalmology, including procedure-specific consent forms, can be found at www.omic.com.

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4TH ANNUALRETINAL RESEARCH REPORT

2005

>> RETINAL RESEARCH REPORT

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CLINICAL TRIALSThe ASRS Research & Development Committee is committed to maintaining an updated forum for members of the Society to have ready access to ongoing clinical trials in vitreoretinal diseases. The R&D Committee has implemented a Web-based access platform for rapid entry of new study information to enable wide dissemination of ongoing clinical research. The R&D Committee is devising a Web-based library of surgical instruments and devices focused toward comparative review by members of the Society. This fourth annual Retinal Research Report provides a current list of ongoing clinical trials.

The information in these tables has been collected from publicly available sources and is by no means inclusive of all clinical trials.The ASRS does not support or en-dorse this information, nor does the ASRS attest to its correctness and validity. This information has been provided as a service to its members to further its mission and nonprofit purposes.

RESEARCH & DEVELOPMENT COMMITTEE:

Mark S. Humayun, MDChairperson

Eugene de Juan, Jr., MD

Sharon Fekrat, MD

Peter K. Kaiser, MD

SriniVas Sadda, MD

DIABETES MELLITUS• B7A-MC-MBCM: Protein Kinase C Beta Inhibitor-Diabetic Retinopathy Study 2 (PKC-DRS2) A Phase 3 Clinical Trial

• Diabetic Macular Edema Vitrectomy Study (DMEVS)

• Phase 2 Study to Evaluate the Safety and Efficacy of an Intravitreal Fluocinolone Acetonide (0.5 or 2mg) Implant in Patients with Diabetic Macular Edema (DME)

• Epidemiology of Diabetes Intervention and Complications (EDIC)

• A Multicenter, Randomized, Masked, Controlled Study to Evaluate the Safety and Efficacy of Retisert, an Intravitreal Fluocinolone Acetonide Implant, in the Treatment of Patients with Diabetic Macular Edema, FAME 4

• A Phase 2 Randomized, Open Label, Multicenter, Controlled Trial to Assess the Safety and Efficacy of Dexamethasone Segment Drug Delivery System (DEX PS DDS) in the Treatment of Persistent Macular Edema

• Vitrase of Vitreous Hemorrhage Study (VVHS)

• MBBK/MBBM

• Pegaptanib Sodium Injection (Macugen)

• Reduction in the Occurrence of Center-threatening DME

• Intravitreal Triamcinolone Acetonide and Laser Photocoagulation for DME

• Laser Photocoagulation for DME

OCULAR MELANOMA• Collaborative Ocular Melanoma Study (COMS)

BRVO• Intravitreal Steroid Injection Study Trials (ISIS)

• European Arteriovenous Sheatotomy Trial (EAST)

• Surgical Decompression of Branch Vein Occlusion

• The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study: to Compare the Efficacy and Safety of Intravitreal Injection(s) of Triamcinolone Acetonide with Standard Care to Treat Macular Edema: 1 for CRVO and 1 for BRVO

UVEITIS• Randomized trial of Acetazolamide for Uveitis-Associated Cystoid Macular Edema (CME)

• A Multicenter, Randomized, Double Masked, Controlled Study to Evaluate the Safety and Efficacy of an Fluocinolone Acetonide (0.5 or 2.0 mg) implant in Patients with Non-Infectious Uveitis Affecting the Posterior Segment of the Eye

• Pilot Study of a Sustained Release Cyclosporine-A Implant for Uveitis

• Longitudinal Study of Ocular Complications of AIDS (LSOCA)

• CMV Retinitis and Viral Drug Resistance (CRVR)

ROP• Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) - Outcome Study of Cryotherapy for Retinopathy of Prematurity

AMD• Submacular Surgery Trials (SST)

• Anecortave Acetate in Age-Related Macular Degeneration

• A Phase I, Open Labeled, Randomized Study of the Safety, Tolerability, and Pharmacokinetics of Escalating Multiple-Dose Intravitreal Injections of Rhufab V2 in Subjects with Neovascular AMD (FVF2425G Study)

• A Phase III, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Rhufab V2 (Ranibizumab) in Subjects with Minimally Classic or Occult Classic Subfoveal Neovascular AMD (FVF2598G Study - MARINA)

• Indocyanine Green (ICG) Risk Factors for Choroidal Neovascularization

• Prophylactic Diode Laser Photo Coagulation for the Prevention of Choroidal Neovascularization in Age-Related Macular Degeneration (PTAMD)

• Visudyne with Altered (Delayed) Light in Occult CNV Study (VALIO)

• Multicenter Investigation of Rheopheresis for Age-Related Macular Degeneration (MIRA-1)

• An Evaluation of Efficacy and Safety of Posterior Juxtascleral Injections of Anecortave Acetate 15mg Versus Visudyne in Patients with Subfoveal Exudative Age-Related Macular Degeneration (AMD) Eligible for Initial Treatment with Photodynamic Therapy (PDT) Using Visudyne

• A Phase II Multi Center Trial to Establish the Safety and Pharmacokinetic Profile of Intravitreal Anti-VEGF Pegylated Aptamer (Eye001) in Age-Related Macular Degeneration Undergoing Photodynamic Therapy

• A phase II/III Randomized, Double Masked, Controlled, Dose Ranging Multi Center Comparative Trial , in Parallel Groups, to Establish the Safety and Efficacy of Intravitreal Injections of Eye001 (Anti-VEGF Pegylated Aptamer) Given Every 6 Wks to 54 Wks, in Patients with Exudative Age-Related Macular Degeneration (AMD)

• Lutetium Taxaphyrin (LuTex/Optrin) in Age-Related Macular Degeneration (Phase I Studies)

• A Phase I/II, Multicenter, Dose Escalation, Controlled Study of the Safety, Tolerability, Pharmacokinetics and Activity of Multiple Dose Intravitreal Injections of Rhufab V2 in Subjects with Neovascular AMD (FVF2128G Study)

• A Randomized, Placebo Controlled, Double Masked, Multi Center Phase III Study of the Effect of Visudyne Therapy in Occult with No Classic Subfoveal Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (VIO)

• Photodynamic Therapy (Visudyne) Early Re-Treatment for Subfoveal Choroidal Neovascularization (VER) Study

• A Phase III, Multicenter, Randomized, Double-Masked, Active Treatment-Controlled Study of the Efficacy and Safety of Rhufab V2 (Ranibizumab) Compared with Verteporfin (Visudyne) Photodynamic Therapy in Subjects with Predominantly Classic Subfoveal Neovascular AMD (FVF2587G Study - Anchor)

• Limited Macular Translocation Study

• A Phase II, Randomized, Double Masked, Placebo Controlled Study of the Matrix Metalloproteinase Inhibitor AG3340 in Patients with Subfoveal Choroidal Neovascularization Associated with Age-Related Macular Degeneration

• Women’s Health Initiative Sight Examination Study (WHI-SE)

• Randomized Trial of Beta-Carotene and Macular Degeneration

• Age-Related Eye Disease Study

• Transpupillary Thermotherapy for Choroidal Neovascularization Clinical Trial (TTT4CNV)

• Dry Age-Related Macular Degeneration (AMD) Trial

• Complications of Age-Related Macular Degeneration Prevention Trial (CAPT)

• Photodynamic Therapy (VISUDYNE) in Minimally Classic Subretinal Neovascularization (VIM) Study

• Submacular Surgery Trials (SST)

• Randomized Trials of Vitamin Supplements and Eye Disease

• Anecortave Acetate Risk Reduction Trial (AART)

• SIRNA 0401

• Visudyne with Intravitreal Triamcinolone Acetonide (VisTA) Trial

• Preservative-free Triamcinolone Acetonide (PFTA)

• Combretastatin A-4 Phosphate (CA4P) in Patients with Neovascular AMD (FBO-206)

• ANCHOR

• MARINA

• Evaluation of Safety and Efficacy of Anecortave Acetate vs. Placebo in Patients with Subfoveal CNV due to Exudative AMD (C-02-29)

• Evaluation and Tolerability of 4-dose Levels of Cand5 Administered by Single Intravitreal Injection in Patients with Wet AMD

• PIER

• The Effect of Pegaptanib Sodium on Foveal Thickening in Patients with Exudative Subfoveal AMD

• Squalamine

• Noncomparative Protocol for Use of Intravitreous Macugen Injections in Patients with AMD

• PrONTO

• Safety and Efficacy of AG-013958 in subjects with subfoveal choroidal neovascularization associated with age-related macular degeneration

• TheraSight Ocular Brachytherapy System for Treatment of AMD

• AdGVPEDF.11D in Neovascular Age-Related Macular Degeneration (Wet AMD).

• Interval Dose Evaluation of Anecortave Acetate (IDEAA) I

• Interval Dose Evaluation of Anecortave Acetate (IDEAA) II

• Denufosol Tetrasodium (INS37217 Ophthalmic), P2Y2 Receptor Agonist for Intravitreal Injection

• Genetics and Clinical Characteristics of Bardet-Biedl Syndrome

• Cell Transplantation to Replace Retinal Cells and RPE in Retinal Dystrophies

• Optical Coherence Tomography Study of Retinal Thickness

• Phase I Trial for Wet Age-Related Macular Degeneration with VEGF Trap

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DIABETES MELLITUS

StudyB7A-MC-MBCM: Protein Kinase C Beta Inhibitor-Diabetic Retinopathy Study 2 (PKC-DRS2) a Phase 3 Clinical TrialSponsorEli Lilly Co.Study PurposeTo determine whether an inhibitor of the beta-isoform Protein Kinase C (PKC), relative to placebo, will inhibit visual loss or the development of PDRStudy Design• Phase 3, multicenter, parallel, randomized, double masked, placebo controlled study • Subjects with Type I or II diabetes, ETDRS retinopathy severity of 47A-53E in at least one eye will receive a once a day tablet (either the investigational drug or placebo) with a mealEligibility/Exclusion• Subjects 18 years of age and older• Type I or II DM with HbA1C of < 13.0% at time of screening and enrollment• History of PRP for DR, uncontrolled HTN, unstable anginaResultsPending

StudyDiabetic Macular Edema Vitrectomy Study (DMEVS)SponsorJuvenile Diabetes Research Foundation and Rush Medical CollegeStudy Purpose• To investigate whether the use of vitrectomy can preserve or improve visual acuity in individuals with diffuse diabetic macular edema compared to standard laser therapy. • To determine whether optical coherence tomography (OCT) has value in the evaluation of this disorderStudy DesignRandomized, prospective clinical trialNumber of Patients EnrolledNot availableFollow Up6 monthsEligibility/ExclusionEntry criteria include: • Best-corrected ETDRS visual acuity 20/40-20/800• Foveal avascular zone less than 1000 microns • No benefit from previous medical or laser treatments within previous 3 months• Stable systemic healthResultsPending

StudyPhase II Study to Evaluate the Safety and Efficacy of an Intravitreal Fluocinolone Acetonide (0.5 or 2mg) Implant in Patients with Diabetic Macular Edema (DME)SponsorBausch & Lomb, Inc.Study Purpose• To evaluate the safety and efficacy of intravitreal fluocinolone implant in the management of patients with Diabetic Macular Edema (DME)• To compare the safety and efficacy of two doses of fluocinolone (0.8 or 2.0 mg) delivered by an intraocular/intravitreal implant in patients with macular edemaStudy Design• Eligible patients include those with diabetic macular edema that have had previous treatment with laser photocoagulation and have persistent retinal thickening involving the center of the macula • Patients are randomized to pars plana insertion of either the 0.5 or 2mg fluocinolone implant

• Patients are followed for clinical response with monitoring of ETDRS visual acuity, intraocular pressure, color photography and fluorescein angiographyEligibility/ExclusionEligibility:• Diabetic Macular Edema in the study eye• Pregnant lactating females• DME must involve fixation and be at least one disc area in size• Males and non-pregnant females must be at least 18 years of ageExclusion:• Allergy to fluocinolone or any component of the delivery system• Visual acuity of >20 and <68 letters by ETDRS in the study eye• Presence of history of uncontrolled ocular pressure (IOP) while on steroid therapy resulting in loss of vision • IOP >25 mm Hg requiring 2 types of anti-glaucoma medication to lower to <25 mm HG. • The study eye must have received at least one macular laser treatment >3 months prior to entry into the studyResultsPending

StudyEpidemiology of Diabetes Intervention and Complications (EDIC)SponsorNational Institute of HealthStudy Purpose• Overall goal of this study is to help determine factors that are associated with the development of kidney, large blood vessel, eye and nerve complications in diabetes.• A new study indicates that despite increased hyperglycemia, a reduction in the risk of progressive retinopathy and nephropathy persists for at least 4 years in patients with Type I diabetes who manage their condition through intensive therapy• This research was part of the Multicenter Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications Research Group (EDIC)Study Design• EDIC is an observational study to compare the long term effects of intensive or conventional therapy provided during the DCCT on the development of more advanced retinal and renal complications of diabetes • The study compared the effects of two treatment regimens- standard therapy and intensive control- on the complications of diabetes • Patients were randomly assigned to each treatment groupEligibility/Exclusion• Patients with Type I diabetes• Patients with Type I DM for at least 1 year but no longer than 15 years• Required to have either no DR or early NPDRResultsPending

StudyA Multicenter, Randomized, Masked, Controlled Study to Evaluate the Safety and Efficacy of Retisert, an Intravitreal Fluocinolone Acetonide Implant, in the Treatment of Patients with Diabetic Macular Edema, FAME 4SponsorControl Delivery Systems, Inc.StatusActively enrollingPatient Accrual DateTBAStudy CenterControl Delivery Systems, Inc; 313 Pleasant Street, Watertown, MA 02472Study ChairmanNot availableStudy PurposeTo evaluate the safety and efficacy of Retisert in the management of patients with Diabetic Macular Edema (DME)Study DesignTrial comparing eyes receiving a Retisert

implant and eye receiving Retisert in conjunction with a PPV to control eyes receiving a placebo implant in conjunction with PPVNumber of Patients EnrolledUp to 180 pts Follow Up4 yearsEligibility/Exclusion• Patients 18 yrs and older with diffuse DME involving fixation • DME should be at least one disc area in sizeParticipating Centers25 centersResultsPending

StudyA Phase 2 Randomized, Open Label, Multicenter, Controlled Trial to Assess the Safety and Efficacy of Dexamethasone Segment Drug Delivery System (DEX PS DDS) in the Treatment of Persistent Macular EdemaSponsorOculex Pharmaceuticals, Incl. 601 W. California Ave, Sunnyvale, CA 94086StatusNot availablePatient Accrual DatePendingStudy CenterNot availableStudy ChairmanCynthia Selfridge, RN; Oculex PharmStudy PurposeTo compare the effectiveness of DEX PS DDS to observation in the treatment of persistent macular edemaStudy DesignRandomized, open label, multi center, and controlled studyNumber of Patients Enrolled160 ptsFollow Up6 monthsEligibility/Exclusion• Persistent macular edema due to: • Diabetic Retinopathy (DR) • Branch Retinal Vein Occlusion (BRVO) • Irvine-Gass Syndrome • UveitisParticipating CentersNot availableResultsPending

StudyVitrase of Vitreous Hemorrhage Study (VVHS)SponsorAdvanced Corneal SystemsStudy Purpose• To evaluate the safety and efficacy of an injection of Vitrase for intravitreal injection for facilitating the clearance of severe vitreous hemorrhageStudy Design• The Vitrase study is a prospective, randomized, parallel, double-masked studyEligibility/Exclusion• Patients with severe vitreous hemorrhage of a minimum of 1 month’s duration due to diabetic retinopathy or bleeding of any etiology except those listed in the subject exclusion criteria, randomized by computer into four study groups• Subject is 18 years of age or older, severe vitreous hemorrhage that obscures visualization of the fundus on indirect ophthalmoscopy that was • A: red reflex with no retinal detail visible posterior to the equator or • B: no red reflex is visible • Severe vitreous hemorrhage as defined above that has been present > 1 month by history or exam• Best corrected visual acuity is worse than 20/200 at the time of the screening visit

Participating CentersNot available Number of PatientsNot availableParticipating CentersNot availableResultsPending

StudyMBBK/MBBM SponsorEli Lilly Co.Study PurposeThe objective is to test the hypothesis that the oral administration of the study drug will inhibit the action of Protein Kinase C and prevent or delay the development of macular edema and proliferative diabetic retinopathy in diabetics with mild to moderately severe Diabetic RetinopathyStudy DesignProspective, randomized, placebo controlled, double masked studyEligibility/Exclusion• 18 yrs or older • Type I or II diabetes • Visual acuity of 20/100 or better in the eye under study and have moderately severe Diabetic Retinopathy or have visual acuity or 20/32 or better in the eye under study and have swelling of the macular region of the eyeResultsPending

StudyPegaptanib Sodium Injection (Macugen) SponsorEyetech Pharmaceuticals and Pfizer Inc. StatusNo longer enrolling patients. Study completion expected Q1 2005 Study PurposeCompare the safety and efficacy of pegaptanib with placebo in patients with DME Study DesignPhase 2, multicenter, randomized, placebo-control, double-masked. Patients received varying doses (0.3 mg, 1 mg, 3 mg) of drug or sham injection every 6 weeks for at least 12 weeks and then at the discretion of the investigators Eligibility/ExclusionEligibility for thermal laser therapy for DME Number of Patients169 Participating Centers41ResultsPending

StudyReduction in the Occurrence of Center-threatening DME SponsorEli Lilly and Company StatusRecruiting Study PurposeDetermine whether ruboxistaurin can slow the progression of DME Study DesignRandomization 1:1, ruboxistaurin/ placebo Eligibility/ExclusionInclusion Criteria: Macular edema: if >= 1/6 DA up to < 1DA, location must be >500 mm 3000 mm from center of macula or if >=1 DA location must be >1500 mm 3000 mm from center of macula, ETDRS retinopathy level of >=20 and 47D in the study eye, best refracted visual acuity in the study eye of 20/32 or better Exclusion Criteria: H/o any focal, grid, or scatter laser for DME in the study eye; retinal artery/vein occlusions, macular degeneration, chorioretinal scars; any intraocular surgery, including YAG laser, within the previous 6 months; preretinal or vitreous hemorrhage (currently); treatment for DME with any therapy, including intravitreal or sub-

>> RETINAL RESEARCH REPORT

26 retina times

Tenon’s steroid, in the previous 6 months; h/o vitrectomy; poorly controlled DM (HA1c >11%), hypertension greater than 170 systolic; chronic renal failure on dialysis; s/p renal transplant or creatinine >4.0; treatment with or planned treatment with topical or oral carbonic anhydrase inhibitors; participation in previous Lilly ruboxistaurin studyParticipating CentersNot available Number of PatientsNot availableParticipating CentersNot availableResultsPending

StudyIntravitreal Triamcinolone Acetonide and Laser Photocoagulation for DME SponsorDiabetic Retinopathy Clinical Research Network StatusRecruiting Study PurposeDetermine whether intravitreal triamcinolone at doses of 1 mg or 4 mg provides greater benefit, with an acceptable safety profile, than macular laser in the treatment of DME Study DesignOne eye eligible: randomization, 1:1:1, laser/1 mg triamcinolone/4 mg triamcinolone. Both eyes eligible: 1 eye randomized to laser, the other to 1 mg or 4 mg of triamcinolone Eligibility/ExclusionAge >=18 years, study eye with best corrected E-ETDRS acuity >24 letters (20/320 or better) and <68 letters (worse than 20/40), study eye with center-involved DME present on clinical exam and on OCT, mean retinal thickness on 2 OCT measurements >250 microns in the central subfield, fellow eye either eligible or has acuity >19 letters (20/400 or better) has not been previously treated with intravitreal corticosteroids Number of Patients795Participating Centers1ResultsPending

StudyLaser Photocoagulation for DME SponsorDiabetic Retinopathy Clinical Research Network (DRCR.net) and National Eye Institute StatusRecruiting Study CenterJoslin Diabetes Center. Beetham Eye Institute, 1 Joslin Place, Boston, MA 02215Study ChairmanLloyd P. Aiello, MD, PhDStudy PurposeCompare standard laser treatment with mild, macular-grid treatment that is milder in intensity, but more extensive in number of laser burns Study DesignPilot Study. One eye eligible: randomization, 1:1, standard/mild macular grid. Both eyes eligible: 1 eye randomized to 1 of the treatments, the other eye randomized to the other treatment Eligibility/ExclusionAge >=18 years, study eye with best corrected E-ETDRS acuity >19 letters (20/400 or better), definite retinal thickening due to diabetic macular edema Number of PatientsApproximately 200 patients Participating Centers71 Resultspending

OCULAR MELANOMA

StudyCollaborative Ocular Melanoma Study (COMS)SponsorNational Eye Institute (NEI)StatusOngoingPatient Accrual DatePre-enucleation radiation completed 12/15/94; radioactive plaque completed 8/1/98Study CentersScheie Eye Inst. at U of Penn and Wilmer Eye Inst. ; 550 N. Broadway, Suite 700; Baltimore, MD 21205; 410-955-1966Study ChairmanStuart Fine, MD; Scheie Eye Institute / 215-662-8657Study Purpose• To evaluate therapeutic interventions for patients who have choroidal melanoma, the most common primary eye cancer affecting adults, and to assess the potential life preserving as well as sight-preserving role of radiation therapy• To determine which of two standard treatments, removal of the eye or brachytherapy, is more likely to prolong survival of eligible patients with medium sized choroidal melanoma• To determine whether preoperative radiation prolongs life for patients whose eyes with large choroidal melanoma are enucleated.Study Design• The COMS is a set of long term, multicenter, randomized controlled trials. In the trial for patients with tumors of medium size, enucleation and irradiation with an iodine-125 episcleral plaque are compared on the basis of length of remaining life• All randomized patients will be followed for 5-15 years or until death• For patients randomly assigned to enucleation, the eye was removed following a standard procedure• For patients assigned to plaque radiation, the margins of the tumor were located and the dimensions of the tumor were measured by the ophthalmic surgeon• A gold plaque with a plastic seed carrier that contained the proper dosage and configuration of radioactive iodine seeds was sutured to the outside (sclera) of the eye over the base of the tumor• This procedure made possible the delivery of a high does of radiation to a very localized area (85 Gy [TG-43] to the tumor apex)• The plaque typically was removed from the eye after three to seven days.Number of Patients Enrolled1317Follow UpPatient f/u ongoing in the trial of radioactive plaqueEligibility/Exclusion• Men and women eligible for the study had to be age 21 or older, have primary choroidal melanoma in only one eye, and have no evidence of metastatic disease. • Accurate estimation of tumor thickness by echography also was requiredParticipating Centers40Results• Nonrandomized Small Tumor Pilot Study: the treatment and mortality results of the COMS Nonrandomized Small Tumor Pilot Study were reported in 1997. From 12/86 to 8/89, 204 patients with small choroidal melanoma, defined as 1.0 to 3.0 mm in apical height and at least 5.0mm in basal diameter, were enrolled in a prospective follow up study. The median length of f/u was 92 months. 8% of patients were treated at the time study enrollment and an additional 33% were treated during f/u. Based on 27 deaths, the Kaplan-Meier estimate of 5 year all cause mortality was 6.0% (95% confidence interval, 2.7% - 9.3%) and 8-year all cause mortality was 14.9% (95% confidence interval, 9.6%-20.2%). Mortality findings and analysis of predictors of growth have been published (COMS reports no. 4 and 6)

• Randomized Trial of Pre-Enucleation Radiation for Large Choroidal Melanoma: initial mortality findings published in 1998 (COMS report no. 10) showed that patients with large choroidal melanoma had similar survival rates regardless of whether they were treated with radiation prior to removal of the eye or had their eye removed without prior radiation therapy• 5-year survival rates were approx. 60% in both treatment arms. The COMS large tumor trial found neither benefit nor harm from treating ocular melanoma patients with radiation before removal of the eye. However, patients who had pre-enucleation radiation had fewer local complications (COMS report no. 11). • Randomized Trial of I-125 Brachytherapy for medium choroidal melanoma: initial mortality findings published in 2001 (COMS report no. 18) showed that survival rates for radiation therapy (I-125 brachytherapy) and enucleation (removal of eye) are about the same. The 5-year survival rate of patients who were treated with either radiation therapy or eye removal was 82%, considerably better than the 70% 5-year survival rate that had been projected when the study was designed in 1985. Compared to immediate loss of vision when the eye is removed, eyes treated with radiation steadily lost vision gradually, with 63% having visual acuity of 20/200 or worse by 3 years after treatment (COMS report no. 16)

BRVO

StudyIntravitreal Steroid Injection Study Trials (ISIS)SponsorIllinois Retina Associates, S.CStudy Purpose• Series of five separate prospective FDA and IRB approved studies designed to determine if there is a possible role for intravitreal steroid injections in the management of refractory macular edema secondary to DME, BRVO, CRVO, JRT and post-op CMEStudy DesignThis is a pilot study. Subjects are randomized to either 2mg or 4mg dose of intravitreal Kenalog® injectionNumber of Patients Enrolled30 per treatment groupEligibility/Exclusion• Persistent macular edema due to • Diabetic Retinopathy (DR) • Branch Retinal Vein Occlusion (BRVO) • Central Retinal Vein Occlusion (CRVO) • Irvine-Gass Syndrome ResultsDME arm of study has completed enrollment. Results are pending. Remaining arms are still enrolling.

StudyEuropean Arteriovenous Sheatotomy Trial (EAST)SponsorNot availableStudy Purpose• To compair the efficacy of surgical arterio-venous decompression with the natural cause in patients with BRVOStudy Design• A prospective, randomized multicenter trial, including 216 patients (108 receive vitrectomy AV-decompression no ILM-peeling; 108 observation). If the hematocrit is >40% an optional isovolemic hemodilution may be optional performed.Eligibility/ExclusionPatients with BRVO, onset < 3 months, ETDRS VA< 20/50, no previous treatmentResultsPending

StudySurgical Decompression of Branch Vein OcclusionSponsorNot availableStudy Purpose• To evaluate vitreous surgery as treatment for BRVOStudy Design• A prospective, non-randomized trial.Eligibility/ExclusionNot availableResultsPending

StudyThe Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study: to Compare the Efficacy and Safety of Intravitreal Injection(s) of Triamcinolone Acetonide with Standard Care to Treat Macular Edema: 1 for CRVO and 1 for BRVO SponsorNational Eye Institute, National Institutes of Health, Department of Health and Human Services StatusEnrollment began in October 2004 Study PurposeTo compare the effectiveness and safety of standard care to intravitreal injection(s) of triamcinolone for treating macular edema (swelling of the central part of the retina) associated with CRVO and BRVO Study DesignMulticenter, randomized, phase 3 trial. Eligible patients within each of these 2 disease entities are randomized in a 1:1:1 ratio to 1 of 3 groups: standard care, intravitreal injection(s) of 4 mg of triamcinolone acetonide, or intravitreal injection(s) of 1 mg of triamcinolone acetonide. Enrolled patients are followed for 3 years. The preparation of triamcinolone acetonide used in the study is specially made for injection into the eye and does not contain any preservatives Eligibility/ExclusionParticipants with macular edema associated with CRVO and BRVO who are 18 years of age or older and are willing to provide consent. Detailed Inclusion/Exclusion Criteria are available on the SCORE Web site at http://spitfire.emmes.com/study/score/. Number of Patients1260 total; 630 with CRVO and 630 with BRVO Participating Centers27ResultsPending

UVEITIS

StudyRandomized Trial of Acetazolamide for Uveitis-Associated Cystoid Macular Edema (CME)SponsorNEI/NIHStudy PurposeTo test the efficacy of acetazolamide for the treatment of Uveitis Associated Cystoid Macular Edema (CME)Study Design• This is a double masked randomized crossover trial designed to test the efficacy of acetazolamide compared with a placebo for the treatment of uveitis associated cystoid macular edema • Randomized adult patients received either oral acetazolamide socium 500 mg or a matched placebo every 12 hours for the first 4 weeks of the study• Children 8 years of age or older received a lesser dose based on body weight. Following a 4 week period, during which no medication was given, patients then received a 4 week course of the opposite medication • Primary end points included reduction of Cystoid Macular Edema (graded on fluorescein angiography) and improvement

retina times 27

in visual acuity (measured on standardized ETDRS charts)• Acuity was also assessed as a secondary outcome variable. • Adverse effects of the acetazolamide therapy were monitored by clinical and laboratory techniciansEligibility/ExclusionEligibility:• Males and females 7 years of age and older, weighing at least 35kg were eligible for the study • Patients had to have at best a corrected visual acuity of 20/40 or worse in one eye with Cystoid Macular Edema demonstrable on FA• Patients were allowed to receive systemic therapy for their uveitisExclusion: • Current use of acetazolamide as part of a therapeutic regimen• A history of hypersensitivity reactions to acetazolamide, sulfonamide, or angiography dye• Unclear ocular media that would obscure FA• Macular subretinal neovascularization or a macular hole• Inability to take acetazolamide for medical reasonsResultsThirty-seven patients completed the trial and were available for analysis. Seventeen patients (46 percent) were randomized to receive acetazolamide and 20 (54 percent) to receive placebo during course A. Visual acuity data were available for all 37 patients for all visits. Fluorescein angiography data were available for 145 of the 148 study visits (98 percent). Acetazolamide therapy resulted in 0.5 disc area (25 percent) decrease in cystoid macular edema over that of placebo (p = 0.01; estimated treatment effect = -0.5 disc areas, 95 percent confidence interval [-0.9, -0.1]). In contrast, there was no statistically significant effect of acetazolamide on visual acuity (p = 0.61; estimated treatment effect = 0.6 letters, 95 percent confidence interval [-2, 3]). Possible adverse drug reactions were reported by 34 of the 37 (92 percent) during acetazolamide therapy. In contrast, at least one adverse drug reaction was reported in only 5 of 37 patients (14 percent) during placebo therapy.

Acetazolamide therapy results in a statistically significant but small decrease in cystoid macular edema in patients with chronic uveitis but does not improve visual acuity. Since acetazolamide is associated with a number of adverse effects, patients should be closely monitored and the drug discontinued if no therapeutic benefit is documented.

StudyA Multicenter, Randomized, Double Masked, Controlled Study to Evaluate the Safety and Efficacy of a Fluocinolone Acetonide (0.5 or 2.0 mg) Implant in Patients with Non-Infectious Uveitis Affecting the Posterior Segment of the EyeSponsorBausch & Lomb, Inc.Study PurposeTo evaluate the safety and efficacy of an intravitreal Fluocinolone Acetonide (0.5 or 2.0 mg) implant in patients with non-infectious uveitis affecting the posterior segment of the eyeStudy DesignA 3 year, multi-center, randomized, double-masked, controlled, safety and efficacy study comparing 2 does levels of Fluocinolone Acetonide (0.5 or 2.0mg) in intravitreal implantsEligibility/ExclusionPatients with non-infectious uveitis affecting the posterior segment of the eye will be enrolledResultsThe U.S. Food and Drug Administration has approved the single-indication orphan drug Retisert™ (fluocinolone acetonide intravitreal implant), 0.59 mg, for the treatment of chronic non-infectious uveitis affecting the posterior

segment of the eye, a sight-threatening inflammatory disease that primarily afflicts people between the ages 20 and 50, during their prime working years.

FDA approval of the single-indication orphan drug was based on 34-week results from two three-year randomized, double-masked, multicenter clinical studies demonstrating that in eyes with Retisert there was:• a statistically significant decrease in the recurrence of uveitis from approximately 40% to 54% for the 34-week period pre-implantation to approximately 7% to 14% for the 34-week period post-implantation;• a statistically significant decrease in the use of adjunctive therapy including systemic corticosteroid and/or immunosuppressive therapy from approximately 47% to 63% at the time of implantation to approximately 5% to 10% at 34 weeks post-implantation, and for patients needing periocular corticosteroid injections from approximately 50% to 65% for the 34 week period pre-implantation to approximately 3% to 6% for the 34 week period post-implantation;• statistically significant improvement of three or more lines of visual acuity in approximately 19% to 21% of study eyes at 34 weeks post-implantation.

The most common adverse events include cataract progression, which is managed by standard cataract surgery; increased intraocular pressure, which is managed with the use of IOP-lowering eye drops or filtering surgery; and procedural complications and eye pain.

StudyLongitudinal Study of Ocular Complications of AIDS (LSOCA)SponsorNational Eye InstituteStatusRecruitingPatient Accrual DateContact chairman’s officeStudy CenterCurtis Meinert, PhD; Dept. of Epidemiology, School of Hygiene & Public Health; JHU, 615 N. Wolf Street, #5010; Baltimore, MD 410-955-8198Study ChairmanDouglas Jabs, MD, MD/ 410-955-1966Study Purpose• CMV retinitis and other ocular complications of AIDS• To determine the effect of highly active anti-retroviral therapy (HAART)-induced immune status on the risk of developing CMV retinitis and other ocular complications of AIDS• To determine the characteristics (clinical, virologic, hematologic, and biochemical) of a population at high risk for CMV retinitis and other ocular complications of AIDS• To evaluate the effects of treatments for CMV retinitis and other ocular complications on visual function, quality of life, and survival.Study Design• The longitudinal study of ocular complications of AIDS (LSOCA) is prospective observational study of patients with AIDS• Patients with prior diagnosis of AIDS according to the 1993 CDC criteria with or without ocular complications will be enrolled over a 4 year period• Approx. 2000 patients will be enrolled in the study. enrollments of patients with CMV retinitis at baseline will be between 300 and 600 patients• Follow up visits for patients with ocular complications at baseline or diagnosed during follow up will be every 3 months• Follow up data will include eye examinations, fundus photographs, visual function testing, medical history, hematology, and serum chemistry, and collection of plasma and blood cells for banking• Analysis of banked specimens will include HIV RNA levels and CMV DNA levelsNumber of Patients EnrolledOngoingFollow UpNot available

Eligibility/ExclusionMales and females age 13 years and older with diagnosis of AIDS will be eligible.Participating Centers19ResultsPending

StudyCMV Retinitis and Viral Drug Resistance (CRVR)SponsorNational Institute of HealthStudy Purpose• To determine the incidence and prevalence of CMV drug resistance in patients with AIDS and CMV retinitis• To determine risk factors for the development of resistance, clinical correlates of viral drug resistance, phenotype-genotype correlation, ocular blood CMV correlations and determination of blood PCR and CMV viral load resistance correlationsStudy DesignProspective, cohort clinical trialEligibility/Exclusion• Inclusion: newly diagnosed CMV retinitis not previously treated, confirmed HIV diagnosis• Exclusion: treatment of extraocular CMV within the past 28 days, subjects under 18 years of ageResultsPending

StudyA Pilot Study of a Sustained Release Cyclosporine-A Implant for UveitisSponsorNational Eye Institute 98-EI-0110Study PurposeCyclosporine is a medication that is useful for treating patients with inflammation in the eye (uveitis)Study DesignPatients with active uveitis and poor vision in one eye will receive a surgically place cyclosproine implant that will release the medication into the eyeEligibility/ExclusionNot availableResultsPending

ROP

StudyCryotherapy for Retinopathy of Prematurity (CRYO-ROP) - Outcome Study of Cryotherapy for Retinopathy of PrematuritySponsorNational Eye InstituteStatusOngoing. Comments: The 15-year examination period has ended, and study centers are closed. Currently, data from this final study examination are being analyzed to determine if the benefits of cryotherapy are sustained in adolescence, when late structural complications and loss of visual acuity have been reported to occur. A comparison will be made between treated and untreated eyes for many conditions, such as late retinal detachment, macular degeneration, and vision failure. This information will be used for evaluating the overall outcome for these teenagers. A manuscript reporting the results of this examination is in process.Patient Accrual DateNo longer recruiting. Comments: Recruitment, which began in January 1986, was stopped January 22, 1988.Study CenterRobert J. Hardy, PhD, Principal Investigator School of Public Health University of Texas-Houston Health Science Center Coordinating Center for Clinical Trials 1200 Herman Pressler Street, E827 Houston, TX 77030

Study ChairmanEarl A. Palmer, MD, Chairman Casey Eye Institute Oregon Health & Science University 3375 S.W. Terwilliger Boulevard Portland, OR 97239-4197Study Purpose• To determine the safety and efficacy of trans-scleral cryotherapy of the peripheral retina in certain low birth-weight infants with retinopathy of prematurity (ROP) for reducing blindness from ROP. • To determine the long-term outcome for eyes that had severe (“threshold”) ROP, both with and without cryotherapy.Study DesignThe randomized, controlled, single-blind, multicenter trial of cryotherapy for ROP enrolled more than 4,000 premature infants who weighed no more than 1,250 grams at birth. The eyes of the infants enrolled in the study were examined at predetermined intervals while the subjects were still in the intensive care nursery. After the pupils were dilated with eye drops, the eyes were examined by an ophthalmologist using a binocular indirect ophthalmoscope to visualize the developing retina. The natural history of the condition of each infant’s retina was recorded. When examination disclosed the severe form of ROP (threshold ROP) in both eyes, and the parents gave informed consent, one of the infant’s eyes was randomly selected to receive cryotherapy.

Outcome of the therapy was assessed at 3 months and 12 months following randomization by an extensive examination that included photography of the interior of both the treated and the control eyes. The 12-month exam also measured visual function with preferential-looking techniques. Neither the trained photograph readers who evaluated the pictures from both eyes nor the specially trained vision testers knew which eyes had received cryotherapy. Additional assessments of visual acuity and retinal status have been made approximately each year through age 10, with a final examination at age 15 for patients in the randomized trial of cryotherapy who did not have bilateral total retinal detachment and blindness.Number of Patients Enrolled4099Follow-up15 yearsEligibility/ExclusionPremature infants of either gender who were eligible for the natural history study had weighed less than 1,251 grams at birth and had survived the first 28 days of life. They had no major ocular or systemic congenital anomalies. Infants who met these criteria and also had a threshold level of ROP (defined as stage 3+ of the International Classification of Retinopathy of Prematurity occupying five or more contiguous or eight cumulative 30° sectors [clock hours] of stage 3 ROP in zone I or II in the presence of plus disease) could be referred for examination to determine eligibility for entry to the cryotherapy trial.Participating Centers23ResultsThe Cryotherapy for Retinopathy of Prematurity Cooperative Group reported preliminary results in 1988. This study registered 9,751 infants with birth weights less than 1,251 grams at 23 study centers. Of these infants, 4,099 were systematically examined. The defined threshold severity of ROP developed in 291 infants.

Cryotherapy was performed in half the eligible eyes of the 291 infants. Twelve months after randomization, the results of masked grading of fundus photographs of the posterior pole indicated an unfavorable outcome in 25.7 percent of the eyes that had received cryotherapy and in 47.4 percent of the control eyes. Masked Teller Acuity Card assessment of grating acuity indicated an unfavorable functional outcome in 35 percent of the treated eyes, compared with 56.3 percent of the control eyes. These results indicate that cryotherapy reduces the risk of unfavorable retinal and functional outcome from threshold ROP.

Although the surgery was stressful, no major complications occurred during or following treatment. Physicians’ diagnoses and the unbiased photograph gradings were statistically similar. These data support the efficacy of cryotherapy in reducing by approximately one-half the risk of unfavorable retinal outcome from threshold ROP.

Results at 31⁄2 years and 51⁄2 years following randomization continue to support the long-term efficacy and safety of cryotherapy in the treatment of severe ROP. However, the 51⁄2-year data suggested that cryotherapy could reduce the chance of normal vision in some cases. Findings from the 10-year examination showed fewer unfavorable outcomes for both visual acuity and structure in treated vs untreated eyes. The examination at age 10 included measurement of contrast sensitivity and visual fields. Results of contrast sensitivity testing demonstrated no evidence of adverse treatment effects in eyes that received cryotherapy. The findings for visual field testing with Goldmann Perimetry showed a visual field area that was 24 percent to 26 percent larger in treated eyes versus untreated eyes, when blind eyes were included and assigned a score of 0. When blind eyes were excluded, visual field area was 5 percent smaller for treated eyes than for untreated eyes, indicating that cryotherapy slightly reduces the visual field area in eyes with severe ROP. This small reduction in visual field area in treated eyes is minor when compared with the much greater risk that an eye will be blind without treatment. However, this and any other possible adverse side effects are important considerations in determining whether to treat milder cases of ROP that have a relatively good prognosis for vision without treatment.

Cryotherapy is now recommended for both eyes whenever stage 3+ retinopathy of prematurity involves the posterior retina (zone I) of both eyes and for both eyes (in most patients) in cases of threshold ROP in zone II. There are, as yet, insufficient data to mandate cryotherapy in any method different from the one used in this trial, or to apply it to patients with less severe disease. Following the publication of the positive results of this study in 1988, the U.S. pattern of care changed rapidly to embrace these guidelines as standard practice.

Laser therapy has been shown to have similar value to cryotherapy. Currently the risk data from the CRYO-ROP study are being used to test the value of ealier interventions in selected high risk eyes, in the Early Treatment for ROP study (ETROP).

AMD

StudySubmacular Surgery Trials (SST)SponsorNEIStudy Purpose• To determine whether surgical removal of subfoveal choroidal neovascularization (CNV) and associated hemorrhage in patients with Age-Related Macular Degeneration (AMD), the Ocular Histoplasmosis Syndrome (OHS), or idiopathic CNV stabilizes or improves vision more often than observation.• To determine how surgical removal compared to observation of subfoveal CNV due to AMD, OHS, or idiopathic causes changes the patient’s perception of health- and vision-related “quality of life,” as measured by telephone interview using the Medical Outcomes Survey Short Form-36 (MOS SF-36) instrument, the Hospital Anxiety and Depression Scale, and the National Eye Institute Visual Function Questionnaire (NEI VFQ-25).• To determine whether randomized trials of surgery are warranted for patients with subfoveal CNV associated with Age-Related Macular Degeneration not suitable for laser treatment.Study Design• Vision data collected at baseline include a protocol refraction, best-corrected logMAR visual acuity (ETDRS charts), contrast threshold (Pelli-Robson charts), and reading

speed (enlarged text). Other baseline data recorded include stereoscopic color fundus photographs, fluorescein angiograms, and lens photographs, as well as health- and vision-related quality of life interview data (by telephone).• Eligible patients who gave signed, informed consent were randomly assigned to surgery (within 8 days of randomization) or observation. Patients, assigned to surgery, are seen one month post-surgery for an examination and photographs. All participants are examined at 3, 6, 12, 24, 36, and 48 months after randomization to collect vision data (collected in a masked fashion at 24 and 48 months after randomization) and to repeat photography. Quality of life telephone interviews are repeated at 6, 12, 24, 36, and 48 months after randomization. • The primary outcome is improvement in visual acuity from baseline to the two-year examination or retention of baseline visual acuity through the two-year examination. Secondary outcomes include change in quality of life from baseline to the 2- and 4-year examinations, change in visual acuity over 4 years, large losses of visual acuity, and adverse ocular outcomes (e.g., those requiring additional treatment such as cataract, retinal detachment, or recurrent CNV).Eligibility/Exclusion• Group B: Patients with evidence of large hemorrhages from subfoveal neovascular AMD lesions, visual acuity (SST protocol) of 20/100 to light perception, with the area of hemorrhage larger than the area of fluorescein angiographically visible CNV, with any visible CNV < 9 MPS disc areas, and ability to return for 4 years of follow up may be eligible for the Group B (Blood) protocol. • Group N: Patients with new CNV (no prior laser) due to AMD, visual acuity (SST protocol) of 20/100 to 20/800, fluorescein angiographic evidence of subfoveal CNV lesion which is < 9 MPS disc areas, and ability to return for 4 years of follow up may be eligible for the Group N (New CNV) protocol.• Group H: Patients with evidence of CNV due to OHS or idiopathic cause, visual acuity (SST protocol) 20/50 to 20/800, fluorescein angiographic evidence of subfoveal CNV lesion (new or recurrent) which is < 9 MPS disc areas, and ability to return for 4 years of follow up may be eligible for inclusion in the Group H (Histoplasmosis/Idiopathic CNV) protocol. • Exclusion criteria include other ocular diseases compromising vision, history of submacular surgery in the study eye, history of subfoveal laser photocoagulation that extends under the foveal avascular zone, recent intraocular surgery, or previous investigational therapy for CNV.ResultsOf 454 patients enrolled, 228 study eyes were assigned to observation and 226 to surgery. The percentages of eyes that had successful outcomes were similar in the 2 arms: 44% assigned to observation and 41% assigned to surgery. Median VA losses from baseline to the 24-month examination were 2.1 lines (10.5 letters) in the observation arm and 2.0 lines (10 letters) in the surgery arm. Median VA declined from 20/100 at baseline to 20/400 at 24 months in both arms. No subgroup of patients was identified in which submacular surgery led to better VA outcomes. In the surgery arm, 55 (39%) of 142 initially phakic eyes had cataract surgery by the 24-month examination, compared with 6 (5%) of 133 eyes in the observation arm. Rhegmatogenous retinal detachment occurred in 12 surgery eyes (5%) and 1 observation eye. Submacular surgery, as performed in this clinical trial, did not improve or preserve VA for 24 months in more eyes than observation and is not recommended for patients with similar lesions.

Of 454 patients enrolled, 228 were assigned to observation and 226 to surgery. At baseline, median overall NEI-VFQ scores were 67 in the observation group and 69 in the surgery group; by 2 years, the observation group had lost a median of 3 points (95% confidence interval [CI]: −6 to −2), and the surgery group gained a median of 1 point (CI: −1 to 3). The largest difference was observed for the mental health subscale,

where the observation group lost a median of 5 points (CI: −5 to 0), and the surgery group gained a median of 5 points (CI: 0–10) by 2 years. Treatment differences in median 2-year changes in NEI-VFQ scores favored surgery by up to 10 points for unilateral cases and up to 8 points for bilateral cases. No treatment difference in 2-year change was observed for the SF-36 physical component summary; 2-year change in the mental component summary favored surgery by 2 points. Few patients (2%–4%) had HADS definite anxiety or depression at baseline or at 24 months. Although HRQOL outcomes were better in the submacular surgery arm than in the observation arm, surgery (per protocol) is not recommended because VA outcomes (reported elsewhere) were similar in the treatment arms.

StudyAnecortave Acetate in Age-Related Macular DegenerationSponsorAlcon Research; South Freeway Drive; Ft. Worth, TX 817-615-2583Study PurposeThis study is an evaluation of the safety and duration of efficacy of Anecortave Acetate sterile suspension (30mg, 15mg, or 3mg) versus placebo after a single (subtenon) injection for the inhibition of neovascularization in patients with exudative Age-Related Macular Degeneration following laser treatment of extrafoveal or juxtafoveal neovascular membranes.Study DesignDose duration studyEligibility/Exclusion• AMD with lesion 12 disc areas or less and 50% or more of the total lesion with choroidal neovascularization (CNV), and either the classic component is 50% or more of the total CNV or the classic component of the CNV is > 0.75 DA in total size• Visual Acuity: • ETDRS vision in the study eye = Log MAR~0.0 0.9 (20/20-20/160) • ETDRS vision in the non study eye = Log MAR 1.6 (20/800) or better ResultsOutcomes following anecortave acetate injection were compared with outcomes without anecortave acetate treatment. 73 percent of patients treated with anecortave acetate 15 mg had stable or improved vision from baseline to 24 months after treatment, significantly more than the 47 percent of patients in the placebo group who did not receive anecortave acetate (p=0.035).

Patients treated with anecortave acetate 15 mg had no increase in growth of the classic component of the subfoveal choroidal neovascular membrane (CNV) between months 12 and 24, and the total lesion size remained stable over this period. Additionally, at 24 months, in the sub-group of patients with the more aggressive, predominantly classic CNV lesions, no patients treated with anecortave acetate 15 mg had severe vision loss (> 6 lines loss) compared to a 23 percent rate in the placebo group, (p=0.023). The U.S. Food and Drug Administration (FDA) issued an approvable letter for its New Drug Application (NDA) for Retaane(R) 15 mg (anecortave acetate suspension) in May, 2005.

StudyIndocyanine Green (ICG) Risk Factors for Choroidal NeovascularizationSponsorMacula Society; Scheie Eye Institute, Philadelphia, PAStudy Purpose• To determine risk factors of ICG for CNVStudy DesignNot availableEligibility/ExclusionNot availableResultsPending

StudyLutetium Taxaphyrin (LuTex/Optrin) in Age-Related Macular Degeneration (Phase I Studies)SponsorAlcon Research; South Freeway Drive; Ft. Worth, TX 817-615-2583Study Purpose• To evaluate the safety and efficacy of Lutetium texaphyrin combined with light laser treatment for the occlusion of abnormal vessels and membranes in people with AMD and CNV (CNV-abnormal growth of new blood vessels) for whom traditional heat laser therapy is not an option, or who have refused the recommended heat laser therapyStudy Design• Multicenter, dose ranging, prospective, non randomized clinical study • Patients with AMD will be entered and evaluated in 2 phase I and IB studies • The first trial involves a dose and light ranging study to evaluate the utility of lutetium taxaphyrin as an imaging and photodynamic therapy agent in choroidal neovascularization • Second study will evaluate lutetium taxaphyrin as an imaging agent alone, with subsequent therapy with standard thermal photocoagulation or verteporfin photodynamic therapyEligibility/ExclusionNot availableResultsPending

StudyA Phase I, Open-Labeled, Randomized Study of the Safety, Tolerability, and Pharmacokinetics of Escalating Multiple-dose Intravitreal Injections of RhuFab V2 in Subjects with Neovascular AMD (FVF2425G Study)SponsorGenentech, Inc. 888-662-6728Study Purpose• To investigate the safety and tolerability of recombinant humanized anti-VEGF monoclonal antibody fragment (RhuFab V2) administered as multiple, intravitreal injections up to a final dose of 2mgStudy Design• This phase I, multicenter, randomized trial enrolled 30 patients into three dosing regimens. • All patients were treated for a total of 16 weeks and followed through 20 weeks.• Group 1 received escalating doses from 300µg to 1.0mg every 2 weeks over 6 weeks followed by 1.0mg of RhuFab V2 every 4 weeks. • Group 2 received escalating doses from 300µg to 2.0mg every 2 weeks over 14 weeks followed by a final 2mg dose at week 16. • Group 3 received escalating doses from 300µg to 2mg every 4 weeks over 16 weeks. • All patients underwent ETDRS visual acuity testing, ophthalmological examination, and adverse event assessment at each study visit, with fundus photography, fluorescein angiography, OCT, and pharmacokinetic evaluations at selected visits.Eligibility/Exclusion• Inclusion: active subfoveal CNV, visual acuity in the study eye of 20/40 to 20/400 and better or equal to 20/800 in the fellow eye, age >50 years old; • Exclusion: more than 3 prior treatments with Visudyne in the study eye within 12 months, lesions larger Participating CentersMulticenterResults• Twenty-one of the 30 patients were enrolled at the Bascom Palmer Eye Institute; Group1 (n=5), Group 2 (n=8), and Group 3 (n=8). • The types of subfoveal CNV lesions enrolled included occult CNV with no classic CNV (n=6), minimally classic CNV (n=6), predominantly classic CNV (n=2), predominantly classic CNV after PDT (n=4), and CNV with RPE tears (n=3).• Intravitreal injections as frequent as every 2 weeks were well tolerated by the patients. • The most frequent adverse event was mild inflammation. • Significant intraocular inflammation was not observed when RhuFab was escalated from an initial dose of 300µg to doses as

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high as 2mg. At week 20 (Day 140), 19 of the 21 patients (90%) had stable (± 4 letters) or improved (> 5 letters) vision with 11 patients (52%) gaining at least 3 lines (15 letters). • Stable and improved visual acuity correlated well with decreased fluorescein angiographic leakage and decreased retinal thickness measured by OCT.

StudyA Phase III, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of rhuFab V2 (Ranibizumab) in Subjects with Minimally Classic or Occult Classic Subfoveal Neovascular AMD (FVF2598G Study - MARINA)SponsorGenentech, Inc. 888-662-6728StatusActively enrollingStudy CenterGenentech, Inc., 1 DNA way, South San Francisco, CA 94080-4990Study ChairmanRobert Y. Kim, MD, GenentechStudy Purpose• To investigate the efficacy, safety, and tolerability of monthly intravitreal injections of rhuFab V2 in preventing visual lossStudy Design• Phase III, multicenter, randomized pivotal study.• 1:1:1 Randomization: Sham injection: 300 micrograms rhuFab V2: 500 micrograms RhuFab V2 by 24 monthly intravitreal injections• All patients to receive ETDRS visual acuity testing, ophthalmological examination, and adverse event assessment at each study visit, with fundus photography, fluorescein angiography, OCT, visual function questionnaires and health surveys, and pharmacokinetic evaluations at selected visits.Number of Patients EnrolledFully enrolled. 716Follow UpOngoingEligibility/Exclusion• Inclusion: active primary or recurrent subfoveal CNV lesions due to AMD with occult or minimally classic CNV, CNV must be 50% of lesion GLD , total lesion < 12 MPS DA; visual acuity in the study eye of 20/40 to 20/320• Exclusion: prior PDT, TTT, XRT, or other experimental CNV treatment. Previous intravitreal drug delivery. Prior vitrectomy, submacular surgery, or other surgical intervention for AMD. Subfoveal atrophy or fibrosis. Other cause of CNV. RPE tear. Selected subfoveal hemorrhage ( 1 Disk area or 50% of lesion)Participating CentersMulticenter (100 sites)ResultsPending

StudyVisudyne With Altered (Delayed) Light in Occult CNV Study (VALIO)SponsorQLT Inc/Novartis Ophthalmics, IncStudy Purpose• To determine the potential of delaying light application to 30 minutes after initiation of infusion to improve outcomes of photodynamic therapy with verteporfin (Visudyne®, Novartis AG) in AMD patients with occult with no classic CNVStudy Design• AMD patients (>50 years of age) with subfoveal CNV were randomized 1:1 to receive verteporfin therapy with delayed light or verteporfin therapy with standard light application (15 minutes after initiation of infusion)• Patients were followed for at least 6 months after initial treatment. Inclusion criteria comprised a lesion composition that was occult with no classic CNV, in which <50% of the lesion area was CNV and in which the greatest linear dimension of the lesion was <5400 microns on the retina, presumed

recent disease progression, and baseline best-corrected visual acuity (approximate Snellen equivalent) 20/50-20/200. • Verteporfin therapy was administered at baseline, with the option of an additional treatment at month 3, 6, and 9 if there was evidence of fluorescein leakage from CNV• Best-corrected visual acuity, color fundus photography, and fluorescein and Indocyanine Green (ICG) angiography were assessed at scheduled follow up visits through month 6• Potential treatment benefit was assessed based on angiographic outcomes and visual acuity change from baseline • Safety was assessed by evaluating adverse events, visual acuity, color fundus photographs, fluorescein and ICG angiogramsEligibility/ExclusionInclusion:• Subfoveal CNV, occult CNV with no classic CNV• Vision 20/40-20/200• Recent progression of diseaseExclusion:• Lesions larger than 9MPS DA• Cataract surgery within previous 3 monthsResults• Most baseline characteristics did not appear different between the two treatment groups (median age 78, 42% men, median total lesion size 8.59 mm [approximately 4.85 MPS DA]• The baseline median visual acuity score was higher in the standard light application group (58 letters vs. 52 letters [approximate Snellen equivalent 20/64-2 vs. 20/100+2] as measured by ETDRS criteria).• Angiographic and vision outcomes and safety results through 12 months showed no statistically significant difference.

StudyProphylactic Diode Laser Photo Coagulation for the Prevention of Choroidal Neovascularization in Age-Related Macular Degeneration (PTAMD)SponsorUniversity of Pittsburgh StatusActivePatient Accrual Date3rd year of recruitmentStudy CenterUniversity of PittsburgStudy ChairmanThomas Friberg, MD; U of Pittsburg; Pittsburg, PA 412-647-7212Study Purpose• To determine whether a specific laser treatment will prevent individuals who have the less severe dry macular degeneration from progressing to the more severe wet form of macular degenerationStudy Design• Bilateral Dry AMD patients with both eyes eligible will have one eye randomized to laser treatment and the fellow eye assigned to observation• Unilateral patients with only one eye eligible will have the eligible eye randomized to either laser treatment or observation• Laser treatment consists of a grid of 48 subthreshold (ophthalmoscopically invisible) diode laser spots placed around the maculaNumber of Patients Enrolled150Follow Up5 yrsEligibility/Exclusion• Inclusion: males and females, 50 yrs or older, able to understand and give written informed consent before treatment, vision 20/60 or better with at least 5 Drusen in each eye or 5 large Drusen in one eye with an event occurring in the other eye, no major health problems • Exclusion: worse vision than 20/60, event or drusen, size/amounts, inhibiting health factorsParticipating Centers13ResultsPending

StudyMulticenter Investigation of Rheopheresis for Age-Related Macular Degeneration (MIRA-1)SponsorOccuLogix; 2575 Ulmerton Road, suite 210; Clearwater, FL 33762; 727-561-4181StatusOngoingPatient Accrual DateNot availableStudy CenterOccuLogix, Inc.Study ChairmanNot availableStudy PurposeThis study is designed to determine if the removal of LDL cholesterol and other harmful substances from the blood will improve vision in people with Dry AMD Study Design• At entry, patients undergo a complete ocular and physical examination, including a series of baseline blood tests • Patients will be randomly assigned to one of two study treatment groups: the Rheopheresis treatment group (120 patients) or placebo treatment group (60 patients) • The design is single masked with a 2:1 chance of being in the apheresis group. Patients undergo 8 treatments over a period of 2 1/2-months • Patients in the Rheopheresis treatment group will have their blood pumped through the filter system being investigated • Patients in the placebo treatment group will not have blood filtered. At each visit, patients’ vital signs will be recorded, and blood samples obtained pre- and post- treatment• Between the 4th and 5th treatments, two weeks after the 8th treatment, and at 6, 9, and 12 months, patients will receive the same blood tests and examinations performed at entryNumber of Patients EnrolledApprox. 200. Follow Up• In either of these groups, patients will undergo 8 treatments over a period of about 2-1/2 months• Patients in the Rheopheresis treatment group will have their blood pumped through the filter system being investigated• Patients in the placebo treatment group will not have their blood filtered• At each visit, patients’ vital signs will be recorded, and they will be asked to give blood samples for complete testing prior to and immediately after each treatment, which takes about 3 hours to complete• Between the 4th and 5th treatments and two weeks after the 8th treatment, patients will come back to the clinic for a visit where they will receive many of the same tests taken at the initial qualifying visit• There will be three more evaluations at approx. 6 months, 9 months, and 12 months • At those evaluations, the patients’ blood will be tested and another complete set of ocular examinations will be performedEligibility/ExclusionNot availableParticipating CentersNot availableResultsPending

StudyAn Evaluation Of Efficacy And Safety of Posterior Juxtascleral Injections of Anecortave Acetate 15mg Versus Visudyne in Patients with Subfoveal Exudative Age- Related Macular Degeneration (AMD) Eligible for Initial Treatment with Photodynamic Therapy (PDT) Using VisudyneSponsorAlcon Research; South Freeway Drive; Ft. Worth, TX 817-615-2583Study PurposeTo demonstrate that Anecortave Acetate is non-inferior after 12 months of treatment to PDT with Visudyne in patients eligible for initial PDT treatmentStudy Design• Patients randomized to the Anecortave Acetate treatment group will also receive

at the same visit and prior to the posterior juxtascleral inject a sham PDT treatment• Patients randomized to PDT with Visudyne will also receive at the same visit following the PDT treatment a sham posterior juxtascleral injection Eligibility/ExclusionEligibility: • Lesion area less than or equal to 5400 microns in GLD; 50% or more of the total lesion is CNV; the classic component of the total CNV must be at least 50% of the total lesionExclusion:• Ophthalmic disease in the study eye that would compromise visual acuity • Previous PDT treatment, previous laser photocoagulation is allowed if performed 30 days before enrollment • Patient has scleral buckle in the study eye • Patient is on anticoagulant therapy, with the exception of aspirin and anti-platelet therapy ResultsThere was no statistical difference between the anecortave acetate treatment and the PDT treatment outcomes regarding the primary endpoint of loss of fewer than 3 lines of visual acuity. Forty-five percent of the patients in the anecortave acetate group had less than a 3-line loss of visual acuity, and 49% of patients had less than a 3-line loss of visual acuity in the PDT group. The statistical endpoint, however, was not reached regarding non-inferiority of anecortave acetate compared with PDT. Both groups had approximately the same number of adverse ocular and systemic events.

StudyA Phase II Multicenter Trial to Establish the Safety and Pharmacokinetic Profile of Intravitreal Anti-VEGF Pegylated Aptamer (EYE001) in Age-Related Macular Degeneration Undergoing Photodynamic TherapySponsorEyetech Pharmaceuticals, Inc.; 666 Fifth Avenue; 35th floor; New York, NY 10103; 212-582-8376Study Purpose• The primary objective of this study will be to evaluate the safety of 3 repeat doses of EYEO01 administered after photodynamic therapy. • Secondary objectives include the evaluation of the pharmacokinetic profile, preliminary efficacy, and patient’s immune response to EYEO01 when given as intravitreal injections (3mg/eye) once every 28 days for 3 doses in patients with the neovascular form of AMD.Study Design• This is a multi-center, open-label, repeat dose phase 18 study of 3mg/eye of EYEO01 following PDT, inpatients with choroidal subfoveal neovascular AMD with a visual acuity worse than 20/100 in the study eye or equal to 20/400 in the fellow eye. • If 3 or more patients experience Dose- Limiting Toxicity (DLTs), the dose will be reduced to 2mg and 1 mg, if necessary in a further 10 patients. • Patient accrual into the trial is expected to be completed within 2 to 3 months. Four to 10 sites in the U.S. will provide 1 to 8 patients per site.Eligibility/Exclusion• Age-Related Macular Degeneration with subfoveal sub-retinal neovascularization. • Visual acuity less than or equal to 20/80. Results• 87.5% of patients who received the anti-VEGF drug alone showed stable or improved vision 3 months after treatment.• Vision improved by 3 or more lines in 25% of eyes that received this drug alone. • However when combined with photodynamic therapy, many more eyes (60% ) gained 3 or more lines of vision.

This study has reported short term (3 month) results, which look encouraging. Further clinical trials are necessary to demonstrate the efficacy and long-term safety of anti-VEGF therapy for wet macular degeneration. No definitive conclusions regarding the

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efficacy of the drug can be deduced from this study because of the absence of a control group, small sample size, and short follow-up period. Phase II/III trials using this drug are presently underway to evaluate this potential treatment in more than a 1000 patients in more than 100 centers worldwide.

StudyA Phase II/III Randomized, Double Masked, Controlled, Dose Ranging Multi Center Comparative Trial , in Parallel Groups, to Establish the Safety and Efficacy of Intravitreal Injections of EYE001 (Anti-VEGF Pegylated Aptamer) Given Every 6 wks to 54 wks, in Patients with Exudative Age-Related Macular Degeneration (AMD)SponsorEyetech Pharmaceuticals, Inc.; 666 Fifth Avenue; 35th floor; New York, NY 10103; 212-582-8376StatusOngoingPatient Accrual DateTBAStudy CenterEyetech Pharmaceuticals, Inc.Study ChairmanNot availableStudy PurposeTo establish a safe and effective dose of EYEOO1. Patients will be randomized to intravitreal injections of either EYEO01 or placebo every 6 weeks Study DesignThe study is a randomized, double-masked, controlled, dose-ranging, multi-center comparative trialNumber of Patients Enrolled540Follow Up54 weeks Eligibility/ExclusionNot availableParticipating CentersNot availableResultsPending

StudyA Phase I/II, Multicenter, Dose Escalation, Controlled Study of the Safety, Tolerability, Pharmacokinetics and Activity of Multiple Dose Intravitreal Injections of rhuFab V2 in Subjects with Neovascular AMD (FVF2128g study)SponsorGenentech, Inc. 888-662-6728Study Purpose• To investigate the safety and tolerability of recombinant humanized anti-VEGF monoclonal antibody fragment (RhuFab V2) administered as multiple, intravitreal injectionsStudy Design• Phase I/II multi-center. Dose excalation controlled studyEligibility/Exclusion• Inclusion: active subfoveal CNV, visual acuity in the study eye of 20/40 to 20/400 and better or equal to 20/800 in the fellow eye, age >50 years old; • Exclusion: more than 3 prior treatments with Visudyne in the study eye within 12 months, lesions larger than 9MPS disc areas, cataract surgery within the previous 30 days, current or recent use of oral or parental anticoagulants or anti-platelets other than aspiring, ticlopididne, clopidogrel and/or nosteroidal anti-inflammatory agentsResultsPending

StudyA Randomized, Placebo Controlled, Double Masked, Multi Center Phase III Study of the Effect of Visudyne Therapy

in Occult with No Classic Subfoveal Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (VIO)SponsorQLT Inc/Novartis Ophthalmics, IncStudy PurposeTo demonstrate that Visudyne therapy in patients who have occult with no classic subfoveal CNV lesions will, with an acceptable safety profile significantly reduce the risk of vision loss compared with placebo Study Design• A randomized, placebo-controlled, double-masked, multi-center, Phase III study• Patients stratified by study center and randomized to Visudyne therapy or placebo in a 2:1 ratioEligibility/ExclusionEligible:• Must have occult with no classic subfoveal CNV secondary to AMD BCVA between 73 and 34 letters (approx. Snellen equivalent of 20/40 to 20/200) • GLD of entire lesions must no exceed 5400 microns • Must not have a CNV lesions size that is >4 MPS disc areas, associated with a BCVA of >65 letters (approx. Snellen Equivalent of 20/50 or better) • Presumed recent progression of occult CNV within the preceding 3 months before randomization to treatment Exclusion: • Any additional ocular disease that may compromise visual acuity in the study eye.• No previous PDT, m or other local treatment in study eye ResultsPending

StudyPhotodynamic Therapy (Visudyne) Early Re-Treatment For Subfoveal Choroidal Neovascularization (VER) StudySponsorQLT Inc/Novartis Ophthalmics, Inc.Study PurposeTo determine whether early retreatment with Visudyne therapy in patients with predominantly classic subfoveal choroidal neovascularization secondary to AMD will reduce the risk of vision loss Study DesignMulti-center, randomized, parallel group, double-masked, controlled phase III, 2 year study using standard treatment and an experimental retreatment schedule (as often as every 1.5 months retreatment interval during the first 6 months)Eligibility/ExclusionEligible:• Subfoveal, predominantly classic CNV (area of classic> 50% area of entire lesion) I GLD not to exceed 5400 microns BCVA between 20/40 and 20/200 Exclusion: • Any additional ocular disease that may compromise visual acuity in the study eye• No previous PDT, or other local treatment in study eye ResultsResults from the Phase III early retreatment (VER) study with Visudyne showed that the early retreatment regimen did not result in a significant improvement in vision outcomes over the standard retreatment regimen every 3 months. The data did reconfirm the vision benefits and safety shown in the original TAP or Treatment in Age-related macular degeneration with Photodynamic therapy study.

StudyA Phase III, Multicenter, Randomized, Double-Masked, Active Treatment-Controlled Study of the Efficacy and Safety of rhuFab V2 (Ranibizumab) Compared with Verteporfin (Visudyne) Photodynamic Therapy in Subjects with Predominantly Classic Subfoveal Neovascular AMD (FVF2587G Study - ANCHOR)SponsorGenentech, Inc. 888-662-6728StatusActively Enrolling

Study CenterGenentech, Inc., 1 DNA way, South San Francisco, CA 94080-4990Study ChairmanRobert Y. Kim, MD, Genentech, Inc.Study Purpose• To investigate the efficacy, safety, and tolerability of monthly intravitreal injections of rhuFab V2 compared with verteporfin PDTStudy Design• Phase III, multicenter, randomized pivotal study.• 1:1:1 Randomization : Sham injection: 300 micrograms rhuFab V2: 500 micrograms rhuFab V2 by 24 monthly intravitreal injections• Sham injection group to receive PDT, and rhuFab injection groups to receive sham PDT q3 months. • All patients to receive ETDRS visual acuity testing, ophthalmological examination, and adverse event assessment at each study visit, with fundus photography, fluorescein angiography, OCT, visual function questionnaires and health surveys, and pharmacokinetic evaluations at selected visitsNumber of Patients EnrolledTBA. Target enrollment = 426Follow UpOngoingEligibility/Exclusion• Inclusion: primary or recurrent subfoveal CNV lesions due to AMD eligible for PDT with Verteporfin, >50% classic CNV, lesion GLD <5400 microns; visual acuity in the study eye of 20/40 to 20/320, age >50 years old • Exclusion: prior PDT, TTT, XRT, or other experimental CNV treatment. Previous intravitreal drug delivery. Prior vitrectomy. Subfoveal atrophy or fibrosis. Other cause of CNV. RPE tear. Selected subfoveal hemorrhage (1 disk area or 50% of lesion)Participating CentersMulticenter (100 sites)ResultsPending

StudyLimited Macular Translocation StudySponsorPilot study - self fundedStudy PurposeTo determine whether translocation plus standard laser is better than PDT or observation aloneStudy DesignRandomized, prospective, multi center study. Patients randomized: • Translocation versus PDT -100 patients• Translocation versus observation - 100 patients. • Vision <20/40 to >20/800. • Subfoveal, choroidal neovascularization (classic, occult, both) • CNV secondary to Age-Related Macular Degeneration • Inferior border of lesion 1000um or less from foveal center • Ages greater than 49 years. • > Light perception vision in fellow eye. ResultsPending

StudyA Phase II, Multicenter, Randomized, Double-Masked, Placebo Controlled Study of the Matrix Metalloproteinase Inhibitor AG3340 in Patients with Subfoveal Choroidal Neovascularization Associated with Age- Related Macular DegenerationSponsorAgouron Pharmaceuticals, Inc.Study Purpose• This phase II clinical trial will assess the safety and efficacy of AG3340 (prinomastat) in approx. 200 patients aged 50 years and older affected with the neovascular form of Age-Related Macular Degeneration (AMD)• To determine the optimal dose and regimen to use in subsequent phase III trials.Study DesignA phase II, randomized, double-masked, placebo-controlled, multicenter study.Eligibility/Exclusion• Patients age 50 years and older with new

or recurrent choroidal neovascular lesions associated with AMD, subfoveal, or mostly classic. • Visual acuity score by ETDRS chart> 39 (Snellen equivalent of 20/160). • Patients must not have other serious ocular diseases or conditions present. • Patients must not currently be using systemic steroids or other drugs which may affect the macula. • No unstable or severe concurrent medical conditions or active uncontrolled infections present. ResultsPending

StudyWomen’s Health Initiative Sight Examination Study (WHI-SE)SponsorUniversity of MichiganStatusRecruitment endedPatient Accrual Date5/2000-12/2001Study CenterWomen’s Health Initiative Sight Examination Coordination Center; 611 Church St, Ann Arbor, MI 48104; 734-615-8190Study ChairmanDr. Mary Haan; University of Michigan, 734-615-8190Study Purpose• To evaluate whether exogenous estrogen use through hormone replacement therapy can prevent incident cases of AMD, or slow the progression of this disease in women who already have AMD. To evaluate if exogenous estrogen reduces the risk of late forms of age related maculopathy, including geographic atrophy, retinal pigment epithelial detachments and choroidal neovascular membranes Study Design• The WHI-SE study is an 8 year project and will involve 19 clinical centers across the country to obtain eye exams on approx. 5,000 women who are 65 years of age and older enrolled in the Women’s Health Initiative’s main clinical trial of hormone replacement therapy • The participants in this study are a component of the larger clinical trial funded by NIH, the Women’s Health InitiativeNumber of Patients Enrolled4688 people participated in a baseline examination done between 1998 - 2002Follow Up• The cohort may be reexamined if new funding is received. • The cohort is being reexamined (10 year follow-up), with approx. 3,000 participants expected to be seen • The 10-year examinations conclude on May 31, 2000Eligibility/Exclusion• Only women who were enrolled in the WH1 were eligible to participate in WHI-SE.• Women in the study received Premarin or Prempro, forms of estrogen, or a placebo sugar pill. • In addition, women asked to: • Undergo a vision exam when enrolling in WHI-SE and again in 3-4 years to check visual acuity and to photograph the retina (require dilation) • Complete two questionnaires on vision, history of eye disease and medication use • Complete brief questionnaire on vision each year between the two eye exams • Have blood collected for studies on the effect of diet and cardiovascular disease on macular degenerationParticipating Centers15-20ResultsCurrently pending funding to do follow-up exams.

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StudyPhotodynamic Therapy (Visudyne) in Minimally Classic Subretinal Neovascularization (VIM) StudySponsorQLT Inc/Novartis Ophthalmics, IncStudy Purpose• To compare potential treatment benefit and safety of verteporfin (Visudyne, Novartis AG) therapy and placebo for minimally classic subfoveal CNV due to AMD using a standard light dose and one delivered with reduced fluence rateStudy Design• Patients (>50 years of age) with minimally classic lesions of <6 MPS disc areas (DA) (1 MPS DA=2.54mm2) in this double-masked study were randomized (1:1:1) to one of three treatment groups: • (1) Verteporfin therapy with reduced light fluence rate (300 mW/cm2) for 83 seconds (25 J/cm2); • (2) Verteporfin therapy with standard light fluence rate (600 mW/cm2) for 83 seconds (50 J/cm2); • (3) Placebo; half with reduced and half with standard light fluence rate• Fluorescein and ICG angiography and best-corrected visual acuity were assessed 1 week after treatment in 10 patients from each group. • All patients were assessed at 6 weeks, 3 months, and 6 months after initial visit• Changes in total area of the lesion and individual components were assessed through month 3 and change in visual acuity from baseline was assessed at all visits • Safety was evaluated by adverse events, visual acuity, fluorescein angiograms, and color fundus photographsEligibility/Exclusion• Minimally Classic CNV lesions secondary to AMD• Baseline VA between 20/40 and 20/200 • Lesion size up to 4 DA Results• At baseline, main demographic variables did not appear different among treatment groups: overall, mean age 78, 64% women, mean study eye visual acuity (approximate Snellen equivalent) 20/100-1• At baseline, for the reduced fluorescence, standard fluorescence, and placebo groups, respectively• Mean total lesion area was 3.65, 3.91, 3.25 MPS DA• Mean area of occult CNV 3.28, 3.36, 2.89 MPS DA; and classic CNV 0.26, 0.41, 0.29 MPS DA • Six-month vision and fluorescein angiographic outcomes will be reportedResultsPending

StudyAge-Related Eye Disease StudySponsorEye 92-EI-0250Study Purpose• To assess the clinical course, prognosis, and risk factors of Age-Related Macular Degeneration (AMD) and cataract• To evaluate, in randomized clinical trials, the effects of pharmacologic doses of (1) antioxidants and zinc on the progression of AMD and (2) antioxidants on the development and progression of lens opacitiesStudy Design• The Age-Related Eye Disease Study (AREDS) is a major research program to improve our understanding of the predisposing factors, clinical course, and prognostic factors of AMD and cataract. • Eligible patients are randomized to treatment with placebo, antioxidants, zinc, or antioxidants plus zinc, and are followed for a minimum of 5 yearsEligibility/Exclusion• Men and women between the ages of 55 and 80 years whose macular status ranges from no evidence of AMD in either eye to relatively severe disease with vision loss in one eye but good vision in the fellow eye

(20/30 or better) are eligible for the study provided that their ocular media are clear enough to allow good fundus photographyResults• AREDS researchers found that people at high risk of developing advanced stages of AMD lowered their risk by about 25 percent when treated with a high-dose combination of vitamin C, vitamin E, beta-carotene, and zinc • In the same high risk group -- which includes people with intermediate AMD, or advanced AMD in one eye but not the other eye -- the nutrients reduced the risk of vision loss caused by advanced AMD by about 19 percent• For those study participants who had either no AMD or early AMD, the supplements did not provide an apparent benefit.• In the cataract portion of the study, researchers discovered that the same nutrients had no significant effect on the development or progression of age-related cataractResultsPending

StudyRandomized Trial of Beta-Carotene and Macular DegenerationSponsorNEIStatusOngoing; randomized treatment complete; collection of medical reports for reported cases of AMD is continuingPatient Accrual DateRecruitment for the Physicians Health Study began in 4/82 and was completed in 12/84. The randomized trial of beta-carotene and macular degeneration began evaluating from that study in 1990Study CenterCharles Hennekens, MD; Brigham & Women’s Hospital; 900 Commonwealth Ave, E; Brookline, MA 02215; 617-732-4965Study ChairmanWilliam Christen, MD / 617-278-0795Study Purpose• To determine whether 50mg of beta carotene taken every other day reduces the risk of developing Age-Related Macular Degeneration (AMD) among male US physicians who were aged 40-84 in 1982 • To investigate the possible relationship of AMD with other antioxidants including selenium and vitamins A, C, and E • To identify potential risk factors for development of AMDM • Possible risk factors include height, systemic hypertension, cardiovascular disease, blood cholesterol, cigarette smoking, iris and skin color, sunlight exposure, body mass index, diabetes, and alcohol intakeStudy Design• It is an ongoing, randomized placebo-controlled trial of aspirin in the prevention of cardiovascular mortality and of beta-carotene in the prevention of cancer • Following randomization, each of the 22,071 patients enrolled was assigned to one of four groups to take either aspirin or its placebo and beta-carotene or its placebo • Follow up questionnaires are sent 6 and 12 months after randomization and every 21 months thereafterNumber of Patients Enrolled22,071Follow UpMore than 12 yearsEligibility/Exclusion• The study population consists of 22,071 male US physicians who were aged 40-84 years in 1982. • The subjects have no history of myocardial infarction, cancer, kidney disease, renal disease, or any other contraindication to the use of aspirin or beta-carotene. Including regular use of corticosteroidsParticipating CentersFor information call the chairman’s officeResults532 cases of ARM confirmed (261 in beta-carotene grp & 271 in placebo). Results suggest that 12 years of beta-carotene supplementation has no appreciable effect on ARM during the treatment period. (ARVO 2004 program #2111)

StudyTranspupillary Thermotherapy for Choroidal Neovascularization Clinical Trial (TTT4CNV)SponsorIridex, Inc.; 1212 Terra Bella Avenue; Mountain View, CA 94043; 650-962-8840Study Purpose• To determine whether TTT is a safe and effective treatment for occult subfoveal choroidal neovascularization in AMDStudy Design• Prospective randomized multicentered clinical trial. 112 patients are observed, 224 treated with TTT Outcome variable: best corrected visual acuity pre and post treatment, exudation measured by stereo fundus photos and FAEligibility/Exclusion• Inclusion: AMD, 50 yrs or older, visual acuity: 20/50 - 20/400 ETDRS, occult CNVM • Exclusion: prior retinal laser/surgery, ocular surgery within 3 months, medication toxic to retina, lens or optic nerve, glaucoma • Angiographic eligibility: total lesions <3000mm (2DD) in diameter, CNV underlying or surrounding center of macula, occult CNV is required: late leakage or fibrovascular PED, subretinal fluid or exudate is required; if present, classic CNV if <10% of the lesion; if present, serous PED must be <25% of the lesion; if present, subretinal hemorrhage must be <50% of the lesion; if present, subretinal fibrosis <25% of the lesion, cannot have chorioretinal anastomosis, cannot have geographic atrophy >0.5 DA within 500mm of the foveal centerResultsResults confirmed that a subgroup of patients, who were enrolled into the study with baseline visual acuity of 20/100 or worse, benefited from TTT treatment. Within the TTT4CNV Clinical Trial, about 41% of the patients enrolled had baseline vision of 20/100 or worse. (Baseline vision means that was the vision the patient had when he/she entered the study). Specifically, at 12 months following treatment 23% of TTT treated eyes in this subgroup improved vision by one or more lines and 14% of TTT treated eyes improved vision by three or more lines. None of the eyes in the placebo treated control group showed any improvement of vision. After 18 months, the patients in this subgroup who did lose vision (as one would expect over time), did better than the placebo treated eyes. Specifically, TTT treated eyes on average lost 2 lines of visual acuity while placebo treated eyes lost 4 lines. These findings were statistically significant.ResultsPending

StudyDry Age-Related Macular Degeneration (AMD) TrialSponsorApheresis Technologies, Inc.Study PurposeTo determine whether patients with Dry AMD experience improvement in their vision after apheresis treatmentsStudy Design• Multi-center study, enrolling a total of 180 patients to be randomized into 2 groups: 120 in the treatment group and 60 in the placebo control group • Patients will receive 8 treatments (actual or placebo) and the results between the groups will be compared during follow up visits• The treatments are provided at no cost to qualifying patients • The quality of life questionnaires VFQ-25 and AMD will be utilized to determine how much the patients’ life is affected by their visual problemsEligibility/Exclusion• Between the ages of 50 and 85 years of age and weigh greater than 110 lbs. • Have some vision loss in at least one eye due to macular degeneration, with no other major eye diseases. • Patient must be in reasonably good health with a visual acuity between 20/32 and 20/125 and have more than 10 large soft drusen.ResultsPending

StudyComplications of Age-Related Macular Degeneration Prevention Trial (CAPT)SponsorNational Eye Institute/NIHStatusRecruitment CompletedPatient Accrual Date5/1/99.Study CenterMaureen Maguire, PhD; Director CAPT Coordinating Center; 3535 Market Street, Suite 700; Philadelphia, PA 19104. 215-615-1531Study ChairmanStuart Fine, MD; Scheie Eye Institute / 215-662-8142Study Purpose• To determine whether application of low intensity laser treatment of eyes with drusen in the macula can prevent later complications of Age-Related Macular Degeneration and thereby preserve visual functionStudy Design• The CAPT is a multi-center, prospective, randomized clinical trial designed to assess the safety and effectiveness of low intensity laser treatment in preventing vision loss among patients with large drusen in both eyes • Eligible patients will have one eye randomly assigned to laser treatment performed by CAPT-certified ophthalmologists. The other eye is not treated. Both eyes are observed carefully for any changes for a period of five years • The effectiveness of the treatment will be assessed using the following criteria: • Change in visual acuity (primary outcome measure of the study), incidence of complications of AMD such as neovascularization, serous detachment of the pigment epithelium and geographic atrophy, changes in contrast threshold and critical print size for reading • QOL assessments for patients, using the VFQ 25 will be conducted at the time of enrollment and at 5 yearsNumber of Patients Enrolled1052Follow UpMinimum of 5 yearsEligibility/Exclusion• Patients eligible for CAPT can be either male or female and meet the following criteria: • Age at least 50 years old, vision in each eye must measure 20/40 or better, • At least 10 large Drusen in each eye, available for follow-up exams for 5 years after enrollmentParticipating Centers22 centersResultsPending

StudyRandomized Trials of Vitamin Supplements and Eye Disease SponsorNational Eye InstituteStatusOngoing. Comments: Both studies ongoing.Patient Accrual DateNo longer recruiting. Comments: Women’s Health Study: Recruitment began in November 1992 and was completed in July 1995. Women’s Antioxidant Cardiovascular Study: Recruitment began in August 1993 and was completed in October 1996.Study CenterJulie E. Buring Sc.D.Charles H. Hennekens, M.D. Brigham and Women’s Hospital 900 Commonwealth Avenue East Boston, MA 02215-1204 Study ChairmanWilliam G. Christen, Ph.D. Brigham and Women’s Hospital 900 Commonwealth Avenue East Boston, MA 02215-1204

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Study Purpose • To determine whether vitamin E supplementation reduces the risk of cataract and age-related macular degeneration (AMD) in women. • To determine whether vitamin C supplementation reduces the risk of cataract and AMD in women. • To determine whether beta-carotene supplementation reduces the risk of cataract and AMD in women. • To determine whether alternate day, low-dose aspirin reduces the risk of cataract and AMD in women. • To identify potential risk factors for cataract and AMD including cigarette smoking, alcohol intake, blood pressure, blood cholesterol, cardiovascular disease, height, body mass index, and diabetes. Study DesignThese randomized, double-masked, placebo-controlled trials will test the hypotheses that supplementation with antioxidant vitamins and with low-dose aspirin reduces the risk of age-related cataract and AMD. The study populations are the Women’s Health Study (WHS) and the Women’s Antioxidant Cardiovascular Study (WACS). The WHS is a randomized, double-masked, placebo-controlled trial using a 2x2 factorial design to test low-dose aspirin (100 mg on alternate days) and vitamin E (600 IU on alternate days) in the primary prevention of cardiovascular disease (CVD) and cancer. It is being conducted among 39,876 apparently healthy female health professionals age 45 years and older. The WACS is a randomized, double-masked, placebo-controlled secondary prevention trial using a 2x2x2x2 factorial design to test antioxidant vitamins (vitamins E [600 IU on alternate days] and C [500 mg daily], beta carotene [50 mg on alternate days]), and a combination of folate (800 mg daily), vitamin B6 (25 mg daily), and vitamin B12 (1 mg daily) among women who are at high risk for CVD morbidity and mortality. It is being conducted among 8,171 female health professionals, ages 40 years or older, who either have preexisting CVD or have at least three coronary risk factors and therefore are at high risk for the development of CVD. Number of Patients EnrolledWomen’s Health Study: 39,876Women’s Antioxidant Cardiovascular Study: 8,171Follow UpNot availableEligibility/ExclusionWomen’s Health Study:A participant must have met all of the following criteria: (a) female;(b) aged 45 years or older;(c) postmenopausal or with no intention of becoming pregnant;(d) no reported personal history of cardiovascular disease, cancer (other than non-melanoma skin cancer), gout, peptic ulcer, chronic renal or liver disease, or other serious illness precluding participation;(e) no reported history of serious side effects to the study treatments;(f) not currently taking aspirin, aspirin containing medication, or nonsteroidal anti-inflammatory drugs (NSAIDs) more than 1 day per week or, if so doing, willing to forego use of these medications;(g) not currently taking individual supplements of vitamin E or beta carotene more than 1 day per week;(h) not currently taking anticoagulants or corticosteroids.

Women’s Antioxidant Cardiovascular Study: Potentially eligible female health professionals for WACS were identified from the pool of respondents to the Women’s Health Study initial mailing and must have met the following criteria: (a) female;(b) date of birth before January 1, 1955; (c) a reported history of myocardial infarction (MI), stroke (CVA), angina pectoris (AP), coronary artery bypass grafting (CABG), percutaneous transluminal angioplasty (PCTA), transient ischemic attack (TIA), carotid endarterectomy (CEA), or peripheral artery surgery (PAS);(d) no history of cancer (except non-melanoma skin cancer) within the past 10 years and no active liver disease or cirrhosis;(e) pregnancy physiologically impossible due

to menopause (natural or surgical) or tubal ligation, or the participant does not intend to become pregnant in the future as indicated on the initial WHS questionnaire;(f) no current use of a vitamin K-depleting anticoagulant agent (e.g., Coumadin). Individuals taking aspirin or other NSAIDs were not excluded.Participating CentersNot available ResultsPending

StudyAnecortave Acetate Risk Reduction Trial (AART) SponsorAlcon Research, Ltd. StatusEnrollment is ongoing Study PurposeDemonstrate that anecortave acetate (15 mg or 30 mg) is safe and effective in arresting the progression of nonexudative AMD in patients who are at risk for progressing to exudative AMD Study DesignPhase 3, double-masked, randomized, parallel group, no-treatment (sham administration), safety/efficacy study Eligibility/ExclusionPatients at least 50 years of age, any race and either sex, with a clinical diagnosis of exudative AMD in the nonstudy eye, and at least 5 or more intermediate (>63 microns) or larger soft drusen within 3000 microns of the foveal center and/or confluent drusen within 3000 microns of the foveal center, and hyperpigmentation within 3000 microns of the foveal center in the study eye. ResultsPending

StudySIRNA 0401SponsorSirna Therapeutics, Inc., Boulder, CO StatusEnrolling patients Study PurposeAssess the safety and tolerability of Sirna-027; assess the presence of Sirna-027 in plasma; determine the range of doses for the phase 2 clinical trial; and assess biological and anatomical changes in the retina.Study DesignPhase 1, open-label, dose-escalation -4 to 6 dose cohorts, 1 intravitreal injection Number of Patients12¬-30 Participating Centers4Eligibility/Exclusion 50 years of age or older; subfoveal to AMD, classic and/or occult; no other causes of CNV; total lesion size 12 MPS disc area; subretinal hemorrhage < 50% of lesion; subfoveal scaring < 50% of lesion; lesion thickness 250 m ; inter occular pressure 25 mm Hg; visual acuity 20/100 to 20/800 ETDRS; fellow eye visual acuity not worse than 20/800 ETDRS ResultsPending

StudyVisudyne with Intravitreal Triamcinolone Acetonide (VisTA) TrialSponsorLuEsther T. Mertz Retinal Research Center StatusRecruiting Study PurposeEvaluate the effect of photodynamic therapy in conjunction with intravitreous triamcinolone acetonide in subjects with occult or minimally classic subfoveal CNV secondary to AMD

Study Design Randomization 1:1:1, PDT and 0 mg of triamcinolone/PDT and 1 mg of triamcinolone/PDT and 4 mg of triamcinolone Eligibility/ExclusionInclusion Criteria: 50 years or older, occult or minimally classic subfoveal CNV, presence of blood associated with the lesion, vision loss or growth of lesion objectively recorded within preceding 3 months, baseline VA score between 20/40¬-20/400, lesion 5400 microns Exclusion Criteria: Predominantly classic CNV, additional eye disease, CNV not involving geometric center of FAZ, inability to be photographed; fluorescein allergy; photophobia; lens opacities expected to progress during study; previous treatment for CNV, other than confluent laser photocoagulation (eg, PDT, submacular surgery, radiotherapy, macular grid); participation in another clinical trial; IOP >21 mm Hg on or off meds; prior treatment with another antiangiogenic compound within 6 months of screening; inability to comply with all study-related procedures; concomitant therapy with systemic or topical corticosteroids or NSAIDS (chronic concomitant therapy is defined as multiple doses taken daily for 3 or more consecutive days at any time during the course of the 12-month study); a low dose of ASA (up to 100 mg PO qd) taken for prophylaxis of MI and/or stroke is permitted during the study; concomitant coumadin therapy Number of Patients to be Enrolled120 ResultsPending

StudyPreservative-free Triamcinolone Acetonide (PFTA) SponsorQLT Inc., National Eye Institute StatusEnrolling patients Study PurposeInvestigate the long-term safety and potential efficacy of PFTA in patients with wet AMD (all types) undergoing Visudyne therapy Study DesignPhase 3, randomized, prospective Number of Patients300 Eligibility/ExclusionInclusion Criteria: Age greater than or equal to 50 years; in the study eye, diagnosis of AMD defined by the presence of drusen larger than 63 micro m; visual acuity of 20/40 - 20/200 (73-34 letter score) as measured on an ETDRS chart; in the study eye, the presence of choroidal neovascularization under the fovea Exclusion Criteria: Choroidal neovascularization, in the study eye, associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc.; presence of geographic atrophy under the fovea in the study eye; the presence of a chorio-retinal anastomosis; presence of fibrosis, hemorrhage, pigment epithelial detachments, and other hypofluorescent lesions obscuring greater than 50% of the CNV lesionResultsPending

StudyCombretastatin A-4 Phosphate (CA4P) in Patients with Neovascular AMD (FBO-206) SponsorOXiGENE StatusEnrolling patients Study PurposeAssess the safety and tolerability of combretastatin administered intravenously in patients with all forms of neovascular AMD (classic and occult) Study DesignPhase 1/2, open label, safety and tolerability study. The study cycle consists of a prestudy evaluation period (2¬4 weeks), a 22-day treatment period, and an 8-week post-treatment evaluation period

Number of Patients15¬-20 Participating Centers1Eligibility/ExclusionAge 50 or older, study eye BCVA of 20/40 or less, fellow eye better or equal to 20/800 ETDRS, no history of previous subfoveal thermal laser therapy

StudyANCHOR SponsorGenentech StatusOngoing Study PurposeEvaluate the safety and efficacy of ranibizumab (Lucentis) compared with verteporfin photodynamic therapy in preventing vision loss associated with AMD Study DesignPhase 3, randomized, double-blind, active control, parallel assignment. Three treatment arms: PDT and sham injection, sham PDT and Lucentis dose A, sham PDT and Lucentis dose B Eligibility/Exclusion50 or older; predominantly classic; subfoveal CNV due to AMD; study eye BCVA equal to or worse than 20/40, but no worse than 20/320; lesion eligible for PDT per labeling; no prior laser treatment involving the center of the fovea; no prior PDT; no prior experimental treatments for AMD Number of Patients426 Participating Centers100

StudyEvaluation of Safety and Efficacy of Anecortave Acetate vs. Placebo in Patients with Subfoveal CNV due to Exudative AMD (C-02-29) SponsorAlcon Research, Ltd. StatusEnrollment is ongoing in South America Study PurposeDemonstrate that anecortave acetate 15 mg is superior to placebo in maintenance of visual acuity Study DesignPhase 3, double-masked, randomized, parallel group, placebo-control, safety and efficacy study Inclusion/Exclusion CriteriaPatients at least 50 years of age, any race and either sex with minimally classic and occult exudative AMD with subfoveal choroidal neovascularizationResultsPending

StudyEvaluation and Tolerability of 4-dose Levels of Cand5 Administered by Single Intravitreal Injection in Patients with Wet AMD SponsorAcuity Pharmaceuticals StatusRecruiting Study PurposeEvaluate 4-dose levels of the small RNA interference therapeutic agent Cand5 in subjects with exudative AMD Study DesignOpen label study. One intravitreal injection; 4-dose levels Eligibility/ExclusionInclusion Criteria: Male or female patients 50 years of age or older; subfoveal CNV, classic or occult; total lesion size <12 total disc areas, of which at least 50% is active CNV; subretinal hemorrhage (if any)-no more than 50% of the lesion; minimally classic or occult lesion must have hemorrhage and/or lipid and or documented loss of 3 or more lines of vision during the previous 3 months; vision 20/50 to 20/320, with better acuity in the fellow eye; IOP 22 mm Hg

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Exclusion Criteria: Concomitant ocular disease, 3 or more prior PDT treatments, thermal laser within the previous 2 weeks, subfoveal scarring or atrophy, h/o abdominal aortic aneurysm, stroke within previous 12 months, diabetes or use of oral hypoglycemics or insulin, h/o peripheral vascular disease, allergy to fluorescein Number of Patients12 Participating Centers2

StudyPIER SponsorGenentech Study PurposeEvaluate safety and efficacy of Lucentis in patients with wet AMD Study DesignLucentis phase 3b, randomized, double-masked, sham injection-controlled trial. Patients will be assigned to 1 of the following treatment arms: Lucentis dose A, Lucentis dose B, sham injection Eligibility/ExclusionInclusion Criteria: Men and women age 50 and older; active primary or recurrent wet AMD involving the center of the fovea (“subfoveal”); best corrected visual acuity of equal to or worse than 20/40, but no worse than 20/320 in the study eye; classic or occult forms of CNV due to AMD and not another cause Exclusion Criteria: Previous verteporfin photodynamic therapy, external beam radiation therapy, transpupillary thermotherapy or intravitreal drug delivery in the study eye, participation in any clinical trial involving antiangiogenic drugs (ie, ranibizumab, pegaptanib, anecortave acetate, protein kinase C inhibitors, etc.) or any other clinical trial within the last month Number of patients180 Participating Centers3

StudyThe Effect of Pegaptanib Sodium on Foveal Thickening in Patients with Exudative Subfoveal AMD SponsorEyetech Pharmaceuticals StatusRecruiting Study PurposeCompare the safety of Macugen with that of sham treatment and to assess Macugen’s effect on foveal thickening Study DesignPhase 2 prospective, randomized, double-masked, sham-controlled, dose-ranging, multicenter trial. First 3 injections: randomization, 1:1:1, 0.3 mg/1 mg/sham; subjects in sham treatment group subsequently rerandomized to 0.3 mg or 1 mg Eligibility/ExclusionInclusion Criteria: CNV with total lesion size of 12 DA or less of which at least 50% is active CNV; subretinal hemorrhage not more than 50% of total lesion size; no subfoveal scarring, atrophy, fibrosis, or blood over fovea; no more than 25% of the total lesion made up of scarring or atrophy, for minimally classic or occult lesions: >=3 line vision loss during the previous 12 week and/or subretinal hemorrhage (not more than 50% of the total lesion size); VA approximately 20/40-20/320 in study eye and 20/800 or better in fellow eye; foveal thickness on OCT >=300 mm; classic CVN for which PDT can be deferred for 54 weeks Exclusion Criteria: Previous subfoveal thermal laser or PDT laser; intraocular surgery, including extrafoveal/juxtafoveal laser within the previous 3 months; h/o PPV or SB; pigment epithelial tears or rips; any other conditions that may be causing CNV, diabetic

retinopathy; h/o stroke within 12 months of study entry; h/o peripheral vascular disease or severe cardiac disease; significant hematologic, renal, or hepatic diseaseResultsPending

StudySqualamine SponsorGenaera Corporation StatusEnrolling patients Study PurposeEvaluate the safety and efficacy of intravenously administered squalamine as a first-line therapy for wet AMD Study DesignPhase 2, randomized, double-masked, controlled study; 2 dose levels once weekly for 4 weeks, followed by maintenance doses once every 4 weeks through week 48. At the end of therapy, each patient will be followed for an additional year Number of Patients100 Participating CentersMulticenter

StudyNoncomparative Protocol for Use of Intravitreous Macugen Injections in Patients with AMD SponsorEyetech Pharmaceuticals StatusRecruiting Study PurposeProvide Macugen to patients who have subfoveal CNV secondary to AMD and who are unable to participate in any other clinical studies of Macugen for AMD, until such time as the patient’s lesion is considered to have resolved or stabilized or Macugen becomes commercially available Study DesignOpen label study, 0.3 mg intravitreous injection every 6 weeks Eligibility/ExclusionInclusion Criteria: CNV with total lesion size of 12 DA or less of which at least 50% is active CNV; subretinal hemorrhage not more than 50% of the total lesion size; no subfoveal scarring, atrophy, or fibrosis; no more than 25% of the total lesion is scarring or atrophy; VA approximately 20/40-20/320 in the study eye; no fellow eye requirement; IOP 23 Exclusion Criteria: Eligibility for PDT with Visudyne (including patients for whom prior PDTs have been deemed ineffective); eligibility for any other Macugen trials, presence of other causes of CNV - myopia > 8 diopters, ocular histoplasmosis, angioid streaks, choroidal rupture, multifocal choroiditis; h/o severe cardiac disease; MI within previous 6 months; ventricular tachyarrhythmias requiring ongoing treatment; unstable angina; stroke within previous 12 months; acute ocular or periocular infection; serious allergy to FAParticipating CentersNot availableResultsPending

StudyPrONTO SponsorBascom Palmer Eye Institute and Genentech, Inc StatusRecruiting Study PurposeDetermine how quickly the central retinal thickness decreases following ranibizumab (Lucentis) therapy using OCT and then, after 3 monthly doses determine the durability of the treatment response with intermittent therapy offered only if needed based on OCT findings

Study DesignProspective, open-label, uncontrolled, clinical study Eligibility/Inclusion Neovascular AMD; subfoveal CNV; all lesion types; recent disease progression, central retinal thickness at least 300 microns; multiple visits required--6 visits each month for the first 3 months, then visits once a month thereafter for a total of 2 years ResultsPending

StudySafety and Efficacy of AG-013958 in subjects with subfoveal choroidal neovascularization associated with age-related macular degeneration SponsorPfizer StatusRecruiting Study PurposeAssess the safety, efficacy, and pharmacokinetics of the investigational drug AG-013958 in subjects with exudative AMD Study DesignPhase 1/2, randomized, masked, single and multiple-dose, single and multiple-dose, sequential dose-escalation Eligibility/ExclusionInclusion Criteria: AMD, minimally classic & occult-classic eligible in stage 2 of study (after first 46 pts), no subfoveal fibrosis; total lesion fibrosis or scar <25% total area; hemorrhage <50% of total lesion area, total lesion area 9 DA; ETDRS best corrected score of approximately 20/40-20/230; fellow eye VA >=24 letters (20/320 or better); normal ECG or nonsignificant changes Exclusion Criteria: Prior PDT >3 months before entry; serous pigment epithelial detachment without surrounding neovascularization; diabetic retinopathy, glaucoma, or other serious ocular diseases or conditions; prior subfoveal photocoagulation of the macula; prior intravitreal, sub-Tenon’s, or systemic therapy for AMD; prior TTT (transpupillary thermotherapy) or intravitreal steroids in study eye or likely to undergo these procedures within 6 months of entry; cataract surgery within previous 12 months; intraocular surgery within previous 3 months; prior vitrectomy or submacular surgery; prior scleral buckling, myopia >= 6 diopters; sitting BP >159/99 mm Hg on 2 out of 3 evaluations; stroke within the previous 12 months; h/o severe cardiac disease; peripheral vascular disease; unstable angina; MI within 6 months; ventricular tachycardia requiring treatment; inability to stop anticoagulants 4 days prior to injection (ASA okay to continue); participation in any clinical trials within the previous 60 days; use of systemic steroids currently or within the previous 30 days ResultsPending

StudyTheraSight Ocular Brachytherapy System for Treatment of AMD SponsorTheragenics Corporation StatusEnrolling Study PurposeInvestigate the safety, feasibility, and tolerability of the TheraSight Brachytherapy System for treatment of wet AMD Study DesignA multicenter, randomized study of 3 doses of radiation (assigned 1:1:1) delivered by the TheraSight Brachytherapy System in participants with CNV secondary to AMD

Eligibility/ExclusionInclusion Criteria: Age 50 years or older; active primary or recurrent subfoveal CNV secondary to AMD with minimally classic or occult lesion; where an active lesion is defined, lesion < 6 mm greatest linear dimension (GLD); submacular blood must comprise less than 75% of the total lesion; subretinal fibrosis must comprise less than 25% of the total lesion; study eye best-corrected vision of 20/100 or poorer measured on an ETDRS chart (<48 letters correct); fellow eye best-corrected vision that is at least 1 line better on an ETDRS chart than the best-corrected vision of the study eye; HbA1c <6%, signed informed consent Exclusion Criteria: Prior AMD therapy treatment; presence of other eye diseases that could compromise visual acuity in the study eye; CNV due to other causes; hypertensive retinopathy, major cardiovascular or cerebrovascular event within the last year; inability to complete follow-up; allergy to fluorescein dye; previous radiation to the study eye; pregnancy at time of surgical procedure Number of Patients30ResultsPending

StudyAdGVPEDF.11D in Neovascular Age-Related Macular Degeneration (Wet AMD). SponsorGenVec, Inc. StatusPart 1 is complete; Part 2 is Enrolling Patients Study PurposeTo assess the safety, tolerability and feasibility of single direct intravitreal injection of AdPEDF, identify an appropriate dose range for Phase II testing of AdPEDF and assess the biologic activity of AdPEDF. Study DesignPhase I, open-label, dose-escalating study of a single intravitreal administration of AdPEDF. Part 1 of the study is complete; AdPEDF (at eight ascending dose levels) was administered to twenty-eight (28) patients with severe wet AMD and was generally well-tolerated at all dose levels, with no dose-limiting toxicities, endophthalmitis, retinal or vitreous detachment, cataracts or glaucoma. Part 2 will treat twenty (20) additional patients with less advanced (moderate to severe) wet AMD at two of the highest doses tested in part 1. Eligibility/ExclusionInclusion Criteria: Patients of at least 50 years in age, with moderate to severe wet AMD (best corrected vision of 20/40 to 20/320 in the most impaired eye), active leakage or CNV with lesion diameter less than or equal to 5400 microns and no significant subretinal fluid, who are not candidates for, or who have refused treatment with, subfoveal laser photocoagulation or PDT. Exclusion Criteria: Significant retinal disease other than neovascular AMD; Significant non-retinal disease; Cataract or other significant media opacity; Other causes of choroidal neovascularization such as pathologic myopia (>8 diopters), ocular histoplasmosis or angioid streaks; Evidence of inflammation (grade 1 or higher) in the anterior and/or posterior chambers; Cataract surgery or submacular surgery within 3 months; Prior ocular treatment with radiation; Known allergy to fluorescein; Liver enzymes > 2 x ULN (ALT, AST, bilirubin); Clinical evidence of active infection of any type, including adenovirus, hepatitis A, B, or C virus or HIV virus; Other treatment for AMD in the study eye within the last twelve weeks prior to Day 1; Other experimental medications within the last four weeks prior to Day 1; Abnormal prothrombin or partial thromboplastin time (>1.5 X ULN) or anticoagulant therapy that cannot be withheld for treatment; Prior or current glaucoma or any atrophic change in the fovea. Number of PatientsUp to 48 Participating Centers7

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StudyInterval Dose Evaluation of Anecortave Acetate (IDEAA) SponsorAlcon StatusRecruiting Study PurposeCompare anecortave acetate 15 mg administered every 3 months vs. anecortave acetate 15 mg administered every 6 months vs. anecortave acetate 30 mg administered every 6 months in patients with exudative AMD Study DesignProspective, randomized 1:1:1 Eligibility/ExclusionInclusion Criteria: Clinical diagnosis of exudative AMD and a primary or recurrent (after laser photocoagulation) subfoveal CNV lesion, lesion area 12 disc areas (30.5 mm) of any lesion type (predominantly classic, minimally classic, or occult.), choroidal neovascularization (CNV) >=50% of the total lesion (defined as angiographic evidence of neovascularization, associated contiguous areas of serous elevation of the RPE, elevated blocked fluorescence, and/or late staining), evidence of recent disease progression for occult lesions (defined as having experienced a loss of at least 1 line of vision or change in lesion size of more than 1 disc area [2.54 mm] or the appearance of new blood in the lesion within the past 3 months) Snellen equivalent of 20/40 to 20/200 visual acuity in the study eye (no vision criteria for the non-study eye). Exclusion Criteria: Amblyopia, uncontrolled glaucoma with an IOP > 30 mmHg, ischemic optic neuropathy, PDR, clinically relevant NPDR, clinically relevant diabetic macular edema, significant active uveitis ,clinical signs of myopic retinopathy, or refraction of >-8.00 diopters in the patient’s current Rx, more than 1 PDT treatment in the study eye, extrafoveal or juxtafoveal thermal laser treatment less than 30 days prior to enrollment, more than 2 Macugen injections in the study eye, more than one Triamcinolone treatment in the study eye, previous treatment with anecortave acetate in the study eye, intraocular surgery in the study eye within 60 days prior to enrollment., scleral buckle in the study eye Any previous systemic anti-angiogenic therapy for AMD, radiation treatment in the study eye, scleral thinning, any unstable medical condition that would preclude ability to keep study visits, coumadin therapy that cannot be interrupted for a 5-day period ResultsPending

StudyInterval Dose Evaluation of Anecortave Acetate (IDEAA) SponsorAlcon StatusRecruiting Study PurposeTo evaluate the safety and efficacy of 2 doses of dexamethasone vs. sham treatment with the dexamethasone posterior segment drug delivery system applicator in patients with macular edema following central retinal vein occlusion or branch retinal vein occlusion Study DesignPhase 3, prospective; first 6 months randomized, additional 6 months open label if patient is eligible Eligibility/ExclusionInclusion Criteria: Macular edema due to branch vein occlusion (duration of 3-12 months) or central retinal vein occlusion (duration of 3-9 months), patient unlikely to be adversely affected by not being treated for 6 months, BCVA20/50 to 20/200, retinal thickness >= 300 by OCT Exclusion Criteria: Minimum age, 18 years, any ocular condition that would prevent a 15-letter improvement in visual acuity, epiretinal membrane as the primary cause of the macular edema, history of elevated intraocular pressure in response to steroid treatment, history of glaucoma or optic nerve change consistent with glaucoma,

ocular HTN requiring more than one medication, aphakia or presence of ACIOL, active retinal neovascularization, diabetic retinopathy, rubeosis, active or previous CNV, active ocular infection, active or inactive toxoplasmosis, scleral thinning, intraocular surgery including cataract surgery or laser of any type within 90 days prior to baseline examination, history of central serous retinopathy, history of pars plana vitrectomy, anticipated need for ocular surgery during the 12-month study period, previous treatment with intravitreal steroid or any intravitreal injectable drug, periocular steroid treatment within 6 months prior to baseline, systemic steroid treatment within 1 month prior to baseline, dexamethasone treatment within 1 month prior to baseline, treatment with topical ophthalmic steroids or topical NSAIDS, warfarin or heparin therapy within 1 month prior to baseline, allergy to fluorescein or iodine, uncontrolled systemic disease, female patients who are pregnant, planning on becoming pregnant, or nursing ResultsPending

StudyDenufosol Tetrasodium (INS37217 Ophthalmic), P2Y2 Receptor Agonist for Intravitreal Injection SponsorInspire Pharmaceuticals StatusEnrolling patients Study PurposeCompare the safety and efficacy of INS37217 Ophthalmic to placebo as a first-line therapy in patients with rhegmatogenous retinal detachment Study DesignPhase 2, double-masked, randomized, placebo-controlled, parallel-dose. Patients will be given a single intravitreal injection of drug or placebo and allows for up to 2 additional consecutive daily injections for patients who show signs of improvement following the previous injection Eligibility/ExclusionInclusion Criteria: Rhegmatogenous retinal detachment (RRD) in only 1 eye; >=18 years of age; no more than 3 separate breaks; all breaks must be clustered together and confined within an area that is no more than 2 clock hours in extent on the fundus; total area of all open breaks in the detached part of the retina is no greater than 1 clock hour in extent; retinal detachment is large enough that it cannot be immediately repaired with laser or cryo (eg, accumulated subretinal fluid extends at least 3 disk diameters from the edges of the break); macula on¬VA 20/50 or better in both eyes, macula off¬VA 20/50 nonstudy eye, plus history prior to this detachment of reading capability in the study eye Exclusion Criteria: Nonrhegmatogenous (tractional or exudative); atrophic RPE or choroid; choroidal detachment; demarcation lines; coexisting pathology; > 0.8 cup/disc ratio; prior RD repair (surgical or nonsurgical); intravitreal corticosteroid treatment within the previous 3 months; symptoms consistent with RRD for >14 days prior to screening if macula-on or h/o loss of reading vision in the study eye for more than 6 days prior to screening if macula-off; if macula-off and enrolled in study subject must be able to receive study drug injections (possibly up to 3) and be repaired or rescued all by the 10th day of the detachment. If enrolled in the study, subject must not be macula-off for >10 days; ongoing treatment with Diamox or Trusopt (dorzolamide); known sensitivity to P2Y2 Number of Patients160 Participating Centers25 Results Expected Mid-2005

StudyGenetics and Clinical Characteristics of Bardet-Biedl SyndromePurposeThe purpose of this study is to increase knowledge about the genetics and clinical characteristics of Bardet-Biedl syndrome.EligibilityEnrollment includes adult and pediatric patients and close family members.The researchers will include in the study patients who present with four primary features OR three primary features and two secondary features:Primary features1) rod-cone dystrophy 2) polydactyly 3) obesity 4) learning disabilities 5) hypogonadism in males 6) renal anomalies

Secondary features1) speech disorder/delay 2) strabismus, cataracts, astigmatism 3) developmental delay 4) poly-uria/dipsia (nephrogenic diabetes insipidus) 5) ataxia, poor coordination, imbalance 6) spasticity 7) diabetes mellitus 8) dental crowding/hypodontia 9) left ventricular hypertrophy/congenital heart disease 10) hepatic fibrosisA durable power of attorney (DPA) will be obtained for all cognitively impaired adults. ResultsPending

StudyCell Transplantation to Replace Retinal Cells and RPE in Retinal DystrophiesSponsorsUniversity of Louisville Department of Ophthalmology and Visual SciencesVitreoretinal Research FoundationStatusEnrolling patients for a Phase II clinical trail.Patient Accrual DateOngoingStudy CenterRetina Vitreous Resource Center3 Audubon Plaza Drive, Suite 240Louisville, KY 40217Study ChairmanNorman D. Radtke, MDStudy PurposeThe aim of this clinical trial is to test the safety of transplanting human fetal neural retinal tissue and retinal pigment epithelium into the eyes of human patients with age-related macular degeneration or retinitis pigmentosa.Study DesignTen patients with AMD, five with dry and five with wet age-related macular degeneration, and a vision of 20/400 or worse in one eye will be selected for the study and will undergo an operation to implant fetal neural retina with RPE under the retina. Two complete examinations will be performed at least 30 days apart to confirm the visual acuity, and only one eye will be subject to surgery. Postoperatively, the patients will be evaluated at one week, one month, three months, six months, nine months, twelve months, and twenty-four months for follow-up(F/U).Number of Patients EnrolledNot availableFollow-up2 yearsEligibility/ExclusionTo participate a person must be at least 21 years of age, have no diabetes or glaucoma, and have vision of 20/200 or worse in one eye. The transplant is in that one eye only. Pregnancy rules out eligibility.Participating Centers1ResultsPending

StudyOptical Coherence Tomography Study of Retinal ThicknessSponsorNational Eye Institute (NEI)StatusCurrently Recruiting PatientsPatient Accrual DateOngoingStudy CenterNational Eye Institute (NEI), 9000 Rockville Pike, Bethesda, Maryland 20892Study ChairmanNot availableStudy PurposeThis study, conducted at the NIH Clinical Center and the University of Wisconsin University, will compare measurements obtained using older and newer models of a machine called an optical coherence tomography (OCT) scanner.Study DesignObservational, prospective, randomized clinical trial.Number of PatientsExpected Total Enrollment: 120Follow Up3 monthsEligibility/ExclusionInclusion Criteria:1. Patient must understand and sign the informed consent.2. Patient must be at least 18 years of age.3. Pupillary dilation to at least 6 mm must be possible.4. Ocular media must be sufficiently clear to allow for quality images.Exclusion Criteria:1. Any condition such as corneal opacifiation that precludes adequate slit lamp examination and photography of the fundus.Participating CentersNot availableResultsPending

StudyPhase I Trial for Wet Age-Related Macular Degeneration with VEGF TrapSponsorRegeneron/AventisStatusCurrently recruiting patientsPatient Accrual DateOngoingStudy CenterWilmer Eye Institute at Johns Hopkins Hospital (Baltimore, Maryland)Study ChairmanNot availableStudy PurposeTo determine the safety of the VEGF Trap and obtain a preliminary assessment of the potential effect of the VEGF Trap on visual acuity.Study DesignThis is a Phase I randomized, placebo-controlled, dose-escalating study. Based on safety and visual outcome measurements in the initial study period, subjects may be allowed to continue treatment with VEGF Trap in a one-year, open-label safety extension study.Number of PatientsNot availableFollow Up1-2 yearsEligibility/ExclusionSubjects must be 50 years or older, currently have wet AMD in at least one eye and be in general good health.Participating Centers4ResultsPending

>> RETINAL RESEARCH REPORT

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As a retina specialist, you may be fielding questions from your patients about RNA interference (RNAi), or small interfering RNA (siRNA), technologies. They may have heard some of the buzz about RNAi applications in the treatment of age-related macular degeneration to prevent vision loss. One goal of research in the treatment of neovascular AMD is to find ways to lower vascular endothelial growth factor (VEGF) levels. VEGF is known to be a major culprit in the process of neovascularization. Currently, the focus is on molecules that bind and inactivate VEGF, such as aptamers and antibodies, but some researchers believe that an attractive alternate approach lies in trying to shut down VEGF production at the source. It is believed that RNAi technologies, with their ability to silence the message of a gene, could potentially shut down VEGF production rather than block existing VEGF molecules. Is one approach better than the other? How effective is RNAi in treating neovascular AMD? Answers to these questions continue to develop, because the technology is still in its infancy. However, there is widespread optimism about its efficacy, and it is being studied for treatments in cancer, asthma, hepatitis, diabetes, Huntington’s disease and other afflictions. Most of the research is in proof-of-concept or pre-clinical stages, with RNAi research in AMD further along than for most conditions.

RNAi was introduced to the retina literature by Michael Tolentino, MD, and colleagues from Scheie Eye Institute and Acuity Pharmaceuticals. In their study, reported in Retina, a single intravitreal injection of siRNA molecules directed against VEGF production was performed in monkeys. During 5 weeks of follow up, the injections were found to reduce leakage in a laser-induced CNV model. Importantly, no inflammation or toxic effects of the treatment were identified. According to Dr. Tolentino and colleagues, siRNA may be 100 to 1,000 times more potent than protein antagonists such as aptamers and antibodies, which could allow for lower and less-frequent dosing. This is because it intervenes earlier in the VEGF production process, preventing the production of multiple VEGF protein molecules every time it disables a single VEGF mRNA molecule–and each siRNA molecule can inactivate multiple mRNA molecules, further amplifying the effect. By contrast, protein antagonists must bind the VEGF molecules in a one-to-one ratio. Tolentino, who is now in private practice with the Center for Retina and Macular Disease in Lakeland and Winter Haven, FL, said, “It’s like anything else–if you can prevent something from being produced, it’s better than dealing with it once it has been produced.” Safety is another positive aspect of the technology. “They are made from RNA, which is similar to the product that makes aptamers, and we know from the Macugen data that aptamers are very safe in the eyes, and RNA is safe in the eyes,” Tolentino said. “They are inert molecules that are well-tolerated in the human body.”

How it WorksIn order to understand how one might “turn off” the production of VEGF or any other protein, it is important to recall basic principles of molecular biology. Genes are encoded in DNA, which resides in the cell nucleus. The first step toward the making of a protein is transcription of the gene into messenger RNA (mRNA). After the mRNA moves from the nucleus to the cytoplasm, it

encounters the ribosome. The ribosome allows the genetic message to be translated into a chain of amino acids, which comprise the newly formed protein, in this case VEGF.

It is clear from this sequence of events that mRNA plays a key role as a “middleman” between the gene encoded in DNA and the final protein product. With this in mind, researchers have been looking at ways to stop the action of mRNA. Recent insights from plant biology have provided a possible answer to this challenge. Within the past decade, researchers have come to recognize that introduction of specific short double-stranded RNA sequences (siRNA) into cells can induce the degradation of the targeted mRNA molecules. In plants, this has evolved as a natural defense mechanism against viruses. The strategy, also known as “gene silencing,” inactivates (mRNA) molecules inside cells by interacting with a protein known as the RNA-induced silencing complex, which cleaves mRNA molecules that are homologous to the short (a.k.a. small) interfering RNA (siRNA) sequence. Investigators have shown that similar antiviral defenses exist in Drosophila fruit flies, proving the existence of the RNAi mechanisms in animals. Further studies have shown that the replication of viruses such as respiratory syncytial virus (RSV) and HIV-1 can be successfully inhibited in vitro using siRNA.

Researchers Eye RNA Interference Technologies

Jay M. Stewart, MDSection Editor

>> IN THE PIPELINE

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.

Figure 1. RNA silencing depends upon double-stranded RNA sequences (shown here interacting with a plant viral protein). This figure reprinted with permission from Dr. Keqiong Ye, Memorial Sloan-Kettering Cancer Center, New York.

Figure 2. After delivery into the cell, siRNA molecules activate RISC, a protein complex that disrupts messenger RNA and thereby prevents translation of the gene into a protein. In this example, the targeted mRNA sequence encodes the gene for VEGF.

Paul E. Tornambe, M.D.

RNAi Strategies for Retinal DiseaseIt is this process that shows promise in eye disease. Researchers believe that they can target the mRNA that is required for VEGF production by using siRNA sequences that are tailored to the VEGF gene. It is hoped that when delivered locally to the eye, siRNA will shut down the production of VEGF, preventing the development of ocular neovascularization and vision loss in neovascular AMD, diabetic retinopathy, and other conditions. Approaches to the use of siRNA technology vary among those involved in its research and development related to retinal disease. One approach uses a synthetic polymer (nanoparticles) to protect the RNA from serum degradation and excretion, while another[JS1] uses native RNA, and yet another[JS2] uses chemically modified RNA.

The Future of RNAi in OphthalmologyRetinal specialists can expect to hear more

about clinical trials for RNAi treatments of eye disease in the near future. Currently a number of companies are spearheading the effort to get RNAi ready for the clinics. Acuity Pharmaceuticals’ siRNA product that targets VEGF production is in phase 1 trials for AMD and diabetic retinopathy and is expected to enter phase 2 by the end of this year. Acuity also recently signed a deal giving it the rights to the ophthalmic technologies of Intradigm Pharmaceuticals, another company developing siRNA products that had been working on a treatment to block production of VEGF and its receptors. Alnylam Pharmaceuticals, which has partnered with Merck for commercialization of its ophthalmic products, uses siRNA to target VEGF production and expects to enter phase 1 trials in the near future. Sirna Therapeutics is in phase 1 trials with its RNAi treatment, an siRNA therapy blocking production of VEGF receptor-1. According to Sirna, the rationale for targeting VEGF receptor-1 rather than VEGF itself is

that it allows effective inhibition of pathologic angiogenesis without affecting normal VEGF pathways: the literature suggests that VEGF receptor-1, which binds both VEGF and placental growth factor, is important in pathologic processes, whereas VEGF receptor-2, which binds only VEGF, has more of a role in normal pathways. Sirna is in phase 1 trials and expects results by the end of the year, with a phase 2 trial scheduled to begin soon thereafter. There is still considerable debate over whether blocking VEGF pathways with treatments such as RNAi can be more effective than rendering existing VEGF ineffective with treatments such as aptamers. As clinical trials progress, the Retina Times will continue to report progress on the developing technology of RNAi and its application to treating diseases of the back of the eye.

I advocate pneumatic retinopexy for retinal detachment repair because it results in the best and quickest visual outcome and restores the eye to its predetachment state better than any other procedure. I have given many lectures on pneumatic retinopexy and the following are the most common misconceptions about pneumatic retinopexy voiced by the audience. I am frequently told by audience members that my results following pneumatic retinopexy are better than theirs. The following misconceptions may be the reasons why:

1. Pneumatic retinopexy is only for young, educated people with no skeletal abnormalities.In my experience, more than 90% of patients who present with a retinal

detachment are able to comply with instructions and may undergo pneumatic retinopexy. The secret is informing the patient and the family what is expected beforehand, and educating them regarding the operation and why positioning is so important. The Escalon pneumo level (which costs about $ 5) attached to the eye patch makes positioning almost fool-proof. The patient is your co-surgeon!

2. Retrobulbar anesthesia is required if cryopexy is needed.I never use retrobulbar anesthesia. Subconjunctival anesthesia works very well. Try it–you’ll like it.

3. Laser is preferable to cryopexy.The pneumatic trial showed no benefit of laser over cryopexy with regard to ERM formation, PVR, or attachment rates. I prefer focal 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 is not very posterior. Cryopexy is advised for breaks in the horizontal meridian which may reopen when the patient ceases positioning to come to your office the next day for laser treatment. Retinal breaks are hard to find once the retina attaches and can be missed or inadequately treated with laser once the retina is attached. Be generous with cryopexy about the break(s), and extend the cryopexy to the ora, for it is the only force counteracting vitreous traction in the region of the break.

4. Five percent povidone-iodine is used to prep the eye.There was a single infection reported in the pneumatic retinopexy clinical trial, and that case was done in an outpatient OR with a full prep and drape. The nurse prepped the eye with diluted povidone-iodine. I strongly advise 10% Betadine. It is irritating to the cornea but I have had no cases of endophthalmitis (and I perform an anterior chamber paracentesis in every case in addition to gas injection). 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 drop for five days after surgery. I also give a subconjunctival gentamicin (20 mg) injection at the end of each case, but that may be more for the surgeon’s peace of mind than the patient’s eye.

Ingrid U. Scott, MD, MPHSection Editor

>> TIPS AND TECHNIQUES

Pneumatic Retinopexy Misconceptions

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 patch, there is an air bubble in the level and the patient is instructed to ‘put the bubble’ on a certain clock hour. This device helps greatly with positioning.

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5. One should perform an anterior chamber paracentesis after injecting gas only if the central retinal artery is compromised. Although an anterior chamber paracentesis is usually not necessary if a small volume (0.25-0.3cc) of C3F8 gas is used, for most cases C3F8 is “overkill” and should not be used. I routinely perform a paracentesis before gas injection because 0.5cc or more of 100% SF6 gas is usually injected. I use a plungerless TB syringe and a #27 needle and try to stay over iris. The needle is slowly ‘twisted’ with gentle pressure so it enters the anterior chamber without a ‘jumping’ motion which could strike the lens. I never use a knife. Usually 0.2-0.3mls of aqueous can be removed passively and in some cases 0.4-0.6mls (probably liquid vitreous exiting around the zonules) may be removed in this manner. A small amount of vitreous in the anterior chamber is not a contraindication to paracentesis. If the paracentesis is performed slowly, and if the #27 or #30 needle is directed away from the vitreous, incarceration of the vitreous can be avoided. If vitreous is incarcerated, YAG laser lysis of the vitreous membrane a week or two later will restore the pupil shape and relieve vitreous traction. A paracentesis prior to gas injection avoids a temporary high spike in IOP and is very kind to the optic nerve. The most important point to document in your record at the end of the procedure is not the IOP, or the status of the central retinal artery; it is light perception.

6. C3F8 gas is used so one can inject a small gas volume and not perform a paracentesis.Patients with ‘no life’ should have a C3F8 injection. An eight week gas bubble drives most patients crazy and is usually unnecessary. The gas bubble is your friend when the retina is detached and becomes your enemy after the retina attaches. All the bubble can do after the retina attaches is irritate the vitreous and exert traction in other areas of the retina, especially when the patient becomes more mobile. One should use the shortest acting gas bubble which gets the job done. I use C3F8 in about 5% of all cases. C3F8 should be reserved for large eyes, with large and/or posterior breaks. The purpose of the bubble is to isolate the break from liquid vitreous long enough for a chorioretinal adhesion to form to counteract vitreous traction. Three to five days of tamponade is usually enough (16 hours per day). It is not necessary for patients to position themselves during sleep although I suggest that for the first 24 hours they position as much as tolerated. 0.5cc of 100% SF6 is usually adequate to treat the majority of retinal detachments. When more than 0.25cc of gas is injected a paracentesis is advised. Therefore, I always perform a paracentesis before I inject 0.5cc of SF6. I use SF6 ninety-five percent of the time.

7. How can I avoid subretinal and anterior hyaloidal gas?Most complications of pneumatic retinopexy are avoidable. I have had only a few complications in approximately 500 cases. If one injects away from the break in an area where the bubble will not rise in the direction of the tear, subretinal gas is rare. Never inject inferiorly, which allows fish egg gas bubbles to rise into the region of the break. Always penetrate the eye deeply to be sure the needle has penetrated the anterior hyaloid to avoid gas in the space of Petit (sausage sign). A small gas bubble beneath the retina absorbs more quickly than a bubble in the vitreous cavity and, so long as the vitreous bubble is large enough to close/isolate the edges of the break, the retina will attach. Larger amounts of subretinal gas require vitrectomy.

8. The gas bubble must cover all breaks simultaneously.Sequential positioning works well to close separated breaks in the superior quadrants. Close the break which detaches the macula first. It is not necessary to pump in a very large gas bubble to try to cover all the breaks simultaneously. Such a large bubble may create new breaks.

9. I don’t use PR because it is associated with new breaks.Although an open break is the primary cause for failure, I believe the majority of breaks are missed breaks and not new breaks. The better

you examine the retina preoperatively, the fewer “new” breaks you will discover postoperatively. If you cannot examine the peripheral retina well for any reason, don’t perform pneumatic retinopexy.

10. I perform PR in phakic eyes but don’t perform it in pseudophakic eyes because the success rate is lower, perhaps in the 70% range.Sandy Grizzard states “the phakic status of the eye is not a consideration when I evaluate an eye for RD repair”, and I agree with this statement. The most important parameter is the ability to examine the entire retina. Many papers have reported that the success rate in pseudophakic eyes with retinal detachments is lower than in phakic eyes across the board, regardless of the procedure used to repair the detachment. Many papers have also shown that a failed pneumatic does not disadvantage the eye to ultimate attachment or vision return. For argument’s sake, let’s assume the single operation success rate for pseudophakic detachments treated with pneumatic retinopexy is 70%, and for scleral buckle is 90%. If there are ten patients with a pseudophakic retinal detachment, seven of the ten will be cured with a single pneumatic and nine will be cured with a single buckle. Therefore a surgeon selecting scleral buckling exclusively is willing to expose nine patients to an OR procedure so that perhaps two will be saved a second operation. If a failed pneumatic doesn’t disadvantage the eye, why not try pneumatic retinopexy first?

11. How can I increase the overall success rate?The best way to improve your batting average is to select the correct patient and identify all pathology. Once pneumatic retinopexy is selected, and especially for pseudophakic eyes, 360 retinopexy between the insertion of the vitreous base and ora will improve the success rate by 5-10%. Data from the pneumatic retinopexy trial revealed that most new/missed breaks were noted within three clock hours of the initial break. Therefore, treating these areas prophylactically should prevent redetachment if a break develops within the treated area. If 360 retinopexy is considered, it should be staged. Treat the recognized elevated break(s) with focal cryopexy, and treat attached retina with light laser, avoiding the edge of the detachment by one clock hour so that if fluid is displaced by the bubble, it will not detach freshly treated areas of laser burns and possibly result in new break formation. The steamroller technique can be used in such instances to “debulk” the subretinal fluid load. Once the retina attaches, complete the laser treatment. Never laser elevated retina.

12. For a particular patient, is there a way to “guesstimate” success?We all like to give our patients “odds” for success before surgery so they have realistic expectations. I reviewed over 300 of my cases and came up with the following formula: a phakic one quadrant retinal detachment with one superior break (3 to 9) carries a 97% success rate. If the eye is pseudophakic subtract 10%; if there are multiple breaks (broader vitreous traction) subtract 10%; if there is more than a quadrant detached (more likely you’ll miss a small break) subtract 10%; if you perform 360 retinopexy add 5-10%. Thus, a pseudophakic patient with a total retinal detachment and several retinal breaks has a 67% chance of attachment with one pneumatic procedure if 360 retinopexy is not performed; with 360 retinopexy it increases to about 75%. No matter how ‘simple’ the procedure, one cannot separate the surgeon from the surgery. The secret of pneumatic retinopexy is case selection, which means identifying all pathology before the gas bubble is injected. I believe most failed cases are due to missed breaks. Some breaks are very difficult or impossible to see. Don’t beat yourself up over a failed pneumatic, no harm is done and if it works, the patient has dodged a big bullet! Check out the ASRS online journal for my AOS thesis which goes into the subject in much greater detail.

>> TIPS AND TECHNIQUES

Any practice has a “business process”, the purpose of which is to transform clinical activity into 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 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. 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 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 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.

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

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

>> PRACTICE MANAGEMENT

Ron Rosenberg, PA.-C, MPH

The Retina Practice Business Process

About the AuthorRon 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.

Scott G. Foxman, MD Section Editor

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CLINICAL SERVICE

CHARGE CAPTURE

CODING

FEES

CLAIMS SUBMISSION

RECEIVABLES MANAGEMENT

MANAGEMENT REPORTING

PRACTICE OVERHEAD

These are the steps included in the business process after the provision of the clinical services.

This is a component of the business process that, along with CPT coding, is somewhat more complex for Retina than for General Ophthalmology. There is more office “testing” (e.g., FAs, Photos, OCT/HRT, etc.), office procedures, and surgeries with multiple components. These require vigilance in capturing all services as they are provided, as well as processes to allow retrospective audits to measure charge-capture effectiveness.

CODINGThe Step – Each service is described by a procedure code (CPT), and the justification for providing the service is made with a diagnosis code (ICD-9).

The Register – Coding “patterns” should be regularly reviewed to assess accuracy and to identify “over-coding” and “under-coding.” This includes CPT codes for both Evaluation and Management (E&M) and procedural services. There is often a blurred boundary between charge-capture and coding. For example, is the inclusion of all component procedures in a multi-part surgery a function of coding or of charge-capture? It may well be that the answer is immaterial. What is important is that all of the components are accurately and appropriately captured and described. Another coding pattern to be closely monitored is the distribution of the “Levels of Service” for the Evaluation and Management services.

FEESThe Step – The practice should have a fee schedule that is rational–that is, there is a relationship between the fees for various services that follows the relationship between the allowable payments for those same services from the major insurers. This prevents overpriced and underpriced services, and allows for the calculation and monitoring of the practice’s collection target. An example would be a fee schedule calculated as a multiple of the local Medicare Fee Schedule. Since many of the insurance carriers base their allowable payments on that same Medicare Fee Schedule, a fairly constant relationship is created between the practice’s fees and the allowable payments. If the practice set its fees at two times the Medicare Fee Schedule, the maximum collection ratio for Medicare services would be 50% (100% ÷ 200% = 50%). If a local insurance plan paid at 150% of the Medicare Fee Schedule, the maximum collection for those services would be 75% (150% ÷ 200% = 75%).

The Register – A fee schedule evaluation and re-calculation should be done at least annually.

CLAIMS SUBMISSIONThe Step – Claims for services should be entered into the billing computer system and transmitted to the insurers accurately and in a timely manner.

The Register – A “lag” report can be developed showing the average time between date-of-service, date of charge-entry, and date of claim submission. Additionally, a “Denials Log” can be kept to identify patterns of rejected claims so errors can be corrected (and prevented).

RECEIVABLES MANAGEMENTThe Step – This is the most crucial part of the process because it is the source of more lost practice income than any other part of the business process. Receivables management is the process of receiving payments and posting those payments into the computer system. It is a system for knowing the level of payment expected for each charge, the time frame in which the payment should be received, and actions needing to be taken when the payment is not the expected amount and/or not received within the expected time frame.

The Registers – There are several important registers to monitor receivables management (and by extension, financial performance of the practice). In order to accurately monitor receivables management, a competent, properly set-up practice management computer system is required. The key registers it should include are:• Collection target calculation – Given the practice’s fees, payor

allowable payment levels, and payor-mix, what are the expected collections for a set of charges?

• Collection performance – What are the totals received and how do those totals compare to the target?

• Revenue flow – How quickly are payments received?• Accounts Receivable (AR) – This is an analysis of outstanding

claims. While the collection performance report shows what HAS happened, the AR analysis is a report of what HAS NOT yet happened. It is a valuable report for following up on individual unpaid claims as well as patterns of late or missing payments from insurance plans.

MANAGEMENT REPORTINGThe Step – The reports required to measure the registers described in each piece of the business process. The reports most valuable to monitor can be broken down into two categories. These are Operational Reports (e.g., charge-capture, collection performance, etc.) and Productivity Reports. The operational reports measure the effectiveness of the business process, while the productivity reports are used to measure the practice’s service volumes, and source of patients. This productivity information is used for charting the practice’s strategic direction.

PRACTICE OVERHEADThe Step – A measure of the non-physician practice expenses, by category.

The Register – The practice’s Income Statement, showing cost by category, and displayed as monthly and year-to-date totals, comparison to year-to-date totals for the same periods in previous years, and the year-to-date totals expressed as a percentage of practice income. That percentage of income represented by non-physician cost is the practice’s “overhead rate”.

SUMMARYThis set of steps will provide the practice’s owners and managers with an accurate picture of their business process, and expected financial performance. If that performance is below the calculated target level, this monitoring system will show the areas where improvement is needed, and the steps required to bring the performance back into the expected range. At the same time, data will be generated to show the growth and direction of the practice, allowing for effective strategic management.

40 retina times

Anne M. Menke, RN, PhDOMIC Risk Manager

Arthur W. Allen, MDSection Editor

>> RETINAL RISK MANAGEMENT

Retinopathy of Prematurity: Creating a Safety Net

Due to space restrictions, the tables and letters referred to in the article are not included here. You can access the complete text of “Retinopathy of Prematurity: Creating A Safety Net” in the “Risk Management Recommendations” section of the OMIC website (www.omic.com); articles are in alphabetical order.

DISCLAIMER: Recommendations presented here should not be considered inclusive of all proper methods of care or exclusive of other methods of care reasonably directed to obtain the same results. The ultimate judgment regarding the propriety of any specific procedure or treatment must be made by the ophthalmologist in light of the individual circumstances presented by the patient. This information is intended solely to provide risk management recommendations. It is not intended to constitute legal advice and should not be relied upon as a source for legal advice. If legal advice is desired or needed, an attorney should be consulted.

Screening and treating premature infants for retinopathy of prematurity (ROP) is an important aspect of pediatric ophthalmic care that provides a valuable service to not only the individual patient but also to society as a whole. Although claims against ophthalmologists for mismanagement of ROP are relatively infrequent, indemnity payments for these claims can be high due to the young age of the plaintiffs and the significant loss of vision that can result even with treatment. Concerned about their liability exposure, numerous screening and treating ophthalmologists called OMIC to request sample protocols to help standardize care at the hospitals where they care for ROP patients. The goal of the risk management recommendations offered here is to promote patient safety and minimize the liability exposures related to ROP care. They were developed after a detailed analysis of OMIC ROP cases and of data from the Physician Insurer’s Association of America (PIAA), Jury Verdict Reports, and IDEX (an expert witness database), as well as a Failure Mode and Effects Analysis (FMEA), designed to identify vulnerable points in the care process. They have been reviewed by a number of pediatric ophthalmologists and retina specialists, risk managers, and attorneys. These suggested practices are designed to complement the clinical recommendations found in published studies and summarized in “Screening Examination of Premature Infants for Retinopathy of Prematurity,” the Joint Statement issued by the Ophthalmology Division of the American Academy of Pediatrics (AAP), the American Academy of Pediatric Ophthalmology and Strabismus (AAPOS), and the American Academy of Ophthalmology (AAO), and published in Pediatrics 2001; 108:809-811. The Joint Statement has recently been revised, and approved by the Boards of AAO and AAPOS. As soon as it is approved by the AAP Board, it will be published in Pediatrics. Information given here is from the 2001 version (referred to as “Joint Statement”) or other articles. Risk management recommendations do not establish a standard of care, but rather, serve as suggestions on how the healthcare team–the ophthalmologist, neonatologist/pediatrician, NICU (Neonatal Intensive Care Unit) nurses, hospital, and parents–can create a safety net for these at-risk infants. They also serve to both reduce the likelihood of a professional liability lawsuit and improve the defensibility of care if it is ever questioned.

This document assigns responsibility for each task in the ROP care process (see Table 1), based upon the fact that the neonatologist is the primary care physician, whereas the screening and treating ophthalmologist serve as consultants, while the baby is in the hospital. Accordingly, while the baby remains in the hospital, we have assigned the neonatologist and NICU nurses the principle role for coordinating and tracking appointments with consultants and for communicating with the baby’s parents. At critical junctures in the ROP care process, however, the entire team needs to be involved. These points are the ongoing education of the parents and coordinating transfer of care to ophthalmologists at another hospital or in an outpatient practice. Once the baby has been discharged, the ophthalmologist is responsible for tracking outpatient ophthalmic care (this assumes that the ophthalmologist has been notified of the discharge/transfer, and has agreed to treat the baby). We want to acknowledge that during the hospital-care phase, you as the ophthalmologist will not be able to implement all of these recommendations without the cooperation of the hospital, neonatologist/pediatrician, NICU nurses, and parents (by “parents,” we mean whoever has current custody of the baby and is responsible for making medical decisions on the baby’s behalf). You can, however, act as a patient advocate, and use these recommendations as the starting point for constructive dialogue. OMIC’s Risk Manager can be an important source of information and support for policyholders engaged in these discussions. Conduct a risk analysis of your current process of care by identifying any steps in the following sequence for which responsibility has not been assigned, or when care is not being provided according to current clinical guidelines (e.g., the “Joint Statement”).

RISK MANAGEMENT RECOMMENDATIONS FOR HOSPITAL-BASED ROP CARE

1. The neonatologist can use Table 3 to determine which babies need screening, and Table 4 to determine the timing of the first eye examination.2. SAFETY NET: Hospital ROP Tracking System. Most medical malpractice lawsuits related to ROP occur when the baby is “lost to follow up,” either in the hospital or after discharge or transfer. To prevent this, the hospital needs to develop and maintain a hospital ROP tracking system. Ideally, one highly-educated and trained person is designated as the ROP coordinator, and back-up is available when this person is on vacation. (For simplicity’s sake, we have assigned this function to the NICU. Some hospitals appoint the NICU nurse responsible for discharge planning). Information to be tracked includes: name, date of birth, weight, gestational age, parent’s name and phone number, hospital account number, date of visit, findings, and date of next follow-up visit. When the neonatologist identifies a baby for screening, the NICU enters the baby into the system. After the ophthalmologist hasconducted the initial examination, he or she determines when the baby should be seen again, and documents the follow-up interval. The screening or treating ophthalmologist writes an order indicating the follow up interval. The NICU updates the tracking system each time the baby is evaluated or treated, noting the current condition and follow up interval, and evaluates

retina times 43

the tracking system at least once a week to ensure that all follow-up appointments are scheduled and kept. The NICU immediately notifies the neonatologist of any missed, cancelled, or rescheduled ROP appointments while the baby is in the hospital. The NICU tracks the baby until one of these conditions is met: 1) the screening ophthalmologist verifies that both eyes have met the conclusion-of-acute-phase-ROP-screening criteria, 2) the treating ophthalmologist verifies that treatment and necessary follow-up examinations are completed, 3) an ophthalmologist at the hospital to which the baby is transferred accepts responsibility for further ophthalmic care and an initial appointment is scheduled, or 4) an outpatient ophthalmologist accepts responsibility and an initial outpatient appointment is scheduled. The hospital’s role in tracking is complete when all of these conditions have been met: 1) the ophthalmologist who will be providing care has been notified of the discharge/transfer and has agreed to treat the baby, 2) a ROP appointment is scheduled at the second hospital or with an outpatient ophthalmologist, 3) the baby’s pertinent medical records have been sent, and 4) the parents/guardian’s contact information has been sent. 3. The ophthalmologist should have sufficient knowledge and expertise to enable accurate identification of the location and sequential retinal changes of ROP after pupillary dilation using binocular indirect ophthalmoscopy (Joint Statement).4. The ophthalmologist should include an ROP consult note in the infant’s hospital chart, and use the International Classification of Retinopathy of Prematurity (ICROP) to classify, diagram, and record the retinal findings at the time of the examination or treatment (Table 2). Some ophthalmologists now also categorize pre-threshold ROP as Type 1 and Type 2. See Table 7.5. Table 5 is helpful in determining the follow up interval during the screening phase. The screening ophthalmologist should write follow-up orders in the hospital chart, and the NICU should update the tracking system and schedule the follow-up appointment. 6. The screening ophthalmologist should screen until both eyes have met the conclusion-of-acute-phase-ROP screening criteria (Table 6) or until the treating ophthalmologist has verified that treatment and all follow-up examinations are completed. One examination is sufficient only if it unequivocally shows the retina to be fully vascularized in each eye.7. Table 7 provides guidance on when to initiate treatment and explains how to further categorize pre-threshold ROP as Type 1 and Type 2 ROP. The screening ophthalmologist should notify the neonatologist and document the recommendation to begin treatment in the hospital record. Depending upon the protocol at the hospital, either the screening ophthalmologist or the neonatologist should write an order for the NICU to both update the tracking system and schedule an appointment with a treating ophthalmologist. The screening ophthalmologist conducts and documents a transfer-of-care discussion with the treating ophthalmologist, conveying the urgency of the referral, and ensures that the second doctor has access to, or copies of, the patient’s previous history and eye examinations.8. SAFETY NET: Parent Education. All members of the team need to help educate the parents about ROP, the need for careful follow up until both of the baby’s eyes have either met the conclusion-of-acute-screening criteria or treatment and follow-up examinations are completed during the acute phase, the consequences of missing screening or treatment appointments, and the need for long-term ophthalmic care. Verify the parents’ understanding of the information, and carefully document all educational efforts. The neonatologist should inform the parents when the baby needs screening evaluations, and when treatment is recommended. The neonatal nurse should educate the parents before and after screening

and treatment, and prior to transfer or discharge. The screening and treating ophthalmologists should complete the attached document, “Parents: Read This About Your Premature Baby’s Eyes,” each time an infant is first screened/treated for ROP, and whenever the infant’s ROP status changes. The NICU should ask the parents to sign this document and place it in the hospital record, as well as give the parents a copy to take home. If the hospital is unwilling to give the parents the document and/or ask them to sign it, the ophthalmologist can mail it to the parents. 9. SAFETY NET: Transfer/Discharge. This is the most vulnerable point in the ROP care process, so all members of the team need to be involved in discharge/transfer planning to ensure proper ophthalmic follow up. No baby should be transferred/discharged until an initial appointment has been made with the new screening or treating ophthalmologist and all pertinent records and current contact information for the baby’s parents/guardian are sent. The neonatologist informs the neonatal nurse and the screening or treating ophthalmologist of a planned discharge or transfer, in order to allow the ophthalmologist to assess the baby from an ophthalmic perspective, and determine current follow-up needs. The ophthalmologist conveys the recommendations orally to the neonatologist, and writes a final ophthalmic consult note, unless a screening examination or treatment took place and was documented very recently. The neonatologist speaks with the pediatrician at the other hospital, or the baby’s outpatient pediatrician, and includes the ophthalmic care needs in the discharge/transfer orders. The neonatologist and pediatrician together ensure that a new screening or treating ophthalmologist has been found to assume the ophthalmic care (with recommendations, if possible, from the screening or treating ophthalmologist). Experience shows that parents cannot be relied upon to schedule this care. Cultural, language, and health literacy issues, as well as difficulties inherent in assuming the care of premature infants, often interfere with the accurate transmission of key information, and place these babies at great risk. To protect the infant, the NICU nurse talks with a nurse at the nursery at the new hospital, or with the ophthalmologist’s office staff, to schedule the initial ophthalmic appointment and provide all necessary information. If the current ophthalmologist will continue to see the baby after transfer or discharge, he or she also notifies office staff to expect a call from the NICU, and instructs staff to enter the baby in the office ROP tracking system. If the NICU is unwilling to help coordinate the initial 2nd hospital or outpatient visit, and you as the ophthalmologist are asked to see the baby, ensure that the appropriate records, including recent contact information for the parents, are sent to you.10. To ensure the standardization, reliability, and effectiveness of ROP care, the ophthalmologist, neonatologist, and hospital need to have a written agreement or protocol (see sample protocol).

RISK MANAGEMENT RECOMMENDATIONS FOR OUTPATIENT ROP CARE

1. The ophthalmologist should have sufficient knowledge and expertise to enable accurate identification of the location and sequential retinal changes of ROP after pupillary dilation using binocular indirect ophthalmoscopy (Joint Statement).2. SAFETY NET: Coordinate transfer of care to the outpatient setting. This is the most vulnerable point in the ROP care process, so all members of the team need to be involved in discharge planning to ensure proper ophthalmic follow up. Conduct and document a transfer-of-care discussion with the current screening or treating ophthalmologist. Instruct your staff to speak to the NICU nurse to determine the discharge date, schedule the initial outpatient

>> RETINAL RISK MANAGEMENT

44 retina times

appointment, and obtain all relevant medical records and current contact information for the parents. Instruct staff to enter the baby into the ROP tracking system. 3. SAFETY NET: Telephone Screening of Ophthalmic Problems. If the NICU in your hospital is unwilling to speak with your office to coordinate the transfer of care, ensure that staff members who answer phones are trained in telephone screening and know how to identify babies who need ROP care. Some babies have been lost to follow up because the parents did not identify the need for ROP care, and the staff member who scheduled the appointment did not ask if the baby was premature or had been seen in the hospital. Other parents have changed the name of the baby since the baby was seen in the hospital, so the practice did not recognize the infant as one who had already been seen when the parents scheduled the appointment. If the baby is identified as premature, staff should be directed to ask the gestational age in weeks, and the date of birth, so postmenstrual age can be calculated (see Table 4). Also see OMIC’s “Telephone Screening of Ophthalmic Problems” guidelines for forms and general telephone screening recommendations (available in the Risk Management Recommendations section at www.omic.com).4. SAFETY NET: Office ROP Tracking System. Most medical malpractice lawsuits related to ROP occur when the baby is “lost to follow up.” To prevent this, the practice must create and maintain a ROP tracking system. When the initial outpatient appointment is scheduled, the baby is entered into the system. Each time the baby is evaluated or treated, the ophthalmologist indicates the follow up interval, and the office schedules the follow-up appointment before the parents leave the office. The tracking system is then updated to note the current condition and follow up interval. The tracking system is evaluated at least once a week to ensure that all follow-up appointments are scheduled and kept. The ophthalmologist is notified immediately of any missed, cancelled, or rescheduled ROP appointments (see Follow Up, below). The baby is tracked until one of these conditions is met: 1) the screening ophthalmologist verifies that both eyes have met the conclusion-of-acute-phase-ROP-screening criteria (Table 6), 2) the treating ophthalmologist has verified that treatment and follow-up examinations are completed, or 3) care is transferred to another ophthalmologist. If care is transferred to another ophthalmologist, the office’s role in tracking is complete when all of these tasks have been accomplished: 1) a ROP appointment is scheduled at the other ophthalmologist’s office, 2) the baby’s medical records have been sent, and 3) the parents’ contact information has been sent.5. Use the International Classification of Retinopathy of Prematurity (ICROP) to classify, diagram, and record the retinal findings at the time of the examination or treatment (Table 2). Table 7 explains how to differentiate between Type 1 and Type 2 ROP.6. Use Table 5 to determine and note the follow up interval. Instruct your staff to schedule the next appointment before the parents leave the office, and to update the tracking system. Do not rely upon the parents to schedule the follow-up appointments. Cultural, language, and health literacy issues, as well as difficulties inherent in assuming care of premature infants, often interfere with the parents’ ability to understand ROP and can place the infant at great risk.7. SAFETY NET: Parent Education. Enlist appropriate members of your staff to help educate the parents about ROP, the need for careful follow up until both of the baby’s eyes have met the conclusion-of-acute-ROP-screening criteria or treatment and follow-up examinations are completed, the consequences of missing screening or treatment appointments, and the need for long-term ophthalmic care. Verify the parents’ understanding of the information, and carefully document all educational efforts. Fill out the attached document, “Parents: Read This About Your Premature

Baby’s Eyes,” each time an infant is first screened or treated for ROP, and whenever the infant’s ROP status changes. Ask parents to read and sign the form, put the form in the chart, and give them a copy to take home (see sample letter). 8. Screen until both eyes have met the conclusion-of-acute-phase-ROP-screening criteria (Table 6). One examination is sufficient only if it unequivocally shows the retina to be fully vascularized in each eye. 9. See Table 7 for when to initiate treatment.10. Carefully document in the infant’s medical record your referral of any ROP patient to another physician (e.g., for treatment), and include the physician’s contact information. In addition, conduct and document all transfer of care discussions and forward to the second doctor documentation noting the indication and urgency of the referral, along with a copy of a record of the patient’s previous history and eye exams.11. SAFETY NET: Follow up on all changes in appointments. To ensure that missed appointments are noticed, instruct your staff to schedule the next appointment before the parents leave the office, and to update the tracking system. Do not rely upon the parents to schedule the follow-up appointments. Instruct your staff to review appointments on a daily basis, and to notify you immediately of any change in ROP appointments, including no-shows and cancelled or rescheduled appointments. Instruct staff on the type and urgency of follow-up needed (e.g., “Need to see baby tomorrow at the latest, call parents immediately”). The follow up should be tailored to the level of risk to the infant’s vision. Implement your ROP follow-up protocol for all of these schedule changes and document all follow-up efforts. Recommended follow-up efforts: 1) Instruct staff member to call same day of changed appointment. 2) Send “missed appointment” letter, with a copy to the baby’s pediatrician, if staff member doesn’t speak to parent, or parent is unwilling/unable to bring infant at designated interval. Letter should explain the urgency of the needed care and consequences of noncompliance (see sample “Missed ROP Appointment” letter). For further instructions, see OMIC “Noncompliance” guidelines (available in the Risk Management Recommendations section at www.omic.com). If the infant is at high risk for vision loss, send by regular and certified mail. 3) Notify the baby’s pediatrician of noncompliance by phone, and by faxing a copy of the letter to the parents, and document the discussion. 4) Consider contacting your state’s Child Protective Services office for extremely high risk infants who may meet treatment criteria at the time of the missed examination, or for treated infants with a suboptimal treatment response.OMIC policyholders who have additional questions or concerns about ROP are invited to call Anne M. Menke, R.N., Ph.D., OMIC Risk Manager, at (800) 562-6642, extension 651.

ELEMENTS OF A SAMPLE PROTOCOL/AGREEMENT FOR HANDLING ROP CARE IN THE HOSPITAL

To ensure the standardization, reliability, and effectiveness of ROP care, the ophthalmologist, neonatologist, and hospital need to have a written agreement or protocol that addresses:• Task assignments (see Table 1 for a summary)• The guidelines used to identify at-risk infants º The recently revised AAP/AAO/AAPOS Joint Statement, when available, provides an excellent summary of current research and recommendations• Identifying infants to be screened º Responsibility: neonatologist º See Table 3 for infants needing ROP screening examination• Dilating protocol: that clarifies drugs, dosages, RN administration

retina times 45

• Talking to the parents about screening the baby for ROP º Responsibility: • Neonatologist • NICU nurse• Scheduling the initial eye examination with the screening ophthalmologist º Responsibility: • Neonatologist to order initial examination • NICU to schedule and administer drops per dilating protocol º Based upon the infant’s postmenstrual age (gestational age plus chronologic age) º See Table 4 for timing of initial examination• Entering the baby into the ROP tracking system. Track infant

until 1) screening ophthalmologist verifies that both eyes have met conclusion-of-acute-ROP-screening criteria, 2) the treating ophthalmologist verifies that treatment and follow-up examinations are completed, or 3) NICU has scheduled initial appointment with screening or treating ophthalmologist at other hospital or in office

º Responsibility: NICU º The tracking system must be updated for each new baby, and after each screening or treating appointment• How the ROP examinations and treatments will be documented º Responsibility: screening and treating ophthalmologists º Use ICROP º See Table 2 for ICROP system. See Table 7 for how to classify pre-threshold ROP as Type 1 or Type 2 ROP.• Determining follow up interval after screening º Responsibility: Screening ophthalmologist by writing order in chart º See Table 5 for timing of follow-up examinations• Informing the parents of the results of the screening evaluation,

follow up interval, consequences of no follow up º Responsibility: • Neonatologist and NICU nurse talk to parents • Screening ophthalmologist completes letter for NICU to give to parent • See sample letter• The need to screen after pupillary dilation using binocular indirect

ophthalmoscopy until both eyes have met the conclusion-of-acute-screening criteria

º One examination is sufficient only if it unequivocally shows the retina to be fully vascularized in each eye º See Table 6 for conclusion-of-acute-phase-ROP screening criteria• Scheduling follow-up screening appointments in the hospital º Responsibility: NICU based upon order of screening ophthalmologist • Deciding when treatment for ROP is needed º Responsibility: Screening ophthalmologist º See Table 7 for when to initiate treatment• Informing the neonatologist about need for ROP treatment º Responsibility: Screening ophthalmologist (talk and progress note)• Informing the parents about the proposed ROP treatment º Responsibility: • Neonatologist (talk to parents) • NICU nurse (talk to parents) • Screening ophthalmologist (by phone and by completing letter that NICU gives to parents)• Finding an ophthalmologist to treat the ROP º Responsibility: Neonatologist or screening ophthalmologist by written order, depending upon protocol• Conducting and documenting a transfer-of-care discussion with the

treating ophthalmologist

º Responsibility: Screening ophthalmologist• Scheduling the treatment appointment with the treating

ophthalmologist º Responsibility: NICU based upon written order from neonatologist or screening ophthalmologist • Obtaining informed consent for the ROP treatment º Responsibility: Treating ophthalmologist • Use procedure-specific consent form that clarifies that even with treatment, some babies still develop retinal detachments and blindness, and that long-term follow up is required• Informing parents of results of treatment, need for follow up, and

consequences of no follow up º Responsibility: • Treating ophthalmologist (by letter given to parents by NICU) • Neonatologist (talk to parents) • NICU nurse (talk to parents)• Following the infant after treatment º Responsibility: Treating ophthalmologist by written order• Scheduling follow-up treatment appointments in the hospital º Responsibility: NICU based upon written order from treating ophthalmologist• Determining that the baby is ready for transfer/discharge º Responsibility: Neonatologist• Notifying the screening or treatment ophthalmologist that the infant

is ready for transfer/discharge º Responsibility: Neonatologist• Writing an ophthalmic consultant note prior to discharge/

transfer that summarizes ROP status and screening/treatment recommendations

º Responsibility: Screening or treating ophthalmologist, depending upon who is currently providing ROP care • If the ophthalmologist has evaluated or treated the baby very recently, no further note may be needed• Writing discharge/transfer orders that address ROP if the infant is

transferred/discharged before the screening ophthalmologist verifies that the retina has met conclusion-of-acute-phase-ROP-screening criteria or the treating ophthalmologist verifies that treatment and follow-up examinations are completed

º Responsibility: Neonatologist• Conducting and documenting a pre-transfer discussion with the

pediatrician who will be assuming role of primary care provider after transfer/discharge

º Responsibility: Neonatologist• Finding a screening or treating ophthalmologist at the other hospital

or in an office prior to transfer/discharge º Responsibility: Neonatologist and pediatrician, with recommendations when possible from the screening or treating ophthalmologist• Conducting and documenting a pre-transfer/discharge discussion

with the parents regarding the infant’s ROP status, follow up interval, and consequences of no follow up

º Responsibility: • Neonatologist (talk to parents) • NICU nurse (talk to parents) • Current screening or treating ophthalmologist (phone and letter, which the NICU gives to parents)• Scheduling the initial follow-up appointment after transfer/

discharge with the screening or treating ophthalmologist º Responsibility: NICU• Conducting and documenting a transfer-of-care discussion with the

new ophthalmologist º Responsibility: Current ophthalmologist

r>> RETINAL RISK MANAGEMENT

46 retina times

>> UNCLE RICH

William L. Rich, III, MDAAO Medical Director of Health Policy

ri

ch

Dear Uncle Rich:What is the story on our ability to buy retinal drugs in 2006? There have been so many changes in the past couple years in Medicare payment for drugs given in the office for ARMD: 95% of AWP (Average Wholesale Price), 85% of AWP, ASP (Average Sales Price) + 6%, etc., etc. This has been very disruptive to my practice and has resulted in large monetary losses because of our inability to collect co-payments for these expensive drugs! I am tired of acting as a billing agent for the pharmaceutical industry!! Is there any relief in sight? Overwhelmed in Oneida

Dear Overwhelmed:Relief is in sight. As part of the Medicare Prescription Drug, Improvement and Modernization Act of 2003 (a.k.a. MMA), Congress mandated that CMS establish a competitive acquisition program (CAP) for Part B drugs and biologicals administered in physicians’ offices. An initial proposal from CMS was going to limit the CAP program to 2-3 regions in the country and only deal with oncology. With ASP+6% payment, there was huge frustration in the retinal community with billing complexity and the financial risks being borne by retinologists. The AAO, working with George Williams and Reggie Sanders of the ASRS, strongly advised CMS to make the initial program national in scope and to include retinal drugs. In a final rule published this summer in the Federal Register, CMS agreed with our comments. As a result, in 2006 retinal docs may participate in CAP to obtain drugs like Visudyne from national vendors or continue to buy drugs directly from the manufacturer at ASP+6.

How is CAP going to operate? When a patient comes in and is determined to need the use of a retinal drug, the doctor will fax an order to the vendor. The vendor must supply the drug to the physician’s office within two business days for a routine service and one day for an emergency. The physician’s office must store the drug until

it is administered but it does not have to have separate physical storage from other pharmaceuticals. If state law permits and the drug is unused and unopened, the doctor may retain the drug and administer it to another patient after a new order is sent to the vendor. The retina doc must submit a claim to CMS for the drug administration service (67028 for intravitreal injections or 67221 for PDT) within 14 days of treatment. CMS will not pay the vendor for the drug unless they have received documentation from the doctor that the service was provided in the office. When a patient is seen in consultation in the office and it is deemed necessary to treat that same day, the retina doc may dispense the drug from inventory if: 1) the drugs are required immediately,2) the doc could not have known the drugs were needed prior to the visit,3) the vendor could not have delivered the drugs in a timely manner, and4) the drugs were administered on the same day as the consultation. The office must add a new modifier to the administration code if the drug is delivered as an emergency. If the doc has signed a CAP agreement and the emergency falls within these guidelines, a drug may not be delivered under direct purchase from the manufacturer under ASP. Once the vendor receives verification from CMS that you have administered the drug, they will proceed to bill Medicare and the patient/Medigap plan for the 20% co-pay. The vendor takes on all the financial liability of billing and collections.

Advantages:The physician is out of the drug business! You are no longer the middleman and have no more financial liability. There may be some retinal practices with a superb record of collecting all co-pays and they may want to forgo the CAP program and continue to purchase the drugs from the manufacturer at the ASP+6% price. However, informal surveys of retina specialists

showed an overwhelming preference for the establishment of a CAP program. Our ability to get CMS to change its original plans and include retinal drugs is a major victory for the profession. As of this date the CAP program will include verteporfrin (Visudyne), triamcinolone, bevacizumab (Avastin), and the IV solutions for Visudyne. Macugen did not have the minimum sales volume when the list of covered drugs was first published but the AAO and Eyetech approached CMS and we feel confident it will be included for 2006. Lucentis will not have approval in time for inclusion in 2006.

Disadvantages:The AAO has expressed concern about the billing of wastage under the CAP program. We hope to have this issue clarified by the time physicians decide on their participation. If you do elect to participate, you are locked into the chosen CAP vendor for one full year. Your staff should educate your patients that shortly after the delivery of the service they will be billed for the drug from the vendor. You will be responsible for verifying that the planned use of the drug is consistent with any relevant carrier coverage policies but this doesn’t preclude the use off label. If a patient fails to pay the vendor or requested financial assistance within 45 days from the postmark date of the vendor’s bill, the vendor may decline to ship more drug to the physician for that beneficiary.

Participation:Retinalogists will be asked to sign a CAP participation agreement and select a vendor.

In summary, there is some hope of sanity on the horizon after four years of chaos dealing with the acquisition of retinal drugs administered in the office. You will be notified of the specifics of CAP participation later this year in the AAO Washington Report and on the ASRS Message Board. Good luck. Hang in there.

Competitive Acquisition Program

retina times 47

>> MEDICAL ETHICS

Nancy M. Holekamp, MDSection Editor

retina times 49

As noted in the last issue, we had planned to bring you the “AAO Rules of Ethics” in this issue. It was decided instead to run the following article, due to its particular importance and timeliness. Part 2 of “Your Code of Ethics” will appear in a future issue.

Great strides in ophthalmology research are making headlines–but that is not necessarily good news. Reported in the Seattle Times on August 7, 2005 in an article entitled, “Drug Researchers Leak Secrets to Wall Street”: 1

“Recently, Citigroup Smith Barney penetrated a major study to see how an experimental drug fared against a just-approved drug for treating macular degeneration, an incurable eye disease and the leading cause of blindness in the elderly.

The brokerage talked to 26 eye doctors, but they weren’t just any doctors. Twenty of the 26 had researched the experimental drug; 23 of the 26 had researched the other one, meaning that more than half had worked on both. The doctors were able to give Smith Barney valuable comparative information.

Nearly all agreed that the drug still being studied, a product called Lucentis from biotech powerhouse Genentech, would prove vastly superior to the drug that recently had gone on the market, Macugen, made by Eyetech, a smaller company.

But the doctors were more explicit than that. Based on its survey, Smith Barney predicted remarkable results: 97 percent of patients on Lucentis would have stable or improved vision, as measured by how many lines of an eye chart they could read. Smith Barney summarized those findings in a report to select customers May 5.

As it turned out, the numbers were almost exactly on the money. On May 23, not long after Smith Barney’s report, Genentech announced results from its Lucentis study: 95 percent of patients had stable or improved vision–just as predicted by the doctors Smith Barney talked to.

The announcement battered Eyetech’s stock, which lost nearly half of its value in a day. Any hedge fund or other investor who had acted on Smith Barney’s research by betting against Eyetech would have made better than a 40 percent return in just three weeks.”

The ethical issue at hand is respect for confidentiality agreements. The 20 or 23 doctors involved in the clinical research on Lucentis and Macugen had undoubtedly signed confidentiality agreements with the respective pharmaceutical companies. In general, such documents will include something like the following:

“Except as otherwise expressly provided in this agreement, university (including investigator) shall keep the information confidential and shall not disclose to others either the information or any result of the discussions or evaluations.”2

Was there an unethical breach of confidentiality? We may never know. But what would entice intelligent researchers to divulge confidential information, even if unintentionally? The answer: physicians may get paid $200 - $1000 per hour to talk to investment firms. This is yet another financial conflict of interest for our profession. And ophthalmologists are not alone. A June 1, 2005 article in JAMA3 estimates that 10% of the 700,000 U.S. physicians receive payment from investment firms for their opinion. A “matchmaker” company, Gerson Lehrman boasts contractual agreements between over 60,000 physicians and roughly 50 investment firms. The Seattle Times article uncovered 26 instances where doctors leaked important details of ongoing clinical research to investment firms. In 24 of those 26 cases the firms then issued reports to select investment clients with advice to buy or sell a stock. Physicians serving as consultants to analysts for investment companies may be risky business. If it leads to divulging material information prior to public release, such ethical breaches of confidentiality agreements may be illegal. In the words of renowned ethicist Arthur Caplan, director for the Center of Bioethics at the University of Pennsylvania, “If this isn’t insider trading, I don’t know what is.” In response to the Seattle Times article, the American Association of Medical Colleges is urging its members to be aware that such communications may be governed by federal securities law and is recommending that agreements prohibiting disclosure of clinical trial information to third parties be scrupulously honored. Senator Charles E. Grassley, chairman of the Finance Committee, has called on the Justice Department as well as the S.E.C. to investigate the issue of payment for drug trial results. Genentech said it was too early to decide if it will take action against

Physicians as Investment Consultants:

Risky Business

FILESX-

Calvin A. Grant, MDSection Editor

>> THE ASRS X-FILES

All readers are cordially invited to submit a case for discussion and publication in the next X-files section. Please submit your entry to [email protected].

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 defectSlit Lamp Exam: Unremarkable both eyesDilated Funduscopic exam: Vascular constriction (greater than the appropriate age) both eyes, macula with RPE atrophy and hyperplasia, both eyes, OD>OS

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

the 20 doctors who reportedly discussed clinical trial results with Citigroup Smith Barney.

An editorial for the New York Times on August 17, 2005 suggests a solution:4

“The best antidote would be a pledge of abstinence backed by

the ethical guidelines of medical societies. Any doctor who has inside information about clinical trials or the F.D.A.’s thinking should not do consulting work for investment firms.”

So, when the next investment banking firm calls and offers $400 to discuss a clinical researcher’s impression of the latest treatments for macular degeneration, he or she may want to think about it and consider their prior contractual obligations.

References: 1. “Drug Researchers Leak Secrets to Wall Street”Seattle TimesAugust 7, 2005By Luke Timmerman and David Heathhttp://seattletimes.nwsource.com/html/businesstechnology/drugsecrets1.html

2. “Doctors’ Links With Investors Raise Concerns”New York TimesAugust 16, 2005By Stephanie Saul and Jenny Andersonhttp://www.nytimes.com/2005/08/16/business/16research.html

3. Topol EJ, Blumenthal D., Physicians and the Investment Industry,JAMA.2005;293:2654-2657http://jama.ama-assn.org/cgi/content/full/293/21/2654

4. Editorial: “When Doctors Advise Investors”New York TimesAugust 17, 2005Editorialhttp://www.nytimes.com/2005/08/17/opinion/17wed2.html

50 retina times

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.

>> MEDICAL ETHICS

CMS reimbursement for Macugen has been relatively uneventful compared to our previous history with Visudyne. Billing Medicare for the drug itself and the injection (CPT 67028) is not controversial; however, that is not all we do in following macular degeneration. Four areas of potential increased reimbursement need to be discussed; increased treatment frequency, diagnostic testing, combination treatment and same day examination. The study protocol for intraocular Macugen was treatment every 6 weeks. Medicare Carriers will reimburse for treatments according to “standard of care”. One issue that might trigger a review for medically unnecessary would be an injection that occurs in less than 6 weeks, or an increase in the total number of injections in a year, exceeding 9. The Medicare Carriers Cahaba, Noridian and Trailblazer have issued coding and billing guidance stating that they don’t expect subsequent injections to be less than 6 weeks apart. The Macugen studies did not use fluorescein angiograms or OCT to determine the need for each subsequent treatment. There are presently no medical coverage policies that prohibit angiography. In fact, First Coast Services of Florida and Connecticut allow for the potential use of an angiogram prior to each treatment. The rationalization is that this may be needed to monitor disease progression. Empire of New York has a draft policy that prohibits non-angiogram testing for follow-up injections. This is only a draft and is not ready to be enforced. Currently, there are no written national or Carrier policies prohibiting Medicare reimbursement for Macugen combined with other intraocular injections. This is more than just a reimbursement issue; it is a standard of care question. Medicare has a blanket prohibition against medically unnecessary services so the responsibility to defend combination use rests with the physician. Empire of New York has proposed a draft policy specifically stating that they won’t pay for combination Macugen (pegaptanib sodium injection) and Visudyne (verteporfin) treatments. Billing Medicare for an exam on the same day as a Macugen treatment may be open to interpretation. Intravitreal injections (CPT 67028) are defined as minor surgery; with no post-operative period. The relative value units for this minor surgery include the pre-operative and post-operative work done on that same day as treatment. If the purpose of the examination is only to determine

the need for the procedure then the same day evaluation is included in the payment. CMS will pay for this same day evaluation only when you and the carrier consider it a “significant and separate identifiable service” and you attach modifier 25 to the exam. Be careful to realize that even if you have been reimbursed that doesn’t mean you were paid appropriately. Your carrier can always ask for the money back if an audit determines you were paid incorrectly. The Office of Inspector General has listed the inappropriate use of modifier 25 as a target for investigation. Several carriers have ruled on this problem with written policies. The initial evaluation requiring intraocular Macugen and resulting in same day treatment allows for a reimbursable exam. Subsequent exam/treatments are a different story. Cigna has written that, “review of previous treatment’s effectiveness is not a separate service.” Empire of New York writes “evaluation of the effect of a prior injection is not considered a separate identifiable service.” The Medicare Carrier for Kansas, Nebraska and northwest Missouri has a written policy on macular degeneration and photodynamic therapy; “if a problem distinct from macular degeneration and OPT is addressed then modifier 25 should be attached.” However, this scenario is not the typical “one time” surgery that CPT originally described. A significant and separate evaluation may be necessary considering the progressive nature of macular degeneration. After all, study protocols only answer a specific question and are not meant to be a substitute for the practice of medicine. The point is that your local CMS Carrier may be the limiting factor for reimbursement. There is no Carrier written policy that limits reimbursement when following the explicit guidelines outlined in the Macugen label. Your changes to this protocol may be “reasonable and necessary” if the carrier’s policy has no additional limitations and they agree to your definition and assumptions for the specific patient being treated. Macugen therapy is still relatively new to the CMS bureaucracy; Empire of New York is the only carrier to suggest such specific restrictions but more could follow. Their draft policy can be implemented only after a public comment period. Now is the time to be vigilant checking your own Carrier’s website and join the political process. Speak out when you see draft policies that are not allowing you the discretion to decide what is in your patient’s best interest.

Mark Levitan, MDDirector, Carrier Network

>> CARRIER NETWORK

Billing Macugen– and what else?

retina times 51

This may seem like an unlikely topic, but it is one that has much to do with how we as ophthalmologists are paid. The RBRVS (Resource Based Relative Value System) pays us on the basis of several factors–the physician work, the practice expense, and the practice liability (malpractice insurance) risk. The practice expense is based on the specific practice expense items related to the particular code (use of an exam lane, cost of ophthalmic tech, cost of the laser, etc.) and is also based on the overall practice expense of ophthalmology. Based on the SMS survey of practice expense in many specialties of medicine and surgery previously performed by the AMA, the practice expense for ophthalmology is one of the highest in medicine and surgery, running at about $140 per hour. Each code we bill for Medicare patients is associated with a physician time (the time the doctor expends in supplying the service, e.g. 92014 Comprehensive eye, established patient, is 39 minutes, and 67107 Scleral buckle is 298 minutes for all surgery and post-op visits). Thus CMS (Center for Medicare and Medicaid Services) can take all codes submitted by ophthalmologists on Medicare patients for a year, and add up all of the minutes eye MDs have spent with Medicare patients. CMS then multiplies the number of hours eye MDs spent with Medicare patients and multiplies that by the ophthalmology practice expense per hour (about $140) and that number represents the value of the ophthalmology practice expense pool. Then this expense pool is used to pay the practice expense portion of all the codes performed by ophthalmologists. Why is such an arcane bit of information of value to a retina specialist? Well, the Five Year Review is currently underway. This is a congressionally mandated process where CMS reviews a number of codes to see if there has been a significant change in the value of services in the last five years. A number of ophthalmology codes have been submitted including vitrectomy with membrane peeling, panretinal laser photocoagulation, fluorescein angiography, extended ophthalmoscopy, and, significantly–cataract surgery. Why do I include cataract? Well, cataract may be the most important of the lot to all of us. Currently cataract surgery is credited with 50 minutes of intraservice time (skin to skin time). By the time you read this, the data will all be in, but if the intraservice time for a phaco is reduced say to 30 minutes, then with almost 2 million Medicare cataracts performed in a year, there would be 20 min X 2 million, 67,000 fewer hours @ $140/hr less spent on Medicare patients. That one little change would mean almost $100 million less in the ophthalmology practice expense pool. This decline would be spread over all of the eye codes, meaning about $5,000 less to each ophthalmologist solely based on the impact of potential reduction of time of cataract surgery on our practice expense pool. The whole process of code valuation and reimbursement is complex and often not apparent on the surface. Over the last fifteen years of working with coding and reimbursement, I have learned unfortunately that we are not paid fairly. I have labored to try to prevent wholesale cuts in our reimbursements, and have tried to

help strategize how to avoid specific cuts. Guys and gals, there is no free lunch out there. We are not going to get special treatment and be paid better than others. I personally feel there is little doubt that physicians are greatly underpaid. Because of the SGR (sustainable growth rate formula which is used to calculate the conversion factor which CMS employs to calculate reimbursement for each code and to penalize us for increased utilization) we are currently scheduled to suffer a 1.5% reimbursement cut beginning in January of 2006. This is in the face of our costs going up all the time with more expensive equipment and supplies, higher rent, and of course we all gave our staffs 3% or greater raises last year. Patients mostly feel doctors are overpaid (they look at the billed charges on the EOB, but usually fail to look at the amount Medicare or the insurance company actually pays.) Whenever I deal with a disgruntled patient, or more frequently a corporate CEO who is dealing with selecting health insurance for his company, or when dealing with legislators or with patients working in the media, I give them a three minute course in health care finance. I point out that our ‘charges’ are irrelevant. We get paid virtually the same by Medicare and private insurance. Those without insurance seldom pay, and rarely pay above Medicare allowable. Thus physician fees are controlled. I then say if they need to go to the hospital for surgery, the hospital reimbursement is set by DRGs. There is a zone of medical expense which is truly ‘free trade’, the sector including drugs and expendable supplies (pacemakers, stents, catheters, devices). I then point out the average Medicare patient spends more out of pocket for their medications than for all physician and hospital services combined. I then urge them to speak to or write to their Congressmen about this. In summary, cuts are likely to come partially based on some diminution of the ophthalmology practice expense pool, and further losses are predicted for next year based on a declining Conversion Factor. The system is unfair to all physicians, and I am afraid the only hope will come through legislation. My friends, the onus is on you. Your future and your well being as a physician depend on it. Talk or write to your congressmen and ask your patients to contact them also.

Trexler M. Topping, MDSection Editor

X-FILES DISCUSSION (continued from page 50)

The patient presents in an interesting manner. The CME and the vascular constriction make the possibility of a primary retinal degeneration a possibility. Other entities have to be entertained including AZOOR as well as other post-inflammatory entities. The patient was given Diamox 250mg sequels P.O. BID with the vision increasing to the 20/30 range. I believe other entities such as Stargardt’s disease are less likely given the presentation of edema. Input from all would be welcome regarding this fascinating case.

>> CODING TIP

52 retina times

The Time Has Come

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

One of the Foundation’s major efforts includes the goal of fostering the exchange of information between retinal specialists, their patients and other health care specialists. With this goal in mind, the Foundation invites opportunities for future projects that involve a relationship between the physician, patient and retina specialist, including patient awareness campaigns and other educational initiatives.

AMD Patient Education ProjectThe Foundation recently received an educational grant from Alcon Laboratories to fund an AMD campaign focused on the importance of ocular vitamin therapy for patients with moderate to severe risk of AMD. In October 2005, a select test market of ophthalmologists in Phoenix, AZ

and Tampa, FL will receive AMD Patient Education Kits that contain a DVD, brochure, recipe cards, Amsler grid, and a coupon for vitamins. A four month local PR campaign will coincide with the kit distribution, followed by a survey and follow-up calls to recipients for feedback. Kits will be revised based on the feedback received and then sent out nationally, at which time ASRS members will also receive kits.

Pediatric Training CD-ROMIn addition to the AMD patient kit campaign, The Foundation has also recently become a joint sponsor for a pediatric eye CD that will be

distributed to pediatricians. This interactive video disc describes common pediatric eye diseases and eye examination techniques for infants and toddlers and will be released later in the year. Our focus in this project has to do with the early recognition of retinoblastoma.

Foundation Activities at the ASRS Annual MeetingEach year, the ASRS selects one fellow to receive The Fellow Travel Grant, funded by the ARF. Kartik Patel, MD, from Houston, TX was awarded this year’s Travel Grant at the meeting.

Congratulations to Joseph L. Wilhelm, MD, from East Lansing, MI, 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.

Roy Levit, MDAmerican Retina Foundation Chairman

>> FOUNDATION UPDATE

This year’s silent auction raised $23,575 for the Foundation. The ARF gratefully acknowledges and thanks all ASRS members for their participation, as well as the companies who donated the items up for bid. The winners, items, and companies who donated are listed below:

SILENT AUCTION WINNERSUmberto Albanese, MD, Snyder, NYLaserex Laser Elbow Pads, five sets Sheldon P. Braverman MD, San Antonio, TXVolk Disposable Chalam Direct View® Steryl® Flat SSV Vit Lens, one box

John Carver, MD, Provo, UT Labtician Wong Buckling Forceps

Lenin Gomez, MD, Guadalajara, MexicoAAO Basic and Clinical Science Course Section #12: Retina and Vitreous

Roy Levit, MD, New York, NYTwo night stay in a Junior Suite at the Fairmont Queen Elizabeth Hotel, Montreal, Quebec

Sanjay Logani, MD, Northridge, CAVolk Digital Wide Field Diagnostic Ophthalmic Lens

G. Matthews, MD, Ft. Worth, TXAlcon Greishaber DSP Instruments, three boxes

Kenneth Moffat, MD, Nashville, TN Millennium Leather Roller Compu-Brief donated by OccuLogix

Pablo Munoz Rodriguez, Guadalajara, MexicoBausch & Lomb Millennium™ Photocoagulating Green LaserSynergetics 09.05 Low Mass Pick Forceps and 10.01 Vertical Scissors

Jeffrey S. Taylor, MD, Raleigh, NCAAO Ophthalmic Coding Coach 2005

Tanu Thomas, MD, Chicago, ILCutter & Buck leather wine tote donated by Priority Healthcare

Paul Weishaar, MD, Wichita, KS Two night stay at the Hotel del Coronado, Coronado, CA

CONTRIBUTING COMPANIESAlcon Laboratories, Inc.American Academy of OphthalmologyBausch & LombCompass Management & Consulting, Inc.Fairmont Queen Elizabeth HotelGulden OphthalmicsHotel del CoronadoLabticianLaserexOccuLogixPark West GalleryPriority HealthcareSynergetics, Inc.Volk Optical, Inc.

>> JCAHPO NEWS

Judy E. Kim, MDSection Editor

retina times 57

American Retina Foundation Update

Macular Degeneration Research Fellow AwardBeginning in 2006, the Foundation will award a fellow $2,000 for the best macular degeneration poster at the ASRS Annual Meeting. More information about this award will be available soon.

retina times 59

>> AAO LIAISON REPORT

ASRS selected by AAO as Outstanding Coalition Partner The Academy announced the selection of the American Society of Retina Specialists as an Outstanding Coalition Partner at the Partners in Advocacy Reception, held in conjunction with the 2005 Mid-Year Forum last April. This honor was bestowed in recognition of the ASRS’ contribution as a society to the Surgical Scope Fund.

Optometric Scope of Practice and YouYou may be wondering why our Society’s contribution to this fund is important. You likely are not alone, as many vitreoretinal specialists have considered themselves to be above the optometrist-ophthalmologist fray. The Surgical Scope Fund provides monies to aid the AAO as it strives to address optometric scope of practice initiatives–whereby optometry gains the privilege of practicing ophthalmology by legislation versus education and training. Though you may be aware of initiatives in the area of general/comprehensive ophthalmology, you may not be aware that optometric scope of practice has the specialty of vitreoretinal diseases and surgery in its sights. There is an optometric retina society–the ORS (http://optometricretinasociety.org/). In Oklahoma, for example, optometrists are moving to add Macugen to their injectable privilege list, not to mention attacks in other states. Look for more on this in upcoming issues of The Retina Times.

Pay For Performance (P4P)Relief has finally been proposed for problems with the Medicare fee schedule. As is true in politics, something has been requested in return. That “something” is in the form of what is known as the Pay for Performance initiative–P4P for short. Congressional leaders are developing legislation that would tie a 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. CMS recently announced the success of their current hospital P4P program in improving quality of care with over 98 percent of hospitals voluntarily participating. 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 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.) The Starter Set of Ophthalmology Performance Measures includes 8 preliminary measures, based on input from all the societies. They include:1. Counseling on importance of blood sugar control and monitoring of HgAlc in patients with diabetes mellitus.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 open angle suspect, or measurement was already recorded in their medical record.4. Counseling and education about medication adherence for the patient with glaucoma.5. Documentation of optic nerve appearance (by stereo photography, optic nerve head analysis or drawing) for a patient with glaucoma or glaucoma suspect.6. Consideration of causes of visual impairment other than cataract in the prognosis presented to the patient candidate for cataract surgery.7. Questioning the patient about his/her visual function (includes a review of the patient’s self-assessment of visual status and visual needs; for a candidate for cataract surgery, this would include questions about difficulties reading, difficulties in driving, and other activities of daily living).8. A 5% solution of povidone-iodine for the purpose of infection

prophylaxis provided in the preoperative period for intraocular surgery. The Academy will submit at least two or three measures for review by the AMA Physician Consortium for Performance Improvement and the National Quality Forum. Review will involve more complex evidence-based measures, and is likely to be a rigorous process requiring considerable time and effort for measurement definition, development and approval. AAO Liaison representatives from all three vitreoretinal subspecialties will be consulted in this process.

Practicing Ophthalmologists Curriculum (POC)In the past two years, the Knowledge Base Panels (now known as the Practicing Ophthalmologists Curriculum (POC) Panels) have worked to prioritize topics according to clinical relevancy, develop outlines on Most Relevant topics, and come to agreement on the appropriate content that should be included, incorporating input from our society and other reviewers (ABO and AAO Self-Assessment Committee). The Chair of the Retina/Vitreous Panel is Travis Meredith, M.D. The POC will serve as knowledge base for ophthalmologic credentialing examinations. Version 1.0 of the Practicing Ophthalmologists’ Curriculum will be launched on the Academy’s website in October 2005. A MOC Review Course is planned for July 2006 to review the curriculum for MOC candidates. In addition, the revision of the Practicing Ophthalmologists’ Curriculum, to be known as Version 2.0, will occur by January 2006. All of the existing information will be reviewed for currency, and new information will be added as appropriate. There will be a rotation of 2-3 members off of each panel at the end of this year, in order to maintain continuity and to bring new members into the process as we begin working on Version 2.0. There will be an emphasis on including time-limited certificate holders among the new members rotating on to the panels.

ADVERTISER INDEX

Alcon Laboratories, Inc. 1Alcon Laboratories, Inc. 58Alcon/Grieshaber 61Bausch & Lomb 53Dutch Ophthalmic, USA 48Eyetech / Pfizer Ophthalmics 54Genentech 35Insight Instruments, Inc back coverLabtician Ophthalmics, Inc. 17MedOne 22Novartis 41Ophthalmic Imaging Systems 5Quantel Medical 9

Antonio Capone, Jr., MD AAO/Federal Affairs Liason

Next year’s ASRS practice management seminar will take place in the Spring, 2006 in Orlando, Florida. Comprehensive retinal coding will comprise the Saturday session and for Sunday, various practice management issues will be presented. Look for more details on the ASRS website (www.retinaspecialists.org) in October. Hope to see all of you there.

>> PRACTICE MANAGEMENT MEETING

G. Philip MatthewsSection Editor

ASRS members and organizations that are planning a meeting, course or similar event of interest to retinal specialists are invited to list the event in the “The Retinal World.” Meeting listings are free and published on a space-available basis as a service to ASRS members. Listings will be listed and linked at the ASRS Website:www.retinaspecialists.org.

Send meeting information including sponsor, course director, contact name, phone, fax, and e-mail/website to: American Society of Retina Specialists, PMB #A, 2485 Notre Dame Blvd., Suite 370, Chico, CA 95928;fax to 530-566-9192; or e-mail [email protected].

2005

October 12005 Washington Retina SymposiumWashington, DCThe St. Regis HotelCourse Directors: Mohammed K. Barazi, MD, Daniel M. Berinstein, MD, Michael H. Osman, MDContact: Mohammed K. Barazi, MDPhone: (703) 421-0931Fax: (703) 421-7206E-mail: [email protected]

October 14-15Retina 2005: Changing Concepts and Controversies(AAO Retina Subspecialty Day)Chicago, ILMcCormick PlacePhone: (415) 561-8500Fax: (415) 561-8535E-mail: [email protected]: www.aao.org/aao/annual_meeting/subspecialty/retina.cfm

October 15-182005 American Academy of Ophthalmology Annual Meeting Chicago, IL Phone: (415) 561-8500Fax: (415) 561-8535E-mail: [email protected]: www.aao.org

October 30-31Workshop with International Faculty: Retinal and Vitreous SurgeryHangzhou, ChinaSponsor: University of Tuebingen, Prof. Ingrid KreissigContact: Jing WangPhone: +86-571-8721-4083Fax: +86-571-8721-4128E-mail: [email protected]: www.kreissig.uni-hd.de

November 19Advanced Retinal TherapyVienna, AustriaHotel IntercontinentalSponsor: Alcon LaboratoriesCourse Directors: Ursula Schmidt-Erfurth, MDChristoph Scholda, MDContact: Andrea HiermannPhone: +43 1 5966970 17Fax: +43 1 5966970 11E-mail: [email protected]: www.artvienna.at.tt

2006

January 14-1610th Annual American Uveitis Society Winter SymposiumVail, COVail Marriott Mountain Resort & SpaProgram Chairman: Russell N. Van Gelder, MD, PhDContact: Karen Baranick, Medical Conference Planners, Inc.Phone: (914) 722-0664Fax: (914) 722-0465E-mail: [email protected]: www.medconfs.com

January 15-20Retina 2006Held in conjunction with Hawaiian Eye 2006 Maui, HIGrand Wailea Resort & SpaContact: Registration Manager at SLACK IncorporatedPhone: (877) 307-5225 (US/CN only), (856) 848-1000 E-mail: [email protected].

January 27-296th Annual Retinal Fellows’ ForumChicago, ILWestin River North Program Chairmen: Carl C. Awh, MD, Tarek S. Hassan, MD, David R. Chow, MDContact: Karen BaranickMedical Conference Planners, Inc.Phone: (914) 722-0664Fax: (914) 722-0465E-mail: [email protected]: www.medconfs.com

February 9-12The 25th Annual Squaw ValleyRetinal SymposiumOlympic Valley (Lake Tahoe), CAThe Resort at Squaw CreekCourse Directors: Rob Wendel, M.D., Reece Landers, M.D.Contact: Laura WendelTel: (916) 483-6299Fax (916) 483-6297E-mail: [email protected]: www.squawvalleyretina.com

February 17-18Twentieth Annual Sarasota Vitreo-Retinal Update CourseSarasota, FLRitz-Carlton HotelContact: Sherrie Colangelo Phone: (941) 921-5335Fax: (941) 921-1741E-mail: [email protected].

Feb. 19-24XXX International Congress of OphthalmologyHeld in conjunction withXVI Panamerican Congress of OphthalmologyXXXIV Brazilian Congress of OphthalmologyThe World Congress Of The 150,000 OphthalmologistsSão Paulo - BrazilE-mail: [email protected]: www.ophthalmology2006.com.br

March 5-1034th Annual Aspen Retinal Detachment Society MeetingSnowmass (Aspen), COSnowmass Conference Center at The Silvertree HotelProgram Chairman: Donald J. D’Amico, MDContact: Karen BaranickMedical Conference Planners, Inc.Phone: (914) 722-0664Fax: (914) 722-0465E-mail: [email protected]: www.medconfs.com

March 25Rush Retina Update: New Drugs & Devices for Retinal DiseasesChicago, ILContact: Jennifer Cruz, Education Coordinator at Rush University Medical Phone: (312) 563-2302E-mail: [email protected]

March 30-April 26th International Symposium on Ocular Pharmacolgy and Therapeutics (ISOPT)Berlin, GermanyContact: SecretariatKenes BuildingAirport City 70151, P.O.Box 56Ben-Gurion Airport 70100, IsraelTel: +972 3 9727510 Fax: +972 3 9727555E-mail: [email protected]: http://www.kenes.com/isopt/

April 22-23Frankfurt Retina Meeting 2006Städtische Kliniken Frankfurt am Main-HöchstGotenstraße 6 - 8, D-65929 Frankfurt am MainProgram Chairman: Claus Eckardt, MDContact: Anne-Marie Ebert, AugenklinikPhone: ++49 (0)69 3106-2972Fax: ++49 (0)69 3087938E-mail: [email protected]: www.eckardt-frankfurt.de

April 24Retinal and Vitreous SurgeryEkaterinburg, RussiaScientific Contact: Ingrid KreissigLocal Organ.: Oleg ShilovskikhPhone: + 7 343 2406292Fax: + 7 343 2403370E-mail: [email protected]: [email protected]

April 30 - May 42006 ARVO Annual MeetingGreater Fort Lauderdale/Broward County Convention CenterFort Lauderdale, FLContact: Ellyn Terry, Director of Meetings and EducationPhone: (240) 221-2935E-mail: [email protected]: www.arvo.org

May 31 - June 3Retinal Physician Symposium 2006Current Concepts in Retinal MedicineAtlantis Paradise Island, BahamasPhone: (800) 549-3656Web: www.RPS2006.com

May 20New Developments in Retina: Trials, Drugs and New Techniques Cleveland, OHContact: Jane Sardelle at Cole Eye Institute, Cleveland Clinic Foundation Phone: (216) 444-2010E-mail: [email protected]

June 24-25 Retinal and Vitreous SurgeryQingdao, ChinaScientific Contact: Ingrid KreissigLocal Organ.: Xiaoguang DongPhone: 0086-532-8587-6483Fax: 0086-532-8589-1110E-mail: [email protected]: [email protected]

June 29-July 1VII International Symposium on Ocular TraumaRome, ItalyContact: Francesca GalilE-mail: [email protected]: www.forlinicesare.com/

September 9-1324th Annual Meeting of the ASRS6th Annual Meeting of the EVRSCannes, FranceWeb: www.retinaspecialists.org www.evrs.org

November 11-142006 American Academy of Ophthalmology Annual Meeting Las Vegas, NVPhone: (415) 561-8500Fax: (415) 561-8535E-mail: [email protected]: www.aao.org

2007

December 1-525th Annual Meeting of theAmerican Society of Retina SpecialistsMaui, HIWeb: www.retinaspecialists.org

>> THE RETINAL WORLD

Upcoming Meetings for the Retinal Specialist

Suzanne Demming, MDSection Editor

Retina Fellows’ ForumJanuary 27-29, 2006Westin Chicago River NorthChicago, ILCourse Directors: Carl C. Awh, MD, Tarek S. Hassan, MD, David R. Chow, MD

The American Society of Retina Specialists is pleased to announce its support of the Sixth Retina Fellows’ Forum, an all-expenses-paid meeting for eligible North American vitreoretinal fellows in their final year of training. During this intensive day-and-a-half of education, invited speakers will present topics of universal interest to the beginning retinal specialist. The goals of the Fellows’ Forum are to provide a review of current vitreoretinal treatments, to allow fellows to meet and interact with their peers, to encourage research, and to introduce fellows to industry. All fellows in attendance will receive a number of valuable gifts, as well as a chance to receive the American Retina Foundation’s Travel Grant. In addition, the winner of the Bausch & Lomb Fellows’ Research Award will be announced. This award includes free registration and travel support for the winning fellow to present his or her paper at the Annual Meeting of the American Society of Retina Specialists. The ASRS thanks Bausch & Lomb Surgical as the major corporate sponsor of the Retina Fellows’ Forum and applauds their support of retinal fellows’ education.

For further meeting information please contact Karen Baranick at (914) 722-0664 or by email at [email protected].

>> FELLOWS’ FORUM

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