RETINA

TIMESThe Official Publication of the American Society of Retina Specialists

Fall 2012 Issue 46 46 RETINA TIMES

Boston, MA Retina Times (ISSN 2164-4411) is published 5 times a year Editor-in-Chief Suber S. Huang, MD, MBA by the American Society of Retina Specialists (ASRS) San Francisco, CA [email protected] President, Foundation of the ASRS as a service to its membership. Cleveland, OH Susan Raef, MSMC Managing Editor G. Baker Hubbard, III, MD The mission of the publication is to strive to be the definitive Chicago, IL Pediatric Retina Section Co-Editor information source for ASRS members on Society news, [email protected] Atlanta, GA meeting plans, socioeconomic topics, international news, and Ana Schedler J. Michael Jumper, MD other relevant information on issues, instruments, and study Graphic Designer PAT Survey Section Editor San Francisco, CA updates for the practicing retinal specialist. Toby Zallman Production Artist Peter K. Kaiser, MD Schedler Brennan Design + Consulting ASRS-AAO Councilor Representative Articles published herein are reviewed by the editor-in-chief Chicago, IL Cleveland, OH and managing editor for editorial content only. The accuracy Oonagh Petrizzi Stacy Kiff of information contained is the responsibility of the individual Proofreader Annual Meeting Section Editor author. Letters and other unsolicited material are assumed to be Stamford, CT Chicago, IL intended for publication and are subject to rejection or editing. John T. Thompson, MD William T. Koch, COA, COE, CPC ASRS President Coding Pitfalls Section Editor Baltimore, MD St. Louis, MO All articles which appear in Retina Times are intended for Gaurav K. Shah, MD informational purposes only and should not be relied on by Mathew W. MacCumber, MD, PhD ASRS Communications Committee Chair ASRS-AAO Councilor Representative any reader for any other purpose. The opinions and positions St. Louis, MO Chicago, IL expressed in Retina Times articles are solely those of Jill F. Blim, MS Charles W. Mango, MD the authors and do not represent the opinions or positions ASRS Executive Vice President E-Retina Section Editor of the American Society of Retina Specialists Board of Chicago, IL New York, NY Directors, members, employees, or Retina Times editorial John R. Minarcik Jr, MD, CDR, MC, USN Section Editors staff and volunteers. Retina in the Military Section Co-Editor Michael M. Altaweel, MD Fairfax, VA Literature Roundup Section Co-Editor Funding for Retina Times is provided by advertisements Robert A. Mittra, MD Madison, WI PAT Survey Section Co-Editor contained within. Carl C. Awh, MD Minneapolis, MN Fellows’ Forum Section Editor Prithvi Mruthyunjaya, MD Nashville, TN Retina Education Section Co-Editor Jerald A. Bovino, MD Durham, NC Jerry’s Wisdom Section Editor Joel Pearlman, MD, PhD Aspen, CO Retina Genetics Section Co-Editor Marcus H. Colyer, MD, MAJ, MC, USA Sacramento, CA Retina in the Military Section Co-Editor Dante J. Pieramici, MD Bethesda, MD What’s News Section Editor Zélia M. Corrêa, MD, PhD Santa Barbara, CA Ocular Oncology Section Co-Editor P. Kumar Rao, MD 20 North Wacker Drive, Suite 2030 Cincinnati, OH Uveitis Section Editor Chicago, IL 60606 Pravin U. Dugel, MD St. Louis, MO Research & Development Section Editor phone: 312-578-8760 Carl D. Regillo, MD Phoenix, AZ KOL Corner Section Editor www.asrs.org Nicholas E. Engelbrecht, MD Philadelphia, PA Pediatric Retina Section Co-Editor © 2012 American Society of Retina Specialists. David Rhee, MD St. Louis, MO Road Test Section Editor Philadelphia, PA All rights reserved. No part of this publication may be reproduced or Philip J. Ferrone, MD Site Selection Section Editor transmitted, in any form, without the prior written permission of the William L. Rich III, MD Great Neck, NY American Society of Retina Specialists. AAO Medical Director of Health Policy Mitchell S. Fineman, MD Falls Church, VA Block Time Section Co-Editor <_dWdY_Wb
:_iYbeikh[i
Eh]Wd_pWj_edWb
IjW\\ SriniVas R. Sadda, MD Philadelphia, PA Ocular Imaging Section Editor Dr. Jumper – COVALENT MEDICAL, INC: Equity Owner, Stock; Dutch Brett T. Foxman, MD Los Angeles, CA Ophthalmics USA: Speaker, Honoraria. Film Festival Section Editor Ms. Blim – None. Ms. Raef – None. Ms. Schedler – None. Ms. Zallman – None. Michael A. Samuel, MD Northfield, NJ In the Spotlight Section Editor Ms. Petrizzi – None. K. Bailey Freund, MD Pasadena, CA X-Files Section Editor Dr. Thompson – GENENTECH: Investigator, Grants; REGENERON Reginald J. Sanders, MD New York, NY PHARMACEUTICALS, INC: Investigator, Grants; PFIZER, INC: Practice Management Meeting Section Editor Chevy Chase, MD Investigator, Grants. Sunir J. Garg, MD Block Time Section Co-Editor Chirag P. Shah, MD, MPH Philadelphia, PA Dr. Shah – ALCON LABORATORIES, INC: Consultant, Equipment Clinical Trials: Future Pathways Section Co-Editor Boston, MA (department or practice); ALLERGAN, INC: Consultant, Equjpment Omesh Gupta, MD, MBA Retina Education Section Co-Editor (department or practice); QLT, INC: Consultant, Equipment (department Marc J. Spirn, MD Philadelphia, PA or practice); DORC: Consultant, Equipment (department or practice). KOL Corner Section Co-Editor Larry Halperin, MD Philadelphia, PA Retinomics Section Editor Asheesh Tewari, MD Ft. Lauderdale, FL Literature Roundup Section Co-Editor On the Cover J. William Harbour, MD Detroit, MI Intraretinal neovascularization associated with Ocular Oncology Section Co-Editor Trexler M. Topping, MD Miami, FL Tea Leaves Section Editor macular fibrosis in Coats disease, courtesy Tarek S. Hassan, MD Boston, MA J. Michael Jumper, MD. Road Test Section Editor Kang Zhang, MD, PhD Royal Oak, MI Retina Genetics Section Co-Editor San Diego, CA CONTENTS >> Photo courtesy J. Michael Jumper, MD

Color photograph corresponding to the angiographic image on the cover. The macular fibrosis is associated with an intraretinal vascular anastamosis and neovascularization.

7 FROM THE PRESIDENT 20 INTERNATIONAL CORNER 42 THE KOL CORNER ASRS Version 3.0: Moving the Bringing the International Retina Wet AMD: The Changing Landscape Vision Forward Community Together 44 RETINA PRACTICE PEARLS 22 RETINOMICS 8 FOUNDATION UPDATE Foundation Seeks Volunteers in 4 Key Areas The Patient Protection and 46 BLOCK TIME Affordable Care Act: 2010-2012— How Has the Retina Subspecialty Changed 9 FROM THE EDITOR’S DESK a Curmudgeon’s Report Card Since Vitrectomy? A Special Thanks to Our Active-Duty Military Retina Specialists The ACA Opens the Door to Health 50 JERRY’S WISDOM Coverage for Millions Everybody Is Sellin’ Somethin’ 10 FILM FESTIVAL 26 ASRS SYMPOSIUM Film Festival Honors Winners from Clinical Trials ‘Unplugged’— 51 TEA LEAVES 5 Countries Part 1: Applying AMD Trial Results Concierge Retina—That’s What We to Clinical Practice Already Provide!

ASRS 30TH Anniversary 33 RETINA IN THE MILITARY 52 THE ASRS X-FILES Serving in Afghanistan: 3 Deployed Retina Specialists Share Their Stories 53 LITERATURE ROUNDUP 12 ASRS 30th ANNUAL MEETING HIGHLIGHTS NEW 38 POINT/COUNTERPOINT 56 X-FILES SOLUTION ASRS Celebrates 30th Anniversary at Annual Meeting Point: Scleral Buckling Has a Continuing 57 ADVERTISER INDEX Role in Repairing Retinal Detachment

16 CLINICAL TRIALS: Counterpoint: Most Primary Retinal FUTURE PATHWAYS Detachments Can Be Repaired With Understanding Time-to-Event Analysis a Vitrectomy

4 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | FROM THE PRESIDENT >>

John T. Thompson, MD President, ASRS ASRS Version 3.0: Moving the Vision Forward

I am honored to serve you as I begin my term as the 18th president of the ASRS, and I look forward to helping the Society advocate on behalf of retina specialists. As you know, we just celebrated our 30th annual meeting in Las Vegas—an outstanding event with record attendance of nearly 1000 retina specialists. (For a recap of the meeting, including photos, please see page 12.)

This year’s gala dinner and Umbo Lounge Our Society’s first 2 administrators, Dee addition to a much larger annual meeting at the Haze Nightclub were as memorable Smith (Roy’s secretary) and Jerry Lewis (Allen’s and ancillary conferences such as the practice as the 1999 Rome meeting gala, which office manager), were focused primarily management and masters meetings. featured chariots, Roman centurians, and on admitting new members, processing dues, attendees wearing togas. (The togas were and organizing the annual meetings. The 7IHI
)$&0
?cfb[c[dj_d]
j^[
Kirk Packo’s idea.) 2 accomplished much, even though Jerry ijhWj[]_Y
]hemj^
fbWd worked out of her home and the membership The field of retina has changed substantially David Williams, president from 2008 to 2010, records were kept on file cards. The Vitreous since the first ASRS meeting in 1983. Being a recognized that the ASRS infrastructure Society was granted ACCME accreditation retina specialist 30 years ago meant spending was limiting the Society and needed to during Jerry Lewis’ tenure, and it was under about half of your time in the OR and seeing change if we wished to implement many of her leadership that a club became a society some patients in the office for preop/postop our members’ great ideas. He assembled a with 1400 members. visits and laser treatments. Vitreous surgery committee of leaders and future leaders early was relatively new, and the early Vitreous The first Vitreous Society meeting I attended in his presidency. Their mission: to develop Society meetings were devoted mostly to was in 1992 at the Ritz-Carlton, Laguna a strategic plan to take advantage of our sharing surgical techniques and insights Niguel in Dana Point, California, an idyllic increasing size and influence. about new indications for vitrectomy. cliff-side resort overlooking the Pacific Ocean. I brought my family to another The recent advent of anti-VEGF agents for Vitreous Society meeting at the Ritz-Carlton ‘ Today, I am assuming choroidal neovascularization, venous occlusive in Aspen, Colorado during the summer of disease, and diabetic macular edema has been the presidency of 1994 and realized this group knew how to the most transformative change in retina since ensure a great time for my family as well the development of vitreous surgery. All of our an organization as me. (The meeting itself was pretty good, practices are adapting to the new paradigm where too.) One afternoon, all attendees went with substantially most of our time is spent in the office seeing whitewater rafting on the Colorado River more patients and less time is spent in the OR. improved capacity and we enjoyed dumping buckets of water I have titled my first column “ASRS Version on nearby members’ rafts. for managing change.’ 3.0” to highlight where our Society has come from and what we hope to accomplish in the 7IHI
($&0
;nfWdZ_d]
m_j^
A multiyear plan was formulated to move next few years. W
d[m
dWc["
W
m_Z[h
iYef[ ASRS forward. This required a major Cordie Miller became our executive director improvement in the capabilities of ASRS that 7IHI
'$&0
BWkdY^_d]
Wd
after the 2000 Annual Meeting in Cancun, was made possible when Jill Blim was hired as _dYbki_l[
h[j_dW
ieY_[jo Mexico, and opened the first Vitreous Society our executive vice president in 2010. The first few Vitreous Society meetings were office in Chico, California. She helped the The ASRS headquarters moved to Chicago organized by founders Jerry Bovino, Roy Vitreous Society to evolve into the American and the organization quickly outgrew its office Levit, and Allen Verne with an emphasis on Society of Retina Specialists by moving space. Suber Huang implemented many new collegiality and informality. In the mid-1980s, many Society activities online and managing initiatives during his presidency, including the idea of a retina meeting where any retina an organization that became larger and integrating the Foundation with ASRS and specialist could attend was a novel one—pre- more complex. overseeing development of an enhanced dating the AAO Retina Subspecialty Day— By 2002, the scope of ASRS had increased ASRS website, new educational initiatives, and the organization grew from 3 founders to include The Vitreous Society Times (now redesigned ASRS/Foundation logos, and the and 44 charter members as word spread Retina Times) published 4 times a year, in Retina Image Bank. within the retina community.

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 7 FROM THE PRESIDENT >>

Today, I am assuming the presidency of an outstanding Executive Committee consisting through reimbursements. I wish to safeguard organization with substantially improved of Tarek Hassan, Mark Humayun, John the power of patients to make medical capacity for managing change. I visited the Pollack, Tim Murray, and Carl Awh. decisions based on the best advice from new, larger ASRS office this summer and can Suber Huang has completed his term as their physicians. assure you that Jill has assembled a talented president, but he is not leaving us. He has staff to improve the Society’s ability to expand The vitreoretinal specialty was virtually agreed to serve as president of the Foundation existing programs and initiate new ones. unknown by the Centers for Medicare & of the ASRS and will be expanding the role ASRS has grown from 1 full-time employee Medicaid Services and private insurers in of the Foundation in physician and patient in the summer of 2010 to 7 today. Chicago the past; however, the advent of expensive education as well as in philanthropic work. is a great place to find experienced people pharmaceuticals has increased their desire to to staff medical organizations, as many have Educating our members will require more understand the growing costs of retina care headquarters in this area. than just gathering at an annual meeting. and ultimately to manage them. We are also We plan to produce more online educational working more closely with our members The fiscal conservatives among you will content and will promptly apprise you of around the world with a new International question how we can afford such growth. the latest developments in the treatment of Affairs Committee to understand how ASRS used to subcontract many services to retinal diseases. We’ve had great meetings in ASRS can help them and how international external vendors, but now most of those the past and will organize even better ones in members can enhance our Society. functions have been moved in-house. The the future. new ASRS employees also help with many I certainly don’t know what ASRS will look other important activities throughout the The changing needs of our members will like in 10 years for its 40th anniversary, but I year, further increasing the Society’s ability require ASRS to take a more active role in will work diligently to help move it forward. to work for you. protecting retina specialists and patients in Please email me at [email protected] if you a rapidly changing health care environment. have ideas that will help me to serve you better Staff support is especially important with the Our new Retinal Advocacy and Federal Affairs as your president. Society’s increasing reliance on work Committee (RAFA) will increase our efforts by committees, as we are fortunate to have in the socioeconomic arena with federal and many talented members who have offered state government, as well as with insurers Financial Disclosures their skill and time. I will be working with an :h$
J^ecfied – GENENTECH: Investigator, Grants; who try to regulate the practice of medicine REGENERON PHARMACEUTICALS, INC: Investigator, Grants; PFIZER, INC: Investigator, Grants

FOUNDATION UPDATE >> Foundation Seeks Volunteers

Suber S. Huang, MD, MBA in 4 Key Areas President, Foundation of the American Society of Retina Specialists

As I write my first column as President of the sThe Corporate Fundraising Committee Our Foundation is at an advantage because Foundation of the American Society of Retina will increase the number and type of corporate we are focused on things that matter most to Specialists (FASRS), I am reminded of the donors as well as the level of contributions. donors. We are guided by a well-defined list many positive changes the Foundation has of projects, so contributors will know exactly sThe Member Fundraising Committee recently undergone. We have a new name and where their support dollars are going. will establish a culture of philanthropy and a new branding that exemplify our synergy will increase the number of contributions with the ASRS. We have a new mission as 8[Yec[
W
kWd] – SEQUENOM: Advisory Board, Honoraria; SECOND SIGHT: Consultant, Honoraria; NOTAL VISION: is to build our leadership team to assist us in The committees will educate the public on our Consultant, Honoraria; BAUSCH+LOMB: Advisory Board, achieving these goals. We are now actively recruit- specialty, identify new revenue streams, and Honoraria; ALCON: Speaker, Honoraria ing members for the following committees: build a solid infrastructure for ASRS projects.

8 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | FROM THE EDITOR’S DESK >>

J. Michael Jumper, MD Editor-in-Chief A Special Thanks to Our Active-Duty Military Retina Specialists

All ASRS members know that retina specialists almost always become When on duty at their military medical center in the United States, involved with any case of globe trauma. What you may not know is that these vitreoretinal surgeons are incredibly busy with the most complex ocular trauma accounts for approximately 13% of all injuries due to trauma repairs on soldiers evacuated from the battlefield. There have modern armed conflict. been many important publications over the past decade describing injury patterns, surgical techniques, and outcomes of the many eye Considering that there have been nearly 50,000 injuries to American injuries during this time. One such publication (co-authored by our soldiers engaged in Operation Enduring Freedom in Afghanistan (2001-present) and Operation Iraqi Freedom (2003-2008), military retina specialists have been very busy. The stories of 3 recently deployed ‘Our current military ophthalmologists military retina specialists are featured on page 33. Their experiences have been remarkable. have risen to the challenges brought I joined the United States Air Force as a retina specialist in 1998, during on by the horrible epidemic of ocular the same month that the US Embassies in Kenya and Tanzania were attacked, leaving 258 dead and 5000 injured. A small fraction of those trauma resulting from the wars in with eye injuries were evacuated to US military hospitals. The mean Iraq and Afghanistan.’ time to initial evaluation by an ophthalmologist was 4 days; the time to initial globe rupture repair was 5 days; and the time to intraocular foreign body (IOFB) removal was 9 days. I, along with others, worked to decrease the time to definitive ophthal- mic surgery by developing a rapidly deployable, self-contained surgical unit. A year later, as a part of a humanitarian mission and joint military exercise, I was performing vitreous surgery in a small village in Camer- oon using equipment we checked onto a commercial airliner. This was pre-9/11. Imagine checking an argon laser as your carry-on today!

‘ [O]cular trauma accounts for approximately 13% of all injuries due to modern armed conflict.’

Of course, September 11, 2001 changed everything. The residents I Maj Mike Jumper, MD, USAF, performing vitrectomy and lensectomy in Garoua, Cameroon in 1998. worked with in San Antonio, Texas at Wilford Hall Medical Center and Brooke Army Medical Center became part of the first wave of oph- thalmologists to be deployed to Iraq and Afghanistan. Now, 11 years Retina in the Military Section Editor, Marcus Colyer) relates the experi- later, many advances have allowed injured soldiers to receive definitive ence at Walter Reed Army Medical Center during the height of the care sooner. In the case of the conflicts in Iraq and Afghanistan, conflict in Iraq from 2003-2006. They treated 523 eyes in 387 soldiers, ophthalmologists have become an important part of the trauma teams 198 of which were open-globe injuries. at the hospitals in theater. Our current military ophthalmologists have risen to the challenges The 3 retina specialists featured in the story on page 33—Maj Darrell brought on by the horrible epidemic of ocular trauma resulting Baskin, MD, USAF; Capt Steve O’Connell, MD, USN; and LCDR Bryan from the wars in Iraq and Afghanistan. I am proud to have worked Propes, MD, USN—represent the latest of the vitreoretinal surgeons with some of them. I think I can speak for the ASRS when I offer my who have served in the United States military since the “war on terror” gratitude and appreciation for their efforts. began in 2001. When overseas, these retina specialists are called on to be comprehensive ophthalmologists in the greatest sense of the word. For the local civilians, allied soldiers, and adversaries with an eye Financial Disclosures :h$
@kcf[h – COVALENT MEDICAL, INC: Equity Owner, Stock; Dutch Ophthalmics USA: problem, if they can’t do it, it won’t get done. Speaker, Honoraria.

| Issue ** | Volume )&, Number 2 | Summer 2012 | retina times | 9 FILM FESTIVAL >>

Brett T. Foxman MD Chair, ASRS Film Festival Film Festival Honors Winners from 5 Countries

The 14th Annual ASRS Film Festival featured 37 outstanding films from Society members around the globe, with topics ranging from vitrectomy to vitreous humor. If you missed the 30th ASRS Annual Meeting in Las Vegas, you can view the films at http://meeting.asrs.org/Film-Festival/Films.

We sincerely thank the 45 judges who spent many Use of Perfluoron for Large-Volume hours watching, reviewing, and grading the films Vitreous Biopsy—Or, How We Learned for the 9 Rhett Buckler Awards presented at the From Aesop’s Crow Annual Meeting’s gala dinner. After the meeting, Pauline T. Merrill, MD (Oak Park, Illinois); we also presented the new Doctors’ Choice Award Renaud Duval, MD, FRCSC (Chicago, Illinois); based on voting from ASRS members. Kirk H. Packo, MD, FACS (Chicago, Illinois) If you would like to be a judge for next year’s Surgical Management of Myopic Traction Film Festival, please email chayal.patel@asrs. Maculopathy (Myopic Foveoschisis) org. It’s not too early to start thinking of ideas Sung Pyo Park, MD, PhD; Gregory Chang, for the 2013 Annual Film Festival in Toronto. BA; Gonzalo A. Sepulveda Moreno, MD; and Stanley Chang, MD (all of New York, (&'(
H^[jj
8kYab[h
7mWhZ
M_dd[hi New York) A New Technique for Safe, Atraumatic BEST OF SHOW Removal of Intraocular Foreign Bodies Post-Traumatic Aniridia: Artificial Iris Jeffrey L. Olson, MD; and Douglas L. Combined With IOL Implantation MacKenzie, MD (both of Aurora, Colorado) Cesare Forlini, MD (Ravenna, Italy) Scleral-fixated IOL Using a 25-Gauge Needle The winning films earned the coveted Rhett Buckler “Vitreoschisis”—Live! Scleral Tunnel Award, an impressive 8-pound, 24-carat-gold-plated statuette custom-sculpted by RS Owens & Company, Malhar Soni, DO, MS, DNB, FRCS Phoebe Lin, MD, PhD; and Sharon Fekrat, MD, manufacturer of the famous Oscar. (London, England) FACS (both of Durham, North Carolina) The True Nature of OCTs Sutureless Scleral Fixation of a Gilles Desroches, MD, FRCSC Dislocated Three-Piece Intraocular Lens Jersey); Harold M. Wheatley, MD (Edison, (Ottawa, Canada) Jonathan L. Prenner, MD (Lawrenceville, New New Jersey); and Leonard Feiner, MD, PhD (Teaneck, New Jersey) OutVITing the Humor: The Art of PVD Induction Manish Nagpal, MD, FRCS; Navneet Mehrotra, DNB; and Siddharth Bhardwaj, MS (all of Ahmedabad, Gujarat, India)

DOCTORS’ CHOICE AWARD

Endoscopic Vitrectomy in Pediatric Vitreo- retinal Diseases: Improving Visualization and Outcomes S. Chien Wong, MBBS, FRCSEd(ophth), MRCOphth (Los Angeles, California)

Financial Disclosures: Dr. Foxman – GENENTECH: Investigator, Other Financial Film Festival winners Gilles Desroches, MD, FRCSC; Jeffrey L. Olson, MD; Pauline T. Merrill, MD; Renaud Duval, MD, FRCSC; Benefit; REGENERON PHARMACEUTICALS, INC: Investiga- Manish Nagpal, MD, FRCS; Cesare Forlini, MD; Sung Pyo Park, MD, PhD; and Film Festival Chair Brett T. Foxman, MD. tor, Other Financial Benefit.

10 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | ASRS 30TH Anniversary HIGHLIGHTS >>

@e^d
J$
J^ecfied"
C: IjWYo
A_\\ ASRS Scientific Program Chair ASRS Director of Education ASRS Celebrates 30th Anniversary at Annual Meeting

On August 25-29, nearly 1000 retina specialists from around the world gathered at the Aria Resort in Las Vegas for the 2012 Annual Scientific Meeting. The 30th anniversary conference presented 149 scientific papers, 155 posters, 23 instructional courses, 37 films, and a full array of social events.

Incoming ASRS President John Thompson, MD, and his wife, Mary Ann; ASRS President John Thompson, MD, (right) congratulates Harry Flynn Jr, MD, Pyron Award winner Daniel Martin, MD, and his wife, Pam; outgoing President co-author of the winning AMD poster, “Management of Submacular Hemorrhage Suber Huang, MD, MBA; Gloria Sternberg; Emily Chew, MD; and keynote speaker Secondary to Neovascular Age-Related Macular Degeneration With Anti-Vascular Paul Sternberg, MD. Endothelial Growth Factor Monotherapy.” The Foundation grant was awarded to poster author Gary Shienbaum, MD; other co-authors included Carlos A de A Garcia-Filho, MD; and Philip J. Rosenfeld, MD, PhD.

)&j^
7ddkWb
C[[j_d]
>_]^b_]^ji
Conference, featuring 26 clinical presenta- Suber Huang, MD, MBA, presented the tions. Saturday night concluded with a Founders Award to David Parke II, MD, for IWjkhZWo0
IkXif[Y_Wbjo
h[l_[mi"
welcome reception at the Aria Resort. excellence in vitreoretinal medicine. Retina Case Conference John Kitchens, MD, head of the Young The ASRS 30th Annual Meeting opened on IkdZWo0
Iocfei_W"
WmWhZi
Y[h[cedo Physicians Section, presented the Crystal Saturday afternoon with uveitis, glaucoma, Sunday’s activities started at 6:00 AM with Apple Award to Dean Eliott, MD. Outgoing and neuro-ophthalmology subspecialty the Foundation’s 6th Annual 5K Indoor/ Foundation President Mark Hammer, MD, reviews. Narsing Rao, MD, noted infectious Outdoor Run/Walk for Retina. Nearly 60 presented the Foundation Report, and uveitis entities not to miss: treponema runners and walkers participated in the Retina Image Bank Curator Suber Huang, pallidum (syphilis), tuberculosis, fundraising event. MD, MBA, presented the Retina Image toxoplasmosis, and herpetic infection, as Bank Report. The Foundation grant was well as masquerade syndromes such as The scientific symposia began Sunday awarded to Gary Shienbaum, MD, for the primary intraocular lymphoma. morning after opening remarks by Program Chair and incoming President best AMD poster. Rohit Varma, MD, MPH, pointed out that a John Thompson, MD. In the AMD I The morning concluded with a presenta- diagnosis of chronic open-angle glaucoma Symposium, presenters Zohar Yehoshua, tion of the 2012 ASRS Preferences and is determined by optic nerve damage and MD, MHA, and Philip Rosenfeld, MD, PhD, Trends (PAT) Survey by Survey Editor glaucomatous visual fields, not by IOP level. noted that COMPLETE study results show J. Michael Jumper, MD. Results showed Anthony Arnold, MD, gave an entertaining systemic complement inhibition with that 67% of US and Canadian respondents review of specific neuro-ophthalmic eculizumab anti-C5 antibody does not slow follow a treat-and-extend protocol in conditions, including optic neuritis, the progression of dry AMD nor reduce managing wet AMD, whereas International nonarteritic anterior ischemic optic drusen volume. members see patients monthly and treat neuropathy, arteritic AION, “Viagra blind- At Sunday’s awards ceremony, John as needed. Complete PAT Survey results— ness,” and optic nerve sheath meningioma. Thompson, MD, presented Daniel Martin, as well as multi-year trending data—are available at www.asrs.org/asrs-community/ Drs. Carl Awh, William Mieler, and Richard MD, the Pyron Award for his outstanding pat-survey. Spaide moderated the Retina Case contributions to knowledge about vitreoretinal disease. Outgoing President

12 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | Nearly 60 early risers participated in the Foundation’s 6th Annual Indoor/Outdoor Run/Walk for Retina, held at the Aria Resort and Crystals at CityCenter Las Vegas.

RETINAWS panelists. Front row: Alay Banker, MD; Ehab El-Rayes, MD, PhD; Women in Retina Case Conference organizers Alice Lyon, MD; Jennifer Lim, MD; moderator Kourous Rezaei, MD; José Garcia Arumi, MD. Back row: Mathew and Pauline Merrill, MD. MacCumber, MD, PhD; George Williams, MD; Homayoun Tabandeh, MD; ASRS Past-President Kirk Packo, MD.

Sunday afternoon began with the Macular that telemedicine screening is effective Monday’s symposia also included Ocular Surgery I Symposium. Presenter Emmanuel at identifying patients who need Oncology and Retinal Surgery I. The Chang, MD, PhD, reported on his retrospec- further examinations. evening concluded with social events tive study of all patients who underwent including the wine and cheese reception, bilateral macular hole surgery between In the Socioeconomic Sessions, Wiley new member/International Delegate 1985 and 2011. He reported an incidence of Chambers, MD, who has worked for the reception, Young Physicians Section bilateral macular holes of 3.1%, with a 3:1 FDA for 25 years, gave an overview of the dinner, and the Fellows-in-Training female-to-male ratio. The study concluded FDA drug approval process. He noted that Section dinner. that the outcomes of bilateral macular the biggest reason that a pharmaceutical holes are excellent with the indocyanine product is not approved by the FDA is that Tuesday: Instructional courses, gala dinner green-assisted ILM peeling technique. no one submitted an application. Tuesday morning began with symposia on Trauma/Pharmacology, Inflammation, and Afternoon sessions also included the The AMD II Symposium presented Infections. Harry Flynn Jr, MD, reported Imaging Symposium, Retinal Vascular rapid-fire papers on initial experiences that after studying the recent endo- Symposium, and the Women in Retina with aflibercept. Presenter Allen Ho, MD, phthalmitis outbreak following intravitreal (WinR) Case Conference. reported on the 96-week results of the injections in South Florida, the CDC and VIEW 1 and VIEW 2 studies; 2457 patients the Florida Health Department studies Monday: Scientific sessions, social events were randomized to ranibizumab 0.5 mg confirmed Streptococcus mitis/oralis Monday morning began with the Diabetic q4 weeks, aflibercept 0.5 mg q4 weeks, contamination of the bevacizumab as the Retinopathy I Symposium. Ingrid Zimmer- aflibercept 2.0 mg q4 weeks, or aflibercept most likely source of the outbreak. Galler, MD, reported on a study in which 2.0 mg q8 weeks. In the second year, she and her colleagues imaged 1151 patients patients were treated PRN with a minimum At the AMD III Symposium, Tarek Hassan, with a remote non-mydriatic camera to test of quarterly aflibercept injections. There MD, presented the results of a patient the feasibility of a telemedicine screening was a similar treatment effect in all 4 treat- questionnaire showing that retina program. They found that 25% had diabetic ment arms, with a faster fluid resolution in surgeons and industry representatives retinopathy and 41% had non-diabetic the 2.0 mg aflibercept arms. underestimate patients willingness’ retinopathy ocular findings, suggesting

| Issue 46 | Volume 30, Number 4 | Fall 2012 | retina times | 13 HIGHLIGHTS >>

At the third annual “Unplugged” Symposium, physicians and investigators discussed the real-world implications of clinical trial results. Panelists included (l-r): Peter Kaiser, MD, Jeffrey Heier, MD, Jay Duker, MD, David Boyer, MD, and moderator Pravin Dugel, MD. In foreground: Panelist William Mieler, MD.

Allen Verne, MD, and Jerry Bovino, MD, 2 of the Society’s founders, offer a toast Incoming President John Thompson, MD, enjoys the welcome reception with to the ASRS’s 30th anniversary at the gala dinner. ASRS co-founder Roy Levit, MD, and ASRS Board Member and Retina Times Tea Leaves Section Editor Trexler Topping, MD. to continue intravitreal injections indefi- š
Challenge the Masters, moderated by continued at the Aria’s Haze Nightclub nitely to maintain their vision. Calvin Mein, MD with performances by dancers, aerialists, and magicians. The Retinal Surgery II Symposium featured š
Anterior Segment Surgery for the Timothy Murray, MD, MBA, describing how Vitreoretinal Surgeon: Discussion and Wednesday: Symposia, wrap-up MIVS 23-gauge pars plana vitrectomy Wetlab, led by Carl Awh, MD In the Macular Surgery II/Anterior Segment can effectively manage complex retinal Surgery Symposium, Maziar Lalezary, MD, detachments in eyes having undergone š
Vitreous Manipulation with reported baseline findings on the 125-iodine brachytherapy for uveal Ocriplasmin, by Michael Trese, MD Prospective Retinal and Optic Nerve Vitrec- melanoma. Nearly half (48%) achieved tomy Evaluation (PROVE) study. PROVE is a š
Pneumatic Retinopexy: Pearls and a visual outcome of 20/40 or better. 5-year longitudinal analysis of eyes undergo- Pitfalls, by Emmanouil Mavrikakis, MD, PhD ing unilateral pars plana vitrectomy (PPV) to Sophie Bakri, MD, organized the Special š
RETINAWS: When the Going Gets evaluate long-term outcomes compared with Interest Group luncheons featuring casual Tough, the Tough Get Going: the non-vitrectomized fellow eye. Patients roundtable discussions on a variety of Challenging Cases in Vitreoretinal undergoing routine PPV for epiretinal conditions, treatments, and procedures. Surgery, by Kourous Rezaei, MD membrane, macular hole, or vitreous opacity may have unidentified risks for glaucoma at Tuesday afternoon featured 23 instruc- š
High-Stakes Vitrectomy: Vitreoretinal baseline, specifically narrow angles, found in tional courses, a few of which included: Surgery in Inflamed Eyes, by 13%, and abnormal visual fields, found in 18%. š
The Third Annual ASRS Research and Thomas Albini, MD The AMD IV Symposium featured Christine Development Committee Symposium: Tuesday evening concluded with the 30th Gonzales, MD, reporting on a Phase I study Clinical Trials “Unplugged”—Real, anniversary gala dinner and Umbo Lounge, targeting tissue factor with a single dose of Practical Questions and Answers, featuring opening remarks by ASRS founders intravitreal hI-con1 for wet AMD. In the study, led by Pravin Dugel, MD (see page 26) Jerry Bovino, MD, and Allen Verne, MD. Brett just one injection demonstrated safety and š
Newer Advances in Vitreo-Retina Foxman presented this year’s Film Festival biologic activity—regression of choroidal Surgeries: Tools and Techniques, by winners (see page 10), and the celebration neovascularization, reduced OCT thickness, S. Natarajan, MD

14 | retina times | Fall 2012 | Volume 30, Number 4 | Issue 46 | The wet lab provided hands-on instruction. Cesare Forlini, MD, of Ravenna, Italy, winner of the ASRS Film Festival’s Best of Show Award, enjoys the festivities with Carl Awh, MD; Dr. Forlini’s daughter-in- law Caterina Benatti, MD; his son Matteo Forlini, MD; and Philip Ferrone, MD.

Dean Eliott, MD, winner of the Crystal Apple Award, and John Kitchens, MD, Reginald Sanders, MD; Adrienne Scott, MD; and William Rich III, MD attend the ASRS Board member and head of the Young Physicians Section. wine and cheese reception in the exhibit hall. and improved vision. HI-con1 is a novel reporting that initial experience shows oral MD; Jeremiah Brown Jr, MD, MS; Mina Chung, agent that binds tissue factor, leading to rifampin was found to have an apparent MD; Pouya N. Dayani, MD; Nicholas E. Engel- natural killer cell destruction of abnormal therapeutic effect on patients with central brecht, MD; Mitchell J. Goff, MD; Judy E. Kim, vascular endothelial cells. serous chorioretinopathy. MD; Tamer H. Mahmoud, MD, PhD; Andrew A. Moshfeghi, MD, MBA; Prithvi Mruthyunjaya, In the Pediatric Retina Symposium, Following the Wednesday morning sym- MD; Joel Pearlman, MD, PhD; Polly A. Quiram, Audina Berrocal, MD, FACS, demonstrated posia, John Thompson, MD, concluded the MD, PhD; Chirag P. Shah, MD, MPH; Michael A. the importance of digital fluorescein meeting just before noon. Singer, MD; Asheesh Tewari, MD; and Robert angiography-guided laser treatment for W. Wong, MD. various pediatric retinal diseases including 7jj[dZ[[i
hWj[
j^[
c[[j_d]
^_]^bo
Coats and FEVR. She noted that wide-field Evaluations by more than 400 FbWd
je
Wjj[dZ
(&')
7ddkWb
C[[j_d]
angiography is especially good at detect- attendees showed: in Toronto ing areas of capillary dropout. Mark your calendar for the 31st Annual š
//
mekbZ
h[Yecc[dZ
j^[
c[[j_d]
Meeting, August 24-28, 2013, at the Sheraton to their colleagues. The Diabetic Retinopathy II Symposium Centre Toronto. The ASRS Annual Scientific featured Elliott Sohn, MD, presenting the š
/-
iW_Z
j^[
c[[j_d]
^[bf[Z
_dYh[Wi[
Meeting has earned its place as the premiere outcomes of pars plana vitrectomy for confidence in their ability to do their job. educational event for retina specialists. tractional retinal detachment secondary Beginning in January 2013, online registra- to proliferative diabetic retinopathy. The š
/'
m_bb
cWa[
Y^Wd][i
_d
fhWYj_Y[
Wi
W
tion and abstract submission will be available 10-year data on 240 eyes of 203 patients result of the knowledge or skills gained at www.asrs.org/annual-meeting. Questions? showed that 12% of patients had a through the meeting. Contact ASRS Director of Education combined traction/rhegmatogenous retinal Stacy Kiff at [email protected]. detachment; 6.3% required reoperation, If[Y_Wb
j^Wdai
je
ekh
f^oi_Y_Wd
h[fehj[hi and 1.3% required enucleation. Retina Times thanks the physician reporting Financial Disclosures: team who gathered the news for the daily The Instrumentation/Pharmacology Dr. Thompson – GENENTECH: Investigator, Grants; REGEN- email updates at the Las Vegas meeting: ERON PHARMACEUTICALS, INC: Investigator, Grants; PFIZER Symposium featured Zac Ravage, MD, Thomas M. Aaberg Jr, MD; Kevin J. Blinder, INC: Investigator, Grants. Ms. Kiff – None.

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 15 CLINICAL TRIALS: FUTURE PATHWAYS >>

Desmond E. Thompson, PhD DES Enterprises Chirag P. Shah, MD, MPH Jeffrey S. Heier, MD New Hope, Pennsylvania Section Co-Editor Section Editor Understanding Time-to-Event Analysis

Time-to-event analysis is often used in s#ANMULTIPLECAUSESOFTHEEVENTBETAKEN group B. When the data are viewed medical, epidemiological, and sales research. into account? with regard to time-to-event, it is clear that Survival analysis—or more generally, time- s(OWDOPARTICULARCIRCUMSTANCESOR there is a substantial treatment advantage not to-event analysis—is of interest when the data characteristics increase or decrease the odds revealed by the initial analysis based represent the time to a defined event. of being event-free? on proportions.

While well-established in oncology and Interpreting rates vs proportions Perhaps the simplest way to evaluate time-to- cardiology, time-to-event analysis has not been event analysis is to examine the ratio of the widely applied to ophthalmology research, The following hypothetical example illustrates rates. This is often called the hazard ratio or possibly because the data are usually collected some key concepts in time-to-event analysis. the relative risk.!RATIOOFMEANSTHEREISNO intermittently rather than continuously, and )NIT PATIENTSWITHWET!-$ARERANDOMLY DIFFERENCEBETWEENTHETREATMENTGROUPS! because of the awkwardness of interpreting ASSIGNEDTOTREATMENTGROUPS!PATIENTS RATIOOFGREATERTHANOFTREATMENT!TREAT- treatment effect in survival terms. However, and B (10 patients) and will be followed ment B (and all members of the confidence this method is an interesting approach for for 360 days. The outcome of interest is the interval are >1) supports the hypothesis that analyzing time to elevated IOP, absence of fluid, incidence of gaining 10 or more letters on the THERATEINGROUP!ISGREATERTHANTHATIN gain of 15 or more letters, or loss of 5 letters. %4$23SCALEDURINGTHESTUDY GROUP"!RATIOSUPPORTSTHEHYPOTHESIS THATTHERATEINGROUP!ISLESSTHANTHERATEIN Time-to-event analysis can address the !SSUMETHATTHETREATMENTGROUPSARE group B. If the confidence interval of the ratio clinically relevant question of who improves balanced at baseline as to outcome-influencing contains 1, one cannot rule out equality of the sooner (eg, gain of 15 or more letters) or characteristics. In each treatment group, rates in the 2 treatment groups. who gets worse earlier (eg, loss of 5 or there were 5 events. Thus, the proportion more letters). Such analysis uses data from experiencing the event is 50% in each group Understanding Kaplan- all time-points to define the likelihood of and the relative risk = 50%/50% or 1. Meier curves getting better or worsening throughout the Is it correct to infer that the treatments entire assessment period. These data can then The usual method of analyzing binary data were equally effective without knowing be used to quantify and test the difference is to compute the simple proportion of when the events occurred? Figure 1 shows that between 2 or more therapies. those with the event of interest at the end INTREATMENTGROUP! THEEVENTSOCCURRED of the study and compare these proportions Time-to-event analysis attempts to answer at 30 days (2 patients), 60 days (1 patient), BETWEENTHEORMORETREATMENTGROUPS!S questions such as: and 90 days (2 patients). One patient discon- noted earlier, this method ignores the time tinued the study at day 50. In treatment s7HATFRACTIONOFAPOPULATIONWILLBEEVENT at which the events occur and can lead to group B, the events occurred at 300 days free past a certain time? erroneous conclusions. (1 patient), 330 days (2 patients), and at s!TWHATRATEWILLTHOSEWHOAREEVENT FREE 360 days (2 patients). One patient discontinued There is a method that uses proportions, at a given time experience the event in the study on day 60. The total time at risk yet takes into account the time of event and the future? INGROUP!X X X X the fact that not all patients can complete 360x4 = 1790 days at risk. THESTUDY!TEACHVISITDURINGACLINICALTRIAL patients are assessed for the presence or The event rate equals the total number of absence of the event. For example, did the Kaplan-Meier curves events divided by the total time at risk, or patient gain 10 or more letters? The cumula- 5/1790 (0.0028 events per day or 2.8 events š

M_bb
WbmWoi
jh[dZ
kfmWhZÆWi
j^[
tive incidence of the event is computed using per 1000 days at risk). The total time at risk l[ho
Z[Ód_j_ed
e\
YkckbWj_l[
a special method called the product-limit _dY_Z[dY[
ik]][iji
INTREATMENTGROUP"X X formula. The resulting curves provide Kaplan- X X XDAYSATRISK š

9Wd
Wbie
Yheii"
Wi
mWi
i[[d
_d
j^[
-EIERESTIMATES4HESTEPSINTHECURVESOCCUR The event rate is 5/3180 (0.0016 events per :_WX[j[i
9edjheb
WdZ
9ecfb_YWj_edi
only when there is an event at the visit. Jh_Wb
:99J "
m^[h[
j^[h[
mWi
Wd
day or 1.6 events per 1000 days at risk). Thus, [Whbo
mehi[d_d]
e\
h[j_defWj^o
_d
j^[
the ratio of the rates is 2.8/1.6 = 1.75. The +APLAN -EIERMETHODOLOGYATTEMPTSTOESTI- ]hekf
jh[Wj[Z
m_j^
_dj[di_l[
j^[hWfo
simple interpretation would be that patients mate the cumulative incidence at each point

š

I^em
ZWjW
Yedi_ij[dj
m_j^
W
YedijWdj
INTREATMENTGROUP!WERETIMESMORE during the follow-up period. These curves are h[bWj_l[
h_ia
eh
^WpWhZ
_d
ceij
likely to gain 10 or more letters than patients a simple means to visualize the cumulative YWi[iÆjhWdibWj_d]
_dje
W
kd_\ehcbo
in treatment group B. incidence of an event, enabling one to see if _dYh[Wi_d]
i[fWhWj_ed
X[jm[[d
j^[
there is evidence of an early effect and—more )TCANBESEENTHATALLTHEEVENTSINGROUP! AWfbWd#C[_[h
Ykhl[i
important—to estimate the difference in the occurred earlier in the study than those in effect between groups.

16 | retina times | Fall 2012 | Volume 30, Number 4 | Issue 46 | Kaplan-Meier curves are presented in 2 ways: other in a statistically meaningful manner. The method most often used for this purpose Three steps to evaluate time-to- 1. A downward-trending plot displays the is the log-rank test, based on comparing the event analysis proportion of patients free of the event (see observed data with the expected data. Figure 2A on page 18). This proportion will, 1. A figure of course, decline over time. If the log-rank test identifies a significant
š
KikWbbo
AWfbWd#C[_[h
Ykhl[i difference between the curves, methods are
š
I[fWhWj[
fbej
\eh
[WY^
]hekf 2. An upward-trending plot shows the cumula- needed to quantify it. The Cox proportional 2. A test of whether the curves are tive proportion of patients experiencing the hazard model is widely used to calculate the different event by time (see Figure 2B on page 18). relative hazard (ratio of rates). The difference š
J^[
be]#hWda
j[ij
fheXWXbo
j^[
between the curves can be reported with a most widely used statistic called the hazard ratio, with confi- š
J[ij
cWa[i
l[ho
\[m
Wiikcfj_edi


about the data ‘ The Kaplan-Meier dence intervals to show its precision and a test of significance to determine the likelihood 3. The means to quantify the risk reduction method computes the that any difference is due to chance. š
9en
fhefehj_edWb
^WpWhZ
ceZ[b

expected proportion normally used M^o
_i
Y[dieh_d]
ki[Z5



š
J
his procedure requires having an event at some assumptions Patients not followed long enough for the the end of the study. event to occur have their event times censored can take that into account. In evaluating the at the last follow-up. One reason for censoring difference between curves, it is assumed that This is not exactly the is that patients cannot be followed forever. the censoring pattern is random and the same At some point, the study must end and not same as the observed in both treatment groups. all people will have experienced the event. proportion …’ Another common cause is that people are lost Each step in a Kaplan-Meier curve provides to follow-up during a study—whether due to evidence of the time the patient experienced death, relocation, an adverse drug reaction, or the event. There are no steps to recognize In principle, both curves contain the same simply a wish to discontinue participation. the time of a censored observation. In some information, but the visual perceptions of reports, the times of the censored observations treatment group comparisons can be quite These are examples of random censoring, are indicated on the Kaplan-Meier curves. In different.1 There is no statistical advantage of when follow-up ends for reasons not under others, the number at risk and the cumulative one representation over the other—it can be the investigator’s control. However, in number of events are provided at the bottom viewed as the cup being half-full or half-empty. time-to-event analysis, censored observations of the graph. contribute to the total number at risk up to An essential feature of the Kaplan-Meier the time that they ceased to be followed. One This information enables the reader to methodology is that the 2 curves are generated advantage: the length of time an individual determine whether the number at risk toward independent of each other. Means are needed is followed does not have to be equal for the end of the follow-up period is large to establish whether the time-to-event data everyone. All observations can have different enough to make meaningful comparisons represented in these curves differ from each amounts of follow-up time, and the analysis between the treatment groups. In essence, it can question whether the extreme right >em
je
9ecfkj[
J_c[
Wj
H_ia
WdZ
j^[
HWj[
e\
Wd
;l[dj of the Kaplan-Meier curves should have influence in the overall conclusion. The concept of time at risk means that all available follow-up is put to good use; this reduces the bias that can creep into analyses if only Group data at the end of a study are used to assess A the treatment effect. The summary table that provides the rate of events and the relative hazard (or risk) has not been frequently used in ophthalmology. 36 72 108 144 180 216 252 288 324 360 Rates when expressed as the number of events Time in Days per unit of time at risk can be very flexible. In epidemiology, the rate is expressed as events per 100,000 patient years at risk. In clinical trials, smaller numbers are used. as the Group number of events is low. It is strongly recom- B mended that summary statistics be included in a table or on the curve. This should include the rates, the relative risk, and the 95% confidence interval. FIGURE 1 Rates can be large if the number of events Redfern JS, Thompson D. The risks and hazards of interpreting and reporting health study measures: a simple, practical overview. AMWA Journal. 2011;26(3):111-116. is large, or if the time at risk is small—

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 17 CLINICAL TRIALS: FUTURE PATHWAYS >>

particularly when assessing early effects of a treatment in one group compared with Kaplan Meier Survival Estimate, by Era, late effects in the control group. The number of events may be the same in both groups, Va = 20/200 or Worse (n = 58) but the time to event—and hence the time at risk—is the key that differentiates the 1.00 treatment groups. In addition to describing the treatment 0.75 difference for selected baseline characteristics, time-to-event analysis can be very useful in visualizing the role of treatment factors. 0.50 Interpretation of Kaplan-Meier curves comes with experience. An important point of interest is the time point at which the curves 0.25

appear to begin to separate. There is no of Event Free Proportion statistical test to determine that point; it is mainly a descriptive measure. 0.00 0 2 4 6 One cannot determine from Kaplan-Meier Analysis time (years) analysis the point at which the drug begins to be effective; Kaplan-Meier analyses were not Newer antivirals Acyclovir-only intended for that purpose. It is not appropriate to ask at what point the differences between FIGURE 2A the curves become significant, although it is Tibbetts MD, Shah CP, Young LH, Duker JS, Maguire JI, Morley MG. Treatment of acute retinal necrosis. Ophthalmol. 2010;117(4):818-824. sometimes useful to speculate on the shape of the curve. The use of time-to-event analysis in ophthalmology is increasing and represents a modern way of looking at data. Such analysis Cumulative Incidence of a Sustained Change provides valuable information on the patient in Retinopathy in Patients With IDDM Receiving experience during the follow-up period. Intensive or Conventional Therapy Ignoring the temporal information, which is not provided when simple proportions are used, can lead to less-than-optimal use of the 60 information collected during the study. This loss of information can potentially lead to 50 erroneous conclusions. 40 Conventional Reference

1.Pocock SJ, Clayton TC, Altman DG. Survival plots of time-to-event outcomes in clinical trials: goodpractice and 30 P<0.001 pitfalls. Lancet. 2002;359(9318):1686-1689.

20 Financial Disclosures Dr. Shah – ALCON: Grant Support; ALIMERA SCIENCES: Intensive Percentage of Patients Percentage Grant Support; ALLERGAN, INC: Grant Support; 10 GENENTECH: Grant Support; GENZYME: Grant Support; GLAXOSMITHKLINE: Grant Support; MOLECULAR PARTNERS: Grant Support; NEOVISTA: Grant Support; PALOMA PHARMACEUTICALS, INC: Grant Support; REGENERON 0 PHARMACEUTICALS, INC: Grant Support. 010 2 3 4 5 6 7 8 9 Dr. Heier – ACUCELA INC: Consultant, Consulting Year of Study Fees; ALLERGAN, INC: Consultant, Consulting Fees; BAUSCH+LOMB: Consultant, Consulting Fees; BAYER HEALTHCARE: Consultant, Consulting Fees; ENDO OPTIKS Number Conventional 348 324 128 79 INC: Consultant, Consulting Fees; FORSIGHT LABS, LLC: at Risk Intensive 354 335 136 93 Consultant, Consulting Fees; FOVEA PHARMACEUTICALS SA: Consultant, Consulting Fees; GENENTECH: Consultant, Consulting Fees; GENZYME: Consultant, Consulting Fees; HEIDELBERG ENGINEERING: Consultant, Consulting FIGURE 2B Fees ; KATO PHARMACEUTICALS: Consultant, Consulting The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the Fees; NEOVISTA, INC: Consultant, Consulting Fees; NOTAL VISION: Consultant, Consulting Fees; ORAYA development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. THERAPEUTICS, INC: Consultant, Consulting Fees; PALOMA 1993;(329)14:977-986. PHARMACEUTICALS, INC: Consultant, Consulting Fees; QLT OPHTHALMICS: Consultant, Consulting Fees; QUARK PHARMACEUTICALS, INC: Consultant, Consulting Fees; REGENERON PHARMACEUTICALS, INC: Consultant, Consulting Fees; SEQUENOM: Consultant, Consulting Fees. Dr. Thompson – REGENERON PHARMACEUTICALS, INC: Consultant, Other Financial Benefit.

18 | retina times | Fall 2012 | Volume 30, Number 4 | Issue 46 | INTERNATIONAL CORNER >>

Kourous A. Rezaei, MD Chair, International Affairs Committee Bringing the International Retina Community Together ASRS has members in 55 nations. Beginning with this issue of Retina Times, the International Corner will profile retina societies from countries around the world. We encourage you to visit their websites, find out more about their conferences, and become involved in the international retina community.

Brazilian Retina The meeting will feature leading experts from WdZ
L_jh[eki
Europe, the US, and Latin America. ® IeY_[jo For information and registration, visit The Brazilian Retina www.retina2013.com.br. and Vitreous Society (SBRV), head- quartered in São International Delegates Attend Paulo, Brazil, was ASRS Annual Meeting founded in 1977 and Many of the more than 20 international has grown to 920 delegates nominated by their countries’ members. SBRV’s retina societies attended the ASRS 30th goal is to promote educational and professional Annual Meeting in Las Vegas. Their interaction among retina and vitreous specialists response was most enthusiastic: by sponsoring meetings and offering support “ Best retina meeting I have for collaborative scientific research. ever attended.” 7hWX
7\h_YWd
IeY_[jo
e\
Retina Specialists Each quarter, the Society publishes “ Great meeting, meeting old friends The Brazilian Retina and Vitreous Society Journal, and making new ones ...” The idea to form the Arab African Society of which will soon be indexed. Retina Specialists (AASRS) originated in 2004 “ This is my first time at ASRS ... I hope I could bring more retina specialists at the first Cairo Retina Meeting. AASRS’s aim FbWd
je
Wjj[dZ
j^[
(&')
to ASRS.” is to promote collaboration and continuing I8HL
7ddkWb
C[[j_d] education between retina specialists in the “ ASRS was outstanding as usual ... It Arab world and Africa, as well as with their was a unique experience to meet many colleagues from different countries ....” scientific colleagues around the world. In 2010 at the third Cairo Retina Meeting, the AASRS was launched with Egypt as its headquarters. The Cairo Retina Meeting, now Financial Disclosures held every 2 years, became the official meeting SBRV invites ASRS members to participate in Dr. Rezaei – ALCON LABORATORIES, INC: Other, Grants, of the AASRS in 2012. The AASRS and the the 38th Annual Meeting, to be held in Belo Honoraria; GENENTECH: Other, Grants, Honoraria; BMC Horizonte, Minas Gerais, Brazil on April 11-13, OPHTHALMOLOGY: Consultant, Honoraria; ALIMERA European School for Advanced Studies in SCIENCES: Advisory Board, Honoraria; THROMBOGENICS: Ophthalmology organized the 2012 meeting 2013 at the Minas Centro Convention Center. Advisory Board, Honoraria; REGENERON PHARMACEUTI- CALS, INC: Other, Grants. with 24 invited guest speakers, attracting more than 600 participants from 24 countries. AASRS now has 412 members representing 18 nations. 77IHI
?dl_j[i
oek
je
j^[
+j^
9W_he
H[j_dW
C[[j_d] The 5th Cairo Retina Meeting will be held in January 2014 at the Cairo Marriott Hotel and Omar Khayyam Casino in Cairo, Egypt. For information, visit www.crmaasrs.com.

20 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | RETINOMICS >>

William L. Rich III, MD, FACS President, Northern Virginia Larry Halperin, MD Ophthalmology Associates Section Editor Falls Church, Virginia Retina Group of Florida Medical Director of Health Policy Boca Raton and American Academy of Ophthalmology Fort Lauderdale, Florida The Patient Protection and Affordable Care Act: 2010-2012—A Curmudgeon’s Report Card

The Affordable Care Act, or “Obamacare”, will affect all of us, our practices, and our patients, for years to come. The US Supreme Court legitimized certain aspects of the Act; thus, presidential politics aside, healthcare reform is upon us.

Following are perspectives from Bill Rich, a hero of our contributions for existing Medicaid programs. However, hospitals and profession, and from Chris Fisher, the health care advisor care providers would be left bearing the burden of uncompensated care. to Florida Democratic Representative Ted Deutch. These providers are aggressively lobbying Republican governors to take the federal money. Please contact me with comments at [email protected]. —Larry Halperin ‘ The cost of insurance will far In 1915, Theodore Roosevelt first proposed compulsory health insur- outweigh the small tax/penalty ance. It failed to pass. FDR, Truman, and Kennedy also pursued this unsuccessfully. Finally, President Johnson proposed limited programs for not obtaining coverage.’ to cover the elderly, poor, and disabled. Medicaid and Medicare were enacted in 1965. However, the number of uninsured continues to Hurdles include the complexity and cost of implementing state insurance expand annually and costs have exceeded predictions. exchanges, as well as the definition of the minimum benefit package. What led to the passage of President Obama’s historic Patient Expanded Medicaid and state insurance exchanges are slated to start in Protection and Affordable Care Act (ACA)? 2014—a short time line. sMILLIONUNINSURED ACCORDINGTOTHE53#ENSUS"UREAU The strength of the ACA is that it could: s(EALTHCARESPENDINGONAMETEORICRISE s%XPANDCOVERAGETOANADDITIONALMILLION!MERICANSWITHAMODEL s.OCOMPARATIVEEFFECTIVENESSRESEARCHONGROWINGTECHNOLOGY THE that has worked in other countries major cause of increased utilization of services s"UILDONOURSYSTEMOFPRIVATEINSURANCE s0ERCEIVEDPOORQUALITY s%XPANDOURCURRENTPUBLICPROGRAMS The ACA is complex, comprehensive, and evolving legislation. However, s)NTRODUCETYPICALLY!MERICANPRINCIPLESOFCOMPETITIONINTHEPRIVATESECTOR the administration’s implementation plans can be evaluated. s!VOIDASINGLE PAYERSYSTEMSUPPORTEDONLYBYPROGRESSIVE$EMOCRATS The individual mandate is a prerequisite for 2 popular ACA reforms: J^[
kd_dikh[Z “guaranteed issue” and “community rating.” A major weakness is the The ACA has taken a moderate approach to the uninsured; it is not low “tax” for noncompliance with the individual mandate. the “socialistic” insurance plan favored by liberal Democrats, where The cost of insurance will far outweigh the small tax/penalty for not government is the single payer as in Canada and Great Britain. The obtaining coverage. Some economists predict that up to 30% of eligible ACA more closely models the approach developed by the conservative patients may elect to pay the tax. This would negatively affect the risk Heritage Foundation. Consider the Dutch system, where benefits are pool and increase the costs for those purchasing insurance. For political defined; there are individual and employer mandates to purchase reasons, the ACA fails to make insurance available to the more than insurance from competing private insurance firms. Patients can select 7 million undocumented workers, leaving an uncompensated burden a plan to meet their needs. Sound familiar? Massachusetts? The ACA? for hospitals and physicians. The ACA individual mandate was reaffirmed by the recent Supreme Court decision. Competing plans offered in state exchanges will be available to Scorecard: Design: A /
?cfb[c[djWj_ed: Incomplete, but patients in 2014 for those whose employer declined to offer insurance the model has proved successful in the Netherlands and Germany. or who qualify for government subsidies to purchase insurance. Republicans might try to limit the implementation, but will not be able to repeal the legislation. Even if the Republicans did Federal subsidies are provided for the working poor—both individuals overturn the ACA, they would still face the same problems that and small firms. For those at less than 133% of the poverty level, expan- led to its passage. sion of state Medicaid is available. The Supreme Court also ruled that states that decline to expand their Medicaid rolls will not lose federal Continued on page 24

22 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | RETINOMICS >>

Chris Fisher Legislative Assistant to Congressman Ted Deutch (D-FL-19) The ACA Opens the Door to Health Coverage for Millions

The Patient Protection and Affordable Care Act (ACA) makes access to The recent Supreme Court case considered whether the federal govern- quality, affordable health insurance part of the American experience. ment could: For the tens of millions of uninsured and underinsured Americans, s-ANDATETHEPURCHASEOFPRIVATEHEALTHINSURANCE this law represents the only path to comprehensive coverage and access s#OMPELSTATESTOEXPANDTHEIR-EDICAIDROLLSBYUSINGEXISTING to the health care system. Ophthalmologists know that comprehensive Medicaid funding as leverage coverage and access to primary care can stem the tide of preventable The government argued that because all Americans participate in the vision loss if, for example, patients with early macular degeneration can health care system, the mandate was simply regulating how care was talk to their doctors about recent vision changes. financed. The law’s supporters were concerned that a conservative court Overhauling the nation’s health care system and reforming a broken would not only strike the mandate, but be unwilling to sever the provision, insurance market faced peculiar headwinds. Despite the poor comparative striking down insurance reforms and affordability credits as well. scores of the US health care system, most Americans are satisfied with their coverage. Fear of the unknown, distrust of a president committed to extending coverage to the working poor, or even a sincere belief ‘ The ACA will use Medicare’s market that American health care outperforms the world in critical metrics left policymakers with severely limited options. influence to accelerate delivery- Asking taxpayers to further subsidize a health care system that spends side reforms, provide performance almost twice as much per capita as the rest of the world—without incentives, and curb excessive billing.’ better outcomes—would have surely been unsustainable. The popular private insurance market reforms alone would have caused premiums to skyrocket, leading to a complete market collapse. Provisions like In the end, a slight majority found that the mandate could survive as bans on pre-existing conditions, rescissions, and coverage limits were a tax, but that the federal government could not compel the expansion designed by insurance companies for actuarial soundness in the absence of Medicaid. This reversal of widely used federal power may preclude of a regulated marketplace with coverage mandates. Medicaid coverage for millions of working poor Americans in states that choose to opt out of federal health care dollars. The ACA’s success in improving the nation’s health and health care ‘ For the tens of millions of uninsured finances depends almost exclusively on absolute implementation. The and underinsured Americans, [the numerous, interdependent provisions of this public-private health partnership will function most efficiently in states that aggressively take ACA] represents the only path to ownership of the health of their populace. comprehensive coverage and access Any successful efforts to repeal or sabotage the ACA will necessarily take place prior to successful implementation. Once the promise of to the health care system.’ health care has been delivered to millions of Americans and adequately financed, it will become exceedingly difficult to undo. We have seen “Obamacare” become characterized positively by those already affected: Health care reformers were left with the unenviable task of restraining newly insured young adults, seniors in the donut hole, and small costs and mandating coverage, while navigating the waters of politically businesses that can now afford to cover their workers. powerful health care interests. Fortunately, all stakeholders agreed on the dual premise: the system is broken, and this may be the last chance While those in health care and politics know that the ACA will mean to repair it. expanded coverage and consumer-friendly reforms, most Americans remain focused on keeping their current situations from getting worse. The Affordable Care Act will extend Medicaid to all adults up to 133% of When it yields better access to more cost-effective insurance instead the poverty level and will make private insurance affordable for families of death panels and government takeovers, the ACA will join Social up to 400% of the poverty level. It will create state-based exchanges Security and Medicare in the minds of middle-class families as an where insurance companies, bound by new federal pro-patient regulations, historic American achievement. can compete for customers. The ACA will use Medicare’s market influ- ence to accelerate delivery-side reforms, provide performance incentives,

and curb excessive billing. Financial Disclosures Ch$
<_i^[h – None.

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 23 RETINOMICS >> Continued from page 22

Costs telemedicine program to improve renal dialysis patient adherence and education, creating only 3 new jobs, and affecting patients who already Exploding health care costs have been a monumental problem for our congregate in a delivery site 3 times a week? Enough said. society for decades. Past attempts to curb costs have all failed: Nixon’s price controls, the Health Planning Act, managed care and managed Most CMMI payment models are no more promising. competition, a resource-based physician fee schedule, and prospective payment of hospitals. Accountable Care Organizations The financing problems that stimulated passage of the ACA include: Elliot Fisher, MD, Dartmouth Institute for Health Policy, and Glenn Hackbarth, JD, chair of MedPac, hypothesized a new model for s0ROJECTEDBANKRUPTCYOF-EDICARE0ART!IN integrating care to improve quality and decrease costs: an accountable s$OUBLINGOFPATIENT0ART"PREMIUMSINYEARS care organization (ACO). An ACO is an organization, virtual or real, s/UT OF POCKETCOSTSFORAFAMILYOFWERE IN RISINGTO that provides care for a particular population while achieving specified  IN quality objectives and containing costs. An ACO emphasizes integration s!DOUBLINGOFEMPLOYERHEALTHCAREPREMIUMSINYEARS of care and shared savings. s(EALTHCARECOSTSˆTHELEADINGCAUSEOFDECREASESINDISPOSABLEHOUSE- hold income, leading to economic stagnation over the last decade There are 2 types of ACOs: s!SHAREDSAVINGSMODELDEVELOPEDAROUNDHOSPITALSYSTEMSORLARGE The ACA is based on a belief that moving from fee-for-service to medical groups like California independent physician associations (IPAs) paying providers based on quality and efficiency will lead to decreased s!0IONEER!#/-ODELFORMEDBYLARGEINTEGRATEDSYSTEMSLIKE+AISER expenditures—a more than problematic assumption. or Geisinger The Obama administration has claimed that passage of the ACA has Market share consolidation by hospitals and large IPAs will lead to little already led to “bending the cost curve.” Ridiculous. Health care spending change for Medicare, but will very likely drive up overall health care growth began to moderate in 2005, well before the recession, and has spending. The Pioneer ACOs will probably be successful, but their small continued to the present day. Physician revenue growth has been lower number will result in little impact on federal Medicare expenditures. than any other sector of health care spending, probably a result of flat public payments and more cost-sharing for private patients. The ACA The ACO concept is based on the CMS Group Demonstration Project, had no impact. in which 10 large medical groups agreed to be measured on quality and costs over 5 years. Those who achieved savings and met quality goals would get a bonus. Many achieved targets on measures of simple ‘ The ACA is based on a belief quality process measures. that moving from fee-for-service Three received no bonus at all. Only 2 received a bonus in all 5 years. ACO DEVELOPMENTCOSTSSTARTAROUNDMILLION4HEDEMOCOVERED LIVES to paying providers based on -EDICARESAVEDMILLIONOVERYEARSORPERBENElCIARY0EANUTS

quality and efficiency will lead to Bundling of services

decreased expenditures—a more Most of the new payment models being considered by Congress entail than problematic assumption.’ large penalties for physicians not involved in one of the new value-based payment models. CMMI elected to develop its initial bundled payment initiatives around a high-cost hospital episode of care—eg, a major joint replacement. However, disputes over allocation of revenue and costs The ACA mandated the formation of the Center for Medicare and among hospitals, surgeons, anesthesia, radiology services, short-stay Medicaid Innovation (CMMI) within the Centers for Medicare & nursing facilities, and rehabilitation services have been problematic. -EDICAID3ERVICES#-3 WITHABUDGETOFBILLIONTODEVELOPNEW value-based payment methodologies and innovative care delivery models. CMMI has recruited many bright staffers with a primary care ‘ Market share consolidation by and master of public health (MPH) orientation who have had little or no experience leading physicians, administering care delivery, or hospitals and large IPAs will lead to understanding how to change physician behavior. little change for Medicare, but will Because these staffers have eschewed cooperation with long-time CMS administrators, their policies have been top-down, focused on primary very likely drive up overall health care, insular, and unresponsive to specialty care input. care spending.’ Examples of CMMI initiatives: Partnership for Patients: s !BILLIONDOLLARINITIATIVETOIMPROVEPATIENT CMMI declined to develop bundling for outpatient chronic disease treat- safety in hospitals and develop new care models post-discharge. Result: A ment provided by a single specialty, even though this would have been easier proliferation of consulting contracts with no evidence of efficacy. to develop and would have saved money and improved outcomes. Wet sChallenge grants: 7ELL MEANING BILLIONTOP DOWNAPPROACHTO AMD and diabetic macular edema, 2 clinical entities with huge costs and improving care, lowering costs, and creating jobs through 3-year grants. wide variation in resource use, would have been successful bundling efforts. !GRANTOFMILLIONTO'EORGE7ASHINGTON5NIVERSITYWOULDFUNDA Continued on page 36

24 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | ASRS SYMPOSIUM >>

Pravin U. Dugel, MD ASRS Research and Therapeutics Committee Chair Phoenix, Arizona ASRS Research and Therapeutics Symposium: Clinical Trials ‘Unplugged’ Part 1: Applying AMD Trial Results to Clinical Practice The third annual ASRS Research and Therapeutics “Unplugged” Symposium, moderated by Pravin Dugel, MD, focused on the real-world applications of key clinical trial results. Practicing retina specialists and leading researchers engaged in a spirited discussion, seeking to understand differences between clinical trial findings and what is done in everyday practice.

Pravin Dugel opened the discussion by presenting 2009 Medicare utilization data: In the first year after neovascular AMD diagnosis, the number of anti-VEGF injections per patient averaged between 5.8 for ranibizumab and 4.5 for bevacizumab.

Robert L. Avery, MD J. Michael Jumper, MD California Retina Consultants West Coast Retina Santa Barbara, California San Francisco, California ANTI-VEGF USE IN NV AMD

1122

Average 9 David S. Boyer, MD Peter K. Kaiser, MD number = Retina-Vitreous Associates Cole Eye Institute  Medical Group Cleveland, Ohio 6 Los Angeles, California

3

2006 2007 2008 0 2009 ANCHOR (2006) MARINA (2006) Ranibizumab Jay S. Duker, MD William F. Mieler, MD 1212 New England Eye Center University of Illinois, Chicago Boston, Massachusetts Chicago, Illinois Average number = 9  6

3

Harry W. Flynn Jr, MD Timothy G. Murray, MD, MBA 2006 2007 0 Bascom Palmer Eye Institute Murray Ocular Oncology and Retina 2008 2009 University of Miami Miami, Florida ANCHOR (2006) MARINA (2006) Miller School of Medicine Bevacizumab Miami, Florida

FIGURE 1*

Yet, according to randomized controlled trials (ANCHOR and MARINA), patients should receive 11 to 12 injections in that first year. The Medicare data showed similar discrepancies from other clinical trials:

Jeffrey S. Heier, MD Michael A. Singer, MD s !NTI 6%'&USEINBRANCHVEINOCCLUSION"6/ WAS Ophthalmic Consultants of Boston Medical Center Ophthalmology Boston, Massachusetts Associates INJECTIONSCOMPAREDTO"2!6/AT San Antonio, Texas s &ORCENTRALVEINOCCLUSION #6/ ANTI 6%'&USEWAS compared with CRUISE at 8.8

s $IABETICMACULAREDEMA$-% USEOFANTI 6%'&WAS compared with DRCR.net Protocol I at 9 injections

26 | retina times | Fall 2012 | Volume 30, Number 4 | Issue 46 | Practical considerations weigh into the decision to treat on a monthly ANTI-VEGFANTIVEGF USE IN BVO basis or individualize treatment. If the latter, what treatment strategy does one employ? While treat and extend has not yet been proven effec- tive in a randomized clinical trial, most panelists felt it was a reasonable strategy. Jeffrey Heier stated that the “best data show that you either 9 treat monthly or, at a minimum, any non-monthly regimen mandates Average monthly follow-up.” number = 7  5 ‘ I don’t see my patients every month 2 when I’m treating and extending, and 2006 2007 2008 0 2009 I don’t think it’s a disservice. I think BRAVO (2011) Bevacizumab it may be better to treat them before ANTI-VEGANTIVEGFF USE IN CVO they recur every time instead of after they recur.’ —Robert Avery, MD

9 Monthly follow-ups, however, are not always practical. “When you can find the interval where they don’t recur, I feel it’s not unsafe to extend Average a few weeks beyond the monthly visit,” said Robert Avery. “I don’t see 7 number = my patients every month when I’m treating and extending, and I don’t  5 think it’s a disservice. I think it may be better to treat them before they recur every time instead of after they recur.” 2 Michael Jumper added that “in some ways, it is emotionally easier on 2006 2007 0 2008 the patient to say, ‘You’re going to get an injection every time you come. 2009 We’re hoping that you get to the point where you are coming in every 6 CR I  (2011) Bevacizumab weeks and then every 8 or 10 weeks.’” Peter Kaiser noted that it is easy to become lulled into complacency in our own practice patterns as we do not critically look at our visual acu- ANTI-VEGFANTIVEGF USE IN DME ity results, anatomic outcomes, and number of injections in the same way as in a randomized clinical trial. He recommended periodically looking at your results to ensure you are 9 achieving similar visual results as the clinical trials. Average “Now I’m interested in hearing about what we’re treating,” said Pravin 7 number = Dugel. “We’ll start with the case studies.  5 AMD Case #1: Persistent fluid 2

2006 Pravin Dugel presented a case from his practice, a 65-year-old monocu- 2007 0 2008 2009 lar woman who is an occasional smoker. “She lives alone, so her 20/40

RCRne4 I (Ran'e) a3e2) (2011) vision is important to her,” he noted. “I started treating this patient in Bevacizumab 2005 with Macugen and continued to treat her with Lucentis. She did FIGURE 2* well with both; actually, the OCT improved nicely.” The clinical trial data show a direct correlation between the treatment “If you had spectral-domain OCT available early on, you would have frequency and visual acuity, approximating a one-to-one relationship for said there’s fluid there,” Peter Kaiser observed. AMD, DME, and vein occlusion. When asked to explain why patients received significantly fewer injec- tions in practice than in clinical trials, the panelists offered a number of ‘[O]ur patients don’t live in patient-centric explanations and identified data deficiencies. Jay Duker pointed out that “our patients don’t live in clinical trials,” and, as William clinical trials.’ —Jay S. Duker, MD Mieler noted, some patients would not be eligible for many reasons including presenting vision, disease characteristics, and comorbidities. “For nonfinancial reasons, the patient wanted Avastin,” Dr. Dugel added. “Recall that at that time, we thought Avastin lasted longer, * Slater D, Yeh WS, Chia YJ, Kowalski JW. Real-world utilization of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in common retinal because it is a larger molecule—and now she loves Avastin. She does diseases. Poster presented at: Academy of Managed Care Pharmacy not want to switch.” Educational Conference; October 19-21, 2011; Atlanta, GA.

| Issue 46 | Volume 30, Number 4 | Fall 2012 | retina times | 27 ASRS SYMPOSIUM >>

AMD Case #1— By 2011, after continued Avastin treatment, the fluid appeared to have Presented by Pravin Dugel, MD increased, but the patient’s vision remained 20/40. Jay Duker commented, “Maybe this is no longer VEGF-mediated disease; perhaps those are cysts over the fibrotic scar and they’re never going to go away.” “You can figure that out that very easily,” said Peter Kaiser. “Do an injection; bring her back in a week. If it’s VEGF-responsive, you’ll see an effect at one week. If not, I would have to think about doing something else and obtain indocyanine green (ICG) imaging to see if there’s any other pathology, especially a masquerade syndrome. If it’s truly choroidal neovascularization (CNV) or polypoidal choroidal vasculopathy, I’d probably add verteporfin photodynamic therapy (PDT) to see if I can dry the macula better.”

9/27/05 MACUGEN ‘ [The] best data show that you either treat [with anti-VEGF agents] monthly or, at a minimum, any non- monthly regimen mandates monthly follow-up.’ —Jeffrey S. Heier, MD

Jeffrey Heier commented that to determine whether a patient is VEGF- responsive, he would follow a similar protocol, but double the dose and bring the patient back at 2 weeks. “I want to know if she is anti-VEGF 2/16/06 LUCENTIS responsive,” he explained. “It’s been a number of years now,” said Pravin Dugel. “This is starting in 2005. She’s perfectly happy with her vision. The fluid may be a little bit more there. She’s still 20/40. Is it wrong to just keep going? Is this treatment failure?” “She’s reading and driving,” said Jay Duker. “You haven’t failed, no.” Peter Kaiser said that even though the patient is happy, he would con- sider switching her to Eylea for 2 reasons. “At the minimum, I’m hoping that I can get the Q2 month dosing of Eylea maybe even a longer interval. My reasoning is that normally I do not switch someone who is happy to another medication, but since she’s monocular, I would want 5/14/07 AVASTIN to limit the number of injections as much as possible,” he explained.

‘ [W]e like to get patients as dry as possible, but I’m not convinced that in every case we have to do that. [If the patient is happy], I can live with a little bit of fluid there.’ —William F. Mieler, MD

William Mieler recommended a slightly different approach. “I agree that we like to get patients as dry as possible, but I’m not convinced that in every case we have to do that. This patient has been very stable; 8/24/11 AVASTIN vision is 20/40 and she’s happy. I’d be pretty happy. I can live with a

FIGURE 3 little bit of fluid there.”

28 | retina times | Fall 2012 | Volume 30, Number 4 | Issue 46 | AMD Case #2— After 65 monthly Lucentis injections, the patient was back to 20/40, Presented by Robert Avery, MD with a small amount of persistent fluid. He started to lose a bit of vision in 2012, so he was switched to Eylea. “I hoped this would last BaselineBaseline 20/200 Avastin #1 longer and dry the fluid out,” Dr. Avery explained. The intraretinal fluid 20/200 Avastin #1 decreased and his vision slowly came back to 20/30 after 6 or 7 Eylea Month 1 Month 1 Avastin #2 injections. 20/7020/70 Avastin #2 “This is indicative of what I see—a slight improvement in some patients with Eylea, just as I saw with Lucentis over Avastin for a few

MonthMonth 5 5 Avastin #6 patients,” Dr. Avery added. “But what’s going to happen in the future? Is 20/60-120/60-1 Avastin #6 the patient going to continue to dry up and develop atrophy? Should I have chased this fluid?” “In a lot of cases, the location of the fluid is what matters,” noted Peter 10/26/11 Month 80 Kaiser. “The beginning images of this case showed a lot of the fluid was 20/3020/30 LucentisLucentis #65 #65 intraretinal or subretinal. Now it’s almost all sub-RPE.” Michael Singer queried the panel and the audience on whether they Month1/4/12 83 had extended patients on Eylea who previously had been nonrespon- 20/6020/60 LucentisLucentis #67 #67 sive to Lucentis. “When the patients have dried out, have you been able to extend them to 2 months?” he asked. No one raised their hand. “This has been my experience as well,” said Dr. Singer. “I have been able 8/15/12 Month 90 to extend treatment-naïve patients, but have not been able to extend 20/30 EyleaEylea #7 #7 patients whose lesions have been resistant to treatment such as PEDs.” “I think we’re biased,” said Michael Jumper. “In our practice, the only FIGURE 4 people we treat with Eylea are those who have persistent fluid on Jeffrey Heier said the patient seems to be one of a group that may have another drug. When reimbursement issues allow for patients to start a higher VEGF load. “They respond to the Eylea; but then if I try to out on Eylea, we might have the sort of treatment-naïve patients who extend them out at all, I can’t,” he said. are more like those in the VIEW studies.”

“Although to date there’s no well-performed clinical study to show that AMD Case #3: Bilateral choroidal vascularization switching someone from Avastin to Eylea is any more beneficial than continuing the anti-VEGF they’re on,” said Peter Kaiser, “there have Jay Duker presented the case of an elderly woman, still quite sharp, who been numerous anecdotal reports suggesting that we have a possibility recently noticed a rather sudden vision decrease in her left eye. “She’s of improving outcomes in this patient by switching. If this were a 20/50 right eye, 20/400 left. Her fluorescein clearly shows bilateral 2-eyed patient, you could take the risk and say, ‘Okay, we’ll skip this choroidal vascularization, and in the right eye, it’s extrafoveal.” shot and we’ll see you in a month and see if the fluid increases and your Dr. Duker noted that the patient was treatment-naïve and asked vision drops.’ But getting that vision back once it drops is much harder whether the panel was comfortable treating her bilaterally on the than preventing it from dropping in the first place. We can’t make a first visit. mistake in this patient.” William Mieler commented, “I have no trouble treating bilaterally, but After a discussion of the pharmacokinetic issues of anti-angiogenesis usually at the first visit I’ll treat just one eye so the patient understands agents, Pravin Dugel asked, “Would you be worried about safety issues the process. You hate to induce a problem bilaterally on day one.” with long-term Avastin use in a patient like this?” “I’m not particularly worried if the patient is not at a high risk for stroke,” said Robert Avery. “The people I worry about are those who ‘ In a lot of cases, the location of the have had previous strokes or arrhythmias, or who are at high risk for fluid is what matters.’—Peter K. Kaiser, MD stroke. I look at the safety data in the VIEW 1, VIEW 2, CATT, and IVAN, and I don’t see much stroke risk in the average person. A meta-analysis in the October 2012 Retina seems to imply that if you are Others commented that they would inject both eyes the first time, 1 at high risk for stroke, your risk with these drugs may be higher.” which is what Dr. Duker did after discussion with the patient. Peter Kaiser offered a caveat: “I assume all of you are saying you would AMD Case #2: Early Avastin patient treat bilaterally with Lucentis the first time, because if you’re going to Robert Avery presented a case of a patient with 20/200 vision from neo- use Avastin … Whenever I use bilateral Avastin, I always use different vascular AMD in his better eye. “We began Avastin therapy on him in lots of the compounded medication.” 2005,” he explained. “He did well and came back to about 20/60 vision “Excellent point,” Dr. Duker responded, adding, “And you always record after 6 injections, but still had persistent fluid and pigment epithelial that in your document chart.” detachment (PED). After a year of Avastin, we changed him to Lucentis, and he stayed in the 20/60 range with monthly treatment. He still had Harry Flynn asked, “Does it matter if it’s the same PED and some fluid at the edge of it.” compounding pharmacy?”

| Issue 46 | Volume 30, Number 4 | Fall 2012 | retina times | 29 ASRS SYMPOSIUM >>

This question prompted a discussion surrounding Avastin safety. AMD Case #3— “At the Cole Eye Institute, our Avastin is compounded by our own Presented by Jay Duker, MD Cleveland Clinic pharmacy,” Peter Kaiser explained. “They send samples of each lot to the microbiology lab to test for contamination before the lot can be used. It’s done in the same place, so that you could Right eye argue that it’s an issue if there’s a systemic problem, but at least I’m Baseline using 2 different lots.” “I use Avastin from 2 different compounding pharamacies to minimize the risk,” David Boyer commented. VA = 20/50 Month 12, Lucentis #12 “We at the University of Miami take 1 out of every 10 syringes, culture it, and quarantine it for 2 weeks,” said Harry Flynn. “Once it’s culture-negative, we release the other 9.” He added that none of the VA = 20/30 approximately 60,000 syringes at Bascom Palmer have tested culture Month 24, Lucentis #22 positive.

Dr. Duker presented a slide showing the patient’s eyes after one VA = 20/30 ranibizumab injection in both eyes. “She didn’t want an off-label medication,” he noted. “She had a little less fluid in both eyes and improvement in her vision. We treated her again and went to 3 Left eye monthly injections. The right eye showed just a trace subretinal fluid; Baseline VA = 20/400 the left eye still showed subretinal fluid. “At that point we started to talk about the maintenance phase,” Dr. Duker added, “with the idea that you treat monthly until dry or until VA = 20/30 you get no further improvement in the fluid or vision and then go into Month 12, Lucentis #12 maintenance. The patient had several options, and after I discussed them with her, she said, ‘I want continued monthly injections in both eyes,’ so that’s what we did.” Month 24, Lucentis #21 VA = 20/30 Dr. Duker presented a slide showing the patient after a year of treat- and Eylea#1 ment. “The right eye 20/50, initially 20/30. I think we’d all agree she’s doing just fine with monthly injections,” he said. “And after a year, the left eye is visually doing great. She perceives no difference between the FIGURE 5 vision in her 2 eyes, but she still has subretinal fluid in the PED in her left eye. “I think this illustrates what we’ve been talking about—that sometimes Do AREDS supplements help a little bit of subretinal fluid in the PED doesn’t preclude good vision,” bilateral wet-AMD patients? Dr. Duker continued. “And I don’t believe that holding off treatment in PAT Survey Editor Michael Jumper posed a question referring to past a PRN fashion puts this kind of patient at higher risk for a hemorrhage. years’ survey responses: If patients with bilateral wet AMD are being The worst hemorrhages I’ve gotten in the last couple years have been maintained and their condition is controlled, should they continue tak- within a month of treatment.” ing AREDS vitamins even though there’s no proof that it’s worthwhile “Here again, the location of the fluid is important,” said Pravin Dugel. for advanced AMD patients? The panelists agreed they would be willing to do bilateral same-day “We know CATT data about atrophy being a potential problem,” Dr. injections on those patients. Jumper explained. “Do you consider keeping patients with bilateral wet AMD on AREDS vitamins? “We get asked that all the time, don’t we?” Jay Duker commented—and ‘ We at the University of Miami take other panelists and audience members concurred. 1 out of every 10 syringes, culture it, “My response is that continuing AREDS supplements is essentially locking the barn door when the cow’s out, but it’s only costing $20 or and quarantine it for 2 weeks. Once $30 a month,” said Dr. Duker. “I tell patients, ‘If you want to keep doing it’s culture-negative, we release the it, fine. I don’t think it’s helping you.’” other 9.’ —Harry W. Flynn Jr, MD Lack of data on switching anti-VEGF agents Pravin Dugel noted the lack of clinical data on patients who switched from one anti-VEGF agent to another. “I remember meetings where case reports were presented of patients switching from Lucentis to Avastin and improving vision. There were also accounts of the reverse

30 | retina times | Fall 2012 | Volume 30, Number 4 | Issue 46 | with similar results. Now we have reports of patients switching from “It is not that we cannot act without level-one scientific evidence; we Avastin or Lucentis to Eylea who have improved. can, and often do so,” Dr. Dugel concluded. “Rather, if we chose to do that, we must be truthful and transparent about our dearth of scientific “We must be appropriately skeptical of all these case reports and must knowledge to our patients, to our colleagues, and to ourselves.” not fall in the trap of extrapolating their results,” Dr. Dugel cautioned.

“There is no credible scientific data whatsoever that switching patients Reference from one anti-VEGF drug to another is of any benefit.” 1. Bressler NM, Boyer DS, Williams DF, et al. Cerebrovascular accidents in patients treated for cho- roidal neovascularization with ranibizumab in randomized controlled trials. Retina. 2012;32(9):1821- 1828. doi:10.1097/IAE.0b013e31825db6ba ‘ I use Avastin from 2 different compounding pharmacies to Financial Disclosures Dr. Dugel – ABBOTT LABORATORIES: Consultant, Honoraria; ALCON LABORATORIES, INC: Consultant, Honoraria; ALLERGAN, INC: Consultant, Honoraria; ARCTICDX: Consultant, minimize the risk.’ —David S. Boyer, MD Honoraria, Stockholder, Stock; GENENTECH: Consultant, Honoraria; MACUSIGHT INC: Con- sultant, Honoraria, Stockholder, Stock; NEOVISTA, INC: Consultant, Honoraria, Stockholder, Stock; ORA: Consultant, Honoraria; THROMBOGENICS: Consultant, Honoraria; REGENERON If fluid increases, it might have done so if the patient had stayed with PHARMACEUTICALS, INC: Consultant, Honoraria; OPHTHOTECH CORP: Consultant, Stockholder, Honoraria; ALIMERA SCIENCES: Consultant, Honoraria; Bausch+Lomb: [ed: the previous anti-VEGF agent as well. “In those studies, it’s important Please specify relationship, eg, consultant] Honoraria; LUX BIOSCIENCES, INC: Consultant, Honoraria; ACUCELA, INC: Consultant, Honoraria; NEUROTECH INC: Consultant, Stock; QLT to ask how many injections were done before the switch,” Dr. Dugel INC: Consultant, Honoraria; NOVARTIS PHARMACEUTICALS CORPORATION: Consultant, Honoraria; TOPCON MEDICAL SYSTEMS: Consultant, Honoraria; HEIDELBERG ENGINEER- advised. “Ultimately, you’ll see in most reports that there may not have ING: Consultant, Honoraria; DIGISIGHT: Consultant, Stock.. been an optimal injection frequency prior to declaring failure; the Dr. Avery – ALCON LABORATORIES, INC: Consultant, Investigator, Speaker, Grants, patients were often in a treat-and-extend phase. Then they switched Honoraria; ALLERGAN, INC: Consultant, Investigator, Grants, Honoraria; GENENTECH: Consultant, Investigator, Speaker, Grants, Honoraria; NOVARTIS PHARMACEUTICALS anti-VEGF agents, went into a monthly injection regimen, and did CORPORATION: Consultant, Stockholder, Honoraria, Stock; NOTAL VISION: Consultant, Honoraria; OPHTHOTECH CORPORATION: Consultant, Honoraria; REPLENISH, INC: Advisory better. This improvement may have occurred had the same monthly Board, Consultant, Stockholder, Intellectual Property Rights, Royalty, Stock; REGENERON PHARMACEUTICALS, INC: Consultant, Stockholder, Honoraria; Stock; ALEXION PHARMA- frequency been adopted with the original anti-VEGF agent. We must CEUTICALS: Stockholder, Stock; QLT INC: Consultant, Honoraria; I-TECH JV DEVELOPMENT not draw unwarranted conclusions without head-to-head data—and COMPANY, LLC: Stockholder, Stock. Dr. Boyer – ALCON LABORATORIES, INC: Advisory Board, Consultant, Investigator, we do not have this.” Speaker, Grants, Honoraria; ALLERGAN, INC: Advisory Board, Consultant, Investigator, Speaker, Grants, Honoraria; ALLEGRO OPHTHALMICS: Advisory Board, Stockholder, Jeffrey Heier asked, “Are you saying that we should be careful and not Honoraria; GENENTECH: Consultant, Investigator, Speaker, Grants, Honoraria; REGENERON PHARMACEUTICALS, INC: Consultant, Investigator, Grants, Honoraria; iCo THERAPEUTICS switch them?” INC: Consultant, Investigator, No Compensation Received; GLAXOSMITHKLINE: Consultant, Honoraria; NOVARTIS PHARMACEUTICALS CORPORATION: Consultant, Investigator, Grants, Honoraria; BAYER HEALTHCARE: Consultant, Honoraria; QUARK PHARMACEUTICALS, INC: Dr. Dugel answered, “No. What I’m saying is that we should Investigator, Grants. understand and admit where we have data and where we don’t. There’s Dr. Duker – HEMERA BIOSCIENCES INC: Founder, Stock; OPHTHOTECH CORPORATION: Consultant, Stock; EYENETRA: Consultant, Stock; PALOMA PHARMACEUTICALS: no reason not to switch if you feel that’s a proper thing to do—but Advisory Board, No Compensation Received; EMC/SERONO, INC: Consultant, Honoraria; we must be honest and admit that this is not based on any level-one GENENTECH: Consultant, Honoraria; ALCON LABORATORIES, INC: Consultant, Honoraria; REGENERON PHARMACEUTICALS, INC: Consultant, Honoraria; THROMBOGENICS: scientific evidence. Consultant, Honoraria; CARL ZEISS MEDITEC: Other, Equipment (Department or Practice); TOPCON MEDICAL SYSTEMS, INC: Other, Equipment (Department or Practice); OPTOVUE: Other, Equipment (Department or Practice); NEOVISTA, INC: Advisory Board, Honoraria; NOVARTIS PHARMACEUTICALS CORPORATION: Consultant, Honoraria; QLT INC: Consul- tant, Honoraria. Dr. Flynn – ALIMERA SCIENCES: Consultant, Honoraria; PFIZER, INC: Consultant, Honoraria; ‘ There is no credible scientific data SANTEN: Consultant, Honoraria. Dr. Heier – Dr. Heier – ACUCELA INC: Consultant, Consulting Fees; ALLERGAN, INC: Consul- whatsoever that switching patients tant, Consulting Fees; BAUSCH+LOMB: Consultant, Consulting Fees; BAYER HEALTHCARE: Consultant, Consulting Fees; ENDO OPTIKS INC: Consultant, Consulting Fees; FORSIGHT LABS, LLC: Consultant, Consulting Fees; FOVEA PHARMACEUTICALS SA: Consultant, from one anti-VEGF drug to another Consulting Fees; GENENTECH: Consultant, Consulting Fees; GENZYME: Consultant, Consult- ing Fees; HEIDELBERG ENGINEERING: Consultant, Consulting Fees ; KATO PHARMACEU- TICALS: Consultant, Consulting Fees; NEOVISTA, INC: Consultant, Consulting Fees; NOTAL is of any benefit.’ —Pravin U. Dugel, MD VISION: Consultant, Consulting Fees; ORAYA THERAPEUTICS, INC: Consultant, Consulting Fees; PALOMA PHARMACEUTICALS, INC: Consultant, Consulting Fees; QLT OPHTHALMICS: Consultant, Consulting Fees; QUARK PHARMACEUTICALS, INC: Consultant, Consulting Fees; REGENERON PHARMACEUTICALS, INC: Consultant, Consulting Fees; SEQUENOM: Consultant, Consulting Fees. “This highlights the danger of cross-trial comparisons and unwar- Dr. Jumper – COVALENT MEDICAL, INC: Equity Owner, Stock; Dutch Ophthalmics USA: ranted extrapolations,” Dr. Dugel explained. “We must recognize the Speaker, Honoraria. Dr. Kaiser – ALCON LABORATORIES, INC: Consultant, Honoraria; NOVARTIS PHARMACEU- nature of disease itself, as well as the level of credibility of studies. The TICALS CORPORATION: Consultant, Grants, Honoraria; REGENERON PHARMACEUTICALS, INC: Consultant, Grants, Honoraria; BAYER HEALTHCARE: Consultant, Honoraria; SKS disease is variable and is influenced by intrinsic and extrinsic factors. OCULAR, LLC: Stockholder, Stock; ARCTICDX: Consultant, Stock Options; ALIMERA SCIENCES: Consultant, Honoraria; OPHTHOTECH CORPORATION: Consultant, Honoraria; For instance, the baseline neovascular lesion size will have a direct ORAYA THERAPEUTICS, INC: Consultant, Honoraria. and profound impact on the vision outcome. Cross-trial comparisons Dr. Mieler – GENENTECH: Consultant, Honoraria; ALCON LABORATORIES, INC: Consultant, Honoraria; ALLERGAN, INC: Consultant, Honoraria; QLT INC/NOVARTIS PHARMACEUTI- cannot be done because such biases cannot be controlled. However, in CALS CORPORATION: Consultant, Honoraria; ALIMERA SCIENCES: Consultant, Honoraria. a properly randomized and powered clinical trial, such biases can be Dr. Murray – ALCON LABORATORIES, INC: Consultant, Honoraria; THROMBOGENICS: negated, or at least minimized. Consultant, Honoraria. Dr. Singer – GENENTECH: Investigator, Speaker, Grants, Honoraria; ALLERGAN, INC: Advisory Board, Consultant, Investigator, Speaker, Grants, Honoraria; DRCR.NET: Investiga- “Finally, we must subject untested recommendations to the appropriate tor, Other, Grants, No Compensation Received; NEOVISTA, INC: Investigator, Other, Grants, No Compensation Received; ISTA PHARMACEUTICALS: Investigator, Grants; OPTOS scientific rigor,” Dr. Dugel added. “Remember that there is no level-one PLC: Investigator, Equipment (Department or Practice), No Compensation Received; data to recommend a particular anti-VEGF agent or to switch to a REGENERON PHARMACEUTICALS, INC: Speaker, Investigator, Grants; SANTEN: Consultant, Consulting Fees. particular anti-VEGF agent based on efficacy. None of the 3 anti-VEGF drugs have been proven to be superior.

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 31 RETINA IN THE MILITARY >>

Marcus H. Colyer, MD, John R. Minarcik Jr, MD, MAJ, MC, USA CDR, MC, USN Section Co-Editor Section Co-Editor Serving in Afghanistan: 3 Deployed Retina Specialists Share Their Stories

After a decade of combat in Southeast Asia, the US military continues to see a steady stream of eye injuries, from corneal abrasions to complex globe and oculoplastics injuries. In recent years, ophthalmology care has evolved in Afghanistan; and with rising combat activity, there has been a commensurate increase in the number of deployed ophthalmologists.

Most deployed ophthalmologists acid burns to ocular prosthesis fittings. The are not retina-trained, but there have range of conditions could easily have covered been several military retina specialists half of the topics in The Wills Eye Manual. in the recent past. We asked 3 of our Given the complexity of the wounds, I was recently deployed retina specialist grateful for the coaching I received from our brethren—Darrell Baskin (Craig Joint deployed oculoplastic surgeon, Daniel Elizondo, Theater Hospital, Bagram Air Base, MD, the first ophthalmologist in Kandahar, 2010), Bryan Propes (Kandahar for many oculoplastics procedures beyond my Airfield, 2011), and Steve O’Connell comfort zone. I was particularly appreciative of (Kandahar Airfield, 2012) to comment his help when I had to perform my first and only on their experiences. dermis fat graft for an infected and extruding Maj Darrell Baskin, polymethylmethacrylate orbital implant. MD, USAF Typical deplaning at Bagram But my retina training did not completely I took over the reins from a wither on the vine during my deployment. close friend and fellow oph- Gary Lane, MD, one of the best retina thalmologist in August 2010; as surgeons I know, coordinated the transport Chris Kurz, MD, detailed and demonstrated my new responsibilities, I quickly realized my vastly expanded scope of practice. We ran a 24/7 clinic ‘The range of conditions for our US military servicemen and women to field any ocular complaints, and we could air- [treated] could easily have evacuate any who required an escalation in care. covered half of the topics Nearly every single active-duty person who received a globe repair or enucleation by my in The Wills Eye Manual.’ hands was evacuated before I rounded on the —Maj Darrell Baskin, first postoperative day. I also took care of many Dr. Baskin’s first scleral buckle procedure in Afghanistan International Security Assistance Force coalition MD, USAF troops and even some members of the media. of an Alcon Accurus system to Afghanistan. For the rest of my patients, though, air With 2 weeks remaining in my 3-month evacuation was not an option. During my deployment, I was able to perform 7 vitrectomies. time in particular, we accepted civilian Most cases were for retained lens material patients from the host nation, Afghan associated with open-globe injuries in the National Army and police, and even hostile local Afghan population. Thanks to Gary, we forces. For these patients, I was the only eye performed the first posterior vitrectomy in the doctor they might ever encounter. If I could history of deployed US warfare. not or would not fix their ocular problem, there weren’t any other options. I am grateful for the experience and the opportunity to serve, but I was terribly Tuesdays and Thursdays were particularly relieved to come home 2 weeks before my difficult, as my clinic was populated with local beautiful wife was due with our fourth child. An enucleation specimen; much of the sclera could not Afghans with a broad range of ailments, from be located in the orbit.

| Issue 46 | Volume 30, Number 4 | Fall 2012 | retina times | 33 RETINA IN THE MILITARY >>

Capt Steve O’Connell, Often, someone will walk in saying they can MD, USN no longer see well enough to drive a convoy Greetings from the other vehicle, fly their jet, or aim their weapon side of the world and thanks with their current spectacles. Performing a to all who have supported refraction is a simple but essential task to me in the Kandahar Airfield (KAF) NATO ensure our forces have good acuity for the Role 3 Multinational Medical Unit mission. mission. Lives depend on good vision. It’s a privilege to be given this responsibility There’s plenty of nonsurgical ophthalmology and of course a daunting challenge. I’m the here, eg, patients whose vision is not only fourth ophthalmologist to attend here as we blurry, but their eyes are red and/or they wind down our Afghanistan involvement. hurt. An unbelievable variety of foreign At the moment, there seems to be as much bodies seem to make their way into the military action as ever. eye. Other diagnoses are those typical of Dr. Propes at Kandahar “Role 3” Hospital The concept is One Deep. There’s only one any general ophthalmology practice: syphilis, neurosurgeon, one oral surgeon, and one chlamydia, multiple sclerosis causing inter- ophthalmologist in southern Afghanistan. nuclear ophthalmoplegia, cataract, thalamic Like a modern day Noah’s Ark, there are pairs infarct producing a skew deviation, herpes or multiples of other specialties and non- simplex virus, epidemic keratoconjunctivitis, physicians. There are usually about 5 surgeons anesthetic abuse, new-onset Harada’s disease, (vascular, plastic, general, trauma) and bacterial keratitis, pituitary tumor producing 5 orthopedic surgeons (spine, trauma, foot, a bitemporal field deficit, chalazia, reactive hand, general), but only one ophthalmologist. arthritis/iritis—the list goes on. We have 2 or 3 additional general surgeons, The nature of the typical injury is shocking orthopedic surgeons, and anesthesiologists and shockingly predictable. Most injuries from Australia and Belgium for the next involve a local national army or police couple of months. The plastic and maxillofacial member engaged in hazardous duty without surgeons can do facial skin and bones, but eye protection. Many times, defusing a bomb Dr. Propes teaching an Afghani doctor no one does globes except the ophthalmologist. is performed by someone wearing only light What this means is careful planning for clothing and no eye protection, even though 6 to 7 months. it has been given to them. Trauma is inherently unpredictable. No one knows when there will be multiple casualties, ‘ Lives depend on so we must always be prepared, whether going to the gym, meals, the exchange, etc. Within good vision.’ 2 weeks of my arrival, I had 7 open globes in 36 hours. As I sit here writing this on a Sunday —Capt Steve O’Connell, afternoon, I’ve already been to the hospital MD, USN 3 times to see patients with a migraine and a trailer hitch to the orbit, and a sailor with shrapnel to the cornea who took his eye The force of the blast rips off limbs, macerates protection off for just a few moments. facial skin, and propels dirt deep into the tissues. It’s as if they’ve been tattooed with Dr. Propes at the surgical microscope On my way back to the barracks, I saw the dirt. Brown ooze will continue to exit burned ER crew gearing up and passed one of the skin for days. The cornea is usually extremely 2 radiologists on his way in to review edematous. Defects are not lacerations as essentially whole-body CT scans on every much as they are punch-type wounds with trauma patient. I make sure the pager missing tissue—difficult to close with suture is nearby at all times with a good battery. material alone. I know it will sound off shortly. Fortunately, there is a little time to treat a There used to be an Army optometrist ruptured globe. Unlike a chemical burn or a stationed here. Apparently this position was retro-bulbar hemorrhage that needs and gets simply terminated, even though there was immediate attention, a ruptured globe can no commensurate reduction in personnel or sometimes wait hours while life-saving need. The duties that used to be performed procedures (transfusions, chest tubes, by the optometrist have now fallen to the amputations) are carried out. ophthalmologist by default. There are roughly 30,000 personnel on KAF, and numerous The typical sequence is the notification that Entrance to the Kandahar OR forward operating bases that rely on KAF multiple Afghan National Army or coalition for routine eye care services. personnel have been involved in an improvised

34 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | RETINA IN THE MILITARY >> explosive device (IED) explosion and trained to save sight. It’s what we do. It’s multiple eye injuries have been sustained. why we are here. There are some obvious The duty general surgeon will act as traffic reasons—there’s only one of me and I’ll need cop, orchestrating the use of ER and OR to sleep sometime, there is a finite supply resources to prioritize and accomplish all of of drugs, equipment, etc, and these must the required procedures. Three rooms and a be judiciously used to ensure proper treatment minor procedure room are available. of patients who meet the medical rules of engagement. When a room is open, an excellent, but ever-changing cadre of nursing and corps Regardless, I find it very difficult to turn away staff helps you accomplish your globe closure, a patient who needs to be treated. I took an enucleation, lid laceration, etc. Rarely, you’ll oath; there is a moral obligation to treat a be asked to give up the room before you’re suffering patient, and seeing a patient could done if suddenly there’s a double or a triple help the wider goal of winning the hearts and Dr. O’Connell preparing for a Sunday drive amputation coming in. When possible, you minds of the Afghan people. So it was for my may bring your patient back in. Life, limbs, first couple of months here that I would agree and eyesight are given the highest priority. to see essentially anyone who asked to be seen.

LCDR Bryan Propes, MD, USN ‘ The ethical Every day you see young people—our fighting soldiers, obligation to train sailors, and marines— children, enemy combatants, and innocent an ophthalmologist civilians—all horribly injured. Not an has never been more individual with a wounded leg or extremity, or an eye wound or abdominal wound, but apparent than in someone with all of the above, and bilateral Afghanistan.’ open globes and a facial degloving injury with a fractured mandible and a Le Fort —LCDR Bryan Propes, A medevac helicopter lands at Kandahar type III all at the same time. MD, USN And not just that person, but 3 or 4 just like him, all arriving at the same time, all needing Halfway through my deployment, I met a multiple surgical procedures. As soon as those senior Naval officer. One of his responsibilities patients are triaged, 3 or 4 more are just as is the state of Afghanistan health care after likely to come in; sometimes before you get we leave, and he was giving a presentation through the first batch, more will arrive. Mostly at a mini-meeting set up by our command. they come in stable, or at least with tourniquets During his talk, he explained that by seeing on and not exsanguinating. At least once or patients who don’t meet the medical rules twice a week, someone comes in and requires of engagement, we are putting the local immediate life-saving surgery and undergoes doctors out of business. Thus, when we leave, massive transfusion—20-30 units of PRBCs. there will be no one to take care of the local They live, almost always, but they often lack population. Quite a simple concept, really, extremities and other vital pelvic organs. but one that I had completely overlooked. Typical American muscle car in Afghanistan The ethical obligation to train an ophthal- Now, I require any local national who was not mologist has never been more apparent than involved in conflict-related injury to obtain in Afghanistan. In the entire country, there a referral from a local ophthalmologist. are only about 40 or so ophthalmologists Disclaimer: The views expressed in this presen- practicing. There are a few frustrations tation are those of the authors and do not reflect practicing ophthalmology here, most having the official policy of the Department of the to do with practicing on the local population. Army, Navy, Air Force, Department of Defense, First, you must work to do everything during or US government. a single surgery with as little follow-up as possible. This requires performing slightly different surgeries than you ordinarily would. Financial Disclosures Your patients are unlikely to ever again see Dr. Colyer – None. Dr. Minarcik – None. a properly trained surgeon, and are even Dr. Baskin – None. unlikely to follow up with you. Dr. O’Connell – None. Dr. Propes – None. Dr. O’Connell at Kandahar Airfield Secondly, you must refuse to see some local national patients. This kills me, as we are

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 35 RETINOMICS >> Continued from page 24

Some CMMI initiatives were brilliantly conceived and have great GkWb_jo promise, such as the Comprehensive Primary Care Initiative headed The ACA has mandated National Quality Forum-endorsed measurement by Richard Baron, MD, MACP. This initiative will coordinate public in ACOs, bundled payments, and all their new payment initiatives. Few and private insurer funding of comprehensive medical homes not measures address eye care because of the ACA and CMMI singular constrained by the top-down NCQA criteria. emphasis on primary care and public health, and because there are no payment models that invite meaningful ophthalmic participation. ‘ [I]mplementation of the ACA follows Scorecard: Design: B+ / : B+ a disturbing pattern of overreliance
?cfb[c[djWj_ed on MPH public policy mavens rather As a physician in a large ophthalmic group in a suburban Northern Virginia than listening to concerned and county with the highest per-capita household education and income in the United States, I was depressed by the 35% uninsured status of obstetrical cooperative physicians.’ patients in our large referral hospital. Three pediatric ophthalmologists in my group have an even higher number of uninsured patients. Many of us have been infuriated by the disjointed care received by an elderly, frail parent that CMMI has failed to meet the lofty triple-aim goals of former CMS resulted in medical errors and needless hospital admissions. Administrator Donald Berwick, MD: improved health, better experience of care, and lower costs. We are all frustrated by the disruptive commercial insurance policies on coverage limits, exclusions for pre-existing conditions, and admin- When these new models fail in 2015-2017, we will face a financing istrative hassles. (Under the ACA, there is relief in 2014.) For these crisis and physician payments will be targeted, despite the fact that reasons, I strongly supported passage of health care reform legislation. expenditures on physician services have lagged behind all other sectors However, implementation of the ACA follows a disturbing pattern of of health care spending growth since 2005. over-reliance on MPH public policy mavens rather than listening to concerned and cooperative physicians. Scorecard: Design: D /
?cfb[c[djWj_ed: D The strength of the ACA lies in the expansion of health care coverage. However, the weak individual mandate and state decisions not to 9ecfWhWj_l[
[\\[Yj_l[d[ii
h[i[WhY^
9;H expand Medicaid may result in less than half the projected patients attaining coverage. More important, the new payment models will not True evidence-based CER benefits all except providers or developers of lead to lower costs and will result in a funding crisis within 5 years. marginal technologies who gain market share via marketing strategies rather than demonstrated value. The promise of CER is exemplified by the CATT trial. ‘ The strength of the ACA lies in the The ACA established the Patient Centered Outcomes Research Institute 0#/2) WITHABUDGETOFBILLIONTOMEETTHISNEED(OWEVER THE expansion of health care coverage. design by Congress emphasized “patient centeredness” rather than true CER. As a result, the initial PCORI grants financed studies to measure However, the weak individual mandate “patient centeredness” rather than patient-centered outcomes research. and state decisions not to expand The PCORI policies have proven a great benefit to industry that doesn’t Medicaid may result in less than half the really want CER, and a great disservice to patients suffering from diseases where there are treatment controversies. projected patients attaining coverage.’ The flawed PCORI approach is the fault of the congressional design. The Foundation for Informed Decision Making is a successful The failure to achieve the ACA cost savings envisioned by Congress is entity that educates patients and their families on treatment options due to hubris, an overemphasis on primary care, and the revenge of the independent of the professional providing the service when there are Harvard MPHers. Stay tuned. Change will be forthcoming to address competing approaches. Wouldn’t it have made more sense to fund these deficiencies in the ACA. needed CER and utilize an extant patient-centered educational tool rather than funding measurement of “patient centeredness”?

Financial Disclosures Scorecard: Design: D /
?cfb[c[djWj_ed: B- PCORI staff :h$
H_Y^ – None. are limited by the legislative language Dr. Halperin – ALIMERA SCIENCES: Consultant, Honoraria.

36 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | POINT/COUNTERPOINT >>

Robert A. Mittra, MD Edwin H. Ryan Jr, MD VitreoRetinal Surgery, PA VitreoRetinal Surgery, PA Minneapolis/St. Paul, Minnesota Minneapolis/St. Paul, Minnesota Point: Scleral Buckling Has a Continuing Role in Repairing Retinal Detachment

Scleral buckling (SB) with an episcleral exoplant was popularized buckling. In these patients, the vitreous is typically not detached, and by Charles Schepens, MD, and others in the 1950s as a means to repair segmental or encircling scleral buckling is almost invariably successful rhegmatogenous retinal detachment (RRD), and was successful for in repairing these detachments with minimal refractive change.11-13 a variety of cases.1,2 After the introduction of pars plana vitrectomy A middle-aged person, typically a phakic myope, who presents with a (PPV) in the early 1970s by Robert Machemer, MD,3 this technique posterior vitreous detachment and one or more retinal tears with a sub- began to be employed for RRD repair, especially in complex cases,4,5 total acute retinal detachment, can also be repaired with scleral buckling post-trauma,6,7 and when proliferative vitreoretinopathy was present.8-10 alone. The reported single-surgery success rate if the macula is attached was 97%,14 with an overall success rate of 99% in a second series.15 ‘ While some cases can be managed Retinal detachment due to dialysis is most commonly seen in young successfully with PPV, a significant people, and usually the vitreous remains attached centrally. This detachment is usually amenable to treatment with a segmental subset of patients will benefit from sponge or silicone element with or without encircling buckle, with SB surgery, either alone or in a greater than 90% likelihood of stable reattachment noted with one operation.11,16 conjunction with PPV.’ Scleral buckling as an adjunct to vitrectomy

The use of PPV has expanded greatly in recent years with advances in PPV is beneficial for repair of pseudophakic retinal detachment, instrumentation and the widespread availability of wide-angle viewing particularly when the breaks are small, anteriorly located, and prob- systems. Some have suggested that PPV alone should be employed for lematic to find and treat using indirect ophthalmoscopy. During PPV, nearly all RRDs. While some cases can be managed successfully with especially with wide-field viewing, these peripheral breaks are often PPV, a significant subset of patients will benefit from SB surgery, either easily identified.17 PPV alone can be sufficient for the repair of RRD in alone or in conjunction with PPV. APSEUDOPHAKICSETTINGASLONGASTHEPATIENTSVITREOUSISSEPARATEDOR can be separated far into the periphery. All RRDs are not created equal The issue of vitreous separation arises repeatedly when discussing The underlying problem with suggesting that PPV or SB alone is whether scleral buckling is necessary in repair of retinal detachment, superior is that RRD is not a homogenous condition that can be treated as the status of the vitreous is by far the most important variable to similarly in all cases. While this may be possible with most cataract consider. Young patients generally have vitreous that is attached or only cases, as any clinician can attest, a wide variety of presentations of RRD partially separated. When these patients develop RRD, removal of core and several key factors can affect the choice of the required procedure vitreous is relatively straightforward. However, separation of the pos- to ensure the highest success rate. terior hyaloid and other areas of adherent vitreous in the periphery of an eye that has very mobile retina can be technically intricate, especially These factors include, but are not limited to the: when concurrent lattice degeneration is present.18 s0ATIENTSAGE s3TATUSOFTHEVITREOUS s0RESENCEORABSENCEOFLATTICEDEGENERATION ‘ The underlying problem with s3TATUSOFTHELENS s0RESENCEOFHYPOTONYANDCHOROIDALS PROLIFERATIVEVITREORETINOPATHY suggesting that PPV or SB alone and/or significant vitreous hemorrhage is superior is that RRD is not Patient systemic factors such as use of anticoagulant medications can also be a mitigating factor. Following are some clinical scenarios where a homogenous condition that can SB might be superior to PPV, and other situations where adding SB to be treated similarly in all cases.’ PPV can increase the success rate.

Clinical settings where scleral buckling alone These eyes have an elevated risk of recurrent detachment, either from is superior new breaks resulting from contraction of the residual vitreous or from proliferative vitreoretinopathy (PVR) with residual vitreous serving as Young phakic patients with a limited retinal detachment, particularly a scaffolding for fibrous proliferation.19 While most pseudophakes with with holes in lattice and an inferior location, are ideal for scleral Continued on page 40

38 | retina times | Fall 2012 | Volume 30, Number 4 | Issue 46 | Manfred von Fricken, MD Retina Group of Washington Fairfax and Tysons Corner, Virginia Counterpoint: Most Primary Retinal Detachments Can Be Repaired With a Vitrectomy

Leo Tolstoy wrote, “Happy families are all alike; every unhappy family regardless of the RRD’s size or location. These are eyes with chronic is unhappy in its own way.” Similarly, all successful retinal detachment RRD and RPE changes with subretinal bands and subretinal demarca- repairs resemble one another, but all unsuccessful surgical procedures tion lines. There is often associated moderate or high myopia and are memorable and imperfect in their own way. There is no consensus lattice degeneration with atrophic holes. among vitreoretinal surgeons on the optimal management of primary rhegmatogenous retinal detachment (RRD), although a recent evaluation of peer-reviewed literature suggests that scleral buckling ‘ Older patients with some and primary pars plana vitrectomy (PPV) may yield comparable pre-existing nuclear sclerosis or success rates.1 Historically, retinal detachment repair has evolved from ignipuncture existing cataract and very high to diathermy and dissected scleral beds; from polyethylene tubes to myopes who may need future large encircling elements and bands, segmental and circumferential sponges, in-office pneumatic retinopexy, and PPVs—with or without cataract surgery are encouraged scleral buckles.2-6 We can choose from a wide variety of procedures and to have primary vitrectomy ...’ techniques, all of which have merit, precedent, and support in the literature. Management consists of external drainage of usually proteinaceous Primary vitrectomy alone for RRD repair has also evolved and gained subretinal fluid and cryopexy and/or laser to the breaks. The minimal support.7-14 Most literature on retinal detachment repair is retrospec- scleral buckle needed is used to support the breaks, usually a circumfer- tive. Efforts have been made to perform prospective comparisons ential segmental sponge, but occasionally a #41 encircling band or radial of primary buckles and vitrectomy, although patient selection and sponge element. This approach also works for idiopathic or traumatic surgeon bias can materially affect these reports.15-18 inferotemporal dialyses. Likewise, a buckle can be used for select PVR cases and for some recurrent RRDs, especially with inferior disease or in ‘ The primary vitrectomy became patients unable to position postoperatively for gas tamponade. the preferred procedure for Some RRDs can be repaired in-office with pneumatic retinopexy, although patient selection is important. In my practice, all aphakic or many surgeons in the early 1990s pseudophakic patients presenting with RRD are treated with primary vitrectomy, and most other retinal detachments are preferentially when wide-angle viewing systems approached with PPV, my technique since the early 1990s with the were developed …’ advent of wide-angle viewing systems. Since 2005, almost all primary RRDs have been done with small-gauge More than 30 years ago, scleral buckle surgery involved hospital stays, instruments, mostly 25-gauge, and occasionally 23-gauge. Phakic eyes often for several days, bed rest with bilateral patching, positioning, undergoing vitrectomy are faced with the almost certain progression and pain management. The advent of primary vitrectomy has allowed of nuclear sclerosis; this must be disclosed and discussed with the this surgery to be done as an outpatient procedure; and the evolution patient when obtaining consent and may result in the patient choosing of minimally invasive small-gauge vitrectomy with 25- and 23-gauge a primary scleral buckle. instrumentation has lessened trauma and significantly reduced patient Older patients with some pre-existing nuclear sclerosis or existing discomfort without creating refractive or myopic shifts. cataract and very high myopes who may need future cataract surgery The primary vitrectomy became the preferred procedure for many are encouraged to have primary vitrectomy, as are patients with: surgeons in the early 1990s when wide-angle viewing systems were devel- s0OSTERIORBREAKSASSOCIATEDWITHLATTICEDEGENERATION oped, allowing visualization of the peripheral retina for the first time s$ENSEVITREOUSHEMORRHAGE without using the indirect ophthalmoscope or a mirrored contact lens. s7AGNER 3TICKLERDISEASE s/THERVITREO RETINOPATHIESSUCHASCICATRICIALRETINOPATHYOF FWj_[dj
i[b[Yj_ed0
7
a[o
\WYjeh prematurity (ROP) s#OMBINEDTRACTION22$S The scleral buckle is emphatically not obsolete and remains the s#OMPLEXRETINOSCHISIS22$ procedure of choice in specific settings. It is the preferred procedure in young patients with an RRD in the absence of a vitreous detachment, Continued on page 41

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 39 POINT/COUNTERPOINT >>

Drs. Mittra and Ryan, continued from page 38 There are several situations in which scleral buckling is superior to PPV and others in which it is helpful as an adjunct to PPV. Scleral buckling RRD are older, younger pseudophakes with RRD (patients still has a role in retinal detachment repair, and it remains an important younger than 55-60 years old) often have peripheral vitreous skill for retinal surgeons. still adherent during PPV when excision is attempted. In these cases, a scleral buckle encircling the globe is often quite helpful in reducing the risk of recurrent detachment from either new breaks in the periphery References or PVR arising from areas of residual vitreous attachment. 1. Custodis E. Treatment of retinal detachment by circumscribed diathermal coagulation and by scleral depression in the area of tear caused by imbedding of a plastic implant There are several other RRD repair scenarios in which an SB should be [in German]. Klin Monatsblatter Augenheilkd Augenarztl Fortbild. 1956;129(4):476-495. considered to supplement PPV. One example is eyes with significant 2. Schepens CL, Okamura ID, Brockhurst RJ. The scleral buckling procedures. 1. Surgical 20 PVR on presentation. Support in the inferior quadrants with a buckle techniques and management. Arch Ophthalmol. 1957;58(6):797-811. can sometimes prevent recurrent RD.21 3. Machemer R, Buettner H, Norton EW, Parel JM. Vitrectomy: a pars plana approach. Trans Am Acad Ophthalmol Otolaryngol. 1971;75(4):813-820. Other indications for adding an SB to PPV revolve around the issue of visualization (especially of the periphery) during vitrectomy. Eyes with 4. Machemer R, Allen AW. Retinal tears 180 degrees and greater. Management with vitrectomy and intravitreal gas. Arch Ophthalmol. 1976;94(8):1340-1346. dense peripheral vitreous hemorrhage, phakic patients with marked 5. Michels RG. Vitrectomy techniques in retinal reattachment surgery. Ophthalmol. cortical spoking, and pseudophakic eyes with peripheral capsular opaci- 1979;86(4):556-585. fication will all have areas of peripheral vitreous that may be difficult to 6. Hutton WL, Snyder WB, Vaiser A. Vitrectomy in the treatment of ocular perforating safely remove. These eyes can benefit from an SB to support the remaining injuries. Am J Ophthalmol. 1976; 81(6):733-739. vitreous should it contract and/or form anterior fibrous proliferation. 7. Peyman GA, Huamonte FU, Rose M. Management of traumatic retinal detachment with pars plana vitrectomy, scleral buckling, and gas injection. Acta Ophthalmol (Copenh). Why is scleral buckling falling out of favor? 1975; 53(5):731-737. 8. Michels RG. Surgery of retinal detachment with proliferative vitreoretinopathy. Retina. Significant skill and practice are needed to place a scleral buckle in the 1984;4(2):63-83. correct location with the desired indentation to support the retinal 9. Hanneken AM, Michels RG. Vitrectomy and scleral buckling methods for proliferative breaks and to drain subretinal fluid without complications. Scleral vitreoretinopathy. Ophthalmol. 1988;95(7):865-869. buckling is very different from microscope-based ophthalmic surgery, 10. de Bustros S, Michels RG. Surgical treatment of retinal detachments complicated by and there appears to be a significant learning curve associated with it.22 proliferative vitreoretinopathy. Am J Ophthalmol. 1984;98(6):694-699.

11. Häring G, Wiechens B. Long-term results after scleral buckling surgery in uncom- Those who train surgeons find that microscope-based surgery is plicated juvenile retinal detachment without proliferative vitreoretinopathy. Retina. easier to monitor than indirect ophthalmoscopy, and many fellowship 1998;18(6):501-505. programs correspondingly allow their trainees to do only a small 12. Lincoff H, Kreissig I. Extraocular repeat surgery of retinal detachment. A minimal number of these cases on their own. Surgeons end up getting trained approach. Ophthalmol. 1996;103(10):1586-1592. predominantly with vitrectomy for RRD and often find themselves 13. Tillery WV, Lucier AC. Round atrophic holes in lattice degeneration--an important cause of phakic retinal detachment. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol. uncomfortable unless the retina is completely flat at the end of the case. 1976;81(3 Pt 1):509-518.

14. Wilkinson CP. Visual results following scleral buckling for retinal detachments sparing the macula. Retina. 1981;1(2):113-116. ‘ Scleral buckling is very different 15. Tani P, Robertson DM, Langworthy A. Rhegmatogenous retinal detachment without macular involvement treated with scleral buckling. Am J Ophthalmol. 1980;90(4): from microscope-based ophthalmic 503-508.

16. Stoffelns BM, Richard G. Is Buckle Surgery Still the State of the Art for Retinal Detach- surgery, and there appears to be a ments Due to Retinal Dialysis? J Pediatr Ophthalmol Strabismus. 2010;47(5):281-287. doi:10.3928/01913913-20091019-10. significant learning curve associated 17. Campo RV, Sipperley JO, Sneed SR, et al. Pars plana vitrectomy without scleral buckle with it.’ for pseudophakic retinal detachments. Ophthalmol. 1999;106(9):1811-1815. 18. Michels RG, Wilkinson CP, Rice TA. Retinal Detachment. St. Louis, MO: Mosby; 1990:16

A failure of vitrectomy for retinal reattachment may not be apparent to 19. Michels RG, Wilkinson CP, Rice TA. Retinal Detachment. St. Louis, MO: Mosby; 1990:1068. the surgeon for many weeks, whereas a failed scleral buckling operation 20. Wickham L, Connor M, Aylward GW. Vitrectomy and gas for inferior break retinal is apparent often within days. Those with a cynical view as to why detachments: are the results comparable to vitrectomy, gas, and scleral buckle? Br J Ophthalmol. 2004;88(11):1376-1379. physicians make choices between procedures would point out that 21. Alexander P, Ang A, Poulson A, Snead MP. Scleral buckling combined with vitrectomy because vitrectomy reimburses more than SB and can take less time for the management of rhegmatogenous retinal detachment associated with inferior (and SB is not reimbursed at all when combined with PPV), many are retinal breaks. Eye (Lond). 2008;22(2):200-203. 23 apt to forego placement of a buckle despite any potential benefit. 22. Sagong M, Chang W. Learning curve of the scleral buckling operation: lessons from the first 97 cases. Ophthalmologica. 2010;224(1):22-29.

23. Ryan EH Jr, Mittra RA. Scleral buckling versus vitrectomy, the continued role for scleral ‘ Scleral buckling still has a role in buckling in the vitrectomy era. Arch Ophthalmol. 2010;128(9):1202-1205 retinal detachment repair, and it Financial Disclosures remains an important skill for Dr. Mittra – None. retinal surgeons.’ Dr. Ryan – ALCON LABORATORIES, INC: Consultant, Intellectual Property Rights.

40 | retina times | Fall 2012 | Volume 30, Number 4 | Issue 46 | Dr. von Fricken, continued from page 39 diabetic and PVR cases. The retinotomy and all breaks are treated with endolaser or indirect ophthalmoscopic laser photocoagulation. Gas Patients who present with RRD associated with giant tears tamponade is usually 20% SF6 and slightly expansile SF6 for inferior are managed with primary lens-sparing PPV and no scleral RRDs. C3F8 is probably not necessary in primary RRDs. buckle. The anterior vitreous is carefully shaved where it is attached to the anterior retinal flap, followed by a perfluorocarbon-1000 CS silicone Postoperative positioning and compliance are crucial for the success oil exchange. Not doing a fluid-air exchange reduces retinal slippage and of primary PPV, and the importance of patient education can’t be minimizes the surface area of exposed RPE. This may reduce the severe overemphasized. There is a role for scleral buckle in patients who have PVR historically associated with giant tears. physical disability and are unable to position, although primarily with inferior retinal detachments. In macula-off RRDs, the patients remain The silicone oil is removed after several months unless there is prolifera- supine in the recovery room or are positioned with the temporal retina tion of membranes or PVR in which case the membranes are removed in a down or dependent position to avoid creating a macular fold. under silicone oil. Giant tears should be thought of as staged procedures. All patients leave the operating room with a wristband identifying the intraocular gas bubble. Determining a surgical technique Using a routine encircling element such as a #240 band or #41 band ‘ We are all products of our training, when performing a small-gauge PPV for RRD is more invasive than necessary, especially in sutureless surgery. A limbal conjunctival but we must continue to evolve and peritomy may affect future filtering surgery, a point made emphatically by a glaucoma surgery colleague. An encircling band in a primary mature as surgeons and apply new PPV creates an unneeded safety net and may imply to the patient that surgical developments.’ “everything that can be done has been done.” However, the original intent of encircling elements was to create a new ora serrata, preventing Our retinal community has been fortunate to have had input from the posterior movement or guttering of subretinal fluid over the extremely talented and innovative surgeons and the commitment of encircling element. manufacturers. This has led to the development of vastly improved vitrectomy platforms, more rigid small-gauge cutters with improved ‘ Primary vitrectomy for the repair fluidics, superior endoilluminators, and wide-angle viewing systems. of retinal detachment is an elegant Primary vitrectomy for the repair of retinal detachment is an elegant and highly effective procedure. While there will always be a role for the and highly effective procedure.’ scleral buckle in select cases, my preference is to approach RRD with vitrectomy alone, except in the cases described above. Arguably, this remains a complex and controversial topic, and there is no real “right” Vitreous traction is best reduced by carefully shaving or excising the or “wrong” way to fix a detached retina. vitreous base with external scleral depression. This scleral depression can be done by the surgeon with chandelier illumination, or bimanually with All surgical approaches should be driven by what is in that patient’s a skilled assistant depressing 360°. This removes traction from flap tears best interest and what best fits the particular circumstances of the and allows careful shaving and debulking of the vitreous base using a patient. The 2012 ASRS Preferences and Trends (PAT) survey shows mostly closed port duty cycle and low infusion pressure, even in areas of trends toward more vitrectomies or vitrectomies with scleral buckle detached retina, with minimal risk for forming iatrogenic breaks. and fewer primary scleral buckles.19 I look forward to future surveys and believe that vitrectomy will continue to be embraced and widely Eyes with very posterior lattice degeneration have the vitreous adopted. debulked over the areas of lattice degeneration, as further anterior vitreous separation is not physically possible. Using diluted triam- We are all products of our training, but we must continue to evolve cinolone acetonide to identify and better visualize the vitreous base and mature as surgeons and apply new surgical developments. The is advocated by some. Clearly, in the absence of an encircling element principle of surgical evolution has always been to make procedures less or scleral buckle, it is crucial to perform a meticulous peripheral invasive, safer, and with quicker recovery and good outcomes. vitrectomy and to ensure that all breaks are identified and treated.

A benefit of primary PPV is that the surgeon can remove all vitreous References

opacities, deal with opacified lens capsules, and address macular 1. Schwartz SG, Flynn HW. Primary retinal detachment: scleral buckle or pars plana puckers. It is possible to peel epiretinal membrane (ERM) and inner vitrectomy? Curr Opin Ophthalmol. 2006;17(3):245-250. limiting membrane (ILM) in cases where there is substantial macular 2. Gonin J. The treatment of detached retina by sealing the retinal tears. Arch Ophthalmol. distortion from puckers or mild PVR involving the macula. Fluid-fluid 1930;4(5):621-625. exchange followed by fluid-air exchange removes viscous subretinal 3. Custodis E. Bedeutet die plombenaufnahung auf die sclera einen fortschritt in der operatven behandlung der netzhautablosung. Ber Dtsch Ophthalmol Ges. 1953;58:102. fluid. It is rare to have chronic and persistent submacular fluid in vitrectomized eyes, which can occur in macula-off RRDs repaired with 4. Schepens CL. Scleral buckling procedures. Trans Am Acad Ophthalmol Otolaryngol. 1958;(62)2:206-218. a scleral buckle. 5. Schepens CL. Symposium: Present Status of Retinal Detachment Surgery. Scleral Buck- Subretinal fluid is removed with a soft-tip extrusion cannula through ling with Circling Element. Trans Am Acad Ophthalmol Otolaryngol. 1964;68:959-979. a small internal retinotomy or through existing breaks. Some surgeons effectively use perfluorocarbon (PFO) liquids in primary RRD, while Continued on page 55 others tend to reserve PFO in cases of giant retinal tears or select

| Issue 46 | Volume 30, Number 4 | Fall 2012 | retina times | 41 THE KOL CORNER >>

Marc J. Spirn, MD Carl D. Regillo, MD Section Co-Editor Section Editor Wet AMD: The Changing Landscape

Since 2005, when intravitreal bevacizumab was first recognized as a treatment for neovascular age-related macular degeneration (AMD), patient outcomes have been greatly enhanced. Visual acuity gains with bevacizumab and ranibizumab were typically far better than with thermal laser, photodynamic therapy (PDT), and pegaptanib.

J^_i
?iik[Êi
A[o
Ef_d_ed
B[WZ[hi Yet after several years and hundreds of retreat. If she is dry or has had a significant thousands of patients treated, several improvement in OCT, I would continue the questions remained: bevacizumab and schedule the next visit 4-5 weeks later. s7ERERANIBIZUMABAND bevacizumab equivalent? I would use a treat-and-extend protocol. If s(OWOFTENSHOULDPATIENTSBETREATED there is continued fluid on OCT, I would David Boyer, MD Omesh P. Gupta, and/or followed? switch to ranibizumab or aflibercept to dry Retina-Vitreous Associates MD, MBA s7HATISTHEBESTWAYTOTREAT the OCT and continue to treat until dry. If an Medical Group Mid Atlantic Retina Los Angeles, California Philadelphia, Pennsylvania suboptimal responders? RPE detachment were also present, I would s7HATWOULDBETHENEXTBLOCKBUSTER probably favor aflibercept. pharmacotherapy for neovascular AMD? Omesh Gupta: This patient would be In the last year, new light has been shed treated as most patients in my practice, with on several of these questions. The CATT anti-VEGF agents. I would initially treat trial showed that with possible small-scale monthly until there are no signs of exudation. differences, bevacizumab and ranibizumab David M. Brown, MD Treatment regimen is a continually evolving Retina Consultants of Houston are largely equivalent. Aflibercept, which Houston, Texas issue, and is often tailored to individual inhibits placental growth factor in addition to needs. Patients with a very active lesion, a VEGF-A, was introduced in November 2011 fellow eye with a disciform scar, or monocular with much fanfare. So now, instead of 2 highly vision for any other reason are treated much effective treatment options, we have 3. more aggressively. As the HARBOR trial comparing high-dose Patients with minimally active lesions (2.0 mg) to standard-dose Lucentis (0.5mg) or a pigment epithelial detachment as the (Genentech, South San Francisco, CA), comes only remaining sign of exudation are to a close and with the drug pipeline full of treated less aggressively. In these patients, exciting new therapies, the treatment choices the treatment interval might be gradually for neovascular AMD will likely become even extended or, in some cases, intravitreal more complex and effective. In this environ- injections might be stopped until signs of ment, we sought several key opinion leaders to exudation recur. discuss how they are treating wet AMD. David Brown: My preferred treatment An 86-year-old woman presents would be induction with either Eylea with new-onset, predominantly (Regeneron Pharmaceuticals, Tarrytown, NY) classic, subfoveal neovascular or Lucentis for 3 months. If dry at 3 months, AMD and visual acuity of 20/100 we would discuss the option of very close in her right eye. What treatment observation—particularly if the other eye is and regimen would you use for relatively good, as 20% of patients are lucky this patient? enough to dry out with induction and not require ongoing injections. David Boyer: I would start with an anti-VEGF agent. If there is any doubt on If there is any fluid at 3 months, I would insurance status, I would use bevacizumab continue monthly therapy until dry. Should and obtain co-pay assistance forms to be filled the fluid ever recur with close observation, I out. I would see the patient in one month and would use a treat-and-extend regimen—never

42 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | extending more than 2 weeks at a time. patient doesn’t have a thickened choroid— reported a significantly greater number I’m more conservative on the extension in indicative of central serous retinopathy of bevacizumab patients suffered serious monocular patients, typically not going more (CSR)—or polyps on ICG angiography. If systemic adverse events. than 6 weeks. either CSR or idiopathic polypoidal cho- David Brown: As CATT 2-year data show roidopathy (IPC) is suspected, I would treat For a patient with a Medicare Advantage Plan that Avastin is not as durable as Lucentis, with concomitant photodynamic therapy. (HMO) that discourages Eylea or Lucentis use, I treat more aggressively (more injections) I would typically recommend Avastin (Genen- How have the CATT and IVAN in patients who are on Avastin. I am also tech, South San Francisco, CA) monthly for trials affected your prescribing more reticent to use Avastin in patients with 3 months with very cautious extension, as the of bevacizumab and ranibi- systemic heart disease or CVA, given the CATT 2-year data imply that very few patients zumab? Have they altered your anti-VEGF systemic suppression shown in dry up on monthly Avastin, and PRN Avastin daily practice? If so, how? IVAN. The anti-VEGF suppression seen with therapy is detrimental. intravitreal use shown in IVAN was recently David Boyer: The CATT trial made me added to the European Avastin warning label. After 6 monthly intravitreal realize that a PRN treatment of ranibizumab bevacizumab injections, a can result in good vision, but the patient A 72-year-old man with 67-year-old man with neovas- needs to be followed monthly. I also felt new-onset neovascular AMD and cular AMD has decreased, but better that I was not compromising vision decreased visual acuity asks to persistent, subretinal fluid on by using bevacizumab. be treated with aflibercept. You OCT and visual acuity of agree and begin treatment. After Because I tend to treat and extend, I would the third injection, despite a 20/70. Do you change your probably favor ranibizumab due to its treatment regimen? superior drying effect. The CATT and IVAN significant improvement in subretinal fluid, mild subretinal David Boyer: I assume the patient has trials did not allay my concern for systemic fluid persists. You inject him received monthly injections of bevacizumab. safety, though the biologic mechanism for the At this point, I would switch the drug to increase signal is not apparent. again. When would you ask the patient to return for repeat ranibizumab or aflibercept and have the Omesh Gupta: While a significant amount evaluation? Under what circum- patient return in 10 days. If the OCT shows a of information can still be extracted from response, I would reevaluate 4 weeks after the these data sets, the 2-year results of the CATT stances would you extend your last injection and continue monthly injections study have changed my practice patterns. treatment interval? with the hope of eventually extending the This study demonstrated that monthly dosing David Boyer: I treat until dry, so I would treatment intervals. produced slightly more vision gain than an see the patient in 4 weeks. I have found that If there has been no response on the OCT as-needed regimen. Treating patients with there are patients who have persistence of at 10 days, I would have to assume this individualized protocol, such as treat and subretinal fluid despite monthly injections. is a non-VEGF-related disease such as extend, has become a popular approach in Though the studies showed injections of polypoidal and would re-image the my practice. aflibercept given every 2 months (after patient with indocyanine green (ICG), While I still attempt to individualize care 3 loading doses) yielded the same visual autofluorescence and intravenous fluorescein based on a number of factors, I tend to results as ranibizumab or aflibercept given angiography (IVFA), though aflibercept be a bit more conservative with extending monthly, I treat until dry if possible. I extend may work on polypoidal disease. follow-up. In fact, in some “high-risk” patients my interval only when the OCT is dry. If it has Omesh Gupta: With other very good as described above, I may recommend taken a long time to dry the patient out, options available, my threshold to consider monthly dosing. I proceed very slowly. other treatments is very low. I may not change However, in the CATT study, the final visual Omesh Gupta: While there are a lot of treatment in every case in which there is results were also similar in all treatment factors to consider, I would still continue with persistent subretinal fluid at 6 months of groups, regardless of dosing frequency. As Eylea. After 3 monthly injections, it has been monotherapy. At this time, I would consider more data are obtained, my treatment proposed that Eylea be dosed every 2 months. switching to intravitreal ranibizumab. regimen will also evolve. For all patients I treat with Eylea, I always While bevacizumab and ranibizumab are We must be careful in interpreting results discuss this unique treatment protocol before similar, differences in response have been well regarding systemic adverse events (SAEs). initiating treatment. At this point, similar described. In time, as aflibercept eventually The CATT and IVAN studies were neither efficacy was demonstrated with every- is covered by more insurance carriers, it will designed nor powered to evaluate SAEs. 2-month dosing compared with monthly become a more compelling option. I would In the CATT trial, more events occurred dosing. Again, I would continue with Eylea q2 also consider using photodynamic therapy in in the patient group that received fewer month dosing. combination therapy. injections, which is not the typical dose- If the subretinal improvement and/or visual David Brown: I would prefer to switch the response relationship. acuity do not continue to improve with patient to Eylea or Lucentis if the insurance The IVAN trial observed more arterio- subsequent injections, I would consider coverage allows it. If this is not an option, I thromboembolic events or heart failure bevacizumab, ranibizumab, or photodynamic would continue monthly therapy, as many with ranibizumab than with bevacizumab. therapy. I would also discuss surgical options of these patients with subretinal fluid (SRF) On the other hand, the CATT study for patients with a concurrent epiretinal maintain VA. I would also make sure the membrane or vitreomacular traction.

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 43 THE KOL CORNER >>

David Brown: I would treat monthly Omesh Gupta: Photodynamic therapy ceuticals, Inc, Tarrytown, NY) as part until dry. In my experience, approximately is the only option I still use—typically in of the regimen, as this will control the 30%-40% of Eylea patients need dosing more patients in whom I want to limit the injection AMD process without the need for ongoing frequently than q8 weeks. If all intraretinal burden. There are a couple of scenarios where intravitreal injections. fluid is gone but SRF persists, I really look PDT has worked really well. at the EDI-OCT and ICG. If the patient One patient was receiving monthly dosing and has evidence of a thickened choroid (CSR), Financial Disclosures the treatment interval could not be extended Dr. Regillo – GENENTECH: Consultant, Investigator, Speaker, hyperpermeability (CSR) or polyps (IPC), Grants, Honoraria; REGENERON PHARMACEUTICALS, without an exudative recurrence. She lived a INC: Consultant, Investigator, Speaker, Grants, Honoraria; I recommend concomitant PDT therapy. GLAXOSMITHKLINE: Consultant, Investigator, Grants, significant distance from our nearest office Honoraria; OPHTHOTECH CORPORATION: Investigator, Are there instances when you and was inquiring about other options. After Grants; NEOVISTA, INC: Investigator, Grants; SECOND SIGHT: Investigator, Grants; ACT: Investigator, Grants; AMO: consider therapies other than one round of half-fluence PDT, I was able to Advisory Board, Consultant, Honoraria; ALCON LABORA- TORIES, INC: Consultant, Investigator, Grants, Honoraria; bevacizumab, ranibizumab, stabilize her treatment interval at 2-3 months. ALLERGAN, INC: Consultant, Investigator, Grants, Honoraria. and aflibercept when treating I may also use PDT in patients who refuse Dr. Spirn – None. injections or are “high-risk.” :h$
8eo[h – ALCON LABORATORIES, INC: Advisory Board, neovascular AMD, such as Consultant, Investigator, Speaker, Grants, Honoraria; ALLERGAN, INC: Advisory Board, Consultant, Investigator, pegaptanib, focal choroidal laser, David Brown: As mentioned, masquerade Speaker, Grants, Honoraria; ALLEGRO OPHTHALMICS: Advisory Board, Stockholder, Honoraria; GENENTECH: or PDT? syndromes of CSR and IPC should be consid- Consultant, Investigator, Speaker, Grants, Honoraria; ered, particularly in patients with persistent REGENERON PHARMACEUTICALS, INC: Consultant, David Boyer: I still use PDT with Investigator, Grants, Honoraria; iCo THERAPEUTICS INC: fluid despite monthly therapy; if present, they Consultant, Investigator, No Compensation Received; anti-VEGF in patients with extrafoveal GLAXOSMITHKLINE: Consultant, Honoraria; NOVARTIS should be treated with PDT. However, I would PHARMACEUTICALS CORPORATION: Consultant, Investigator, choroidal neovascularization (CNV) or Grants, Honoraria; BAYER HEALTHCARE: Consultant, caution against using PDT if the choroid is growing peripapillary CNV lesions. I also Honoraria; QUARK PHARMACEUTICALS, INC: atrophic as determined by EDI-OCT, as PDT Investigator, Grants. treat patients with PDT and anti-VEGF for :h$
=kfjW – None. causes choroidal hypoperfusion, which may reactivation of previously quiescent scars Dr. Brown – GENENTECH/ROCHE: Advisory Board, lead to decreased VA in these eyes. Consultant, Investigator, Grants, Honoraria; REGENERON that begin to activate on the margin (usually PHARMACEUTICALS, INC: Advisory Board, Consultant, Investigator, Grants, Honoraria; ALLERGAN, INC: Advisory in the better eye of the patient) with fluid I occasionally recommend Macular Board, Consultant, Investigator, Grants, Honoraria; ALCON LABORATORIES, INC: Advisory Board, Consultant, and/or hemorrhage. Photocoagulation Study (MPS)-style laser Investigator, Grants, Honoraria. for extrafoveal and peripapillary lesions I rarely use focal choroidal laser, but would if if the lesions require ongoing monthly the lesion were extrafoveal and well demar- injections. If the patient is undergoing cated (mostly non-AMD patients). I have not chemotherapy for colon cancer, I sometimes used the LEVEL trial results very much and suggest that the oncologist consider systemic can think of only 1 or 2 patients I converted Avastin or Zaltrap (Sanofi-Aventis US, LLC, to Macugen (Eyetech, Inc, Cedar Knolls, NJ) Bridgewater, NJ; and Regeneron Pharma- after a stroke when I discussed the potential risks of an additional stroke.

RETINA PRACTICE PEARLS >>

‘ Follow the 5-year plan: At ‘Gratitude is a memory of ‘ Learn and be accountable for the end of 5 years in your the heart.’’ your mistakes. Try not to make practice, you and your spouse —Credited to Jean Baptiste Massieu (1772-1846), the same mistake twice.’ pioneering deaf educator or significant other should vote Submitted by Suber Huang, MD, MBA —Submitted by Paul E. Tornambe, MD on whether to stay or leave. One Send us your Retina Practice Pearls vote to leave means you both leave and find a new practice ‘ The things you do for yourself Have a Retina Practice Pearl to share? Please send it to [email protected], noting location. I have shared this are gone when you are gone, whether the quote is your own; if it is, we advice with all of my fellows over but the things you do for others will give you full attribution. If the quote is the last 25 years, and Judy and remain as your legacy.’ attributable to someone else, please specify the originator. We will credit the source and —Credited to Kalu Kalu, Professor of Political Science, I both firmly believe in it.’ Auburn University Montgomery acknowledge you for submitting the quote. —Submitted by Trexler Topping, MD; Submitted by Suber Huang, MD, MBA credited to his wife, Judy

44 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | BLOCK TIME >>

Sunir J. Garg, MD Mitchell S. Fineman, MD Section Co-Editor Section Co-Editor

PART 2 How Has the Retina Subspecialty Changed Since Vitrectomy?

In the 30th Anniversary Retina Times, Block Time asked 6 veteran retina educators how the retina subspecialty has progressed from its inception in the 1960s and 1970s. Part 2 of this series explores the evolution in treatment of diabetic patients, as well as how vitrectomy has changed the practice of retina.

What happened to diabetic patients allowed us to manage the most severe in the pre-vitrectomy era? complications of diabetic retinopathy.

Lov Sarin: They often did poorly. Prior Jay Federman: Xenon arc photocoagula- to vitrectomy, we had contact lens laser, but tion (Meyer Schwickerath, MD) and then

Thomas Aaberg Sr, Jay Federman, MD pars plana vitrectomy (PPV) was a boon for laser photocoagulation (Frank L’Esperance, MD, MSPH Professor of diabetic patients. Panretinal photocoagulation MD) led the way both in Europe and the Former Chair, Department Ophthalmology of Ophthalmology Wills Eye Institute (PRP) became accepted around the time we US to cause regression of the proliferative Emory University Philadelphia, Pennsylvania started using vitrectomy routinely, so both component. But even then, traction RDs could Atlanta, Georgia technologies developed together. be managed only with large buckles and 360° scleral resections and infoldings. Thomas Aaberg Sr: We were using PRP and focal ablative laser for neovascularization William Tasman: What happened before elsewhere (NVE), but little was done for vitrectomy? There were diabetic traction diabetic cystoid macular edema until after detachments, some of which we did cure, Gary Abrams, MD Lov Sarin, MD the ETDRS trial was completed. miraculously enough, with scleral buckles. Professor of Ophthalmology Professor of Ophthalmology Before scleral buckling, diabetic retinopathy Former Chair Wills Eye Institute Kresge Eye Institute Philadelphia, Pennsylvania was treated with all kinds of witchcraft. For Wayne State University ‘ In the pre-vitrectomy example, some patients were put on rhubarb Detroit, Michigan era, if the PRP didn’t to treat their vitreous hemorrhages. Vitrec- tomy was a real blessing—one of the major contain the proliferative advances of the 20th century. retinopathy, diabetic William Benson: In the pre-vitrectomy era, if the PRP didn’t contain the proliferative William Benson, MD William Tasman, MD patients would get retinopathy, diabetic patients would get Former Director Professor and Emeritus horrible traction RDs or a vitreous hemor- The Retina Service Chairman horrible traction RDs or Wills Eye Institute Wills Eye Institute rhage and go blind. Philadelphia, and Jefferson Pennsylvania Medical College a vitreous hemorrhage Philadelphia, Pennsylvania When vitrectomy was introduced, did and go blind.’ retina specialists think it was a major —William Benson, MD advance, or simply another fad? Lov Sarin: Until Robert Machemer invented a closed system to remove vitreous, a lot of people Gary Abrams: If a traction retinal detach- thought you should never touch the vitreous, so ment (TRD) wouldn’t settle with a scleral all we had were buckles. Can you imagine how buckle (SB) or scleral shortening procedure, difficult it is to find a hole in a bullous RD even there was really nothing to do. In the early with the indirect ophthalmoscope? PPV made 1970s, PRP was introduced only shortly before life easier and less stressful for these types of vitrectomy; both of these major advances cases, and also had a better success rate.

46 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | Thomas Aaberg Sr: Some thought it was operate and remove the blood, but they will just of long-acting gases (Stanley Chang), and heresy to interfere with the anatomic structure bleed again,” and people didn’t initially realize perfluorocarbon liquids (Stanley Chang, of the vitreous, although “open-sky” vitrectomy that once you took the traction off the neovascu- separately and simultaneously Gholam through the limbus had been used for several larization it often regressed. Some of the patients Peyman), and more creative instrumentation, years and localized vitreous “bands” had been did re-bleed, but many did not. the debate of scleral buckle vs vitrectomy or severed (in part) with pars plana insertion combined procedures became more prominent of scissors or forceps. However, the advent of When did vitrectomy become a in the early 2000s. Although some of us closed-eye mechanical pars plana vitrectomy regular surgical option for RD repair? used vitrectomy a little earlier for non-PVR made believers of most retina specialists. detachments, I think this is relatively new Lov Sarin: Initially, PPV was used for cases thinking in the past decade. Jay Federman: Most felt vitrectomy was a with proliferative vitreoretinopathy (PVR). major advance, as it was the most efficient way There was a movement toward vitrectomy to manage nonclearing vitreous hemorrhage, because it was easier to find the breaks, ‘ PPV was used for PVR but that it was a very aggressive procedure especially in bullous RD. PPV also reduced fraught with potential complications and how often we used cryo, which was starting to repair in the early to performed by only a few retina specialists. be recognized as a contributor to PVR. Once people realized they could find breaks during mid-1970s, but success Gary Abrams: At first I don’t think vitrectomy, it began to be used even more for everybody realized the importance of the rates were poor until routine RD repairs. advance. Robert Machemer said that Ron the intraocular argon Michaels was the first fellow at Miami to With buckles, we had to find all the holes, and truly grasp the importance of the procedure in many cases, there could be holes anteriorly, laser was developed in and to make vitrectomy his main fellowship posteriorly, etc—and all had to be identified objective. I think Robert had been doing and supported. During PPV, all we had to do the early 1980s …’ vitrectomies for about 3 years by the time Ron was remove the gel and do 360° laser. PPV —Thomas Aaberg Sr, MD started his fellowship. increased success and made life less stressful. Thomas Aaberg Sr: PPV was used for ‘ Until Robert Machemer PVR repair in the early to mid-1970s, but Gary Abrams: For the first 15 years, success rates were poor until the intraocular vitrectomy was used only for complex retinal invented a closed argon laser was developed in the early 1980s, detachments and never for primary, uncompli- as xenon photocoagulation could not be read- cated detachments. Rich Escoffery and the group system to remove ily employed in an air-filled eye. in St. Louis presented their series of primary detachments managed with vitrectomy without vitreous, a lot of Jay Federman: When I completed my an SB at the Vail Vitrectomy Meeting, and the retinal fellowship at the Retina Service of paper was published in the American Journal people thought you the Wills Eye Hospital in 1971, all the retina of Ophthalmology in 1985.1 The presentation surgeons only resected scleral beds, creating should never touch and paper were not well-received initially, and buckles, and used diathermy with scleral/ vitrectomy for primary retinal detachment did the vitreous, so all we transchoroidal drainage. The attendings were all not become common until the mid-1990s. had were buckles.’ scleral buckle-trained and vitrectomy did not exist. In 1972, I started to do vitrectomy at Wills, The report by Bartz-Schmidt, et al in the British —Lov Sarin, MD mainly for nonclearing vitreous hemorrhage, Journal of Ophthalmology in 19962 that showed traction RDs, recurrent RDs with PVR, retained excellent results in pseudophakic RDs was lens material and vitreous incarceration after important; vitrectomy gradually became the I was a first-year resident in the fall of 1973 with cataract surgery, and endophthalmitis. most common technique for pseudophakic Tom Aaberg in Milwaukee. Interestingly, the detachments after that. From 1997 to 2007, fellow let me scrub on all of the vitrectomies For complicated RDs, the vitrectomy was according to the Medicare database, vitrectomy during my 2-month retina rotation because he usually combined with a buckling procedure with or without SB increased 72%, while SB wanted to scrub on all the scleral buckles. I think with a silicone plate, band, or sponge and cryo. without vitrectomy decreased by 69%.3 that is a comment on the attitude at that time. We did not have the laser delivery systems of today, so if a posterior lesion needed William Tasman: Vitrectomy became a William Tasman: It was obvious to me that treatment, we used external transscleral cryo; regular part of retinal detachment repair in the vitrectomy was a major advance, and we got if you could not reach the posterior problem, 1980s. There were other techniques that came in on this very early because Dr. Machemer you used internal cryo. This was a challenge. along in the interim, like pneumoretinopexy, was generous enough to spread his knowledge which is obviously still done. But vitrectomy around the world. There was a real learning In the late 1970s and 1980s as the viewing matured and was more and more accepted. curve when you started to do vitrectomy, systems, instruments, and techniques Today it seems to be the most popular which can be true for any operation. improved, we began to find more uses where procedure—even for primary detachments. vitrectomy was beneficial, such as for giant William Benson: I think most people tears and macular puckers. In the 1980s and William Benson: I stopped doing surgery recognized that vitrectomy was a great thing. 1990s as more retina specialists were trained in 2000, but we were still doing primary Initially when people started doing vitrectomies, in vitrectomy, and with the development buckles. The real breakthrough was pneumatic some ophthalmologists thought, “So what? You

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 47 BLOCK TIME >>

retinopexy. At first, I was afraid that putting long-acting gas, silicone oil, retinectomy was detached, and all you had to do was get gas into the vitreous would increase the techniques, and perfluorcarbon liquids. We through the yellow ochre membranes so you incidence of PVR, and then you wouldn’t started doing vitrectomy for giant tears early, could identify the retina, and then just eat up be able to fix the detachment with a buckle. but we couldn’t unfold them with the patient the vitreous. But when I saw the results of a collaborative in a supine position. Following that, of course, vitrectomy trial indicating that even if pneumatic failed, expanded into difficult retinal detachments— you still would be able to fix the RDs at the those with PVR—and I think it was helpful in accustomed rate, I became somebody who ‘ The introduction traumatic cases, especially perforating injuries really enjoyed doing pneumatics. of perfluorocarbon where the missile might have gone in and out of the eye. It became helpful there because we In the early days, which cases liquids took giant-tear could reach exit sites in the posterior pole that underwent vitrectomy? management out of were inaccessible prior to vitrectomy. Giant Lov Sarin: Ninety percent of the cases were tears were also important; we found we could vitreous hemorrhage (VH) due to diabetes. the medical center and do much better with a vitrectomy than we We did some complicated PVR detachments as into the community.’ had with all of the earlier procedures. well. However, some people got a little carried William Benson: Diabetic hemorrhages away with vitrectomy and spent 90 minutes —Gary Abrams, MD and giant tears are the 2 I can think of right fixing an RD with PPV, when a number of now. I was there when Machemer unrolled those cases could be fixed in 10 minutes with the retina—he took a needle, unrolled the a buckle. We used a Stryker table modified to make retina, and the giant tear rolled over. That was the patient prone following vitrectomy, then Jay Federman: As mentioned, nonclearing a miracle. unfolded the giant tear with a prone fluid-air vitreous hemorrhage, traction RD, and PVR exchange (with the surgeon on the floor, RD followed. The development of intraocular How has training of your fellows looking up at the prone patient). It was very lenses (IOLs) and phacoemulsification was just changed since the 1970s? difficult and fraught with potential complica- in its infancy and most cataract procedures tions and failure. Lov Sarin: Certain aspects have been the were open-sky; vitrectomy proved most effective same throughout. Some of the fellows were in managing many complications resulting I remember when Kim Frumar from Sydney, exceptionally talented. The fellowship went from these anterior segment procedures. Australia, who had trained with Peter Leaver from 1 to 2 years, which was a big change. Vitrectomy was also performed very early for at Moorfields Eye Hospital in the United At one point, we had 6 or 7 fellows per year. endophthalmitis. Kingdom, came through Milwaukee in 1984; We got a lot of complaints about how many he drew me a diagram on a dinner napkin on specialists we as a retina community were how to manage a giant tear with silicone oil training, so we went to 2 or 3 for a 1-year ‘ For complicated RDs with the patient in a supine position. On fellowship. Then our volume and the amount July 4, 1984, I repaired a 270° giant tear with [in the early 1970s], to learn became so great that the fellowship the technique on a young woman and never went to 2 years. the vitrectomy was did another prone fluid-air exchange for a giant tear again. Thomas Aaberg Sr: Retina fellows now usually combined with a get great experience with office intravitreal It was really exhilarating to be able to let go of injections, OCT and real-time ultrasonography, buckling procedure with that terrible technique. Many of us used fluid- photocoagulation, and vitrectomy, but their silicone oil exchange to unfold giant tears until training in scleral buckling is often deficient. a silicone plate, band, perfluorocarbon liquids were introduced. It or sponge and cryo.’ was a good technique that few people outside Gary Abrams: Until the 1990s, most of a few major centers did, so I got to do a fellowships lasted only 1 year and that was —Jay Federman, MD lot of giant tears in the mid to late 1980s. The plenty of time to learn what was necessary to introduction of perfluorocarbon liquids took do vitrectomy and repair retinal detachments giant-tear management out of the medical with scleral buckles. However, as vitrectomy Thomas Aaberg Sr: I began doing center and into the community. became more complex and we were doing closed-eye pars plana mechanical vitrectomy more technically challenging procedures, it William Tasman: The first cases were in 1970, and the vast majority of the early was apparent that clinical fellowships should diabetic vitreous hemorrhages, especially the series that I, as well as others, reported were be 2 years. long-standing ones that had so-called yellow for eyes with vitreous opacification, most ochre membranes. These lent themselves My approach to fellowship training has not commonly hemorrhage. beautifully to vitrectomy, as these were changed much over the years. I firmly believe Gary Abrams: Diabetic vitreous hemorrhage patients who might not have been able to see that fellows learn best by doing, so I have was the most common indication. Trauma for years, and then you took this opacification always allowed fellows to do what they can was also an early indication. We operated out of the vitreous cavity and their sight was safely do. I closely supervise them and let on complex detachments even early in the restored. It was not one of the more difficult them continue until I detect that they are vitrectomy era, but the success rate was not vitrectomies—in fact, it wasn’t difficult at not making progress or are struggling with good until advances of air pump, endolaser, all because most of the time the vitreous technique. At that point, I usually take over,

48 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | but try to let them back in at some later time is much shorter. Other improvements day—it was difficult. The fellows also had to point in the case so they will feel a sense of include use of silicone oil and long-acting show up to make rounds on the people in the accomplishment at the end of the case. gases, vitreous and membrane stains, more hospital for 4 days post-op. They had to make varied disposable instruments, and improved rounds on them every day before surgery. Now With each new advance, we usually get the viewing systems. with surgery centers, 4 cases can be done by fellows involved relatively early with the 10:00 AM. Fellows used to work a lot longer process. Be it use of perfluorcarbon liquids, William Tasman: The big change was hours; the current fellows that I see are going membrane peeling, retinectomy, or internal switching from buckles to vitrectomy. Over home some days at 1:00 or 2:00 PM. limiting membrane peeling, once we as teach- the last 10-15 years, training of fellows has References ers became comfortable with a technique, accentuated vitrectomy. Fellows today don’t 1. Escoffery RF,Olk RJ,Grand MG,Boniuk I (1985) Vitrectomy we allowed the fellow to begin doing it. We have to know how to do an old-time scleral withoutscleral buckling for primary rhegmatogenous buckle—and their idea of a buckle compared retinal detachment.Am J Ophthalmol 99:275–281Escoffery are doing different techniques than many RF,Olk RJ,Grand MG,Boniuk I (1985) Vitrectomy with- years ago, but I don’t think the approach to with mine can be very different. Sometimes a outscleral buckling for primary rhegmatogenous retinal detachment.Am J Ophthalmol 99:275–2811. Escoffery RF, training has changed much. Fellows now buckle is referred to as just a band around the Olk RJ, Grand MG, Boniuk I. Vitrectomy without scleral buckling for primary rhegmatogenous retinal detachment. have the opportunity for early training with eye, and I think that’s pretty common today. Am J Ophthalmol. 1985;99(3):275-281. computerized surgical simulators, but it is still Of course, buckles were much more involved 2. Bartz-Schmidt KU, Kirchhof B, Heimann K. Br J Ophthalmol. a specialty that requires direct apprenticeship when they were the procedure of choice. 1996;80:4 346-349. doi:10.1136/bjo.80.4.346. with great surgeons to gain skill. The emphasis now is on vitrectomy training, 3. Ramulu PY, Do DV, Corcoran KJ, Corcoran SL, Robin AL. Use of retinal procedures in Medicare beneficiaries from and rightly so. I think the surgical results 1997 to 2007. Arch Ophthalmol. 2010;128(10):1335-1340. ‘ The first [vitrectomy] speak for themselves and that the training changes as the field evolves. Fellows have

cases were diabetic moved to operating with the microscope Financial Disclosures rather than simply operating on the outside :h$
=Wh]
Å
MD INTELLISYS: Stockholder, No Compensation vitreous hemorrhages, Received; GENENTECH: Investigator, Grants; REGENERON of the eye. The fellows become proficient in PHARMACEUTICALS, IN C: Investigator, Grants; LUX BIOSCIENCES: Investigator, Grants; EYE GATE: Investigator, especially the long- vitrectomy, learn how to peel membranes, and No Compensation Received; ALLERGAN, INC: Speaker, do not have to use a buckle as the primary Honoraria; QLT INC: Consultant, Honoraria. standing ones that had :h$
<_d[cWd—THROMBOGENICS: Consultant, Grants; method of attack in many cases. PHYSICIAN RECOMMENDED NUTRICEUTICALS: Consultant, Honoraria. so-called yellow ochre William Benson: Training fellows changed :h$
7WX[h]
Å
None. because as new techniques were developed, we :h$
7XhWci
Å
ALCON RESEARCH INSTITUTE: Advisory membranes.’ Board, Honoraria. added them to their training. I remember Lov :h$
8[died
Å NATIONAL EYE INSTITUTE: Investigator, Sarin telling me that doing 4 cases was a really Grants; GENENTECH: Investigator, Grants; ALCON LABO- —William Tasman, MD RATORIES, INC: Investigator, Grants; LUX BIOSCIENCES: busy day. Part of the problem we had was with Investigator, Grants; JOHNSON & JOHNSON: Investigator, Grants; GLAXOSMITHKLINE: Investigator, Grants. general anesthesia and the turnover time was Jay Federman: The fellowship has :h$
<[Z[hcWd
Å
OMTI (telemedicine software company): long and it was hard to do more than 4 cases. Director/Principal, No Compensation; ESCALON MEDICAL evolved with time, mostly as the technology CORP: Director, Stock Options; RETINA IMPLANT AG: Sometimes you’d do 5 or 6, but you really had Consultant. improved. Vitrectomy machines improved to press to get it done. Dr. Sarin – None. with the development of full-function units, :h$
JWicWd
Å
None. smaller-diameter instruments resulted in After the fellows had finished the day in the smaller incisions, viewing systems improved, OR at 5:00 or 6:00 PM, they had to work up the infusion fluids have been made safer, operating patients who had been admitted for the next

The American Society of Retina Specialists gratefully acknowledges the following Corporate Members who have committed generous support to the Society for 2012.

Emerald Corporate Member Silver Corporate Members Bronze Corporate Members Genentech Bausch + Lomb Carl Zeiss Meditec Insight Instruments, Inc. DORC International BV/ Platinum Corporate Member QLT, Inc. Dutch Ophthalmic USA Alcon Laboratories, Inc. Santen Pharmaceutical Co, Ltd. IRIDEX Corporation Allergan, Inc. ThromboGenics PanOptica, Inc. Regeneron Pharmaceuticals, Inc. Synergetics™ USA, Inc.

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 49 JERRY’S WISDOM >>

Jerald A. Bovino, MD Section Editor Everybody Is Sellin’ Somethin’

The hospital dinner was running late and the you until he had the back of your head pinned rich kids just made Johnny cry because of my doctors were furious. Hospital dinners seem firmly against the wall. To make the situation line of work,” she told the boys. “I am going anachronistic in this age of outpatient surgery. even more desperate, he had the world’s worst to tell you something now and I want you to However, those of you who started out with me case of bad breath. If the Iranians could put remember it your entire life.” in the early Pleistocene era will remember when that breath in centrifuges and weaponize it, As the boys cowered and held their breath, she we were forced to attend hospital staff dinners they would have no need to build an atomic said “Everybody is sellin’ somethin’!” each month to keep our surgical privileges. bomb. The Western world would just surrender after one whiff. Just a sniff of concentrated We are a lot more fortunate than the young neurosurgeon breath, and all American women lady in the yellow sun dress. You and I have ‘ They ran to Johnny and would be wearing burkas. been able to get a sound education, a medical degree, specialized training in an ophthalmology started taunting him: The neurosurgeon proceeded to tell us in great residency, and a great fellowship in retina detail how he was raised in an affluent family surgery. We can be proud of our profession “Your mom’s a whore!”’ in New Jersey horse country. As a boy, he spent and our accomplishments and the wonderful his summer vacations at the beach in Atlantic things we do every day to help patients. On this particular night, the executives droned City, which was actually quite fashionable and on about the waves of HMOs and PPOs that even chic back in the late 1940s and early 1950s. However, just like Johnny’s mother, to be were washing across the medical landscape. Of course, that all changed as the honky-tonk successful, you will be “sellin’ somethin’” your They told us that we would have to discount of the boardwalk took over and evolved into entire life. It might be convincing your chairman this or that and work harder and be happy the messy vitality of the casino era, but Atlantic that you are a great researcher. Maybe it’s being a member of the hospital team. In return, City, especially before air conditioning, was a trying to get your paper published in the AJO. the doctors were all lamenting the undesirable playground of the rich. It could be demonstrating to a patient that you and unwanted commercialization of medicine. are a compassionate physician. It can happen The clock was pushing 11:00 PM as the neuro- “Why can’t they just let us be doctors and when you get up to give a lecture to your peers surgeon reminisced about playing on the beach practice medicine?” we wondered. “Why does about a new instrument or procedure or with 10 or 12 other privileged boys from his medicine have to be like a Turkish bazaar?” drug at the ASRS meeting. elite private school. However, there was one boy As we digested the last of our overcooked who joined the group who simply did not fit chicken and prepared to dash for the exits, one into the affluent mold. It was clear that Johnny of the neurosurgeons invited himself to the was from the wrong side of the tracks, but he ‘ [Johnny’s mom] told podium, grabbed the mike, and started telling was ebullient and athletic and a great ballplayer, the boys, “I am going a seemingly irrelevant and out-of-place story and they all became fast summer friends. about his boyhood. “Has he lost his mind?” we to tell you something One day toward the end of the summer, one of thought. “Shut the guy up so we can get home!” the horse-country-boys’ parents told her son now and I want you to This particular neurosurgeon was even more the most horrifying thing that he could possibly peculiar than most in his specialty. That says imagine. It seems that Johnny’s mother was remember it your a lot! The doctor wore tweedy bespoke British “working” the boardwalk. The boys were stunned. entire life … “Everybody suits, shoes that didn’t match, and striped Ivy They ran to Johnny and started taunting him: League ties that were always wrinkled. “Your mom’s a whore! Your mom’s a whore!” is sellin’ somethin’!”’ He was a tall man with rigid posture, but he Johnny was embarrassed, started crying had a high-pitched, squeaky voice that made uncontrollably, and dashed out of sight. We serve our patients as part of a noble it sound like he had just been sucking on Fifteen minutes later, Johnny’s mom, a pretty profession, but never lose sight of the fact that a helium balloon. He was one of those guys woman in her early 30s, walked toward the almost everyone in our field is promoting who always had Phi Beta Kappa and AOA keys group. Terrified, the boys ducked under the something. Sometimes they are simply and fobs hanging from a gold chain attached boardwalk to hide, but she quickly stuck promoting themselves. It’s neither good nor to the middle buttonhole on his vest, and he her head beneath the timbers. She was wearing bad—but it’s important to evaluate every fondled them excessively as he talked. a bright yellow sundress with big white flowers lecture, every new drug, and every new device Another idiosyncrasy was that he had and the young boys’ eyes were as wide as through the prism of this knowledge. absolutely no understanding of the concept saucers as she started to talk. of personal space. The neurosurgeon was bril- She spoke in slow, measured tones. “I under- liant beyond compare, but if he stopped you Financial Disclosures stand that you are only 10 years old, but you :h$
8el_de
– EYE SCIENCE OCULAR VITAMIN COMPANY: in the hallway, he would keep inching toward Board of Directors, No Compensation Received.

50 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | BREAKINGTEA LEAVES NEWS >> >>

Trexler M. Topping, MD Section Editor Concierge Retina—That’s What We Already Provide!

Those of us who are deeply involved with health policy feel that we will experience a 15% income drop in the next 5 to 10 years due to the inevitable juggernaut of health care reform. Not surprisingly, all branches of medicine are contemplating how to maintain income.

The internists and primary care physicians right in for evaluation and possible immediate As retina specialists, we will enhance both our are selling concierge medicine, a process by treatment with the best modalities known practice efficiency and delivery paradigms WHICHAPATIENTPAYSTOAYEAR to mankind. to give personalized, patient-centered care to ensure access to the doctor, usually by in less time. We won’t bellyache about low But wait a minute—that is exactly the current phone or email. Patients are normally reimbursement levels as many internists do, standard of care in American retina practices! also permitted an appointment within 24 but will creatively develop improved systems Like it or not, we already provide a concierge level hours. Can we do this in ophthalmology— of patient management and care delivery. of retina medicine at no premium. In a sense, we specifically in retina practices? give Mercedes-Benz care at Yugo prices. In concierge medicine, your retainer covers Meanwhile, our surgical approaches, techniques, ‘ Like it or not, we already services that are typically not covered, such as and instrumentation have improved to the refractions, corneal topography, etc. However, extent that our surgery works better, takes less provide a concierge virtually all that we as retina specialists do is time, and has better outcomes with much less already covered by Medicare and insurance level of retina medicine patient morbidity. In the world of free enterprise, companies—so what “extra” can we sell to be this would merit increases in physician income. at no premium.’ concierge retina specialists? However, in the real world of medicine, these improvements across the board result in Thinking out of the box has distinguished us decreasing payment for you, the physician. ‘ [V]irtually all that we vitreoretinal specialists from the beginning. (Thank you, RVS Update Committee!) as retina specialists Didn’t they say the vitreous was inviolate 50 So how can we retina specialists cope with the years ago? We did not listen then, and we will do is already covered forthcoming changes? We have an increasing not listen now. patient population, we have more therapies by Medicare and We retina specialists will gather in small or that will improve the health of Americans, and large groups and solve the delivery problem. yet we face decreasing reimbursement. Retina insurance companies— We will develop best-practice solutions, and specialists accept these challenges in stride. will share the approaches with each other at so what “extra” can And we will do what we have always done. our local meetings and at ASRS. As a group we sell to be concierge We will address the issues, see where care is who already provides a concierge level of required—looking at the increasing number retina care, that is how we will succeed in retina specialists?’ of graying Americans like me—and see the face of the significant health care funding where new treatment modalities are leading obstacle ahead. Well, we can assure patients that we, or our toward changes in practice needs. For Contact Trexler Topping at tmtopping@ staff, will speak with them on the phone example, just as the advent of anti-VEGF eyeboston.com. whenever they call. We can see patients right therapy for AMD caused changes, we will away if they call with new flashes, floaters, or see similar changes caused by adding diabetic

a field defect—and if AMD patients have new retinopathy to the conditions responding to Financial Disclosures distortion in the fellow eye, they can come anti-VEGF injections. Dr. Topping – OPHTHALMIC MUTUAL INSURANCE COMPANY: Board of Directors, Honoraria; NATIONAL EYE INSTITUTE: Contract Research, Grants.

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 51 THE ASRS X-FILES >>

K. Bailey Freund, MD Jerome Giovinazzo Sarah Mrejen, MD Section Editor

Case History: A 21-year-old male with no medical or family history experienced the sudden onset of a central scotoma in his left eye 3 days prior to presentation. On examination, his best-corrected visual acuity was 20/20 in the right eye and 20/200 in the left eye. The anterior segment examination of both eyes was normal. Color photographs showing the funduscopic findings and spectral-domain optical coherence tomography (SD-OCT) of both eyes at presentation are shown in Figure 1.

Two weeks later, the patient returned after being developed a partial left hemiparesis and began ‘ [T]he patient returned seen in the emergency room for acute abdominal slurring his words while in his internist’s office. pain. His best-corrected visual acuity was 20/20 in after being seen in the the right eye and 20/70 in the left eye. Color pho- What is your diagnosis? emergency room for tographs and SD-OCT of both eyes at follow-up See discussion on page 56 are shown in Figure 2. The next day, the patient acute abdominal pain.’

Figure 1: Color photographs and SD-OCT of both eyes at presentation Color photograph of the right eye (A) shows an area of intraretinal hemorrhage and nerve fiber layer whitening along the superotemporal arcades, with slight obscuration of vessels at the nasal margin of the optic nerve. Color photograph of the left eye (B) shows a sub-internal limiting membrane hemorrhage overlying the fovea, some obscuration of the disc margins, a few intraretinal hemorrhages at the superior and inferior poles of the optic disc, a small cotton-wool spot superiorly in the macular region, and moderate congestion of the venous system. SD-OCT horizontal scan of the right fovea (C) is normal. SD-OCT vertical scan through the left fovea (D) shows a sub-internal limiting membrane hemorrhage overlying the fovea with a fluid-erythrocyte separation.

Figure 2: Color photograph montages and SD-OCT scans of both eyes at 2-week follow-up

Color montage photograph of the right eye (A) shows 3 Roth’s spots in the superior and temporal mid-periphery of the fundus. Color montage photograph of the left eye (B) shows a foveolar hemorrhage, more intraretinal hemorrhages and cotton-wool spots, and more pronounced optic disc edema compared with initial presentation (Figure 1).

SD-OCT scan through a Roth’s spot (C) shows a hyper- reflective lesion at the level of the superficial and inner retina with underlying subretinal fluid and overlying numerous hyper-reflective dots in the vitreous. SD-OCT vertical scan through the left foveal hemorrhage (D) shows an intraretinal isoreflective lesion that contains numerous hyper-reflective dots.

52 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | LITERATURE ROUNDUP >>

Michael M. Altaweel, MD Asheesh Tewari, MD Amol Kulkarni, MD Section Co-Editor Section Co-Editor

7
(#O[Wh
Fheif[Yj_l[
HWdZec_p[Z
9edjhebb[Z
CRUISE studies respectively. Bevacizumab has also been shown to be Jh_Wb
e\
?djhWl_jh[Wb
8[lWY_pkcWX
eh
BWi[h
efficacious in the treatment of ME secondary to RVO. J^[hWfo
8EBJ
_d
j^[
CWdW][c[dj
e\
:_WX[j_Y
This prospective, interventional case series consisted of 34 eyes of CWYkbWh
;Z[cW0
(*#Cedj^
:WjW0
H[fehj
) 33 patients with ME associated with RVO who were injected with [published online ahead of print April 9, 2012] bevacizumab, followed by dexamethasone intravitreal implant Rajendram R, Fraser-Bell S, Kaines A, et al. Arch injection 2 weeks later. These patients were reexamined monthly Ophthalmol. 2012;130(8):972-979. doi:10.1001/ and retreated with bevacizumab when ME recurred during the archophthalmol.2012.393. 6-month study period.

The Early Treatment Diabetic Retinopathy Study (ETDRS) showed The primary outcome measure was the time to reinjection based on that macular laser photocoagulation decreased the risk of vision loss OCT and vision criteria. Thirty-five percent of patients had central of 15 letters due to clinically significant macular edema (CSME) by RVO (CRVO) and 65% had branch RVO (BRVO); 82% (28 of 34) 50% compared with eyes that did not receive treatment. However, needed at least 1 more injection before month 6, while 18% (6 of 34) there is a subset of patients unresponsive to this therapy. Intravitreal did not need an additional injection of bevacizumab. Ninety-seven injections with bevacizumab have been demonstrated to be safe and percent of patients gained vision during the study, and mean visual effective for treating persistent diabetic macular edema (DME) acuity improved from initially 11 letters to a maximum of 25 letters despite laser treatment. during the study period. OCT showed macular thickness decreased with the combination treatment, and the effect continued an average of The Bevacizumab or Laser Therapy (BOLT) in the Management of 126 days from the initial bevacizumab treatment. Diabetic Macular Edema study is a prospective, randomized controlled trial evaluating the role of intravitreal bevacizumab and modified Eighteen percent (6 of 34) of patients had an IOP of 23 mmHg or ETDRS macular laser therapy (MLT) in patients with persistent DME. greater. Five of these 6 subjects were controlled with drops alone, while The study consisted of 80 patients with center-involved DME who had one required an additional selective laser trabeculoplasty. This study previously received focal laser and had visual acuity of 20/40 to 20/320. demonstrates efficacy and the duration of effect using a combination of bevacizumab and dexamethasone vs dexamethasone alone. The Patients were randomly assigned to a bevacizumab arm receiving combination is synergistic, increasing visual acuity and prolonging the injections every 6 weeks for the first 3 months and every 6 weeks as time between injections, compared with either medication alone. needed thereafter, and a laser arm receiving as-needed macular laser every 4 months. At 2 years, the bevacizumab arm gained a median Application to Practice: Various treatment options are available of 9 ETDRS letters vs 2.5 letters for laser group. Forty-nine percent for treatment of macular edema associated with RVO. This study dem- of patients treated with bevacizumab gained 10 or more letters as onstrates that the combination of a vascular endothelial growth factor compared with 7% in the laser group. The median number of treatments inhibitor and a dexamethasone implant may be a valuable option for over 24 months was 13 for bevacizumab and 4 for laser. A mean of RVO treatment. The study design is applicable to many patients with 4 injections were required in the second year. persistent ME secondary to RVO in the typical ophthalmology practice.

Application to Practice: Persistent center-involving macular H_ia
\eh
H[j_dWb
:[jWY^c[dj
7\j[h
edema despite previous laser photocoagulation is a common clinical F^WYe[ckbi_ÓYWj_ed0
7
M^eb[#FefkbWj_ed
dilemma faced by practitioners. The BOLT trial specifically focused on IjkZo
e\
9WjWhWYj
Ikh][ho
EkjYec[i this subgroup with persistent DME; results support the longer term use of bevacizumab. This trial reconfirms that the benefits of laser Clark A, Morlet N, Ng JQ, Preen DB, Semmens JB. photocoagulation may not be fully realized until at least the second Arch Ophthalmol. 2012;130(7):882-888. doi:10.1001/ year of follow-up. archophthalmol.2012.164. There is 1% overall incidence of retinal detachment (RD) following ;\\[Yj
e\
9ecX_dWj_ed
J^[hWfo
M_j^
8[lWY_pkcWX
cataract surgery. The risks include patient factors (younger age, male WdZ
:[nWc[j^Wied[
?djhWl_jh[Wb
?cfbWdj
_d
sex, and long axial length), surgical factors (operative technique, FWj_[dji
M_j^
H[j_dWb
L[_d
EYYbki_ed vitreous loss, and posterior capsule rupture), and postoperative factors Singer MA, Bell DJ, Woods P, et al. Retina. (Nd:YAG laser posterior capsulotomy). There has been a significant 2012;32(7):1289-1294. doi:10.1097/IAE.0b013e318242b838. reduction in incidence of RD subsequent to adoption of phacoemulsi- fication compared with intracapsular cataract extraction. Retinal vein occlusions (RVOs) cause macular edema (ME), which can be treated with laser photocoagulation and/or intravitreal pharmaco- The long-term risk for RD after phacoemulsification was studied in therapy. The intravitreal medications available include triamcinolone, the entire Western Australia (WA) population using validated linked dexamethasone intravitreal implant (Ozurdex; Allergan, Inc, Irvine, health administrative data from January 1989 to December 2001. CA), and ranibizumab (Lucentis; Genentech, Inc, South San Francisco, Kaplan-Meier analysis was used to calculate a cumulative incidence CA), as described in the SCORE, OZURDEX GENEVA, and BRAVO/ (CI) of RD as a percentage of cataract procedures. Cox proportional

| Issue *, | Volume )&, Number * | Fall 2012 | retina times | 53 LITERATURE ROUNDUP >> hazards regression modeling was used to calculate hazard ratios (HRs), photoreceptors were found overlying small choroidal melanoma in which were 95% CIs for each risk factor examined. 18 eyes (49%), but were not observed overlying choroidal nevus (P < .001). Thus, EDI-SD-OCT provides in vivo quantification of There were 237 RD cases following 65,055 phacoemulsification tumor dimensions and cross-sectional detail of the tumor and procedures, with a 10-year cumulative incidence of 0.68%. Significant surrounding choroidal tissues that previously were not depicted. risk factors were year of surgery (hazard ratio, 0.43; 95% CI, 0.28-0.66 [1999-2001 compared with 1989-1993] for each 5-year period after Application to Practice: EDI-SD-OCT is an exciting technology 1985), age younger than 60 years, male gender, and anterior vitrectomy. for imaging small choroidal lesions. It shows numerous changes in the overlying retina, especially shaggy photoreceptors, which can help Hospital location, patient rural or remote locality, hospital cataract differentiate small choroidal melanoma from similar-sized choroidal surgery volume, failed intraocular lens insertion, length of stay, and nevus. EDI-SD-OCT imaging is ideal only for smaller choroidal tumors patient insurance status were not significantly associated with RD. (< 3 mm), particularly those located in the macula. The axial length and need for Nd:YAG laser posterior capsulotomy in the RD cases were not examined. Thus, risk for RD after phacoemul- Ijhea[
HWj[i
7\j[h
?djheZkYj_ed
e\
LWiYkbWh
sification has almost halved for each 5-year period since its adoption ;dZej^[b_Wb
=hemj^

54 | retina times | Fall 2012 | Volume )&, Number * | Issue *, | Incidence of Endophthalmitis and Use of Nine eyes of 9 patients with suspected endophthalmitis after injection Antibiotic Prophylaxis After Intravitreal Injections were identified. Three of the 9 cases had culture-positive results. The overall incidence of endophthalmitis per injection was 5 in 8259 for [published online ahead of print April 4, 2012] patients who were given antibiotics for 5 days after injection, 2 in 2370 Cheung CS, Wong AW, Lui A, Kertes PJ, Devenyi RG, for those who received antibiotics immediately after each injection, Lam WC. Ophthalmol. 2012;119(8):1609-1614. and 2 in 5266 who received no antibiotics. Intravitreal injections of VEGF inhibitors and triamcinolone acetonide However, if considering culture-proven endophthalmitis alone, are rapidly becoming the mainstay in treating various retinal diseases. the use of topical antibiotics given immediately or for 5 days after A rare but sight-threatening complication of this procedure is endo- injection showed lower rates of endophthalmitis compared with those phthalmitis. The reported rates of endophthalmitis after intravitreal without postinjection antibiotics. The incidence of endophthalmitis injections are low (0.019% to 1.4%). The preferred prophylactic per injection was 2 in 935 for triamcinolone acetonide, 3 in 9453 for method to minimize risk of endophthalmitis involves preparation of ranibizumab, and 4 in 5386 for bevacizumab. the injection site with topical povidone-iodine. There is conflicting evidence on the effectiveness of topical antibiotic prophylaxis in Thus, the overall rate of intravitreal injection-related endophthalmitis preventing endophthalmitis after intravitreal injections. is greater with the use of topical antibiotics, given immediately or for 5 days after the injection, compared with no antibiotics. The retrospective, comparative case series studied the incidence of endophthalmitis in association with different antibiotic prophylaxis Application to Practice: These findings recommend no topical strategies after intravitreal injections of anti-VEGF and triamcinolone antibiotic use after intravitreal injection, and they raise concern about acetonide. Three strategies of topical antibiotic prophylaxis were a higher rate of endophthalmitis after administration of topical used by the treating physicians: antibiotics given for 5 days after each antibiotics. However, because the study is retrospective, with a small injection; antibiotics given immediately after each injection; and no sample of patients, the conclusions may be the result of a random antibiotics given. sampling error. A total of 15,895 intravitreal injections (9453 ranibizumab, 5386 bevacizumab, 935 triamcinolone acetonide, 121 pegaptanib sodium) Financial Disclosures were reviewed for 2465 patients between January 5, 2005, and Dr. Altaweel – NATIONAL EYE INSTITUTE: Investigator, Grants; GLAXOSMITHKLINE: Investigator, Grants; PFIZER, INC: Investigator, Grants; REGENERON PHARMACEUTICALS, August 31, 2010. INC: Investigator, Grants. Dr. Tewari – SYNERGETICS USA: Consultant, Honoraria. Dr. Kulkarni – None.

POINT/COUNTERPOINT >>

Dr. von Fricken, continued from page 41

6. Lincoff HA, Baras I, McLean J. Modifications to the Custodis Procedure for Retinal 14. Colyer MH, Barazi MK, von Fricken MA. Retrospective comparison of 25-gauge transcon- Detachment. Arch Ophthalmol. 1965;73(2):160-163. junctival sutureless vitrectomy to 20-gauge vitrectomy for the repair of pseudophakic primary inferior rhegmatogenous retinal detachment. Retina. 2010;30(10):1678-1684. 7. Fujii GY, De Juan E, Jr., Humayun MS, et al. A new 25-gauge instrument system for transconjunctival sutureless vitrectomy surgery. Ophthalmol. 15. Brazitikos PD, Androudi S, Christen WG, Stangos NT. Primary pars plana vitrectomy 2002;109(10):1807-1812; discussion 1813. versus scleral buckle surgery for the treatment of pseudophakic retinal detachment: a randomized clinical trial. Retina. 2005;25(8):957-964. 8. Escoffery RF, Olk RJ, Grand MG, Boniuk I. Vitrectomy without scleral buckling for primary rhegmatogenous retinal detachment. Am J Ophthalmol. 1985; 99(3): 275-281. 16. Ahmadieh H, Moradian S, Faghihi H, et al. Anatomic and visual outcomes of scleral buckling versus primary vitrectomy in pseudophakic and aphakic retinal detach- 9. Campo RV, Sipperley JO, Sneed SR, et al. Pars plana vitrectomy without scleral buckle for ment: six-month follow-up results of a single operation—report no. 1. Ophthalmol. pseudophakic retinal detachments. Ophthalmol. 1999; 106(9):1811-1815; discussion 1816. 2005;112(8):1421-1429.

10. Speicher MA, Fu AD, Martin JP, von Fricken MA. Primary vitrectomy alone for repair of 17. Heiman H, Bartz-Schmidt KU, Bornfeld N, et al. Scleral buckling versus primary vitrectomy retinal detachments following cataract surgery. Retina. 2000;20(5):459-464. in rhegmatogenous retinal detachment: a prospective randomized multicenter clinical study. Ophthalmol. 2007;114(12):2142-2154. 11. von Fricken MA, Kunjukunju N, Weber C, Ko G. 25-Gauge sutureless vitrectomy versus 20-gauge vitrectomy for the repair of primary rhegmatogenous retinal detachment. 18. Koriyama M, Nishimura T, Matsubara T, Taomoto M, Takahashi K, Matsumura M. Retina. 2009;29(4):444-450. Prospective study comparing the effectiveness of scleral buckling to vitreous surgery for rhegmatogenous retinal detachment. Jpn J Ophthalmol. 2007;51(5):360-367. 12. Weichel ED, Martidis A, Fineman MS, et al. Pars plana vitrectomy versus combined pars plana vitrectomy-scleral buckle for primary repair of pseudophakic retinal detachment. 19. Jumper JM, Mittra RA, eds. ASRS 2012 Preferences and Trends Membership Survey. Ophthalmol. 2006;113(11):2033-2040. Chicago, IL. American Society of Retina Specialists. 2012.

13. Martínez-Castillo V, Boixadera A, Verdugo A, García-Arumí J. Pars plana vitrectomy alone for the management of inferior breaks in pseudophakic retinal detachment without facedown position. Ophthalmol. 2005;112(7):1222-1226. Financial Disclosures Dr. von Fricken – None.

| Issue 46 | Volume 30, Number 4 | Fall 2012 | retina times | 55 X-FILES SOLUTION >> Continued from page 52

Case History: Discussion At initial presentation (Figure 1, page 52), the that time are shown in Figures 3 (right eye) dots in the vitreous and a complete resolution of right color photograph (B) shows an area of and 4 (left eye). the subretinal fluid. intraretinal hemorrhage and nerve fiber layer The color photograph of the right eye (Figure 3) In the left eye (Figure 4), the color photograph whitening along the superotemporal arcades. shows a near-complete resolution of the Roth’s shows the complete resolution of the sub- There is slight obscuration of vessels at the nasal spots. The SD-OCT horizontal scan through one internal limiting membrane hemorrhage, margin of the optic nerve. The photograph of Roth’s spot shows a major decrease in the size of intraretinal hemorrhages, and cotton-wool the left eye (A) shows a sub-internal limiting the hyper-reflective lesion that seems to be located spots. The SD-OCT scan through the fovea membrane hemorrhage overlying the fovea. at the level of the retinal nerve fiber layer, with a shows the resolution of the sub-internal limiting There is some obscuration of the disc margins near-complete resolution of the hyper-reflective membrane hemorrhage with consequent focal with a few intraretinal hemorrhages at the superior and inferior poles of the optic disc and a small cotton-wool spot superiorly in the macular region. There is moderate congestion of the venous system with some mild tortuosity. SD-OCT vertical scan through the left fovea shows a sub-internal limiting membrane hemorrhage overlying the fovea with a fluid- erythrocyte separation. The SD-OCT horizontal scan of the right fovea is normal. The patient’s visual symptoms appeared to be related to a sub-internal limiting membrane hemorrhage overlying the left fovea. Blood pressure at that time was normal. The patient was referred to his internist to rule out hematologic abnormalities causing hyperviscosity or vasculitic entities with associated retinal vascular changes. A medical work-up revealed blood on urinalysis, an elevated C-reactive protein (CRP) at 10.1 mg/l, an elevated erythrocyte sedimentation rate (ESR) at 66 mm per hour, a normal white blood cell count and platelets. The complete blood count (CBC) showed low hemoglobin and hematocrit.

When the patient returned for 2-week follow-up, Figure 3: Color photographs and SD-OCT scans of the right eye at second (2 weeks) and last (6 weeks) follow-up examinations the left color photograph (A—Figure 2, page Color photograph at last follow-up (B) shows near-complete resolution of Roth’s spots compared with previous examination (A). SD-OCT horizontal scan through one Roth’s spot at last follow-up (D) shows a decrease in the size of 52) showed more intraretinal hemorrhages the hyper-reflective lesion that seems to be now located at the level of the retinal nerve fiber layer, a near-complete and cotton-wool spots and more pronounced resolution of the hyper-reflective dots in the vitreous, and a complete resolution of the subretinal fluid as compared with previous examination (C). optic disc edema. The right color photograph (B) showed multiple intraretinal hemorrhages centered by a white spot characteristic of Roth’s spots. The SD-OCT scan through a Roth’s spot showed a hyper-reflective lesion at the level of the superficial and inner retina with underlying subretinal fluid and overlying numerous hyper-reflective dots in the vitreous. At that time, the patient was immediately referred back to the internist for a complete work-up and had symptoms suggestive of a stroke in his office. He was medically evaluated and subsequently diagnosed with infectious endocarditis related to a congenital bicuspid aortic valve. Cultures from his recent emergency room visit grew Streptococcus viridans. He underwent an aortic valve replacement after 4 weeks of intravenous antibiotics and had a full recovery from the stroke. Four weeks later, the best-corrected visual acuity recovered to 20/20 in both eyes. Figure 4: Color photographs and SD-OCT scans of the left eye at second (2 weeks) and last (6 weeks) follow-up examinations Color photographs at last follow-up (B) shows resolution of intraretinal hemorrhages, cotton-wool spots, and optic disc edema His color photographs and SD-OCT scans at compared with previous examination (A). SD-OCT vertical foveal scan at last follow-up (D) shows resolution of the intraretinal isoreflective lesion with consequent thinning of the inner nuclear layer compared with previous examination (C).

56 | retina times | Fall 2012 | Volume 30, Number 4 | Issue 46 | X-FILES SOLUTION >> inner retinal thinning. Roth first described of disease is high, immediate tests should be the lesion. We believe these SD-OCT findings seeing white retinal lesions and separate oval ordered. Blood cultures should be obtained show that the Roth’s spots in subacute bacterial hemorrhages in patients with sepsis in 1872. prior to antibiotic therapy. A CBC with a endocarditis are more likely to represent In 1878, Litten, a French ophthalmologist, differential, ESR, CRP, urinalysis, and an elec- inflammatory lesions than cotton-wool spots described oval hemorrhages with pale centers trocardiogram (ECG) also should be included surrounded by hemorrhage. These images may in patients with endocarditis and named these in the work-up, and an echocardiogram should support Roth’s and Litten’s original theory that spots “Roth’s spots.” Roth’s spots are non- be obtained. Once the tests have returned, Roth’s spots represent septic emboli. specific and there have been conflicting reports the modified Duke criteria should be used to in the literature concerning their composition. establish the possibility of endocarditis.9 References

Roth originally hypothesized that the white centers To the best of our knowledge, this is the 1. Gass JD. Inflammatory Diseases of the Retina and Choroid. In: Gass JD, ed. Stereoscopic Atlas of Macular may contain bacteria but may also be composed first time a Roth’s spot has been evaluated Diseases. 4th ed. St Louis, MO: Mosby; 1997:601-603. of collections of sterile white blood cells.1 with high-resolution SD-OCT imaging. Past histological studies have shown that the white 2. Duane TD, Osher RH, Green WR. White centered hemor- The white center has also been hypothesized to rhages: their significance. Ophthalmol. 1980;87(1):66-69. centers surrounded by hemorrhages are be composed of fibrin thrombus at the site of 3. Kapadia RK, Steeves JH. Roth spots in chronic myelog- fibrin-platelet aggregates or thrombi.10 Subacute the capillary rupture.2 These lesions can be seen enous leukemia. CMAJ. 2011;183(18):E1352. doi:10.1503/ bacterial endocarditis is thought to produce cmaj.100561. in patients with leukemia,3 subacute bacterial 4. Falcone PM, Larrison WI. Roth spots seen on ophthal- 4 septic thrombi which can embolize to distant endocarditis, severe anemia, hypertensive states, moscopy: diseases with which they may be associated. locations. One of the organs affected is the eye. rheumatologic disorders, trauma, and HIV.5 Conn Med. 1995;59(5):271-273. Another presumptive cause of Roth’s spots pro- 5. Vose MJ, Charles SJ. Roth’s spots: an unusual presenta- Our patient initially presented with a sub- tion of HIV. Postgrad Med J. 2003;79(928):108-109. posed in more recent literature is a generalized doi:10.1136/pmj.79.928.108. internal limiting membrane hemorrhage thrombocytopenia from increased intravascular directly overlying the fovea in the left eye and 6. Kim JE, Han DP. Premacular hemorrhage as a sign of coagulation; this can lead to increased capillary subacute bacterial endocarditis. Am J Ophthalmol. a few intraretinal hemorrhages, cotton-wool 1995;120(2):250-251. bleeding in the retina.11 Compared with the spots, and mild optic disc edema in both eyes. typical high-resolution OCT imaging of 7. Li G, Kapusta MA. Preretinal hemorrhages as the Sub-internal limiting membrane hemorrhages presenting sign of subacute bacterial endocarditis. cotton-wool spots, the OCT scan through the Can J Ophthalmol. 2004;39(1):80-82. can occur in a variety of settings including Roth’s spot in our patient showed additional increased venous pressure from a Valsalva 8. Silverman ME, Upshaw CB Jr. Extracardiac manifesta- findings: numerous hyper-reflective dots in the tions of infective endocarditis and their historical maneuver, ocular trauma, and various retinal descriptions. Am J Cardiol. 2007;100(12):1802-1807. vitreous adjacent to the lesion and subretinal doi:10.1016/j.amjcard.2007.07.034. vascular diseases. Preretinal hemorrhages have fluid underlying the lesion. These hyper- been reported to be the presenting sign for 9. Moreillon P, Que YA. Infective endocarditis. reflective dots were seen focally in the vitreous Lancet. 2004;363(9403):139-149. doi:10.1016/ subacute bacterial endocarditis.6-7 Li and Kapusta S0140-6736(03)15266-X. directly overlying the lesion. argued that the hemorrhage may be concealing 10. von Barsewisch B, ed. Perinatal Retinal Haemorrhages. retinal findings more consistent with subacute Based on their distribution, size, shape, and Berlin, NY: Springer-Verlag; 1979. 7 bacterial endocarditis, such as Roth’s spots. decrease in number over time (Figure 3), these 11. Ling R, James B. White-centred retinal haemorrhages hyper-reflective dots in the vitreous likely (Roth spots). Postgrad Med J. 1998;74(876):581-582. We suggest that patients presenting with a doi:10.1136/pgmj.74.876.581. represent inflammatory cells. We hypothesize sub-internal limiting membrane hemorrhage that these hyper-reflective dots may represent associated with other retinal vascular and a “shedding” of inflammatory cells from the optic nerve abnormalities be questioned Financial Disclosures Roth’s spot lesion into the vitreous. There was regarding other manifestations of subacute Dr. Freund – GENENTECH: Advisory Board, Investigator, also subretinal fluid below the Roth’s spot that Honoraria; REGENERON PHARMACEUTICALS, INC: Advi- bacterial endocarditis such as splinter hemor- sory Board, Consultant, Honoraria; QLT, INC: Consultant, resolved over time (Figure 3). Honoraria; ALIMERA SCIENCES: Advisory Board, Honoraria; rhages, petechiae, clubbing, Janeway lesions, DIGISIGHT: Advisory Board, Honoraria. Osler’s nodes, and cardiac murmurs. We hypothesize that this subretinal detachment Dr. Mrejen – None. underlying the lesion likely indicates a Mr. Giovinazzo – None. Patients with a cardiac history are more transient inflammatory reaction adjacent to likely to have infectious endocarditis than those without.8 When the clinical likelihood

ADVERTISER INDEX Alcon Laboratories, Inc...... 45 Regeneron Pharmaceuticals, Inc...... insert Allergan, Inc...... insert Retina Image Bank ...... bellyband, 19 Dutch Ophthalmics USA...... 21 Santen ...... 25 Genentech ...... 1, 5 Synergetics USA, Inc...... 37 Insight Instruments, Inc...... back cover ThromboGenics ...... 11 MedOne...... 32

| Issue 46 | Volume 30, Number 4 | Fall 2012 | retina times | 57