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Cutting-edge AdvAnCements CliniCal Diagnosis OphthalmologyTimes.com follow us online: Focal Points Taming The ReSidency leaRning cuRve surgery September 15, 2016 VOL. 41, NO. 15 Drug therapy Reverse optic capture When the posterior capsule tears Why wait? Considering option for decentered, single-piece IOL as result of compromised posterior capsule support a b with the continuous advances in ophthalmic techniques and technologies, it can be challenging for even the most experienced surgeons to keep up—let alone residents. To that end, an educational website designed by ophthalmology residents for ophthalmology residents offers just the right amount of information, according to its founders. c ( See story on page 8 : Residency ) Special Report Silicone oil challenge moSTly manageable IN VIEW: a Vitreous incarceration in bimanual aspirating canula. b Three-month postoperative photo showing well-centered IOL with reverse optic capture. c OCT imaging showing good clearance between anterior IOL surface and posterior iris. (Images courtesy of Richard S. Hoffman, MD) Visit us at Booth 2356 for AAO 2016 paR adisE Val l E y, a Z :: use of silicone oil for retinal tamponade can result in a range of complications. Most By Lynda Charters; Reviewed by Richard S. Hoffman, MD of these events can be avoided with careful attention to surgical technique EugEnE, OR :: or successfully treated if they occur, All surgeons, no matter how experienced, whereas those without any known preencounter tough cases that require creative approaches. ventive strategies are very rare, said Richard S. Hoffman, MD, described such a case Derek Kunimoto, MD, JD. Reviewing the with a 2+ nuclear sclerotic cataract that he removed complications associated with silicone using a standard bimanual technique, which prooil based on anatomic location, he said EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc. gressed routinely. that silicone oil in the subconjunctival A horizontal chopping technique was used to respace presents a cosmetic issue and move the nucleus and the capsular bag was filled can also lead to granuloma formation. ©2016, Regeneron Inc., with a cohesive viscoelastic (OVD). All rights reserved Avoiding siliconePharmaceuticals, oil in the subconjuncti777 Old Saw Mill River Road, Tarrytown, NY 10591 The anterior capsulorhexis and posterior capsule val space requires good scleral closure were intact, explained Dr. Hoffman, clinical associwith small-gauge vitrectomy. Science University, Eugene, OR. He then injected a See our enclosed advertisement. single-piece, hydrophobic acrylic IOL into the bag. ( See story on page 36 : Silicone oil ) ate professor of ophthalmology, Oregon Health and iS The woRld a beTTeR Place becauSe oF youR PRacTice? The haptics were covered with polymethylmethacrylate “mittens” to prevent them from sticking to the optic. During the centering of the IOL, a crease in the posterior capsule was visible. Dr. Hoffman hypothesized it was a zonular dialysis with a wrinkled bag that might resolve with gentle pushing on the IOL. Repeated pushing did not reach the desired end. Since the lens was centered, Dr. Hoffman started to remove the OVD. In doing so, the IOL began to shimmy and 06/2016 vitreUS-LEA-11943a ous was visible in the aspirating cannula. The IOL appeared slightly tilted and moved down toward ( Continues on page 28 : Reverse optic ) How visionary leadership sets the tone. PAGe 68 CUTTING-EDGE ADVANCEMENTS CLINICAL DIAGNOSIS OphthalmologyTimes.com FOLLOW US ONLINE: Focal Points TAMING THE RESIDENCY LEARNING CURVE SURGERY September 15, 2016 VOL. 41, NO. 15 DRUG THERAPY Reverse optic capture When the posterior capsule tears Considering option for decentered, single-piece IOL as result of compromised posterior capsule support A B WITH THE continuous advances in ophthalmic techniques and technologies, it can be challenging for even the most experienced surgeons to keep up—let alone residents. To that end, an educational website designed by ophthalmology residents for ophthalmology residents offers just the right amount of information, according to its founders. C ( See story on page 8 : Residency ) Special Report SILICONE OIL CHALLENGE MOSTLY MANAGEABLE PAR ADISE VAL L E Y, A Z :: USE OF silicone oil for retinal tamponade can result in a range of complications. Most of these events can be avoided with careful attention to surgical technique or successfully treated if they occur, whereas those without any known preventive strategies are very rare, said Derek Kunimoto, MD, JD. Reviewing the complications associated with silicone oil based on anatomic location, he said that silicone oil in the subconjunctival space presents a cosmetic issue and can also lead to granuloma formation. Avoiding silicone oil in the subconjunctival space requires good scleral closure with small-gauge vitrectomy. ( See story on page 36 : Silicone oil ) IN VIEW: A Vitreous incarceration in bimanual aspirating canula. B Three-month postoperative photo showing well-centered IOL with reverse optic capture. C OCT imaging showing good clearance between anterior IOL surface and posterior iris. (Images courtesy of Richard S. Hoffman, MD) By Lynda Charters; Reviewed by Richard S. Hoffman, MD EUGENE, OR :: ALL SURGEONS, no matter how experienced, encounter tough cases that require creative approaches. Richard S. Hoffman, MD, described such a case with a 2+ nuclear sclerotic cataract that he removed using a standard bimanual technique, which progressed routinely. A horizontal chopping technique was used to remove the nucleus and the capsular bag was filled with a cohesive viscoelastic (OVD). The anterior capsulorhexis and posterior capsule were intact, explained Dr. Hoffman, clinical associate professor of ophthalmology, Oregon Health and IS THE WORLD A BETTER PLACE BECAUSE OF YOUR PRACTICE? Science University, Eugene, OR. He then injected a single-piece, hydrophobic acrylic IOL into the bag. The haptics were covered with polymethylmethacrylate “mittens” to prevent them from sticking to the optic. During the centering of the IOL, a crease in the posterior capsule was visible. Dr. Hoffman hypothesized it was a zonular dialysis with a wrinkled bag that might resolve with gentle pushing on the IOL. Repeated pushing did not reach the desired end. Since the lens was centered, Dr. Hoffman started to remove the OVD. In doing so, the IOL began to shimmy and vitreous was visible in the aspirating cannula. The IOL appeared slightly tilted and moved down toward ( Continues on page 28 : Reverse optic ) How visionary leadership sets the tone. PAGE 68 BACITRACIN OPHTHALMIC OINTMENT USP %GXMZIEKEMRWXXSSJMHIRXM¿IHOI] gram-positive isolates from conjunctivitis and blepharitis from in vitroWXYHMIW².ERYEV]1 In Vitro Susceptibility Data Provided Through the University of Pittsburgh Medical Center. In Vitro Data Should Not Be Considered Representative of Clinical Efficacy1 Established therapeutic utility in blepharitis, conjunctivitis, and other superficial ocular infections caused by Bacitracin-susceptible organisms OExcellent safety profile—low incidence of adverse events2 OOintment provides long-lasting ocular surface contact time and greater bioavailability3 OAnti-infective OFlexible efficacy in a lubricating base2 dosing—1 to 3 times daily2 OTier 1 pharmacy benefit status— on most insurance plans4 Indication Bacitracin Ophthalmic Ointment is indicated for the treatment of superficial ocular infections involving the conjunctiva and/or cornea caused by Bacitracin susceptible organisms. Important Safety Information This product should not be used in patients with a history of hypersensitivity to Bacitracin. Bacitracin Ophthalmic Ointment should not be used in deep-seated ocular infections or in those that are likely to become systemic. There is a low incidence of allergenicity exhibited by Bacitracin. If such reactions do occur, therapy should be discontinued. Please see adjacent page for full prescribing information. Logo is a trademark of Perrigo. ©2016 Perrigo Company plc Printed in USA 0S4-PAD01-ver02 3/16 For a closer look, visit www.perrigobacitracin.com SEPTEMBER 15, 2016 :: Ophthalmology Times contents Bacitracin Ophthalmic Ointment USP Rx Only STERILE DESCRIPTION: Each gram of ointment contains 500 units of Bacitracin in a low melting special base containing White Petrolatum and Mineral Oil. 62 CLINICAL PHARMACOLOGY: The antibiotic, Bacitracin, exerts a profound action against many gram-positive pathogens, including the common Streptococci and Staphylococci. It is also destructive for certain gramnegative organisms. It is ineffective against fungi. INDICATIONS AND USAGE: For the treatment of superficial ocular infections involving the conjunctiva and/or cornea caused by Bacitracin susceptible organisms. CONTRAINDICATIONS: This product should not be used in patients with a history of hypersensitivity to Bacitracin. PRECAUTIONS: Bacitracin ophthalmic ointment should not be used in deep-seated ocular infections or in those that are likely to become systemic. The prolonged use of antibiotic containing preparations may result in overgrowth of nonsusceptible organisms particularly fungi. If new infections develop during treatment appropriate antibiotic or chemotherapy should be instituted. ADVERSE REACTIONS: Bacitracin has such a low incidence of allergenicity that for all practical purposes side reactions are practically non-existent. However, if such reaction should occur, therapy should be discontinued. To report SUSPECTED ADVERSE REACTIONS, contact Perrigo at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DOSAGE AND ADMINISTRATION: The ointment should be applied directly into the conjunctival sac 1 to 3 times daily. In blepharitis all scales and crusts should be carefully removed and the ointment then spread uniformly over the lid margins. Patients should be instructed to take appropriate measures to avoid gross contamination of the ointment when applying the ointment directly to the infected eye. HOW SUPPLIED: NDC 0574-4022-13 3 - 1 g sterile tamper evident tubes with ophthalmic tip. NDC 0574-4022-35 3.5 g (1/8 oz.) sterile tamper evident tubes with ophthalmic tip. 50 30 Surgery Special Report 18 CXL REMAINS AS TREATMENT FOR KERATOCONUS, ECTASIA 34 FACE-DOWN POSITION NOT NEEDED FOR MACULAR HOLES Patient cohort reported improved topography, visual acuity, satisfaction Positioning may include any position in which head is tilted forward, eyes look downward Clinical Diagnosis Practice Management 50 UPDATED CORNEAL DYSTROPHY CLASSIFICATIONS 68 IS THE WORLD A BETTER PLACE BECAUSE OF YOUR PRACTICE? Updated categories aimed to offer more precise diagnosis, treatment These seven focal points will help communicate your values, ideas with your team Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. In This Issue Manufactured For 4 EDITORIAL 71 MARKETPLACE ® Minneapolis, MN 55427 0S400 RC J1 Rev 08-13 A References: 1. Antibiotic susceptibility: conjunctivitis and blepharitis. University of Pittsburgh Medical Center, Charles T. Campbell Eye Microbiology Lab Web site. http://eyemicrobiology.upmc.com/ AntibioticSusceptibilities/Conjunctivitis.htm. Accessed March 21, 2016. 2. Bacitracin Ophthalmic Ointment [package insert]. Minneapolis, MN: Perrigo Company; August 2013. 3. Hecht G. Ophthalmic preparations. In: Gennaro AR, ed. Remington: the Science and Practice of Pharmacy. 20th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2000. 4. Data on file. Perrigo Company. eReport Video Sign up for Ophthalmology Times’ weekly eReport at OphthalmologyTimes. com/eReport. Watch a 27-gauge diabetic vitrectomy. Go to OphthalmologyTimes.com/27gauge (Video courtesy of Yusuke Oshima, MD, PhD) 4 SEPTEMBER 15, 2016 :: Ophthalmology Times editorial SEPTEMBER 15, 2016 ◾ VOL. 41, NO. 15 How to choose a subspecialty Shub-ad knew her wise chairman would help her weigh options By Peter J. McDonnell, MD director of the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, and chief medical editor of Ophthalmology Times. He can be reached at 727 Maumenee Building 600 N. Wolfe St. Baltimore, MD 21287-9278 Phone: 443/287-1511 Fax: 443/287-1514 E-mail: [email protected] SHUB-AD WALKED into the office of her department chairman. It was the year 1745 B.C. and Shub-ad’s residency in ophthalmology was almost complete. Always an excellent student, she had graduated in the top of her class at Baghdad University and then at The Hammurabi School of Medicine, allowing her to secure a highly coveted residency slot in this competitive specialty. A great resident and conscientious physician, she had a tremendous fund of knowledge; cared for each patient like he or she was a family member; was respected by the faculty, nurses, and her fellow residents; and (most im- rative crystals and framed certificates from his numerous named lectureships, along with the usual smattering of autographed photos of him with various politicians and celebrities. Shub-ad began with the standard greeting of a resident to her chairman: “Greetings to Your Excellency, whose tireless efforts alone make all good things happen in this department but goeth unrecognized by so many.” “Arise, my child,” responded Pay-Dro, “and let your chairman know how he may further thy career.” “Well, here’s the thing,” Shub-ad said. “I am having trouble deciding on a specialty. Cataract surgery restoreth sight to my patients quickly and is most gratifying. But oculoplastic surgery alloweth me to rid my patients of their ptosis and wrinkles, giving them back their youthful beauty. And it goeth without saying that injecting the miraculous anti-VEGF agents into the vitreous cavity all day is a joy. I love it all. “So what subspecialty shall I select? Also, there is the matter of repaying my student loans. Tuition and room-and-board in Baghdad are not cheap these days. As my chairman, I know thou art all-knowing and will not steer me wrong.” Pay-Dro smiled. He remembered pondering these same issues as a resident. “Young Shub-ad,” he replied, “you have great surgical abilities and are already an excellent cataract surgeon. “Plus, our great King Hammurabi, whose enemies tremble at the sound of his name, issued his Code just 5 years ago providing professional fee reimbursement of ten shekels for successful surgery. Ten shekels is nothing to sneeze at, as we chairmen like to say, and such a fee will allow you to quickly repay your loans and purchase fine luxury items like you see scattered around my office, and perhaps even a nice convertible chariot from Germany. “Just be sure to document all elements of the history and examination on thy clay tablets to comply with meaningful use rules. So the path for you should be that of busy cataract surgeon. Continues on page 6 : Subspecialty ‘If all my residents were like this young woman,’ Pay-Dro thought to himself, ‘being chairman would be the easiest job in the world.’ portantly) had scored at the 90th percentile or higher each year on her OKAP examinations. Shub-ad loved ophthalmology, but was having trouble deciding on her subspecialty. She knew her wise chairman, Pay-Dro, would help her think through the options. Pay-Dro welcomed her warmly into his office. He liked Shub-ad very much. “If all my residents were like this young woman,” he thought to himself, “being chairman would be the easiest job in the world.” Befitting his exalted position of chairman, Pay-Dro’s office was richly adorned with fine carpets, golden statues, and various commemo- CONTENT Chief Medical Editor Peter J. McDonnell, MD Group Content Director Mark L. Dlugoss [email protected] 440/891-2703 Content Channel Director Sheryl Stevenson [email protected] 440/891-2625 Content Specialist Jolie Higazi [email protected] 440/891-2608 VP, Content & Strategy Sara Michael [email protected] 203/523-7107 Director, Design and Digital Production Nancy Bitteker [email protected] 203/523-7074 Art Director Nicole Davis-Slocum Anterior Segment Techniques Ernest W. Kornmehl, MD coding.doc L. Neal Freeman, MD, MBA Money Matters John J. Grande, Traudy F. Grande, and John S. Grande, CFPs® Neuro-Ophthalmology Andrew G. Lee, MD Ophthalmic Heritage Norman B. Medow, MD Tech Talk H. 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FOR MORE INFORMATION, CONTACT YOUR ALCON REPRESENTATIVE © 2016 Novartis 08/16 US-CYP-16-E-3239 W FD AA PP RO VE D SEPTEMBER 15, 2016 :: Ophthalmology Times letters LETTING HAPPINESS FIND US CyPass® Micro-Stent IMPORTANT PRODUCT INFORMATION CAUTION: FEDERAL (USA) LAW RESTRICTS THIS DEVICE TO SALE BY OR ON THE ORDER OF A PHYSICIAN. INDICATION: The CyPass® Micro-Stent is indicated for use in conjunction with cataract surgery for the reduction of intraocular pressure (IOP) in adult patients with mild to moderate primary open-angle glaucoma (POAG). CONTRAINDICATIONS: Use of the CyPass Micro-Stent is contraindicated in the following circumstances or conditions: (1) in eyes with angle-closure glaucoma; and (2) in eyes with traumatic, malignant, uveitic, or neovascular glaucoma or discernible congenital anomalies of the anterior chamber angle. MRI INFORMATION: The CyPass Micro-Stent is magnetic resonance (MR) Safe: the implant is constructed of polyimide material, a non-conducting, non-metallic, non-magnetic polymer that poses no known hazards in all magnetic resonance imaging environments. WARNINGS: Gonioscopy should be performed prior to surgery to exclude peripheral anterior synechiae (PAS), rubeosis, and other angle abnormalities or conditions that would prohibit adequate visualization of the angle that could lead to improper placement of the stent and pose a hazard. PRECAUTIONS: The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. The safety and effectiveness of the CyPass Micro-Stent has not been established as an alternative to the primary treatment of glaucoma with medications, in patients 21 years or younger, in eyes with significant prior trauma, chronic inflammation, eyes with an abnormal anterior segment, eyes with chronic inflammation, eyes with glaucoma associated with vascular disorders, pseudophakic eyes with glaucoma, eyes with uveitic glaucoma, eyes with pseudoexfoliative or pigmentary glaucoma, eyes with other secondary open-angle glaucomas, eyes that have undergone prior incisional glaucoma surgery or cilioablative procedures, eyes with laser trabeculoplasty performed ≤ 3 months prior to the surgical screening visit, eyes with unmedicated IOP less than 21 mmHg or greater than 33 mmHg, eyes with medicated IOP greater than 25 mmHg, in the setting of complicated cataract surgery with iatrogenic injury to the anterior or posterior segment, and when implantation is without concomitant cataract surgery with IOL implantation for visually significant cataract. The safety and effectiveness of use of more than a single CyPass Micro-Stent has not been established. ADVERSE EVENTS: In a randomized, multicenter clinical trial comparing cataract surgery with the CyPass Micro-Stent to cataract surgery alone, the most common postoperative adverse events included: BCVA loss of 10 or more letters at 3 months after surgery (8.8% for the CyPass Micro-Stent vs. 15.3% for cataract surgery only); anterior chamber cell and flare requiring steroid treatment 30 or more days after surgery (8.6% vs. 3.8%); worsening of visual field mean deviation by 2.5 or more decibels (6.7% vs. 9.9%); IOP increase of 10 or more mmHg 30 or more days after surgery (4.3% vs. 2.3%); and corneal edema 30 or more days after surgery, or severe in nature (3.5% vs. 1.5%). ATTENTION: PLEASE REFER TO THE INSTRUCTIONS FOR A COMPLETE LIST OF CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS. © 2016 Novartis 08/16 US-CYP-16-E-3239 EVER SINCE I SAT WITH Arnall Patz, MD, at my interview for a Wilmer Residency, during that first year of the SF Match in 1978, I have held the Wilmer Eye Institute in very high regard. Dr. Patz made it very clear that Wilmer was looking to train ophthalmologists who were invested in research and wanted to chair departments across America. I truly appreciated his candor and still am in awe of his accomplishments. As a student at Columbia University’s School of Engineering and Applied Science, majoring in Chemical Engineering (bioengineering was not even a major in 1971-1975) I felt my calling was private practice, teaching, and living a life that I chose to create on my own terms. I matriculated at Columbia University’s College of Physicians and Surgeons where my desire to pursue a clinical practice in ophthalmology was nurtured. Fred Jakobiec, MD, gave me a wonderful opportunity to do some important clinical research on pigmented lesions of the iris which occupied 4 months of my fourth year at Columbia. That research experience, although superb, further confirmed my desire to enter private practice upon completing my residency. I was especially touched by the recent editorial by Peter J. McDonnell, MD, entitled, “Are you really happy?” (Ophthalmology Times, July 15, 2016). SUBSPECIALTY ( Continued from page 4) Plus, there is only the one downside.” As already mentioned, Shub-ad was sharp as a tack and nothing ever got past her. “Downside? What downside?” she inquired. THE DOW NSIDE “Well, our great King Hammurabi, whose knowledge of health care policy exceeds that of all other policy wonks, has included in his reimbursement formula the caveat that if the surgery is unsuccessful and the patient loses his sight, the surgeon shall have his/her hands cut off.” “You’re kidding!” exclaimed Shub-ad, who had grown rather fond of her hands. “Not at all,” Pay-Dro responded. “Perhaps you have noticed that almost all of your senior faculty have no hands. My 5,000th cataract surgery patient regrettably developed postoperative endophthalmitis from a strain of multiple drug-resistant Staphylococcus au- I think happiness finds us more easily when we are kind, generous, grateful, and compassionate in our ways; with our families, our friends, and our patients as well. Being attached to a material world and competing for “more money and more rewards” makes it much more difficult to allow happiness into our lives. I presently spend 2 days a week in the Comprehensive Eye Clinic at New York Eye and Ear Infirmary, mentoring our great residents in the skills of our profession and guiding them towards living empowered lives. There is much for them to learn over a nice dinner and a glass of wine about what it means to live life fully and what it takes in one’s mind to set the stage for that wonderful and “happy” life. —Glenn R. Silbert, MD Associate clinical professor of ophthalmology The Carl Icahn School of Medicine at Mount Sinai The Mount Sinai Health System New York Letters to the Editor may be submitted to [email protected]. Letters may be edited for clarity and length. reus and lost his vision. Statistically, a 1-in5,000 rate of infection is pretty darn good and superior to what is published in the literature, but rules are rules, so my hands were cut off. So what do you say?” “I think neuro-ophthalmology seemeth like a good option. It is a very intellectually challenging field,” responded Shub-ad, as she backed out of the office while being careful to constantly bow toward her chairman. Q References 1. Shub-ad is the name of a queen and priestess historically documented to have lived in ancient Mesopotamia. http://www.womeninworldhistory.com/lesson2.html 2. The sixth Babylonian King, Hammurabi, issued his legal system code around 1750 BC. https://en.wikipedia.org/ wiki/Code_of_Hammurabi 3. One shekel of silver equaled 180 grains or 5.5 grams of silver. According to the Ishnuna Code of Law, a labourer received the monthly wage of one shekel plus his food. http://www.ishtartv.com/en/viewarticle,35322.html SEPTEMBER 15, 2016 2014 :: Ophthalmology Times editorial advisory board 7 Official publication sponsor of EDITORIAL ADVISORY BOARD Chief Medical Editor Peter J. McDonnell, MD Wilmer Eye Institute Johns Hopkins University Baltimore, MD Anne L. Coleman, MD Joan Miller, MD Jules Stein Eye Institute, UCLA Los Angeles, CA Massachusetts Eye & Ear Infirmary Harvard University Boston, MA Ernest W. Kornmehl, MD Harvard & Tufts Universities Boston, MA Associate Medical Editors Robert K. Maloney, MD Dimitri Azar, MD Los Angeles, CA University of Illinois, Chicago Chicago, IL Ashley Behrens, MD Wilmer Eye Institute, Johns Hopkins University Baltimore, MD Elizabeth A. Davis, MD Randall Olson, MD University of Utah Salt Lake City, UT Ophthalmology Times’ vision is to be the leading content resource for ophthalmologists. Robert Osher, MD Through its multifaceted content channels, Ophthalmology Times will assist physicians with the tools and knowledge necessary to provide advanced quality patient care in the global world of medicine. Kuldev Singh, MD Jonathan H. Talamo, MD Stanford University Stanford, CA Harvard University Boston, MA Joshua D. Stein, MD Kazuo Tsubota, MD University of Michigan Ann Arbor, MI Keio University School of Medicine Tokyo, Japan Robert N. Weinreb, MD University of Minnesota, Minneapolis, MN Hamilton Glaucoma Center University of California, San Diego Uday Devgan, MD Neuro-Ophthalmology Jules Stein Eye Institute,UCLA Los Angeles, CA Andrew G. Lee, MD Richard S. Hoffman, MD Retina/Vitreous Stanley Chang, MD Columbia University New York, NY David Chow, MD Blanton Eye Institute, Houston Methodist Hospital University of Toronto Toronto, Canada Houston, TX Oregon Health & Science University Portland, OR Oculoplastics/ Reconstructive Surgery Samuel Masket, MD Jules Stein Eye Institute,UCLA Los Angeles, CA Robert Goldberg, MD Bartly J. Mondino, MD Jules Stein Eye Institute, UCLA Los Angeles, CA Jules Stein Eye Institute,UCLA Los Angeles, CA John T. LiVecchi, MD Mark Packer, MD Boulder, CO St. Luke’s Cataract & Laser Institute Tarpon Springs, FL Michael Raizman, MD Shannath L. Merbs, MD Massachusetts Eye & Ear, Harvard University Boston, MA Ehsan “Ethan” Sadri, MD, FACS Newport Beach, CA Wilmer Eye Institute, Johns Hopkins University Baltimore, MD Pediatric Ophthalmology Pravin U. Dugel, MD Phoenix, AZ Sharon Fekrat, MD Duke University Durham, NC Julia Haller, MD Wills Eye Institute, Thomas Jefferson University Philadelphia, PA Tarek S. Hassan, MD Oakland University Rochester, MI Michael Ip, MD Doheny Eye Institute Los Angeles, CA Michael Snyder, MD Norman B. Medow, MD Carmen A. Puliafito, MD Cincinnati Eye Institute Cincinnati, OH Albert Einstein College of Medicine Bronx, NY Keck School of Medicine, USC Los Angeles, CA Walter J. Stark, MD Jennifer Simpson, MD Carl D. Regillo, MD Wilmer Eye Institute, Johns Hopkins University Baltimore, MD University of California, Irvine Irvine, CA Wills Eye Institute, Thomas Jefferson University Philadelphia, PA Farrell “Toby” Tyson, MD H. Jay Wisnicki, MD Lawrence J. Singerman, MD Cape Coral, FL New York Eye & Ear Infirmary, Beth Israel Medical Case Western Reserve University Center, Albert Einstein College of Medicine Cleveland, OH New York, NY Glaucoma Robert D. Fechtner, MD University of Medicine & Dentistry of New Jersey Newark, NJ University of Toronto Toronto, Canada Richard K. Parrish II, MD Uveitis Practice Management Joseph C. Noreika, MD Medina, OH Stanford University Stanford, CA Frank Weinstock, MD Chief Medical EditorsEmeritus Boca Raton, FL Refractive Surgery New York, NY Peter S. Hersh, MD Joel Schuman, MD University of Medicine & Dentistry of New Jersey Newark, NJ yness redness sore tired ey gritty pain irritation dry visio sitivity foreign body sensa edness Your LASIK drynes ation results speak for fatig e vision themselves. redne yness redness sore tired ey rritation burning dry itching sitivity foreign body sensa y fatigue Don’t let irritation ness post-op dry eye sore tired talk over them. tired n excess watering gritty sa nsitivity foreign body sensa ing burning gritty excess te Emmett T. Cunningham Jr., MD, PhD Bascom Palmer Eye Institute, University of Miami Jack M. Dodick, MD Miami, FL William Culbertson, MD New York University School of Medicine Bascom Palmer Eye Institute, University of Miami New York, NY (1976–1996) Robert Ritch, MD Miami, FL New York Eye & Ear Infirmary NYU Langone Medical Center New York, NY Ophthalmology Times is a physician-driven media brand that presents cutting-edge advancements and analysis from around the world in surgery, drug therapy, technology, and clinical diagnosis to elevate the delivery of progressive eye health from physician to patient. University of Cincinnati Cincinnati, OH Anterior Segment/Cataract Cornea/External Disease Neeru Gupta, MD Ophthalmology Times Mission Statement David R. Guyer, MD New York, NY (1996–2004) Fight post-op dry eye with the VeraPlug™ Ophthalmology Times Industry Council and let your patients enjoy the enhanced John Bee Bob Gibson Aziz Mottiwala Rhein Medical Inc. President and CEO Topcon Medical Systems Inc. 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All rights reserved. 8 focal points SEPTEMBER 15, 2016 :: Ophthalmology Times Website serves as residency educational resource Content designed for ‘rapid learning,’ tailored to knowledge residents already have By Stephanie Skernivitz; Reviewed by David Xu, MD ith the continuous advances idency can expect to discover what Dr. Xu in ophthalmic techniques and calls the “highest-yield information” needed technologies, it can be chal- to begin evaluating patients and running a lenging for even the most clinic. Such information might include basic experienced surgeons to keep tips (how to use an indirect ophthalmoscope, for example) to advanced material, including up—let alone residents. To that end, a new educational-based web- using ophthalmic ultrasound. The site features what is called an EyeGuru site (EyeGuru.org) designed by ophthalmology residents for ophthalmology residents offers Deck, or an ability to acquire knowledge with just the right amount of information, accord- the help of spaced-repetition flash cards. So far, news about the site is ing to its founder, David Xu, traveling quickly via word of MD, ophthalmology resident mouth, e-mails to colleagues at University of California, Los of Dr. Xu and his team, and Angeles (UCLA), and his colEyeGuru.org is by the founders participating leagues, Shawn Lin, MD, also an educational in interviews across the nation. of UCLA, and Ben Lin, MD, website designed Already there are 4,000-plus a UCLA medical student—all by ophthalmology page views a month, with 200 who founded the site earlier residents for registered members and 52% this year. The website states ophthalmology return users. The site also curupfront, “You get no more and residents. The website rently holds a 12% sign-up rate. no less information than exstates upfront, “You “We’re already getting posiactly what’s needed.” get no more and tive feedback from a lot of dif“With the help of some colno less information ferent hospitals from East Coast leagues in residency, the reason than exactly what’s to the West Coast, from places EyeGuru.org got started was to needed.” such as the Bascom Palmer Eye find a new way for ophthalInstitute and Case Western Remology residents to access and know how to use the latest generation of serve,” he said. In determining the content to post on the tools that have been recently developed,” Dr. Xu said. “We want to bring the power of the site, Dr. Xu explained, “What residents need Internet and a new generation of educational to know at each point in their career is well known. It’s material that people would agree on.” tools to them.” And that’s exactly the type of content residents will find on the site. HOW IT GOT STARTED “We have detailed experience because we EyeGuru.org was created by residents who realized the need for an efficient learning tool are so close to that point in time ourselves,” he during the busy training years. Article content said. “We are trying to figure what we know on the site is designed for “rapid learning” op- so that we can make things incredibly relevant portunities for residents and is tailored to the for new residents.” The site originally included a set of 12 arknowledge residents already have, according ticles, which already have garnered positive to the website. “We did this because ophthalmology is so reviews from people who have returned to the highly specialized. Residents are faced with a EyeGuru.org team with feedback, noting, “These challenge,” Dr. Xu continued. “They are need- were just what we needed.” Article topics address, for example, intering to tackle clinical, surgical, and basic science preting optical coherence tomography (OCT) material with steep learning curves.” On the site, students who are new to res- and management of glaucoma. W TAKE-HOME By residents, for residents The website’s mission aims to provide residents with “Everything you wanted to know about succeeding in ophthalmology in one easy source.” W R I T T E N BY R E SIDE N T S . Highyield concepts are explained simply in 5-minute tutorials to bring residents up to speed, according to the website. R ESIDENCY ESSENTIALS. Material is provided about the most common conditions residents must know for clinic (glaucoma, AMD, and diabetic retinopathy, for example). CLINICAL TECHNIQUES. Technique guides answer common questions: Worried about using the slit lamp? The indirect? Interpreting OCTs? Fluorescein angiography? “Some people we have heard from are from our own program—new residents who say the site is incredibly helpful,” Dr. Xu said. “They can go back during clinic and look through articles to help them manage cases.” Going forward, the plan remains to continue to use the digital-based platform for residents, he said. “While going to meetings and learning about the website there can be helpful,” Dr. Xu said, “we really want to make other residents aware of us through e-mail, web forums, etc. Our vision is for every resident to use this content as a key part of how they learn.” COMPETITORS What about competitor sites? Dr. Xu is quick to note that other sites may have an educational focus but are not really viewed as competitors. Continues on page 11 : Residency Down, Boy. Help Tame Postoperative Ocular Inflammation and Pain With LOTEMAX® GEL Indication LOTEMAX® GEL (loteprednol etabonate ophthalmic gel) 0.5% is indicated for the treatment of post-operative inflammation and pain following ocular surgery. Important Safety Information about LOTEMAX® GEL 2 ® GEL is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. 2 )&#&%,*&&)+ &*+)& *$0)*,#+ %#,&$. +$+&+&'+ %)-+* %- *,# , +0% #*&- * &%+ *')&,+ *,*&)0*&)#&%)*&,#$&% +&) 2 *&&)+ &*+)& *$0)*,#+ %'&*+) &)*,'*,#)+)+&)$+ &% 2 *&*+)& *+)+)+*,))0$0#0# %% %)*+ % %&#&)$+ &%% occurrence of perforations in those with diseases causing corneal and scleral thinning. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification, and where appropriate, fluorescein staining. 2 )&#&%,*&&)+ &*+)& *$0*,'')**+&*+)*'&%*%+,* %)*+1)&*&%)0&,#) infection. In acute purulent conditions, steroids may mask infection or enhance existing infection. 2 *&&)+ &*+)& $ + &% %++)+$%+&'+ %+*. + *+&)0&)'** $'#/)(, )*)+ ,+ &%*&&,#)*+)& *$0')&#&%+&,)*%/)++*-) +0&$%0- )# %+ &%*& the eye (including herpes simplex). 2 ,%# %+ &%*&+&)%)')+ ,#)#0')&%+&-#&'& % %+##0 . +#&%+)$#&#*+)& ''# + &%,%,* %-* &%$,*+&%* ) in any persistent corneal ulceration where a steroid has been used or is in use. 2 + %+**&,#%&+.)&%++#%**.%,* %® GEL. 2 $&*+&$$&%&,#)-)*),)+ &%*)'&)+.)%+) &) chamber inflammation (5%), eye pain (2%) and foreign body sensation (2%). Please see brief summary of Prescribing Information on adjacent page. ®/™ are trademarks of Bausch & Lomb Incorporated or its affiliates. © 2015 Bausch & Lomb Incorporated. All rights reserved. Printed in USA. US/LGX/15/0041(1) BRIEF SUMMARY OF PRESCRIBING INFORMATION This Brief Summary does not include all the information needed to prescribe Lotemax Gel safely and effectively. See full prescribing information for Lotemax Gel. Lotemax (loteprednol etabonate ophthalmic gel) 0.5% Rx only Initial Rx Approval: 1998 INDICATIONS AND USAGE LOTEMAX is a corticosteroid indicated for the treatment of post-operative inflammation and pain following ocular surgery. DOSAGE AND ADMINISTRATION Invert closed bottle and shake once to fill tip before instilling drops. Apply one to two drops of LOTEMAX into the conjunctival sac of the affected eye four times daily beginning the day after surgery and continuing throughout the first 2 weeks of the post-operative period. CONTRAINDICATIONS LOTEMAX, as with other ophthalmic corticosteroids, is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. WARNINGS AND PRECAUTIONS Intraocular Pressure (IOP) Increase Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma. If this product is used for 10 days or longer, intraocular pressure should be monitored. Cataracts Use of corticosteroids may result in posterior subcapsular cataract formation. Delayed Healing The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. Bacterial Infections Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions of the eye, steroids may mask infection or enhance existing infection. Viral Infections Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Fungal Infections Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Fungal cultures should be taken when appropriate. Contact Lens Wear Patients should not wear contact lenses during their course of therapy with LOTEMAX. ADVERSE REACTIONS Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with infrequent optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, delayed wound healing and secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera. The most common adverse drug reactions reported were anterior chamber inflammation (5%), eye pain (2%), and foreign body sensation (2%). USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects: Pregnancy Category C. Loteprednol etabonate has been shown to be embryotoxic (delayed ossification) and teratogenic (increased incidence of meningocele, abnormal left common carotid artery, and limb flexures) when administered orally to rabbits during organogenesis at a dose of 3 mg/kg/day (35 times the maximum daily clinical dose), a dose which caused no maternal toxicity. The no-observed-effect-level (NOEL) for these effects was 0.5 mg/kg/day (6 times the maximum daily clinical dose). Oral treatment of rats during organogenesis resulted in teratogenicity (absent innominate artery at ≥5 mg/kg/day doses, and cleft palate and umbilical hernia at ≥50 mg/kg/day) and embryotoxicity (increased post-implantation losses at 100 mg/kg/day and decreased fetal body weight and skeletal ossification with ≥50 mg/kg/day). Treatment of rats with 0.5 mg/kg/day (6 times the maximum clinical dose) during organogenesis did not result in any reproductive toxicity. Loteprednol etabonate was maternally toxic (significantly reduced body weight gain during treatment) when administered to pregnant rats during organogenesis at doses of ≥5 mg/kg/day. Oral exposure of female rats to 50 mg/kg/day of loteprednol etabonate from the start of the fetal period through the end of lactation, a maternally toxic treatment regimen (significantly decreased body weight gain), gave rise to decreased growth and survival, and retarded development in the offspring during lactation; the NOEL for these effects was 5 mg/kg/day. Loteprednol etabonate had no effect on the duration of gestation or parturition when administered orally to pregnant rats at doses up to 50 mg/kg/day during the fetal period. There are no adequate and well controlled studies in pregnant women. LOTEMAX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Systemic steroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Caution should be exercised when LOTEMAX is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use No overall differences in safety and effectiveness have been observed between elderly and younger patients. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment Of Fertility Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma tk assay, or in a chromosome aberration test in human lymphocytes, or in vivo in the single dose mouse micronucleus assay. Treatment of male and female rats with up to 50 mg/kg/day and 25 mg/kg/day of loteprednol etabonate, respectively, (600 and 300 times the maximum clinical dose, respectively) prior to and during mating did not impair fertility in either gender. PATIENT COUNSELING INFORMATION Administration Invert closed bottle and shake once to fill tip before instilling drops. Risk of Contamination Patients should be advised not to allow the dropper tip to touch any surface, as this may contaminate the gel. Contact Lens Wear Patients should be advised not to wear contact lenses when using LOTEMAX. Risk of Secondary Infection If pain develops, redness, itching or inflammation becomes aggravated, the patient should be advised to consult a physician. Bausch & Lomb Incorporated Tampa, Florida 33637 USA US Patent No. 5,800,807 ©Bausch & Lomb Incorporated ®/™ are trademarks of Bausch & Lomb Incorporated or its affiliates. US/LGX/15/0042 Based on 9269100-9269200 Revised: 9/2012 SEPTEMBER 15, 2016 :: Ophthalmology Times RESIDENCY focal points 11 TAKE A TOUR OF EYEGURU.ORG ( Continued from page 8 ) “We mainly made our site as an educational resource, but we also made ours different,” he said. “In one way, we use spaced repetition as a format of learning. Students can review information and get it fed back to them at appropriate pace for them, instead of the traditional textbook cramming.” The website also offers a virtual clinic where residents can learn from clinical examples. Through the exam, residents can learn from history and learn to manage in a digital fashion. “Because we are web-based, residents can use EyeGuru.org during downtime allowing distributed learning to happen whether they are at home, in clinic, or on the road,” Dr. Xu said. Currently, the site is social mediafriendly, with regular posts on Twitter, Facebook, and Google Plus. “We are working with a millennial generation of ophthalmology practitioners,” Dr. Xu said. “They need a new, efficient way to learn in the complex medical landscape.” ‘Our vision is for every resident to use this content as a key part of how they learn.’ — David Xu, MD As for future plans, Dr. Xu said he and his colleagues are seeking faculty sponsors. They’re also working on supplying personal impressions of clinical events via video modality. “It’s an important way to share information,” he said. “We can offer video demonstrations and educational material.” Though the site primarily targets ophthalmology residents, “as ophthalmologists turn Ophthalmolgy residents will have access to timely blog content that touches upon ophthalmic lasers, intravitreal injection doses, and more. Clinical information on the website includes many tutorials, such as an overview of four types of hyperfluorescence in fluorescein angiography. (Images courtesy of David Xu, MD) into young and mid-career ophthalmologists, we will evolve, too, and generate video relevant to these guys,” Dr. Xu said. “Ophthalmologists strive to be lifelong learners. If we want to ultimately create the most efficient learning platform for ophthalmology residents, then it’s our goal to make more residents aware.” ■ 12 MEETING PREVIEW Special Report ) AAO 2016 INNOVATION RISING TO OCCASION AT AAO 2016 120th annual meeting returns to Windy City with cutting-edge clinical education By Beth Thomas Hertz O CHICAGO :: The 2016 meeting of the American Academy of Ophthalmology will convene in Chicago from Oct. 15 to 18. Visit www.aao.org for the latest updates. Held in conjunction with the Asia-Pacific Academy of Ophthalmology (APAO), the annual meeting also includes eight subspecialty days over Oct. 14 and 15 (see “Innovation Abounds at Subspecialty Day” on Page 14). In addition, the American Academy of Ophthalmic Executive (AAOE)’s Practice Management Program will convene from Oct. 15 to 18. With this year’s theme of “Innovate,” the annual meeting is “the best place to learn about these innovations and connect with the top innovators in our field,” said Jonathan B. Rubenstein, MD, secretary for the AAO meeting. “We hope that attendees will be inspired to formulate their own innovative ideas. “As this is our 120th annual meeting, it’s exciting to think about how much advancement has taken place over the years and how innovation has dramatically improved outcomes for our patients,” Dr. Rubenstein added. “Diseases that were once ‘one-way tickets’ to blindness are now treatable thanks to research presented at AAO meetings.” He added that the theme also relates to the host city of Chicago, with a long history of being innovative. AC A DEM Y PLUS COU R SE PA S S New this year is the Academy Plus—a course pass that offers unlimited access to more than 350 AAO and AAOE instruction courses. There is no need to plan ahead or pre-select courses. Attendees can float among all instruction courses at will. Individual tickets for AAO and AAOE instruction courses are no longer sold. However, seating capacities for course rooms is limited and seating is available on a first-come basis. Attendees can buy the pass when registering for the annual meeting, or buy it onsite at the conference. Attendees will not receive an actual separate pass, but will get an “Academy Plus” symbol on badges that provides their admission. The pass is non-transferable. Academy Plus does not cover sessions that require an individual ticket, including AAOE Practice Management Master Classes, AAOE Coding Sessions, Breakfast with the Experts, Skills Transfer labs, and Subspecialty Day meetings. OPENING SESSION The Opening Session will be held Sunday, Oct. 16, from 8:30 a.m. to 10 a.m. In addition to addresses from leaders of AAO and APAO, the event will feature the annual Jackson Memorial Lecture. This year’s lecture is being given by Douglas D. Koch, MD, professor at the Baylor College Continues on page 14 : AAO 2016 Getty Images/Swapan Jha take-home phthalmic professionals looking for leading-edge research and developments need look no further than this year’s meeting of the American Academy of Ophthalmology (AAO) at Chicago’s McCormick Place from Oct. 15 to 18. THIS IS YOUR OPENING. Make a once-in-a-lifetime difference with the safe MIGS procedure for cataract patients with glaucoma. + The complete procedure. AAO Booth 626 800.GLAUKOS (452.8567) Glaukos.com INDICATION FOR USE. The iStent® Trabecular Micro-Bypass Stent (Models GTS100R and GTS100L) is indicated for use in conjunction with cataract surgery for the reduction of intraocular pressure (IOP) in adult patients with mild to moderate open-angle glaucoma currently treated with ocular hypotensive medication. CONTRAINDICATIONS. The iStent® is contraindicated in eyes with primary or secondary angle closure glaucoma, including neovascular glaucoma, as well as in patients with retrobulbar tumor, thyroid eye disease, Sturge-Weber Syndrome or any other type of condition that may cause elevated episcleral venous pressure. WARNINGS. Gonioscopy should be performed prior to surgery to exclude PAS, rubeosis, and other angle abnormalities or conditions that would prohibit adequate visualization of the angle that could lead to improper placement of the stent and pose a hazard. The iStent ® is MR-Conditional meaning that the device is safe for use in a specified MR environment under specified conditions, please see label for details. PRECAUTIONS. The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. The safety and effectiveness of the iStent ® has not been established as an alternative to the primary treatment of glaucoma with medications, in children, in eyes with significant prior trauma, chronic inflammation, or an abnormal anterior segment, in pseudophakic patients with glaucoma, in patients with pseudoexfoliative glaucoma, pigmentary, and uveitic glaucoma, in patients with unmedicated IOP less than 22 mmHg or greater than 36 mmHg after “washout” of medications, or in patients with prior glaucoma surgery of any type including argon laser trabeculoplasty, for implantation of more than a single stent, after complications during cataract surgery, and when implantation has been without concomitant cataract surgery with IOL implantation for visually significant cataract. ADVERSE EVENTS. The most common post-operative adverse events reported in the randomized pivotal trial included early post-operative corneal edema (8%), BCVA loss of * 1 line at or after the 3 month visit (7%), posterior capsular opacification (6%), stent obstruction (4%) early post-operative anterior chamber cells (3%), and early post-operative corneal abrasion (3%). Please refer to Directions for Use for additional adverse event information. CAUTION: Federal law restricts this device to sale by, or on the order of, a physician. Please reference the Directions for Use labeling for a complete list of contraindications, warnings, precautions, and adverse events. GLKOS-14346 Professional Trade Ad-OSN.indd ©2016 Glaukos Corporation. Glaukos and iStent are registered trademarks of Glaukos Corporation. 400-0285-2016-US Rev. 0 8/9/16 4c 9.5" x 13" OCULAR SURGERY NEWS 0 10.5" x 14" +.125" 14 SEPTEMBER 15, 2016 :: Ophthalmology Times MEETING PREVIEW AAO 2016 AAO 2016 INNOVATION ABOUNDS AT SUBSPECIALTY DAY ( Continued from page 12 ) FRIDAY of Medicine Ophthalmology Department, on the topic “Hiding in Plain Sight: The Enigmatic Cornea and IOL Calculations.” The lecture will address the current focus of improving IOL calculations in cataract and refractive surgery as well as shed light on new corneal imaging technology and IOL calculation formulas that are improving outcomes and promise more progress, according to the AAO. Also at the Opening Session, Matthew D. Davis, MD, will receive the Laureate Recognition Award. Dr. Davis is the emeritus director of the Fundus Photograph Reading Center, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison. From 1972 to 1979, he chaired the Diabetic Retinopathy Study, the first randomized, multicenter clinical trial sponsored by the National Eye Institute. The trial documented the value of photocoagulation in reducing the risk of visual loss from diabetic retinopathy, then a leading cause of blindness. To analyze the retinal photographs collected in the trial, Dr. Davis established the FPRC, which is an invaluable, international resource for researchers, according to the AAO. Other awards being presented at the Opening Session include: > Guests of Honor: Stephen A. Kamenetzky, MD, James A. Loreto, MD, and A. Raymond Pilkerton, MD, FACS > Distinguished Service Award: Association of University Professors of Ophthalmology > Special Recognition Award: European Board of Ophthalmology > Outstanding Humanitarian Service Award: Paul S. Bernstein, MD, PhD, and Benjamin W. Roberts, MD > Outstanding Advocate Award: Donald J. Cinotti, MD > International Blindness Prevention Award: Van C. Lansingh, MD > Straatsma Award for Excellence in Resident Education: Steven J. Gedde, MD > Visionary Society Award: David E. I. Pyott, CBE, MD(HON) NAMED LECTURES In addition to the Jackson Memorial lecture, the AAO also many other named lectures planned: Refractive Surgery Subspecialty Day 2016 – Friday, “Pursuit of Perfection” is also the Annual Meeting of the International Society of Refractive Surgery Retina Subspecialty Day 2016 – Friday and Saturday, “Winds of Innovations.” Being held in conjunction with the American Society of Retina Specialists, the Macula Society, the Retina Society, and Club Jules Gonin SATURDAY Cornea Subspecialty Day 2016 “Advancements in Cornea and External Disease: Essential Tools for Success in 2016.” Being held in conjunction with The Cornea Society Glaucoma Subspecialty Day 2016 “Innovations in Glaucoma Care: Evolution and Revolution.” Being held in conjunction with the American Glaucoma Society > > > SUNDAY: > Marshall M. Parks Lecture: “Ocular Motor Misbehavior in Children: Where Neuro- > Ophthalmology Meets Strabismus,” given by Michael Brodsky, MD. Cosponsored by the American Association of Pediatric Ophthalmology and Strabismus Castroviejo Lecture: “Surgical Treatment of Presbyopia: The Journey from Corneal Refractive Surgery to Smart Intraocular Lenses,” given by Dimitri T. Azar, MD. Cosponsored by the Cornea Society and Sektion Kornea of the German Ophthalmological Society Michael F. Marmor, MD, Lecture in Ophthalmology and the Arts: “The Alchemy of Color in 19th Century Art,” given by Francesca Casadio, PhD, A.W. Mellon Senior Conservation Scientist with The Art Institute of Chicago Ruedemann Lecture: “Past, Present, and Future,” given by James V. Strauss, BCO, FASO. Cosponsored by the American Society of Ocularists Wendell L. Hughes Lecture: “Advances in Military Ocular and Combat Casualty Care: Ocular Oncology and Pathology Subspecialty Day 2016 “Breezing Along in Ocular Oncology and Pathology in the Windy City.” Being held in conjunction with American Association of Ophthalmic Oncologists and Pathologists Oculofacial Plastic Surgery Subspecialty Day 2016 “Beauty and the Beast: From Aesthetics to Advanced Orbital Disease.” Being held in conjunction with the American Society of Ophthalmic Plastic and Reconstructive Surgery Pediatric Ophthalmology and Strabismus Subspecialty Day 2016 “Decision 2016 - Cast Your Votes Wisely.” Being held in conjunction with the American Association for Pediatric Ophthalmology and Strabismus and the American Academy of Pediatrics Uveitis Subspecialty Day 2016 “To Bootcamp and Beyond.” Being held in conjunction with the American Uveitis Society > > > > Translating Lessons Learned In War To Peacetime Practice,” given by Col. Robert A. Mazzoli, MD. Cosponsored by the American Society of Ophthalmic Plastic and Reconstructive Surgery Whitney G. Sampson Lecture: “Myth Busting in Refractive Surgery: Corneal Inlays for Presbyopia, and More,” given by Julian D. Stevens, MD. Cosponsored by the Contact Lens Association of Ophthalmologists Straatsma Lecture: “Career Choices in Ophthalmology,” given by Steven J. Gedde, MD. Cosponsored by the Association for University Professors of Ophthalmology Jones/Smolin Lecture: “Trachoma, From Control To Eradication,” given by Thomas M. Lietman, MD. Cosponsored by the Ocular Microbiology and Immunology Group Arnall Patz Lecture: “The Retina Specialist: Do We Practice Evidence-Based Medicine?” given by Paul Sternberg, Jr., MD. This lecture is new this year. Continues on page 16 : Innovate Getty Images/Ken Ilio Special Report ) 16 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) MEETING PREVIEW AAO 2016 INNOVATE ( Continued from page 14 ) MONDAY: TUESDAY: > Zimmerman Lecture: “Changes in Diagnosis and Treatment of Orbital Tumors in 50 Years,” given by Zeynel A. Karcioglu, MD. Cosponsored by the American Association of Ophthalmic Oncologists and Pathologists > William F. Hoyt Lecture: “Can A Unique Little Specialty Show Us Some Pervasive Issues With The Old And New Models Of Healthcare Delivery?” given by Larry P. Frohman, MD. Cosponsored by the North American Neuro-Ophthalmology Society SYMPOSIA Here are several highlighted symposia that may be of interest: > Case-Based Corneal Conundrums: Review a variety of diagnostic and therapeutic dilemmas commonly encountered by anterior segment specialists. Sunday, 10:30 a.m.to 12:30 p.m. > Clinical Dilemmas in Neuro-Ophthalmology: Who to Admit and Why? Hear discussion of the considerations for urgent hospital admission, imaging and treatment. Tuesday, 8:30 to 10 a.m. VISIT OPHTHALMOLOGY TIMES > Areas of Controversy Regarding Cataract Surgical Preferred Practices: Join the debate on two hot topics: (1) Whether intracameral antibiotic is a superior postoperative endophthalmitis prophylaxis and (2) whether femtosecond laser-assisted cataract surgery results in superior outcomes at a reasonable cost. Audience members will listen to both sides and then vote on which argument they find the most persuasive. Monday, 12:15 to 1:30 p.m. OTHER HIGHLIGHTS With 250 instruction courses scheduled, the AAO has identified these as among the hottest topics: > Management of Malpositioned IOLs > Corneal Inlays for Treatment of Presbyopia > iGlaucoma: The Latest Innovations in Glaucoma Therapy > Optical Coherence Tomography Angiography in Retinal Diseases > Panel discussion: A panel discussion, “Physician Payment under MACRA: Choices for Ophthalmologists,” will be moderated by Mike X. Repka, MD. The panel will include George A. Williams, MD, Cynthia Mattox, MD and David A. Glaser, MD. Learn more about the Medicare Access and CHIP Reauthorization Act, which will affect up to 836,000 clinicians and allocate more than $1.2 billion in payment bonuses and penalties in its first year alone. > Skills Transfer Labs: A total of 57 will be AT BOOTH 2473 > > > > offered this year, including these new ones: Laser Retinopexy for Retinal Breaks: Simulation Workshop Smartphone Fundus Photography Advanced Suturing: Scleral and Iris Fixation of Posterior Chamber IOLs plus Intraocular Knot Tying Breakfast with the Experts: These roundtables are an opportunity to combine a buffet breakfast with informative conversations. These will be held Sunday through Tuesday from 7:30-8:30 a.m. Purchase tickets when you register for the meeting for $30, or upon arrival in Chicago for $40. Seating is limited, so register early for best selection. N AV I G A T I N G I T A L L Although the scope of the meeting may seem large and intimidating, the ability to navigate the meeting content and the location of exhibits and sessions is greatly enhanced by the use of the Mobile Meeting Guide (http://www.aao. org/annual-meeting/mobile-meeting-guide), Dr. Rubenstein advised. “This smartphone app has proven to be invaluable to me,” he said. “There is no other ophthalmology meeting in the world that provides the wide breadth of content and the ability to meet and interact with local and international colleagues. Dr. Rubenstein added, “I am really looking forward to this year’s meeting and I hope to see my many friends and colleagues from around the world there.” ■ Getty Images/MattFrankel > Charles D. Kelman Lecture: Given Roger F. Steinert, MD > Parker Heath Lecture: “Assessing Late Stage Physicians, The State of the Art,” given by Stephen R. Permut, MD, JD > Dr. Allan Jensen & Claire Jensen Lecture in Professionalism and Ethics: “Ophthalmology Took a Stand!” given by Alfred Sommer, MD, MHS. Cosponsored by the Ethics Committee > Robert N. Shaffer Lecture: “Glaucoma Population Management,” given by George A. Cioffi, MD. Cosponsored by Prevent Blindness > C. Stephen and Frances Foster Lecture on Uveitis and Immunology: “Immunosuppression for the Uveitides: Current Status and Future Directions,” given by Douglas A. Jabs, MD, MBA. This lecture also is new this year. > Barraquer Lecture: “Keratoconus: Progressive Management of a Progressive Disease,” given by Alaa M. Eldanasoury, MD. Cosponsored by the International Society of Refractive Surgery 18 surgery SePtember 15, 2016 :: Ophthalmology Times CXL advances treatment of keratoconus, ectasia Patient cohort provides opportunity to consider other aspects of crosslinking outcomes By Peter S. Hersh, MD, Special to Ophthalmology Times e T e aneck , n J :: arlier this year, the corneal collagen crosslinking (CXL) procedure was approved by the FDA for the treatment of progressive keratoconus in patients >14 years of age as well as for ectasia after refractive surgery. The treatment is designed to decrease the progression of keratoconus, a disease typified by distortion of the normal corneal optical dome secondary to biomechanical structural weakening. CXL aims to mitigate the progression of this distortion by strengthening the corneal stroma. Approval was granted to Avedro, using its riboflavin products (Photrexa Viscous and Photrexa). The first comprises riboflavin 5’-phosphate 0.146% in solution containing 20% dextran and is used for riboflavin loading and during UV exposure, whereas the latter is riboflavin 5’-phosphate 0.146% without dextran and is used for corneal swelling after the loading phase in corneas which have an intraoperative thickness <400 um. The riboflavin drops are used in conjunction with the Avedro KXL System, which operates at 365 nm UVA at a power of 3mW/cm 2. The approved procedure is similar to the method used internationally for many years: 1. The eye is prepped and draped in the usual fashion and a lid speculum is placed. 2. A 9.0 mm removal of the central epithelium is performed per the surgeon’s preference. Usually, either a spatula or 20% alcohol is used to remove the epithelium. 3. With the lid speculum removed, riboflavin with dextran (Photrexa Viscous) is applied topically every 2 minutes for 30 minutes. The patient is instructed to keep eyes closed between drops. 4. After 30 minutes, confirm adequate riboflavin uptake by slit lamp examination. Uptake is confirmed by a homogeneous green fluorescence throughout the corneal stroma and by the presence of a yellow/green flare in the anterior chamber. If uptake is not adequate, ad- ditional riboflavin is administered until flare is observed. (Figure 1) 5. UV administration should not be started in corneas thinner than 400 microns. If the corneal thickness is less than 400 microns, instill Photrexa drops (riboflavin without dextran) every 5 to 10 seconds until the corneal thickness increases to at least 400 microns. Photrexa is a relatively hypotonic solution which swells the corneal stroma, the goal of which is to protect the endothelium from damage by the riboflavin/UV interaction. Typically, we apply the drops for two minute intervals and then recheck pachymetry until this 400 micron threshold is met. 6. Place the patient under the KXL System. Place lid speculum and use the controller to center the treatment in the x,y, and z planes over the central cornea. Irradiate the eye for 30 minutes, assuring that the patient maintains gaze and the treatment is centered. During irradiation, continue topical instillation of Photrexa Viscous onto the eye every 2 minutes. (Figure 2) Trial criTeria FDA approvals of CXL for the two indications were each based on the results of two randomized, controlled clinical trials sponsored by Avedro. The primary efficacy criterion was a difference in the change in maximum keratometry on corneal topography analysis between treatment and sham control groups. Maximum keratometry was chosen as a quantitative descriptor of keratoconus severity. Change in maximum keratometry can be thought of as an indicator for progression or stability of keratoconus. For the multicenter studies of progressive keratoconus, average maximum keratometry improved by 1.6 D for patients enrolled with keratoconus, compared with average progression in control eyes. In corneal ectasia, average maximum keratometry improved by about 0.7 D. In our own patient cohort treated within the U.S. multicenter trials we looked at a number of other aspects of crosslinking outcomes: Corneal topography: In a 71 eye study, we (Figure 1) Slit lamp photo showing homogeneous saturation of riboflavin throughout cornea. (Images courtesy of Peter S. Hersh, MD) (Figure 2) The corneal collagen crosslinking procedure. (Figure 3) Topography improvement 1 year after crosslinking. noted an improvement in corneal topography indices using Scheimpflug imaging, including the keratoconus index (KI), index of surface Continues on page 20 : CXL THE POWER OF PREEMPTION OMIDRIA® is the first and only FDA-approved drug that provides continuous intracameral delivery of NSAID and mydriatic/anti-miotic therapy during cataract surgery1 LEARN MORE AT AAO BOOTH #4536 CHOOSE OMIDRIA FOR YOUR NEXT CATARACT SURGERY PATIENT • Preempt miosis and inhibit postoperative pain1 • Block the surgically induced inflammatory cascade with the first and only NSAID FDA-approved for intracameral use1 • Eliminate the risks and liabilities of compounded products by using FDA-approved, GMP-manufactured OMIDRIA • Avoid reimbursement difficulties by using broadly covered OMIDRIA and the OMIDRIAssure™ services (OMIDRIAssure.com)* IMPORTANT SAFETY INFORMATION OMIDRIA (phenylephrine and ketorolac injection) 1% / 0.3% must be added to irrigation solution prior to intraocular use. OMIDRIA is contraindicated in patients with a known hypersensitivity to any of its ingredients. Systemic exposure of phenylephrine may cause elevations in blood pressure. Use OMIDRIA with caution in individuals who have previously exhibited sensitivities to acetylsalicylic acid, phenylacetic acid derivatives, and other nonsteroidal anti-inflammatory drugs (NSAIDs), or have a past medical history of asthma. The most commonly reported adverse reactions at 2-24% are eye irritation, posterior capsule opacification, increased intraocular pressure, and anterior chamber inflammation. Use of OMIDRIA in children has not been established. INDICATIONS AND USAGE OMIDRIA is added to ophthalmic irrigation solution used during cataract surgery or intraocular lens replacement and is indicated for maintaining pupil size by preventing intraoperative miosis and reducing postoperative ocular pain. Reference: 1. OMIDRIA [package insert]. Seattle, WA: Omeros Corporation; 2015. Please see the Full Prescribing Information at www.omidria.com/prescribinginformation. *Individual insurance coverage and policies may vary, and Omeros does not guarantee insurance coverage or payment. Omeros offers payments under the OMIDRIAssure “We Pay the Difference” program on behalf of qualifying patients. OMIDRIAssure is subject to change without notice. Visit www.omidria.com OMEROS®, the OMEROS logo®, OMIDRIA®, and the OMIDRIA logo® are registered trademarks and OMIDRIAssure™ is a trademark of Omeros Corporation. © Omeros Corporation 2016, all rights reserved. 2016-131 20 SEPTEMBER 15, 2016 :: Ophthalmology Times variance (ISV) and index of vertical asymmetry (IVA). The improvements observed in ISV indicate a decrease of the curvature variation compared to the mean curvature of the cornea, and IVA, a measurement of the difference between the superior and inferior curvature of the cornea, is analogous to an improvement in the more commonly used inferior-superior steepness. Improvement in KI may indicate that there is an improvement normalization of the keratoconic topographic appearance postoperatively. The overall improvements in corneal topography indices suggest, in general, that the cone is flattening and that the post-CXL cornea is becoming more optically regular and symmetric. (Figure 3) Higher- order aberrat ions (HOAs): Corroborating our findings from corneal topography, we analysed HOAs in 96 eyes undergoing crosslinking and found significant improvements in ocular and anterior corneal HOAs 1 year after CXL. We found that the average total anterior corneal HOAs, total coma, third-order coma, and vertical coma all improved after crosslinking. Looking at total ocular HOAs, total coma, third-order coma, trefoil, and spherical aberration all improved. (Figure 4) Patient satisfaction: In an effort to expand on the objective postoperative assessment of the crosslinking procedure and to further elucidate the expected clinical response, self-reported patients’ optical symptoms and visual function were analyzed in 107 cases. In our study, patients generally noted subjective improvement in visual symptoms. Specifically, night driving, difficulty reading, diplopia, glare, halo, starbursts, and foreign body sensation were all improved one year after CXL. (Figure 5) Postoperative timecourse and corneal haze/demarcation line: It is important for surgeons and patients alike to be aware of the time- 3.0 2.8 2.6* 2.0 2.6 2.4 1.0 1.0 0.9* 0.9 0.8* 0.0 Total HOA Spherical Aberration Coma Trefoil (FIGURE 4) Changes in higher-order aberrations preoperatively to 1 year after crosslinking. (All figures/images courtesy of Peter S. Hersh, MD) 3.5 Patient ratings (0–5) ( Continued from page 18 ) 3.2 3.0 3.1 2.8 2.7 2.5 Preop 1 year 3.1 2.9 2.5 2.6 2.7 2.5 2.4 2.0 1.8 1.6 1.5 * ng rivi D ht re* Gla Nig lo* Ha * * rts rbu Sta u fic Dif ing ad re lty gn rei dy * ion sat sen 2.1 2.0 Dry n ess 2.5 2.6 2.4 1.6 1.6 in Pa ion ia ob ph to ho P bo in ns vis tio tua c Flu Fo (FIGURE 5) Changes in subjective vision surgery preoperatively to 1 year after crosslinking. 62.5 Keratometry CXL Higher order aberrations (RMS wavefront error in μm) surgery 60.0 58.0 58.5 59.8 58.2 56.0 57.1 56.9 54.0 52.0 Baseline 1 month 3 months 6 months 1 year (FIGURE 6) Timecourse of improvement in maximum keratometry after CXL. Note worsening, on average, at 1 month. course of healing and vision recovery after crosslinking. In general, there is a worsening of vision and steepening of the keratoconic cone at 1 month postoperatively with improvement thereafter. (Figure 6) On examination, corneal haze is generally noted after the CXL procedure. It appears initially as a dust-like change in the corneal stroma and evolves over time to a mid-stromal demarcation line, delineating the posterior extent of the crosslinking reaction. (Figure 7) We quantified the natural history of corneal haze over time after crosslinking using Sheimp- flug densitometry. Similar to the timecourse of clinical outcomes after crosslinking, there appears to be an increase in haze, which peaks at one month, and plateaus between 1 and 3 months. Between 3 and 6 months the cornea begins to clear, and continues to return toward baseline at 1 year. (Figure 8) It remains unclear whether this postoperative haze is an unwanted side effect or rather a desired wound healing affect demonstrating the efficacy of the crosslinking procedure. We also looked at corneal thickness after CXL and found that mild corneal thinning is a general con- comitant of the early CXL postoperative course. Similar to the timecourse of crosslinking associated corneal haze and crosslinking clinical outcomes, the cornea appears to thin at 1 and 3 months, and to re-thicken between 3 and 12 months. In our study, at 1 year, corneas remained slightly thinner than preoperative measurements. Predictors of outcomes: The essential goal of collagen crosslinking is to stabilize the progression of the ectatic cornea. With regard to this disease stabilization, crosslinking certainly appears efficacious. In our study, 98.1% of eyes showed <2 D and 91.6% showed <1.0 D of topographic progression over one year postoperatively. Although there was, on average, 1.7 D flattening of the cone, looking at individual eyes, the maximum K value decreased by 2.00 D or more in 31% patients, remained unchanged within 1 D in 65%, and increased by 2 D or more in 4%. To determine preoperative patient characteristics that may predict topography and visual acuity outcomes of CXL, we performed multiple regression and odds ratio analysis on a cohort of 104 eyes. The finding was that eyes with more preoperative steepening tended to have a greater improvement in topography; specifically, those with maximum K >55 D were 5.4x more likely to have topographic flattening >2 D after CXL compared with eyes with flatter corneas. With regard to eyes in which corneal topography continued to steepen, that is, those in which the crosslinking procedure failed to completely stabilize the disease, there were no independent predictors of continued disease progression even at the more refined >1D level; all eyes were equivalently likely to be stabilized by the CXL procedure. Specifically, in patients with an initial maximum K >55 D, 40/44 (90%) eyes showed less than 1 D of progression, one year after CXL; similarly, in patients with initial maximum K <55.0D, 55/60 (92%) eyes were stable. Finally, preoperative cone location may play an important role in the efficacy of the CXL. There appears to be more topographic 21 SEPTEMBER 15, 2016 :: Ophthalmology Times surgery (FIGURE 7) Early general haze evolves to demarcation line after crosslinking. (FIGURE 8) Scheimpflug densitometry showing evolution of corneal haze, peaking at one month, plateauing at 3 months, and improving to baseline at 6 and 12 months. flattening in those eyes with centrally located cones. We found that maximum keratometry flattened by 2.6 D in eyes with centrally located cones, and by only 1 D and 0.05 D, in those eyes with paracentral and peripheral cones, respectively. With regard to corrected visual acuity, we found, on average, an approximately 1-line improvement in the cohort analyzed. When stratified by individual eyes, however, vision improved by 2 or more Snellen lines in 21% and remained stable within 1 line in 78%; 1 eye in our patient cohort lost 2 Snellen lines. In our analysis, the only independent predictor of a change in postoperative best-corrected vision after CXL was preoperative best corrected visual acuity. Those eyes with worse preoperative best corrected visual acuity were more likely to experience an improvement of >2 Snellen lines. Specifically, eyes with a preoperative Snellen visual acuity of 20/40 or worse were 5.9 times more likely to improve by two lines or more; 43% of eyes with best corrected vision 20/40 or worse had on improvement of >2 lines compared with only 11% of eyes who were better than 20/40 preoperatively. With regard to eyes which lost vision from the procedure, the most salient indicator of an unwanted outcome, there was no independent preoperative indicator; however, it is very important to advise those patients with very good correctable vision before crosslinking of the changes in vision that may be experienced during the healing process. ■ References 1. Hersh PS, Greenstein SA, Fry KL. Corneal cCollagen crosslinking for keratoconus and Corneal ectasia: One year results of a randomized prospective Study. J Cat Refract Surg. 2011:37:149-160. 2. Greenstein SA, Fry KL, Bhatt J, Hersh PS. Natural history of corneal haze after collagen crosslinking for keratoconus and corneal ectasia: A Scheimpflug and biomicroscopic analysis. J Cat Refract Surg. 2010:35:2105-2114. 3. Greenstein SA, Fry KL, Hersh PS. Corneal topography indices after corneal collagen crosslinking for keratoconus and corneal ectasia: one year results. J Cat Refract Surg. 2011:37:1282-1290 4. Greenstein SA, Fry KL, Hersh, MJ, Hersh, PS. Higher-order aberrations after corneal collagen crosslinking for keratoconus and corneal ectasia. J Cat Refract Surg. 2012;38:292-302. 5. Greenstein SA, Shah VP, Fry KL, Hersh PS. Corneal thickness changes after corneal collagen crosslinking for keratoconus and corneal ectasia: one year results. J Cat Refract Surg 2011:37:691-700. 6. Brooks NO, Greenstein SA, Fry KL, Hersh, PS. Patient subjective visual function after corneal collagen crosslinking for keratoconus and corneal ectasia. J Cat Refract Surg 2012;38:615-619. 7. Greenstein SA, Hersh PS. Characteristics influencing outcomes of corneal collagen crosslinking for keratoconus and ectasia: Implications for patient selection. J Cat Refract Surg. 2013;39:1133-1140. 8. Greenstein SA, Fry KL, Hersh, PS. Effect of topographic cone location on outcomes of corneal collagen cross-linking for keratoconus and corneal Ectasia. J Cat Refract Surg 2012; 28: 397-405. PETER S. HERSH, MD, FACS E: [email protected] Dr. Hersh discloses he is medical monitor with Avedro Inc., Waltham MA. HANDYREF-K ARK-1a or ARK-1s M3 ARK OPD-Scan III Portable Handheld Refractor/Keratometer ® Autorefractor/Keratometer & Non-Contact Tonometer Autorefractor/ keratometer ARK-1s adds subjective refractions and glare testing Autorefractor/Keratometer, Corneal Topographer, Pupillometer and Integrated Wavefront Aberrometer REFRACTIONS M3 Product / Model name: AUTOREF/KERATO/TONOMETER TONOREF II All Marco table top ARKs are automated, multi-modality autorefractors/keratometers, that feature: super luminescent diodes (SLD), rotary prism, double ring technology, confidence index and automatic fogging for accurate, reliable data. X, Y, Z eye tracking makes it possible to measure patients with cataracts, IOLs, and post LASIK procedures. The M3 adds tonometry; the ARK-1s adds subjective refractions and glare testing; and the OPD-Scan III integrates wavefront aberrometry, corneal analysis, and pupillometry. The Difference is Marco. AAO 2326 PETER S. HERSH, MD Peter S. Hersh, MD, is director, CLEI Center for Keratoconus–Hersh Vision Group, Manufactured Represented by Marco Teaneck, NJ. He did not Designed indicate anyand financial interest in by the NIDEK subject-matter. 800-874-5274 % marco.com SEPTEMBER 15, 2016 :: Ophthalmology Times surgery Optimizing toric IOL outcomes via techniques, technologies Accuracy of results requires attention to multiple sources for residual astigmatism By Cheryl Guttman Krader; Reviewed by Rudy M.M.A. Nuijts, MD, PhD MA AS T RICH T, T HE NE T HERL ANDS :: A LARGE MAJORITY of cataract surgery patients with a toric IOL implanted will achieve spectacle independence for distance vision, but a sizeable proportion are left with significant residual astigmatism and find themselves needing glasses at least sometimes. Understanding the sources of residual astigmatism allows surgeons to choose techniques and technologies that will optimize outcomes for toric IOL surgery, according to Rudy M.M.A. Nuijts, MD, PhD. “Results from a trial we conducted showed that 70% of patients who underwent bilateral toric IOL implantation could see 20/25 uncorrected at distance and 84% of patients were spectacle independent for distance vision,” said Dr. Nuijts, professor of ophthalmology, Maastricht University Medical Center, Maastricht, The Netherlands. However, 26% of patients had more than 1 D of residual stigmatism and 54% were left with at least 0.5 D of residual astigmatism. (Figure 1) He reviewed factors affecting the astigmatic outcome, including preoperative measurement errors; surgically induced astigmatism (SIA); calculation inaccuracies, including the effect of posterior corneal astigmatism, and toric IOL misalignment. PR EOPER ATIVE ISSUES Accuracy of preoperative measurements is critical, and different instruments can be used for determining keratometry values. Dr. Nuijts noted that a study performed by his group found there was not a large difference between the measurements obtained when using several different instruments for autorefraction, a manual keratometer, or the sim K value measured with a topographer or a Scheimpflug tomographer (Pentacam, Oculus). However, the equivalent K value measured with the latter device was significantly lower than the values obtained with the other devices. The explanation for the difference is that the equivalent K incorporates astigmatism of the posterior corneal surface, Dr. Nuijts said. He noted that the influence of the posterior cornea on total astigmatism has been described RCT Toric versus Monofocal IOLs 100 99 Toric Monofocal 80 Percentage of patients 22 74 60 40* 46 41 30 20 10 0 ≤0.50 ≤1.00 ≤1.50 Refractive astigmatism ´ 26% of eyes still had >1.0 D of residual astigmatism ´ 54% of eyes still had >0.5 D of residual astigmatism *p < 0.05 (FIGURE 1) Residual refractive astigmatism after toric IOL implantation. (FIGURE 2) Influence of the posterior corneal surface showing 1.5 D of posterior corneal astigmatism. (Images courtesy of Rudy M.M.A. Nuijts, MD, PhD) by Douglas Koch, MD, and colleagues. Essentially, the posterior cornea acts as a minus lens and is generally steep vertically, inducing against-the-rule (ATR) corneal astigmatism that compensates for some of the with-the-rule astigmatism on the anterior corneal surface. On a population basis, the magnitude of posterior corneal astigmatism is about 0.3 D, SEPTEMBER 15, 2016 :: Ophthalmology Times surgery and in about 10% of eyes, the value PER IOPER ATIV E ISSUES Misalignment of the toric IOL afexceeds 0.5 D. Results from various studies show fects the astigmatic outcome as that the accuracy of the astigmatic there is about a 3% loss of effioutcome with toric IOL implanta- cacy for every degree of misaligntion can be improved when the ment. For surgeons who manually posterior corneal astigmatism is mark the eye, accuracy of toric IOL factored into power calculations, alignment depends on the accuracy of the preoperative markings, Dr. Nuijts said. “Especially in cases with high including both the reference and anterior corneal astigmatism, the in- axis alignment marks. Dr. Nuijts said fluence of the postethat he likes to use a rior corneal surface bubble marker, but can be significant noted that research and has to be taken Achieving spectacle conducted by Oliver into consideration independence for Findl, MD, comparwhen performing distance vision after ing marking at the the toric IOL power toric IOL implantation slit lamp, a penducalculation,” said depends on the lar marker, bubble Dr. Nuijts. refractive outcome. marker, and tonomHe presented a Factors affecting eter marker showed case to illustrate residual astigmatism the most predictthis point (Figure and studies able outcomes were 2) and discussed evaluating the use achieved using the resu lt s of one of various surgical pendular marker. study investigattechniques and Intraoperative ing showing that technologies relating digital guidance in eyes with ATR to those factors are techniques have total corneal astigdiscussed. been developed to matism, the proporovercome the inaction of eyes left with <0.45 D of refractive astigmatism curacies of manual marking. However, there is still room for decreased from 67% to 42% using a method that accounted for pos- error when using this technology because digital marking cannot terior corneal astigmatism. Another study comparing differ- eliminate human error from malent methods for measuring kera- positioning of the IOL relative to tometry and different formulas for the intended meridian. “A study we conducted found that power calculations found that the most accurate results were achieved even when using a digital markusing an optical low coherence re- ing system, there was still an averflectometry device and a calcu- age inaccuracy of 2.6° in this last lation method that compensates step of toric IOL positioning,” Dr. for the effect of posterior corneal Nuijts said. In addition, there is still the poastigmatism (Barrett calculator). SIA also influences the astigmatic tential for the toric IOL to rotate outcome and needs to be factored postoperatively, although on averinto toric IOL power calculations. age, modern toric IOLs demonstrate Dr. Nuijts noted that the amount of excellent postoperative stability. ■ SIA varies depending on incision size, location, and level of preoperative astigmatism. However, he pointed out that in a study his group conducted evaluRUDY M.M.A. NUIJTS, MD, PHD ating the effect of incision size on E: [email protected] SIA, the standard deviation of the This article was adapted from Dr. Nuijts’ presentation during average error was the same across Refractive Surgery Subspecialty Day at the 2015 meeting the different incision sizes (0.52 to of the American Academy of Ophthalmology. Dr. Nuijts is 0.54 D), indicating there is still a a consultant, lecturer, and or receives grant support from problem with predictability of SIA. companies that market toric IOLs. TAKE-HOME ion IMAGING SM Anterior Segment Imaging EMPOWERMENT Marco has redefined slit lamp imaging by combining a new intra-optics beamsplitter, adapter and camera mount, with the tremendous computing and imaging power of Apple Technology. The result is iON IMAGINGSM –a highly sophisticated ‘mainstream’ system that emphasizes image quality, simplicity and efficiency. Finally, a fully integrated imaging solution like no other. The Difference is Marco. AAO 2326 800-874-5274 | marco.com 24 SEPTEMBER 15, 2016 :: Ophthalmology Times surgery Creating corneal inlay pockets with femtosecond laser technology Surgeons should be familiar with laser parameters, techniques to achieve best outcomes By Fred Gebhart; Reviewed by Majid Moshirfar, MD SALT L AK E CI T Y :: CREATING A CORNEAL pocket for One notable pearl for surgeons is to crea small-aperture corneal inlay (Kamra, Acu- ate a pocket that penetrates at least 40% of Focus) in itself is not a difficult process. Using the cornea depth. a femtosecond laser to create the proper pocket “LASIK flaps today are around 100 to 120 in the correct position to allow precise place- μm,” he explained. “For a corneal inlay, a ment for optimal vision correction requires pocket as deep as 225, 250, or even 300 μm finesse and expertise. is advantageous for placement. The deeper “We have three different platforms that can you go, as long as you respect the stromal create pockets for the inlay and they can all bed of 250 μm, the more you reduce the risk do an excellent job in experienced hands,” of hyperopic shift, visual fluctuations, and said Majid Moshirfar, MD. dry eye symptoms in patients.” “I personally use the Intralase iFS and the Alcon FS200 to create pockets and I can’t find PR ACTIC A L PE A R LS a difference between them in performance,” Dr. Moshirfar offered five additional tips for said Dr. Moshirfar, clinical professor of oph- successful corneal pocket creation and pinthalmology, University of Utah Moran Eye hole-aperture vision correction: > Good patient selection Center and medical research director, Hoopes > Manage patient expectations Vision, Salt Lake City. > Proper centration But the Intralase iFS, Alcon FS200, and > Surgical microscope Ziemer FEMTO LDV Z8 are not identical. The > Decentered suction ring iFS was the first femtosecond laser on the U.S. market, Dr. Moshirfar said. U.S. surgeons have more experience on Patient selection is vital. Good surgical canthe iFS system than any other platform and didates are in good health, Dr. Moshirfar said, have devoted more time and attention to with no underlying disease. tweaking and calibrating its operational paGood surgical candidates also have a smallrameters, he noted. angle kappa, the distance between the center of “The limitation with this device is that it the pupil and the Purkinje reflex. The smaller can only create a pocket along the angle kappa, the more likely the temporal aspect of the corthe patient is to see significant nea,” he added. “That can be vision improvement. Patients A surgeon a limitation when you have a whose angle kappa is 500 μm or with clinical patient who could be better larger are not good candidates experience with treated with an incision from for Kamra vision correction. three femtosecond another direction.” Patients should also have minlasers discusses The FS200 and the Z8 have imal refractive error before surthe practicalities their own advantages and limigery and little to no astigmatism. of creating ideal tations. Both can create pockPatients with significant refracfemtosecond laser ets at any angle. tive error may need LASIK or inlay pockets. The Z8 creates wider pockets PRK correction before the inlay than the other two platforms, pocket is created. Patients with which gives more space for insignificant astigmatism must strumentation and maneuvering while placing have it corrected before inlay surgery. the inlay. Docking is very easy and the de“You have to talk with your patients about vice gives the familiar feel of microkeratome. expectations,” Dr. Moshirfar continued. “PinThe FS200 is quick and easy to operate and hole-aperture technology can allow most paallows the operator to trace the path of the tients to attain good near vision, but it won’t incision for more precise placement. make everyone a J1. If you look at the FDA ap- TAKE-HOME proval study, more than 87% of patients were 20/40 or better for near vision and 31% were 20/20 or better for near vision at the end of the 60 months study period. We cannot promise all patient that they will become 20/20 at near after surgery.” Proper centration of the inlay is also crucial. In an ideal world, the center of the pupil would be coaxial with the four Purkinje images. In the real world, surgeons must assess the eye preoperatively. If distance from the center of the pupil and the Purkinje reflex is less than 300 μm, Dr. Moshirfar advised centering the device on the Purkinje. If the distance is more than 300 μm, he advised centering the device between the center of the pupil and the Purkinje reflex. Patients with a larger gap are not good candidates for the device. SURGICAL MICROSCOPE Dr. Moshirfar also advised using a surgical microscope for optimal device placement. Current femtosecond laser platforms lack a microscope, which has prompted many surgeons to use the microscope on an excimer laser to implant the device. A conventional surgical microscope provides better visualization and more precise movement when inserting and placing the inlay. The final tip is to decenter the suction ring slightly in the direction of the incision. Decentering the ring to visualize a small bit of conjunctiva makes it easier to open the incision closer to the limbus. The closer the incision is to the limbus, the lower the risk of astigmatism and the less likely the pocket is to interfere with any later surgery. ■ MAJID MOSHIRFAR, MD P: 801/568-0200 This article was adapted from Dr. Moshirfar’s presentation at the 2016 meeting of the American Society of Cataract and Refractive Surgery. He did not indicate any proprietary interest in the subject matter. FROM SUN OPHTHALMICS Announcing BromSite, the first product from Sun Ophthalmics. Visit bromsite.com to find out more. Sun Ophthalmics is a division of Sun Pharmaceutical Industries, Inc. © 2016 Sun Pharmaceutical Industries, Inc. All rights reserved. BromSite is a trademark of Sun Pharma Global FZE. SUN-OPH-BRO-009 06/2016 26 SEPTEMBER 15, 2016 :: Ophthalmology Times surgery Combination therapy targets pupil maintenance, pain during surgery Analysis finds positive results compared with placebo in two pooled phase III studies By Vanessa Caceres; Reviewed by Thomas Walters, MD Intraoperative Mean AUC Change-from-Baseline in Pupil Diameter p < 0.0001 p < 0.0001 p < 0.0001 Mean Area Under Curve (mm) 0.0 0.0 0.0 -0.5 -0.4 0.6 -0.7 -1.0 -0.9 -0.9 -1.5 -2.0 p < 0.0001 p < 0.0001 p < 0.0035 p < 0.0620 14.2 17.2 40 Less Pain 0.0 -0.0 Decrease in Pupil Size 0.5 0.1 p < 0.0001 p < 0.0053 1.0 Mean Area Under Curve (mm) p < 0.0001 Postoperative Mean AUC Subject-Reported Ocular Pain Measured by Visual Analog Scale 30 20 7.5 13.0 11.9 -0.9 10 5.3 3.5 5.1 4.9 4.8 0 ≤ 10 min > 10 min > 12 min > 15 min > 20 min ≤ 10 min > 10 min > 12 min > 15 min > 20 min n = 242 N = 249 n = 138 N = 130 n = 105 N = 94 n = 52 N = 43 n = 19 N = 11 n = 258 N = 261 n = 145 N = 142 n = 111 N = 103 n = 57 N = 48 n = 22 N = 15 Placebo Phenylephrine/Ketorolac Error bars depict standard deviation Placebo Phenylephrine/Ketorolac Error bars depict standard deviation (Figures courtesy of Thomas Walters, MD) AUS T IN, T X :: PATIENTS WHO RECEIVED the utes or less, longer than 10 minutes, longer combination medication phenylephrine/ than 12 minutes, longer than 15 minutes, and ketorolac (Omidria, Omeros Corp.) during cata- longer than 20 minutes. Researchers used the ract surgery were better able to maintain their mean area under the curve analysis to measure pupil diameter during surgery compared with intraoperative change from baseline in pupil placebo, according to Thomas Walters, MD. diameter (figure, above left) and postoperative The investigation looked at the subject-reported ocular pain as pooled results from two phase measured by a Visual Analog III randomized, double-masked, Scale (figure, above right). The combination placebo-controlled studies inAll procedures were recorded, of phenylephrine and cluding 808 subjects—403 reand changes in pupil diameter ketorolac helped ceived phenylephrine/ketorolac were measured at 1-minute inmaintain pupil and 405 received placebo, said tervals from time of incision to diameter and lowered Dr. Walters, who is in private wound closure (end of surgery). postoperative pain practice in Austin, TX. A single masked central reader compared with The study objectives were to made the measurements. placebo in patients measure maintenance of pupil having cataract diameter during cataract surBETTER PUPIL surgery in two pooled gery or refractive lens exchange MAINTENANCE phase III studies. and postoperative ocular pain Demographics and cataract charduring the first 10 to 12 hours acteristics were similar between after surgery. the group receiving phenylephThe medication was administered in stan- rine/ketorolac and the placebo group. The group dard irrigation solution during the procedure, receiving phenylephrine/ketorolac had better and all subjects in both areas received standard pupil maintenance at all time points, and there preoperative mydriatic and anesthetic agents. was less postoperative pain, he said. Procedure times were categorized as 10 minAs for postoperative ocular pain, “it increased TAKE-HOME in the placebo group with increasing surgical duration, but was numerically similar in the phenylephrine/ketorolac group,” Dr. Walters said. The addition of phenylephrine/ketorolac to the cataract surgeon’s armamentarium is important because of the risks associated with pupil constriction, he said. “You can get iris touch with the phaco probe, which induces miosis and inflammation,” Dr. Walters explained. “When you have reduced visibility of the lens, it makes the procedure more difficult for the surgeon and potentially more complicated for the patient with iris trauma and postop inflammation.” Dr. Walters concluded that the medication aids with ease of the procedure and quicker visual recovery. ■ THOMAS WALTERS, MD E: [email protected] This article was adapted from Dr. Walters’ presentation at the 2016 meeting of the American Society of Cataract and Refractive Surgery. Dr. Walters is a consultant for Omeros Corp. JOIN US AT AAO 2016 ASTIGMATISM MANAGEMENT: A JOURNEY OF O INNOVATION ON (YHUZRQGHUKRZRWKHUVXUJHRQVSUHSDUHWKHLUSDWLHQWVIRUUHDOLVWLFRXWFRPHV"b VWLF R R HV" Join us Friday evening for a video symposium and live conversation to see how Drs. Bob Cionni*, John Davidson*, Dan Tran* and Kerry Solomon* have adopted an Astigmatism Management mindset and what this means for their patients. See the latest technologies from Alcon: 3UHYLHZWKHZRUOGȇVUVWΖPDJH*XLGHG$EHUURPHWHUXVLQJ ORA SYSTEM™ with VerifEye Lynk™ technology Preview the next generation Verion® 3.0 software Launch of the new Alcon Toric Calculator featuring the Barrett Toric Algorithm Register today to join some of today’s top surgeons as they show us new innovations and techniques demonstrating how they have adopted an Astigmatism Management mindset. http://bit.ly/AAOAstigmatismManagement Friday, October 14th Hilton Chicago – International Ballroom North† Registration: 5:30 – 6:15 PM Symposium: 6:15 – 7:15 PM Bridging the gap to cataract refractive surgery. *Paid Alcon consultants. Shuttle transportation from the McCormick Center to the Hilton Chicago will be provided. 7KLVV\PSRVLXPLVQRWDɝOLDWHGZLWKWKHRɝFLDOSURJUDPRI$$2 † © 2016 Novartis 8/16 US-CRS-16-E-3330 28 SEPTEMBER 15, 2016 :: Ophthalmology Times surgery REVERSE OPTIC ( Continued from page 1 ) what Dr. Hoffman described as an obvious opening in the equator of the bag. He noted that surgical options for a torn posterior include: > Leave the IOL in place and address it if it subluxates further; > Levitate the IOL into the ciliary sulcus (not an option for a single-piece IOL); > Levitate the IOL into the ciliary sulcus and suture the haptics (also not a viable option); > Use the capsulorhexis to capture the optic; > Exchange the IOL for a three-piece IOL in the sulcus and kept the irrigator in the eye to maintain the pressure and prevent vitreous from coming from around the lens. “The reality was that with the optic captured on the rhexis, even if the chamber did become shallow, additional vitreous probably would not have come forward,” Dr. Hoffman said. He finished by hydrating the wounds, removing the infusing cannula, and injecting acetylcholine (Miochol-E, Bausch + Lomb) into the anterior chamber. Three months postoperatively, the IOL remained centered. OCT showed good clearance between the anterior surface of the IOL and the posterior surface of the iris. CONSIDER ATIONS The Cataract Clinical Committee of the American Society of Cataract and Refractive Surgery has emphasized that single-piece IOLs should not be implanted into the ciliary sulcus without fixation because of the risk of pigment disperDr. Hoffman opted to perform a reverse optic sion, glaucoma, uveitis, and recurrent vitreous capture. He first injected an OVD in front of hemorrhages, Dr. Hoffman noted. “However, it may be okay to put single-piece the lens and more behind the lens to push the vitreous back behind the capsule. He then used IOLs in the bag and perform reverse optic capture,” said Dr. Hoffman, recountthe same viscoelastic cannula to ing a recent study of the proceprolapse the optic up in front of dure performed in 16 eyes, with the anterior rhexis, which proved Reverse optic 12 of the fellow eyes serving as to be successful. capture may be controls (Ophthalmic Surg La“At this point, the IOL was a viable option sers Imaging. 2012;43:480-488). centered and stable,” he said. for addressing a The authors reported that paBecause vitreous was in the decentered singletients achieved 20/25 or better anterior chamber previously, Dr. piece IOL as the result vision in 94% of the eyes in Hoffman removed the OVD using of a compromised which the reverse optic capa 23-gauge vitrector. A 20-gauge posterior capsule or a ture was performed compared irrigating cannula was positioned posterior capsular tear. to 92% in the control eyes. In through the left-hand incision. both groups, 94% and 100%, Hindsight suggested a 20-gauge respectively, were within 1 D vitrector would have prevented fluid from egressing from the bimanual incision. of the intended correction. The IOLs in all eyes After removing as much of the OVD as pos- that underwent reverse optic capture remained sible, Dr. Hoffman removed the vitrector and centered, and no vision-threatening complicakept the irrigator in the eye. He injected tri- tions occurred after 19 months of follow-up. The study concluded that reverse optic capamcinolone to identify any vitreous in the anterior chamber, and used the irrigator to wash ture of a single-piece acrylic IOL through an anterior capsulorhexis merits consideration for the triamcinolone out of the eye. When no vitreous was seen in the anterior IOL placement in selected cases of insufficient chamber, Dr. Hoffman hydrated the incision posterior capsule support. ■ SURGICAL CASE VIDEO Following “high-speed” removal of this routine 2+ nuclear sclerotic cataract, a single-piece IOL is injected into the capsular bag resulting in a “crease” in the posterior capsule. During viscoelastic removal, it became apparent the crease was a large opening in the posterior capsule, which resulted in vitreous prolapsed and aspiration into the aspirating bimanual cannula. (Videos courtesy of Richard S. Hoffman, MD) TAKE-HOME VIDEO The IOL optic is prolapsed in front of the capsulorhexis (reverse optic capture) with an OVD cannula following by removal of the OVD with a 23-gauge vitrector and a 20-gauge irrigating cannula. Triamcinolone is injected into the anterior chamber to check for vitreous followed by stromal hydration of the wounds and injection of miochol to constrict the pupil. Go to OphthalmologyTimes.com/ ReverseOpticCapture RICHARD S. HOFFMAN, MD E: [email protected] This article was adapted from Dr. Hoffman’s presentation at the 2015 meeting of the American Academy of Ophthalmology. He has no financial interest in the subject matter. AAO, societies issue post-surgery, co-management guidance THE AMERICAN Academy of Ophthalmology (AAO)—along with 60 other ophthalmic societies—has issued new, more patient-centric guidelines (http://bit.ly/2ccuiu6) for postoperative co-management of ophthalmic procedures. A principal aim of the revision is to better inform patients with full disclosure of compensation arrangements for the non-operating practitioner and fees that practitioners may charge beyond those that Medicare and other third-party payors would cover, said the AAO in a prepared statement. The new guidelines call for written informed consent and financial disclosure; reflect that co-management goes beyond cataract surgery to all ophthalmic surgery; and address the distinction between the legal and ethical aspects of co-management. ■ TURNING RESEARCH INTO RECOVERY — FASTER. THAT’S THE DIFFERENCE BETWEEN PRACTICING MEDICINE AND LEADING IT. At Houston Methodist, we focus on innovative research that directly benefits our patients. Through more than 700 clinical studies across the Houston Methodist system and many national studies we exclusively offer in Texas, we are discovering new technologies and treatments for some of medicine’s toughest challenges, and getting them to our patients — faster. Visit houstonmethodist.org/research and explore all the ways we’re leading medicine. 30 NEXT FRONTIER IN MANAGEMENT OF Special Report ) RETINA DISEASE ADVANCES CONTINUE TO PROGRESS IN THE AREAS OF PHARMACOLOGY, SURGERY, AND DIAGNOSIS CASE 1: 29-year-old male 20/60 20/60 Macula is flat, foveal yellow spot (FIGURE 1) This 29-year-old male had no relevant previous of family history but had blurry vision in both eyes for the past 4 days, seeing a yellow spot in the center. The macula is flat and there is a small yellowish spot, which, in OCT, looks like a stop in the photoreceptor continuation in the ellipsoid and interdigitation area. There is also some hyperreflective material from the retinal pigment epithelium toward the outer nuclear layer. (Images courtesy of Anat Loewenstein, MD, MHA) SD-OCT ENHANCES VISUALIZATION EARLIER IN DISEASE PROCESS Detailed imaging facilitates evaluation of foveal disorders By Lynda Charters; Reviewed by Anat Loewenstein, MD, MHA S T EL AVIV, ISR AEL :: take-home Spectral-domain optical coherence tomography facilitates detailed evaluation of foveal disorders even in the very earliest disease stages. pectral-domain optical coherence tomography (SD-OCT) has become indispensable for visualizing the fovea and diagnosing retinal diseases. Importantly, detailed visualization facilitates diagnosis during the early disease stages, according to Anat Loewenstein, MD, MHA. SOL A R M ACU LOPAT H Y The first case (Figure 1) illustrating the importance of high-detailed imaging was that of a 29-year-old male, as described by Dr. Loewenstein. The patient’s past ocular medical and family histories were not remarkable. The patient reported blurry vision in both eyes over the past 4 days with a yellow spot centrally. He denied any recent exposure to drugs, however, he had used cocaine and cannabis “crystal” 1 year previously. SD-OCT examination showed a normal flat macula with a small yellow spot. However, there was a stop in the photoreceptor continuity in the ellipsoid and inter-digitation zones. “A hyper-reflective material was seen emerging from the retinal pigment epithelium [RPE] toward the outer nuclear layer,” said Dr. Loewenstein, professor of ophthalmology, deputy dean of the medical school, Sackler Faculty of Medicine, Tel Aviv University, Israel, and chairman of ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv. The patient later admitted to lying on the beach exposed to sunlight for the entire day when symptoms began. The diagnosis was solar retinopathy, secondary to sun gazing. During follow-up, SD-OCT showed the hyperreflective material was absorbed with abrupt continuation of the photoreceptor layer in the fovea and the external limiting membrane (ELM) was preserved. This status was maintained at 2 and 4 months of follow-up. “Solar retinopathy occurs mainly during celestial events—such as eclipses, religious rituals, and sunbathing—and in psychiatric patients,” Dr. Loewenstein said. “The light is of Continues on page 33 : SD-OCT INDICATIONS AND USAGE IMPORTANT SAFETY INFORMATION (continued) ZYLET® (loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension) is a topical anti-infective and corticosteroid combination for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocular infection or a risk of bacterial ocular infection exists. Ocular steroids are indicated in inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, and where the inherent risk of steroid use in certain infective conjunctivitides is accepted to obtain a diminution in edema and inflammation. They are also indicated in chronic anterior uveitis and corneal injury from chemical, radiation or thermal burns, or penetration of foreign bodies. The use of a combination drug with an anti-infective component is indicated where the risk of superficial ocular infection is high or where there is an expectation that potentially dangerous numbers of bacteria will be present in the eye. The particular anti-infective drug in this product (tobramycin) is active against the following common bacterial eye pathogens: Staphylococci, including S. aureus and S. epidermidis (coagulase-positive and coagulasenegative), including penicillin-resistant strains. Streptococci, including some of the Group A-beta-hemolytic species, some nonhemolytic species, and some Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus mirabilis, Morganella morganii, most Proteus vulgaris strains, Haemophilus influenzae, and H. aegyptius, Moraxella lacunata, Acinetobacter calcoaceticus and some Neisseria species. 6-*'*)" 0. *!*-/$*./ -*$.(4- .0'/$)"'0*(2$/# damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma. If this product is used for 10 days or longer, intraocular pressure should be monitored. 6. *!*-/$*./ -*$.(4- .0'/$)+*./ -$*-.0+.0'- cataract formation. 6# 0. *!./ -*$.!/ -/-/.0-" -4(4 '4# '$)") increase the incidence of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification such as a slit lamp biomicroscopy and, where appropriate, fluorescein staining. 6-*'*)" 0. *!*-/$*./ -*$.(4.0++- ../# #*./- .+*). and thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infections. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated. 6(+'*4( )/*!*-/$*./ -*$( $/$*)$)/# /- /( )/*!+/$ )/. 2$/##$./*-4*!# -+ ..$(+' 3- ,0$- ."- /0/$*). *!*0'- steroids may prolong the course and exacerbate the severity of many viral infections of the eye (including herpes simplex). 60)"'$)! /$*).*!/# *-) - +-/$0'-'4+-*) /* 1 '*+ *$)$ )/''42$/#'*)"/ -('*'./ -*$++'$/$*)0)"0.$)1.$*) must be considered in any persistent corneal ulceration where a steroid has been used or is in use. 6*./*((*)1 -. - /$*).- +*-/ $)+/$ )/.2 - $)% /$*) and superficial punctate keratitis, increased intraocular pressure, burning and stinging upon instillation. Please see Brief Summary of Prescribing Information for ZYLET® on adjacent page. IMPORTANT SAFETY INFORMATION 67$.*)/-$)$/ $)(*./1$-'$. . .*!/# *-) ) conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. ®/™ are trademarks of Bausch & Lomb Incorporated or its affiliates. © 2015 Bausch & Lomb Incorporated. All rights reserved. Printed in USA. US/ZYL/15/0013 BRIEF SUMMARY OF PRESCRIBING INFORMATION This Brief Summary does not include all the information needed to use Zylet safely and effectively. See full prescribing information for Zylet. Zylet®(loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension) Initial U.S. Approval: 2004 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing Apply one or two drops of Zylet into the conjunctival sac of the affected eye every four to six hours. During the initial 24 to 48 hours, the dosing may be increased, to every one to two hours. Frequency should be decreased gradually as warranted by improvement in clinical signs. Care should be taken not to discontinue therapy prematurely. 2.2 Prescription Guideline Not more than 20 mL should be prescribed initially and the prescription should not be refilled without further evaluation [see Warnings and Precautions (5.3)]. CONTRAINDICATIONS 4.1 Nonbacterial Etiology Zylet, as with other steroid anti-infective ophthalmic combination drugs, is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. WARNINGS AND PRECAUTIONS 5.1 Intraocular Pressure (IOP) Increase Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma. If this product is used for 10 days or longer, intraocular pressure should be monitored. 5.2 Cataracts Use of corticosteroids may result in posterior subcapsular cataract formation. 5.3 Delayed Healing The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification such as a slit lamp biomicroscopy and, where appropriate, fluorescein staining. 5.4 Bacterial Infections Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions of the eye, steroids may mask infection or enhance existing infection. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated. 5.5 Viral Infections Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). 5.6 Fungal Infections Fungal infections of the cornea are particularly prone to develop coincidentally with longterm local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Fungal cultures should be taken when appropriate. 5.7 Aminoglycoside Hypersensitivity Sensitivity to topically applied aminoglycosides may occur in some patients. If hypersensitivity develops with this product, discontinue use and institute appropriate therapy. ADVERSE REACTIONS Adverse reactions have occurred with steroid/anti-infective combination drugs which can be attributed to the steroid component, the anti-infective component, or the combination. Zylet: In a 42 day safety study comparing Zylet to placebo, ocular adverse reactions included injection (approximately 20%) and superficial punctate keratitis (approximately 15%). Increased intraocular pressure was reported in 10% (Zylet) and 4% (placebo) of subjects. Nine percent (9%) of Zylet subjects reported burning and stinging upon instillation. Ocular reactions reported with an incidence less than 4% include vision disorders, discharge, itching, lacrimation disorder, photophobia, corneal deposits, ocular discomfort, eyelid disorder, and other unspecified eye disorders. The incidence of non-ocular reactions reported in approximately 14% of subjects was headache; all other non-ocular reactions had an incidence of less than 5%. Loteprednol etabonate ophthalmic suspension 0.2% - 0.5%: Reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with infrequent optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, delayed wound healing and secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera. In a summation of controlled, randomized studies of individuals treated for 28 days or longer with loteprednol etabonate, the incidence of significant elevation of intraocular pressure (≥10 mm Hg) was 2% (15/901) among patients receiving loteprednol etabonate, 7% (11/164) among patients receiving 1% prednisolone acetate and 0.5% (3/583) among patients receiving placebo. Tobramycin ophthalmic solution 0.3%: The most frequent adverse reactions to topical tobramycin are hypersensitivity and localized ocular toxicity, including lid itching and swelling and conjunctival erythema. These reactions occur in less than 4% of patients. Similar reactions may occur with the topical use of other aminoglycoside antibiotics. Secondary Infection: The development of secondary infection has occurred after use of combinations containing steroids and antimicrobials. Fungal infections of the cornea are particularly prone to develop coincidentally with long-term applications of steroids. The possibility of fungal invasion must be considered in any persistent corneal ulceration where steroid treatment has been used. Secondary bacterial ocular infection following suppression of host responses also occurs. USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Teratogenic effects: Pregnancy Category C. Loteprednol etabonate has been shown to be embryotoxic (delayed ossification) and teratogenic (increased incidence of meningocele, abnormal left common carotid artery, and limb fixtures) when administered orally to rabbits during organogenesis at a dose of 3 mg/kg/day (35 times the maximum daily clinical dose), a dose which caused no maternal toxicity. The no-observed-effect-level (NOEL) for these effects was 0.5 mg/kg/day (6 times the maximum daily clinical dose). Oral treatment of rats during organogenesis resulted in teratogenicity (absent innominate artery at ≥5 mg/kg/day doses, and cleft palate and umbilical hernia at ≥50 mg/kg/day) and embryotoxicity (increased post-implantation losses at 100 mg/kg/day and decreased fetal body weight and skeletal ossification with ≥50 mg/kg/day). Treatment of rats at 0.5 mg/kg/day (6 times the maximum daily clinical dose) during organogenesis did not result in any reproductive toxicity. Loteprednol etabonate was maternally toxic (significantly reduced body weight gain during treatment) when administered to pregnant rats during organogenesis at doses of ≥5 mg/kg/day. Oral exposure of female rats to 50 mg/kg/day of loteprednol etabonate from the start of the fetal period through the end of lactation, a maternally toxic treatment regimen (significantly decreased body weight gain), gave rise to decreased growth and survival and retarded development in the offspring during lactation; the NOEL for these effects was 5 mg/kg/day. Loteprednol etabonate had no effect on the duration of gestation or parturition when administered orally to pregnant rats at doses up to 50 mg/kg/day during the fetal period. Reproductive studies have been performed in rats and rabbits with tobramycin at doses up to 100 mg/kg/day parenterally and have revealed no evidence of impaired fertility or harm to the fetus. There are no adequate and well controlled studies in pregnant women. Zylet should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 8.3 Nursing Mothers It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Systemic steroids that appear in human milk could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Caution should be exercised when Zylet is administered to a nursing woman. 8.4 Pediatric Use Two trials were conducted to evaluate the safety and efficacy of Zylet® (loteprednol etabonate and tobramycin ophthalmic suspension) in pediatric subjects age zero to six years; one was in subjects with lid inflammation and the other was in subjects with blepharoconjunctivitis. In the lid inflammation trial, Zylet with warm compresses did not demonstrate efficacy compared to vehicle with warm compresses. Patients received warm compress lid treatment plus Zylet or vehicle for 14 days. The majority of patients in both treatment groups showed reduced lid inflammation. In the blepharoconjunctivitis trial, Zylet did not demonstrate efficacy compared to vehicle, loteprednol etabonate ophthalmic suspension, or tobramycin ophthalmic solution. There was no difference between treatment groups in mean change from baseline blepharoconjunctivitis score at Day 15. There were no differences in safety assessments between the treatment groups in either trial. 8.5 Geriatric Use No overall differences in safety and effectiveness have been observed between elderly and younger patients. NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate or tobramycin. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma TK assay, a chromosome aberration test in human lymphocytes, or in an in vivo mouse micronucleus assay. Oral treatment of male and female rats at 50 mg/kg/day and 25 mg/kg/day of loteprednol etabonate, respectively, (500 and 250 times the maximum clinical dose, respectively) prior to and during mating did not impair fertility in either gender. No impairment of fertility was noted in studies of subcutaneous tobramycin in rats at 100 mg/kg/day (1700 times the maximum daily clinical dose). PATIENT COUNSELING INFORMATION This product is sterile when packaged. Patients should be advised not to allow the dropper tip to touch any surface, as this may contaminate the suspension. If pain develops, redness, itching or inflammation becomes aggravated, the patient should be advised to consult a physician. As with all ophthalmic preparations containing benzalkonium chloride, patients should be advised not to wear soft contact lenses when using Zylet. MANUFACTURER INFORMATION BAUSCH & LOMB INCORPORATED TAMPA, FLORIDA 33637 USA ©Bausch & Lomb Incorporated Zylet is a registered trademark of Bausch & Lomb Incorporated. Based on 9007705-9004405 Revised 08/2013 US/ZYL/15/0014 33 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) NEXT FRONTIER IN MANAGEMENT OF RETINA DISEASE CASE 2: 15-year-old boy 20/20 20/20 Macula is flat, foveal yellow spot (FIGURE 2) This 15-year-old boy presented no relevant past of family history. He did admit to staring with one eye and then with the other at a laser pointer, following which he experienced an acute decrease in vision. (Images courtesy of Anat Loewenstein, MD, MHA) SD-OCT ( Continued from page 30 ) low power but exposure was usually for a long duration. The light intensity is amplified by the cornea and the lens by a factor of 10,000. The pathophysiology includes both thermal and photochemical damage. While recovery is possible, permanent damage is a possibility.” The importance of SD-OCT is underscored in this case by the defects that were visible in the ellipsoidal zone as well as the strong correlation between the disruption of the inner photoreceptor junction and the worsened vision. L A S E R-I N DUC E D R ET I NOPAT H Y A second case (Figure 2) was that of a 15-yearold boy who experienced an acute decrease in vision in both eyes after staring at a laser pointer. The patient’s medical and ocular histories and that of his family were unremarkable. The macula was flat with a yellow spot in the fovea. Similar to the first case report, SD-OCT showed the contour of the fovea was normal with a stop in the photoreceptors continuity in the ellipsoid and interdigitation zones and the presence of a hyperreflective material emerging from the RPE toward the outer nuclear layer. SD-OCT follow-up of this patient showed the reabsorption of the hyperreflective material, abrupt discontinuation of the photoreceptor layer in the fovea, and preservation of the ELM. “The size of the outer macular hole in the right eye decreased between the examinations at 2 weeks and 2 months,” Dr. Loewenstein said. “Laser-induced retinopathy is caused by the coherent, monochromatic, unidirectional, minimally divergent laser beam,” she said. “The exposure to the light is short, about 0.25 second, as a result of the blink reflex. The light intensity is intensified by the cornea and lens by a factor of 10,000. The pathophysiology includes thermal damage primarily in the RPE, and photochemical and mechanical plasma formation damage.” The vast majority of patients (95%) with laser-induced retinopathy experience improvement; 32% have vision better than 20/40. In this case, SD-OCT showed defects in the ellipsoid zone, hyper-reflectivity at the retinal surface, and retinal or intraretinal hemorrhages and even neovascularization. HYDROXYCHLOROQUINE R ET I NOPAT H Y Another case was a 29-year-old woman who had been treated for 13 years with prednisone, azathioprine (Imuran, Aspen Australia), and hydroxychloroquine for systemic lupus erythemathosus. The patient presented with the complaint of a central visual defect. Examination showed a paracentral scotoma that developed between 2004 and 2013. This was the consequence of retinal toxicity resulting from hydroxychloroquine. “In this case, SD-OCT showed loss of the perifoveal and macular ellipsoid zones, thinning of the outer nuclear layer, and sparing OphthalmologyTimes.com Online Exclusive PLASMA KALLIKREIN INHIBITOR SHOWING PROMISE FOR DME RESULTS FROM a phase I study of KVD001 for the treatment of central involved diabetic macular edema show that this plasma kallikrein inhibitor was well tolerated, according to Jennifer Sun, MD. Go to OphthalmologyTimes.com/Kallikrein of the fovea with establishment of the ‘flying saucer’ sign,” Dr. Loewenstein said. “Hydroxychloroquine maculopathy is characterized by a bull’s eye appearance and a dense central scotoma,” she said. The drug was discontinued but the damage was permanent. Dr. Loewenstein summarized that SD-OCT has dramatically enhanced the ability to diagnose foveal disorders even during the stage when they are not visible using other technologies. ■ ANAT LOEWENSTEIN, MD, MHA E: [email protected] Dr. Loewenstein in a consultant to Allergan, Alcon Laboratories, Bayer Healthcare, Notal Vision, and Novartis. Michaela Goldstein, MD, and Dafna Goldenberg, MD, from Dr. Loewenstein’s department participated in the care of the patients under discussion. 34 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) NEXT FRONTIER IN MANAGEMENT OF RETINA DISEASE Considering patient body posture after macular hole surgery Advice on positioning recognizes ‘face-down’ is a matter of degree By Cheryl Guttman Krader; Reviewed by John S. Pollack, MD, and Ehab N. El Rayes, MD, PhD IT IS THE RESPONSIBILITY of surgeons to provide patients the opportunity for their best chance at success. With that in mind, retina surgeons should know that while macular hole surgery can be effective without face-down positioning, the highest success rates are achieved with some form of face-down positioning, said John S. Pollack, MD. “Patients can be counseled that face-down positioning does not require lying in the prone Dr. Pollack position, but only that the head be tilted forward so that the eyes are looking down, such as in a position used for reading or texting,” said Dr. Pollack, assistant professor of ophthalmology, Rush University Medical Center, Chicago. “Armed with all of this information, individuals can then decide for themselves whether face-down positioning is worth the effort.” CONDITIONS FOR SUCCESS Ehab N. El Rayes, MD, PhD, offered a somewhat different perspective on the issue of face-down positioning after macular hole surgery that is based on his review of outcomes data, knowledge about mechanisms of macular hole closure and healing, and the aim of obtaining patient consent for surgery and increasing postoperative comfort. Dr. El Rayes However, he still advises patients about postoperative positioning, telling them to avoid lying supine on their backs, but that it is okay to sit or sleep on their side. Dr. El Rayes said that vitrectomy with internal limiting membrane (ILM) peeling and 95% gas fill provides the conditions needed for success—these techniques increase retinal elasticity, keep the edges of the hole dry for at least 7 days without supine positioning, and trigger and support the process of retinal healing. Phacoemulsification is also performed to avoid cataractous changes and maintain optical clarity. “Then, surgeons speaking to elderly patients are more likely to encourage their acceptance surgery with face-down positioning (includof the macular hole procedure by saying: ‘For 1 ing supine or reading position) that met the week, you should stay sitting or sleep on your criteria of having at least 50 subjects and not side opposite to the side of your surgery, but being reported either as a poster or in an onnot on your back’ than to say: ‘You have to line-only journal. Across those eight studies, stay strictly in a face-down position,’” said Dr. the closure rate was consistently above 90%, El Rayes, professor of ophthalmoland it ranged from 97.4% to 100% ogy, retina department Institute of in four of the studies. Ophthalmology, Cairo, Egypt. Pooling data from these “credLooking at the world’s literature, ible” studies, Dr. Pollack said the Dr. El Rayes identified 21 articles average closure rate was 95% for Retina surgeons published in major peer-review jour- discuss the need for surgeries with face-down positionnals reporting on 867 eyes that un- face-down positioning ing and only 83% for no positioning. derwent macular hole surgery with- after macular out face-down positioning. The pri- hole surgery. The SURGERY R EFINED mary success rate ranged from 79% interpretation of what In the 25-plus years since macular to 98%, and was at least 90% for constitutes “facehole surgery was first performed, hole closure without a face-down down” is key to their the technique has been refined and position in 16 of the 21 reports that messages. its outcomes have improved thanks included a total of 763 eyes. to instrumentation, visualization, Taking a more critical look at the literature, and imaging, Dr. El Rayes noted. Dr. Pollack said that after excluding posters, Advances have also contributed to better unarticles appearing in online only journals, and derstanding of the mechanisms of macular hole studies with fewer than 50 subjects, only four closure that provides a foundation for understudies on macular hole surgery without face- standing why strict face-down positioning is down positioning remain. not necessary. Hole closure requires increasing However, the data are credible in only two retinal elasticity and eliminating all forms of of the four studies, and they represent the two surface traction, which is accomplished through studies that report the lowest closure rates, 81% posterior vitreous detachment and ILM peeling. and 87%, respectively. In addition, retinal detergence is necessary One of the two remaining studies reported and is created by injecting a gas bubble. Therea 96% closure rate. However, the authors also after, the tissue repair process begins, and acnote that 20% of patients used face-down po- cording to several published articles, healing can sitioning for at least 30 hours. happen within 1 to 2 days, Dr. El Rayes said. In the fourth study, which was designed “With intraoperative OCT we can see how as a retrospective review of 102 consecutive efficiently we removed epiretinal traction and cases, only 70% of the eyes were included in even begin to see the hole edges begin to flatthe final analysis, which raises concern about ten while the patient is still on the table,” he selection bias, Dr. Pollack said. said. “Postoperatively, OCT studies have shown He noted, “The best paper of the four was a retinal changes such as healing, flattening, reprospective multicenter trial that included ILM sorption of cystic fluid, and approximation of peeling with dye, gas selection based on hole the hole edges and closure within 1 to 2 days size, and randomized patients to face-down or after surgery.” no positioning. In that study, the closure rate In addition, measurements of postsurgical was 87% for the 72 eyes in the no positioning intraocular cytokines show they are at their group and 97.4% for the 78 eyes assigned to highest levels on day 1 after surgery, and that face-down positioning.” seems to correspond to hole closure and the Including the latter study, Dr. Pollack identi- reparative process, he said. fied eight papers on outcomes of macular hole Continues on page 35 : Macular hole take-home We’ll tell you how it works. Your patients can see it for themselves. | Without continuous microdosing | IMPORTANT SAFETY INFORMATION Indication ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg is indicated for the treatment of diabetic macular edema (DME) in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure. Contraindications • ILUVIEN is contraindicated in patients with active or suspected ocular or periocular infections including most viral disease of the cornea and conjunctiva including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections and fungal diseases. • ILUVIEN is contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8. • ILUVIEN is contraindicated in patients with known hypersensitivity to any components of this product. Warnings and Precautions • Intravitreal injections, including those with ILUVIEN, have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored following the intravitreal injection. • Use of corticosteroids including ILUVIEN may produce posterior subcapsular cataracts, increased intraocular pressure and glaucoma. Use of corticosteroids may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. Corticosteroids are not recommended to be used in patients with a history of ocular herpes simplex because of the potential for reactivation of the viral infection. • Patients in whom the posterior capsule of the lens is absent or has a tear are at risk of implant migration into the anterior chamber. Adverse Reactions • In controlled studies, the most common adverse reactions reported were cataract development (ILUVIEN 82%; sham 50%) and intraocular pressure elevation of ≥ 10 mm Hg (ILUVIEN 34%; sham 10%). Please see Brief Summary of full Prescribing Information on reverse side of following page. | With continuous microdosing | CONTINUOUS MICRODOSINGTM Delivery for Continuous Therapy in Patients With Diabetic Macular Edema (DME) ILUVIEN® has been implanted in over eyes worldwide.1 0.37 mm diameter 5,000 ILUVIEN is a CONTINUOUS MICRODOSINGTM Delivery System specifically engineered for the release of fluocinolone acetonide (FAc) for the treatment of DME in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure. In pivotal studies, ILUVIEN demonstrated a proven increase in visual acuity through 24 months (primary endpoint) and sustained up to 36 months.2-4 Engineered to deliver FAc for 36 months 3.5 mm length Adverse reactions in the ILUVIEN Phase 3 clinical trials were consistent with other corticosteroid treatments.2 Learn more at ILUVIEN.com. 1. Data on file. Alimera Sciences, Inc. 2. Iluvien [package insert]. Alpharetta, GA: Alimera Sciences, Inc; 2014. 3. Campochiaro PA, Brown DM, Pearson A, et al. Long-term benefit of sustained delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology. 2011;118(4):626-635.e2. 4. Campochiaro PA, Brown DM, Pearson A, et al. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012;119(10):2125-2132. Please see Brief Summary of full Prescribing Information on the following page. CONTINUOUS MICRODOSING is a trademark of Alimera Sciences, Inc. ILUVIEN is a registered trademark of Alimera Sciences, Inc. Copyright © 2016 Alimera Sciences, Inc. All rights reserved. 1-844-445-8843. Printed in USA. US-ILV-MMM-0312. 6/16 BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION Table 1 (continued) ® ILUVIEN (fluocinolone acetonide intravitreal implant) 0.19 mg For Intravitreal Injection Adverse Reactions INDICATIONS AND USAGE ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg is indicated for the treatment of diabetic macular edema in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure. CONTRAINDICATIONS Ocular or Periocular Infections: ILUVIEN is contraindicated in patients with active or suspected ocular or periocular infections including most viral disease of the cornea and conjunctiva including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections and fungal diseases. Glaucoma: ILUVIEN is contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8. Hypersensitivity: ILUVIEN is contraindicated in patients with known hypersensitivity to any components of this product. WARNINGS AND PRECAUTIONS Intravitreal Injection-related Effects: Intravitreal injections, including those with ILUVIEN, have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored following the intravitreal injection. Steroid-related Effects: Use of corticosteroids including ILUVIEN may produce posterior subcapsular cataracts, increased intraocular pressure and glaucoma. Use of corticosteroids may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. Corticosteroids are not recommended to be used in patients with a history of ocular herpes simplex because of the potential for reactivation of the viral infection. Risk of Implant Migration: Patients in whom the posterior capsule of the lens is absent or has a tear are at risk of implant migration into the anterior chamber. ILUVIEN (N=375) n (%) Sham (N=185) n (%) Non-ocular Anemia 40 (11%) 10 (5%) Headache 33 (9%) 11 (6%) Renal failure 32 (9%) 10 (5%) Pneumonia 28 (7%) 8 (4%) 1 Includes cataract, cataract nuclear, cataract subcapsular, cataract cortical and cataract diabetic in patients who were phakic at baseline. Among these patients, 80% of ILUVIEN subjects vs. 27% of sham-controlled subjects underwent cataract surgery. 2 235 of the 375 ILUVIEN subjects were phakic at baseline; 121 of 185 sham-controlled subjects were phakic at baseline. Increased Intraocular Pressure Table 2: Summary of Elevated IOP-Related Adverse Reactions Event ILUVIEN (N=375) Sham (N=185) n (%) n (%) Non-ocular IOP elevation ≥ 10 mm Hg from baseline 127 (34%) 18 (10%) IOP elevation ≥ 30 mm Hg 75 (20%) 8 (4%) Any IOP-lowering medication 144 (38%) 26 (14%) Any surgical intervention for elevated intraocular pressure 18 (5%) 1 (1%) Figure 1: Mean IOP during the study ADVERSE REACTIONS Clinical Studies Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions associated with ophthalmic steroids including ILUVIEN include cataract formation and subsequent cataract surgery, elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera. ILUVIEN was studied in two multicenter, randomized, sham-controlled, masked trials in which patients with diabetic macular edema were treated with either ILUVIEN (n=375) or sham (n=185). Table 1 summarizes safety data available when the last subject completed the last 36-month follow up visit for the two primary ILUVIEN trials. In these trials, subjects were eligible for retreatment no earlier than 12 months after study entry. Over the three-year follow up period, approximately 75% of the ILUVIEN treated subjects received only one ILUVIEN implant. Table 1: Ocular Adverse Reactions Reported by ≥1% of Patients and Non-ocular Adverse Reactions Reported by ≥5% of Patients Cataract1 192/2352 (82%) Myodesopsia 80 (21%) 17 (9%) Eye pain 57 (15%) 25 (14%) Conjunctival haemorrhage 50 (13%) 21 (11%) Posterior capsule opacification 35 (9%) 6 (3%) Eye irritation 30 (8%) 11 (6%) Vitreous detachment 26 (7%) 12 (7%) Cataracts and Cataract Surgery At baseline, 235 of the 375 ILUVIEN subjects were phakic; 121 of 185 sham-controlled subjects were phakic. The incidence of cataract development in patients who had a phakic study eye was higher in the ILUVIEN group (82%) compared with sham (50%). The median time of cataract being reported as an adverse event was approximately 12 months in the ILUVIEN group and 19 months in the sham group. Among these patients, 80% of ILUVIEN subjects vs. 27% of sham-controlled subjects underwent cataract surgery, generally within the first 18 months (Median Month 15 for both ILUVIEN group and for sham) of the studies. Postmarketing Experience: The following reactions have been identified during post-marketing use of ILUVIEN in clinical practice. Because they are reported voluntarily, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to ILUVIEN, or a combination of these factors, include reports of drug administration error and reports of the drug being ineffective. Conjunctivitis 14 (4%) 5 (3%) USE IN SPECIFIC POPULATIONS Corneal oedema 13 (4%) 3 (2%) Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies of ILUVIEN in pregnant women. Animal reproduction studies have not been conducted with fluocinolone acetonide. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. ILUVIEN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers: Systemically administered corticosteroids are present in human milk and could suppress growth and interfere with endogenous corticosteroid production. The systemic concentration of fluocinolone acetonide following intravitreal treatment with ILUVIEN is low. It is not known whether intravitreal treatment with ILUVIEN could result in sufficient systemic absorption to produce detectable quantities in human milk. Exercise caution when ILUVIEN is administered to a nursing woman. Pediatric Use: Safety and effectiveness of ILUVIEN in pediatric patients have not been established. Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients. Adverse Reactions ILUVIEN (N=375) n (%) Sham (N=185) n (%) Ocular 61/1212 (50%) Foreign body sensation in eyes 12 (3%) 4 (2%) Eye pruritus 10 (3%) 3 (2%) Ocular hyperaemia 10 (3%) 3 (2%) Optic atrophy 9 (2%) 2 (1%) Ocular discomfort 8 (2%) 1 (1%) Photophobia 7 (2%) 2 (1%) Retinal exudates 7 (2%) 0 (0%) Anterior chamber cell 6 (2%) 1 (1%) Eye discharge 6 (2%) 1 (1%) Manufactured for: Alimera Sciences, Inc. • 6120 Windward Parkway Alpharetta, GA 30005 • Patented. • See: www.alimerasciences.com All Rights Reserved; Issue Date December 2014; ILUVIEN is a registered trademark of Alimera Sciences, Inc. Copyright © 2016 Alimera Sciences, Inc. All rights reserved. 1-844-445-8843. Printed in USA. US-ILV-MMM-0312. 6/16 35 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) NEXT FRONTIER IN MANAGEMENT OF RETINA DISEASE Innovations bringing benefits of 27-gauge vitrectomy to more eyes Vitrectomy surgery with equipment, technology improving for greater efficiency, functionality By Cheryl Guttman Krader; Reviewed by Yusuke Oshima, MD, PhD TAK T SUK I, JAPAN :: CONTINUED ADVANCES in vitrectomy machines and instrumentation have led to progressive improvements in the efficiency of 27-gauge vitrectomy and made ultra-smallgauge surgery suitable for the full spectrum of vitreoretinal pathologies, said Yusuke Oshima, MD, PhD. Use of a three-dimensional heads-up surgery platform (Tr ueVision 3D Surgical, TrueVision) that minimizes phototoxicity risk provides yet Dr. Oshima another novel benefit and represents the next step toward achieving ultraminimally invasive vitrectomy surgery, added Dr. Oshima, founder and director, Oshima Eye Clinic, Taktsuki, Japan. “In 2010, we [reported] our initial experience with 27-gauge vitrectomy that showed very favorable results in a set of selected cases comprised mainly of eyes with macular disease and simple vitreous hemorrhage,” he said. Five years later, the introduction of an ultrahigh-speed cutter (Dutch Ophthalmic Research Center International BV) that exerts less tractional force allowed expansion of 27-gauge vitrectomy to a broader range of eyes, including those with challenging tractional detachments. Most recently, a 27-gauge, twin-duty cycle MACULAR HOLE ( Continued from page 34 ) Citing a theory on mechanisms of surgical repair of macular hole developed by Mark Blumenkranz, MD, Dr. El Rayes said that removal of vitreous releases traction and allows apposition of a foreign non-porous surface (i.e., gas bubble or silicone) to the edges of the macular hole. Membrane peeling or ILM removal stimulates an intrinsic retinal wound healing response through gene activation, and these events in concert stimulate the migration of cutter with a double-port (TDC cutter, Dutch Ophthalmic Research Center International BV) has been developed to provide a very high duty cycle regardless of the cutting rate and provides even better cutting efficiency than a conventional 25-gauge cutter, he noted. “Now, we are using the 3-D heads-up surgery system that provides a sufficiently bright and clear fundus view on the display monitor with only 10% to 20% of the illumination power that is used for viewing through the surgical microscope,” he said. The standardized 27-gauge vitrectomy procedures are performed with chandelier endoillumination and wide-angle viewing systems. The small port of the 27-gauge vitreous cutter with its position near to the top of the tip enables direct dissection of fibrotic neovascular membranes because it is easy to insert into the small space between the membrane and retina. Using a bimanual technique for membrane dissection in which the membrane is lifted with a forceps in one hand, the 27-gauge cutter is used to sever the anchoring point before cutting the membrane en bloc. “The ease of insertion of the 27-gauge cutter under the membrane makes it easier to cut the anchor point first without causing bleeding,” Dr. Oshima said. He added he likes to peel the internal limiting Mueller cells and associated retinal neurons that fill in the defect. Intrinsic photoreceptor paracrine and autocrine stimuli result in photoreceptor realignment and synapse repair, resulting in restoration of normal or near normal macular anatomy and function. After complete fluid/gas exchange, the gas bubble serves to isolate the retina from vitreous fluid for the 5 to 7 days that it takes for macular scab contraction to occur. Dr. El Rayes explained that based on the Pascal principle of transmission of fluid pressure, the gas bubble transmits pressure equally in all directions and creates the necessary conditions to keep the hole edges dry. 27-GAUGE DIABETIC VITRECTOMY VIDEO Watch 27-gauge diabetic vitrectomy for fibrovascular membrane dissection. (Video courtesy of Yusuke Oshima, MD, PhD) Go to OphthalmologyTimes.com/27Gauge membrane in eyes with diabetic tractional detachment because that step eliminates any scaffold for postoperative membrane proliferation. After laser photocoagulation, the 27-gauge procedure is easily concluded by simply removing the trocar cannula and the optical fiber. ■ YUSUKE OSHIMA, MD, PHD E: [email protected] This article was adapted from Dr. Oshima’s presentation during Retina Subspecialty Day at the 2015 meeting of the American Academy of Ophthalmology. Dr. Oshima receives lecture fees from Alcon Laboratories and is a consultant to Synergetics. “The idea of first week face-down positioning is inconsistent with this principle,” Dr. El Rayes said. “The gases used have a long enough half-life to isolate the macula from the vitreous in all positions except face-up supine.” ■ JOHN S. POLLACK, MD E: [email protected] EHAB N. EL RAYES, MD, PHD E: [email protected] This article was adapted from presentations by Dr. Pollack and Dr. El Rayes during Retina Subspecialty Day at the 2015 meeting of the American Academy of Ophthalmology. Dr. Pollack and Dr. El Rayes have no relevant financial interests to disclose. 36 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) NEXT FRONTIER IN MANAGEMENT OF RETINA DISEASE Managing silicone oil complications in anterior, posterior segments Many events can be avoided with attention to technique or successfully treated if they occur By Cheryl Guttman Krader; Reviewed by Derek Kunimoto, MD, JD PAR ADISE VAL L E Y, A Z:: USE OF SILICONE OIL (SO) for retinal tamponade can result in a range of complications. Fortunately, most of these events can be avoided with careful attention to surgical technique or successfully treated if they occur, while those without any known preventive strategies are very rare, said Derek Kunimoto, MD, JD. Treatment of silicone oil in the anterior chamber is performed by creating a paracentesis through which the oil can drain passively. “As long as there is posterior infusion, the oil will follow itself out of the small opening in the cornea,” Dr. Kunimoto said. POSTERIOR SEGMENT COMPLICATIONS ANTERIOR SEGMENT Although oil is supposed to be present in the COMPLICATIONS vitreous cavity, its presence does decrease aqueUsage of SO in the subconjunctival space pres- ous volume that can pose a problem in patients ents a cosmetic issue and can lead to granuloma who are receiving ongoing intravitreal injecformation; avoiding it requires tions. Surgeons can either remove the SO or, good scleral closure with the according to anecdotal reports, compensate use of small-gauge vitrectomy, for the change by adjusting the dosage of the said Dr. Kunimoto, managing intravitreal injection. partner, Retinal Consultants of Oil in the vitreous can also migrate into the Arizona, and director, Scotts- subhyaloid space. This complication, which ocdale Eye Surgery Center, Scott- curs more commonly in pediatric cases, will Dr. Kunimoto sdale, AZ. prevent complete oil fill and leave vitreoretinal “SO in the subconjunctival space is becom- tractional forces in place that can predispose ing more common because of the use of small- to recurrent retinal detachment. gauge vitrectomy, but it can be avoided with “Ensuring creation of a complete posterior a good mattress suture and good apposition,” vitreous detachment during surgery will avoid Dr. Kunimoto said. SO getting into the subhyaloid space,” Dr. KunThe options for managing oil in the subcon- imoto said. Another posterior segment comjunctival space include observation plication is SO emulsification in a if the cosmetic appearance is acthin layer over the retina. Treatment ceptable to the patient and watching of that situation requires silicone for granuloma formation or surgioil exchange or removal. cal intervention by performing a Complications “SO droplets can also become simple conjunctival cutdown. of silicone oil occur embedded within the layers of the “As long as the cutdown is in when it is inadvertently retina, and there is no known way the correct plane, the SO will come placed in anatomic to avoid these intraretinal deposout nicely,” he said. areas other than the its,” Dr. Kunimoto said. SO can also be present in the an- vitreous cavity. Derek The oil can also penetrate or be terior chamber, which can lead to Kunimoto, MD, JD, inadvertently placed into the subsecondary open-angle glaucoma, discusses methods retinal space where it will interfere inaccurate IOP measurements, and for managing and with retinal detachment repair. SO in severe cases, corneal decompen- avoiding these issues. in the subretinal space raises posation. Keeping the zonules intact during vitrectomy will prevent SO from getting tential concern about retinal pigment epitheinto the anterior chamber. In the setting of an lium (RPE) or retina toxicity. Chronic presence aphakic eye, placement of an anterior cham- of oil in the subretinal space can also lead to ber IOL or anterior chamber maintaining su- retinal atrophy and large retinal cysts, and silitures is advised to provide a physical barrier cone oil can emulsify in the subretinal space. “To avoid getting SO in the subretinal space, against anterior migration. take-home SILICONE OIL REMOVAL VIDEO Derek Kunimoto, MD, JD, shows the proper removal of silicone oil from the anterior chamber using small-gauge vitrectomy. (Video courtesy of Derek Kunimoto, MD, JD) Go to OphthalmologyTimes.com/SiliconeOil surgeons should visually confirm that the cannula tip is not in the subretinal space,” Dr. Kunimoto said. In addition, surgeons should be cautious about using SO in eyes with large retinal tears, retinectomy greater than 3 clock hours, as well as in those with retinal detachments associated with optic nerve pits or macular holes, he said. The oil can also be present in the sub-RPE or choroidal space that will cause a choroidal detachment, preventing retinal detachment repair. Potentially, silicone oil in the sub-RPE or choroidal space might also be toxic to the RPE or compromise choroidal vasculature. Proper cannula selection and positioning is the solution for avoiding these complications. “Do not use a short cannula and make sure the cannula tip is not in the choroidal space,” Dr. Kunimoto said. The approach to management of oil in the sub-RPE or choroidal space is similar to the treatment of choroidal hemorrhage or effusion. Surgeons should create a cutdown in the sclera with vitreous cavity infusion and then slightly gape open the sclerotomy to allow passive drainage of the oil. Increasing the infusion pressure will facilitate the passive egress of SO. The choroidal detachment will then flatten, enabling repair of the retinal detachment. Continues on page 37 : Silicone oil tips 37 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) NEXT FRONTIER IN MANAGEMENT OF RETINA DISEASE Anti-VEGF in high-risk populace drives regression of diabetic retinopathy Patients who benefited most from ranibizumab had highest risk of proliferative progression By Lynda Charters; Reviewed by Charles C. Wykoff, MD HOUS TON :: INVESTIGATORS IN a follow-up RISE/ Ranibizumab also was found to significantly RIDE analysis of patients who had the high- (p < 0.05) decrease worsening of retinal non-perest risk of progression to proliferative dia- fusion compared with sham treatment (Campobetic retinopathy (PDR) saw “robust” regres- chiaro et al. Ophthalmology. 2014;121:1783-1789). sion of diabetic retinopathy (DR) in high percentages of patients treated with ranibizumab R ANIBIZUMAB EFFECT (Lucentis, Genentech) independent of baseline Investigators analyzed patients at high risk of characteristics. PDR progression—i.e., those who had moderWith the incidence rate of ately severe or severe NPDR/ETDRS DR seDR expected to nearly double verity, or levels 47/53 at baseline—and evalufrom 2010 to 2050, identification ated the effect of baseline characteristics and of effective treatments is para- macular non-perfusion on patient outcomes. mount, according to Charles C. To assess DR, several stereoscopic seven-field Wykoff, MD, who is in private color fundus photographs were obtained and Dr. Wykoff practice in Houston. evaluated. To assess macular non-perfusion, The Early Treatment Diabetic Retinopathy fluorescein angiograms were obtained at the Study (ETDRS) Diabetic Retinopathy Severity same time points and analyzed by masked Scale and other studies have demongraders to measure the area of strated decreases in patients’ healththe macular non-perfusion. related quality of life when the DR The levels of DR at baseline severity worsens beyond the 43 level, were similar in the three treatwhich is then moderate non-proliferment groups—i.e., sham, 0.3-, and About 75% of ative diabetic retinopathy (NPDR). 0.5-mg ranibizumab. The most patients in the RIDE/ “It is at this level that difficulty in RISE trials who had ranibizumab benefits were in padriving begins to increase,” he said. the highest risk tients with moderately severe or Patients with DR and diabetic mac- of progression to severe NPDR at baseline, he noted. ular edema were randomly assigned proliferative diabetic “Importantly, 75% of patients sham injections or treatment with retinopathy benefited treated with ranibizumab who 0.3- or 0.5-mg doses of ranibizumab. from ranibizumab with had a DR level of 47/53 at baseTime to PDR was significantly de- “robust” regression of line had a two-step or greater imlayed in the ranibizumab group. provement in DR compared with DR severity levels. Both ranibizumab doses signifisham treatment by month 12,” cantly (p < 0.001) improved DR levels based Dr. Wykoff said. on the pooled RIDE/RISE data (Ip et al. OphPatients in the sham group with moderately thalmology. 2015;122:367-374). severe and severe NPDR at baseline were six take-home SILICONE OIL TIPS ( Continued from page 36 ) SO can also emulsify in the vitreous cavity, though the risk is lower with use of higher centistoke oil (5000 versus 1000). Management requires vitrectomy or SO exchange. Migration of SO into the optic nerve, optic chiasm, and cerebral ventricles as well as unexplained central vision loss with a decrease of visual acuity to the 20/200 level are other complications that can occur with SO tamponade that have no known avoidance strategy. Surgeons should be aware the risk for SO times more likely to progress to PDR through 24 months, he said. Baseline characteristics such as central foveal thickness (CFT), best-corrected visual acuity (BCVA), and duration of diabetes were not predictive of two-step or greater improvements in patients with a DR severity level of 47/53. Investigators also found no predictive value of subscale levels within DR severity levels 47 and 53 in predicting a two-step or greater improvement in DR severity at month 24 for patients with the highest-risk NPDR at baseline. M ACUL A R NON-PER FUSION Data indicated that macular non-perfusion at baseline did not affect the two-step or greater improvements in DR that occurred as the result of treatment with ranibizumab in patients with a baseline DR level of 47/53. The proportions of patients with macular non-perfusion increased in the sham group and remained stable in the ranibizumab groups. In conclusion, ranibizumab led to robust improvements in DR severity scores in patients with the highest risk of progression to PDR. “Such disease-modifying effects of ranibizumab indicate a substantial role in DR management beyond simple mitigation of diabetic macular edema,” Dr. Wykoff said. ■ CHARLES C. WYKOFF, MD E: [email protected] This article was adapted from Dr. Wykoff’s presentation at the 2016 meeting of the Association for Research in Vision and Ophthalmology. Dr. Wykoff is a consultant to Genentech. migration into the central nervous system is increased when optic nerve pits are present. ■ DEREK KUNIMOTO, MD, JD E: [email protected] This article was adapted from Dr. Kunimoto’s presentation during Retina Subspecialty Day at the 2015 meeting of the American Academy of Ophthalmology. Dr. Kunimoto is a consultant to Allergan, Bausch+ Lomb, DORC, Genentech, and Synergetics. it’s time for some What’s eyelove? Eyelove is all about taking care of eyes— especially now. Eyes need more love than ever, because they’ve never been asked to do so much. That’s why Shire has entered the world of eye care. Shire is committed to educating patients about Dry Eye Disease—so let’s start with some eyelove. Feel the love at sharesomeeyelove.com 40 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) NEXT FRONTIER IN MANAGEMENT OF RETINA DISEASE CATT follow-up explores long-term outcomes with anti-VEGF in AMD Mean visual acuity at 5 years points to unmet need; still, 50% of eyes were 20/40 or better By Lynda Charters; Reviewed by Maureen Maguire, PhD PHIL ADEL PHIA :: THE COMPARISON OF Age-related angiography, the images Macular Degeneration Treatments Trials (CATT) showed that the mean follow-up study found that the gains in visual size of the lesions was acuity achieved at the end of the 2-year CATT 12.9 mm 2, which was a study, a clinical trial of the anti-vascular en- mean of 4.8 mm 2 larger dothelial growth factor (VEGF) drugs ranibi- than that at the 2-year visit. zumab (Lucentis, Genentech) and bevacizumab The investigators observed (Avastin, Genentech), were not sustained 3 geographic atrophy in 41% years later. of the eyes that could be In the CATT clinical trial, patients were ran- graded and it was subfodomly assigned to either ranibizumab or beva- veal in 17% of those eyes. cizumab and followed for 2 years after assignSpectral-domain optical ment to one of three dosing regimens. coherence tomography imIn this study, 3 years after the end of the ages were available for 555 CATT clinical trial, the investigators, led by eyes. Among them, fluid Maureen Maguire, PhD, from the Department was seen in 83%, specifiof Ophthalmology, University of Pennsylvania, cally, intraretinal in 61%, Philadelphia, and Daniel Martin, MD, from the subretinal in 38%, and subCole Eye Institute, Cleveland Clinic Founda- retinal pigment epithelial in 36%. The mean tion, Cleveland, evaluated 647 patients who foveal thickness was 278 μm, which was lower were recalled from the original CATT clinical by 182 μm from the baseline value and 20 μm trial cohort to determine how the visual acuity below that from the 2-year evaluation, they relevels and anatomic outcomes survived over ported. The retina was less than 120 μm thick time in the CATT follow-up study. in 36% of eyes. The CATT Research Group found Interestingly, the patients who that in these patients, who had an had been randomly assigned to raaverage follow-up of 5.5 years, half nibizumab for 2 years had a greater of the eyes had a visual acuity of decrease in visual acuity, i.e., -4 The Comparison of 20/40 or better, 20% had a visual Age-related Macular letters, compared with those who acuity of 20/200 or worse, and al- Degeneration Treatment had been assigned to bevacizumab. most 10% had 20/20. The authors Trial (CATT) follow-up This difference reached significance reported their findings in Ophthal- study found that the (p = 0.008). The investigators did mology (Maguire et al. Ophthalmol- initial gains in visual not find significant differences in ogy 2016;123:1751-1761). visual acuity or morphologic outacuity achieved with They reported “the mean change two anti-vascular comes between the groups. in visual acuity was -3 letters from endothelial growth Dr. Maguire pointed out that in baseline and -11 letters from 2 factor drugs were lower the CATT Follow-up Study there years.” were multiple processes that caused than those achieved at These patients underwent ex- the end of the 2-year the visual acuity decreases, but they aminations for age-related macu- CATT study. seemed to be associated with an lar degeneration (AMD) a mean increase in the numbers of patients of 25.3 times after the end of the CATT study with abnormally thin retinas, that is, less than and received a mean of 15.4 treatments. Re- 120 μm; a greater prevalence of geographic atgarding the treatments, more than half of the rophy, and an increase in the size of the lesions. patients (60%) were treated with a drug other The investigators noted, “The CATT Followthan the one to which they had been assigned up Study results provided the most complete in the CATT study, according to Dr. Maguire. follow-up reported to date on the long-term outAmong 467 eyes that underwent fluorescein comes for the treatment of neovascular AMD The investigators noted, ‘The CATT Follow-up Study results provided the most complete follow-up reported to date on the long-term outcomes for the treatment of neovascular AMD with anti-VEGF drugs.’ take-home with anti-VEGF drugs. …Because very few patients continued to receive the originally assigned drug or dosing schedule between the end of year 2 and the follow-up of approximately 5 years, the CATT Follow-up Study results provide information primarily on overall treatment outcomes with anti-VEGF drugs and limited information on effects of different drugs and dosing regimens. The mean visual acuity at 5 years was 3 letters worse than baseline, highlighting an unmet need for further therapeutic advances.” They also considered that with 50% of the patients having 20/40 or better visual acuity and 10% having 20/20, these results are a great step forward and would not have been possible before the anti-VEGF drugs were developed. ■ MAUREEN MAGUIRE, PHD E: [email protected] Dr. Maguire has received financial support from Roche/Genentech for service on a Data Safety and Monitoring Committee for Genentech. DANIEL MARTIN, MD E: [email protected] Dr. Martin has no financial interest in this subject matter. This article was adapted from a presentation by Dr. Maguire and Dr. Martin at the 2016 meeting of the Association for Research in Vision and Ophthalmology. 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EPIC Refraction System AAO 2326 Designed and Manufactured by NIDEK - Represented by Marco 800-874-5274 % marco.com 42 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) NEXT FRONTIER IN MANAGEMENT OF RETINA DISEASE Protocol T: Anti-VEGF DME therapies maintain impressive results at 2 years Vision gains from baseline seen in all 3 groups with fewer injections, decreased visits, less laser By Laird Harrison Building the Ophthalmic Tech’s Community of Practice modernmedicine.com/iTech Resource Center for Technician Education WEB EXCLUSIVE CONTENT Related Articles Continuing Education Clinical Tools & Tips iTech provides educational presentations and information for ophthalmic and optometric technicians, helping them work effectively with their doctors to enhance the practice. 1 AND SUPPLEM ENT TO Y , EVER Y DAY , EVER ery practice CLEAN ntial for ev G ITprogram is esse KEEioPnIN control Infect TIME is hygiene Hand important just as rument as inst tion steriliza comes it when solid ing a to hav n control infectio m. gra pro ros ent only elem said be the m, uld not progra ents sho ction control Instrum infe ctice’s , CRNO. Health of a pra RN, MN ty and Lamb, ters for al Safe Cen Patricia tion upa versal and the The Occ lined uni (OSHA) tration have out ction (CDC) Adminis s for infe every Control caution Disease nt for dard pre are importa day, se and stan e, every , and the every practic of the control in sident mber, past pre Registered team me who is the ic alm b, cialist. hth said Lam Society of Op ical nurse spe er an a clin in and Americ ) ne ord od, (ASORN s into medici cly to blo Nurses ted infe y goe tions app ons -associa , to practice “Nobod d precau , and excreti lthcare less cous standar ons vent hea b. “Neverthe prevent These secreti to pre , and mu to y fluids, ct skin said Lam st be able all bod noninta tions,” A or ctions.” you mu causweat, infe ne, s, OSH ments ion sal pre except medici ployee ociated detach A univer an ential of em ranes. eous the opt es, are-ass or vitr surgery is memb h a pot cas tection healthc ing to the OSH certain hum wit pro s some lmic posteri ur, be nd in For the all employee to be When breaks occ fluids Accord an blood and Ophtha age—a body known er by s that retinal the dam lost vision. some of all hum treated as if od and , paid and oth air dictate tions, to blo virus, cination to rep even restore be aware of are osure atitis B fluids is B vac for exp it may ans should body HIV, hep . hepatit for the uire nici and us s tech offered yer. yees req cedure infectio ne pathogens t plo the pro rations tha h emplo bor limited the em ition, all suc bloodbut not conside lmologists rd ens, g uding In add standa the concept of pathog ophtha n choosin l g, incl borne ed versal to trainin s. surgica face whe annual owing: bloodFrom uni CDC expand changed theed ir etinal onomic vitreor ches for the foll and erg n control 6, the s” and lain to the ence, In 199 s,” exp caution approa ines lace viol Lamb, infectio that cause sal pre ts. caution guidel workp nts patien to rd pre “univer caution of eve uce ording “standa in pre red d to Acc cha to ed the term standar Page 3 follow break and n. These IONS on uld be borne aims to infectio Lamb. ECT sho odof INF all blo CDC ead See to n of the spr applied ir from the transmissio of must be the risk of and the less ens , regard status. pathog n other ng care ts receivi sumed infectio patien sis or pre diagno 2012 | Winter issue 04 e 01 | volum Mesza By Liz E: ocedures INSIDetina l pr to treat es ks approach Surgicalments and brea detach Vitreor PAGE 11 Brought to you by TWO-YEAR RESULTS from a comparative effectiveness trial may help clinicians faced with the difficult choice among the three anti-vascular endothelial growth factor (VEGF) drugs approved for diabetic macular edema (DME). Among eyes with worse baseline visual acuity, aflibercept (Eylea, Regeneron) had superior 2-year visual acuity outcomes compared with bevacizumab (Avastin, Genentech), but superiority of aflibercept over ranibizumab (Lucentis, Genentech), noted at 1 year, was no longer identified, researchers said. “Vision gains from baseline at 2 years were seen in all three groups with about half the number of injections, slightly decreased frequency of visits, and decreased amounts of laser in the second year,” said John A. Wells, MD, Palmetto Retina Center, Columbia, SC. Dr. Wells and colleagues from the Diabetic Retinopathy Clinical Research Network (DRCR.net) published findings from the Protocol T trial in Ophthalmology (http://bit.ly/2csX6yu). ABOUT THE RESEARCH The DRCR.net investigators enrolled 660 people with DME at 88 sites across the United States. At baseline, the patients had a mean age of 61 years and had type 1 or type 2 diabetes for a mean of 17 years. The investigators restricted the trial to people with a visual acuity of 20/32 or worse. At enrollment, about half of the participants had 20/32 to 20/40 vision, and the other half had 20/50 or worse vision. The researchers randomly divided the participants into thirds. One group received 2.0 mg/0.05 mL of aflibercept, one received 1.25 mg/0.05 mL of bevacizumab, and one received 0.3 mg/0.05 mL of ranibizumab. Clinicians evaluated participants every 4 weeks during the first year and every 4 to 16 weeks during the second year, depending on treatment course. At each visit, they assessed the study eyes for re-treatment with the anti-VEGF agent based on visual and ‘Vision gains from baseline at 2 years were seen in all three groups with about half the number of injections.’ — John A. Wells, MD Separately, all three drugs have shown impressive results in restoring or protecting vision in patients with DME, but their prices are very different. Based on Medicare allowable charges, the drugs at the doses used in this study cost about $1,960 for aflibercept, $1,200 for ranibizumab, and about $70 for bevacizumab per injection, according to the National Eye Institute. optical coherence tomography (OCT) criteria. They administered intravitreal injections of the study drugs until the DME resolved or stabilized. Additionally, they administered focal/grid laser photocoagulation treatment if DME persisted without continual improvement after 6 months of injections. Participants did not know which Continues on page 45 : Visual acuity The ® PROLENSA Effect POWERED FOR PENETRATION Advanced Formulation to Facilitate Corneal Penetration1-3 PROLENSA® delivers potency and corneal penetration with QD dosing at a low concentration1-3 INDICATIONS AND USAGE PROLENSA® (bromfenac ophthalmic solution) 0.07% is a nonsteroidal anti-infl ammatory drug (NSAID) indicated for the treatment of postoperative infl ammation and reduction of ocular pain in patients who have undergone cataract surgery. IMPORTANT SAFETY INFORMATION ABOUT PROLENSA® 9PROLENSA® contains sodium sulfite, a sulfite that may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people. 9All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including bromfenac, may slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. 9There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs, including bromfenac. Use with caution in patients who have previously exhibited sensitivities to these drugs. 9There have been reports that ocularly applied NSAIDs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery. Use with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time. PROLENSA is a registered trademark of Bausch & Lomb Incorporated or its affiliates. © Bausch & Lomb Incorporated. All rights reserved. Printed in USA. PRA.0188.USA.15 9Use of topical NSAIDs may result in keratitis. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs, including bromfenac, and should be closely monitored for corneal health. Patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Post-marketing experience with topical NSAIDs suggests that use more than 24 hours prior to surgery or use beyond 14 days post-surgery may increase patient risk for the occurrence and severity of corneal adverse events. 9PROLENSA® should not be instilled while wearing contact lenses. The preservative in PROLENSA®, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of PROLENSA®. 9The most commonly reported adverse reactions in 3%-8% of patients were anterior chamber inflammation, foreign body sensation, eye pain, photophobia, and blurred vision. Please see brief summary of full Prescribing Information for PROLENSA® on adjacent page. References: 1. PROLENSA Prescribing Information, April 2013. 2. Data on file, Bausch & Lomb Incorporated. 3. Baklayan GA, Patterson HM, Song CK, Gow JA, McNamara TR. 24-hour evaluation of the ocular distribution of (14)C-labeled bromfenac following topical instillation into the eyes of New Zealand white rabbits. J Ocul Pharmacol Ther. 2008;24(4):392-398. PROLENSA® (bromfenac ophthalmic solution) 0.07% Brief Summary INDICATIONS AND USAGE PROLENSA® (bromfenac ophthalmic solution) 0.07% is indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery. PROLENSA® ophthalmic solution following cataract surgery include: anterior chamber inflammation, foreign body sensation, eye pain, photophobia and vision blurred. These reactions were reported in 3 to 8% of patients. USE IN SPECIFIC POPULATIONS Pregnancy Treatment of rats at oral doses up to 0.9 mg/kg/day (systemic exposure 90 times the systemic exposure predicted from the recommended human ophthalmic dose [RHOD] assuming the human systemic concentration is at the limit of quantification) and rabbits at oral doses up to 7.5 mg/kg/day (150 times the predicted human systemic exposure) produced no treatment-related malformations in reproduction studies. However, embryo-fetal lethality and maternal toxicity were produced in rats and rabbits at 0.9 mg/kg/day and 7.5 mg/kg/day, respectively. In rats, bromfenac treatment caused delayed parturition at 0.3 mg/kg/day (30 times the predicted human CONTRAINDICATIONS exposure), and caused dystocia, increased neonatal mortality and None reduced postnatal growth at 0.9 mg/kg/day. WARNINGS AND PRECAUTIONS There are no adequate and well-controlled studies in pregnant women. Sulfite Allergic Reactions Because animal reproduction studies are not always predictive of Contains sodium sulfite, a sulfite that may cause allergic-type reactions human response, this drug should be used during pregnancy only if including anaphylactic symptoms and life-threatening or less severe the potential benefit justifies the potential risk to the fetus. asthmatic episodes in certain susceptible people. The overall prevalence Because of the known effects of prostaglandin biosynthesisof sulfite sensitivity in the general population is unknown and probably inhibiting drugs on the fetal cardiovascular system (closure of ductus low. Sulfite sensitivity is seen more frequently in asthmatic than in nonarteriosus), the use of PROLENSA® ophthalmic solution during late asthmatic people. pregnancy should be avoided. Slow or Delayed Healing Nursing Mothers All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including Caution should be exercised when PROLENSA is administered to a bromfenac, may slow or delay healing. Topical corticosteroids are also nursing woman. known to slow or delay healing. Concomitant use of topical NSAIDs and Pediatric Use topical steroids may increase the potential for healing problems. Safety and efficacy in pediatric patients below the age of 18 have not Potential for Cross-Sensitivity been established. There is the potential for cross-sensitivity to acetylsalicylic acid, Geriatric Use phenylacetic acid derivatives, and other NSAIDs, including bromfenac. There is no evidence that the efficacy or safety profiles for Therefore, caution should be used when treating individuals who have PROLENSA differ in patients 70 years of age and older compared to previously exhibited sensitivities to these drugs. younger adult patients. Increased Bleeding Time NONCLINICAL TOXICOLOGY With some NSAIDs, including bromfenac, there exists the potential for Carcinogenesis, Mutagenesis and Impairment of Fertility increased bleeding time due to interference with platelet aggregation. Long-term carcinogenicity studies in rats and mice given oral There have been reports that ocularly applied NSAIDs may cause doses of bromfenac up to 0.6 mg/kg/day (systemic exposure 30 increased bleeding of ocular tissues (including hyphemas) in conjunction times the systemic exposure predicted from the recommended with ocular surgery. human ophthalmic dose [RHOD] assuming the human systemic It is recommended that PROLENSA® ophthalmic solution be used with concentration is at the limit of quantification) and 5 mg/kg/day (340 caution in patients with known bleeding tendencies or who are receiving times the predicted human systemic exposure), respectively, revealed other medications which may prolong bleeding time. no significant increases in tumor incidence. Keratitis and Corneal Reactions Bromfenac did not show mutagenic potential in various mutagenicity Use of topical NSAIDs may result in keratitis. In some susceptible studies, including the reverse mutation, chromosomal aberration, and patients, continued use of topical NSAIDs may result in epithelial micronucleus tests. breakdown, corneal thinning, corneal erosion, corneal ulceration or Bromfenac did not impair fertility when administered orally to male corneal perforation. These events may be sight threatening. Patients with and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, evidence of corneal epithelial breakdown should immediately discontinue respectively (systemic exposure 90 and 30 times the predicted human use of topical NSAIDs, including bromfenac, and should be closely exposure, respectively). monitored for corneal health. Post-marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial PATIENT COUNSELING INFORMATION defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), Slowed or Delayed Healing Advise patients of the possibility that slow or delayed healing may rheumatoid arthritis, or repeat ocular surgeries within a short period occur while using NSAIDs. of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution Sterility of Dropper Tip Advise patients to replace bottle cap after using and to not touch in these patients. dropper tip to any surface, as this may contaminate the contents. Post-marketing experience with topical NSAIDs also suggests that use Advise patients that a single bottle of PROLENSA® ophthalmic more than 24 hours prior to surgery or use beyond 14 days post-surgery solution, be used to treat only one eye. may increase patient risk for the occurrence and severity of corneal Concomitant Use of Contact Lenses adverse events. Advise patients to remove contact lenses prior to instillation of Contact Lens Wear PROLENSA. The preservative in PROLENSA, benzalkonium PROLENSA should not be instilled while wearing contact lenses. chloride, may be absorbed by soft contact lenses. Lenses may be Remove contact lenses prior to instillation of PROLENSA. The reinserted after 10 minutes following administration of PROLENSA. preservative in PROLENSA, benzalkonium chloride may be absorbed by Concomitant Topical Ocular Therapy soft contact lenses. Lenses may be reinserted after 10 minutes following If more than one topical ophthalmic medication is being used, the administration of PROLENSA. medicines should be administered at least 5 minutes apart ADVERSE REACTIONS Rx Only Clinical Trial Experience Manufactured by: Bausch & Lomb Incorporated, Tampa, FL 33637 Because clinical trials are conducted under widely varying conditions, Under license from: adverse reaction rates observed in the clinical trials of a drug cannot be Senju Pharmaceuticals Co., Ltd. directly compared to rates in the clinical trials of another drug and may Osaka, Japan 541-0046 not reflect the rates observed in clinical practice. Prolensa is a trademark of Bausch & Lomb Incorporated or its affiliates. The most commonly reported adverse reactions following use of © Bausch & Lomb Incorporated. 9317600 US/PRA/14/0024 DOSAGE AND ADMINISTRATION Recommended Dosing One drop of PROLENSA® ophthalmic solution should be applied to the affected eye once daily beginning 1 day prior to cataract surgery, continued on the day of surgery, and through the first 14 days of the postoperative period. Use with Other Topical Ophthalmic Medications PROLENSA ophthalmic solution may be administered in conjunction with other topical ophthalmic medications such as alpha-agonists, betablockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics. Drops should be administered at least 5 minutes apart. 45 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) VISUAL ACUITY ( Continued from page 42 ) drug they were receiving until the primary results were published in February 2015. At that time, if the investigators considered it to be warranted, the study participant could switch anti-VEGF agents. After 2 years, 201 patients (90%) remained in the aflibercept group, 185 (85%) in the bevacizumab group, and 218 (88%) in the ranibizumab group. At that point, the aflibercept group had received a median of 15 injections, the bevacizumab had received 16, and the ranibizumab group had received 15. Sixty-four percent of the bevacizumab group received laser treatment, compared with 41% of the aflibercept group and 52% of the ranibizumab group. V ISUA L ACU I T Y EF F ECT S On average, visual acuity improved over the 2 years by 12.8 letters with aflibercept, 10.0 with bevacizumab, and 12.3 with ranibizumab. The difference was statistically significant (p = 0.02) for aflibercept versus bevacizumab, but not for aflibercept versus ranibizumab (p = 0.47) and not for ranibizumab versus bevacizumab (p = 0.11). Among patients with an initial visual acuity of 20/50 or worse, improvement was 18.1 letters with aflibercept, 13.3 with bevacizumab, and 16.1 with ranibizumab. Once again, this difference was only statistically significant for aflibercept versus bevacizumab (p = 0.02). With visual acuity of 20/32 or 20/40, mean improvement at 2 years was 7.8 letters for aflibercept, 6.8 for bevacizumab, and 8.6 for ranibizumab, and none of these differences were statistically significant. These findings carried forward many of the trends from the previous year. At the 1-year follow-up, when visual acuity was 20/32 to 20/40 at the start of the trial, vision improved on average almost 2 lines in all three treatment groups. At the end of the first year, for NEXT FRONTIER IN MANAGEMENT OF participants whose visual acuity was 20/50 or worse at the start of the trial, aflibercept improved vision on average almost 18.9 letters, bevacizumab 11.8 letters, and ranibizumab 14.2 letters, with a statistically significant difference between aflibercept and bevacizumab (p < 0.001) as well as between aflibercept and ranibizumab (p = 0.003), but not between ranibizumab and bevacizumab (p = 0.21). Averaging the results over the 2 years, aflibercept maintained its statistically significant superiority over the other two drugs. The mean change in central subfield thickness was greatest with aflibercept, with a drop of 172 μm by the end of the second year. This was better than the drop of 149 μm for ranibizumab and 126 μm for bevacizumab, with the differences between aflibercept and bevacizumab (p < 0.001) and ranibizumab (p = 0.08) statistically significant, but not between ranibizumab and bevacizumab (p = 0.001). Among patients with a baseline visual acuity of 20/50 or worse, bevacizumab reduced central subfield thickness by 185 μm, which was more than ranibizumab’s 174 μm, though still not as much as aflibercept’s 211 μm. In patients with visual acuity of 20/32 to 20/40, on the other hand, bevacizumab only reduced central subfield thickness by 68 μm, versus 125 μm for ranibizumab and 133 μm for aflibercept. There were no statistically significant differences in the percentages of patients suffering adverse events among the groups. Elevated IOP was the most frequently reported complication. RETINA DISEASE In eyes with better vision, he prefers ranibizumab because it is less expensive than aflibercept and because in these patients, it might reduce edema more than bevacizumab. ■ JOHN A. WELLS, MD P: 803/252-1953 This article was adapted from Dr. Wells’ presentation during the 2016 meeting of the American Society of Retina Surgeons. Dr. Wells discloses grants and non-financial support from Genentech and Regeneron during the conduct of the study. A) B) # Femto Dissectors A) 08-07160 Dewey1 Horizontal Femto Chopper. B) 08-07161 Friedman 2 Double-Ended Femto Incision Dissector. D) # 08-14561 Toyos 3 Femto Dissector. D) 08-10143 Femtosecond DoubleEnded Incision Dissector, 1mm & 2mm. E) 08-10144 Folden4 Femto DoubleEnded Dissector, 0.7mm & 1.2mm. E) WEIGHING OPTIONS In his own practice, Dr. Wells said, he still prefers aflibercept for patients with the weakest vision. “I would think clearly baseline vision is important. And if baseline vision were 20/50 or worse, I would choose [aflibercept],” he said. “It’s obviously more effective at 1 year, and even though the difference with ranibizumab is narrowed at the 2-year endpoint, you want to give people better vision as quickly as you can.” Call 727-209-2244 For More Information. 3360 Scherer Drive, Suite B, St. Petersburg, FL 33716 s4ELs&AX %MAIL)NFO 2HEIN-EDICALCOMs7EBSITEWWW2HEIN-EDICALCOM 1 $EVELOPED)N#OORDINATION7ITH3TEVEN$EWEY-$ $EVELOPED)N#OORDINATION7ITH.EIL&RIEDMAN-$ $EVELOPED)N#OORDINATION7ITH2OLANDO4OYOS-$ 4 $EVELOPED)N#OORDINATION7ITH$AVID&OLDEN-$ 3 1368 Rev.A 3ARTO'IRLWITHAPETRARCHINO ACBG 46 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) NEXT FRONTIER IN MANAGEMENT OF RETINA DISEASE Real-world study tracks clinical use of dexamethasone implant for DME Interim analysis from REINFORCE trial finds vision gains, no new safety concerns By Vanessa Caceres; Reviewed by Howard F. Fine, MD, MHSc NE W BRUNSWICK , N J :: USE OF a dexamethasone intra- take-home ‘Since this is a real-world study, the majority of patients (93.6%) had received prior treatment for DME.’ — Howard F. Fine, MD, MHSc Dexamethasone implant injection Mean (SE) BCVA change from baseline (EDTRS letters) tive or monotherapy in patients, all vitreal implant (Ozurdex, Allergan) of whom had DME. Eighty-eight was associated with 1- to 2-line vi- patients (93.6%) were previously sion gains on average in patients treated prior to the first dexamethwith diabetic macular edema (DME) asone injection. The mean DME in the phase IV REINFORCE study, duration was more than 1 year in 73 eyes (72.3%) and more than 2 said Howard F. Fine, MD, MHSc. The steroid implant has been years in 51 eyes (50.5%). In 63 eyes approved by the FDA for macular (62.4%), the injection was used as edema secondary to retinal vein monotherapy. The mean injection frequency occlusion and noninfectious uveitis, noted Dr. Fine, clinical asso- was 1.5, and the mean re-injection ciate professor, Rutgers Robert interval in patients receiving mulWood Johnson Medical School, tiple implants was 135.4 days, according to the study New Brunswick, NJ. abstract. It also was approved “The top-line study for DME after positive data are the mean peak results from the phase improvement from III MEAD study. A 6-month baseline was 8.2 letThe prospective, analysis from the ters following the first multicenter, observa- REINFORCE study of [injection] and 8.7 lettional registry REIN- the dexamethasone ters following the secFORCE study—short intravitreal implant ond injection,” Dr. Fine for Real-World Assess- found an average of said. The proportion of ment of Dexametha- 1- to 2-line vision gains 3-line gainers at any sone Intravitreal Im- and no new safety follow-up visit was plant in Diabetic Macu- concerns. 27.6%, and the re-inlar Edema—measured real-world outcomes of the implant jection interval was 4.5 months when used to treat DME, Dr. Fine on average. “What was most impressive said. The data he presented were an interim analysis of the 1-year to me is that since this is a realstudy of 101 study eyes (94 pa- world study, the majority of patients tients) that had completed at least (93.6%) had received prior treatment for DME, particularly anti-vascular 6 months of follow-up. The implant was used as adjunc- endothelial growth factor [VEGF] 8.7 ± 2.6 12 10 8.2 ± 1.3 8 6 4 2 n=98 eyes n=35 eyes 1st 2nd 0 (FIGURE 1) Mean (±SE) peak improvement (from baseline) in BCVA after first and second steroid implant injection. (Figure courtesy of Howard F. Fine, MD, MHSc) injections and/or laser,” Dr. Fine said. “Therefore, this study demonstrates a significant role for [the steroid implant] in patients treated for DME, such as incomplete antiVEGF responders and those who cannot tolerate a high anti-VEGF injection frequency.” Patients’ central retinal thickness improved from baseline each month over the first 6 months after the first injection, with a mean peak change of –122.5 μm from baseline at month 2. IOP increased in 7.2% of eyes; 8.2% had an IOP greater than 25 mm Hg, and 1% had an IOP greater than 35 mm Hg. Dr. Fine and fellow investigators concluded that as either monotherapy or combination therapy, patients receiving the dexametha- sone intravitreal implant had improved best corrected visual acuity and central retinal thickness, and there were no new safety concerns. The 1-year results from REINFORCE should be ready by the end of 2016. Dr. Fine said he is particularly interested in data regarding combination therapy of both antiVEGF and dexamethasone injections. ■ HOWARD F. FINE, MD, MHSC E: [email protected] This article was adapted from Dr. Fine’s presentation at the 2016 meeting of the Association for Research in Vision and Ophthalmology. Dr. Fine is a consultant for Allergan. As demonstrated in phase 3 clinical trials in patients with Wet AMD, Macular Edema following RVO, DME, and DR in patients with DME Choose EYLEA® (aflibercept) Injection from the start Learn about EYLEA at EYLEA.us/ot INDICATIONS AND IMPORTANT SAFETY INFORMATION INDICATIONS EYLEA® (aflibercept) Injection is indicated for the treatment of patients with Neovascular (Wet) Age-related Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR) in Patients with DME. CONTRAINDICATIONS EYLEA® (aflibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA. WARNINGS AND PRECAUTIONS Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. Intraocular inflammation has been reported with the use of EYLEA. Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately. There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with EYLEA. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with EYLEA compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies. ADVERSE REACTIONS Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with EYLEA including endophthalmitis and retinal detachment. The most common adverse reactions (≥5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous floaters, intraocular pressure increased, and vitreous detachment. Please see brief summary of full Prescribing Information on the following page. EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc. ©2016, Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591 All rights reserved 06/2016 US-LEA-1648(1) BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION FOR COMPLETE DETAILS, SEE FULL PRESCRIBING INFORMATION. 1 INDICATIONS AND USAGE EYLEA® (aflibercept) Injection is indicated for the treatment of patients with Neovascular (Wet) Age-Related Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR) in Patients with DME. 2 DOSAGE AND ADMINISTRATION 2.1 Important Injection Instructions. For ophthalmic intravitreal injection. EYLEA must only be administered by a qualified physician. 2.2 Neovascular (Wet) Age-Related Macular Degeneration (AMD). The recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters) administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months). Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated in most patients when EYLEA was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the "%./0āĂƬ3!!'/Ĩă)+*0$/ĩċ 2.3 Macular Edema Following Retinal Vein Occlusion (RVO). The recommended dose for EYLEA is (0.05 mL or 50 microliters) administered by intravitreal injection once every 4 weeks (monthly). 2.4 Diabetic Macular Edema (DME). The recommended dose for EYLEA is (0.05 mL or 50 microliters) administered by intravitreal injection every 4 weeks (monthly) for the first 5 injections followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months). Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated in most patients when EYLEA was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 20 weeks (5 months). 2.5 Diabetic Retinopathy (DR) in Patients with DME. The recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters) administered by intravitreal injection every 4 weeks (monthly) for the first 5 injections, followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months). Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated in most patients when EYLEA was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first ĂĀƬ3!!'/ĨĆ)+*0$/ĩċ 2.6 Preparation for Administration. EYLEA should be inspected visually prior to administration. If particulates, cloudiness, or discoloration are visible, the vial must not be used. Using aseptic technique, the intravitreal injection should be performed with a 30-gauge x ½-inch injection needle. For complete preparation for administration instructions, see full prescribing information. 2.7 Injection Procedure. The intravitreal injection procedure should be carried out under controlled aseptic conditions, which include surgical hand disinfection and the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a topical broad– spectrum microbicide should be given prior to the injection. Immediately following the intravitreal injection, patients should be monitored for elevation in intraocular pressure. Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry. If required, a sterile paracentesis needle should be available. Following intravitreal injection, patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment (e.g., eye pain, redness of the eye, photophobia, blurring of vision) without delay (see Patient Counseling Information). Each vial should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles should be changed before EYLEA is administered to the other eye. After injection, any unused product must be discarded. 3 DOSAGE FORMS AND STRENGTHS Single-use, glass vial designed to provide 0.05 mL of 40 mg/mL solution (2 mg) for intravitreal injection. 4 CONTRAINDICATIONS EYLEA is contraindicated in patients with G $/A8->;><1>5;/A8->5:21/@5;:? G /@5B15:@>-;/A8->5:28-99-@5;: G :;C:4E<1>?1:?5@5B5@E@;-285.1>/1<@;>-:E;2@411D/5<51:@?5:,! Hypersensitivity reactions may manifest as severe intraocular inflammation. 5 WARNINGS AND PRECAUTIONS 5.1 Endophthalmitis and Retinal Detachments. Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments (see Adverse Reactions). Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately (see Dosage and Administration and Patient Counseling Information). 5.2 Increase in Intraocular Pressure. Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA (see Adverse Reactions). Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with vascular edothelial growth factor (VEGF) inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately (see Dosage and Administration). 5.3 Thromboembolic Events. There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with EYLEA. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with EYLEA compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies. 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in the Warnings and Precautions section of the labeling: Endophthalmitis and retinal detachments Increased intraocular pressure Thromboembolic events 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials of the same or another drug and may not reflect the rates observed in practice. A total of 2711 patients treated with EYLEA constituted the safety population in seven phase 3 studies. Among those, 2110 patients were treated with the recommended dose of 2 mg. Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with EYLEA including endophthalmitis and retinal detachment. The most common adverse reactions (*5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous floaters, intraocular pressure increased, and vitreous detachment. Neovascular (Wet) Age-Related Macular Degeneration (AMD). The data described below reflect exposure to EYLEA in 1824 patients with wet AMD, including 1223 patients treated with the 2-mg dose, in 2 double-masked, active-controlled clinical studies (VIEW1 and VIEW2) for 12 months. Table 1: Most Common Adverse Reactions (*1%) in Wet AMD Studies Active Control EYLEA Adverse Reactions (ranibizumab) (N=1824) (N=595) Conjunctival hemorrhage 25% 28% Eye pain 9% 9% Cataract 7% 7% Vitreous detachment 6% 6% Vitreous floaters 6% 7% Intraocular pressure increased 5% 7% Ocular hyperemia 4% 8% Corneal epithelium defect 4% 5% Detachment of the retinal pigment 3% 3% epithelium Injection site pain 3% 3% Foreign body sensation in eyes 3% 4% Lacrimation increased 3% 1% Vision blurred 2% 2% Intraocular inflammation 2% 3% Retinal pigment epithelium tear 2% 1% Injection site hemorrhage 1% 2% Eyelid edema 1% 2% Corneal edema 1% 1% Less common serious adverse reactions reported in <1% of the patients treated with EYLEA were hypersensitivity, retinal detachment, retinal tear, and endophthalmitis. Macular Edema Following Retinal Vein Occlusion (RVO). The data described below reflect 6 months exposure to EYLEA with a monthly 2 mg dose in 218 patients following CRVO in 2 clinical studies (COPERNICUS and GALILEO) and 91 patients following BRVO in one clinical study (VIBRANT). Table 2: Most Common Adverse Reactions (*1%) in RVO Studies Adverse Reactions CRVO BRVO EYLEA Control EYLEA Control (N=218) (N=142) (N=91) (N=92) Eye pain 13% 5% 4% 5% Conjunctival hemorrhage 12% 11% 20% 4% Intraocular pressure increased 8% 6% 2% 0% Corneal epithelium defect 5% 4% 2% 0% Vitreous floaters 5% 1% 1% 0% Ocular hyperemia 5% 3% 2% 2% Foreign body sensation in eyes 3% 5% 3% 0% Vitreous detachment 3% 4% 2% 0% Lacrimation increased 3% 4% 3% 0% Injection site pain 3% 1% 1% 0% Vision blurred 1% <1% 1% 1% Intraocular inflammation 1% 1% 0% 0% Cataract <1% 1% 5% 0% Eyelid edema <1% 1% 1% 0% Less common adverse reactions reported in <1% of the patients treated with EYLEA in the CRVO studies were corneal edema, retinal tear, hypersensitivity, and endophthalmitis. Diabetic Macular Edema (DME). The data described below reflect exposure to EYLEA in 578 patients with DME treated with the 2-mg dose in 2 double-masked, controlled clinical studies (VIVID and VISTA) from baseline to week 52 and from baseline to week 100. Table 3: Most Common Adverse Reactions (*1%) in DME Studies Adverse Reactions Baseline to Week 52 Baseline to Week 100 EYLEA Control EYLEA Control (N=578) (N=287) (N=578) (N=287) Conjunctival hemorrhage 28% 17% 31% 21% Eye pain 9% 6% 11% 9% Cataract 8% 9% 19% 17% Vitreous floaters 6% 3% 8% 6% Corneal epithelium defect 5% 3% 7% 5% Intraocular pressure increased 5% 3% 9% 5% Ocular hyperemia 5% 6% 5% 6% Vitreous detachment 3% 3% 8% 6% Foreign body sensation in eyes 3% 3% 3% 3% Lacrimation increased 3% 2% 4% 2% Vision blurred 2% 2% 3% 4% Intraocular inflammation 2% <1% 3% 1% Injection site pain 2% <1% 2% <1% Eyelid edema <1% 1% 2% 1% Less common adverse reactions reported in <1% of the patients treated with EYLEA were hypersensitivity, retinal detachment, retinal tear, corneal edema, and injection site hemorrhage. 6.2 Immunogenicity. As with all therapeutic proteins, there is a potential for an immune response in patients treated with EYLEA. The immunogenicity of EYLEA was evaluated in serum samples. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to EYLEA in immunoassays. The detection of an immune response is highly dependent on the sensitivity and specificity of the assays used, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to EYLEA with the incidence of antibodies to other products may be misleading. In the wet AMD, RVO, and DME studies, the pre-treatment incidence of immunoreactivity to EYLEA was approximately 1% to 3% across treatment groups. After dosing with EYLEA for 24-100 weeks, antibodies to EYLEA were detected in a similar percentage range of patients. There were no differences in efficacy or safety between patients with or without immunoreactivity. 6.3 Postmarketing Experience. The following adverse reactions have been identified during postapproval use of EYLEA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. G E<1>?1:?5@5B5@E5:/8A05:3>-?4<>A>5@A?-:0A>@5/->5--?C188-?5?;8-@10 cases of severe anaphylactic/anaphylactoid reactions. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy. Pregnancy Category C. Aflibercept produced embryo-fetal toxicity when administered every three days during organogenesis to pregnant rabbits at intravenous doses *3 mg per kg, or every six days at subcutaneous doses *0.1 mg per kg. Adverse embryo-fetal effects included increased incidences of postimplantation loss and fetal malformations, including anasarca, umbilical hernia, diaphragmatic hernia, gastroschisis, cleft palate, ectrodactyly, intestinal atresia, spina bifida, encephalomeningocele, heart and major vessel defects, and skeletal malformations (fused vertebrae, sternebrae, and ribs; supernumerary vertebral arches and ribs; and incomplete ossification). The maternal No Observed Adverse Effect Level (NOAEL) in these studies was 3 mg per kg. Aflibercept produced fetal malformations at all doses assessed in rabbits and the fetal NOAEL was less than 0.1 mg per kg. Administration of the lowest dose assessed in rabbits (0.1 mg per kg) resulted in systemic exposure (AUC) that was approximately 10 times the systemic exposure observed in humans after an intravitreal dose of 2 mg. There are no adequate and well-controlled studies in pregnant women. EYLEA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Females of reproductive potential should use effective contraception prior to the initial dose, during treatment, and for at least 3 months after the last intravitreal injection of EYLEA. 8.3 Nursing Mothers. It is unknown whether aflibercept is excreted in human milk. Because many drugs are excreted in human milk, a risk to the breastfed child cannot be excluded. EYLEA is not recommended during breastfeeding. A decision must be made whether to discontinue nursing or to discontinue treatment with EYLEA, taking into account the importance of the drug to the mother. 8.4 Pediatric Use. The safety and effectiveness of EYLEA in pediatric patients have not been established. 8.5 Geriatric Use. In the clinical studies, approximately 76% (2049/2701) of patients randomized to treatment with EYLEA were *65 years of age and approximately 46% (1250/2701) were *75 years of age. No significant differences in efficacy or safety were seen with increasing age in these studies. 17 PATIENT COUNSELING INFORMATION In the days following EYLEA administration, patients are at risk of developing endophthalmitis or retinal detachment. If the eye becomes red, sensitive to light, painful, or develops a change in vision, advise patients to seek immediate care from an ophthalmologist (see Warnings and Precautions). Patients may experience temporary visual disturbances after an intravitreal injection with EYLEA and the associated eye examinations (see Adverse Reactions). Advise patients not to drive or use machinery until visual function has recovered sufficiently. Manufactured by: Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road Tarrytown, NY 10591-6707 EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc. © 2016, Regeneron Pharmaceuticals, Inc. All rights reserved. Issue Date: June 2016 Initial U.S. Approval: 2011 June 2016 49 SEPTEMBER 15, 2016 :: Ophthalmology Times Special Report ) NEXT FRONTIER IN MANAGEMENT OF RETINA DISEASE Retinal prosthesis system ranks high in safety, performance endpoints Follow-up at 5 years continues to show positive results for vision-restoring device Lynda Charters; Reviewed by Lyndon da Cruz, MD, and Jessy D. Dorn, PhD LONDON AND SY L MAR, CA :: RECENTLY PUBLISHED results from an ongoing 10-year clinical study of a retinal prosthesis system (Argus II Retinal Prosthesis System, Second Sight) showed the device has continued to maintain a high safety profile as of the 5-year time point in 30 patients with retinitis pigmentosa implanted with the device. “[It] is the first retinal prostheses approved for commercialization in the European Economic Area that can help restore some visual function in patients with retinitis pigmentosa, and the only one to receive FDA approval in the United States and Health Canada approval,” according to Lyndon da Cruz, MD, consultant ophthalmic surgeon, Department of Vitreoretinal Surgery, Moorfields Eye Hospital, London, and lead author of the paper (da Cruz et al. Ophthalmology. 2016 Jul 19. pii: S0161-6420(16)30579-6. doi: 10.1016/j.ophtha.2016.06.049. [Epub ahead of print]). Patients will continue to be followed for an additional 5 years. The prospective trial, conducted at 10 centers in the United States and Europe, enrolled processing unit in their pocket or slung over their shoulder, explained Jessy D. Dorn, PhD, study co-author and senior director of Clinical and Scientific Research, Second Sight. The processing unit converted the images into stimulation patterns sent wirelessly to the electrode array. patients, 24 serious adverse events occurred, all of which were treatable and no patient required enucleation. By 5 years, one additional adverse event, a rhegmatogenous retinal detachment, occurred and was treated successfully. In addition, two implants had failed due to the inability to maintain the radioSAFETY The retinal prosthesis frequency link between the antenIn measuring the primary safety nae mounted on the glasses and endpoint, investigators recorded system is providing implanted in the eye, Dr. Dorn the number, type, and the severity a safe option for explained. of serious or non-serious adverse restoration of some events associated with the surgery visual function in PERFORMANCE or the device. Visual function, as- patients with severe “Overall, the patients performed sessed using three computer-based vision loss associated better on computerized and realtests, was the secondary endpoint. with retinitis life tests to evaluate their level of All of the visual assessments were pigmentosa. functional vision when they wore performed with the device turned on and off, with the latter relying only on re- the system compared to when the system was sidual vision. Secondary endpoints included turned off,” Dr. da Cruz said. For example, when patients were instructed a number of “real world” tasks the patients were asked to perform to determine the prac- to find a white square on a black background of the computer screen, 81% scored significantly ticality of the device. At the 5-yea r better using the system, he explained, nottime point, 24 pa- ing about half of the patients did better while tients still had the using the system for identifying the direction prosthesis system in which a bar was moving across the screen. “The device has gone on to be implanted i m pl a n te d a n d functioning. None in many patients; in many countries, it reof the 30 patients mains the only currently available treatment were completely for profound vision loss resulting from [retinilost to follow-up, tis pigmentosa] and outer retinal dystrophy,” and safety data the authors concluded. “The new long-term could be obtained data from the original study continue to demfrom 27 patients at onstrate that this therapy remains an option evaluation, as three for patients with [retinitis pigmentosa] and devices were ex- may allow for stable and reliable restoration planted due to re- of some basic visual function.” ■ current conjunctival erosions in two patients and hypotLYNDON DA CRUZ, MD ony and ptosis in E: [email protected] one patient, Dr. da Dr. da Cruz did not indicate any proprietary interest in the subject matter. Cruz reported. At the 3-year time point, 18 (60%) of the 30 JESSY D. DORN, PHD patients had no serious adverse event related E: [email protected] to surgery or the device. In the remaining 12 Dr. Dorn is a senior director of Clinical and Scientific Research at Second Sight. ‘The device has gone on to be implanted in many patients; in many countries, it remains the only currently available treatment for profound vision loss resulting from [retinitis pigmentosa] and outer retinal dystrophy.’ 30 patients implanted with an electrode array on the retinal surface of the worse eye. Patients wore glasses on which a video camera had been mounted and carried a video take-home 50 SeptemBer 15, 2016 :: Ophthalmology Times clinical diagnosis Updated classification gives order to corneal dystrophy Better diagnosis can help patients, physicians chart out best approach to treatment By Laird Harrison; Reviewed by Jayne S. Weiss, MD Ne w Orl e aNs :: hat’s in a name? Would lead to multiple opacities in adults. The condiSchnyder corneal dystrotion is autosomal dominant disease. > A chromosome 10 dystrophy was eliminated phy (SCD) cause as much vision loss by any other from the Thiel-Behnke category. Earlier reports name? Perhaps, but it may of a Thiel-Behnke dystrophy on chromosome not be properly diagnosed, 10 were not substantiated by further research, said Jayne S. Weiss, MD. which confirmed that all Thiel-Behnke dystroToo often the condition has been referred phies are on the TGFBI gene on chromosome to as Schnyder crystalline corneal dystrophy, 5. The dystrophy resembles Thiel-Behnke and leading clinicians to misdiagnose patients who may belong in the ERED category. > Congenital hereditary endothelial dystrophy 1 had no crystals in their corneas, said Dr. Weiss, chairman, Department of Ophthalmology, Lou(CHED 1) was eliminated. The autosomal domiisiana State University, New Orleans. nant condition that was being called CHED 1 was That is only one example of many confusing actually a different dystrophy called posterior and misleading names of dystrophies which polymorphous corneal dystrophy. Consequently, inspired Dr. Weiss to lead an effort to properly the autosomal recessive corneal dystrophy predifferentiate and name corneal dystrophies. viously called CHED 2 is now named CHED. “If we don’t know what we’re looking at, how will we ever make any headway into sciThe new document builds on the work in entific investigation for a better treatment or the original document, which replaced categoprevention?” she asked. “That, ultimately, as ries based on anatomy with categories based a clinician scientist, was my goal for this.” on genes. In 2005, she organized the International Com“Two things that look the same, if they have mittee for the Classification of Corneal Dystro- a different genetic origin, are probably not the phies (IC3D), whose results were first published same,” Dr. Weiss said. “We may have some disin 2008. Between 2008 and 2012, new infor- eases on the same gene that may look very difmation about the dystrophies became avail- ferent, but if they’re on the same gene, maybe able, for which Dr. Weiss also led the update. with different mutations, there could be more The updated classification appears in Cornea similarity . . . than you might guess at first under the title “IC3D classificaglance.” tion of corneal dystrophies— The researchers also found edition 2,” and is most easily exceptions to the commonly An updated accessed by selecting the pubused definition of corneal dysclassifcation of lisher’s button in its Pubmed trophy—an inherited, bilateral, corneal dystrophies listing (http://bit.ly/2c9WFMf). slowly progressing corneal diswill help clinicians The most important changes ease without systemic associawith properly in the update included: tions. In some cases, the oppodifferentiating and > A new anatomic category for site can also be true, she said. naming the disorders. The document offers one-page dystrophies that map to the descriptions of each dystrophy, TGFBI gene. > Expansion of the epithelial how it is inherited, genetic information, the age of onset, signs and symprecurrent erosion dystrophy (ERED) category. toms, how rapidly it progresses, and photos. Recent research has uncovered more subtypes “There are levels of detail in the article that of ERED, which often causes recurrent unexare certainly relevant to many physicians in plained corneal erosions in children and can w Take-Home magenta cyan yellow black Schnyder corneal dystrophy TOP Central subepithelial crystals are present. BOTTOM Central panstromal corneal opacity, peripheral arcus lipoides, and more subtle midperipheral corneal haze are visible, though no corneal crystals are present. (Images courtesy of Jayne S. Weiss, MD) terms of assisting them to make the diagnosis and helping inform the patient what the prognosis is,” Dr. Weiss said. Some corneal dystrophies cause few symptoms. Others can lead to opacification, but corneal transplants can usually restore good vision in these patients, she noted. “One of my goals is for us to get to the next level that we have gotten to in many other diseases, where we can intervene to prevent disease progression and avoid visual loss,” she said. In the meantime, better diagnosis can help patients plan for the future, Dr. Weiss said. Continues on page 52 : Corneal dystrophy ES838947_OT091516_050.pgs 09.12.2016 22:37 ADV Photo by: J. Bradley Randleman, MD Extreme example of visual distortion from keratoconus. Corneal Cross-linking can help improve vision. YOUR VISION, OUR FOCUS Corneal Cross Linking—the recent FDA approved treatment to reverse corneal warpage and visual distortion from keratoconus and complications of LASIK is now available at the USC Roski Eye Institute. Find out more at AAO, 2016 Therapeutic & Refractive Crosslinking Refractive Surgery by J. Bradley Randleman, MD Monday, October 17, 2016 — 3:45-5:20PM, Grand Ballroom S100AB For Referring Physicians: 323-442-eyes or visit www.usceye.org # "## 52 SEPTEMBER 15, 2016 :: Ophthalmology Times clinical diagnosis How pregnancy can affect Sjögren’s ectopic lymphoid structures Early detection of cell organization in lacrimal glands may enable disease interventions By Nancy Groves; Reviewed by Austin K. Mircheff, PhD LOS ANGEL ES :: RESEARCH IN AN ANIMAL model shows pregnancy can increase accumulation and activation of cells and functions associated with ectopic lymphoid structures (ELS) in Sjögren’s syndrome. Further research on the mechanisms in ELS development could lead to interventions preventing the onset of Sjögren’s syndrome, said Austin K. Mircheff, PhD, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles. Dr. Mircheff and colleagues are exploring an approach to describe what happens during pregnancy that could cause Sjögren’s syndrome. “It’s not just a way of visualizing the precursors of a disease process, but also seeing what the biological mechanisms and signaling interactions are between the various types of cells that have to organize themselves into rather complex structures,” Dr. Mircheff said. CELLS ORGANIZING Earlier research discovered a cluster of very strongly correlating transcripts in the lacrimal glands of rabbits that seemed to organize into a network resembling an ELS, Dr. Mircheff noted. The team hypothesized that pregnancy might influence the development of the cellular network. Additional studies testing six pregnant CORNEAL DYSTROPHY ( Continued from page 50 ) “When we see patients, they want to know what do they have and what can they expect as their life goes on,” she said. “Are they going to need surgery? Is their vision going to be impaired? What are the chances of them giving this to their progeny? Unless we really understand what we’re looking at, we can’t give the disease the correct name and most importantly we can’t really give the patient an accurate idea about what they may face in the future.” For example, Dr. Weiss, an authority on rabbits and six virgin rabbits using q-RT-PCR aimed to determine the abundances of 62 transcripts in each lacrimal gland. The researchers used Pearson’s test to identify clusters of positively and negatively correlating transcripts.1 There were few statistically significant differences between the lacrimal glands of pregnant and virgin rabbits for the network transcripts. “There was a bigger range of variation among the glands from the pregnant animals than the glands from the virgin animals,” Dr. Mircheff said, adding that the individual glands sorted into two clusters: one with transcripts higher than normal, and one where they were lower. MOV ING TO SJÖGR EN’S ELS Pregnancy affects the cells that form the network that eventually may become Sjögren’s ELS. “They can either become more numerous and more highly activated or less numerous and less highly activated in pregnancy,” Dr. Mircheff said. “The obvious inference . . . is that the glands that become more active or more prevalent are the ones that will go on to develop Sjögren’s because this network will continue developing of its own with time.” Still, that inference may not entirely be correct. “At the same time, we find evidence for negative crosstalk between that network and cells Schnyder corneal dystrophy, had a young patient with this dystrophy who wanted to be a pilot. She showed the patient a chart indicating how the patient’s vision would likely be affected at each age. The patient decided to become a pilot while understanding the career might not last past the age of 30 or 40 years. “Many times when I’m in a room with patients I’ll open the IC3D article and show them where they are,” Dr. Weiss said. “I find my patients are always appreciative of the information.” In another case, a patient with Schnyder was considering laser treatment for corneal crystals. She explained the treatment would not entirely restore the patient’s vision because of coexistent corneal haze underneath the crystals. or types of cells that express other proteins involved in ELS,” he said. “That may prevent all of the cells from coming together to form those structures, and it may be in the glands where the first cluster is poorly developed . . . you may have reciprocal networks developing.” The ability to detect the networks of cells organizing themselves, while they’re still precursors to the ELS, may enable possible interventions to prevent them from coalescing, he said. It is significant the study involved rabbits instead of mice, given persistent questions on how closely immunological mechanisms in mice or rats correspond to those in humans, he said. “Histologically, and in some functional aspects, rabbit lacrimal glands are more similar to humans,” Dr. Mircheff said. “If we had done this study with rodents, we may not have seen anything like the results we’ve gotten.” ■ Reference 1. Mircheff et al. Potentially pathogenic immune cells and networks in apparently healthy lacrimal cell glands. Ocul Surf. 2015;13:47-81. AUSTIN K. MIRCHEFF, PHD P: 323/442-1242 E: [email protected] This article was adapted from Dr. Mircheff and colleagues’ poster presentation at the 2015 meeting of the Association for Research in Vision and Ophthalmology. A correct diagnosis might help uncover systemic conditions as well. Since families with Schnyder often have elevated cholesterol levels whether or not the eye is affected, clinicians should advise these patients to have their systemic cholesterol levels checked, Dr. Weiss noted. “No one wants a disease,” she said, “but the unknown is often more frightening than the known.” ■ JAYNE S. WEISS, MD E: [email protected] This article was adapted from Dr. Weiss’ delivery of the Richard L. Lindstrom, MD, Lecture during the 2016 meeting of the American Society of Cataract and Refractive Surgery. She did not indicate any proprietary interest in the subject matter. Corneal Hysteresis is more associated with visual field progression than CCT or IOP. 1-3 Introducing the all-new: Ocular Response Analyzer® G3 Auto Tonometer + Corneal Hysteresis Make a more confident glaucoma risk assessment with Corneal Hysteresis. Only from Reichert®. Corneal Hysteresis: CPT® Code 92145 Learn more at AAO, Booth 1020 and www.reichert.com/ora Advancing Eye Care. American Innovation. © 2016 AMETEK, Inc. & Reichert, Inc. (8-2016) Made in USA -www.reichert.com References: 1. Medeiros FA, Meira-Freitas D, Lisboa R, Kuang TM, Zangwill LM, Weinreb RN. Corneal hysteresis as a risk factor for glaucoma progression: a prospective longitudinal study. Ophthalmology. 2013 Aug;120(8):153340. 2. De Moraes CV, Hill V, Tello C, Liebmann JM, Ritch R. Lower corneal hysteresis is associated with more rapid glaucomatous visual fi eld progression. J Glaucoma. 2012 Apr-May;21(4):209-13. 3. Aashish Anand, MD, Carlos Gustavo De Moraes, MD, Christopher C Teng, MD, Celso Tello, MD, Jeffrey M Liebmann, MD Robert Ritch, MD. Lower Corneal Hysteresis Predicts Laterality in Asymmetric Open Angle Glaucoma, IOVS Papers in Press. Published on June 23, 2010 as Manuscript iovs.10-5580. CPT is registered trademark of the American Medical Association. 54 SEPTEMBER 15, 2016 :: Ophthalmology Times clinical diagnosis Using structure, function analysis to track progression of glaucoma Mapping best treatment requires consideration of individualized disease progression rates By Laird Harrison MEASURES OF STRUCTURE and function change can help ophthalmologists individualize treatment of glaucoma patients, according to Robert Chang, MD. Since glaucoma progresses faster in some patients than others, optical coherence tomography (OCT) and visual field progression analysis can be more useful than IOP in guiding treatment decisions, said Dr. Chang, assistant professor of ophthalmology, Stanford University Medical Center, Stanford, CA. “I use structure and function glaucoma progression analysis to really customize therapy over a lifetime,” he said. “That’s my method of precision medicine in treating glaucoma patients today.” The concept of precision medicine has received growing attention in recent years, he said, citing the Precision Medicine Initiative presented by President Barack Obama in his 2015 State of the Union address. The initiative calls on health-care providers to take into consideration genetic, lifestyle, and environmental factors to tailor treatments to patients. “How are we going to apply precision medicine when we don’t have much genetic data and we don’t know what the patient’s environmental effects are?” Dr. Chang asked. “Maybe there aren’t any specifically for glaucoma.” CONSIDER ATIONS The answer to treating glaucoma starts with preserving ganglion cells as long as the patient lives, Dr. Chang said. Clinicians must consider the rate the disease is progressing in each patient in order to choose a treatment that strikes the right balance between probable efficacy and the risk of adverse reactions. “We need something quantitative,” he said, “not just looking at the nerve or asking them how their vision is doing.” OCT-guided progression analysis in early stages of glaucoma and visual field progression analysis in later stages can provide the data to monitor progression, he said. OCT is highly repeatable, so clinicians can compare a patient’s status to baseline measurements. Additionally, visual field index can be calculated against the patient’s age. “Everyone should know that there is no agerelated loss progression correction on these OCT calculations,” Dr. Chang said. “On average, age-related loss is about 2 to 3 μm every decade or 0.2 μm per year.” In some patients, the disease may progress very slowly, Dr. Chang said. He cited the Canadian Glaucoma Study (Arch Ophthalmol. 2010;128:1249-1255), in which 216 patients were followed up at 4-month intervals with perimetry and were monitored for progression. The patients who reached an endpoint based on total deviation analysis underwent 20% or greater reduction in IOP. The researchers found the median mean deviation rate in progressing patients prior to the first endpoint was −0.35dB/y. USEFUL INFOR MATION Dr. Chang recalled a patient he had followed for about 5 years who was “very noncompliant.” At baseline, the patient’s untreated IOP was a maximum of 32 mm Hg. The patient refused surgery, so Dr. Chang was “almost just documenting the natural course of disease.” Interestingly, the patient’s right eye did not progress as fast as the right, despite high pressure in both. The structural changes generally precede the functional changes, but eventually if a patient loses a certain amount of nerve fiber layer, the patient will experience a visual field defect, he said. How can clinicians make use of this information? Dr. Chang pointed out more glaucoma treatments that are available than in the past. Ophthalmologists have to decide whether to prescribe medications, perform conventional surgery, or implant a minimally invasive glaucoma surgery device. “While we have a lot of studies, major trials that give us the target range pressures, it may not be the absolute value of the pressure that you should reach for in every single patient,” Dr. Chang said. “Instead, start looking at what their individualized rates of progressions are over time.” Because glaucoma doesn’t change overnight, it might be worthwhile to “sacrifice a PRECISION MEDICINE VIDEO Watch as Dr. Chang discusses portable technology options that help provide better patient care. Go to OphthalmologyTimes. com/PrecisionMedicine few neurons” to avoid subjecting patients to a treatment that may cause side effects, he said. “What we’re really getting at here is their personalized rate of progression.” He uses a grid to figure out what treatment might work best, and to present it to the patient. On the left column is “high-efficacy, but high side-effects” treatments, like filtering surgery. On the right is “watchful waiting.” In between are treatments with medium efficacy and medium risk. The faster the patient’s disease is progressing, the farther the left the patient belongs, and vice versa. Dr. Chang still sets initial target pressures, and he lowers the patient’s pressure if he thinks the patient’s condition is deteriorating. “That’s what I’m focusing on, using visual fields maximally . . . to know if they are getting a little worse,” he said. “Therefore, I’m going to think about all the new treatments available.” ■ ROBERT CHANG, MD E: [email protected] This article was adapted from Dr. Chang’s presentation during the Glaucoma Symposium CME at the 2016 Glaucoma 360 meeting. Dr. Chang disclosed that he does research for Carl Zeiss Meditec. with OCT2 The Platform for Advanced Imaging Now available as a module upgrade for existing SPECTRALIS systems!† Faster Scan Speed (85 kHz) More than twice the scan speed, allowing for: 303034-001 US.AE16 © Heidelberg Engineering, Inc. Enhanced Image Quality SPECTRALIS with OCT2 provides the platform for future advanced applications such as OCT angiography.* Experience it at AAO - Booth #2344 † Advanced models only. *OCT angiography is under development and not for sale. www.HeidelbergEngineering.com 56 SEPTEMBER 15, 2016 :: Ophthalmology Times clinical diagnosis Coin-sized scanner may enable early diagnosis of retinal diseases Technology may also expand individuals who can be screened outside of hospitals, practices By Nancy Groves; Reviewed by Prof. Wolfgang Drexler VIENNA :: A CONSORTIUM OF EUROPEAN experts in academia and industry is collaboratElectrical ing on an ambitious, 4-year project to shrink Swept Interposer PIC both the size and cost of optical coherence toMicrolens Source Array mography (OCT) systems. The OCTChip (ophthalmic OCT on a chip) Reference project aims to use photonic integrated cirArm cuits to produce a coin-sized retinal scanner that will improve the screening and diagnosis of retinal diseases, such as age-related macular degeneration, diabetic retinopathy, and ages conveyed to a reading center via a wireless glaucoma. Wolfgang Drexler, professor of medical phys- or Bluetooth connection using a cellphone or ics, head of the Center for Medical Physics and tablet. This arrangement would also allow for Biomedical Engineering, Medical University rapid feedback and open a pathway to quicker of Vienna, is leading the project, which began diagnosis and treatment. The research and development team is at the start of 2016. Less than a year in, his team has come up with preliminary designs also envisioning that an extremely compact OCT system could one day be on store and ideas for packaging. “I’m quite positive that in a year or so we’ll shelves as a consumer product for self-dihave the first prototype, and then in 2 or 3 agnosis of retinal or dermatologic diseases, years we will go into clinical trials with an Prof. Drexler said. The miniaturized OCT system would repreimproved prototype,” Prof. Drexler said. sent a significant leap in OCT Commercialization and mass technology. OCT is now 25 years production could be achieved old and reigns as the gold stanby 2020, he noted. By shrinking the dard in the diagnosis of eye dis“It’s something that will revocore technology of eases, as well as being used in lutionize the biomedical or biooptical coherence such specialties as cardiology optical imaging world because tomography to the and gastroenterology. it can be made very compact size of a coin—and But according to Prof. Drexand it is maintenance-free,” reducing its cost—a ler, despite steady improvement Prof. Drexler added. team of European in OCT technology over the The chip will be packaged in scientists hopes years, miniaturization has a format that could be handto improve early never been a priority as it has held or maneuvered in front diagnosis and been in fields, such as conof a patient’s eyes, perhaps rescreening of retinal sumer electronics, where tabsembling a larger laser pointer. diseases. lets and mobile phones have This could broaden the specsupplanted desktop computers trum of patients who could for many users. more readily undergo imagIn addition, the bulk and cost of current ing, such as premature infants or elderly patients who have difficulty traveling to medi- OCT systems have limited their use to facilities and practitioners that could afford them cal facilities. and support the technology. Prof. Drexler was already thinking about R EMOTE USAGE Such a compact tool scanner could also be eas- how to transfer the optical set-up of OCT to ily transported to developing or remote areas of a chip a decade ago and began collaborating the world where electricity is scarce, with im- with academic experts who were working on TAKE-HOME As a miniaturized imaging system, the core component of the device targets the size of a 1-cent coin. (Image courtesy of Photonics21) ‘It’s something that will revolutionize the biomedical or bio-optical imaging world because it can be made very compact and it is maintenance-free.’ — Prof. Wolfgang Drexler photonic integrated circuits in telecommunications. One of the thornier problems they had to solve was how to minimize optical losses when transferring optical imaging technology to a chip, since high optical losses are common in telecommunications. Prof. Drexler subsequently initiated not only the OCTChip project that he now heads but another for dermatologic OCT on a chip, which has now been commercialized for cancer diagnosis. The novel approach the OCTChip team of scientists and engineers is using to ensure suContinues on page 59 : Scanner Best in the West, Top 5 in the Nation International Glaucoma Symposium 70Years 1947 to 2017 Saturday, November 5 The Inaugural Doheny-UCLA International Glaucoma Symposium brings together experts in glaucoma to better define current challenges and initiate the discovery of innovative solutions. This full-day event is organized into cutting-edge anterior and posterior segment glaucoma sessions. The course material will involve a combination of clinical scenarios, translational research, and bench investigation. Featured Speakers Jonathan Crowston, BSc, MBBS, PhD, FRCOphth, FRANZCO Ringland Anderson Professor of Ophthalmology University of Melbourne Managing Director, Centre for Eye Research Australia Ike Ahmed, MD Assistant Professor, University of Toronto Clinical Assistant Professor, University of Utah Research Director, Kensington Eye Institute Robert Weinreb, MD Jeffrey Liebmann, MD Chairman and Distinguished Professor of Ophthalmology Director, Shiley Eye Institute University of California, San Diego Vice-Chair and Professor of Ophthalmology Columbia University Medical Center Complimentary registration Register online at www.doheny.org/cme For more information, contact the Doheny CME office at (323) 442-6427 or email [email protected]. Accreditation Statement: Doheny Eye Institute is accredited by the Institute for Medical Quality/California Medical Association (IMQ/CMA) to provide continuing medical education for physicians. Credit Designation Statement: Credit Designation Statement: Doheny Eye Institute designates these live activities for a maximum of 7.5 of AMA PRA Category 1 Credits™, where noted and depending on the course. Physicians should only claim credit commensurate with the extent of their participation in the activity. 58 SEPTEMBER 15, 2016 :: Ophthalmology Times clinical diagnosis Strategies may eliminate issues impeding Tunisian pediatric care Tactics include improving public/physician education, access to quality care, patient follow-up By Cheryl Guttman Krader; Reviewed by Lamia El Fekih, MD T UNIS, T UNISIA :: DELAYED PATIENT presentation, compounded by problems relating to insufficient resources and lack of follow-up, explain why pediatric cataract remains an important cause of visual impairment in Tunisia. Thorough understanding of these existing challenges is providing a framework for developing solutions, according to Lamia El Fekih, MD. “It is important that strategies for managing congenital cataract be developed and adopted according to regional conditions,” said Dr. El Fekih, faculty of medicine, University of Tunis-El Manar, Tunisia. “In Tunisia, we are working together to eliminate surgical disequalities, and we have to focus on improving public and physician education, access to good quality care, and patient follow-up.” Dr. El Fekih suggested that maldistribution of services is the principal reason why children with cataract do not receive the surgical care and follow-up they need for successful vision rehabilitation. There are few centers in Tunisia where pediatric ophthalmology and pediatric anesthesiology services are available, she noted. Consequently, families are faced with the need to travel long distances to procure care for their child, and they may lack a means of transportation. In addition, there are multiple other factors limiting access to care. For example, although surgery is available at no charge for the poor in Tunisia, inability to pay for other necessary services remains an important barrier, considering the low socioeconomic level of the population in some regions of the country. HER EDITARY COMPONENT “Moreover, congenital cataract in Tunisia appears to have a hereditary component,” Dr. El Fekih said. “When a family has more than one child needing treatment, the financial impact increases. In addition, these children with congenital cataract often have other medical and physical issues that can make it difficult for families to bring them for care.” Even if children undergo surgery, their visual prognosis depends on proper follow-up care. In Tunisia, there is also a scarcity of practitioners who can provide contact lenses for aphakic refractive correction. Furthermore, compliance with amblyopia therapy among families in Tunisia is poor. Dr. El Fekih noted that a review of a series of children operated for congenital cataract at her institution showed that about half of those who needed occlusion therapy to prevent amblyopia did not receive it. Children who develop amblyopia need low vision training, but there are only two low vision centers in Tunisia, and even when physical access to these services is not an issue, a financial obstacle can exist. “Children may need more than one low vision device or there may be a need to replace devices that get broken. Low vision aids, however, can be expensive,” Dr. El Fekih said. Dr. El Fekih said that overcoming these challenges requires a multipronged approach. The development of health education targeting parents and health providers is imporBy 2020, tant to raise awareness about pedithe hope is specialist atric cataract and its management centers will be prepared so more children are presented for and able to provide surgery ophthalmic care. and effective optical Increasing parental knowledge correction to all children also leads to improved compliance with congenital said. “And, new trainees with postoperative follow-up and amcataract. are showing little interest blyopia treatment protocols. in specializing in pediatric Focusing on education and other stratophthalmology.” egies to increase patient access, Dr. El Fekih She added that “by 2020, [the hope is] we and others are working with the government to strengthen programs for early detection for will have prepared equipped specialist centers all causes of childhood blindness and to imple- and be able to provide surgery to all of our children with congenital cataract along with ment or improve referral systems. In addition, they are mapping and identify- immediate and effective optical correction.” ■ ing tertiary eye care centers that have facilities for pediatric patients. They also are trying to encourage young ophthalmologists to train in pediatrics. “Although there are about 600 ophthalmologists in Tunisia serving our country’s popLAMIA EL FEKIH, MD ulation of about 12 million people, there are E: [email protected] few pediatric ophthalmologists,” Dr. El Fekih Dr. El Fekih has no relevant financial interests to disclose. Tunisia has a population of about 12 million people. There are about 600 ophthalmologists. But few specialize in pediatric ophthalmology. ALGERIA TUNISIA LIBYA SEPTEMBER 15, 2016 :: Ophthalmology Times clinical diagnosis SCANNER ( Continued from page 56 ) perior optical quality while shrinking the core OCT technology is the use of photonic integrated circuits. “By using photonic integrated circuits we can combine planar optical waveguides, and we also use microelectronics packaged on these chips so that it’s extremely compact and low cost and hopefully even higher performing than recent commercial OCT systems,” Prof. Drexler said. Participants in the OCTChip project include the Medical University of Vienna, which is coordinating the effort, University College Cork in Ireland, the Austrian Institute of Technology, the Fraunhofer Network in Germany, Carl Zeiss Meditec, Austrian sensor firm AMS, and the Swiss company Exalos AG. ■ 59 PROF. WOLFGANG DREXLER E: [email protected] Prof. Drexler is a consultant for Carl Zeiss Meditec as well as Exalos regarding OCTChip and the topic it covers. 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P640 REV 08/16 60 SEPTEMBER 15, 2016 :: Ophthalmology Times clinical diagnosis Mild corticosteroids may safely reduce Sjögren’s inflammation Pilot study also helps investigators refine technique for tear analysis By Nancy Groves; Reviewed by Ranjini Kottaiyan, OD, MBA ROCHES T ER, N Y :: A MILD TOPICAL corticosteroid could be effective in treating the symptoms of Sjögren’s syndrome by reducing the inflammatory tear cytokines and the rate of evaporation, suggest findings from a small pilot study. Ocular surface metrology performed with tools—such as wavefront sensing and thermal imaging—appear to be effective in analyzing the effects of treatment, said Ranjini Kottaiyan, OD, MBA, lead researcher, Ocular Surface Laboratory, Flaum Eye Institute, University of Rochester, Rochester, NY. Corticosteroids have been used to treat dry eye symptoms of Sjögren’s syndrome. However, the risk of adverse effects, such as increased IOP and cataract formation after prolonged use, has prompted interest in a lower-strength steroid, such as loteprednol etabonate ophthalmic suspension 0.5% (Lotemax, Bausch + Lomb). Loteprednol was administered QID for 2 weeks in this study, which enrolled 10 subjects (20 eyes) with Sjögren’s syndrome. All measurements were taken in a controlled-environmental chamber, a 12- × 12-foot room in which the temperature, humidity, and airflow could be controlled precisely. (Image courtesy of Ranjini Kottaiyan, OD, MBA) parameters,” Dr. Kottaiyan added. “We comCYTOKINES pared the objective measures to the presence HARD TO DETECT According to Dr. Kottaiyan, it appears all cy- of inflammatory mediators in the eye after treatment.” tokines are not easily detectAt baseline, Dr. Kottaiyan able in all patients. For examand colleagues recorded clinical ple, IL-17 was detected in 13% A mild topical characteristics, such as Schirmof patients in one study. TNFa corticosteroid may be er’s test results, tear break-up was detected in only 2% of paeffective in treating time, entrance and exit IOP, ostients in one study and 12% in the symptoms of molarity, and corneal staining. another (LaFrance et al., Curr Sjögren’s disease They also used a customEye Res. 2008;33:525-544. doi: without causing built Shack-Hartmann wave10.1080/02713680802190085; the adverse effects front sensor, which measured Enriquez-de-Salamanca et al., associated with visual quality changes caused Mol Vis. 2010;16:862-873.). higher-dose steroids. by aberrations in tear film dy“The goal of the study was Findings from a pilot namics, and a thermal camera to evaluate tear cytokines bestudy also suggest (Thermovision A40, FLIR Sysfore and after a treatment regithat ocular surface tems) to assess ocular surface men, and we chose people with metrology is useful in temperature. Sjögren’s syndrome because they evaluating the effects All measurements were taken have inflammatory mediators in of the steroid. in a controlled-environmental their eyes,” Dr. Kottaiyan said. chamber, a 12- × 12-foot room in “The unique thing about this which the temperature, humidstudy is that we utilized our ocular metrology in conjunction with tear analy- ity, and airflow could be controlled precisely. The subjects were asked to present for 3 sis to noninvasively and objectively study tear TAKE-HOME weekly visits. After baseline measurements were taken at the first visit, loteprednol was administered, and then measurements were taken again 30 minutes later with the wavefront sensor and thermal imaging to evaluate the drug’s short-term effect. Tears were collected by two techniques, with and without a saline wash. “We found that with the saline wash, the data was highly variable, and did not show trends across the sampling time points,” Dr. Kottaiyan said. “So we published data just from native tear collection.” TESTING CONDITIONS The subjects were then directed to use the steroid QID for the remainder of the study. At the first and second visits, patients were tested in nominal environmental conditions in which the temperature was about 75° F and relative humidity 45%. In the final visit, the subjects were tested as soon as they arrived and again after spending 30 minutes under stressed environmental conditions (temperature 80° F, relative humidity 20%). SEPTEMBER 15, 2016 :: Ophthalmology Times clinical diagnosis Changes in visual quality and ocular surface temperature were observed throughout the study. During the first visit, testing of the short-term effect showed that 30 minutes after instillation of the steroid, the visual quality worsened and the average ocular surface temperature increased. This trend was not significant but was indicative of reduced surface evaporation, Dr. Kottaiyan said. However, long-term effects were more apparent. “The ocular surface temperature significantly increased at 2 weeks after treatment (p = 0.02),” Dr. Kottaiyan said. “This shows that this is a good way to objectively measure how the ocular surface responds.” NORMAL, STRESSED CONDITIONS The researchers also compared the subjects based on their responses under normal and stressed environmental conditions. “In the stressed environment, we found that the ocular surface temperature increases but visual quality decreases,” Dr. Kottaiyan said. The study also included Luminex analysis of tear cytokines. Only 6 of 9 tear samples collected could be evaluated due to low tear-volume collection. “We chose people with severe form of dry eye, so it was very challenging to collect tears from them,” Dr. Kottaiyan said. The results showed that at least 6 cytokines were elevated in the study population before treatment, and all of them were reduced after loteprednol treatment at 2 weeks. In at least 3 of the 9 patients, all 6 of the cytokines were reduced, while concentrations of some, but not all cytokines, were lower in other subjects. This analysis could be considered a pilot study that will help researchers refine the technique for tear analysis. The ocular surface metrology, using the wavefront sensing, thermal imaging, combined cytokine analysis, is equally important, Dr. Kottaiyan said. “We can extend this technique to a bigger study where we can study cytokines in other types of dry eye patients and perform ocular surface metrology to study dry eye in other Mark S. Humayun, MD, PhD, elected as new president of ASRS CHICAGO :: MARK S. HUMAYUN, MD, PhD, who recently received the National Medal of Technology and Innovation—the nation's highest honor for technological achievement—has been elected president of the American Society of Retina Specialists (ASRS) for a 2-year term through August 2018. Dr. Humayun is co-director of the University of Southern California (USC) Roski Eye Institute, director of the USC Institute for Biomedical Therapeutics, and is a professor with joint appointments in both USC’s Keck School of Medicine and Viterbi School of Engineering. He is the only ophthalmologist to be elected as a member of both U.S. National Academies of Medicine and Engineering, according to a prepared statement. Over the years, he has served in numerous ASRS leadership roles. In his more than 25 years of research, Dr. Humayun has secured over 100 patents and co-invented the Argus Series retinal implants, the world’s first artificial retinal prostheses, manufactured by Second Sight Medical Products. The Argus technology, which has been in commercial use in Europe since 2011, gained FDA approval in the United States in 2013 and is successfully restoring useful vision to patients who suffer from certain blinding diseases, such as retina pigmentosa. ASRS is the largest retinal organization in the world, representing nearly 3,000 members across the United States, District of Columbia, Puerto Rico, and 59 countries. ■ To read more about the latest Argus 5-year safety results, go to Page 49. treatments to see how the disease progresses,” Dr. Kottaiyan added. “We observed that thermal imaging and wavefrontsensing techniques were very effective.” ■ RANJINI KOTTAIYAN, OD, MBA E: Ranjini_Kottaiyan@ URMC.Rochester.edu This article was adapted from Dr. Kottaiyan’s poster presentation at the 2015 meeting of the Association for Research in Vision and Ophthalmology. The researchers received grant support from Bausch + Lomb and Research to Prevent Blindness. 61 62 drug therapy SEPTEMBER 15, 2016 :: Ophthalmology Times Exploring oral anti-VEGF/PDGF inhibitor for AMD therapy Oral administration makes agent suitable for treating patients with bilateral disease By Cheryl Guttman Krader; Reviewed by Nauman Chaudhry, MD NE W LONDON, C T :: phase II study investigating oral X-82 (Tyrogenex) in patients with Baseline Month 1 Month 2 exudative age-related macular degeneration (AMD) requiring frequent anti-vascular endothelial growth factor (VEGF) therapy is under way after positive results were achieved in a phase I study, said Nauman Chaudhry, MD. (FIGURE 1) The central subslice of SD-OCT images are shown for a naïve patient in the X-82 phase Ib study. The main objective of the phase I study was From left: at baseline, after 1 month of treatment, and after 2 months of treatment. Over the 2 months, to evaluate the safety of X-82 and any dose-limvisual acuity had improved from 70 letters to 84 letters. (Images courtesy of Nauman Chaudhry, MD) iting toxicity. The open-label, ascending, repeat-dose study enrolled 35 patients with exuPHASE I TRIAL Of the 10 patients who did not complete 6 dative AMD. Six regimens were The phase I study enrolled 35 patients who months of treatment, 6 were withdrawn for evaluated with doses ranging were treated for up to 6 months with one of six adverse event-related reasons, including transfrom 50 mg every other day regimens: 50 mg every other day, 50 mg daily, aminase elevations (n = 2), leg cramps (n = to 300 mg daily. 100 mg every other day, 100 mg daily, 200 mg 2), and gastrointestinal symptoms (diarrhea Dr. Chaudhry Initially, only patients with daily, or 300 mg daily. Patients returned every or nausea/mild anorexia, n = 2). heavily treated refractory disease were enrolled 4 weeks for assessment of BCVA and central (patients unable to achieve a dry macula despite foveal thickness (CFT) measured by spectral E X PA N DI NG R E SE A RCH frequent anti-VEGF injections), but treatment- domain OCT. Patients were eligible for anti- The phase II study is a randomized, doublenaïve patients were eligible for participation VEGF rescue therapy if they had a 5-letter de- masked, comparative dose (50, 100, and 200 as the study progressed. crease in BCVA or ≥50-μm increase in CFT. mg daily) and placebo-controlled study. It is During treatment lasting up Twenty-five of the 35 enrolled enrolling previously treated patients who have to 6 months, no dose-limiting patients completed 6 months demonstrated the ability to achieve a reductoxicity was identified for X-82, of treatment. BCVA was main- tion in CFT in response to anti-VEGF injection. An oral anti-VEGF/ and the investigational agent tained or improved in most paPatients must have wet AMD and received PDGF inhibitor had showed evidence of biological tients and was improved in the at least two prior anti-VEGF injections at inno dose-limiting activity based on functional and majority of patients who com- tervals of not greater than 6 weeks. They will toxicity and improved anatomic endpoints. pleted the study. Mean CFT was be followed monthly and be eligible to receive visual acuity and OCT Dr. Chaudhry, principal invesalso significantly reduced in pa- injections as needed. findings in patients tigator for the X-82 AMD studies tients who completed the study, The primary endpoint of the study is change with exudative and clinical assistant professor with some patients achieving in visual acuity in X-82 patients compared with age-related macular of ophthalmology, Yale Univercomplete resolution of fluid. placebo at 1 year. Secondary endpoints include degeneration in a sity, New Haven, CT, noted the Of the 25 patients who com- number of anti-VEGF injections received durphase I study. investigational tyrosine kinase pleted the 6 months of treat- ing the first year of the study and anatomical inhibitor has features that make ment, 15 (60%) did not require changes on SD-OCT imaging. ■ it attractive for treating wet AMD. any rescue anti-VEGF injections. “X-82 blocks kinase activity associated with “The proportion of patients in each dose coall receptor subtypes of VEGF and also platelet- hort who did not require any rescue injections NAUMAN CHAUDHRY MD derived growth factor (PDGF), which is impor- increased as the dose of X-82 increased,” said E: [email protected] tant because anti-VEGF effects are enhanced Dr. Chaudhry, who also is in private practice, This article was adapted from Dr. Chaudhry’s presentation during Retina Subspecialty by anti-PGDF activity,” he said. “Its oral route New London, CT. “None of the patients in the Day at the 2015 meeting of the American Academy of Ophthalmology. He is principal of administration makes X-82 suitable for treat- 300-mg daily dose group who completed the investigator for the Tyrogenex AMD studies but has no other relevant financial interest ing patients with bilateral disease.” study required anti-VEGF injections.” in the material. A TAKE-HOME SEPTEMBER 15, 2016 :: Ophthalmology Times drug therapy Sustained-release implant is viable alternative to anti-VEGFs for DME Fluocinolone acetonide implant showed positive results for DME refractory to other treatments By Lynda Charters; Reviewed by Usha Chakravarthy, MBBS BEL FAS T, NOR T HERN IREL AND :: ANALYSIS OF REAL-WORLD interim data from patients treated with fluocinolone acetonide intravitreal implant (Iluvien, Alimera Sciences), a sustained-release intravitreal implant and the subject of a safety trial in Europe, showed that most patients with chronic diabetic macular edema (DME) who received the therapy did not require mediDr. Chakravarthy cation to reduce IOP. Importantly, a substantial percentage of patients experienced sustained gains in visual acuity over the course of the study following one injection. The implant, which contains 190 milligrams of the drug, was used in patients with DME in the Iluvien Registry Safety Study (IRISS). At least twothirds of the patients had undergone previous injections of anti-vascular endothelial growth factor (VEGF) agents and a course of corticosteroids. The implant releases fluocinolone acetone over a period of 36 months. The medication fills an important gap in this patient population, according to Usha Chakravarthy, MBBS, clinical professor, School of Medicine, Dentistry and Biomedical Sciences, Centre for Public Health, Queen’s University of Belfast, Belfast, Northern Ireland, and principal investigator of the IRISS. In patients with DME refractory to anti-VEGF medication, patients were switched to the steroid implant when it had been determined that their vision was decreasing and the macular appearance was worsening. “Following the switch, there were improvements in visual acuity and retinal morphology in the majority of patients,” she said. “This finding indicated that [the implant] is an important addition to our therapeutic armamentarium.” The IRISS is a 5-year post-authorization registry study required for all markets in which the product is sold: currently, the United Kingdom (26 study sites), Germany (10 study sites), and Portugal (1 study site). The study examined the incidence of IOP increases and their management after patients were treated and evaluated the status of their visual acuity. The interim data available from 328 eyes of 292 patients had a mean age of 61.7 years and a mean IOP of 15.4 mm Hg, Dr. Chakravarthy noted. I O P E L E VA T I O N S A ND M A NAGEMEN T Fifty-four (18.4%) patients required treatment to lower the IOP and two (0.6%) patients needed surgery to control the IOP, she said. More than three-quarters of the eyes treated (77.4%, n = 255 eyes) did not need additional treatments during the period of the study. Of those who did require additional therapies, laser was applied in 5.2%, intravitreal injection of an anti-VEGF drug in 16.8%, steroids in 4.0%, and an implant retreatment in 0.3%. V ISUA L ACUIT Y EFFECTS The mean change in visual acuity at month 6 after implantation was a gain of about 5 letters (from 50.9 to 55.7 letters), which was sustained up to 18 months after implantation of the device, Dr. Chakravarthy said. After this time point, the mean gain in visual acuity diminished, which was most likely explained by the small number of patients in this cohort who were followed for 21 months or longer, heavily affecting the mean by loss of visual acuity in three patients, according to the study investigators. At month 6, 15.9% of patients gained Continues on page 64 : DME implant 63 64 SEPTEMBER 15, 2016 :: Ophthalmology Times drug therapy DME IMPLANT ( Continued from page 63 ) ment of Diabetic Retinopathy Study provements in a significant proportion of patients, some of whom were (ETDRS) letters. After implantation, the distribution able to resume driving. The vision imchanged with more patients having a vi- proved in 58% of patients 6 months after implantation and sual acuity between 69 61% at 1 year. and 100 ETDRS letters. The safety profile of Most of the patients A real-world the drug was positive, in this study had latesafety study of with 81.6% of patients stage DME. However, fluocinolone not requiring any meddespite this, 3 months acetonide intravitreal ications to control the after implantation, 58% implant in patients IOP. The patients will of patients had a gain in with chronic DME continue to be followed visual acuity that was (328 eyes from 292 for 3 more years. sustained to month 21 patients) showed that Another study, the (57%) with a peak of 81.6% of patients did ongoing MediSOFT 74% at month 15. not require initiation audit, is a post hoc The percentage of of IOP-lowering chart review of elecpatients achieving the therapy during the tronic medical records needed 6/12 (20/40) study and 60% of data systems used in 13 acuity for driving level patients included in study centers. Interim vision increased from a this registry study data were extracted in baseline of 18% to 34% gained vision after February 2016. at M 12 representing a injection that was “The introduction of 16% rate of improvesustained over the [the implant] has been ment, the investigators study period. an important addition reported. to our therapeutic arThe results of the mamentarium and in interim analysis indicated the patients with long-term DME particular for managing DME that is benefitted from the implant in a way persistent or insufficiently responsive they did not from previous treatment to anti-VEGF therapies,” Dr. Chakrawith anti-VEGF drugs, other steroids, varthy concluded. ■ and laser application. The results of the use of the device, which was considered a last-line therUSHA CHAKRAVARTHY, MBBS apy to be used in an attempt to save E: [email protected] or maintain vision in these patients, Dr. Chakravarthy has no proprietary interest in any aspect of this resulted in useful visual acuity imreport. TAKE-HOME 15 letters of vision or more and 20.8% of patients gained 15 letters or more at month 12, the investigators reported. Most patients had a visual acuity between 34 and 68 Early Treat- Digital and HD Video Imaging Solutions for Slit Lamps and Surgical Microscopes Digital SLR Camera Upgrades Universal Smart Phone Adaptor for Slit Lamp Imaging Allergan acquires gene therapy company RetroSense Therapeutics DUBL IN AND ANN ARBOR, MI :: ALLERGAN AND RetroSense Ikegami HD Video for Surgical Microscopes & Slit Lamps Made in USA TTI Medical TƌĂŶƐĂŵĞƌŝĐĂŶ TĞĐŚŶŽůŽŐŝĞs InternaƟŽŶĂl Phone: +1-925-553-7828 email: info@ƫŵĞĚŝĐĂů.ĐŽm www.ƫŵĞĚŝĐĂů Đom Therapeutics entered into a $60 million all-cash transaction in which Allergan has purchased substantially all of the assets of the therapeutics company. Allergan has agreed to also pay potential milestone payments related to the development of RST-001, a gene therapy for the potential treatment of retinitis pigmentosa (RP), according to a prepared statement. RST-001 is a gene therapy application of optogenetics, a therapeutic approach conferring light sensitivity to cells that were not previously light sensitive. The technology introduces light sensitivity to the retina by applying optogenetics to retinas in which rod and cone photoreceptors have degenerated. RetroSense’s Investigational New Drug (IND) application for RST-001 received clearance from the FDA in 2015. The phase I/IIa clinical trial evaluating the safety of RST-001 was completed safely in 2016, according to the company. ■ SEPTEMBER 15, 2016 :: Ophthalmology Times technology Handheld device offers early screening of amblyopia With high degree of accuracy, device can be used to screen nonverbal children in seconds By Fred Gebhart; Reviewed by David G. Hunter, MD, PhD BOS TON :: here’s a new tool on the market for amblyopia and strabismus screening of even very young children: the Pediatric Vision Scanner (PVS), which received FDA clearance this year. The device offers pediatricians, school nurses, and other health-care providers a screening method that not only is easy to use, but also more reliable than manual examination or photoscreening, said co-developer David G. Hunter, MD, PhD. Scanning with the handheld device is completed in 2.5 seconds, and independent clinical trials show that the accuracy is about 95%, exceeding that of existing screening products, said Dr. Hunter, who serves as ophthalmologist-in-chief at Boston Children’s Hospital and co-founded the medical device start-up, REBIScan, in 2009 to commercialize the product and other ocular scanning technology. T ‘We want to get these kids when they’re preschoolers because that’s when it’s easier to treat the amblyopia.’ — David G. Hunter, MD, PhD Developing the scanner and getting it into the hands of users has taken more than 20 years. The effort to secure investor funding and mass produce the device is an ongoing challenge, Dr. Hunter said, but attaining FDA marketing clearance was a crucial step. The FDA approved the device via the de novo pathway, meaning that there is no other device with the same indication. The portable, handheld device will reduce false referrals to eye-care professionals while improving detection of disease and bringing children to care earlier, according to REBIScan. “Even today, most pediatric practices use manual methods of screening kids for vision problems,” Dr. Hunter said. “That is, they have them hold a cover over one eye and try to read an eye chart across the room. While that works okay for kids who are already in school, it doesn’t work so well for preschoolers, and it doesn’t work at all for kids who can’t yet read or talk. “As a result, there are lots of kids who don’t get any kind of efficient eye screening until school age,” he said. “The problem is, we want to get these kids when they’re preschoolers because that’s when it’s easier to treat the amblyopia.” Over the years, a number of photoscreeners or refractors have been developed to look for amblyopia by checking for refractive error. “The problem with those is that risk factors aren’t the same as disease,” Dr. Hunter said. “Only a small fraction of kids who have risk factors for amblyopia actually need to have any kind of treatment,” he said. “You end up referring a lot of kids who will never need treatment, and that’s not going to be an effective screening program.” Instead, Dr. Hunter and colleagues, including his mentor, David L. Guyton, MD, currently Zanvyl Krieger professor of pediatric ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, wanted to screen for strabismus since most patients who have amblyopia also have this companion condition. Continues on page 66 : Screening 65 66 SEPTEMBER 15, 2016 :: Ophthalmology Times technology SCREENING ( Continued from page 65 ) Their idea was to scan the retina with polarized light, examine the pattern of nerve fibers emanating from the fovea, and use this as a means of detecting fixation. In the early 1990s, they built a scanner that could reliably identify fixation of the eye, although the first model could only scan one eye at a time. The next steps were to condense the device to handheld dimensions, and then to combine two scanners so both eyes could be analyzed simultaneously. After many years of refinement, the result was the recently approved product. The current device works even better than the developers hoped, Dr. Hunter said. “We thought we were going to have to have two steps: One, look for strabismus; and two, look for risk factors. But it turns out that we were able to completely dispense with the whole risk factor piece because the [device] not only detects strabismus but it detects amblyopia as well.” This feature will allow the device to be used by eye-care professionals for early diagnosis of amblyopia in preverbal children. Interpreting results is simple: If two lights on top of the scanner both turn green, then child’s eyes are normal. The portable, handheld device uses retinal birefringence scanning to detect amblyopia and strabismus when they develop. (Images courtesy of David G. Hunter, MD, PhD) TAKE-HOME be more cost-effective in public CLINICAL TRIALS health campaigns than sending Studies have tested the device A new handheld squads of nurses to schools, on children as young as 2 years, pediatric vision clinics, or other sites to conthough outside of that formal scanner can detect duct vision screenings by more setting it has been used to screen amblyopia and conventional methods. infants. As long as a child can strabismus with Because the device is small, sit still and look at the smiley>90% accuracy. The easy to use, and accurate, it face target inside the machine device can be used would be ideal for remote areas for a few seconds, he or she can to screen children once a durable, battery-powered be tested, Dr. Hunter explained. too young to read version is available, he said. Interpreting results is simor recognize letters Potentially, Dr. Hunter noted, ple: If two lights on top of the as well as those of thousands of children could scanner both turn green, then school age since the be scanned in a day by a team child’s eyes are normal. Howonly requirements using several scanners, and the ever, a child’s eyes will change are to sit still for small percentage with apparent during development, so annual a few seconds and problems—not just strabismus screenings are recommended. look at a smileyand amblyopia but cataracts, “If the day could ever come face target in the tumors, and retinal abnormalwhere every pediatrician is machine. ities—could then be referred scanning every child at the for further evaluation. ■ well-child visit starting at age 2 with this device, considering its accuracy, then we could eliminate severe vision loss from amblyopia,” he said. DAVID G. HUNTER, MD, PHD This is a problem in both developed and E: [email protected] developing countries. Using the device would Dr. Hunter is co-developer of the device. OphthalmologyTimes.com Online Exclusive B + L DEDICATED TO EYE CARE WITH STRONG PORTFOLIO, NEW PROGRAMS IN AN INDUSTRY SPOTLIGHT session at the 2016 Glaucoma 360 meeting, Bausch + Lomb—as one of the oldest names in eye care— outlined how the company continues its investment in eye care. Valeant Pharmaceuticals’ acquisition of the company has not changed its dedication to eye care or its continuing investment in glaucoma and other eye-care categories, noted Tracy M. Valorie, senior vice president and general manager of ophthalmology Rx, Bausch + Lomb. The acquisition has enabled the company to focus on new products and programs for expanded growth opportunities, including a 20-year partnership with Walgreens to improve patient access to health care at affordable pricing. Go to OphthalmologyTimes.com/B+LPortfolio INAUGURAL RETINA WORLD CONGRESS UR Y! YO A I T TO D BM T SU RAC ST AB GET READY TO UNITE THE WORLD OF RETINA UNITE. EXCHANGE. ADVANCE. FEBRUARY 23-26, 2017 FORT LAUDERDALE MARRIOTT HARBOR BEACH FORT LAUDERDALE, FLORIDA, USA Retina World Congress (RWC) is an international professional congress that will support global scientific and clinical exchanges on advances in retina health. Target Audience – The Retina World Congress is for retina specialists, retina fellows, and health care providers. 500+ participants are expected to participate. For information about the accreditation of this program, please contact Global at 303-395-1782 or [email protected] REGISTER TODAY w w w. r eti n awo r l d co n g r e s s .o r g This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group (Global), MCME Global, and Retina World Congress (RWC). Global is accredited by the ACCME to provide continuing medical education for physicians. This activity is jointly provided by Global Education Group and MCME Global. Physician Credit Designation – Global Education Group designates this live activity for a maximum of 18.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. practice management 68 September 15, 2016 :: Ophthalmology Times Is the world a better place because of your practice? Visionary leaders have ability to communicate values, ideas in way that connects Let's Chat By donna suter W hen Martin Luther King said, “I have a dream,” he had a vision for people, not a program. Visionary leaders have the ability to communicate values and ideas in a way that connects. In your practice, they bring certainty into the uncertain world of reimbursement rates and rapid change. What is your capacity to bring vision and direction into times of uncertainty? If there is one thing that sets a practice apart, it is the leadership ability of the owner/physician/administrator. Any one of these positions may be where a truly visionary leader is found. Why do people reluctantly comply with one leader, while passionately following another to the end of the earth? The answer lies in the focus of the individual. He or she has an uncanny ability to infuse every employee with a clearly articulated vision of where the practice is going. A visionary is a leader that sets the tone in the workplace and insists that patients be treated with respect, excellence, and has revenue-generating ideas for the future. Offices that have an “I can” attitude when it comes to excellence in patient care and collaborative teamwork are often ran by leaders with vision. On a daily basis, the emphasis is on quick, pleasant patient interactions and fast, accurate treatment. The cultures of today’s practices are so diverse. How does a leader even know which model to pick? And then it’s a question of how to communicate it day after day to employees and eye-care practitioners alike. Despite all of the images, signals, forecasts, alternatives, and hypothetical possibilities they must consider, the best leaders are able to formulate a comprehensive goal based on a myriad of influencing factors, and then achieve it in a manner that supports the earning power and net worth of the practice. Leadership can be developed. Sure, natural leaders excel quicker, but leadership can magenta cyan yellow black and should be developed (or recruited) by all practice owners. Improve your leadership abilities by developing vision at these seven “focal points.” 1. For esight This is the ability to judge how a leader's visions or goals will fit into his or her practice’s evolving mission and environment. A positive process is dependent to a great extent on the quality of the leader’s dialogue with his or her team. Employees must be able to raise issues that may be sensitive and to give and receive feedback. Everyone in the practice should be clear on the goals of the practice. Take time to discuss department goals and individual tactics that support the practice’s overall goal. 2. hindsight Leaders take their practice’s history and traditions into consideration, so their goals and visions won’t contradict their practice culture. On one level, this means collecting the data and producing metrics but not being so busy crunching the numbers that employees feel neglected. The ongoing shortage of qualified workers means an ever-growing need to retain the good ones. According to countless workforce polls, people connect and commit themselves to a practice when they feel respected. They stay when they are fulfilling their skills and when they find meaning in their workday community. A leader with clear hindsight knows the importance of giving employee feedback. He or she is a leader that allows the harsh cold light of facts to illuminate performance and highlight training needs. 3 . A wor ldv iew This is essential when analyzing and interpreting new developments and trends. Look outward so you can make the best decisions possible. A worldview means knowing which services will next be impacted by third-party payers as well as the demographics of your community. What is changing? Are you changing with it? What are you doing about the changes that you see? A visionary has a plan for the worst possible outcomes. How is your understanding of not just marketing but advertising and public relations? Because it is new, there is a lot of chatter about online marketing. Yes, controlling your online image is important, but so is the impact the practice has on the community in which you practice. 4. insight How good are you at looking within the practice and using your insight to identify internal conflict and facilitate communication and resolution? Dynamic practices encourage everyone to share what they learn in the course of performing their jobs. This often means visionaries listen more than they talk at staff meetings. One must be silent to truly listen. This means silencing your thoughts, questions, and preconceived notions to understand what the other person is trying to say. Listening, almost by itself, can eliminate misunderstanding and give you greater insight. 5. depth perception Leaders know how to keep things in perspective. They must view the entire picture and see things in appropriate detail. Describing all the details for effectively managing your patient flow would fill several large books. On a scale of 1 to 10, everything isn’t a 10. The practice will not go broke if you insist that all lanes are equipped with the same instrumentation and drops. The doctor isn’t going to die if the patient isn’t worked up properly. The lead tech should not be able to bully you into giving her a raise. Make expectations about communication, problem-solving, and conflict resolution part of your new-employee orientation program. Continues on page 70 : Visionary leader ES839170_OT091516_068.pgs 09.13.2016 02:40 ADV Available Online at ophthalmologytimes.com/DME for a Limited Time! Go to ophthalmologytimes.com/DME to access these educational discussions. 70 SEPTEMBER 15, 2016 :: Ophthalmology Times practice management VISIONARY LEADER ( Continued from page 68 ) Depth perception also means seeing a ringing phone and a complaining patient as an opportunity rather than an annoyance. Train and empower everyone with patient contact to resolve conflict before it escalates. And the ringing phone? The phone tree should not be an excuse not to answer the phone. Everyone with patient phone contact should know how to schedule appointments. 6. PERIPHER AL VISION Visionaries leaders must keep a watchful eye on their competitors and stakeholders. Be an active member in at least one professional organization and one local civic organization or charity. When was the last time you paid someone to mystery shop your competition? Reimburse a friend for an eye exam and complete pair of eyewear from the private practice that your former patients seem to prefer. The insights you gain point the way toward staff training and process improvement. Stakeholders are there to help you. A conference is the perfect opportunity to build stronger relationships. Spend at least a day in the exhibit hall. Reach out to vendors to schedule a time to view new products. what you see. Does it increase your resolve to improve your practice or are you depressed? Proceed as if success is inevitable. Believe in yourself and let other people see your self-confidence. What needs your focused attention? It could be financial, adverse work hours, patient mix, or toxic internal politics. Break the issues down to their component parts. Work with the doctors and senior staff to come up with an action plan that puts you back on track. In just a matter of months, you’ll enjoy the view! ■ 7. R E V I S I O N Leaders must be able to open-mindedly review and revise their goals, opinions, attitudes, and direction so they can act and react in the most effective, efficient manner possible. How is your vision? Do you see clearly at all seven focal points? Now that you are really looking at your practice, you may not like To read more blogs from Donna and others, visit OphthalmologyTimes.com/ Blogs. DONNA SUTER P: 423/400-3727 Donna Suter is president of Suter Consulting Group. Advertiser Index Advertiser Page Abbott Medical Optics www.abbottmedicaloptics.com CV4 Akorn Pharmaceuticals P: 267/483-4010 www.akorn.com 59 Alcon Laboratories Inc. 800/862-5266 www.alcon.com 5-6, 27, 74, CV3 Bausch + Lomb 800/227-1427 www.bausch.com 9-10, 17, 31-32, 43-44 P: 57 13 55 P: Lacrivera P: 855/857-0518 www.lacrivera.com 29 Micro Medical Devices Inc. 866/730-0663 www.micromedinc.com 61 Omeros Corp. www.omeros.com 19 Perrigo Pharmaceuticals 866/634-9120 www.perrigo.com 7 45 Rumex 727/535-9600 www.rumex.net 63 Shire Ophthalmic 800/828-2088 www.shire-eyes.com 38-39 P: CV2, 3 Sun Pharmaceutical Industries Inc. 800/818-4555 www.sunpharma.com 25 TearLab Corp. 855/832-7522 www.tearlab.com 15 TTI Medical 800/322-7373 www.ttimedical.com 64 USC Roski Eye Institute 323/745-2223 www.usceye.org 51 P: CVTIP, 47A-48A* 914/345-7400 www.regeneron.com P: Reichert Ophthalmic Instrument 888/849-8955 www.reichert.com 53 Retina World Congress 303/395-1782 www.retinaworldcongress.org 67 P: OPHTHALMOLOGY TIMES (Print ISSN 0193-032X, Digital ISSN 2150-7333) is published semimonthly except for one issue in Jan, May, Aug and Dec (20 issues yearly) by UBM Medica, 131 W First Street, Duluth, MN 55802-2065. 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Interviewing for: Comprehensive Ophthalmologist Glaucoma Specialist Medical Retina Specialist Overall practice growth has and will continually provide ample opportunities for new physicians to grow with the practice. We offer a competitive base salary commensurate with experience, full Benefits, 401 k and performance bonus. Candidates should email CV and cover letter to Anabel Sousa BTPVTB!BSBOFZFDPNt All inquirers will remain confidential. Principals only, no recruiters. Recruitment Advertising Can Work For You! Reach highly-targeted, marketspecific business professionals, industry experts and prospects by placing your ad here! NEW YORK FQMGhhgjlmfala]k^gjGh`l`Ydegdg_aklk <]hYjle]flg^Gh`l`Ydegdg_q FQMDYf_gf]E]\a[Yd;]fl]j FQMDE;! 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Content Licensing for Every Marketing Strategy Call Joanna Shippoli to place Marketing solutions fit for: Outdoor | Direct Mail | Print Advertising Tradeshow/POP Displays | Social Media | Radio & TV your Recruitment ad at 800-225-4569, ext. 2615 [email protected] Leverage branded content from Opthalmology Times to create a more powerful and sophisticated statement about your product, service, or company in your next marketing campaign. Contact Wright’s Media to find out more about how we can customize your acknowledgements and recognitions to enhance your marketing strategies. For information, call Wright’s Media at 877.652.5295 or visit our website at www.wrightsmedia.com IN DISPENSABLE 73 ( In Brief ) Wearable technology USC, VSP TAKES DIGITAL HEALTH TO EYEGLASSES Making rebates work for patients, practice In age of online retailing, strategy can boost compliance with contact lens wear, improve clinical care Getty Images/Peathegee Inc.; Video courtesy of USC CBC By Charissa D. Young, OD evenue lost from patients not purchasing their contact lenses at the practice also relates to revenue lost from missed annual exams. In a study of 151 college students,1 23% reported having ordered contact lenses online rather than purchasing from their eyecare professional (ECP). Of those surveyed who exclusively bought contact lenses online, 24% admitted to not having regular annual eye exams (the survey was conducted in a state with contact lens prescriptions limited to 1 year), and the same number of people acknowledged ordering contact lenses online with an expired prescription. Using manufacturer rebates to promote in-office purchases not only helps patients’ R bottom line, but also (most importantly) their long-term eye health. In a review of major contact lens manufacturer rebates, I found patient savings as high as $130 for an annual supply. Offsetting the sticker shock of a contact lens supply order by informing patients of rebates can encourage them not only to support business but also can foster lens wear compliance. A 2013 study showed patients who purchased contact lenses from their ECP returned for annual eye examinations sooner than those who did not by almost 2 months (466 versus 522 days).2 Unsurprisingly, those who did not buy contact lenses from their ECP not only took longer to return for annual appointments, but also were less compliant following the manufacturer’s recommended replacement frequency. Continues on page 74 : Compliance LOS ANGEL ES :: THE UNIVERSITY of Southern California (USC) Center for Body Computing (CBC) has teamed with VSP Global’s innovation lab, The Shop, and the USC Roski Eye Institute to take wearable health to the eyes. A pilot study, which kicked off last month at USC, will assess users’ engagement with and feedback of the smartphone app synched to the embedded sensor in a prototype optical frame (Level, The Shop). The study of USC employee daily eyeglass wearers has participants tracking steps, calories burned, distance traveled, and activity time. Biometrics are tracked by technology embedded in the temple of the frame—including an accelerometer, a magnetometer and a gyroscope—and synched wirelessly via Bluetooth to an accompanying smartphone app. USC Roski Eye Institute is the optometric care partner in the study having its ophthalmologists and optometrists at its USC clinics on the school’s main campus and health sciences campus perform the eye exams and ensure accurate prescriptions for the participants. “We’re thrilled to be partnering with [VSP] to maximize the wearable sensor in eyeglasses by engaging wearers in improved health fueled by philanthropic endeavors,” said Leslie Saxon, MD, founder and executive director, USC Center for Body Computing. “Offering our patients digital health tools and wearable technology in our eye clinics is the wave of the future,” said Rohit Varma, MD, MPH, interim dean, USC Keck School of Medicine, and director, USC Roski Eye Institute. “As one of the key medical partners in the USC CBC’s Virtual Care Clinic, we’re proud to be at the forefront of digital health innovation.” ■ VIDEO For more about the pilot study, go to OphthalmologyTimes.com/SensorGlasses 74 SEPTEMBER 15, 2016 :: Ophthalmology Times indispensable COMPLIANCE ( Continued from page 73 ) Some 75% of subjects reported wearing contact lenses every day, but only 43% purchased the suggested annual supply. If ECPs can provide a seamless transition from exam chair to order at the same visit, it truly is in patients’ best interest. BR EAK OUT R EBATE SHEETS Rebate tear sheets overview the discount based on boxes bought as well as a time-sensitive offer code. Patients typically need to register the code on the manufacturer’s website with their information and mail the manufacturer the original eye exam receipt, original contact lens purchase receipt, and original UPC codes from the contact lens boxes once they’ve received them. Patients usually receive rebates in the form of a prepaid gift card within 60 days of receipt of materials. In an age of competing with online contact lens retailers, rebates can make a practice shine by highlighting personalized service. I’ve worked at a private practice that addressed, stamped, and included in the envelope a copy of the contact lens purchase receipt for patients as an amenity they hadn’t experienced at any other office. Free shipping regardless of order amount should always be available. Also offer free replacements, within reason, for any ripped or defective lenses. At checkout, staff should lead with annual supply information to support the ECP’s recommendation and will be backed up with the best rebates, which usually are for annual supplies. I recommend having staff explain how unilateral pricing policies work or offer to pricematch competitors if patients are wary to order at checkout, which gives patients little reason to spend their dollars for contact lenses outside the practice. And speaking of competition, most rebates cannot be used at big box stores. Save patients an extra trip with in-practice purchases. MISSED OPPORTUNITY If you are not offering manufacturer rebates for contact lens orders, why not? Rebates support patients purchasing annual lens supplies from their ECP, and we know patients who not only purchase their lenses (as well as an annual supply) from the practice see their ECPs more regularly and are at less risk of overwear and associated side effects. Let’s end the noncompliance cycle and break out the rebate sheets. ■ EDITOR’S NOTE: The full text of this article originally appeared in sister publication, Optometry Times. OptometryTimes.com/Rebates References 1. Fogel J, Zidile C. Contact lenses purchased over the Internet place individuals potentially at risk for harmful eye care practices. Optometry. 2008;79:23-35. 2. Dumbleton K, Richter D, Bergenske P, Jones LW. Compliance with lens replacement and the interval between eye examinations. Optom Vis Sci. 2013;90:351-358. CHARISSA D. YOUNG, OD, is interested in dry eye and specialty contact lenses. As the current anterior segment fellow at Specialty Eyecare Group, Seattle, she is involved in active research, particularly in the areas of meibomian gland dysfunction and ocular surface inflammation. She can be reached [email protected] of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Post marketing experience with topical NSAIDs also suggests that use more than 1 day prior to surgery or use beyond 14 days post-surgery may increase patient risk and severity of corneal adverse events. Nursing Mothers ILEVRO® Suspension is excreted in the milk of lactating rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ILEVRO® Suspension is administered to a nursing woman. Pediatric Use Contact Lens Wear ILEVRO® Suspension should not be administered while using contact lenses. BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE ILEVRO® (nepafenac ophthalmic suspension) 0.3% is associated with cataract surgery. DOSAGE AND ADMINISTRATION Recommended Dosing One drop of ILEVRO® Suspension should be applied to to cataract surgery, continued on the day of surgery period. An additional drop should be administered 30 to 120 minutes prior to surgery. Use with Other Topical Ophthalmic Medications ILEVRO® Suspension may be administered in conjunction with other topical ophthalmic medications such as beta-blockers, carbonic anhydrase inhibitors, alpha-agonists, cycloplegics, and mydriatics. If more than one topical ophthalmic medication is being used, the medicines must be administered at least 5 minutes apart. CONTRAINDICATIONS ILEVRO® Suspension is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formula or to other NSAIDs. WARNINGS AND PRECAUTIONS Increased Bleeding Time including ILEVRO® Suspension, there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal of ocular tissues (including hyphemas) in conjunction with ocular surgery. It is recommended that ILEVRO® Suspension be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time. Delayed Healing including ILEVRO® Suspension, may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs including ILEVRO® Suspension and should be closely monitored for corneal health. Post marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period ADVERSE REACTIONS Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another Serious and Otherwise Important Adverse Reactions The following adverse reactions are discussed in greater detail in other sections of labeling: > 94)45Time (Warnings and Precautions) >+=4,5(Warnings and Precautions) Ocular Adverse Reactions The most frequently reported ocular adverse reactions following cataract surgery were capsular opacity, decreased visual acuity, foreign body sensation, increased intraocular pressure, and sticky sensation. These reactions occurred in approximately 5 to 10% of patients. Other ocular adverse reactions occurring at an incidence of approximately 1 to 5% included conjunctival edema, corneal edema, dry eye, lid margin crusting, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, photophobia, tearing and vitreous detachment. Some of these reactions may be the consequence of the cataract surgical procedure. Non-Ocular Adverse Reactions Non-ocular adverse reactions reported at an incidence of 1 to 4% included headache, hypertension, nausea/ vomiting, and sinusitis. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C: Reproduction studies performed with nepafenac in rabbits and rats at oral doses up to 10 mg/kg/day have revealed no evidence of teratogenicity due to nepafenac, despite the induction of maternal toxicity. At this dose, the animal plasma exposure to nepafenac and amfenac was approximately 70 and 630 times human plasma exposure at the recommended human topical ophthalmic dose for rats and 20 and 180 times human plasma exposure for rabbits, respectively. In rats, maternally toxic doses ≥10 mg/kg were associated with dystocia, increased postimplantation loss, reduced fetal weights and growth, and reduced fetal survival. Nepafenac has been shown to cross the placental barrier in rats. There are no adequate and wellcontrolled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ILEVRO® Suspension should be used pediatric patients below the age of 10 years have not been established. Geriatric Use been observed between elderly and younger patients. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Nepafenac has not been evaluated in long-term carcinogenicity studies. Increased chromosomal aberrations were observed in Chinese hamster ovary cells exposed JOWJUSP to nepafenac suspension. Nepafenac was not mutagenic in the Ames assay or in the mouse lymphoma forward mutation assay. Oral doses up to 5,000 mg/kg did not result in an increase in the formation of micronucleated polychromatic erythrocytes JOWJWP in the mouse micronucleus assay in the bone marrow of mice. Nepafenac did not impair fertility when administered orally to male and female rats at 3 mg/kg. PATIENT COUNSELING INFORMATION Slow or Delayed Healing Patients should be informed of the possibility that slow or delayed healing may occur while using nonsteroidal Avoiding Contamination of the Product Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures because this could cause the tip to become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. Use of the same bottle for both eyes is not recommended with topical eye drops that are used in association with surgery. Contact Lens Wear ILEVRO® Suspension should not be administered while wearing contact lens. Intercurrent Ocular Conditions Patients should be advised that if they develop an intercurrent ocular condition (e.g., trauma, or infection) or have ocular surgery, they should immediately seek their physician’s advice concerning the continued use of the multi-dose container. Concomitant Topical Ocular Therapy If more than one topical ophthalmic medication is being used, the medicines must be administered at least 5 minutes apart. Shake Well Before Use Patients should be instructed to shake well before each use. Released: February 2014 the potential risk to the fetus. U.S. Patent Nos. 5,475,034; 6,403,609; and 7,169,767. ©2016 Novartis 2/16 US-ILV-16-E-0334 biosynthesis inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of ILEVRO® Suspension during late pregnancy should be avoided. WHEN TREATING INFLAMMATION AND PAIN IN YOUR CATARACT SURGERY PATIENTS # POTENCY, PRECISELY WHERE YOU NEED IT 1 Prescribed Branded Ophthalmic NSAID1 ILEVRO® Suspension offers proven efficacy, once-daily postoperative dosing, and affordable access for your patients2-4 INFLAMMATION C O M P L E T E LY CLEARED IN O C U L A R PA I N C O M P L E T E LY R E S O LV E D I N 2 OUT OF 3 >80% PATIENTS AT OF PATIENTS AT 2,3 † 3†‡ DAY14 * • ILEVRO® Suspension should be applied to the affected eye one-time-daily beginning 1 day prior to cataract surgery, continued on the day of surgery and through the first 2 weeks of the postoperative period. An additional drop should be administered 30 to 120 minutes prior to surgery3 POSTOPERATIVE • Use of ILEVRO® Suspension more than 1 day prior to surgery or use beyond 14 days D O S I N G post-surgery may increase patient risk and R E G I M E N3 severity of corneal adverse events3 1x DAILY DAY 14 B R O A D COVERAG E 4 ELIGIBLE COMMERCIAL PAT I E N T S M AY PAY AS LITTLE AS $35 OUT OF POCKET§ To learn more about treating postoperative inflammation and pain with ILEVRO® Suspension, visit myalcon.com/ilevro INDICATIONS AND USAGE ILEVRO® (nepafenac ophthalmic suspension) 0.3% is a nonsteroidal, anti-inflammatory prodrug indicated for the treatment of pain and inflammation associated with cataract surgery. Dosage and Administration One drop of ILEVRO® Suspension should be applied to the affected eye one-time-daily beginning 1 day prior to cataract surgery, continued on the day of surgery and through the first 2 weeks of the postoperative period. An additional drop should be administered 30 to 120 minutes prior to surgery. IMPORTANT SAFETY INFORMATION Contraindications ILEVRO® Suspension is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formula or to other NSAIDs. Warnings and Precautions • Increased Bleeding Time – With some nonsteroidal antiinflammatory drugs including ILEVRO® Suspension there exists the potential for increased bleeding time. Ocularly applied nonsteroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphema) in conjunction with ocular surgery. • Delayed Healing – Topical nonsteroidal anti-inflammatory drugs (NSAIDs) including ILEVRO® Suspension may slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. • Corneal Effects – Use of topical NSAIDs may result in keratitis. In some patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use. Patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface © 2016 Novartis 04/16 US-ILV-16-E-0586 diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Use more than 1 day prior to surgery or use beyond 14 days post-surgery may increase patient risk and severity of corneal adverse events. • Contact Lens Wear – ILEVRO® Suspension should not be administered while using contact lenses. Adverse Reactions The most frequently reported ocular adverse reactions following cataract surgery occurring in approximately 5 to 10% of patients were capsular opacity, decreased visual acuity, foreign body sensation, increased intraocular pressure, and sticky sensation. For additional information about ILEVRO® Suspension, please refer to the brief summary of prescribing information on adjacent page. *With ILEVRO® Suspension versus 24% to 32% with vehicle; P<0.05.3 Results from 2 randomized, multicenter, controlled, double-masked trials of adult patients undergoing cataract extraction. In Study 1, patients were randomized to receive either ILEVRO® Suspension (n=851), NEVANAC® Suspension (n=845), ILEVRO® Suspension vehicle (n=211), or NEVANAC® Suspension vehicle (n=213). In Study 2, patients were randomized to receive either ILEVRO® Suspension (n=540) or ILEVRO® Suspension vehicle (n=268).2,3 ‡ 84% to 86% with ILEVRO® Suspension versus 38% to 46% with vehicle; P<0.05.3 § This offer is not valid for patients who are enrolled in Medicare Part D, Medicaid, Medigap, VA, DOD, Tricare, or any other government-run or government-sponsored health care program with a pharmacy benefit. Additional eligibility terms apply. See copay savings material for specific details. † References: 1. IMS Health Xponent, January 2015-December 2015. Accessed December 2015. 2. Data on file. 3. Ilevro [package insert]. Fort Worth, TX: Alcon Laboratories, Inc; 2014. 4. Fingertip Formulary, October 2015 (estimate derived from information used under license from Fingertip Formulary, LLC, which expressly reserves all rights, including rights of copying, distribution and republication). ® First Extended Depth of Focus IOL LEAVE A LEGACY OF SEAMLESS BRILLIANCE. Start with ME. TECNIS Symfony IOLs and TECNIS Symfony Toric IOLs deliver state-of-the-art presbyopia mitigation and astigmatism correction so you can give your patients a full range of continuous high quality vision at all distances. ® ® Visit us at AAO BOOTH #3808 or learn more at Tecnisiol.com INDICATIONS and IMPORTANT SAFETY INFORMATION for TECNIS SYMFONY and TECNIS SYMFONY TORIC EXTENDED RANGE OF VISION IOLs Rx Only INDICATIONS FOR USEdŚĞdE/^^LJŵĨŽŶLJdžƚĞŶĚĞĚZĂŶŐĞŽĨsŝƐŝŽŶ/K>DŽĚĞůyZϬϬŝƐŝŶĚŝĐĂƚĞĚĨŽƌƉƌŝŵĂƌLJŝŵƉůĂŶƚĂƟŽŶĨŽƌƚŚĞǀŝƐƵĂůĐŽƌƌĞĐƟŽŶŽĨ ĂƉŚĂŬŝĂŝŶĂĚƵůƚƉĂƟĞŶƚƐǁŝƚŚůĞƐƐƚŚĂŶϭĚŝŽƉƚĞƌŽĨƉƌĞ"ĞdžŝƐƟŶŐĐŽƌŶĞĂůĂƐƟŐŵĂƟƐŵŝŶǁŚŽŵĂĐĂƚĂƌĂĐƚŽƵƐůĞŶƐŚĂƐďĞĞŶƌĞŵŽǀĞĚdŚĞůĞŶƐŵŝƟŐĂƚĞƐƚŚĞ ĞīĞĐƚƐŽĨƉƌĞƐďLJŽƉŝĂďLJƉƌŽǀŝĚŝŶŐĂŶĞdžƚĞŶĚĞĚĚĞƉƚŚŽĨĨŽĐƵƐŽŵƉĂƌĞĚƚŽĂŶĂƐƉŚĞƌŝĐŵŽŶŽĨŽĐĂů/K>ƚŚĞůĞŶƐƉƌŽǀŝĚĞƐŝŵƉƌŽǀĞĚŝŶƚĞƌŵĞĚŝĂƚĞĂŶĚŶĞĂƌ ǀŝƐƵĂůĂĐƵŝƚLJǁŚŝůĞŵĂŝŶƚĂŝŶŝŶŐĐŽŵƉĂƌĂďůĞĚŝƐƚĂŶĐĞǀŝƐƵĂůĂĐƵŝƚLJdŚĞDŽĚĞůyZϬϬ/K>ŝƐŝŶƚĞŶĚĞĚĨŽƌĐĂƉƐƵůĂƌďĂŐƉůĂĐĞŵĞŶƚŽŶůLJdŚĞdE/^^LJŵĨŽŶLJ dŽƌŝĐdžƚĞŶĚĞĚZĂŶŐĞŽĨsŝƐŝŽŶ/K>ƐDŽĚĞůƐydϭϱϬydϮϮϱydϯϬϬĂŶĚydϯϳϱĂƌĞŝŶĚŝĐĂƚĞĚĨŽƌƉƌŝŵĂƌLJŝŵƉůĂŶƚĂƟŽŶĨŽƌƚŚĞǀŝƐƵĂůĐŽƌƌĞĐƟŽŶŽĨ ĂƉŚĂŬŝĂĂŶĚĨŽƌƌĞĚƵĐƟŽŶŽĨƌĞƐŝĚƵĂůƌĞĨƌĂĐƟǀĞĂƐƟŐŵĂƟƐŵŝŶĂĚƵůƚƉĂƟĞŶƚƐǁŝƚŚŐƌĞĂƚĞƌƚŚĂŶŽƌĞƋƵĂůƚŽϭĚŝŽƉƚĞƌŽĨƉƌĞŽƉĞƌĂƟǀĞĐŽƌŶĞĂůĂƐƟŐŵĂƟƐŵŝŶ ǁŚŽŵĂĐĂƚĂƌĂĐƚŽƵƐůĞŶƐŚĂƐďĞĞŶƌĞŵŽǀĞĚdŚĞůĞŶƐŵŝƟŐĂƚĞƐƚŚĞĞīĞĐƚƐŽĨƉƌĞƐďLJŽƉŝĂďLJƉƌŽǀŝĚŝŶŐĂŶĞdžƚĞŶĚĞĚĚĞƉƚŚŽĨĨŽĐƵƐŽŵƉĂƌĞĚƚŽĂŶĂƐƉŚĞƌŝĐ ŵŽŶŽĨŽĐĂů/K>ƚŚĞůĞŶƐƉƌŽǀŝĚĞƐŝŵƉƌŽǀĞĚŝŶƚĞƌŵĞĚŝĂƚĞĂŶĚŶĞĂƌǀŝƐƵĂůĂĐƵŝƚLJǁŚŝůĞŵĂŝŶƚĂŝŶŝŶŐĐŽŵƉĂƌĂďůĞĚŝƐƚĂŶĐĞǀŝƐƵĂůĂĐƵŝƚLJdŚĞDŽĚĞů^ĞƌŝĞƐyd /K>ƐĂƌĞŝŶƚĞŶĚĞĚĨŽƌĐĂƉƐƵůĂƌďĂŐƉůĂĐĞŵĞŶƚŽŶůLJWARNINGSWĂƟĞŶƚƐǁŝƚŚĂŶLJŽĨƚŚĞĐŽŶĚŝƟŽŶƐĚĞƐĐƌŝďĞĚŝŶƚŚĞŝƌĞĐƟŽŶƐĨŽƌhƐĞŵĂLJŶŽƚďĞƐƵŝƚĂďůĞ ĐĂŶĚŝĚĂƚĞƐĨŽƌĂŶŝŶƚƌĂŽĐƵůĂƌůĞŶƐďĞĐĂƵƐĞƚŚĞůĞŶƐŵĂLJĞdžĂĐĞƌďĂƚĞĂŶĞdžŝƐƟŶŐĐŽŶĚŝƟŽŶŵĂLJŝŶƚĞƌĨĞƌĞǁŝƚŚĚŝĂŐŶŽƐŝƐŽƌƚƌĞĂƚŵĞŶƚŽĨĂĐŽŶĚŝƟŽŶŽƌŵĂLJ ƉŽƐĞĂŶƵŶƌĞĂƐŽŶĂďůĞƌŝƐŬƚŽƚŚĞƉĂƟĞŶƚ,ƐĞLJĞƐŝŐŚƚ>ĞŶƐĞƐƐŚŽƵůĚŶŽƚďĞƉůĂĐĞĚŝŶƚŚĞĐŝůŝĂƌLJƐƵůĐƵƐDĂLJĐĂƵƐĞĂƌĞĚƵĐƟŽŶŝŶĐŽŶƚƌĂƐƚƐĞŶƐŝƟǀŝƚLJƵŶĚĞƌ ĐĞƌƚĂŝŶĐŽŶĚŝƟŽŶƐĐŽŵƉĂƌĞĚƚŽĂŶĂƐƉŚĞƌŝĐŵŽŶŽĨŽĐĂů/K>0ĨƵůůLJŝŶĨŽƌŵƚŚĞƉĂƟĞŶƚŽĨƚŚŝƐƌŝƐŬďĞĨŽƌĞŝŵƉůĂŶƟŶŐƚŚĞůĞŶƐ^ƉĞĐŝĂůĐŽŶƐŝĚĞƌĂƟŽŶƐŚŽƵůĚďĞ ŵĂĚĞŝŶƉĂƟĞŶƚƐǁŝƚŚŵĂĐƵůĂƌĚŝƐĞĂƐĞĂŵďůLJŽƉŝĂĐŽƌŶĞĂůŝƌƌĞŐƵůĂƌŝƟĞƐŽƌŽƚŚĞƌŽĐƵůĂƌĚŝƐĞĂƐĞ/ŶĨŽƌŵƉĂƟĞŶƚƐƚŽĞdžĞƌĐŝƐĞƐƉĞĐŝĂůĐĂƵƟŽŶǁŚĞŶĚƌŝǀŝŶŐ ĂƚŶŝŐŚƚŽƌŝŶƉŽŽƌǀŝƐŝďŝůŝƚLJĐŽŶĚŝƟŽŶƐ^ŽŵĞǀŝƐƵĂůĞīĞĐƚƐŵĂLJďĞĞdžƉĞĐƚĞĚĚƵĞƚŽƚŚĞůĞŶƐĚĞƐŝŐŶŝŶĐůƵĚŝŶŐ4ĂƉĞƌĐĞƉƟŽŶŽĨŚĂůŽƐŐůĂƌĞŽƌƐƚĂƌďƵƌƐƚƐ ĂƌŽƵŶĚůŝŐŚƚƐƵŶĚĞƌŶŝŐŚƫŵĞĐŽŶĚŝƟŽŶƐdŚĞƐĞǁŝůůďĞďŽƚŚĞƌƐŽŵĞŽƌǀĞƌLJďŽƚŚĞƌƐŽŵĞŝŶƐŽŵĞƉĞŽƉůĞƉĂƌƟĐƵůĂƌůLJŝŶůŽǁ"ŝůůƵŵŝŶĂƟŽŶĐŽŶĚŝƟŽŶƐĂŶĚ ŽŶƌĂƌĞŽĐĐĂƐŝŽŶƐŵĂLJďĞƐŝŐŶŝĮĐĂŶƚĞŶŽƵŐŚƚŚĂƚƚŚĞƉĂƟĞŶƚŵĂLJƌĞƋƵĞƐƚƌĞŵŽǀĂůŽĨƚŚĞ/K>ZŽƚĂƟŽŶŽĨƚŚĞdĞĐŶŝƐ^LJŵĨŽŶLJdŽƌŝĐ/K>ƐĂǁĂLJĨƌŽŵƚŚĞŝƌ ŝŶƚĞŶĚĞĚĂdžŝƐĐĂŶƌĞĚƵĐĞƚŚĞŝƌĂƐƟŐŵĂƟĐĐŽƌƌĞĐƟŽŶĂŶĚŵŝƐĂůŝŐŶŵĞŶƚग़ϯϬΣŵĂLJŝŶĐƌĞĂƐĞƉŽƐƚŽƉĞƌĂƟǀĞƌĞĨƌĂĐƟǀĞĐLJůŝŶĚĞƌ/ĨŶĞĐĞƐƐĂƌLJůĞŶƐƌĞƉŽƐŝƟŽŶŝŶŐ ƐŚŽƵůĚŽĐĐƵƌĂƐĞĂƌůLJĂƐƉŽƐƐŝďůĞƉƌŝŽƌƚŽůĞŶƐĞŶĐĂƉƐƵůĂƟŽŶPRECAUTIONS/ŶƚĞƌƉƌĞƚƌĞƐƵůƚƐǁŝƚŚĐĂƵƟŽŶǁŚĞŶƌĞĨƌĂĐƟŶŐƵƐŝŶŐĂƵƚŽƌĞĨƌĂĐƚŽƌƐŽƌǁĂǀĞĨƌŽŶƚ ĂďĞƌƌŽŵĞƚĞƌƐƚŚĂƚƵƟůŝnjĞŝŶĨƌĂƌĞĚůŝŐŚƚŽƌǁŚĞŶƉĞƌĨŽƌŵŝŶŐĂĚƵŽĐŚƌŽŵĞƚĞƐƚŽŶĮƌŵĂƟŽŶŽĨƌĞĨƌĂĐƟŽŶǁŝƚŚŵĂdžŝŵƵŵƉůƵƐŵĂŶŝĨĞƐƚƌĞĨƌĂĐƟŽŶƚĞĐŚŶŝƋƵĞ ŝƐƌĞĐŽŵŵĞŶĚĞĚdŚĞĂďŝůŝƚLJƚŽƉĞƌĨŽƌŵƐŽŵĞĞLJĞƚƌĞĂƚŵĞŶƚƐ;ĞŐƌĞƟŶĂůƉŚŽƚŽĐŽĂŐƵůĂƟŽŶAŵĂLJďĞĂīĞĐƚĞĚďLJƚŚĞŽƉƟĐĂůĚĞƐŝŐŶdĂƌŐĞƚĞŵŵĞƚƌŽƉŝĂĨŽƌ ŽƉƟŵƵŵǀŝƐƵĂůƉĞƌĨŽƌŵĂŶĐĞĂƌĞƐŚŽƵůĚďĞƚĂŬĞŶƚŽĂĐŚŝĞǀĞ/K>ĐĞŶƚƌĂƟŽŶĂƐůĞŶƐĚĞĐĞŶƚƌĂƟŽŶŵĂLJƌĞƐƵůƚŝŶĂƉĂƟĞŶƚĞdžƉĞƌŝĞŶĐŝŶŐǀŝƐƵĂůĚŝƐƚƵƌďĂŶĐĞƐ ƵŶĚĞƌĐĞƌƚĂŝŶůŝŐŚƟŶŐĐŽŶĚŝƟŽŶƐ&ŽƌƚŚĞdĞĐŶŝƐ^LJŵĨŽŶLJdŽƌŝĐ/K>ǀĂƌŝĂďŝůŝƚLJŝŶĂŶLJƉƌĞŽƉĞƌĂƟǀĞƐƵƌŐŝĐĂůƉĂƌĂŵĞƚĞƌƐ;ĞŐŬĞƌĂƚŽŵĞƚƌŝĐĐLJůŝŶĚĞƌŝŶĐŝƐŝŽŶ ůŽĐĂƟŽŶƐƵƌŐĞŽŶ,ƐĞƐƟŵĂƚĞĚƐƵƌŐŝĐĂůůLJŝŶĚƵĐĞĚĂƐƟŐŵĂƟƐŵĂŶĚďŝŽŵĞƚƌLJAĐĂŶŝŶŇƵĞŶĐĞƉĂƟĞŶƚŽƵƚĐŽŵĞƐĂƌĞĨƵůůLJƌĞŵŽǀĞĂůůǀŝƐĐŽĞůĂƐƟĐĂŶĚĚŽŶŽƚ ŽǀĞƌ"ŝŶŇĂƚĞƚŚĞĐĂƉƐƵůĂƌďĂŐĂƚƚŚĞĞŶĚŽĨƚŚĞĐĂƐĞƚŽƉƌĞǀĞŶƚůĞŶƐƌŽƚĂƟŽŶSERIOUS ADVERSE EVENTS dŚĞŵŽƐƚĨƌĞƋƵĞŶƚůLJƌĞƉŽƌƚĞĚƐĞƌŝŽƵƐĂĚǀĞƌƐĞ ĞǀĞŶƚƐƚŚĂƚŽĐĐƵƌƌĞĚĚƵƌŝŶŐƚŚĞĐůŝŶŝĐĂůƚƌŝĂůŽĨƚŚĞdĞĐŶŝƐ^LJŵĨŽŶLJůĞŶƐǁĞƌĞĐLJƐƚŽŝĚŵĂĐƵůĂƌĞĚĞŵĂ;ϮĞLJĞƐϬϳйAĂŶĚƐƵƌŐŝĐĂůƌĞŝŶƚĞƌǀĞŶƟŽŶ;ƚƌĞĂƚŵĞŶƚ ŝŶũĞĐƟŽŶƐĨŽƌĐLJƐƚŽŝĚŵĂĐƵůĂƌĞĚĞŵĂĂŶĚĞŶĚŽƉŚƚŚĂůŵŝƟƐϮĞLJĞƐϬϳйAEŽůĞŶƐ"ƌĞůĂƚĞĚĂĚǀĞƌƐĞĞǀĞŶƚƐŽĐĐƵƌƌĞĚĚƵƌŝŶŐƚŚĞƚƌŝĂůATTENTION Reference ƚŚĞŝƌĞĐƟŽŶƐĨŽƌhƐĞĨŽƌĂĐŽŵƉůĞƚĞůŝƐƟŶŐŽĨ/ŶĚŝĐĂƟŽŶƐĂŶĚ/ŵƉŽƌƚĂŶƚ^ĂĨĞƚLJ/ŶĨŽƌŵĂƟŽŶ dE/^ĂŶĚdE/^^zD&KEzĂƌĞƚƌĂĚĞŵĂƌŬƐŽǁŶĞĚďLJŽƌůŝĐĞŶƐĞĚƚŽďďŽƩ>ĂďŽƌĂƚŽƌŝĞƐŝƚƐƐƵďƐŝĚŝĂƌŝĞƐŽƌĂĸůŝĂƚĞƐ ΞϮϬϭϲďďŽƩDĞĚŝĐĂůKƉƟĐƐ/ŶĐOǁǁǁďďŽƩDĞĚŝĐĂůKƉƟĐƐĐŽŵOWWϮϬϭϲdϭϭϰϲ