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CUTTING-EDGE ADVANCEMENTS CLINICAL DIAGNOSIS OphthalmologyTimes.com FOLLOW US ONLINE: Drug Therapy RETINAL GENE THERAPY ENTERING CLINICAL REALITY SURGERY April 15, 2015 VOL. 40, NO. 7 DRUG THERAPY Take second look at Endophthalmitis Surgeons’ ability to reduce its rate, understand risk factors grows as population at risk expands IN VIEW: Hypoyon in the eye of a patient with acute bacterial endophthalmitis complicating cataract extraction. ALACHUA, FL :: MANY DISEASES have a genetic aspect whereby a mutated gene is passed down from generation to generation. Mutated genes may encode abnormal proteins or disable the production of a protein completely, either of which can cause disease. Gene therapy introduces a functional copy of the gene into a patient’s own cells. By correcting the underlying genetic defect that causes disease, gene therapy can potentially provide lifelong clinical benefits after a single administration, according to Jeffrey D. Chulay, MD. (Image courtesy of Peter J. McDonnell, MD) ( See story on page 23 : Gene therapy ) Clinical Diagnosis WHY CONTRAST SENSITIVITY IS MORE THAN VISION METRIC CONTRAST sensitivity is a more valuable metric than many ophthalmologists realize, with applications in preoperative and postoperative management of corneal and refractive surgery patients and routine screening of patients’ quality of vision. Contrast sensitivity has perhaps been underused in ophthalmology practices despite the wealth of data on its application in various procedures, according to Gregory J. Pamel, MD, and Prof. Dan Reinstein, MD, FRCSC. ( See story on page 56 : Contrast ) By Stephanie Skernivitz; Reviewed by Oliver D. Schein, MD, MPH by 2020 and almost triple by 2030,” he said. “You’ll be busy—you may not be paid for it, but you will be busy taking care of patients with cataracts.” BALT IMORE :: IN THE UNITED STATES, the moderately rare condition endophthalmitis impacts 1 case per 1,100 cataract surgeries. The question may surface: Why should physicians care with a rate that is so low? “For one, the population at risk is expanding,” explained Oliver D. Schein, MD, MPH, Grossman Professor of Ophthalmology, vice chairman for quality and safety, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore. With several risk factors—though many are not modifiable—there are strategies to counter the risk factors that really make a difference, Dr. Schein said. “If you apply the current cataract surgical rate to the projected age distribution of our population, the number of cataract surgeries will at least double WHAT HAS CHANGED? The disease itself has not changed in any way, but ophthalmologists’ ability to reduce its rate and understand its risk factors has grown substantially, Dr. Schein noted. He addressed acute endophthalmitis that occurs within the first week or so of cataract surgery. Virtually all (95% plus), according to Dr. Schein, are gram positive. “We either let these organisms in during surgery or they get in [during] the first 12 to 24 hours,” he said. The rate of the condition has varied according to results of various studies in Europe and the United States, including trials from Denmark and the Netherlands. ( Continues on page 34 : Second look ) CUTTING-EDGE ADVANCEMENTS CLINICAL DIAGNOSIS OphthalmologyTimes.com FOLLOW US ONLINE: Drug Therapy RETINAL GENE THERAPY ENTERING CLINICAL REALITY SURGERY April 15, 2015 VOL. 40, NO. 7 DRUG THERAPY Take second look at Endophthalmitis Surgeons’ ability to reduce its rate, understand risk factors grows as population at risk expands IN VIEW: Hypoyon in the eye of a patient with acute bacterial endophthalmitis complicating cataract extraction. ALACHUA, FL :: MANY DISEASES have a genetic aspect whereby a mutated gene is passed down from generation to generation. Mutated genes may encode abnormal proteins or disable the production of a protein completely, either of which can cause disease. Gene therapy introduces a functional copy of the gene into a patient’s own cells. By correcting the underlying genetic defect that causes disease, gene therapy can potentially provide lifelong clinical benefits after a single administration, according to Jeffrey D. Chulay, MD. (Image courtesy of Peter J. McDonnell, MD) ( See story on page 23 : Gene therapy ) Clinical Diagnosis WHY CONTRAST SENSITIVITY IS MORE THAN VISION METRIC CONTRAST sensitivity is a more valuable metric than many ophthalmologists realize, with applications in preoperative and postoperative management of corneal and refractive surgery patients and routine screening of patients’ quality of vision. Contrast sensitivity has perhaps been underused in ophthalmology practices despite the wealth of data on its application in various procedures, according to Gregory J. Pamel, MD, and Prof. Dan Reinstein, MD, FRCSC. ( See story on page 56 : Contrast ) By Stephanie Skernivitz; Reviewed by Oliver D. Schein, MD, MPH by 2020 and almost triple by 2030,” he said. “You’ll be busy—you may not be paid for it, but you will be busy taking care of patients with cataracts.” BALT IMORE :: IN THE UNITED STATES, the moderately rare condition endophthalmitis impacts 1 case per 1,100 cataract surgeries. The question may surface: Why should physicians care with a rate that is so low? “For one, the population at risk is expanding,” explained Oliver D. Schein, MD, MPH, Grossman Professor of Ophthalmology, vice chairman for quality and safety, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore. With several risk factors—though many are not modifiable—there are strategies to counter the risk factors that really make a difference, Dr. Schein said. “If you apply the current cataract surgical rate to the projected age distribution of our population, the number of cataract surgeries will at least double WHAT HAS CHANGED? The disease itself has not changed in any way, but ophthalmologists’ ability to reduce its rate and understand its risk factors has grown substantially, Dr. Schein noted. He addressed acute endophthalmitis that occurs within the first week or so of cataract surgery. Virtually all (95% plus), according to Dr. Schein, are gram positive. “We either let these organisms in during surgery or they get in [during] the first 12 to 24 hours,” he said. The rate of the condition has varied according to results of various studies in Europe and the United States, including trials from Denmark and the Netherlands. ( Continues on page 34 : Second look ) FDA APPROVED IS THE TIME TO PREVENT INTRAOPERATIVE MIOSIS AND REDUCE POSTOPERATIVE OCULAR PAIN OMIDRIA™ (phenylephrine and ketorolac injection) 1% / 0.3% is the first and only FDA-approved treatment that both1: Preemptively inhibits intraoperative miosis Decreases postoperative ocular pain for 10 to 12 hours Easy to integrate into routine operating procedures Add preoperatively to irrigation solution One 4-mL single-patient-use vial to 500 mL1 Can be added to irrigation solution in the surgical suite No other preparation required 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. OMIDRIA™ IS NOW AVAILABLE TO ORDER NDC#: 62225-600-04 Unit quantity: One (1) carton contains four (4) single-patient-use vials OMIDRIA is reimbursed by CMS For ordering information or for live reimbursement support for OMIDRIA, contact 1-844-OMEROS1 (1-844-663-7671), or visit www.omidria.com. IMPORTANT SAFETY INFORMATION OMIDRIA 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 non-steroidal anti-inflammatories (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. Please see the Full Prescribing Information for OMIDRIA at www.omidria.com/prescribinginformation. You are encouraged to report Suspected Adverse Reactions to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Reference: 1. OMIDRIA [package insert]. Seattle, WA: Omeros Corporation; 2014. Omeros® and the Omeros logo® are registered trademarks, and Omidria™ and the Omidria logo™ are trademarks, of Omeros Corporation. © Omeros Corporation 2015, all rights reserved. 2015-062 4 APRIL 15, 2015 contents 8 62 36 52 Meeting Preview Clinical Diagnosis Practice Management 8 ARVO 2015 MAKING POWERFUL CONNECTIONS 58 YIN-YANG OF OPIOID GROWTH REGULATORY SYSTEM 78 MOVING EHR BEYOND CLINICAL PRACTICE New Saturday session focuses on vision, traumatic brain injury in veterans and athletes In Every Issue 6 EDITORIAL What’s Trending See what the ophthalmic community is reading on OphthalmologyTimes.com 1 In defense of Sen. Rand Paul http://bit.ly/1GNrpfv 2 A cautionary surgical tale http://bit.ly/186lEKD Gene therapy link shows promise for epithelial wound healing, corneal sensitivity, dry eye 66 FOCAL POINT Digital App Vendors cater to needs of ASC with software that increases efficiency, quality of care, profits 75 MARKETPLACE Video Introducing the Ophthalmology Times app for iPad and iPhone. Download it for free today at OphthalmologyTimes. com/OTapp. 3 When a doctor is at the center of a political scandal http://bit.ly/1C4BEuT 4 Managing the dissatisfied multifocal IOL patient http://bit.ly/18y0wNP eReport Sign up for Ophthalmology Times’ weekly eReport at http:// bit.ly/XjksXX. To watch a phacotrabeculectomy surgical video, go to http://bit.ly/1rOQAED (Video courtesy of Ronald L. Fellman, MD) Facebook Like Ophthalmology Times at Facebook.com/OphthalmologyTimes CATARACT SURGERY SO POWERFUL IT CAN EVEN HELP YOU SEE THE FUTURE Visit Us At Booth # 2622 LENS EXTRACTION CATALYS® PRECISION LASER SYSTEM & WHITESTAR SIGNATURE® SYSTEM It’s tough to make capital investments in the middle of a technology evolution. How do you choose the platform that prepares you for the future of cataract surgery? Consider this: the CATALYS® Precision Laser System offers precise incisions and complete cataract segmentation and softening.1 The WHITESTAR SIGNATURE® Phacoemulsification System provides switch-on-the-fly transition between peristaltic and venturi pump modalities, for true low-energy lens extraction.2 Let the future come; you’ll be ready. Plan your future in lens extraction at ExtractTheFuture.com INDICATIONS AND IMPORTANT SAFETY INFORMATION for the CATALYS® Precision Laser System and WHITESTAR SIGNATURE® System Reference the labeling for a complete listing of Indications and Important Safety Information. CAUTION: Federal law restricts these devices to sale by or on order of a physician. CATALYS® Precision Laser System INDICATIONS: The CATALYS® System is indicated for use in patients undergoing cataract surgery for removal of the crystalline lens. Intended uses in cataract surgery include anterior capsulotomy, phacofragmentation, and the creation of single-plane and multi-plane arc cuts/incisions in the cornea, each of which may be performed either individually or consecutively during the same procedure. CONTRAINDICATIONS: Should not be used in patients with corneal ring and/or inlay implants, severe corneal opacities, corneal abnormalities, significant corneal edema or diminished aqueous clarity that obscures OCT imaging of the anterior lens capsule, patients younger than 22 years of age, descemetocele with impending corneal rupture, and any contraindications to cataract surgery. ADVERSE EFFECTS: Complications include mild Petechiae and subconjunctival hemorrhage due to vacuum pressure of the LIQUID OPTICS Interface suction ring. Potential complications and adverse events include those generally associated with the performance of capsulotomy and lens fragmentation, or creation of a partial-thickness or full-thickness cut or incision of the cornea. CAUTION: Should be used only by qualified physicians who have extensive knowledge of the use of this device and have been trained and certified by Abbott Medical Optics/OptiMedica. WHITESTAR SIGNATURE® System INDICATIONS: The WHITESTAR SIGNATURE® System incorporating FUSION® Fluidics is a modular ophthalmic microsurgical system that facilitates anterior segment (cataract) ophthalmic surgery. The modular design allows the users to configure the system to meet their surgical requirements. WARNINGS: Risks and complications of cataract surgery may include broken ocular capsule or corneal burn. This device is only to be used by a trained licensed physician. 1. Conrad-Hengerer et al. J Cat Refract Surg. 2012; Conrad-Hengerer et al, JCRS 2012; 38(11): 1888-94. 2. Fabian E et al. New Phaco Fluidics Control: Case to Prevent Surge. Presented at ESCRS, Sept 2006, London, U.K. WHITESTAR SIGNATURE, CATALYS, LIQUID OPTICS and FUSION are trademarks owned by or licensed to Abbott Laboratories, its subsidiaries or affiliates. © 2015 Abbott Medical Optics Inc. www.AbbottMedicalOptics.com PP2015CT0141 6 APRIL 15, 2015 :: Ophthalmology Times editorial APRIL 15, 2015 ◾ VOL. 40, NO. 7 CONTENT Ronald McDonald for Surgeon General Building ‘golden arches’ in the fight against antibiotic-fed animals 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] ONCE AGAIN, IT WAS A CHILLY winter in the Mid-Atlantic and Northeastern regions of our fair land. And once again, I ask myself why all ophthalmologists haven’t moved to Southern California or southern Florida (as opposed to only 95% of them). As I write this, two of my family members are on antibiotics for sinusitis and other sequelae from the waning cold and flu season. Within 24 hours of starting their medicines, their symptoms were noticeably improved. Fortunately, no resistant organisms here. Antibiotic-resistant “super bugs,” however, are frequently mentioned in the lay press. The Centers for Disease Control and Prevention says that at least 2 million people become infected each year in the United States, and at least 23,000 die as the direct result of these infections. Many more die from other conditions complicated by an antibiotic-resistant infection.1 Although other countries have the same problem, the magnitude is substantially greater in the United States. Antibiotic resistance may relate to overuse of antibiotics by physicians in patients with viral illnesses. The major culprit is thought by many to be use of these drugs in farming. Staggering amounts are used not as treatment of infected animals, but as prophylaxis in feed and drinking water to encourage faster growth of larger animals. For every antibiotic prescription written for a human being in our country, the rough equivalent of a dump truck full of antimicrobials is being used on our farms. In most other countries of the world, antibiotic usage in healthy animals is either discouraged and limited or specifically banned. Many experts cite this as the key reason why patients in those nations experience fewer infections with super bugs. Recently, McDonald’s announced it would stop purchasing chickens treated with antibiotics commonly used in humans. Because this purveyor of fast food buys an estimated 3% to 4% of all chicken produced in the United States, the decision is expected to put pressure on the industry overall to remove these drugs from the diets of their fowl. “This is a landmark announcement in the fight to keep life-saving antibiotics working for us and our children,” said Jonathan Kaplan, director of the Natural Resources Defense Council.2 SOLID PL A N OF ACTION Time will prove whether this decision has a measurable beneficial impact on public health on the United States. If it does, I think we are led to only one reasonable plan of action. In a room full of physicians, I asked each if he or she could name the Surgeon General of the United States. All respondents said they did not know the name; one asked whether we even have a surgeon general now. “Who is the last surgeon general whose name you can remember?” I asked. One physician in the room thought of C. Everett Koop, MD, whereas another could recall the name of Jocelyn Elders, MD. My concern is this person is intended to be “the leading spokesperson on matters of public health in the federal government of the United States.” Yet, very few physicians in the United States know whether we have one—or can even name the person, let alone articulate what he or she has done to improve public health. Hence, my proposal: If this ban on antibiotic-fed chicken results in fewer infections and deaths from resistant organisms, I nominate Ronald McDonald (no relation) for Surgeon General. Q 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 Rose Schneider [email protected] 440/891-2707 Group Art Director Robert McGarr 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. Jay Wisnicki, MD The Glaucoma Angle Malik Y. Kahook, MD Uveitis Update Emmett T. 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Ext. 121 List Account Executive Renée Schuster [email protected] 440/891-2613 Permissions/International Licensing Maureen Cannon [email protected] 440/891-2742 PRODUCTION Senior Production Manager Karen Lenzen AUDIENCE DEV ELOPMEN T Corporate Director Joy Puzzo Director Christine Shappell Manager Tammy Sundbom-Otterson UBM Advanstar Chief Executive Officer: Joe Loggia Executive Vice-President, Life Sciences: Tom Ehardt Executive Vice-President: Georgiann DeCenzo Executive Vice-President: Chris DeMoulin Executive Vice-President, Business Systems: Rebecca Evangelou Executive Vice-President, Human Resources: Julie Molleston Executive Vice-President, Strategy & Business Development: Mike Alic Sr Vice-President: Tracy Harris Vice-President, General Manager Pharm/Science Group: Dave Esola Vice-President, Legal: Michael Bernstein Vice-President, Media Operations: Francis Heid Vice-President, Treasurer & Controller: Adele Hartwick UBM Americas Chief Executive Officer: Sally Shankland Chief Operating Officer: Brian Field Chief Financial Officer: Margaret Kohler UBM plc Chief Executive Officer: Tim Cobbold Group Operations Director: Andrew Crow Chief Financial Officer: Robert Gray Chairman: Dame Helen Alexander UBM Advanstar provides certain customer contact data (such as customers’ names, References 1. www.cdc.gov/drugresistance/threat-report-2013 2. McDonald’s to ban chicken treated with human antibiotics. USA Today. March 5, 2015. addresses, phone numbers, and e-mail addresses) to third parties who wish to promote relevant products, services, and other opportunities that may be of interest to you. If you do not want UBM Advanstar to make your contact information available to third parties for marketing purposes, simply call toll-free 866-529-2922 between the hours of 7:30 a.m. and 5 p.m. CST and a customer service representative will assist you in removing your name from UBM Advanstar’s lists. Outside the U.S., please phone 218-740-6477. Ophthalmology Times does not verify any claims or other information appearing in any of the advertisements contained in the publication, and cannot take responsibility for any losses or other damages incurred by readers in reliance of such content. Ophthalmology Times cannot be held responsible for the safekeeping or return of unsolicited articles, manuscripts, photographs, illustrations or other materials. Ophthalmology Times is a member of the Association of Independent Clinical Publications Inc. Library Access Libraries offer online access to current and back issues of Ophthalmology Times through the EBSCO host databases. To subscribe, call toll-free 888-527-7008. Outside the U.S. call 218-740-6477. PRINTED IN U.S.A. APRIL 15, 2015 2014 :: Ophthalmology Times 7 editorial advisory board 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 University of Minnesota, Minneapolis, MN Uday Devgan, 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. Joel Schuman, MD Peter S. Hersh, MD University of Pittsburgh Medical Center Pittsburgh, PA University of Medicine & Dentistry of New Jersey Newark, NJ 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 Jules Stein Eye Institute,UCLA Los Angeles, CA Hamilton Glaucoma Center University of California, San Diego Richard S. Hoffman, MD Neuro-Ophthalmology Oregon Health & Science University Portland, OR Andrew G. Lee, MD Samuel Masket, MD Methodist Hospital, Texas Medical Center Houston, TX Jules Stein Eye Institute,UCLA Los Angeles, CA Oculoplastics/ Reconstructive Surgery Bartly J. Mondino, MD Jules Stein Eye Institute,UCLA Los Angeles, CA Robert Goldberg, MD Mark Packer, MD Bowie, MD Jules Stein Eye Institute, UCLA Los Angeles, CA Michael Raizman, MD John T. LiVecchi, MD Massachusetts Eye & Ear, Harvard University Boston, MA Ehsan “Ethan” Sadri, MD, FACS Newport Beach, CA St. Luke’s Cataract & Laser Institute Tarpon Springs, FL Shannath L. Merbs, MD Wilmer Eye Institute, Johns Hopkins University Baltimore, MD Michael Snyder, MD Cincinnati Eye Institute Cincinnati, OH Pediatric Ophthalmology Retina/Vitreous Stanley Chang, MD Columbia University New York, NY David Chow, MD Pravin U. Dugel, MD Phoenix, AZ Sharon Fekrat, MD Duke University Durham, NC Wills Eye Institute, Thomas Jefferson University Philadelphia, PA Farrell “Toby” Tyson, MD Jennifer Simpson, MD Carl D. Regillo, MD Cape Coral, FL University of California, Irvine Irvine, CA Wills Eye Institute, Thomas Jefferson University Philadelphia, PA H. Jay Wisnicki, MD Lawrence J. Singerman, MD University of Toronto Toronto, Canada Malik Kahook, MD University of Colorado,Denver Denver, CO Richard K. Parrish II, MD New York Eye & Ear Infirmary, Beth Israel Medical Case Western Reserve University Center, Albert Einstein College of Medicine Cleveland, OH New York, NY Practice Management Joseph C. Noreika, MD Medina, OH Uveitis Emmett T. Cunningham Jr., MD, PhD Stanford University Stanford, CA Frank Weinstock, MD Chief Medical EditorsEmeritus Boca Raton, FL Refractive Surgery 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 David R. Guyer, MD New York, NY New York, NY (1996–2004) Ophthalmology Times Industry Council John Bee Bob Gibson Chris Thatcher Rhein Medical Inc. President and CEO Topcon Medical Systems Inc. Vice President of Marketing Alastair Douglas Aziz Mottiwala Reichert Technologies Division Vice President and Reichert Business Unit Manager Alcon Laboratories Inc. Director of U.S. Commercial Support Allergan Vice President of Marketing, U.S. Eye Care to Subscription Services Advertising 24950 Country Club Blvd., Toll-Free: 888/527-7008 or 218/740-6477 Suite 200 North Olmsted, OH 44070-5351 FAX: 218/740-6417 440/243-8100 FAX: 440/756-5227 485 Route 1 South Building F, Suite 210, Iselin, NJ 08830-3009 732/596-0276 FAX: 732/596-0003 n de l Fo Di n -E Do m Fe 4 14 10 8- The Folden Femto Dissector Is A Single Instrument Designed For Smooth Opening Of All Femtosecond Laser – Created Corneal Incisions During Cataract Surgery. The Double-Ended Instrument Measures 0.7mm At One End, And 1.2mm At The Other. The Polished, Semi-Blunted Leading Tip Allows For “Scoring” Of The Epithelium And Provides Easy, Glided Entry Into The Femtosecond Laser – Created Corneal Incision. The Unique Sharp Edge Design Cleanly Separates Residual Tissue Bridges And Stromal Adhesions That Provide Resistance To Entry Using Standard Instruments. s #LEAR#ORNEAL)NCISIONS##)34HEMM%ND0ROVIDES%ASY %NTRY)NTO3TANDARD3MALL)NCISIONS!S7ELL!S3UBMM -ICRO)NCISIONS 4HE MM %ND 0ROVIDES !MPLE #LEARANCE &OR%NTRY)NTO4HE0ARACENTESIS s ! R C U A T E ) N C I S I O N S ! ) 3 ! R C U A T E ) N C I S I O N S & O R !STIGMATISM!RE/PENED1UICKLY!ND#LEANLY$OWN4O4HEIR "ASE 7ITHOUT 2ISK /F 0ERFORATION 4HE 0OLISHED 3EMI "LUNTED ,EADING 4IP 'LIDES 3MOOTHLY !LONG 4HE "ASE /F 4HE!RCUATE)NCISION7HILE4HE3HARP%DGE0ROVIDES3MOOTH /PENING /F 3TROMAL 4ISSUE "RIDGES !ND -AINTAINS #LEAN %PITHELIAL %DGES &EWER 3URFACE !BRASIONS 2ESULT )N ,ESS &OREIGN "ODY 3ENSATION !ND )MPROVED 0ATIENT #OMFORT 0OSTOPERATIVELY 0LEASE7ATCH4HE6IDEO/R#ONTACT &OR-ORE)NFORMATION How to Contact Ophthalmology Times Editorial c se le ub University of Wisconsin Madison, WI Keck School of Medicine, USC Los Angeles, CA Neeru Gupta, MD d de Michael Ip, MD Albert Einstein College of Medicine Bronx, NY 1. s Oakland University Rochester, MI Wilmer Eye Institute, Johns Hopkins University Baltimore, MD & m .7 0 r, m to Tarek S. Hassan, MD Carmen A. Puliafito, MD University of Medicine & Dentistry of New Jersey Newark, NJ m 2m Julia Haller, MD Norman B. Medow, MD Glaucoma The Folden* Femto Double-Ended Dissector University of Toronto Toronto, Canada Walter J. Stark, MD Robert D. Fechtner, MD 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. Randall Olson, MD University of Cincinnati Cincinnati, OH Anterior Segment/Cataract Cornea/External Disease Ophthalmology Times Mission Statement #OME3EE5S!T!3#23"OOTH.O Production 131 W. First St. Duluth, MN 55802-2065 800/346-0085 FAX: 218/740-7223, 218/740-6576 3360 Scherer Drive, Suite B, St. Petersburg, FL 33716 s4ELs&AX %MAIL)NFO 2HEIN-EDICALCOMs7EBSITEWWW2HEIN-EDICALCOM $EVELOPED)N#OORDINATION7ITH$AVID&OLDEN-$ 1360 Rev.A ,AMENTATION-ICHELANGELO ACBF 8 APRIL 15, 2015 :: Ophthalmology Times meeting preview ARVO 2015: Making powerful connections in research New Saturday session focuses on vision, traumatic brain injury in veterans and athletes ARVO View By Katrina Norfleet TAKE-HOME More than 11,000 clinicians and researchers will gather in Denver to learn more about leading eye and vision research at the 2015 meeting of the Association for Research in Vision and Ophthalmology. ARVO at the Colorado Convention Center in Denver from May 3-7 DENVER :: he Association for Research in Vision and Ophthalmology (ARVO) is weeks away from hosting its 2015 annual meeting in Denver—where more than 11,000 attendees from more than 75 countries are expected to gather May 3 to 7 under the theme, “Powerful Connections: Vision Research and Online Networking.” Starting with a Sunday keynote address by Gary Shapiro, president and CEO of Consumer Electronics Association, ARVO will explore how online networking is changing the way clinicians communicate, collaborate, and conduct research. Attendees will discover and discuss the increasing importance of these networks in exchanging ideas, promoting scientific discourse, sharing discoveries, building global collaborations, and advancing careers. T NEW THIS YEAR: A SAT UR DAY SESSION athletes and combat veterans, and > Experimental models of impact and blast neurotrauma: implications for ophthalmology and vision research This session, free and open to the public, will address the interface between traumatic brain injury (TBI) and visual function. Learn about the research that is uncovering important similarities between military blast TBIrelated visual dysfunction and ocular pathology resulting from sports-related head injuries. Following an introduction by Rep. Diana DeGette (D-CO), four of the field’s most prominent researchers will discuss: > Retinal pathology in chronic traumatic Vision and Traumatic Brain Injury in Veterans and Athletes > Visual sensory impairments and progression Saturday, May 2, 10 a.m. to noon following mild TBI, encephalopathy, Plus, attendees will hear from a panel of blinded veterans affected by TBI and visual disorders. A R V O /A L C O N K E Y N O T E S E R I E S Ninja Innovation – Where Technology is Taking Us Sunday, May 3, Noon to 1:15 p.m. Shapiro—head of the largest technology trade association in the United States—will share with attendees the next trends in technology and their implications for health, lifestyle, privacy, and safety. Shapiro will also describe coming changes in display technology. Attendees also should learn how these changes might affect your practice. Continues on page 10 : ARVO photos courtesy Scott Dressel-Martin and VISIT DENVER NEED CME UNITS? ARVO is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Physicians can choose from more than 130 CME-approved activities. The maximum amount of credit attendees can earn is 31.25 AMA PRA Category 1 Credits. To view the complete ARVO 2015 CME program, visit arvo.org/cme. > Afferent visual function in veterans with TBI, > TBI and chronic traumatic encephalopathy in LET’S KEEP SOMETHING STRAIGHT ABOUT AREDS2 Only PreserVision® AREDS 2 Formula contains the exact ingredient dosages recommended by the National Eye Institute† based on the evidence from the AREDS2 study.1,2* Get patient samples and education materials at 1-844-BL-VITES. † For patients with moderate to advanced age-related macular degeneration. *This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. PreserVision. Exactly. References: 1. Yong JJ, Scott IU, and Greenberg PB. Ocular nutritional supplements. Ophthalmology. 2014:1-5. 2. Chew EY, Clemens TE, SanGiovanni JP, et al. Lutein and zeaxanthin and omega-3 fatty acids for age-related macular degeneration. JAMA. 2013;309(19):1-11. PreserVision is a trademark of Bausch & Lomb Incorporated or its affiliates. AREDS2 is a registered trademark of the United States Department of Health and Human Services (HHS). ©2015 Bausch & Lomb Incorporated. PREV-56994 US/PV2/15/0006a SEE BETTER. LIVE BETTER. 10 APRIL 15, 2015 :: Ophthalmology Times meeting preview ARVO ( Continued from page 8 ) vascular mechanisms involving the vasculatures of the retina, hyaloid and choroid, and six associated diseases in order to expand and broaden the understanding of neurovascular interactions in the posterior eye. Champalimaud Vision Award Lecture Joan Miller, MD, FARVO and Napoleone Ferrara, MD Tuesday, May 5, 5:45 p.m. to 7 p.m. Thursday, May 7, 1:55 p.m. to 3:15 p.m. Dr. Miller and Dr. Ferrara—two of the seven ARVO members named as the recipients of the 2014 Antonio Champalimaud Vision Award—will present on their pioneering work to treat age-related macular degeneration and diabetic retinopathy. Dr. Miller will present on the topic, “VEGF: From Discovery to Therapy.” Dr. Ferrara’s presentation is titled, “Discovery of VEGF-A, a Key Regulator of Intraocular Neovascularization.” The 2014 Champalimaud recipients are: > NAPOLEONE FERRARA, MD — University of Ian Crozier, MD, an infectious disease specialist, was living in Uganda where he was teaching physicians and providing care for patients with HIV/AIDS, when the Ebola outbreak began in West Africa. He signed on with the World Health Organization and arrived in Kenema, Sierra Leone to help in the fight against the outbreak in August 2014. Within a few weeks, he himself contracted the disease and was evacuated to Emory University Hospital in critical condition. Dr. Crozier and a team of ophthalmology and infectious disease physicians from Emory University and the Centers for Disease Control and Prevention will share their perspectives into Crozier's evacuation, treatment, recovery and subsequent vision-threatening condition, as each of them dealt with the uncertainty and long-term implications of this virus. Moderated by ARVO president William Mieler, the panel and discussion will include: > Update and Challenges in the Management of the Ebola Outbreak in West Africa — Tim Uyeki, MD, Centers for Disease Control and Prevention, Atlanta. > Hospital Course and Infection Control in the Emory Serious Communicable Diseases Unit — Jay B. Varkey, MD, Division of Infectious Disease, Department of Internal Medicine, Atlanta. > Ophthalmic Course and Management of Panuveitis Due to Ebola Virus Disease — Steven Yeh, MD, Department of Ophthalmology, Emory Eye Center, Atlanta. > Diagnostic and Treatment Uncertainty in a Novel, Sight-Threatening Disease — Jessica G. Shantha, MD, Department of Ophthalmology, Emory Eye Center, Atlanta. > Perspectives on Ebola Virus Disease: Both Sides of the Curtain — Ian Crozier, MD, Infectious Diseases Institute, Mulago Hospital Complex, Kampala, Uganda BASIC CLINICAL LECTURE Neurovascular Interactions in Diseases of the Eye California, San Diego School of Medicine and Moores Cancer Center > JOAN WHITTEN MILLER, MD, FARVO — Massachusetts Eye and Ear Infirmary in Boston > EVANGELOS S. GRAGOUDAS, MD, FARVO — Massachusetts Eye and Ear Infirmary in Boston > PATRICIA A. D'AMORE, PHD, MBA, FARVO — Massachusetts Eye and Ear Infirmary > ANTHONY P. ADAMIS, MD, FARVO — Genentech; also affiliated with HMS Ophthalmology and Massachusetts Eye and Ear Infirmary > GEORGE L. KING, MD, FARVO — Joslin Diabetes Center > LLOYD PAUL AIELLO, MD, PhD, FARVO — Massachusetts Eye and Ear Infirmary and Joslin Diabetes Center in Boston ST U DE N T/T R A I N E E EV E N T S ARVO Education Course Strategies for Effective Grant Writing Saturday, May 2, 8:30 a.m. to 4 p.m. Led by an international faculty, including experts in grantsmanship, this full-day course will focus on grant-targeting strategies, planning, writing impactful proposal, and responding to reviews. The course will be interactive, with time dedicated throughout the day to address questions from participants. The training will focus on strategies that apply to any grantmaking organization, including NIH, private foundations, and non-U.S. funding agencies. These popular sessions offer informal discussions over pizza lunch on Sunday or breakfast on Wednesday on a wide range of topics. Experienced colleagues provide personal guidance, insight, and skills to help students and trainees advance their career. Topics focus on professional development in academic clinical medicine and clinician-scientists careers. Career Forum Monday, May 5, 1 p.m. to 2:30 p.m. Small-group roundtable discussions will focus on helping students, fellows and residents prepare for their next career move. Attendees should bring their lunch. Clinician-Scientist Forum: How to Become a Successful Clinician-Scientist Wednesday, May 6, 1 p.m. to 2:30 p.m. Clinician-scientists at various stages in their career will share their experiences with attendees. Plus, an extramural representative from the National Eye Institute will be available to discuss funding mechanisms for clinician-scientists. GET R E A DY F OR A RVO 2 016 It’s not too early to start planning for the ARVO 2016 annual meeting in Seattle, May 1 to 5. The Washington State Convention Center is conveniently located in Seattle’s downtown center, within walking distance from hotels and only blocks away from the popular Pike Place Market. To learn more about ARVO 2016 registration, hotel, program, or social events, visit arvo.org/am. Q Sunday, May 3, 5:15 p.m. to 7:15 p.m. This symposium will address an NEI Audacious Goal, “Neural Connections in the Eye and Visual System.” Experts will highlight neuro- Pizza and Breakfast with an expert Sunday, May 3, 1:30 p.m. to 3 p.m. Wednesday, May 6, 7 a.m. to 8:30 a.m. KATRINA NORFLEET is assistant director of communications, Association for Research in Vision and Ophthalmology. Readers may contact Norfleet at 240/221-2924 or [email protected]. photo courtesy VISIT DENVER Ebola and the Eye: A Story of Discovery and Uncertainty Important Safety Information with known hypersensitivity to any Contraindications components of this product. sILUVIEN is contraindicated in patients Warnings and Precautions with active or suspected ocular or periocular infections including most s)NTRAVITREALINJECTIONSHAVEBEEN viral disease of the cornea and associated with endophthalmitis, eye conjunctiva including active epithelial inflammation, increased intraocular herpes simplex keratitis (dendritic pressure, and retinal detachments. keratitis), vaccinia, varicella, mycobacterial Patients should be monitored following infections and fungal diseases. the intravitreal injection. sILUVIEN is contraindicated in patients sUse of corticosteroids may produce with glaucoma, who have cup to disc posterior subcapsular cataracts, ratios of greater than 0.8. increased intraocular pressure, glaucoma, and may enhance the sILUVIEN is contraindicated in patients Please see brief summary of full Prescribing Information on following page. 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. Make the move to ILUVIEN and provide sustained, submicrogram levels of fluocinolone acetonide (FAc) for 36 months from a single intravitreal implant.1 Primary month-24 endpoint met. Significantly more patients treated with ILUVIEN achieved ≥15-letter improvement from baseline.1 The most common adverse reactions reported were cataract development (ILUVIEN 82%; sham 50%) and intraocular pressure elevation of >10 mmHg (ILUVIEN 34%; sham 10%).1 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. s0ATIENTSINWHOMTHEposterior capsule of the lens is absent or has a tear are at risk of implant migration into the anterior chamber. Adverse Reactions sThe most common adverse reactions reported were cataract development (ILUVIEN 82%; sham 50%) and intraocular pressure elevation of >10 mmHg (ILUVIEN 34%; sham 10%). Nonbioerodable, implant designed to deliver submicrogram levels of steroid.1 Learn more at ILUVIEN.com 1.ILUVIEN® [package insert]. Alpharetta, GA: Alimera Sciences, Inc.; 2014. 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. 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. 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 Adverse Reactions ILUVIEN (N=375) n (%) Sham (N=185) n (%) Ocular Cataract1 192/2352 (82%) 61/1212 (50%) 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%) Conjunctivitis 14 (4%) 5 (3%) Corneal oedema 13 (4%) 3 (2%) 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%) US-ILV-MMM-0034-02 02/15 Non-ocular Anemia Headache Renal failure Pneumonia 40 (11%) 33 (9%) 32 (9%) 28 (7%) Sham (N=185) n (%) 10 (5%) 11 (6%) 10 (5%) 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) n (%) Non-ocular IOP elevation ≥ 10 mm Hg from baseline IOP elevation ≥ 30 mm Hg Any IOP-lowering medication Any surgical intervention for elevated intraocular pressure Sham (N=185) n (%) 127 (34%) 75 (20%) 144 (38%) 18 (10%) 8 (4%) 26 (14%) 18 (5%) 1 (1%) 25 Mean Intraocular Pressure (mm Hg) 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. ILUVIEN (N=375) n (%) 20 15 10 5 0 0 6 12 18 Month ILUVIEN (N=375) 24 30 36 Sham (N=185) Figure 1: Mean IOP during the study 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 postmarketing 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. USE IN SPECIFIC POPULATIONS 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. Manufactured for: "MJNFSB4DJFODFT*ODt8JOEXBSE1BSLXBZ "MQIBSFUUB("t1BUFOUFE4FFXXXBMJNFSBTDJFODFTDPN All Rights Reserved; Issue Date September 2014; ILUVIEN is a registered trademark of Alimera Sciences, Inc. APRIL 15, 2015 :: Ophthalmology Times surgery Strategies for handling complex pterygium surgery, complications Spotlighting aggressive pterygia, recurrent pterygia, symblepharon, corneal scars, scleral melts Gloves Off with Gulani By Arun C. Gulani, MD TAKE-HOME In this second of a two-part series on pterygia and pinguecula surgery with cosmetic expectations, Arun C. Gulani, MD, addresses the complex pterygia and complications. RECURRENT PTERYGIUM Day 1 Postop JACKSONVIL L E, F L :: ith a worldwide referral base for complex pterygia and pinguecula complication cases, I have condensed my observations and approach over the past two decades to share in this column. Personally I have seen less than 1% recurrence rate over 14 years with my technique despite doing very complex pterygia. Additionally, I have had a case of muscle adhesion and a case of pupil abnormality (probably ischemia) in aggressive bitemporal cases. My approach always as emphasized in the first part of this column (http://bit. ly/1NGKqiJ) is to make sure patients understand the seriousness of this surgery and that complications can happen. Once again, I must first emphasize that the mindset associated with treating recurrent pterygia and associated complications is the same as when dealing with the virgin pterygial surgery. Surgeons should not adopt the notion that the previous surgeon did a bad job or that they are now trying to help a patient and therefore aim for a mediocre outcome. Rather, the mindset should be the same as when treating the primary pterygium with the expectation of achieving outstanding cosmetic outcomes on the next postoperative day that will remain stable in the future. Every step should not only correct the problem but also enhance the appearance of the eye and possibly improve vision. W Day 2 Postop (FIGURE 1) Recurrent pterygium excision, next the appearance. (Photos courtesy of Arun C. Gulani, MD) VIDEO Learn more about the technique. Go to http://bit.ly/1JlOZ1i (Videos courtesy of Arun C. Gulani, MD) More Video http://bit.ly/1yanO8N http://bit.ly/1afWECd http://bit.ly/1DfmAJw http://bit.ly/1yRWsz5 http://bit.ly/1yanQ0x When correcting recurrences and complications arising in pterygia/pinguecula surgery, I have suggested three facets that surgeons must consider: the recurrence and or complications of the lesion itself; the associated conditions such as fornix shortening, corneal and conjunctival scarring, symblepharon, and ischemia or scleral melts; and the predisposing factor for such a recurrence/complication. Regardless of the expertise of the surgeon who performed the initial surgery, complications can develop that require devising a treatment plan with realistic expectations for the patient but without lowering our own desire to achieve excellence. I always presume and reiterate to patients that their initial surgeon did the best they could to remove the lesion; the goals of the second surgeon now are to pick up the baton and take it to the end zone by beautiContinues on page 12 : Strategies 11 12 APRIL 15, 2015 :: Ophthalmology Times surgery (FIGURE 2) Aggressive, recurrent pterygium with next day and long term outcome (FIGURE 3) Residual Salzmann nodules in aggressive recurrent pteygium surgery, corrected by PROKERA application Self Resolving Scleral Melt In an elderly patient resolved with lubrication over time Scleral Melt (FIGURE 4) Residual corneal scars the following recurrent pterygium surgery can undergo laser Corneoplastique to emmetropic vision STRATEGIES ( Continued from page 11 ) fying the eye, correcting the comorbidity of associated problems, and enhancing vision. RESECTING RECURRENT LESIONS To perform minimal dissection, the goal is to identify the bare sclera by careful and gentle cut down through the recurrent scar tissue. The first surgeon has usually done a nice job of preparing a clear/bare sclera. Once that plane is reached the most difficult part is over. In most cases now the rest of the scariform tissue lifts off like a “plate of armor” from the underlying sclera. Following this approach there is minimal bleeding. Bleeding usually occurs when sur- Scleral Melt One Month Scleral Melt Six Months (FIGURE 5) Self-resolving scleral thinning geons chase the scar tissue from different approaches and cut into it causing multiple planes with a messy and distorted anatomy that further complicates the surgical steps. In most recurrent cases referred to me, the original pterygium was removed only partially. The surgical steps described in Part 1 of this column can now be followed. These include mitomycin C application and application of Tisseel Glue (Baxter International) along with amniotic graft reconstruction. FOCUSING ON A S SOCI AT ED PAT HOLOGY After the mass of the pterygium is removed, the surgeon should consider the anatomy and methods to improve the ocular appearance and address the associated comorbidities. One such adjustment is forming the forni- ces. This is done by redeepening and relieving the conjunctival scarring and symblepharon, clearing the corneal area using a number 64 blade without cutting in a smooth rapid fashion, and then applying an amniotic graft to reconstruct the fornix by deepening it and arranging the conjunctiva in an elaborate fashion such that it is cosmetically hidden under the lids but is functionally viable. As described in part 1 of this column, the amniotic membrane can be used to cover the sclera. This can also be multilayered to strengthen the thin sclera. The membrane is attached using Tisseel Glue. The area of the corneal scar is smoothed and application of the amniotic membrane can be extended beyond the limbus onto the cornea for better healing. In many of these cases, I use ProKera (Bio-Tissue) or AmbioDisk (IOP OphContinues on page 14 : Appearance SYMPTOMATIC VITREOMACULAR ADHESION (VMA) SYMPTOMATIC VMA MAY LEAD TO VISUAL IMPAIRMENT FOR YOUR PATIENTS1-3 IDENTIFY REFER Recognize metamorphopsia as a key sign of symptomatic VMA and utilize OCT scans to confirm vitreomacular traction. Because symptomatic VMA is a progressive condition that may lead to a loss of vision, your partnering retina specialist can determine if treatment is necessary.1-3 THE STEPS YOU TAKE TODAY MAY MAKE A DIFFERENCE FOR YOUR PATIENTS TOMORROW © 2014 ThromboGenics, Inc. All rights reserved. ThromboGenics, Inc., 101 Wood Avenue South, Suite 610, Iselin, NJ 08830 – USA. THROMBOGENICS and the THROMBOGENICS logo are trademarks or registered trademarks of ThromboGenics NV. 9/14 OCRVMA0220 References: 1. Sonmez K, Capone A, Trese M, et al. Vitreomacular traction syndrome: impact of anatomical configuration on anatomical and visual outcomes. Retina. 2008;28:1207-1214. 2. Hikichi T, Yoshida A, Trempe CL. Course of vitreomacular traction syndrome. Am J Ophthalmol. 1995;119(1):55-56. 3. Stalmans P, Lescrauwaet B, Blot K. A retrospective cohort study in patients with diseases of the vitreomacular interface (ReCoVit). Poster presented at: The Association for Research in Vision and Ophthalmology (ARVO) 2014 Annual Meeting; May 4-8, 2014; Orlando, Florida. 14 APRIL 15, 2015 :: Ophthalmology Times surgery APPEARANCE ( Continued from page 12 ) thalmics) on the day after the surgery. Sclera melts are another possible complication of pterygium surgery; some of these are self-resolving while others require a tis- Lateral Recurrent Pterygium sue intervention such as lamellar cornea, conjunctival, or Tenon’s pedicles, and amniotic graft reconstruction. In severe cases, I also use Tutoplast (Tutogen Medical GmbH) with amniotic graft combination to further reconstruct and strengthen the sclera. The Tenon’s pedicle can be used to supply vascularity to a usually ischemic sclera and the lamellar cornea can be used in cases with superficial scleral thinning and glued in place for a cosmetically appealing endpoint. Granulomas also can occur in some case and can resolve spontaneously with steroids or gentle cautery excision. In extensive and deeper scleral involvement, I also have used Tutoplast and tried Continues on page 17 : Scleral Day One Post op with Tenons Reinforcement Scleral Melt Scleral Melt with Lateral Calcification Day One Post op with Tenons Reinforcement—High Mag (FIGURE 6) Tenon’s pedicle reinforcement for areas of scleral thinning in aggressive lateral recurrent pterygium 2.5 years post Rec Pterygium surgery Scleral Melt 1 Day Postop Day 1 Post-op 2 Months Post-op 1 Week Postop 1 Month Post-op 6 Months Post-op 2.5 years post Rec Pterygium surgery 2 Years Postop 6 Years Postop 1 Month Postop 4 Years Postop 8 Years Postop (FIGURE 9, 10 & 11) Glued Tutoplast used for scleral melt (FIGURE 7 & 8) Lamellar corneal graft used in scleral thinning to retain cosmetic appearance and ocular integrity. ALREX : ® TREATS THE ITCH AND MORE. SHORT-TERM TREATMENT FOR THE FULL SPECTRUM OF SAC* SIGNS AND SYMPTOMS1-3 *Seasonal allergic conjunctivitis. INDICATION ALREX® (loteprednol etabonate ophthalmic suspension) is indicated for the temporary relief of the signs and symptoms of seasonal allergic conjunctivitis. IMPORTANT SAFETY INFORMATION ALREX® 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 the ocular structures. ALREX® is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation and to other corticosteroids. Prolonged use of ALREX® is associated with several warnings and precautions, including glaucoma with optic nerve damage, defects in visual acuity, cataract formation, secondary ocular infections, and exacerbation or prolongation of viral ocular infections (including herpes simplex). If this product is used for 10 days or longer, intraocular pressure should be monitored. The initial prescription and renewal of the medication order beyond 14 days should be made by a physician only after reexamination of the patient with the aid of magnification. Fungal infections of the cornea may develop with prolonged use of corticosteroids. Ocular adverse reactions occurring in 5-15% of patients treated with loteprednol etabonate ophthalmic suspension (0.2%-0.5%) in clinical studies included abnormal vision/blurring, burning on instillation, chemosis, discharge, dry eyes, epiphora, foreign body sensation, itching, infection, and photophobia. Please see brief summary of full Prescribing Information on the following page. References: 1. ALREX [package insert]. Tampa, FL: Bausch & Lomb Incorporated; 2013. 2. Dell SJ, Lowry GM, Northcutt JA, Howes J, Novack GD, Hart K. A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis. J Allergy Clin Immunol. 1998;102(2):251-255. 3. Shulman DG, Lothringer LL, Rubin JM, et al. A randomized, double-masked, placebo-controlled parallel study of loteprednol etabonate 0.2% in patients with seasonal allergic conjunctivitis. Ophthalmology. 1999;106(2):362-369. ALREX is a trademark of Bausch & Lomb Incorporated or its affiliates. ©Bausch & Lomb Incorporated. US/ALX/15/0001 BRIEF SUMMARY OF PRESCRIBING INFORMATION This Brief Summary does not include all the information needed to use Alrex® (loteprednol etabonate ophthalmic suspension 0.2%) safely and effectively. See full prescribing information for Alrex. Alrex ® loteprednol etabonate ophthalmic suspension 0.2% Sterile Ophthalmic Suspension Rx only INDICATIONS AND USAGE ALREX Ophthalmic Suspension is indicated for the temporary relief of the signs and symptoms of seasonal allergic conjunctivitis. CONTRAINDICATIONS ALREX, 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. ALREX is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation and to other corticosteroids. WARNINGS Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Steroids should be used with caution in the presence of glaucoma. Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. In acute purulent conditions of the eye, steroids may mask infection or enhance existing infection. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. PRECAUTIONS General: For ophthalmic use only. The initial prescription and renewal of the medication order beyond 14 days 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. If signs and symptoms fail to improve after two days, the patient should be re-evaluated. If this product is used for 10 days or longer, intraocular pressure should be monitored. 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. Information for Patients: 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 redness or itching becomes aggravated, the patient should be advised to consult a physician. Patients should be advised not to wear a contact lens if their eye is red. ALREX should not be used to treat contact lens related irritation. The preservative in ALREX, benzalkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red, should be instructed to wait at least ten minutes after instilling ALREX before they insert their contact lenses. 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, (1500 and 750 times the maximum clinical dose, respectively) prior to and during mating did not impair fertility in either gender. 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 (85 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 (15 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 postimplantation 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 (15 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. ALREX Ophthalmic Suspension 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 ALREX is administered to a nursing woman. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. ADVERSE REACTIONS Reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera. Ocular adverse reactions occurring in 5-15% of patients treated with loteprednol etabonate ophthalmic suspension (0.2% - 0.5%) in clinical studies included abnormal vision/blurring, burning on instillation, chemosis, discharge, dry eyes, epiphora, foreign body sensation, itching, injection, and photophobia. Other ocular adverse reactions occurring in less than 5% of patients include conjunctivitis, corneal abnormalities, eyelid erythema, keratoconjunctivitis, ocular irritation/pain/discomfort, papillae, and uveitis. Some of these events were similar to the underlying ocular disease being studied. Non-ocular adverse reactions occurred in less than 15% of patients. These include headache, rhinitis and pharyngitis. 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. Among the smaller group of patients who were studied with ALREX, the incidence of clinically significant increases in IOP (≥10 mm Hg) was 1% (1/133) with ALREX and 1% (1/135) with placebo. DOSAGE AND ADMINISTRATION SHAKE VIGOROUSLY BEFORE USING. One drop instilled into the affected eye(s) four times daily. Revised: August 2013. Bausch & Lomb Incorporated, Tampa, Florida 33637 ©Bausch & Lomb Incorporated Alrex® is a registered trademark of Bausch & Lomb Incorporated Based on 9007904-9005504 US/ALX/15/0005 Issued: 02/2015 APRIL 15, 2015 :: Ophthalmology Times surgery (FIGURE 12) Correcting the “Eye Brightening” surgery with amniotic graft reconstruction to cosmetic outcomes SCLERAL ( Continued from page 14 ) to always keep it the least bulky as possible. While these are salvage cases, the extraocular movement and appearance should be preserved as best as possible. These cases can look cosmetically appealing the next day after surgery and remain that way for years to come. An anchor suture can be used if needed. Clearing and strengthening are the main objectives, although cosmesis and vision are the primary desires. Corneal scars can be easily addressed using Laser Corneoplastique principles as explained in previous columns (Decoding Corneal Scars) and the patients can achieve emmetropia. PR EDISPOSING COMORBIDITIES If predisposing conditions such as rheumatoid arthritis, Sjögrens syndrome, dry eye, or collagen vascular diseases are present, we must involve the patient’s physician for a systemic workup and management. In addition, every attempt at surgery raises the chances of a recurrence so we must strive to do it right the first time following the principles of the Iceberg concept. This minimalistic approach results in surprisingly good results for these patients with its elegant arrangement of tissue. The cosmetic outcomes, high functionality, and improved vision are the final goals of this 17 (FIGURE 13) Staged surgery using amniotic graft for aggressive recurrent pterygium with laminar fill of amniotic graft on the cornea followed by Multifocal lens implant for cataract and Laser ASA in Corneoplastique mode to emmetropia and cosmetic appearance. surgery regardless of the preoperative appearance. Therefore, recurrent pterygia can be addressed in the same fashion but with a slightly different approach and the same mindset as the initial surgeries. Importantly, numerous patients of mine who have undergone complex pterygial surgery and complication correction have also undergone subsequent laser vision surgery and premium cataract surgery with excellent visual outcomes. A C AV E A T Given the unique nature of my practice with a large number of patients referred for cosmetic outcomes, their expectations need to be addressed because doing a mediocre job on a case in which the pterygium/pinguecula was primary and small but with a resultant scar is less tolerable and more agonizing than a recurrence in a complex pterygium case. This is very similar to present-day premium cataract surgery where patients with 20/60 vision and easily extractable cataracts expect perfection as opposed to patients with 20/400 vision even if the latter may have a mature, hard, and complex cataracts. This is the price we must pay for our desire to excel for our patients by undertaking this level of commitment as long as the patients are educated about the fact that complications can occur. Mastering the art of pterygium and pinguecula surgery to treat emerging cases as well as complications and side effects empowers the surgeon to become a fullspectrum ocular surface surgeon who re- lentlessly follows the goals of raising the bar on ocular surface surgery to cosmetic outcomes along with enhancing vision simultaneously. In an upcoming “Gloves Off with Gulani” column, I look forward to discussing “Designer Cataract Surgery: Beyond Premium Technology; The Time Is Now.” ■ References 1. Gulani AC. Sutureless amniotic surgery for pterygium: cosmetic outcomes for ocular surface surgery. Techniques in Ophthalmology. 2008;6:41-4. 2. Gulani AC. No-stitch pterygium surgery: next day cosmetic outcomes. Video Journal of Ophthalmology. 2009. 3. Gulani AC. Corneoplastique. Video Journal of Cataract and Refractive Surgery. 2006;22:3. 4. Gulani A, Gulani A. pterygium surgery: raising ocular surface surgery to cosmetic outcomes. Mastering corneal surgery: recent advances and current techniques. Thorofare, NJ: SLACK Incorporated. 2015;25:269-276. 5. Gulani AC. Gulani Iceberg Technique. Cataract & Refractive Surgery Today Europe. 2014;9:48-49. 6. Gulani, AC. A cornea-friendly pterygium procedure. Rev Ophthalmol. 2012;52-56. 7. Gulani AC. Shaping the future and reshaping the past: the art of vision surgery. Chapter 98. In: Copeland and Afshari’s Principles and Practice of Cornea. New Delhi, India: Jaypee Brothers Medical Publishers 2013;2: 1252-1273. 8. Gulani AC. Corneoplastique. Ind J Ophthalmol. 2014;62:3-11. 9. Gulani, AC. Competencies in oculoplastics: anatomy, trauma, involutions, and exam preparation. New Retina MD. 2013;1-2. ARUN C. GULANI, MD, is founding director and chief surgeon of the Gulani Vision Institute, Jacksonville, FL. Dr. Gulani has no financial interests to declare. 18 APRIL 15, 2015 :: Ophthalmology Times surgery Presbyopic-correcting devices poised for growing patient sector Potential for excellent near vision independent of lens replacement closer to reality Focus on Refractive Surgery By Ehsan “Ethan” Sadri, MD, FACS BE ACH, CA :: “typical” patient who comes in for cataract surgery has extremely high expectations regarding the visual outcomes at all visual distances and is not willing to settle for less. Because of the large number of patients who will need cataract surgery, the pool of patients willing to spend money on the most advanced technologies to provide the highest level of vision is expanding exponentially. With this potential market, many companies are designing presbyopia-correcting devices, and the attention they are getting is just the tip of the iceberg. In excess of 100,000 inlays have been implanted worldwide. The devices are currently approved in 51 countries in Europe, the Asia-Pacific, the Middle East, North and South America, and India. But this is just the beginning. Product milestones in this area include development of the: > Kamra corneal inlay (Acufocus), > Raindrop Near Vision Corneal Inlay (ReVi- A sion Optics), > PresbyLens (in the United States)/the PresbyVue+ (in Europe)—both from ReVision Optics, > Flexivue Microlens (Presbia), and > the corneal onlay, which is still in the experimental stages. The devices that are further along in the testing process are highlighted in this article. K A MR A COR NE A L INL AY This inlay—which is on the verge of approval by the FDA—is made of polyvinyledene fluoride and carbon nanoparticles and is highly biocompatible. The device improves near vision by extending the depth of focus. A typical patient with presbyopia may have only 0.25 D of depth of focus. Following implantation of the Kamra inlay, that can increase to in excess of 2.5 D. The central aperture is a hole in the inlay Investigators have reported a small dethat has no power. The inlay is designed crease in the photopic and mesopic contrast to provide an unobstructed pathway for fosensitivity, but the values are within the cused light to reach the retina. Advantages normal range 2 years postoperatively. are its small size with a diameter of 3.8 However, at the end of the day compared mm, a 1.6-mm aperture, and with the benefits provided a thickness of only 5 μm. by the inlay the reduction in The device has 8,400 holes contrast is considered minor. ranging in size from 5 to 11 Patients also reported Because of the μm, which provide its high a low incidence of visual large number of permeability. symptoms 2 years after surpatients who will Two surgical procedures gery that included glare, need cataract can be used to implant the halos, and night-vision probsurgery, many Kamra inlay, i.e., in a pocket lems. In line with these posicompanies are or a dual interface. The fortive results, patients reported designing presbyopiamer approach, which can be significantly increased readcorrecting devices. used with emmetropic presing speed and reading abilbyopes, involves creation of ity and decreased distance at a pocket about 200 to 250 μm deep in the which they could read. stroma into which the inlay is placed. The increased reading ability at J2 after The latter surgery is good for patients implantation was sustained out to 5 years with ametropic presbyopia and presbyopia postoperatively. who had undergone a LASIK procedure or Another benefit of the technology is that were to undergo a LASIK-Kamra procedure. the procedure is reversible and does not reWith the combination procedure, LASIK is strict future refractive options. performed under a 100-μm flap. With the Cataracts and lens opacities can be seen other approach, a minimum of 1 month easily through a dilated pupil with the imafter LASIK, a pocket is created 100 μm plant in place. When a patient with a Kamra under the LASIK interface and the inlay is inlay develops a cataract, there are several inserted. options— namely, performance of phacoThe mean near uncorrected visual acuemulsification and implantation of a monoity that is achieved is quite good at J2 12 focal IOL with the inlay in place, removal of months postoperatively. Importantly, at the inlay after implantation of a monofocal the same time point the uncorrected disIOL, and removal of the inlay followed by tance visual acuity remains stable at about implantation of a posterior chamber IOL. 20/30. Patients with the inlay implanted in While this was the first and most extena pocket had no change in the mean dissively used of the inlays, it still is not aptance stereoacuity scores between preoperproved in the United States. atively and 6 months after implantation of the inlay. R AINDROP NEAR VISION At 2 years post-implantation, the ease of COR NE A L INL AY performing distance visual tasks remained This corneal inlay is constructed from a perstable after implantation of the inlay using a meable hydrogel with the same refractive pocket procedure. Patients rated the ease of index as that of the cornea. The device is 2 performing near visual tasks with both eyes mm in diameter and the central thickness without wearing glasses as 7 on the ranking is 32 μm. This inlay affects the patient’s acscale, with 1 indicating “not easy at all” and commodative power by causing the central 7 “very easy.” radius of corneal curvature over the implant TAKE-HOME Bio ics han ec M BioM ate ri al NO MATTER THE CASE, THE ACRYSOF® PLATFORM PROVIDES AN OPTION FOR ACHIEVING PATIENT SATISFACTION Bonnie An Henderson, MD Ophthalmic Consultants of Boston BioOptics Patients have their concerns before cataract surgery. These concerns can vary as much as the patients themselves. AcrySof® IOLs deliver top quality vision to address the visual goals of my patients. This supplement presents actual case studies. Individual results may vary. Advancing CATARACT SURGERY CASE 1 PROFESSIONAL DRIVER. GLARE SUFFERER. APPREHENSIVE. Patient Study 63-year-old male Bilateral cataracts Works two jobs as a van and bus driver; regularly works morning and late night shifts &RPSODLQVRILQFUHDVLQJGLɝ FXOW\GULYLQJGXHWRJODUH Concerned about improving visual quality to maintain work No additional ocular concerns (ie, glaucoma, retina) Clinical Assessment Preoperative VA (OD): 20/40 Preoperative VA (OS): 20/40 Preoperative MRx (OD): +3.00 –1.25 X 85 Preoperative MRx (OS): +2.50 –1.00 X 105 Recommendations “This patient was primarily concerned about his ability to keep driving for work once he received his IOLs, since he alternates between daytime and nighttime shifts. Following a thorough conversation about his visual goals, he selected the monofocal lens, particularly since he wanted to achieve the clearest possible distance vision for his nighttime driving. I recommended an AcrySof®Ζ2/ZLWKDEOXHOLJKWOWHULQJ chromophore in order to give him excellent vision with minimal glare. He is quite happy with his results and is truly grateful he achieved such outstanding visual quality following surgery.” – Bonnie An Henderson, MD AcrySof® IQ Aspheric IOL (SN60WF 19.0) Results Postoperative uncorrected vision: 20/20 (OD), 20/25 (OS) 3DWLHQWLVVDWLVHGZLWK Overall visual quality Visual acuity Newfound comfort with both daytime and nighttime driving 6LJQLFDQWJODUHUHGXFWLRQ Driving vision during photopic/scotopic/mesopic conditions This is an actual case study; the photograph is an actor portrayal. ARTIST. RETIRED. PRIORITIZES COLOR VISION. CASE 2 Patient Study 76-year-old female Unilateral cataract (OD) Retired graphics design artist; works part time as freelance artist ΖQFUHDVLQJGLɝ FXOW\VHHLQJSDLQWLQJVFOHDUO\ Extremely worried about color perception loss; does not want vision options to compromise color perception No additional ocular concerns (ie, glaucoma, retina) Clinical Assessment Preoperative VA (OD): 20/50 Preoperative MRx (OD): +3.00 –1.25 X 107 Recommendations AcrySof® IQ Aspheric IOL (SN60WF 21.5) Results Postoperative uncorrected vision: 20/20 (OD) 3DWLHQWLVVDWLVHGZLWK Overall visual quality Overall color contrast vision across photopic/scotopic/ mesopic conditions Visual acuity, particularly near vision quality This is an actual case study; the photograph is an actor portrayal. “This patient felt her world ‘was becoming a faded canvas’ and was absolutely adamant about her need to preserve and improve her RYHUDOOFRORUYLVLRQ%HFDXVHVKHVSHFLFDOO\ZDQWHGWRPDLQWDLQ perfect color perception, I thought she would be a great candidate for the AcrySof®Ζ4OHQVVLQFHWKHEOXHOLJKWOWHULQJ\HOORZ chromophore would cut down on her glare while mimicking the natural crystalline lens. Following surgery, she was completely thrilled with her vision. She recalled previously how she was increasingly missing details in her work. Since the surgery, she feels her improved vision now fully supports her talent, and that the details in her work are now much more apparent. When I saw her recently, she burst into tears of gratitude over her outcome, and she shared her prior fears that she would have to give up painting altogether. She even brought me a painting as a thank you gift! An incredibly gratifying case for me personally.” – Bonnie An Henderson, MD CASE 3 PHYSICIAN. NIGHT SHIFT. SLEEP CONCERNS. Patient Study 70-year-old male Bilateral cataracts Works as an obstetrician/gynecologist Frequently works long, late night shifts at a local hospital 1RWHGLQFUHDVLQJGLɝ FXOW\PDQDJLQJKLVJODUH Does not desire an advanced technology IOL Reports some sleep issues; concerned that his IOL will impact his sleep and driving habits No additional ocular concerns (ie, glaucoma, retina) Clinical Assessment “As a physician who works late at night, maintaining sleep quality was as precious to this patient as improving his visual quality. He noted that since he often works day–night GRXEOHVKLIWVLWLVGLɝ FXOWIRUKLPWRURXWLQHO\UHJXODWHKLV VOHHSȂZDNHF\FOHKHVSHFLFDOO\GLGQRWZDQWKLVΖ2/WR interfere with this challenge. Based on his stated vision goals and concerns, I recommended the AcrySof® IQ lens. Following surgery, he was incredibly pleased with his visual outcome. He also reported his overall sleep quality actually LPSURYHGZLWKOHVVGLɝ FXOW\IDOOLQJDVOHHSDQGUHJXODWLQJ his sleep–wake cycle. This isn’t typical and it is important to note that no controlled clinical studies have shown DSRVLWLYHHHFWRQVOHHSTXDOLW\+RZHYHUDWOHDVWRQH UHSRUWHGVWXG\KDVIRXQGQRQHJDWLYHHHFWRQVOHHS1“ – Bonnie An Henderson, MD Preoperative VA (OD): 20/200 Preoperative MRx (OD): –11.00 –1.25 X 095 Recommendations AcrySof® IQ Aspheric IOL (SN60WF 14.0) Results Postoperative uncorrected vision: 20/20 (OD) 3DWLHQWLVVDWLVHGZLWK Overall visual quality and acuity Improved vision for driving and reading Reduction in glare Overall sleep quality This is an actual case study; the photograph is an actor portrayal. DENTAL HYGIENIST. ASTIGMATIC. DRIVING CHALLENGES. CASE 4 Patient Study 62-year-old female Bilateral cataracts with bilateral astigmatism Works as a dental hygienist; requires daily driving Complains of poor vision interfering with ability to read VWUHHWVLJQVDQGQHSULQW Seeks spectacle independence No additional ocular concerns (ie, glaucoma, retina) Reports no sleep issues Clinical Assessment Preoperative VA (OD): 20/40 Preoperative VA (OS): 20/200 Preoperative MRx (OD): +0.75 –3.25 X 001 Preoperative MRx (OS): +0.25 –2.50 X 116 Recommendations AcrySof® IQ Toric IOL (SN6AT7 21.0) Results Postoperative uncorrected vision: 20/20 (OU) 3DWLHQWLVVDWLVHGZLWK Overall visual quality and clarity Astigmatism correction Spectacle independence for distance vision Photopic/scotopic/mesopic contrast sensitivity Vision for driving This is an actual case study; the photograph is an actor portrayal. “This patient was primarily concerned with maintaining her visual FODULW\SDUWLFXODUO\IRUGULYLQJDQGUHDGLQJQHSULQWDWZRUN and home. During her examination and our conversation about treatment options, she did not realize that she could actually correct the astigmatism that she had been living with her entire life. After surgery, she was over the moon with her visual outcome– she was so happy that she could simply get out of bed every day and immediately begin enjoying her new vision. She uses simple reading glasses now instead of expensive corrective lenses, and she feels the long-term cost savings associated with spectacle independence far outweighs the one-time cost of her AcrySof® IQ Toric IOL.” – Bonnie An Henderson, MD IMPORTANT PRODUCT INFORMATION ACRYSOF® IQ IOL CAUTION: Federal (USA) law restricts this device to the sale by or on the order of a physician. INDICATIONS: The AcrySof® IQ posterior chamber intraocular lens is intended for the replacement of the human lens to achieve visual correction of aphakia in adult patients following cataract surgery. This lens is intended for placement in the capsular bag. WARNING/PRECAUTION: &DUHIXOSUHRSHUDWLYHHYDOXDWLRQDQGVRXQGFOLQLFDOMXGJPHQWVKRXOGEHXVHGE\WKHVXUJHRQWRGHFLGHWKHULVNEHQHWUDWLREHIRUH implanting a lens in a patient with any of the conditions described in the Directions for Use labeling. Caution should be used prior to lens encapsulation to avoid lens decentrations or dislocations. 6WXGLHVKDYHVKRZQWKDWFRORUYLVLRQGLVFULPLQDWLRQLVQRWDGYHUVHO\DHFWHGLQLQGLYLGXDOVZLWKWKH$FU\6RI® Natural IOL and QRUPDOFRORUYLVLRQ7KHHHFWRQYLVLRQRIWKH$FU\6RI® Natural IOL in subjects with hereditary color vision defects and acquired color vision defects secondary to ocular disease (e.g., glaucoma, diabetic retinopathy, chronic uveitis, and other retinal or optic nerve diseases) has not been studied. Do not resterilize; do not store over 45°C; use only sterile irrigating solutions such as BSS® or BSS PLUS® Sterile Intraocular Irrigating Solutions. ATTENTION: Reference the Directions for Use labeling for a complete listing of indications, warnings and precautions. ACRYSOF® IQ TORIC IOL CAUTION: Federal (USA) law restricts this device to the sale by or on the order of a physician. INDICATIONS: The AcrySof® IQ Toric posterior chamber intraocular lenses are intended for primary implantation in the capsular bag of the eye for visual correction of aphakia and pre-existing corneal astigmatism secondary to removal of a cataractous lens in adult patients with or without presbyopia, who desire improved uncorrected distance vision, reduction of residual refractive cylinder and increased spectacle independence for distance vision. WARNING/PRECAUTION: &DUHIXOSUHRSHUDWLYHHYDOXDWLRQDQGVRXQGFOLQLFDOMXGJPHQWVKRXOGEHXVHGE\WKHVXUJHRQWRGHFLGHWKHULVNEHQHWUDWLR before implanting a lens in a patient with any of the conditions described in the Directions for Use labeling. Toric IOLs should not be implanted if the posterior capsule is ruptured, if the zonules are damaged, or if a primary posterior capsulotomy is planned. Rotation can reduce astigmatic correction; if necessary lens repositioning should occur as early as possible prior to lens encapsulation. All viscoelastics should be removed from both the anterior and posterior sides of the lens; residual viscoelastics may allow the lens to rotate. Optical theory suggests that high astigmatic patients (i.e. > 2.5 D) may experience spatial distortions. Possible toric IOL related factors may include residual cylindrical error or axis misalignments. Prior to surgery, physicians should provide prospective patients with a copy of the Patient Information Brochure available from Alcon for this product informing them of possible risks DQGEHQHWVDVVRFLDWHGZLWKWKH$FU\6RI® IQ Toric Cylinder Power IOLs. 6WXGLHVKDYHVKRZQWKDWFRORUYLVLRQGLVFULPLQDWLRQLVQRWDGYHUVHO\DHFWHGLQLQGLYLGXDOVZLWKWKH$FU\6RI® Natural IOL and QRUPDOFRORUYLVLRQ7KHHHFWRQYLVLRQRIWKH$FU\6RI® Natural IOL in subjects with hereditary color vision defects and acquired color vision defects secondary to ocular disease (e.g., glaucoma, diabetic retinopathy, chronic uveitis, and other retinal or optic nerve diseases) has not been studied. Do not resterilize; do not store over 45° C; use only sterile irrigating solutions such as BSS® or BSS PLUS® Sterile Intraocular Irrigating Solutions. ATTENTION: Reference the Directions for Use labeling for a complete listing of indications, warnings and precautions. REFERENCES: /DQGHUV-$7DPEO\Q'3HUULDP'(HFWRIDEOXHOLJKWEORFNLQJLQWUDRFXODUOHQVRQWKHTXDOLW\RIVOHHS J Cataract Refract Surg. 35(1):83–88. ©2015 Novartis 03/15 ACR14039MS APRIL 15, 2015 :: Ophthalmology Times surgery to increase in the non-dominant eye. The inlay is implanted under a corneal flap created by a femtosecond laser. Study of this inlay is still in its infancy: > A small study of the inlay was undertaken by Jose Guell, MD, and associates in which 38 patients aged 45 to 56 years who received the implant in their nondominant eye. Most of the subjects did not need glasses to perform intermediate tasks, such as when reading a computer screen. All had 20/25 or better distance vision in both eyes. In this study, the only adverse effect was the need for repositioning of one inlay. > Another study (Chayet et al. J Cataract Refract Surg. 2013;39:1713-1721) of 16 patients with hyperopia found that as early as 1 day after implantation, the uncorrected near visual acuity significantly improved in the implanted eyes compared with preoperatively. The uncorrected distance visual acuity also improved significantly and remained stable out to the 12-month visit. FLEXIVUE MICROLENS This device is made of a hydrophilic polymer (hydroxyethylmethacrylate and meth- ylmethacrylate), is 3 mm in diameter, and only 20 μm thick at the edges. The microlens is designed to change the refractive power in the center of the cornea to facilitate near visual function. The device is implanted using an injector roughly 300 μm deep into a corneal pocket created using a femtosecond laser. In a study of 47 patients with emmetropia, Limnopoulou et al. (J Refract Surg. 2013; 29:12-28) reported that 1 year after implantation of the microlens, the mean uncorrected near vision had improved significantly compared with preoperatively. The mean uncorrected distance vision decreased significantly following implantation in the eye that received the implant, but the binocular distance vision did not change substantially. COR NE A L ONL AYS The synthetic corneal onlay differs from inlays because it is implanted in a pocket in the outer corneal tissue rather than under a flap. The procedure—which is adjustable and reversible—is minimally invasive to the central optical zone. The epithelium in the central cornea is debrided and the lenticule is placed on the exposed stroma where the pocket maintains the position of the onlay. This pocket then holds the onlay in place 19 until the disturbed epithelial cells grow back to cover the device. The device is comprised of a genetically engineered material resembling collagen. Currently, the microlens has not been tested in humans, only experimentally. In a study in which the device was implanted in cats, the investigators found that the epithelium began to regrow as soon as 1 to 2 days after implantation and after 5 to 11 days full epithelialization had taken place (Evans et al. Invest Ophthalmol Vis Sci. 2002;43:3196-3201). This onlay has been on hold because of other competing technologies. The future of presbyopic correcting inlays is very strong. The promise of having excellent near vision independent of lens replacement is soon to be a reality. In addition, the competing technologies will allow the best results as choices for surgeons for their patients. ■ EHSAN “ETHAN” SADRI, MD, FACS E: [email protected] Dr. Sadri is in private practice in Newport Beach, CA. Dr. Sadri is a consultant for AcuFocus. Making the move to MIGS in practice By Cheryl Guttman Krader BOS TON :: WHEN WEIGHING the decision to adopt minimally invasive glaucoma surgery (MIGS) into their practice, several advantages may support surgeons’ rationale, according to Richard A. Lewis, MD. “MIGS, defined as a minimally invasive procedure performed through an ab interno incision, is changing how we manage glaucoma,” said Dr. Lewis, a glaucoma specialist in private practice, Sacramento, CA. “We know that glaucoma is a spectrum of disease and that one procedure will not be effective for each different type. Thus, there is a need for different approaches to manage the range of conditions glaucoma represents, and MIGS is the first effort to be more specific.” Explaining the advantages of MIGS, Dr. Lewis said it fits with an evolving truism for all glaucoma surgery in that it strives for greater safety. Compared with filtering and tube surgery, MIGS causes less tissue trauma, has fewer complications, and allows for earlier intervention while not precluding the opportunity for other types of glaucoma surgery. Another major advantage of MIGS is that it focuses on the target tissue that is the root of the problem in Schlemms canal. In addition, it coincides with the concept that glaucoma is a surgical disease. “The simplicity of treating glaucoma with surgery and the benefit of having a surgical cure as an alternative to a lifetime of medical treatment with its issues of compliance, cost, and side effects cannot be denied. If we had a surgical procedure that was safe and simple, I don’t believe anyone would opt not to use it,” Dr. Lewis said. “Up until the present, the safety element has been the missing factor in an acceptable surgical solution.” In order to understand the procedure and develop skills, Dr. Lewis said surgeons need to read about it, take training courses, consult with experienced colleagues, and practice. He recommended watching videos of their own procedures and those performed by other surgeons, learning from differences in technique and their colleagues’ approaches for managing complications. In addition, he emphasized making education an ongoing process. ■ 20 APRIL 15, 2015 :: Ophthalmology Times surgery Transepithelial surface ablation Clinical experience in myopic eyes with or without astigmatism By Dr Amir Hamid, FRCOphth, CertLRS, Dr Sajjad Mughal, FRCS, CertLRS and Arif Sokwala, BSc; Special from Ophthalmology Times Europe TAKE-HOME PRK has been an established method for laser vision correction for nearly 30 years, however, its popularity has reduced somewhat due to the advent of LASIK. With a recent renewed interest in surface ablation techniques some modifications have been made to alleviate disadvantages of the procedure. In this article, the authors highlight their clinical experience of TESA in myopic eyes with or without astigmatism. P hotorefractive keratectomy has been an established method for laser vision correction for nearly 30 years.1,2 Its popularity amongst both patients and surgeons has reduced since the advent of laser-assisted in situ keratomile- usis (LASIK). However, there has been a renewed interest in surface ablation as a method for correcting refractive errors due to the advantages of maintaining corneal biomechanical strength and elimination of flap-related complications and optimization of the methods for epithelial removal. The disadvantages of surface ablations have traditionally been postoperative pain, delayed epithelial healing and stromal haze. Modifications to PRK have been introduced to alleviate these issues. The key area that has been addressed in this respect is that of epithelial removal prior to excimer laser ablation. Ethanol has commonly been used as an alternative to mechanical debridement with preservation of the epithelial flap. An even more recent development is Transepithelial PRK (t-PRK) where epithelial removal is performed via laser phototherapeutic keratectomy (PTK) either through a two step or single step process. E P I T H E L I A L R E M OVA L W ITH SUR FACE A BL ATION (T W O S T E P V S S I N G L E S T E P) T-PRK (2 STEP METHOD) Several studies have looked at the results of 2-step surgery using older generation broad beam laser systems in comparison to ethanol assisted PRK.3-5 The results of two studies4.5 demonstrated better outcomes but in one there were overcorrections.3 In these studies the epithelium was ablated using a broad beam (even) PTK profile. A PTK treatment was initially performed to ablate the epithelium followed by a PRK procedure for correction of refractive error. TRANSEPITHELIAL SURFACE ABLATION (TESA) (1 STEP METHOD) The Schwind Amaris excimer laser (Schwind eye-tech-solutions, Kleinostheim, Germany) achieves epithelial and stromal ablation in a single uninterrupted step that consists of uniform precise epithelial removal followed by stromal ablation. TESA differs from the earlier two-step methods by using a customized epithelial profile derived from population based high frequency digital ultrasonography. These studies demonstrated that the corneal epithelium is thicker in the periphery.6 This customized profile ablates 55 um centrally and 65 um peripherally for a typical 8 mm total ablation zone. There is a further compensation for differential ablation between epithelium and stroma. Furthermore, TESA will also compensate for the phenomena of ‘epithelial masking’ in areas of stromal irregularity to achieve smoother ablations. V ISUA L OUTCOMES O F S I N G L E S T E P T- P R K / T E S A Fadlallah et al.7 found the visual outcomes comparable between single step t-PRK and a conventional alcohol-assisted PRK group. The postoperative mean sphere and mean astigmatism in the single step t-PRK group was -0.21 ± 0.61 and +0.43 ± 0.62 respectively. There was significantly less postoperative pain and rapid complete epithelial healing in the single step t-PRK group. Uncorrected distance visual acuity (UDVA) was not significantly different between the two groups at 3 months. Postoperative corneal haze can also occur after PRK and their study found at postoperative 3 months, 10% of eyes in the single step t-PRK group had grade 1 haze compared to 26% in the alcohol-assisted PRK group. Aslanides et al.8 found both single step t-PRK and the alcohol-assisted PRK groups to have safe outcomes. Their primary finding was that in the single step t-PRK group, patients had less early postoperative pain and photophobia on the third postoperative day with rapid epithelialization. Patients in this group also had better vision by 3 Snellen lines on this day. Corneal haze was significantly less at 1, 3 and 6 months (0.2 versus 0.43) but by year 1 there was no haze present in both groups. At postoperative 1-month, there was no significant difference in the unaided Snellen visual acuity (0.94 versus 0.97). Similarly, Fadlallah et al.7 also found no significant difference in visual acuity between the 2 groups at the 1 month and 3 month postoperative periods. Luger et al.9 found that between the single step t-PRK group and an alcohol-assisted PRK, the postoperative mean spherical equivalent (SE) 1 year after surgery was +0.07 D ± 0.23 and +0.01 D ± 0.27 respectively and 97% of eyes in both groups achieved an UDVA of 0.1 logMAR or better. T E S A : OU R R E SU LT S We recently presented our unpublished clinical results at the 15th International Schwind Users Meeting 2014 in Vancouver, Canada,9 and at the XXXII Congress of the ESCRS 2014 in London.10 In our retrospective analysis of patients treated in our Optimax Laser Eye Clinics in UK by five surgeons, 399 eyes underwent single-step laser epithelial removal and stromal ablation using the transepithelial PRK nomogram of the Amaris laser’s ORK-CAM software (Schwind eye-tech-solutions). All eyes underwent ablation with an Aberration-Free algorithm with the Schwind Amaris at a repetition rate of 750 Hz pulse with 1050 Hz eye tracking. The laser ablation was centred on the pupillary axis. The intended refractive aim for all eyes was emmetropia and there were no retreatments included. Adjunct mitomycin C was not used in any patient. The preoperative manifest SE was –3.88 ± 1.47 D (range: –1.25 to –8.00 D). At 1 month the Continues on page 22 : Ablation 22 APRIL 15, 2015 :: Ophthalmology Times surgery ABLATION ( Continued from page 20 ) postoperative manifest SE was reduced to –0.20 ± 0.53 D (range: –4.88 to 1.88) and at 3 months it was –0.17 ± 0.18 D (range: 0.88 to –1.25 D). The manifest SE was within 0.50 D and 1.00 D of emmetropia in 89% and 99% of eyes, respectively. At 3 months, the preoperative manifest sphere was reduced from –3.58 ± 1.44 D (range: –0.50 to –7.75 D) to –0.05 ± 0.33 D (range: +1.25 to –1.00 D) and the preoperative manifest astigmatism was reduced from –0.60 ± 0.53 (range: 0 to –3.50 D) to –0.25 ± 0.25 D (range: 0 to –1.75 D). UDVA of 20/25, 20/20 and 20/16 or better was achieved in 20%, 45% and 24% of 399 eyes, respectively. A gain of 1 or more lines was observed in 25% of eyes. Postoperative corneal haze of ≥1.5 was observed in 2% of eyes only. TESA IN SUMMARY TESA is effective at producing very safe and predictable visual outcomes for mild to moderate simple myopia or compound myopic astigmatism. We have also been able to demonstrate refractive stability and safety (clinically significant corneal haze is uncommon). The role of the corneal epithelium as a smoothing agent in relation to any underlying stromal topographical irregularity allows transmission of the smoothness of the aspheric ablation profile to the underlying stroma. This yields more predictable refractive results and less induction of clinically significant corneal aberrations. When t-PRK/TESA is used instead of ethanol assisted PRK there is the theoretical benefits of reduced postoperative dry eye, chronic ocular surface disease and recurrent corneal erosions. This is due to the reduced levels of keratocyte apoptosis and hence reduced generation of proinflam- matory mediators.11,12 This may also explain the lower levels of postoperative pain reported and more rapid epithelial healing.8 TESA represents an effective new method of surface ablation which is safe, predictable, stable and effective. Intraoperatively it is a very easy experience for a patient to undergo as it is painless, no touch technique (bladeless). ■ References 1. J. Marshall et al., Lasers Ophthalmol., 1986;21–48. 2. S.L. Trokel, R. Srinivasan and B. Braren, Am. J. Ophthalmol., 1983;96(6):710–715. 3. H.K. Lee et al., Am. J. Ophthalmol., 2005;139:56–63. 4. F. Ghadhfan, A. Al-Rajhi and M.D. Wagoner, J. Cataract Refract. Surg., 2007;33:2041–2048. 5. L. Buzzonetti et al., J. Refract. Surg., 2009;25:S122–S124. 6. D.Z. Reinstein et al., J. Refract. Surg., 2008;24:571–581. 7. A. Fadlallah et al., J. Cataract Refract. Surg., 2011;37:1852–1857 8. I.M. Aslanides et al., Clin. Ophhalmol., 2012;67:973–980 9. http://www.eye-tech-solutions. com/en/home/information-centre/ events/ (S. Mughal et al.) 10. http://www.escrs.org/london2014/ programme/free-papers-details. asp?id=21925 (S. Mughal et al.) 11. W.-J. Kim, S. Shah and S.E. Wilson, J. Refract. Surg., 1998;14:526– 533. 12. J.Y. Oh, J.M. Yu and J.H. Ko, Invest. Ophthalmol. Vis. Sci., 2013;54(6):3852–3856. DR AMIR HAMID, FRCOPHTH, CERTLRS E: [email protected] Dr. Hamid is Consultant Ophthalmic Surgeon and Medical Director at Optimax and Ultralase, London, UK. DR SAJJAD MUGHAL, FRCS, CERTLRS Dr. Mughal is a Corneal Laser Surgeon at Optimax and Ultralase, Birmingham, UK. ARIF SOKWALA, BSC Sokwala is Head Optometrist at Optimax and Ultralase, Leicester, UK. The authors have no financial interests to disclose. APRIL 15, 2015 :: Ophthalmology Times drug therapy Retinal gene therapy moving closer to clinical reality Developments have potentially lifelong benefits after single therapeutic administration By Jeffrey D. Chulay, MD, Special to Ophthalmology Times AL ACHUA, F L :: enes encode proteins that perform an array of functions. Many diseases have a genetic aspect whereby a mutated gene is passed down from generation to generation. Mutated genes may encode abnormal proteins or disable the production of a protein completely, either of which can cause disease. Gene therapy introduces a functional copy of the gene into a patient’s own cells. By correcting the underlying genetic defect that causes disease, gene therapy can potentially provide lifelong clinical benefits after a single administration. G A DENO -AS SOCI AT ED V IRUSE S Gene therapy uses viral vectors to deliver genes into cells affected by disease. Viral vectors have been optimized for this purpose by removing pathogenic elements and severely impairing the viruses’ ability to replicate. Adeno-associated virus (AAV) vectors are well suited for treating retinal diseases. AAV is a small, simple, non-enveloped virus with only two native genes, making the virus straightforward to work with from a vector-engineering standpoint. AAV vectors can carry gene sequences up to 4,000 base pairs in length.1 More than 90% of human genes have coding sequences less than 3,000 base pairs in length. AAV vectors have been used in more than 100 human clinical trials with no serious adverse events traced to the use of AAV as the gene delivery vector and are considered to be the safest viral vector for use in human gene therapy. AAV has never been linked to human disease and elicits only a mild immune response. AAV vectors have no viral genes remaining, virtually eliminating the possibility that any viral genes will cause an adverse event.1 AAV vectors can now be produced at a commercial scale in compliance with current Good Manufacturing Practice for use in clinical trials and future marketed products. As many as 2.4 x 1014 vector copies per liter have been (FIGURE 1) X-linked retinoschisis (XLRS) is an inherited retinal disease associated with splitting of the retinal layers and caused by mutations in the RS1 gene, which encodes the retinoschisin protein produced, with batches up to 100 liters, using the latest advances in large-scale viral vector production technology.2 Studies have confirmed that the purification process eliminates all but a trace amount of the raw materials used during manufacture, in many cases below assay detection levels.3 GENE THER APIES FOR RETINAL DISEASES Leber congenital amaurosis (LCA) is an inherited, early-onset retinal degenerative disease caused by mutations in any one of 16 genes. One form is caused by mutations in the RPE65 gene. The safety of AAV vector expressing RPE65 is supported by multiple phase I clinical trials.4-6 The safety and efficacy of RPE65 gene therapy for LCA continues to be evaluated in ongoing clinical trials including a phase III study. Wet age-related macular degeneration (AMD) is a major cause of visual impairment in older adults that is associated with neovascularization and macular edema. Current standard of care is intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors that must be administered monthly or bimonthly. An emerging wet AMD gene therapy approach uses an AAV vector to deliver the sFLT01 gene into retinal cells. The sFLT01 gene is an engineered version of the VEGF receptor that binds and inhibits VEGF ligand.7 The safety and tolerability of sFLT01 gene therapy for wet AMD is under investigation in an active phase I trial. Other AMD gene therapy programs include an active phase I/ II trial evaluating the safety of an AAV vector expressing the naturally occurring VEGF decoy receptor sFlt-1, and an active phase I trial evaluating the safety of a lentiviral vector expressing the anti-angiogenic proteins endostatin and angiostatin. Choroideremia is an inherited X-linked degenerative disease of the retina and choroid caused by mutations in the CHM gene. An ongoing phase I/II clinical trial reported promising 6-month findings with an AAV vector expressing the CHM gene.8Recruitment for a second phase I/II trial has recently commenced. X-linked retinoschisis (XLRS) is an inherited retinal disease associated with splitting of the retinal layers and caused by mutations in the RS1 gene, which encodes the retinoschisin protein (Figure 1). Two phase I/II trials are planned to evaluate safety and tolerability of AAV vectors expressing RS1 (Figure 2 on Page 24). One trial is currently recruiting and the other is scheduled to start recruitment in the first half of 2015. Stargardt disease is an inherited retinal dysContinues on page 24 : Gene therapy 23 24 APRIL 15, 2015 :: Ophthalmology Times drug therapy GENE THERAPY Preclinical evaluations of gene therapy for color vision deficiencies, including BCM, are ongoing. ( Continued from page 23 ) trophy characterized by photoreceptor degeneration in the macula. Most cases are caused by mutations in the ABCA4 gene.9Patients are currently being enrolled in a phase I/II trial that will evaluate the safety and tolerability of a lentiviral vector expressing the ABCA4 gene. Usher syndrome type 1 is an inherited disease associated with congenital deafness and early-onset photoreceptor loss. About half of Usher type 1 cases are caused by mutations in the MYO7A gene (type 1B). Patients are currently being enrolled in a phase I/II trial that will evaluate the safety and tolerability of a lentiviral vector expressing the MYO7A gene. Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by loss of retinal ganglion cells and optic nerve atrophy. Nearly all cases are caused by mutations in any one of three mitochondrial genes (ND1, ND4, and ND6). About half of LHON cases are caused by the same mutation in the ND4 gene.10,11 Recruitment is ongoing for two phase I trials that will evaluate the safety and tolerability of AAV vectors expressing the ND4 gene. Achromatopsia is an inherited retinal disease characterized by lack of cone photoreceptor function. The most common causes are mutations in the CNGA3 and CNGB3 genes. A preclinical study in dog models of achromatopsia with CNGB3 mutations showed restoration of cone function and improved ability to navigate mazes under bright light conditions after treatment with AAV vector expressing CNGB3.12 Clinical gene therapy programs to develop treatments for CNGB3 and CNGA3 mutations are under way. Retinitis pigmentosa is an inherited retinal dystrophy associated with progressive vision loss. In the United States about 10 to 15% of retinitis pigmentosa cases are X-linked (XLRP) and three-fourths of these cases are caused by mutations in the RPGR gene. Studies in dog models of XLRP with RPGR mutations showed delayed disease progression after treatment with AAV vector expressing RPGR.13Preclinical evaluation is ongoing. Blue cone monochromacy (BCM) is an inherited color vision deficiency characterized by lack of functional long-wavelength (L) and medium-wavelength (M) cone photoreceptors. BCM is caused by mutations in an area of the X chromosome that regulates expression of the L and M opsin genes.14 FUTURE OUTLOOK The once theoretical promise of gene therapy is evolving into clinical reality. Gene therapy can provide transformative disease-modifying effects by correcting the underlying defect that causes disease, potentially with lifelong clinical benefits after a single administration. An additional advancement in the treatment of retinal degeneration is an approach that delivers a lightsensitive protein to neurons in the retina. One such light-sensitive protein is channelrhodopsin 2. When channelrhodopsin 2 is inserted into a neuron and the neuron is stimulated by light, the neuron is activated and can transmit a signal to (FIGURE 2) Two phase I/II trials are planned to evaluate safety and tolerability of AAV vectors expressing RS1. the visual cortex. (Figures courtesy of Mark Pennesi) This technique, called optogenetics, is being applied to the design of therapeutic genes that can be exchimeric molecules delivered by AAV vectors for pressed by AAV vectors for the treatment of inhibition of retinal neovascularization. Gene Ther. 2009;16:10-16. advanced retinal degeneration.15 8. MacLaren RE, Groppe M, Barnard AR, et al. Retinal The current status of preclinical and clinigene therapy in patients with choroideremia: initial cal evaluation supports continued investment findings from a phase 1/2 clinical trial. Lancet. in the development of AAV-based gene thera2014;383:1129-1137. pies for retinal diseases, with ongoing research 9. Testa F, Melillo P, Di Iorio V, et al. Macular function and morphologic features in juvenile stargardt bringing these treatments closer to the clinic. References 1. Le Bec C and Douar AM. Gene therapy progress and prospects–vectorology: design and production of expression cassettes in AAV vectors. Gene Ther. 2006;13:805-813. 2. Thomas DL, Wang L, Niamke J, et al. Scalable recombinant adeno-associated virus production using recombinant herpes simplex virus type 1 coinfection of suspension-adapted mammalian cells. Hum Gene Ther. 2009;20:861-870. 3. Ye GJ, Scotti MM, Thomas DL, Wang L, Knop DR and Chulay JD. Herpes Simplex Virus Clearance During Purification of a Recombinant Adeno-Associated Virus Serotype 1 Vector. Hum Gene Ther Clin Dev. 2014;25:212-217. 4. Bainbridge JW, Smith AJ, Barker SS, et al. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med. 2008;358:2231-2239. 5. Jacobson SG, Cideciyan AV, Ratnakaram R, et al. Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Arch Ophthalmol. 2012;130:9-24. 6. Testa F, Maguire AM, Rossi S, et al. Three-year follow-up after unilateral subretinal delivery of adenoassociated virus in patients with Leber congenital Amaurosis type 2. Ophthalmology. 2013;120:12831291. 7. Pechan P, Rubin H, Lukason M, et al. Novel anti-VEGF 10. 11. 12. 13. 14. 15. disease: longitudinal study. Ophthalmology. 2014;121:2399-2405. Gueven N and Faldu D. Therapeutic strategies for Leber's hereditary optic neuropathy: A current update. Intractable Rare Dis Res. 2013;2:130-135. Lam BL, Feuer WJ, Abukhalil F, Porciatti V, Hauswirth WW and Guy J. Leber hereditary optic neuropathy gene therapy clinical trial recruitment: year 1. Arch Ophthalmol. 2010;128:1129-1135. Komaromy AM, Alexander JJ, Rowlan JS, et al. Gene therapy rescues cone function in congenital achromatopsia. Hum Mol Genet. 2010;19:2581-2593. Beltran WA, Cideciyan AV, Lewin AS, et al. Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. Proc Natl Acad Sci U S A. 2012;109:2132-2137. Gardner JC, Michaelides M, Holder GE, et al. Blue cone monochromacy: causative mutations and associated phenotypes. Mol Vis. 2009;15:876-884. Busskamp V, Picaud S, Sahel JA and Roska B. Optogenetic therapy for retinitis pigmentosa. Gene Ther. 2012;19:169-175. JEFFREY D. CHULAY, MD, is vice president and chief medical officer at Applied Genetic Technologies Corp. (AGTC). The Cataract Refractive Suite BY ALCON Advancing CATARACT SURGERY 1 Talk to your Alcon representative to experience superior visualization today. © 2015 Novartis 3/15 LUX15008JAD $OFRQGDWDRQOH 26 APRIL 15, 2015 :: Ophthalmology Times drug therapy Observations may provide evidence of systemic effect of anti-VEGF therapy About one-half of patients had significant reduction in DME of more than 50 μm in fellow eye By Lynda Charters; Reviewed by Lawrence J. Singerman, MD, FACS SAN TA BARBAR A, CA :: flibercept (Eylea, Regeneron) administered intravitreally may be associated with systemic effects based on an observable reaction in the fellow eyes of patients with diabetic macular edema (DME), according to Robert L. Avery, MD. The reduction in DME in the fellow eyes exceeded 50 μm in almost half of the patients, a reduction that exceeds a routine variation. The serum levels of three major intravitreally administered, anti-vascular endothelial growth factor (VEGF) drugs—ranibizumab (Lucentis, Genentech); bevacizumab (Avastin, Genentech); aflibercept—differ when measured 1 and 3 months after monthly injections. Bevacizumab was found to have the highest serum level followed by aflibercept and ranibizumab. “There was about a 70-fold difference in the area under the curve with bevacizumab compared with ranibizumab regarding systemic exposure,” said Dr. Avery, who is in private practice in Santa Barbara, CA. Differences of opinion exist regarding the relevance of this finding, with some believing that the intravitreal doses of the drugs are too small to have a systemic effect, the good safety profiles of the drugs negate concern, and no fellow-eye effect has been observed. A FELLOW-EYE EFFECTS However, fellow-eye effects have occurred. About a decade previously, when bevacizumab was used to treat proliferative vitreoretinopathy, the new vessels on the disc in the fellow eye stopped leaking about a week after treatment, Dr. Avery noted. The leakage resumed 2 weeks after treatment. “This caused me to consider that if this is a real effect, the doses must be much higher than needed to cause regression of the new vessels on the disc,” he said, and undertook an inverse dose response curve study. With 1/100 of the usual intravitreal dose, the new vessels on the disc stopped leaking. He also achieved the same effect with 1/200 of the dose. Dr. Avery and colleagues performed a retro“A reason that a fellow-eye effect is not seen is that the pharmacokinetics of the drug var- spective review of patients with bilateral DME. In this study, one eye of each patient was treated ies,” he said. The Harbor Study reported a wide range in with 2.0 mg of aflibercept. The fellow eye had the levels of ranibizumab at a concentration been untreated for 3 months before the start of measured 1 month after the last injection. At the study. Investigators determined that significant effects would be a 50-μm the time point because of the decrease in the retinal thickness high therapeutic level of the drug and at least a 10% decrease in still in patients, VEGF could be Intravitreal the maximal thickness seen on inhibited. aflibercept may be optical coherence tomography. Another reason that the felassociated with The study included 25 eyes, low-eye effect may have been systemic effects 12 eyes of which had a signifioverlooked is that investigators based on an cant decrease in retinal thickare not evaluating the patients observable reaction ness exceeding 50 μm and 3 eyes at the 1-week time point after in the fellow eyes of had an increase in the retinal treatment when the drug levels patients with diabetic thickness. are highest. macular edema. Compared with 19 control paHowever, a number of case tients with DME, “not nearly the reports have described, for exsame reduction in retinal thickample, regression of edema in the fellow eye of a patient with uveitic cystoid ness was seen and there clearly is variability in macular edema after ranibizumab, regressed these patients with diabetes,” Dr. Avery said. He reported that the mean change in retinal neovascularization of a disc in the fellow eye after treatment, and regressed scarring in the thickness in the fellow-eye patients was 43 μm compared with 6 μm in the control group, a fellow eye after ranibizumab injection. The effects of bevacizumab treatment in significant difference. Dr. Avery demonstrated the variable effects the fellow eye also have been reported in pain patients, with subtle fellow-eye changes aptients treated for retinopathy of prematurity. The Comparison of AMD Treatment Trial parent as early as 1 day after treatment. “The meaning of decreased circulating VEGF (Ophthalmology. 2013;120:2035-2041) also hinted at an effect of treatment in the fellow eye, ac- levels related to systemic serious adverse efcording to Dr. Avery, in that the fellow eyes fects after injection of anti-VEGF drugs is conwithout choroidal neovascularization (CNV) troversial,” he said. “In our small study of aflibercept, about half had a nonsignificant reduction in the incidence of CNV when treated with bevacizumab com- the patients had a significant reduction in DME of more than 50 μm in the fellow eye, which pared with ranibizumab. A mouse model also showed an effect of is beyond what is typically considered to be a injecting bevacizumab in the fellow eye that routine variation,” Dr. Avery said. “These obwas greater than the fellow-eye effect with servations may provide evidence that there is a systemic effect associated with intravitreal ranibizumab. aflibercept.” ■ VA R I A B L E E F F E C T S Regarding DME, a large study of the felloweye effects by Bakbak and colleagues (Retina. ROBERT L. AVERY, MD 2009;29:20-26) showed a significant decrease E: [email protected] in DME with bevacizumab, but not ranibiThis article was adapted from Dr. Avery’s presentation at the 2014 meeting of the zumab, which agreed with the pharmacokiAmerican Academy of Ophthalmology. Dr. Avery is a consultant to and shareholder in netics of the drugs, Dr. Avery noted. Genentech and Regeneron Pharmaceuticals. TAKE-HOME ZYLET® (LOTEPREDNOL ETABONATE 0.5% AND TOBRAMYCIN 0.3% OPHTHALMIC SUSPENSION) TECHNICAL PAPER 1 Blepharitis Management: A Clinical Approach John R. Favetta, MD Blepharitis refers to a variety of eyelid conditions with multiple, often concomitant, etiologies. Characterized by eyelid inflammation, bacterial overgrowth or infection—or the risk of infection—is also frequently present in blepharitis. As definitions and sub-categories of blepharitis have changed over the years, clear-cut estimates of prevalence have been challenging to obtain; but blepharitis is very frequently seen in ophthalmology practices. Left untreated, the presence of blepharitis may affect the risk of infection following ocular surgery and can limit the success of contact lens wear. A detailed history and careful attention to the lids, lashes, and meibomian glands during the slit lamp examination will aid in blepharitis detection and diagnosis. At a minimum, treatment includes eyelid hygiene; and acute presentations may benefit from combined antiinflammatory/antiinfective therapy. Combination agents can be particularly useful in the treatment of blepharitis. Blepharitis is a catchall term encompassing the many, often overlapping, inflammatory and infectious conditions of the eyelids. Without a single, etiology-based definition, it has not been possible to gain a good idea of the prevalence of blepharitis. But the conditions that comprise blepharitis are among the most common encountered in a comprehensive ophthalmology practice.1 Indeed, nearly a third of the patients I see—from young adults to seniors—present with signs and/or symptoms of blepharitis. It is often useful to distinguish types of blepharitis based on anatomical location. Thus, we have anterior blepharitis, which affects the area around the lashes and follicles, and posterior blepharitis, which affects the meibomian glands and proximate tissues. In either form, multiple causative factors and disease processes may be involved; and anterior and posterior blepharitis often coexist. Comorbidities, including chalazion and hordeolum, conjunctivitis, keratopathy (from superficial punctate keratitis to peripheral ulceration), and dry eye disease may be present with blepharitis.2 Blepharitis affects a broad swath of our patients: we see it in younger patients, who may have associated seborrheic dermatitis or acne rosacea; we see it in contact lens wearers, and in candidates for refractive, cataract, or other ocular surgeries; and we see it in patients who Sponsored by Bausch + Lomb come in simply because they are bothered by its symptoms. I consider it imperative to treat even mild blepharitis, as treatment can reduce the risk of infection and inflammation, and—of particular importance to me as a surgeon—help ensure success for surgical candidates. PATHOGENESIS Anterior blepharitis is often associated with excessive bacterial growth on the lid margins. The microbes involved are typically the same species that normally reside there, including Staphylococcus epidermidis and Staphylococcus aureus.2 While questions remain about the role(s) of bacteria in blepharitis, it appears that toxic exoenzymes produced by the colonizing species—particularly S. epidermidis—irritate the eyelids and ocular surface, causing the release of inflammatory mediators.1 In some cases, altered meibomian gland secretions may be an initiating factor, offering a supportive environment for bacterial proliferation.3 But bacteria can INDICATIONS AND USAGE 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 coagulase-negative), 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. IMPORTANT RISK INFORMATION ZYLET 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. 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 sued for 10 days or longer, intraocular pressure should be monitored. Use of corticosteroids may result in posterior subcapsular cataract formation. 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. Prolonged use of corticosteroids may suppress the host response 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. Employment of 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 exacerbate the severity of many viral infections of the eye (including herpes simplex). 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. ADVERSE REACTIONS Most common adverse reactions reported in patients were injection and superficial punctate keratitis, increased intraocular pressure, burning and stinging upon instillation. Please see the full prescribing information for ZYLET® on pages 3 and 4. ZYLET® (LOTEPREDNOL ETABONATE 0.5% AND TOBRAMYCIN 0.3% OPHTHALMIC SUSPENSION) TECHNICAL PAPER 2 also alter ocular surface lipids. For example, lipolytic staphylococcal enzymes break down the wax and sterol esters in the tear film; and the release of irritating breakdown products, including free fatty acids, as well as the resulting tear film instability, contribute to inflammation of the lid margin and conjunctiva.2 A number of potential non-microbial factors (eg, age and hormonal changes, medication use) can contribute to the changes in meibum quality and the ductal keratinization that underlies posterior blepharitis.3 Obstructive meibomian gland dysfunction (MGD) may not be inflammatory in its early stages, but the tear film changes (instability and hyperosmolarity), ocular surface irritation, increased ductal pressure, and bacterial involvement all contribute to inflammation and frank posterior blepharitis.3 blepharitis may report discomfort and significantly reduced wearing time. A close look at the lids forms a key part of the examination. Patients with anterior blepharitis often have reddened, swollen lids, telangiectasia, and debris or collarettes along the lashes. In addition, the tear meniscus may be foamy, a result of bacterial lipases causing breakdown of the meibomian lipids. In posterior blepharitis, we often see plugged, pouting meibomian glands that yield turbid, viscous meibum—or no meibum at all. Diagnostic gland expression is helpful in evaluating and grading a patient’s underlying MGD. Again, because either anterior or posterior blepharitis can affect the ocular surface, corneal and conjunctival staining with lissamine green, rose bengal, or fluorescein can help identify tissue changes indicative of blepharoconjunctivitis or blepharokeratoconjunctivitis. DIAGNOSIS In blepharitis diagnosis, history is paramount. Questioning patients about their ocular symptoms throughout the day can be very revealing: when patients describe stickiness and burning upon waking, with improvement through the day and a worsening in the evening, I know to look closely for signs of posterior blepharitis on my examination. Patients with anterior blepharitis report a gamut of symptoms. Some patients have red and swollen lids; others complain of irritation and burning. Contact lens wearers with anterior or posterior TREATMENT Eyelid hygiene is a mainstay of my treatment regimen for virtually every stage and subtype of blepharitis. Cleaning the crust, keratinized tissue, and bacteria and bacterial byproducts off the lid margin removes some contributors to the condition. I recommend any of several commercially available lid cleansing pads for my patients, giving a brief demonstration of their use in the office. For patients with posterior blepharitis, especially, I also add a hot compress and massage step to follow the cleans- CASE STUDY: PREOPERATIVE BLEPHARITIS A 65-year-old male patient presented to our clinic complaining of decreased vision, which upon examination was attributable to cataract. The patient was motivated to undergo surgery, but because the examination also revealed significant lid swelling, telangiectasia, and inspissated meibomian glands, I opted to delay the operation in order to address his blepharitis. I explained to the patient that treating his inflamed and possibly infected eyelids was important prior to undergoing ocular surgery. I believe that we have the best chance for a good surgical result when the lids and ocular surface are healthy at the outset. In addition to a routine of eyelid hygiene and warm compresses, I prescribed ZYLET® four times a day for 2 weeks. When the patient returned, his IOP was normal and the redness and edema of his lid margins had greatly decreased. In my opinion, the patient responded to ZYLET® therapy. At this point, I felt comfortable scheduling the patient for surgery—but I did make clear to him that blepharitis is a chronic condition; and that while his blepharitis was under control at the moment, he would need to continue regular eyelid hygiene and warm compresses, and to return to our office in the event of a significant flare-up. Sponsored by Bausch + Lomb ing scrub; an omega-3 fatty acid dietary supplement may also be part of the regimen.4,5 Lid hygiene may be performed once or twice a day; in cases where I add a topical pharmaceutical agent, I tell patients to instill their final dose of drug after performing their bedtime lid cleaning and warm compresses. Because blepharitis is often chronic and recurring, I emphasize to patients that even after we bring their acute condition under control, continued eyelid hygiene and warm compresses will help them maintain a healthy ocular surface. PHARMACOLOGIC INTERVENTION Lid hygiene alone is often insufficient to bring the coexisting and mutually-reinforcing inflammatory and infectious aspects of blepharitis under control. Topical corticosteroids, powerful inhibitors of inflammation, can be extremely useful for treating the acutely inflammed lid margin and ocular surface. The risks associated with corticosteroid use—particularly increased intraocular pressure (IOP) and cataractogenesis—are important considerations when selecting an agent and determining the duration of therapy. In many cases, the presence of bacterial overgrowth and the risk of superficial ocular infection also warrant the use of an antibiotic in treating blepharitis.6 A combination antibiotic/steroid agent is therefore well suited to address both the inflammatory and the potentially infectious components of this condition. My agent of choice for treating blepharitis is ZYLET® (loteprednol etabonate and tobramycin ophthalmic suspension 0.5%/0.3%). The steroid component, loteprednol etabonate 0.5%, is one key reason I favor ZYLET® in the treatment of blepharitis. Loteprednol etabonate combines antiinflammatory potency with an established safety profile.6,7 The loteprednol etabonate molecule contains an ester group in place of a ketone at the C-20 position. In the eye, the drug undergoes predictable hydrolysis into inactive metabolites, which is thought to contribute to its safety profile.6,7 Tobramycin, the antibiotic in ZYLET®, is broadly effective against common ocular pathogens, including the staphylococci often implicated in blepharitis.6,8 Please see Important Risk Information on page 1 and the full prescribing information for ZYLET® on pages 3 and 4. ZYLET® (LOTEPREDNOL ETABONATE 0.5% AND TOBRAMYCIN 0.3% OPHTHALMIC SUSPENSION) TECHNICAL PAPER I typically prescribe ZYLET® QID for 10 to 14 days, depending on severity. To this I add eyelid hygiene and, where applicable, warm compresses and omega-3 supplements. I bring patients back within about 10 days to evaluate sign and symptom resolution and to check IOP. When I prescribe ZYLET® for blepharitis, I emphasize to patients that it is intended as shortterm therapy only, and that long-term continuation of eyelid hygiene should help reduce the likelihood of recurrence. CONCLUSION Paying close attention to the lid margins can be beneficial for patients and practitioners. Neither a pristine surgical outcome nor successful contact lens wear is likely without a healthy ocular surface. Indeed, I have postponed surgeries for patients who present with significant blepharitis. To help get the acute inflammation and bacterial overgrowth of blepharitis under control, treatment with ZYLET® can be important. John R. Favetta, MD, practices in North Arlington, NJ. Please see Important Risk Information on page 1 and the full prescribing information for ZYLET® on this page and the next. REFERENCES 1. Lemp MA, Nichols KK. Blepharitis in the Unites States 2009: A survey-based perspective on prevalence and treatment. Ocul Surf. 2009;7(2) Suppl:A1-A22. 2. Jackson WB. Blepharitis: current strategies for diagnosis and management. Can J Ophthalmol. 2008;43:170-9. 3. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011;52(4):1922-9. 4. Macsai MS. The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:336-56. 5. Olenik A, Jimenez-Alfaro I, Alejandre-Alba N, Mahillo-Fernandez I. A randomized, double-masked study to evaluate the effect of omega-3 fatty acids supplementation in meibomian gland dysfunction. Clin Interv Aging. 2013;8:1133-8. 6. Comstock TL, Holland EJ. Loteprednol and tobramycin in combination: a review of their impact on current treatment regimens. Expert Opin Pharmacother. 2010;11(5):843-50. 7. Chen M, Gong L, Sun X, et al. A multicenter, randomized, parallel-group, clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of Chinese patients with blepharokeratoconjunctivitis. Curr Med Res Opin. 2012;28(3):385-94. 8. Zylet (loteprednol etabonate and tobramycin ophthalmic suspension 0.5%/0.3%) prescribing information. Tampa, FL: Bausch & Lomb, Inc; 2013. Sponsored by Bausch + Lomb ® HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use ZYLET® (loteprednol etabonate and tobramycin ophthalmic suspension) safely and effectively. See full prescribing information for ZYLET (loteprednol etabonate and tobramycin ophthalmic suspension, 0.5%/0.3%). Zylet (loteprednol etabonate and tobramycin ophthalmic suspension) 0.5%/0.3% Initial U.S. Approval: 2004 - - - -- - - -- - - -- - - -- INDICATIONS AND USAGE - - - -- - - -- - - -- - - -Zylet is a topical anti-infective and steroid combination for steroidresponsive inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocular infection or a risk of bacterial ocular infection exists. (1) - - - -- - - -- - - -- - DOSAGE AND ADMINISTRATION- -- - - -- - - -- - - -Apply one or two drops of Zylet into the conjunctival sac of the affected eye every four to six hours. (2.1) - - - -- - - -- - - -- - DOSAGE FORMS AND STRENGTHS -- - - -- - - -- - - -Zylet contains 5 mg/mL loteprednol etabonate and 3 mg/mL tobramycin. (3) - - - -- - - -- - - -- - - -- - CONTRAINDICATIONS -- - - -- - - -- - - -- - - -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. (4.1) - - - -- - - -- - - -- - -WARNINGS AND PRECAUTIONS - -- - - -- - - -- - - -D7=;*8,>5*;9;.<<>;. !!;85870.-><.8/,8;=2,8<=.;82-<6*B result in glaucoma with damage to the optic nerve, defects in visual *,>2=B*7-/2.5-<8/?2<287/=12<9;8->,=2<><.-/8; -*B<8; 5870.; !<18>5-+.6872=8;.- D*=*;*,=<%<.8/,8;=2,8<=.;82-<6*B;.<>5=2798<=.;28;<>+,*9<>5*; FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION ".,866.7-.-8<270 !;.<,;29=287>2-.527. 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 87+*,=.;2*5=28580B 5 WARNINGS AND PRECAUTIONS 7=;*8,>5*;!;.<<>;. !7,;.*<. *=*;*,=< .5*B.-.*5270 *,=.;2*57/.,=287< &2;*57/.,=287< >70*57/.,=287< 627805B,8<2-.B9.;<.7<2=2?2=B 3 cataract formation. (5.2) D.5*B.-1.*5270F$1.><.8/<=.;82-<*/=.;,*=*;*,=<>;0.;B6*B -.5*B1.*5270*7-27,;.*<.=1.27,2-.7,.8/+5.+/8;6*=2877=18<. diseases causing thinning of the cornea or sclera, perforations have +..7478@7=88,,>;@2=1=1.><.8/=892,*5<=.;82-<$1.272=2*5 prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of a magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. (5.3) D*,=.;2*527/.,=287<F!;85870.-><.8/,8;=2,8<=.;82-<6*B<>99;.<< the host response and thus increase the hazard of secondary ocular 27/.,=2877*,>=.9>;>5.7=,87-2=287<<=.;82-<6*B6*<427/.,=287 8;.71*7,..A2<=27027/.,=287/<207<*7-<B69=86</*25=8269;8?. after 2 days, the patient should be re-evaluated. (5.4) D&2;*527/.,=287<F6958B6.7=8/*,8;=2,8<=.;82-6.-2,*=28727=1. treatment of patients with a history of herpes simplex requires great ,*>=287%<.8/8,>5*;<=.;82-<6*B9;85870=1.,8>;<.*7-6*B exacerbate the severity of many viral infections of the eye (including herpes simplex). (5.5) D>70*527/.,=287<F>70*527/.,=287<8/=1.,8;7.**;.9*;=2,>5*;5B prone to develop coincidentally with long-term local steroid applica=287>70><27?*<2876><=+.,87<2-.;.-27*7B9.;<2<=.7=,8;7.*5 ulceration where a steroid has been used or is in use. (5.6) - - - -- - - -- - - -- - - -- - ADVERSE REACTIONS- -- - - -- - - -- - - -- - - -Most common adverse reactions reported in patients were injection and superficial punctate keratitis, increased intraocular pressure, burning and stinging upon instillation. (6) To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb at 1-800-323-0000 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch See 17 for PATIENT COUNSELING INFORMATION Revised: 08/2013 6 ADVERSE REACTIONS 8 USE IN SPECIFIC POPULATIONS !;.07*7,B 8.3 Nursing Mothers !.-2*=;2,%<. .;2*=;2,%<. 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action !1*;6*,8427.=2,< 13 NONCLINICAL TOXICOLOGY *;,2780.7.<2<>=*0.7.<2<69*2;6.7=8/.;=252=B 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION *Sections or subsections omitted from the full prescribing information are not listed FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE Zylet® 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. ,>5*;<=.;82-<*;.27-2,*=.-2727/5*66*=8;B,87-2=287<8/=1.9*59.+;*5*7-+>5+*;,873>7,=2?*,8;7.**7-*7=.;28;<.06.7=8/=1.058+. such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, and where the inherent risk 8/<=.;82-><.27,.;=*2727/.,=2?.,873>7,=2?2=2-.<2<*,,.9=.-=88+=*27*-2627>=28727.-.6**7-27/5*66*=287$1.B*;.*5<827-2,*=.-27 chronic anterior uveitis and corneal injury from chemical, radiation or thermal burns, or penetration of foreign bodies. $1.><.8/*,86+27*=287-;>0@2=1*7*7=227/.,=2?.,86987.7=2<27-2,*=.-@1.;.=1.;2<48/<>9.;/2,2*58,>5*;27/.,=2872<12018;@1.;. there is an expectation that potentially dangerous numbers of bacteria will be present in the eye. $1.9*;=2,>5*;*7=227/.,=2?.-;>027=12<9;8->,==8+;*6B,272<*,=2?.*0*27<==1./8558@270,86687+*,=.;2*5.B.9*=180.7< Staphylococci, including S. aureus and S. epidermidis (coagulase-positive and coagulase-negative), including penicillin-resistant strains. #=;.9=8,8,,227,5>-270<86.8/=1.;8>9+.=*1.685B=2,<9.,2.<<86.7871.685B=2,<9.,2.<*7-<86.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. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing 995B87.8;=@8-;89<8/'B5.=27=8=1.,873>7,=2?*5<*,8/=1.*//.,=.-.B..?.;B/8>;=8<2A18>;<>;270=1.272=2*5=818>;<=1. -8<2706*B+.27,;.*<.-=8.?.;B87.=8=@818>;<;.:>.7,B<18>5-+.-.,;.*<.-0;*->*55B*<@*;;*7=.-+B269;8?.6.7=27,5272,*5<207< *;.<18>5-+.=*4.778==8-2<,87=27>.=1.;*9B9;.6*=>;.5B 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)]. 3 DOSAGE FORMS AND STRENGTHS Zylet (loteprednol etabonate and tobramycin ophthalmic suspension) 0.5%/0.3% contains 5 mg/mL loteprednol etabonate and 3 mg/mL tobramycin. 4 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. 5 WARNINGS AND PRECAUTIONS 5.1 Intraocular Pressure (IOP) Increase !;85870.-><.8/,8;=2,8<=.;82-<6*B;.<>5=2705*>,86*@2=1-*6*0.=8=1.89=2,7.;?.-./.,=<27?2<>*5*,>2=B*7-/2.5-<8/?2<287#=.;82-< should be used with caution in the presence of glaucoma. /=12<9;8->,=2<><.-/8; -*B<8;5870.;27=;*8,>5*;9;.<<>;.<18>5-+.6872=8;.- 5.2 Cataracts %<.8/,8;=2,8<=.;82-<6*B;.<>5=2798<=.;28;<>+,*9<>5*;,*=*;*,=/8;6*=287 /™ are trademarks of Bausch & Lomb Incorporated or its affiliates. All other product/brand names are trademarks of their respective owners. ©2014 Bausch & Lomb Incorporated US/ZYL/14/0002 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 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. 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. 6 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. 8 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 noobserved-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. Sponsored by Bausch + Lomb C24H31ClO7 Mol. Wt. 466.96 C18H37N5O9 Mol. Wt. 467.52 Chemical Name: O-3-Amino-3-deoxy-α-D-glucopyranosyl-(1¤ 4)-O- [2,6-diamino2,3,6-trideoxy-α-D-ribo-hexopyranosyl- (1¤ 6)] -2-deoxystreptamine Each mL contains: Actives: Loteprednol Etabonate 5 mg (0.5%) and Tobramycin 3 mg (0.3%). Inactives: Edetate Disodium, Glycerin, Povidone, Purified Water, Tyloxapol, and Benzalkonium Chloride 0.01% (preservative). Sulfuric Acid and/or Sodium Hydroxide may be added to adjust the pH to 5.7-5.9. The suspension is essentially isotonic with a tonicity of 260 to 320 mOsm/kg. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation. There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Corticosteroids are capable of producing a rise in intraocular pressure. Loteprednol etabonate is structurally similar to other corticosteroids. However, the number 20 position ketone group is absent. The anti-infective component in the combination (tobramycin) is included to provide action against susceptible organisms. In vitro studies have demonstrated that tobramycin is active against susceptible strains of the following microorganisms: Staphylococci, including S. aureus and S. epidermidis (coagulase-positive and coagulase-negative), including penicillin-resistant strains. Streptococci, including some of the Group A-beta-hemolytic species, some nonhemolytic species, and some Streptococcuspneumoniae. 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. 12.3 Pharmacokinetics In a controlled clinical study of ocular penetration, the levels of loteprednol etabonate in the aqueous humor were found to be comparable between Lotemax and Zylet treatment groups. Results from a bioavailability study in normal volunteers established that plasma levels of loteprednol etabonate and Δ1 cortienic acid etabonate (PJ 91), its primary, inactive metabolite, were below the limit of quantitation (1 ng/mL) at all sampling times. The results were obtained following the ocular administration of one drop in each eye of 0.5% loteprednol etabonate ophthalmic suspension 8 times daily for 2 days or 4 times daily for 42 days. This study suggests that limited (<1 ng/mL) systemic absorption occurs with 0.5% loteprednol etabonate. 13 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). 16 HOW SUPPLIED/STORAGE AND HANDLING Zylet (loteprednol etabonate and tobramycin ophthalmic suspension) is supplied in a white low density polyethylene plastic bottle with a white controlled drop tip and a white polypropylene cap in the following sizes: 5 mL (NDC 24208-358-05) in a 7.5 mL bottle 10 mL (NDC 24208-358-10) in a 10 mL bottle USE ONLY IF IMPRINTED NECKBAND IS INTACT. Storage: Store upright at 15º-25º C (59º-77º F). PROTECT FROM FREEZING 17 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. 9007705 (FOLDED) 9004405 (FLAT) Tobramycin: Chemical name: chloromethyl 17α-[(ethoxycarbonyl)oxy]11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate 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. 11 DESCRIPTION Zylet (loteprednol etabonate and tobramycin ophthalmic suspension) is a sterile, multiple dose topical anti-inflammatory corticosteroid and anti-infective combination for ophthalmic use. Both loteprednol etabonate and tobramycin are white to off-white powders. The chemical structures of loteprednol etabonate and tobramycin are shown below. Loteprednol etabonate: 4 ZYLET® (LOTEPREDNOL ETABONATE 0.5% AND TOBRAMYCIN 0.3% OPHTHALMIC SUSPENSION) TECHNICAL PAPER Please see Important Risk Information for ZYLET® on page 1. APRIL 15, 2015 :: Ophthalmology Times technology Capsule retractor improves challenge of weak zonules Design mimics artificial zonules to help achieve sufficient capsular bag stabilization By Luigi Fontana, MD, PhD, Special to Ophthalmology Times TAKE-HOME Capsule Retractor Placement Weak zonules are known to add intraoperative complications and affect every step of the cataract procedure. Luigi Fontana, MD, PhD, describes how capsule retractors have helped him tackle this issue in his cataract practice. REGGIO EMIL IA, I TALY :: onular weakness on occasion can be well foreseen before surgery, but most usually has been known to occur unexpectedly. Surgeons typically try to stabilize the capsular bag by inserting a capsular tension ring to reinforce the weak part of the capsular bag in the presence of focal zonular dialysis or weakness. Tension rings can be somewhat difficult to insert in these patients, however, and they Z Place through a 0.8 mm or larger paracentesis. If needed slip the working end under the capsulorhexis. Move the silicone stopper forward and into place. Capsule Retractor Removal MANAGING ZONULAR WEAKNESS Move the silicone stopper back and then the entire MST Capsule Retractor centrally to disengage. VIDEO Go to http://bit.ly/1JkPTLA (Videos courtesy of Luigi Fontana, MD, PhD) More Video http://bit.ly/1Fy6472 http://bit.ly/1DgbPqd Remove the silicone stopper. have often proved inefficient in successfully stabilizing the zonular capsular complex. Typically, iris hooks have been used to support the capsular bag when there have been cases of focal or diffusely loose zonules. However, as the hooked ends are short and flexible, these commonly used iris retractors may Dr. Fontana tend to slip off the anterior capsular edge during phacoemulsification and provide little or no support to the equator of the capsular bag. Furthermore, because iris hooks also have Remove from the main incision using forceps and cutting the tail end off if necessary. sharp ends, this may pose a risk in causing damage by tearing the anterior capsule. A new and useful capsule retractor (MST Capsule Retractor, MicroSurgical Technology) has allowed for easier and safer management of weak zonules during cataract surgery. The shape and elongation of the hooks provide a broader area of contact that gently supports the peripheral capsular bag equator, as well as the capsulorhexis edge. This allows the retractors to mimic and act as artificial zonules that help the surgeon to achieve sufficient stabilization throughout the Continues on page 31 : Retractor 27 OZURDEX ® (dexamethasone intravitreal implant) 0.7 mg Brief Summary—Please see the OZURDEX® package insert for full Prescribing Information. INDICATIONS AND USAGE Retinal Vein Occlusion: OZURDEX® (dexamethasone intravitreal implant) is a corticosteroid indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Posterior Segment Uveitis: OZURDEX® is indicated for the treatment of non-infectious uveitis affecting the posterior segment of the eye. Diabetic Macular Edema OZURDEX® is indicated for the treatment of diabetic macular edema. CONTRAINDICATIONS Ocular or Periocular Infections: OZURDEX® (dexamethasone intravitreal implant) is contraindicated in patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases. Glaucoma: OZURDEX® is contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8. Torn or Ruptured Posterior Lens Capsule: OZURDEX® is contraindicated in patients whose posterior lens capsule is torn or ruptured because of the risk of migration into the anterior chamber. Laser posterior capsulotomy in pseudophakic patients is not a contraindication for OZURDEX® use. Hypersensitivity: OZURDEX® is contraindicated in patients with known hypersensitivity to any components of this product [see Adverse Reactions]. WARNINGS AND PRECAUTIONS Intravitreal Injection-related Effects: Intravitreal injections, including those with OZURDEX®, have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored regularly following the injection [see Patient Counseling Information]. Steroid-related Effects: Use of corticosteroids including OZURDEX® may produce posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses [see Adverse Reactions]. Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex because of the potential for reactivation of the viral infection. ADVERSE REACTIONS Clinical Studies Experience: 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 rates in the clinical studies of another drug and may not reflect the rates observed in practice. Adverse reactions associated with ophthalmic steroids including OZURDEX® include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera. Retinal Vein Occlusion and Posterior Segment Uveitis The following information is based on the combined clinical trial results from 3 initial, randomized, 6-month, sham-controlled studies (2 for retinal vein occlusion and 1 for posterior segment uveitis): Adverse Reactions Reported by Greater than 2% of Patients MedDRA Term Intraocular pressure increased Conjunctival hemorrhage Eye pain Conjunctival hyperemia Ocular hypertension Cataract Vitreous detachment Headache OZURDEX® N=497 (%) 125 (25%) 108 (22%) 40 (8%) 33 (7%) 23 (5%) 24 (5%) 12 (2%) 19 (4%) Sham N=498 (%) 10 (2%) 79 (16%) 26 (5%) 27 (5%) 3 (1%) 10 (2%) 8 (2%) 12 (2%) Increased IOP with OZURDEX® peaked at approximately week 8. During the initial treatment period, 1% (3/421) of the patients who received OZURDEX® required surgical procedures for management of elevated IOP. Following a second injection of OZURDEX® (dexamethasone intravitreal implant) in cases where a second injection was indicated, the overall incidence of cataracts was higher after 1 year. Diabetic Macular Edema The following information is based on the combined clinical trial results from 2 randomized, 3-year, sham-controlled studies in patients with diabetic macular edema. Discontinuation rates due to the adverse reactions listed in the table below were 3% in the OZURDEX® group and 1% in the Sham group. The most common ocular (study eye) and non-ocular adverse reactions are as follows: Ocular Adverse Reactions Reported by ≥ 1% of Patients and Non-ocular Adverse Reactions Reported by ≥ 5% of Patients MedDRA Term Ocular Cataract1 Conjunctival hemorrhage Visual acuity reduced Conjunctivitis Vitreous floaters Conjunctival edema Dry eye Vitreous detachment Vitreous opacities Retinal aneurysm Foreign body sensation Corneal erosion Keratitis Anterior Chamber Inflammation Retinal tear Eyelid ptosis Non-ocular Hypertension Bronchitis OZURDEX® N=324 (%) Sham N=328 (%) 166/2432 (68%) 73 (23%) 28 (9%) 19 (6%) 16 (5%) 15 (5%) 15 (5%) 14 (4%) 11 (3%) 10 (3%) 7 (2%) 7 (2%) 6 (2%) 6 (2%) 49/230 (21%) 44 (13%) 13 (4%) 8 (2%) 6 (2%) 4 (1%) 7 (2%) 8 (2%) 3 (1%) 5 (2%) 4 (1%) 3 (1%) 3 (1%) 0 (0%) 5 (2%) 5 (2%) 2 (1%) 2 (1%) 41 (13%) 15 (5%) 21 (6%) 8 (2%) Includes cataract, cataract nuclear, cataract subcapsular, lenticular opacities in patients who were phakic at baseline. Among these patients, 61% of OZURDEX® subjects vs. 8% of sham-controlled subjects underwent cataract surgery. 2 243 of the 324 OZURDEX® subjects were phakic at baseline; 230 of 328 sham-controlled subjects were phakic at baseline. Increased Intraocular Pressure Summary of Elevated IOP Related Adverse Reactions 1 Treatment: N (%) IOP OZURDEX® N=324 Sham N=328 IOP elevation ≥10 mm Hg from Baseline at any visit ≥30 mm Hg IOP at any visit 91 (28%) 13 (4%) 50 (15%) 5 (2%) Any IOP lowering medication 136 (42%) 32 (10%) Any surgical intervention for elevated IOP* 4 (1.2%) 1 (0.3%) * OZURDEX®: 1 surgical trabeculectomy for steroid-induced IOP increase, 1 surgical trabeculectomy for iris neovascularization,1 laser iridotomy, 1 surgical iridectomy Sham: 1 laser iridotomy Cataracts and Cataract Surgery At baseline, 243 of the 324 OZURDEX® subjects were phakic; 230 of 328 sham-controlled subjects were phakic. The incidence of cataract development in patients who had a phakic study eye was higher in the OZURDEX® group (68%) compared with Sham (21%). The median time of cataract being reported as an adverse event was approximately 15 months in the OZURDEX® group and 12 months in the Sham group. Among these patients, 61% of OZURDEX® subjects vs. 8% of sham-controlled subjects underwent cataract surgery, generally between Month 18 and Month 39 (Median Month 21 for OZURDEX® group and 20 for Sham) of the studies. APRIL 15, 2015 :: Ophthalmology Times technology RETRACTOR ( Continued from page 27 ) The MST Capsule Retractor allows for safe and easier management of weak zonules during surgery. (Images courtesy of MicroSurgical Technology) entire bag during phacoemulsification and cortical cleanup. This minimizes any hindering during cortical lens material aspiration. This has not been the case when using capsular tension rings. The retractors allow the surgeon to get the required support vitally needed in the anterior-posterior direction and not trap the cortex. The capsule retractors also have a smooth looped tip that reduces the risk of puncturing the equatorial capsule or tearing the anterior capsule edge. In addition, a silicone button slides to allow for precise adjustment and monitoring of the degree of required tension during every procedure from patient to patient. REDUCED COMPLICATIONS The instrument can also reduce the number of complications occurring in patients presenting with zonular weakness, such as vitreous loss and lens fragment dislocation in the vitreous. This is typically because the surgeon is able to pull the capsule and distribute gentle force in the equator, achieve a broader area of contact with the capsulorhexis margin, and also easily direct and control the tension. Managing zonular weakness has been improved with the thought of knowing that there are minimal or no intraoperative complications. As every surgeon will lament, complications in patients with The retractor can also reduce the number of complications occurring in patients with zonular weakness. zonular weakness during cataract surgery prolongs operating time and further increases the risk of re-operation. Capsular retractors have helped to control and possibly reduce the risk of complication and, therefore, reduce operating room time with these complicated cases. As an example to illustrate how convenient and easy the retractors have made patient management, a recent case presented with posttraumatic cataract and 120° zonular weakness with iris dialysis. With use of the retractors, it was possible to successfully and simultaneously pull the iris remnants aside and stabilize the capsular bag. In this otherwise-difficult case, the capsule retractors allowed safe and easy emulsification of the hard cataract and preservation of the capsular bag, as well as the implantation of a capsular tension ring and an IOL in the capsular bag. The use of the capsular retractors have made the approach much more proficient and adept in tackling complicated anterior segment surgery cases and managing zonular weakness with ease. ■ LUIGI FONTANA, MD, PHD E: [email protected] Dr. Fontana is director of the ophthalmology department of the hospital Santa Maria Nuova IRCCS, Reggio Emilia, Italy. Dr. Fontana has no financial disclosure with MicroSurgical Technology (MST). The increase in mean IOP was seen with each treatment cycle, and the mean IOP generally returned to baseline between treatment cycles (at the end of the 6 month period). USE IN SPECIFIC POPULATIONS Pregnancy Category C Risk Summary There are no adequate and well-controlled studies with OZURDEX® in pregnant women. Animal reproduction studies using topical ocular administration of dexamethasone were conducted in mice and rabbits. Cleft palate and embryofetal death in mice and malformations of the intestines and kidneys in rabbits were observed. OZURDEX® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data Topical ocular administration of 0.15% dexamethasone (0.375 mg/kg/day) on gestational days 10 to 13 produced embryofetal lethality and a high incidence of cleft palate in mice. A dose of 0.375 mg/kg/day in the mouse is approximately 3 times an OZURDEX® injection in humans (0.7 mg dexamethasone) on a mg/m2 basis. In rabbits, topical ocular administration of 0.1% dexamethasone throughout organogenesis (0.13 mg/kg/day, on gestational day 6 followed by 0.20 mg/kg/ day on gestational days 7-18) produced intestinal anomalies, intestinal aplasia, gastroschisis and hypoplastic kidneys. A dose of 0.13 mg/kg/day in the rabbit is approximately 4 times an OZURDEX® injection in humans (0.7 mg dexamethasone) on a mg/m2 basis. Nursing Mothers: Systemically administered corticosteroids are present in human milk and can suppress growth and interfere with endogenous corticosteroid production. The systemic concentration of dexamethasone following intravitreal treatment with OZURDEX® is low. It is not known whether intravitreal treatment with OZURDEX® could result in sufficient systemic absorption to produce detectable quantities in human milk. Exercise caution when OZURDEX® is administered to a nursing woman. Pediatric Use: Safety and effectiveness of OZURDEX® in pediatric patients have not been established. Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility No adequate studies in animals have been conducted to determine whether OZURDEX® (dexamethasone intravitreal implant) has the potential for carcinogenesis. Although no adequate studies have been conducted to determine the mutagenic potential of OZURDEX®, dexamethasone has been shown to have no mutagenic effects in bacterial and mammalian cells in vitro or in the in vivo mouse micronucleus test. Adequate fertility studies have not been conducted in animals. PATIENT COUNSELING INFORMATION Steroid-related Effects Advise patients that a cataract may occur after repeated treatment with OZURDEX®. If this occurs, advise patients that their vision will decrease, and they will need an operation to remove the cataract and restore their vision. Advise patients that they may develop increased intraocular pressure with OZURDEX® treatment, and the increased IOP will need to be managed with eye drops, and, rarely, with surgery. Intravitreal Injection-related Effects Advise patients that in the days following intravitreal injection of OZURDEX®, patients are at risk for potential complications including in particular, but not limited to, the development of endophthalmitis or elevated intraocular pressure. When to Seek Physician Advice Advise patients that if the eye becomes red, sensitive to light, painful, or develops a change in vision, they should seek immediate care from an ophthalmologist. Driving and Using Machines Inform patients that they may experience temporary visual blurring after receiving an intravitreal injection. Advise patients not to drive or use machines until this has been resolved. ©2014 Allergan, Inc., Irvine, CA 92612, U.S.A. ® marks owned by Allergan, Inc. Patented. See: www.allergan.com/products/patent_notices Made in Ireland. Based on 72212US18 Re-order: APC02BN14 Rx only 32 Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL ADVANCES CONTINUE TO PROGRESS FOR REDUCING RISK AND INCIDENCE OF INFECTION (FIGURE 1) No prospective study has ever been conducted to prove that topical antibiotics lowers the risk of endophthalmitis. (Photo courtesy of Francis S. Mah, MD) INTRACAMERAL ANTIBIOTICS STILL RAISING CONCERNS Topical drugs widely used despite the lack of direct evidence proving their efficacy By Cheryl Guttman Krader; Reviewed by Francis S. Mah, MD A L A JOL L A, CA :: take-home Accumulating evidence shows intracameral antibiotics decrease the risk of endophthalmitis after cataract surgery, but questions and concerns remain. ntibiotic prophylaxis for cataract surgery remains a controversial topic, despite convincing data showing the efficacy of intracameral antibiotic use for reducing the risk of postoperative endophthalmitis, said Francis S. Mah, MD. “The low rate of postoperative infection and the potential for many different variables to affect the risk make it difficult to conduct an appropriate large-scale clinical trial,” said Dr. Mah, director, corneal and external disease, and co-director, refractive surgery, Scripps Clinic, La Jolla, CA. The prospective study undertaken by the European Society of Cataract and Refractive Surgeons (ESCRS) provides the best evidence available, and subsequently, the efficacy of intracameral antibiotic prophylaxis has been demonstrated in other prospective studies, Dr. Mah said. “However, there are still concerns about that approach and questions about the optimal technique,” he said. Reviewing the outcomes of the ESCRS study, members of the Infectious Disease Task Force of the American Society of Cataract and Refractive Surgery (ASCRS) concluded that intracameral antibiotic use may be a paradigm shift for endophthalmitis prophylaxis. However, continued research was needed to examine the optimal drug, dose, and method of delivery, as well as the short- and long-term effects. In addition, widespread adoption would depend on access to a product that would be safe and simple to use with minimal risk of dilution errors and contamination, Dr. Mah said. SINGLE-USE CEFUROXIME In 2012, single-use cefuroxime for intracameral use became commercially available in some countries in Europe. This product represents a step forward as it significantly reduces safety concerns associated with extemporaneous preparation. However, it does not completely eliminate the potential for dilution errors and contamination, and there have been reports of anaphylaxis associated with its use. “The risk of an allergic reaction is much lower with cefuroxime compared with penicillin, but it still exists,” Dr. Mah said. Interestingly, in a survey of ESCRS members published in 2014, only 74% of respondents were always or usually using an intracameral antibiotic in cataract surgery, despite the fact that it is recommended by the ESCRS and various European national ophthalmology societies. “Many of the respondents still questioned the scientific merit or need for intracameral antibiotic use, but concern over risks associated with compounding the dose was also common,” Dr. Mah said. No prospective study has ever been conducted to provide direct proof that topical antibiotic use decreases the risk of endophthalmitis. In the ESCRS study, perioperative use of topical levofloxacin was associated with a decreased rate of endophthalmitis, but the benefit did not achieve statistical significance. Dr. Mah said use of topical antibiotics for endophthalmitis prophylaxis is supported by surrogate evidence derived from microbiology studies demonstrating reduced bacteria Continues on page 35 : Raising concerns Visit us at AAO Booth 1207 The Quintessential Proven therapeutic utility in blepharitis, conjunctivitis, and other superficial ocular infections Profound bactericidal effect against gram-positive pathogens1 O Excellent, continued resistance profile—maintains susceptibility,2,3 even against methicillin-resistant Staphylococcus aureus 4 OOintment provides long-lasting ocular surface contact time and greater bioavailability5 OAnti-infective efficacy in a lubricating base6 OUnsurpassed safety profile—low incidence of adverse events6 OConvenient dosing—1 to 3 times daily6 OTier 1 pharmacy benefit status—on most insurance plans7 O 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 The low incidence of allergenicity exhibited by Bacitracin means that adverse events are practically non-existent. If such reactions do occur, therapy should be discontinued. Bacitracin Ophthalmic Ointment should not be used in deep-seated ocular infections or in those that are likely to become systemic. This product should not be used in patients with a history of hypersensitivity to Bacitracin. Please see adjacent page for full prescribing information. References: 1. Kempe CH. The use of antibacterial agents: summary of round table discussion. Pediatrics. 1955;15(2):221-230. 2. Kowalski RP. Is antibiotic resistance a problem in the treatment of ophthalmic infections? Expert Rev Ophthalmol. 2013;8(2):119-126. 3. Recchia FM, Busbee BG, Pearlman RB, Carvalho-Recchia CA, Ho AC. Changing trends in the microbiologic aspects of postcataract endophthalmitis. Arch Ophthalmol. 2005;123(3):341-346. 4. Freidlin J, Acharya N, Lietman TM, Cevallos V, Whitcher JP, Margolis TP. Spectrum of eye disease caused by methicillin-resistant Staphylococcus aureus. Am J Ophthalmol. 2007;144(2):313-315. 5. Hecht G. Ophthalmic preparations. In: Gennaro AR, ed. Remington: the Science and Practice of Pharmacy. 20th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2000. 6. Bacitracin Ophthalmic Ointment [package insert]. Minneapolis, MN: Perrigo Company; August 2013. 7. Data on file. Perrigo Company. Logo is a trademark of Perrigo. ©2014 Perrigo Company Printed in USA 4022-05-01-JA 01/14 www.perrigobacitracin.com APRIL 15, 2015 :: Ophthalmology Times Bacitracin Ophthalmic Ointment USP Special Report ) OCULAR INFECTION CONTROL 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. 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 gram-negative 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. Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Manufactured For ® Minneapolis, MN 55427 0S400 RC J1 Rev 08-13 A EFFECTIVE CONCEPTS IN SECOND LOOK dence whatsoever that one antibiotic is better than another,” he said. ( Continued from page 1 ) WHAT ABOUT SURGICAL TECHNIQUE? Evidence based on results of a randomized trial from Japan and two case-control studies from the United States all found a three-fold excessive risk of corneal versus scleral incisions. “I interpret this in a simplistic manner that wound is important whether doing corneal or scleral incisions,” Dr. Schein said. “Blood is a good adhesive, and it has antibacterial properties.” Sweden has a unique approach to endophthalmitis. In reviewing national data in Sweden with the same methodology over a decade or so, there is evidence that its rate of endophthalmitis has progressively declined and then leveled out at about 0.02%, he noted. Beginning in the late 1990s, Sweden started using intracameral cefuroxime and published a series of case-control studies. Lack of use of cefuroxime intracamerally became the dominant risk factor for endophthalmitis, even greater than vitreous access or older age. “In Sweden, they don’t use preoperative topical antibiotics as a rule, and they don’t use topical antibiotics postoperatively,” Dr. Schein said. “They use cefuroxime intraoperatively almost entirely. “So, with all this evidence, why are we not doing it in United States?” he asked. For one, he noted that the United States does not yet have ready access to safe, available, and predictable intracameral antibiotic. “If you put the wrong antibiotic in or use the wrong concentration, you can blind a patient,” he said. “Because endophthalmitis is a known risk, as a surgeon you hate to be the person responsible for a catastrophe when trying to prevent it.” U.S. regulatory barriers also add a layer of obstacles. The FDA has gone on record that to approve a drug’s intracameral use requires one, if not two, randomized clinical trials. It would take many millions of dollars to prove again what has been quite well substantiated, he noted. “Finally, despite the enormous costs to Medicare and patients of perioperative topical antibiotics, there is not a good mechanism for facilities to be reimbursed the cost of delivering antibiotics on the day of surgery—even if those drugs were sufficiently long lasting in effect to substitute for eye drops currently used postoperatively,” Dr. Schein said. ■ Dr. Schein shared data on incidence taken from the U.S. National Medicare Database and explained that rates in the late 1990s were as high as about 1 in 700. Most recent reliable U.S. estimates put the rate at about 1 in 1,100 cases per year. “Interestingly, higher-volume surgeons have lower rates,” he said. “Data can’t tell you why that’s true. I expect it’s because they have less of the known major risk factors, such as vitreous loss.” The same results are found in Canada— about 1 in 700. Again, risk factors are similar whether in the United States, Canada, or elsewhere—older age, vitrectomy, higher-volume surgeons with less risk of disease. “What do we know from these national studies? Vitreous access, older age, men more than women, and lower surgical volume are all chief risk factors. R ATE R EDUCTION Dr. Schein sifted through pre-, intra-, and postoperative opportunities for reducing the rate. “Preoperatively, it’s essentially standard in the United States to use topical antibiotics on the day of surgery—ones that were all approved for conjunctivitis, though there is no indication for preoperative use and little evidence of any benefit in reducing endophthalmitis,” he said. Evidence supports the standard use of povidone-iodine in preparing the ocular surface. What is not confirmed is whether povidoneiodine works better than other antiseptics, for example, 0.05% chlorhexidine, he said. Dr. Schein is working on a national study which represents a huge series of endophthalmitis from around the country—about 92% gram positive. Of those, 90% were staph and 10% were streptococcus, along with a few cases of gram negatives, he noted. “If you did believe that using topical antibiotics before surgery was important, and you’re wanting to kill the bugs that are most frequent, you could do what Bascom Palmer Eye Institute did in 2005 when they asked the question: ‘If you took our cases of endophthalmitis and wanted to kill the bugs preoperatively, which were the most effective antibiotics, and what did they cost?’” Dr. Schein said. Gentamycin fared much better than the more current antibiotics primarily because “it’s a good staph drug. But evidence that adding an antibiotic to a preoperative regimen is beneficial is very minimal,” he said. “There is no evi- OLIVER D. SCHEIN, MD, MPH E: [email protected] This article was adapted from Dr. Schein’s presentation during Wilmer Eye Institute’s 27th Annual Current Concepts in Ophthalmology meeting in 2014. He did not indicate any financial interest relevant to the subject matter. 35 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN RAISING CONCERNS ( Continued from page 32 ) counts in cultures grown from conjunctiva and aqueous humor specimens. In addition, there are data from retrospective studies showing benefit. Despite the lack of definitive evidence demonstrating its efficacy, topical antibiotics are widely used for endophthalmitis prophylaxis, especially in the United States. Findings from a member survey conducted by the ASCRS Cataract Committee in 2007 showed 88% of respondents were using a topical anti biotic preoperatively and 98% used a topical antibiotic postoperatively. U.S. surgeons accounted for about three-fourths of survey participants. The advanced-generation fluoroquinolones have become the most commonly used antibiotics for topical endophthalmitis prophylaxis due to their broader spectrum of antimicrobial activity and superior ocular penetration characteristics compared with earlier-generation fluoroquinolones and other alternatives. Dr. Mah noted that regimens vary among surgeons. However, based on pharmacokinetics and pharmacodynamics data, there are recommendations to initiate treatment 1 to 3 days prior to surgery or to increase the frequency of dosing immediately prior to surgery in order to increase the concentration of antibiotic in the anterior chamber. Certain strategies for reducing risk of postoperative endophthalmitis are well accepted as standard of care. They include the need to preoperatively identify and treat periocular conditions that have been associated with an increased risk of endophthalmitis—e.g., conjunctivitis, blepharitis, and dry eye. Meticulous lid draping is also mandatory, recognizing that lid flora are the predominant patho- Correction An error occurred in a recent article (“Compounded combination drops safe, effective for postLASIK management,” Ophthalmology Times, March 15, 2015, Page 26). The second paragraph under the heading “Patient series” should be replaced with this text: The typical dosage for the “less drops” technique was q.i.d. for 1 week then b.i.d. for one additional week. With that said, some patients only required 1 week of drops at the q.i.d. level, whereas others had the additional week of b.i.d. drops. Ophthalmolgens in cases of postoperative endophthalmitis, ogy Times regrets the error. and preoperative antisepsis with povidone-iodine OCULAR INFECTION CONTROL should always be performed. “The povidone-iodine prep should include not only use of the 10% scrub on the lids and lashes but also placing a drop of the 5% solution in the conjunctival cul de sac for a minimum 5-minute contact time,” Dr. Mah said. ■ FRANCIS S. MAH, MD E: [email protected] This article was adapted from Dr. Mah’s presentation during Cornea Subspecialty Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. Mah is a consultant to Alcon Laboratories, Allergan, Bausch + Lomb/Valeant, Ocular Therapeutix, and PolyActiva. 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 SUPPLE TO MENT GI N G MANA A R ET I N N TS PATIE d on time an at any t one y. Abou any da gical my sur third of unschedare is cones It . cas ing encies is excit ound. emerg after ina ab d ret ule ies of rm rtunit The field t I perfo g. 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Ta MD a, OD, : E INSID ct ney nt’s jour ract patie The cata Catara Brought to you by ue 2 | e 2 | iss volum er 2013 Summ PAGE 10 2013 06.07. 00:09 & A 36 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL Systematic approach key for treating pediatric atopic keratoconjunctivitis Starting patients on calcineurin inhibitors beneficial to reducing conjunctival inflammation By Lynda Charters; Reviewed by Stephen Pflugfelder, MD HOUS TON :: WHEN FACED with challenging pediatric to treat bacteria, topical calcineurin inhibitor (tacrolimus or cyclosporine), or referral of the patient to a cornea specialist. cases of atopic keratoconjunctivitis, a treatment strategy based on disease severity may be the most beneficial, said Stephen Pflugfelder, MD. CALCINEURIN INHIBITOR “It is fine to start treatment with antihista- Dr. Pflugfelder opted for treatment with a topimines and mast cell stabilizers and then pre- cal calcineurin inhibitor to treat the patient’s scribe topical corticosteroids, with dose adjust- atopic keratoconjunctivitis. In this condition, T ments based on disease sever- helper 1 (Th1) and Th2 cells contribute to the ity,” said Dr. Pflugfelder, pro- goblet cell and mucus hyperplasia, subepithelial fessor of ophthalmology, Baylor fibrosis, and eosinophil and mast cell recruitCollege of Medicine, Houston. ment that amplify disease severity and contrib“However, children cannot be ute to corneal epithelial disease. Tacrolimus treated with high-dose topical and cyclosporine reportedly improve the signs steroids over the long term.” and symptoms of atopic keratoconjunctivitis. Dr. Pflugfelder shared some “Calcineurin inhibitors prevent calcineurin Dr. Pflugfelder clinical pearls for treating a pa- phosphatase activity on the nuclear factor of actient with persistent ocular redness and eye- tivated T cells, which is important for translocalid swelling. In one case, an 11-year-old boy tion of the nucleus and a cause of T-cell producpresented with a history of ocular redness of tion of a variety of factors that can amplify the several years duration, tearing, and itching. severity of atopic disease,” Dr. Pflugfelder said. Most recently, the boy complained of diffi“These drugs limit T-cell activation in the culty seeing the board at school. His mother cytokines that the cells produce,” he added. reported eyelid swelling. Such cases require aggressive anti-inflamThe patient was healthy with the exception matory therapy to treat the severe conjunctival of asthma that was controlled. Treatment of inflammation that contributes to the corneal the redness with olopatadine drops (Patanol, epithelial disease that reduces visual acuity, Alcon Laboratories) resulted in minimal ben- he emphasized. efit. Symptom improvement did occur with The treatment plan for this patient included prednisolone acetate. olopatadine instillation once daily to reduce the Bilateral best-corrected visual acuity was conjunctival edema and itching, prednisolone 20/50. Examination showed mild acetate 1% drops four times daily swelling of the upper eyelids and for 2 weeks, and then twice daily edematous inferior puncta. Tears for 2 weeks, and preservative-free overflowed from the inferior tear tacrolimus 0.03% ointment twice meniscus. The eyelids had a veldaily first applied on the eyelid Pediatric vet papillary reaction and thick- patients with atopic margin and later instilled into the ened inferior and superior palpe- keratoconjunctivitis inferior fornix if the patient does bral conjunctiva. A vortex pattern affecting the eyes may not complain of burning or irritaof fluorescein staining was seen best be treated with tion. The last treatment is an offfrom the superior limbus to the topical calcineurin label use of tacrolimus. central cornea in both eyes. The patient had marked improveinhibitors to decrease While no dermatitis was pres- the conjunctival ment by 1 month after the start ent on the child’s head and face, inflammation. of treatment in the conjunctival dermatitis was present in the aninflammation and corneal epithetecubital fossa on both arms. lial disease. The dose of prednisolone acetate Possible treatment considerations were ar- was decreased to once daily for 1 month and tificial tears, moxifloxacin 0.5% (Vigamox, the tacrolimus was stopped. Cyclosporine A Alcon Laboratories) drops three times daily 0.05% (Restasis, Allergan) was started twice take-home (FIGURE 1) TOP A patient with atopic keratoconjunctivitis before tacrolimus therapy. BOTTOM A patient with atopic keratoconjunctivitis after tacrolimus therapy was started. (Photos courtesy of Stephen Pflugfelder, MD) daily with the instruction to continue it indefinitely. This is an off-label indication for cyclosporine A. Before tacrolimus therapy was started, a great deal of limbal and conjunctival inflammation was present. One month later, the limbal inflammation had decreased. “It is not unusual to observe at least a 50% decrease in the superior tarsal edema and inflammation that can minimize the frictional force exerted by the upper eyelid on the cornea, which, in this case, was likely contributing to the corneal epithelial disease,” Dr. Pflugfelder said. Among the noteworthy points in this care are: > Atopic dermatitis is a cause of substantial ocular morbidity, with eyelid involvement in 20% to 43% of patients; > Atopic keratoconjunctivitis is a chronic, po- 37 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN tentially blinding condition, the diagnosis of which can be overlooked in patients with mild eczema or when it affects skin other than that on the eyelid; > Corneal involvement occurs frequently, ranging from punctate epithelial erosion to epithelial defects, epithelial filaments, and stem cell dysfunction; and > Corneal scarring and neovascularization from chronic conjunctival inflammation and corneal trauma can cause loss of vision. OCULAR INFECTION CONTROL “Starting patients on topical calcineurin inhibitors can be extremely valuable because of the steroid-sparing effects and for decreasing the conjunctival inflammation,” Dr. Pflugfelder said. “In severe cases with corneal epithelial defects that do not heal and potentially blinding inflammation, systemic calcineurin inhibitors or pulse oral corticosteroids can be used.” ■ STEPHEN PFLUGFELDER, MD E: [email protected] This article was adapted from Dr. Pflugfelder’s presentation during Pediatric Subspecialty Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. Pflugfelder did not indicate any proprietary interest in the subject matter. New CDC: Ocular syphilis advisory Double-X Speculums parallel retraction. less pressure. better docking. AT L AN TA :: THE CENTERS for Disease Control and Prevention (CDC) has issued a clinical advisory on ocular syphilis. At least 15 cases of ocular syphilis from California and Washington have been reported to the CDC since December 2014, and at least five other states have suspected cases under investigation. The majority of cases have been among HIV-infected MSM, and a few cases have occurred among HIV-uninfected persons including heterosexual men and women. Several of the cases have resulted in significant sequelae including blindness. Neurosyphilis can occur during any stage of syphilis including primary and secondary syphilis. Ocular syphilis, a clinical manifestation of neurosyphilis, can involve almost any eye structure, but posterior uveitis and panuveitis are the most common. Additional manifestations may include anterior uveitis, optic neuropathy, retinal vasculitis and interstitial keratitis. Ocular syphilis may lead to decreased visual acuity including permanent blindness. While previous research supports evidence of neuropathogenic strains of syphilis, it remains unknown if some Treponema pallidum strains have a greater likelihood of causing ocular infections. To receive advice from CDC regarding clinical management of ocular syphilis, or assistance with shipment of clinical samples for molecular typing, physicians may contact Robyn Neblett Fanfair, MD, MPH at 404/639-6044 or [email protected]. Updates to this clinical advisory will be posted on the “Syphilis: Treatment and Care” section of the CDC website (http://1.usa.gov/1NRHMGY). ■ patent pending K1-5691 K-Wire, 15mm K1-5696 K1-5695 V-Wire, 15mm Katena introduces a new family of speculums that feature the patented “Double - X” mechanism. Their unique action opens the lids in a parallel motion for minimal K1-5696 Chu, 17mm external pressure on the globe. In addition, the mechanism is GHVLJQHGWRPRYHDZD\IURPWKHVXUJLFDOÀHOGDVWKHEODGHVRSHQ IRUXQREVWUXFWHGDFFHVVWRWKHVXUJLFDOÀHOG K1-5697 Chu, 13mm Ideal for cataract, refractive, glaucoma and corneal procedures. Key Features: 1 Unique “Double - X” mechanism retracts blades in a parallel motion for even tension along the lid. 2 As the lids are retracted the mechanism moves out of the way for unobstructed access. 3 Ball tips eliminate discomfort for patients with excess lid tissue. 2 1 3 ® Watch it! 973-989-1600 r 800-225-1195 r www.katena.com 38 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL Proper case management required to address pediatric herpes simplex Acyclovir is effective in children, but dosage needs adjustment to maintain suppressive levels By Lynda Charters; Reviewed by Kathryn Colby, MD, PhD BOS TON :: PEDIATRIC HERPES SIMPLEX virus is an important disease in children, a high percentage of whom have stromal disease. The disease is associated with a high risk of recurrence and a risk of induced astigmatism from corneal scarring and reduced vision, said Kathryn Colby, MD, PhD. “[Treatment with] oral acyclovir is safe, although not FDA-approved for use in children,” said Dr. Colby, associate professor of ophthalmology, Harvard Medical School, Boston, and director, Pediatric Cornea Service, Boston Children’s Hospital. “The dose of acyclovir must be adjusted with growth in children,” she added. STR ATEGY FOR CASE M A NAGEMEN T Dr. Colby recounted the case of a 4-year-old girl from Bermuda with recurrent red eye in the right eye only since 8 months of age. She had been treated multiple times with topical antibiotics and steroids, but the disease continued to recur. Previous diagnoses included staphylococcal marginal disease, limbal ver- Next, Dr. Colby measured the corneal sensa- risk of recurrence, a 75% risk of stromal distion, which was decreased in the affected eye. ease, and a 30% rate of misdiagnosis.” The working diagnosis was recurrent herDr. Colby added that 80% of children with pes simplex keratitis. The clinical findings herpes simplex keratitis develop scarring, and history did not support the mostly in the central cornea. Howpreviously entertained diagnoses ever, the induced irregular astiglisted above. matism accompanying bouts of The patient was started on a stromal keratitis is an even more treatment of oral acyclovir, which, clinically relevant factor in these Pediatric herpes in children, is an off-label use of patients. this medication. Taken into con- simplex virus should be Twenty-five percent of children sideration were the patient’s his- part of the differential have more than 2 D of astigmatory of recurrent unilateral disease, diagnosis when a tism, most of which is irregular. decreased corneal sensation, and patient has unilateral Visual acuity is less than 20/40 in recurrent disease in anterior stromal footprints. about 25% of children and 60% “Her mother noted an almost the anterior segment. of children have reduced corneal immediate improvement,” Dr. sensation. Colby said. However, another ophthalmoloAcyclovir is well tolerated by pediatric pagist stopped the acyclovir treatment because tients, but Dr. Colby advised that ophthalmoloof the improved clinical picture. Symptoms gists be aware of lactose intolerance. The drug recurred almost immediately. has a wide therapeutic and safety index. Dr. Colby restarted the acyclovir treatment and also began low-dose prednisolone acetate PROPER DOSAGE 0.12% to help with the corneal vasculariza- Dr. Colby prescribes 100 mg of acyclovir twice tion and azithromycin applied to the eyelashes daily as prophylaxis for very young infants, for blepharitis. 200 mg twice daily for toddlers, 300 mg twice daily for children older than toddlers, and 400 mg twice daily for older children. When a child presents with acute infectious herpes simplex virus, she prescribes the same number of milligrams three-times daily based on age and — Kathryn Colby, MD, PhD weight. “When treating children with topical steroids, tapering of the drugs should be done “The neovascularization regressed over sev- slowly, over a long period,” Dr. Colby said. eral months with no recurrences,” Dr. Colby “Management of amblyopia is key. said. “Always consider pediatric herpes simplex Once the child’s symptoms were stable, virus when a patient has unilateral recurrent Dr. Colby was able to taper the topical ste- disease in the anterior segment, with awareness roid therapy. The child completed a 1-year of the protean manifestations of this virus,” course of a prophylactic dose of acyclovir and she concluded. ■ symptoms remained “quiet” without further recurrences. “Herpes simplex virus is a very important KATHRYN COLBY, MD, PHD common disease in children,” she said. “The E: [email protected] end result of stromal herpes simplex virus is This article was adapted from Dr. Colby’s presentation during Pediatric Subspecialty a scarred vascularized cornea. We know that Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. Colby has no pediatric herpes simplex keratitis has an 80% financial interest in any aspect of this report. take-home ‘The end result of stromal herpes simplex virus is a scarred vascularized cornea.’ nal keratoconjunctivitis, and phlyctenular keratoconjunctivitis. Dr. Colby first considered the relevant historical patient information, such as familial corneal disease, systemic allergies or atopy, and duration and frequency of episodes. The child had no history of systemic allergic disease. Examination showed extensive corneal neovascularization and swelling at the inferior limbus in the affected eye. Peripheral anterior stromal footprints and mild blepharitis were seen, but no giant papillary conjunctivitis or limbal follicles were noted on clinical exam. The contralateral eye was normal. NOW APPROVED ANTICIPATED RETAIL AVAILABILITY MARCH 10 From Alcon, committed to providing new treatment options for patients. Olopatadine is licensed from Kyowa Hakko Kirin Co., Ltd. Japan ©2015 Novartis 01/15 PAZ15017JAD 40 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL DALK explored as early approach to refractory Acanthamoeba keratitis Procedure should be done by experienced surgeons with low rates of conversion to PK By Lynda Charters; Reviewed by Enrica Sarnicola, MD SIENA, I TALY :: DEEP ANTERIOR LAMELLAR keratoplasty (DALK) should be considered as an early approach for treating refractory acanthamoeba keratitis with substantial corneal ulceration, said Enrica Sarnicola, MD. “DALK is a safe procedure with good, longterm graft survival; that is, 99% after 10 years has been reported in the literature,” said Dr. Sarnicola, a resident in ophthalmology, Siena University, Italy. “The procedure has a low rejection rate with a low risk of secondary complications.” Dr. Sarnicola and colleagues conducted a retrospective, noncomparative study of 12 eyes of 11 consecutive patients who had been diagnosed previously with Acanthamoeba keratitis. All patients had been followed for 2 years. In these patients, the investigators performed a DALK procedure in 9 eyes with a post-infective stromal scar and in 3 eyes with active infection. All 3 eyes with active infection were refractory to medical therapy. DALK, as a therapeutic approach, was performed from 30 to 60 days from the time of symptom onset. All patients had extensive ulcers in the optical zone that exceeded 150 μm, but less than 300 μm in depth, according to Dr. Sarnicola. The DALK technique they performed included either a cannula big-bubble technique or manual dissection. The DALK diameter was as large as possible; that is, 8.5 mm in 8 eyes and 9 mm in 4 eyes. Interrupted sutures were placed. A histologic examination was performed after the lamellar tissue was removed. 3 DRUGS USED Patients used three drugs preoperatively and postoperatively: the antiseptic drug chlorhexidine gluconate, a DNA synthesis inhibitor propamidine isethionate, and a protein synthesis inhibitor neomycin sulfate. Postoperatively, the drugs were instilled 4 times daily for 1 month. Propamidine isethionate was instilled 4 times daily for other 2 months. “Most importantly, Descemet’s membrane did not rupture in any eye,” Dr. Sarnicola said. mitis developed, which required vitrectomy. Visual recovery was very good, she pointed One month later, a fungal keratitis infection out. Best spectacle-corrected visual acuities required a second penetrating keratoplasty. ranged from 14/20 to 20/20 (average, 17/20). However, the graft was rejected, and a retNone of the infections recurred and no com- inal detachment developed in addition to plications, such as secondary cataract or glau- secondary glaucoma, limbal deficiency, and perforation. Ultimately, the eye was enuclecoma, developed. “The histopathologic evaluation confirmed ated, Dr. Sarnicola said. In another case, a 15-year-old our diagnoses with cysts in the girl who wore contact lenses was stromal specimens,” she said. diagnosed late with biopsy-conThe peripheral margin was free firmed acanthamoeba keratitis. of infection in all cases. The deep She was treated with targeted margin was free of infection in Therapeutic deep therapy that included topical eight cases, but not so in four anterior lamellar polyhexamethylene biguanide, cases. Dr. Sarnicola speculated keratoplasty performed hexamidine, and chlorhexidine. that these four cases were all des- early should be However, despite treatment the cemetic DALK (dDALK). considered in cases lesion enlarged, and intense pan“We believe this is the reason of acanthamoeba nus and deep stromal vascularwhy the surgery was still radi- keratitis refractory to ization developed. The vision decal,” she said. medical therapy with DALK seems to be a very good substantial optical zone creased to counting fingers. Therapeutic DALK was perprocedure in eyes with active and ulceration. formed early using the big-bubquiescent acanthamoeba infection, she said. However, she noted the importance ble technique. A 9-mm graft was applied of a larger study to confirm the success rate centered on the infection. “One year postoperatively, the visual rewith the procedure and to determine any covery was good at 20/30,” Dr. Sarnicola possible late complications. said. “The acanthamoeba keratitis did not recur. The endothelial cell count is good CASE REPORTS Dr. Sarnicola recounted the case of a 61-year-old and stable.” In acanthamoeba infections, an early DALK man with acanthamoeba keratitis who was misdiagnosed as bacterial. Delayed antiamoe- procedure must be considered in cases of bic therapy was unable to prevent and avoid acanthamoeba keratitis refractory to mediinfection progression and corneal melting, cal therapy with substantial optical zone ulceration, she noted. so therapeutic keratoplasty was indicated. “The only caveat is that the procedure “Usually, surgeons prefer to perform keratoplasty when the infection is controlled, should be performed by highly experienced because with penetrating keratoplasty, open- surgeons with low rates of conversion to pening of the anterior chamber can allow intra- etrating keratoplasty,” Dr. Sarnicola said. ■ ocular spread of infection,” she said. “In addition, using a graft with a large diameter in the presence of inflammation in the eye carries a very high risk of rejection and graft failure,” she said. “Therefore, deENRICA SARNICOLA, MD laying the surgery is the last option.” E: [email protected] By the time the surgery was performed, This article was adapted from Dr. Sarnicola’s presentation at the 2014 meting of the the full corneal thickness had become inAmerican Academy of Ophthalmology. Dr. Sarnicola has no financial interest in any fected. Five days postoperatively, endopthalaspect of this report. take-home As Demonstrated in 2 Pivotal, Phase 3 Trials in Patients With DME Evaluating Mean Change in BCVA* at 52 Weeks vs Baseline1 EYLEA® (aflibercept) Injection Offers Extended Dosing in DME—2-mg Every 8 Weeks Following 5 Initial Monthly Doses1 Initial Dosing Follow-Up Dosing 5 Initial 2-mg Injections Monthly (Every 4 Weeks) 2-mg Every 2 Months (Every 8 Weeks) Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks. *BCVA = best-corrected visual acuity, as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letters. IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION 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. 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 use of intravitreal VEGF inhibitors, including EYLEA, 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 during the first year 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. There were no reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies. Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with EYLEA including endophthalmitis and retinal detachment. *'/156%1//10#&8'45'4'#%6+105j¢Ik4'2146'&+02#6+'065 receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous floaters, intraocular pressure increased, and vitreous detachment. IMPORTANT PRESCRIBING INFORMATION FOR EYLEA® (aflibercept) INJECTION EYLEA® (aflibercept) Injection is indicated for the treatment of patients with Neovascular (Wet) Age-related Macular Degeneration (AMD): The recommended dose is 2 mg administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg 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 when EYLEA was dosed every 4 weeks compared to every 8 weeks. Macular Edema following Retinal Vein Occlusion (RVO): The recommended dose is 2 mg administered by intravitreal injection every 4 weeks (monthly). Diabetic Macular Edema (DME): The recommended dose is 2 mg administered by intravitreal injection every 4 weeks (monthly) for the first 5 injections, followed by 2 mg 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 when EYLEA was dosed every 4 weeks compared to every 8 weeks. For more information, visit www.EYLEA.com. Reference: 1. EYLEA® (aflibercept) Injection full U.S. Prescribing Information. Regeneron Pharmaceuticals, Inc. October 2014. Please see brief summary of full Prescribing Information on the following page. EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc. © 2015, Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road, Tarrytown, NY 10591 All rights reserved 1/2015 LEA-0685 43 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL Latest option for fungal keratitis draws interest; new study prefers to differ MUTT I confirms that while voriconazole may work in some cases, it is not recommended By Nancy Groves; Reviewed by Namperumalsamy Venkatesh Prajna, MBBS azole had captured their imagination worldwide,” Dr. Prajna said. “Sixty-eight percent of Trial I (MUTT I), visual acuity and perfora- the ophthalmologists would prefer voriconazole tion outcomes were significantly better in pa- if the choice was given to them.” These findings set the stage for the MUTT tients with fungal keratitis who were randomly I trial comparing the efficacy of assigned to treatment with natanatamycin, the gold standard, mycin (Natacyn, Alcon Laboratoand the newer alternative, voriries) than to voriconazole (Vfend, conazole, in patients with fungal Pfizer), said principal investigator corneal ulcers. MUTT I, sponsored Namperumalsamy Venkatesh PraNatamycin was by the National Eye Institute, was jna, MBBS. superior to voriconazole Patients randomly assigned to in a randomized clinical a double-masked, randomized trial in which more than 300 patients voriconazole were more likely to trial for outcome from three centers in South India perforate and to require therapeutic measures, such as were enrolled. penetrating keratoplasty, said Dr. visual acuity and Patients with corneal ulcers who Prajna, chief, Department of Medi- perforations. were smear positive for fungus cal Education, Aravind Eye Care were screened and then randomly assigned System, Madurai, Tamil Nadu, India. However, the differences in efficacy in this to receive either natamycin (5%) or voriconstudy were primarily attributable to the high azole (1%), Dr. Prajna noted. Study participants remained at the treatnumber of cases caused by Fusarium, about ment centers for at least a week to ensure that 50% of the positive cultures. “It’s a well-known fact that different bacteria the drugs were administered on schedule. have different susceptibility patterns. But for Masking was conducted to the extent posfungus, it was always antifungals,” Dr. Prajna sible (the drugs were dispensed in similar said. “We never realized that there could be bottles), although natamycin could be identified by its tendency to precipitate. a differential sensitivity to different drugs.” The primary endpoint was best-corrected visual acuity (BVCA) at 3 months compared NO R ECOMMENDATION In this study, Fusarium responded much bet- with baseline. Secondary endpoints included ter to natamycin than to voriconazole. In light treatment failure as evidenced by perforations, of these results—where differential antifun- size of infiltrate, scarring post-treatment comgal susceptibility has been clearly established pared to pre-treatment, and time to resolution and in light of the fact that culture is not per- of epithelial defect. After screening, 323 patients were enrolled formed for all patients with fungal keratitis— voriconazole as monotherapy for filamentous in the study. Of the 323 ulcers, 256 (79%) fungal keratitis is not recommended, Dr. Pra- had positive cultures; 128 (50%) were Fusarium, 54 (21%) were Aspergillus species, jna noted. For almost 50 years, natamycin was the 20 (8%) were Curvularia, and 54 (21%) were only drug available for treating fungal kerati- other species. Patients had significantly poor visual acuity tis. However, isolated case reports and small cases on the efficacy of voriconazole began with a median Snellen visual acuity of 20/90. to appear within the past decade. A survey, The median scar size was 3.2 mm, and 35% whose results were published in Cornea in of hypopyon were more than 1 mm. 2009, revealed that the majority of cornea OLDER TR EATMENT OPTION specialists preferred voriconazole for topiThe results—which were inconsistent with the cal treatment. “The results were very clear that voricon- preference of corneal specialists worldwide— MADUR AI, TAMIL NADU, INDIA :: IN THE MYCOTIC ULCER Treatment take-home showed better efficacy for the older treatment than the newer option. “At 3 months, very clearly natamycin-treated cases had significantly better BCVA than voriconazole-treated cases (95% CI, p = 0.006),” Dr. Prajna said. In the entire study population, 52 perforations were reported, with almost twice as many in the voriconazole group (34 versus 18, p = 0.009). SU B GR OU P A N A LY S I S A subgroup analysis showed that patients positive for Fusarium healed significantly more rapidly with natamycin than voriconazole (p = 0.005), while there was no significant difference in healing time with non-Fusarium cases. The investigators also explored an association between in vitro susceptibility to antifungal medication and clinical outcomes. “We found out that voriconazole was not a great drug for Fusarium,” Dr. Prajna said. A. flavus had the highest minimum inhibitory concentration (MIC) 50 and MIC 90 among natamycin-treated organisms, and Fusarium species had the highest MIC 50 and MIC 90 among voriconazole-treated organisms. “When we correlated MIC with the final visual outcome, we found that decreased susceptibility to natamycin correlated with increased odds of perforation, while susceptibility to voriconazole was not clearly associated with measured outcomes,” he added. Limitations to the study included enrollment exclusively of patients in South India, exclusion of contact lens wearers, comparison only of monotherapies, and the predominance of Fusarium cases, the organism most prevalent in fungal keratitis cases in South India. ■ NAMPERUMALSAMY VENKATESH PRAJNA, MBBS P: 91(452)4356-100 E: [email protected] This article was adapted from Dr. Prajna’s presentation during Cornea Subspecialty Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. Prajna reported no financial interests or relationships. 44 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL Early intervention considered key in diagnosis and treatment of scleritis Steroids, followed by cytotoxic immunosuppressives have shown efficacy in treating disease By Vanessa Caceres; Reviewed by Vincent de Luise, MD, FACS NE W HAVEN, C T :: SCLERITIS REQUIRES AN EARLY and accurate diagnosis to help patients recover from this potentially sight- and life-threatening disease, said Vincent de Luise, MD, FACS. “We need to confront these cases confidently, diagnose them accurately, and provide prompt, correct intervention,” said Dr. de Luise, assistant clinical professor of ophthalmology, Yale University School of Medicine, New Haven, CT. Scleritis is a painful, progressive disease characterized by inflammation and edema in In the photo at left, a patient presents with anterior scleritis; at right, a patient with diffuse episcleritis. the sclera and deep episclera. Corneal and exPain is a distinguishing factor between scleritis and episcleritis. If there is pain, physicians may consider ternal disease specialists are more likely than scleritis. If it’s just itching, they may consider episcleritis. (Photos courtesy of Vincent de Luise, MD, FACS) general ophthalmologists to see scleritis regularly. Scleritis is more common in females. In 50% of cases, it is idiopathic. “In the other 50%, there is an underlying ally blanch with episcleritis but not scleritis. with caution as they have the risks of scleral systemic disease,” Dr. de Luise said. Ocular sequelae for scleritis include cata- melt and perforation. The underlying disease could be an immune- ract, glaucoma, uveitis, and peripheral ulcerOral tumor necrosis factor inhibitors (TNFmediated systemic disease, and the ative keratitis. alpha inhibitors) and other biologics have also strongest association is with vasLaboratory testing can help shown efficacy in patients with scleritis but culitis. Associated diseases include identify the type of scleritis, Dr. should be prescribed in collaboration with a rheumatoid arthritis, Wegener’s de Luise said. rheumatologist, as they have serious systemic granulomatosis, polyarteritis noDepending on the history, testing side effects, Dr. de Luise said. Scleritis can indicate dosa, and herpes zoster. should include rheumatoid factor, Of the biologics, infliximab, adalimumab, serious systemic In a quarter of the cases where disease and requires anti-nuclear antibodies, human leu- daclizumab, rituximab, and etanercept have there is underlying disease, the eye prompt diagnosis and kocyte antigen, anti-neutrophilic been used in the management of recalcitrant is the presenting sign. cycloplasmic antibodies, and tests cases of scleritis, with variable degrees of treatment. Episcleritis “In these cases, the eye is the also has certain for tuberculosis, Lyme disease, sar- effectiveness. barometer, and the initial sign of treatment pearls. coidosis, and gout. Imaging tests For necrotizing scleritis, IV corticosteroids a potentially lethal disease,” Dr. include CXR, B-scan, sinus films, and IV methylprednisolone should be considde Luise said. and CT or MRI tests. ered, Dr. de Luise advised. Scleritis is almost always anterior, and it If there is impending scleral perforation, Dr. is classified as diffuse, nodular, necrotizing de Luise said tectonic scleral patch graft surTR EATMENT STR ATEGIES with inflammation, or necrotizing without in- To treat scleritis, Dr. de Luise has found oral gery is the recommended initial management flammation. Posterior scleritis is rare and can nonsteroidal anti-inflammatory drugs (NSAIDs) as the diagnosis is being pursued and oral mimic a choroidal tumor. to be of little value, and he advised moving treatment begun. immediately to oral steroids followed by oral MAKING THE DISTINCTION EPISCLER ITIS IDEN TIFICATION, cytotoxic immunosuppressives, assuming no Pain is a distinguishing factor between scleri- systemic contraindications. TR EATMENT tis and episcleritis, Dr. de Luise said. Methotrexate, azathioprine, and cyclophos- In contrasting the presentation of scleritis with “If there is pain, consider scleritis; if it’s just phamide, are cytotoxic immunosuppressives that of episcleritis, Dr. de Luise said the latter itching, consider episcleritis,” he said. that have shown efficacy in scleritis, Dr. de is a self-limited disease of the episclera. In an examination under natural light, pa- Luise said. “In episcleritis, the inflammation is supertients with scleritis will present with a bluMycophenolate mofetil and cyclosporine ficial, and the sclera is minimally engorged, ish-red discoloration in the area with scleritis. have also been employed. if at all,” he said. Using neosynephrine 2.5%, vessels will usuDr. de Luise said to use periocular steroids Continues on page 46 : Scleritis take-home INCREDIBLE RED REFLEX. (SO GOOD, THE OTHER COLORS ARE JEALOUS.) Red Reflex is crucial to the success of your cataract procedure. It’s equally crucial to know that Haag-Streit has engineered outstanding technology for illuminating the anterior segment, even in low light. C.RED features a revolutionary LED light which provides brilliant red reflex with outstanding stability, and only one cornea reflection. Learn more at HSmicroscopes.com/OPH 80O.787.5426 HSmicroscopes.com/OPH © 2015 Haag-Streit USA. All Rights Reserved. 46 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL Tacrolimus viable option for treating vernal keratoconjunctivitis patients Small study finds low dose of macrolide antibiotic to be effective, safe, with few side effects By Vanessa Caceres; Reviewed by Samir Shoughy, MD, FRCS (Glasg.) RI YADH, SAUDI AR ABIA :: A LOW DOSE OF TOPICAL tacro- helper cell-mediated B-cell proliferation, and cytokine formation. limus was a safe and effective treatment for vernal keratoconjunctivitis (VKC) in a recent OUTCOMES FROM SMALL SER IES study, said Samir Shoughy, MD, FRCS (Glasg.). Dr. Shoughy shared results from a study of 62 Vernal keratoconjunctivitis is a leading cause patients with refractory VKC. Patients—who of outpatient ophthalmic morbidity, said Dr. ranged in age from 5 to 47 years old (mean Shoughy, The Eye Center and The Eye Founda- age, 18 years)—had symptoms and signs of tion for Research in Ophthalmology, Riyadh, VKC even though they had used conventional Saudi Arabia. medications. VKC was diagnosed by itching, “If not properly treated, it can lead to scar- redness, foreign body sensation, and discharge. ring, microbial keratitis, limbal tisResearchers excluded patients sue hyperplasia, amblyopia, and with known hypersensitivity to tadry eye syndrome,” he said. crolimus, infectious eye disease, VKC is more common in dry those who were pregnant, and those and hot climates and in children on systemic therapy for other alTacrolimus 0.01% or young adults with an atopic back- was effective for the lergic diseases. ground. More males than females treatment of vernal Clinical symptoms were graded have VKC. as normal (0), mild (1+), moderate keratoconjunctivitis Typical treatment for VKC in- in a study with 62 (2+), or severe (3+). Researchers cludes antihistamines, mast cell patients. assessed patients before tacrolimus stabilizers, vasoconstrictors, cortreatment began and at one month ticosteroids, and immunomodulaafter treatment. tors, Dr. Shoughy said. Tacrolimus eye drops were reconstituted at “Corticosteroids are an important line of Dr. Shoughy’s center in a sterile environment treatment but are associated with complica- by adding balanced salt solution to the contions like increased IOP and cataract forma- tents of a tacrolimus capsule, to achieve a dose tion,” he said. “We are in need of more safe of 0.01%. Patients used the solution twice a and effective drugs.” day for a month. Tacrolimus is a macrolide antibiotic that is Itching improved in 82% of patients, red10 to 100 times more potent than cyclospo- ness improved in 75%, discharge reduced in rine, he explained. 84%, and foreign body sensation reduced in The drug suppresses T-cell activation, T 77%. All percentages were based on the actual take-home SCLERITIS ( Continued from page 44 ) Patients usually have a history of allergy. Episcleritis can be divided into two types: simple (diffuse) and nodular. Although episcleritis is usually idiopathic, it may be associated with trauma, gout, atopy, rheumatoid arthritis, lupus, or inflammatory bowel disease. There is rarely an anterior chamber reaction in episcleritis. There is also a related form, called pingueculitis, where the episcleritis manifests as an inflamed pinguecula, he said. Treatment for mild episcleritis includes sunglasses and artificial tears. If the patient has itching, the specialist can recommend topical anti-allergics. For discomfort, Dr. de Luise advised the use of topical NSAIDS. In recalcitrant number of patients experiencing a symptom, not the full study group. The improved signs included conjunctival hyperemia, limbal infiltrates, Trantas dots, and superficial punctate keratitis. Papillary hypertrophy also improved but to a lesser degree compared with the other signs. Five percent (three patients) experienced side effects from the treatment. Two felt a burning sensation, and one felt irritation. When asked why such a low percentage of patients had side effects compared with others’ use of tacrolimus, Dr. Shoughy said it was likely because the study dose was particularly low. “We use one-tenth of the concentration used in most trials,” he said. Dr. Shoughy also reported that a maintenance dose of 0.01% could be used by patients. He and study researchers have prescribed this dose safely for once daily or once every other day. He also said that he uses tacrolimus as a first-line therapy, without the use of steroids. After one week of therapy, he typically sees 70% to 80% of the needed response in patients, and itching usually resolves in 2 to 3 days after patients begin to use it. ■ SAMIR SHOUGHY, MD, FRCS (GLASG.) E: [email protected] This article was adapted from Dr. Shoughy’s presentation at the 2014 meeting of the American Academy of Ophthalmology. Dr. Shoughy did not indicate any proprietary interest in the subject matter. cases, oral NSAIDs such as indomethacin 75 mg to 100 mg orally per day, and/or topical pulsed corticosteroids, can be used. ■ VINCENT DE LUISE, MD, FACS E: [email protected] This article was adapted from Dr. de Luise’s presentation during Cornea Subspecialty Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. de Luise did not indicate any proprietary interest in the subject matter. 47 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL Infectious scleritis exists in many forms Treatments and causes can vary widely; diagnosis crucial part of managing disease By Vanessa Caceres; Reviewed by Ana Luisa Höfling-Lima, MD, MBA roids and systemic antivirals. “The drug of choice is acyclovir for three in only 5% to 10% of scleritis patients, but it to eight weeks,” she said. “If the patient has can have poor visual outcomes, said Ana Luisa had previous treatment with immunotherapy, this can worsen their inflammation.” Höfling-Lima, MD, MBA. Inflammation may last 5 months to more “Since it’s uncommon, there is usually a late diagnosis,” said Dr. Höfling-Lima, head than 2 years. Bacterial scleritis includes professor, Ophthalmology Department at Escola Paulista de Medicina – UNIFESP, São Pseudomonas aeruginosa, MyPaulo, Brazil. “The visual outcome can be cobacterium chelonae, Mycobacpoor because of aggressive infection and dif- teriumabsessus, and Mycobacficulty in penetration of drugs in the scleral teriumtuberculosis. Bacterial scleritis has been seen after tissue.” It is crucial to evaluate if the tests for infec- pterygium surgery. It can sometious scleritis are negative before proceeding times have a delayed occurwith treatment for rheumatological disease rence after surgery or trauma as in most situations, high doses of steroids and could be caused by a dormant organism, or immunosuppressors will be prescribed, Dr. Höfling-Lima said. “We have to pay attention to that possibilshe said. Infectious scleritis can be caused by bacte- ity,” she said. In her home country of Brazil, Dr. Höflingria, virus, fungi and protozoan, and the infections can be endogenous or exogenous. Cases Lima and fellow ophthalmologists have seen are often traced back to trauma, immunosup- Pseudomonas scleritis caused by trauma caused pression, conjunctiva or pterygium surgery, by sugar cane leaves. They treated these cases or geographic-specific systemic diseases that with topical and systemic amikacin. Treatment for Pseudomonas scleritis can include syphillis, tuberculosis, toxoplasmotypically include intravenous ceftazidime sis, and leprosy. Patients will present with redness, pain, lac- and aminoglycosides, which may be more rimation, intraocular inflammation, scleral ne- effective with single-intravenous agents when used in addition to topicrosis anterior chamber reaction cal antibiotics. with anterior and posterior involve“These may obviate the need ment, scleral abscesses, and tissue for adjunctive surgical procedures, damage beyond obvious clinical such as cryotherapy, surgical exfindings. Consider infectious tirpation, or conjunctival recesscleritis if a patient with sion,” she said. TR ACK ING DISE ASE Topical ceftazidime 5% and forUltrasound biomicroscopy, opti- scleritis tests negative tified aminoglycosides 1.4% also cal coherence tomography, scleral for rheumatological may be useful, safe, and effective scrapings when possible, poly- disease. therapy for pseudomonal keratimerase chain reaction used with tissue specimens from the scleral biopsy, and tis, she added. Another possibility in infectious scleritis, immunofluorescence are all useful in helping to diagnose and track infectious scleri- although it is not that common, is Nocardia scleritis, Dr. Höfling-Lima said. Signs of this tis, Dr. Höfling-Lima said. Also, “new CT technology has become a tool include scleritis with multiple nodules that for us not for diagnosis but to follow patients do not respond to fluoroquinolones. Mycotic scleritis can also occur and often with necrotizing scleritis,” she said. Dr. Höfling-Lima outlined several forms of progresses quickly despite treatment. This infectious scleritis and how to treat it. For ex- can turn quickly into cataracts, serious retample, she said that herpes scleritis is hard inal or choroidal detachments, and endoto diagnose and requires both systemic ste- phthalmitis, Dr. Höfling-Lima said. How- SÃO PAULO, BR A ZIL :: INFECTIOUS SCLERITIS OCCURS ever, prognosis is often poor because of late diagnosis, poor penetration of antifungal drugs into the avascular sclera, and the ability of organisms to remain in the avascular scleral tissue without inciting an inflammatory response. ‘New CT technology has become a tool . . . to follow patients with necrotizing scleritis.’ — Ana Luisa Höfling-Lima, MD, MBA take-home Dr. Höfling-Lima addressed Acanthamoeba scleritis, noting that 14% of Acanthamoeba keratitis cases have associated scleritis that can be anterior, diffuse, or nodular necrotizing. Causes include scleral invasion by Acanthamoeba and immune-mediated response to dead and dying ameba. Treatment in these cases can include systemic treatment with miltefosine or voriconazole as well as cryotherapy. Sometimes, enucleation is required. If a patient presents with M. tuberculosis scleritis, it is secondary to a primary spot, such as on the lung. However, it can also be seen without systemic symptoms, Dr. Höfling-Lima said. Diagnosis is made with a PPD test, a chest X-ray, and a smear of the scleral lesion. The most common treatment is systemic steroids as well as a fixed combination with rifampcin, isoniazid, and pyrazinamide. For Mycobacterium other than tuberculosis scleritis, treatments are commonly clarithroymycin 500 mg every 12 hours and amikacin 7.5 mg/kg three times a day for 3 weeks. Yet another infectious possibility is toxopolasmosis, Dr. Höfling-Lima said. ■ ANA LUISA HÖFLING-LIMA, MD, MBA E: [email protected] This article was adapted from Dr. Höfling-Lima’s presentation at the 2014 meeting of the American Academy of Ophthalmology. She did not indicate any proprietary interest in the subject matter. ADVANCEMENT NEVER STOPS. 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ORA System ™ WITH VERIFEYE+™ Advancing CATARACT SURGERY 50 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL Preop focus on patient best offense against postoperative infection Identifying specific risk factors more effective approach rather than reacting to organisms By Lynda Charters; Reviewed by Terrence P. O’Brien, MD MIAMI :: THE OCULAR ISOLATES that are most likely to be recovered in the United States from infections related to ophthalmic surgeries are predominantly grampositive bacterial organisms, especially coagulasepositive and coagulase-negative Dr. O’Brien staphylococci. These organisms are linked in upward of 95% of post-cataract in- fections with gram negative and fungal organisms being much less commonly implicated. “This trend to recovery of grampositive organisms, while not new, is continuing, and studies over the past few years have documented the preponderance,” said Terrence P. O’Brien, MD, professor of ophthalmology, University of Miami, and co-director, Ocular Microbiology Laboratory, Bascom Palmer Eye Institute, Miami. The most recent laboratory research has reinforced that no sin- trast to that enjoyed four decades gle antibiotic agent is universally ago,” he said. effective for eradicating these bacOphthalmic surgeons recogteria and suggests that a combinize the eye’s precarious and nation of antibacterial agents may vulnerable situation because of be more effective. its unique structure and the easy However, turning one’s attenaccess through which organisms tion on the host, i.e., the patient, can gain entry during ophthalmic and identifying specific risk facsurgery. tors may be a more effective ap“Because bacteria can be sequesproach for beating these culprits tered in a relatively closed environof infection rather than reacting to ment, this a unique risk factor for the organisms—given their abilall ophthalmic procedures, includity to rapidly evolve and become ing cataract and glaucoma surgerresistant to prevention as well as ies, LASIK, and even treatment. injections into the vitAn alarming trend reous cavity for retinal that has surfaced over disorders,” Dr. O’Brien the past several years said. is the evolving resisPostoperative “Ocular surgeons tance seen among infections with ocular must gain an underocular pathogens to surgeries may be standing of those risk commonly used an- reduced substantially factors and use stratetibiotics, especially by effectively treating gies to improve or ref luoroqu i nolones, active ocular disease duce the likelihood of as well as other fre- in advance before the patients contracting inquently prescribed an- patient enters the fection,” he added. tibiotics. Among the operating room. These strategies inpredominantly recovclude adopting universal precautions ered, gram-positive organisms, reto prevent infection and special atduced susceptibility to the comtention that is unique to the eye. One monly used antibiotics is being important step is to treat patients observed, he noted. who may have chronic external ocular infections, such as blepharitis FEW DRUGS DEV ELOPED and blepharoconjunctivitis, before Another unfortunate trend comthey undergo an ocular surgery, he pounds this problem, according noted. to Dr. O’Brien. Fewer new drugs “Many studies have found that are being investigated by fewer these external ocular infections companies because of the dauntare the sources of the organism’s ing costs of research and developaccess at the time of an ocular ment (R&D), he observed. surgery,” Dr. O’Brien said. “Pre“Compared with the golden age treatment is a recognized approach of R&D of antibiotics in the 1970s that prevents patients from going when multiple new agents were into surgery with an active exterintroduced every year, now the nal ocular disease.” situation for drug development … Having said this, Dr. O’Brien to treat systemic, as well as ocualso noted there is controversy surlar infections, is in marked con- take-home ORA™ SYSTEM IMPORTANT PRODUCT INFORMATION CAUTION: Federal (USA) law restricts this device to sale by, or on the order of, a physician. INTENDED USE: The ORA™ System uses wavefront aberrometry data in the measurement and analysis of the refractive power of the eye (i.e. sphere, cylinder, and axis measurements) to support cataract surgical procedures. CONTRAINDICATIONS: The ORA™ System is contraindicated for patients: who have progressive retinal pathology such as diabetic retinopathy, macular degeneration, or any other pathology that the SK\VLFLDQGHHPVZRXOGLQWHUIHUHZLWKSDWLHQW[DWLRQZKRKDYHFRUQHDOSDWKRORJ\VXFK as Fuchs’, EBMD, keratoconus, advanced pterygium impairing the cornea, or any other SDWKRORJ\ WKDW WKH SK\VLFLDQ GHHPV ZRXOG LQWHUIHUH ZLWK WKH PHDVXUHPHQW SURFHVV whose preoperative regimen includes residual viscous substances left on the corneal VXUIDFH VXFK DV OLGRFDLQH JHO RU YLVFRHODVWLFV ZLWK YLVXDOO\ VLJQLFDQW PHGLD RSDFLW\ VXFKDVSURPLQHQWRDWHUVRUDVWHURLGK\DORVLVZKDWZLOOHLWKHUOLPLWRUSURKLELWWKH PHDVXUHPHQW SURFHVV RU ZKR KDYH UHFHLYHG UHWUR RU SHULEXOEDU EORFN RU DQ\ RWKHU WUHDWPHQWWKDWLPSDLUVWKHLUDELOLW\WRYLVXDOL]HWKH[DWLRQOLJKWΖQDGGLWLRQXWLOL]DWLRQ of iris hooks during an ORA™ System image capture is contraindicated, because the use of iris hooks will yield inaccurate measurements. WARNINGS AND PRECAUTIONS: 6LJQLFDQW FHQWUDO FRUQHDO LUUHJXODULWLHV UHVXOWLQJ LQ KLJKHU RUGHU DEHUUDWLRQV PLJKW yield inaccurate refractive measurements. Post refractive keratectomy eyes might yield LQDFFXUDWHUHIUDFWLYHPHDVXUHPHQW7KHVDIHW\DQGHHFWLYHQHVVRIXVLQJWKHGDWDIURP the ORA™ System have not been established for determining treatments involving higher order aberrations of the eye such as coma and spherical aberrations. The ORA ™ System LVLQWHQGHGIRUXVHE\TXDOLHGKHDOWKSHUVRQQHORQO\ΖPSURSHUXVHRIWKLVGHYLFHPD\ result in exposure to dangerous voltage or hazardous laser-like radiation exposure. Do not operate the ORA™6\VWHPLQWKHSUHVHQFHRIDPPDEOHDQHVWKHWLFVRUYRODWLOH solvents such as alcohol or benzene, or in locations that present an explosion hazard. ATTENTION: Refer to the ORA™ System Operator’s Manual for a complete description of proper use and maintenance of the ORA™ System, as well as a complete list of contraindications, warnings and precautions. Advancing CATARACT SURGERY © 2015 Novartis 3/15 ORA15009JAD-C 51 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN (FIGURE 1) Postoperative pseudophakic endophthalmitis due to culture-proven Staphylococcus aureus with intense hypopyon. rounding the use of antibiotics before, during, and following cataract surgeries regarding their effectiveness and the most optimal route of administration. “Topical antibiotics, which have been the mainstay of ophthalmic care, have not been shown conclusively to universally lower the risk of infection during ocular surgery,” he said. “There is a rationale for their use, but no large-scale multicenter study that definitively proves their effectiveness has been completed.” To date, two steps have been shown to reduce infections, especially during cataract surgeries: > Topical antiseptic (povidone iodine) during patient preparation for surgery, and > Intracameral injection of antibiotic. While the latter was proven beneficial in a large European study, questions remained about which antibiotic was preferred for delivery and the manner in which the drug should be made and delivered. In the United States, no such commercial drugs are yet approved for intracameral use in a prophylactic fashion. With the goal of reducing ocular infections associated with surgery, Dr. O’Brien noted a trend away from the use of nondisposable instruments. This is the result of investigations into development of toxic anterior segment syndrome (TASS) after cataract surgery because of incomplete processing and handling of the instruments. In the same way, surgeons have recognized that small-gauge cannulas are hard to clean and material can be retained in the absence of proper cleaning and sterilization. Cataract surgeons are using more IOLs that are preloaded and injected, which eliminates excessive handling and lowers the risk of contamination. OCULAR INFECTION CONTROL (FIGURE 2) Preoperative prospective cataract surgery patient with active anterior blepharitis. Cultures from the lid margins grew heavy methicillin-resistant Staphylococcus epidermidis. (Images courtesy of Terrence P. O’Brien, MD) “Alternatives to conventional antibiotics—such as antimicrobial peptides, antisense agents, or natural killers, like hypochlorous acid, present in human neutrophils—may have an increasing role in both treatment and prevention of infection,” Dr. O’Brien predicted. These alternatives are attractive because of their novel mechanisms of action and resistance to the development of resistance, he noted. New drug delivery systems are being considered to transport and distribute available antibiotics and thereby extend their usefulness. “Some strategies are afoot to use drug delivery, especially nanotechnology, that may enhance the penetration and potency of the existing compounds so that higher concentrations can be achieved in the target tissues and even greater contact time to facilitate greater drug activity,” Dr. O’Brien explained. T H E A R MOR ST U DY The ongoing Antibiotic Resistance Monitoring in Ocular MicroRganisms (ARMOR) study of bacterial resistance underscores the importance of concern about this growing resistance problem. Dr. O’Brien commends surveillance efforts, such as the ARMOR Study and other such large undertakings, to maintain awareness of the evolving trends in organisms that cause ocular infections and in the antimicrobial susceptibility patterns. “These surveillance strategies are essential for a better understanding of the enemy, as well as the rational choices of optimal agents for treatment and prevention of infection,” he said. The ARMOR Study has been an important tool for monitoring trends in resistance to antibiotics, especially fluoroquinolones, he noted. The latest data collected over the previous few years have reinforced the concern about growing microbial resistance to available drugs. Resistance is growing among the commonly seen organisms to the most commonly administered ocular antibiotics. “These data suggested that in some instances a single agent may be insufficient, but rather a combination of more than one agent may be preferred for treating an active infection or for prophylaxis,” Dr. O’Brien said. The latest data from the ARMOR study are expected to be presented at the 2015 annual meeting of the Association for Research in Vision and Ophthalmology in Denver. A KEY STR ATEGY Dr. O’Brien emphasized the importance of heightened preoperative awareness about the patients who may be at unique risk of developing an infection by focusing attention on the hosts first, and not reacting later to the organisms. “The latter approach over the years has shown that the bugs tend to win because they are clever and have evolved over time,” he said. “They have devised increasingly cunning strategies to evade our efforts to eliminate them. Extra endeavors exerted preoperatively aimed to protect the patient during the window of vulnerability can eliminate problems postoperatively in these altered hosts.” Focusing on the host may help uncover newer strategies to protect patients who are uniquely at risk of infection, he said. ■ TERRENCE P. O’BRIEN, MD E: [email protected] Dr. O’Brien is an ad hoc non-salaried consultant for Alcon Laboratories, Allergan, Bausch + Lomb, Santen Pharmaceuticals, Senju, and Shire. 52 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL Postop topical antibiotic minimizes infection rate after blepharoplasty Surgeons should always consider possible presence of community-acquired MRSA By Cheryl Guttman Krader; Reviewed by Mark A. Alford, MD FOR T WOR T H, T X :: SURGICAL SITE INFECTIONS after blepharoplasty surgery are uncommon whether or not patients receive antibiotic prophylaxis. However, postoperative use of a topical antibiotic ointment significantly reduces the risk, according to a prospective, observational, cohort study undertaken by Mark A. Alford, MD. The findings of the study should also alert surgeons to suspect methicillin-resistant Staphylococcus aureus (MRSA) as the causative pathogen if infection occurs, said Dr. Alford, the oculoplastic surgeon in private practice, Fort Worth, TX, who conducted the single-surgeon study. Dr. Alford was motivated to Dr. Alford conduct the study recognizing that while antibiotic ointment is widely used by oculoplastic surgeons to reduce the risk of infection after blepharoplasty, there is very little scientific evidence to support the practice. POTENTIAL CONCERNS Moreover, there are potential concerns as antibiotic use may lead to contact sensitivity reactions, promote bacterial resistance, and increased cost. To evaluate its benefits and risks, Dr. Alford conducted an IRB-approved study comparing two similar consecutive groups of patients undergoing upper lid blepharoplasty. The first cohort included 384 patients operated on from November 2011 to April 2013, who were instructed to use bacitracin ointment twice daily for 7 days, beginning immediately after the surgery. The second cohort comprised 158 patients operated on from April to December 2013, who used a sterile ocular lubricant ointment (Refresh P.M., Allergan) with the same application regimen. Patients were excluded if they had a history of allergy to bacitracin or had used any antibiotic within the week before surgery. They were all operated on with the same technique, which involved a full sterile prep and running suture closure with 6-0 silk. One patient using antibiotic ointment developed a surgical site infection (0.26%), which did not culture positive for MRSA. In the control group, there were 10 patients with a surgical site infection (6.3%). Nine of the patients had a bilateral event and all were positive for communityacquired MRSA (CA-MRSA). All of the infections were managed by suture removal and treatment with an oral antibiotic chosen based on culture and sensitivity testing. All of the infections cleared, but all patients with a CA-MRSA infection were left with hypertrophic scars. Photos of a patient in the study who underwent blepharoplasty “I stopped enrolling patients in the surgery. Later, the eye became infected. (Photos courtesy of Mark A. second cohort earlier than planned Alford, MD) because the between-group difference in infection rate was statistiIn addition, all personnel who came into cally significant,” said Dr. Alford. “The hypertrophic scarring that developed contact with the patients in the operating room in patients with the CA-MRSA is improving, were negative for MRSA colonization. Only 1 but they are all finding the scarring is cos- patient who developed an MRSA infection was a health-care worker. None had a previous metically significant.” Among the patients who used bacitracin, Staphylococcal infection or smoked. “The finding that all of the infections were 14 (3.6%) developed an allergic reaction characterized by bilateral erythema, edema, and caused by CA-MRSA is really not unexpected, itching. Cultures were done in all cases and considering it is a virulent pathogen that has were negative, and the reactions resolved after become epidemic in the United States,” Dr. Alford said. discontinuation of the antibiotic. “We believe the surgical wounds became “The rate of allergic reactions to bacitracin ointment in this study is lower than what contaminated by exposure to a community has been previously reported,” Dr. Alford said. source or self-inoculation from a colonized nasal cavity,” he said. Dr. Alford also emphasized that he was not CONSISTENT APPEAR ANCE Dr. Alford noted that the CA-MRSA infections promoting the use of bacitracin ointment to were characterized by the presence of signifi- prevent infection after blepharoplasty. “Any antibiotic ointment that provides good cant erythema, purulent material, and elevation along the suture line along with areas of coverage against gram-positive organisms might tissue necrosis at the site of the sutures and have similar effects,” he said. ■ only minimal edema. Concerning the possible source of the pathogens, Dr. Alford noted the cultured organisms MARK A. ALFORD, MD represented various strains and subtypes of E: [email protected] MRSA. He said that the infection rates were low This article was adapted from Dr. Alford’s presentation at the 2014 meeting of the (<0.2%) over the past 2 years at both surgery American Academy of Ophthalmology. Dr. Alford has no relevant financial interests to centers where the procedures were performed. disclose. 46TH ANNUAL DOHENY DAYS CONFERENCE JUNE 19-20, 2015 GUEST SPEAKERS The Irvine Memorial Lecturer Julia A. Haller, MD Ophthalmologist-in-Chief, Wills Eye Hospital Professor and Chair, Thomas Jeīerson University Philadelphia, Pennsylvania The Doheny Memorial Lecturer Simmons Lessell, MD Professor of Ophthalmology, Harvard Medical School DOHENY SOCIETY OF SCHOLARS 2015 HONOREES Donald S. Minckler, MD Young Hee Yoon, MD Director Ophthalmic Pathology, University of California at Irvine Professor of Ophthalmology, Asan Medical Center University of Ulsan Seoul, South Korea THE ANNUAL DOHENY DAYS CONFERENCE HOSTS DOZENS OF PRESENTERS REPRESENTING A WIDE RANGE OF OPHTHALMIC SPECIALTIES AIMED AT DISSEMINATING STATE-OF-THE-ART RESEARCH FINDINGS TO IMPROVE CLINICIANS’ ABILITY TO BETTER DIAGNOSE AND MANAGE PATIENTS WITH OCULAR DISEASE. Please contact: Sandra Espinoza, CME Coordinator 323-442-6427 l [email protected] 54 APRIL 15, 2015 :: Ophthalmology Times Special Report ) EFFECTIVE CONCEPTS IN OCULAR INFECTION CONTROL Analysis confirms previous conclusion with intracameral antibiotic use Kaiser Permanente Northern California study again shows benefit for postop endophthalmitis By Cheryl Guttman Krader; Reviewed by Neal H. Shorstein, MD two-thirds of intracameral antibiotic use and moxifloxacin was used in almost all of the reexpanded patient cohort corroborates the ben- maining cases. Overall, intracameral antibiotic was injected in 39.5% of study eyes and efit of intracameral antibiotic use. “We can conclude that intracameral antibi- was almost always used together with a topiotic injections are effective in reducing endo- cal antibiotic. The analysis excluded eyes that had planned phthalmitis risk,” said Neal H. Shorstein, MD, ophthalmologist and associate chief of quality, complex surgery, cases that were performed Kaiser Permanente, Walnut Creek, CA, and by a retina specialist or oculoplastic surgeon, and cases with combined glaucoma or corlead author of the original study. “However, due to the low incidence of this nea surgery. Cases of endophthalmitis occurring within infection and because of the effectiveness of intracameral treatment, no definite conclusion 90 days of surgery were identified from diagcan be drawn to differentiate between cefu- nostic codes in Kaiser Permanente’s Healthroxime and moxifloxacin,” Dr. Shorstein said Connect electronic health record. To validate “Given the very high concentration of agent in the diagnosis, pertinent information from all the anterior chamber achieved with intracam- of those cases was thoroughly reviewed by a eral injection, there may be little difference trained medical abstractor and research ophthalmologist using defined criteria. A total of between them.” In 2013, ophthalmologists from Kaiser Per- 113 validated cases of endophthalmitis were manente Northern California published the identified. Risk of endophthalmitis was analyzed by lofirst United States study demonstrating the efficacy of intracameral antibiotic injection for gistic regression analysis that was conditioned on the surgeon to account for techreducing the rate of postoperative nique and unmeasured factors reendophthalmitis [J Cataract Refract lated to the surgeon and adjusted Surg. 2013;39:8-14]. for age, year of surgery, ocular and The study analyzed data from systemic comorbidities, posterior 16,264 eyes operated on between An updated analysis capsule rupture, and topical anti2007 and 2011, including 12, 609 from cataract surgeons biotic use. Using eyes treated with that received intracameral injection at Kaiser Permanente topical antibiotic only as the refprimarily with cefuroxime (84%), Northern California erence group, the results showed and found adoption of intracam- again shows the that the combination of topical and eral antibiotic use was associated benefit of intracameral intracameral antibiotic use signifiwith a 22-fold decline in the rate antibiotic use for cantly reduced the risk of postoperaof clinical endophthalmitis. reducing the rate tive endophthalmitis by almost half The updated analysis included of postoperative (adjusted odds ratio = 0.55; 95% data for 129,077 procedures per- endophthalmitis. confidence interval 0.32 to 0.93). formed by 99 community-based The intracameral only group had a simisurgeons in 20 surgical centers over the years lar adjusted odds ratio of infection (0.47), al2005 to 2012. Use of intracameral antibiotic for endophthal- though the confidence interval overlapped 1. mitis prophylaxis began in late 2007 with in- Patients with no record of pharmacy dispensjection of cefuroxime 1 to 2 mg into the an- ing of a topical antibiotic were over 3 times as terior chamber. The intracameral technique likely to develop endophthalmitis compared was increasingly adopted over time, and at with the reference group (adjusted odds ratio many centers, moxifloxacin 100 mcg was the = 3.10; 95% confidence interval 1.64 to 5.84). “Intracameral antibiotic injection eliminates preferred antibiotic. In the series, cefuroxime accounted for about the added risk that occurs with failure of pharWAL NU T CREEK , CA :: AN UPDATED ANALYSIS based on an take-home MAKING THE INJECTION VIDEO Watch as intracameral antibiotic (0.1 mL) is injected. Go to http://bit.ly/1IGSSx1 (Video courtesy of Neal H. Shorstein, MD) macy dispensing or improper administration of topical drops,” Dr. Shorstein said. In the analysis comparing intracameral antibiotic effectiveness, the risk of endophthalmitis was higher when moxifloxacin was used compared with cefuroxime (adjusted odds ratio = 1.3). However, the difference between groups was not statistically significant. “When intracameral antibiotic use was introduced at Kaiser Permanente Northern California, the endophthalmitis rate decreased dramatically and it has continued to fall over time. “As a paradoxical effect of the increasing adoption of intracameral injection, the plummeting incidence of endophthalmitis makes statistical conclusion of the comparative effectiveness of this already rare complication even more difficult,” Dr. Shorstein commented. In 2013, intracameral antibiotic was used in 79% of cataract surgery cases, he noted. Among about 25,000 injected eyes, the rate of endophthalmitis was just 1 in 12,000. ■ NEAL H. SHORSTEIN, MD E: [email protected] This article was adapted from a presentation at the 2014 meeting of the American Academy of Ophthalmology. Dr. Shorstein has no relevant financial interests to disclose. 56 APRIL 15, 2015 :: Ophthalmology Times clinical diagnosis Contrast sensitivity reaches beyond measure of vision Valuable screening tool for pre- and postop management, IOLs, CXL, diagnostic aid By Nancy Groves; Reviewed by Gregory J. Pamel, MD, and Prof. Dan Reinstein, MD, FRCSC ontrast sensitivity provides an objective measurement of quality of vision to complement the standard routine measurement of visual acuity, or quantity of vision, and is a useful metric in routine care as well as preoperative and postoperative patient management. Routine contrast sensitivity testing gives the ophthalmologist, and particularly the refractive surgeon, another string to their bow and provides a more complete understanding of the patient’s visual function. C BASELINE MEASUREMENT For both corneal and intraocular refractive surgery applications, it is important to measure contrast sensitivity routinely to provide a baseline measurement so that a comparison is always possible postoperatively, said Prof. Dan Reinstein, MD, FRCSC, medical director, London Vision Clinic, London. Preoperatively, contrast sensitivity can aid the physician to pick up signs of deteriorating vision earlier than visual acuity testing. For example, patients with early cataract might be diagnosed earlier by a drop in contrast sensitivity before the visual acuity is affected. This could help a surgeon decide whether corneal or intraocular refractive surgery might be best for the patient, said Prof. Reinstein, who is also adjunct professor of ophthalmology, Department of Ophthalmology, Columbia University Medical Center, New York, and professor associé, Centre Hospitalier National D’Ophthalmologie, Paris. Postoperatively, contrast sensitivity is used to assess the quality of vision. In cases of patients complaining of poor vision, a postoperative contrast sensitivity measurement can be compared to the baseline measurement to evaluate the change in the quality of vision. This information can then be used along with topography and wavefront data to make a diagnosis of the cause of a drop in quality of vision. The surgeon can then consider the differ- ent options available to treat the patient, Prof. In this example, contrast sensitivity is a useReinstein said. ful measurement to assess the impact of aberFor corneal surgery, in the past, older-generation rations on visual quality. Similarly, with new laser surgery platexcimer lasers have been shown to reduce contrast forms—such as topographysensitivity. However, modern exguided LASIK—clinicians use cimer lasers have been shown to contrast sensitivity to show pamaintain or even slightly increase Contrast sensitivity tients that their quality of vicontrast sensitivity. is a more valuable sion has improved because treat“For example, we have previmetric than many ment was customized to their ously reported no reduction in ophthalmologists needs, and corneal aberrations contrast sensitivity at 3, 6, 12, realize, with were reduced to improve qualor 18 cpd for myopic and hyperapplications in ity of vision. opic LASIK with the Carl Zeiss preoperative and Meditec MEL80 excimer laser,” postoperative Prof. Reinstein said. W E A LT H OF DATA management of “In comparison, a statistically Contrast sensitivity has perhaps corneal and refractive significant decrease in contrast been underused in ophthalmolsurgery patients and sensitivity has been reported ogy practices despite the wealth routine screening of after multifocal IOL surgery,” he of data on its application in varipatients’ quality of added. “Studies such as these ous procedures. vision. help to educate ophthalmolo“In intraocular optics, any gists on the changes in vision time you attempt to expand the that might be expected for difrange of vision with a multifoferent refractive procedures.” cal IOL, you’re going to lose some contrast sensitivity,” said Gregory J. Pamel, MD, a LASIK D I A G N O S I S O F C O M P L I C A T I O N S and vision correction surgery specialist in New Finally, contrast sensitivity is a useful mea- York and clinical assistant professor of ophsurement to consider as part of the diagnosis thalmology at New York University School of of optical complications following refractive Medicine. “That’s been well documented in surgery. Contrast sensitivity has been shown the literature.” to be correlated with wavefront measurements. He added that when a patient is dissatisfied For example, in a previous study, Prof. Re- following a multifocal lens implant despite exinstein and colleagues compared contrast sen- cellent visual acuity on the Snellen chart, ophsitivity between 2 groups of patients: a repair thalmologists already understand that vision group of eyes selected for wavefront-guided re- has been impacted by the procedure and don’t pair because of debilitating night vision distur- need contrast sensitivity testing to prove it. bances following primary myopic LASIK, and a Consequently, they may not consider it neccontrol group matched for spherical equivalent essary as a routine component of postoperatreated but with no night vision complaints. tive patient management. In the control group, there was an increase Another reason why contrast sensitivity testin spherical aberration but no change in con- ing has had a limited postoperative role is that trast sensitivity. In the wavefront-guided re- it is challenging to determine when it might pair group, there was a reduction of spheri- be worthwhile. cal aberration by 27%, and although spheri“We’ve all had patients who can see very cal aberration was still much higher than that well postoperatively, seeing 20/20 at distance of the normal group, contrast sensitivity re- and J1 up close with a multifocal lens who are turned to normal. unhappy, and there are those who don’t nec- TAKE-HOME APRIL 15, 2015 :: Ophthalmology Times clinical diagnosis essarily see 20/20 at distance and don’t necessarily read 20/20 at near after a multifocal lens implant who are very happy,” Dr. Pamel said. “Contrast sensitivity doesn’t always differentiate those patients.” The explanation may lie in part with the neuroadaptivity of the brain and how well it is allowing patients to see to their level of satisfaction. However, contrast sensitivity testing may still play a role by a circuitous route. “We know that contrast sensitivity improves in the first 6 months after implantation of a multifocal lens as a result of neuroadaptation,” Dr. Pamel said. “So if a patient is not happy at 1 month we could take their contrast sensitivity and check it again at 6 months to show them that it has improved. That may be a way to continue to educate the patient after surgery.” Contrast sensitivity may be even more valuable as advancements continue in the technology of multifocal lenses, Dr. Pamel said. Soon, surgeons may perform comparative studies of older versus newer lens technologies and use the contrast sensitivity results to show future cataract patients the dramatically better real-world results they are likely to have with the improved lenses. HELPFUL IN ENHANCEMENTS Contrast sensitivity could also be helpful when performing enhancements on patients who may have had laser surgery 10 or more years ago with earlier versions of technology and are experiencing problems, such as glare and halos or poor night vision. Often, these patients have gone to a number of physicians who have corrected their vision in a darkened exam room to see the 20/20 or 20/25 line, yet they are still unhappy with their vision and its impact on their quality of life. “This really is a function of their loss of contrast sensitivity, and the laser technology that is out there now can improve upon that dramatically,” Dr. Pamel said. “Contrast sensitivity would be very beneficial in explaining to the patient why they’re not seeing well.” Yet another aspect of vision correction in which contrast sensitivity could be helpful is corneal collagen crosslinking (CXL) for keratoconus. Sometimes patients subjectively report improved vision after this procedure despite modest gains in visual acuity, and this may be due to enhanced contrast sensitivity. Dr. Pamel and colleagues are performing a study on contrast sensitivity before and after CXL to determine if they can better understand potential benefits and apply this knowledge to future cases. Contrast sensitivity testing has been part of the clinical trial process for presbyopic cor- neal inlays. Results have shown that contrast sensitivity does not change significantly after corneal inlays have been implanted. Contrast sensitivity testing will be important for physicians to perform both preoperatively and postoperatively to demonstrate to patients that their visual quality has not changed, Dr. Pamel suggested. ■ 57 GREGORY J. PAMEL, MD E: [email protected] Dr. Pamel has no financial interests in any of the products mentioned in this article. PROF. DAN REINSTEIN, MD, FRCSC E: [email protected] Dr. Reinstein is a consultant for Carl Zeiss Meditec. Finding the right angle can be challenging ! Sign up for the Pentacam® educational events at www.pentacamseminar.com Finding the correct orientation of a Toric IOL implant is not an easy task ! The OCULUS Pentacam® can help: 9 9 9 9 Topography of anterior and posterior corneal surface Total #orneal 2efractive 0ower Evaluation of corneal optical densitometry Support for selection, orientation and calculation of Toric IOLs Visit the OCULUS Booth #1845 at the ASCRS 2015 in San Diego www.oculususa.com + (* #0-"2*2020 "-+4Tel: 888-519-5375 58 APRIL 15, 2015 :: Ophthalmology Times clinical diagnosis Yin-yang of OGRS has implications for diabetic ocular complications Gene therapy link shows promise for epithelial wound healing, corneal sensitivity, dry eye By Nancy Groves; Reviewed by Joseph W. Sassani, MD, MHA HERSHE Y, PA :: he opioid growth regulatory system (OGRS) is inadequately recognized for its implications in the pathobiology and treatment of the complications of diabetes, said Joseph W. Sassani, MD. The OGRS appears to be disordered in diabetic animals, added Dr. Sassani, professor of ophthalmology and pathology, Penn State University’s Hershey Medical Center (HMC), Hershey, PA. Studies have shown, however, that function can be restored to normalize corneal epithelial wound healing, corneal sensitivity, and tear production in models of both type 1 and type 2 diabetes through treatment with naltrexone, the pharmacologic antagonist of naturally occurring opioid growth factor (OGF, [MET5]-Enkephalin). Dr. Sassani described OGF and naltrexone as the “yin and yang” of the OGRS, whose main components are OGF and its specific receptor, OGFr. OGF is a naturally occurring opioid that suppresses cell division when bound to OGFr. It is tonically produced, and its level in tissue is usually neither maximized nor minimized. As a result of this characteristic, manipulation of the OGRS can decrease or increase cell division. T regulates cell division, while cell division could be accelerated by decreasing the interaction of OGF with its receptor, either by decreasing the production of OGF or its receptor or by utilizing a blocking agent, like naltrexone, to directly block OGFOGFr interaction, Dr. Sassani said. TWO DECADES OF RESEARCH Over past 25 years, the research team—including Ian S. Zagon, PhD, and Patricia J. McLaughlin, PhD, of the HMC Department of Neural and Behavioral Science—has delineated Ian Zagon, PhD (left), and Patricia McLaughlin, PhD, were the role of the OGF-OGFr system in part of the research team that linked the OGF-OGFr system to the homeostasis and healing of ocdiabetic ocular complications. (Photo courtesy of Joseph Sassani, MD) ular tissues and demonstrated its role in the pathobiology of diabetic ocular complications. The researchers initially demonwhile antisense diminished the expression and strated that the OGRS modulates outgrowth of accelerated wound healing. the corneal epithelium in organ culture, then Next, a series of studies showed that naldemonstrated the ability of OGF treatment to trexone accelerated re-epithelialization, while suppress DNA synthesis in the cornea of the OGF suppressed epithelial wound healing. The living rat and that of naltrexone to increase it. results also showed that naltrexone increased Building on these findings, the researchers DNA synthesis and OGF decreased the process. conducted a series of investigations determining Connecting these laboratory findings to pathat treatment with either systemic or topical tient care, Dr. Sassani explained that keratopathy and neuropathy are common complications of this disease, and both type 1 and type 2 diabetes are associated with delayed corneal epithelial wound healing, abnormal corneal sensitivity, and dry eye. ‘These yin-and-yang characteristics make it uniquely suitable for therapeutic manipulation.’ — Joseph W. Sassani, MD “These ‘yin-and-yang’ characteristics make it uniquely suitable for therapeutic manipulation,” Dr. Sassani said. The OGF-OGFr axis can be manipulated in several ways to regulate cell division. OGF is a negative or inhibitory growth factor, while naltrexone, which blocks OGFr, stimulates growth. The addition of exogenous OGF or an increase in the number of its receptors down- naltrexone resulted in an increased rate of rat corneal epithelial wound healing. Treatment with topical naltrexone also led to more rapid healing in rabbit corneas. The team also studied regulation of wound healing by using a gene gun to deliver sense and antisense OGFr cDNA into corneal epithelial cells in rat eyes. Sense caused overexpression of OGFr and delayed wound healing, LINK WITH DIABETES The link between endogenous opioids and diabetes is that elevated levels of OGF have been found in the plasma of diabetic humans, as well as in genetically obese diabetic mice, and both OGF and OGFr have been found in the epithelium of diabetic animals. “We postulated that abnormalities of opioid regulation could contribute to the complications of diabetes and that blockade of the OGRS by naltrexone might reverse or ameliorate these complications,” Dr. Sassani said. APRIL 15, 2015 :: Ophthalmology Times clinical diagnosis ‘We postulated that abnormalities of opioid regulation could contribute to the complications of diabetes . . .’ — Jospeh W. Sassani, MD eye and compiled data that support Summarizing a series of studies, the concept of OGRS modulation he explained that in diabetic aniof tear production even in nondiamals, topical naltrexone restores betic rats. Naltrexone treatment of corneal epithelial wound healing diabetic dry eye has restored tear to levels comparable to systemiproduction to normal levels for up cally or topically insulin-treated to 3 days following discontinuation animals without apparent epitheof the naltrexone therapy in type lial toxicity. 1 or type 2 diabetic rats. He also referred to results indiProposing broader implicacating that combined insulin and tions for the OGRS, Dr. Sassani naltrexone were no more effective suggested that it than either one used is important in the independently. pathobiology of di“The possibilResearch supports abetic ocular surity exists that inthe hypothesis that face disease and sulin and naltrexmanipulation of that blockade of one have their efthe opioid growth the OGFr may have fect through simiregulatory system can systemic implicalar mechanisms in restore function and tions for OGRS and diabetic animals or normalize corneal diabetes. that each has the epithelial wound Dr. Sassani and potential to maxhealing, corneal h i s c ol lea g ue s imize epit helial sensitivity, and tear have e x tende d wound healing in production in models their research to these animals, leavof both type 1 and non-ocular diaing no opportunity type 2 diabetes. betic complicafor further increase tions, such as deby the complemenlayed skin wound healing. A 2011 tary modality,” Dr. Sassani said. study showed that topical treat“Insulin has no effect on wound ment with naltrexone facilitates healing in normal animals, and closure of full-thickness wounds naltrexone has no impact on blood in diabetic rats. glucose levels in diabetic animals,” Further research suggests that he added. naltrexone accelerates wound cloData from various studies also sure in part by stimulating the suggest that the route of adminisexpression of angiogenic factors tration could be a factor and that within healing tissue in diabetic systemic insulin may be unable to animals. reach the tear film in a concentra“Obviously, there is the potential tion equivalent to that of topical for a significant impact on faciliadministration. tating the initial closure of such wounds,” Dr. Sassani said. BROADER He also observed that naltrexone IMPLICATIONS has a more pervasive impact on the Turning to diabetic corneal neuoverall process of wound healing beropathy, Dr. Sassani noted that sevyond wound closure. For example, eral studies suggest that it can be research showed that diminished reversible with naltrexone therapy. collagen formation and maturation The team has also studied dry in healing granulation tissue were restored to normal by topical treatment with the opioid antagonist. In another study, inadequate healing at 60 days after wounding in type 1 diabetic rats, reflected in reduced tensile strength, was reversed by naltrexone. ■ 59 JOSEPH W. SASSANI, MD, MHA P: 717/531-5690 E: [email protected] This article was adapted from Dr. Sassani’s presentation of the Zimmerman Lecture at the 2014 meeting of the American Academy of Ophthalmology. Dr. Sassani has patent interests through Pennsylvania State University in the clinical applications of opioid growth regulatory system. icare-usa.com 888.422.7313 TAKE-HOME VISIT ASCRS #752! ICARE REBOUND TONOMETER ACCURATE AND EASY IOP MEASUREMENTS DR. MING WANG, MD, PHD, DIRECTOR, WANG VISION INSTITUTE, NASHVILLE TN “Icare has been a unique device for our cataract and LASIK clinic in that it not only gives us a reliable IOP reading, but also and even more importantly it does not cause any corneal epithelium damage at all and can be used safely even right after a LASIK procedure.” 60 APRIL 15, 2015 :: Ophthalmology Times clinical diagnosis Palinopsia: Peeking behind doors of visual perception, visual memory Pathological afterimages split into two categories: hallucinatory, illusory palinopsia The Neuro-Connection By David Gersztenkorn, MD, MS, and Andrew G. Lee, MD THE PATIENT with palinopsia may be particularly challenging, because of the strange and sometimes bizarre descriptions that are reminiscent of what might be heard on a psychiatric ward. In addition, the physical exam and workup are usually negative. Illusory or hallucinatory visual symptoms can cause patients considerable mental distress, and these challenging encounters often result in a referral to neuro-ophthalmology. In this article, we discuss the clinical considerations for a general ophthalmologist seeing a patient with palinopsia (Greek: opsia for “seeing”, palin for “again”). Palinoptic afterimages are pathological and should be distinguished from physiological afterimages, common and benign phenomena that occur after viewing a bright stimulus, such as seeing stars after a retinal exam. Palinopsia thus describes a heterogeneous group of pathological symptoms, which we split into two categories: hallucinatory palinopsia and illusory palinopsia.1Each group has similarities in symptom description, etiology, mechanism, prognosis, and treatment. A palinoptic scene consists of a short, stereotyped action sequence that continuously replays for several minutes (e.g., a patient views a person throwing a ball and then sees the same scene repeated many times). The palinoptic image or scene may occur immediately following the stimulus or may be delayed. Hallucinatory palinopsia can also refer to seeing an object or physical feature which is superimposed onto other objects or people in the same context for a few minutes (Figure B). For example, a patient sees a man with a beard and then observes the same beard on every subsequent person viewed. Another example might be seeing a person wearing distinctive shoes and then the same footwear is observed on every other person. Hallucinatory palinoptic afterimages are a dysfunction of visual memory and are caused by seizures or cortical lesions, such as neoplasms, infarctions, and abscesses. ILLUSORY PA LI NOPSI A A visual illusion is the altered perception of a real external stimulus, such as seeing distortions in shape, size, or color. Illusory palinopsia is similar to a visual illusion in that there is a dysfunction in the original perception of H A LLUCI NAT ORY PA LI NOPSI A A visual hallucination is the creation of an a stimulus, and the afterimages are unformed image or scene where none exists and can and indistinct. For example, when viewing a light or other be simple/unformed (e.g., lights, colors, lines, bright stimulus—such as a comgeometric designs) or complex/ puter screen and shifting visual formed (e.g., objects, animals, focus—a prolonged, indiscrete people, scenes). Hallucinatory afterimage remains for several palinopsia is similar to a comPalinopsia can minutes in the same location in plex hallucination but describes be broadly defined the visual field. These illusory the persistence or recurrence as the persistence palinoptic afterimages are difof a previously seen, formed, or recurrence of ferentiated from physiological high-resolution image or scene an image after the afterimages based on the after(Figure A). stimulus has been image intensity and duration. For example, after seeing a removed. Formed, Illusory palinopsia may also cat, an almost identical copy of high-resolution refer to an object or light in mothe cat may remain fixed in the afterimages are tion leaving a comet-like tail in field of view. The hallucinatory typically more its wake (Figure C). afterimage usually is transitory alarming to patients The visual trails may be disand of short duration (e.g., lastthan unformed, continuous, such as in a film ing seconds to minutes) but may blurred afterimages. reel, or may be blurred together, persist for hours. TAKE-HOME A B C Various examples of hallucinatory palinopsia (Figures A and B) and illusory palinopsia (Figure C). (Images courtesy of Kelli Gross) such as in a long-exposure photograph. These movement-induced afterimages persist for several seconds before fading and are usually identical in color and shape to the original object or light, but may be vague or less intense. Illusory palinopsia occurs in migraineurs, after concussions, after hallucinogen use, and as a prescription drug side effect (e.g., trazodone, clomiphene, oral contraceptives, topiramate). ILLUSORY VERSUS HALLUCINATORY Illusory palinopsia is due to an abnormality in the original perception of a stimulus, whereas hallucinatory palinopsia is due to an abnormality after a stimulus has been encoded in APRIL 15, 2015 :: Ophthalmology Times clinical diagnosis visual memory. External conditions—such as stimulus intensity, background contrast, fixation time, and movement—typically affect the generation and severity of illusory palinopsia but not hallucinatory palinopsia. Illusory palinopsia occurs immediately after seeing the original stimulus in the same location in the visual field, while hallucinatory palinopsia may appear anywhere in the visual field and can be delayed in time. Illusory palinopsia occurs continuously or predictably, such as in the morning or during light adaptation. However, hallucinatory palinopsia is unpredictable. Visual field deficits are often present with hallucinatory palinopsia, but not with illusory palinopsia. Illusory palinopsia may be caused by diffuse neuronal pathology, such as global alterations in neurotransmitter receptors, while hallucinatory palinopsia is typically caused by focal cortical pathology. The clinical characteristics that separate illusory from hallucinatory palinopsia also help differentiate and assess risk in visual illusions and hallucinations. Complex visual hallucinations are usually more worrisome to patients than simple visual hallucinations or visual illusions.2 CLINICAL ENCOUNTER The examiner should obtain the details of the palinopsia to determine if it is hallucinatory or illusory. A full neuro-ophthalmologic exam including automated visual fields should then be performed. Hallucinatory palinopsia, usually caused by a cortical lesion or seizure, can be the presenting symptom of a serious neurological disease and typically resolves after treating the underlying disturbance. A patient reporting even one such episode should probably be offered an MRI and a possible referral to neurology or neuro-ophthalmology. In contrast, illusory palinopsia is more common and usually less worrisome. Patients often have multiple types of illusory palinopsia, along with visual illusions and simple hallucinations like visual snow, Alice in Wonderland Syndrome, and entoptic phenomena. These illusory symptoms are generally benign and long standing, but are often refractory to treatment. Diagnosing the etiology of illusory palinopsia is based on clinical history, with the physical exam and work-up usually being noncontributory. Illusory palinopsia can be attributed to prescription drugs, head trauma, migrainous neuronal dysfunction, hallucinogen ingestion, or symptoms may be idiopathic. There is occasional treatment success with pharmaceuticals that reduce cortical excitability, such as gabapentin. Sunglasses or tinted lenses or filters may improve symptoms. Many patients with illusory palinopsia have played referral pinball between neurologists and ophthalmologists and have already received extensive work-ups. Due to the subjective nature of the symptoms and the absence of physical findings, clinicians are sometimes dismissive or mention non-organic disease. There is considerable evidence in the literature confirming the symptom legitimacy, so validating and explaining the patient’s symptoms can help ease anxiety and should be of primary concern. Illusory palinopsia is presumably due to a modified neural excitability state causing dysfunction in light and DAVID GERSZTENKORN, MD, MS, is an ophthalmology resident affiliated with the Department of Ophthalmology, Houston Methodist Hospital, Houston, and the Department of Ophthalmology, UTMB, Galveston, TX. He did not indicate any proprietary interest in the subject matter. ANDREW G. LEE, MD, is editor of “The Neuro-Connection” column. Dr. Lee is chairman, Department of Ophthalmology, Houston Methodist Hospital, Houston; adjunct professor of ophthalmology, Baylor College of Medicine, Houston; professor of ophthalmology, neurology, and neurosurgery, Weill Cornell Medical College, Houston; clinical professor of ophthalmology, The University of Texas Medical Branch, Galveston, TX and The UT MD Anderson Cancer Center; and adjunct professor of ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, IA and the University of Buffalo, SUNY, Buffalo, NY. motion processing mechanisms, thus there is an exaggeration of normal phenomena, such as physiological afterimages from bright lights and trails behind quicklymoving objects. For more information on palinopsia, refer to the review article.1 ■ References 1. Gersztenkorn D, Lee AG. Palinopsia revamped: A systematic review of the literature. Surv Ophthalmol. 2014. 2. Teeple RC, Caplan JP, Stern TA. Visual hallucinations: differential diagnosis and treatment. Prim Care Companion J Clin Psychiatry. 2009;11:26-32. 61 62 APRIL 15, 2015 :: Ophthalmology Times clinical diagnosis Treatment of TBI, concussions an underutilized focus in ophthalmology Visual performance training can improve rehabilitation course, generate more patient visits By Barry L. Seiller, MD, MBA, Special to Ophthalmology Times The severity or number of AS ONE OF THE FEW visual problems does not apophthalmologists who specialpear to relate to the severity izes in the evaluation and trainof the brain injury. While ing of visual skills and how moderate-to-severe brain those skills impact athletics, injury can understandably academics, and rehabilitation, cause significant problems, it I am surprised by how many is now postulated that even of my colleagues are unfamilminor brain injuries can disiar with this area of the visual rupt the overall speed, efsystem. ficiency, and integration of While the area of visual permental and central nervous formance is given little expofunction. sure during residency trainThese symptoms frequently ing, it has an impact on many do not correlate with the functions of patients’ everyamount of pathology and day lives. are not found on radiologic I became interested in this imaging. There may be sefield in the 1990s through an vere cognitive and behavioral optometrist who received an impairments causing headeducation in the field of viaches, dizziness, photophosual performance as part of Patient measures his vision skills on the Vizual Edge Performance Trainer, a Web-based bia, delay in return to play his training. Visual perforvisual performance program that allows reproducible results that are portable and to or work, inability to drive, mance services can generwhich users can gain easy access to the technology. (Photo courtesy of Barry Seiler, MD) emotional instability, and ate more patient visits, and memory difficulties. Sympdepending on the business toms may be a combination model, the ophthalmologist or optometrist can charge “out of pocket” military environments, the topic of TBI—par- of organic and psychological factors. The impact of visual deficits may be furticularly concussions—has recently received a for the services. great deal of media exposure and has created ther complicated by the injured person not being aware of a change in vision. Without high visibility in the athletic arena. VISUAL FUNCTION AR EAS As mentioned in the Physical Medicine & appreciation for the deficit, the injured person Four main areas of visual function include: vithereby fails to compensate for sual acuity, visual field, oculomotor control, Rehabilitation textbook chapthe deficit. ter, which I authored, patients and central visual processing. Also, because visual percepOne of the parts of the visual system—the may experience a variety of tion is a subjective experience, visual-motor portion—comprises such com- visual impairments after TBI Though given little the person may have difficulty ponents as tracking, convergence/divergence, or post-concussion syndrome, attention during articulating his or her difficulties visual recognition/memory, and depth percep- which can result in both overt residency training, and relating them to impairtion. While interrelated, these components can and insidious symptoms. the area of visual ment in vision. Impairment of ocular motor be isolated, are measurable, and in many inperformance should Conversely, the patient may control is one of the most frestances are trainable. become the standard also have developed a comStudents with reading issues may be born quently associated with TBI. It of care in patients pensatory strategy as a result with reduced visual skills; athletes may want is estimated that between 40% with traumatic brain of the impairment that interto enhance their existing visual skills to im- and 75% of patients with TBI injury, explains Barry feres with his or her ability prove athletic performance; and civilians and/ experience some reduction of L. Seiller, MD, MBA. to compensate in other areas or athletes with traumatic brain injury (TBI) oculomotor control. A dysfuncof visual functioning and that tion in this area can lead to a would like to restore them. Although there have always been large num- spectrum of issues affecting athletic play and may confuse both the person and the rehabilitation team. bers of head injuries in both the civilian and daily activities. TAKE-HOME 63 APRIL 15, 2015 :: Ophthalmology Times clinical diagnosis However, if the visual impairment can be correctly and promptly diagnosed and provided appropriate therapeutic intervention, the patient's rehabilitation course may be improved and the medical outcome enhanced. In order for survivors of acquired brain injury to benefit during the acute phase of trauma, there may be a variety of disciplines available to them in the inpatient or outpatient setting. Most concussion programs do not include an ophthalmologist and only some include an optometrist. Unfortunately, for those patients in the subacute or chronic phase of concussions, the rehabilitation team has less to offer, while the patient/athlete frustratingly is waiting for the symptoms to dissipate and return to work or play. The patients, usually athletes, are frequently in the chronic phase and have continued symptoms years after the initial event. Although they have seen numerous physicians, only rarely will these physicians have considered a compromised visual system as the basis of the dysfunctionality. Now the landscape is changing for these patients. VISION PERFORMANCE PROGR AMS In 1989, I founded the Visual Fitness Institute to investigate and implement vision performance programs for athletes and head injuries. Up until recently, there were a multitude of visual devices that existed that attempted to measure the most important visual skills. A vast majority of these devices were produced by a variety of clinicians, but most had no credible basis especially for researchers looking to examine the validity of this field. As a result of the work performed at Visual Fitness, the Vizual Edge Performance Trainer (VEPT) was developed to address the issues inherent in these previous devices. This Webbased visual performance program allows for consistently reproducible results that are portable and to which users can gain easy, economical access to the technology. The commercially available program reliably collects metrics that are used to measure the most important visual skills and create a database of scores for each user. The system offers valuable information to athletes, coaches, researchers, and now rehabilitation staff. The program can be used by oneself or by a coach or trainer. On the clinical side, it allows for a comparison of one user’s skills to another and also a method to monitor training progress. Researchers have utilized the program for a variety of investigational studies in multiple sports. This has also lent new credibility to visual performance testing and vision training that now can be correlated to performance on-court, field, or ice. Many high school, collegiate, Olympic, and professional athletes take advantage of the technology for athletic enhancement. Just as access to athletes has grown, so has the use of the program in determining the visual effects of a concussion and its remediation. The program can help determine affected visual skills and a method to rehabilitate them either at home on their own computer or in an office setting. This includes a number of eye-care professionals’ offices, facilities, and hospitals in the United States and Canada. Utilizing the program can help to determine dysfunctions, such as convergence insufficiency, which is one of the most common problems post-trauma and the most overlooked. Athletes are also being visually tested pre-injury similar to the popular ImPACT program that tests cognitive function for similar purposes. We will continue to educate the eye-care practitioner in this seldomconsidered area of the visual system. However, given the frequency of visual symptomatology that results from mild-to-moderate brain injury, the epidemic of concussions, readily available new technology such as the VEPT, ophthalmologists or optometrists should be integrated either as a member of an interdisciplinary concussion team or as a value-added service in the practice. The visual performance program provides a new depth of understanding that should become the standard of care in patients with TBI. ■ BARRY L. SEILLER, MD, MBA is the developer and owner of the Vizual Edge Performance Trainer and lead consultant of visual performance research in the newly opened Sport Performance Research Lab at Texas A&M University Corpus Christi. Digital Acuity Suite We Provide Complete All In One Systems or Software Only to Add to Your Current Windows EHR System ALREADY HAVE ACUITY PRO? Version 9 adds many features. Check our homepage for a history of new features since Version 7. ' #"! #"&esting '""#" ' " " ' o Cr" #!"%#! '" ! No Annual FTech Support FForced Upgrades DAVID HETTLER, O.D. The best things about Acuity Pro are never changing a bulb, and unlimitied flexibility with letters, pictures, and videos. Once you have this system, you will never go back to a projector. AcuityPr.$.,7 [email protected] Like Us on Facebook W CELEBRATING OUR 15TH ANNIVERSARY In 50 States, Over 20 Countries, And On Board The International Space Station! 64 APRIL 15, 2015 :: Ophthalmology Times clinical diagnosis Invisible portions of Bruch's membrane influence rim estimates An examination of why current methods are inaccurate and what should change By Felicity Thomas, Ophthalmology Times Europe; Reviewed by Balwantray C. Chauhan, PhD, and Claude Burgoyne, MD SINCE THE INTRODUCTION of the ophthalmoscope by Helmholtz in 1851,1 the health of the neuroretinal rim has been determined through the appearance of the optic disc. “In its essence, we, as clinicians, try to identify the disc margin and the rim margin, and then conceptualize that the disc margin is a true outer boundary of the neural tissues, as is the rim margin,” said Claude Burgoyne, MD, Devers Eye Institute, Portland, OR, at the Heidelberg Engineering-sponsored symposium which took place during the EGS congress in Nice, France. Technological advancements in spectraldomain optical coherence tomography (SDOCT) have allowed clinicians to better visualize optic nerve head (ONH) anatomy and have led clinicians to question the accuracy of current methods used to estimate the health of the neuroretinal rim. “I want to highlight the fact,” Dr. Burgoyne continued, “that there’s absolutely no agreement among us on what the disc margin is in any given eye or what it should be.” To address this uncertainty, Dr. Burgoyne and Balwantray Chauhan, PhD, Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, explained how recent SD-OCT-detected anatomy challenge current concepts of the clinical disc margin and neuroretinal rim quantification.2 INVISIBLE ANATOMY Three and a half years ago, Drs. Burgoyne and Chauhan discovered there are portions of Bruch’s membrane anatomy that are clinically invisible. Working in their respective labs, they co-localized stereo optic disc photographs to SD-OCT data to precisely identify optic disc anatomy that corresponds to features seen with direct ophthalmoscopy, slit lamp biomicroscopy, or optic disc photography.3,4 “So, for every one of the patients we examined, we had a clinical disc margin and we had SD-OCT-detected, Bruch’s Membrane Opening (BMO) that we could co-localize,” Dr. Burgoyne continued. “However, in most of the 40 eyes we looked at, there was at least some portion in which there was a mismatch between OCT anatomy and the clinical disc margin. This led us to believe that OCT imaging was seeing things that the clinician couldn’t see.”5 “What we are seeing currently today as a disc margin does not correspond to a fixed anatomic structure,” explained Dr. Chauhan. “So, if this is the basis with which we make our neuroretinal rim measurements, then we don’t actually have a solid foundation to make those measurements, simply because it isn’t a consistent structure and the problem is that it varies in individual eyes and between eyes. So, we can’t really predict in which eyes and where a mismatch will occur as it is present in all eyes.” “BMO is a border, not the only (FIGURE 1) Identification of individual fovea to BMO centre one, but it is a border that we can (FoBMO) axis enables measurements to be placed according see quite well today with SD-OCT,” to individual anatomy of the eye. As opposed to a horizontal reference plane, the analysis and classification according he continued. to individual anatomy of the eye is adjusted to take the Furthermore, Drs. Burgoyne FoBMO axis into account. (Figure adapted from ref. 10: L. He et al., and Chauhan pointed out that ‘Anatomic vs. Acquired Image Frame Discordance in Spectral Domain Optical the current clinical assessment Coherence Tomography Minimum Rim Measurements’, PLoS One, 2014;9:e92225. of the neuroretinal rim is made doi:10.1371/journal.pone.0092225.) along a two-dimensional plane of the perceived optic disc margin. that can be done within each individual BThey showed examples of how, in a single eye, the orientation of the rim tis- scan and it can be done in all 24 or 48 radial sue varies around the ONH. Axons may exit B-scans so that a continuous measurement of the eye parallel or perpendicular to the visual BMO-minimum rim area can be estimated.” Although this measurement has previously axis, causing potentially significant errors in assessment of the neuroretinal rim width to been proposed,6–8 Drs. Burgoyne’s and Chaube made if the measurement plane is fixed. han’s work has shown that the BMO-minimum Drs. Burgoyne and Chauhan suggested that rim width (BMO-MRW) parameter significantly this potential error can be omitted if the neu- enhances the ability to detect glaucoma comroretinal rim width is assessed using the most pared with current analyses.9 geometrically accurate measurement, repreDrs. Burgoyne and Chauhan highlighted that sented by the minimum distance from BMO there are additional geometric errors arising to the internal limiting membrane. from current assumptions to consider. “In other words,” explained Dr. Burgoyne, “Currently, we assume that when a patient “it’s a minimum measurement, the smallest places their head into the imaging device, rethickness that’s present at that location. And, gionalization works according to a fixed-image 65 APRIL 15, 2015 :: Ophthalmology Times clinical diagnosis frame, so everyone’s superior temporal sector refers to the same anatomical location,” Dr. Chauhan said. “Of course, this is not the case.” NOV E L S OF T WA R E Based on the findings of Drs. Burgoyne and Chauhan, Heidelberg Engineering has developed software to enable the identification, in real time, of the BMO, the fovea, the varying trajectory of the rim around the ONH, and to adjust measurements according to the path of retinal nerve fibre layer bundles relative to the axis between the fovea and the ONH. (Editor’s Note: The software is available in Canada and Europe and is pending FDA clearance in the United States.) To determine whether rim parameters based on BMO, measured using SD-OCT, are better identifiers of glaucomatous discs, Drs. Burgoyne and Chauhan performed a case controlled study.9 They found that BMO-MRW measurements not only offered an anatomically accurate border of the rim from which to measure but also accounted for the variances in trajectory relative to the point of measurement. As such, it was deemed that BMO-MRW may be used as a new structural marker for the detection and risk profiling of glaucoma. To overcome these flaws, an independent normative database was collected from a different set of glaucoma subjects. CONCLUSIONS “SD-OCT should not mimic what the clinician does. We should not expect new technologies to fit into our clinical mold, otherwise science will never progress,” Dr. Chauhan said. “Rim measurements should be made in an anatomically and geometrically accurate manner and this, in our view today, should be done from BMO and perpendicular to the orientation of BMO. “With any technology, any advances that you make do not mean that a clinical examination isn’t necessary. The clinical examination is still the core of what you do or what you should do." References 1. H. von Helmholtz, Beschreibung eines Augenspiegels zur Untersuchung der Netzhaut am lebenden Auge. Berlin: A Förstner’sche Verlagsbuchhandlung; 1851. 2. B.C. Chauhan and C.F. Burgoyne, Am J Ophthalmol. 2013:156:218–227 e212. 3. A.S. Reis et al., Ophthalmology. 2012;119:738–747. 4. A.S. Reis et al., Invest Ophthalmol Vis Sci. 2012;53:1852–1860. 5. http://ophthalmology.medicine.dal.ca/research/onh.html 6. T.C. Chen, Trans Am Ophthalmol Soc. 2009;107: 254–281. 7. B. Povazay et al., J Biomed Opt. 2007;12:041204. 8. N.G. Strouthidis et al., Invest Ophthalmol Vis Sci. 2011;52:1206–1219. BALWANTRAY C. CHAUHAN, PHD is Mathers Professor and research director, Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada. Dr. Chauhan has received research and travel support and is a consultant for Heidelberg Engineering, and has received travel support and is a consultant for Allergan. CLAUDE BURGOYNE, MD is senior scientist and Van Buskirk Chair for Ophthalmic Research; director, Optic Nerve Head Research Laboratory; Devers Eye Institute, Portland, OR. Dr. Burgoyne has received research support, instruments occasional travel support and is a consultant to Heidelberg Engineering, and has received instruments from Reichert. 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Caution: U.S. Federal Law restricts this device to sale, distribution, and use by or on the order of a physician or other licensed eye care practitioner. Specifications may vary depending on circumstances in each country. Specifications and design are subject to change without notice. March 10, 2015 15-0023 66 APRIL 15, 2015 :: Ophthalmology Times focal points Antique book collection brings ophthalmic history to life Seminal works on medicine, diagnostic instruments featured in Museum of Vision display Our Ophthalmic Heritage By Norman B. Medow, MD, FACS SAN F R ANCISCO :: hilanthropy and the collecting and preservation of important books have not been relegated to the pages of history thanks to a “lasting monument to early pioneers of ocular science.” The Museum of Vision of the Foundation of the American Academy of Ophthalmology (AAO) has received a donation of the Spencer E. Sherman Collection of Antique Ophthalmology Books. More than 130 rare books and catalogs represent the lifelong collection of Dr. Sherman, a New York ophthalmologist and one of the founders of the museum and early chairman of its board of directors. The collection is important for the breadth of ophthalmology subjects covered, as well as the history it spans (16th through 19th centuries). Seminal works in glaucoma, cataract, cornea, embryology, refraction, and ophthalmic history are featured. P SIGNIFICANT TEXTS Two important books in the history of ophthalmology are included in this collection. One book, entitled “Ophthalmodouleia: Das ist Augendienst” (“In the service of the Eyes”), was written by Georg Bartisch in 1583. Bartisch is considered by many to be the father of modern ophthalmology. This book is considered to be the first on ophthalmic medicine and comprehensive surgery written in the vernacular. The folio edition book was published with 92 pages of woodcuts—one of the first books to have such woodprints—and described all of the surgery and medicine related to the eyes known at this period. Some of the woodcuts are in overlay and are mobile. The book’s popularity remained so strong that a second edition—with the woodcuts The title pages of two seminal texts in ophthalmic history are reflective of the period in which they were written. (Images courtesy of Norman B. Medow, MD, FACS) reflecting the clothing of the period—was published in 1686. The title page is classical for the great books of the period, such as “De Humani Corporis Fabrica,” published in 1543 by Andreas Vesalius. The second book—“Beschreibung eines Augenspiegels zur Untersuchung der netzhaut in Lebenden Auge” (“Description of an ophthalmoscope for examination of the retina in a living eye”)—written by Hermann Helmholtz in 1851 is equally as important. It describes what is arguably considered to be one of the two most important portable clinical diagnostic instruments in all of medicine—the ophthalmoscope. (The other instrument being the stethoscope first described in 1816.) The discovery was made because Helmholtz wanted to aid his physiology class in understanding the eye. He used his wife to develop the ophthalmoscope and thereby she was the first person whose fundus of the eye was seen in the living eye. The ophthalmoscope’s discovery revolu- tionized eye care, and within a short period all of the leading eye-care practitioners in the world had one. Helmholtz sent one of his instruments to Bowman in London, Von Graefe in Berlin, and Donders in Holland. Their descriptions of the fundus led to the publishing of a number of atlases of the retina— two of which are present in the Sherman collection: “Atlas of Ophthalmoscopy” by Otto Haab published in 1898, and the “Atlas of the Ophthalmoscopy” by Liebreich published in 1870. Also included in the collection is Volume I of the transactions of the American Ophthalmological Society, as well as classic textbooks of the period by Scarpa, Beer, Fuchs, and Desmarres. Knowledge of what instruments were present and used at any period is gained by looking at instrument manufacturers’ catalogs of the time. The Sherman collection has a large number of these catalogues—most importantly, by those of the following companies: Queen, Maw, American Optical, and Mueller, as well as others. This collection will be on display on a rotating basis in specially designed cabinets at the AAO’s Museum of Vision in San Francisco (http://bit.ly/19SqQTA). There is something special about holding a book in your hands that is 200 years old and first described an important historical event or invention—the content of which can be found on the Internet, but it is not the same! Q NORMAN B. MEDOW, FACS, is director, pediatric ophthalmology and strabismus, Montefiore Hospital Medical Center, and professor of ophthalmology and pediatrics, Albert Einstein College of Medicine, Bronx, NY. He did not indicate a financial interest in the subject matter. IN DISPENSABLE ( In Brief ) Patient Education Low Vision Rehabilitation Services OT Low Vision Evaluation and Supervision OD/MD FROM STAFF REPORTS Bright color scheme CRVT CLVT COMS Support Services /FVSPr(FSJBUSJDT $PNNVOJUZSFTPVSDFT 4VQQPSUHSPVQT $PVOTFMJOH 5SBOTQPSUBUJPOTFSWJDFT "HJOHTFSWJDFT Disease Diagnosis, Management and Ongoing Eye Care Marketing to the low vision patient Specialized techniques and tips target how, why, where low vision aids can help individual needs Figure courtesy of Dan Roberts, MME By Rose Schneider, Content Specialist, Ophthalmology Times atients with low vision can come in many forms—a young child just starting school, a teenager who lives and breathes the Internet, or a senior citizen who prefers reading the newspaper than watching television. Each of these patients requires specific needs to fit his or her lifestyle. But how do eye-care professionals ensure these patients receive the proper knowledge and devices to aid their low vision? “The information is the same, but the approaches (must) come from different places,” said Dan Roberts, MME, editor-in-chief of “Living Well with Low Vision” (http://lowvi- Roberts sion.preventblindness.org). The online resource is an educational program launched by Prevent Blindness. Continues on page 68 : Low vision P 67 OKIA LAUNCHES HAPPY FRAMES COLLECTION HONG KONG :: OKIA RECENTLY LAUNCHED its latest line of optical and sunglasses frames called Happy Frames, full of bright colors and fun patterns. Each style in the collection is named after a different cocktail—including Tequila Sunrise, Apple Martini, and Mojito—and features bright color contrasts, dots, animal prints, or houndstooth patterns, and glitter. According to Okia, all of the styles in the Happy Frames line feature its HDA Technology, which showcases colors and textures in high definition, and its CSB technique, which combines acetate with shining materials and allows random or controlled patterns with a non-delaminated effect. June product launch MARCOLIN + MARCEL LAUNCH SUNWEAR LINE V IL L A NOVA , I TALY :: MARCOLIN RECENTLY launched a new sunwear line with Marcel Burlon County of Milan. Each of the three new styles feature premium materials, original patterns, and handmade details. The line will be available in June 2015. Madre Tierra Leather is an acetate frame with a square-shaped silhouette covered with matte black leather and finished with handstitched details and metal inserts. Madre Tierra Pixel is a square-shaped black acetate frame with a white-gradient, pixel texture on the internal side of the temples. This style also features a shiny metal clipon with gold lenses. Madre Tierra All Black is a square-shaped black acetate frame with a metallic clip-on and gold lenses. This style also features metal details, including the County of Milan’s logo, on the temples and front. ■ 68 APRIL 15, 2015 :: Ophthalmology Times indispensable ate e-mail and phone-based guidance), and make sure they get what they came for (e.g., immediate news reports, plus a large library of audiovisual and printed information pro( Continued from page 67) duced in layman’s terms and backed by trusted professionals), he explained. “We challenge children and teens to develop This approach works best for teenage pagood health habits that will become natural tients and those who recognize they have a to them,” Roberts said. “We challenge young need and have already begun looking for help, adults to take care of themselves for the sake according to Roberts. of their children and their personal future. “In the early days of the InAnd we challenge senior adults ternet, we had to depend solely to do everything they can to upon the media and professional maintain their quality of life Subject matter referrals,” he continued. “Now, as they age.” experts weigh in on the majority of people begin Furthermore, because of these marketing techniques their search on the Web, so we differences, it is a necessity to to reach every make sure we are visible by utilize specialized marketing generation of patients not only staying high in the approaches to figure out how, with low vision. search engine ratings, but by why, and where a low vision aid partnering and linking with is needed for each patient, acother highly-recognizable orcording to Terri Griffin, product ganizations and maintaining a presence at manager for School Health, Hanover Park, IL. local and national conferences.” “Marketing to all ages is important to help But what about elderly patients—a signifipeople maintain their independence and abilicant portion of the population—who may not ties to work, study, read, do hobbies, and more,” utilize the Internet? Roberts recommended Griffin said. staying in touch via live support groups and state affiliates, and encouraging eye-care proMAR K ETING TO INDIV IDUA L fessionals to inform their patients further about Needs that vary by age can be age-related vilow vision aid—an important aspect of consion impairment versus physical- or diseasetinued care from diagnosis through rehabilirelated impairment, she explained. tation and personal support. “The focus (then) is more about individual Using a similar approach to reach young ability and willingness to use or learn a level patients with low vision has proven successof technology that will best suit their needs, ful over the years, Roberts said. based on their impairment and the activities These techniques include programs in schools they do,” Griffin said. and libraries, and educational materials and The changing needs of patients as they age lesson plans for teachers. is a highly important factor to address contin“To target different groups, advertise in pubually throughout their lives. lications or websites that appeal to them and “Vision impairment can change over time tailor the message to their lifestyles or interalong with tasks, goals, and technology,” she ests,” Griffin advised. “For example, heavy said. “Whether an individual has used low computer users may be more interested in vision aids for years, for a short time, or is screen magnifier/reader software, while peoconsidering them (for the first time), the indiple who are active may be interested in lightvidual should periodically re-evaluate the low weight, portable devices, and people who enjoy vision aids he or she needs or uses.” reading may want a device that can magnify Having the ability to connect with patients full pages. is key to the conversation that leads to inves“Use images or models that represent the tigating which low vision aids are best for group you are directing the message,” she each individual continued. Whichever method physicians decide to go MARKETING TO GENER ATION about connecting with patients with low vi“After trying virtually every marketing tool sion, Griffin stressed remembering that each available over the past 20 years, the method person is unique and requires specific needs that works best for me is to remain visible, and solutions. reachable, and content-rich,” Roberts said. “(This is) critical to getting the best outCompare it with a church: construct a tall come from aids and technology,” she said. steeple so people know you’re there (e.g., large To do so, Griffin offered several tips to help Internet presence), greet newcomers warmly understand each patient’s individual needs: at the front door (e.g., personal and immedi- LOW VISION TAKE-HOME Tailoring techniques to specific audience needs Dan Roberts, MME, suggests possible techniques that either may flourish or fail when marketing to patients with low vision: SUCCESSFUL TECHNIQUES W I T H CHILDR EN: Programs in schools and libraries, educational materials and lesson plans for teachers U N SUC C E S SF U L T ECH N IQU E S W ITH CHILDR EN: Flyer distribution SUCCESSFUL TECHNIQUES WITH YOU NG A DULT S: Websites, newsletters, kiosks, social media, Internet support groups, telephone help line U N SUC C E S SF U L T ECH N IQU E S W I T H Y O U N G A DU LT S : Information provided to clinics for distribution, broadcast media, e-mail broadcasts SUCCESSFUL TECHNIQUES WITH SENIOR A DULT S: Websites, newsletters, telephone help line, telephone support groups, live support groups, presentations to community groups, retirement centers, churches, libraries, Internet support groups (listservs and message boards), direct mail U N SUC C E S SF U L T ECH N IQU E S W I T H S E N IOR A DU LT S : Information provided to clinics for distribution, broadcast media, e-mail broadcasts > Investigate the type of vision impairment and degree of loss. > Find out how and where the patient will use the product (e.g., work, school, hobbies, near or far magnification, etc.). > Ask the patient about his or her ability to handle and operate a device. > Discover the goals/budget of the patient. “There are dozens of different low vision aids to help improve the lives of people with low vision,” Griffin said. “Each aid has its own advantages and limitations. To get the most from a low vision aid, it’s important to see and understand what that device can and cannot do (for the patient).” By considering these factors, patients will not only be paired with the appropriate aid for their low vision, but will continue to be informed through the best channel they understand. ■ APRIL 15, 2015 :: Ophthalmology Times indispensable 69 Post-closing issues deserve attention to avoid optical buyer’s remorse Take notice of details of creating positive customer experience at all steps of retail sale Dispensing Solutions By Arthur De Gennaro JUST BECAUSE a shopper becomes a buyer (makes a purchase) does not mean the sale is over. A lot of things can happen after the optical shopper agrees to become a buyer. Let’s look at some post-closing issues. All of us have purchased something and almost immediately questioned the decision. This is known as “buyer’s remorse.” In some cases, the buyer is so convinced the decision was a bad one that he or she will call to cancel the order or the eyeglasses are returned for a refund. Customers who are completely convinced that their purchase decision was a good one will not return it. How can you limit the number of customers who cancel or return their purchase? The answer is to deliver a customer experience that is outstanding. Some retail consultants would use the word “legendary.” Creating such a customer experience is hard work. It requires scrutinizing and reengineering all of the elements that make up the customer experience. This is one additional reason for following all of the steps in the selling process and doing them as expertly as possible. At the moment customers question their purchase, what you said and did during the sales presentation will play over in their mind. That is the moment of truth for your work, not the fact that the customers said, “yes.” If the customers received exceptional, knowledgeable, personalized service that resulted in them getting just what they were looking for, they are more likely not to return the purchase. This suggests that you should be considering what you can do to create and consistently deliver such a legendary experience. REASSUR ANCE We humans are often insecure. We derive much of our self-image from the positive reinforcement we receive from those around us. The more we trust a person, the more valuable the reinforcement. This is why re- inforcing the buyer’s decision to make the purchase is a productive selling technique. Simply reiterating the benefits of the frame, lenses, and add-ons allows the buyer mentally to double check those decisions. If the customer questions the decision later the double check should help minimize buyer’s remorse, because the buyer has already made this mental review with you. POSITIVE PROGR AMMING When customers pick up their new eyeglasses the last thing many opticians say is, “If you have any problems with your new eyeglasses or if they need adjusting please feel free to come back to see me.” This is negative programming. Essentially, the optician is telling the customer that he or she could potentially have problems with their new eyeglasses. This programs the customer to be on the lookout for problems. Although you are probably trying to express your willingness to be available and help, I doubt this is the outcome for which you are looking. A better way is to program the customer positively. Instead of talking about potential problems, ask, “Would you be willing to do me a favor? I know you will get a lot of compliments on your new eyeglasses. Would you be willing to stop by or call to let me know how you are enjoying your new eyeglasses?” In this instance the customer will be programmed to watch for compliments—compliments he or she will surely get. Each time a compliment is received, the purchasing decision will be reinforced and the customer will be reassured that the decision was a good one. BUILDING YOUR BUSINESS Businesses are built one transaction and one customer at a time. Each successful transaction fosters another, and each enthusiastic customer tells his or her friends, which builds the business overall and over time. Successful opticians know this; so does 7 Steps of a Retail Sale 1. OPENING http://bit.ly/1CCzqzY 2. INTERVIEW http://bit.ly/1Iw7Upf 3. DEMONSTRATION http://bit.ly/1ESb1tK 4. TRIAL CLOSE http://bit.ly/1CCzuQ4 5. OVERCOMING OBJECTIONS http://bit.ly/1AsAntC 6. CLOSING http://bit.ly/1yKmm7W 7. MAINTAINING AN ONGOING RELATIONSHIP every successful businessperson I know. Every successful transaction is a chance to build your business. When customers have had an extremely positive experience they are likely to tell others. Programming customers to refer you to other potential customers will encourage them to do so. Doing so is as easy as asking. Saying something as simple as, “Mr. Arthur, I have enjoyed working with you. If you have enjoyed working with me, I would appreciate it you would mention me to any of your friends or family who you feel I can help at this time.” Handing the customer a few of your business cards will give him or her something to pass along. Notice I did not say “… if you have enjoyed working with us.” That is because the customer did not do business with your dispensary; he or she did business with you and you are a unique commodity. If customers want your superior level of customer serContinues on page 70 : Post-closing 70 APRIL 15, 2015 :: Ophthalmology Times indispensable POST-CLOSING ( Continued from page 69 ) vice they must get it from you. In essence, you are your dispensary’s “secret weapon.” As basic as it may seem, this simple technique of asking for referrals can dramatically increase a dispensary’s business. It goes without saying that the more skillful the optician, the more likely it is that he or she will build a significant personal clientele. As a sometimes recruiter I can attest to the fact that some opticians have loyal customers who follow them from job to job. That is a wonderful asset for whatever practice for which they work. ORDER FULFILLMENT From an operations standpoint, what happens after the sale is known as order fulfillment. In other words, your optical dispensary must have the eyeglasses fabricated and deliver them to the customer on time, as promised. There is a long list of things that can go wrong with this process—too long to review here. Since the customer has already made a purchase, suffice it to say that this is your game to lose at this point. All of the hard work you did to gain the buyer’s trust can be ruined by having flawed logistical processes in place or by just not following through. Remember, “The devil is in the details.” A buyer can quickly go from excitement about a purchase to distress when the order is not ready on time or if the new eyeglasses are flawed in any way. PROCESS M A NAGEMEN T If you have not done so lately, I suggest you create a map of your order fulfillment processes. This begins with order entry into your dispensary’s management system and ends with the finished eyeglasses being delivered to the patient, on time, after passing rigorous, quality-assurance testing. One pro- cess I recommend is to check the status of each job each day. Be sure you are getting updates from your laboratory every day. Billing errors are irksome to customers. Not filing their managed vision care claim or filing it incorrectly signals to the customer a certain lack of attention to details. I cannot think of a practice that would want that reputation connected to its brand and image. CONCLUSION We have come to the end of this series on the selling process. It is my sincere hope that you have found these articles helpful and that they will contribute in some way to your continued success. I look forward to your comments. ■ ARTHUR DE GENNARO is president of Arthur De Gennaro & Associates LLC, an ophthalmic practice management firm that specializes in optical dispensary issues. De Gennaro is the author of the book The Dispensing Ophthalmologist. He can be reached at 803/359-7887, [email protected], or through the company’s Web site, www. adegennaro.com. He maintains a blog at www.adgablog.wordpress.com. LensFerry offers alternative to online contact lens retail By Colleen McCarthy PL E ASAN TON, CA :: A NEW CONTACT lens delivery service offers convenience to patients and financial benefits for eye-care professionals (ECPs)—while offering an alternative to other online contact lens retailers. LensFerry allows patients to order contact lenses via a mobile device, tablet, or computer for direct shipment to their homes. The contact lenses are sold at ECPs’ specified prices, and the prescribing practice receives the sales revenue. “With the marketplace going mobile, we want to make it very easy for the consumer to make a purchase from the storefront,” said Jeremy Godsil, general manager of WebSystems3. WebSystem3 is CooperVision’s cloud-based software to automate office communications and improve practice productivity. LensFerry is able to work in conjunction with WebSystem3. Patients can purchase their lenses in several ways: > A monthly plan to purchase a year’s supply of lenses—ideally, increasing compliance. > By enrolling in LensFerry, the company can contact patients via text or e-mail when it’s time to purchase new lenses. Lenses are shipped directly to patients. > When patients are ready to order lenses, they are able to contact LensFerry via text with a specified number. The company will respond with the product and pricing, and patients confirm the order by replying “yes” via text. A nationwide rollout is planned for later this year. LensFerry will be open to both ophthalmologists and optometrists. ■ APRIL 15, 2015 :: Ophthalmology Times practice management The revenue cycle decision Should practice billing be handled in-house or contracted through external vendors? By Susan Kreimer ven the most experienced phy- tion of insourcing or outsourcing collections sicians and practice managers from a scale and internal capability perspecface a daunting dilemma on the tive,” said Jim Lazarus, managing director of financial front: Should they han- strategy and innovation in revenue cycle soludle billing and collections inter- tions at The Advisory Board Co., a healthcare nally or hand over these tasks consulting firm in Washington, DC. For a practice with 15 or fewer physicians, to an external vendor? There are strategies that physicians can use internal billing is usually a more cost-effective to evaluate potential vendors and make the approach. It may be prudent to hire a capable person to focus on billing, but best decision for their practice. to serve also as a “jack of all In these challenging times for trades,” overseeing medical rephysician practices, the busiA cost analysis cords and providing other office ness side of medicine requires is essential to support, Lazarus said. navigating reimbursement dedetermining whether If a practice consists of 15 clines and rising costs while to outsource revenue to 30 physicians, the decision conforming to the Affordable cycle management to outsource depends on the Care Act and transitioning to services. market and the staff’s experithe International Classification ence with billing and collecof Diseases-10th revision (ICDA company with tions. The existence of multiple 10) code set. And while deliverstate-of-the-art office sites doesn’t necessarily ing high-quality care remains technology offers tip the scales in favor of exterphysicians’ top priority, sound greater security nal billing, according to Lazarevenue cycle management noneassurance for rus. Once a practice exceeds 30 theless dovetails closely with protecting patient physicians, however, the numthe success of their practices. information in ber of locations factors into the About 35% of respondents— compliance with the decision, along with the billing mainly acute-care hospitals and Health Insurance staff’s expertise. clinics/physician practices—to Portability and “Vendors bring advantages,” a 2014 survey by the American Accountability Act Lazarus said. “They have the Health Information Management (HIPAA). ability to field operations that leAssociation/eHealth Initiative verage technology and dedication believe ICD-10 will have a negative effect on their revenue; 18% are uncer- of functions.” For example, one employee may tain of its impact; and 27% haven’t conducted answer billing inquiries from patients, while another may enter data from insurance companies. financial impact assessments. Selecting a reputable vendor is critical. A Many physicians ponder whether to seek outside expertise for revenue cycle management. company with state-of-the-art technology offers An estimated 95% of independent physicians greater assurance for protecting patient informaperceive outsourcing these services and tech- tion in compliance with the Health Insurance nology processes as the most sensible solu- Portability and Accountability Act (HIPAA). The vendor should offer a business associate tion, according to the Black Book Report 2015, a healthcare market research entity. Of those agreement—a formal arrangement in the healthpractices, 64% are contemplating a combination care industry for anyone dealing with highly of new software and outsourcing help to im- sensitive patient data. “If the vendor doesn’t prove their revenue cycle management systems. insist on a business associate agreement, you Before making these decisions, a practice should walk away immediately,” Lazarus said. While it’s important for a billing company’s must weigh the pros and cons carefully. There are multiple aspects to consider, such as the size coders to safeguard personal health informaof the practice and the capabilities of its staff. tion, they should also feel comfortable reading “Physicians really need to approach the ques- medical terminology in patients’ charts. There E TAKE-HOME Keep the revenue cycle in mind KEEP THE FOLLOWING POINTS IN MIND WHEN EVALUATING YOUR PRACTICE’S REVENUE CYCLE AND ACCOUNTS RECEIVABLE (A/R) PROCESSES: WHERE’S PAYMENT? Some payers take longer to pay claims than the average number of days in A/R. For example, if your practice’s average number of days in A/R is 49.94, but Medicaid claims average 75 days, this should be addressed. CONSIDER ACCOUNTS IN COLLECTION Accounts sent to a collection agency are written off of current receivables, and the revenue may not be accounted for in the calculation of days in A/R. Be sure to calculate days in A/R with and without the inclusion of collection revenue. BUILD A PAYMENT PLANS ACCOUNT Payment plans that extend the time patients have to pay accounts can result in an increase in days in A/R. Consider creating a separate account that includes all patients on payment plans and determine whether your practice should or should not include this “payer” in the calculation of days in A/R. FACTOR IN OLDER CLAIMS Good overall days in A/R can also mask elevated amounts in older receivables, so it is important to use the “A/R greater than 120 days” benchmark. may be additional security concerns if a company uses coders in a different country, where HIPAA rules don’t apply, said Margo J. Williams, MHA, CMPE, a senior associate in practice management for the American College of Physicians. Employee turnover is another consideration, with a billing company missing out on some of its revenue collections as balls are dropped between employees departing and new employees coming on board. Questions to ask: “What kind of turnover does the billing company have? Are they doing your specialty, or do they know other specialties better?,” Williams said. Continues on page 72 : Revenue cycle 71 72 APRIL 15, 2015 :: Ophthalmology Times practice management REVENUE CYCLE ( Continued from page 71 ) In Williams' experience, a practice maintains greater control over internal billing. From knowing the nuances of different insurance carriers to being familiar with the region and patients’ records, “all steps of the billing process are there in your office,” she said. “Collection rates will be better. You’re on top of it, and you have more at stake.” However, Williams acknowledged that “not everybody has the ability or knowledge to do it themselves.” It is possible to outsource all or only part of revenue cycle management. Many physician practices decide to use the influence of the third party’s name in outsourcing bad debt collections. QUESTION BECOMES WHEN “The question becomes: when does the physician practice send the patient account to a third-party collection outsourcer?” asked Tom Gavinski, a member of the board of directors at ACA International, the Association of Credit and Collection Professionals and vice president of healthcare market and industry initiatives at I.C. System Inc. in St. Paul, MN, a debt collection agency. “That depends on when they want to use the outsourcer’s services.” Those services can be tailored to begin anywhere between one and 150 days after a payment is past due. For payments up to 90 days past due, services can be outsourced to collections as a self-pay account in the name of the physician practice. Accounts that are 90 or more days past due are usually sent to an outsourcer as a third-party bad debt account, said Gavinski. PE R F OR M A C O ST A N A LY S I S A cost analysis is essential to determine whether to outsource. The practice may choose to enlist the advice of an independent consultant to evaluate the pros and cons of each scenario and to assist in decision making, Gavinski said. Any in-depth analysis should include a future forecast that accounts for increases in employee wages and benefit packages. This would compare the current costs of billing internally with the costs of employing an outside vendor. In addition to staffing, the tally should quantify the current costs that would be eliminated with an outside vendor, identifying them as a percentage of total expenses and comparing that to the costs of using the vendor, according to Jeff Akers, CPA, vice president of financial management at McKesson Business Performance Services, Reading, MA. Evaluating RCM Vendors: 10 Questions to Ask WHAT IS THE COST AND WHAT DO I GET FOR THAT PRICE? The cost of revenue cycle management (RCM) services can vary significantly depending on the size and complexity of services. Some charge monthly fees while others charge a percentage of the total amount collected. Two vendors may charge similar rates, but what is included in that price can vary. It’s important for the vendor to spell out everything included in its fees, and be transparent about the services it charges extra to provide. WHAT ARE THE PERFORMANCE GUARANTEES? The potential vendor should explain how it will solve the problems the practice identified during its discovery phase and its success rate with previous clients. Some vendor proposals may include incentives for exceeding set goals, or penalties if goals are not met. WHAT TECHNOLOGY WILL THE VENDOR PROVIDE AND HOW WILL IT INTERFACE WITH EXISTING SYSTEMS? RCM companies have economies of scale that allow them to offer a practice technology it would otherwise be unable to afford or maintain. But it should be clear from the outset what technology the vendor will supply and what will be expected from the practice, and how the vendor-supplied technology will interface with existing technology. WHERE ARE THE CALL CENTER EMPLOYEES LOCATED? A growing number of RCM companies employ people abroad, a fact that they should disclose. Practices should find out what the call center hours will be, the employees’ language skills, and their knowledge of local laws and regulations. HOW LONG IS THE CONTRACT? A practice may want to outsource RCM for only a short time to get through a growth or transition period. If short-term contracts aren’t an option, the practice may lose money if it decides to terminate early. For example, current expenses may amount to 10% of the total cost, whereas outsourcing expenditures typically run in the 5% to 8% range. “While the immediate cost seems to be reduced, the real key is the 5-year impact, as the 10% likely will creep up over time due to raises, benefits and increased expenses,” Akers said. Even with sound management, operational oversight also takes away from a physician’s focus on direct patient care. Physician groups that choose an in-house solution should anticipate future costs to maintain their systems of practice management and WHAT ARE THE TERMINATION CLAUSES? Find out how the practice can get out of the contract if the vendor doesn’t hold up its end of the contract or what penalties, if any, will apply if the practice opts out of the contract early. ARE EMPLOYEES CERTIFIED AND FAMILIAR WITH INDUSTRY BEST PRACTICES? The Healthcare Financial Management Association, the American Association of Healthcare Administrative Management, and others set industry best practices vendors should know. These organizations also certify RCM professionals, ensuring that clients have knowledgeable representatives working on their behalf. WHAT SECURITY MECHANISMS ARE IN PLACE TO DEAL WITH SENSITIVE PROTECTED HEALTH INFORMATION? As a business associate to the practice, the RCM company should be able to provide potential clients with risk assessments and explain what measures they take to remain compliant with the Health Insurance Portability and Accountability Act (HIPAA). WHAT REPORTING IS PROVIDED? The most effective way for a practice to assess its vendor’s performance is through reporting. Reports should be provided regularly that include, at minimum, an analysis of accounts receivable, the percentage of accounts in receivable for 60 days, 90 days or 120 days, and a breakdown of payers and providers with accounts in each category. In addition, the reports should provide a breakdown of the who and why of denials, and the lag time between date of service and when bills are sent out. WHERE TO AND HOW OFTEN IS MONEY TRANSFERRED? Some RCM vendors first collect on behalf of their clients, then send a check once a month, or send the money to a lock box. Others post the collections in real-time via direct deposit. The way the RCM vendor handles this could affect a practice’s ability to meet its financial obligations. electronic health records. Akers estimates that in general, a practice can expect a 6% to 10% improvement in its revenues from outsourcing its billing. As changes take place in billing and coding, “the need for a vendor who has its finger on the pulse of healthcare reform is critical to ensure there are no missed opportunities,” Akers said. “The risk of compliance issues can be devastating to a practice. Having an outside vendor with extremely high compliance policies and protocols in place will help mitigate risks to your practice.” ■ APRIL 15, 2015 :: Ophthalmology Times practice management How to prevent payer denials Physician’s roadmap must include best practices to reduce and reverse unpaid claims By Debra Beaulieu-Volk ou may be thinking you’re doing everything possible to submit clean, accurate claims to payers—yet denials persist. And if it seems that every day insurers are sending back different types of denials, you’re probably right. "That’s the way it is,” said Elizabeth Woodcock, MBA, FACMPE, CPC, a healthcare consultant and author with Woodcock and Associates, Atlanta. “No matter how hard you try to make everything perfect, denials still happen. But you have to recognize that the insurance companies have an economic incentive to deny claims, so you’re never going to get it down to zero.” That’s the bad news. The good news, however, is that with a strong parallel strategy of denial prevention and follow-up, you can significantly reduce your denial rate and ensure that almost all denied claims get paid. to analyze the reasons claims are rejected in ported by Medicare rules. Those types of denithe first place only perpetuates the problem. als we like to be able to build them back into “Denials are your treasure our contracting efforts, but it’s chest for performance improveexceedingly difficult to call those ment,” Woodcock said. “This out and have them addressed Review all denials is your guide to really make a specifically in our contract.” within 72 hours and difference.” Another complicating factake action on them For example, by reviewing tor in this process is lack of within seven days. your explanations of benefits consistency in the terminology Leverage your you might learn that you’ve payers use to describe their team’s insights and been submitting procedure reasons for denial. expertise, and take codes that are inconsistent “So getting them translated, advantage of claimswith diagnosis codes, indicross-referenced, and put into scrubbing systems cating that you need to work actionable information for those that help you catch on coding. Or you may find a three sections is very difficult errors. pattern of missing or inaccuand manual,” he added. rate demographic information, This process is cumbersome indicating possible problems for large systems like Tenet and with your front-desk registration procedures. small practices alike, but is too important to overlook, Woodcock said. “Even though it’s frustrating, we’re in a battle, and this battle 3. DIVIDE AND CONQUER But to really put this information to work, you is fought every single day,” she said. “If we 1. F OL L OW U P PR OM P T LY need to organize it. For Brett Waress, MHA, give up, we’re going to give up money as well.” To maximize reimbursements, review all de- FACMPE, chief operating officer at Tenet Florida 4. SET PRIORITIES nials within 72 hours and act on them within Physician Services, Boca Raton, the first phase seven days, Woodcock said. Gone are the of that process is dividing denials into those Addressing denials is far less daunting, howdays billing staff can simply reprint a denied the practice understands and those it does not. ever, if you prioritize well. “Don’t try to fix demographics, coding, and claim and send it back to the payer with a “There are denials for reasons that are rubber stamp that says “appeal,” she added. specified by insurance companies that we so forth in a month,” said Owen Dahl, MBA, “Insurance companies would laugh at you.” can understand, such as maybe we didn’t get FACHE, principal of Owen Dahl Consulting in But by correcting claims, such as by add- the middle initial or get the patient registra- The Woodlands, Texas. “Focus on your biging requested information, and sending them tion right," Waress said. "Those are denials gest impact point first." Once the first item is resolved, move down back to payers quickly, Woodcock said that we know how to handle.” at least 80% of them eventually will get paid. Denials in this group then go through an- to the next-biggest problem. “It’s hard to chase more than one rabbit other (but not the last) round of sorting so at a time,” Waress added. Where to begin is a matter of preference. “You either pick the high-dollar, high effort or the low-dollar, low effort,” he said. Either way, prioritization is extremely helpful for a practice of any size. —Elizabeth Woodcock, MBA, FACMPE, CPC Y TAKE-HOME ‘Denials are your treasure chest for performance improvement. This is your guide to really make a difference.’ 2. OPEN YOUR TR EASUR E CHEST The key to long-term, revenue-cycle improvement, however, is learning from and correcting recurrent mistakes. Your most valuable resource in this quest is the denial report, Woodcock said. It can be tempting simply to correct denied claims and send them back, but failing they are addressed by the correct department: front office; billing office; or clinical staff, including physicians, notes Waress. “But there’s a whole other category of denials for reasons that we may not understand or appreciate," Waress explained. "It may be a denial for bundling of services in a surgical procedure that is payer-specific and not sup- 5 . R A L LY (D ON ’ T PU N I S H) YOUR TEAM Another common mistake is for a practice manager to attempt to come up with the solutions to identified problems alone, Dahl said. “Talk and brainstorm with your staff and identify what the real source of the problem is,” he said. Continues on page 74 : Denials 73 74 APRIL 15, 2015 :: Ophthalmology Times practice management DENIALS Common reasons for claim denials ( Continued from page 73 ) This approach not only eases the burden on managers, it also enhances buy-in among employees to follow through with the solutions they helped create. Keep in mind, too, that firing an employee who may be responsible for a discovered mistake may not be a productive move. “Eighty-five percent of the time an employee is involved in an error, a system causes the error, not the employee,” Dahl said. And such systems aren’t necessarily ITrelated, but may have to do with inadequate training, poor tools, or too many tasks being assigned to employees, which winds up compromising their performance. “Look at this as a teachable or fixable moment,” Dahl said. “Don’t make the mistake of perpetuating the problem by firing one person and hiring a new one.” 6. OPTIMIZE TECHNOLOGY In addition to leveraging your team’s insights and expertise, take advantage of claimsscrubbing systems that help you catch errors before you submit them. “The clearinghouse world has gotten much better and more sophisticated," Dahl said. "There are tools available that practices may not be fully aware of or taking advantage of.” Some basic versions of these tools may be bundled into general practice management software that practices already use, Dahl said, adding the caveat that practices might need to spend some time to understand the technology and how it works. “People need to look at both what’s in their practice management system (PMS) package and what’s in their claims management package from the clearinghouse, and then the compatibility of the two,” Dahl outlined. “Do I fix a claim in the scrubber or the PMS and how do I make sure that data is being recorded properly?” Furthermore, practices should determine whether their PMS allows them to build in their own edits on top of the basic pre-loaded rules. “You might say it’s kind of a pain to put in all those edits, all those rules," Woodcock added. "But remember, if I can prevent five, six, 15, or 25 errors from happening by building the rule each and every time, it’s definitely going to be worth the 30 to 45 minutes I spend researching and inputting that rule.” DUPLICATE CLAIMS PROBLEM WITH MODIFIERS A duplicate claim was submitted when a practice has not received reimbursement. The claim form is missing a modifier or modifiers, or the modifier(s) are invalid for the procedure code. TYPOS CODING MIX UP Errors or typos were made while collecting pertinent information from the patient or during the data entry process for a claim. There is a coding or data error with mismatched totals or codes that are mutually exclusive. OUTDATED CODES DEDUCTIBLE The service will not be reimbursed because the patient has not yet met their insurance plan’s deductible. The claim includes outdated current procedural terminology codes, or it lists deleted or truncated diagnosis codes. HEALTH PLAN BENEFITS EXCEEDED SERVICE NOT COVERED The patient has exceeded his or her health plan’s benefit for the provided service. A particular service is not covered under the health plan’s benefits. INSUFFICIENT INFORMATION LACK OF MEDICAL NECESSITY The claim is deficient in certain information. It may be missing a prior authorization or the effective period of time within which the service must be provided for reimbursement to occur. The health plan could deny a claim if it appears that a service was not medically necessary, or if there is a mismatch between the actual diagnosis and the service performed. SITE OF SERVICE PROBLEM OUT OF NETWORK An inconsistent site of service is marked on the claim form, such as an inpatient procedure billed in an outpatient setting. When the physician is not an in-network provider for the patient, the payer may reimburse a lesser amount if the patient has out-of-network benefits. 7. F I N D A S U PP O R T S Y S T E M Despite the influx of technology into claims processing in recent years, interpersonal relationships with payers still matter. “Payers are getting more sophisticated and doing more things electronically just like we are," Dahl said, "but there’s still no substitute for the fact that I’ve known Mary from insurance company X for all these years and she always tries her best to help me. "How you communicate with Mary could change to e-mail, instant messaging, or texting, but I still recommend you contact Mary verbally on occasion just to say, 'hi.'” Woodcock agreed, noting that such relationships may help give your practice a voice at the payer if you find that a claims-scrubbing rule built into the insurer’s system isn’t accurate. “So that relationship may recognize that they’re working for a company just like us," Woodcock said. "Sometimes humans make mistakes in what they input and we need humans to correct them.” Unfortunately, when Waress experienced just such a problem with a payer incorrectly denying claims, he was unable to reach payer employees empowered to resolve the error. “Even if they agree with and are sympathetic to your problem, people can’t always affect systemic changes in insurance algorithms,” he said. As a result, his practice ultimately had to undertake a formal dispute process involving the state medical society and department of insurance, which took 18 months to complete. Because the denials were found to violate the group’s contract as well as department of insurance rules, Waress was successful in obtaining a settlement from the payer that included penalties and interest. “The department of insurance of the state I was in, particularly their health insurance division, was instrumental in helping us get the attention of payers and getting them to change the way they denied or paid claims,” he added. For situations that require less extreme efforts, professional organizations, such as the Medical Group Management Association and state medical societies, can often help practices get in touch with other offices tackling the same challenges. “The important thing to remember is that you’re not alone,” Waress said. ■ 75 APRIL 15, 2015 :: Ophthalmology Times marketplace For Products & Services advertising information, contact: Karen Gerome BUFYUt'BYt&NBJMLHFSPNF!BEWBOTUBSDPN For Recruitment advertising information, contact: Joanna Shippoli BUFYUt'BYt&NBJMKTIJQQPMJ!BEWBOTUBSDPN PRODUCTS & SERVICES BILLING SERVICES PRACTICE SHARING PM Medical Billing & Consulting PRACTICE SHARING OPPORTUNITY Exclusive Ophthalmology Billers Expert Ophthalmology Billers Excellent Ophthalmology Billers Triple E = Everything gets Paid Concentrating on one Specialty makes the difference. We are a Nationwide Ophthalmology Billing Service. We have been in business over twenty years. Our staff consists of billers who are certified Ophthalmic Techs, Ophthalmic assistants, and fundus photographers who are dual certified ophthalmic coders and billers. This combination of clinical backgrounds in ophthalmology with the certified coding degree is the ideal combination of expertise that you need to dramatically increase your revenue. We will get you paid on every procedure every single time. No more bundling, downcoding or denials… Primary, Secondary, Tertiary and Patient Billing Relentless and meticulous follow up. t Experts in Forensic Billing. Specializing in old AR cleanup t Credentialing and Re credentialing our Specialty. We have a separate Credentialing Department who has cultivated years of contacts to expedite the process as well as getting providers on plans that are technically closed. t We can offer you our own Practice Management software at no cost to you or we can VPN into your system if that is what you prefer. t Totally Hippa compliant. We are certified Hippa and have invested in the most secure Hippa connection that Google and Cisco use. t Monthly custom reports provided. We presently work on all of the following Practice Management systems : NextGen, MD Office, Centricity, Medisoft, Office Mate, MD Intellus, Medware, Medcomp, Management Plus, ADS, Revolution EHR, EyeMd EMR, Next Tec, Open Practice Solutions, Cerner Works and more…. All of our clients were paid the PQRI and E-prescribe bonuses and we are ready for the ICD-10 change Our staff has years of Attendance at AAO and ASCRS and attends all ongoing Ophthalmology billing and Practice Management continuing education classes. We are always knowledgeable and prepared for all government and commercial changes. On staff MBA consultants Call today to schedule a free on site consultation. We will travel to you anytime to evaluate your AR and show you how we can dramatically increase your Revenue. Call toll free at 1-888-PM-BILLING (1-888-762-4554) Email: JOGP!QNCJMMFSDPNtWeb: www.pmbiller.com 24 hours: 516-830-1500 Our Prestigious National Ophthalmology Clients reference list will be provided at your request Near Pomona/LA County. MARKETPLACE ADVERTISING Looking for Ophthalmologist Call Karen Gerome to share existing space to place your Marketplace ad with optometrist. Please call (909) 621-3952 at 800-225-4569, ext. 2670 [email protected] Content Licensing for Every Marketing Strategy Marketing solutions fit for: Outdoor | Direct Mail | Print Advertising Tradeshow/POP Displays | Social Media Radio & TV 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 PM (Practice Management) Billing will keep an EYE on your Billing so you can keep an EYE on your patients. 76 APRIL 15, 2015 :: Ophthalmology Times marketplace For Products & Services advertising information, contact: Karen Gerome BUFYUt'BYt&NBJMLHFSPNF!BEWBOTUBSDPN For Recruitment advertising information, contact: Joanna Shippoli BUFYUt'BYt&NBJMKTIJQQPMJ!BEWBOTUBSDPN CAREERS FELLOWSHIP LOUISIANA OCULOPLASTIC FELLOWSHIP One year fellowship offered by Dr. Roger E. Bassin of the Bassin Center for Plastic Surgery. Learn about face lift, lazerlift, blepharoplasty, brow lift, cheek lift, laser resurfacing, fat transfer and body liposuction as well as basic oculoplastic surgery. Please submit resumes to: [email protected] ADVERTISE NOW! 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Driven by a mission to Serve, Heal, Lead, Educate and Innovate, coordinated clinical and hospital patient care is provided across the region by Ochsner’s 13 owned, managed and affiliated hospitals and more than 50 health centers. Ochsner is the only Louisiana hospital recognized by 2014-15 U.S. News & World Report as a “Best Hospital” across nine specialty categories. Ochsner employs more than 15,000 employees, over 900 physicians in over 90 medical specialties and subspecialties and conducts over 750 clinical research studies. Please visit us at www.ochsner.org. Ochsner Health System and The University of Queensland Medical School in Brisbane, Australia began a unique, joint partnership in 2009 by opening the University of Queensland School of Medicine Clinical School at Ochsner, providing U.S. medical students with an unprecedented educational experience. New Orleans is one of the most exciting and vibrant cities in America. Amenities include multiple universities, academic centers, professional sports teams, world-class dining, cultural interests, renowned live entertainment and music. Please e-mail your CV to: [email protected], Ref# ARETNO3 or call (800) 488-2240 Ochsner is an equal opportunity employer and all qualified applicants will receive consideration for employment without regard to race, color, religion, sex, national origin, sexual orientation, disability status, protected veteran status, or any other characteristic protected by law. RECRUITMENT ADVERTISING WORKS! 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Ochsner Health System is southeast Louisiana’s largest non-profit, academic, multi-specialty, healthcare delivery system. Driven by a mission to Serve, Heal, Lead, Educate and Innovate, coordinated clinical and hospital patient care is provided across the region by Ochsner’s 13 owned, managed and affiliated hospitals and more than 50 health centers. Ochsner is the only Louisiana hospital recognized by 2014-15 U.S. News & World Report as a “Best Hospital” across nine specialty categories. Ochsner employs more than 15,000 employees, over 900 physicians in over 90 medical specialties and subspecialties and conducts over 750 clinical research studies. Please visit us at www.ochsner.org. Ochsner Health System and The University of Queensland Medical School in Brisbane, Australia began a unique, joint partnership in 2009 by opening The University of Queensland School of Medicine Clinical School at Ochsner, providing U.S. medical students with an unprecedented educational experience. RECRUITMENT ADVERTISING Can Work For You! Reach highly-targeted, market-specific business professionals, industry New Orleans is one of the most exciting and vibrant cities in America. Amenities include multiple universities, academic centers, professional sports teams, world-class dining, cultural interests, renowned live entertainment and music. experts and prospects by Please e-mail your CV to: [email protected], Ref# AOCU13 or call (800) 488-2240 placing your ad here! Ochsner is an equal opportunity employer and all qualified applicants will receive consideration for employment without regard to race, color, religion, sex, national origin, sexual orientation, disability status, protected veteran status, or any other characteristic protected by law. CONNECT with qualified leads and career professionals Post a job today Joanna Shippoli ZZZPRGHUQPHGLFLQHFRPSK\VLFLDQFDUHHUV RECRUITMENT MARKETING ADVISOR (800) 225-4569, ext. 2615 [email protected] 78 APRIL 15, 2015 :: Ophthalmology Times practice management Moving EHR beyond clinical practice Vendors cater to needs of ASC with software that increases efficiency, quality of care, profits By William L. Watson and Lizbeth Alicea odern health-care facilities like ambulatory surgery centers (ASCs) are a primary source for surgical procedures by providing same-day care. Prior to the advent of ASCs, surgery was performed in hospitals and required that patients waited weeks for an appointment and spent days in the hospital. As a result, electronic health record (EHR) vendors are beginning to cater to the unique needs of ASCs with the advent of software that increases efficiency, quality of care, and profits. Tomoka Eye Associates recently incorporated an EHR that is ideally suited for an ASC environment. Some of the lessons learned are shared in this article. According to the American Society of Ophthalmic Administrators’ technician benchmarking study (http://bit.ly/1ajPHk0), EHR increases efficiency. In the operating room, surgeons are able to chart quickly, as well as capture images from surgical monitors during the procedure, integrating all components into the patient’s file. Compartmentalizing communication between staff and employees also plays a role in increasing efficiency. For example, users can access test results through an EHR chart, rather than relying on a staff member to make a physical transfer of a paper chart to the surgery center for the M an electronic chart at the same time. All data are stored in one place, which makes access easier logistically compared with paper. MITIGATE RISKS EHR for ASCs not only eliminates the need for paper charts and streamlines workflow, but it also lowers the risk of errors by standardizing processes. For example, it ensures that a patient’s record is complete and has undergone proper review by the necessary physicians prior to the patient’s discharge. EHR in an ASC also mitigates risks by reducing legal exposure and improving compliance with the Health Insurance Portability and Accountability Act. Staff can easily access any data requested during accreditation or surveys by Centers for Medicare and Medicaid Services, as well as provide documented proof for compliance issues when needed. Additionally, it is possible to incorporate a mobile computer that can travel from bedside to bedside to ensure privacy for each patient— although extreme care is still given to what information is displayed on the screen when patients are present. PAT I E N T, PH Y S IC I A N SATISFACTION In the combined practice-ASC, both physicians and staff have experienced increased satisfaction with use of an EHR. For e x a mple, physicians can access patient records from any location in real time, which eliminates the need for them to travel to the ASC to fill a prescription or to carry files home in order to manage a patient case remotely. EHR in an ASC also reduce costs associated with paper-related administrative duties, such as buying paper, printing copies, and storing and retrieving paper charts. Streamlining an EHR from a clinic to an ASC allows data to become easily available on both ends with less room for error or lost data. day, then retrieve the record and file it back with the clinic. As a result, more than one person can read Tips for ASC-EHR Implementation CHOOSE A V EN DOR that provides exceptional support and whose representatives are reliable and accessible. SELECT A N ASC-EHR TEMPL ATE that is easily customizable. TA K E T IME . There are no meaningful use requirements to meet for ASCs. ST R AT E GIC A L LY S E L E C T K E Y INDIV IDUALS for the install team. A nurse manager, business manager, and IT specialist are ideal. Keep the group small to streamline the decision-making and implementation processes. TR AIN THE PHYSICIANS FIRST as champions of the system. Ensure that physicians do not speak negatively about the system in front of staff. However, this also translates into reallocating staff responsibilities that are spent on time-consuming tasks associated with managing paper charts. Physician and staff reap the benefits of spending time on more rewarding tasks. INCORPOR ATE AN EHR INTO AN ASC Streamlining an EHR from a clinic to an ASC allows data to become easily available on both ends with less room for error or lost data. When the decision was made to implement EHR into the ASC, ManagementPlus’ eye-care-specific EHR had already been implemented into the clinic. Therefore, there was complete comfort with the software. Prior to purchasing the EHR, peers who were utilizing the software were shadowed to witness how the vendor engaged with its clients as partners. It was kept in mind that the purchase also included the people behind the company, because it is a given that software is often in a constant state of change. 79 APRIL 15, 2015 :: Ophthalmology Times practice management business managers from the ASC to customManagementPlus worked alongside as a partize every template to fit the needs of the ASC. ner to help create an ASC-EHR that now serves Clinics that have already as a model for the vendor. invested in EHR will find that Involvement at this level was transition to an ASC will benan important component for sucefit both the clinic and the ASC cessful implementation. Because Implementing alike, and will continue to foster there was no time frame manelectronic health efficiency and increase patient dated by meeting meaningful records into an and staff satisfaction. use requirements, the practice ambulatory surgery Fortunately, there is EHR softwas able to take the time needed center fosters ware designed to fit the unique to customize the software with efficiency and needs of many types of ophthalthe EHR specialist. increases patient and mic specialties and health-care In addition, weekly meetings staff satisfaction. organizations. were held with the nurse and EHR software designed specifically for ASCs can conform to the needs of an ASC without adding complexity to its protocols. ■ TAKE-HOME WILLIAM L. WATSON is chief executive officer, Tomoka Eye Associates, Ormond Beach, FL. He may be reached at 386/672-4448 or [email protected]. LIZBETH ALICEA is IT Manager, Tomoka Eye Associates, Ormond Beach, FL. She may be reached at 386/672-4244 or lizbetha@ tomokaeye.com. Advertiser Index Advertiser Abbott Medical Optics Page Advertiser Page 5 Haag Streit 45 www.amo-inc.com P: 513/658-0574 www.haag-streit-usa.com AcuityPro Vision Science Software Alcon Laboratories Inc. Perrigo Specialty Pharmaceuticals ICare USA 59 P: 866/634-9120 www.perrigo.com 37 Regeneron Pharmaceuticals www.icare-usa.com 18A-D, 25, 39, 48-50, 81-82, CV3, CV4 P: 800/862-5266 www.alcon.com Omeros Katena Products Inc. Page CV2, 3 www.omeros.com 63 P: 877/228-4890 www.AcuityPro.com Advertiser P: 973/989-1600 F: 973/989-8175 www.katena.com 33-34 41A*-42A* P: 914/345-7400 www.regeneron.com Rhein Medical Alimera Sciences CVTIP, 10A–D* www.iluvien.com Allergan Inc. Maine Society of Eye Physicians 70 P: 207/445-2260 www.maineeyemds.com 21-22, 28-31 P: 714/246-4500 or 800/433-8871 (Customer Service) F: 714/246-4971 www.allergan.com Rumex Micro Medical Devices 61 P: 866/730-0663 www.micromedinc.com Nidek Inc. 9, 15-16, 26A–D P: 800/227-1427 or 800/323-0000 (Customer Service) www.bausch.com 53 www.doheny.org 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 Advanstar, 131 W First Street, Duluth, MN 55802-2065. Subscription rates: $200 for one year in the United States & Possessions, Canada and Mexico; all other countries $263 for one year. Pricing includes air-expedited service. Single copies (prepaid only): $13 in the United States & Possessions, Canada and Mexico; $20 all other countries. Back issues, if available are $25 in the U.S. $ Possessions; $30 in Canada and Mexico; $35 in all other countries. Include $6.50 per order plus $2 per additional copy for U.S. postage and handling. 65 P: 800/223-9044 www.usa.nidek.com Oculus Inc. Doheny Eye Institute 55 www.rumex.net ThromboGenics Bausch + Lomb 7 P: 800/637-4346 www.rheinmedical.com 13 P: 732/590-2900 www.thrombogenics.com This index is provided as an additional service. The publisher does not assume any liability for errors or omissions. 57 *Indicates a demographic advertisement. P: 425/670-9977 F: 425/670-0742 www.oculususa.com If shipping outside the U.S., include an additional $10 per order plus $5 per additional copy. Periodicals postage paid at Duluth, MN 55806 and additional mailing offices. POSTMASTER: Please send address changes to OPHTHALMOLOGY TIMES, P.O. Box 6009, Duluth, MN 55806-6009. Canadian G.S.T. number: R-124213133RT001, Publications Mail Agreement Number 40612608. Return undeliverable Canadian addresses to: IMEX Global Solutions, PO Box 25542 London, ON N6C 6B2 CANADA. 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For uses beyond those listed above, please direct your written request to Permission Dept. fax 440-756-5255 or email: mcannon@ advanstar.com. 80 APRIL 15, 2015 :: Ophthalmology Times practice management Unchecked supply chain process can degrade a product's safety, efficacy Refrigeration, system of checks and balances implemented by phenylephrine manufacturer By Paul S. Koch, MD, Special to Ophthalmology Times inition of room temperature is general storage henylephrine hydrochloride solu- between 68° F and 78° F, but also allowing for tion has traditionally been used temporary excursions as low as 59° F and as as a topical agent to dilate the pu- high as 86° F.” pils. While physicians have had many choices between branded and generic solutions, many do not realize that they had likely been using a non-FDA-approved solution. The first of these phenylephrine hydrochloride ophthalmic solutions to undergo the FDA’s rigorous approval process belongs to Paragon BioTeck Inc., Portland, OR. Physicians may also be unaware that phenylephrine hydrochloride is a drug that can oxidize and degrade in ophthalmic solutions when exposed to light and higher temperatures.1-3 The article went on to explain that experts This degradation process can often be visibly suggest that storing medications over 86° F—a observed, as the solution may become discol- fairly typical summer temperature in many areas of the country—can have a significant ored turning dark yellow or brown.4 Even in light-controlled packaging, certain phys- effect on their potency. For example, when stored at temperatures ical and chemical degradation can occur, which has been reported to result in decreased potency.5-8 over 98° F, lorazepam and diazepam decrease To combat this degradation, it has been sug- in potency by 75% and 25% respectively. Ingested that minimizing light exposure and higher sulin and thyroid hormones are widely pubtemperature conditions may be important in lished as being sensitive to heat, and can lose optimizing efficacy and performance of this effectiveness in higher temperatures. Concentrated epinephrine can lose potency by 64% commonly used drug. During a busy day at the clinic, it may not when exposed to cyclical heating (repetitive be practical or efficient to return a bottle of heating and cooling). While this may be of less concern in an drops that is used on virtually every patient office setting, what about the to the refrigerator. multiple warehouses that a prodHowever, maintaining labeled uct touches prior to the clinic? storage conditions when the botPhysicians may Or, even worse, how about the tle is out of use at the end of the know how a product is back of a delivery truck in July? day may be more important than stored once it reaches previously understood. If this their offices, but there SYSTEM OF CHECKS is true for the limited amount is no way of knowing AND BALANCES of time that a drug, such as the supply chain Phenylephrine is just one examphenylephrine hydrochloride, storage conditions ple of one drug that has been is stored in an office setting, during manufacture shown to degrade and oxidize then it certainly should be a and transit. under higher temperatures. So consideration throughout the for this drug, maintaining refrigentire supply chain. erated storage conditions whenIn a recent online article (http://bit.ly/1DAWrFC) Amy Peak, director ever possible—for example, in transition and of drug information services for Butler Uni- transport and in the office—may be key. Leaving the solution unrefrigerated for an undeterversity, Indianapolis, states: “The technical defWARWICK , RI :: P mined amount of time in unmonitored climate and temperature conditions through the supply chain may be cause for physician and patient concern. Paragon BioTeck is one company that has ‘Certain physical and chemical degradation can occur, which has been reported to result in decreased potency.’ — Paul S. Koch, MD TAKE-HOME a system of checks and balances in place for proper storage procedures that are implemented through distribution. These standards of transport are upheld to ensure the stability of the phenylephrine hydrochloride, as any sort of oxidation or degradation of the product may lead to the drug becoming less stable over time. DEGR ADATION AND POTENCY If degradation occurs and the phenylephrine hydrochloride becomes less active, physicians may experience difficulty with dilation. In response, this may lead to increased chair time for physicians and their staff, and the use of more drops than the recommended dosage in order to obtain the desired result. Using any product above recommended dosage can contribute to adverse events and should be avoided. For companies with drug products that are historically stored at room temperature, this means that throughout manufacture and the supply chain, little attention may be paid to maintain optimum temperatures and storage conditions. With the significant distances products like phenylephrine often travel to reach a practice, it is possible they have sat in a truck on a hot tarmac with unregulated temperatures or have gone through a variety of environmental climate and temperature changes. Physicians may know how a product is stored once it reaches their offices, but there is no way Continues on page 82 : Supply chain DUOVISC® OVD BRIEF STATEMENT DESCRIPTION: DUOVISC®9LVFRHODVWLF6\VWHPLVGHVLJQHGWRJLYHWZR9LVFRHODVWLFPDWHULDOVZLWKGLHUHQWSK\VLFRFKHPLFDOSURSHUWLHVWKDWFDQEHXVHG GLHUHQWO\ DQGRU VHTXHQWLDOO\ WR SHUIRUP VSHFLF WDVNV GXULQJ D FDWDUDFW SURFHGXUH '829Ζ6&® 9LVFRHODVWLF 6\VWHP FRQVLVWV RI 9Ζ6&2$7® 2SKWKDOPLF 9LVFRVXUJLFDO'HYLFHDQG3529Ζ6&®2SKWKDOPLF9LVFRVXUJLFDO'HYLFH CAUTION:)HGHUDO86$ODZUHVWULFWVWKLVGHYLFHWRVDOHE\RURQWKHRUGHURIDSK\VLFLDQ DESCRIPTION:9Ζ6&2$7®6RGLXP&KRQGURLWLQ6XOIDWHȂ6RGLXP+\DOXURQDWH2SKWKDOPLF9LVFRVXUJLFDO'HYLFH INDICATIONS:9Ζ6&2$7®29'LVLQGLFDWHGIRUXVHDVDQRSKWKDOPLFVXUJLFDODLGLQDQWHULRUVHJPHQWSURFHGXUHVLQFOXGLQJFDWDUDFWH[WUDFWLRQDQGLQWUDRFXODU OHQVΖ2/LPSODQWDWLRQ9Ζ6&2$7®29'PDLQWDLQVDGHHSDQWHULRUFKDPEHUGXULQJDQWHULRUVHJPHQWVXUJHULHVHQKDQFHVYLVXDOL]DWLRQGXULQJWKHVXUJLFDO 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SRWHQWLDODOOHUJLFULVNVLQKHUHQWLQWKHXVHRIDQ\ELRORJLFDOPDWHULDOFDUHVKRXOGEHXVHGLQSDWLHQWVZLWKK\SHUVHQVLWLYLW\WRDQ\FRPSRQHQWVLQWKLVPDWHULDO &DQQXODDVVHPEO\LQVWUXFWLRQVVKRXOGEHIROORZHGWRSUHYHQWSDWLHQWLQMXU\ ADVERSE REACTIONS:3RVWRSHUDWLYHLQDPPDWRU\UHDFWLRQVVXFKDVK\SRS\RQDQGLULWLVKDYHEHHQUHSRUWHGZLWKWKHXVHRIRSKWKDOPLFYLVFRHODVWLFVDV ZHOODVLQFLGHQWVRIFRUQHDOHGHPDFRUQHDOGHFRPSHQVDWLRQDQGDWUDQVLHQWULVHLQLQWUDRFXODUSUHVVXUHΖWLVWKHUHIRUHUHFRPPHQGHGWKDW3529Ζ6&® OVD EHUHPRYHGIURPWKHDQWHULRUFKDPEHUE\WKRURXJKLUULJDWLRQDQGRUDVSLUDWLRQDWWKHHQGRIVXUJHU\WRPLQLPL]HSRVWRSHUDWLYHΖ23LQFUHDVHV'RQRWRYHUOO DQWHULRUFKDPEHU ATTENTION:3OHDVHUHIHUWRWKHGLUHFWLRQVIRUXVHIRUDFRPSOHWHOLVWLQJRILQGLFDWLRQVZDUQLQJVDQGSUHFDXWLRQV ACRYSOF® IQ TORIC INTRAOCULAR LENSES IMPORTANT PRODUCT INFORMATION CAUTION:)HGHUDO86$ODZUHVWULFWVWKLVGHYLFHWRWKHVDOHE\RURQWKHRUGHURIDSK\VLFLDQ INDICATIONS:7KH$FU\6RI®Ζ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Ζ2/VVKRXOGQRWEHLPSODQWHGLIWKHSRVWHULRUFDSVXOHLV UXSWXUHGLIWKH]RQXOHVDUHGDPDJHGRULIDSULPDU\SRVWHULRUFDSVXORWRP\LVSODQQHG5RWDWLRQFDQUHGXFHDVWLJPDWLFFRUUHFWLRQLIQHFHVVDU\OHQVUHSRVLWLRQLQJVKRXOG RFFXUDVHDUO\DVSRVVLEOHSULRUWROHQVHQFDSVXODWLRQ$OOYLVFRHODVWLFVVKRXOGEHUHPRYHGIURPERWKWKHDQWHULRUDQGSRVWHULRUVLGHVRIWKHOHQVUHVLGXDOYLVFRHODVWLFV PD\DOORZWKHOHQVWRURWDWH 2SWLFDOWKHRU\VXJJHVWVWKDWKLJKDVWLJPDWLFSDWLHQWVLH!'PD\H[SHULHQFHVSDWLDOGLVWRUWLRQV3RVVLEOHWRULFΖ2/UHODWHGIDFWRUVPD\LQFOXGHUHVLGXDOF\OLQGULFDO HUURURUD[LVPLVDOLJQPHQWV3ULRUWRVXUJHU\SK\VLFLDQVVKRXOGSURYLGHSURVSHFWLYHSDWLHQWVZLWKDFRS\RIWKH3DWLHQWΖQIRUPDWLRQ%URFKXUHDYDLODEOHIURP$OFRQIRUWKLV SURGXFWLQIRUPLQJWKHPRISRVVLEOHULVNVDQGEHQHWVDVVRFLDWHGZLWKWKH$FU\6RI®Ζ47RULF&\OLQGHU3RZHUΖ2/V 6WXGLHVKDYHVKRZQWKDWFRORUYLVLRQGLVFULPLQDWLRQLVQRWDGYHUVHO\DHFWHGLQLQGLYLGXDOVZLWKWKH$FU\6RI®1DWXUDOΖ2/DQGQRUPDOFRORUYLVLRQ7KHHHFWRQYLVLRQ RIWKH$FU\6RI®1DWXUDOΖ2/LQVXEMHFWVZLWKKHUHGLWDU\FRORUYLVLRQGHIHFWVDQGDFTXLUHGFRORUYLVLRQGHIHFWVVHFRQGDU\WRRFXODUGLVHDVHHJJODXFRPDGLDEHWLF UHWLQRSDWK\FKURQLFXYHLWLVDQGRWKHUUHWLQDORURSWLFQHUYHGLVHDVHVKDVQRWEHHQVWXGLHG'RQRWUHVWHULOL]HGRQRWVWRUHRYHUr&XVHRQO\VWHULOHLUULJDWLQJVROXWLRQV VXFKDV%66®RU%663/86®6WHULOHΖQWUDRFXODUΖUULJDWLQJ6ROXWLRQV ATTENTION:5HIHUHQFHWKH'LUHFWLRQVIRU8VHODEHOLQJIRUDFRPSOHWHOLVWLQJRILQGLFDWLRQVZDUQLQJVDQGSUHFDXWLRQV Advancing CATARACT SURGERY © 2015 Novartis 2/15 CRS15003JAD-A 82 APRIL 15, 2015 :: Ophthalmology Times practice management SUPPLY CHAIN ( Continued from page 80 ) of knowing the storage conditions during manufacture and transit. When products like phenylephrine are proven to perform with higher efficacy under refrigeration, it stands to reason that they should be maintained in cold storage from start to finish. The increased safety and efficacy of a properly stored product far outweighs the minimal, one-time inconvenience of installing a mini-fridge in the office. ■ References 1. “Sterile Drug Products: Formulation, Packaging, Manufacturing and Quality.” Michael J. Akers p. 100. 2. “Remington: The Science and Practice of Pharmacy.” Ed. David B. Troy, Paul Beringer p. 1030. 3. US 20090047343 A1 4. “Photochemical Hydroxylation of Phenylephrine to Epinephrine CAUTION: Federal (USA) law restricts this device to the sale by or on the order of a physician. INDICATIONS: The AcrySof® IQ posterior chamber intraocular lens is intended for the replacement of the human lens to achieve visual correction of aphakia in adult patients following cataract surgery. This lens is intended for placement in the capsular bag. WARNING/PRECAUTION: Careful preoperative evaluation and sound clinical judgment should be used by the surgeon to decide the risk/benefit ratio before implanting a lens in a patient with any of the conditions described in the Directions for Use labeling. Caution should be used prior to lens encapsulation to avoid lens decentrations or dislocations. (Adrenaline).” Journal of Pharmaceutical and Biomedical Analysis, Vol. 6, No. 5, pps. 511-514 1988. 5. Douša M, Gibala P, Havlícek J, et al. Drug-excipient compatibility testing-Identification and characterization of degradation products of phenylephrine in several pharmaceutical formulations against the common cold. Journal of Pharmaceutical and Biomedical Analysis. 2011;55:949-956. 6. Luduena FP, Snyder AL, Lands AM. Effect of ultra-violet irradiation of phenylephrine. J Pharm Pharmacol. 1963;15:538–543. 7. Al Taji RAAA, Stanford JB, Sugden JK. Some aspects of the photolysis of aqueous solutions of phenylephrine hydrochloride. Pharm Acta Helv. 1982;57:56–60. 8. El-Shibini HAM, Daabis NA, Motawi MM. The Stability of Phenylephrine: Part I The Rate of Degradation of the Amino Group., 19 (1969) pgs. 676–678. PAUL S. KOCH, MD E: [email protected] Dr. Koch is founder and medical director of Koch Eye Associates. Studies have shown that color vision discrimination is not adversely affected in individuals with the AcrySof® Natural IOL and normal color vision. The effect on vision of the AcrySof® Natural IOL in subjects with hereditary color vision defects and acquired color vision defects secondary to ocular disease (e.g., glaucoma, diabetic retinopathy, chronic uveitis, and other retinal or optic nerve diseases) has not been studied. Do not resterilize; do not store over 45° C; use only sterile irrigating solutions such as BSS® or BSS PLUS® Sterile Intraocular Irrigating Solutions. ATTENTION: Reference the Directions for Use labeling for a complete listing of indications, warnings and precautions. © 2013 Novartis 2/13 NIQ14041JAD From quantity to quality: Meeting new demands of value-based care WITH MEDICARE and commercial insurers increasingly tying physicians’ reimbursement to their ability to report on—and meet—outcome measurements, the question logically arises, is it working? Is the growing emphasis on quality and value having an impact on patient health, and/ or healthcare spending? The short answer is, it’s too soon to tell. Still, intriguing— if scattered—evidence is beginning to emerge that it might be. For example: > Medicare spending for 2014 was projected to be about $1,200 less per beneficiary than had been forecast in 2010, the year the Affordable Care Act was passed, according to a Kaiser Family Foundation study. The slowdown in spending is partially attributable to “reductions in provider payment updates and Medicare Advantage payments” as well as cuts resulting from the 2013 budget sequester, the authors say, while adding that “providers may be tightening their belts and looking to deliver care more efficiently in response to financial incentives included in the ACA, and it is possible that these changes are having a bigger effect than expected.” > The National Council of Quality Assurance found improvements in 46% of the 139 Healthcare Effectiveness Data and Information Set performance measures it tracked over the previous three to five years, performance declines in 8%, and mixed results or no trend in 46%. > Medicare’s evaluation of the first year of its Comprehensive Primary Care (CPC) initiative con- cluded that “CPC appears to have reduce total monthly Medicare Part A and B expenditures per beneficiary . . . by $14, or 2%. The reductions appear to be due to the favorable . . . impacts on hospitalizations and emergency department visits (total and outpatient.)” The evaluation also found a 4% reduction in unplanned 30day hospital readmissions, a decline it calls “sizable but not quite statistically significant.” > The national 30-day, all-cause hospital readmission rate average for Medicare fee-for-service beneficiaries fell from 19% in the 2007-2011 period to 18.4% in 2012, according to a 2013 study in Medicare & Medicaid Research Review. The re-admission rate fell below 18% for the first part of 2013. “I’m a contract negotiator, and from my perspective I can tell you payers wouldn’t be investing (in quality initiatives) if they hadn’t already seen the outcome and the return on investment,” said Doral Jacobsen, MBA, FACMPE, senior manager with DHG healthcare. “Pieces of this are working, though it varies by market and practice.” Nitin Damle, MD, FACP, a member of the American College of Physicians Board of Regents, is more cautious. “We feel a more value-based approach to practicing medicine is important, so moving away from pure fee-for-service to a more valuebased reimbursement system is the direction we want to move in. We’re not sure yet if we are moving the needle in terms of whether patients overall are getting a higher quality of care,” Dr. Damle said. ■ Visual Performance. AcrySof ® IQ – The monofocal IOL proven to deliver excellent visual performance. Give your patients more time to react with the performance of AcrySof ® IQ IOL. CONFIDENCE Simulated image For important product information, please see adjacent page. © 2014 Novartis 7/14 NIQ14041JAD YOUR SPECIALTY. ALCON TECHNOLOGIES. The Cataract Refractive Suite by Alcon. AcrySof IQ ® IOL FAMILY Visit MyAlcon.com to see how you can take your cataract refractive outcomes a step further. Advancing CATARACT SURGERY See adjacent page for important product information. © 2015 Novartis 2/15 CRS15003JAD-A See product instructions for use for indications, warnings, precautions and adverse events for all referenced devices. Caution: Federal law restricts all referenced devices to sale by or on the order of a physician.