September 1, 2013 VOL. 38, NO. 17

CLINICAL NEWS & ANALYSIS

SPECIAL REPORT AdVANceS iN MyOPic LaSiK wFg ABLATioNS gLAucomA +POINT/COUNTERPOINT ‘IDEaL’ DME THEraPY

ophthalmologyTimes.com FolloW uS oNlINE: editorial SLT as standard for THe eLeMenTS OF SUcceSS By Peter J. McDonnell, MD The country of Brazil has changed dra- f rst-line IOP lowering matically in the past two decades. After emerging from a military government, Large retrospective successive democratically elected gov- ernments have overseen dramatic eco- analysis supports nomic growth—Brazil is 5th or 6th in terms of gross domestic product—with approach for an unemployment rate lower than the United States, plus the emergence of reducing pressure an extremely large middle class. With this success comes greater demand with durable benef t for health-care services. My friend, Mauro, is an ophthalmolo- By Cheryl Guttman Krader; gist in the largest city (by population) Reviewed by Lawrence F. Jindra, MD in the Western Hemisphere. ( See story on page 4 : Editorial ) nEW YorK :: the success oF selectiVe laseR cataract (SLT) as a primary therapy for glau- coma is supported by a review of a large series of 3 STraTeGieS with long-term follow-up. The analysis included data from 1,983 eyes identi- FOr TraUMaTic fied from a consecutive series of 4,048 eyes treated with SLT over a period of 10 years. Suggested prac- caTaracT tice guidelines were used from the American Acad- DUrHaM, nc :: mAnAging trAu- emy of Ophthalmology, the Glaucoma Laser Trial, mAtic cAtArActs in children requires the Ocular Hypertension Treatment Study (OHTS), attention to three issues when implant- and the Early Management of Glaucoma Trial. ing an IOL: the timing of the implanta- All patients had a minimum follow-up of 2 months. tion, the lens type, and the IOL calcu- Average follow-up for the 1,983 eyes was 917 days. lations, said Edward G. Buckley MD. Mean IOP was 18.1 mm Hg prior to SLT, and it However, there are several controversies decreased to 12.8 mm Hg (–29%) at last follow-up. Applications for SLT therapy Selective laser trabeculoplasty (SLT) is regarding IOL implantation in children. ( Continues on page 21 : SLT) ( See story on page 30 : Traumatic ) a highly effective approach for first-line glaucoma therapy. It is also effective as adjunct therapy with drugs, and as alternative therapy when drugs or surgery fail. Most importantly, SLT enables ophthalmologists to manage patients’ glaucoma treatment without the compliance issues and side effects associated with drug therapy. (Figure courtesy of Ellex)

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magentablackcyanyellow ES312045_OT090113_CV2_FP.pgs 08.29.2013 23:37 ADV :: September 1, 2013 ophthalmology times contents 3

28

8 16

22 surgical tEchniquE

Neuro-Ophthalmology Cataract 24 tracking visual loss 30 3 strategies for Special Report in multiPle sclerosis traumatic cataract Glaucoma Time-domain OCT used to determine Timing, IOL type, and lens calculations if thinning of RNFL continued are important for pediatrics 8 a non-invasive look at Retina Refractive trabecular meshWork How novel OCT platform detects motion, 28 Point: laser treatment 32 hoW Wfg ablations may advance glaucoma research necessary for dme comPare 11 controlling circadian Subthreshold micropulse laser preferred No clear patient preference for wavefront- ioP fluctuation over conventional laser guided excimer lasers for myopic LASIK Neurons may offer novel glaucoma 29 counterPoint: factors therapeutic target, animal study shows Practice Management limit subthreshold 19 When fixed-combination laser 37 taking one for the team is viable oPtion Why laser treatment currently not an When putting others before self Brinzolamide-brimonidine may beneft important therapeutic modality for the good of the group can have patients who have contraindications meaningful outcomes to beta-blocker

In Every Issue 4 Editorial 6 ophthalmic nEws 34 markEtplacE

magentablackcyanyellow ES316820_OT090113_003.pgs 09.06.2013 01:43 ADV 4 editorial SEPTEMBER 1, 2013 :: Ophthalmology Times

SEPTEMBER 1, 2013 ◾ VOL. 38, NO. 17

CONTENT Chief Medical Editor Peter J. McDonnell, MD Group Content Director Mark L. Dlugoss [email protected] 440/891-2703 Content Channel Director Sheryl Stevenson [email protected] 440/891-2625 Content Specialist Rose Schneider [email protected] 440/891-2707 The elements of success Digital & Interactive Content Manager Brandon Glenn Group Art Director Robert McGarr Art Director Nicole Davis-Slocum Anterior Segment Techniques Ernest W. Kornmehl, MD Cataract Corner Richard S. Hoffman, MD and Mark Packer, MD Technology may be important, but employees are the real key coding.doc L. Neal Freeman, MD, MBA Money Matters John J. Grande, Traudy F. Grande, and John S. Grande, CFPs® hospital. He has a formal orientation program Neuro-Ophthalmology Andrew G. Lee, MD By Peter J. McDonnell, MD to train employees as they join, and continuing Ophthalmic Heritage Norman B. Medow, MD Panretinal View Allen C. Ho, MD education for everyone. Every employee is to Plastics Pearls Richard Anderson, MD director of the Wilmer Institute, Tech Talk H. Jay Wisnicki, MD have a career plan within the organization. Uveitis Update Emmett T. Cunningham Jr., MD, PhD, MPH Johns Hopkins University School of What’s New at the AAO John Gallagher Medicine, Baltimore, and chief medical The educational programs are intended not simply to enhance the skill level of employees, PUBLISHING/ADVERTISING editor of Ophthalmology Times. Executive Vice President Georgiann DeCenzo but also to help them feel that they are engag- [email protected] 440/891-2778 VP, Group Publisher Ken Sylvia He can be reached at 727 Maumenee Building ing in personal development. [email protected] 732/346-3017 Group Publisher Leonardo Avila 600 N. Wolfe St. Baltimore, MD 21287-9278 “Our goal is not to get them to perform a lit- [email protected] 302/239-5665 Associate Publisher Erin Schlussel Phone: 443/287-1511 Fax: 443/287-1514 tle better, but to encourage critical thinking [email protected] 215/886-3804 National Account Manager Rebecca A. Hussain E-mail: [email protected] and problem solving,” he said. [email protected] 415/932-6332 Account Manager, Classif ed/ Educational programs must have excellent Display Advertising Darlene Balzano [email protected] 440/891-2779 “I am not led. I lead.” trainers, mix employees from different areas of Account Manager, Recruitment Advertising Jacqueline Moran [email protected] 440/891-2762 —Motto of the city of São Paulo, Brazil the hospital, be less than 2 hours in length, and Business Director, eMedia Don Berman be formally assessed and improved with time. [email protected] 212/951-6745 Director, Sales Data Gail Kaye THE COUNTRY OF BRAZIL has Trainers are required to make sure their ses- Sales Support Hannah Curis Reprints 877-652-5295 ext. 121 / [email protected] changed dramatically in the past two decades. sions are informative, interesting, and partici- Outside US, UK, direct dial: 281-419-5725. Ext. 121 List Account Executive Renée Schuster After emerging from a military government, patory. Teamwork is emphasized. [email protected] 440/891-2613 Permissions/International Licensing Maureen Cannon successive democratically elected governments Mauro regularly measures employee satisfac- [email protected] 440/891-2742 have overseen dramatic economic growth—Bra- tion to determine the effectiveness of various PRODUCTION zil is 5th or 6th in terms of gross domestic prod- employee development and retention initiatives. Senior Production Manager Karen Lenzen uct—with an unemployment rate lower than In his research of the literature, he finds that AUDIENCE DEVELOPMENT Corporate Director Joy Puzzo the United States, plus the emergence of an ex- an overall satisfaction score of 45% is consid- Director Christine Shappell Manager Wendy Bong tremely large middle class. With this success ered quite high, and his hospital has exceeded comes greater demand for health-care services. this with a score of 65%.

My friend, Mauro, is an ophthalmologist in the Also, he has found that employee satisfaction Chief Executive Off cer: Joe Loggia largest city (by population) in the Western Hemi- scores are correlated with age. Employees aged Chief Executive Off cer Fashion Group, Executive Vice-President: Tom Florio sphere. In 2010, he opened the first large eye hos- fewer than 30 years consistently report lower Executive Vice-President, Chief Administrative Off cer & Chief Financial Off cer: Tom Ehardt pital in this city of 16 million-plus people. By all satisfaction scores than do older workers. Executive Vice-President: Georgiann DeCenzo measures, this hospital has been a great success. In the largest country of South America, as Executive Vice-President: Chris DeMoulin Executive Vice-President: Ron Wall From 2010 to 2012, surgeries increased by in the largest of North America, there is the be- Executive Vice-President, Business Systems: Rebecca Evangelou 68%, emergency referrals by 600%, routine lief that younger people—and younger physi- Sr Vice-President: Tracy Harris Vice-President, Media Operations: Francis Heid exams by 376%, and ophthalmologists using cians—have a different approach to work and Vice-President, Legal: Michael Bernstein the hospital grew from 13 in 2010 to 198 in work-life balance. People in Mauro’s position Vice-President, Electronic Information Technology: J. Vaughn

2012. Any eye hospital in the United States must recognize and respond to that reality. Advanstar Communications Inc. provides certain customer contact data (such as customers’ names, addresses, phone numbers, and e-mail addresses) to third parties would be delighted with such numbers. who wish to promote relevant products, services, and other opportunities that may be of interest to you. If you do not want Advanstar Communications Inc. to make your Among Mauro’s elements of success: LESSONS TO LEARN 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 > Assembly-line efficiency What can we ophthalmologists in the wealthiest representative will assist you in removing your name from Advanstar’s lists. Outside the U.S., please phone 218-740-6477. > Strict quality norms country in the Western Hemisphere learn from Ophthalmology Times does not verify any claims or other information appearing in any > Brand recognition the success of ophthalmic institutions in other 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. > Standardization countries with different cultures, histories, and Ophthalmology Times cannot be held responsible for the safekeeping or return of > Consistency degrees of wealth? A great deal, I believe. unsolicited articles, manuscripts, photographs, illustrations or other materials. Ophthalmology Times is a member of the Association of Independent Clinical > Ruthless cost control As downward pressure on health-care reim- Publications Inc. > Library Access Libraries offer online access to current and back issues of Ophthalmology Economies of scale that accompany high volume bursement continues in the United States, the Times through the EBSCO host databases. “What is the key element that explains your institutions that survive and thrive will be the To subscribe, call toll-free 888-527-7008. Outside the U.S. call 218-740-6477. success?” I asked my friend. ones that adopt many of Mauro’s strategies. ■ “Having the best technology is important,” he said, “but the real key is having the best people.”

INVESTING IN EMPLOYEES PRINTED IN Mauro has devoted a lot of attention to attract- U.S.A. ing and retaining the best employees for his

magentablackcyanyellow ES312518_OT090113_004.pgs 08.30.2013 02:13 ADV September 1, 2013 :: Ophthalmology Times editorial advisory board 5

Official publication sponsor of Editorial advisory Board Ophthalmology Times Mission Statement Chief Medical Editor Anne L. Coleman, MD Joan Miller, MD Ophthalmology Times is a physician-driven publication that disseminates news and information of Peter J. McDonnell, MD Jules Stein Eye Institute, UCLA Massachusetts Eye & Ear Infirmary Los Angeles, CA Harvard University a clinical, socioeconomic, and political nature in a timely and accurate manner for members of the Wilmer Eye Institute Boston, MA Johns Hopkins University Ernest W. Kornmehl, MD ophthalmic community. Baltimore, MD Harvard & Tufts Universities Randall Olson, MD Boston, MA University of Utah In partnership with our readers, we will achieve mutual success by: Salt Lake City, UT ◾ Being a forum for ophthalmologists to communicate their clinical knowledge, insights, and discoveries. Associate Medical Editors Robert K. Maloney, MD Dimitri Azar, MD Los Angeles, CA Robert Osher, MD ◾ Providing management information that allows ophthalmologists to improve and expand their practices. University of Illinois, Chicago University of Cincinnati Chicago, IL Cincinnati, OH ◾ Addressing political and socioeconomic issues that may either assist or hinder the ophthalmic community, and reporting those issues and their potential outcomes to our readers.

Anterior Segment/Cataract Robert Ritch, MD Peter S. Hersh, MD /External Disease New York Eye & Ear Infirmary University of Medicine & Dentistry of New Jersey New York, NY Newark, NJ Ashley Behrens, MD Joel Schuman, MD Jonathan H. Talamo, MD Wilmer Eye Institute, Johns Hopkins University University of Pittsburgh Medical Center Harvard University Baltimore, MD Pittsburgh, PA Boston, MA Rubens Belfort Jr., MD Kuldev Singh, MD Kazuo Tsubota, MD Federal University of São Paulo Stanford University Keio University School of Medicine São Paulo, Brazil Stanford, CA Tokyo, Japan Elizabeth A. Davis, MD Robert N. Weinreb, MD University of Minnesota, Retina/Vitreous Hamilton Glaucoma Center Minneapolis, MN University of California, San Diego Stanley Chang, MD Uday Devgan, MD Columbia University Jules Stein Eye Institute,UCLA Neuro-Ophthalmology New York, NY Los Angeles, CA Andrew G. Lee, MD David Chow, MD Richard S. Hoffman, MD Methodist Hospital, Texas Medical Center University of Toronto Oregon Health & Science University Houston, TX Toronto, Canada Portland, OR Pravin U. Dugel, MD Samuel Masket, MD / Phoenix, AZ Jules Stein Eye Institute,UCLA Reconstructive Surgery Sharon Fekrat, MD Los Angeles, CA Rhein Fire & Ice Mask Robert Goldberg, MD Duke University Aids In Reducing Dry Eye Symptoms Bartly J. Mondino, MD Jules Stein Eye Institute, UCLA Durham, NC Jules Stein Eye Institute,UCLA Los Angeles, CA Julia Haller, MD Los Angeles, CA John T. LiVecchi, MD Wills Eye Institute, Thomas Jefferson University Mark Packer, MD St. Luke’s Cataract & Laser Institute Philadelphia, PA Oregon Health & Science University Tarpon Springs, FL Tarek S. Hassan, MD Portland, OR Shannath L. Merbs, MD Oakland University Michael Raizman, MD Wilmer Eye Institute, Johns Hopkins University Rochester, MI Massachusetts Eye & Ear, Harvard University Baltimore, MD Michael Ip, MD Boston, MA University of Wisconsin Michael Snyder, MD Pediatric Ophthalmology Madison, WI Cincinnati Eye Institute Carmen A. Puliafito, MD Cincinnati, OH Norman B. Medow, MD Albert Einstein College of Medicine Keck School of Medicine, USC Walter J. Stark, MD Bronx, NY Los Angeles, CA Wilmer Eye Institute, Johns Hopkins University Jennifer Simpson, MD Carl D. Regillo, MD Baltimore, MD University of California, Irvine Wills Eye Institute, Thomas Jefferson University Farrell “Toby” Tyson, MD Irvine, CA Philadelphia, PA Cape Coral, FL H. Jay Wisnicki, MD Lawrence J. Singerman, MD Glaucoma New York Eye & Ear Infirmary, Beth Israel Medical Case Western Reserve University Center, Albert Einstein College of Medicine Cleveland, OH Robert D. Fechtner, MD New York, NY Uveitis University of Medicine & Dentistry of New Jersey Practice Management Newark, NJ Emmett T. Cunningham Jr., MD, PhD Neeru Gupta, MD Joseph C. Noreika, MD Stanford University University of Toronto Medina, OH Stanford, CA Toronto, Canada Frank Weinstock, MD Malik Kahook, MD Boca Raton, FL Chief Medical Editors- University of Colorado,Denver Emeritus For Heat Therapy! Denver, CO Refractive Surgery Jack M. Dodick, MD Richard K. Parrish II, MD William Culbertson, MD New York University School of Medicine For Cold Therapy! Bascom Palmer Eye Institute, University of Miami Bascom Palmer Eye Institute, University of Miami New York, NY (1976-1996) Miami, FL Miami, FL David R. Guyer, MD Can Be Used Multiple Times! Harry A. Quigley, MD Kenneth A. Greenberg, MD New York, NY (1996-2004) Wilmer Eye Institute, Johns Hopkins University Danbury Hospital Baltimore, MD Danbury, CT New York University New York, NY Ophthalmology Times Industry Council John Bee Marc Gleeson Daina Schmidt VIDEO Rhein Medical Inc. Allergan Inc. Bausch + Lomb Surgical President and CEO Vice President, U.S. Eye Care Pharmaceuticals Global Executive Director of Product Strategy Glaucoma and External Disease Marketing   ‹0UJS\KLZ*SV[O:SLL]L William Burnham, OD Kelly Smoyer  -VY(KKP[PVUHS3PK7YV[LJ[PVU Carl Zeiss Meditec Inc. Mark Newkirk Essilor of America Director of Market Development, Americas Reichert Technologies Product Director  ‹(]HPSHISL

How to Contact Ophthalmology Times Editorial Subscription Services Advertising Production 3360 Scherer Drive, Suite B, St. Petersburg, FL 33716 ‹;LS! ‹-H_!  24950 Country Club Blvd., Toll-Free: 888/527-7008 or 485 Route 1 South 131 W. First St. ,THPS!0UMV'9OLPU4LKPJHSJVT Suite 200 218/740-6477 Building F, Suite 210, Duluth, MN 55802-2065 North Olmsted, OH 44070-5351 FAX: 218/740-6417 Iselin, NJ 08830-3009 800/346-0085 >LIZP[L!^^^9OLPU4LKPJHSJVT 440/243-8100 732/596-0276 FAX: 218/740-7223, Woman Wearing Dry Eye Heat Mask FAX: 440/756-5227 FAX: 732/596-0003 218/740-6576 1301 Rev.D ACBD

magentablackcyanyellow ES312519_OT090113_005.pgs 08.30.2013 02:13 ADV 6 ophthalmic news SEPTEMBER 1, 2013 :: Ophthalmology Times

( In Brief ) HEADLINES YOU

In memoriam Washington University is planning a memorial MIGHT HAVE MISSED service for Dr. Becker, who donated his body to the university’s school of medicine. GLAUCOMA RESEARCHER AS SEEN IN Ophthalmology Times’ weekly DR. BERNARD BECKER DIES eReport. Sign up at http://www.modernmedicine. Af ibercept indication com/OphthalmologyTimes/enewssignup ST. LOUIS :: BERNARD BECKER, MD, chairman of the ophthalmology department at the Wash- REGENERON INJECTION GAINS CMS CLEARS RETINAL ington University School of Medicine in St. Louis EUROPEAN APPROVAL for 35 years, has died. PROSTHESIS SYSTEM Dr. Becker, 93, passed away Aug. 28 at his TARRYTOWN, NY :: REGENERON PHARMACEUTI- SECOND SIGHT MEDICAL PRODUCTS’ retinal home in St. Louis after a battle CALS’ new treatment for visual impairment due prosthesis system has been approved by the with lung cancer. to macular edema secondary to central retinal Centers for Medicare and Medicaid Services Dr. Becker was known for dis- vein occlusion (CRVO) has been approved by the for both inpatient and outpatient settings of covering one of the first treatments European Commission. care payments beginning Oct. 1. for glaucoma—a drug called acet- Aflibercept (Eylea) was approved in the United http://bit.ly/14gaM8H azolamide used to decrease pres- States for the treatment of neovascular (wet) age- sure in the brain. He determined related macular degeneration (AMD) in 2011, and Dr. Becker the drug could also be used to for macular edema following CRVO in 2012. INSITE VISION EARNS decrease pressure in the eyes. “We are pleased with the approval of (afliber- PATENT ISSUANCE From 1953 to 1988, Dr. Becker helped Wash- cept) in the European Union in a second indication,” INSITE VISION INC.’S DRUG DELIVERY SYS- ington University build its Department of Ophthal- said George D. Yancopoulos, MD, PhD, chief scien- TEM has received a patent from the U.S. Patent mology and Visual Arts. He was also one of the tific officer of Regeneron and president of Regen- and Trademark Office. The patent will provide founders of the Association for Research in Vision eron Laboratories. “Our phase III studies showed utility-composition of matter protection until and Ophthalmology, and helped establish the Na- that (aflibercept) improved visual outcomes signifi- 2029 for InSite Vision’s DuraSite 2 for both its tional Eye Institute. cantly. . . . This additional approval of (aflibercept) delivery system and drugs. In 1995, Washington University renamed its is great news for patients in Europe.” http://bit.ly/1anYtLa medical library in his honor. Aflibercept has also been approved in Europe, Dr. Becker grew up in Brooklyn, NY, and gradu- Japan, Australia, and in several other countries ated from Princeton University and Harvard Medi- for use in wet AMD and in selected countries in VMA TREATMENT cal School. He was also an army psychiatrist dur- South American for macular edema following CRVO. ing World War II. OK’D IN CANADA HEALTH CANADA HAS CLEARED Thrombo- Following the war, Dr. Becker trained in ophthal- Genics NV’s treatment for symptomatic vitreo- mology at Johns Hopkins University. CLARIFICATION macular adhesion. Canada is now the first mar- Dr. Becker has received many awards, including The f rst installment of the new ket where ocriplasmin (Jetrea) is approved out- the American Academy of Ophthalmology’s high- “Gloves Off with Gulani” series will begin in the Oct. 1 issue of Ophthalmology Times. Missed the side the United States and Europe. est honor. He has also co-written the first two edi- series introduction? Go to http://bit.ly/15memRo. http://bit.ly/12lU5r8 tions of “Diagnosis and Therapy of the Glaucomas.”

On Twitter Digital App Video Recent hashtags Ophthalmology Times Introducing the See how an has used on twitter.com/OphthTimes Ophthalmology Times iPhone can be used in place of app for iPad and #ophthalmology #eyehealth a traditional slit #eyecare #cataract iPhone. Download lamp camera. it for free today at Go to http://bit. #astigmatism #dryeye OphthalmologyTimes. ly/15mzBCL #retina #dispensing com/OTapp. #AMD #optical

#myopia #AMD Academy of Ophthalmology American Becker courtesy of the Photo of Dr.

magentablackcyanyellow ES316902_OT090113_006.pgs 09.06.2013 02:53 ADV THE 1960s CALLED. THEY WANT THEIR FILTRATION SURGERY BACK.

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CAUTION: Federal law restricts this device to sale by or on the order of a physician. INDICATION: The EX-PRESS® Glaucoma Filtration Device is intended to reduce intraocular pressure in glaucoma patients where medical and conventional surgical treatments have failed. GUIDANCE REGARDING THE SELECTION OF THE APPROPRIATE VERSION: Prior clinical studies were not designed to compare between the various versions of the EX-PRESS® Glaucoma Filtration Device. The selection of the appropriate version is according to the doctor’s discretion. CONTRAINDICATIONS: The use of this device is contraindicated if one or more of the following conditions exist: • Presence of ocular disease such as uveitis, ocular infection, severe dry eye, severe blepharitis. • Pre-existing ocular or systemic pathology that, in the opinion of the surgeon, is likely to cause postoperative complications following implantation of the device. • Patients diagnosed with angle closure glaucoma. WARNINGS/PRECAUTIONS: • The surgeon should be familiar with the instructions for use. • The integrity of the package should be examined prior to use and the device should not be used if the package is damaged and sterility is compromised. • This device is for single use only. • MRI of the head is permitted, however not recommended, in the fi rst two weeks post implantation. ATTENTION: Reference the Directions for Use labeling for a complete listing of indications, warnings, precautions, complications and adverse events.

magentablackcyanyellow ES312056_OT090113_007_FP.pgs 08.29.2013 23:37 ADV 8

Special Report ) Glaucoma AdvANces coNtiNue to progress for the treAtmeNt ANd mANAgemeNt of glAucomA

(Figure 1) Aqueous outfow from Schlemm’s canal (SC) is pulsatile, being dependent tm movement necessary to account for aqueous outfow? on trabecular meshwork (TM) motion with optical coherence tomography measurements ~0.03 µl Volume indicating the TM motion is adequate to 2 μl/min ÷ 60 bpm = 0.03 μl/sec each Heartbeat account for all of aqueous outfow. (A-P is anterior-posterior SC length. (Figure courtesy of Murray Johnstone, MD)

~350 µm A-P 38 mm Circumference sue movement correlated to a simulated car- diac pulse with amplitude trabecular motion sufficient to account for aqueous outflow.

~ SC 38 mm ExamininG thE human study Circumference A second study using PhS-OCT was then con- ~2.7 µm TM Movement ducted in 10 human adults to investigate pulse- SC A-P Length each Heartbeat induced trabecular meshwork motion, said Dr. ~350 μm Johnstone, clinical professor of ophthalmology, University of Washington. As in the animal study, PhS-OCT was highly sensi- tive for detecting trabecular meshwork motion. Analyses of the trabecu- lar meshwork tissue motion wave, in relation to the digi- tal pulsimetry wave, showed Dr. Johnstone A NoN-iNvAsive look a high correlation between trabecular meshwork wave minima and digital pulse peaks. The research also showed PhS- At trAbeculAr OCT could be used to measure velocity of the trabecular meshwork motion and the strain rate. meshwork “This technology opens a new window into understanding abnormalities of trabecular mesh- work biomechanics leading to glaucoma,” Dr. How novel OCT platform detects and measures motion, Johnstone said. “It will eventually revolution- may advance glaucoma research and patient care ize our approaches to glaucoma management.”

By Cheryl Guttman Krader; Reviewed by Murray Johnstone, MD EvaluatinG nEEd for traBECular mEshworK Seattle :: Interest in developing technology for evaluat- hase-sensitive optical coherence tomog- ing trabecular meshwork motion derives from revised concepts about aqueous outflow and raphy (PhS-OCT) for in vivo evalua- resistance. take-home tion is a promising tool for advancing Whereas initial work by Morton Grant, MD, P posited that the trabecular meshwork acted as An investigational glaucoma research and patient care, a rigid, restrictive filter creating resistance, non-invasive imaging according to findings from a human study presented additional research demonstrated that the tool—phase-sensitive tissue was highly compliant. This indicated optical coherence by Murray Johnstone, MD. that movement of the trabecular meshwork tomography—can be The investigational device—developed by Ruikang Wang, PhD, becomes appositional with the external wall used to detect and professor of bioengineering, University of Washington, Seattle— of Schlemm’s canal and represented the most measure movement has resolution at the nanometer scale and moves OCT technology, important source of resistance. of the trabecular which is limited to structural imaging, to a new realm involving Findings from histological studies provided meshwork in vivo. characterization of motion and function. support for this concept, but direct evidence of PhS-OCT was highly sensitive for detecting trabecular mesh- trabecular meshwork motion in vivo was lack- work motion, according to results of an initial laboratory study ing until the development of PhS-OCT. involving enucleated primate eyes. The study also showed the tis- Continues on page 15 : Non-invasive

magentablackcyanyellow ES316326_OT090113_008.pgs 09.05.2013 01:59 ADV magentablackcyanyellow ES315118_OT090113_009_FP.pgs 08.31.2013 04:21 ADV ® USE IN SPECIFIC POPULATIONS LUMIGAN 0.01% AND 0.03% Pregnancy: Pregnancy Category C Teratogenic effects: In embryo/fetal developmental studies in pregnant mice and rats, abortion was observed at oral doses of bimatoprost which achieved at least 33 (bimatoprost ophthalmic solution) or 97 times, respectively, the maximum intended human exposure based on blood Brief Summary—Please see the LUMIGAN® 0.01% and 0.03% package AUC levels. insert for full Prescribing Information. At doses at least 41 times the maximum intended human exposure based on blood INDICATIONS AND USAGE AUC levels, the gestation length was reduced in the dams, the incidence of dead LUMIGAN® 0.01% and 0.03% (bimatoprost ophthalmic solution) is indicated for the fetuses, late resorptions, peri- and postnatal pup mortality was increased, and pup reduction of elevated intraocular pressure in patients with open angle glaucoma or body weights were reduced. ocular hypertension. There are no adequate and well-controlled studies of LUMIGAN® 0.01% and 0.03% (bimatoprost ophthalmic solution) administration in pregnant women. Because CONTRAINDICATIONS animal reproductive studies are not always predictive of human response LUMIGAN® None should be administered during pregnancy only if the potential benefit justifies the WARNINGS AND PRECAUTIONS potential risk to the fetus. Pigmentation: Bimatoprost ophthalmic solution has been reported to cause changes Nursing Mothers: It is not known whether LUMIGAN® 0.01% and 0.03% is excreted to pigmented tissues. The most frequently reported changes have been increased in human milk, although in animal studies, bimatoprost has been shown to be pigmentation of the iris, periorbital tissue () and eyelashes. Pigmentation is excreted in breast milk. Because many drugs are excreted in human milk, caution expected to increase as long as bimatoprost is administered. The pigmentation should be exercised when LUMIGAN® is administered to a nursing woman. change is due to increased melanin content in the melanocytes rather than to Pediatric Use: Use in pediatric patients below the age of 16 years is not an increase in the number of melanocytes. After discontinuation of bimatoprost, recommended because of potential safety concerns related to increased pigmen- pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tation following long-term chronic use. tissue and eyelash changes have been reported to be reversible in some patients. Geriatric Use: No overall clinical differences in safety or effectiveness have been Patients who receive treatment should be informed of the possibility of increased observed between elderly and other adult patients. pigmentation. The long term effects of increased pigmentation are not known. Hepatic Impairment: In patients with a history of liver disease or abnormal ALT, Iris color change may not be noticeable for several months to years. Typically, the AST and/or bilirubin at baseline, bimatoprost 0.03% had no adverse effect on liver brown pigmentation around the pupil spreads concentrically towards the periphery function over 48 months. of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with OVERDOSAGE ® LUMIGAN® 0.01% and 0.03% (bimatoprost ophthalmic solution) can be continued in No information is available on overdosage in humans. If overdose with LUMIGAN patients who develop noticeably increased iris pigmentation, these patients should 0.01% and 0.03% (bimatoprost ophthalmic solution) occurs, treatment should be examined regularly. be symptomatic. Eyelash Changes: LUMIGAN® 0.01% and 0.03% may gradually change eyelashes In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not and vellus hair in the treated eye. These changes include increased length, thickness, produce any toxicity. This dose expressed as mg/m2 is at least 70 times higher ® and number of lashes. Eyelash changes are usually reversible upon discontinuation than the accidental dose of one bottle of LUMIGAN 0.03% for a 10 kg child. of treatment. NONCLINICAL TOXICOLOGY Intraocular Inflammation: LUMIGAN® 0.01% and 0.03% should be used with Carcinogenesis, Mutagenesis, Impairment of Fertility: Bimatoprost was not caution in patients with active intraocular inflammation (e.g., uveitis) because the carcinogenic in either mice or rats when administered by oral gavage at doses inflammation may be exacerbated. of up to 2 mg/kg/day and 1 mg/kg/day respectively (at least 192 and 291 times Macular Edema: Macular edema, including cystoid macular edema, has been the recommended human exposure based on blood AUC levels respectively) for reported during treatment with bimatoprost ophthalmic solution. LUMIGAN® 0.01% 104 weeks. and 0.03% should be used with caution in aphakic patients, in pseudophakic Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse patients with a torn posterior lens capsule, or in patients with known risk factors for lymphoma test, or in the in vivo mouse micronucleus tests. macular edema. Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day Angle-closure, Inflammatory, or Neovascular Glaucoma: LUMIGAN® 0.01% and (at least 103 times the recommended human exposure based on blood AUC levels). 0.03% has not been evaluated for the treatment of angle-closure, inflammatory or PATIENT COUNSELING INFORMATION neovascular glaucoma. Potential for Pigmentation: Patients should be advised about the potential for Bacterial Keratitis: There have been reports of bacterial keratitis associated with increased brown pigmentation of the iris, which may be permanent. Patients the use of multiple-dose containers of topical ophthalmic products. These containers should also be informed about the possibility of eyelid skin darkening, which may had been inadvertently contaminated by patients who, in most cases, had a be reversible after discontinuation of LUMIGAN® 0.01% and 0.03% (bimatoprost concurrent corneal disease or a disruption of the ocular epithelial surface. ophthalmic solution). Use With Contact Lenses: Contact lenses should be removed prior to instillation ® Potential for Eyelash Changes: Patients should also be informed of the possibility of LUMIGAN 0.01% and 0.03% and may be reinserted 15 minutes following of eyelash and vellus hair changes in the treated eye during treatment with its administration. LUMIGAN® 0.01% and 0.03%. These changes may result in a disparity between ADVERSE REACTIONS eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, Clinical Studies Experience: Because clinical studies are conducted under widely and/or direction of eyelash growth. Eyelash changes are usually reversible upon varying conditions, adverse reaction rates observed in the clinical studies of a drug discontinuation of treatment. cannot be directly compared to rates in the clinical studies of another drug and may Handling the Container: Patients should be instructed to avoid allowing the tip of not reflect the rates observed in practice. the dispensing container to contact the eye, surrounding structures, fingers, or any In clinical studies with bimatoprost ophthalmic solutions (0.01% or 0.03%) the other surface in order to avoid contamination of the solution by common bacteria most common adverse reaction was conjunctival hyperemia (range 25%–45%). known to cause ocular infections. Serious damage to the eye and subsequent loss of Approximately 0.5% to 3% of patients discontinued therapy due to conjunctival vision may result from using contaminated solutions. hyperemia with 0.01% or 0.03% bimatoprost ophthalmic solutions. Other common When to Seek Physician Advice: Patients should also be advised that if they reactions (>10%) included growth of eyelashes, and ocular pruritus. develop an intercurrent ocular condition (e.g., trauma or infection), have ocular Additional ocular adverse reactions (reported in 1 to 10% of patients) with surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid bimatoprost ophthalmic solutions included ocular dryness, visual disturbance, reactions, they should immediately seek their physician’s advice concerning the ocular burning, foreign body sensation, eye pain, pigmentation of the periocular continued use of LUMIGAN® 0.01% and 0.03%. skin, blepharitis, cataract, superficial punctate keratitis, periorbital erythema, Use with Contact Lenses: Patients should be advised that LUMIGAN® 0.01% and ocular irritation, eyelash darkening, eye discharge, tearing, photophobia, allergic 0.03% contains benzalkonium chloride, which may be absorbed by soft contact conjunctivitis, asthenopia, increases in iris pigmentation, conjunctival edema, lenses. Contact lenses should be removed prior to instillation of LUMIGAN® and may conjunctival hemorrhage, and abnormal hair growth. Intraocular inflammation, be reinserted 15 minutes following its administration. reported as iritis, was reported in less than 1% of patients. Use with Other Ophthalmic Drugs: Patients should be advised that if more than one Systemic adverse reactions reported in approximately 10% of patients with topical ophthalmic drug is being used, the drugs should be administered at least five bimatoprost ophthalmic solutions were infections (primarily colds and upper (5) minutes between applications. respiratory tract infections). Other systemic adverse reactions (reported in 1 to 5% of patients) included headaches, abnormal liver function tests, and asthenia. © 2012 Allergan, Inc., Irvine, CA 92612 Postmarketing Experience: The following reactions have been identified during ® ® marks owned by Allergan, Inc postmarketing use of LUMIGAN 0.01% and 0.03% in clinical practice. Because they Patented. See: www.allergan.com/products/patent_notices are reported voluntarily from a population of unknown size, estimates of frequency Made in the U.S.A. cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to LUMIGAN®, or APC70EN12 based on 71807US13. Rx only a combination of these factors, include: dizziness, eyelid edema, hypertension, nausea, and periorbital and lid changes associated with a deepening of the eyelid sulcus.

black ES315115_OT090113_010_FP.pgs 08.31.2013 04:21 ADV September 1, 2013 :: Ophthalmology Times 11 Special Report ) Glaucoma

Controlling circadian IOP fuctuation Neurons may offer novel glaucoma therapeutic target, animal study results show By Cheryl guttman krader; Reviewed by Brian C. Samuels, MD, PhD

IndIanapolIs :: A possible role for a specific For the study, responses to chemical stim- “The availability of human safety data makes type of hypothalamic neuron in mediating cir- ulation of the hypothalamus were evaluated an orexin antagonist well-positioned for en- cadian variations in IOP has been identified, when animals were pre-treated with an orexin tering clinical trials as a potential treatment according to research findings presented by receptor antagonist or vehicle control. for glaucoma, assuming there are positive ef- Brian C. Samuels, MD, PhD. Increases in IOP were found and ICP induced ficacy findings from further animal studies,” The study, which was con- by chemical stimulation were significantly at- Dr. Samuels said. “Considering how poorly ducted in an animal model, tenuated by orexin receptor antagonist pre- patients [with glaucoma] comply with use of was approached from the per- treatment in a dose-dependent fashion. their topical medications, perhaps an orally spective that the condition is Vital sign monitoring showed no attenua- administered drug would be beneficial.” a neurologic disease, rather tion of the increases in the animals’ heart rate than one involving only the or blood pressure. Looking to thE futurE Dr. Samuels eye. The focus was on the “We are excited about these initial findings, The next step, Dr. Samuels said, will be to effects of neurons contain- considering fluctuation in IOP is a known in- describe the afferent and efferent pathways ing orexin neuropeptides located dependent risk factor for glaucoma for the orexin-containing neurons, as well as in the dorsomedial/periformical progression and because recent work characterizing the pharmacology of orexin an- hypothalamus (DMH/PeF). has shown an aberrancy in the trans- tagonists that are selective for type 1 or type Chemical stimulation of this re- take-home laminar gradient in patients with 2 receptors. gion of the hypothalamus results glaucoma,” Dr. Samuels said. “Like the parent molecule and other orexin Research shows in increases in heart rate, blood “However, additional research antagonists in clinical trials, the compound we circadian variations in pressure, IOP, intracranial pressure is needed to establish the efficacy tested in this animal study was a dual orexin IOP can be regulated (ICP), and the translaminar pres- and safety of orexin antagonists receptor antagonist that affects both type 1 and by orexin-containing sure gradient, said Dr. Samuels, as a clinical approach to stabiliz- type 2 orexin receptors,” he said. “We would neurons located in the assistant professor of ophthalmol- ing IOP, ICP, and the translaminar like to determine if there may be any efficacy hypothalamus. ogy, Indiana University School of pressure gradient,” he said. and/or safety advantages of an agent that spe- Medicine, Indianapolis. The orexin antagonist used in the cifically targets just one receptor subtype.” ■ study was supplied by Merck and is a derivative Examining thE study of a compound that has been investigated as Knowing that the DMH/PeF is rich in orexin- a treatment for insomnia in a phase III study. containing neurons that have been shown to Because there is already clinical trial data Brian C. SamuelS, mD, PhD regulate circadian rhythmicity of various physi- demonstrating an acceptable safety profile for e: [email protected] ological processes—and that IOP displays cir- orexin receptor antagonists—together with their Dr. Samuels receives speaking honoraria from Merck, but it is not related to this cadian patterns—it was investigated to find if oral mode of administration—enhance inter- research. He holds a patent for the use of orexin antagonists for the treatment of orexin-containing neurons may also regulate est in investigating this class of drugs as novel glaucoma. The patent has not been optioned by outside companies and Dr. Samuels is circadian fluctuations in IOP and ICP. therapy for glaucoma. not currently receiving payments for the patent.

Ellex’s SLT technology launches in U.S.

adelaIde, australIa :: ellex MedicAl lAsers ltd. ogy in the United States, the company said in and patients alike,” according to Tom Spurl- announced the launch of its proprietary selec- a prepared statement. ing, chief executive officer of Ellex. tive laser trabeculoplasty (SLT) technology in SLT advanced laser therapy, which is non- As a highly effective approach for first-line the United States. invasive and non-thermal, stimulates a natural glaucoma treatment, SLT can also be used as an The launch comes following the expira- healing response in the eye to treat glaucoma. adjunct therapy with medications and as alter- tion of a patent held by Massachusetts Gen- “[SLT] also overcomes the compliance is- native therapy when medications or surgery fail eral Hospital (sub-licensed to Lumenis), which sues and side effects of anti-glaucoma medi- Ellex’s SLT platform is available in Tango SLT/ prevented Ellex from selling its SLT technol- cations, which have long plagued physicians YAG combination laser and Solo SLT laser. ■

magentablackcyanyellow ES316803_OT090113_011.pgs 09.06.2013 01:37 ADV 12 SePtember 1, 2013 :: Ophthalmology Times Special Report ) Glaucoma

Phaco + microinvasive safe, effective Study results show the procedure reduces medication burden in eyes with IOP By Cheryl guttman krader; Reviewed by Steven D. Vold, MD

Fayetteville, aR :: ImplantatIon of an Inves- as there were no serious compli- tIgatIonal supraciliary micro-stent cations,” Dr. Vold said. “Now, we (CyPass Micro-Stent, Transcend Medical) com- are waiting for results from the bined with in patients with randomized, controlled FDA IDE mild-to-moderate open-angle study (COMPASS) to substantiate glaucoma is safe and controls the long-term efficacy and benefit IOP, according to study re- of the combined procedure over sults presented by Steven D. alone.” Vold, MD. The safety review showed there The CyPass Clinical Ex- were no cases of: perience study (CyCLE) is a Dr. Vold multicenter, interventional > Hypotony maculopathy European clinical trial that > Suprachoroidal hemorrhage enrolled 248 patients with Shaffer Grade III or > Retinal detachment IV glaucoma undergoing phacoemulsification > Other retinal complications > with micro-stent implantation and has planned Iris atrophy (Figure 1) The follow-up to 3 years. > Endophthalmitis Supraciliary micro-stent – Polyimide tube supraciliary – retention features micro-stent The findings The device explantation rate and (CyPass Micro- The results focus on 2 years of follow-up from repositioning rate were each 0.7%. Stent, Transcend Medical), a cohort of 136 patients that entered the study Obstruction of the device was as shown in on 1 to 2 medications, said Dr. Vold, founder the most common adverse event Supraciliary position. (Images micro-stent courtesy of Steven D. and chief executive officer, Vold Vision, Fay- (8.8%), followed by endothelial loaded onto etteville, AR. touch (3.7%), elevated IOP lasting >1 applier Vold, MD) Among 85 patients with IOP controlled at month (2.9%), transient hyphema <21 mm Hg at baseline, IOP remained stable lasting <1 month (1.5%), and iritis after surgery, but the need for IOP medication persisting >1 month (0.7%). was significantly reduced. There were no cases of best-corrected visual incisional surgery procedures can be per- At baseline, mean IOP was 16.4 mm Hg and acuity loss related to the device. formed in the future if necessary. patients were using an average of 2.0 medica- Dr. Vold said insertion of the device using tions daily. There were 59 patients in the sub- how iT works a gonio lens (Vold Gonio Lens, Transcend group evaluated at 2 years, at which time mean The supraciliary micro-stent reduces IOP by Medical) he developed specifically for use IOP was 16.1 mm Hg, while mean daily medi- increasing aqueous outflow toward the supra- in the procedure could also be used. cation use had decreased ~50% choroidal space. It is made of a “This lens can be held in either hand, and to just 1.1. non-degradable, biocompatible as one of its advantages, it minimizes any There were 51 patients who had take-home polyimide material, measures 6.35 need for tilting the surgical microscope,” Dr. IOP ≥21 mm Hg at baseline. This mm in length, and has a 300-µm Vold said. “It features a stabilization ring subgroup had a mean baseline Data from 2 years of internal lumen. that prevents the eye from moving, giving IOP of 25.5 mm Hg and a 35% re- follow-up from a case The micro-stent is implanted the surgeon increased control, and it has a duction at 1 year to 15.8 mm Hg, series of patients with in a microinvasive glaucoma pro- floating lens that minimizes pressure on along with a >50% reduction in open-angle glaucoma cedure using an ab interno ap- the cornea, which can lead to image dis- mean daily medication use from show implantation proach through a 1.5-mm clear tortion.” ■ 2.2 to 1.0. of an investigational corneal incision or other size supraciliary micro- phaco incision. The procedure examining safeTy stent has IOP- and spares conjunctiva and sclera, Steven D. volD, MD “The safety of this glaucoma pro- medication-reducing and also preserves the trabecu- e: [email protected] cedure was also very impressive benefts in eyes. lar meshwork, so that laser and Dr. Vold is a consultant to Transcend Medical.

magentablackcyanyellow ES316812_OT090113_012.pgs 09.06.2013 01:37 ADV PATADAY® Solution: The #1 Prescription Allergy Eye Drop1

Season after season, your allergic conjunctivitis patients can rely on PATADAY® Solution for proven ocular itch relief2 with excellent payer coverage and affordability • Broad Tier 2 formulary coverage for both commercial and Medicare Part D plans3 • Patient Rebate Programs for eligible patients*

* This offer is not valid for patients who are enrolled in Medicaid, Medicare, or other federal or state prescription benefit programs including medical assistance programs. Please refer to the terms and conditions on the rebate materials.

INDICATION AND DOSING Patients should be advised not to wear contact lenses PATADAY ® Solution is a mast cell stabilizer indicated for if their eyes are red. the treatment of ocular itching associated with allergic PATADAY® Solution should not be used to treat contact conjunctivitis. The recommended dose is one drop in each lens-related irritation. The preservative in PATADAY® Solution, affected eye once a day. benzalkonium chloride, may be absorbed by soft contact IMPORTANT SAFETY INFORMATION lenses. Patients who wear soft contact lenses and whose PATADAY® Solution is for topical ocular use only. It is not for eyes are not red should be instructed to wait at least ten injection or oral use. minutes after instilling PATADAY® Solution before they insert their contact lenses. To prevent contaminating the dropper tip and solution, care should be taken not to touch the or surrounding areas Symptoms similar to cold syndrome and pharyngitis were with the dropper tip of the bottle. Keep the bottle tightly closed reported at an incidence of approximately 10%. when not in use. For additional information about PATADAY® Solution, References: 1. IMS Health, IMS National Prescription AuditTM, August 2010 to December 2012, USC 61500 OPHTH ANTI-ALLERGY. 2. PATADAY® Solution package insert. 3. Formulary data provided by Pinsonault please refer to the brief summary of prescribing Associates, LLC, Pathfi nderRx, April 2013. information on adjacent page.

©2013 Novartis 5/13 PAT13131JAD Visit PatadayToday.com

magentablackcyanyellow ES312070_OT090113_013_FP.pgs 08.29.2013 23:39 ADV 14 SePTember 1, 2013 :: Ophthalmology Times Special Report ) Glaucoma

INDICATIONS AND USAGE PATADAY® solution is indicated for the treatment of ocular itching associated with allergic conjunctivitis. CONTRAINDICATIONS None. Novel glaucoma agent WARNINGS For topical ocular use only. Not for injection or oral use. PRECAUTIONS Information for Patients rivals standard therapy As with any eye drop, to prevent contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use. Patients Latanoprostene bunod may produce greater reductions should be advised not to wear a contact lens if their eye is red. PATADAY® (olopatadine hydrochloride ophthalmic solution) 0.2% should not in IOP than latanoprost ophthalmic solution in study be used to treat contact lens related irritation. The preservative in PATADAY® solution, benzalkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red, should be By roxanne nelson; Reviewed by L. Jay Katz, MD instructed to wait at least ten minutes after instilling PATADAY® (olopatadine hydrochloride ophthalmic solution) 0.2% before they insert their contact lenses. PhiladelPhia :: Carcinogenesis, Mutagenesis, Impairment of Fertility Olopatadine administered orally was not carcinogenic in mice and rats in A new drug shows potential as a In addition, almost one-half (43%) were treat- doses up to 500 mg/kg/day and 200 mg/kg/day, respectively. Based on a 40 therapy for glaucoma, according to study re- ment naïve at enrollment. Patients received µL drop size and a 50 kg person, these doses were approximately 150,000 and 50,000 times higher than the maximum recommended ocular human sults showing that it performed better than a their drug dosage once a day in the evening dose (MROHD). No mutagenic potential was observed when olopatadine was tested in an in vivo bacterial reverse mutation (Ames) test, an in vivo standard therapy. for a total of 28 days. Evaluations for safety mammalian chromosome aberration assay or an in vivo mouse micronucleus Treatment with latanoprostene bunod 0.024% and efficacy occurred on days 7, 14, 28, and 29. test. Olopatadine administered to male and female rats at oral doses of approximately 100,000 times MROHD level resulted in a slight decrease in resulted in significantly greater reductions in Efficacy assessments included evaluating the fertility index and reduced implantation rate; no effects on reproductive mean diurnal IOP than with latano- the mean diurnal IOP and the pro- function were observed at doses of approximately 15,000 times the MROHD level. prost ophthalmic solution in patients portion of patients who were able Pregnancy with open-angle glaucoma (OAG) to maintain a mean diurnal IOP Teratogenic effects: Pregnancy Category C Olopatadine was found not to be teratogenic in rats and rabbits. However, or ocular hypertension. take-home at ≤18 mm Hg. rats treated at 600 mg/kg/day, or 150,000 times the MROHD and rabbits “(However, the drug) is not yet For safety assessment, the re- treated at 400 mg/kg/day, or approximately 100,000 times the MROHD, during Latanoprostene bunod organogenesis showed a decrease in live fetuses. In addition, rats treated with FDA approved,” said L. Jay Katz, searchers measured adverse events, is a probable new drug 600 mg/kg/day of olopatadine during organogenesis showed a decrease in MD, director of the Glaucoma Ser- best-corrected visual acuity, ocu- fetal weight. Further, rats treated with 600 mg/kg/day of olopatadine during for the treatment of late gestation through the lactation period showed a decrease in neonatal vice, Wills Eye Institute and pro- lar tolerability, ocular signs, and survival and body weight. glaucoma that seems fessor of ophthalmology, Thomas vital signs. An analysis of covari- There are, however, no adequate and well-controlled studies in pregnant to be well tolerated and women. Because animal studies are not always predictive of human responses, Jefferson University, Philadelphia. ance model with fixed-effect terms this drug should be used in pregnant women only if the potential benefit to the potent in lowering IOP. mother justifies the potential risk to the embryo or fetus. “Latanoprost is the most commonly was performed, and for measur- Nursing Mothers used glaucoma medication.” ing changes from baseline IOP, t- Olopatadine has been identified in the milk of nursing rats following oral Latanoprostene bunod is a nitric oxide-do- tests were performed for all treatment groups. administration. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the nating prostaglandin F2-alpha analog that is human breast milk. Nevertheless, caution should be exercised when PATADAY® (olopatadine hydrochloride ophthalmic solution) 0.2% is administered to a currently in development for the treatment of thE findinGs nursing mother. glaucoma and ocular hypertension. It is in- Results showed that at days 7, 14, and 28, there Pediatric Use Safety and effectiveness in pediatric patients below the age of 2 years have tended for the reduction of IOP in patients with were statistically greater reductions in mean not been established. elevated pressure due to glaucoma or ocular diurnal IOP for patients treated with latanopro- Geriatric Use hypertension. stene bunod 0.024%, as compared with latano- No overall differences in safety and effectiveness have been observed between elderly and younger patients. prost 0.005% at day 7 (8.3 versus 7.3 mm Hg, ADVERSE REACTIONS ExamininG thE study respectively; p = 0.0325), day 14 (8.9 versus Symptoms similar to cold syndrome and pharyngitis were reported at an incidence of approximately 10%. The following adverse experiences have been Results of the study were very promising, said 7.7 mm Hg; p = 0.0145), and day 28 (9 versus reported in 5% or less of patients: Dr. Katz, noting that the drug has the potential 7.8 mm Hg; p = 0.0051). Ocular: blurred vision, burning or stinging, conjunctivitis, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, pain and ocular to be a first-line agent if confirmed in larger There were significantly more patients who pruritus. Non-ocular: asthenia, back pain, flu syndrome, headache, increased cough, clinical trials. received latanoprostene bunod 0.024% that had infection, nausea, rhinitis, sinusitis and taste perversion. In this study, latanoprostene bunod 0.024% a study eye mean diurnal IOP ≤18 mm Hg at Some of these events were similar to the underlying disease being studied. was compared with latanoprost 0.005% oph- days 7 (p = 0.0057), 14 (p = 0.0464), 28 (p DOSAGE AND ADMINISTRATION The recommended dose is one drop in each affected eye once a day. thalmic solution in a randomized trial. = 0.0061), and 29 (p = 0.026), as compared HOW SUPPLIED The goal was to assess the efficacy of the with those who received latanoprost 0.005%. PATADAY® (olopatadine hydrochloride ophthalmic solution) 0.2% is supplied in a white, oval, low density polyethylene DROP-TAINER® dispenser with a agent in reducing and maintaining mean diur- All adverse events related to the treatment natural low density polyethylene dispensing plug and a white polypropylene cap. Tamper evidence is provided with a shrink band around the closure and nal IOP for up to 29 days in patients with OAG were mild or moderate in severity, and the per- neck area of the package. or ocular hypertension, and its performance centages of patients with conjunctival hyper- NDC 0065-0272-25 against a standard therapy. emia were similar across both treatment groups. 2.5 mL fill in 4 mL oval bottle The study participants were randomly as- Latanoprostene bunod 0.024% produced sig- Storage Store at 2°C to 25°C (36°F to 77°F) signed to either latanoprostene bunod 0.024% nificantly greater reductions (~1 mm Hg) in U.S. Patents Nos. 5,641,805; 6,995,186; 7,402,609 (n = 83) or latanoprost 0.005% ophthalmic mean diurnal IOP for up to 29 days as com- Rx Only solution (n = 82). All patients had an IOP ≥26 pared with latanoprost 0.005%. ■ and ≤32 mm Hg and a diagnosis of OAG or ocular hypertension. The two groups had similar demographics. L. JAy KATz, MD The mean age of the patients was 61 years, p: 215/928-3197 e: [email protected]

© 2013 Novartis 5/13 PAT13131JAD 77.6% were white, and 66.7% were women. Dr. Katz has no fnancial interest in the subject matter.

magentablackcyanyellow ES316325_OT090113_014.pgs 09.05.2013 01:59 ADV SePTember 1, 2013 :: Ophthalmology Times 15 Special Report ) Glaucoma

P o s s i Bl E “PhS-OCT might allow non-inVASiVe CliniCal aPPliCations screening of canaloplasty can- MurrAy JoHnSTone, MD PhS-OCT may also be used to guide didates without going to the op- e: [email protected] ( Continued from page 8 ) medical and surgical therapy decisions. erating room, and it might also Dr. Johnstone has fnancial interests with Alcon Ocular hypotensive medications allow us to select better candi- Laboratories, Allergan, Cascade Ophthalmics, “Color velocity maps obtained with that increase pulsatile aqueous out- dates for laser trabeculoplasty Healionics, Sensimed, and the University of Washington this technology show the trabecular flow (i.e., miotics, adrenergics, prosta- or ab interno trabeculotomy,” Center for Commercialization. meshwork in motion, changing con- glandin analogues) exert their effects Dr. Johnstone said. ■ figuration as it moves outward toward on trabecular meshwork motion and the external wall of Schlemm’s canal occur very quickly, he said. Thus, in- during systole, then rebounds toward office PhS-OCT might be used to deter- the anterior chamber during diastole,” mine if a patient will be a responder Dr. Johnstone said. following test dose administration. By providing information about The ability to characterize trabecu- issue motion, he said, PhS-OCT pro- lar meshwork motion at different sites vides an objective measurement of could also be useful for guiding opti- trabecular meshwork tissue elasticity mal placement of stent devices used and compliance, and thus its ability in microinvasive glaucoma surgical to control IOP. procedures. “Just as HbA1c measurements pro- The technology might be applied as vide a better indication of diabetes a non-invasive method to determine control than random blood glucose whether patients are good candidates testing,” Dr. Johnstone said, “mea- for canaloplasty, Dr. Johnstone said. suring the biomechanical properties Canaloplasty pioneer, Robert Steg- of the trabecular meshwork to deter- mann, MD, has shown that response mine the function of the outflow sys- after canaloplasty can be predicted by tem may prove to be a better assess- the ability of intraoperative provoca- ment tool than IOP for evaluating eyes tive to cause Schlemm’s with glaucoma and their response to canal blood reflux—a surrogate for treatment.” trabecular meshwork motion.

Microshunt OAG trial given approval by FDA from staf reports

MiaMi :: InnFocus Inc. hAs re- to 60% with the average pressure re- ceIved authorization from the siding between 10 and 12 mm Hg. FDA to begin the phase I trial of the “This is particularly important in InnFocus MicroShunt to treat open- view of many well-documented studies angle glaucoma (OAG). showing that reducing pressure below The trial will be the first to use 14 mm Hg arrests progression of the with mitomycin C disease,” Dr. Pinchuk said. as a study control, according to the About 90% of the patients’ pres- company. sures are below 14 mm Hg and simi- “We believe that the excellent clini- lar numbers of patients are totally off cal results achieved by [this shunt] in glaucoma medication, he said. earlier clinical evaluations indicate that “The key to our success is our pro- the device will perform well against prietary biomaterial which demon- the current gold standard of trabecu- strates a clinically insignificant for- lectomy,” said Leonard Pinchuk, PhD, eign body reaction in the eye,” Dr. president of InnFocus. Pinchuk said. An ongoing study, now in its third InnFocus has also announced a $13.4 year in the Dominican Republic, shows million financing led by HOYA and that the device can lower IOP by 50% Saints Capital Everest. ■

magentablackcyanyellow ES316324_OT090113_015.pgs 09.05.2013 01:59 ADV 16 SePteMBer 1, 2013 :: Ophthalmology times Special Report ) Glaucoma

Lack of data fuels glaucoma shunt study Mean IOP and success rates similar between device, trabeculectomy groups after 1 year By Cheryl Guttman Krader; Reviewed by Yvonne M. Buys, MD

toronto :: A CompArison of GuArded data on its outcomes motivated researchers to due to reasons not directly related to the sur- implantation of a glaucoma filtration device undertake this study, according to Dr. Buys. gery, Dr. Buys noted. (Ex-PRESS P-50, Alcon Laboratories) with stan- “In our study, only cost emerged as a major Other secondary outcomes included num- dard trabeculectomy shows no between-group factor differentiating between the two proce- ber of glaucoma medications, complications, differences in IOP reduction or safety outcomes, dures through 1 year,” she said. “However, the need for additional procedures, bleb morphol- according to results from 1 year of follow-up faster visual recovery after the miniature shunt ogy, central corneal thickness, endothelial cell in a prospective, randomized study. procedure compared with trabeculectomy is count, and surgical time, and there were no The device-based procedure was associated an interesting difference that deserves further significant differences between study groups with faster visual recovery, but its use carried a study, and longer follow-up is certainly needed.” in any of these endpoints. higher cost, according to Yvonne M. Buys, MD. IOP was analyzed as the primary efficacy The study enrolled 64 con- outcome measure for the randomized trial. CoSt ConSiderationS secutive patients with open- Mean IOP was similar in the shunt and tra- Economic analysis took into account the costs angle glaucoma who were beculectomy groups at baseline (22.6 and 22 of surgery and follow-up care through 1 year. scheduled to undergo filtra- mm Hg, respectively) and at all follow-up vis- Postoperative cost was lower for the shunt group tion surgery because IOP was its, which were scheduled at 1 day, 1 and 2 than for the trabeculectomy eyes by about $125. uncontrolled on maximally weeks, and 1, 2, 3, 4, 6, and 12 months. However, due to the cost of the device, the total tolerated medical therapy. At 1 year, mean IOP was 11 mm Hg in the cost per case through 1 year was nearly $1,000 Dr. Buys The device was implanted shunt group and 10 mm Hg in the more for the shunt procedure. under a scleral flap, and both trabeculectomy eyes. Dr. Buys noted that at the time surgeries were performed using intraoperative The rate of complete success— the study was launched, there was mitomycin-C 0.4 mg/ml for 2 minutes. Sixty- defined as IOP between 5 and 18 take-home a single published report of a ran- one of the 64 patients were evaluated at 1 year. mm Hg with a ≥20% reduction from domized controlled study compar- “The surgical procedure for its implantation baseline without medication—was A prospective study ing the miniature glaucoma shunt has several potential advantages, including a higher in the miniature shunt group randomly assigned with trabeculectomy. While it re- short-learning curve, consistency, and less tis- compared with the trabeculectomy 64 patients with ported significantly greater success sue manipulation,” said Dr. Buys, professor, eyes, 71% versus 57%. The differ- open-angle glaucoma in the device group after 1 year, by Department of Ophthalmology and Vision Sci- ence, however, was not statistically to surgery with a 3 years and continuing through 5 ences, University of Toronto. significant. miniature glaucoma years of follow-up, there was no Mean logMAR visual acuity de- shunt or standard difference between groups. Study motivation creased significantly immediately trabeculectomy, both “Subsequently, another pro- The miniature glaucoma shunt has been available after surgery in both groups and with mitomycin-C. spective, randomized study was since 2002. However, a lack of evidence-based then began to improve. published that compared the two In the trabeculectomy group, best mean procedures in fellow eyes of patients with bi- visual acuity after surgery was not achieved lateral glaucoma,” Dr. Buys said. “While this surgIcal tEchnIquE until 2 months after surgery, but it worsened study found the success rate was significantly thereafter. Mean visual acuity was significantly higher for the miniature shunt after a mean below the baseline level at all follow-up visits. follow-up of almost 2 years, it enrolled only In the miniature shunt group, mean visual 15 patients of which 3 dropped out. acuity never returned to baseline, but it did “Our study enrollment surpassed our tar- recover to a level that was no longer signifi- get sample size of 52 patients, which was the cantly different from baseline by 1 month after number needed to detect a 2-mm Hg difference surgery and was stable thereafter. in IOP between groups with 80% power,” she At 1 year, both groups had a median visual said. “Now we are looking at our data from acuity loss from baseline of 1 Snellen line. follow-up at 2 and 3 years.” ■ However, the proportion of eyes with a >2 line loss of visual acuity was significantly higher VIDEO to view a surgical technique showing the glaucoma shunt implanted under a in the trabeculectomy group than in the min- Yvonne M. BuYs, MD scleral fap, go to http://bit.ly/15YLnk3. iature shunt eyes, 30% versus 3%. e: [email protected] (Video courtesy of Yvonne M. Buys, MD) Four of the nine eyes in the trabeculectomy Dr. Buys received some of the devices used in the study at no charge from Alcon group that lost more than 2 Snellen lines were Canada and I-Med, and has received speaking fees from Alcon for unrelated topics.

magentablackcyanyellow ES316135_OT090113_016.pgs 09.04.2013 23:54 ADV Introducing an advanced formulation of BROMDAY® (bromfenac ophthalmic solution) 0.09% PROLENSA™ POWERED FOR PENETRATION

PROLENSA™ delivers potency and penetration with QD effi cacy1,2 Advanced formulation delivers corneal penetration1-3 Proven effi cacy at a lower concentration1

Available in 1.6-mL and 3-mL bottle sizes

IMPORTANT RISK INFORMATION ABOUT PROLENSA™ Indications and Usage Warnings and Precautions PROLENSA™ (bromfenac ophthalmic solution) 0.07% is a nonsteroidal anti- • Sulfi te allergic reactions • Increased bleeding of ocular tissues infl ammatory drug (NSAID) indicated for the treatment of postoperative infl ammation • Slow or delayed healing • Corneal effects, including keratitis and reduction of ocular pain in patients who have undergone cataract surgery. • Potential for cross-sensitivity • Contact lens wear Dosage and Administration Adverse Reactions Instill one drop into the affected eye once daily beginning 1 day prior to surgery, The most commonly reported adverse reactions in 3%-8% of patients continued on the day of surgery, and through the fi rst 14 days post surgery. were anterior chamber infl ammation, foreign body sensation, eye pain, photophobia, and blurred vision. Please see brief summary of full Prescribing Information on adjacent page. References: 1. PROLENSA™ Prescribing Information, April 2013. 2. Data on fi le, Bausch & Lomb Incorporated. 3. Baklayan GA, Patterson HM, Song CK, Gow JA, McNamara TR. 24-hour evaluation of the ocular distribution of 14C-labeled bromfenac following topical instillation into the eyes of New Zealand White rabbits. J Ocul Pharmacol Ther. 2008;24(4):392-398. ®/™ are trademarks of Bausch & Lomb Incorporated or its affi liates. ©2013 Bausch & Lomb Incorporated. Printed in USA US/PRA/13/0044a 4/13

magentablackcyanyellow ES312038_OT090113_017_FP.pgs 08.29.2013 23:36 ADV PROLENSATM (bromfenac ophthalmic solution) 0.07% Brief Summary

INDICATIONS AND USAGE the limit of quantifcation) and rabbits at oral doses up to 7.5 mg/kg/day (150 PROLENSA (bromfenac ophthalmic solution) 0.07% is indicated for the treatment times the predicted human systemic exposure) produced no treatment-related of postoperative infammation and reduction of ocular pain in patients who have malformations in reproduction studies. However, embryo-fetal lethality and undergone cataract surgery. maternal toxicity were produced in rats and rabbits at 0.9 mg/kg/day and 7.5 mg/kg/day, respectively. In rats, bromfenac treatment caused delayed DOSAGE AND ADMINISTRATION parturition at 0.3 mg/kg/day (30 times the predicted human exposure), and Recommended Dosing caused dystocia, increased neonatal mortality and reduced postnatal One drop of PROLENSA ophthalmic solution should be applied to the affected growth at 0.9 mg/kg/day. eye once daily beginning 1 day prior to cataract surgery, continued on the day of There are no adequate and well-controlled studies in pregnant women. Because surgery, and through the frst 14 days of the postoperative period. animal reproduction studies are not always predictive of human response, this Use with Other Topical Ophthalmic Medications drug should be used during pregnancy only if the potential beneft justifes the PROLENSA ophthalmic solution may be administered in conjunction with other potential risk to the fetus. topical ophthalmic medications such as alpha-agonists, beta-blockers, carbonic Because of the known effects of prostaglandin biosynthesis-inhibiting drugs anhydrase inhibitors, cycloplegics, and mydriatics. Drops should be administered at on the fetal cardiovascular system (closure of ductus arteriosus), the use of least 5 minutes apart. PROLENSA ophthalmic solution during late pregnancy should be avoided.

CONTRAINDICATIONS Nursing Mothers None Caution should be exercised when PROLENSA is administered to a nursing WARNINGS AND PRECAUTIONS woman. Sulfte Allergic Reactions Contains sodium sulfte, a sulfte that may cause allergic-type reactions including Pediatric Use anaphylactic symptoms and life-threatening or less severe asthmatic episodes Safety and effcacy in pediatric patients below the age of 18 have not been in certain susceptible people. The overall prevalence of sulfte sensitivity in the established. general population is unknown and probably low. Sulfte sensitivity is seen more frequently in asthmatic than in non-asthmatic people. Geriatric Use Slow or Delayed Healing There is no evidence that the effcacy or safety profles for PROLENSA differ in All topical nonsteroidal anti-infammatory drugs (NSAIDs), including bromfenac, patients 70 years of age and older compared to younger adult patients. may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the NONCLINICAL TOXICOLOGY potential for healing problems. Carcinogenesis, Mutagenesis and Impairment of Fertility Potential for Cross-Sensitivity Long-term carcinogenicity studies in rats and mice given oral doses of There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid bromfenac up to 0.6 mg/kg/day (systemic exposure 30 times the systemic derivatives, and other NSAIDs, including bromfenac. Therefore, caution should be exposure predicted from the recommended human ophthalmic dose [RHOD] used when treating individuals who have previously exhibited sensitivities to these assuming the human systemic concentration is at the limit of quantifcation) drugs. and 5 mg/kg/day (340 times the predicted human systemic exposure), Increased Bleeding Time respectively, revealed no signifcant increases in tumor incidence. With some NSAIDs, including bromfenac, there exists the potential for increased bleeding time due to interference with platelet aggregation. There have been reports Bromfenac did not show mutagenic potential in various mutagenicity studies, that ocularly applied NSAIDs may cause increased bleeding of ocular tissues including the reverse mutation, chromosomal aberration, and micronucleus (including hyphemas) in conjunction with ocular surgery. tests.

It is recommended that PROLENSA ophthalmic solution be used with caution in Bromfenac did not impair fertility when administered orally to male and female patients with known bleeding tendencies or who are receiving other medications rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, respectively (systemic which may prolong bleeding time. exposure 90 and 30 times the predicted human exposure, respectively). Keratitis and Corneal Reactions Use of topical NSAIDs may result in keratitis. In some susceptible patients, PATIENT COUNSELING INFORMATION continued use of topical NSAIDs may result in epithelial breakdown, corneal Slowed or Delayed Healing thinning, corneal erosion, corneal ulceration or corneal perforation. These events Advise patients of the possibility that slow or delayed healing may occur while may be sight threatening. Patients with evidence of corneal epithelial breakdown using NSAIDs. should immediately discontinue use of topical NSAIDs, including bromfenac, and should be closely monitored for corneal health. Sterility of Dropper Tip Advise patients to replace bottle cap after using and to not touch dropper tip to Post-marketing experience with topical NSAIDs suggests that patients with any surface, as this may contaminate the contents. complicated ocular surgeries, corneal denervation, corneal epithelial defects, Advise patients that a single bottle of PROLENSA, be used to treat only one diabetes mellitus, ocular surface diseases (e.g., ), rheumatoid eye. arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Concomitant Use of Contact Lenses Topical NSAIDs should be used with caution in these patients. Advise patients to remove contact lenses prior to instillation of PROLENSA. The preservative in PROLENSA, benzalkonium chloride, may be absorbed Post-marketing experience with topical NSAIDs also suggests that use more than by soft contact lenses. Lenses may be reinserted after 10 minutes following 24 hours prior to surgery or use beyond 14 days post-surgery may increase patient administration of PROLENSA. risk for the occurrence and severity of corneal adverse events. Concomitant Topical Ocular Therapy Contact Lens Wear If more than one topical ophthalmic medication is being used, the medicines PROLENSA should not be instilled while wearing contact lenses. Remove contact should be administered at least 5 minutes apart lenses prior to instillation of PROLENSA. The preservative in PROLENSA, benzalkonium chloride may be absorbed by soft contact lenses. Lenses may be Rx Only reinserted after 10 minutes following administration of PROLENSA.

ADVERSE REACTIONS Manufactured by: Bausch & Lomb Incorporated, Tampa, FL 33637 Clinical Trial Experience Under license from: Because clinical trials are conducted under widely varying conditions, adverse Senju Pharmaceuticals Co., Ltd. reaction rates observed in the clinical trials of a drug cannot be directly compared Osaka, Japan 541-0046 to rates in the clinical trials of another drug and may not refect the rates observed in clinical practice. Prolensa is a trademark of Bausch & Lomb Incorporated or its affliates. The most commonly reported adverse reactions following use of PROLENSA © Bausch & Lomb Incorporated. following cataract surgery include: anterior chamber infammation, foreign body sensation, eye pain, photophobia and vision blurred. These reactions were reported in 3 to 8% of patients.

USE IN SPECIFIC POPULATIONS Pregnancy Treatment of rats at oral doses up to 0.9 mg/kg/day (systemic exposure 90 times the systemic exposure predicted from the recommended human ophthalmic dose [RHOD] assuming the human systemic concentration is at 9317400

black ES312037_OT090113_018_FP.pgs 08.29.2013 23:36 ADV SePtemBer 1, 2013 :: Ophthalmology Times 19 Special Report ) Glaucoma

When fxed-combination is viable option Brinzolamide-brimonidine may beneft patients who have contraindications to beta-blocker by cheryl Guttman Krader; Reviewed by Jess T. Whitson, MD

Dallas :: The new fixed-combinaTion Why fixed-combination strated that the fixed-combination had good agent of brinzolamide 1%–brimonidine 0.2% may be best option systemic safety. Local ocular adverse events (Simbrinza Suspension, Alcon Laboratories) There are many reasons to choose a fixed- accounted for the majority of adverse event is a safe and effective option for lowering IOP combination for these individuals. reports in all groups. in patients with glaucoma or ocular hyperten- Patient compliance may be enhanced be- The types of adverse events reported were sion uncontrolled on monotherapy. cause of the simplicity of instilling one drop those expected based on experience with The medication also brings the benefits instead of two and by the lower cost of hav- brinzolamide and brimonidine, Dr. Whit- of fixed-combination therapy to individuals ing just one co-payment. son noted. who have contraindications “In addition, a fixed-combination avoids Use of brinzolamide alone or in combina- to a beta-blocker, said Jess the potential for drop washout if patients do tion was associated with all cases of blurred T. Whitson, MD. not wait a sufficient Dr. Whitson is professor time between instill- of ophthalmology, Univer- ing their medications, sity of Texas Southwest- and its use lessens ocu- ‘As many as 40% of patients with ern Medical Center, Dal- lar surface exposure to Dr. Whitson las, and the lead author of preservatives like ben- glaucoma are [taking] more than a recently published paper zalkonium chloride,” (Clin Ophthalmol. 2013;7:1053-1060) present- Dr. Whitson said. one medication to control IOP.’ ing the 6-month results from one of the two However, there has pivotal clinical trials that led to FDA approval been a need for a beta- — Jess T. Whitson, MD of brinzolamide-brimonidine. blocker-free fixed-com- The randomized study began with a 3-month, bination, since cardiac double-masked phase comparing three times- and pulmonary conditions—which are contra- vision and nearly all reports of dysgeusia, daily treatment with brinzolamide-brimoni- indications to an ophthalmic beta-blocker— whereas use of brimonidine alone or in com- dine against the carbonic anhydrase inhibi- are prevalent in the elderly population of pa- bination was associated with all or nearly tor (brinzolamide) or alpha-agonist (brimo- tients being treated for ocular hypertension all cases of conjunctivitis, dry mouth, and nidine) alone. After 3 months, mean IOP at and glaucoma. ocular allergy. all measured time points (8 a.m., 10 a.m., 3 The new combination of brinzolamide plus “This 6-month study has a relatively short p.m., and 5 p.m.) was significantly brimonidine meets this need, Dr. duration, and some cases of allergy or other lower in patients using the fixed- Whitson noted. adverse events may only develop over longer- combination than in the mono- term use,” Dr. Whitson said. therapy groups. pivotal trial Seventy-two of 77 patients who discon- The study was continued for take-home The pivotal trial randomly as- tinued study participation because of an ad- a 3-month safety extension. At 6 A new fixed- signed 690 patients with ocular verse event were using brimonidine either months, mean IOP was stable in combination of hypertension or open-angle glau- alone (34 patients) or as the fixed-combi- all treatment groups. No new or brinzolamide- coma. Eligible participants un- nation (38 patients). increased safety signals emerged. brimonidine is a safe derwent a washout period rang- There were no serious treatment-related After 6 months in the fixed- and effective option ing from 5 to 28 days, depend- adverse events in any study group. ■ combination group, percent IOP for lowering IOP in ing on what medication(s) they reduction from baseline ranged patients who are were taking. The patients had Do you use a fxed-combination therapy from 20% at trough to 30.7% at to have IOP at two consecutive not candidates for a for patients with glaucoma? Weigh in at peak. beta-blocker. visits ranging from 24 to 36 mm Facebook.com/OphthalmologyTimes. “There is a large pool of poten- Hg at 8 a.m. and from 21 to 36 tial candidates for a fixed-com- mm Hg at 10 a.m. bination IOP-lowering agent,” Patients were instructed to ad- Dr. Whitson said. “Recent studies and na- minister the medication at 8 a.m., 3 p.m., and tional drug plan prescription data show that 10 p.m., and returned for follow-up visits after Jess T. WhiTson, MD as many as 40% of patients with glaucoma 2 weeks, 6 weeks, 3 months, and 6 months. e: [email protected] are [taking] more than one medication to Data on adverse events and from pulse Dr. Whitson is on the speaker’s bureau for Alcon Laboratories, Allergan, Merck, c ont rol IOP.” rate and blood pressure monitoring demon- and Sucampo.

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Topical tactics for the ocular surface How preservatives in topical ophthalmic medications may have adverse consequences By fred gebhart; Reviewed by Douglas Rhee, MD

Boston :: Preservatives in toPical oph- themselves have an effect on ocular tissues,” Those experimental findings support clini- thalmic medications are not benign, but may Dr. Rhee said. “That drug-related effect is un- cal observations that patients treated with non- have adverse consequences for the ocular sur- avoidable, at least when you are using a topi- preserved timolol for more than 1 year had face, the success of bleb-dependent procedures, cal delivery system. more normal cytology than similar patients and the trabecular meshwork. “We may eventually get around surface dis- treated with preserved latanoprost or timolol. “There is excellent evidence in the litera- ease issues and trabeculectomy issues by going “There is excellent evidence that topically ture to support the claim that alternatively to a different, non-topical delivery route, but delivered glaucoma medications—preserved preserved and non-preserved medications are those systems are still in develop- and possibly non-preserved—cause more gentle than medications preserved with ment and testing,” he said. an increase in conjunctival inflam- benzalkonium chloride,” said Douglas Rhee, Various in vitro studies have mation,” Dr. Rhee said. “That has MD, associate professor of ophthalmology, Har- confirmed that benzalkonium chlo- take-home been shown using impression cy- vard Medical School, Boston. ride can cause inflammation in the Ophthalmologists tology, confocal microscopy, and Editor’s Note: ( Dr. Rhee has recently been conjunctiva and that it is lethal to need to weigh the conjunctival biopsy. The major named Chairman of Ophthalmology and Vi- trabecular meshwork cells—both evidence regarding confounder is the pharmacologic sual Sciences at Case Western Reserve Univer- as a single agent and as a preser- the best use for agents themselves.” sity School of Medicine and University Hospi- vative in ophthalmic medications. medications that The good news is pre-treating tals’ Case Medical Center, Cleveland, where he “There is very good evidence are non-preserved, with topical corticosteroids before is expected to start this month.) that preservatives, or at least ben- alternatively preserved, surgery may reverse inflammation Topical ophthalmic medications typically zalkonium chloride, does have a or benzalkonium and increase success rates for bleb- come in three forms, he said. deleterious effect on the ocular chloride-preserved. dependent trabeculectomies, he said. surface,” Dr. Rhee said. “Whether Blebless procedures—such as ab > The most common formulation uses benzalko- there is a difference in ocular sur- interno trabeculectomy, laser trabec- nium chloride as a preservative. These medica- face disease between non-preserved medica- uloplasty, tube shunt, trabecular micro-bypass tions are usually less expensive compared with tion and alternatively preserved medications stent (iStent, Glaukos) or similar device implan- other formulations and are the agents preferred— is less clear—there is not a lot of evidence ei- tation, and endoscopic cyclophotocoagulation— and sometimes required—by third-party payers. ther way—but when it comes to benzalkonium are less affected by conjunctival inflammation. chloride, the evidence of ocular surface dis- Evidence suggesting that intraocular ben- > Alternatively preserved medications typically ease is convincing. zalkonium chloride contributes to trabecular use one of two preservatives: Purite, which is a “There is little question, based on my own meshwork pathology is less convincing. stabilized oxychloro complex containing oxygen, clinical experience, that alternatively preserved In vitro exposure to benzalkonium chloride sodium, and chlorine free radicals, and SofZia, and non-preserved agents are more gentle, bet- and other preservatives kill cultured trabecular which is an ionic buffer containing borate, wor- ter tolerated, and induce fewer symptomatic meshwork cells in a dose-dependent manner. bitol, polylene, glycol, and zinc. side effects compared with the same drugs pre- Dr. Rhee and others are actively investigat- served with benzalkonium chloride,” he said. ing the potential in vivo effects of preserva- > Preservative-free formulations are often re- There is also evidence that preserved topical tives on the trabecular meshwork. ferred to as non-preserved medications. medication can reduce the success rate of tra- “If it is feasible clinically and economically, beculectomy surgeries that use a filtering bleb. there is convincing evidence that non-preserved Preservative versus The problem is that benzalkonium chloride and alternatively preserved medications are non-Preserved drugs increases inflammation in the conjunctiva, Dr. better than benzalkonium chloride-preserved There is ample evidence to consider medica- Rhee said. medications, because they are more gentle and tions that are not preserved or are preserved Topical ophthalmic medications also induce better tolerated,” he said. “Reducing those side with alternative agents as being more gentle inflammation in the conjunctiva. effects is an important positive step, because to ocular tissues, Dr. Rhee said. side effects are a major barrier to adherence.” ■ However, the evidence is less convincing Looking further when it comes to the potential effect of pre- The degree of inflammation that is due to the servatives on bleb-dependent trabeculectomies medications versus the inflammatory effects Douglas Rhee, MD and the trabecular meshwork. of preservatives is difficult to tease out. How- e: [email protected] The primary factor is that ophthalmic drugs ever, rabbits treated with non-preserved timolol Dr. Rhee is an ad hoc consultant to Aerie Pharmaceuticals, Alcon Laboratories, Allergan, can have adverse effects on ocular tissue. had less conjunctival inflammation than simi- Johnson & Johnson, Merck, and Santen and has research relationships with Alcon, “It is certainly true that pharmacologic agents lar rabbits given preserved timolol. Aquesys, and Merck.

magentablackcyanyellow ES316800_OT090113_020.pgs 09.06.2013 01:37 ADV September 1, 2013 :: Ophthalmology Times 21 Special Report ) Glaucoma

SLT ophthalmologyTimes.com OnlinE ExclusiVE

( Continued from page 1 ) SLT: A New STANdArd iN gLAucomA TreATmeNT As society continues to become more technologically advanced and patient expecta- Probability of success tions grow alongside, there is no better time for physicians to rework the antiquated eyedrop- Based on criteria for defining success—a de- centered glaucoma treatment regime. SLT offers the treatment efficacy and convenience crease in IOP and subsequent maintenance patients today need and stands to give the 1970s-based management of glaucoma a long- below goal IOP without any awaited shake-up in the 2010s, suggests Lawrence F. Jindra, MD. Go to http://bit.ly/17PkFNs. need for hypotensive medi- cation, repeat SLT, or filtra- tion/shunt surgery—the cu- mulative probability of suc- cess of SLT as primary ther- apy was 97% at 1 year, 92% Dr. Jindra at 5 years, and still 90% at years 7 through 10. “The Glaucoma Laser Trial established the ef- ficacy of laser trabeculoplasty in lowering IOP in previously untreated patients, while results from the OHTS and Early Manifest Glaucoma Trial established the efficacy of early and effec- tive treatment to preserve long-term visual func- tion in [patients with] glaucoma,” said Lawrence F. Jindra, MD, co-author of the study and chief emeritus, Winthrop University Hospital and as- sistant clinical professor of ophthalmology, Co- lumbia University, New York. The findings build on these studies in dem- onstrating SLT produces significant IOP lower- ing and with durable benefit, he said. “Further study of SLT in controlled trials is in- dicated,” Dr. Jindra said. “But given the amount of data and experience on SLT, we believe that prescribing medications instead of SLT for pri- mary treatment of glaucoma today is analogous to performing intracapsular cataract extraction rather than phacoemulsification. It can be done, but why would you?” ( Continues on page 22 : Safety )

SLT OVEr ThE LOng TErm

VIDEO In this video interview, Lawrence F. Jindra, MD, shares his long-term results for SLT when used as a primary, secondary, and replacement therapy. Go to http://bit.ly/17PkFNs. (Video courtesy of Ellex)

magentablackcyanyellow ES316825_OT090113_021.pgs 09.06.2013 01:55 ADV 22 September 1, 2013 :: Ophthalmology Times Special Report ) Glaucoma

SaFeTy MIGS with ( Continued from page 21 ) stents may Dr. Jindra also commented on safety of SLT, noting it is not “argon laser trabeculoplasty-lite.” beneft OAG SLT—performed using a Q-switched, fre- quency-doubled (532 nm), low-energy Nd:YAG By Lynda Charters laser—targets me- lanocytes in the San FrancISco :: trabecular mesh- Patients with oPen-angle take-home work. The treat- glaucoma (oag) had a significant in an analysis of almost ment induces a SLT Treatment Protocol reduction in IOP and did not require anti- 2,000 eyes treated biologic response SLT is a relatively quick and easy glaucoma medications over 1 year postopera- with selective laser that involves re- outpatient procedure. During treatment tively when micro-invasive glaucoma surgery about 100 confluent spots are applied trabeculoplasty as primary lease of cytokines (MIGS) was performed, according to interim along meshwork to treat a 360° angle. therapy for glaucoma, that trigger macro- results for a MIGS study group that were re- mean iOP decreased phage recruitment ported by David F. Chang, MD. 29% and the cumulative and other changes The surgery, in which two first-generation probability of success at leading to reduction trabecular micro-bypass stents (iStent, Glau- 10 years was 90%. i n IOP. kos) were implanted as the only treatment, ap- SLT is distinctly peared effective for treating OAG, which was different from uncontrolled by one anti-glaucoma medication. argon laser trabeculoplasty, and it requires The MIGS study group consisted of sub- the surgeon to make and accept an intel- jects at the Malayan Center in Yerevan, Ar- lectual and practical paradigm shift, ac- menia. Patients who were phakic or pseudo- cording to Dr. Jindra. phakic (n = 39) with OAG and treated with “SLT has less energy than the average laser one medication were included. used to scan groceries at the checkout,” he All patients had a cup-to-disc ratio of 0.9 said. “So it treats the trabecular meshwork or less and IOP between 18 and 30 mm Hg. without causing thermal or coagulative dam- After a medication washout period, the pre- age, without producing peripheral anterior Energy Selection operative IOP ranged from 22 to 38 mm Hg. synechiae, but allowing for clinically effec- After the threshold level is found (the One-year efficacy endpoints were IOP re- tive repeatability.” ■ point at which mini-bubble formation duction without anti-glaucoma mediations of occurs), the energy level is decreased 20% or more, an IOP of 18 mm Hg or lower in 0.1 mJs steps as treatment continues without medication, and mean change in IOP. until bubble formation ceases. This Lawrence F. Jindra, Md In the 39 eyes followed for 1 year, compared energy is then used for treatment. e: [email protected] (Images courtesy of Ellex) with baseline, mean IOP reduction overall Dr. Jindra has received honoraria from Ellex Corp. in the past year. was 44%: 67% of eyes had a reduction of 40% or more, 85% had a reduction of 30% or more, and 92% of eyes met the primary endpoint of an IOP reduction of 20% or more. GRF receives largest bequest in its history At the 1-year evaluation, 92% of eyes met the secondary endpoint of postoperative IOP of 18 mm Hg or lower without medication San FrancISco :: and 77% of eyes had an IOP of 15 mm Hg or the glAucomA reseArch foundAtion particularly meaningful—as it is a testament to the lower without medication. BCVA remained (grF) has received a $3 million bequest, the larg- quality and excellence of the care and compassion the same or improved in 35 of 39 eyes. At 1 est gift in its history. Dr. Iwach provides to all of his patients,” Brunner year, 74% had 20/40 or better visual acuity, The bequest, which was given by henry Adolph added. compared with 67% preoperatively. Sutro, DDS, of Oakland, CA, was made in honor of The bequest will establish the Dr. henry A. Sutro “In the United States, the (trabecular micro- his ophthalmologist, Andrew g. Iwach, mD. Family grant for research and the Drs. henry and bypass stent) is only approved as a combined Dr. Iwach is the executive director of the glaucoma Frederick Sutro memorial Lecture. procedure with phaco, and it is therefore hard Center of San Francisco and board chairman of grF. The lecture will be held each year at the glaucoma to know how much of any resulting IOP low- “We are incredibly grateful to Dr. Sutro for this 360° annual meeting. It was created to promote in- ering is due to cataract surgery alone,” Dr. remarkable gift,” said Thomas m. Brunner, president novation in glaucoma therapy, as well as continuing Change said. The iStent is FDA-approved in and chief executive officer of grF. education program for clinicians to highlight the lat- the United States, CE marked in Europe, and “his thoughtful contribution in honor of Dr. Iwach is est advances in glaucoma management. has medical device approval in Canada. ■

magentablackcyanyellow ES316826_OT090113_022.pgs 09.06.2013 01:55 ADV WHO SAYS YOU CAN’T GO BEYOND INFINITI®*?

GO FURTHER. 2013 AT AAO.

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magentablackcyanyellow ES312046_OT090113_023_FP.pgs 08.29.2013 23:37 ADV 24 neuro-ophthalmology SepTeMber 1, 2013 :: Ophthalmology Times

Tracking visual loss in MS Time-domain OCT used to determine if thinning of retinal nerve fber layer continued by Lynda Charters; Reviewed by Stephen Moster, MS

Take-Home continued and was associated with visual loss in patients with MS. Patients with multiple sclerosis seem to have visual About the study loss and progressive thinning In this multicenter study, patients were of the retinal nerve fber layer followed every 6 to 12 months after over time, according to a baseline evaluation. Patients under- longitudinal study. went high- and low-contrast acuity testing and measurement of the RNFL (Stratus OCT-3, Carl Zeiss Meditec). PhiladelPhia :: The study included 196 patients isual loss and progres- (mean age, 44 years; 379 eyes). Three- sive thinning of the ret- quarters of patients were women. inal nerve fiber layer More than 80% had the relapsing/ (RNFL) occur over time remitting form of MS. Forty-three in patients with multi- percent of patients had a history of ple sclerosis (MS), ac- optic neuritis. cording to results from Results showed a trend in RNFL aV longitudinal study of visual func- thinning over time (Figure 1). tion and optical coherence tomog- “Notably, the trend continued past raphy (OCT). the 3-year time point and did not level “Axonal and neuronal loss are com- off,” he said. mon in (the disease) and have been Compared with baseline, at 5 to Parasol® shown pathologi- 7 years the RNFL decreased by –9.2 cally in the ante- µm (p < 0.001). rior visual pathway, An evaluation of the subgroup of A PERFECT FIT even in patients 153 eyes of patients with a history with no history of of optic neuritis also indicated the ODYSSEY MEDICAL + BEAVER VISITEC optic neuritis,” said same trend in thinning of the RNFL. Stephen Moster, MS. The same thinning was seen in the The Odyssey Parasol® Punctal Occluder is now part of Moster “The introduc- eyes of patients without a history of Beaver-Visitec International (BVI), a leader of trusted tion of OCT has optic neuritis. world ophthalmic brands. Not only is the Parasol® a perfect allowed research- “When we compared the amount fi t for your dry eye patients, but combining BVI with the ers to capture the structure/function of RNFL thinning between eyes with outstanding success of the Parasol®, continues the tradition correlations in MS and has brought and without a history of optic neuritis, of superior knowledge, products and services. the anterior visual pathway to the there was no significant difference in forefront as a model for testing new the amount of thinning between the For those of you who depend on a quality product from therapies,” said Moster, a fourth-year two groups,” Moster said. Odyssey Medical, WELCOME TO BVI. medical student at the University of Thinning of the RNFL progressed Your new ordering information: Pennsylvania, Philadelphia. by an average of about 1.9 µm annu- 866-906-8080 Data from the longitudinal study ally at the 7-year time point, which [email protected] showed that baseline RNFL in the eyes agreed with the rate of progression www.odysseymed.com of patients with MS was 91 µm com- at 3 years (Figure 2). www.beaver-visitec.com pared with 104 µm in healthy controls. In healthy controls, the annual rate The initial 3-year study showed sig- of RNFL thinning was about 0.16 µm. nificant progressive RNFL thinning “These results indicated that there from baseline to 3 years. is a steady subclinical axonal loss in Using time-domain OCT, Moster the anterior visual pathway in pa- Beaver-Visitec International, Inc. | 411 Waverley Oaks Road Waltham, MA 02452 USA | BVI, BVI Logo and all other trademarks (unless noted otherwise) are property of a Beaver-Visitec and colleagues extended the study tients with MS that continues beyond International (“BVI”) company © 2013 BVI to determine if the RNFL thinning 3 years,” Moster said.

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RNFL T inning, All Ms eyes (n = 379) RNFL T inning Versus time average thinning 1.9 μm/year (p < 0.001) 0 20 –0.6 (5.5) n = 95 -2 0 –2.6 (5.9) n = 190, p = 0.004 -4 -20

-6 –5.8 (8.9) n = 73, p < 0.001 -40 RNFL Thinning -8 95% Conf dence Interval Degree of RNFL thinning RNFL Thinning From Baseline (μm) RNFL Thinning From Baseline (μm) RNFL Thinning From signif cantly greater for all compared –9.2 (7.3) Regression Line with 0.5- to 1-year interval n = 22, p < 0.001 -60 -10 0 2 4 6 0.5 to 1 Year 1 to 3 Years 3 to 5 Years 5 to 7 Years Follow-up From Baseline, MS Eyes (Years)

( FIGURe 1) Patients were followed every 6 to 12 months after baseline (FIGURe 2) Thinning of the retinal nerve f ber layer progressed by an evaluation. Compared with baseline, at 5 to 7 years the retinal nerve average of ~1.9 µm annually at the 7-year time point, agreeing with the f ber layer decreased by –9.2 µm (p < 0.001). rate of progression at 3 years. (Figures courtesy of Stephen Moster, MS)

The percentage of eyes in patients with RNFL A notable finding was that eyes of patients a steady decrease in the RNFL thickness over loss also increased from 19% at 1 to 2 years after with visual loss over time did not have dif- time—suggesting progressive axonal loss in baseline to 56% at 5 to 7 years after baseline. ferences in the baseline RNFL thickness com- the anterior visual pathway that continues be- A history of optic neuritis was not predictive pared with the eyes of patients with steady yond 3 years after baseline. of the amount of RNFL thinning over time. vision, Moster said. The study findings also supported the use “Eyes with low-contrast visual loss over of OCT and low-contrast visual acuity test- VIsuAL ACuIty time had significant (p < 0.001) differences ing in MS trials. ■ Regarding visual acuity loss, researchers found in the amount of thinning of the RNFL over that eyes with greater visual loss had greater time compared with eyes with steady vision,” RNFL thinning. The percentage of eyes with Moster said. STePHeN moSTeR, mS visual loss by low-contrast visual acuity testing Based on these findings, the study concluded E: [email protected] increased from 7% during the early years of fol- that visual loss and thinning of the RNFL occur Moster has no f nancial interest in the subject matter. Research is supported by the low-up to 40% from 5 to 7 years after baseline. as a function of time in MS, and that there is National MS Society, National Eye Institute, McNeill Foundation, and DADs Foundation.

Retinal imaging may reveal stroke risk From staff Reports

SiNGaPORe :: A RETINAL EXAMINATION MAY to recommend changes in clinical practice. They found the risk of stroke was 35% higher be valuable for the assessment of stroke risk Other studies need to confirm the findings and in those with mild hypertensive retinopathy in patients with hypertension, suggests find- examine whether retinal imaging can be use- and 137% higher in those with moderate or ings from a recent study. ful in providing additional information about severe hypertensive retinopathy. “The retina provides information on the sta- stroke risk in people with high blood pressure. Even in patients taking medication and achiev- tus of blood vessels in the brain,” said Moham- Researchers tracked stroke occurrence for ing good blood pressure control, the risk of a mad Kamran Ikram, MD, PhD, lead author of an average 13 years in 2,907 patients with high blood clot was 96% higher in those with mild the study and assistant professor, Singapore blood pressure who had not previously expe- hypertensive retinopathy and 198% higher in Eye Research Institute, Department of Oph- rienced a stroke. Damage to the retinal blood those with moderate or severe hypertensive thalmology and Memory Aging & Cognition vessels attributed to hypertension (hyperten- retinopathy. Centre, National University of Singapore. sive retinopathy) evident on the imaging was The study was published Aug. 12 in the jour- However, Dr. Ikram noted that it is too early scored as none, mild, or moderate/severe. nal Hypertension. ■

magentablackcyanyellow ES316160_OT090113_025.pgs 09.05.2013 00:10 ADV This activity is supported by an unrestricted cme educational grant from Allergan, Inc. Release Date: September 1, 2013 article series Expiration Date: September 1, 2014 Learning Objectives The Vicious Cycle of Dry Eye Disease • Describe recent guideline protocols for diagnosing dry eye disease (DED), classifying DED severity, and differentiating underlying etiologies of DED yron, a 63-year-old farmer • List the current recommendations for the treatment with rosacea, comes to Additional CME Opportunity and follow-up of DED by level of severity and your ofÀce approximately underlying etiologies B 3 years after being diagnosed with

Ophthalmologist Accreditation dry eye secondary to meibomian gland dysfunction. Since the initial For further details about Byron, The Institute for Continuing Healthcare Education including insight into his long- is accredited by the Accreditation Council for diagnosis, his symptoms had Continuing Medical Education to provide continuing term treatment plan and possible been well controlled with topical complications, check out our medical education for physicians. cyclosporine 0.05% and lid hygiene. The Institute for Continuing Healthcare Education separate CME activity at designates this enduring material for a maximum of However, the recent exacerbation of www.iche.edu/dryeyecase2 0.75 AMA PRA Category 1 Credit(s)™. Physicians his dry eye-related visual discomfort should only claim credit commensurate with the and photophobia have made it extent of their participation in the activity. difÀcult for Byron to work outdoors. in the course of the disease and recognizing Claiming Credit It is important to note that Byron is that patients with DED secondary to a Please go to www.iche.edu/dryeye2 to claim AMA also being treated for rheumatoid chronic systemic condition (see Table 1) or credit. You will be directed to a host site for further arthritis (RA), with a regimen of oral ongoing, exacerbating medication will need to instruction. A complete reference list can also be prednisone and methotrexate. incorporate such strategies beyond the time of found online. initial symptom relief may prevent potentially To understand the complex nature of the 1 Disclosures serious complications of DED. vicious cycle of dry eye disease (DED), it may Relationships are abbreviated as follows: E, Educational help to envision the disorder as a disturbance of Hyperosmolarity is Key Planning Committee; G, Grant/research support the lacrimal functional unit, an integrated system recipient; A, Advisor/review panel member/educational One of the principal intrinsic causes of planning committee; C, Consultant/Independent that includes the lacrimal glands, the ocular chronic evaporative dry eye is meibomian Contractor; SS, Stock shareholder; SB, Speaker bureau; surface (cornea, conjunctiva, and meibomian gland dysfunction (MGD), which leads to an PE, Promotional Event Talks; H, Honoraria; O, Other. glands), the lids, and the sensory and motor unstable tear Àlm lipid layer, allowing excessive Faculty nerves that connect to these structures. When tear evaporation (for more on MGD, see last Mark Bloomenstein, OD: Allergan, Bausch and functioning properly, the lacrimal functional unit month’s article in this CME series). This excessive Lomb, Inc., AMO, TearLab/A, Allergan, Bausch helps to preserve the integrity of the tear Àlm, evaporation leads to an increase in the osmolarity and Lomb, Inc., AMO/PE, Allergan/G, Odyssey, the transparency of the cornea, and the quality Allergan, Bausch and Lomb, Inc., TearLab, Alcon/SB of the tear Àlm. Hyperosmolarity may also be of the visual image produced by the anterior- caused by dysfunction of the lacrimal secretory Mark T. Dunbar, OD: H, Carl Zeiss, Allergan, Artic most interface in the eye’s optical system.1 Dx, Sucampo, Reed Exhibitions/A, PE, G, H, Carl glands, which can occur, for instance, with RA Zeiss, Allergan, Artic Dx, Sucampo/SB DED varies in duration, severity, and cause. and/or Sjögren’s syndrome.2 Whatever the cause Stephen C. PÁugfelder, MD: Allergan, In most patients, it is marked by symptoms of or causes, hyperosmolarity is regarded as a central GlaxoSmithKline/A, Bausch and Lomb, Inc./C, ocular irritation and periods of blurred vision mechanism of dry eye, causing inÁammation Allergan, GlaxoSmithKline/G but is typically not sight-threatening. However, of and damage to the ocular surface, leading to Kelly Nichols, OD, MPH, PhD: Allergan, Alcon, DED that is left untreated and becomes severe symptom onset.1 Bausch and Lomb, Inc./PE, Allergan, Alcon, Bausch can lead to rare but serious complications, and Lomb, Inc., Sarcode, Nicox, RPS, TearLab/C, Hyperosmolarity and instability of the tear Àlm Allergan, NIH, TearLab, Alcon/CIBA, Vistakon/G, such as corneal damage (scarring, thinning, are drivers of the core mechanisms of DED. Sarcode, TearLab/SS neovascularization, or ulceration), ocular surface Hyperosmolarity leads to inÁammation of the 2 Clark Springs, MD: Santen, Tear Science/A, R-Tech, keratinization, and severe loss of vision. ocular surface and the release of inÁammatory Veno/G, Merck, Alcon/H In order to improve quality of life for patients mediators into the tear Àlm. The damage to the Neda Shamie, MD: Allergan, Bausch and Lomb, with DED, strategies that stimulate tear epithelium that results from this inÁammation, Inc., Nicox/C production, maintain the quality of the ocular including apoptosis, loss of goblet cells, and Medical Writer surface epithelium, and inhibit inÁammatory disruption of mucin production, leads to tear Tim Donald, Medical Writer, no relationships factors that impair tear production are Àlm instability, which further elevates tear to disclose recommended. Initiating such strategies early osmolarity. This is the vicious cycle of DED.1,3 Peer Reviewer Mark E. Schaeffer, OD: no relationships to disclose Conditions Contributing to Chronic Dry Eye Disease2 (Table 1) Activity Development and Management Team Conditions Examples Cathy Pagano, CCMEP; Allison A. Muller, Pharm.D, D.ABAT; Scott Kober, MBA, CCMEP; Chronic viral infections HIV, hepatitis C April Reynolds, MS, ELS; Sandra Davidson; and Megan Small; are employees of the Institute and Neurological conditions Parkinson’s disease, Bell’s palsy, trigeminal neuralgia have no relationships to disclose. Systemic medications Antihistamines, diuretics, hormones/hormone antagonists, Off-label Product Disclosure antidepressants, anticholinergic drugs, beta-adrenergic This educational activity includes discussion of antagonists, cardiac antiarrhythmic drugs published and/or investigational uses of agents that are not indicated by the U.S. Food and Drug Systemic inÁammatory diseases Sjögren’s syndrome, rheumatoid arthritis, systemic lupus Administration. Please refer to the ofÀcial prescribing erythematosus, scleroderma information for each product for discussion of Dermatological diseases Rosacea approved indications, contraindications, and warnings. Allergic conjunctivitis

magentablackcyanyellow ES312057_OT090113_026_FP.pgs 08.29.2013 23:37 ADV Diagnostic Workup Emerging Treatments for Dry Eye Disease (Table 2) Diagnostic workup of the patient with DED Treatment Action should include a careful ocular and systemic ® 13 history, external examination, visual acuity LipiFlow Thermal Pulsation System Applies controlled heat to the upper and lower inner eyelids, along with pulsation to evacuate meibomian glands measurement, and slit-lamp exam. Examination of the lids should include meibomian gland Maskin® Meibomian Gland Intraductal Provides symptomatic relief for patients with 14 expression to assess the functioning quality of Probes and Tubes obstructive MGD the secretions. Tests should include tear breakup Rebamipide ophthalmic suspension 2%15 Mucin secretagogue improved objective dry eye-related signs time to evaluate tear-Àlm stability, ocular surface (Regulatory approval in Japan, but not in the U.S.) and subjective ocular symptoms in a phase 3 trial staining with vital dyes (rose bengal, lissamine Topical anakinra 2.5%16 IL- antagonist signiÀcantly reduced symptoms green, or Áuorescein to evaluate ocular surface in patients with dry eye in a phase 1/2 trial disease, and Schirmer·s and Áuorescein clearance Diquafosol ophthalmic solution 3%17 Secretagogue had high clinical efÀcacy and was well tolerated tests to evaluate tear production and clearance. (Regulatory approval in Japan, but not in the U.S.) with a good safety proÀle in a phase  trial These tests can help to determine whether the 18 cause of an individual patient’s dry eye is an Recombinant human serum albumin Topical compound, RU-101: phase 2 trial has begun enrolling patients aTueous deÀciency, excessive evaporation, or a mixture of both.2 Recombinant hyaluronic acid19 Preclinical work has been presented A relatively new addition to the diagnostic IL=interleukin, MGD=meibomian gland dysfunction arsenal is tear osmolarity testing, which has punctal occlusion. In the most severe cases, the underlying corneal nerves. InÁammation on been shown to be more sensitive than other surgical correction of eyelid abnormalities or the ocular surface can interfere with the normal tests for grading the severity of DED.2,4 tarsorrhaphy may be necessary.2,8 neural connections that drive the tear reÁex. In one commercially available “lab-on-a-chip” If this type of nerve damage has occurred in a The Role of Inflammation test, which requires a tear sample of only 50 nL, patient with moderate DED, it is possible that a measurement of 316 mOsmol/L or greater Because inÁammation plays a central role in successful therapy may paradoxically appear is considered hyperosmolar, and an inter-eye the pathogenesis of DED, anti-inÁammatory to be making the patient worse. That is, when therapies have become a mainstay of treatment. difference greater than 8 mOsmol/L therapy begins to reverse the dry eye cascade 5 These include topical corticosteroids, is indicative of dry eye. Reduction in osmolarity and restore function to the ocular surface over time appears to precede symptomatic cyclosporine ophthalmic emulsion, and 1-3,8 nerves, the patient may once again become 6 tetracycline derivatives. Topical steroids and improvement. sensitive to the irritation caused by DED. cyclosporine are the anti-inÁammatory agents If this is the case, increased patient complaints Another promising lab-on-a-chip technology most frequently prescribed for DED.2 measures the level in the tears of matrix of irritation may actually indicate an metalloproteinase- MMP- , an inÁammatory Topical corticosteroids reduce symptoms improvement in the dry eye condition. It is marker that is elevated in DED.7 This technology of ocular irritation and decrease Áuorescein hoped that these new symptoms will eventually 9,10 has received regulatory approval in Europe staining. Short courses of topical steroids diminish as the patient continues to improve. and Canada, but not yet in the United States. at infrequent intervals can help suppress A number of new treatment options for DED Utilization of these and other objective tests for inÁammation and related irritation, but patients are now on the horizon. Several of these are diagnosis and follow-up of dry eye patients may must be monitored for ocular complications of listed in Table 2. improve the future management of DED. steroid use, such as cataract formation, elevation of intraocular pressure, and corneal melting.2 Conclusion Multifactorial Treatment Topical cyclosporine has been shown in DED is a complex disease that can require Approach clinical trials to decrease subjective measures multifactorial treatment. Effective diagnosis of DED, such as the need for artiÀcial tears depends on recognition of the presence DED can have multiple contributory factors, and symptoms of blurred vision, as well as of aTueous deÀcient and/or evaporative and it is therefore important to address as objective measures, such as corneal Áuorescein components, and management must address many as possible with appropriate therapy. Tear staining and anesthetized Schirmer test values.8 all aspects of the disease. As the multifaceted supplements may bring temporary relief, but In addition, artiÀcial tears prepared from nature of dry eye is increasingly recognized, these are palliative and not sufÀcient as a sole autologous serum can improve symptoms in new diagnostic modalities and treatments are treatment modality, especially in patients with most patients and help heal persistent epithelial emerging to help clinicians better manage the chronic DED. Patient education regarding the defects associated with DED.2 individual manifestations of DED present in causes and chronic nature of the individual’s each patient. particular form of DED is vital for successful Reversing the Dry Eye Cascade management.2 One result of the disruption of the lacrimal For DED due to evaporative tear loss, effective functional unit in DED may be dysfunction in Claiming Credit therapies include environmental modiÀcations Please go to www.iche.edu/dryeye2 and moisture chamber spectacles; eyelid therapy to claim AMA credit. A complete set to address blepharitis and meibomianitis; artiÀcial of references can be found online. tear supplements, gels, and ointments; omega-3 fatty acid supplementation; and a tetracycline antibiotic to address meibomianitis and rosacea.2,8 This activity is sponsored by In patients with severe DED, more aggressive treatments may be considered. These include systemic cholinergic agonists, systemic anti-inÁammatory agents, mucolytic agents, Image showing severe corneal staining in a patient with RA autologous serum tears, and permanent magentablackcyanyellow ES312055_OT090113_027_FP.pgs 08.29.2013 23:37 ADV 28 retina September 1, 2013 :: Ophthalmology Times

Defining the ‘iDeal’ DMe treatMent Point Laser treatment necessary for DME Subthreshold micropulse laser preferred over conventional laser By cheryl guttman Krader; Reviewed by Victor Chong, MD

Take-Home

Lasers continue to have a place in the treatment of diabetic macular edema with foveal involvement, despite the advent of anti-vascular endothelial growth factor therapy.

OxfOrd, England :: aser treatment—specifically, subthreshold micropulse laser treatment—has an important role in the management of diabetic macular edema (DME), accord- ing to Victor Chong, MD. “Historically, it was thought ldirect coagulation of the microaneurysms was the goal for laser treatment,” said Dr. PRE- AND POST-LASER Defending the role of subthreshold micropulse laser, Victor Chong, MD, Chong, department director, Oxford Eye Hos- reviewed randomized, controlled clinical trial evidence supporting laser treatment for diabetic pital, Oxford University Hospitals, Oxford, macular edema. Shown here are images preoperatively (left) and 12 months postoperatively (right) England. with subthreshold micropulse laser treatment. (Images courtesy of Victor Chong, MD) Now researchers know that the target is retinal pigment involvement with DME. In the study, patients tients treated with ranibizumab alone than epithelium cells—not the ret- were randomly assigned to treatment with: in those receiving ranibizumab plus laser, 7.6 ina—and that absorption of > Ranibizumab (Lucentis, Genentech) plus sham versus 4.5 letters, respectively. the laser energy by those cells laser. However, among the non-treated eyes, BCVA changes the microenviron- > Ranibizumab plus active (not deferred) laser. gain was greater for the group treated with both Dr. Chong ment, leading to closure of > Or, sham injection with active laser. ranibizumab and laser than for those receiv- microaneurysms and reduc- ing ranibizumab monotherapy, 8 versus 5.9 tion of edema, Dr. Chong said. With patients’ eyes categorized into three letters, respectively. “If one is going to use a laser, it needs to subgroups contingent on baseline retinal thick- “Eyes with prior laser treatment joined the be asked: Why would you want to scar the ness, it was clear that the anti-vascular endo- study as laser treatment failures, and so it is not retina?” he said. “Subthreshold micropulse thelial growth factor (VEGF) treatment was surprising to find in that situation [the] laser laser [treatment] delivers enough energy to best in the subgroup with the thickest retinas treatment did not add much value to ranibiz- produce the desired effect—but delivers the (>400 μm on time-domain optical coherence umab,” Dr. Chong said. “However, the out- energy in pulses so there is less collateral tomography), Dr. Chong said. comes were reversed for eyes with no prior retinal damage and no visible damage.” However, any benefit of anti-VEGF injec- laser treatment.” tion over laser monotherapy was minimal in Role of laseR eyes with retinal thickness of 300 μm or less. fuRtheR eviDence photocoagulation foR DMe Another subgroup analysis in RESTORE Results from the DRCR.net protocol I study Laser photocoagulation is still recognized as grouped eyes by whether they had prior laser show that even with ranibizumab injections, the standard of care when the fovea is not in- treatment. Though the differences between treat- laser treatment is often needed. volved, Dr. Chong said. ment arms were not statistically significant, Over the study period of 3 years, 46% of eyes However, data from the RESTORE study sup- within the subgroup that had prior laser, mean treated with ranibizumab with deferred laser port a place for laser treatment in eyes of patients change in best-corrected visual acuity (BCVA) still needed laser treatment. This was despite with visual impairment, secondary to foveal from baseline to 12 months was greater in pa- Continues on page 29 : Necessary

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Defining the ‘iDeal’ DMe treatMent CoUntERPoint Factors limit subthreshold laser for DME Why laser treatment currently not an important therapeutic modality By cheryl guttman Krader; Reviewed by Lloyd Paul Aiello, MD, PhD

Take-Home substantive visual sequelae from the laser than one-half of eyes in the anti-VEGF plus treatment. deferred laser group (54%) received no laser Presenting an opposing view, Dr. There have also been relatively few random- treatment by the end of 3 years. Aiello reviews effcacy and practical ized controlled trials investigating this tech- “If the idea for using subthreshold treat- limitations of subthreshold laser nique for treatment of DME, Dr. Aiello said. ment is to laser as little as possible, it then treatment for diabetic macular edema. The results from those reported do not indi- begs the question: Why laser at all?” said Dr. cate subthreshold laser treatment provides any Aiello, who is also director, Section of Eye Re- BOstOn :: major visual acuity improvement compared search and director, Beetham Eye Institute, he answer to the question of whether with standard laser approaches. Joslin Diabetes Center, Boston. “Indeed, as subthreshold laser treatment is an The subthreshold laser treatment also has seen in DRCR.net protocol I, we are finding important treatment for diabetic some practical limitations—it is difficult to tell with anti-VEGF therapy that the need for laser macular edema (DME) is “not at where the treatment was performed, and there- is markedly reduced.” this time,” according to Lloyd Paul fore difficult to assess treatment adequacy, lo- Current laser technology works for treating Aiello, MD, PhD. cation, efficacy, or re-treatment areas, he said. DME with no major sequelae, whereas sub- t threshold laser is difficult to visualize, has “The concept that subthreshold The availability of nondestructive, pharma- laser treatment may not cause substantial or cological approaches for treating DME is an- limited randomized trial data to support its permanent structural changes in the retina is other issue to consider. use, and no clear evidence at this time that it attractive,” said Dr. Aiello, professor of oph- As shown by results from the phase III RISE provides a better visual acuity outcome. thalmology, Harvard Medical School, Boston. and RIDE studies investigating ranibizumab The need for focal/grid laser treatment has “However, there are multiple factors that limit (Lucentis, Genentech), anti-VEGF injection re- also been reduced by the emergence of VEGF the importance of this treatment in the cur- sults in marked visual improvement in the inhibition and steroids, Dr. Aiello said. rent management of DME.” large majority of patients with DME. “Therefore, the answer to the question of In addition, outcomes from the DRCR.net whether subthreshold laser is currently an efficacy anD safety protocol I study indicate that adding laser when important treatment for DME has to be ‘no’,” of laseR photocoagulation initiating anti-VEGF therapy may not be ben- he said. ■ The benefit of focal/grid laser treatment for eficial in the long term. DME, Dr. Aiello said, is not as rapid or great In the latter study, patients randomly as- as what can be achieved with anti-vascular signed to anti-VEGF injection with prompt LLoyD PauL aieLLo, mD, PHD endothelial growth factor (VEGF) injections. laser had a significantly lower visual out- e: [email protected] Nevertheless, patients can achieve signifi- come at 3 years than those assigned to anti- Dr. Aiello is a consultant to Genentech and scientifc founder of Kalvista, which is cant gains in vision and reductions in central VEGF therapy with deferred laser. developing pharmaceutical treatment for diabetic macular edema. He has no fnancial subfield thickness over time, and without DRCR.net protocol I results also showed more interest or competing fnancial interest in any laser technology.

more than 70% of the ranibizumab-treated said, is a common reason retina specialists Necessary eyes had laser treatment at some point dur- give for not performing subthreshold micro- ing 3 years, even in the deferred laser group, pulse laser treatment for DME. However, he ( Continued from page 28 ) according to Dr. Chong. noted that anyone who has a transpupillary “If you are saying laser is not important in thermotherapy laser in fact has a micropulse receiving 14 intravitreal injections at a cost of the anti-VEGF era, it is like spending $30,000 laser because it is the same 810 diode laser. ■ about $28,000 over time (based on drug cost to buy a car and being told that about half of of about $2,000 per injection, not including the time you need to do something else to keep VicTor cHoNg, mD surgeon and facility fees). it working, but that something else is not im- e: [email protected] Considering about one-half of the eyes en- portant,” Dr. Chong said. Dr. Chong is a consultant for Iridex and Novartis, a speaker for Quantel, and tered into the trial had previous laser treatment, Not having a micropulse laser, Dr. Chong receives donated equipment from Iridex and Quantel.

magentablackcyanyellow ES316529_OT090113_029.pgs 09.05.2013 22:20 ADV 30 cataract SepTemBer 1, 2013 :: Ophthalmology Times

3 strategies for managing traumatic cataract in children Timing, IOL type, and lens calculations are important factors to recognize for pediatrics By lynda charters; Reviewed by Edward G. Buckley, MD

Take-Home “The answer depends on the anterior cham- Inflammation is an important factor when ber,” Dr. Buckley said. “If the chamber is not choosing the appropriate lens in these cases. There are several vital components in good shape after the initial surgery, waiting Acrylic IOLs can develop a great deal of de- surgeons need to take into is likely a better option to avoid a rocky post- posits and are not a good choice in an eye that consideration when treating children operative course with further complications. may have severe inflammation. who have traumatic cataracts. “The general rule is: When in doubt, don’t PMMA IOLs, however, are easier to clean do it,” he said. than acrylic lenses. No long-term data suggest a difference re- In the absence of adequate capsular sup- Durham, NC :: garding capsular implantation or sulcus fixa- port, the surgeon is faced with the choice of anaging traumatic cataracts tion in children with traumatic cataract. an anterior chamber lens or suturing a lens in children requires atten- “Exerting heroic efforts to put the IOL in the in the posterior chamber. tion to three issues when bag is probably not a good idea, especially in the “In children, the anterior chamber IOLs do implanting an IOL: namely, presence of a poor anterior segment,” he said. not have a good track record because of pupil the timing of the implanta- problems, persistent inflammation, hyphema, tion, the type of lens, and iol Types and glaucoma,” Dr. Buckley said. the IOL calculations, ac- There are two IOL options for use in children. A new lens (Artisan Iris Clip Lens, Ophtec) cordingm to Edward G. Buckley MD. may be advantageous, but the long-term per- However, there are several controversies re- > A single-piece polymethylmethacrylate (PMMA) formance is unknown. garding IOL implantation in children. lens is the hallmark IOL for use in inflamed IOLs that are sutured in place are associated Whether to implant the IOL eyes, Dr. Buckley said. This lens is implanted with complications during the initial surgery. in the sulcus or capsule, if through a 7-mm incision and is more suitable The long-term safety is a question that cen- the surgery is primary or sec- in the sulcus. ters around the 10-0 Prolene suture material, ondary, and how to deal with which tends to break (average time to break- the lack of capsular support > Other lenses include an acrylic, single-piece age, 6 years) in up to 33% of patients, accord- are some of the concerns, IOL (AcrySof IOL MA60AC, Alcon Laboratories) ing to Dr. Buckley. This can be avoided by said Dr. Buckley, professor that is foldable and implantable through a 4-mm using 9-0 Prolene. Dr. Buckley of ophthalmology and pedi- incision and another model (SA60AT, Alcon) that atrics and vice dean of medi- is injectable through a 2.75-mm incision. iol calculaTions cal education, Duke University School of Medi- There is a myopic shift in children over time cine, Durham, NC. The SA60AT IOL is by far the lens of choice that extends into the teen years. by 93.3% of pediatric ophthalmologists for in- “Surgeons need to consider the myopic shift Timing the-bag fixation, and not for implantation in ahead of time,” Dr. Buckley said. “The eye As a general rule in terms of the timing for the sulcus, he noted. should be undercorrected early to avoid very IOL implantation, Dr. Buckley said, “the later, The MA60AC IOL should be considered for high myopia later.” the better.” eyes with a great deal of inflammation. The formula used to calculate IOL powers If surgery in a patient’s inflamed eye can When sulcus fixation is desired, a three- does not matter. be avoided, the clinician will experience that: piece acrylic lens or a one-piece PMMA lens “Because timing is an issue, waiting until is the best choice, he said. the eye is ‘quiet’ is best,” he said. “The IOL > The procedure will be easier. To determine if a PMMA lens can be im- type depends on the implant location, which > The cornea will be clearer. planted in the sulcus, surgeons need to find dictates the optimal lens material. > The tissue will be less reactive. the degree of optic support that is available, “The myopic shift must be considered when > The IOL calculations will be more accurate. Dr. Buckley said. doing the IOL calculations,” Dr. Buckley said. ■ > There is a better chance of in-the-bag placement. If the capsule can support the optic, a MA60AC > There will be fewer postoperative issues. IOL is “perfectly satisfactory,” he said. The surgeon must determine if the IOL is in- In the absence of optic support, a PMMA edward G. Buckley, md serted during the primary surgery or during a lens may be a better choice, because it is suf- e: [email protected] secondary procedure. ficiently rigid to achieve adequate support. Dr. Buckley has no fnancial interest in the subject matter.

magentablackcyanyellow ES316051_OT090113_030.pgs 09.04.2013 23:22 ADV Current Concepts in Ophthalmology Presented by The Wilmer Eye Institute at Topics : Johns Hopkins University School of Medicine Activity Directors: • Glaucoma Walter J. Stark, MD and Neil M. Bressler, MD • Cataract and Anterior Segment Surgery • Laser-Assisted Cataract Baltimore, Surgery • Management of Maryland IOL Complications December 5-7, 2013 • Macular Degeneration Johns Hopkins University and Diabetic Retinopathy School of Medicine • Oculoplastics Thomas B. Turner Building • Refractive Surgery • Practice Management • Descemet’s Stripping Vail, and Descemet’s Membrane Endothelial Keratoplasty Colorado March 9-14, 2014 Special Features: Vail Marriott • OCT • Non-Surgical Supported by: Facial Rejuvenation • All the Clinical News in Sight Coding and Reimbursement

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magentablackcyanyellow ES312071_OT090113_031_FP.pgs 08.29.2013 23:39 ADV 32 refractive SepteMber 1, 2013 :: Ophthalmology Times

How WFG ablations compare No clear patient preference for wavefront-guided excimer lasers for myopic LASIK By fred Gebhart; Reviewed by Edward E. Manche, MD

Take-Home “What we’ve found . . . was that WFG abla- P a t i e n t , P h y S i c i a n tions yielded better results than WFO on both PreferenceS In a comparison of two wavefront- the VISX and the Allegretto,” he said. “If WFG There was no clear patient preference for one guided excimer lasers, one platform is better than WFO on both machines, it was platform over the other. About 23% of patients provides better clinical results on some only logical to compare WFG ablations.” preferred both the Allegretto and CustomVue measures but cannot image certain The prospective, randomized, contralateral lasers, just under 45% had no preference, and eyes. The other system can image nearly study treated both eyes in 50 subjects, a total the balance were unsure which they preferred. all eyes, but has slightly less robust of 100 eyes. One eye of each patient had WFG Though the Allegretto laser offered statisti- clinical results, research suggests. LASIK with the Allegretto laser, whereas the cally significantly better outcomes on several contralateral eye had WFG LASIK with the Cus- measures, patients themselves had no pref- tomVue laser. Eyes were randomly assigned by erence for one treatment over the other, Dr. Stanford, Ca :: ocular dominance, and all LASIK flaps were Manche said. ultiple trials suggest that constructed using a 150-kHz femtosecond laser The two surgeons, however, had very clear wavefront-guided (WFG) (IntraLase iFS, AMO). preferences. excimer ablations yield Eyes were closely matched by age, gender, “We imaged the patients on both machines better results for myo- and most visual measurements. The only statis- preoperatively and postoperatively,” he said. pic LASIK than wave- tically significant difference was slightly worse Preoperatively, the surgeons obtained im- front-optimized (WFO) myopia in the CustomVue group, –4.18 D com- ages of 100% of eyes on an aberrometer (VISX procedures. pared with –3.89 D in the Allegretto group. WaveScan, AMO), but could only obtain im- MBut how do WFG platform results compare? ages on 70% to 75% of eyes on another aber- A recent head-to-head comparison found that SimilaritieS, differenceS rometer (Allegretto Allegro Analyzer, Alcon). though one system (WaveLight Allegretto Wave One year after surgery, the two groups were sta- “It is very difficult to obtain good quality im- Eye-Q 400 Hz, Alcon Laboratories) produced tistically identical in terms of residual spherical ages on the Allegro Analyzer, and the ones we slightly better results for some clinical out- equivalent and residual cylinder, Dr. Manche obtained often took an extremely long time,” come measures than a similar excimer plat- noted. There were significant differences, how- Dr. Manche said. “Most people who use the form (VISX CustomVue S4 IR, Abbott Medical ever, in higher-order aberrations at 1 month (p Allegretto use the WFO treatment ablations, Optics [AMO]), the latter was easier to use and = 0.04) and at 12 months (p = 0.01). because the Allegro Anayzer is difficult to use.” could be used on eyes that The Allegretto eyes went from 0.38 µm pre- That may put clinicians in a bind, he ex- the first unit could not image. operatively to 0.33 µm after surgery compared plained. The Allegretto produces better results for “The take home is that you with 0.37 µm preoperatively in CustomVue eyes certain clinical outcome meaures, but imaging had excellent safety in both to 0.40 µm after surgery. Trefoil was reduced by can be difficult to impossible. The Custom Vue groups,” said lead author Ed- similar amounts in both groups. Coma was un- results are slightly lower for certain outcome ward E. Manche, MD, direc- changed in the Allegretto group and increased measures, but imaging rarely fails, he noted. tor of refractive and cornea slightly in the CustomVue group. Spherical ab- “I do 100% WFG procedures,” Dr. Manche Dr. Manche surgery and professor of oph- erration decreased in the Allegretto group and said. “If I can’t image [eyes of patients] on the thalmology, Byers Eye Insti- increased in the CustomVue group. Allegretto Allegro Analyzer, I [use] the VISX tute, Stanford University School of Medicine, Predictability was better in the Allegretto WaveScan. The VISX WaveScan can image al- Stanford, CA. group at 3 months (p = 0.04), 6 months (p = most anyone, with the exception of patients “No eyes lost more than 1 line of best-cor- 0.02), and 12 months (p = 0.04). with very small pupils or corneal scarring. It rected visual acuity (BCVA),” Dr. Manche said. Best uncorrected visual acuity was similar is an extremely robust system.” ■ “We had gains in both groups that were es- in the two groups at 1 month, 3 months, and sentially equivalent, with almost 50% gaining 12 months, but was significantly better in the discuss the merits of wavefront- 1 or more lines of BCVA. Allegretto group at 6 months (p = 0.04). There guided ablations at Facebook.com/ “It’s very difficult to obtain good quality im- was no statistically significant difference in OphthalmologyTimes. ages on the Allegretto,” he said. “You can only BCVA between the two groups. image about three-quarters of eyes . . . preopera- Subjective clarity presented the biggest dif- tively. Postoperatively, it was even more difficult.” ference between groups. Patients judged their Dr. Manche has conducted a number of prior Allegretto-treated eyes better both during the edward e. mancHe, md studies using both WFG and WFO platforms day (p = 0.005) and at night (p = 0.001) com- e: [email protected] from multiple manufacturers. pared with their CustomVue-treated eyes. Dr. Manche has no fnancial disclosures that relate to this story.

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magentablackcyanyellow ES310140_OT090113_036_CL.pgs 08.28.2013 22:23 ADV SeptemBer 1, 2013 :: Ophthalmology Times practice management 37

Taking one for the team When putting others before self for the good of the group can have meaningful outcomes putting it in view By Dianna E. Graves, COMT, BS Ed

Take-Home demonstrated they had matured enough in criSiS averted the past year to be groomed to become the I went over one morning to share the news The act of willingly making a next lead. with Patti, but she was already aware of the sacrifce for the beneft of others can As in the past, I would have spoke to the problem. reap rewards both in the short and candidates, discussed the potential of train- “So, it’s not too late. Should we choose long term. ing to be a lead, and waited for the reaction. one of the other technicians and wait a bit I have seen every possible reaction when more on Mandy?” I asked her. potentially moving a technician into a role “I can’t believe I am saying this—but, ecently, we needed to add a new outside of his or her comfort level—whether no,” Patti said. “[Mandy] is ready and I lead technician to the group. it be diagnostics, minor procedures, or being guess she should have my clinic so she can We have seven clinics located the lead. Reactions can range from: get a good start under her belt. I will go to throughout the St. Paul area, and Sara’s clinic and run it while she is gone. R the leads are in charge of running > Elation to absolute terror Then can we revisit it down the line when their respective clinic. things are settled down?” A lead technician works to ensure that: > Instant megalomaniac

> The technical staff is running up to speed and > The often-witnessed sullen behavior because working as a team. they don’t want be in charge–even though for ‘Being a lead is a years they have stated they could do it better! > The clinics are clean and safe for patients. different breed of For some reason, this time I spoke to three > The day is coordinated with the staffs at the of our seasoned leads and asked what they technician.’ front desk and in optical to ensure that all goes thought of my choices. Two agreed with my — Dianna E. Graves, COMT, BS Ed smoothly and calmly—or as calmly as it poten- selections, whereas the other, Patti, went tially can be. 180° and threw another name in the hat. In that moment, Patti had matured above By nature, some days are just whirlwinds running into trouble and beyond by taking one for the team and and other days are gentle breezes. Patti felt that a third technician, Mandy, was continuing to push for her teammate to be A couple of months ago, one of our cur- the best candidate. the next lead—even if it meant disrupting rent lead technicians from a busy two-physi- This sent me hurtling back to a day about her whole work life for a while. I was quietly cian office asked for a break from the action. 7 months ago, when Mandy walked in my so proud of Patti for stepping up into that She requested to be moved from her lead office and declared she wanted to be given a situation for the good of the group. role in order to go back to the general tech- chance to step up to a leadership role. And it stayed in the back of my mind— nician population and give her brain a rest. She felt she had matured enough to do so until last week. Losing a lead technician, even for a rest, and it was time for me to consider making can be very disruptive. However, I would her a lead when I had the next opportunity. not the only one rather let this technician relax a bit and be I was willing to give her a chance, but I was watching the evening news and saw a “just a tech” than to insist he or she stay in now I had a problem. story about Lance Cpl. Bradley O’Keefe who the role, burn out, and then possibly leave I needed one of the smaller, one-physician had been injured while on duty in Afghani- the practice. clinics to put her in so she could train and stan. He had finally been reunited with his Thus we began a search of the current learn—without being blown away by trying black labrador retriever, Earl, whose train- staff for the next lead. to run one of the manic and larger two- or ing was in bomb detection. three-physician clinics. Earl was a hero because he saved 13 Searching for the So where’s the problem? members of O’Keefe’s Army unit. The dog perfect lead The lead who recommended Mandy had has alerted them to a hidden explosive This is not an easy endeavor. Though all of the clinic where I needed Mandy to go! nearby just before it was set off by an un- the technicians in our group have laudable Patti would need to leave so that Mandy known enemy soldier. skills and talents, being a lead is a different could call it her own. Patti was going to O’Keefe was seriously injured by the breed of technician. have to go to our newest clinic that was a blast and was sent back home to the United I felt we had two technicians who had two-physician clinic and very busy. Continues on page 38 : For the team

magentablackcyanyellow ES312642_OT090113_037.pgs 08.30.2013 03:04 ADV BACITRACIN 38 SEPTEMBER 1, 2013 :: Ophthalmology Times OPHTHALMIC practice management OINTMENT USP STERILE

ter called and told the Rhode Island police DESCRIPTION: Each gram of ointment FOR THE TEAM chief of her brother’s story, the final decision contains 500 units of Bacitracin in a low was delegated to Maddox, who agreed with- melting special base containing White ( Continued from page 37 ) out hesitation. Petrolatum and Mineral Oil. “O’Keefe needs Earl more than I do,” said States, whereas Earl was sent back to an- Maddox, as he gave Earl’s leash to O’Keefe. ACTION: The antibiotic, Bacitracin, exerts other unit to continue service. O’Keefe and Earl were finally reunited at a profound action against many gram- While recovering, O’Keefe had lost hope the Rhode Island State Police headquarters, positive pathogens, including the com- of ever seeing his former partner again, where O'Keefe received a Purple Heart for mon Streptococci and Staphylococci. It is until his step-sister intervened on a mission his injuries in Afghanistan. also destructive for certain gram-negative of her own to track down Earl and reunite There are many forms of taking one for organisms. It is ineffective against fungi. him with her brother. the team—from O’Keefe’s injuries serving INDICATIONS: For the treatment of After a long year of looking, his sister was his country to Maddox returning his partner super fi cial ocular infections involving finally able to locate Earl. back to O’Keefe. the conjunctiva and/or cornea caused by When the military began to downsize its Of course, last but not least, there’s Patti Bacitracin susceptible organisms. K-9 corps, Earl was transferred to the United giving up her clinic so someone else could States. shine CONTRAINDICATIONS: This product Earl eventually was sent to Rhode Island, Who says there are no heroes left? Q should not be used in patients with a where he was assigned to Trooper Damien history of hypersensitivity to Bacitracin. Maddox. One of Earl’s and Maddox’s missions was PRECAUTIONS: Bacitracin ophthalmic responding to the Boston marathon bomb- DIANNA E. GRAVES, COMT, BS ED, is clinical services ointment should not be used in deep- ings to sweep for any additional explosives. manager at St. Paul Eye Clinic PA, in Woodbury, MN. Graves is a seated ocular infections or in those Even though Earl had been partnered graduate of the School of Ophthalmic Medical Technology, St. Paul, that are likely to become systemic. with Maddox—and might have worked 4 or MN, and has been a member of its teaching faculty since 1983. She The prolonged use of antibiotic con- 5 more years with him—when O’Keefe’s sis- can be reached at [email protected]. taining preparations may result in over growth of nonsusceptible organ- isms particularly fungi. If new infections Advertiser Index develop during treatment appropri- Advertiser Page Advertiser Page ate antibiotic or chemotherapy should be instituted. Alcon Laboratories Inc. 7, 13-14, 23 Lumenis CV3 Tel: 800/862-5266 Internet: www.opthalmic.lumenis.com ADVERSE REACTIONS: Bacitracin has Internet: www.alcon.com Micro Medical Devices 15 such a low incidence of allergenicity that Allergan Inc. 9-10 Tel: 866/730-0663 for all practical purposes side reactions are Tel: 714/246-4500 Internet: www.micromedinc.com practically non-existent. However, if such Customer Service: 800/433-8871 Fax: 714/246-4971 Odyssey Medical Inc. 24 reaction should occur, therapy should be Internet: www.allergan.com Tel: 901/383-7777 discontinued. Fax: 901/382-2712 Bausch + Lomb 17-18 Internet: www.odysseymed.com DOSAGE AND ADMINISTRATION: The Tel: 800/227-1427 Customer Service: 800/323-0000 Rhein Medical 5 ointment should be applied directly into Internet: www.bausch.com Tel: 800/637-4346 the conjunctival sac 1 to 3 times daily. Internet: www.rheinmedical.com In blepharitis all scales and crusts should Ellex CV2 Tel: 800/824-7444 Tissue Banks International 21 be carefully removed and the ointment Internet: www.slt-ellex.com Tel: 877/824-8113 then spread uniformly over the lid mar- Internet: www.visiongraft.org gins. Patients should be instructed to take Fera Pharmaceuticals Inc. 38, CV4 Tel: 414/434-6604 Wilmer Eye Institute 31 appropriate measures to avoid gross con- Fax: 414/434-4603 Tel: 410/502-9635 tamination of the ointment when applying Internet: www.ferapharma.com Internet: www.HopkinsCME.edu the ointment directly to the infected eye. ICHE 26-27 This index is provided as an additional service. Internet: www.bizmedicine.org The publisher does not assume any liability for errors HOW SUPPLIED: 3.5 g (1/8 Oz) sterile or omissions. tamper proof tubes, NDC 48102-007-35.

OPHTHALMOLOGY TIMES (Print ISSN 0193-032X, Digital ISSN 2150-7333) is published semi-monthly (24 issues yearly) by Advanstar Communications Inc., 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. 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. Printed in the U.S.A. Manufactured for: ©2013 Advanstar Communications Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical including Fera Pharmaceuticals, LLC by photocopy, recording, or information storage and retrieval without permission in writing from the publisher. Authorization to photocopy items for internal/educational or personal use, or the internal/educational or personal use of specific clients is granted by Advanstar Communications Inc. for libraries and other users registered with the Copyright Clearance Center, 222 Locust Valley, NY 11560 Rosewood Dr. Danvers, MA 01923, 978-750-8400 fax 978-646-8700 or visit http://www.copyright.com online. For uses beyond those listed above, please direct your written request to Permission Dept. fax 440-756-5255 or email: [email protected]. FPBC00N Rev. 08/09 You’ll Know the Real Thing when you see it

The superior choice for SLT is Lumenis SLT

ŽŵƉƌĞŚĞŶƐŝǀĞĐƵƐƚŽŵĞƌƐƵƉƉŽƌƚĐĂƉĂďŝůŝƟĞƐŝŶ ĂůŽĐĂƟŽŶŶĞĂƌLJŽƵ The largest installed-base of SLT products worldwide ĚŝǀĞƌƐŝĮĞĚ^>dĂŶĚŽŵďŝŶĂƟŽŶƉƌŽĚƵĐƚ ƉŽƌƞŽůŝŽ The only SLT product made in the USA The company that pioneered SLT technology and brought it to market KǀĞƌϰϱLJĞĂƌƐŽĨKƉŚƚŚĂůŵŝĐ>ĂƐĞƌ/ŶŶŽǀĂƟŽŶ

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O Proven therapeutic utility in a variety of superf cial ocular Important Safety Information infections—including blepharitis, conjunctivitis, and others Bacitracin ophthalmic ointment should not be used in OProfound activity against common gram-positive deep-seated ocular infections or in those that are likely pathogens—Streptococci, Staphylococci,1 and MRSA2,3 to become systemic. OA sensitivity and resistance prof le that’s remained virtually This product should not be used in patients with a unchanged over time4 history of hypersensitivity to Bacitracin. OUnsurpassed safety prof le—allergenicity and side reactions are practically non-existent1 BACITRACIN OPHTHALMIC O  1 Convenient dosing—1-3 times daily OINTMENT USP OTier 1 co pay vs. leading brands5

Please see adjacent page for full prescribing information

www.ferapharma.com

References: 1. Bacitracin Ophthalmic Ointment [Package Insert]. Locust Valley, NY; Fera Pharmaceuticals, LLC;2009. 2. Kowalski RP, Karenchak LM, Romanowski EG. Infectious disease: changing antibiotic susceptibility. Ophthalmol Clin N Am 2003;16:1-9. 3. 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;144:313-315. 4. Recchia FM, Busbee BG, Pearlman RB, Carvalho-Recchia CA, Ho AC. Changing trends in the microbiologic aspects of postcataract endophthalmitis. Arch Ophthalmol 2005;123:341-346. 5. http://fingertipformulary.com/drugs/Bacitracinopthalmicointment/ ©2012 Fera Pharmaceuticals, LLC Printed in USA FAB-001 02/12

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