Rivals Manual Technique

Cutting-edge AdvAnCements february 15, 2014 Vol. 39, No. 4 CliniCal Diagnosis surgery Drug therapy

OphthalmologyTimes.com follow us online: laser refractive lens surgery surgery TreaTmenT TacTics for lymphaTic rivals manual technique malformaTions a Femtosecond laser brings both advantages and distinct challenges to lens procedure Columbus, oH :: a decade of follow- up indicates percutaneous drainage and By Cheryl Guttman Krader; ablation of lymphatic malformations is VIDEO Reviewed by Michael Lawless, MD, and a safe and effective treatment. “We’re To watch the procedure, go to http:// Robert K. Maloney, MD able to achieve permanent remission bit.ly/1hgSOLh (Video courtesy of Robert K. Maloney, MD) and decrease the progression of the AccumulAting dAtA published fibrotic component of these lesions,” in the peer-reviewed literature demonstrate that said Kenneth V. Cahill, MD, FACS. b laser refractive lens surgery (LRLS) performed with ( See story on page 13 : Lesions ) a femtosecond laser offers certain safety advantages compared with manual surgery. special report However, surgeons who undertake the laser-assisted procedure must be aware that unique safety issues algoriThm gives accompany it, making appropriate patient selec- tion critical. boosT To allergic “If we can remove unpredictable events, perform specific tasks with greater precision, decrease the conjuncTiviTis chance of damage to collateral structures, introduce New bruNswiCk, NJ :: an algo- a The hydrodissection fuid wave is very subtle previously impossible maneuvers, and do all of that rithm for the management of aller- in femtosecond laser treatment, because the wave reproducibly, then we have a safer operation,” said gic conjunctivitis aims to increase con- travels between epinucleus and cortex, rather than Michael Lawless, MD, medical director, Vision Eye sensus among a variety of specialists between cortex and capsule. It is important to Institute, Chatswood, NSW, Australia, and clinical notice the wave and not continue to inject, which who may be dealing with ocular allergy. senior lecturer, Department of Ophthalmology, Syd- could result in overpressurization of the bag and The algorithm also addresses comor- posterior rupture. ney University Medical School. bidities such as dry eye and the possible impact on the ocular surface of b Complete free-foating capsulotomy. Point: safer than manual? (Image courtesy of Michael Lawless, MD) medications customarily used to treat “There is now a body of evidence in the peer-reviewed allergies, said Leonard Bielory, MD. literature from which we can say that LRLS has ( See story on page 21 : Allergy ) been shown to be or is likely to be safer than a manual procedure,” Dr. Lawless said. At the time of his discussion, he identified 74 pa- pers reporting on outcomes of LRLS, of which four were randomized controlled trials, 12 were controlled longitudinal studies, seven were considered to provide grade A or B evidence, and seven would be given a grade C evidence rating. Summarizing the findings, Dr. Lawless said that use of the laser creates more precise and more pre- ( Continues on page 18 : Safety )

magentablackcyanyellow ES390095_OT021514_CV1.pgs 02.15.2014 03:49 ADV Visual Performance. AcrySof ® IQ – The monofocal IOL proven to deliver excellent visual performance. Give your patients more time to react with the performance of AcrySof ® IQ IOL.

CONFIDENCE

magentablackcyanyellow ES388118_OT021514_CV2_FP.pgs 02.05.2014 19:09 ADV :: FEBRUARY 15, 2014 Ophthalmology Times contents 3

28 Special Report on page 21 CLINICAL CONCEPTS IN OCULAR ALLERGY

Surgery Clinical Diagnosis 13 6 DECODING CORNEAL 28 THE VITREOUS: SCARS TO 20/20 ORPHAN OF THE EYE Addressing anterior corneal Reversing degenerative changes scars with laser PRK may yield protective effect 13 TACTICS FOR 9 LYMPHATIC Drug T erapy MALFORMATIONS 34 ANTI-VEGF THERAPY: Therapy minimally invasive, Studies have shown that more preferable to surgical SAFETY TRENDS color vision discrimination resection Data provide limited insights is not adversely affected in on systemic effects individuals with the AcrySof® Natural IOL and normal color 14 CORNEAL INLAY vision. The effect on vision CAUTION : Federal (USA) law of the AcrySof® Natural IOL AND PRESBYOPIC InDispensable restricts this device to the in subjects with hereditary sale by or on the order of a THERAPY color vision defects and Long-term data show device 35 TRENDING: OPTICAL physician. acquired color vision defects gives boost to treatment INDICATIONS: The AcrySof® secondary to ocular disease DISPENSARY DESIGNS IQ posterior chamber (e.g., glaucoma, diabetic LED lighting, color contrasting, intraocular lens is intended retinopathy, chronic uveitis, 17 THREE SURGICAL and modernization transforming for the replacement of the and other retinal or optic optical displays human lens to achieve visual nerve diseases) has not been TIPS FOR ECP correction of aphakia in adult studied. Do not resterilize; patients following cataract do not store over 45° C; use WITH PHACO surgery. This lens is intended only sterile irrigating solutions Maximizing endoscopic Practice for placement in the capsular such as BSS® or BSS PLUS® cyclophotocoagulation bag. Sterile Intraocular Irrigating with cataract surgery Management Solutions. WARNING/PRECAUTION: Careful preoperative ATTENTION: Reference the 40 ‘OBAMACARE’ evaluation and sound clinical Directions for Use labeling AND EYE HEALTH judgment should be used for a complete listing of In Every Issue indications, warnings and DISPARITIES by the surgeon to decide 4 EDITORIAL the risk/beneft ratio before precautions. Provisions may help reduce implanting a lens in a patient 38 MARKETPLACE vision health inequalities with any of the conditions described in the Directions for Use labeling. Caution should be used prior to lens encapsulation to avoid lens decentrations or dislocations.

magentablackcyanyellow ES390079_OT021514_003.pgs 02.15.2014 03:18 ADV 4 editorial FEBRUARY 15, 2014 :: Ophthalmology Times

FEBRUARY 15, 2014 ◾ VOL. 39, NO. 4

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 ‘Best’ ways to die? 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 Two ophthalmologists go for a walk and contemplate death coding.doc L. Neal Freeman, MD, MBA Money Matters John J. Grande, Traudy F. Grande, and John S. Grande, CFPs® Neuro-Ophthalmology Andrew G. Lee, MD “Certainly,” he replied. “And will you do the Ophthalmic Heritage Norman B. Medow, MD By Peter J. McDonnell, MD same for mine?” Panretinal View Allen C. Ho, MD Plastics Pearls Richard Anderson, MD “Of course,” I said. Tech Talk H. Jay Wisnicki, MD director of the Wilmer Eye Institute, 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 GOOD AND BAD WAYS PUBLISHING/ADVERTISING Executive Vice President Georgiann DeCenzo editor of Ophthalmology Times. We then contemplated that if doctors really do [email protected] 440/891-2778 die better than other people, what would be the VP, Group Publisher Ken Sylvia [email protected] 732/346-3017 He can be reached at 727 Maumenee Building better and worse ways. Our list of good and bad Group Publisher Leonardo Avila [email protected] 302/239-5665 600 N. Wolfe St. Baltimore, MD 21287-9278 ways to “buy the farm” included: Associate Publisher Erin Schlussel [email protected] 215/886-3804 Phone: 443/287-1511 Fax: 443/287-1514 National Account Manager Rebecca A. Hussain [email protected] 415/932-6332 E-mail: [email protected] > Being bored to death listening to billing and Vice President Healthcare Technology Sales Drew DeSarle [email protected] 440/826-2848 coding experts. (Bad way to die.) Account Manager, Classif ed/Display Advertising Karen Gerome > [email protected] 440/891-2670 “The fear of death follows from the fear of life. A Being annoyed to death by the transition to Account Manager, Recruitment Advertising Christina Adkins [email protected] 440/891-2762 man who lives fully is prepared to die at any time.” ICD-10. (Even worse.) Account Manager, Recruitment Advertising Joanna Shippoli —Mark Twain > Death from laughing. (This has been docu- [email protected] 440/891-2615 Business Director, eMedia Don Berman mented to occur, and strikes me as a relatively [email protected] 212/951-6745 Director, Sales Data Gail Kaye A RECENT ARTICLE in The New York good way to go.) Sales Support Hannah Curis Reprints 877-652-5295 ext. 121 / [email protected] Times1 suggests that physicians—because we > Death from embarrassment. (Although I fre- Outside US, UK, direct dial: 281-419-5725. Ext. 121 List Account Executive Renée Schuster understand the implications of a serious illness quently hear people say they were so embar- [email protected] 440/891-2613 Permissions/International Licensing Maureen Cannon diagnosis and the implications of treatment rassed they nearly died, I am not aware of this [email protected] 440/891-2742 and associated morbidity—die “better” than do having actually occurred.) PRODUCTION non-physicians. Also, a study of graduates of > Death on the toilet (like Elvis Presley). (We Senior Production Manager Karen Lenzen my medical school showed these doctors were agreed this is not a great way to go, but defi- AUDIENCE DEVELOPMENT Corporate Director Joy Puzzo much more likely to have advanced directives nitely not the worst.) Director Christine Shappell (“living wills”) than other American adults. > Death in a whirlpool bath (like Orville Reden- Manager Wendy Bong Perhaps reading that article put me in the bacher). (Respect for the dead prevents me from frame of mind to contemplate my own mortal- making a joke about this, but I assume the whirl- Chief Executive Off cer: Joe Loggia ity while taking a walk for exercise with an- pool bath was more comfortable and pleasant Chief Executive Off cer Fashion Group, Executive Vice-President: Tom Florio other ophthalmologist. Although my ophthal- than Elvis’ toilet seat.) Executive Vice-President, Chief Administrative Off cer & Chief Financial Off cer: Tom Ehardt mologist friend practices in a city literally on Executive Vice-President: Georgiann DeCenzo the other side of the world from my own, we “Death from laughter has been known to Executive Vice-President: Chris DeMoulin Executive Vice-President: Ron Wall shared the same concerns: occur since the time of ancient Greece,” I told Executive Vice-President, Business Systems: Rebecca Evangelou Will our children be okay? Will our savings my friend. “People who write about the phe- Executive Vice-President, Human Resources: Julie Molleston Sr Vice-President: Tracy Harris be adequate to provide for the needs of our nomenon suggest it may result in either a heart Vice-President, Information Technology: Joel Horner loved ones? How should we make investments attack or asphyxiation.” Vice-President, Legal: Michael Bernstein Vice-President, Media Operations: Francis Heid today so that—if something bad happens to us “I see now why you studiously avoid any sem- Vice-President, Treasurer & Controller: Adele Hartwick tomorrow—people who count on us and may blance of humor in your editorials,” he replied. Advanstar Communications Inc. provides certain customer contact data (such as not have much financial sophistication will un- “Everyone says the best way to pass on is customers’ names, addresses, phone numbers, and e-mail addresses) to third parties who wish to promote relevant products, services, and other opportunities that may derstand what to do? probably quietly in one’s sleep. So that is proba- be of interest to you. If you do not want Advanstar Communications Inc. to make your contact information available to third parties for marketing purposes, simply call toll-free bly going to be my preference,” I told my friend. 866-529-2922 between the hours of 7:30 a.m. and 5 p.m. CST and a customer service representative will assist you in removing your name from Advanstar’s lists. Outside the BEING PREPARED “Nonsense,” was his reply. “The best way to die U.S., please phone 218-740-6477. ■ Ophthalmology Times does not verify any claims or other information appearing in any We discussed ways to allocate our investments is to follow the example of Nelson Rockefeller.” of the advertisements contained in the publication, and cannot take responsibility for any and prepare for the small chance that—despite losses or other damages incurred by readers in reliance of such content. Ophthalmology Times cannot be held responsible for the safekeeping or return of our both being healthy today and at the young- unsolicited articles, manuscripts, photographs, illustrations or other materials. Ophthalmology Times is a member of the Association of Independent Clinical est end of the baby boomer generation—some Publications Inc. sort of catastrophic injury or illness might lurk Library Access Libraries offer online access to current and back issues of Ophthalmology around the corner. Times through the EBSCO host databases. To subscribe, call toll-free 888-527-7008. Outside the U.S. call 218-740-6477. “This is what fathers like us have to do,” my friend said.

“If something bad happens to me, will you PRINTED IN help my family understand what to do?” I asked Reference U.S.A. my friend. 1. How doctors die. The New York Times, Nov. 20, 2013

magentablackcyanyellow ES389208_OT021514_004.pgs 02.13.2014 20:36 ADV February 15, 2014 :: 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 media brand that presents cutting-edge Peter J. McDonnell, MD Jules Stein Eye Institute, UCLA Massachusetts Eye & Ear Infirmary Los Angeles, CA Harvard University advancements and analysis from around the world in surgery, drug therapy, technology, and Wilmer Eye Institute Boston, MA Johns Hopkins University Ernest W. Kornmehl, MD clinical diagnosis to elevate the delivery of progressive eye health from physician to patient. Baltimore, MD Harvard & Tufts Universities Randall Olson, MD Boston, MA University of Utah Salt Lake City, UT Ophthalmology Times’ vision is to be the leading content resource for ophthalmologists. Associate Medical Editors Robert K. Maloney, MD Dimitri Azar, MD Los Angeles, CA Robert Osher, MD Through its multifaceted content channels, Ophthalmology Times will assist physicians University of Illinois, Chicago University of Cincinnati Chicago, IL Cincinnati, OH with the tools and knowledge necessary to provide advanced quality patient care in the global world of medicine.

Anterior Segment/Cataract Joel Schuman, MD Peter S. Hersh, MD Cornea/External Disease University of Pittsburgh Medical Center University of Medicine & Dentistry of New Jersey Pittsburgh, PA Newark, NJ Ashley Behrens, MD Wilmer Eye Institute, Johns Hopkins University Kuldev Singh, MD Jonathan H. Talamo, MD Baltimore, MD Stanford University Harvard University Stanford, CA Boston, MA Rubens Belfort Jr., MD Federal University of São Paulo Robert N. Weinreb, MD Kazuo Tsubota, MD São Paulo, Brazil Hamilton Glaucoma Center Keio University School of Medicine University of California, San Diego Tokyo, Japan Elizabeth A. Davis, MD University of Minnesota, Neuro-Ophthalmology Retina/Vitreous Minneapolis, MN Andrew G. Lee, MD Stanley Chang, MD Uday Devgan, MD Methodist Hospital, Texas Medical Center Columbia University Jules Stein Eye Institute,UCLA Houston, TX New York, NY Los Angeles, CA David Chow, MD Richard S. Hoffman, MD Oculoplastics/ University of Toronto Oregon Health & Science University Reconstructive Surgery Toronto, Canada Portland, OR Robert Goldberg, MD Pravin U. Dugel, MD Samuel Masket, MD Jules Stein Eye Institute, UCLA Phoenix, AZ Jules Stein Eye Institute,UCLA Los Angeles, CA Los Angeles, CA Sharon Fekrat, MD Nichamin* Femto Chopper John T. LiVecchi, MD Duke University Bartly J. Mondino, MD St. Luke’s Cataract & Laser Institute Durham, NC Jules Stein Eye Institute,UCLA Tarpon Springs, FL Los Angeles, CA Julia Haller, MD Shannath L. Merbs, MD Wills Eye Institute, Thomas Jefferson University Mark Packer, MD Wilmer Eye Institute, Johns Hopkins University Philadelphia, PA Oregon Health & Science University Baltimore, MD Portland, OR Tarek S. Hassan, MD Pediatric Ophthalmology Oakland University Michael Raizman, MD Rochester, MI Massachusetts Eye & Ear, Harvard University Norman B. Medow, MD Boston, MA Michael Ip, MD Albert Einstein College of Medicine University of Wisconsin Michael Snyder, MD Bronx, NY Madison, WI Cincinnati Eye Institute Jennifer Simpson, MD Carmen A. Puliafito, MD G Cincinnati, OH N University of California, Irvine LI Keck School of Medicine, USC E Walter J. Stark, MD V Irvine, CA Los Angeles, CA E Wilmer Eye Institute, Johns Hopkins University " H. Jay Wisnicki, MD T Baltimore, MD Carl D. Regillo, MD SE New York Eye & Ear Infirmary, Beth Israel Medical FF Wills Eye Institute, Thomas Jefferson University / Farrell “Toby” Tyson, MD Center, Albert Einstein College of Medicine Philadelphia, PA Cape Coral, FL New York, NY Lawrence J. Singerman, MD Glaucoma Practice Management Case Western Reserve University Cleveland, OH Robert D. Fechtner, MD Joseph C. Noreika, MD University of Medicine & Dentistry of New Jersey Medina, OH Uveitis Newark, NJ Frank Weinstock, MD Emmett T. Cunningham Jr., MD, PhD Neeru Gupta, MD Boca Raton, FL Stanford University 08-14569: Nichamin* Femto Chopper, Right Hand Dominant Surgeon University of Toronto Stanford, CA 08-14569-L Nichamin* Femto Chopper, Left Hand Dominant Surgeon Toronto, Canada Refractive Surgery Chief Medical Editors- G Malik Kahook, MD William Culbertson, MD N LI University of Colorado,Denver Emeritus E Bascom Palmer Eye Institute, University of Miami V E Denver, CO Miami, FL " Jack M. Dodick, MD T Richard K. Parrish II, MD SE Kenneth A. Greenberg, MD New York University School of Medicine FF Bascom Palmer Eye Institute, University of Miami / Danbury Hospital New York, NY (1976-1996) Miami, FL Danbury, CT David R. Guyer, MD Robert Ritch, MD New York University New York, NY (1996-2004) New York Eye & Ear Infirmary New York, NY s 5NIQUE$ISTAL4IP3PECIFICALLY$ESIGNED4O&IT)NTO New York, NY &EMTO,ASER#REATED#LEAVAGE0LANES Ophthalmology Times Industry Council s 4IP!NGULATION"END0ROMOTE3IMPLE%FFORTLESS John Bee Marc Gleeson Kelly Smoyer 3EPARATION/F,ASER&RAGMENTED3ECTIONS Rhein Medical Inc. Allergan Inc. Essilor of America President and CEO Vice President, U.S. Eye Care Pharmaceuticals Product Director Glaucoma and External Disease Marketing s 3PECIAL%RGONOMIC$ESIGN&ACILITATES)NTRA /CULAR William Burnham, OD John Snisarenko Carl Zeiss Meditec Inc. Ram Palanki Genentech USA Inc. -ANIPULATION!ND(ELPS4O0REVENT)NSTABILITY&ROM Director of Market Development, Americas ThromboGenics Inc. Vice President, Sales and Marketing 3IDEPORT,EAKAGE %NHANCING!NTERIOR#HAMBER Alastair Douglas Global Head – Marketing and Sales Chris Thatcher 3TABILITY Alcon Laboratories Inc. Daina Schmidt Reichert Technologies Director of U.S. Commercial Support Bausch + Lomb Surgical Division Vice President and Reichert Business Bob Gibson Global Executive Director of Product Strategy Unit Manager #ALL &OR-ORE)NFORMATION Topcon Medical Systems Inc. Vice President of Marketing

How to Contact Ophthalmology Times

Editorial Subscription Services Advertising Production 3360 Scherer Drive, Suite B, St. Petersburg, FL 33716 24950 Country Club Blvd., Toll-Free: 888/527-7008 or 485 Route 1 South 131 W. First St. s 4EL s &AX Suite 200 218/740-6477 Building F, Suite 210, Duluth, MN 55802-2065 %MAIL )NFO 2HEIN-EDICALCOM s 7EBSITE WWW2HEIN-EDICALCOM North Olmsted, OH 44070-5351 FAX: 218/740-6417 Iselin, NJ 08830-3009 800/346-0085 $EVELOPED )N #OORDINATIO 7ITH ,OUIS $ .ICHAMIN -$ 440/243-8100 732/596-0276 FAX: 218/740-7223, ,IBIAN 3IBYL -ICHEANGELO FAX: 440/756-5227 FAX: 732/596-0003 218/740-6576 1346 Rev.A AHBC

magentablackcyanyellow ES389207_OT021514_005.pgs 02.13.2014 20:36 ADV 6 surgery February 15, 2014 :: Ophthalmology Times

Decoding corneal scars: Straight to 20/20 vision First of a two-part article focuses on addressing anterior corneal scars with laser PrK Gloves Oﬀ with Gulani By arun c. Gulani, Md

Take-HoMe Arun C. Gulani, MD, explains his Gulani ‘corneal scar’ laser prk algorithm concept of addressing anterior corneal scars with laser PRK (not PTK) straight to 20/20. In the next article, Dr. Gulani will explain how to build the cornea DepTH reFracTion pacH TopoGrapHY paTTern with various modalities in presenting it for laser PRK.

In CorneaOn Cornea >20/30 <20/40 >400 <250 Reg Irreg Diffuse Focal y desire in these columns is simple— to change ophthalmolo- LK LK + AMT gists’ mindset! To free Laser PRK >20/30 Hard CL Rx eye surgeons from the Laser PRK DLK Laser PRK burden of technology NI PKP and terminology. MWhen looking at a corneal scar, the in- 2 Staged Laser PRK herent mindset is: “There is the culprit. Let’s eradicate it.” The refraction is the mainstay of the corneal scar algorithm, where vision better than 20/30 suggests straight laser Numerous diagnostic technologies are PRK and where vision less than 20/40, following a hard contact lens trial, can determine staged laser in two stages then deployed to “understand the scar and or a scar peel, followed by myopic ablation. its obviously criminal impact on vision.” Then, many ophthalmologists go through an elegant and complicated thought process how to build the cornea with various modal- For the sake of simplicity, I have divided to determine whether to choose laser PTK ities in presenting it for laser PRK. corneal scars into “on-cornea” scars, which (an optically incorrect surgery), diamond are above the Bowman’s membrane and lead burr application (a barbaric procedure on HOW cOrneaL scar to a camouflaged topography and mislead- an elegant visual organ), or a corneal trans- aFFecTs VisiOn ing refractive error and “in-cornea” scars, plant (a relatively interventional procedure Anterior corneal scars affect vision directly which actually become part of the cornea that should be the last resort, very much by blocking the optical pathway and indi- and are directly responsible for the topog- like having to open the entire abdomen to rectly, by altering the shape, and hence the raphy, and have a direct correlate to the re- get to the gall bladder) as the correct treat- refractive status. Using “Corneoplastique” fractive error. These can be lasered through. ment for this corneal scar. principles, we can use these very factors Instead of laser PTK, which chases the What I suggest instead is to look at the and reverse them to our advantage. scar and distorts the shape (costing us in vi- corneal scar and ask, “How can I use this In the Gulani 5S algorithm, surgeons can sion currency), why not reshape the cornea or modify this to help the patient see better see the impact of the corneal scar on vision and take it straight to vision (in many cases, with the least intervention?” and “Is it nec- and determine the patterned approach of cor- despite a residual scar)? essary to remove this and at what cost?” neal rehabilitation and laser or direct laser, For example, one of my patients presented By cost, I mean, the cost in “vision” cur- and straight reshaping to vision. The refrac- with a case of dense corneal scar following rency. Chasing the scar at the cost of vision tion is the mainstay of the corneal scar algo- herpetic infection 20 years ago. After removal is not acceptable. rithm, where vision better than 20/30 sug- of epithelium and confirming “in-cornea” In this article focusing on corneal scars, I gests straight laser PRK and where vision status (herpetic scars usually become part of will explain my concepts of addressing ante- less than 20/40, following a hard contact lens the cornea, thus producing a smooth surface rior corneal scars with laser PRK (not PTK) trial, can determine staged laser in two stages once the epithelium is removed), I proceeded straight to 20/20. In part 2, I shall explain or a scar peel, followed by myopic ablation. Continues on page 9 : Corneal scars

magentablackcyanyellow ES389821_OT021514_006.pgs 02.14.2014 22:56 ADV For the treatment of elevated IOP UNLOCK TREATMENT POSSIBILITIES

SIMBRINZA™ Suspension provided additional 1-3 mm Hg IOP lowering compared to the individual components1

■ IOP measured at 8 AM, 10 AM, 3 PM, and 5 PM was reduced by 21-35% at Month 32-4 ■ Efﬁ cacy proven in two pivotal Phase 3 randomized, multicenter, double-masked, parallel-group, 3-month, 3-arm, contribution-of-elements studies2,3 ■ The most frequently reported adverse reactions (3-7%) in a six month clinical trial were eye irritation, eye allergy, conjunctivitis, blurred vision, dysgeusia (bad taste), conjunctivitis allergic, eye pruritus, and dry mouth5 ■ Only available beta-blocker-free ﬁ xed combination2,3

INDICATIONS AND USAGE Severe Hepatic or Renal Impairment (CrCl <30 mL/min)—SIMBRINZA™ SIMBRINZA™ (brinzolamide/brimonidine tartrate ophthalmic suspension) Suspension has not been specifi cally studied in these patients and 1%/0.2% is a fi xed combination indicated in the reduction of elevated is not recommended. intraocular pressure (IOP) in patients with open-angle glaucoma or Adverse Reactions ocular hypertension. In two clinical trials of 3 months’ duration with SIMBRINZA™ Suspension, Dosage and Administration the most frequent reactions associated with its use occurring in The recommended dose is one drop of SIMBRINZA™ Suspension approximately 3-5% of patients in descending order of incidence included: in the affected eye(s) three times daily. Shake well before use. blurred vision, eye irritation, dysgeusia (bad taste), dry mouth, and eye allergy. SIMBRINZA™ Suspension may be used concomitantly with other topical Adverse reaction rates with SIMBRINZA™ Suspension were comparable to ophthalmic drug products to lower intraocular pressure. If more than one those of the individual components. Treatment discontinuation, mainly due to topical ophthalmic drug is being used, the drugs should be administered adverse reactions, was reported in 11% of SIMBRINZA™ Suspension patients. at least fi ve (5) minutes apart. Drug Interactions—Consider the following when prescribing IMPORTANT SAFETY INFORMATION SIMBRINZA™ Suspension: Contraindications Concomitant administration with oral carbonic anhydrase inhibitors is not recommended due to the potential additive effect. Use with high-dose SIMBRINZA™ Suspension is contraindicated in patients who are hypersensitive to any component of this product and neonates and salicylate may result in acid-base and electrolyte alterations. Use with infants under the age of 2 years. CNS depressants may result in an additive or potentiating effect. Use with antihypertensives/cardiac glycosides may result in additive or potentiating Warnings and Precautions effect on lowering blood pressure. Use with tricyclic antidepressants may Sulfonamide Hypersensitivity Reactions —Brinzolamide is a sulfonamide, blunt the hypotensive effect of systemic clonidine and it is unknown if use and although administered topically, is absorbed systemically. Sulfonamide with this class of drugs interferes with IOP lowering. Use with monoamine attributable adverse reactions may occur. Fatalities have occurred due oxidase inhibitors may result in increased hypotension. to severe reactions to sulfonamides. Sensitization may recur when a ™ sulfonamide is readministered irrespective of the route of administration. For additional information about SIMBRINZA Suspension, If signs of serious reactions or hypersensitivity occur, discontinue the use please see Brief Summary of full Prescribing Information on of this preparation. adjacent page. Corneal Endothelium—There is an increased potential for developing Learn more at myalcon.com/simbrinza corneal edema in patients with low endothelial cell counts.

™ References: 1. SIMBRINZA Suspension Package Insert. 2. Katz G, DuBiner H, TM Samples J, et al. Three-month randomized trial of fi xed-combination brinzolamide, 1%, and brimonidine, 0.2% [published online ahead of print April 11, 2013]. JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2013.188. 3. Nguyen QH, McMenemy MG, Realini T, et al. Phase 3 randomized 3-month trial with an ongoing 3-month safety extension of fi xed-combination brinzolamide 1%/brimonidine 0.2%. J Ocul Pharmacol Ther. (brinzolamide/brimonidine 2013;29(3): 290-297. 4. Data on fi le, 2013. 5. Whitson JT, Realini T, Nguyen QH, McMenemy MG, tartrate ophthalmic suspension) Goode SM. Six-month results from a Phase III randomized trial of fi xed-combination brinzolamide 1% + brimonidine 0.2% versus brinzolamide or brimonidine monotherapy in 1%/0.2% glaucoma or ocular hypertension. Clin Ophthalmol. 2013;7:1053-1060. ONE BOTTLE. MANY POSSIBILITIES.

magentablackcyanyellow ES388120_OT021514_007_FP.pgs 02.05.2014 19:09 ADV BRIEF SUMMARY OF PRESCRIBING INFORMATION Brinzolamide 1% - In clinical studies of brinzolamide ophthalmic tration of 14C-brinzolamide to pregnant rats, radioactivity was found INDICATIONS AND USAGE suspension 1%, the most frequently reported adverse reactions to cross the placenta and was present in the fetal tissues and blood. SIMBRINZA™ (brinzolamide/brimonidine tartrate ophthalmic reported in 5 to 10% of patients were blurred vision and bitter, Developmental toxicity studies performed in rats with oral doses of suspension) 1%/0.2% is a fixed combination of a carbonic anhydrase sour or unusual taste. Adverse reactions occurring in 1 to 5% of 0.66 mg brimonidine base/kg revealed no evidence of harm to the inhibitor and an alpha 2 adrenergic receptor agonist indicated for patients were blepharitis, dermatitis, dry eye, foreign body sensation, fetus. Dosing at this level resulted in a plasma drug concentration the reduction of elevated intraocular pressure (IOP) in patients with headache, hyperemia, ocular discharge, ocular discomfort, ocular approximately 100 times higher than that seen in humans at the open-angle glaucoma or ocular hypertension. keratitis, ocular pain, ocular pruritus and rhinitis. recommended human ophthalmic dose. In animal studies, brimoni- DOSAGE AND ADMINISTRATION The following adverse reactions were reported at an incidence dine crossed the placenta and entered into the fetal circulation to a The recommended dose is one drop of SIMBRINZA™ Suspension below 1%: allergic reactions, alopecia, chest pain, conjunctivitis, limited extent. in the affected eye(s) three times daily. Shake well before use. SIM- diarrhea, diplopia, dizziness, dry mouth, dyspnea, dyspepsia, eye There are no adequate and well-controlled studies in pregnant wom- BRINZA™ Suspension may be used concomitantly with other topical fatigue, hypertonia, keratoconjunctivitis, keratopathy, kidney pain, en. SIMBRINZA™ Suspension should be used during pregnancy ophthalmic drug products to lower intraocular pressure. If more lid margin crusting or sticky sensation, nausea, pharyngitis, tearing only if the potential benefit justifies the potential risk to the fetus. and urticaria. than one topical ophthalmic drug is being used, the drugs should be Nursing Mothers - In a study of brinzolamide in lactating rats, administered at least five (5) minutes apart. Brimonidine Tartrate 0.2% - In clinical studies of brimonidine decreases in body weight gain in offspring at an oral dose of 15 mg/ tartrate 0.2%, adverse reactions occurring in approximately 10 to DOSAGE FORMS AND STRENGTHS kg/day (150 times the recommended human ophthalmic dose) were 30% of the subjects, in descending order of incidence, included oral Suspension containing 10 mg/mL brinzolamide and 2 mg/mL observed during lactation. No other effects were observed. However, dryness, ocular hyperemia, burning and stinging, headache, blurring, brimonidine tartrate. following oral administration of 14C-brinzolamide to lactating rats, foreign body sensation, fatigue/drowsiness, conjunctival follicles, radioactivity was found in milk at concentrations below those in the CONTRAINDICATIONS ocular allergic reactions, and ocular pruritus. Hypersensitivity - SIMBRINZA™ Suspension is contraindicated in blood and plasma. In animal studies, brimonidine was excreted in Reactions occurring in approximately 3 to 9% of the subjects, in patients who are hypersensitive to any component of this product. breast milk. descending order included corneal staining/erosion, photophobia, It is not known whether brinzolamide and brimonidine tartrate are Neonates and Infants (under the age of 2 years) - SIMBRINZA™ eyelid erythema, ocular ache/pain, ocular dryness, tearing, upper Suspension is contraindicated in neonates and infants (under the age excreted in human milk following topical ocular administration. respiratory symptoms, eyelid edema, conjunctival edema, dizziness, Because many drugs are excreted in human milk and because of the of 2 years) see Use in Specific Populations blepharitis, ocular irritation, gastrointestinal symptoms, asthenia, potential for serious adverse reactions in nursing infants from SIM- WARNINGS AND PRECAUTIONS conjunctival blanching, abnormal vision and muscular pain. BRINZA™ (brinzolamide/brimonidine tartrate ophthalmic suspension) Sulfonamide Hypersensitivity Reactions - SIMBRINZA™ The following adverse reactions were reported in less than 3% of 1%/0.2%, a decision should be made whether to discontinue nursing Suspension contains brinzolamide, a sulfonamide, and although the patients: lid crusting, conjunctival hemorrhage, abnormal taste, or to discontinue the drug, taking into account the importance of the administered topically is absorbed systemically. Therefore, the same insomnia, conjunctival discharge, depression, hypertension, anxiety, drug to the mother. types of adverse reactions that are attributable to sulfonamides palpitations/arrhythmias, nasal dryness and syncope. Pediatric Use - The individual component, brinzolamide, has been may occur with topical administration of SIMBRINZA™ Suspension. Postmarketing Experience - The following reactions have studied in pediatric glaucoma patients 4 weeks to 5 years of age. The Fatalities have occurred due to severe reactions to sulfonamides been identified during postmarketing use of brimonidine tartrate individual component, brimonidine tartrate, has been studied in pedi- including Stevens-Johnson syndrome, toxic epidermal necrolysis, ophthalmic solutions in clinical practice. Because they are reported atric patients 2 to 7 years old. Somnolence (50-83%) and decreased fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and voluntarily from a population of unknown size, estimates of frequency alertness was seen in patients 2 to 6 years old. SIMBRINZA™ other blood dyscrasias. Sensitization may recur when a sulfonamide cannot be made. The reactions, which have been chosen for Suspension is contraindicated in children under the age of 2 years is re-administered irrespective of the route of administration. If signs inclusion due to either their seriousness, frequency of reporting, [see Contraindications]. of serious reactions or hypersensitivity occur, discontinue the use of possible causal connection to brimonidine tartrate ophthalmic Geriatric Use - No overall differences in safety or effectiveness have this preparation [see Patient Counseling Information] solutions, or a combination of these factors, include: bradycardia, been observed between elderly and adult patients. Corneal Endothelium - Carbonic anhydrase activity has been hypersensitivity, iritis, keratoconjunctivitis sicca, miosis, nausea, skin observed in both the cytoplasm and around the plasma membranes reactions (including erythema, eyelid pruritus, rash, and vasodilation), OVERDOSAGE of the corneal endothelium. There is an increased potential for de- and tachycardia. Although no human data are available, electrolyte imbalance, development of an acidotic state, and possible nervous system veloping corneal edema in patients with low endothelial cell counts. Apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, effects may occur following an oral overdose of brinzolamide. Serum Caution should be used when prescribing SIMBRINZA™ Suspension lethargy, pallor, respiratory depression, and somnolence have electrolyte levels (particularly potassium) and blood pH levels should to this group of patients. been reported in infants receiving brimonidine tartrate ophthalmic be monitored. Severe Renal Impairment - SIMBRINZA™ Suspension has not been solutions [see Contraindications]. Very limited information exists on accidental ingestion of brimonidine specifically studied in patients with severe renal impairment (CrCl DRUG INTERACTIONS in adults; the only adverse event reported to date has been hypo- < 30 mL/min). Since brinzolamide and its metabolite are excreted Oral Carbonic Anhydrase Inhibitors - There is a potential for an tension. Symptoms of brimonidine overdose have been reported in predominantly by the kidney, SIMBRINZA™ Suspension is not recom- additive effect on the known systemic effects of carbonic anhydrase neonates, infants, and children receiving brimonidine as part of med- mended in such patients. inhibition in patients receiving an oral carbonic anhydrase inhibitor ical treatment of congenital glaucoma or by accidental oral ingestion. Acute Angle-Closure Glaucoma - The management of patients with and brinzolamide ophthalmic suspension 1%, a component of Treatment of an oral overdose includes supportive and symptomatic acute angle-closure glaucoma requires therapeutic interventions in SIMBRINZA™ Suspension. The concomitant administration of therapy; a patent airway should be maintained. addition to ocular hypotensive agents. SIMBRINZA™ Suspension has SIMBRINZA™ Suspension and oral carbonic anhydrase inhibitors is not been studied in patients with acute angle-closure glaucoma. not recommended. PATIENT COUNSELING INFORMATION Sulfonamide Reactions - Advise patients that if serious or unusual Contact Lens Wear - The preservative in SIMBRINZA™, benzalkoni- High-Dose Salicylate Therapy - Carbonic anhydrase inhibitors ocular or systemic reactions or signs of hypersensitivity occur, they um chloride, may be absorbed by soft contact lenses. Contact lenses may produce acid-base and electrolyte alterations. These alterations should discontinue the use of the product and consult their physician. should be removed during instillation of SIMBRINZA™ Suspension were not reported in the clinical trials with brinzolamide ophthalmic but may be reinserted 15 minutes after instillation [see Patient suspension 1%. However, in patients treated with oral carbonic Temporary Blurred Vision - Vision may be temporarily blurred Counseling Information]. anhydrase inhibitors, rare instances of acid-base alterations have following dosing with SIMBRINZA™ Suspension. Care should be exercised in operating machinery or driving a motor vehicle. Severe Cardiovascular Disease - Brimonidine tartrate, a component occurred with high-dose salicylate therapy. Therefore, the potential of SIMBRINZATM Suspension, has a less than 5% mean decrease in for such drug interactions should be considered in patients receiving Effect on Ability to Drive and Use Machinery - As with other drugs blood pressure 2 hours after dosing in clinical studies; caution should SIMBRINZA™ Suspension. in this class, SIMBRINZA™ Suspension may cause fatigue and/or be exercised in treating patients with severe cardiovascular disease. CNS Depressants - Although specific drug interaction studies have drowsiness in some patients. Caution patients who engage in haz- ™, the possibility of an additive ardous activities of the potential for a decrease in mental alertness. Severe Hepatic Impairment - Because brimonidine tartrate, a not been conducted with SIMBRINZA or potentiating effect with CNS depressants (alcohol, opiates, barbitu- component of SIMBRINZA™ Suspension, has not been studied in Avoiding Contamination of the Product - Instruct patients that rates, sedatives, or anesthetics) should be considered. patients with hepatic impairment, caution should be exercised in ocular solutions, if handled improperly or if the tip of the dispensing such patients. Antihypertensives/Cardiac Glycosides - Because brimonidine tar- container contacts the eye or surrounding structures, can become trate, a component of SIMBRINZA™ Suspension, may reduce blood contaminated by common bacteria known to cause ocular infections. Potentiation of Vascular Insufficiency - Brimonidine tartrate, a pressure, caution in using drugs such as antihypertensives and/or Serious damage to the eye and subsequent loss of vision may result component of SIMBRINZATM Suspension, may potentiate syndromes cardiac glycosides with SIMBRINZA™ Suspension is advised. from using contaminated solutions [see Warnings and Precau- associated with vascular insufficiency. SIMBRINZA™ Suspension tions ]. Always replace the cap after using. If solution changes color Tricyclic Antidepressants - Tricyclic antidepressants have been should be used with caution in patients with depression, cerebral or or becomes cloudy, do not use. Do not use the product after the reported to blunt the hypotensive effect of systemic clonidine. It is not coronary insufficiency, Raynaud’s phenomenon, orthostatic hypoten- expiration date marked on the bottle. sion, or thromboangitis obliterans. known whether the concurrent use of these agents with SIMBRINZA™ Suspension in humans can lead to resulting interference with the Intercurrent Ocular Conditions - Advise patients that if they have Contamination of Topical Ophthalmic Products After Use - There IOP lowering effect. Caution is advised in patients taking tricyclic ocular surgery or develop an intercurrent ocular condition (e.g., trau- have been reports of bacterial keratitis associated with the use antidepressants which can affect the metabolism and uptake of ma or infection), they should immediately seek their physician’s ad- of multiple-dose containers of topical ophthalmic products. These circulating amines. vice concerning the continued use of the present multidose container. containers have been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the Monoamine Oxidase Inhibitors - Monoamine oxidase (MAO) inhib- Concomitant Topical Ocular Therapy - If more than one topical ocular epithelial surface [see Patient Counseling Information]. itors may theoretically interfere with the metabolism of brimonidine ophthalmic drug is being used, the drugs should be administered at tartrate and potentially result in an increased systemic side-effect least five minutes apart. ADVERSE REACTIONS such as hypotension. Caution is advised in patients taking MAO Clinical Studies Experience - Because clinical studies are conduct- Contact Lens Wear - The preservative in SIMBRINZA™, benzalkoni- inhibitors which can affect the metabolism and uptake of circulating ed under widely varying conditions, adverse reaction rates observed um chloride, may be absorbed by soft contact lenses. Contact lenses amines. in the clinical studies of a drug cannot be directly compared to the should be removed during instillation of SIMBRINZA™ Suspension, rates in the clinical studies of another drug and may not reflect the USE IN SPECIFIC POPULATIONS but may be reinserted 15 minutes after instillation. rates observed in practice. Pregnancy - Pregnancy Category C: Developmental toxicity ©2013 Novartis studies with brinzolamide in rabbits at oral doses of 1, 3, and 6 mg/ SIMBRINZA™ Suspension - In two clinical trials of 3 months U.S. Patent No: kg/day (20, 60, and 120 times the recommended human ophthalmic 6,316,441 duration 435 patients were treated with SIMBRINZA™ Suspension, dose) produced maternal toxicity at 6 mg/kg/day and a significant and 915 were treated with the two individual components. The most increase in the number of fetal variations, such as accessory skull ALCON LABORATORIES, INC. frequently reported adverse reactions in patients treated with SIM- bones, which was only slightly higher than the historic value at 1 and Fort Worth, Texas 76134 USA BRINZA™ Suspension occurring in approximately 3 to 5% of patients 6 mg/kg. In rats, statistically decreased body weights of fetuses from 1-800-757-9195 in descending order of incidence were blurred vision, eye irritation, dams receiving oral doses of 18 mg/kg/day (180 times the recom- [email protected] dysgeusia (bad taste), dry mouth, and eye allergy. Rates of adverse mended human ophthalmic dose) during gestation were proportional reactions reported with the individual components were comparable. to the reduced maternal weight gain, with no statistically significant Treatment discontinuation, mainly due to adverse reactions, was effects on organ or tissue development. Increases in unossified reported in 11% of SIMBRINZA™ Suspension patients. sternebrae, reduced ossification of the skull, and unossified hyoid Other adverse reactions that have been reported with the individual that occurred at 6 and 18 mg/kg were not statistically significant. No components during clinical trials are listed below. treatment-related malformations were seen. Following oral adminis- © 2013 Novartis 8/13 SMB13064JAD

black ES388119_OT021514_008_FP.pgs 02.05.2014 19:09 ADV February 15, 2014 :: Ophthalmology Times 9 surgery

corneal scars a B

( Continued from page 6 )

with a refractive laser ablation, and applied mitomycin-C for 30 seconds to the central cornea. Upon application of balanced saline solution, the light reflex had become circular, which translates to vision. This patient ended with uncorrected vision of 20/25+ and was scar Pre-laser Post-laser Vsc 20/15 thrilled with her outcome. c D On-cOrnea and in-cOrnea scars On-cornea scars can be peeled off right under the laser using the cornea as what I call a “resistance-guided platform” which is comprised of pulling on the scar, making sure to remove it completely, in one piece, using the rest of the cornea as your resistance platform. This is followed by refractive PRK (always with mitomycin-C appli- scar Pre-laser Post-laser Vsc 20/20 cation) as single stage or myopic PRK to be Laser Trough in-cornea scars: This in-cornea scar refects the true topography and true followed by stage two for refractive PRK to refraction. Surgeons may also notice some postoperative residual scar in cases, but the vision is still 20/20 and emmetropia. better. (Images courtesy of Arun C. Gulani, MD) Deeper on-cornea scars can also be peeled off using patience and a resistance- guided technique as well to peel them gen- a B tly off of the rest of the cornea. Once again, try to maintain the entire piece as a single removal technique. Once it clears the visual axis, you can proceed with refractive laser PRK ablation, followed again by the application of mitomycin-C. This can result in complete central clarity, to an excellent outcome. In this case, the patient’s on-cornea scar was peeled of gently using the cornea as a resistance-guided platform followed by my- Preop corneal scar Postop corneal scar Vsc 20/20 opic laser application with mitomycin-C for 20 seconds, resulting in an outcome of 20/20 c D uncorrected vision. In summary, in-cornea scars can be lasered directly in the PRK mode, shaping the cornea, and indirectly removing the scar, straight to a visual outcome. In cases of on-cornea scars, the scar can be gently peeled off, maintaining all the principles we discussed about using the corneal platform as a resistance-guided technique in lifting the entire scar gently, in full Preop corneal scar Postop corneal scar Vsc 20/25 completion, off the remaining cornea. Laser + scar Peel (On-cornea): Notice how the topography is a camoufage due to the on- This is followed by laser PRK with mi- cornea scar with false refractive error prior to laser refraction. (Images courtesy of Arun C. Gulani, MD) tomycin-C and a bandage contact lens to reach tremendous visual outcomes (single or two-staged). stage (the endpoint always being emmetro- egance possible, maintaining the princi- Intraocular optical manipulation in the pia, with an indirect goal of scar removal). ples of “Corneoplastique” surgery—topical, form of lens based (pseudophakic and pha- No matter how bad the scar looks, let us brief, aesthetically pleasing, and visually kic implants) techniques can be combined to use our algorithm to insist on taking pa- promising. aim for myopic PRK before or after as second tients straight to vision, with the most el- Continues on page 12 : Laser PRK

magentablackcyanyellow ES389822_OT021514_009.pgs 02.14.2014 22:56 ADV Today, she presents with dry eye symptoms.

magentablackcyanyellow ES388135_OT021514_010_FP.pgs 02.05.2014 19:10 ADV What will she look like by the time she is diagnosed?

For millions of dry eye patients, their symptoms could be an early sign of a progressive autoimmune disease.1,2

As many as 1 in 10 patients with dry eye also have Sjögren’s Syndrome, a chronic condition of deteriorating exocrine glands that can have signiÄcant systemic ramiÄcations.2-4 Today, it takes an average of 4.7 years to receive an accurate diagnosis.2 Together with the Sjögren’s Syndrome Foundation, Nicox is out to change that.

1oin us in the Äght at morethandryeye.com, or call 1.855.MY.NICOX (1.855.6 6.426 ) to learn more.

References: 1. Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjögren syndrome. Arch Intern Med. 2004;164:1275-1284. 2. Sjögren’s Syndrome Foundation. Sjögren’s Syndrome Foundation. 2001. Available at http://www.sjogrens.org. Accessed September 5, 2013. 3. Liew M, Zhang M, Kim E, et al. Prevalence and predictors of Sjögren’s syndrome in a prospective cohort of patients with aqueous-defcient dry eye. Br J Ophthalmol. 2012;96:1498-1503. 4. Martin LS, Massafra U, Migliore A. Sjögren’s syndrome: an under-diagnosed disorder. CLI. May 2004.

magentablackcyanyellow ES388134_OT021514_011_FP.pgs 02.05.2014 19:10 ADV 12 February 15, 2014 :: Ophthalmology Times surgery

Arun C. Gulani, MD, explains his concept Both of these video clips show two unique cases of corneal scars with what is considered of addressing anterior corneal scars with laser “irreparable” and yet can be corrected to 20/20 in a matter of minutes, according to Arun C. Gulani, MD. PRK (not PTK) straight to 20/20 vision. Go to http://bit.ly/1kyJYcm and http://bit.ly/1h81PGz. (Videos courtesy of Arun C. Gulani, MD) Go to http://bit.ly/1bJtAgO

corneal scar Before/clear cornea after Laser: Left: Dense central scarring in post-RK cornea. Right: Clear postoperative cornea.

Laser + scar Peel (On-cornea): Scar peel in action.

Postop day 4 http://www.healio.com/ophthalmology/ laser prk cornea-external-disease/news/print/ ocular-surgery-news/%7Bc9f4a51f- cba8-472c-afc9-0d688d30a7cc%7D/ ( Continued from page 9 ) combined-corneal-scar-excision-prk- surgery-seeks-unaided-emmetropia. Refractive laser PRK surgery— • Gulani AC. Corneoplastique system repairs cornea before or after laser when practiced as an art—not stem cell scar: Laser PRK to 20/20. only can address virgin eyes refractive surgery. Ocular Surgery News. 2007;25:124-125. with all levels of ametropia, but • Gulani AC. “Excimer laser PRK and also reverse and correct com- corneal scars: Refractive surgery to the plex as well as complicated cases rescue.” In: Textbook Mastering Advance with corneal scars back to 20/20. Surface Ablation Techniques. New Dehli, Refractive surgery truly then can India: JP Publishers. 2007;246-248. • Gulani AC. “Irregular astigmatism ■ come to its own rescue! management in unstable cornea.” In: Textbook of Irregular Astigmatism. References Thorofare, NJ: Slack Inc. 2007;251-261. • Gulani AC. Using excimer laser PRK— not PTK—for corneal scars: Straight to 20/20 vision. Advanced Ocular Care. 2012(Sept/Oct);1-3. Herpes scar: Dense herpetic scar with divot corrected with laser PRK • Gulani AC. Combined corneal scar arun c. Gulani, MD, is director to 20/30. (Images courtesy of Arun C. Gulani, MD) excision, laser PRK surgery seeks of the Gulani Vision Institute, Jacksonville, unaided emmetropia. Ocular Surgery FL. Dr. Gulani has no fnancial interests News. June 20, 2008. to declare.

magentablackcyanyellow ES389823_OT021514_012.pgs 02.14.2014 22:56 ADV February 15, 2014 :: Ophthalmology Times 13 surgery

Tactics for lymphatic malformations Percutaneous drainage and ablation minimally invasive, preferable to surgical resection By nancy Groves; Reviewed by Kenneth V. Cahill, MD, FACS

Take-home trast to confirm the extent of the a b cyst, make sure there is no commu- Percutaneous ablation of nication of cysts within the orbit, lymphatic malformations is and check for leakage around the a safe, effective alternative catheter. Ultrasound can be used to surgical resection, based instead of fluoroscopy to document on extensive follow-up the catheter placement. of a large series of cases Once the macrocyst has been performed at a leading drained and its extent and intact- pediatric hospital in the ness have been evaluated, sodium United States. c D morrhuate is introduced then withdrawn and rinsed after its dwell time. The second step is introduction Columbus, oH :: of absolute alcohol, which is also more thAn A decAde then withdrawn and rinsed. Next, of follow-up indicates that percu- the catheter that had been left in taneous drainage and ablation of place is attached to a suction bulb. lymphatic malformations is a safe “We find that draining out any and effective treatment approach. serous fluid that leaks from the de- e f “We find that we’re able to achieve endothelialized cyst decreases post- permanent remission and decrease operative swelling and seems to im- the progression of the fibrotic com- prove the success rate of collapsing ponent of these lesions,” said Ken- these cysts,” Dr. Cahill said. neth V. Cahill, MD, FACS, in prac- Follow-up includes ophthalmic tice in Columbus, OH. exams and B-scan ultrasound to Observation of a series of more monitor recovery. More than one than 80 patients followed up to 12 treatment is necessary for most years demonstrates that the best patients. road map for treatment is T2 images on magnetic resonance imag- other treatment ing, judicious use of fluoroscopy ProtoCols with radiation minimization, and Variation in lesions may alter the ultrasonography for evaluation and treatment protocol. Some are la- a Pre-treatment clinical photo b Post-treatment photo after treatment, Dr. Cahill said. beled venolymphatic, a clinical showing severe right proptosis two sclerotherapy treatments with This minimally invasive outpa- rather than histopathological de- and hypoglobus with conjunctival sodium tetradecyl sulfate and injection. ethanol showing signifcant reduction tient procedure is preferable to sur- scription. In these cases, a bloody in proptosis and hypoglobus. gical management, he added. fluid rather than serous fluid slowly c Pre-treatment T2 magnetic reaccumulates in the cavity, and resonance imaging (MRI) in D Post-treatment T2 MRI in the how the ProCedure no vascular communication can be the axial plane showing a large axial plane after sclerotherapy worKs detected radiographically. Patients macrocyst occupying the majority showing resolution of the macrocyst. The approach that Dr. Cahill, Wil- with a microscopic amount of blood of the right orbit causing severe liam E. Shiels II, DO, and others at in their cystic fluid tend to require proptosis. f Intraoperative fuoroscopic image Nationwide Children’s Hospital, Co- more treatments than those who during treatment of a large macrocyst lumbus, pioneered to manage lymph- have “pure” lymphangiomas or a e Intraoperative photo using with injection of contrast through a angioma macrocysts (>1 cm) is to non-bloody fluid. ultrasound-guided aspiration and pigtail catheter to defne the extent enter the lesion with an angiocath- Pupil dilation is a side effect that injection of the orbital lymphatic of the lymphatic malformation and malformation. ensure no extravasation into normal eter through which a flexible pig- may occur with treatment of large orbital tissue and no active vascular tail catheter is introduced. retrobulbar cysts, but in all cases it communication. (Images courtesy of The catheter remains in place to has fully resolved, Dr. Cahill said. Kenneth V. Cahill, MD, FACS) withdraw fluid and instill radiocon- Continues on page 20 : Lesions

magentablackcyanyellow ES390094_OT021514_013.pgs 02.15.2014 03:49 ADV 14 February 15, 2014 :: Ophthalmology Times surgery

Long-term data for corneal inlay expanding outcomes for presbyopia Monocular uncorrected near visual acuity improved by an average 3.4 lines at 3 years By lynda Charters; Reviewed by John A. Vukich, MD

Take-home Implantation of the corneal inlay—a monocular procedure that is performed in the OphthalmologyTimes.com Long-term clinical trial data non-dominant eye—is performed during an Online Exclusive for a small-aperture corneal inlay intralamellar dissection that resembles a (Kamra, AcuFocus) for presbyopia pocket into which the device is positioned PhySICIan-PaTIenT turned in superb results. over the pupil. Eyes with the inlay had an average gain ReCeIveS CORneaL in monocular UNVA of 3.4 lines preopera- InLay In hIS Own eye madisoN, wi :: tively to 36 months after implantation, Dr. A smAll-Aperture corneal inlay Vukich noted. (Kamra, AcuFocus) for presbyopia yielded superb results in an analysis of long-term data. 3 6 - m o n t h Monocular uncorrected near visual acuity follow-uP Period (UNVA) improved by an average 3.4 lines, in- “Importantly, this gain in vision was a sustained termediate visual acuity improved slightly, and improvement that was maintained over the distance visual acuity was unchanged—all of 36-month follow-up period,” Dr. Vukich said. which is very encouraging All study eyes completed the 36-month fol- for patients with presbyopia, low-up examination. said John A. Vukich, MD, sur- An important consideration in patients with gical director, Davis Duehr presbyopia is the status of intermediate vision. Dean Center for Refractive In the study eyes, monocular uncorrected in- Surgery, Madison, WI. termediate visual acuity (UIVA) improved, but Dr. Vukich highlighted as expected not to the same extent as near Dr. Vukich 3-year data from the pro- vision. The mean UIVA was 20/25. spective, non-randomized “It is important that there was no loss of U.S. clinical trial with the inlay that included intermediate vision during the follow-up pe- turning the tables 507 patients who were naturally occurring riod,” he said. to become a corneal inlay patient himself, Jeffrey Machat, MD, FRSCS, presbyopic emmetropes (age range, 45 to 60 In addition, monocular uncorrected dis- underwent implantation of the presbyopic years). tance visual acuity was maintained over the device (Kamra, AcuFocus) in his own eye. To course of the study in the learn more about Dr. Machat’s surgery and the eyes with the inlay. visual outcomes, go to http://bit.ly/1dOPM8y. “The average distance ‘It is important that there was visual acuity remained better than 20/20,” Dr. no loss of intermediate vision Vukich said. He noted that—while 5 years after surgery, Excellent uncorrected normal progression of presbyopia would be during the follow-up period.’ distance binocular visual expected as a result of lessening of the accom- acuity also was main- modative ability—the patients continue to do — John A. Vukich, MD tained at an average of well despite natural presbyopic progression. 20/16 over the duration “This indicates that the vision is unaffected of the study. by the continuing presbyopic changes,” Dr. Vu- Long-term results kich said. “This is certainly encouraging.” ■ Refractive errors in this patient popula- showed that UNVA improved from a mean tion were low levels of myopia and hypero- of J8 to J2 in the eyes with the inlay from pre- pia (–0.75 and 0.5 D) with no more than 0.5 operatively to 1 month postoperatively and D of astigmatism. was maintained to 5 years after surgery. The john a. vukich, mD All patients had UNVA worse than 20/40 vision in the eye with the inlay and in both e: [email protected] and better than 20/100. Best-corrected distance eyes was unaffected by the progression of Dr. vukich is a consultant to and chairman of the medical advisory board of acuFocus. visual acuity was 20/20 or better bilaterally. presbyopia, Dr. Vukich said. the device is investigational and not available commercially in the united states.

magentablackcyanyellow ES390091_OT021514_014.pgs 02.15.2014 03:50 ADV magentablackcyanyellow ES388117_OT021514_015_FP.pgs 02.05.2014 19:09 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 (eyelid) 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 ES388114_OT021514_016_FP.pgs 02.05.2014 19:09 ADV February 15, 2014 :: ophthalmology Times 17 surgery

3 surgical tips for ECP combined with phaco Pearls focus on maximizing endoscopic cyclophotocoagulation with cataract surgery By cheryl Guttman krader; Reviewed by Robert J. Noecker, MD, MBA

Take-Home appointed with the outcome of ECP in pha kic patients. ECP and PhaCo Thorough treatment of the ciliary “Therefore, a good tip when combining ECP processes—combined with measures with cataract surgery is to treat the ciliary for minimizing postoperative IOP processes through the capsule,” Dr. Noecker spikes and infammation—will lead to continued. improved outcomes when performing endoscopic cyclophotocoagulation with cataract surgery. avoid postoperative 2 iop spikes. All cataract surgeons recognize the importance of meticulous removal of viscoelastic at the FairField, CT :: end of the case in order to avoid postopera Endoscopic cyclophotoco- tive IOP spikes, and the need is even greater agulation (Ecp) can be performed when combining cataract surgery with ECP in combination with cataract surgery with for two reasons. out any need for surgeons to Dr. Noecker explained that the combined modify their standard cata procedure involves placing more viscoelastic VIdEo To watch a video clip ract technique. into the eye—into the capsular bag as well showing endoscopic cyclophotocoagulation To optimize both the effi as in the area of the zonules. performed in combination with cataract surgery, cacy and safety of ECP, how In addition, there is no buffer against visco go to http://bit.ly/1g6Rzeu. ever, surgeons should take elasticrelated IOP spikes with ECP because— (Video courtesy of Robert J. Noecker, MD, MBA) care to treat the ciliary pro unlike some other glaucoma procedures that Dr. Noecker cesses fully, avoid postoper may be combined with cataract surgery—ECP ative IOP spikes, and mini does not increase outflow and lead to an im mize inflammation, said Robert J. Noecker, mediate decrease in IOP. dure, but you will have given something up MD, MBA, director of glaucoma, Ophthalmic Since the zonules are semipermeable to by causing inflammation.” Consultants of Connecticut, Fairfield, CT. the viscoelastic, surgeons should be spend Secondly, surgeons should be aggressive ing about twice as much time as they nor with their approach to antiinflammatory treat mally would during irrigation and aspiration ment. To suppress inflammation and improve Fully treat the to remove viscoelastic. patient comfort, Dr. Noecker recommended 1 ciliary processes. Thoroughness may also necessitate going having the anesthesiologist administer intra Dr. Noecker observed that inadequate treat behind the iris, Dr. Noecker said. venous dexamethasone. ment of the ciliary processes is perhaps the Also to minimize IOP spikes, Dr. Noecker In addition, Dr. Noecker administers dexa biggest mistake surgeons make when perform recommended aggressive prophylaxis with methasone by intracameral injection at the ing ECP in combination with cataract surgery. IOPreducing medications, including oral ac end of the procedure and treats aggressively To enable 360° treatment of the ciliary pro etazolamide and topical agents. postoperatively with a potent topical corti cesses, Dr. Noecker said he inserts the laser In addition, existing glaucoma medications costeroid. ■ through two incisions—the primary temporal should be continued while awaiting the onset cataract incision and a superonasal incision of the ECP treatment effect. made 120° away. Weigh in on the discussion about performing endoscopic cyclophoto However, he also pointed out that treatment coagulation with cataract surgery at of the posterior aspect of the ciliary processes MiniMize Facebook.com/OphthalmologyTimes. is another component to achieving thorough 3 inFlaMMation. treatment, and that can be accomplished by With recognition of the importance of mini treating through the capsule. mizing inflammation when performing ECP, “When performing ECP through an anterior the first consideration for surgeons is to be RobeRT J. NoeckeR, mD, mba approach, it is impossible to treat all of the careful in their technique. e: [email protected] ciliary epithelium because the anatomy limits “If you see bubbles when performing ECP, Dr. Noecker is a paid consultant to and on the speakers’ bureau for Endo Optiks. full access,” Dr. Noecker explained. “That is you are overtreating,” Dr. Noecker said. “The He is also a paid consultant to, speakers’ bureau member, and/or receives research the reason why surgeons are sometimes dis patient may still get a benefit from the proce support from other companies with products for glaucoma management.

magentablackcyanyellow ES390035_OT021514_017.pgs 02.15.2014 02:08 ADV 18 February 15, 2014 :: Ophthalmology Times surgery

analyzed outcomes in a prospective cohort of OphthalmologyTimes.com safeTy 1,500 eyes consecutive eyes [Roberts TV, et al. Online Exclusive Ophthalmology. 2013;120:227-233]. ( Continued from page 1 ) Using published data for manual surgery to benchmark the results, Dr. Lawless observed ePITheLIaL ReMOvaL dictable corneal incisions. It can also be stated that the rates of posterior capsular tears, in- unequivocally that the capsulotomy created cluding events with and without vitreous loss, by PTK benefICIaL with the laser is more precise relative to a and of anterior capsular tears were lower than fOR PeRfORMIng CXL manual capsulorhexis and has equivalent if the best published historical results. not better strength. The rate of posterior capsule complications studies evaluating treatment of Dr. Lawless noted some studies have sug- using the laser (0.08% or 0.23% for cases with progressive keratoconus with corneal gested the laser-created capsulotomy is inferior vitreous loss) were also far better than the crosslinking (CXL) show greater benefit using an in terms of smoothness of the cut surface. That 2% rate reported in an analysis of data from epithelium-off versus epithelium-on technique. However, epithelial removal by laser-assisted research, however, was conducted with older 600,000 eyes in the Swedish National Cataract phototherapeutic keratectomy (PTK) may give laser technology and higher energies than are Register, Dr. Lawless said. better results than manual debridement, currently used. A recent study [Mastropasqua “In my personal series of 981 eyes, I have according to a study presented by Ronald N. L, et al. J Cataract Refract Surg. 2013;39:1581- a 0.1% anterior capsular tear rate and a 0% Gaster, MD. Go to http://bit.ly/1lOoeOa. 1586] showed irregularity of the cut surface rate of posterior capsule tears,” he added. “I was similar comparing manual and laser cap- could never achieve those outcomes with man- sulotomies when the latter was performed with ual surgery.” a low-energy setting of just 7 microJ. Discussing a laser-assisted case, Dr. Malo- CounterPoint: ney pointed out how the cortex peels off in Take-home not safer tiny fragments and the particular difficulty Robert K. Maloney, MD—director, Maloney of removing subincisional cortex. Surgeons with experience using the Vision Institute, and clinical professor of oph- Discussing anterior capsular tears, Dr. Ma- femtosecond laser for refractive lens thalmology, Jules Stein Eye Institute/UCLA, loney observed that with improved technology surgery discuss the safety benefts and Los Angeles—first established his preference and surgeon experience, the rate of anterior challenges accompanying its use. is for using the laser. capsular tears with LRLS has been dramati- Dr. Maloney has been performing LRLS rou- cally reduced. tinely for 2 years and has experience with three This complication has not been eliminated, “We are now in a low-energy environment of the four systems available in the United however, he said. with the use of our lasers, and many systems States, he noted. Dr. Maloney explained that the tears can are even operating below 7 microJ,” Dr. Law- However, Dr. Maloney said arise if the laser has not created a free-float- less said, adding that he expects the quality of he has encountered compli- ing capsulotomy because any irregularity in the capsulotomy edge created with the laser cations using all three sys- the rim can radialize as the surgeon works to will soon be as good or exceed that of the tems and emphasized that break the adhesions. manual capsulorhexis for most systems. How the laser introduces differ- However, the tear can also develop even edge quality relates to capsule integrity is still ent safety issues. before the eye is opened because the nucleus to be determined. He cited the paper from might prolapse forward due to pressure cre- Multiple studies investigating the effect of Dr. Maloney Dr. Lawless to highlight the ated by intralenticular gas bubbles. laser-assisted surgery on ultrasound energy learning curve for the laser- Dr. Maloney also highlighted cases where the usage show effective phaco time is reduced assisted procedure. anterior capsule tear extended to the posterior 40% to 90% relative to a manual procedure. In addition, Dr. Maloney reviewed the po- capsule, and depending on their extent, necessi- Moreover, the reduction in ultrasound energy tential for anterior capsule tears using the laser tated a change in the plan for IOL implantation. has been directly related to a benefit for mini- along with the challenges of cortex removal Despite these challenges, Dr. Maloney said mizing endothelial cell loss, according to sev- and operating on eyes with small pupils. he still believes that LRLS is the safest way to eral studies. “I try to avoid the femtosecond laser pro- perform cataract surgery in most patients. ■ In addition, two studies and various case cedure in patients with small pupils because reports show macular thickening is reduced I think it makes a challenging situation even by use of the laser, and there are case series more difficult,” Dr. Maloney said. “In addition, michael lawless, mD describing use of the laser to facilitate surgery surgeons should know that cortical removal is e: [email protected] in difficult cases, including eyes with white more difficult in 100% of eyes in procedures Dr. lawless is an alcon laboratories’ advisory board member. cataract, phacomorphic glaucoma, a corneal done with the laser, and that is an issue rarely graft, and those requiring mechanical pupil spoken about.” roberT k. maloney, mD enlargement. He explained that in the laser-assisted pro- e: [email protected] cedure, the hydrodissection wave separates Dr. maloney is a consultant for abbott medical Optics. surGiCal cortex from the epinucleus, not from the cap- ComPliCations sule, and after the laser-created capsulotomy, Dr. lawless and Dr. maloney each were assigned to discuss opposing views of the Focusing on surgical complications, Dr. Law- there are no cortical tags to grab onto with the relative safety of laser refractive lens surgery during refractive surgery subspecialty less cited a paper from his practice group that irrigation/aspiration port. Day at the 2013 meeting of the american academy of Ophthalmology.

magentablackcyanyellow ES390093_OT021514_018.pgs 02.15.2014 03:49 ADV The Quintessential

Proven therapeutic utility in blepharitis, conjunctivitis, and other superficial ocular infections

● Profound bactericidal effect against gram-positive pathogens1 ● Excellent, continued resistance profile—maintains susceptibility,2,3 even against methicillin-resistant Staphylococcus aureus 4 ● Ointment provides long-lasting ocular surface contact time and greater bioavailability5 ● Anti-infective efficacy in a lubricating base6 ● Unsurpassed safety profile—low incidence of adverse events6 ● Convenient dosing—1 to 3 times daily6 ● Tier 1 pharmacy benefit status—on most insurance plans7

Bacitracin Ophthalmic Ointment is indicated for the treatment of superf cial ocular infections involving the conjunctiva and/or cornea caused by Bacitracin susceptible organisms. Important Safety Information The low incidence of allergenicity exhibited by Bacitracin means that adverse events are practically non-existent. If such reactions do occur, therapy should be discontinued. Bacitracin Ophthalmic Ointment should not be used in deep-seated www.perrigobacitracin.com ocular infections or in those that are likely to become systemic. This product should not be used in patients with a history of hypersensitivity to Bacitracin.

Please see adjacent page for full prescribing information.

References: 1. Kempe CH. The use of antibacterial agents: summary of round table discussion. Pediatrics. 1955;15(2):221-230. 2. Kowalski RP. Is antibiotic resistance a problem in the treatment of ophthalmic infections? Expert Rev Ophthalmol. 2013;8(2):119-126. 3. Recchia FM, Busbee BG, Pearlman RB, Carvalho-Recchia CA, Ho AC. Changing trends in the microbiologic aspects of postcataract endophthalmitis. Arch Ophthalmol. 2005;123(3):341-346. 4. Freidlin J, Acharya N, Lietman TM, Cevallos V, Whitcher JP, Margolis TP. Spectrum of eye disease caused by methicillin-resistant Staphylococcus aureus. Am J Ophthalmol. 2007;144(2):313-315. 5. Hecht G. Ophthalmic preparations. In: Gennaro AR, ed. Remington: the Science and Practice of Pharmacy. 20th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2000. 6. Bacitracin Ophthalmic Ointment [package insert]. Minneapolis, MN: Perrigo Company; August 2013. 7. Data on file. Perrigo Company. Logo is a trademark of Perrigo.

magentablackcyanyellow ES388116_OT021514_019_FP.pgs 02.05.2014 19:09 ADV 20 February 15, 2014 :: Ophthalmology Times Bacitracin Ophthalmic surgery Ointment USP STERILE Rx Only

DESCRIPTION: Each gram of ointment contains session,” Dr. Cahill said. “There’s variable in- 500 units of Bacitracin in a low melting special lesions terconnectivity of cysts, and it’s best to treat base containing White Petrolatum and Mineral Oil. the more superficial ones rather than to go CLINICAL PHARMACOLOGY: The antibiotic, ( Continued from page 13 ) through one to treat a deeper one. Bacitracin, exerts a profound action against many “Sometimes it is necessary to limit the gram-positive pathogens, including the common Smaller cysts also require a slightly differ- amount that’s treated in one session because Streptococci and Staphylococci. It is also destructive ent approach. Instead of the pigtail probe, a we’re dealing with a closed space and we for certain gram-negative organisms. It is ineffective small-gauge angiocatheter or double-lumen do not want to create a compartment syn- against fungi. needle is used. drome,” he said. INDICATIONS AND USAGE: For the treatment Dual-agent therapy and prolonged drainage of superficial ocular infections involving the are not feasible. In these cases, ultrasound is side effeCts conjunctiva and/or cornea caused by Bacitracin very helpful to determine the presence and Side effects that may occur include edema susceptible organisms. accuracy of placement of the needle. around cysts, hemorrhage from needle tracts, CONTRAINDICATIONS: This product should not and serous transudate or hemorrhage inside be used in patients with a history of hypersensitivity doxyCyCline cysts from denuded endothelial linings. Sys- to Bacitracin. or BleomyCin foam temic corticosteroids following treatment can PRECAUTIONS: Bacitracin ophthalmic ointment Another useful strategy is to use bleomycin make the recovery easier. should not be used in deep-seated ocular foam mixed with albumin to monitor place- In all of the cases that Dr. Cahill and col- infections or in those that are likely to become ment of the fluid; the foam shows prominently leagues have treated over the years, compli- systemic. The prolonged use of antibiotic containing on the treatment ultrasound. cations have been temporary. These include preparations may result in overgrowth of nonsus- ceptible organisms particularly fungi. If new The foam is also beneficial because it can double vision, corneal exposure, increased infections develop during treatment appropriate fill the cyst and contact the endothelial tis- IOP, mydriasis, optic nerve compromise, and antibiotic or chemotherapy should be instituted. sue lining the cyst with less of the bleomy- one incident of corneal penetration. cin, Dr. Cahill said. The treatment protocol has several short- ADVERSE REACTIONS: Bacitracin has such a low incidence of allergenicity that for all practical This decreases the chance of extravasation, comings, he said. purposes side reactions are practically non-existent. and the amount of bleomycin used can stay At this time, it is not possible to treat all However, if such reaction should occur, therapy below toxic dose levels even when extensive apical cysts and intraconal cysts safely. When should be discontinued. lesions are treated. treatment is possible, multiple treatments may To report SUSPECTED ADVERSE REACTIONS, Doxycycline foam can also be used, follow- be needed—usually at 1- to 3-month intervals— contact Perrigo at 1-866-634-9120 or FDA at ing the same principles as bleomycin foam, and recovery from each treatment takes about 1-800-FDA-1088 or www.fda.gov/medwatch. Dr. Cahill said. There is no toxicity, but doxy- 1 month, Dr. Cahill concluded. ■ cycline foam may cause more inflammation. DOSAGE AND ADMINISTRATION: The ointment should be applied directly into the conjunctival Conjunctival cysts—usually classified as sac 1 to 3 times daily. In blepharitis all scales microcysts—are treated with direct visual- and crusts should be carefully removed and the ization of needle placement, using doxycy- ointment then spread uniformly over the lid cline or bleomycin foam. margins. Patients should be instructed to take “Regardless of the size, the cyst may re- kenneTh v. cahill, mD, facs appropriate measures to avoid gross contamination quire more than one treatment, and we may p: 614/221-7464 e: [email protected] of the ointment when applying the ointment not be able to treat all cysts during a single Dr. cahill did not report any fnancial disclosures. directly to the infected eye. HOW SUPPLIED: NDC 0574-4022-13 3 - 1 g sterile tamper evident tubes with ophthalmic tip. NDC 0574-4022-35 3.5 g (1/8 oz.) sterile tamper evident tubes with ophthalmic tip. Store at 20°-25°C (68°-77°F) Eye health, allergies [see USP Controlled Room Temperature]. resource available

JaCksoNVille, Fl :: As the spring Allergy seA- mation about eye allergies and contact lenses, son ApproAches, Johnson & Johnson including advice on the benefits of daily dis- Vision Care is offering an educational brochure, posable contact lenses. Manufactured For “Eye Health and Allergies.” The complimentary Digital copies can be downloaded from the ® brochure is designed to provide patients with Patient Education section of www.Acuvue useful information on how eye allergies occur, Professional.com. Eye-care professionals may Minneapolis, MN 55427 common signs and symptoms, and practical also order bulk copies for the office by sending 0S400 RC J1 Rev 08-13 A advice on how to treat eye allergies. an e-mail request with their name and mailing The brochure also includes helpful infor- address to [email protected]. ■

magentablackcyanyellow ES390092_OT021514_020.pgs 02.15.2014 03:49 ADV Month 1, 2014 :: Ophthalmology Times 2121 clinical cOncepts in Special Report ) Ocular allergy strAtegies for the diAgnosis And treAtment of Allergic conjunctivitis

Current Best Practices The algorithm presented outlines current best practices regarding diagnosis and treatment of allergic conjunctivitis based on recent medical fndings and expert opinion similar to those provided for asthma and allergic rhinitis. Greater awareness of the allergic conjunctivitis disease state and knowledge of treatment options for symptom relief can improve patient management and encourage healthcare providers to further collaborate in assisting patients to reach closer to their objective of ameliorating the symptoms of ocular allergy. The ocular allergy treatment algorithm includes over-the-counter (OTC) agents and then progresses to include a stepwise approach using prescription medications that build on the various complementary mechanisms of action of therapeutic agents including topical lubricants, cool compresses, decongestants, antihistamines, nonsteroidal anti-infammatory drug (NSAID), mast cell stabilizers, corticosteroids, and subcutaneous (and potentially sublingual*) immunotherapy, but also include the treatment of comorbid conditions such as allergic rhinitis and tear flm dysfunction (dry eye disease). (*Not FDA approved.) (Source: Allergy Asthma Proc. 2013;34:1–13.) Algorithm Addresses Allergic conjunctivitis Management approach urges collaboration, consensus among specialists, non-specialists By Nancy Groves; Reviewed by Leonard Bielory, MD

New BruNswick, NJ :: take-home n algorithm for the management son University Hospital, New Brunswick, NJ, and long- time advocate of a more holistic approach to managing A new algorithm for of allergic conjunctivitis aims allergic conjunctivitis. the management of to increase consensus among a Dr. Bielory et al. reported their recommendations in allergic conjunctivitis A Allergy and Asthma Proceedings (2013;34:1-13). encourages variety of specialists who may Dr. Bielory, whose co-authors included several optom- collaboration and be dealing with ocular allergy. etrists, explained that subspecialists are trained to con- consensus among centrate on one organ. While specialists in areas other colleagues with The algorithm is a stepwise approach that also ad- than eye care may regularly treat patients with ocular al- different expertise dresses comorbidities such as dry eye and the possible lergies, they do not necessarily place sufficient emphasis as well as greater impact on the ocular surface of medications customarily on ocular signs and symptoms. emphasis on ocular used to treat allergies. “The ocular condition is probably equivalent at times, signs and symptoms by In addition, it includes immunotherapy as an alterna- if not more, than the nasal congestion that is the reason physicians who are not tive treatment approach in patients whose symptoms are most patients are referred to an allergist,” he said. eye-care specialists. more severe. The allergist will primarily assess the nasal, skin, and “It’s basically about the ability to collaborate and com- respiratory aspects of the disease, whereas the eye-care municate in improving the care of the patient,” said Leon- specialist will center on the eye, with less focus on the ard Bielory, MD, an allergist-immunologist in the Depart- other aspects of allergic conjunctivitis. ment of Medicine, Rutgers University, Robert Wood John- Continues on page 25 : Algorithm

magentablackcyanyellow ES390016_OT021514_021.pgs 02.15.2014 01:22 ADV 22 FEbruary 15, 2014 :: Ophthalmology Times Special Report ) clinical cOncepts in Ocular allergy

Can immunotherapy play a role in future approaches to ocular allergy therapy? treatment strategy explores desensitization, suppression of allergen-specifc IgE production By Paul Gomes

Recent clinical trials of immunotherapies for allergic conjunctivitis or allergic rhinitis Allergen ClintriAls/sponsor primAry endpoint ConjunCtivitis endpoint study results Grass (phase III) NCT00409409 Stallergenes total symptom itching, watery eyes component complete, not reported score (tss1) of tss Grass (phase III) NCT00550550 Merck total symptom gritty/itchy/red eyes component met primary endpoint score (tcs2) of dss3 versus placebo Grass (phase IIb/III) NCT00367640 Stallergenes total symptom itching, watery eyes component complete, not reported score (tss1) of tss A total of 91 studies found in clintrials database using slit/Ait and grass Ragweed (phase III) NCT01353079 Greer Labs total symptom none specifed complete, not reported score (tcs2) Ragweed (phase II) NCT01198613 Circassia Ltd. total symptom ocular symptom score met primary endpoint score (tcs2) versus placebo Ragweed (phase III) NCT00770315 Merck total symptom gritty/itchy/red eyes component met primary endpoint score (tcs2) of dss3 versus placebo A total of 23 studies found in clintrials database using immunotherapy and ragweed TSS1: a combination of 6 scores: sneezing, rhinorrhoea, nasal itch, nasal congestion, ocular itch, and watery eyes. TCS2: the sum of rhinoconjunctivitis daily symptom score (DSS) and rhinoconjunctivitis daily medication score (DMS) averaged over the entire grass pollen season. DSS3: includes a “gritty/itchy/red eyes” component. (Source: www.clinicaltrials.gov)

TherApeuTic ApproAches To has been referred to as the atopic march. All has been the method of choice for these treat- ocular allergic disease are at a crossroad. Topi- of these conditions involve development of a ments. The protracted nature of the treatment cal and systemic antihistamines have evolved type-2 regulatory T-cell response to common regimes has limited this therapy to the most to once-daily treatments that provide effective environmental allergens, leading to an inap- severely allergic patients. symptomatic relief to a large seg- propriate IgE production and im- In contrast, European physicians have used ment of the population, but for an- munological sensitization. both oral and topical delivery of antigen for other group—perhaps as many as When subsequently exposed to many years. Both of these treatment modali- one-third of the 40 million people take-home the allergenic culprit, these antibod- ties have shown similar efficacy and safety in the United States with seasonal ies can initiate mast cell degranu- profiles when compared with SC antigen de- Numerous clinical or perennial allergy—none of the lation and the entire sequela of an livery. Recent large-scale trials in the United trials are under way current treatments provide consis- allergic response. If the same an- States have focused on sublingual allergen de- that may help to tent relief. tigen is exposed to dendritic cells livery (SLIT), a modality that has the poten- defne the role of One therapeutic strategy common or other antigen-presenting cells at tial to expand the use of immunotherapy to a immunotherapy in outside the United States is immuno- low concentrations, it is possible much greater patient population.2 ocular allergy. therapy, a technique of re-training to initiate a shift in the regulatory A sample of recent trials in the United States or desensitizing the immune sys- balance between the type-2 T-regs is summarized in the table above. Note that tem so that responses to common allergens, and the non-allergenic type-1 T-cells. few of these studies use any primary measures such as pollen, animal dander, or dust mites, Although this desensitization process is not of allergic conjunctivitis as endpoints. are attenuated. Multiple immunotherapy tri- completely understood, suppression of aller- There is a good deal of misinformation sur- als are under way or recently completed in the gen-specific IgE production is also thought to rounding the use of immunotherapy, particu- United States, so it is a good time to consider be important in immunotherapy.1 larly with respect to its safety profile. In a re- this new technique and how it might impact cent meta analyses of SLIT that included thou- therapy of allergic conjunctivitis (AC). SCIT aNd SLIT modaLITIeS sands of subjects over a wide range of allergen Diseases such as atopic dermatitis, rhini- Any type of immunotherapy involves a repeated doses and delivery protocols, there are only a tis, and AC are a related group of disorders presentation of small amounts of antigen. In the handful of reported incidents of anaphylaxis. that—together with asthma—comprise what United States, subcutaneous injection (SCIT) Continues on page 25 : immunotherapy

magentablackcyanyellow ES390015_OT021514_022.pgs 02.15.2014 01:22 ADV magentablackcyanyellow ES388153_OT021514_023_FP.pgs 02.05.2014 19:16 ADV ® Respiratory: Bronchospasm (predominantly in patients with pre-existing bronchospastic disease), dyspnea, nasal COMBIGAN congestion, respiratory failure; Endocrine: Masked symptoms of hypoglycemia in diabetes patients; Special Senses: diplopia, choroidal detachment following filtration surgery, cystoid macular edema, decreased corneal sensitivity, (brimonidine tartrate/timolol maleate ophthalmic solution) 0.2%/0.5% pseudopemphigoid, ptosis, refractive changes, tinnitus; Urogenital: Decreased libido, impotence, Peyronie’s disease, BRIEF SUMMARY retroperitoneal fibrosis. Please see the COMBIGAN® package insert for full prescribing information. Postmarketing Experience: Brimonidine: The following reactions have been identified during post-marketing use of INDICATIONS AND USAGE brimonidine tartrate ophthalmic solutions in clinical practice. Because they are reported voluntarily from a population COMBIGAN® (brimonidine tartrate/timolol maleate ophthalmic solution) 0.2%/0.5% is an alpha adrenergic receptor of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to agonist with a beta adrenergic receptor inhibitor indicated for the reduction of elevated intraocular pressure (IOP) in either their seriousness, frequency of reporting, possible causal connection to brimonidine tartrate ophthalmic solutions, patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy due to inadequately or a combination of these factors, include: bradycardia, depression, iritis, keratoconjunctivitis sicca, miosis, nausea, skin controlled IOP; the IOP-lowering of COMBIGAN® dosed twice a day was slightly less than that seen with the concomitant reactions (including erythema, eyelid pruritus, rash, and vasodilation), and tachycardia. Apnea, bradycardia, hypotension, hypothermia, hypotonia, and somnolence have been reported in infants receiving brimonidine tartrate ophthalmic administration of 0.5% timolol maleate ophthalmic solution dosed twice a day and 0.2% brimonidine tartrate ophthalmic solution dosed three times per day. solutions. Oral Timolol/Oral Beta-blockers: The following additional adverse reactions have been reported in clinical CONTRAINDICATIONS experience with ORAL timolol maleate or other ORAL beta-blocking agents and may be considered potential effects of ® ophthalmic timolol maleate: Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm Asthma, COPD: COMBIGAN is contraindicated in patients with bronchial asthma; a history of bronchial asthma; severe with respiratory distress; Body as a whole: Decreased exercise tolerance, extremity pain, weight loss; Cardiovascular: chronic obstructive pulmonary disease. Vasodilatation, worsening of arterial insufficiency; Digestive: Gastrointestinal pain, hepatomegaly, ischemic colitis, Sinus bradycardia, AV block, Cardiac failure, Cardiogenic shock: COMBIGAN® is contraindicated in patients with mesenteric arterial thrombosis, vomiting; Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic sinus bradycardia; second or third degree atrioventricular block; overt cardiac failure; cardiogenic shock. purpura; Endocrine: Hyperglycemia, hypoglycemia; Skin: Increased pigmentation, pruritus, skin irritation, sweating; Neonates and Infants (Under the Age of 2 Years): COMBIGAN® is contraindicated in neonates and infants Musculoskeletal: Arthralgia; Nervous System/Psychiatric: An acute reversible syndrome characterized by disorientation (under the age of 2 years). for time and place, decreased performance on neuropsychometrics, diminished concentration, emotional lability, local Hypersensitivity reactions: Local hypersensitivity reactions have occurred following the use of different components weakness, reversible mental depression progressing to catatonia, slightly clouded sensorium, vertigo; Respiratory: of COMBIGAN®. COMBIGAN® is contraindicated in patients who have exhibited a hypersensitivity reaction to any Bronchial obstruction, rales; Urogenital: Urination difficulties. component of this medication in the past. DRUG INTERACTIONS WARNINGS AND PRECAUTIONS Antihypertensives/Cardiac Glycosides: Because COMBIGAN® may reduce blood pressure, caution in using drugs Potentiation of respiratory reactions including asthma: COMBIGAN® contains timolol maleate; and although such as antihypertensives and/or cardiac glycosides with COMBIGAN® is advised. Beta-adrenergic Blocking administered topically can be absorbed systemically. Therefore, the same types of adverse reactions found with systemic Agents: Patients who are receiving a beta-adrenergic blocking agent orally and COMBIGAN® should be observed administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory for potential additive effects of beta-blockade, both systemic and on intraocular pressure. The concomitant use of two reactions including death due to bronchospasm in patients with asthma have been reported following systemic or topical beta-adrenergic blocking agents is not recommended. Calcium Antagonists: Caution should be used in the ophthalmic administration of timolol maleate. co-administration of beta-adrenergic blocking agents, such as COMBIGAN®, and oral or intravenous calcium Cardiac Failure: Sympathetic stimulation may be essential for support of the circulation in individuals with diminished antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. In myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure. patients with impaired cardiac function, co-administration should be avoided. Catecholamine-depleting Drugs: Close In patients without a history of cardiac failure, continued depression of the myocardium with beta-blocking agents over observation of the patient is recommended when a beta blocker is administered to patients receiving catecholamine- a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of cardiac failure, COMBIGAN® depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or should be discontinued. marked bradycardia, which may result in vertigo, syncope, or postural hypotension. CNS Depressants: Although specific drug interaction studies have not been conducted with COMBIGAN®, the possibility of an additive or potentiating Obstructive Pulmonary Disease: Patients with chronic obstructive pulmonary disease (e.g., chronic bronchitis, effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered. Digitalis emphysema) of mild or moderate severity, bronchospastic disease, or a history of bronchospastic disease [other than and Calcium Antagonists: The concomitant use of beta-adrenergic blocking agents with digitalis and calcium bronchial asthma or a history of bronchial asthma, in which COMBIGAN® is contraindicated] should, in general, not ® antagonists may have additive effects in prolonging atrioventricular conduction time. CYP2D6 Inhibitors: Potentiated receive beta-blocking agents, including COMBIGAN . systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with Potentiation of vascular insufficiency: COMBIGAN® may potentiate syndromes associated with vascular insufficiency. CYP2D6 inhibitors (e.g., quinidine, SSRIs) and timolol. Tricyclic Antidepressants: Tricyclic antidepressants have been COMBIGAN® should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud’s reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these phenomenon, orthostatic hypotension, or thromboangiitis obliterans. agents with COMBIGAN® in humans can lead to resulting interference with the IOP-lowering effect. Caution, however, Increased reactivity to allergens: While taking beta-blockers, patients with a history of atopy or a history of severe is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines. anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic Monoamine oxidase inhibitors: Monoamine oxidase (MAO) inhibitors may theoretically interfere with the metabolism challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat of brimonidine and potentially result in an increased systemic side-effect such as hypotension. Caution is advised in anaphylactic reactions. patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines. Potentiation of muscle weakness: Beta-adrenergic blockade has been reported to potentiate muscle weakness USE IN SPECIFIC POPULATIONS consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness). Timolol has been Pregnancy: Pregnancy Category C: Teratogenicity studies have been performed in animals. reported rarely to increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms. Brimonidine tartrate was not teratogenic when given orally during gestation days 6 through 15 in rats and days 6 Masking of hypoglycemic symptoms in patients with diabetes mellitus: Beta-adrenergic blocking agents should be through 18 in rabbits. The highest doses of brimonidine tartrate in rats (1.65 mg/kg/day) and rabbits (3.33 mg/kg/day) administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with achieved AUC exposure values 580 and 37-fold higher, respectively, than similar values estimated in humans treated with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may COMBIGAN®, 1 drop in both eyes twice daily. mask the signs and symptoms of acute hypoglycemia. Teratogenicity studies with timolol in mice, rats, and rabbits at oral doses up to 50 mg/kg/day [4,200 times the maximum Masking of thyrotoxicosis: Beta-adrenergic blocking agents may mask certain clinical signs (e.g., tachycardia) of recommended human ocular dose of 0.012 mg/kg/day on a mg/kg basis (MRHOD)] demonstrated no evidence of fetal hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal malformations. Although delayed fetal ossification was observed at this dose in rats, there were no adverse effects on of beta-adrenergic blocking agents that might precipitate a thyroid storm. postnatal development of offspring. Doses of 1,000 mg/kg/day (83,000 times the MRHOD) were maternotoxic in mice Ocular Hypersensitivity: Ocular hypersensitivity reactions have been reported with brimonidine tartrate ophthalmic and resulted in an increased number of fetal resorptions. Increased fetal resorptions were also seen in rabbits at doses solutions 0.2%, with some reported to be associated with an increase in intraocular pressure. 8,300 times the MRHOD without apparent maternotoxicity. Contamination of topical ophthalmic products after use: There have been reports of bacterial keratitis associated with There are no adequate and well-controlled studies in pregnant women; however, in animal studies, brimonidine crossed the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated the placenta and entered into the fetal circulation to a limited extent. Because animal reproduction studies are not always by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. predictive of human response, COMBIGAN® should be used during pregnancy only if the potential benefit to the mother Impairment of beta-adrenergically mediated reflexes during surgery: The necessity or desirability of withdrawal justifies the potential risk to the fetus. of beta-adrenergic blocking agents prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs Nursing Mothers: Timolol has been detected in human milk following oral and ophthalmic drug administration. It is not the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. This may augment the risk of general known whether brimonidine tartrate is excreted in human milk, although in animal studies, brimonidine tartrate has been anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor blocking agents have experienced shown to be excreted in breast milk. Because of the potential for serious adverse reactions from COMBIGAN® in nursing protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the reported. For these reasons, in patients undergoing elective surgery, some authorities recommend gradual withdrawal of importance of the drug to the mother. beta-adrenergic receptor blocking agents. Pediatric Use: COMBIGAN® is not recommended for use in children under the age of 2 years. During post-marketing If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses surveillance, apnea, bradycardia, hypotension, hypothermia, hypotonia, and somnolence have been reported in infants of adrenergic agonists. receiving brimonidine. The safety and effectiveness of brimonidine tartrate and timolol maleate have not been studied in ADVERSE REACTIONS children below the age of two years. Clinical Studies Experience: Because clinical studies are conducted under widely varying conditions, adverse reaction The safety and effectiveness of COMBIGAN® have been established in the age group 2-16 years of age. Use of rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug COMBIGAN® in this age group is supported by evidence from adequate and well-controlled studies of COMBIGAN® in and may not reflect the rates observed in practice. COMBIGAN®: In clinical trials of 12 months duration with COMBIGAN®, adults with additional data from a study of the concomitant use of brimonidine tartrate ophthalmic solution 0.2% and the most frequent reactions associated with its use occurring in approximately 5% to 15% of the patients included: allergic timolol maleate ophthalmic solution in pediatric glaucoma patients (ages 2 to 7 years). In this study, brimonidine tartrate conjunctivitis, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, ocular burning, and stinging. The following ophthalmic solution 0.2% was dosed three times a day as adjunctive therapy to beta-blockers. The most commonly adverse reactions were reported in 1% to 5% of patients: asthenia, blepharitis, corneal erosion, depression, epiphora, eye observed adverse reactions were somnolence (50%-83% in patients 2 to 6 years) and decreased alertness. In pediatric discharge, eye dryness, eye irritation, eye pain, eyelid edema, eyelid erythema, eyelid pruritus, foreign body sensation, patients 7 years of age or older (>20 kg), somnolence appears to occur less frequently (25%). Approximately 16% of headache, hypertension, oral dryness, somnolence, superficial punctate keratitis, and visual disturbance. patients on brimonidine tartrate ophthalmic solution discontinued from the study due to somnolence. Other adverse reactions that have been reported with the individual components are listed below. Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and other adult patients. Brimonidine Tartrate (0.1%-0.2%): Abnormal taste, allergic reaction, blepharoconjunctivitis, blurred vision, bronchitis, OVERDOSAGE cataract, conjunctival edema, conjunctival hemorrhage, conjunctivitis, cough, dizziness, dyspepsia, dyspnea, fatigue, flu No information is available on overdosage with COMBIGAN® in humans. There have been reports of inadvertent syndrome, follicular conjunctivitis, gastrointestinal disorder, hypercholesterolemia, hypotension, infection (primarily colds overdosage with timolol ophthalmic solution resulting in systemic effects similar to those seen with systemic and respiratory infections), hordeolum, insomnia, keratitis, lid disorder, nasal dryness, ocular allergic reaction, pharyngitis, beta-adrenergic blocking agents such as dizziness, headache, shortness of breath, bradycardia, bronchospasm, photophobia, rash, rhinitis, sinus infection, sinusitis, taste perversion, tearing, visual field defect, vitreous detachment, and cardiac arrest. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should vitreous disorder, vitreous floaters, and worsened visual acuity. Timolol (Ocular Administration): Body as a whole: be maintained. chest pain; Cardiovascular: Arrhythmia, bradycardia, cardiac arrest, cardiac failure, cerebral ischemia, cerebral vascular accident, claudication, cold hands and feet, edema, heart block, palpitation, pulmonary edema, Raynaud’s phenomenon, Rx Only syncope, and worsening of angina pectoris; Digestive: Anorexia, diarrhea, nausea; Immunologic: Systemic lupus erythe- ©2013 Allergan, Inc. matosus; Nervous System/Psychiatric: Increase in signs and symptoms of myasthenia gravis, insomnia, nightmares, Irvine, CA 92612, U.S.A. APC33KM13 paresthesia, behavioral changes and psychic disturbances including confusion, hallucinations, anxiety, disorientation, ® marks owned by Allergan, Inc. nervousness, and memory loss; Skin: Alopecia, psoriasiform rash or exacerbation of psoriasis; Hypersensitivity: Signs and Based on package insert 72060US13 revised 10/2012. symptoms of systemic allergic reactions, including anaphylaxis, angioedema, urticaria, and generalized and localized rash; Patented. See: www.allergan.com/products/patent_notices

black ES388106_OT021514_024_FP.pgs 02.05.2014 19:09 ADV FEbruary 15, 2014 :: Ophthalmology Times 25 Special Report ) clinical cOncepts in Ocular allergy

roid therapy. Most studies include rescue drug to 28%, it seems as if some of these early stud- immunotherApy usage (either systemic, nasal, or ocular) as a ies may have omitted a valuable endpoint from secondary endpoint, but this does not provide their trials. The medical community will know ( Continued from page 22 ) a direct comparison between immunotherapy more when the decisions of the FDA on this and established allergy treatments. This study new approach to allergic diseases, such as AC, These trials have established that significant design may be a reflection of the low statisti- are announced later this year. ■ relief from signs and symptoms of allergy can cal power inherent in all environmental trials.4 develop with weeks of therapy initiation, and References that this relief is sustained even after a dis- a meaSure of effICaCy 1. Fujita H, Soyka MB, Akdis M, Akdis CA. Mechanisms continuation of allergen. On the other hand, Allergen challenge has been used to measure of allergen-specific immunotherapy. Clin Transl Allergy. 2012;2:2. despite the large number of trials, there still efficacy of allergen desensitization, and can 2. Nelson HS. Is sublingual immunotherapy ready for use seems considerable debate over dosing issues. provide an objective measure of the treatment in the United States? JAMA. 2013:309;1297-1298. In addition, the high numbers of recent tri- effects on either nasal or ocular symptoms. In 3. Maloney J, Bernstein DI, Nelson H, et al. Efficacy and als for grass, ragweed, and dust mite allergens addition, conjunctival allergen challenge pro- safety of grass sublingual immunotherapy tablet, MK- have been unable to address specifically the tocols (such as the CAC) are validated metrics 7243: a large randomized controlled trial. Ann Allergy Asthma Immunol. 2014;112:146-153. efficacy of SLIT for AC. that have been used in FDA assessment of AC 4. Abelson MB. Comparison of the conjunctival allergen Patients with allergies commonly experience therapies. So it is hard to understand why met- challenge model with the environmental model of a spectrum of symptoms that includes ocular rics like the CAC have not been employed to allergic conjunctivitis. Acta Ophthalmol Scand Suppl. itching, hyperemia, and chemosis. More than develop immunotherapeutics. 1999;228:38-42. 80% of allergy sufferers report experiencing The few studies that include conjunctival 5. Calderon MA, Penagos M, Sheikh A, Canonica GW, Durham SR. Sublingual immunotherapy for allergic some ocular symptomology. Despite this, sev- challenge data suggest that ocular itching may conjunctivitis: Cochrane systematic review and meta- eral recent trials have only limited measures be a more sensitive measure of efficacy. In re- analysis. Clin Exp Allergy. 2011;41:1263-1272. of ocular symptoms often included in scores, cent reports, ocular itching was reduced 30% based upon “gritty eyes or watery eyes.” None to 48% from placebo, whereas the threshold of the scores appear to include direct measures for conjunctival response to allergen provoca- pAul gomes is vice president, allergy at Ora Inc., Andover, MA. of ocular itching, the hallmark symptom of AC.3 tion was significantly increased.5 Of greater impact is the lack of a positive When compared with the best reported nasal comparator group, such as antihistamine or ste- or ocular symptom score improvements of 24%

Algorithm cations in the treatment of patients who come > STeP 2 Patients with mild or intermediate to in complaining of ocular allergy and after a severe itching but no severe redness or concur- ( Continued from page 21 ) time realize that there is no response and that rent ocular conditions should be treated with a they need further assessment as to what is ei- topical ocular antihistamine/mast cell stabilizer, But even when the ocular symptoms seem ther the allergen bothering them or that this or in some cases, corticosteroids. predominant, chances are extremely high that is not an allergic response—that perhaps skin the patient also has nasal allergy, and vice testing and a further assessment would reveal > STeP 3 Patients with moderate to severe versa, Dr. Bielory said, adding that the outcomes that they’re not dealing with an allergic re- symptoms and redness should be treated with would probably be better if allergists retained sponse,” Dr. Bielory said. “That would be im- a topical ocular antihistamine/mast cell sta- their broad approach of evaluating the nasal, portant before adding more and more medi- bilizer, a topical ocular corticosteroid, or both. respiratory, dermal, gastrointestinal, and ocu- cations that don’t work.” lar symptoms but had heightened awareness The algorithm that Dr. Bielory et al. devel- The other concept within the algorithm is of the ocular aspects and more appreciation of oped begins with patient history and exami- the addition of immunotherapy for those who the role that ophthalmologists or optometrists nation evaluating for severity of itching and have chronic allergic disorders in addition to could play in co-managing patients. whether the itch is intermittent or persistent. nasal and respiratory symptoms. Immunother- As chairman of a joint task force of the Amer- Other ocular symptoms, such as foreign body apy has been shown to assist in improving ican Academy of Allergy Asthma and Immu- sensation, tearing, burning, and redness, should the overall quality of life while reducing the nology and the American College of Allergy, also be addressed. frequency and amount of other medications Asthma and Immunology focusing on ocular Symptom duration and prior treatments are for the treatment of allergies and asthma. ■ allergy practice parameters, Dr. Bielory often also noted. Each symptom is classified by se- lectures on this topic and is regularly approached verity level, with appropriate first-line and al- by colleagues who want to learn more about ternative treatment recommendations and fol- managing ocular allergy and dry eye. low-up guidelines. leonArd Bielory, md CoLLaBoraTIoN > STeP 1 Treatment of patients with mild, in- e: [email protected] workS BoTh wayS termittent itching may involve nonpharmaceu- Dr. Bielory is a consultant for Allergan and Bausch + Lomb, is on the committees of “There is increasing appreciation by ophthal- tical measures, over-the-counter medication, Merck and GlaxoSmithKline, and has received fnancial support from Sanof and grants mologists—who normally use a variety of medi- or an ocular antihistamine/mast cell stabilizer. from Allergan.

magentablackcyanyellow ES390014_OT021514_025.pgs 02.15.2014 01:22 ADV 26 February 15, 2014 :: Ophthalmology Times Special Report ) CliniCal ConCepts in oCular allergy

Why once-daily drug is physician’s ‘go-to’ therapy for ocular allergy Medication a reliable choice for safe and effective control of seasonal allergic conjunctivitis By Cheryl Guttman Krader; Reviewed by Alan G. Kabat, OD

MeMphis, TN :: Topical anTihisTa- two antihistamine-mast cell stabiliz- mine-masT cell stabilizers are ers that is approved for once-daily regarded as the mainstay treatment dosing,” Dr. Kabat said. “Patients like for seasonal allergic conjunctivitis the convenience of that schedule and Digital Photography (SAC) because of their safety, toler- it is particularly nice for contact lens ability, and ability to provide prompt wearers who do not have to remove Solutions for and ongoing relief. their lenses during the day to instill Though this class of dual-acting a second dose. Slit Lamp Imaging agents contains several medications, “Contact lens wearers whose eyes including over-the-counter are irritated and uncomfort- (OTC) and prescription able toward the end of the agents, Alan G. Kabat, OD, day may find particular ben- said that olopatadine hydro- efit from instilling their daily chloride ophthalmic solution drop of olopatadine 0.2% in Digital SLR 0.2% (Pataday, Alcon Labo- the evening after they take ratories) is his “go-to” prod- out their lenses,” he said. Camera Upgrades uct for managing patients In a worst-case scenario Dr. Kabat with mild-to-moderate SAC. where the environmental “There are other safe and allergen load is extremely effective options for treating SAC,” high, patients might achieve better said Dr. Kabat, professor, Southern round-the-clock allergy control if they College of Optometry, Memphis, TN. use olopatadine 0.2% twice a day, he “However, I like the science support- added. Patients with a more severe ing olopatadine. It is a highly selective flare-up of their allergy may need Digital Eyepiece H1 antagonist and has demonstrated treatment with a topical corticosteroid. superiority for efficacy and tolera- bility when compared with multiple S a f e t y a l l o w S other anti-allergy agents in head-to- Self-treatment head trials. Taking into account the efficacy and “The published study results mirror favorable safety of olopatadine 0.2%, my clinical practice experience,” he Dr. Kabat said that for demonstrated said. “I use olopatadine 0.2% to treat trustworthy patients who regularly my own ocular allergy, and when I return for follow-up visits, he is very HD Video prescribe it for patients with SAC, I comfortable writing a prescription know I can rely on it to be success- for olopatadine 0.2% with open re- Solutions ful 99% of the time.” fills. Patients are instructed to begin Dr. Kabat noted that the compara- using the medication a few weeks tor trials were conducted using the prior to the onset of allergy season original formulation of olopatadine and to continue using it for the du- that contained 0.1% of the active in- ration of the season. gredient. Results of a clinical trial “Ideally, patients who are known Come visit us @ ASCRS in Boston, booth # 707 using a conjunctival allergen chal- to have SAC should start using their Made in USA lenge model established that olopata- antihistamine-mast cell stabilizer as TTI Medical dine 0.2% once-daily dosing was as a preventive strategy before allergen dƌĂŶƐĂŵĞƌŝĐĂŶdĞĐŚŶŽůŽŐŝĞƐ/ŶƚĞƌŶĂƟŽŶĂů effective as olopatadine 0.1% twice levels begin to increase,” he said. “The Toll free: 800-322-7373 a day for preventing ocular itching reality is that most patients turn to associated with allergic conjunctivi- their allergy medication as rescue ĞŵĂŝůŝŶĨŽΛƫŵĞĚŝĐĂůĐŽŵ tis [Curr Eye Res. 2007;32:1017-1022]. therapy only after they are bothered ǁǁǁƫŵĞĚŝĐĂůĐŽŵ “Olopatadine 0.2% is just one of by their signs and symptoms.”

magentablackcyanyellow ES389805_OT021514_026.pgs 02.14.2014 22:55 ADV February 15, 2014 :: Ophthalmology Times 27

Impact your This patient presented with a severe allergic reaction affecting both the conjunctiva and lids. Olopatadine 0.2% alleviated symptoms within 24 hours, according to Alan G. Kabat, OD. (Image courtesy of Alan G. Kabat, OD) practice with

“In either case, it no significant differ- Consult QD. is helpful to allow ences between treat- dependable patients take-home ment groups at the end to have medication Alan G. Kabat, of the study in eval- Introducing an open online on hand so that they OD, discusses why uations of tear film can self-treat,” he olopatadine 0.2% is break-up time, cor- forum from Cole Eye Institute said. “This approach neal and conjunctival his preferred anti- providing daily insights from will also reduce the allergy medication for staining, tear volume possibility that they managing mild-to- and flow, Schirmer us and other thought leaders. turn to OTC anti-al- moderate seasonal test, injection, or lergy medications, allergic conjunctivitis. symptom evaluations which are attractive [Curr Med Res Opin. ConsultQD.org/oph because of their con- 2008;24:441-447]. venience but not as effective as “Oral antihistamines—and par- olopatadine 0.2% and other pre- ticularly older-generation agents, scription antihistamine-mast cell such as diphenhydramine—act at stabilizers.” the level of the autonomic nervous system and can cause drying of DiSpellinG the ocular surface,” Dr. Kabat ex- Dry eye myth plained. “However, it has never Although there has been some been shown conclusively that any discussion about differential an- topical medications with antihis- timuscarinic effects of ophthal- taminic activity cause or worsen mic antihistamines, Dr. Kabat dry eye. noted there has never been any “In contrast, it is my anecdotal translational work showing that observation that patients with al- these pharmacologic differences lergic conjunctivitis and comorbid are clinically meaningful with re- dry eye have a reduction in their spect to propensity to cause or dry eye symptoms when using a exacerbate dry eye. medication that effectively con- In a randomized, double-masked trols their ocular allergy.” ■ Same-day appointments available. clinical trial including 52 patients 855.REFER.12 with allergic conjunctivitis and dry eye who were assigned to AlAn G. KAbAt, OD use olopatadine 0.2% or saline e: [email protected] once daily for 1 week, there were Dr. Kabat is a consultant to Alcon Laboratories.

magentablackcyanyellow ES389806_OT021514_027.pgs 02.14.2014 22:55 ADV 28 clinical diagnosis FebRuaRy 15, 2014 :: Ophthalmology Times

The vitreous: Orphan of the eye Reversing degenerative changes could help protect retina, crystalline lens, trabecular meshwork eye on research By david C. Beebe, Phd, Special to Ophthalmology Times

1 2

1 Color Scheimpfug photo of a nuclear cataract.

2 Diagram of oxygen distribution in the eye before (left) and after (right) vitrectomy. (Images courtesy of David C. Beebe, PhD)

Take-Home sity of Washington–St. Louis suggests that cleus are responsible for presbyopia and nu- degeneration of the vitreous is implicated, clear cataracts, and likely play a role in the Degeneration of the vitreous not only in these retinal conditions, but in development of cortical cataracts, as well. is implicated not only in retinal cataract and glaucoma as well. We’ve come Yet, we understand little about what trig- conditions, but also in cataract to this recognition through a combination of gers this process. and glaucoma, suggests ongoing eye bank tissue research and collaborations A series of clues led us to suspect vitre- laboratory research at the University with observant clinicians who have pro- ous degeneration as the key to lens changes. of Washington–St. Louis. vided access to human subjects undergoing The first clue was the discovery, while I vitreoretinal surgery. was doing some research into lens development, that the genes expressed in 6-day-old he vitreous body—the clear, jelly- The lens and The viTreous chicken embryo lenses were characteristic of like substance that fills the pos- With age, the human crystalline lens nu- cells under hypoxic conditions. terior segment—is a rather ne- cleus hardens and the rate of nutrient diffu- Then, clinicians in Sweden observed that glected segment of the eye. It is sion to the proteins in the center of the lens patients undergoing intensive hyperbaric ox- discarded after vitrectomy and slows down dramatically. As cataract sur- ygen therapy for systemic conditions, such considered of little interest in a geons know, that harder nucleus is typically as artherosclerosis, over a period of >1 year healthy eye. surrounded by a softer outer cortex. The had interesting ophthalmic side effects. All TFew researchers have studied it directly. cortex is full of viable cells with high levels of the subjects became more myopic, with We know that the vitreous is a non-regener- of the protective antioxidant glutathione. increased nuclear opacity, and about half ative tissue that undergoes slow liquefaction In the center of the aged lens, there is developed frank nuclear cataracts.1 with age. At the advanced stages of this de- much less glutathione overall, and what is This suggests that oxygen, if it gets to generation, the risk of retinal tears, retinal there is more likely to be the oxidized form high enough concentrations on the lens, be- detachment, and macular holes is increased. rather than the protective reduced form of comes toxic and can somehow push the lens Ongoing research in my lab at the Univer- glutathione. These changes in the lens nu- toward nuclear cataracts. (Figure 1)

magentablackcyanyellow ES389515_OT021514_028.pgs 02.14.2014 18:14 ADV FebRuaRy 15, 2014 :: Ophthalmology Times 29 clinical diagnosis

It is also well known that patients un- the lens and in the vitreous, which could be dergoing vitrectomy for retinal surgery will protective if oxygen is the culprit in the de- generally develop nuclear cataracts within velopment of nuclear cataract.5 about this series 2 years. It also turns out that diabetic eyes with Based on all these clues—hypoxic chick ischemic retinopathy—clear evidence that embryo lenses and the rapid onset of nuclear the retina is hypoxic—show no significant EyE on REsEaRch is a quarterly series of cataract in eyes exposed to hyperbaric oxy- progression of nuclear opacification for up to articles highlighting cutting-edge ophthalmic re- gen or vitrectomy—we proposed that the vit- one year after vitrectomy.6 search with the potential to have significant im- reous body keeps the lens in the hypoxic en- Nondiabetic and nonischemic diabetic pact on vision and ocular health worldwide. The vironment it needs to remain healthy. eyes progress to cataract at the same rates, series is supported by the Lions Eye Institute for but the intraocular environment in the isch- Transplant and Research Inc. (LEITR), a nonprofit TesTing The hyPoThesis emic retinopathy eyes continues to be hy- organization dedicated to the recovery, evaluation, To test this theory, my associates and I col- poxic even after vitrectomy. and distribution of eye tissue for transplantation, laborated with Nancy Holekamp, MD, a vit- research, and education. Located in Tampa, FL, reoretinal surgeon in our department. Using Beyond The lens LEITR is the only combined eye bank and ocu- a fiber optic device, we measured oxygen Loss of the vitreous may also affect the tra- lar research center in the world. LEITR provides levels adjacent to the lens and in the mid- becular meshwork. Stanley Chang, MD, no- fresh donor globes, corneas, lenses, trabecular vitreous in patients undergoing retinal sur- ticed that his patients had a higher risk of meshwork, and other tissues from diseased and gery. Measures were obtained before and primary open-angle glaucoma after vitrec- healthy human eyes—often within 4 to 6 hours of after vitrectomy. We found that the lenses tomy and cataract surgery. death—to researchers for immediate use in their in the post-vitrectomy eyes were exposed We were able to show that he was right: own labs or in its on-site research facility. For more to significantly more oxygen.2 (Figure 2 on Oxygen levels in the posterior chamber, an- information, contact [email protected] Page 28) terior to the IOL, and in the anterior cham- or visit LionsEyeInstitute.org. ■ The increased exposure to oxygen occurs ber angle were much higher in patients as a result of removing the vitreous and who had had both vitrectomy and cataract is independent of the gauge of vitrectomy surgery.7 instrumentation.3 We also found some important racial dif- retina. Initial feasibility studies are being ferences in oxygen conducted in animal eyes, but in order to levels in the anterior translate this into human clinical trials, segment. Prior to oc- we’ll need to test the compound in donor ‘We proposed that the vitreous ular surgery, African eyes, as well. Americans have much We also hope to compare proteomic anal- body keeps the lens in the higher intraocular ox- ysis of the structural components of the ygen levels, on averaged vitreous with that of vitreous from hypoxic environment it needs age, than European very young eyes to understand better how Americans.8 the vitreous body changes over time. to remain healthy.’ — David C. Beebe, PhD This could be ex- Much of our work to date has been done pected to increase ox- with local donor eyes not suitable for trans- idative damage to the plant. As we begin to require more special- outflow system over ized tissue (such as the very young eyes), Next, we examined the state of the vit- their lifetime. We don’t know whether the there may be opportunities to work with reous in eye bank globes. The eyes were higher oxygen in African American eyes is the Lions Eye Institute for Transplant and graded by the percentage of vitreous lique- due to genetic or environmental factors, but Research (LEITR), which provides exten- faction and degree of lens opacity. It turns it could partly explain the large racial dis- sive resources for ocular tissue research and out that the state of the vitreous is an even crepancies in glaucoma incidence and risk. actively works to facilitate collaboration better predictor of nuclear cataract than age among scientists, clinicians, and industry. in eyes of donors between 50 to 70 years Challenges ahead (See “About this series,” above) old.4 These are fascinating studies, but there Certainly, there are challenges inher- As the vitreous liquefies with age, I be- is much more to be done. Donor eyes and ent in dealing with ocular tissue or with lieve it gradually exposes the lens to more lenses will be a critical resource in the fu- patients in a clinical setting. The variabil- oxygen and that this exposure is largely re- ture, as we examine whether vitreous and ity in human eyes is disconcerting to basic sponsible for the development of age-related lens changes can be prevented or reversed. scientists who are used to tightly control- nuclear cataract. It is still not clear why the For example, we are now investigating ling variables. But we also learn a great vitreous degenerates earlier and more rap- whether specific compounds can be injected deal from this variability about real-world idly in some eyes and less rapidly in others, into the vitreous to restore its structure as applications. but it appears that the latter category of peo- a gel. The first clinical application for such Furthermore, our experience demon- ple are protected against nuclear cataracts compounds would likely be in cases where a strates how much we all have to gain from until later in life. very limited vitrectomy is being performed, collaboration with one another. So often, ob- In subsequent studies we noted that dia- but ideally, it could be injected even before servant clinicians have provided the key in- betics had lower levels of oxygen around there is separation from and damage to the Continues on page 30 : Vitreous

magentablackcyanyellow ES389514_OT021514_029.pgs 02.14.2014 18:14 ADV 30 FebRuaRy 15, 2014 :: Ophthalmology Times clinical diagnosis

Uncovering a neurologic defect: Te importance of visual feld testing In this case, neurological defcit may point to patient’s postoperative visual complaints By lynda Charters; Reviewed by Bradley J. Katz, MD, PhD

Take-Home with BCVA of 20/25 in both eyes. However, the not be useful because some conditions are not patient insisted that there was no improvement characterized by an abnormal retinal nerve Visual feld testing is indispensable in his vision compared with preoperatively. fiber layer (RNFL) early in the disease process in diagnosing neurologic visual defcits. “My first thought when a patient complains and simple myopia can cause thinning of the of no visual acuity improvement is dry eye RNFL. In support of this recommendation, Dr. syndrome, and my second thought is cystoid Katz commented that another cataract patient SalT lake CiTy :: macular edema—but the patient had neither,” of his had a homonymous hemianopsia, which When a patient presents with the he said. would have had a normal RNFL. complaint that he or she is slowly losing vi- Dr. Katz discussed that visual field testing sion, what course of action does a general oph- diagnosTiC oPTions demonstrated a substantial bitemporal visual thalmologist take? When choosing a diagnostic tool, options in- field defect that was worse inferiorly, which That was the task given Bradley J. Katz, MD, clude: topography, multifocal electroretinog- suggested superior compression of the chiasm. PhD, neuro-ophthalmologist, John A. Moran raphy, visual field testing, or magnetic reso- Dr. Rizzo noted the need for MRI imaging Eye Center, University of Utah School of Medi- nance imaging (MRI) of the brain and orbits. of the brain with and without contrast focused cine, Salt Lake City. A poll of ophthalmologists indicated that 85% on the chiasmal region. would order visual field testing to rule out a To avoid missing a lesion, conveying clini- Case rePorT central scotoma and hemianopsia. A panel of cal information to the radiologist is critical. A 68-year-old man presented to Dr. Katz and experts also recommended color vision test- Computed tomography is inadequate in such described gradual painless loss of vision bi- ing. The goal of testing, they pointed out, is to a case, because it is not as sensitive in the chi- laterally. Best-corrected visual acuity (BCVA) determine if there is a neurogenic origin of the asmal region compared with MRI, added Mark levels were 20/40 in the right eye and 20/50 vision loss, according to Joseph Rizzo, III, MD. Moster, MD. He also emphasized the impor- in the left eye. The examination was normal Dr. Rizzo recommended that visual field tance of telling the radiologist that there is a with the exception of 2+ nuclear sclerotic cat- testing be part of a standard visual evaluation. bitemporal hemianopia. aracts bilaterally. With simple confrontation field testing consist- “If a plain MRI brain scan without contrast The patient underwent two uncomplicated ing of finger counting and presentation of a is ordered, the result may be normal and the cataract surgeries 2 weeks apart by Dr. Katz. small object on either side of the midline, 70% patient can progressively go blind because the Recovery was uneventful, and postoperative un- of neurologic field defects can be identified. lesion was missed,” he said. corrected visual acuity was 20/30 in both eyes Optical coherence tomography may or may Continues on page 31 : Visual feld

2. Holekamp NM, Shui YB, Beebe DC. Vitrectomy surgery 7. Siegfried CJ, Shui YB, Holekamp NM, et al. Oxygen ViTreous increases oxygen exposure to the lens: a possible distribution in the human eye: relevance to the etiology mechanism for nuclear cataract formation. Am J of open-angle glaucoma after vitrectomy. Invest ( Continued from page 29 ) Ophthalmol. 2005;139:302-310. Ophthalmol Vis Sci. 2010;51:5731-5738. 3. Almony A, Holekamp NM, Bai F, et al. Small-gauge 8. Siegfried CJ, Shui YB, Holekamp NM, et al. sights that sparked new areas of inquiry for vitrectomy does not protect against nuclear sclerotic Racial differences in ocular oxidative metabolism: cataract. Retina. 2012;32:499-505. implications for ocular disease. Am J Ophthalmol. our laboratory. 4. Harocopos GJ, Shui YB, McKinnon M, et al. Importance 2011;129:849-854. In return, the basic science work that we of vitreous liquefaction in age-related cataract. Invest do with eye bank tissue helps to move new Ophthalmol Vis Sci. 2004;45:77-85. therapies closer to clinical reality. ■ 5. Holekamp NM, Shui YB, Beebe D. Lower intraocular oxygen tension in diabetic patients: possible DaViD C. BeeBe, PHD, is the Janet and Bernard Becker Pro- References contribution to decreased incidence of nuclear sclerotic cataract. Am J Ophthalmol. 2006;141:1027-1032. fessor of Ophthalmology and Cell Biology at Washington University 1. Palmquist BM, Philipson B, Barr PO. Nuclear cataract 6. Holekamp NM, Bai F, Shui YB, et al. Ischemic diabetic of St. Louis, MO. Dr. Beebe has no fnancial interest in the eye banks and myopia during hyperbaric oxygen therapy. Br J retinopathy may protect against nuclear sclerotic discussed or referred to in the article. Readers may contact him at Ophthalmol. 1984;68:113-117. cataract. Am J Ophthalmol. 2010;150:543-550. 314/362-1621 or [email protected].

magentablackcyanyellow ES389513_OT021514_030.pgs 02.14.2014 18:14 ADV FebRuaRy 15, 2014 :: Ophthalmology Times 31 clinical diagnosis

Dr. Katz’s patient has undergone transspe- Visual fielD noidal resection of the pituitary tumor and is doing well. He emphasized the importance ( Continued from page 30 ) of not dismissing patient complaints about blurry vision after uncomplicated cataract BraDley J. kaTz, mD, PHD The case under discussion was that of chronic surgery. Doing so may result in missing an e: [email protected] visual loss, which can be diagnosed on an important neurologic defect: in this case, a Dr. Katz presented this case report for discussion during Neuro-Ophthalmology outpatient basis. pituitary tumor. ■ Subspecialty Day at the 2013 meeting of the American Academy of Ophthalmology. In cases of acute visual loss with head pain and the threat of pituitary apoplexy, the patient should undergo urgent imaging because of the potential for mortality and endocrine complications, Dr. Rizzo said.

Prevent WE’RE Blindness CHANGING seeks award THE WAY PATIENTS WITH applications VISION IMPAIRMENT ENVISION THEIR FUTURE By rose schneider The Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh—a joint ChiCago :: program of the UPMC Eye Center and the prevent blindness is noW ac- McGowan Institute for Regenerative Medicine— is the ﬁ rst national, comprehensive, and cepting applications for its 2014 Joanne Angle multidisciplinary research and clinical program Investigator Award. dedicated to ocular regenerative medicine. The award—which was recently renamed Our ophthalmologists and researchers focus on to honor Joanne Angle, who served with the the discovery of new treatments for blindness Association for Research in Vision and Oph- and impairment through tissue regeneration, enhancement, transplantation, and technology. We’re thalmology, as well as the national Board of working hard to improve the quality of life for the millions Directors for Prevent Blindness—is a research of people affected by vision loss, so that we can all grant provided annually to a public health proj- see a brighter future. Snap the code and learn more at ect that seeks to help save sight. UPMCPhysicianResources.com. The investigator award program has awarded more than $1 million to eye and vision research projects since its inception in 2003. The deadline for the 11th annual investigator award is March 31. Grants are for a 1-year period, up to $30,000, reviewed by a panel of scientists, and commence on July 1. “Supporting eye and vision research today is crucial to finding the answers to blinding eye diseases and conditions,” said Hugh R. Parry, president and chief executive officer of Prevent Blindness. “By starting the next decade of this sight-saving program, we can help to make a real difference in the lives those who have, or potentially could have, significant vision loss. “By renaming this initiative as the Joanne Angle Investigator Award, we honor Ms. An-

gle’s legacy as a pioneer and leader in this im- UPMC is afﬁ liated with the University of Pittsburgh School of Medicine. portant field,” he added. ■

magentablackcyanyellow ES389516_OT021514_031.pgs 02.14.2014 18:14 ADV 32 February 15, 2014 :: Ophthalmology Times clinical diagnosis

New drugs and devices advance strabismus treatment to next level Innovations aim to create permanent change, not cause infammation or collateral damage By nancy Groves; Reviewed by Stephen P. Christiansen, MD

Take-Home Eye Institute, University of Miami Miller School of Medicine, developed the T-plate system, in- a The surgical procedures and troduced in 2010. botulinum toxin A injections widely used today to treat strabismus may be another look at supplanted within a decade or two by pharmaceuticals new drugs and devices that are more Among pharmaceutical approaches, botulinum effective. toxin A (BTX-A) has been used in strabismus treatment for more than 30 years, but it is time for re-assessment, Dr. Christiansen sug- B Boston :: gested. BTX-A may lack the power to control Though sTrabismus TreaT- the alignment in patients with large angles ad- menT in children is generally effective, in- equately—especially with a single injection— vestigators have taken action to improve the although it may still be appropriate in patients success rate further by exploring new drugs with smaller angles, residual strabismus after and developing new devices. recession, or consecutive strabismus. Currently, ophthalmologists seeking to re- Analyzing all cases of strabismus treatment assure parents of children requiring treatment with BTX-A, about 50% of children with infan- for strabismus often cite an 80% success rate tile esotropia will require re-injection. But in C for the surgical procedure. children who have smaller angles (< ±35 prism This is “simply inaccurate,” said Stephen P. diopter [PD]), reports are as good as 63% align- Christiansen, MD, noting that the overall re- ment within 8 PD of straight (range 34 to 63). operation rate for infantile esotropia is about In a study by Tejedor and Rodriguez (IOVS, 34%, and for exotropia it approaches 80%. 2001), the success rate was 53% aligned for “We have seen some changes in the way we patients with acquired esotropia following a treat patients over these last few years,” said Dr. single injection (mean ET = 35 PD). Analysis a Christiansen, chairman and professor of oph- by A. de Alba et al. (Archives of Ophthalmology, Appearance of a 1-year-old child with infantile esotropia prior to treatment. Prism thalmology and pediatrics, Boston University 2010) demonstrated that use of BTX-A has an and alternate cover testing showed a 25 prism- School of Medicine. “But I expect that within extremely low rate of consecutive exotropia, diopter esotropia. 20 years or so the way we treat patients with <3% for all treated patients. B strabismus will have changed dramatically. “Although these patients haven’t been fol- One week after injection of both medial “We have to recognize that if we are doing lowed for long periods, it looks like BTX-A rectus muscles with 4 units of botulinum toxin A. The child has a large-angle exotropia and a mechanical operation for a disease that is may result in good long-term alignment with bilateral asymmetric ptosis. principally electrical, there are going to be long- relatively low consecutive exodeviations,” Dr. C term changes in eye alignment because the Christiansen said. Good long-term alignment was achieved electrical system changes over time,” he said. BTX-A treatment has limitations as well with a single bilateral medial rectus injection as advantages. For instance, it has a limited of botulinum toxin A. (Images courtesy of Stephen P. Christiansen, MD) Development of Devices duration of action and can only weaken, not On the devices front, one of the promising strengthen, the extraocular muscles. It also has new approaches is a titanium T-plate anchor- a relatively modest effect on alignment with have collateral effects on other extraocular ing platform system that could be particularly a single injection, and there are no long-term muscles and perhaps on the ciliary ganglion. helpful as a means for ocular alignment in decreases in force generation. Tonic pupil has also been reported following patients with severe paralytic and restrictive As a result, many patients need re-injections. BTX-A injection. strabismus, Dr. Christiansen said. “Parents do not like that,” Dr. Christiansen These drawbacks have sent investigators in The plate is attached to the nasal orbital said. ”They want their child taken care of in pursuit of an ideal agent for strabismus that wall, and the extraocular muscle insertion is a single operation.” would be titratable, last long enough for sensory tethered to the posterior plate. Hilda Capo, MD, Another issue with BTX-A is orbital leak- and motor adaptation to occur, create perma- and David T. Tse, MD, both of Bascom Palmer age accompanying the injection, which can Continues on page 33 : Strabismus

magentablackcyanyellow ES389807_OT021514_032.pgs 02.14.2014 22:55 ADV February 15, 2014 :: Ophthalmology Times 33 clinical diagnosis

Pearls for penetrating orbital injury advances in imaging technology enhance physicians’ understanding about foreign body By cheryl Guttman krader; Reviewed by James C. Fleming, MD

MeMphis, tn :: The need for inTervenTion inorganic (metal, glass, fiberglass, plastic) or inert and therefore can be left alone if they are in patients with an intraorbital foreign body organic (plant material), no generalizations not causing problems or anticipated to lead to depends on the ability to localize the retained can be made based on those categorizations. issues based on their resting location. material and determine the full extent of in- Among inorganic materials, even minimally Exceptions are in cases of metallic foreign jury. Success with each of these measures de- sized metallic foreign bodies can be detected bodies made of pure copper, iron, or lead in pends on knowledge of the physics of traumatic with plain radiography. Plastic and fiberglass its pure form, and for patients with any me- injuries, features of orbital anatomy, and the look like air, and the identification of glass tallic foreign body needing MRI of the head unique characteristics of different foreign body fragments depends on their size and whether in the future. materials and imaging modalities. the glass contains lead or is colored because Understanding of the physics of traumatic in- of metal content (e.g., cobalt or gold). surGical tips juries is the basis for understanding the extent Dry wood is relatively easy to detect on com- When extracting foreign bodies, Dr. Fleming of intraocular damage, said James C. Fleming, puted tomography (CT) or magnetic resonance recommended placing a ribbon retractor or some MD, chairman, Department of Ophthalmology, imaging (MRI) where it looks like linear air other instrument behind fragments whenever and the Philip M. Lewis Professor of Ophthal- but with a cylindrical shape. Discriminating possible to prevent them from being propelled mology, University of Tennessee Health Science between air and wood on CT requires proper posteriorly during the retrieval attempt. He also Center, Hamilton Eye Institute, Memphis, TN. setting and understanding of the monitors of advised following the missile track carefully The object’s mass and velocity affect its abil- the display scale and using “lung” presets on to find the terminal site of injury and to an- ity to penetrate orbital tissues as well as the the CT views. As another clue, “linear air” as- ticipate that multiple fragments are retained. cavitation effect that is produced, which will sociated with the presence of dry wood will Intraoperative stereotactic localization with determine if there is damage disseminated dis- remain if imaging is repeated after a few days, preoperative CT or MRI may not be helpful tant from the site where the foreign body lies. but will have disappeared if it was only air. in guiding foreign body extraction since soft In terms of anatomic considerations, Dr. Flem- However, due to its water content, green tissue landmarks can change intraoperatively ing said the orbit is a conically shaped com- wood is difficult to find with either CT or MRI. and cannot be tracked. “C” arm localization partment with internal structures, including “Inflammation will be seen surrounding re- may be better, but it provides limited soft tis- extraocular muscles and a septal system. For- tained wood and that can be identified with gad- sue differentiation. eign bodies entering the conical orbit are driven olinium enhancement,” he said. “We are almost Intraoperative MRI and CT systems are now back to the apex, and trauma from a penetrat- doomed to identifying green wood on imaging available that allow for real-time imaging in ing foreign body to the extraocular muscles only after waiting for inflammation to set up.” the operating room or intensive care unit. ■ and septal system can affect ocular movement. Looking for delayed inflammation with re- peat imaging is probably also the best way to characteristics determine complete success in removing wood James C. Fleming, mD The composition of the foreign body deter- foreign bodies, he added. e: [email protected] mines its visibility on imaging and reactiv- Whether it is necessary to remove an in- Dr. Fleming reviewed these principles in his delivery of the Wendell Hughes Lecture ity within the orbit. Although foreign bodies traocular foreign body depends in part on the at the 2013 meeting of the American Academy of Ophthalmology. Dr. Fleming has no can be classified based on whether they are material. Glass, plastic, and many metals are relevant fnancial interests to disclose.

to both weaken and strengthen the muscle. “Bupivacaine by itself doesn’t have a huge sTraBismus Toxins besides BTX-A are being studied, as effect on alignment, but if you weaken a rectus are immunotoxins (ricin-mAb 35 and other muscle with BTX-A and strengthen the antago- ( Continued from page 32 ) fusion proteins). nist with bupivacaine, you do get a significant Injection of the anesthetic bupivacaine, an change in the rotation,” Dr. Christiansen said. ■ nent change in the globe’s rotational position, off-label use of this agent, is another innova- and would not create significant inflammation tion in strabismus treatment, first advocated or cause unwanted collateral damage, he said. by Alan B. Scott, MD, of the Smith-Kettlewell Growth factors, such as IGF I and II, are Eye Institute, San Francisco, about 8 years ago. sTepHen p. CHrisTiansen, mD showing excellent results so far. These agents Bupivacaine causes fiber hypertrophy, creat- p: 617/414-4020 e: [email protected] increase motor strength, giving surgeons a way ing large, stiff muscles. Dr. Christiansen did not report any fnancial interests or relationships.

magentablackcyanyellow ES389808_OT021514_033.pgs 02.14.2014 22:55 ADV 34 drug therapy FEBRUARY 15, 2014 :: Ophthalmology Times

Anti-VEGF therapy: Safety trends Clinical data provide limited insights on anti-vascular endothelial growth factor treatment systemic effects By Cheryl Guttman Krader; Reviewed by Pravin U. Dugel, MD

TAKE-HOME Molecular Dif erences Between VEGF Inhibitors Analyses of data from large clinical trials have been undertaken to determine how patient age and treatment- VEGF STRUCTURE MOLECULAR MOLECULAR specif c variables may inf uence the INHIBITOR WEIGHT CHARACTERISTICS systemic safety of anti-vascular endo- Ranibizumab1 Fab 48 kDa Fab fragment (no Fc portion*) thelial growth factor treatment.

Af ibercept2 Fc portion 115 kDa Fusion protein (Fc-containing) hough it is known that intravitreal treatment with anti-vascular endothe- †3 lial growth factor (VEGF) agents can Bevacizumab Fc portion 149 kDa Full-length monoclonal antibody (Fc-containing) be associated with systemic effects, a paucity of statistically definitive * Responsible for recycling via the FcRn receptor data is the basis for ongoing con- † NB: Bevacizumab is not indicated for intravitreal use troversy about the clinical impact. VEGF, vascular endothelial growth factor; Fab, antigen binding fragment; Fc , fragment crystallizable region; FcRn, the neonatal Fc receptor for T“We won’t ever have definitive clinical trials IgG; kDa, kilodalton on the systemic safety of intravitreal anti-VEGF 1. Highlights of prescribing information. http://www.gene.com/gene/products/information/pdf/lucentis-prescribing.pdf. Accessed May 30, 2012. agents, and so it is all the more important now 2. Highlights of prescribing information. http://www.regeneron.com/Eylea/eylea-fpi.pdf. Accessed May 30, 2012. 3. Highlights of prescribing information. http://www.gene.com/gene/products/information/pdf/avastin-prescribing.pdf. Accessed May 30, 2012. to look at the totality and directionality of the (Figure courtesy of Pravin U. Dugel, MD) important trends in what is the most important of all issues for our patients—their safety,” said Pravin U. Dugel, MD, man- was confirmed in an analysis pooling data for libercept and bevacizumab, achieve a higher aging partner, Retinal Con- patients treated with the commercially available serum concentration than ranbizumab. sultants of Arizona, Phoenix. dose of ranibizumab 0.5 mg in the MARINA, “We know we should [look] ANCHOR, PIER, SAILOR, and HARBOR studies. ADVERSE EVENT RATE at major arteriothromboem- Additional data analyses from MARINA and Comparative data on serious adverse events bolic events (ATEs), and we ANCHOR showed no drug effect or dose effect (SAEs) was first provided by CATT—bevaciz- know the most vulnerable pa- comparing patients treated with ranibizumab umab-treated groups had a higher SAE rate Dr. Dugel tients—those 85 years and 0.3 or 0.5 mg. Also, no dose effect was identi- than ranibizumab groups, and the difference older—are at increased risk,” fied in the HARBOR trial comparing groups among groups continued to increase over time. said Dr. Dugel, also clinical associate professor treated with ranibizumab 0.5 versus 2 mg. More recently, data from the VIEW studies of ophthalmology, Keck School of Medicine, However, an analysis of data from HARBOR comparing ranibizumab and aflibercept was University of Southern California, Los Angeles. showed a treatment regimen effect. Among pa- released in the European Public Assessment There appears to be no drug or dose effect with tients aged ≥85 years, the ATE rate was higher Report. Analyses focusing on patients aged ranibizumab (Lucentis, Genentech), but there among those receiving monthly injections com- ≥85 years showed that after 1 year, the rate of may be a treatment regimen effect. There may pared with those being treated as needed. cardiovascular events was higher among ra- also be differences in systemic exposure and Whether differences in systemic safety exist nibizumab-treated patients whereas the rate safety profiles among different anti-VEGF agents. among the three most commonly used anti- of cerebrovascular events was higher among VEGF agents is perhaps the most controversial patients treated with aflibercept. AT INCREASED RISK? question, Dr. Dugel said. During the second year, the between-treat- The question of whether patients aged ≥85 years The agents differ structurally—aflibercept ment difference in cardiovascular rate trended are at increased risk for ATEs with intravitreal (Eylea, Regeneron) and bevacizumab (Avas- to normalize, but the difference between groups anti-VEGF treatment was investigated in a lo- tin, Genentech) contain the Fc portion of IgG1, in cerebrovascular event rates remained. ■ gistic regression analysis using data from the whereas ranibizumab does not. ranibizumab MARINA and ANCHOR studies. Data from the IVAN study showed bevaci- With patients stratified by age, ATE rates zumab caused more systemic VEGF suppres- PRAVIN U. DUGEL, MD were higher among patients aged ≥85 years sion than ranibizumab, whereas a study by Yu E: [email protected] than in the younger cohort. This effect of age et al. showed the two Fc-containing agents, af- Dr. Dugel is or has been a consultant for Genentech, Novartis, and Regeneron.

magentablackcyanyellow ES389505_OT021514_034.pgs 02.14.2014 18:01 ADV IN dispensable 35

LeD iLLumination ( in Brief ) This optical dispensary is Innovative technology enhanced by B + L Begins roLL out the use of light- emitting diode of new contact Lenses (LED) lighting. BridgewaTer, NJ :: bausch + Lomb has begun the initial rollout of its Ultra monthly replacement silicone hydrogel contact lens with MoistureSeal technology. The new lens technology—which was studied and developed for 7 years—combines a Darker coLoring material with new manufacturing processes to produce a contact lens that breaks the cycle The darker wall paint of discomfort for comfort all day, according and contrasting cream- to the company. colored fooring help “The level of excitement for this new technol- make this dispensary’s ogy among eye-care professionals underscores frame boards stand out. the increasing need for a lens that breaks the (Images courtesy of Eye Designs) cycle of discomfort and better addresses the demands of today’s contact lens user,” said Joseph Barr, OD, MS, FAAO, vice president, medical affairs, Pharmaceuticals and Vision Care, Bausch + Lomb. “With patients spend- ing more than 10 hours each day using digital devices, we know that it is critical to surpass Trending now: current standards for comfort, vision, and eye health. We believe that Bausch + Lomb Ultra does just that.” The Ultra contact lenses are now distrib- Optical dispensary uted in select markets with a national rollout scheduled for this spring.

designs, furnishings Recognition ceremony How LED lighting, color contrasting, and modernization prevent BLinDness hosts are transforming optical shop displays person of vision awarDs New York :: prevent bLindness has cho- By Rose Schneider, Content Specialist, Ophthalmology Times sen Zyloware Eyewear’s Bob Shyer, chairman, and Henry Shyer, vice chairman, as its 2014 Person of Vision Award recipients. The awards he design and functionality of an LED Lighting will be presented at the organization's Person optical dispensary are highly im- “Lighting is now becoming a crucial compo- of Vision Dinner on March 27 at the New York portant aspects to an ophthalmolo- nent of the optical design,” said Melanie Nich- Palace, New York. gist’s practice, but choosing ideal olson, an interior designer for Eye Designs, The Person of Vision Award recognizes an color schemes and fixture plans Collegeville, PA. “Proper illumination of the individual or corporation for outstanding lead- that will optimize patients’ expe- optical (dispensary) can affectively change the ership and dedication in the field of vision and rience is key. mood of the space.” eye health. Zyloware Eyewear is the oldest in- TWhile there are endless options from which In the past, Sloan said LED lighting was less dependent family owned frame supplier in the to choose, Dan Sloan—a designer for Fashion common than standard halogen lighting be- United States. Bob and Henry Shyer were cho- Optical Displays, Paradise, CA—said he has cause it had high Kelvin ratings, which caused sen because of their contributions to the vision recently seen a shift to light-emitting diode light fixtures to look “awfully funny” in the industry and for continuing their family legacy (LED) lighting, hardwood flooring, color, and dispensaries, almost emitting a purplish color. and business which now spans decades. furniture schemes that are a mix between tra- But with growing technology over the years, Co-chairpersons of the 2014 Person of Vision ditional and contemporary, and a focus on im- he said, LED lighting now produces “that nice Committee are Zyloware’s Chris Shyer, presi- proving merchandise display organization. Continues on page 36 : Dispensary design dent, and Jamie Shyer, chief operating officer. ■

magentablackcyanyellow ES390114_OT021514_035.pgs 02.15.2014 04:04 ADV 36 FEbruary 15, 2014 :: Ophthalmology Times indispensable

Dispensary Design organizing ( Continued from page 35 ) frame BoarDs warm glow,” similar to halogen lighting, but Frame boards uses less energy and produces less heat. are broken More physicians are requesting decorative up to make chandeliers, scones, and frame displays with the process of LEDs as well, Nicholson added. fnding the right “Using the proper LED lighting can really pair of frames make the frames and brands that you’re fea- turing pop, drawing customers in and grab- easier. bing their attention,” she said.

FLooRing fusion Both Sloan and Nicholson said physicians have styLing begun to lean more toward wood flooring, as opposed to traditional carpeting. This dispensary “Hard surfaces make it look more high-end,” captures a Nicholson said. combination of modern take-home and traditional Optical dispensary designers discuss furnishing what they have seen this year as far as to create an lighting, fxture plans, visual merchan- updated look. dising, and color scheme trends.

Flooring color requests have begun to shift wooD toward the dark end of the scale, Sloan said, fLoors such as darker stain or espresso coloring, to Wood fooring add more of a contrast between display fix- is utilized in tures and the floor. “That seems to be trending pretty heavily,” this optical Sloan said. dispensary for To accomplish the same outcome, Nicholson a sleeker feel. said she has seen requests for grays and neu- (Images courtesy Fashion tral creams, which are accented by the now Optical Displays) trending splash of color that can be seen incorporated in seating, imagery, and tile in the practice’s reception area. However, some physicians are opting for wood plank ceramic tile or vinyl plank over hardwood flooring, Nicholson noted, due to within the frame board to help distinguish dividers with cutout to create a unique look,” pricing. gender, styles, and brands. she added. Joost Bende, president and principal archi- Updating the optical dispensary’s overall FuRnituRE, oRganization tect for Pacific 33 Architects Inc., San Diego, look to be more up-to-date visually has been Frame boards have had a complete overall, as said he has seen a shift toward opting out of a common theme seen by Sloan, Nicholson, physicians are now realizing that—to make frame boards completely, and instead using and Bende. the process of finding the right pair of frames glass shelves or other unique displays to help “Overall designs of the office are becoming easier for patients—organization is of the up- the products stand out to patients. less clinical and more retain driven,” Nichol- most importance. If the physician would like to stick with son said. “People are looking for the cool fac- “Merchandising elements are key to letting frame boards, Sloan suggested breaking up tor in the design of a new space with more of your customers know what you are selling and the boards with shelving or putting the frames a contemporary feel.” the brands that you carry,” Nicholson said. “It into collections, which would create better ease Bende added that he has seen the trend mov- is so frustrating to walk into a doctor’s practice for patients. ing toward a “very modern look, linear and and see a wall of frames. Frame boards need Feature walls have also become quite popular, simple,” while Sloan said he has seen more visual breaks so the eye can rest and give di- according to Nicholson, along with areas to incor- combinations of old and new. rection to the frames that are meant for them.” porate new products and brand merchandising. “(They) aren’t purely traditional or contem- Nicholson suggested adding small signage “Offices are adding three-dimensional wall porary, but a fusion of the two,” he said. ■

magentablackcyanyellow ES390113_OT021514_036.pgs 02.15.2014 04:04 ADV FEBRUARY 15, 2014 :: Ophthalmology Times 37 indispensable

( In Brief ) Marciano puts a new Range of applications ADLENS LAUNCHES spin on sophisticated VARIABLE-FOCUS EYEWEAR WITH IMPROVED OPTICS eyewear

MODEL GM 201

OXFORD, UNITED KINGDOM :: ADLENS INTRODUCES ADJUSTABLES, its lat- MODEL est variable-focus eyewear product. GM 199 Each lens consists of two wave-shaped plates that glide across each another to alter the power of each lens, correcting more than 90% of spherical errors (lens power –6 D to +3 D). Although the improved optics result in an optimized reading zone, Adjustables were designed for a range of applications—such as up-close work, computer use, yard work, and for managing fluctuating vision in diabetes patients or after eye surgery. Along with enhanced optics, Adjustables offer an aesthetic pair of glasses. The brow bar is more ergonomic for a modern look, the nosepiece is ad- justable for a comfortable fit, and the frame and temple arms were designed to give the glasses a lightweight feel. Adlens Adjustables are available in black, blue, gray/black, and red/black, followed soon by a new range of colors.

NEW YORK :: One-stop service THE MARCIANO optical collection from Viva of black, burgundy, and tortoise, as well as blue International Group updates its signature style and green horn. SANTINELLI BOOSTS with colorful modern details. The retro-inspired model GM 201 offers rich The dramatic cat-eye silhouette of model GM jewel-tone horn colorations in teal, purple, brown, ITS LINE OF DISPENSARY 199 has satin metal finishes in gold, burgundy, and black throughout. Acetate fronts, double- TOOLS, SUPPLIES and black. Transparent horn temple tips com- plated metal temples, and acetate temple tips plement this simple elegant frame in shades set off the rectangular shape. ■ HAUPPAUGE, NY :: SANTINELLI INTERNATIONAL HAS used its 40th anniversary to re-launch its optical supplies product line. According to the company, Santinelli offers one-stop service for both dispensary and fin- line is the Visionary Plier Collection, developed by supplies they need to successfully run their prac- ishing needs. Breit feld & Schliekert, a German company known tice,” said Gerard Santinelli, president and chief Products for in-office labs highlight such sta- for craftsmanship and functional products. executive officer. ples as nose pads, temple tips, and screws, but “We are thrilled to provide our clients the abil- An e-catalog is available on the company’s web-

(Images courtesy of Adlens and Viva International Group) Viva Adlens and courtesy of (Images also include unique workshop items. One featured ity to order a wide array of the optical tools and site: www.santinelli.com. ■

magentablackcyanyellow ES390005_OT021514_037.pgs 02.15.2014 01:21 ADV 38 FEBRUARY 15, 2014 :: Ophthalmology Times marketplace

For Products & Services advertising information, contact: Karen Gerome at 800-225-4569, ext 2670 • Fax 440-756-5271 • Email: [email protected] For Recruitment advertising information, contact: Joanna Shippoli at 800-225-4569, ext 2615 • Fax 440-756-5271 • Email: [email protected] PRODUCTS & SERVICES

BILLING SERVICES DIGITAL IMAGING PM Medical Billing & Consulting DOES YOUR DIGITAL IMAGING SYSTEM Exclusive Ophthalmology Billers CAPTURE IMPRESSIVE 21MP IMAGES? Expert Ophthalmology Billers Excellent Ophthalmology Billers Triple E = Everything gets Paid Concentrating on one Specialty makes the difference. We are a Nationwide Ophthalmology Billing Service. We have been in business over twenty years. Our staff consists of billers who are certifed Ophthalmic Techs, Ophthalmic assistants, and fundus photographers who are dual certifed ophthalmic coders and billers. This combination of clinical backgrounds in ophthalmology with the certifed coding degree is the ideal combination of expertise that you need to dramatically increase your revenue. We will get you paid on every procedure every FUNDUS PHOTO DOES! single time. No more bundling, downcoding or denials… Primary, Secondary, Tertiary and Patient Billing Learn more at www.itsthisgood.com 314.533.6000 Relentless and meticulous follow up. • Experts in Forensic Billing .Specializing in old AR cleanup • Credentialing and Re credentialing our Specialty. EQUIPMENT We have a separate Credentialing Department who has cultivated years of contacts to expedite the process as well as getting providers on plans that The Leading Reseller of Premium are technically closed. Preowned Diagnostic Equipment in the U.S. • We can offer you our own Practice Management software at no cost to you or we can VPN into your system if that is what you prefer. • Totally Hippa compliant. We are certifed Hippa and have invested in the most secure Hippa connection that Google and Cisco use. • Monthly custom reports provided. We presently work on all of the following Practice Management systems : NextGen, MD Ofﬁce, Centricity, Medisoft, Ofﬁce Mate, MD Intellus, Medware, Medcomp, Management Plus, ADS, Revolution EHR, EyeMd EMR, Next Tec, Open Practice Solutions , Cerner Works and more…. All of our clients were paid the PQRI and E-prescribe bonuses and we are ready for the ICD-10 change Our staff has years of Attendance at AAO and ASCRS and attends all ongoing Ophthalmology billing and Practice Management continuing education classes. We are always knowledgeable and prepared for all government and commercial changes. On staff MBA consultants Call today to schedule a free on site consultation. We will travel to you anytime to evaluate your AR and show Repair Services We also buy used equipment you how we can dramatically increase your Revenue. Available! Call toll free at 1-888-PM-BILLING (1-888-762-4554) Call 1-800-328-2020 for a quote today! Email: [email protected] Web: www.pmophthalmologybilling.com 24 hours: 516-830-1500 Buying and Selling Our Prestigious National Ophthalmology Clients Pre-owned Ophthalmic reference list will be provided at your request Instrumentation. Contact Jody Myers at (800) 336-0410 or visit www.floridaeye.com

PM (Practice Management) Billing will keep an EYE on your Billing so you can keep an EYE on your patients.

magentablackcyanyellow ES388954_OT021514_038_CL.pgs 02.12.2014 17:31 ADV FEBRUARY 15, 2014 :: Ophthalmology Times 39 marketplace

RECRUITMENT

CALIFORNIA

PEDIATRIC OPHTHALMOLOGY/ W ADULT STRABISMUS Fellowship Trained BC/BE physician desired a for a prestigious 16 provider multisubspecialty Eye Group on CONNECT n California’s Gold Coast, 55 miles NW of L.A. Candidate will be busy at inception in a multidisciplinary t clinical and surgical setting. with qualifed leads Generous initial salary, benefts, e with equity partnership opportunity. Apply with CV to: and career professionals d [email protected]

FLORIDA

Post a job today OCULOPLASTIC FELLOWSHIP Offered by Dr. Roger E. Bassin of The Bassin Center For Plastic Surgery One year fellowship. Learn about face lift, lazerlift, blepharoplasty, brow lift, cheek www.modernmedicine.com/physician-careers lift, laser resurfacing, fat transfer and body liposuction as well as basic oculoplastic surgery. Please submit resumes to: Joanna Shippoli [email protected] RECRUITMENT MARKETING ADVISOR (800) 225-4569, ext. 2615 [email protected]

Content Licensing for Every Marketing Strategy

Marketing solutions ﬁt for: Outdoor | Direct Mail | Print Advertising Tradeshow/POP Displays Social Media | Radio & TV

Leverage branded content from Opthalmology Times to create a more powerful and sophisticated statement about your product, service, or company in your next marketing campaign. Contact Wright’s Media to fnd out more about how we can customize your acknowledgements and recognitions to enhance your marketing strategies.

For information, call Wright’s Media at 877.652.5295 or visit our website at www.wrightsmedia.com

magentablackcyanyellow ES388953_OT021514_039_CL.pgs 02.12.2014 17:31 ADV 40 practice management FebRuARy 15, 2014 :: Ophthalmology Times

How ‘Obamacare’ impacts eye health disparities Provisions of Affordable Care Act may be able to reduce vision health inequalities By rose schneider, Content Specialist, Ophthalmology Times

Take-Home pact on decreasing vision related disparities preferences using Health and Human Services among minorities: definitions with the goal of ultimately reduc- Vision health disparities are a ing disparities,” he said. serious issue in the United States 1. infrAstruCture: The ACA has el- Another way the ACA is encouraging further among minorities, and many are hoping evated the National Center for Minority Health data collection and research to combat dispari- provisions in the Affordable Care Act and Health Disparities into the NIMHD. The act ties is through electronic health records (EHRs). will be able to alleviate the issue. has given the newly formed agency overall re- Dr. Wilson explained that many physicians sponsibility for strategic planning and program have advocated for some type of national eye coordination for all the health disparities re- health surveillance mechanism to reduce dis- Detroit :: lated to research and training for the entire NIH. parities in vision and eye health. isparities in vision and eye health- The act also established the Office of Minority “There’s a lot of potential for (EHRs here),” care opportunities among minori- Health in the Health and Human Services De- he said. ties is a big problem in the United partment, as well as in other government of- States, according to M. Roy Wil- fices like the Centers for Disease Control and the Centers for Medicare and Medicaid. Inequities in vision D son, MD, MS. Furthermore, these disparities have resulted in a high number of unnecessary vision loss 2. ACCess: The health-care overhaul included and health care among American minorities, as 6.9% of Afri- many increased access provisions, including Med- can Americans and 9.2% of Hispanics have icaid expansion, insurance regulation/the Ameri- extend beyond impaired vision that could be easily remedied can health benefit exchange, community health with eyeglasses, said Dr. Wilson, president of centers creation, as well as prevention and well- access, notes M. Roy Wayne State University, Detroit. ness additions. These specific changes the ACA “There are a number of ophthalmic diseases brings could turn out to make a large impact Wilson, MD, MS. for which there are disparities based on ei- on accessibility to health care by minorities— ther race, ethnicity, or socially economic sta- “simply because more minorities (currently) have This method could still be an issue, because tus,” he said. difficulty with access,” he added. not all physicians have EHRs, Dr. Wilson said. Though many physicians see the dispari- “(However), the ACA is moving most prac- ties problem as exclusively an access issue, Dr. 3. HeAltH-CAre workforCe And titioners in that direction,” he said. “There Wilson said he believes there are more factors CulturAl CompetenCy: There are a is potential for going from individual data to that play a role as well. number of provisions associated with this area, population data, which will facilitate health “There is lots of evidence it’s not just access,” as its intent is to improve the diversity of the surveillance on a population level, which can said Dr. Wilson, who is also the former deputy workforce. then be used to track and monitor progres- director for strategic scientific planning and sion and outcomes of disease better to address program coordination at the National Institute 4. QuAlity improvement: The ACA health disparities.” on Minority and Health Disparities (NIMHD) will increase data collection and research to im- But EHRs cannot accomplish this alone, Dr. of the National Institutes of Health (NIH). prove the quality of health-care for minorities. Wilson said. Some kind of system that brings “The problem is much more widespread,” all the necessary components together and to he continued. reseArCH And analyze them is needed. That is where the Affordable Care Act (ACA) dAtA ColleCtion One of the ways to do this is through clini- will come into play, Dr. Wilson said, as the Dr. Wilson said he believes quality of health care, cal data registry, he said. health-care overhaul has the potential to re- not just access to it, is one of the most critical “This is an area that has much potential, duce the dilemma greatly, while addressing aspects in regard to vision-related disparities. because if you track data by . . . race and eth- its various causes. “To me, one of the most important things nicity and language preference, then you’re the ACA did with respect to health disparities, going to get better care all the way around,” ACA impACt is that all federal funded health programs and Dr. Wilson said. “Hopefully, for most of those There are four areas, Dr. Wilson explained, surveys are now required to collect and report conditions that you’re tracking, you’re going to in which the ACA may have a significant im- on every patient’s race, ethnicity, and language Continues on page 42 : Disparity

magentablackcyanyellow ES390004_OT021514_040.pgs 02.15.2014 01:21 ADV USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects: Pregnancy Category C. Loteprednol etabonate has been shown to be embryotoxic (delayed ossification) and teratogenic (increased incidence of meningocele, abnormal left common carotid artery, and limb flexures) when administered orally to rabbits during organogenesis at a dose of 3 mg/kg/day (35 times the maximum daily clinical dose), a dose which caused no maternal toxicity. The no-observed-effect-level (NOEL) for these effects was 0.5 mg/kg/day Brief Summary: Based on full prescribing information. (6 times the maximum daily clinical dose). Oral treatment of rats during organogenesis resulted in teratogenicity (absent innominate artery at ≥5 mg/ To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb at kg/day doses, and cleft palate and umbilical hernia at ≥50 mg/kg/day) and 1-800-323-0000 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch embryotoxicity (increased post-implantation losses at 100 mg/kg/day and decreased fetal body weight and skeletal ossification with ≥50 mg/kg/day). INDICATIONS AND USAGE Treatment of rats with 0.5 mg/kg/day (6 times the maximum clinical dose) during organogenesis did not result in any reproductive toxicity. Loteprednol LOTEMAX is a corticosteroid indicated for the treatment of post-operative etabonate was maternally toxic (significantly reduced body weight gain during inflammation and pain following ocular surgery. treatment) when administered to pregnant rats during organogenesis at doses DOSAGE AND ADMINISTRATION of ≥5 mg/kg/day. Invert closed bottle and shake once to fill tip before instilling drops. Oral exposure of female rats to 50 mg/kg/day of loteprednol etabonate from Apply one to two drops of LOTEMAX into the conjunctival sac of the affected the start of the fetal period through the end of lactation, a maternally toxic eye four times daily beginning the day after surgery and continuing treatment regimen (significantly decreased body weight gain), gave rise to throughout the first 2 weeks of the post-operative period. decreased growth and survival, and retarded development in the offspring CONTRAINDICATIONS during lactation; the NOEL for these effects was 5 mg/kg/day. Loteprednol LOTEMAX, as with other ophthalmic corticosteroids, is contraindicated in etabonate had no effect on the duration of gestation or parturition when most viral diseases of the cornea and conjunctiva including epithelial herpes administered orally to pregnant rats at doses up to 50 mg/kg/day during the simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in fetal period. mycobacterial infection of the eye and fungal diseases of ocular structures. There are no adequate and well controlled studies in pregnant women. WARNINGS AND PRECAUTIONS LOTEMAX should be used during pregnancy only if the potential benefit Intraocular Pressure (IOP) Increase justifies the potential risk to the fetus. Prolonged use of corticosteroids may result in glaucoma with damage to the Nursing Mothers optic nerve, defects in visual acuity and fields of vision. Steroids should be It is not known whether topical ophthalmic administration of corticosteroids used with caution in the presence of glaucoma. If this product is used for 10 could result in sufficient systemic absorption to produce detectable quantities days or longer, intraocular pressure should be monitored. in human milk. Systemic steroids appear in human milk and could suppress Cataracts growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Caution should be exercised when LOTEMAX is administered Use of corticosteroids may result in posterior subcapsular cataract formation. to a nursing woman. Delayed Healing Pediatric Use The use of steroids after cataract surgery may delay healing and increase the Safety and effectiveness in pediatric patients have not been established. incidence of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical Geriatric Use steroids. The initial prescription and renewal of the medication order should No overall differences in safety and effectiveness have been observed be made by a physician only after examination of the patient with the aid between elderly and younger patients. of magnification such as slit lamp biomicroscopy and, where appropriate, NONCLINICAL TOXICOLOGY fluorescein staining. Carcinogenesis, Mutagenesis, Impairment Of Fertility Bacterial Infections Long-term animal studies have not been conducted to evaluate the Prolonged use of corticosteroids may suppress the host response and carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was thus increase the hazard of secondary ocular infections. In acute purulent not genotoxic in vitro in the Ames test, the mouse lymphoma tk assay, or in conditions of the eye, steroids may mask infection or enhance existing a chromosome aberration test in human lymphocytes, or in vivo in the single infection. dose mouse micronucleus assay. Treatment of male and female rats with up to Viral Infections 50 mg/kg/day and 25 mg/kg/day of loteprednol etabonate, respectively, (600 Employment of a corticosteroid medication in the treatment of patients with and 300 times the maximum clinical dose, respectively) prior to and during a history of herpes simplex requires great caution. Use of ocular steroids may mating did not impair fertility in either gender. prolong the course and may exacerbate the severity of many viral infections PATIENT COUNSELING INFORMATION of the eye (including herpes simplex). Administration Fungal Infections Invert closed bottle and shake once to fill tip before instilling drops. Fungal infections of the cornea are particularly prone to develop coincidentally Risk of Contamination with long-term local steroid application. Fungus invasion must be considered Patients should be advised not to allow the dropper tip to touch any surface, in any persistent corneal ulceration where a steroid has been used or is in as this may contaminate the gel. use. Fungal cultures should be taken when appropriate. Contact Lens Wear Contact Lens Wear Patients should be advised not to wear contact lenses when using LOTEMAX. Patients should not wear contact lenses during their course of therapy with Risk of Secondary Infection LOTEMAX. If pain develops, redness, itching or inflammation becomes aggravated, the ADVERSE REACTIONS patient should be advised to consult a physician. Adverse reactions associated with ophthalmic steroids include elevated FOR MORE DETAILED INFORMATION, PLEASE READ THE PRESCRIBING intraocular pressure, which may be associated with infrequent optic nerve INFORMATION. damage, visual acuity and field defects, posterior subcapsular cataract formation, delayed wound healing and secondary ocular infection from Bausch & Lomb Incorporated pathogens including herpes simplex, and perforation of the globe where there Tampa, Florida 33637 USA is thinning of the cornea or sclera. US Patent No. 5,800,807 ©Bausch & Lomb Incorporated The most common adverse drug reactions reported were anterior chamber inflammation (5%), eye pain (2%), and foreign body sensation (2%). ®/™ are trademarks of Bausch & Lomb Incorporated or its affiliates.

9303400

black ES388105_OT021514_041_FP.pgs 02.05.2014 19:09 ADV 42 FebRuARy 15, 2014 :: Ophthalmology Times practice management

cause of the act’s difficult rollout, the exact DISPaRITY impact is still up in the air. A dvertiser Index “One of the issues with the ACA is a lot of Advertiser Page ( Continued from page 40 ) it hasn’t been implemented and there’s been a lot of hold up,” he said. “So even though a Alcon Laboratories Inc. CV2, 3, 7-8 P: 800/862-5266 reduce the difference between different popu- lot of the provisions have been passed, they www.alcon.com lations’ outcomes.” haven’t been funded. “Because of political considerations, some Allergan Inc. 15-16, 23-24 lookinG furtHer of this is still in doubt,” he added. “How many P: 714/246-4500 Another route the ACA will utilize research to of those are actually implemented . . . will de- F: 714/246-4971 combat health disparities is through the cre- pend on a lot of political factors and will ulti- www.allergan.com ation of the Patient-Centered Outcomes Re- mately determine how effective the ACA is in search Institute (PCORI). addressing health disparities.” ■ Bausch + Lomb 41, CV4 Dr. Wilson said PCORI assures that research P: 800/227-1427 will address the health-care needs of all patient www.bausch.com populations, which is needed, as treatments may not work equally for everyone. Cleveland Clinic 27 Though Dr. Wilson said he believes these m. RoY WILSoN, mD, mS www.consultQD.org/oph ACA provisions and agency creations will most P: 313/577-2230 E: [email protected] certainly alleviate eye health disparities, be- Dr. Wilson did not indicate a f nancial interest in the subject matter. Houston Methodist Hospital CV3 P: 310/280-7800 www.hmleadingmedicine.com

Nicox 10-11 Maneuvering around www.nicox.com Perrigo Specialty Pharmaceuticals 19-20 P: 866/634-9120 problems with the ACA E: [email protected] www.perrigo.com By lynda Charters Rhein Medical 5 P: 800/637-4346 www.rheinmedical.com CoLUMBiA, MD :: THE AFFORDABLE CARE ACT Dr. Glasser said a cost-cutting measure is (ACA) was designed to provide health insur- to limit provider networks to those willing to TTI Medical 26 P: 800/322-7373 ance for millions of uninsured citizens with discount the cost of coverage heavily. www.ttimedical.com no exclusions for pre-existing conditions, ex- “The ability to see patients will depend on pand services like screening and preventive if the carrier accepts physicians into their net- health coverage, and be less costly for patients work and if the carrier payments are accept- University of Pittsburgh Medical Center 31 www:UPMCPhysicianResources.com/vision and the government. able to physicians,” he said. Considering the troublesome initial operation Therapeutic options may be subject to cost- This index is provided as an additional service. of the ACA sign-up website, David Glasser, MD, cutting measures also, he proposed. The publisher does not assume any liability for errors who is in private practice in Columbia, MD, “Carriers will start contracting with limited or omissions. speculated about the future of the program. hospitals and ambulatory surgical centers that “My first prediction is that some form of provide a good deal, which may not be where

‘Obamacare’ will be around long after Presi- a physician has privileges,” he said. 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, dent Obama leaves office,” he said. Dr. Glasser said he wonders if there will 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 However, a number of questions arise when be problems with payments for corneal tissue 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. he considers the future of the ACA, such as and more adverse medical necessity determi- $ Possessions; $30 in Canada and Mexico; $35 in all other countries. Include $6.50 per whether there will be more government regu- nations that may make it more difficult for 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 lations, potential loss of patients, limited thera- certain procedures to be performed. 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. peutic options, and physician reimbursement. Dr. Glasser advised that physicians sim- Canadian G.S.T. number: R-124213133RT001, Publications Mail Agreement Number 40612608. Return undeliverable Canadian addresses to: Pitney Bowes PO Box 25542 “There are definitely more government plify when possible. He recommended using London, ON N6C 6B2 CANADA. Printed in the U.S.A. ‘hoops,’” he noted. the American Academy of Ophthalmology’s ©2014 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 Physicians may also have fewer patients since IRIS Registry to remove the busy work from including by photocopy, recording, or information storage and retrieval without permission in writing from the publisher. Authorization to photocopy items for internal/ healthy individuals may not sign up for health an electronic health records system, read con- 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 coverage because of cost, and with only sick tracts, and tell the ambulatory surgical centers the Copyright Clearance Center, 222 Rosewood Dr. Danvers, MA 01923, 978-750-8400 fax 978-646-8700 or visit http://www.copyright.com online. For uses beyond those individuals signing up, the insurance will be to analyze their contracts for potential tissue listed above, please direct your written request to Permission Dept. fax 440-756-5255 or more expensive. payment issues. ■ email: [email protected].

magentablackcyanyellow ES390003_OT021514_042.pgs 02.15.2014 01:21 ADV A NEW NAME. A LEGACY OF INGENUITY. THE METHODIST HOSPITAL IS NOW HOUSTON METHODIST HOSPITAL.

We’ve changed our name. The Methodist Hospital is now Houston Methodist Hospital. We’re moving forward, and bringing tomorrow’s advances in ophthalmology to our patients today. The ﬁnest researchers and clinicians from around the world are joining us in Houston, to build on our legacy of ingenuity, and accelerate the discovery and delivery of better care and better cures. That’s the difference between practicing medicine and leading it.

See all the ways we’re leading at hmleadingmedicine.com.

magentablackcyanyellow ES388107_OT021514_CV3_FP.pgs 02.05.2014 19:09 ADV NOW AVAILABLE LOTEMAX® GEL

UNIQUE FORMULATION DESIGNED FIRST IN CLASS* TO CONTROL INFLAMMATION GEL DROP

Indications and Usage • Bacterial infections—Prolonged use of corticosteroids may suppress the host • LOTEMAX® GEL is a corticosteroid indicated for the treatment of post-operative response and thus increase the hazard of secondary ocular infection. In acute iný ammation and pain following ocular surgery purulent conditions, steroids may mask infection or enhance existing infections Important Risk Information about LOTEMAX® GEL • Viral infections—Use of corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Use of ocular steroids may prolong • LOTEMAX® GEL is contraindicated in most viral diseases of the cornea and the course and exacerbate the severity of many viral infections of the eye (including conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), herpes simplex) vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures • Fungal infections—Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be • Intraocular pressure (IOP) increase—Prolonged use of corticosteroids may result considered in any persistent corneal ulceration where a steroid has been used or is in use in glaucoma with damage to the optic nerve, defects in visual acuity and å elds of ® vision. If this product is used for 10 days or longer, IOP should be monitored • Contact lens wear—Patients should not wear contact lenses when using LOTEMAX GEL • Cataracts—Use of corticosteroids may result in posterior subcapsular • The most common ocular adverse drug reactions were anterior chamber iný ammation cataract formation (5%), eye pain (2%) and foreign body sensation (2%) • Delayed healing—Use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation and occurrence of perforations in those with diseases causing corneal and scleral thinning. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magniå cation

Please see brief summary of full prescribing information on adjacent page.

*Ophthalmic corticosteroid. References: 1. LOTEMAX GEL Prescribing Information, September 2012. 2. Fong R, Leitritz M, Siou-Mermet R, Erb T. Loteprednol etabonate gel 0.5% for postoperative pain and iný ammation after cataract surgery: results of a multicenter trial. Clin Ophthalmol. 2012;6:1113-1124. 3. Data on å le, Bausch Lomb Incorporated. ®/TM are trademarks of Bausch Lomb Incorporated or its afå liates. ª2012 Bausch Lomb Incorporated. USLGX120066 <1212> DISCOVER THE POWER OF GEL

magentablackcyanyellow ES388115_OT021514_CV4_FP.pgs 02.05.2014 19:09 ADV