Cataract Surgery? P.2P26

Home , Congenital cataract

MASTERS OF SURGERY P. 62 • DEVELOPMENTS IN GENETIC TESTING P. 16 TELEMEDICINE IN PEDIATRIC RETINAL DISEASE P. 60 • WILLS EYE RESIDENT CASE SERIES P. 85 ARE TWO MIGS BETTER THAN ONE? P. 70 • NEW TARGETS FOR ALLERGY TREATMENT P. 66 Review of Ophthalmology Vol. XXII, No. 3 • March 2015 • Who’sReview of Ophthalmology Vol. XXII, Femto Getting Cataract Surgery • Are Two MIGS B etter Than One? • New Targets Treatment for Allergy

March 2015

reviewofophthalmology.com

CATARACT ISSUE Who’s Getting Femto Laser Cataract Surgery? P.2P26

What the Data Says About Femtosecond Cataract Surgery P. 36 Reader Survey: Cataract Surgery P. 44

001_rp0315_fc.indd 1 2/20/15 4:22 PM Cornea. Capsule. Lens. One optimized solution.

Shown with the VERION™ Digital Marker

Demand precision across the entire anterior segment. Part of The Cataract Refractive Suite by Alcon, the LenSx® Laser is designed to optimize performance across the entire anterior segment to deliver: • Precise primary and • Complete, reproducible • Versatile fragmentation secondary corneal incisions, capsulotomies with patterns and arcuate incisions pristine edges1

1. Alcon data on ﬁ le. Visit LenSxLasers.com, or talk to your local Alcon representative about how the LenSx® Laser can help enhance the precision of cataract surgery with AcrySof® IOLs. © 2014 Novartis 11/14 LSX14078JAD COMPLETE PRECISION

RP0315_Alcon Lensx.indd 1 2/9/15 2:23 PM ACRYSOF® IQ INTRAOCULAR LENSES IMPORTANT PRODUCT INFORMATION EVERY MONDAY CAUTION: FEDERAL USA LAW RESTRICTS THIS DEVICE TO THE SALE BY OR ON THE ORDER OF A PHYSICIAN.

INDICATIONS: THE ACRYSOF® IQ POSTERIOR CHAMBER INTRAOCULAR LENS IS INTENDED FOR THE REPLACEMENT OF THE HUMAN LENS TO ACHIEVE VISUAL CORRECTION OF APHAKIA IN ADULT PATIENTS FOLLOWING CATARACT SURGERY. THIS LENS IS INTENDED FOR PLACEMENT IN THE CAPSULAR BAG. E-NEWS WARNINGS/PRECAUTIONS: CAREFUL PREOPERATIVE EVALUATION AND SOUND CLINICAL JUDGMENT SHOULD BE USED BY THE SURGEON TO DECIDE THE RISK/BENEFIT RATIO BEFORE IMPLANTING A LENS IN A PATIENT WITH ANY OF THE CONDITIONS YOU DESCRIBED IN THE DIRECTIONS FOR USE LABELING. CAUTION SHOULD BE USED PRIOR TO LENS ENCAPSULATION TO AVOID LENS DECENTRATIONS OR DISLOCATIONS. CAN STUDIES HAVE SHOWN THAT COLOR VISION DISCRIMINATION IS NOT ADVERSELY AFFECTED IN INDIVIDUALS WITH THE ACRYSOF® NATURAL IOL AND NORMAL COLOR VISION. THE EFFECT ON VISION OF THE ACRYSOF® NATURAL IOL IN SUBJECTS WITH HEREDITARY COLOR VISION DEFECTS AND ACQUIRED COLOR VISION DEFECTS SECONDARY TO OCULAR DISEASE E.G., USE GLAUCOMA, DIABETIC RETINOPATHY, CHRONIC UVEITIS, AND OTHER RETINAL OR OPTIC NERVE DISEASES HAS NOT BEEN STUDIED. DO NOT RESTERILIZE; DO NOT STORE OVER 45° C; USE ONLY STERILE IRRIGATING SOLUTIONS SUCH AS BSS® OR BSS PLUS® STERILE INTRAOCULAR IRRIGATING SOLUTIONS.

ATTENTION: REFERENCE THE DIRECTIONS FOR USE LABELING FOR A COMPLETE LISTING OF INDICATIONS, WARNINGS AND PRECAUTIONS. Have you been receiving and reading custom e-blasts from

LENSX® LASER IMPORTANT PRODUCT INFORMATION Review of Ophthalmology?

CAUTION: UNITED STATES FEDERAL LAW RESTRICTS THIS DEVICE TO SALE AND USE BY OR ON THE ORDER OF A PHYSICIAN OR LICENSED EYE CARE PRACTITIONER. If not, you’re missing out on

INDICATION: THE LENSX® LASER IS INDICATED FOR USE IN PATIENTS UNDERGOING CATARACT SURGERY FOR REMOVAL OF valuable information! THE CRYSTALLINE LENS. INTENDED USES IN CATARACT SURGERY INCLUDE ANTERIOR CAPSULOTOMY, PHACOFRAGMENTATION, AND THE CREATION OF SINGLE PLANE AND MULTIPLANE ARC CUTS/INCISIONS IN THE CORNEA, EACH OF WHICH MAY BE PERFORMED EITHER INDIVIDUALLY OR CONSECUTIVELY DURING THE SAME PROCEDURE. You’re a busy practitioner and not surprisingly, your e-mail inbox is often full. Fortunately, when RESTRICTIONS: PATIENTS MUST BE ABLE TO LIE FLAT AND MOTIONLESS IN A SUPINE POSITION. PATIENT MUST BE ABLE TO you scan through the sender list, determining UNDERSTAND AND GIVE AN INFORMED CONSENT. PATIENTS MUST BE ABLE TO TOLERATE LOCAL OR TOPICAL ANESTHESIA. PATIENTS WITH ELEVATED IOP SHOULD USE TOPICAL STEROIDS ONLY UNDER CLOSE MEDICAL SUPERVISION. which messages to delete and which to save or read, you can feel conﬁ dent knowing that e-blasts CONTRAINDICATIONS: CORNEAL DISEASE THAT PRECLUDES APPLANATION OF THE CORNEA OR TRANSMISSION OF LASER LIGHT AT 1030 NM WAVELENGTH. DESCEMETOCELE WITH IMPENDING CORNEAL RUPTURE. PRESENCE OF BLOOD OR OTHER from Review of Ophthalmology, a Jobson Medical MATERIAL IN THE ANTERIOR CHAMBER. POORLY DILATING PUPIL, SUCH THAT THE IRIS IS NOT PERIPHERAL TO THE INTENDED Information LLC publication, contain the most DIAMETER FOR THE CAPSULOTOMY. CONDITIONS WHICH WOULD CAUSE INADEQUATE CLEARANCE BETWEEN THE INTENDED current and comprehensive information available in CAPSULOTOMY DEPTH AND THE ENDOTHELIUM APPLICABLE TO CAPSULOTOMY ONLY. PREVIOUS CORNEAL INCISIONS THAT the ﬁ eld to keep you on the cutting edge. MIGHT PROVIDE A POTENTIAL SPACE INTO WHICH THE GAS PRODUCED BY THE PROCEDURE CAN ESCAPE. CORNEAL THICKNESS REQUIREMENTS THAT ARE BEYOND THE RANGE OF THE SYSTEM. CORNEAL OPACITY THAT WOULD INTERFERE WITH THE LASER BEAM. HYPOTONY OR THE PRESENCE OF A CORNEAL IMPLANT. RESIDUAL, RECURRENT, ACTIVE OCULAR OR EYELID DISEASE, Review of Ophthalmology’s online stable of prod- INCLUDING ANY CORNEAL ABNORMALITY FOR EXAMPLE, RECURRENT CORNEAL EROSION, SEVERE BASEMENT MEMBRANE ucts includes editorial newsletters and promotional DISEASE. HISTORY OF LENS OR ZONULAR INSTABILITY. ANY CONTRAINDICATION TO CATARACT OR KERATOPLASTY. THIS information about new products, treatments and DEVICE IS NOT INTENDED FOR USE IN PEDIATRIC SURGERY. surgical techniques, as well as alerts on continuing

WARNINGS: THE LENSX® LASER SYSTEM SHOULD ONLY BE OPERATED BY A PHYSICIAN TRAINED IN ITS USE. education courses for ophthalmologists.

THE LENSX® LASER DELIVERY SYSTEM EMPLOYS ONE STERILE DISPOSABLE LENSX® LASER PATIENT INTERFACE CONSISTING OF Our FREE weekly e-newsletter, Review AN APPLANATION LENS AND SUCTION RING. THE PATIENT INTERFACE IS INTENDED FOR SINGLE USE ONLY. THE DISPOSABLES USED IN CONJUNCTION WITH ALCON® INSTRUMENT PRODUCTS CONSTITUTE A COMPLETE SURGICAL SYSTEM. USE OF of Ophthalmology Online, brings you DISPOSABLES OTHER THAN THOSE MANUFACTURED BY ALCON MAY AFFECT SYSTEM PERFORMANCE AND CREATE POTENTIAL the latest in ophthalmic research, as well HAZARDS. as industry news. In an eff ort to keep eyecare professionals informed, this resource is THE PHYSICIAN SHOULD BASE PATIENT SELECTION CRITERIA ON PROFESSIONAL EXPERIENCE, PUBLISHED LITERATURE, AND waiting in your inbox every Monday morning. EDUCATIONAL COURSES. ADULT PATIENTS SHOULD BE SCHEDULED TO UNDERGO CATARACT EXTRACTION.

PRECAUTIONS: DO NOT USE CELL PHONES OR PAGERS OF ANY KIND IN THE SAME ROOM AS THE LENSX® LASER. DISCARD Retina Online, our free monthly USED PATIENT INTERFACES AS MEDICAL WASTE. e-newsletter, is for retina specialists and AES/COMPLICATIONS: CAPSULOTOMY, PHACOFRAGMENTATION, OR CUT OR INCISION DECENTRATION. INCOMPLETE OR general INTERRUPTED CAPSULOTOMY, FRAGMENTATION, OR CORNEAL INCISION PROCEDURE. CAPSULAR TEAR. CORNEAL ABRASION ophthalmologists interested in OR DEFECT. PAIN. INFECTION. BLEEDING. DAMAGE TO INTRAOCULAR STRUCTURES. ANTERIOR CHAMBER FLUID LEAKAGE, enhancing their knowledge on the topics of retina ANTERIOR CHAMBER COLLAPSE. ELEVATED PRESSURE TO THE EYE. and related disease diagnosis and treatment, as ATTENTION: REFER TO THE LENSX® LASER OPERATOR’S MANUAL FOR A COMPLETE LISTING OF INDICATIONS, WARNINGS AND well as the latest in surgical procedures. PRECAUTIONS.

Unfamiliar with our products? Visit www.reviewofophthalmology.com and check out our newsletter archives.

003_rp0315_ads.indd 3 2/20/15 3:21 PM

2015_RPonline_house_half.indd 90 2/12/15 2:43 PM REVIEW NEWS Volume XXII • No. 3 • March 2015 Kellogg Center Study Finds Generics Improve Adherence

When patients with glaucoma switched the study had health insurance. ence, it may be a good idea to switch from a brand name drug to its ge- Dr. Stein and colleagues found from a brand name to a generic drug,” neric counterpart, they were more that patients who remained on advises Dr. Stein. He also encourages likely to take their medication as brand name drugs were 39-percent patients to ask their doctors if a ge- directed compared to those who re- more likely to experience a decline neric alternative is available and ap- mained on the brand name drug, ac- in adherence compared to those propriate for their circumstances. cording to a study published online who switched to the newly available in Ophthalmology. Researchers at generic drug latanoprost. The re- the University of Michigan Kellogg searchers cited several factors associ- Ranibizumab Eye Center and College of Phar- ated with improved adherence rates, macy studied medication adherence among them, the use of the generic Restores Diabetic rates 18 months before and after the drug once it became available and ﬁ rst generic prostaglandin analogue lower copays after the generic drug Vision Loss glaucoma drug became available in became available. Ranibizumab, commonly used to treat March 2011. The Michigan researchers found age-related vision loss, also reverses Despite the potentially dire con- that black patients had decreased vision loss caused by diabetes among sequences for non-adherence, many adherence compared to white pa- Hispanic and non-Hispanic whites, patients struggle with their drug regi- tients, a concern because blacks tend according to a new study led by mens. Along with known barriers— to have more severe disease and of- investigators from the University of eye drops can be difﬁ cult to use, ten require a more complex medica- Southern California Eye Institute. medication regimens may be com- tion regimen. However, a subset of Diabetic retinopathy and diabet- plicated, and patients may not un- blacks—those who switched to the ic macular edema are the leading derstand the consequences of poor generic drug—had a substantial im- causes of vision loss in working-age adherence—the high cost of copays provement in adherence compared adults in the United States, accord- for brand name drugs is also a deter- to blacks who remained on brand ing to the National Eye Institute. La- rent, the study suggests. “Some of my name products. ser surgery is the standard treatment patients take as many as three or four Dr. Stein observed that a sizeable for advanced stages of the disease, different classes of these medications, group of patients—612 individuals but previous research has shown that and a number end up paying as much or 7.3 percent of the study group— only 30 percent of patients saw im- as $100 out-of-pocket every month simply discontinued use of treatment provement in their vision. for their medication,” says Joshua D. altogether at the time the generic “We found that ranibizumab can Stein, MD, MS, glaucoma specialist drug became available. While it was save the sight of thousands of work- and health services researcher at the not clear why this occurred, the re- ing-age individuals suffering from U-M Kellogg Eye Center. searchers urge that clinicians be alert diabetic eye disease, as standard The report drew on a nationwide for patients who stop taking their treatments such as laser are not as health-care claims database to study medicine, which can cause worsen- effective,” said Rohit Varma, MD, 8,427 patients with open-angle glau- ing of the disease and the need for MPH, director of the USC Eye In- coma who were 40 years and older costly surgical or medical treatment stitute, professor and chair of oph- and were taking PGAs, one of the in the future. thalmology at the Keck School of most commonly prescribed class of “If clinicians suspect that a patient Medicine of USC and the study’s lead drugs for glaucoma. All patients in is struggling with medication adher- author.

4 | Review of Ophthalmology | March 2015

0004_rp0315_news.indd04_rp0315_news.indd 4 22/20/15/20/15 2:512:51 PMPM Dr. Varma’s team developed a population-based model that suggests that administering 0.3 milligrams of Johnston* ranibizumab (Lucentis) every four weeks to patients with diabetic macu- LASIK & LASEK Titanium Applanator lar edema would reduce the number of cases of vision impairment by 45

n percent, or 5,134 individuals, and the e

m e number of cases of legal blindness c a l p by 75 percent, or 1,275 individuals. e R p la The model was based on the approxi- F r te Af mately 37,000 Hispanic and non- A a n ne ter or Hispanic white adults with diabetic ior View Of C um macular edema in the United States ni ita -T for whom ranibizumab treatment or at could be used. Because other race lan pp and ethnic groups were not included A ap Fl in the study, the authors contend that IK AS the treatment may beneﬁ t even more n L nso 0 : Joh people than their results show. 5-7003 s Designed To Apply Equal Outward Posterior Pressure To The LASIK Flap For Even Egress Of Fluid To Consistently Enhance The Seating & Healing Of The Flap To The Stromal Bed. Also, Could Laser Designed To Apply Posterior Pressure To Ephthelial Cells During LASEK For More Even Distribution Of Cells.

s Special Concave Posterior Lens Surface Designed To Be Pressed Onto The LASIK Cure AMD? Flap To Outwardly Flatten The Central Cornea To Resolve Striae, Enhancing A new technique reported in the Febru- Centration And Control Over The Distribution Of Applanated Tissue. ary issue of the FASEB Journal sug- s Unique Transparent Applanation Lens Offers Clear Visualization Allowing Full gests that during early stages, it might View Of The Applanated Surface Through A Microscope. Special Convex Anterior be possible to reverse age-related mac- Lens Surface Eliminates Reflection, And Has A 9mm Orientation Ring For Perfect Centration And Confirmation Of The Applanated Surface. ular degeneration, a leading cause of blindness that is currently irreversible. s Easily Applied To The Flap Without Interference From The Speculum, Eyelids, Or Nasal Bridge For Unencumbered Access Around The Clock. Designed To Prevent The treatment involving a nanosecond Striae With A Minimum Of Time & Surgical Skill. laser may also have further implications s Ideal For Treating Post-Operative Striae, And Refloating & Repositioning The Flap for other eye diseases such as diabetic To Insure Consistent Post-Operative Optical Clarity And Performance. macular edema, diabetic retinopathy s Reusable, Autoclaveable, Made In The U.S.A., Guaranteed For Life, Available For and retinopathy of prematurity. A 30-Day Surgical Evaluation Without Obligation. “It is hoped that this study will provide a basis for the clinical use of the low energy nanosecond laser in those with early stage age-related macular degeneration and that such a treatment will limit the progression of the disease to the advanced, sight-threat- Call 800-637-4346 For More ening forms,” said Erica L. Fletcher, Information Or Scan To Our Website OD, PhD, FAAO, a researcher involved in the work from the Depart- ment of Anatomy and Neuroscience at the University of Melbourne in Victo- ria, Australia. To make their discovery, Dr. Fletch- 3360 Scherer Drive, Suite B. St.Petersburg, Florida er and colleagues treated a group of s4EL s&AX %MAIL)NFO 2HEIN-EDICALCOMs7EBSITEWWW2HEIN-EDICALCOM $EVELOPED)N#OORDINATION7ITH2OBERT-*OHNSTON -$

1093 Rev.G 4HE"IRTHOF6ENUSDETAIL 3ANDRO"OTTICELLI BBAE

004_rp0315_news.indd 5 2/20/15 2:52 PM ® REVIEW E DITORIAL STAFF News Editor in Chief Christopher Glenn individuals with intermediate AMD per dose, while bevacizumab is $50 (610) 492-1008 in one eye with a single session of per dose. Researchers at the Stanford [email protected] nanosecond laser treatment. These University School of Medicine sus- individuals underwent eye examina- pected that doctors treating Medicare Managing Editor tions every six months, out to two years patients would have a fi nancial incen- Walter C. Bethke post-treatment and the results were tive to prescribe a more costly drug. So (610) 492-1024 compared to an untreated group with they would be more likely to prescribe [email protected] early AMD. Anatomical examination ranibizumab than doctors in the Veter- Senior Editor of human and mouse eyes was used to ans Health Administration, who do not Christopher Kent determine the effect of the laser on the have that incentive. (814) 861-5559 sensitive light-detecting retina. As it turns out, the prescription prac- [email protected] In order to determine how this laser tices for these two drugs aren’t that may help in limiting AMD, a mouse straightforward, the researchers wrote Associate Editor with a genetic mutation that predis- in a Feb. 2 paper in Health Affairs. Kelly Hills poses it to developing one of the hall- “It’s complicated,” said senior author (610) 492-1025 mark signs of AMD was treated with Kate Bundorf, MBA, MPH, PhD, as- [email protected] the nanosecond laser and structural sociate professor of health research Chief Medical Editor and gene analysis was performed. Re- and policy. “The incentives facing phy- Mark H. Blecher, MD sults showed that treating those with sicians don’t seem to be the only story.” early AMD with this new low-energy Researchers examined data from Senior Director, Art/Production nanosecond laser may limit disease both systems from 2005 to 2011. In Joe Morris progression. Importantly, unlike other 2011, Medicare physicians prescribed (610) 492-1027 lasers currently used to treat eye dis- the less costly bevacizumab (Avastin) [email protected] ease, the nanosecond laser does not 63 percent of the time. Ranibizumab result in damage to the sensitive retina. (Lucentis) was prescribed 37 percent Art Director This study also showed evidence that of the time. If all of those injections Jared Araujo nanosecond laser treatment in one eye had been reimbursed at the rate for (610) 492-1023 [email protected] can also produce positive effects in the bevacizumab, Medicare would have other untreated eye. This raises the saved approximately $1.1 billion, ac- Graphic Designer possibility that monocular treatment cording to a 2011 report by the Offi ce Matt Egger may be suffi cient to treat disease in of Inspector General in the Depart- (610) 492-1029 both eyes. ment of Health and Human Services. [email protected] “This truly remarkable research is In the VA system, ranibizumab was worth watching,” said Gerald Weiss- prescribed 52 percent of the time in International coordinator, Japan mann, MD, editor in chief of the 2011. Interestingly, however, prescrip- Mitz Kaminuma FASEB Journal, “because it may help tion decisions at the VA varied region- [email protected] usher in an era in which age-related ally, with some centers prescribing pri- Business Offi ces macular degeneration is either elimi- marily bevacizumab, others primarily 11 Campus Boulevard, Suite 100 nated or no longer considered a seri- ranibizumab, and others alternating Newtown Square, PA 19073 ous disease.” The FASEB Journal is between the two drugs. (610) 492-1000 published by the Federation of the Dr. Bundorf said she suspects that Fax: (610) 492-1039 American Societies for Experimental patients’ fi nancial incentives may also Biology. be infl uencing prescribing decisions; Subscription inquiries: that is, they may be asking for the less- United States — (877) 529-1746 expensive drug, particularly if they’re Outside U.S. — (847) 763-9630 E-mail: AMD Drug Choice covered by Medicare, whose patient [email protected] co-pays sometimes refl ect the cost of Website: www.reviewofophthalmology.com Goes Beyond Price the drugs. Some physicians may also Two drugs that treat macular degenera- be thinking of the system-wide effects tion are practically interchangeable— when selecting the less expensive drug, except for the price. she said. Ranibizumab costs up to $2,000 Both drugs are about equally effec-

6 | Review of Ophthalmology | March 2015

0004_rp0315_news.indd04_rp0315_news.indd 6 22/20/15/20/15 2:522:52 PMPM Trade Up To Keeler Trade-in your hand-held slit lamp & get $600 towards Keeler’s Advanced PSL Classic!

Powerful & Portable! • Precision machined aluminum chassis • Advanced optics, x10 & x16 magnification • Controllable illumination from maximum to zero • Most Apertures and filters along with 1.mm square light patch for assessing a/c flare

Trade-in & Special Bonus FREE Carrying Case. Only Portable Slitlamps that have a binocular microscope allowed as trade-in. Offer expires March 31, 2015.

Keeler Instruments, Inc. • 456 Parkway • Broomall, PA 19008 • Tel: (800) 523-5620 • Fax: (610) 353-7814 • email: [email protected] Kowa is a trademark KOWA COMPANY LTD.

RP0115_Keeler PSL.indd 1 12/8/14 2:49 PM Editorial

REVIEW Board

BUSINESS OFFICES 11 CAMPUS BOULEVARD, SUITE 100 NEWTOWN SQUARE, PA 19073 ONTRIBUTORS SUBSCRIPTION INQUIRIES (877) 529-1746 C (USA ONLY); OUTSIDE USA, CALL (847) 763-9630 CHIEF MEDICAL EDITOR GLAUCOMA MANAGEMENT REFRACTIVE SURGERY

Mark H. Blecher, MD Peter Netland, MD, PHD Arturo S. Chayet, MD BUSINESS STAFF Kuldev Singh, MD PUBLISHER BOTTOM LINE RETINAL INSIDER JAMES HENNE Dennis D. Sheppard, MD MASTERS OF SURGERY Carl Regillo, MD, FACS (610) 492-1017 [email protected] Taliva D. Martin, MD Emmett T. Cunningham Jr., MD, PHD, MPH CONTACT LENSES Sara J. Haug, MD, PhD REGIONAL SALES MANAGER MICHELE BARRETT Penny Asbell, MD TECHNOLOGY UPDATE (610) 492-1014 [email protected] PEDIATRIC PATIENT Steven T. Charles, MD Michael Colvard, MD CORNEA / ANTERIOR SEGMENT Christopher M. Fecarotta, MD REGIONAL SALES MANAGER Thomas John, MD MICHAEL HOSTER PLASTIC POINTERS THERAPEUTIC TOPICS (610) 492-1028 [email protected] Ann P. Murchison, MD, MPH Mark Abelson, MD CLASSIFIED ADVERTISING WILLS RESIDENT CASE SERIES (888)-498-1460 Alessandra Intili, MD VICE PRESIDENT OF OPERATIONS CASEY FOSTER (610) 492-1007 [email protected]

PRODUCTION MANAGER DVISORY BOARD SCOTT TOBIN A (610) 492-1011 [email protected]

PENNY A. ASBELL, MD, NEW YORK CITY WILLIAM G. MARTIN, MD, OREGON, OHIO SUBSCRIPTIONS $63 A YEAR, $99 (U.S.) IN CANADA, WILLIAM I. BOND, MD, PEKIN, ILL. MIKE S. MCFARLAND, MD, PINE BLUFF, ARK. $158 (U.S.) IN ALL OTHER COUNTRIES. ALAN N. CARLSON, MD, DURHAM, N.C. JEFFREY B. MORRIS, MD, MPH, ENCINITAS, CALIF. SUBSCRIPTIONS E-MAIL: Y. RALPH CHU, MD, EDINA, MINN. MARLENE R. MOSTER, MD, PHILADELPHIA [email protected]

ADAM J. COHEN, MD, DOWNERS GROVE, ILL. ROBERT J. NOECKER, MD, FAIRFIELD, CONN.

UDAY DEVGAN, MD, FACS, LOS ANGELES ROBERT OSHER, MD, CINCINNATI CIRCULATION PO BOX 71, CONGERS, NY 10920-0071 ERIC DONNENFELD, MD, ROCKVILLE CENTRE, N.Y. MARK PACKER, MD, WEST PALM BEACH, FLA. (877) 529-1746 DANIEL S. DURRIE, MD, KANSAS CITY, MO. STEPHEN PASCUCCI, MD, BONITA SPRINGS, FLA. OUTSIDE USA: (845) 267-3065

ROBERT EPSTEIN, MD, MCHENRY, ILL. PAUL PENDER, MD, BEDFORD, N.H. SENIOR CIRCULATION MANAGER ROBERT D. FECHTNER, MD, NEWARK, N.J. CHRISTOPHER J. RAPUANO, MD, PHILADELPHIA HAMILTON MAHER WILLIAM J. FISHKIND, MD, TUCSON, ARIZ. AUGUST READER III, MD, SAN FRANCISCO (212) 219-7870 [email protected]

JAMES P. GILLS, MD, TARPON SPRINGS, FLA. TONY REALINI, MD, MORGANTOWN, W.V.

HARRY GRABOW, MD, SARASOTA, FLA. KENNETH J. ROSENTHAL, MD, GREAT NECK, N.Y. CHIEF OPERATING OFFICER DOUGLAS K. GRAYSON, MD, NEW YORK CITY ERIC ROTHCHILD, MD, DELRAY BEACH, FLA. JEFF MACDONALD R. BRUCE GRENE, MD, WICHITA, KAN. SHERI ROWEN, MD, BALTIMORE CEO, INFORMATION GROUP SERVICES THOMAS S. HARBIN, MD, MBA, ATLANTA JAMES J. SALZ, MD, LOS ANGELES MARC FERRARA DAVID R. HARDTEN, MD, MINNEAPOLIS INGRID U. SCOTT, MD, MPH, HERSHEY, PA. SENIOR VICE PRESIDENT, HUMAN RESOURCES KENNETH J. HOFFER, MD, SANTA MONICA, CALIF. JOEL SCHUMAN, MD, PITTSBURGH LORRAINE ORLANDO JACK T. HOLLADAY, MD, MSEE, HOUSTON GAURAV SHAH, MD, ST. LOUIS

JOHN D. HUNKELER, MD, KANSAS CITY, MO. DAVID R. STAGER JR., MD, DALLAS VICE PRESIDENT, CREATIVE SERVICES & PRODUCTION MONICA TETTAMANZI THOMAS JOHN, MD, TINLEY PARK, ILL. KARL STONECIPHER, MD, GREENSBORO, N.C.

ROBERT M. KERSHNER, MD, MS, FACS, BOSTON JAMES C. TSAI, MD, NEW HAVEN, CONN. VICE PRESIDENT, CIRCULATION EMELDA BAREA GUY M. KEZIRIAN, MD, PARADISE VALLEY, ARIZ. VANCE THOMPSON, MD, SIOUX FALLS, S.D.

TERRY KIM, MD, DURHAM, N.C. FARRELL C. TYSON, MD, CAPE CORAL, FLA.

TOMMY KORN, MD, SAN DIEGO R. BRUCE WALLACE III, MD, ALEXANDRIA, LA.

DAVID A. LEE, MD, HOUSTON ROBERT G. WILEY, MD, CLEVELAND

FRANCIS S. MAH, MD, PITTSBURGH FRANK WEINSTOCK, MD, CANTON, OHIO 100 Avenue of the Americas New York, NY 10013 NICK MAMALIS, MD, SALT LAKE CITY JACQUELINE M.S. WINTERKORN, MD, PHD, NEW YORK CITY

REVIEW OF OPHTHALMOLOGY (ISSN 1081-0226; USPS No. 0012-345) is published monthly, 12 times per year by Jobson Medical Informa- tion. 100 Avenue of the Americas, New York, NY 10013-1678. Periodicals postage paid at New York, NY and additional mailing ofﬁ ces. Postmaster: Send address changes to Review of Ophthalmology, PO Box 71, Congers, NY 10929-0071. Subscription Prices: US One Year $63.00, US Two Year $112.00, Canada One Year $99.00, Canada Two Year $181.00, Int’l One Year $158.00, Int’l Two Year $274.00. For subscription information call (877) 529-1746 (USA only); outside USA, call (845-267-3065. Or email us at [email protected]. Canada Post: Publications Mail Agreement #40612608. Canada Returns to be sent to Bleuchip International, P.O. Box 25542, London, ON N6C 6B2.

8 | Review of Ophthalmology | March 2015

0004_rp0315_news.indd04_rp0315_news.indd 8 22/20/15/20/15 2:522:52 PMPM NOW APPROVED

ANTICIPATED RETAIL AVAILABILITY MARCH 10 From Alcon, committed to providing new treatment options for patients.

RP0315_Alcon Pazeo.indd 1 2/17/15 2:23 PM REVIEW News

tive at treating macular degeneration. whether a retina or brain cell will sur- tools to detect and slow or stop those Bevacizumab was originally developed vive or die when threatened with dis- cellular changes, and ultimately pre- to treat cancer; ranibizumab was de- ease onset. The gene mechanism that serve vision,” said Andrew D. Hu- signed specifi cally for eye conditions. we discovered is the interplay of two berman, PhD, assistant professor Dr. Bundorf said the study illus- genes turned on by the messenger of neurosciences, neurobiology and trates the need for improvement in Neuroprotectin D1.” ophthalmology. Dr. Huberman co- both health-care systems; for example, The research team worked with hu- authored the study with Rana N. El- physicians could be offered incentives man retinal pigment epithelial cells Danaf, PhD, a postdoctoral researcher to select the best drug for the condition and an experimental model of isch- in his lab. and save money. emic stroke. They discovered novel Retinal ganglion cells are specialized mechanisms in cells with the ability neurons that send visual information to activate pathways that crosstalk one from the retina to the brain. Increased Eye/Brain Link to another and then assemble consoli- pressure within the eye can contribute dated responses that decide cell fate. to retinal ganglion cell damage, leading Sought to Treat The researchers found that the pow- to glaucoma. Even with pressure-low- erful messenger, NPD1, is produced ering drugs, these cells eventually die, Disparate Diseases on-demand in the brain and retina and leading to vision loss. Researchers at LSU Health New Orleans that it elicits a network of positive sig- In this study, Drs. Huberman and have discovered gene interactions nals essential for the well-being of vi- El-Danaf used a mouse model engi- that determine whether cells live or sion and cognition. They showed that neered to express a green fl uorescent die in such conditions as age-related NDP1 bioactivity governs key gene protein in specifi c retinal ganglion cells macular degeneration and ischemic interactions decisive in cell survival subtypes. This tool allowed them to ex- stroke. These common molecular when threatened by disease or injury. amine four subtypes of retinal ganglion mechanisms in vision and brain in- They demonstrated that not only does cells. The different cell types differ by tegrity can prevent blindness and also NPD1 protect photoreceptors, but it the location in the eye to which they promote recovery from a stroke. The also promotes remarkable neurological send the majority of their dendrites paper was published online in Cell recovery from the most frequent form (cellular branches). Within seven days Death & Differentiation. of stroke in humans. of elevated eye pressure, all retinal “Studying the eye and the brain ganglion cells that send most or all of might hold the key to creating thera- their dendrites to a region of the eye peutic solutions for blindness, stroke How RGCs Alter known as the OFF sublamina under- and other seemingly unrelated con- went signifi cant rearrangements, such ditions associated with the central Structure Holds as reductions in number and length of nervous system,” says Nicolas Bazan, dendritic branches. Retinal ganglion MD, PhD, Boyd Professor, Ernest C. Clue to Glaucoma cells with connections in the ON part and Yvette C. Villere Chair of Retinal To better understand the cellular changes of the retina did not. Degeneration Research, and director in retinal ganglion cells and how they “We are very excited about this dis- of the Neuroscience Center of Excel- infl uence the progression and severity covery,” Dr. Huberman said. “One of lence at LSU Health New Orleans. of glaucoma, researchers at the Uni- the major challenges to the detection “The eye is a window to the brain.” versity of California, San Diego, School and treatment of glaucoma is that you Dr. Bazan and his research team of Medicine and Shiley Eye Institute have to lose a lot of cells or eye pres- discovered Neuroprotectin D1, which turned to a mouse model of the dis- sure has to go way up before you know is made from the essential fatty acid, ease. Their study, published Feb. 10 in you have the disease. These results tell docosahexaenoic acid. Previous work Journal of Neuroscience, reveals how us we should design visual fi eld tests showed that while it protected cells, some types of retinal ganglion cells al- that specifi cally probe the function of the molecular principles underlying ter their structures within seven days certain retinal cells. In collaboration this protection were not known. of elevated eye pressure, while others with the other researcher members “During the last few years, my labo- do not. of the Glaucoma Research Founda- ratory has been immersed in study- “Understanding the timing and tion Catalyst for a Cure, we are doing ing gene regulation,” Dr. Bazan says. pattern of cellular changes leading to just that and we are confi dent these “We have uncovered a novel control retinal ganglion cell death in glaucoma results will positively impact human that makes defi nitive decisions about should facilitate the development of patients in the near future.”

10 | Review of Ophthalmology | March 2015

0004_rp0315_news.indd04_rp0315_news.indd 1100 22/20/15/20/15 2:522:52 PMPM RP0315_TearLab.indd 1 2/11/15 2:22 PM Imaging With Depth-of-ﬁ eld. Just Dandy.

What if none of your slit images or video had blurry edges? You would have a Haag-Streit, of course. Invest in one and submerge yourself into our extreme world of depth of ﬁ eld.

Visit haag-streit-usa.com to learn about our entire range of slit lamps and imaging systems.

RP0215_Haag Dandy.indd 1 1/20/15 1:45 PM March 2015 • Volume XXII No. 3 | reviewofophthalmology.com Cover Focus 26 | Who’s Getting Femto Laser Cataract Surgery? By Christopher Kent, Senior Editor Surgeons who use this technology share their experience with patient and economic issues.

36 | Femtosecond Cataract: What the Data Says By Walter Bethke, Managing Editor A review of how femtosecond-assisted cataract surgery is faring in the literature.

44 | Survey: New Cataract Technology Gathers Momentum By Walter Bethke, Managing Editor Femtosecond cataract surgery and intraoperative aberrometry are the two key areas of interest in our reader survey. Feature Article 52 | Do Physician Assistants Have a Place in Ophthalmology? By Michelle Stephenson, Contributing Editor As yet, few ophthalmology practices employ PAs; those that do typically use them for primary care.

Cover image: Y. Ralph Chu, MD

March 2015 | Revophth.com | 13

013_rp0315_toc.indd 13 2/20/15 2:53 PM Departments

4 | Review News 60

16 | Technology Update Genetic Testing: New Resources & Challenges New tests are expanding the usefulness of genetic analysis and simplifying diagnosis.

60 | Retinal Insider Telemedicine in Pediatric Retinal Disease ROP screening has succeeded where other telemedicine has not. Here’s what we can learn.

62 | Masters of Surgery Thoughts on Cataract Surgery, 2015 66 How a leading surgeon is adjusting his approach to surgery to meet today’s new challenges.

66 | Therapeutic Topics Sampling New Targets for Allergy Therapy Learning more about ocular allergy reveals a host of potential allergic mediators for researchers.

70 | Glaucoma Management Are Two MIGS Surgeries Better Than One? Multiple stents or combining options that affect different pathways may provide better outcomes.

74 | Refractive Surgery ISRS Members Share Practice Trends Bilateral intraocular procedures, FLACS and 85 LASIK volumes highlight the latest ISRS survey.

77 | Research Review Cataract Surgery Safe For Outpatient Clinic

81 | Products 82 | Classified Ads 85 | Wills Eye Resident Case Series 89 | Advertising Index

14 | Review of Ophthalmology | March 2015

013_rp0315_toc.indd 14 2/20/15 2:54 PM NEW NEW

+4.0 +3.25 +2.75

CHOOSE OUTSTANDING VISION for whatever life’s focus. Introducing the NEW TECNIS® MULTIFOCAL FAMILY OF IOLs Give your patients a full range of outstanding vision with enhanced focus where they need it most — all backed by proven TECNIS® IOL technology.

Discover more at www.tecnismultifocal.com/choice

IMPORTANT SAFETY INFORMATION – TECNIS® MULTIFOCAL 1-PIECE IOLs CAUTION: Federal law restricts this device to sale by or on the order of a physician. INDICATIONS: TECNIS® Multifocal 1-Piece IOLs are indicated for primary implantation for the visual correction of aphakia in adult patients with and without presbyopia in whom a cataractous lens has been removed by phacoemulsifi cation and who desire near, intermediate, and distance vision with increased spectacle independence. The intraocular lenses are intended to be placed in the capsular bag. WARNINGS AND PRECAUTIONS: Inform patients of possible contrast sensitivity reduction and increases in visual disturbances that may aff ect their ability to drive at night or in poor visibility conditions. The lenses are intended for placement in the capsular bag and should not be placed in the sulcus. Weigh the potential risk/benefi t ratio for patients with conditions that could be exacerbated or may interfere with diagnosis or treatment. Secondary glaucoma has been reported occasionally in patients with controlled glaucoma who received lens implants. Multifocal IOL implants may be inadvisable in patients where central visual fi eld reduction may not be tolerated, such as macular degeneration, retinal pigment epithelium changes, and glaucoma. ATTENTION: Reference the Directions for Use for a complete listing of Important Indications, Warnings, Precautions, and Adverse Events. TECNIS is a trademark owned by or licensed to Abbott Laboratories, its subsidiaries or affi liates. © 2015 Abbott Medical Optics, Inc. | www.AbbottMedicalOptics.com | PP2015CT0022

RP0315_Abbott.indd 1 2/9/15 3:23 PM Technology Update

REVIEW Edited by Michael Colvard, MD, and Steven Charles, MD

Genetic Testing: New Resources & Challenges New tests are expanding the usefulness of genetic analysis and promising to simplify the diagnostic process. Christopher Kent, Senior Editor

f you’re looking for an example of tations relating to optic atrophy and to those diseases used to be a long, Ithe rapid evolution of science, look early onset glaucoma. costly and not totally reliable process no further than the fi eld of genetics. Clinical testing results, reported in involving multiple genetic tests and Knowledge in this area is exploding, a recent publication,1 have demon- numerous non-genetic tests, guided and that is translating into a steady strated that the GEDi tests’ ability by a detailed family history. Now, re- increase in the use of genetic test- to detect a single nucleotide variant searchers at the University of Man- ing in the diagnosis and management has a sensitivity and specifi city of 97.9 chester in England have developed of disease. Here, experts in this fi eld percent and 100 percent, respectively. a test using a new DNA-sequencing discuss two major new developments (The study authors note that this com- technology called next-generation se- that will impact ophthalmology; pro- pares favorably with the 88.3-percent quencing, or NGS. The new test looks vide a look at some of the current sensitivity achieved by whole-exome at 115 genes known to be associated resources available to physicians; and sequencing using a commercially with congenital cataracts and can fi nd offer advice on how to make the most available exome capture set; they mutations connected to one of those of these tools. attribute this to better coverage of diseases within a few weeks. (The new targeted genes in the GEDi tests.) test has also uncovered mutations re- Two New Tests Prospective testing of 192 patients lated to the condition that were not with inherited retinal degenerations previously known.) Researchers at the Ocular Genom- found that the retinal GEDi test had a A study assessing the effi cacy of the ics Institute (associated with the Mas- diagnostic rate of 51 percent. test, recently published in Ophthal- sachusetts Eye and Ear Infi rmary and These tests can be ordered by a mology,2 involved 36 patients diag- Harvard Medical School in Boston) medical professional; turnaround is nosed with bilateral congenital cata- have developed a CLIA-certified, 90 days. The retinal test costs $2,500; ract (nonsyndromic or syndromic) next-generation, gene-sequencing the atrophy/glaucoma test costs and a control group. The test was able protocol designed for patients with $1,250. (Health insurance may cover to determine the genetic cause of the inherited eye diseases, including glau- part or all of the cost.) congenital cataract in 75 percent of coma, retinal degenerations and op- Another recent development is an the subjects. Furthermore, 85 per- tic atrophy. The tests are referred to advanced DNA test relating to con- cent of patients with nonsyndromic as Genetic Eye Disease panels, or genital cataracts, a condition that can CC had likely pathogenic mutations. GEDi. The GEDi-R test looks for be a symptom of more than 100 dif- “Congenital cataract is a difficult mutations relating to retinal disor- ferent diseases. Uncovering the muta- condition to diagnose genetically; ders; the GEDi-O test checks for mu- tions linking the congenital cataracts more than 100 genes have been as-

16 | Review of Ophthalmology | March 2015 This article has no commercial sponsorship.

016_rp0315_tech update.indd 16 2/20/15 12:31 PM An NSAID formulated to penetrate target ocular tissues PROLENSA® POWERED FOR PENETRATION

Available in a 3-mL bottle size

PROLENSA® delivers potency and corneal penetration with QD efficacy1,2 • Advanced formulation delivers corneal penetration1-3 • Proven efficacy at a low concentration1,4 INDICATIONS AND USAGE PROLENSA® (bromfenac ophthalmic solution) 0.07% is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery. IMPORTANT SAFETY INFORMATION ABOUT PROLENSA® Warnings and Precautions Adverse Reactions • Sulfite allergic reactions The most commonly reported adverse • Slow or delayed healing reactions in 3%-8% of patients were • Potential for cross-sensitivity anterior chamber inflammation, foreign body sensation, eye pain, photophobia, Increased bleeding of ocular tissues • and blurred vision. • Corneal effects, including keratitis • Contact lens wear

Please see brief summary of full Prescribing Information on adjacent page. References: 1. PROLENSA® Prescribing Information, April 2013. 2. Data on ﬁle, Bausch & Lomb Incorporated. 3. Baklayan GA, Patterson HM, Song CK, Gow JA, McNamara TR. 24-hour evaluation of the ocular distribution of 14C-labeled bromfenac following topical instillation into the eyes of New Zealand White rabbits. J Ocul Pharmacol Ther. 2008;24(4):392-398. 4. BROMDAY® Prescribing Information, October 2012. PROLENSA is a registered trademark of Bausch & Lomb Incorporated or its afﬁliates. © Bausch & Lomb Incorporated. US/PRA/14/0043

RP0315_BL Prolensa.indd 1 2/18/15 10:18 AM PROLENSA® (bromfenac ophthalmic solution) 0.07% Brief Summary

INDICATIONS AND USAGE PROLENSA® ophthalmic solution following cataract surgery include: PROLENSA® (bromfenac ophthalmic solution) 0.07% is indicated for the anterior chamber inflammation, foreign body sensation, eye pain, treatment of postoperative inflammation and reduction of ocular pain in photophobia and vision blurred. These reactions were reported in 3 to patients who have undergone cataract surgery. 8% of patients. DOSAGE AND ADMINISTRATION USE IN SPECIFIC POPULATIONS Recommended Dosing Pregnancy One drop of PROLENSA® ophthalmic solution should be applied to Treatment of rats at oral doses up to 0.9 mg/kg/day (systemic the affected eye once daily beginning 1 day prior to cataract surgery, exposure 90 times the systemic exposure predicted from the continued on the day of surgery, and through the first 14 days of the recommended human ophthalmic dose [RHOD] assuming the human postoperative period. systemic concentration is at the limit of quantification) and rabbits Use with Other Topical Ophthalmic Medications at oral doses up to 7.5 mg/kg/day (150 times the predicted human PROLENSA ophthalmic solution may be administered in conjunction systemic exposure) produced no treatment-related malformations in with other topical ophthalmic medications such as alpha-agonists, beta- reproduction studies. However, embryo-fetal lethality and maternal blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics. toxicity were produced in rats and rabbits at 0.9 mg/kg/day and Drops should be administered at least 5 minutes apart. 7.5 mg/kg/day, respectively. In rats, bromfenac treatment caused delayed parturition at 0.3 mg/kg/day (30 times the predicted human CONTRAINDICATIONS exposure), and caused dystocia, increased neonatal mortality and None reduced postnatal growth at 0.9 mg/kg/day. WARNINGS AND PRECAUTIONS There are no adequate and well-controlled studies in pregnant women. Sulfite Allergic Reactions Because animal reproduction studies are not always predictive of Contains sodium sulfite, a sulfite that may cause allergic-type reactions human response, this drug should be used during pregnancy only if including anaphylactic symptoms and life-threatening or less severe the potential benefit justifies the potential risk to the fetus. asthmatic episodes in certain susceptible people. The overall prevalence Because of the known effects of prostaglandin biosynthesis- of sulfite sensitivity in the general population is unknown and probably inhibiting drugs on the fetal cardiovascular system (closure of ductus low. Sulfite sensitivity is seen more frequently in asthmatic than in non- arteriosus), the use of PROLENSA® ophthalmic solution during late asthmatic people. pregnancy should be avoided. Slow or Delayed Healing Nursing Mothers All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including Caution should be exercised when PROLENSA is administered to a bromfenac, may slow or delay healing. Topical corticosteroids are also nursing woman. known to slow or delay healing. Concomitant use of topical NSAIDs and Pediatric Use topical steroids may increase the potential for healing problems. Safety and efficacy in pediatric patients below the age of 18 have not Potential for Cross-Sensitivity been established. There is the potential for cross-sensitivity to acetylsalicylic acid, Geriatric Use phenylacetic acid derivatives, and other NSAIDs, including bromfenac. There is no evidence that the efficacy or safety profiles for Therefore, caution should be used when treating individuals who have PROLENSA differ in patients 70 years of age and older compared to previously exhibited sensitivities to these drugs. younger adult patients. Increased Bleeding Time With some NSAIDs, including bromfenac, there exists the potential for NONCLINICAL TOXICOLOGY increased bleeding time due to interference with platelet aggregation. Carcinogenesis, Mutagenesis and Impairment of Fertility There have been reports that ocularly applied NSAIDs may cause Long-term carcinogenicity studies in rats and mice given oral increased bleeding of ocular tissues (including hyphemas) in conjunction doses of bromfenac up to 0.6 mg/kg/day (systemic exposure 30 with ocular surgery. times the systemic exposure predicted from the recommended It is recommended that PROLENSA® ophthalmic solution be used with human ophthalmic dose [RHOD] assuming the human systemic caution in patients with known bleeding tendencies or who are receiving concentration is at the limit of quantification) and 5 mg/kg/day (340 other medications which may prolong bleeding time. times the predicted human systemic exposure), respectively, revealed Keratitis and Corneal Reactions no significant increases in tumor incidence. Use of topical NSAIDs may result in keratitis. In some susceptible Bromfenac did not show mutagenic potential in various mutagenicity patients, continued use of topical NSAIDs may result in epithelial studies, including the reverse mutation, chromosomal aberration, and breakdown, corneal thinning, corneal erosion, corneal ulceration or micronucleus tests. corneal perforation. These events may be sight threatening. Patients with Bromfenac did not impair fertility when administered orally to male evidence of corneal epithelial breakdown should immediately discontinue and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, use of topical NSAIDs, including bromfenac, and should be closely respectively (systemic exposure 90 and 30 times the predicted human monitored for corneal health. exposure, respectively). Post-marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial PATIENT COUNSELING INFORMATION defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), Slowed or Delayed Healing rheumatoid arthritis, or repeat ocular surgeries within a short period Advise patients of the possibility that slow or delayed healing may of time may be at increased risk for corneal adverse events which may occur while using NSAIDs. become sight threatening. Topical NSAIDs should be used with caution Sterility of Dropper Tip in these patients. Advise patients to replace bottle cap after using and to not touch Post-marketing experience with topical NSAIDs also suggests that use dropper tip to any surface, as this may contaminate the contents. more than 24 hours prior to surgery or use beyond 14 days post-surgery Advise patients that a single bottle of PROLENSA® ophthalmic may increase patient risk for the occurrence and severity of corneal solution, be used to treat only one eye. adverse events. Concomitant Use of Contact Lenses Contact Lens Wear Advise patients to remove contact lenses prior to instillation of PROLENSA should not be instilled while wearing contact lenses. PROLENSA. The preservative in PROLENSA, benzalkonium Remove contact lenses prior to instillation of PROLENSA. The chloride, may be absorbed by soft contact lenses. Lenses may be preservative in PROLENSA, benzalkonium chloride may be absorbed by reinserted after 10 minutes following administration of PROLENSA. soft contact lenses. Lenses may be reinserted after 10 minutes following Concomitant Topical Ocular Therapy administration of PROLENSA. If more than one topical ophthalmic medication is being used, the medicines should be administered at least 5 minutes apart ADVERSE REACTIONS Rx Only Clinical Trial Experience Manufactured by: Bausch & Lomb Incorporated, Tampa, FL 33637 Because clinical trials are conducted under widely varying conditions, Under license from: adverse reaction rates observed in the clinical trials of a drug cannot be Senju Pharmaceuticals Co., Ltd. directly compared to rates in the clinical trials of another drug and may Osaka, Japan 541-0046 not reflect the rates observed in clinical practice. Prolensa is a trademark of Bausch & Lomb Incorporated or its affiliates. The most commonly reported adverse reactions following use of © Bausch & Lomb Incorporated. 9317600 US/PRA/14/0024

RRP0315_BLP0315_BL PProlensarolensa PPI.inddI.indd 1 22/18/15/18/15 10:2010:20 AMAM Technology

REVIEW Update

Care Pathways for Child Suspected of Congenital Cataract

Traditional Care Pathway Proposed New Care Algorithm

Clinical examination & careful history Clinical examination & careful history

Cataracts conﬁ rmed Cataracts conﬁ rmed

(yes) Genetic testing Parents & relatives affected? (karyotyping and/or Next-generation DNA sequencing (no) individual gene testing) Appropriate surgical Dysmorphic? (yes) (yes) Positive diagnosis? management (no) Pediatric & metabolic with pediatric and Neurodevelopmental problems? (yes) assessment (possible (no) genetic input as Systemic disease? metabolic investigations indicated and/or genetic testing) (no) Further investigations (karyotype, whole exome sequencing) Sporadic/developmental cataract? (yes) Appropriate surgical Careful ocular assessment for management; associated structural abnormalities pediatric and genetic input as indicated

Use of next-generation DNA sequencing—which screens 115 cataract genes simultaneously from a single sample—holds the promise of a quicker diagnosis for many patients, leading to earlier treatment and potentially better outcomes. (Based on Gillespie RL, et al, 2014.2)

sociated with it,” notes Rachel Gil- ing diagnosis much easier and more layed myelination from an MRI scan, lespie, who designed the new test and efficient. We have seen a very high a precise diagnosis was not made. is lead author of the study. “Impor- diagnosis rate: Our test is able to fi nd NGS genetic screening identified a tantly, cataracts in children and babies the likely cause in about 75 percent mutation in the gene CYP27A1 that can present as an isolated problem or of all patients tested. Interestingly, is known to cause cerebrotendinous as an early indication of an underly- for a number of children, our genetic xanthomatosis, a lipid-storage disor- ing multi-system condition. However, fi ndings have enabled a diagnosis of der that can be fatal; we confirmed clinical presentations in infants and specifi c conditions, altering their clin- this mutation as pathogenic by lipid young children can be very mild and ical management and treatment. Fur- profi ling. CTX is very mild in infancy ambiguous, so delineation of the pre- thermore, identifi cation of the genetic (initial presentations are cataract and cise cause is almost impossible. [At cause of congenital cataract within diarrhea), but becomes much more the same time,] prompt diagnosis of families enables counseling for prog- serious with age. Early diagnosis is these conditions is imperative so that nosis, the risk to other family mem- crucial because preventative treat- early preventative treatment and/or bers and advice on prenatal testing in ment is available in the form of che- disease monitoring can commence as future pregnancies. nodeoxycholic acid and statins, which soon as possible. “For example, one family we may prevent disease progression but “Traditional genetic testing meth- worked with had three members— cannot reverse it later on. Luckily, we ods would require screening of cat- two brothers and their cousin—who were able to diagnose this condition aract-causing genes individually and presented with childhood-onset cata- relatively early in this family and they consecutively to find the cause—a racts, seizures and challenging behav- are all doing well on treatment.” process that can take a very long time ior with autistic features that seemed Ms. Gillespie says they’ve been and is often unsuccessful,” she con- to be worsening with age,” she says. working hard on this new technology. tinues. “Our test screens 115 cataract “They had each undergone numerous “We’re currently researching the im- genes simultaneously from a single tests to try and determine the cause, pact this test is having on the care of small blood or saliva sample, mak- and despite additional fi ndings of de- congenital cataract patients,” she says.

March 2015 | Revophth.com | 19

0016_rp0315_tech16_rp0315_tech update.inddupdate.indd 1199 22/20/15/20/15 12:3112:31 PMPM Technology

REVIEW Update

“The test has been available in the genes, as well as ways to better under- who did just fi ne in her life who has U.K. since December 2013, and it can stand the genes that are known. For the same type of genetic mutation as be requested by registered medical example, one of our biologists, Budd your child.’ That kind of information facilities via international referral on Tucker, PhD, is making huge strides is hugely benefi cial for a family, even a diagnostic (rather than research) ba- in using pluripotent stem cells to treat if it doesn’t bring them treatment sis. Referral information can be found people with inherited eye diseases.” today.” at mangen.co.uk, along with sample criteria. To conduct the test we ask for Making the Most of Testing either a minimum of 1 ml of blood in EDTA (Ethylenediaminetetraacetic “A lot of unnecessary Ms. Andorf offers several sugges- acid), or 10 µg of high-quality DNA.” tions regarding genetic testing: testing results from • Your patient may not need Making Testing Accessible physicians not trusting complete exome testing. “Thanks to the existence of exome sequenc- Another laboratory doing notable their own diagnosis. ing, many laboratories will simply work is The John and Marcia Carver Our goal is not to give you all of the data they find,” Nonprofit Genetic Testing Labora- she notes. “However, there are sev- tory, affi liated with the University of diagnose the patient eral diseases that are caused by one Iowa. The lab, headed by Edwin M. ... [but] to confi rm the small gene or just a few genes. A Stone, MD, PhD, and Val C. Shef- whole exome costs several thousand fi eld, MD, PhD, is dedicated to pro- diagnosis.” dollars, whereas a test for that one viding non-profi t genetic testing for — Jean Andorf mutation may cost a couple hundred rare eye diseases. The tests they of- dollars. While exome sequencing fer incorporate the research done by certainly has a place in genetic test- Drs. Stone and Sheffi eld, so the tests ing for inherited eye diseases, it’s not provide the most clinically relevant in- One of the projects under way a good use of anyone’s resources to formation while remaining affordable. at the Carver Lab is referred to as do a complete exome sequencing for “When I started working for the “Project 3,000,” an effort to identify a person with a monogenic disease.” Carver Lab there were probably 20 every person in the United States Ms. Andorf says a lot of unneces- inherited eye disease genes known,” suffering from Leber’s congenital sary testing results from physicians says the lab’s Jean Andorf. “Now there amaurosis—estimated to be about not trusting their own diagnosis. “We are more than 250. So the fi eld has 3,000 in number. “This program has really want doctors to order the right grown fast, and our testing has grown allowed us to offer genetic testing test,” she says. “It’s not good for us if with that gene discovery rate. We to these individuals and populated a a doctor orders multiple tests on our were motivated to offer these ser- number of the RPE65 treatment tri- website for a patient because he’s try- vices because once a gene has been als, while providing a signifi cant pop- ing to fi nd a diagnosis. Doctors have found and studied for a long time you ulation for future clinical research been seeing most of these patients can’t take grant money for the pur- into long-term prognosis,” says Ms. for a long time; they need to trust pose of genotyping more families. So, Andorf. “In addition to fi nding most their clinical expertise to try to match all these research dollars would go to of the LCA patients under the age of the patient’s clinical fi ndings with the discover a gene, and then the genetic 20, we’ve also identifi ed a handful of appropriate test. Our goal is not to testing wouldn’t be available for the older people with the disease. Some diagnose the patient through testing; patients. Our goal was—and still is— didn’t realize they had this disease; our goal is to confirm the diagno- to offer affordable genetic testing to many were simply born blind during sis. In fact, we’re working on sharing anyone who wants it. What we charge an era when little was known about clinical information with physicians for a test is truly just the cost of the lab inherited eye diseases. Many of these that will help them narrow down the technicians and the reagents. adults are cognitively normal with testing for their patients.” “We are also a research lab,” she high intelligence and functioning Ms. Andorf says that for this rea- continues. “About a third of our effort very well. That enables us to give son, they often screen patients who focuses on nonprofi t genetic testing; hope to families with a child sharing have heterogeneous diseases in tiers. and about two-thirds is on research. that particular genetic cause. You “We start by testing for the most like- We’re constantly looking for new can say, ‘I have a 70-year-old patient ly genetic mutation,” she explains.

20 | Review of Ophthalmology | March 2015

0016_rp0315_tech16_rp0315_tech update.inddupdate.indd 2200 22/20/15/20/15 12:3112:31 PMPM NOT A HOLE. Clinicians are often forced to choose between safety and effi cacy. The iStent® Trabecular Micro-Bypass Stent helps to balance this trade AN IDEAL BALANCE OF off by combining signifi cant reductions in IOP with an overall safety profi le comparable to cataract surgery alone. The iStent is the leading SAFETY AND EFFICACY. Micro Invasive Glaucoma Surgery (MIGS) procedure and is a singular option that delivers the best of both worlds.

To learn more, contact Glaukos at 800.452.8567 or visit www.glaukos.com.

INDICATION FOR USE. The iStent® Trabecular Micro-Bypass Stent (Models GTS100R and GTS100L) is indicated for use in conjunction with cataract surgery for the reduction of intraocular pressure (IOP) in adult patients with mild to moderate open-angle glaucoma currently treated with ocular hypotensive medication. CONTRAINDICATIONS. The iStent® is contraindicated in eyes with primary or secondary angle closure glaucoma, including neovascular glaucoma, as well as in patients with retrobulbar tumor, thyroid eye disease, Sturge-Weber Syndrome or any other type of condition that may cause elevated episcleral venous pressure. WARNINGS. Gonioscopy should be performed prior to surgery to exclude PAS, rubeosis, and other angle abnormalities or conditions that would prohibit adequate visualization of the angle that could lead to improper placement of the stent and pose a hazard. The iStent® is MR-Conditional meaning that the device is safe for use in a specifi ed MR environment under specifi ed conditions; please see label for details. PRECAUTIONS. The surgeon should monitor the patient post-operatively for proper maintenance of intraocular pressure. The safety and effectiveness of the iStent® has not been established as an alternative to the primary treatment of glaucoma with medications, in children, in eyes with signifi cant prior trauma, chronic infl ammation, or an abnormal anterior segment, in pseudophakic patients with glaucoma, in patients with pseudoexfoliative glaucoma, pigmentary, and uveitic glaucoma, in patients with unmedicated IOP less than 22 mmHg or greater than 36 mmHg after “washout” of medications, or in patients with prior glaucoma surgery of any type including argon laser trabeculoplasty, for implantation of more than a single stent, after complications during cataract surgery, and when implantation has been without concomitant cataract surgery with IOL implantation for visually signifi cant cataract. ADVERSE EVENTS. The most common post-operative adverse events reported in the randomized pivotal trial included early post-operative corneal edema (8%), BCVA loss of * 1 line at or after the 3-month visit (7%), posterior capsular opacifi cation (6%), stent obstruction (4%) early post-operative anterior chamber cells (3%), and early post-operative corneal abrasion (3%). Please refer to Directions for Use for additional adverse event information. CAUTION: Federal law restricts this device to sale by, or on the order of, a physician. Please reference the Directions for Use labeling for a complete list of contraindications, warnings, precautions, and adverse events. ©2015 Glaukos Corporation. Glaukos and iStent are registered trademarks of Glaukos Corporation.

RP0315_Glaukos.indd 1 2/9/15 3:18 PM Technology

REVIEW Update

“In a significant percentage of pa- have a physician and a genetic coun- information listed with the test,” she tients we identify the mutation with selor to be able to understand these explains. “Some labs include links to a single, inexpensive test using this data.’ We try to get the physician and their test page or requisition forms protocol. The other advantage of this family to think about that in advance that can be downloaded. We ask the approach—which some people criti- of the test.” labs to provide turnaround times, cize us for—is that a complete exome • Turnaround time should not and they are often available on the reveals a lot of irrelevant information be your only consideration. “We test information page. Some tests that can cloud a diagnosis. We screen are sometimes criticized for our long may take less than a week—for ex- the gene most consistent with your turnaround times,” notes Ms. Andorf. ample, some biochemical tests, or clinical features. “That’s true in some cases, but we fluorescence in situ hybridization “It’s even more important to have group patients together in order to [a test that allows visualization and a diagnosis that’s as accurate as pos- keep the costs as low as possible. And mapping of the genetic material in an sible when pursuing exome sequenc- we’re not just a clinical laboratory. individual’s cells]—but others, such ing,” she adds. “On average, exome Some services will offer a complete as full exome sequencing, may take sequencing will reveal very plausible exome sequencing within four weeks, up to 16 weeks. The technology de- disease-causing mutations in eight but we believe it makes more sense to termines the time the test takes.” known inherited eye disease genes. order a specifi c test that’s in line with Ms. Eunpu notes that test usage Thus, patients with inaccurate diag- your own diagnosis, even if it takes is increasing, and options for testing noses will often have misleading fi nd- longer to receive the results.” continue to expand. “In the past year ings in genes consistent with the in- we’ve added nearly 10,000 new tests, accurate diagnosis. We’ve seen cases Locating Resources many due to new technologies,” she in which families and physicians have says. “For example, the availability been misled because of this type of As the number of tests available in- of next-generation sequencing has situation. Too much genetic informa- creases, along with the number of lab- opened the door to testing multiple tion can make the results harder to oratories offering the tests, the need genes at a time. These tests can be interpret.” for a central clearinghouse has be- most helpful if one is not sure which • Make sure the patient is con- come evident. One company attempt- of several related conditions to test sulting with a genetic counselor. ing to meet that need is GeneTests, for. However, when a specifi c diagno- “Lots of patients e-mail us reports based in Elmwood Park, N.J. Its mis- sis is suspected, a single gene can be that they got from another lab—a list sion is to promote the appropriate interrogated.” of mutations with no interpretation of use of genetic testing by providing Ms. Eunpu expects to see even the fi ndings,” says Ms. Andorf. “Here, current, easy-to-access, free informa- more new tests and increased usage. we work with an inherited eye disease tion about test availability. “Genetics continues to be an exciting, specialist who has dealt with inherited According to Deborah L. Eunpu, evolving field in which advances in eye disease for more than 25 years. manager at the company, the most technology and knowledge can lead to Whatever disease you’re dealing with, commonly requested genetic tests rapid changes,” she says. “Will every- we’ve probably screened thousands of relating to eye disease include tests one have full sequencing? Not likely. others with the same disease. Having for Leber’s congenital amaurosis; But as more treatments are based on the ability to see clinical correlations optic atrophy; retinitis pigmentosa; knowing the specific genetic muta- to genetic test results gives you a high- retinoblastoma; age-related macular tion, the reasons to do many tests will er level of confi dence in the interpre- degeneration; oculocutaneous albi- be compelling. With clinical trials and tation and minimizes information that nism; congenital cataracts; congeni- opportunities for improved vision may be confusing. tal glaucoma; malformations of the arising through emerging treatments, “For that reason, the physician re- eye (e.g., aniridia, microphthalmia, testing is being looked at much differ- questing a test from us has to write anophthalmia); and dislocated lens. ently. Now testing may lead to specifi c down who is providing genetic coun- Ms. Eunpu says that once a surgeon treatments.”

seling to the patient,” she says. “Pa- has found a laboratory that offers 1. Consugar MB, Navarro-Gomez D, Place EM, et al. Panel- tients often want us to send the report the services in which the surgeon based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible, and more sensitive for variant directly to them. We say, ‘If your doc- is interested, he can contact the lab detection, than exome sequencing. Genet Med. 2014;Nov 20. tor ordered a kidney function test for directly. “On our website, once a test [Epub ahead of print.] 2. Gillespie RL, O’Sullivan J, Ashworth J, et al. Personalized you, the lab wouldn’t send the results is selected, information about the diagnosis and management of congenital cataract by next- directly to you. You really need to laboratory can be accessed via the generation sequencing. Ophthalmology 2014;121:2124-2137.

22 | Review of Ophthalmology | March 2015

0016_rp0315_tech16_rp0315_tech update.inddupdate.indd 2222 22/20/15/20/15 12:3112:31 PMPM SYMPTOMATIC VITREOMACULAR ADHESION (VMA)

SYMPTOMATIC VMA MAY LEAD TO VISUAL IMPAIRMENT FOR YOUR PATIENTS1-3

IDENTIFY Recognize metamorphopsia as a key sign of symptomatic VMA and utilize OCT scans to conﬁ rm vitreomacular traction.

REFER Because symptomatic VMA is a progressive condition that may lead to a loss of vision, your partnering retina specialist can determine if treatment is necessary.1-3

THE STEPS YOU TAKE TODAY MAY MAKE A DIFFERENCE FOR YOUR PATIENTS TOMORROW

© 2014 ThromboGenics, Inc. All rights reserved. ThromboGenics, Inc., 101 Wood Avenue South, Suite 610, Iselin, NJ 08830 – USA. THROMBOGENICS and the THROMBOGENICS logo are trademarks or registered trademarks of ThromboGenics NV. 10/14 OCRVMA0220 References: 1. Sonmez K, Capone A, Trese M, et al. Vitreomacular traction syndrome: impact of anatomical conﬁ guration on anatomical and visual outcomes. Retina. 2008;28:1207-1214. 2. Hikichi T, Yoshida A, Trempe CL. Course of vitreomacular traction syndrome. Am J Ophthalmol. 1995;119(1):55-56. 3. Stalmans P, Lescrauwaet B, Blot K. A retrospective cohort study in patients with diseases of the vitreomacular interface (ReCoVit). Poster presented at: The Association for Research in Vision and Ophthalmology (ARVO) 2014 Annual Meeting; May 4-8, 2014; Orlando, Florida.

RP1114_Thrombogenics.indd 1 10/22/14 9:30 AM FDA APPROVED

IS THE TIME TO PREVENT INTRAOPERATIVE MIOSIS AND REDUCE POSTOPERATIVE OCULAR PAIN

OMIDRIA™ (phenylephrine and ketorolac injection) 1% / 0.3% is the ﬁrst and only FDA-approved treatment that both1: Preemptively inhibits intraoperative miosis Decreases postoperative ocular pain for 10 to 12 hours

OMIDRIA is preservative- and bisulﬁte-free Easy to integrate into routine operating procedures Add preoperatively to irrigation solution1 One 4-mL single-patient-use vial to 500 mL Can be added to irrigation solution in the surgical suite No other preparation required

INDICATIONS AND USAGE OMIDRIA is added to ophthalmic irrigation solution used during cataract surgery or intraocular lens replacement and is indicated for maintaining pupil size by preventing intraoperative miosis and reducing postoperative ocular pain.

RP0315_Omeros.indd 2 2/18/15 10:30 AM CMS PASS-THROUGH STATUS EFFECTIVE JANUARY 1, 2015

OMIDRIA™ is reimbursed by CMS* OMIDRIA has been granted transitional pass-through payment status under the Medicare hospital outpatient prospective payment system (OPPS) Pass-through status allows for payment for OMIDRIA separate from the bundled Ambulatory Payment Classiﬁcation (APC) payment for the surgical procedure Contact 1-844-OMEROS1 (1-844-663-7671) for more information about how to submit for OMIDRIA reimbursement.

IMPORTANT SAFETY INFORMATION OMIDRIA must be added to irrigation solution prior to intraocular use. OMIDRIA is contraindicated in patients with a known hypersensitivity to any of its ingredients. Systemic exposure of phenylephrine may cause elevations in blood pressure. Use OMIDRIA with caution in individuals who have previously exhibited sensitivities to acetylsalicylic acid, phenylacetic acid derivatives, and other non-steroidal anti-inflammatories (NSAIDs), or have a past medical history of asthma. The most commonly reported adverse reactions at 2-24% are eye irritation, posterior capsule opacification, increased intraocular pressure, and anterior chamber inflammation. Use of OMIDRIA in children has not been established. Please see the Full Prescribing Information for OMIDRIA at www.omidria.com/prescribinginformation. You are encouraged to report Suspected Adverse Reactions to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

*CMS=Centers for Medicare & Medicaid Services. Reference: 1. OMIDRIA [package insert]. Seattle, WA: Omeros Corporation; 2014.

RP0315_Omeros.indd 3 2/18/15 10:30 AM Cataract REVIEW Cover Focus Who’s Getting Femto Laser Cataract Surgery? Christopher Kent, Senior Editor

Surgeons he use of femtosecond laser University of North Carolina, explains technology to perform key that there are three situations in which who use this Tparts of cataract surgery (e.g., most surgeons who have access to the incisions, capsulotomy and softening technology use a femtosecond laser technology share the nucleus) continues to be contro- to perform cataract surgery: as part versial—not because of any problem of a premium procedure; in response their experience with the technology, but because it’s to surgical concerns; or for its diag- with patient and expensive relative to the perceived nostic capability—speciﬁ cally, optical amount of improvement it brings to coherence tomography. “We cannot economic issues. the procedure. Compounding the get reimbursed for using the laser, problem, reimbursement from insur- per se,” he notes. “So if you’re using ance companies and Medicare is very femtosecond laser for cataract, the limited. As a result, many surgeons are patient is probably getting a premium hesitant to invest in the technology. lens of some kind—toric, multifocal or Questions that arise when surgeons accommodating. Most surgeons don’t consider adding this to their arma- use femtosecond laser for a standard mentarium include: Will there be procedure. enough reimbursable uses to make “Of course, there are exceptions to the purchase worthwhile? Will pa- that rule,” he continues. “I’ll perform tients be willing to pay extra for the femtosecond laser cataract surgery if I technology to be used? How much have someone on Flomax, or someone does the economic status of your pa- with a white cataract, narrow angles, tient base matter? And is it possible pseudoexfoliation, previous trauma to earn back the cost of the equip- or a previous vitrectomy; anything I ment in a reasonable amount of time? think will make the surgery harder. Here, three surgeons who have used Sometimes just using the laser mini- this technology for several years share mizes a problem even if you couldn’t their experiences. see it coming. I recently put a lens in a patient and the lens dislocated inferi- When Is the Laser Being Used? orly; I repositioned it and it dislocated again. On the third attempt I sutured Karl Stonecipher, MD, medical di- it to the iris. It turned out the patient rector for TLC Laser Eye Centers in had a coloboma I couldn’t see at the Greensboro, N.C., and clinical associ- slit lamp. If I hadn’t used the femto- ate professor of ophthalmology at the second laser, I would have had vitre-

26 | Review of Ophthalmology | March 2015 This article has no commercial sponsorship.

0026_rp0315_f1.indd26_rp0315_f1.indd 2626 22/20/15/20/15 1:361:36 PMPM All images: Y. Ralph Chu, MD ous everywhere. It would have been a much more complex procedure.” Although the technology may be helpful in a therapeutic capacity, Dr. Stonecipher notes that this raises some questions. “Which patients really need it?” he asks. “Should you use it for every case that’s complicated? I think the laser has been shown to put less stress on the eye. It allows me to do the lion’s share of the procedure before I even go into the eye. If I can make the incisions, do the capsulotomy and soften the lens before I enter the eye, that’s going to make it easier for me to take that lens out.” Many surgeons are using femtosecond laser cataract surgery as part of a premium channel The other way to get reimbursed offering; to help manage challenging surgical situations; or when its optical coherence for use of the laser is to charge for tomographer can help visualize surgical issues (a use that is reimbursable, pictured above). using its OCT as a diagnostic aid—to check the condition of the zonules, thalmology at the University of Min- Inder Paul Singh, MD, president of for example. Dr. Stonecipher says the nesota, says that currently 50 to 60 the Eye Centers of Racine and Keno- diagnostic OCT has helped him avoid percent of his cataract surgery patients sha in Wisconsin, notes that the part trouble in numerous cases. “Recently receive femtosecond laser cataract of the country in which he practices is I discovered that a patient had zonu- surgery. He believes the primary rea- not affl uent and was hit fairly hard in lar dehiscence from trauma,” he says. son patients are open to considering the recent economic downturn. Nev- “The patient never told me about it, femtosecond laser cataract surgery is ertheless, he fi nds that many patients and all I saw at the slit lamp was a little the desire for a refractive result rather are interested in being treated with phacodonesis. Because of the OCT, I than a medical result. advanced technology, even if the cost was prepared to put in a capsular ten- “To me, cataract surgery can be is higher. (He offers the use of the sion ring prior to entering the eye, and seen as falling into two categories,” laser during cataract surgery as a pre- that prevented a very complex surgery. he explains. “For some patients it’s mium service for patients who would “The bottom line,” he says, “is that simply a medical procedure in which like to have it, in addition to those we can charge for the diagnostics; we’re removing a lens and putting in who need arcuate incisions or might we can use the femtosecond laser as an implant, followed by basic refrac- have it bundled into a premium intra- part of a premium channel package; tive care, which means glasses. On ocular lens package. He does not own we can charge for astigmatic surgery the other hand, if the patient wants the laser himself; he convinced a local that uses the laser; we can charge for the ability to function as best he can, hospital to invest in the technology, the premium IOL that is implanted whether at distance or at near, with- and he takes his patients there for the with the help of the laser; but we can’t out glasses—or at least with less de- surgery.) “Right now we have a 60- to charge for the laser itself.” pendence on glasses—that becomes 65-percent adoption rate in our area,” refractive cataract surgery. Patients in he says. “I don’t sell it, I don’t promote Which Patients Want the Laser? the latter category are open to being it, I don’t advertise it. We just educate educated and choosing to receive new patients about it in our offi ce.” Of course, in many cases using the technologies like femtosecond sur- Is it possible to predict which pa- laser means more cost to the patient. gery, use of the ORA device and other tients are more likely to agree to pay That raises a key question: Under technologies.” extra for more advanced technology? what circumstances are patients will- Of course, many surgeons are con- Dr. Chu says no. “You cannot judge a ing to agree to the added cost? cerned that their patients will balk book by its cover,” he notes. “We get a Y. Ralph Chu, MD, founder and at paying extra money for the use of wide range of patients who choose to medical director of Chu Vision In- the laser, but most surgeons using the do this kind of procedure, and their stitute in Bloomington, Minn., and technology seem to agree that this is fi nancial status may have nothing to do adjunct associate professor of oph- less of an issue than they expected. with it. It’s more of an attitude thing.

March 2015 | Revophth.com | 27

026_rp0315_f1.indd 27 2/20/15 1:36 PM Cover Cataract

REVIEW Focus

“One day, for example, I had two good, predictable surgery for the most be a good candidate, either for medi- patients come in; one was a school part; they don’t have to have the laser. cal or psychological reasons. “If the lunch lady, the other was the CEO of I’ll take good care of them either way. patient has the desire to have a refrac- a company,” he says. “You might have I try to be honest and let them know tive outcome,” says Dr. Chu, “then we thought the CEO would have chosen whether or not I think it will make a ask a series of questions to determine to have the best technologies used in signifi cant difference. If it’s a young whether she is a good candidate: Are his surgery regardless of the cost, but person with an early cataract getting her eyes healthy enough to achieve his attitude was one of extreme frugal- a standard lens with half a diopter of value from those extra technologies? ity. That’s how he ran his company. So astigmatism, I can do manual LRIs Does she have macular degenera- he chose not to do a premium IOL and get a good result. I think you have tion or corneal pathology like base- or any lasers. On the other hand, the to use your judgment, and you have to ment membrane dystrophy, or a scar school lunch lady said, ‘You know, I’ve be honest when you help the patient or glaucoma? I don’t think any one never bought anything for myself, and make a decision.” of those things is an absolute contra- this is the one thing I want to buy to indication, but these are things the improve myself.’ She wanted to be surgeon and patient have to consider able to lift the covers on the food and when they’re thinking about femtosec- not have her glasses fog up, so she ond laser cataract surgery.” could see the kids as she delivered the “If a patient expects “Medical contraindications would food to them. She got a great result to have a perfect include corneal issues such as scar- with a premium lens and the lasers. ring that could interfere with docking; So she’s happy—and he’s happy too. outcome because of keratoconus; glaucoma surgery blebs; That experience acts as a reminder to the laser, that’s a people who have corneal pannus, me that I should never restrict which where you’re not going to be able to patients are introduced to these tech- contraindication.” do a good corneal or arcuate incision; nologies, and that everyone deserves —Inder Paul Singh, MD cases in which you don’t have good to know their options so they can make visualization of the extracapsular area; the best choices for themselves. After and patients with small pupils that all, this is elective surgery.” might prevent a good capsulotomy Dr. Singh also says he doesn’t as- Dr. Singh admits that he does see or fragmentation pattern,” says Dr. sume anything about what a given pa- a difference in the interest level of Singh. “All of these medical conditions tient may be willing or able to pay. different age groups. “Patients who are a reason to say no. I’d also say no “My job is not to sell premium pro- are younger than 65 tend to want to to a patient who is fi dgety and appre- cedures,” he says. “However, a lot of have the laser,” he says. “Patients who hensive in general. You don’t want the patients say, ‘Doc, what would you are 75 or 80-plus tend to say, ‘I’m not patient shaking under the laser. do?’ I say, ‘You know what? If it wasn’t really worried about whether I have to “From more of a psychological per- for the money, I’d say why not do this? wear glasses or if I have a couple extra spective, I think patients who have Why not have a precise capsulotomy weeks of recovery. It’s OK, I can deal unrealistic expectations are a poten- and a precise arcuate incision and with that.’ Younger patients are more tial problem,” he says. “If the patient have less total ultrasound energy in inclined to want the latest, best tech- expects to have a perfect outcome the eye?’ I tell them if it wasn’t for the nology. They’re the iPad and iPhone because of the laser, that’s a contrain- money, I wouldn’t be giving them a users who think that if it’s newer, it’s dication. If they say they’ll pay more choice; I’d just use the more advanced got to be better. Some patients come money if I can guarantee something, technology. I really do believe it’s a into our offi ce saying, ‘Doc, give me I wouldn’t want to go that way. I don’t better option for my patients. the best technology, I don’t care what want to use the laser and have them “I tell patients that I’m not here to it is.’ I say, ‘Wait—let’s talk about it.’ not get the outcome they’re expecting tell them what they can or cannot af- They say, ‘No that’s fi ne, just do it.’ ” and then demand to know why.” ford,” he continues. “Some patients Dr. Chu agrees that unrealistic ex- ask me if they need to have the laser. Contraindications pectations could disqualify a patient, They say, ‘I’ll mortgage my house to but believes that’s not limited to this use the laser if you think it will make a Clearly, even if a patient is inter- situation. “I think that’s probably true big difference for me.’ I tell them that ested and/or willing to pay for this across the board for eye care,” he says. manual cataract surgery is still a very technology to be used, he might not “This is elective surgery. I think it’s

28 | Review of Ophthalmology | March 2015

0026_rp0315_f1.indd26_rp0315_f1.indd 2828 22/20/15/20/15 1:361:36 PMPM ARE YOU OPERATING WITH ALL THE RIGHT INFORMATION?

GET ACCURATE, PROCESS:REAL-TIME DIAGNOSTICS VALIDATION: system THROUGHOUT THE PROCEDURE, ALL IN with VerifEye+™ ONE SUITE.

&DWDUDFW5HIUDFWLYH'LDJQRVWLFV(PSRZHULQJVXUJHRQV'HOLYHULQJFRQȴGHQFH The Alcon suite of diagnostic technologies has been designed to help surgeons minimize errors throughout the entire procedure for maximized cataract refractive outcomes and ATIOL predictability:

VERION™ Image Guided System ORA™ System with Streamlines data calculation and VerifEye+™ Technology communicates planning Delivers real-time validation seamlessly to your LenSx® to help you make better-informed Laser and/or surgical microscope clinical decisions in the OR and to help you make the right reduce the number of patients who clinical decisions. fall outside the intended astigmatic target by more than 50%.†,1 ȍΖQWHQGHGWDUJHWLVGHȴQHGDVZLWKLQ'RIWDUJHWHGDVWLJPDWLVP $OFRQGDWDRQȴOH THE CATARACT REFRACTIVE SUITE BY ALCON © 2014 Novartis 12/14 ORA14059JAD-A

UUntitled-1ntitled-1 1 112/23/142/23/14 9:229:22 AMAM Cover Cataract

REVIEW Focus

important to assess whether someone has unrealistic expectations before surgery whether he’s getting the femtosecond laser or not. Some of our most difﬁ cult patients are those who haven’t chosen the femtosecond laser at all. They expect a refractive outcome because that’s what their friends got, even though they don’t opt for refractive cataract surgery using the best technology.”

Patients Who Ask for the Laser

Dr. Chu notes that an increasing number of patients are coming in asking specifi cally for femtosecond laser cataract surgery. “We’re seeing more and more of that,” he says. “As patients are forced to be more responsible for where their health-care dollar goes, they’re starting to look around more. And word does get out that these technologies exist. Patients are interested in seeing better, and they like the concept of laser surgery in general. I think the technology is showing that it can deliver, so if a patient comes in requesting it, that makes the discussion about the options pretty easy. “On the other hand, you have to be careful,” he continues. “Many patients can’t afford the technology, and even if they fi nd the idea appealing, they may not be looking for a refractive result. Right now, we can’t get reimbursed for using the laser unless we’re correcting astigmatism or utilizing the intraoperative imaging for a premium IOL; meanwhile, there’s a cost to the practice each time the laser is used. Ultimately, it’s up to the surgeon to use the tools needed to get the best outcome, whether the laser is reimbursed or not.” Dr. Singh says that recently people have started coming into his practice specifi cally asking for the laser. “I’ve had access to the laser for a year and a half,” he notes. “It wasn’t until about a year after I started performing femtosecond laser cataract that I started seeing patients come in saying they’d heard about the laser and wanted it. Clearly, when a critical mass of patients has had it done, that has a marketing effect. “It’s important to tell patients when you believe the use of the laser made a real difference in the outcome,” he continues. “I had a patient who had 2.5 D of cylinder; he wanted a special lens and it didn’t come in his power. So I had to make arcuate incisions to eliminate a lot of the astigmatism. He ended up 20/20. I said to him, ‘You would not be 20/20 if it wasn’t for those arcuate incisions I made with the laser, so the laser really did help you see better.’ He told his brother, who came in and wanted the laser as well. If the laser really does make a difference and you point that out and explain why, a happy patient will become your advocate out in the community. “Of course, there have been some patients where I

026_rp0315_f1.indd 30 2/20/15 1:36 PM whether it’s lasers, implants or new pharmaceuticals. So cost becomes part of the discussion and part of the decision tree for patients. Unfortunately, cost is going to be an increasingly important factor in decision-making in every aspect of health care. “We’re not offering this option because we want to make more money,” he continues. “We want our patients to have as many options as possible, and when we talk to them we want to make sure they know about every option. I feel that if a patient isn’t educated and told about all of the available IOL A few surgeons in the United States have tried performing femtosecond laser cataract options and all available technologies, surgery on every patient, but the limited reimbursement options have made it a challenge including the excimer laser that can be to remain proﬁ table, even with increased volume. used after cataract surgery to enhance the cataract surgery outcome, that’s made a small arcuate incision with ery cataract patient? “A few people a shame. So we’re passionate about the laser that may or may not have have tried using the laser on every education and letting patients make made a difference in their quality of cataract patient,” Dr. Stonecipher the best choices for themselves. We vision afterwards, but they’re happy says. “Shachar Tauber, MD, is still do- say to the patient, here’s the technol- that they got the laser and tend to as- ing that and says his practice is mak- ogy that’s available. There’s refractive sume the laser deserves the credit,” ing it work with volume by attracting cataract surgery and non-refractive he continues. “I’m careful with those many patients and community sur- cataract surgery. Here’s the technol- patients, because part of my job is to geons. But trying to do femtosecond ogy that helps us achieve the result, be fair and balanced. So I don’t tell laser on everybody without charging and here’s the cost. It’s pretty straight- them it’s because of the laser that they for a premium channel means you’re forward, and there’s no pressure on got their outcome. On the other hand, losing $350 a case. If you’re only mak- the patient to choose one option over if a patient had a pseudoexfoliation ing $350 a case, how’s that going to another. Patients have no problem issue or a tough capsule or a dense work out? You can’t compensate for telling us they don’t want to buy some- cataract, I will tell him that if he’d had that with volume. My partner tried thing. a standard surgery, more than likely I using that business model, but it didn’t “I’d feel bad if a patient who is in- would have had to use more energy work. Without charging a premium to terested in refractive cataract surgery inside the eye and he might have had offset the laser fee it was just economi- or astigmatism correction said no one less-sharp vision the next day. So in cally unworkable.” had told him about these technolo- certain circumstances I will tell the pa- gies,” he adds. “I think that happens in tient that the laser made a difference. Presenting the Option a lot of practices. Sometimes patients For the average patient I just say that come to us after having had surgery I’m glad it went well.” Surgeons have differing opinions elsewhere and say, ‘Gosh, I wish I’d Dr. Stonecipher says he has also regarding whether the option of hav- known about this.’ They may end up seen patients come in asking for the ing femtosecond laser cataract surgery feeling like you hid something from laser. “Of course, even patients who should be presented to every patient. them. So I’m really passionate about want the laser may have a problem Of course, the extra cost weighs heav- patients knowing that we offer all of affording it,” he notes. “You have to ily in that debate. “A lot of people de- these options, even if the patient isn’t provide financing options for those sire refractive outcomes, but insur- a good candidate. If that’s the case, we patients. That’s another one of the op- ance covers less and less nowadays,” still explain all the options, we just also tions you have to offer in order to have notes Dr. Chu. “So we have to talk explain that the patient isn’t a good success with the femtosecond laser.” about the cost. Patients have to pay candidate for this one or that one, and What about simply performing fem- more and more even for basic care, let why.” tosecond laser cataract surgery on ev- alone some of the newer technologies, Dr. Stonecipher says that he used to

March 2015 | Revophth.com | 31

026_rp0315_f1.indd 31 2/20/15 1:36 PM ENRICH YOUR PRACTICE

Review of Ophthalmology delivers current and comprehensive information focusing on topics such as disease diagnosis, surgical techniques and new technologies. The Review Group offers eyecare practitioners quality informational The Review Group’s Ophthalmic Product Guide brings you the latest products and technology on the market. Published every February resources dedicated to the growth and July. and education of the profession. The TheT Review Group also distributes a variety Review Group offers a variety of print ofo supplements, guides and handbooks withw your subscription to Review of and online products to enrich your Ophthalmology. These publications are patient care and practice needs. designedd to keep you informed on what’s newn and innovative in the industry on topics ranging from cataract refractive surgery to ocularo surface disease.

TheT Review Group also offers valuable continuingc medical education sessions in both print and online formats, allowing a convenientc way for you to earn CME credits. In addition, we also offer an impressive fleet of free e-newsletters—such as Review of Ophthalmology Online and Review of Ophthalmology’s Retina Online—so you can keep up to date on breaking news and the latest research.

The Review Group also spearheads meetings and conferences, bringing together experts in the field and providing a forum for practitioners that allows you to educate, and learn from others in the profession. These meetings cover a broad range of topics in the form of educational or promotional roundtables and forums.

www.reviewofophthalmology.com

Jobson Medical Information LLC The Review Group

2014_rp_tsrad.indd 90 10/22/14 2:36 PM Cover Cataract

REVIEW Focus

tell every patient about the laser op- recognize me without glasses!’ But tant to give them enough education tion, but no longer does. “I believe all if they say yes, then I have to explain about the benefits of that option to our patients know that it’s an option,” why they need that better technology ensure that they understand its val- he says. “It comes up somewhere in and, if necessary, offer suggestions as ue,” he says. “It’s also important to the discussions the patient has with to how they can afford it. make sure that everyone in the ofﬁ ce staff members. But if I’m looking at “The other side of the coin is pa- is on the same page, because patients you and you’re glazed over and you tients in whom I want to use the laser get information from everyone. That say you love your glasses and can’t af- to make the surgery safer or easier,” means you need to ensure that every- ford anything, there’s no reason to go he continues. “I do tell those patients one provides similar answers when through that discussion. Talking about about it. I may say, ‘You’ve got pseu- asked common questions like: What is the option when the patient doesn’t doexfoliation syndrome and that’s go- cataract? What is astigmatism? What is want it or can’t afford it is just going to ing to make my job a little more of a a capsulotomy? What are the beneﬁ ts make the patient feel bad or believe challenge; I need you to let me use the of using the laser? Why is it important you’re doing an inferior procedure. diagnostics of this laser that costs $500 to have a perfectly centered, round “I tell my patients that I’m going to to help me do what I believe is a bet- capsulotomy? Why is it important to treat them as if they were members of ter surgery.’ Some patients will refuse, use less energy inside the eye? Why my own family and do what I think is so I document our conversation in the is it important to have astigmatism best for them,” he says. “If the patient chart.” arcs that are perfectly cut to the exact is a candidate for a premium channel, Dr. Singh sees several things as es- depth? What do these factors mean I ask two questions: Do you want to sential if you’re offering femtosecond for postoperative vision? be free of glasses? And if so, are you laser cataract surgery to your patients. “Obviously we don’t want to inun- willing to pay for it? A lot of people “First of all, any time we ask patients date patients with too much knowl- say, ‘No, I’m fine, my wife wouldn’t to pay more for something, it’s impor- edge because that could get confusing,

WHAT CAN A SEAMLESS PROCESS: SURGICAL PROCESS DO FOR YOUR OUTCOMES? Streamlines data calculation and communicates planning seamlessly to your LenSx® Laser From imaging to planning to guiding your and/or surgical microscope to help you make the right clinical decisions. surgical execution, the VERION™ Image Guided System can help reduce the potential for refractive error. Now you FDQFRQȴGHQWO\PDNHDVXUJLFDOSODQWKDW will help you deliver the corrected vision your patients expect and deserve.

026_rp0315_f1.indd 33 2/20/15 1:36 PM Left your Review of Ophthalmology magazine at the ofﬁ ce? No problem!

Get Review sent to your desktop or mobile device! Just simply go to www.reviewofophthalmology.com and click on the digimag link to get your current issue.

2013 Digimag hous ad_RP.indd 1 10/22/14 2:39 PM 026_rp0315_f1.indd 35 tages, that’s adifferentstory. you feelthatitdoeshavesomeadvan- you shouldn’t besuggestingit.Butif the technologyoffersanybeneﬁ agree completely. Ifyoudon’t feelthat and dowhat’s bestforthepatient.’I technology. Icameheretobeadoctor always say, ‘Idon’t wanttohavesell crucial thatyoubelieveinit.Doctors and cheerleadforit;butIthinkit’s mean thatyouhavetogooutthere nology yourself,”hecontinues.“Idon’t done istobeexcitedaboutthetech- fortable abouthavingthisprocedure portant formakingpatientsfeelcom- won’t beinterestedinit. but ifpatientsdon’t understanditthey key. You canadvertiseallyouwant, Singh says.“Forme,educationisthe physician, isworththeextracost,”Dr. stand whythislaser, inmyopinionasa but Iwanttomakesuretheyunder-

“The secondthingthat’s reallyim- REVIEW Focus Cover THAT FALL OUTSIDEOF YOUR ASTIGMATIC TARGET? WHAT IFYOU COULD NUMBER OFPATIENTS REDUCE BYHALFTHE With streamingintraoperativeaberrometrydatain © 2014Novartis12/14ORA14059JAD-C &RPSDUHGWRFRQYHQWLRQDO SUHRSHUDWLYH FDOFXODWLRQRIF\OLQGHUSRZHUDQGD[LV $OFRQGDWDRQȴOH ȍΖQWHQGHGWDUJHWLVGHȴQHGDVZLWKLQ'RIWDUJHWHGDVWLJPDWLVP WRULFΖ2/VZKLOHLPSURYLQJ\RXUDVWLJPDWLFRXWFRPHV WKH25\RXFDQPRUHFRQȴ ORA ™ SystemValidationMap

Cataract t, then GHQWO\FKRRVHDQGLPSODQW ond laser as part of cataract surgery is ond laseraspartofcataractsurgeryis unconvinced thatusingthefemtosec- make hisorherowndecision.” patient willgainsothecan explain thebenefitsyoubelieve apologize fortheincreasedcost;just using itisworthwhile.You shouldn’t afford themoreadvancedtechnology, is true.SoIbelieveifapatientcan best outcome.Inmyexperience,that increase thelikelihoodofgetting very predictable,precisewaythatmay helps meperformtheprocedureina not true.ButIdotellpatientsthatit a betteroutcome,”headds.“That’s ond lasercataractprocedurewillhave every patientwhohasthefemtosec- right thingforeverypatient,orthat But IsItWorth It? Of course,manysurgeonsremain “I certainlywouldnotsaythatit’s the †,1 2

DIAGNOSTICS REFRACTIVE CATARACT CATARACT ALCON

with VerifEye+ system ™ are never going to see well. Using the are nevergoingtoseewell.Usingthe kappa—is offenough,thesepatients continues. “Ifanglealpha—not really importantinthesepatients,”he ﬁ without thelaser?Yes Ican,butwe’re better surgeoninsomeareas. one thingoranother. Itmakesyoua articles sayingthelaserhelpsyouwith we’re seeingmoreandpublished is potentiallymorecomplex.Ithink to haveasaferprocedurewhencase tive, thefemtosecondlaserallowsme Dr. Stonecipher. “Frommyperspec- adds muchtocataractsurgery,” says don’t believethefemtosecondlaser are stillalotofsurgeonsouttherethat have usedthelaserdisagree.“There the patient.Nevertheless,manywho worth theexpensetopracticeand nding thateffectivelenspositionis reduce the number of patients that reduce thenumberofpatientsthat 5HDOWLPHVXUJLFDOYDOLGDWLRQWKDWFDQ IDOORXWVLGHWKHLQWHQGHGDVWLJPDWLF WDUJHWE\PRUHWKDQ “Can IimplantamultifocalIOL SUITEBY ALCON REFRACTIVE THE CATARACT (continued onpage64) VALIDATION: †,1

with VerifEye+ system ™ 2/20/15 1:56 PM Cataract REVIEW Cover Focus Femtosecond Cataract: What the Data Says Walter Bethke, Managing Editor

A review of how think most surgeons would surgery on 2,228 eyes (the controls). recognize that femtosecond The researchers reported 34 tears in femtosecond- “Ilaser cataract surgery is bril- the anterior capsule (1.84 percent) in liant—as long as they didn’t have to the study group vs. fi ve in the control assisted cataract pay for it,” jokes Hyderabad, India, group (0.22 percent), a difference that surgeon Kasu Prasad Reddy. Though was statistically signifi cant (p=0.0001).1 surgery is faring in Dr. Reddy uses the femtosecond in They noted that one case of anterior the literature. his practice, he acknowledges that capsule tear in each group extended his fellow surgeons have to think long to the posterior capsule, necessitating and hard about investing hundreds of an anterior vitrectomy. There were 21 thousands of dollars in a device when incomplete capsulotomies in the laser they already get excellent results from group (1.13 percent) vs. none in the conventional phacoemulsification. conventional patients, as well as 30 an- This thinking logically leads them to terior capsulotomy tags (1.62 percent) wonder what data exists on femtosec- with laser compared to 1 with conven- ond that might shed some light on the tional (0.004 percent; p=0.0001). The kind of results they could expect with surgeons mention that just over half the new procedure. To help surgeons of the anterior radial and posterior answer this question, following is a capsular tears occurred in the later review of the major femtosecond re- cases, which was one of the reasons search from the past several years, as why they didn’t show a learning-curve well as thoughts from researchers on effect during the study. their fi ndings. Posterior tear, the complication that surgeons are more concerned with Safety Signals than anterior rents, also occurred in both groups in the Tasmanian study. Some of the largest studies in fem- However, the authors say that despite tosecond cataract have focused on the eight posterior tears occurring in the safety of the procedure. laser group (0.43 percent) and four in In one of the few prospective, com- the conventional group (0.18 percent), parative studies of femtosecond cata- the difference wasn’t statistically sig- ract surgery vs. conventional surgery, nifi cant. surgeons from Tasmania performed Tim Roberts, MBBS, MMed, con- femtosecond surgery on 1,852 eyes sultant ophthalmic surgeon at the Roy- (the study group) and conventional al North Shore Hospital, University

36 | Review of Ophthalmology | March 2015 This article has no commercial sponsorship.

0036_rp0315_f2.indd36_rp0315_f2.indd 3636 22/20/15/20/15 2:472:47 PMPM of Sydney, believes that the paper by Complications in Large Femtosecond Cataract Studies [the Tasmanian] group is important as it has “focused attention on the laser Chee SP, Roberts T, et al. Roberts T, et Abell R, et al. 1 settings used and surgical techniques et al. Group 1 al. Group 2 (n=4,000) (n=1,105)10 (n=200)3 (n=1,300)3 employed during laser cataract sur- # eyes % # eyes % # eyes % # eyes % gery.” Dr. Roberts adds that, “From a Anterior capsule tear 9 0.81 8 4 4 0.31 34 1.84 surgeon’s perspective, I believe the im- Suction loss 5 0.45 5 2.5 8 0.61 N/A N/A portant question is not whether there Posterior capsule rupture 3 0.27 7 3.5 4 0.31 8 0.43 are ultrastructural differences between Anterior capsule tags N/A N/A 21 10.5 21 1.62 30 1.62 manual and laser-cut capsulotomies, but what the clinical implication, if any, is of these differences.” He points out procedure—the femtosecond surgeon with the small size of the study groups. that his group and others have found can expect a much shorter, predictable As femtosecond goes out into the mar- very low rates of anterior tears. “When learning curve,” says Dr. Roberts. ketplace and you have a million cases you look at papers such as that by the Taking a broad view of the litera- to look at, things may look a little dif- Moorfi elds’ group2 and our own study,3 ture, in 2013 the Veterans Admin- ferent. Also, making things more dif- you see other groups with large num- istration commissioned a task force fi cult is the fact that the complication bers aren’t fi nding those high rates,” to do a meta-analysis of the available rates with conventional surgery are so he says. peer-reviewed reports on femtosecond low. To get something even lower than In Dr. Roberts’ study, he and his co- cataract surgery and then make a rec- that is diffi cult.” authors prospectively analyzed 1,500 ommendation about whether the VA Another safety parameter that is femtosecond cataract cases, which should implement it in its hospitals. emerging is the potential reduction in they broke into two groups: 200 cases The researchers whittled 468 papers ultrasound energy needed to remove to get a sense of the initial skill level’s down to 16 that met their validity cri- the cataract when a femtosecond la- impact on results; and then 1,300 to teria. ser is used to segment the nucleus. determine if experience with the pro- Though femtosecond cataract re- In a study co-authored by Dr. Reddy, cedure improved outcomes. search continues to be generated by surgeons randomized patients to fem- In the first group, the complica- surgeons, and femtosecond technol- tosecond cataract surgery or convention rates were higher. Eight cases (4 ogy continues to evolve, the VA re- tional phaco. Fifty-six eyes had the percent) had anterior radial tears, 21 searchers found femtosecond’s com- laser and 63 underwent conventional (10.5 percent) had anterior capsule plication rates at the time to be similar surgery. The researchers found that tags, seven (3.5 percent) had posterior to conventional surgery. “We tried to the mean effective phaco time was capsule tears and four (2 percent) had break the adverse effects into those signifi cantly lower in the laser group posterior lens dislocation. Twenty-six that you’d only encounter with laser (5.2 ±5.7 seconds) compared to the patients (13 percent) had to have man- cases, such as docking problems, and manual (7.7 ±6 seconds; p=0.025). ual corneal incisions rather than laser- those that the two groups would have There was also a signifi cant difference made cuts because the latter were im- in common, such as endophthalmi- in the mean phaco energy between possible to make or could be made but tis,” says Ken Gleitsmann, MD, an the groups (13.8 ±10.3 percent in la- not opened. ophthalmologist from Hilton Head ser vs. 20.3 ±8.1 percent for manual; In the second group in Dr. Roberts’ Island, S.C., and one of the report’s p<0.001). However, the safety results report, the rates went down: four (0.31 co-authors. “The docking problems of each procedure were equal, with percent) had anterior radial tears; 21 did not lead to greater complications. no adverse events in either at one day (1.62 percent) had anterior capsular Even in cases in which docking might postop.9 The 4,000-eye study from Tas- tags; four (0.31 percent) had a poste- have been a problem, after subsequent mania also found that effective pha- rior capsule tear; and 25 (1.92 percent) docking attempts the surgery would co time was statistically significantly needed their incisions done manually. usually proceed as it did in the other lower in laser patients, but didn’t fi nd There were no cases of posterior lens uncomplicated groups. In terms of an increased risk of complications dislocation. “What our study and oth- other complications, femtosecond and that would be associated with this in- ers are suggesting is that with the sig- conventional surgery had the same ad- creased time.1 nificant improvements in hardware verse events and the rates of complica- Dr. Reddy says that the exact mea- and software that have occurred—and tions were comparable between the surement of phaco time from surgeon the surgeons learning more about the two. However, a lot of this has to do to surgeon, as well as its effect on out-

March 2015 | Revophth.com | 37

0036_rp0315_f2.indd36_rp0315_f2.indd 3737 22/20/15/20/15 2:472:47 PMPM Cover Cataract

REVIEW Focus

comes, isn’t cut-and-dried, however. due to the laser activation having to be “I found that femtosecond cataract aborted, and the second had a tissue helped with regard to reduced effec- tag that became a tear, leading to a tive phaco time,” he says, “but, as a 0.1-percent rate of tearing.2 surgeon, I can’t say there’s a signiﬁ cant Dr. Reddy adds that there are cer- difference between the two modalities. tain patients with an unusual capsule/

Some doctors have a habit of continu- MD Robert Rivera, All images: zonule confi guration who will be easier ing the energy in between one frag- to operate on using a femtosecond la- ment to another and others don’t. It’s a ser, and where the laser capsulotomy factor that’s very surgeon-dependent.” would be preferable. “Whenever the anterior zonules are inserting into the The Capsulotomy Many studies fi nd the laser is adept at anterior capsule, there are some aber- creating well-sized, round capsulotomies. rations in some patients,” Dr. Reddy One particular aspect of femtosec- explains. “Some of them get inserted a ond cataract surgery that’s gotten a lot acknowledged, however, that the sur- little more proximal toward the center. of analysis in the literature is the cre- geon learning curve may be to blame So, when you try to do a manual cap- ation of the capsulotomy. for some of the increased complication sulorhexis, these fi bers will catch it and No one disputes the femtosecond rates with the laser procedure. from then on, it will be a struggle for laser’s ability to create a precise, very Dr. Roberts says rates such as these the surgeon. But when you do a laser circular rent in the capsule, and studies may be outliers, and haven’t been his capsulotomy, it cuts all these micro- have proven how accurate it can be.4,5 experience. “We published our safety scopic fi bers, so you’ll never have that Studies have even shown this may help study of 1,500 patients two years ago problem.” with positioning an intraocular lens and a follow-up study of another 3,000 postop.6 Controversy has begun, how- patients is in press,” he says. “Our an- Visual Results ever, after one recent study reported terior capsular tear rate is 0.2 percent laser capsulotomies may have some now. Other papers, such as that by Ju- In terms of refractive results, pub- weak points that could lead to tearing.7 lian Stevens at Moorfi elds which had lished studies show femtosecond and The tearing paper was a prospective 0.1 percent, aren’t fi nding a high rate conventional surgery both produce analysis of 804 patients undergoing such as this.” very good outcomes. femtosecond cataract surgery and 822 Hyderabad’s Dr. Reddy says he was “As to whether there’s a difference undergoing conventional phaco. In it, involved in an animal model study in visual outcomes between conven- the researchers found a statistically with Heidelberg, Germany’s, Gerd tional and femtosecond cataract sur- significant increased rate of anterior Auffarth, MD, where they specifi cally gery, the short answer from our report capsule tears in the laser group (15; looked at capsulotomy strength in por- is no,” says Dr. Gleitsmann. “Of the 1.87 percent) when compared to the cine corneas. “We stretched capsuloto- studies we looked at, and translating conventional group (1; 0.12 percent). mies created manually and by a laser,” all acuities into decimal equivalents, In seven cases, the anterior tear ex- he says. “The study showed the laser the visual outcomes were no different tended to the posterior capsule. The capsulotomies were as good, if not bet- between those two groups. To make researchers examined tissue samples ter, than manual ones. Also, if the laser a long story short, the outcomes are on scanning electron microscopy and edge is weak from a clinical point of so good for conventional surgery that found irregularities at the margin of view, then there should be tears in ev- it’s pretty hard to improve on them. the capsules, as well as apparently mis- ery case, because as we operate we’re Also, the numbers themselves for vi- placed laser pits in normal segments of pulling fragments through that capsu- sual acuity are actually kind of rough. the tissue.7 The pits are described as lotomy and we catch the edge as we do For instance, if someone says, ‘My re- sitting 2 to 4 µm apart at locations 10 it, but there aren’t.” sults are 20/20,’ and someone else says, to 100 µm radial to the capsule edge. In the study from Moorfi elds, sur- ‘Mine are 20/18,’ it really isn’t clinically The researchers said that, in some geons retrospectively reviewed 1,000 signifi cant.” cases, the anterior capsulotomy integ- laser capsulotomies performed over A study from Singapore that’s cur- rity appeared to be compromised by a period of about a year. They found rently in press, however, has found “postage-stamp” perforations and ab- complete 360-degree capsulotomies in that femtosecond cataract surgery pro- errant laser pulses that may occur due 998 cases (99.8 percent).8 In the two duced better visual outcomes on some to patient eye movement. They also incomplete capsulotomies, one was measurements when compared to a

38 | Review of Ophthalmology | March 2015

036_rp0315_f2.indd 38 2/20/15 2:47 PM ETL Approved

039_rp0315_Varitronics.indd 1 2/9/15 2:21 PM Cover Cataract

REVIEW Focus

random sample of conventional phaco Though there is currently a lot of cases. In the study, 18 surgeons per- equivalence between laser cataract formed femtosecond cataract surgery surgery and conventional phaco in the with the Victus laser (Bausch + Lomb) literature, Dr. Roberts says he expects on 1,105 eyes of 803 patients. They laser technology to improve. “At a re- then compared the visual outcomes of cent Academy meeting, I went to a 794 laser cases to 420 controls. The in- review of corneal laser surgery,” he vestigators found that the percentage says. “During the session, an interest- of patients who saw 20/25 or better un- ing comment was made that it’s taken corrected at six weeks was 68.6 percent many years and many major upgrades in the study group vs. 56.3 percent of to both hardware and software to get the controls (p<0.0001). The manifest Pre-segmenting a nucleus can help reduce where we currently are in terms of refraction spherical equivalent was also the duration of phaco time. the powerful lasers used for corneal statistically signifi cantly lower in the grafts and refractive procedures. So, laser group (-0.08 ±0.36 D compared stress on ocular structures.12 the question becomes: Is the current to -0.13 ±0.4 D; p=0.034). The mean “In our paper, complications didn’t evidence-based literature what one absolute error, however (0.30 ±0.25 D arise in any of these complex cases,”3 would expect for laser cataract sur- for the laser vs. 0.33 ±0.25; p=0.062) says Dr. Roberts. “In fact, we have gery as a new and evolving technology and the mean square error (0.16 found that the laser is particularly that has the potential to make surgery ±0.27 D vs. 0.17 ±0.28 D) were similar. benefi cial in these cases as the capsu- more accurate, safer and predictable? The researchers say the complication lotomy is consistently round and in- I’d argue that it is.” rate was low.10 tact, eliminating the risk of the manual 1. Abell RG, Darian-Smith E, Kan JB, et al. Femtosecond laser- A group from Europe performed a capsulotomy tearing out when the zon- assisted cataract surgery versus standard phacoemulsifi cation prospective, randomized study of the ules are weak. Also, a pre-fragmented cataract surgery: Outcomes and safety in more than 4000 cases at a single center. J Cataract Refract Surg 2015;41:1:47-52. effects on surgically induced astigma- nucleus allows you to do much less 2. Day AC, Gartry DS, Maurino V, Allan BD, Stevens JD. Effi cacy tism of a laser-created entry wound manipulation in the bag—with lower of anterior capsulotomy creation in femtosecond laser-assisted vs. a manual one, since induced astig- phaco power and time—reducing the cataract surgery. J Cataract Refract Surg 2014;40:12:2031-4. 3. Roberts TV, Lawless M, Bali SJ, et al. Surgical outcomes and matism could affect postop vision. risk of zonular dialysis.” safety of femtosecond laser cataract surgery: A prospective study They performed a 2.8-mm clear cor- Research shows, however, that sur- of 1500 consecutive cases. Ophthalmology 2013;120:2:227-33. 4. Nagy Z, Takacs A, Filkorn T, Sarayba M. Initial clinical evaluation neal incision in 20 eyes of 20 patients geons may have to exercise care when of an intraocular femtosecond laser in cataract surgery. J Refract using a disposable keratome and a using the femtosecond laser for cat- Surg 2009;25:12:1053-60. 5. Friedman NJ, Palanker DV, Schuele G, Andersen D, Marcellino 2.8-mm, biplanar clear corneal tunnel aract surgery in patients sensitive to G, Seibel BS, et al. Femtosecond laser capsulotomy. J Cataract in 20 eyes of 20 patients using a femto- intraocular pressure changes, due to Refract Surg 2011;37:1189–1198. 6. Kránitz K, Takacs A, Miháltz K, Kovács I, Knorz MC, Nagy second laser. They found no signifi cant the increase in intraocular pressure ZZ. Femtosecond laser capsulotomy and manual continuous difference in SIA (0.47 ±0.13 D for the that occurs during the suction dur- curvilinear capsulorhexis parameters and their effects on intraocular lens centration. J Refract Surg 2011;27:8:558-63. laser vs. 0.41 ±0.14 D for the manual ing preop laser docking. A prospec- 7. Abell RG, Davies PE, Phelan D, Goemann K, McPherson ZE, incisions; p=0.218), or any difference tive study from Hong Kong used a Vote BJ. Anterior capsulotomy integrity after femtosecond laser- assisted cataract surgery Ophthalmology 2014;121:1:17-24. in induced higher-order aberrations. handheld applanation tonometer to 8. Auffarth GU, Reddy KP, Ritter R, Holzer MP, Rabsilber TM. However, the axis deviation from the measure intraocular pressure during Comparison of the maximum applicable stretch force after planned axis was signifi cantly smaller femtosecond cataract surgery with the femtosecond laser-assisted and manual anterior capsulotomy. J Cataract Refract Surg 2013;39:1:105-9. in the laser group (4.47 ±2.59 degrees Victus in 41 eyes of 35 patients. The 9. Sándor GL, Kiss Z, Bocskai ZI, Kolev K, Takács AI, Juhász vs. 7.38 ±4.72 degrees; p=0.048).11 mean IOP went from 17.2 mmHg pre- E, Kránitz K, Tóth G, Gyenes A, Bojtár I, Juhász T, Nagy ZZ. Comparison of the mechanical properties of the anterior lens suction to 42.1 mmHg during suction, capsule following manual capsulorhexis and femtosecond laser Challenging Cases then back down to 13.8 mmHg after capsulotomy. J Refract Surg 2014;30:10:660-4. 10. Chee SP1, Yang Y2, Ti SE3. Clinical Outcomes in the fi rst 2 suction. The mean suction duration years of Femtosecond Laser-assisted Cataract Surgery. Am J Though there haven’t been studies was 216 seconds. They found the in- Ophthalmol 2015 Jan 26. [Epub ahead of print] 11. Nagy ZZ, Dunai A, Kránitz K, et al. Evaluation of femtosecond specifi cally designed to analyze fem- crease was statistically signifi cant com- laser-assisted and manual clear corneal incisions and their effect tosecond cataract surgery in diffi cult pared to pre-suction levels (25 ±11.3 on surgically induced astigmatism and higher-order aberrations. J Refract Surg 2014;30:8:522-5. cases (such as pseudoexfoliation or mmHg; p<0.01), and concluded that 12. Hatch KM, Talamo JH. Laser-assisted cataract surgery: patients with brunescent lenses), the surgeons should proceed with caution Benefi ts and barriers. Curr Opin Ophthalmol 2014;25:1:54-61. 13. Baig NB, Cheng GP, Lam JK, et al. Intraocular pressure profi les gestalt that has emerged from the lit- in patients with ocular conditions that during femtosecond laser-assisted cataract surgery. J Cataract 13 erature is that the laser may put less are vulnerable to IOP fl uctuations. Refract Surg 2014;40:11:1784-9.

40 | Review of Ophthalmology | March 2015

036_rp0315_f2.indd 40 2/20/15 2:48 PM Prostaglandin Aqueous humor analogues production work better is highest in at night1 the morning2

Classic beta blocker adjunctive therapy for the right patient at the right time3

The concomitant use of two topical beta-adrenergic blocking agents is not recommended4,5

Indications and Usage ISTALOL® (timolol maleate ophthalmic solution) is a non-selective beta-adrenergic receptor blocking agent indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Preservative-free TIMOPTIC® (timolol maleate ophthalmic solution) in OCUDOSE® (dispenser) is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. It may be used when a patient is sensitive to the preservative in TIMOPTIC (timolol maleate ophthalmic solution), benzalkonium chloride, or when use of a preservative-free topical medication is advisable. Important Safety Information for Istalol® and Timoptic® in Ocudose® • Both ISTALOL® (timolol maleate ophthalmic solution) and TIMOPTIC® (timolol maleate ophthalmic solution) in OCUDOSE® (dispenser) are contraindicated in patients with: bronchial asthma; a history of bronchial asthma; severe chronic obstructive pulmonary disease; sinus bradycardia; second or third degree atrioventricular block; overt cardiac failure; cardiogenic shock; hypersensitivity to any component of the product. • The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. Severe respiratory reactions and cardiac reaction, including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported following systemic or ophthalmic administration of timolol maleate. • Patients with a history of atopy or severe anaphylactic reactions to a variety of allergens may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions. • Timolol has been reported rarely to increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms. • Beta-adrenergic blocking agents may mask signs and symptoms of acute hypoglycemia or certain clinical signs of hyperthyroidism. Patients subject to spontaneous hypoglycemia, or diabetic patients receiving either insulin or oral hypoglycemic agents, or patients suspected of developing thyrotoxicosis, should be managed carefully, with caution. • In patients undergoing elective surgery, some authorities recommend gradual withdrawal of beta adrenergic receptor blocking agents because these agents impair the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. • The most frequently reported adverse reactions have been burning and stinging upon instillation. This was seen in 38% of patients treated with ISTALOL and in approximately one in eight patients treated with TIMOPTIC in OCUDOSE. Additional reactions reported with ISTALOL at a frequency of 4 to 10% include: blurred vision, cataract, conjunctival injection, headache, hypertension, infection, itching and decreased visual acuity. Please see Brief Summary of Prescribing Information for ISTALOL and TIMOPTIC in OCUDOSE on the following pages.

For the patients who need incremental IOP For the patients who need incremental IOP reduction in a preservative free form6 reduction in a once a day form6

Preservative-Free

TIMOPTIC® in OCUDOSE® (TIMOLOL MALEATE 0.5% (DISPENSER) OPHTHALMIC SOLUTION)

References: 1. Alm A, Stjernschantz J. Effects on Intraocular Pressure and Side Effects of 0.005% Latanoprost Applied Once Daily, Evening or Morning. Ophthalmology. 1995;102:1743-1752. 2. Brubaker R. Flow of Aqueous Humor in Humans. IOVS. 1991;32:(13)3145-3166. 3. Obstbaum S, Cioffi GA, Krieglstein GK, et al. Gold Standard Medical Therapy for Glaucoma: Defining the Criteria Identifying Measures for an Evidence-Based Analysis. Clin Ther. 2004;26(12)2102-2119. 4. Istalol [package insert]. Bridgewater, NJ: Bausch & Lomb Incorporated; 2013. 5. Timoptic in Ocudose [package insert]. Lawrenceville, NJ: Aton Pharma; 2009. 6. Stewart W, Day DG, Sharpe ED. Efficacy and Safety of Timolol Solution Once Daily vs Timolol Gel Added to Latanoprost. Am J Ophthalmol. 1999;128(6)692-696.

Timoptic and Ocudose are trademarks of Valeant Pharmaceuticals International, Inc. or its affiliates. Bausch + Lomb and Istalol are trademarks of Bausch & Lomb Incorporated or its affiliates.

©Bausch & Lomb Incorporated. US/TOP/14/0017(1)

RP1114_Valeant.indd 1 10/20/14 10:33 AM BRIEF SUMMARY OF PRESCRIBING INFORMATION atrioventricular block, or cardiac failure should be advised not to take this product. phenomenon, and cold hands and feet. This Brief Summary does not include all the information needed to use TIMOPTIC® (See CONTRAINDICATIONS.) DIGESTIVE: Nausea, diarrhea, dyspepsia, anorexia, and dry mouth. 0.25% AND 0.5% (timolol maleate ophthalmic solution) in OCUDOSE® (DISPENSER) Drug Interactions: Although TIMOPTIC (timolol maleate ophthalmic solution) used IMMUNOLOGIC: Systemic lupus erythematosus. safely and effectively. See full prescribing information for TIMOPTIC in OCUDOSE. alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy NERVOUS SYSTEM/PSYCHIATRIC: Dizziness, increase in signs and symptoms of PRESERVATIVE-FREE STERILE OPHTHALMIC SOLUTION with TIMOPTIC (timolol maleate ophthalmic solution) and epinephrine has been myasthenia gravis, paresthesia, somnolence, insomnia, nightmares, behavioral changes in a Sterile Ophthalmic Unit Dose Dispenser reported occasionally. and psychic disturbances including depression, confusion, hallucinations, anxiety, Beta-adrenergic blocking agents: Patients who are receiving a beta-adrenergic disorientation, nervousness, and memory loss. ® blocking agent orally and Preservative-free TIMOPTIC in OCUDOSE should be observed SKIN: Alopecia and psoriasiform rash or exacerbation of psoriasis. TIMOPTIC 0.25% AND 0.5% for potential additive effects of beta-blockade, both systemic and on intraocular HYPERSENSITIVITY: Signs and symptoms of systemic allergic reactions including (TIMOLOL MALEATE OPHTHALMIC SOLUTION) pressure. The concomitant use of two topical beta-adrenergic blocking agents is anaphylaxis, angioedema, urticaria, and localized and generalized rash. ® not recommended. RESPIRATORY: Bronchospasm (predominantly in patients with pre-existing in OCUDOSE (DISPENSER) Calcium antagonists: Caution should be used in the coadministration of beta- bronchospastic disease), respiratory failure, dyspnea, nasal congestion, cough and upper adrenergic blocking agents, such as Preservative-free TIMOPTIC in OCUDOSE, and oral respiratory infections. INDICATIONS AND USAGE or intravenous calcium antagonists, because of possible atrioventricular conduction ENDOCRINE: Masked symptoms of hypoglycemia in diabetic patients (see WARNINGS). Preservative-free TIMOPTIC in OCUDOSE is indicated in the treatment of elevated disturbances, left ventricular failure, and hypotension. In patients with impaired cardiac SPECIAL SENSES: Signs and symptoms of ocular irritation including conjunctivitis, intraocular pressure in patients with ocular hypertension or open-angle glaucoma. function, coadministration should be avoided. blepharitis, keratitis, ocular pain, discharge (e.g., crusting), foreign body sensation, Preservative-free TIMOPTIC in OCUDOSE may be used when a patient is sensitive Catecholamine-depleting drugs: Close observation of the patient is recommended itching and tearing, and dry eyes; ptosis; decreased corneal sensitivity; cystoid to the preservative in TIMOPTIC (timolol maleate ophthalmic solution), benzalkonium when a beta blocker is administered to patients receiving catecholamine-depleting macular edema; visual disturbances including refractive changes and diplopia; chloride, or when use of a preservative-free topical medication is advisable. drugs such as reserpine, because of possible additive effects and the production of pseudopemphigoid; choroidal detachment following filtration surgery (see PRECAUTIONS, hypotension and/or marked bradycardia, which may result in vertigo, syncope, or General); and tinnitus. CONTRAINDICATIONS postural hypotension. UROGENITAL: Retroperitoneal fibrosis, decreased libido, impotence, and Peyronie’s disease. Preservative-free TIMOPTIC in OCUDOSE is contraindicated in patients with (1) Digitalis and calcium antagonists: The concomitant use of beta-adrenergic blocking The following additional adverse effects have been reported in clinical experience bronchial asthma; (2) a history of bronchial asthma; (3) severe chronic obstructive agents with digitalis and calcium antagonists may have additive effects in prolonging with ORAL timolol maleate or other ORAL beta blocking agents, and may be considered pulmonary disease (see WARNINGS); (4) sinus bradycardia; (5) second or third degree atrioventricular conduction time. potential effects of ophthalmic timolol maleate: Allergic: Erythematous rash, fever atrioventricular block; (6) overt cardiac failure (see WARNINGS); (7) cardiogenic shock; or CYP2D6 inhibitors: Potentiated systemic beta-blockade (e.g., decreased heart rate, combined with aching and sore throat, laryngospasm with respiratory distress; Body (8) hypersensitivity to any component of this product. depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g., as a Whole: Extremity pain, decreased exercise tolerance, weight loss; Cardiovascular: quinidine, SSRIs) and timolol. Worsening of arterial insufficiency, vasodilatation; Digestive: Gastrointestinal pain, WARNINGS Clonidine: Oral beta-adrenergic blocking agents may exacerbate the rebound hepatomegaly, vomiting, mesenteric arterial thrombosis, ischemic colitis; Hematologic: As with many topically applied ophthalmic drugs, this drug is absorbed systemically. hypertension which can follow the withdrawal of clonidine. There have been no reports of Nonthrombocytopenic purpura; thrombocytopenic purpura; agranulocytosis; Endocrine: The same adverse reactions found with systemic administration of exacerbation of rebound hypertension with ophthalmic timolol maleate. Hyperglycemia, hypoglycemia; Skin: Pruritus, skin irritation, increased pigmentation, beta-adrenergic blocking agents may occur with topical administration. For Injectable epinephrine: (See PRECAUTIONS, General, Anaphylaxis) sweating; Musculoskeletal: Arthralgia; Nervous System/Psychiatric: Vertigo, local example, severe respiratory reactions and cardiac reactions, including death weakness, diminished concentration, reversible mental depression progressing to due to bronchospasm in patients with asthma, and rarely death in association Carcinogenesis, Mutagenesis, Impairment of Fertility: In a two-year oral study of timolol maleate administered orally to rats, there was a statistically significant catatonia, an acute reversible syndrome characterized by disorientation for time and with cardiac failure, have been reported following systemic or ophthalmic place, emotional lability, slightly clouded sensorium, and decreased performance administration of timolol maleate (see CONTRAINDICATIONS). increase in the incidence of adrenal pheochromocytomas in male rats administered 300 mg/kg/day (approximately 42,000 times the systemic exposure following the on neuropsychometrics; Respiratory: Rales, bronchial obstruction; Urogenital: Cardiac Failure: Sympathetic stimulation may be essential for support of the circulation maximum recommended human ophthalmic dose). Similar differences were not Urination difficulties. in individuals with diminished myocardial contractility, and its inhibition by beta- observed in rats administered oral doses equivalent to approximately 14,000 times the adrenergic receptor blockade may precipitate more severe failure. OVERDOSAGE maximum recommended human ophthalmic dose. There have been reports of inadvertent overdosage with Ophthalmic Solution In Patients Without a History of Cardiac Failure continued depression of the In a lifetime oral study in mice, there were statistically significant increases in myocardium with beta-blocking agents over a period of time can, in some cases, lead to TIMOPTIC (timolol maleate ophthalmic solution) resulting in systemic effects similar the incidence of benign and malignant pulmonary tumors, benign uterine polyps and to those seen with systemic beta-adrenergic blocking agents such as dizziness, cardiac failure. At the first sign or symptom of cardiac failure, Preservative-free TIMOPTIC mammary adenocarcinomas in female mice at 500 mg/kg/day (approximately 71,000 in OCUDOSE should be discontinued. headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest (see times the systemic exposure following the maximum recommended human ophthalmic also ADVERSE REACTIONS). Obstructive Pulmonary Disease: Patients with chronic obstructive pulmonary disease dose), but not at 5 or 50 mg/kg/day (approximately 700 or 7,000 times, respectively, the (e.g., chronic bronchitis, emphysema) of mild or moderate severity, bronchospastic Overdosage has been reported with Tablets BLOCADREN* (timolol maleate tablets). A systemic exposure following the maximum recommended human ophthalmic dose). In 30 year old female ingested 650 mg of BLOCADREN (maximum recommended oral daily disease, or a history of bronchospastic disease (other than bronchial asthma or a subsequent study in female mice, in which post-mortem examinations were limited to a history of bronchial asthma, in which TIMOPTIC in OCUDOSE is contraindicated dose is 60 mg) and experienced second and third degree heart block. She recovered the uterus and the lungs, a statistically significant increase in the incidence of pulmonary without treatment but approximately two months later developed irregular heartbeat, [see CONTRAINDICATIONS]) should, in general, not receive beta-blockers, including tumors was again observed at 500 mg/kg/day. Preservativefree TIMOPTIC in OCUDOSE. hypertension, dizziness, tinnitus, faintness, increased pulse rate, and borderline first The increased occurrence of mammary adenocarcinomas was associated with degree heart block. Major Surgery: The necessity or desirability of withdrawal of beta-adrenergic blocking elevations in serum prolactin which occurred in female mice administered oral timolol An in vitro hemodialysis study, using 14C timolol added to human plasma or whole agents prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs at 500 mg/kg/day, but not at doses of 5 or 50 mg/kg/day. An increased incidence blood, showed that timolol was readily dialyzed from these fluids; however, a study of the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. This of mammary adenocarcinomas in rodents has been associated with administration patients with renal failure showed that timolol did not dialyze readily. may augment the risk of general anesthesia in surgical procedures. Some patients of several other therapeutic agents that elevate serum prolactin, but no correlation receiving beta-adrenergic receptor blocking agents have experienced protracted severe between serum prolactin levels and mammary tumors has been established in humans. DOSAGE AND ADMINISTRATION hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has Furthermore, in adult human female subjects who received oral dosages of up to 60 mg Preservative-free TIMOPTIC in OCUDOSE is a sterile solution that does not contain also been reported. For these reasons, in patients undergoing elective surgery, some of timolol maleate (the maximum recommended human oral dosage), there were no a preservative. The solution from one individual unit is to be used immediately after authorities recommend gradual withdrawal of beta-adrenergic receptor blocking agents. clinically meaningful changes in serum prolactin. opening for administration to one or both eyes. Since sterility cannot be guaranteed after If necessary during surgery, the effects of beta-adrenergic blocking agents may be Timolol maleate was devoid of mutagenic potential when tested in vivo (mouse) in the individual unit is opened, the remaining contents should be discarded immediately reversed by sufficient doses of adrenergic agonists. the micronucleus test and cytogenetic assay (doses up to 800 mg/kg) and in vitro in after administration. Diabetes Mellitus: Beta-adrenergic blocking agents should be administered with a neoplastic cell transformation assay (up to 100 mcg/mL). In Ames tests the highest Preservative-free TIMOPTIC in OCUDOSE is available in concentrations of 0.25 and caution in patients subject to spontaneous hypoglycemia or to diabetic patients concentrations of timolol employed, 5,000 or 10,000 mcg/plate, were associated with 0.5 percent. The usual starting dose is one drop of 0.25 percent Preservative-free (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic statistically significant elevations of revertants observed with tester strain TA100 (in TIMOPTIC in OCUDOSE in the affected eye(s) administered twice a day. Apply enough agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms seven replicate assays), but not in the remaining three strains. In the assays with tester gentle pressure on the individual container to obtain a single drop of solution. If the of acute hypoglycemia. strain TA100, no consistent dose response relationship was observed, and the ratio of clinical response is not adequate, the dosage may be changed to one drop of 0.5 percent Thyrotoxicosis: Beta-adrenergic blocking agents may mask certain clinical signs (e.g., test to control revertants did not reach 2. A ratio of 2 is usually considered the criterion solution in the affected eye(s) administered twice a day. tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should for a positive Ames test. Since in some patients the pressure-lowering response to Preservative-free be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents that Reproduction and fertility studies in rats demonstrated no adverse effect on male TIMOPTIC in OCUDOSE may require a few weeks to stabilize, evaluation should include might precipitate a thyroid storm. or female fertility at doses up to 21,000 times the systemic exposure following the a determination of intraocular pressure after approximately 4 weeks of treatment with maximum recommended human ophthalmic dose. Preservative-free TIMOPTIC in OCUDOSE. PRECAUTIONS Pregnancy: Teratogenic Effects — Pregnancy Category C. Teratogenicity studies with If the intraocular pressure is maintained at satisfactory levels, the dosage schedule General: Because of potential effects of beta-adrenergic blocking agents on blood timolol in mice, rats and rabbits at oral doses up to 50 mg/kg/day (7,000 times the may be changed to one drop once a day in the affected eye(s). Because of diurnal pressure and pulse, these agents should be used with caution in patients with systemic exposure following the maximum recommended human ophthalmic dose) variations in intraocular pressure, satisfactory response to the once-a-day dose is best cerebrovascular insufficiency. If signs or symptoms suggesting reduced cerebral blood demonstrated no evidence of fetal malformations. Although delayed fetal ossification was determined by measuring the intraocular pressure at different times during the day. flow develop following initiation of therapy with Preservative-free TIMOPTIC in OCUDOSE, observed at this dose in rats, there were no adverse effects on postnatal development Dosages above one drop of 0.5 percent TIMOPTIC (timolol maleate ophthalmic alternative therapy should be considered. of offspring. Doses of 1000 mg/kg/day (142,000 times the systemic exposure solution) twice a day generally have not been shown to produce further reduction in Choroidal detachment after filtration procedures has been reported with the following the maximum recommended human ophthalmic dose) were maternotoxic intraocular pressure. If the patient’s intraocular pressure is still not at a satisfactory administration of aqueous suppressant therapy (e.g. timolol). in mice and resulted in an increased number of fetal resorptions. Increased fetal level on this regimen, concomitant therapy with other agent(s) for lowering intraocular Angle-closure glaucoma: In patients with angle-closure glaucoma, the immediate resorptions were also seen in rabbits at doses of 14,000 times the systemic exposure pressure can be instituted taking into consideration that the preparation(s) used objective of treatment is to reopen the angle. This requires constricting the pupil. Timolol following the maximum recommended human ophthalmic dose, in this case without concomitantly may contain one or more preservatives. The concomitant use of two maleate has little or no effect on the pupil. TIMOPTIC in OCUDOSE should not be used apparent maternotoxicity. topical beta-adrenergic blocking agents is not recommended. (See PRECAUTIONS, Drug alone in the treatment of angle-closure glaucoma. There are no adequate and well-controlled studies in pregnant women. Preservative- Interactions, Beta-adrenergic blocking agents.) Anaphylaxis: While taking beta-blockers, patients with a history of atopy or a free TIMOPTIC in OCUDOSE should be used during pregnancy only if the potential benefit ------history of severe anaphylactic reactions to a variety of allergens may be more reactive justifies the potential risk to the fetus. to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Nursing Mothers: Timolol maleate has been detected in human milk following oral and Such patients may be unresponsive to the usual doses of epinephrine used to treat ophthalmic drug administration. Because of the potential for serious adverse reactions anaphylactic reactions. from timolol in nursing infants, a decision should be made whether to discontinue Muscle Weakness: Beta-adrenergic blockade has been reported to potentiate muscle nursing or to discontinue the drug, taking into account the importance of the drug to weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and the mother. generalized weakness). Timolol has been reported rarely to increase muscle weakness in Pediatric Use: Safety and effectiveness in pediatric patients have not been established. By: Laboratories Merck Sharp & Dohme-Chibret some patients with myasthenia gravis or myasthenic symptoms. 63963 Clermont-Ferrand Cedex 9, France Geriatric Use: No overall differences in safety or effectiveness have been observed Information for Patients: Patients should be instructed about the use of Preservative- between elderly and younger patients. free TIMOPTIC in OCUDOSE. Based on PI - 514266Z/069A-03/09/9689-9690 Since sterility cannot be maintained after the individual unit is opened, patients should ADVERSE REACTIONS US/TOP/14/0018 Issued February 2009 be instructed to use the product immediately after opening, and to discard the individual The most frequently reported adverse experiences have been burning and stinging unit and any remaining contents immediately after use. upon instillation (approximately one in eight patients). Patients with bronchial asthma, a history of bronchial asthma, severe chronic The following additional adverse experiences have been reported less frequently with obstructive pulmonary disease, sinus bradycardia, second or third degree ocular administration of this or other timolol maleate formulations: ------BODY AS A WHOLE: Headache, asthenia/fatigue, and chest pain. * Registered trademark of ATON PHARMA, INC. CARDIOVASCULAR: Bradycardia, arrhythmia, hypotension, hypertension, syncope, heart COPYRIGHT © 2009 ATON PHARMA, INC. block, cerebral vascular accident, cerebral ischemia, cardiac failure, worsening of angina All rights reserved pectoris, palpitation, cardiac arrest, pulmonary edema, edema, claudication, Raynaud’s

RP1114_Valeant Timpotic PI.indd 1 10/20/14 10:53 AM BRIEF SUMMARY OF PRESCRIBING INFORMATION symptoms suggesting reduced cerebral blood flow develop following initiation of in rats, there were no adverse effects on postnatal development of offspring. Doses This Brief Summary does not include all the information needed to therapy with Istalol, alternative therapy should be considered. of 1000 mg/kg/day (142,000 times the systemic exposure following the maximum use ISTALOL® (timolol maleate ophthalmic solution) 0.5% safely and 5.12 Choroidal Detachment: Choroidal detachment after filtration procedures recommended human ophthalmic dose) were maternotoxic in mice and resulted effectively. See full prescribing information for ISTALOL. has been reported with the administration of aqueous suppressant therapy (e.g. in an increased number of fetal resorptions. Increased fetal resorptions were also timolol). seen in rabbits at doses of 14,000 times the systemic exposure following the ® (timolol maleate ophthalmic solution) 0.5% ADVERSE REACTIONS maximum recommended human ophthalmic dose, in this case without apparent Istalol maternotoxicity. There are no adequate and well-controlled studies in pregnant Initial U.S. Approval: 1978 6.1 Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a women. Istalol should be used during pregnancy only if the potential benefit justifies STERILE drug cannot be directly compared to rates in the clinical trials of another drug and the potential risk to the fetus. INDICATIONS AND USAGE may not reflect the rates observed in practice. 8.3 Nursing Mothers: Timolol has been detected in human milk following oral Istalol (timolol maleate ophthalmic solution) 0.5% is a non-selective beta-adrenergic The most frequently reported adverse reactions have been burning and stinging and ophthalmic drug administration. Because of the potential for serious adverse receptor blocking agent indicated in the treatment of elevated intraocular pressure upon instillation in 38% of patients treated with Istalol. Additional reactions reported reactions from Istalol in nursing infants, a decision should be made whether to (IOP) in patients with ocular hypertension or open-angle glaucoma. with Istalol at a frequency of 4 to 10% include: blurred vision, cataract, conjunctival discontinue nursing or to discontinue the drug, taking into account the importance CONTRAINDICATIONS injection, headache, hypertension, infection, itching and decreased visual acuity. of the drug to the mother. 4.1 Asthma, COPD: Istalol is contraindicated in patients with bronchial asthma; The following additional adverse reactions have been reported less frequently with 8.4 Pediatric Use: Safety and effectiveness in pediatric patients have not been a history of bronchial asthma; severe chronic obstructive pulmonary disease (see ocular administration of this or other timolol maleate formulations. established. WARNINGS AND PRECAUTIONS, 5.1, 5.3). Timolol (Ocular Administration): Body as a whole: Asthenia/fatigue and chest 8.5 Geriatric Use: No overall differences in safety or effectiveness have been 4.2 Sinus Bradycardia, AV Block, Cardiac Failure, Cardiogenic Shock: pain; Cardiovascular: Bradycardia, arrhythmia, hypotension, syncope, heart observed between elderly and younger patients. Istalol is contraindicated in patients with sinus bradycardia; second block, cerebral vascular accident, cerebral ischemia, cardiac failure, worsening OVERDOSAGE or third degree atrioventricular block; overt cardiac failure (see of angina pectoris, palpitation, cardiac arrest, pulmonary edema, edema, There have been reports of inadvertent overdosage with Istalol resulting in systemic WARNINGS AND PRECAUTIONS, 5.2); cardiogenic shock. claudication, Raynaud’s phenomenon and cold hands and feet; Digestive: Nausea, effects similar to those seen with systemic beta-adrenergic blocking agents such as 4.3 Hypersensitivity Reactions: Istalol is contraindicated in patients who have diarrhea, dyspepsia, anorexia, and dry mouth; Immunologic: Systemic lupus dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac exhibited a hypersensitivity reaction to any component of this product in the past. erythematosus; Nervous System/Psychiatric: Dizziness, increase in signs and arrest. An in vitro hemodialysis study, using 14C timolol added to human plasma or WARNINGS AND PRECAUTIONS symptoms of myasthenia gravis, paresthesia, somnolence, insomnia, nightmares, whole blood, showed that timolol was readily dialyzed from these fluids; however, 5.1 Potentiation of Respiratory Reactions Including Asthma: Istalol behavioral changes and psychic disturbances including depression, confusion, a study of patients with renal failure showed that timolol did not dialyze readily. contains timolol maleate; and although administered topically, it can be absorbed hallucinations, anxiety, disorientation, nervousness and memory loss; Skin: NONCLINICAL TOXICOLOGY systemically. Therefore, the same adverse reactions found with systemic Alopecia and psoriasiform rash or exacerbation of psoriasis; Hypersensitivity: Signs 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility: In a two-year administration of beta-adrenergic blocking agents may occur with topical and symptoms of systemic allergic reactions, including angioedema, urticaria, study of timolol maleate administered orally to rats, there was a statistically administration. For example, severe respiratory reactions and cardiac reactions and localized and generalized rash; Respiratory: Bronchospasm (predominantly significant increase in the incidence of adrenal pheochromocytomas in male rats including death due to bronchospasm in patients with asthma, and rarely death in patients with pre-existing bronchospastic disease), respiratory failure, administered 300 mg/kg/day (approximately 42,000 times the systemic exposure in association with cardiac failure, have been reported following systemic or dyspnea, nasal congestion, cough and upper respiratory infections; Endocrine: following the maximum recommended human ophthalmic dose). Similar differences ophthalmic administration of timolol maleate (see CONTRAINDICATIONS, 4.1). Masked symptoms of hypoglycemia in diabetic patients (see WARNINGS AND were not observed in rats administered oral doses equivalent to approximately PRECAUTIONS, 5.6); Special Senses: Signs and symptoms of ocular irritation 5.2 Cardiac Failure: Sympathetic stimulation may be essential for support 14,000 times the maximum recommended human ophthalmic dose. In a lifetime including conjunctivitis, blepharitis, keratitis, ocular pain, discharge (e.g., crusting), of the circulation in individuals with diminished myocardial contractility, and its oral study in mice, there were statistically significant increases in the incidence foreign body sensation, itching and tearing, and dry eyes; ptosis, decreased corneal inhibition of beta-adrenergic receptor blockade may precipitate more severe failure. of benign and malignant pulmonary tumors, benign uterine polyps and mammary sensitivity; cystoid macular edema; visual disturbances including refractive changes In patients without a history of cardiac failure, continued depression of the adenocarcinomas in female mice at 500 mg/kg/day, (approximately 71,000 times and diplopia; pseudopemphigoid; choroidal detachment following filtration surgery myocardium with beta-blocking agents over a period of time can, in some cases, the systemic exposure following the maximum recommended human ophthalmic (see WARNINGS AND PRECAUTIONS, 5.12); Urogenital: Retroperitoneal fibrosis, lead to cardiac failure. At the first sign or symptom of cardiac failure, Istalol should dose), but not at 5 or 50 mg/kg/day (approximately 700 or 7,000, respectively, decreased libido, impotence, and Peyronie’s disease. be discontinued (see also CONTRAINDICATIONS, 4.2). times the systemic exposure following the maximum recommended human 5.3 Obstructive Pulmonary Disease: Patients with chronic obstructive 6.2 Postmarketing Experience ophthalmic dose). In a subsequent study in female mice, in which post-mortem pulmonary disease (e.g., chronic bronchitis, emphysema) of mild or moderate Oral Timolol/Oral Beta-blockers: The following additional adverse effects have examinations were limited to the uterus and the lungs, a statistically significant severity, bronchospastic disease, or a history of bronchospastic disease [other than been reported in clinical experience with ORAL timolol maleate or other ORAL beta- increase in the incidence of pulmonary tumors was again observed at 500 mg/ bronchial asthma or a history of bronchial asthma in which Istalol is contraindicated blocking agents and may be considered potential effects of ophthalmic timolol kg/day. The increased occurrence of mammary adenocarcinomas was associated (see CONTRAINDICATIONS, 4.2)] should, in general, not receive beta-blocking maleate: Allergic: Erythematous rash, fever combined with aching and sore throat, with elevations in serum prolactin which occurred in female mice administered oral agents, including Istalol. laryngospasm with respiratory distress; Body as a Whole: Extremity pain, decreased timolol at 500 mg/kg/day, but not at doses of 5 or 50 mg/kg/day. An increased incidence of mammary adenocarcinomas in rodents has been associated with 5.4 Increased Reactivity to Allergens: While taking beta-blockers, patients exercise tolerance, weight loss; Cardiovascular: Worsening of arterial insufficiency, administration of several other therapeutic agents that elevate serum prolactin, with a history of atopy or a history of severe anaphylactic reactions to a variety of vasodilatation; Digestive: Gastrointestinal pain, hepatomegaly, vomiting, mesenteric but no correlation between serum prolactin levels and mammary tumors has been allergens may be more reactive to repeated accidental, diagnostic, or therapeutic arterial thrombosis, ischemic colitis; Hematologic: Nonthrombocytopenic established in humans. Furthermore, in adult human female subjects who received challenge with such allergens. Such patients may be unresponsive to the usual purpura; thrombocytopenic purpura, agranulocytosis; Endocrine: Hyperglycemia, oral dosages of up to 60 mg of timolol maleate (the maximum recommended doses of epinephrine used to treat anaphylactic reactions. hypoglycemia; Skin: Pruritus, skin irritation, increased pigmentation, sweating; Musculoskeletal: Arthralgia; Nervous System/Psychiatric: Vertigo, local weakness, human oral dosage), there were no clinically meaningful changes in serum prolactin. 5.5 Potentiation of Muscle Weakness: Beta-adrenergic blockade has been diminished concentration, reversible mental depression progressing to catatonia, Timolol maleate was devoid of mutagenic potential when tested in vivo (mouse) reported to potentiate muscle weakness consistent with certain myasthenic an acute reversible syndrome characterized by disorientation for time and place, in the micronucleus test and cytogenetic assay (doses up to 800 mg/kg) and in symptoms (e.g., diplopia, ptosis, and generalized weakness). Timolol has been emotional lability, slightly clouded sensorium and decreased performance on vitro in a neoplastic cell transformation assay (up to 100 mcg/mL). In Ames tests reported rarely to increase muscle weakness in some patients with myasthenia neuropsychometrics; Respiratory: Rales, bronchial obstruction; Urogenital: Urination the highest concentrations of timolol employed, 5,000 or 10,000 mcg/plate, were gravis or myasthenic symptoms. difficulties. associated with statistically significant elevations of revertants observed with tester 5.6 Masking of Hypoglycemic Symptoms in Patients with Diabetes strain TA100 (in seven replicate assays), but not in the remaining three strains. In Mellitus: Beta-adrenergic blocking agents should be administered with caution DRUG INTERACTIONS 7.1 Beta-Adrenergic Blocking Agents: Patients who are receiving a beta- the assays with tester strain TA100, no consistent dose response relationship was in patients subject to spontaneous hypoglycemia or to diabetic patients (especially ® observed, and the ratio of test to control revertants did not reach 2. A ratio of 2 is those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. adrenergic blocking agent orally and Istalol should be observed for potential additive effects of beta-blockade, both systemic and on intraocular pressure. usually considered the criterion for a positive Ames test. Reproduction and fertility Beta-adrenergic receptor blocking agents may mask the signs and symptoms of studies in rats demonstrated no adverse effect on male or female fertility at doses acute hypoglycemia. The concomitant use of two topical beta-adrenergic blocking agents is not recommended. up to 21,000 times the systemic exposure following the maximum recommended 5.7 Masking of Thyrotoxicosis: Beta-adrenergic blocking agents may mask human ophthalmic dose. certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of 7.2 Calcium Antagonists: Caution should be used in the co-administration of beta-adrenergic blocking agents, such as Istalol, and oral or intravenous calcium PATIENT COUNSELING INFORMATION developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal Patients with bronchial asthma, a history of bronchial asthma, severe chronic of beta-adrenergic blocking agents that might precipitate a thyroid storm. antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. In patients with impaired cardiac function, co- obstructive pulmonary disease, sinus bradycardia, second or third degree 5.8 Contamination of Topical Ophthalmic Products After Use: There administration should be avoided. atrioventricular block, or cardiac failure should be advised not to take this product. have been reports of bacterial keratitis associated with the use of multiple-dose 7.3 Catecholamine-Depleting Drugs: Close observation of the patient (see CONTRAINDICATIONS, 4.1, 4.2) Patients should also be instructed that ocular containers of topical ophthalmic products. These containers had been inadvertently solutions, if handled improperly or if the tip of the dispensing container contacts contaminated by patients who, in most cases, had a concurrent corneal disease is recommended when a beta blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive the eye or surrounding structures, can become contaminated by common bacteria or a disruption of the ocular epithelial surface (see PATIENT COUNSELING known to cause ocular infections. Serious damage to the eye and subsequent INFORMATION, 17). effects and the production of hypotension and/or marked bradycardia, which may result in vertigo, syncope, or postural hypotension. loss of vision may result from using contaminated solutions. (see WARNINGS 5.9 Impairment of Beta-adrenergically Mediated Reflexes During Surgery: 7.4 Digitalis and Calcium Antagonists: The concomitant use of beta- AND PRECAUTIONS 5.8) Patients should also be advised that if they have ocular The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they to major surgery is controversial. Beta-adrenergic receptor blockade impairs the adrenergic blocking agents with digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time. should immediately seek their physician’s advice concerning the continued use of ability of the heart to respond to beta-adrenergically mediated reflex stimuli. This the present multidose container. If more than one topical ophthalmic drug is being may augment the risk of general anesthesia in surgical procedures. Some patients 7.5 CYP2D6 Inhibitors: Potentiated systemic beta-blockade (e.g., decreased heart rate) has been reported during combined treatment with CYP2D6 inhibitors used, the drugs should be administered at least five minutes apart. Patients should receiving beta-adrenergic receptor blocking agents have experienced protracted ® (e.g., quinidine) and timolol. be advised that Istalol contains benzalkonium chloride which may be absorbed by severe hypotension during anesthesia. Difficulty in restarting and maintaining the soft contact lenses. Contact lenses should be removed prior to administration of 7.6 Clonidine: Oral beta-adrenergic blocking agents may exacerbate the heartbeat has also been reported. For these reasons, in patients undergoing elective the solution. Lenses may be reinserted 15 minutes following Istalol® administration. rebound hypertension which can follow the withdrawal of clonidine. There have surgery, some authorities recommend gradual withdrawal of beta-adrenergic Rx Only receptor blocking agents. If necessary during surgery, the effects of beta-adrenergic been no reports of exacerbation of rebound hypertension with ophthalmic timolol Manufactured by: blocking agents may be reversed by sufficient doses of adrenergic agonists. maleate. USE IN SPECIFIC POPULATIONS Bausch & Lomb Incorporated 5.10 Angle-Closure Glaucoma: In patients with angle-closure glaucoma, Tampa, FL 33637 the immediate objective of treatment is to reopen the angle. This may require 8.1 Pregnancy Under License from: constricting the pupil. Timolol maleate has little or no effect on the pupil. Istalol Teratogenic Effects: Pregnancy Category C: Teratogenicity studies have been SENJU Pharmaceutical Co., Ltd should not be used alone in the treatment of angle-closure glaucoma. performed in animals. Teratogenicity studies with timolol in mice, rats, and rabbits Osaka, Japan 541-0046 5.11 Cerebrovascular Insufficiency: Because of potential effects of beta- at oral doses up to 50 mg/kg/day (7,000 times the systemic exposure following the ®/TM are trademarks of Bausch & Lomb Incorporated or its affiliates. adrenergic blocking agents on blood pressure and pulse, these agents should maximum recommended human ophthalmic dose) demonstrated no evidence of © Bausch & Lomb Incorporated be used with caution in patients with cerebrovascular insufficiency. If signs or fetal malformations. Although delayed fetal ossification was observed at this dose Based on 9401500 US/IST/14/0007 Issued 06/2013

RRP1114_ValeantP1114_Valeant IstalolIstalol PI.inddPI.indd 1 110/20/140/20/14 11:0211:02 AMAM Cataract REVIEW Cover Focus New Technology Gains Momentum Walter Bethke, Managing Editor

Burgeoning Technology Femtosecond ew technology for cataract surgery appears to be the pro- Cataract surgeons seem to be lasers and Nverbial snowball rolling down- warming up to the idea of femtosec- hill—it continues to gradually grow in ond cataract, with the percentage say- intraoperative size in terms of users on our annual ing they use it for some aspect of cata- survey of cataract surgeons. Femto- ract surgery growing from 23 percent aberrometry second cataract and, to a lesser extent, on last year’s survey to 31 percent this intrigue surgeons. intraoperative wavefront aberrometry, year. The steps the laser is used for have both garnered new converts over most often are the capsulotomy (91 the past year, and some indicators on percent of respondents) and nuclear the survey point toward more adher- fragmentation (91 percent). The per- ents in the future. centage who say they use it for the These are a couple of the revela- entry and paracentesis incisions actu- tions in this month’s survey of surgeons ally decreased from last year, however. about their cataract techniques. The Last year, 64 percent used it for the e-mail survey was opened by 1,742 of entry wound and 55 percent used it 11,600 subscribers to Review’s elec- for the paracentesis, compared to just tronic mail service (15 percent open 38 percent and 29 percent, respec- rate) and 181 ﬁ lled in their answers. tively, this year. The full results appear To see how your cataract technique in the graph on p. 46. compares to the surgeons on the sur- The surgeons who currently use the vey, read on. technology appreciate many of the

Likelihood of Performing Femto Cataract Surgery Within a Year

% 24

Very likely Somewhat likely Unlikely

44 | Review of Ophthalmology | March 2015 This article has no commercial sponsorship.

0044_rp0315_f3.indd44_rp0315_f3.indd 4444 22/20/15/20/15 4:144:14 PMPM LENSTAR LS 900 Improving outcomes.

Barrett & Olsen Formulas on Board Measured lens thickness and two of the latest generation multivariable IOL formulas allow for premium IOL power prediction with the LENSTAR.

T-Cone Toric Platform The optional t-cone complements LENSTAR’s measurement pallet with true Placido topography of the central cornea and a powerful surgical planner using the Barrett toric calculator.

EyeSuite IOL Toric Planner The optional IOL toric planner allows optimisation of the incision location and planning of the surgery on real eye images to reach advanced refractive results.

RP0315_Haag Lenstar.indd 1 2/18/15 1:50 PM Cover Cataract

REVIEW Focus

Surgeons’ Use of Femtosecond for Cataract Surgery

91 91

79 % 38 29

Entry wound Paracentesis Capsulotomy Nucleus fragmentation Astigmatism correction

things it does for them, but note that manual approach simplifi es things.” steel or diamond blades. I prefer la- it’s not perfect. John Sheppard, MD, Looking ahead, 12 percent of the mellar AK techniques such as bilateral of Norfolk, Va., is one of these physi- surgeons say they’re very likely to per- clear cornea incisions. I like scleral cians. “I enjoy the procedure,” he says. form femtosecond cataract surgery tunnel on the steep, with-the-rule axis “It’s an excellent marketing tool, and in the next year, and 24 percent say (scleral recession) and LVC when a has outstanding advantages for capsu- they’re somewhat likely to do so. The toric IOL isn’t indicated or is unaf- lorhexis and LRIs. I’m enjoying newer main reasons given are, “it’s the fu- fordable.” Douglas Liva, MD, from nucleus fragmentation techniques ture,” or “patient demand.” On the Ridgewood, N.J., is also looking for a like the ‘ice cube.’ The paracentesis other hand, 64 percent say they’re un- better value considering the cost in- and primary incisions don’t yet have likely to do it, though this percentage volved. “I’m unlikely to use it because a clear-cut advantage, though. It’s still is down from last survey’s 73 percent. of cost and the fact that there’s no real costly, but our fastest growing single The main reason given by many of data showing it to be better or safer,” segment of premium surgery is the the uninterested surgeons is the cost/ he says. “In fact, it seems to have more LenSx.” Jeffersonville, Ind., surgeon benefi t ratio. “It works OK but is too complications and take longer. I’m Curtis Jordan says, “It makes a great cumbersome to align the patient,” says also not comfortable with the ethics rhexis, nucleus division and astigmatic an Ohio surgeon who tried the tech- in its presentation to the patient since keratotomy, but the temporal wound nology but is unlikely to go back to it’s sold as an uncovered service as it is too far anterior, so I make my own it. “There’s too much of a reliance on is used to correct astigmatism. What temporal wounds and paracenteses.” the technician, too many extra steps do you tell the patient who wants it A surgeon from California chooses to where things can go wrong or out of and has no signifi cant astigmatism?” make mostly AK cuts with the fem- your control, it takes too long and is George Walters, MD, of Del Rio, Tex- tosecond. “I like that it makes all the expensive without any clear advan- as, says he’s also unlikely to start doing cuts,” he says. “The bubbles [created tage to the patient. The technology is it. “It’s too costly and doesn’t elimi- during laser operation] can block the not currently advanced enough to be nate the need for manual intraocu- view, but I do like the pneumodissec- worth the hassle.” lar manipulation,” he says. “It doesn’t tion. I don’t like the entry incisions Richard Erdey, MD, of Columbus, eliminate complications during phaco, made by it. Also, the suction can break Ohio, also says he’s unlikely to use cortical cleanup or IOL placement. It’s vessels and make the eye very irri- femtosecond for his cataract surgeries. like killing a fl y with a military drone.” tated; the eye looks less traumatized “There’s no peer-reviewed paper dem- The other technology in conten- after regular cataract extraction. I like onstrating any advantage of it versus a tion for cataract surgeons’ attention is making AK incisions with it, primari- very effi cient two-handed phaco chop intraoperative wavefront aberrometry. ly.” A Texas surgeon also gives it mixed technique,” he avers. “There’s also no Twelve percent of the surgeons say reviews. “I like that it makes for a very peer-reviewed report demonstrating they use it, which is up slightly from standardized procedure,” he says. “I the long-term predictability and stabil- last year’s 9 percent, and 34 percent don’t like that cortical cleanup is much ity of vertical corneal incisions made say they’re either very likely or some- more diffi cult with it, but using a bi- with the femto versus those made with what likely to use it in the coming year,

46 | Review of Ophthalmology | March 2015

0044_rp0315_f3.indd44_rp0315_f3.indd 4646 22/20/15/20/15 4:144:14 PMPM NOW APPROVED OUR SCIENCE. MACULAR EDEMA (DME) YOUR ART. FOR DIABETIC

As Demonstrated in 2 Pivotal, Phase 3 Trials in Patients With DME Evaluating Mean Change in BCVA*BCVA at 5252 WeeksWeeks vs BaselineBaseline1

EYLEA® (aflibercept) Injection Offers Extended Dosing in DME—2-mg Every 8 Weeks Following 5 Initial Monthly Doses1 Initial Dosing Follow-Up Dosing 5 Initial 2-mg Injections Monthly 2-mg Every 2 Months (Every 4 Weeks) (Every 8 Weeks)

AlthoughAlth h EYLEA may bbe ddosed d as ffrequently tl as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks.

* BCVA = best-corrected visual acuity, as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letters.

IMPORTANT SAFETY INFORMATION FOR Serious adverse reactions related to the injection procedure have EYLEA® (aflibercept) INJECTION occurred in <0.1% of intravitreal injections with EYLEA including EYLEA® (aflibercept) Injection is contraindicated in patients with endophthalmitis and retinal detachment. ocular or periocular infections, active intraocular inflammation, *'/156%1//10#&8'45'4'#%6+105j¢Ik4'2146'&+02#6+'065 or known hypersensitivity to aflibercept or to any of the excipients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, in EYLEA. vitreous floaters, intraocular pressure increased, and vitreous Intravitreal injections, including those with EYLEA, have been detachment. associated with endophthalmitis and retinal detachments. IMPORTANT PRESCRIBING INFORMATION FOR Proper aseptic injection technique must always be used when EYLEA® (aflibercept) INJECTION administering EYLEA. Patients should be instructed to report any EYLEA® (aflibercept) Injection is indicated for the treatment of symptoms suggestive of endophthalmitis or retinal detachment patients with without delay and should be managed appropriately. Intraocular inflammation has been reported with the use of EYLEA. Neovascular (Wet) Age-related Macular Degeneration (AMD): The recommended dose is 2 mg administered by intravitreal injection Acute increases in intraocular pressure have been seen within every 4 weeks (monthly) for the first 12 weeks (3 months), followed 60 minutes of intravitreal injection, including with EYLEA. Sustained by 2 mg once every 8 weeks (2 months). Although EYLEA may be increases in intraocular pressure have also been reported after dosed as frequently as 2 mg every 4 weeks (monthly), additional repeated intravitreal dosing with VEGF inhibitors. Intraocular efficacy was not demonstrated when EYLEA was dosed every pressure and the perfusion of the optic nerve head should be 4 weeks compared to every 8 weeks. monitored and managed appropriately. Macular Edema following Retinal Vein Occlusion (RVO): The There is a potential risk of arterial thromboembolic events (ATEs) recommended dose is 2 mg administered by intravitreal injection following use of intravitreal VEGF inhibitors, including EYLEA, defined every 4 weeks (monthly). as nonfatal stroke, nonfatal myocardial infarction, or vascular death Diabetic Macular Edema (DME): The recommended dose is 2 mg (including deaths of unknown cause). The incidence of reported administered by intravitreal injection every 4 weeks (monthly) for the thromboembolic events in wet AMD studies during the first year was first 5 injections, followed by 2 mg once every 8 weeks (2 months). 1.8% (32 out of 1824) in the combined group of patients treated Although EYLEA may be dosed as frequently as 2 mg every 4 weeks with EYLEA. The incidence in the DME studies during the first year (monthly), additional efficacy was not demonstrated when EYLEA was was 3.3% (19 out of 578) in the combined group of patients treated dosed every 4 weeks compared to every 8 weeks. with EYLEA compared with 2.8% (8 out of 287) in the control group. There were no reported thromboembolic events in the patients For more information, visit www.EYLEA.com. treated with EYLEA in the first six months of the RVO studies.

Reference: 1. EYLEA® (aﬂibercept) Injection full U.S. Prescribing Information. Regeneron Pharmaceuticals, Inc. October 2014. Please see brief summary of full Prescribing Information on the following page. EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc.

TAARGGETE EDD SCCIENENCCE

RP0215_Regeneron.indd 1 1/13/15 3:59 PM studies during the first year was 1.8% (32 out of 1824) in the combined in 2 double-masked, controlled clinical studies (VIVID and VISTA) for group of patients treated with EYLEA. The incidence in the DME studies 52 weeks. during the first year was 3.3% (19 out of 578) in the combined group Table 3: Most Common Adverse Reactions (≥1%) in DME Studies of patients treated with EYLEA compared with 2.8% (8 out of 287) in EYLEA Control the control group. There were no reported thromboembolic events in the Adverse Reactions patients treated with EYLEA in the first six months of the RVO studies. (N=578) (N=287) 6 ADVERSE REACTIONS Conjunctival hemorrhage 28% 17% The following adverse reactions are discussed in greater detail in the Eye pain 9% 6% Warnings and Precautions section of the labeling: Cataract 8% 9% BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION • Endophthalmitis and retinal detachments Vitreous floaters 6% 3% For complete details, see Full Prescribing Information. • Increased intraocular pressure Corneal erosion 5% 3% • Thromboembolic events 1 INDICATIONS AND USAGE Intraocular pressure increased 5% 3% 6.1 Clinical Trials Experience. Because clinical trials are conducted EYLEA® (aflibercept) Injection is indicated for the treatment of patients Conjunctival hyperemia 5% 6% under widely varying conditions, adverse reaction rates observed in the with Neovascular (Wet) Age-Related Macular Degeneration (AMD), clinical trials of a drug cannot be directly compared to rates in other Vitreous detachment 3% 3% Macular Edema following Retinal Vein Occlusion (RVO), and Diabetic clinical trials of the same or another drug and may not reflect the rates Foreign body sensation in eyes 3% 3% Macular Edema (DME). observed in practice. Lacrimation increased 3% 2% 2 DOSAGE AND ADMINISTRATION A total of 2711 patients treated with EYLEA constituted the safety Vision blurred 2% 2% 2.1 Important Injection Instructions. For ophthalmic intravitreal population in seven phase 3 studies. Among those, 2110 patients Intraocular inflammation 2% <1% injection. EYLEA must only be administered by a qualified physician. were treated with the recommended dose of 2 mg. Serious adverse Injection site pain 2% <1% 2.2 Neovascular (Wet) Age-Related Macular Degeneration (AMD). reactions related to the injection procedure have occurred in <0.1% of The recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters) intravitreal injections with EYLEA including endophthalmitis and retinal Less common adverse reactions reported in <1% of the patients treated administered by intravitreal injection every 4 weeks (monthly) for the detachment. The most common adverse reactions (≥5%) reported with EYLEA were hypersensitivity, eyelid edema, corneal edema, retinal first 12 weeks (3 months), followed by 2 mg (0.05 mL) via intravitreal in patients receiving EYLEA were conjunctival hemorrhage, eye pain, detachment, injection site hemorrhage, and retinal tear. injection once every 8 weeks (2 months). Although EYLEA may be dosed cataract, vitreous floaters, intraocular pressure increased, and vitreous 6.2 Immunogenicity. As with all therapeutic proteins, there is a as frequently as 2 mg every 4 weeks (monthly), additional efficacy was detachment. potential for an immune response in patients treated with EYLEA. not demonstrated when EYLEA was dosed every 4 weeks compared to Neovascular (Wet) Age-Related Macular Degeneration (AMD). The The immunogenicity of EYLEA was evaluated in serum samples. The every 8 weeks. data described below reflect exposure to EYLEA in 1824 patients with immunogenicity data reflect the percentage of patients whose test results 2.3 Macular Edema Following Retinal Vein Occlusion (RVO). The wet AMD, including 1223 patients treated with the 2-mg dose, in 2 were considered positive for antibodies to EYLEA in immunoassays. The recommended dose for EYLEA is (0.05 mL or 50 microliters) administered double-masked, active-controlled clinical studies (VIEW1 and VIEW2) for detection of an immune response is highly dependent on the sensitivity by intravitreal injection once every 4 weeks (monthly). 12 months. and specificity of the assays used, sample handling, timing of sample 2.4 Diabetic Macular Edema (DME). The recommended dose for collection, concomitant medications, and underlying disease. For these Table 1: Most Common Adverse Reactions (≥1%) in Wet AMD EYLEA is (0.05 mL or 50 microliters) administered by intravitreal reasons, comparison of the incidence of antibodies to EYLEA with the injection every 4 weeks (monthly) for the first 5 injections followed by Studies incidence of antibodies to other products may be misleading. Active Control In the wet AMD, RVO, and DME studies, the pre-treatment incidence 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months). EYLEA Although EYLEA may be dosed as frequently as 2 mg every 4 weeks Adverse Reactions (ranibizumab) of immunoreactivity to EYLEA was approximately 1% to 3% across (N=1824) (monthly), additional efficacy was not demonstrated when EYLEA was (N=595) treatment groups. After dosing with EYLEA for 24-52 weeks, antibodies dosed every 4 weeks compared to every 8 weeks. Conjunctival hemorrhage 25% 28% to EYLEA were detected in a similar percentage range of patients. There 2.5 Preparation for Administration. EYLEA should be inspected were no differences in efficacy or safety between patients with or Eye pain 9% 9% without immunoreactivity. visually prior to administration. If particulates, cloudiness, or discoloration Cataract 7% 7% are visible, the vial must not be used. Using aseptic technique, 8 USE IN SPECIFIC POPULATIONS Vitreous detachment 6% 6% the intravitreal injection should be performed with a 30-gauge x 8.1 Pregnancy. Pregnancy Category C. Aflibercept produced embryo- ½-inch injection needle. For complete preparation for administration Vitreous floaters 6% 7% fetal toxicity when administered every three days during organogenesis instructions, see full prescribing information. Intraocular pressure increased 5% 7% to pregnant rabbits at intravenous doses ≥3 mg per kg, or every six 2.6 Injection Procedure. The intravitreal injection procedure should be Conjunctival hyperemia 4% 8% days at subcutaneous doses ≥0.1 mg per kg. Adverse embryo-fetal carried out under controlled aseptic conditions, which include surgical Corneal erosion 4% 5% effects included increased incidences of postimplantation loss and fetal malformations, including anasarca, umbilical hernia, diaphragmatic hand disinfection and the use of sterile gloves, a sterile drape, and a Detachment of the retinal pigment 3% 3% hernia, gastroschisis, cleft palate, ectrodactyly, intestinal atresia, sterile eyelid speculum (or equivalent). Adequate anesthesia and epithelium spina bifida, encephalomeningocele, heart and major vessel defects, a topical broad–spectrum microbicide should be given prior to the Injection site pain 3% 3% injection. and skeletal malformations (fused vertebrae, sternebrae, and ribs; Immediately following the intravitreal injection, patients should be Foreign body sensation in eyes 3% 4% supernumerary vertebral arches and ribs; and incomplete ossification). monitored for elevation in intraocular pressure. Appropriate monitoring Lacrimation increased 3% 1% The maternal No Observed Adverse Effect Level (NOAEL) in these studies may consist of a check for perfusion of the optic nerve head or Vision blurred 2% 2% was 3 mg per kg. Aflibercept produced fetal malformations at all doses assessed in rabbits and the fetal NOAEL was less than 0.1 mg per kg. tonometry. If required, a sterile paracentesis needle should be available. Intraocular inflammation 2% 3% Administration of the lowest dose assessed in rabbits (0.1 mg per kg) Following intravitreal injection, patients should be instructed to report Retinal pigment epithelium tear 2% 1% any symptoms suggestive of endophthalmitis or retinal detachment resulted in systemic exposure (AUC) that was approximately 10 times Injection site hemorrhage 1% 2% (e.g., eye pain, redness of the eye, photophobia, blurring of vision) the systemic exposure observed in humans after an intravitreal dose without delay (see Patient Counseling Information). Eyelid edema 1% 2% of 2 mg. Each vial should only be used for the treatment of a single eye. If the Corneal edema 1% 1% There are no adequate and well-controlled studies in pregnant women. contralateral eye requires treatment, a new vial should be used and EYLEA should be used during pregnancy only if the potential benefit Less common serious adverse reactions reported in <1% of the patients justifies the potential risk to the fetus. the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and treated with EYLEA were hypersensitivity, retinal detachment, retinal injection needles should be changed before EYLEA is administered to tear, and endophthalmitis. 8.3 Nursing Mothers. It is unknown whether aflibercept is excreted in human milk. Because many drugs are excreted in human milk, a risk the other eye. Macular Edema Following Retinal Vein Occlusion (RVO). The After injection, any unused product must be discarded. to the breastfed child cannot be excluded. EYLEA is not recommended data described below reflect 6 months exposure to EYLEA with a during breastfeeding. A decision must be made whether to discontinue 3 DOSAGE FORMS AND STRENGTHS monthly 2 mg dose in 218 patients following CRVO in 2 clinical studies nursing or to discontinue treatment with EYLEA, taking into account the Single-use, glass vial designed to provide 0.05 mL of 40 mg/mL solution (COPERNICUS and GALILEO) and 91 patients following BRVO in one importance of the drug to the mother. (2 mg) for intravitreal injection. clinical study (VIBRANT). 8.4 Pediatric Use. The safety and effectiveness of EYLEA in pediatric 4 CONTRAINDICATIONS Table 2: Most Common Adverse Reactions (≥1%) in RVO Studies patients have not been established. EYLEA is contraindicated in patients with Adverse Reactions CRVO BRVO 8.5 Geriatric Use. In the clinical studies, approximately 76% (2049/2701) • Ocular or periocular infections EYLEA Control EYLEA Control of patients randomized to treatment with EYLEA were ≥65 years of • Active intraocular inflammation (N=218) (N=142) (N=91) (N=92) age and approximately 46% (1250/2701) were ≥75 years of age. No • Known hypersensitivity to aflibercept or any of the excipients in significant differences in efficacy or safety were seen with increasing Eye pain 13% 5% 4% 5% EYLEA. Hypersensitivity reactions may manifest as severe intraocular age in these studies. Conjunctival hemorrhage 12% 11% 20% 4% inflammation 17 PATIENT COUNSELING INFORMATION Intraocular pressure 5 WARNINGS AND PRECAUTIONS 8% 6% 2% 0% In the days following EYLEA administration, patients are at risk of increased 5.1 Endophthalmitis and Retinal Detachments. Intravitreal injections, developing endophthalmitis or retinal detachment. If the eye becomes including those with EYLEA, have been associated with endophthalmitis Corneal epithelium defect 5% 4% 2% 0% red, sensitive to light, painful, or develops a change in vision, advise and retinal detachments (see Adverse Reactions). Proper aseptic Vitreous floaters 5% 1% 1% 0% patients to seek immediate care from an ophthalmologist (see injection technique must always be used when administering EYLEA. Ocular hyperemia 5% 3% 2% 2% Warnings and Precautions). Patients may experience temporary visual Patients should be instructed to report any symptoms suggestive of Foreign body sensation disturbances after an intravitreal injection with EYLEA and the associated 3% 5% 3% 0% endophthalmitis or retinal detachment without delay and should be in eyes eye examinations (see Adverse Reactions). Advise patients not to drive managed appropriately (see Dosage and Administration and Patient Vitreous detachment 3% 4% 2% 0% or use machinery until visual function has recovered sufficiently. Counseling Information). Lacrimation increased 3% 4% 3% 0% 5.2 Increase in Intraocular Pressure. Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, Injection site pain 3% 1% 1% 0% including with EYLEA (see Adverse Reactions). Sustained increases in Vision blurred 1% <1% 1% 1% © 2014, Regeneron intraocular pressure have also been reported after repeated intravitreal Intraocular inflammation 1% 1% 0% 0% Manufactured by: Pharmaceuticals, Inc. dosing with vascular edothelial growth factor (VEGF) inhibitors. Cataract <1% 1% 5% 0% Intraocular pressure and the perfusion of the optic nerve head should be Regeneron Pharmaceuticals, Inc. All rights reserved. Eyelid edema <1% 1% 1% 0% monitored and managed appropriately (see Dosage and Administration). 777 Old Saw Mill River Road Issue Date: October 2014 Initial U.S. Approval: 2011 5.3 Thromboembolic Events. There is a potential risk of arterial Less common adverse reactions reported in <1% of the patients treated Tarrytown, NY 10591-6707 thromboembolic events (ATEs) following intravitreal use of VEGF with EYLEA in the CRVO studies were corneal edema, retinal tear, Regeneron U.S. Patents 7,306,799; inhibitors, including EYLEA. ATEs are defined as nonfatal stroke, nonfatal hypersensitivity, and endophthalmitis. U.S. License Number 1760 7,531,173; 7,608,261; 7,070,959; myocardial infarction, or vascular death (including deaths of unknown Diabetic Macular Edema (DME). The data described below reflect EYLEA is a registered trademark of 7,374,757; 7,374,758, and other cause).The incidence of reported thromboembolic events in wet AMD exposure to EYLEA in 578 patients with DME treated with the 2-mg dose Regeneron Pharmaceuticals, Inc. pending patents LEA-0618

RRP0215_RegeneronP0215_Regeneron PI.inddPI.indd 1 11/13/15/13/15 3:583:58 PMPM Cover Cataract

REVIEW Focus

Preferred Method for Managing Pre-existing Astigmatism in a Cataract Patient

14 7 8 66 Manual limbal Femtosecond Placing the clear Toric IOL Postop refractive Other relaxing incisions astigmatic corneal entry wound procedure keratotomy on the axis of astigmatism

which is an increase over last year’s IOL alignments.” A New York sur- the time spent in surgery and the fact 26 percent. However, this means 88 geon thinks it comes in handy for pa- there’s not a 100-percent guarantee percent of the respondents don’t use tients who are usually diffi cult to pin that the residual refractive error will it, and two-thirds say they’re unlikely down on biometry. “It gives me an ac- be gone.” A surgeon from Nashville to using doing it this year. curate intraocular lens measurement says he isn’t yet convinced. “My IOL Sacramento, Calif., surgeon Rich- in the post-LASIK patient,” he says. predictions are sufficient, and stud- ard Meister says he appreciates the Nick Mamalis, MD, of Salt Lake City, ies have not yet shown signifi cant re- technology. “It yields good readings on however, thinks the technology plays a sult changes of greater than 1 D on a post-refractive patients and those that key role in some cases. “It’s essential to regular basis,” he says. “I don’t use it at we can’t do the IOLMaster on,” he have this technology for patients who this time. A true drawback would be says. “It’s good for acquiring the astig- have had previous refractive surgery that these lenses have to be ordered matism and the axis.” Robert Lehm- and/or have astigmatism,” he says, “es- ahead of time. How do I know that my ann, MD, of Nacogdoches, Texas, pecially with toric IOLs.” surgery center is going to have what I also feels it helps him in the OR. “My Many of the 88 percent who don’t need at all times?” outcomes are closer to the target,” use intraoperative aberrometry say A California surgeon is open to us- he says. “I’m also able to adjust the that they’re concerned it will slow ing the technology down the road. “It’s cylinder and the toric IOL position at them down during surgery without about affordability,” he says. “Some- the expense of a little extra time and giving them a commensurate benefi t. one has to fund the new technologies, cost.” Another surgeon from Texas Will Sawyer, DO, of New Braunfels, so if the patients will pay for it—i.e., if warns that it might not be perfect for Texas, says, “The benefi t is the abil- enough of my practice’s patients will all cases, though, when he says, “It’s ity to recheck your IOL calculations monetarily endorse intraoperative ab- sometimes fi nicky for low-power toric intraoperatively. The cons are cost, errometry—then we will invest in it.”

Steps Taken to Avoid Infection (in Addition to Iodine)

67 69

35 %

9 8 3 Preop topical Intracameral Postop topical Antibiotics in the Subconjunctival Other ﬂ uoroquinolones antibiotic injection ﬂ uoroquinolones infusion antibiotic injection

March 2015 | Revophth.com | 49

0044_rp0315_f3.indd44_rp0315_f3.indd 4949 22/20/15/20/15 4:154:15 PMPM Cover Cataract

REVIEW Focus

Preferred Phacoemulsifi cation Technique A String of Pearls Surgeons also took the time to share 48 their favorite surgical techniques. Kevin Dinowitz, MD, of Bloom- fi eld, Conn., says to pay attention to 22 the use of your viscoelastic. “I fi nd it % 15 better to leave the viscoelastic under the toric IOL and not remove it as 6 6 4 stated in the normal convention,” he 1 says. “When it’s removed, the IOL ac- Quadrant Phaco Sculpting Stop and Divide in Phaco Other tually is more likely to spin and move division chop chop two fl ip/tilt out of position.” Virginia’s Dr. Shep- pard provides both conventional and Managing Astigmatism best in-the-bag control, away from the femtosecond cataract advice: Use the cornea,” says Francisco Tellez, MD, primary blade to make the initial nick Surgeons also weighed in on their of Wyomissing, Pa. “Also, this is the in the anterior capsule,” he says. “For usual method for treating pre-existing procedure I initially trained with and femtosecond, be sure to complete astigmatism in their cataract patients. is the one with which I am most com- your hydrodissection; it makes sub- The most popular option is a to- fortable.” Steven Stiles, MD, of Tar- incisional cortex removal much easier, ric IOL, chosen by 63 percent of the zana, Calif., prefers quadrant division and it’s much safer now, with smaller respondents. In second-place is the because of its effect on the lens. “With bubbles created by the lower laser practice of putting the entry wound it, the nucleus spins,” he says, “and energy and shorter treatment times.” on the steep axis (14 percent). “The it’s easy to make four grooves and use Ohio’s Dr. Erdey likes a scleral re- toric IOL works reasonably well, is a splitter to create four pieces which cession technique. “I perform scleral easy to implant and is profitable,” are easily grasped with aspiration and recession—a scleral tunnel placed on says New Jersey’s Dr. Liva. “The toric pulled to the center for easy remov- the steep corneal meridian with its lens is a perfect example of capitalism al.” A surgeon from Marion, Ohio, length titrated to astigmatism magni- working well: The industry benefits Filmore A. Riego, thinks quadrant di- tude—as a long-term, stable, revers- with increased profits for research, vision is a good all-around technique ible technique for correction of with- the physician benefi ts with increased for different patient presentations. the-rule cylinder less than 2.5 D,” he reimbursement to compensate for the “Most cataracts are best removed us- explains. “I routinely perform scleral unfairly low cataract surgery compen- ing this technique,” he says. recession when a patient can’t afford sation and the patient benefits with As for other techniques, 22 percent a toric IOL or when it’s indicated be- improved uncorrected vision without prefer phaco chop and 15 percent do cause of mild corneal asymmetry or significant risk. It’s a triple win.” A stop-and-chop. Bettendorf, Iowa, sur- warpage.” Dr. Riego modifi es his cap- Texas surgeon says that in most cases geon Lisa Arbisser, explains why she sulorhexis for certain cases. “I make a he uses the placement of the entry prefers phaco chop: “The size of the bigger capsulorhexis for diabetics with wound to control the cylinder. “I like rhexis is always tailored to the optic, retinopathy,” he says, “or for diabet- to go on-axis for low-power cylinder,” not to the nucleus,” she says. “With ics who are most likely going to de- he says. “Anything greater will require vertical chop one stays in view within velop retinopathy. I use it also for high an additional AK or a toric lens. I like the rhexis and only requires a 5- to myopes.” Thomas Castillo, DO, from to reduce the power requirement of 6-mm pupil. One is never pushing on Beaver Dam, Wis., says it pays to hit the toric IOL by operating on-axis.” subincisional zonules. It’s the most the fi lm room. “Record every case,” he ultrasound-sparing technique. One says. “You never know what you may Phaco Technique can adjust the number of sections split learn by watching an instance when based on lens density so there is never things don’t go perfectly.” In terms of breaking up the catarac- a large chunk brought near endotheli- Ligaya Prystowsky, MD, of Nutley, tous lens, the most popular option on um. The posterior capsule is protected N.J., shares a sentiment that most sur- the survey is quadrant division, chosen by the remaining nuclear sections in geons adhere to in the operating room by 48 percent of respondents. the bag until the last fragment is re- and the clinic: “There’s always room “Quadrant division gives me the moved.” for improvement.”

50 | Review of Ophthalmology | March 2015

0044_rp0315_f3.indd44_rp0315_f3.indd 5050 22/20/15/20/15 4:154:15 PMPM RETINA ONLINE E-NEWSLETTER

Once a month, Medical Editor Philip Rosenfeld, MD, PhD, and our editors provide you with timely information and easily accessible reports that keep you up to date on important information affecting the care of patients with vitreoretinal disease.

3 EASY WAYS TO SUBSCRIBE! http://www.jobson.com/globalemail/ Fax: 6610.492.103910.492.1039 oorr CCall:all: 6610.492.102710.492.

0411_Retina Online house Ad.indd 1 7/28/14 3:30 PM Practice Management REVIEW Feature Is There a Place for PAs in Ophthalmology? Michelle Stephenson, Contributing Editor

Few lthough physician assistants my of Physician Assistants, there are have been used successfully as only approximately 70 PAs currently ophthalmology Aphysician extenders in primary working in ophthalmology practices. care and in some subspecialties, they One reason for this low number is practices employ have rarely inﬁ ltrated ophthalmology that PA students receive very little, practices. Even when they are em- if any, training in eye care. Two of PAs, and those ployed by ophthalmology practices, these 70 PAs are employed by Min- that do typically they are rarely practicing eye care. nesota Eye Consultants, and their According to the American Acade- main roles are performing preop-

use them for ©iStock.com/JobsonHealthcare primary care.

52 | Review of Ophthalmology | March 2015 This article has no commercial sponsorship.

052_rp0315_f4.indd 52 2/20/15 2:55 PM Even small leaks can lead to BIG COMPLICATIONS.

The ReSure® Sealant can put you at ease. You take great care to ensure the best possible results, but wound leaks can quickly compromise outcomes. Now there is the ReSure Sealant — the first and only FDA approved ophthalmic sealant to offer superior wound closure over sutures.

Better seal • Fewer adverse events • Comfortable for patients • No need for removal Get superior wound closure. Get the ReSure Sealant.

ReSure Sealant is indicated for intraoperative management of clear corneal incisions (up to 3.5mm) with a demonstrated wound leak for which a temporary dry surface can be achieved, in order to prevent postoperative fluid egress from such incisions following cataract surgery with intraocular lens (IOL) placement in adults.

RP0315_Ocular.indd 1 2/12/15 1:53 PM 052_rp0315_f4.indd 54 Your owncustom App All for$49. Android Marketplace. Nowallyourcustomerscanhavebusinessintheir Apps arethemostpowerfulmobilemarketing tools intheworld! Learn moreat ǡƤ ǡ Ȃ own custom App foriPhone, Android andiPad.Nowyoucanusethesame custom App canbedownloadedbyanyoneintheworldviaiTunes and EyeDocApp technology thatFortune500 companiesareusing,forafractionofthecost! instantly popupontheirphone,justlike atext message. ǡƤ foriPhone, Android, iPadandMobile Website! with theirprimary-careproviders. trying toscheduleanappointment ophthalmologists’ ofﬁ ce ratherthan have theirphysicalsperformedatthe Minnesota EyeConsultants. C. Gundale,PA-C, oneofthePAs at perform thesephysicals,”saysLaura assistants andnursepractitionerscan surgery. Onlyphysicians,physician healthy enoughtoproceedwiththe to determinewhetherornottheyare assess theriskofanesthesiaand preoperative historyandaphysicalto gery, apatientisrequiredtohave form someautoimmunescreening. year, theyhavealsostartedtoper- services toemployees.Inthepast surgery andprovidingurgent-care tients whoarescheduledtoundergo erative historiesandphysicalsforpa-

It isidealforpatientstobeable “Before anytypeofsigniﬁ REVIEW Feature makes iteasyforIndividualsand Businessestohavetheir 99 /month Ǥ Ƥ EyeDocApp.com

Practice Management cant sur- days beforethefi “Typically, Iwilldothephysicalafew tiating withtheschedule,”shesays. later, soitdoesrequiresomenego- and thentheothereyetwoweeks ing cataractsurgery, we’lldooneeye of surgery. “Often,ifapatientishav- physical mustbedonewithin30days ing. AccordingtoMs.Gundale,the streamlined.” cals donehere,thenit’s allpretty lines, butifpatientsgettheirphysi- doesn’t knowourpractice’s guide- perwork, theprimary-carephysician patient forgetstobringalongourpa- Another problemthatcanariseisifa during theappropriatetimeperiod. physicals, sometimestheycan’t getin primary-care doctortohavetheir says Ms.Gundale.“Iftheygototheir “It simplifies thingsforourpatients,” Another benefit iseaseofschedul- rst procedure.For Your Your caused byallergies,”shesays.“We are seenfordryeye,whichcanbe of practice.“Alotourpatients PAs couldeasilyexpandtheir scope that therearesomeareasintowhich eye care,andMs.Gundalenotes of thetime,thatisn’t necessary.” get thatclearance,butthemajority ry-care physicianorcardiologistto surgery, Iwillreferhimtohisprima- that apatientisnotoptimizedfor mation weneed.IfIamconcerned to makesurewehavealloftheinfor- that weliketodoitaheadoftimeis their cardiologist.Partofthereason from theirprimary-carephysicianor surgeries, Iliketorequestrecords patients whohavemorecomplicated procedure. Formorecomplicated of thephysicalssamedayas simple laserprocedures,wedosome A fewpracticesareusingPAs for by JobsonOptical’s Marketed Exclusively Understand. Manage.Grow. 2/20/15 2:55 PM often send patients to their primary- includes ODs and MDs, so for rou- tor to do what the doctor does best. care doctor or to an allergist to get tine eye care, I think the ODs are the That, of course, is the diagnosis of the testing done. We would like to fi nd more appropriate providers.” condition and the recommendation a way for the PAs here to perform for treatment and surgery. An op- that testing to keep everything in- Worth the Training and Money? tometrist can help with that, except house and a little bit more stream- in terms of the procedural surgical lined for the patient. PAs are also John Sheppard, MD, in practice decision. In a routine case, the surgi- testing for Sjögren’s syndrome, and at Virginia Eye Consultants, believes cal decision is pretty straightforward, we do a blood panel for patients who that ODs are the preferred physician too, like a symptomatic cataract, and have significant dry eye and other extenders for ophthalmology practic- extenders can make that call reliably. systemic symptoms.” es. He has employed PAs in the past, That frees up the ophthalmologist to In these cases, the ODs and MDs but says that it wasn’t an optimized perform more surgery.” in the practice refer patients to one experience. “In some of the other He adds that a few select practices of the PAs, who does a brief histo- medical fi elds, the skills that the PA allow PAs to assist with the actual ry and physical and runs the blood can extend are not as highly special- surgery. “The PAs in some of those panel. “If anything comes back posi- ized as the skills we need in ophthal- practices will actually make the inci- tive, we send a letter back to the re- mology,” says Dr. Sheppard. “The sion, and that includes the corneal ferring provider and typically refer ideal clinical physician extender in incision and the capsulorhexis,” he the patient to rheumatology,” says ophthalmology is either a really good says. “That’s pretty outrageous, but Ms. Gundale. “Those are a few ar- tech or an optometrist. The whole that’s what happens every day in car- eas where we are extending our ser- philosophy of physician extenders in diac surgery. The PAs are so highly vices. We have a large practice that ophthalmology is to allow the doc- trained that they will crack the chest,

SECO BOOTH #439

EXPO AT SECO & BOOTH VISION EXPO EAST #3785

Visit Our Booth for Discounted Job Postings!

Visit localeyesite.com/show for more info.

052_rp0315_f4.indd 55 2/20/15 2:55 PM 0052_rp0315_f4.indd 56 5 2 _ r p 0 3 1 5 _ f 4 56 or lasersurgery. Thatincreasesthe the patientswhoneedaninjection, Then, theretinaspecialists only see patient needstohaveaninjection. toms anddecidewhetherornotthe doc, reviewtheOCTs andthesymp- optometrists whoworkwitharetina specialize inourpractice.We have very wellwithoptometristswhosub- those judgments.We areworking have enoughoculartrainingtomake can certainlydothat,buttheydon’t an ophthalmiccodeforaPA. You to anoptometrist.It’s toughtobill eye, butIthinkthat’s bettersuited “They cantreatglaucomaanddry ophthalmology practice,”hesays. ideally fillinanyofthegapsan “PAs arewonderful.Theyjustdon’t to havesubspecializedoptometrists. on thefi technician stafftopushthebutton pay aPA threetimesmorethanmy fi of collegeandhavefarfewerquali- these technicianswhoarefreshout the visualfi tion coursetopushthebuttonsfor they weretakingthesameorienta- competitive graduatedegree,and our technicians.PAs have ahighly had totrainourPA justlikewedo isn’t trainedinthat.We wouldhave all ofthediagnosticdevices.APA thalmic examination,likerunning tation skills,butalsoskillsinoph- needed tohavenotonlydocumen- problem withthatwasthePA help runclinicalresearchforus.The says. “Then,wetriedtousethePA to wasn’t thatmuchforhertodo,”he ting aroundallofthetime,andthere just didn’t makesense.“Shewassit- in ophthalmology, andtrainingher do. Additionally, shewasnottrained his offi coronary anastomosis.” cular surgeonactuallyperformsthe vest thevein.Then,cardiovas- position thechestexpanderandhar- . cations thanPAs do.WhywouldI i n

d REVIEW His practiceﬁ nds itmoreuseful Dr. SheppardnotesthatthePA in d |

Feature Review ofOphthalmology

5 6 ce justdidn’t haveenoughto eld machineandtheOCT?” eld andOCTmachinesas

Practice Management | March 2015 fi tine glaucomacheckup,ifthefi in aweekortwo.Similarly, inarou- everything isfi see patientspostoperatively, andif additional expertiseinglaucomawill glaucoma. Ouroptometristwhohas ing hisskills.Thesamethinggoesfor seeing theretinadoctor, betterutiliz- morbidity leveloftheaveragepatient surgical center. Theyalsodosome are undergoingaprocedure inthe tive physicalexamsforpatients who are mostlyresponsibleforpreopera- to do,”saysDr. Hardten.OurPAs that somepracticesmighthireaPA care-related workthatIhaveheard tice, optometristsdomostoftheeye- Consultants, agrees.“Inourprac- with Ms.GundaleatMinnesotaEye it tousatthatsalarylevel,”hesays. now in-house,andit’s justnotworth all change.“But,thathastobedone tics andeyecare,thenthatwould with hands-ondiagnostics,therapeu- where PAs haveadditionaltraining cardiovascular surgeryorOB/GYN, lum likethoseseeninorthopedics, an eye-specifi have.” ter headstartthanaPA wouldever the practice,whichisamuchbet- training, plushands-ontrainingin has hadatleastfi up tothelevelofanoptometristwho they costmore.You can’t bringher her uptothelevelofagoodtech,but have thatbackground.You canbring cataract surgery. APA justdoesn’t selecting thosepatientsforpremium dure, whichiscataractsurgery, and tients forourmostcommonproce- who areveryadeptatevaluatingpa- to havesubspecializedoptometrists cataract operation.We fi gical decision,noneedforalaseror three tosixmonths.Thereisnosur- disease, thenwewillseepatientsin cines andthereisnoocularsurface fi ne, theOCTisfi ne, thereisnotoxicitytothemedi- David Hardten,MD,inpractice However, hesaysthatiftherewas c PA programcurricu- ne, patientswillreturn ve yearsofformal ne, thepressureis nd ituseful eld is and gointotheworkforcein the typi- schooling whentheycouldgo ahead want togothroughanother yearof program, however, sotheymaynot could bearelativelylengthytraining heavy demandfortheseskills.This ated forthisshouldthereeverbea long trainingprogramcouldbecre- training, butI’msureaspecialyear- be incorporatedintomostPA school but itseemsunlikelythatthiswould “They couldbetrainedtodothat, neal sutures,etc.,”saysDr. Hardten. look forcornealulcers,removecor- ate retinaldetachments,checkIOP, do analysisoftheopticnerve,evalu- care practice,PAs needto be ableto the country. “To beusefulinaneye coming intopracticeinhisareaof because thereisashortageofthem ners orinternalmedicinedoctors, be morehelpfultofamilypractitio- for PAs todoeyecareinour area.” so Idon’t seeatremendousdemand optometrists seemstobeadequate, postoperative care.Thesupplyof uveitis, conjunctivitis,andpre- as wellthetypicalpatientswith ma, Fuchs’dystrophy, keratoconus, very complicatedcasesofglauco- etrists arewell-trainedinmanaging ment skills,”hesays.“Theoptom- and refractivecornealmanage- a yearlearningadvancedglaucoma lowship programwheretheyspend this. “We haveanoptometricfel- practice arealreadytrainedtodo of eyeproblems,optometristsinhis vitis, cornealulcersandothertypes coma checksandtotreatconjuncti- be trainedtodoslitlampsandglau- surgery.” physicals forthosehavingcataract but PAs areprimarilyfordoingpreop makes ourpracticemoreefficient, facilitates effi as muchtimeofffromwork,andit they don’t havetogooutandtake they canbeseeninouroffi care forouremployees,becausethen In contrast,hesaysthatPAs would While hebelievesthatPAs could cient scheduling.This ces, and ces, 22/20/15 2:56 PM / 2 0 / 1 5

2 : 5 6

P M rp0315_Lombart.indd 1 2/20/15 5:49 PM 052_rp0315_f4.indd 58 ally restrictsthemfromperforming small limitationofscopethatgener- Twelve ofthose22stateshaveonlya limit theirscopeinophthalmology.” restriction ofPA practicethatcould states “havesomedegreeofpotential and regulationsfoundthat22 ed areviewofall50states’statutes AAO’s annualmeeting. thalmology thatwaspresentedatthe future ofphysicianassistantsinoph- MD, wroteawhitepaperaboutthe techs. In2011,RachelReinhardt, different rolethanoptometristsand Practicing Ophthalmology management byPAs.” ceive theneedforadvancedeye-care our practice,wedon’t currentlyper- cal ﬁ elds thataPA mightwork.In

Some believethatPAs couldplaya REVIEW Feature

1 Sheconduct- Practice Management medicine withphysiciansupervision. etrists, PAs arelicensedto practice gists. Unliketechniciansandoptom- hope topatientsandophthalmolo- ric caretoincludesurgery, PAs offer some successes,toexpandoptomet- scope ofcare,includingattemptsand tempted expansionofoptometry demand.” where ophthalmologistswillbein to carveoutauniqueroleinfuture tometrist ortechnician,butrather duplicate theophthalmologist,op- mology, itwillnotbetoreplaceor “If PAs enterthefieldofophthal- different fromthatofoptometrists: tices andsaystheyhavearolethatis practicing inophthalmologyprac- contact lenses. refractions orprescribingglasses She addsthat,“Inthisageofat- However, thepapersupportsPAs ogy.” beneﬁ physician assistantteamwouldbea training provides.Thephysician- cal patientsforwhichtheirextensive the morecomplexmedicalandsurgi- up theophthalmologisttocarefor dle theroutinecasesinordertofree sician-led care.” are dedicatedtotheconceptofphy- the PA ﬁ eld hasbeenbuilt,andPAs tionship isthefoundationonwhich physician-physician assistantrela- medical andsurgicaleducation.The like optometrists,PAs haveapurely any servicethephysiciancando.Un- Unlike technicians,PAs canbillfor related/upload/LDPXIII-2011-Abstracts.pdf. meeting ofthe AAO inOrlando. http://www.aao.org/member/ assistants inophthalmology. the2011annual Presentedat 1. ReinhardtRCJ. onthefutureofphysician A whitepaper She alsonotesthat,“PAs canhan- t tothefutureofophthalmol- 2/20/15 2:56 PM The Rick Bay Foundation for Excellence in Eyecare Education www.rickbayfoundation.org Support the Education of Future Healthcare & Eyecare Professionals

About Rick Scholarships will be awarded to advance the education Rick Bay served as the publisher of students in both Optometry and Ophthalmology, of The Review Group since 1991. and will be chosen by their school based on qualities that To those who worked for him, embody Rick’s commitment to the profession, including he was a leader whose essence was based integrity, compassion, partnership and dedication to the in a ﬁ erce and boundless loyalty. greater good. To those in the Interested in being a partner with us? industry and the professions he served, he will be remembered Visit www.rickbayfoundation.org for his unique array of skills (Contributions are tax-deductible in accordance with section 170 of the Internal Revenue Code.) and for his dedication to exceeding the expectations of his customers, making many of them fast friends.

(The Rick Bay Foundation for Excellence in Eyecare Education is a nonproﬁ t, tax-exempt organization under section 501(c)(3) of the Internal Revenue Code.)

rickbay_housead.indd 1 2/28/14 1:14 PM Retinal Insider

REVIEW Edited by Carl Regillo, MD and Emmett T. Cunningham Jr., MD, PhD, MPH

Telemedicine in Pediatric Retinal Disease Retinopathy of prematurity screening has succeeded where other efforts in telemedicine have not and offers lessons for broader use. Darius M. Moshfeghi, MD, Stanford, Calif.

elemedicine can be broadly de- of traditional physician-guided tele- a partnership to commercialize a con- T fined as the remote interpreta- medicine have been employed for tact lens-based insulin monitor for tion of a patient for the purpose of home monitoring of macular disease patients with diabetes, and a similar screening, diagnosis and monitoring. that relies on patient-centric monitor- system is also being developed for In ophthalmology it has been used ing, specifi cally the ForeseeHome de- intraocular pressure monitoring in with variable success in adult popula- vice-based system and the DigiSight patients with glaucoma.5,6 These ap- tions for screening of diabetes and smartphone-based system.3,4 Google proaches have taken a while to gain glaucoma.1,2 In addition, variations and Alcon have recently announced market penetrance due to resistance from patients and physicians, based upon both technological and financial hurdles. It has been diffi cult to develop a fi nancial model that makes sense for both the physician and the patient, creating a barrier to wider ac- ceptance, and patients have demonstrated resistance to spending money for preventive care. Partly, this is a problem of casting too wide a net—if one screens for all diabetic retinopathy, one is likely to fi nd a lot of diabetic retinopathy that does not need intervention, ironically increasing the burden on the same physicians it is intended to be assist- ing. A notable exception has been for retinopathy of prematurity screening. This application has worked for three simple reasons: 1) the remote screening is highly effective at identifying a Right eye. Scattered subretinal blot hemorrhages sparing the fovea in a normal-term treatment intervention time point; 2) infant. the disease is self-limited in that it will

60 | Review of Ophthalmology | March 2015 This article has no commercial sponsorship.

060_rp0315_rtinsider.indd 60 2/20/15 2:10 PM either spontaneously resolve or result in retinal detachment and blindness within a 15-week time frame; and, 3) all neonatal intensive care units (NICUs) are required to perform screening in order to maintain accreditation, removing most of the financial uncer- tainty. These three components give us great insight into greater application of telemedicine in ophthalmology. First, let us review the ROP scenario.

ROP Telemedicine

ROP screening with wide-angle, fi - ber optic cameras was demonstrated to be feasible in the early 2000s,7 equivalent to bedside indirect oph- thalmoscopy for detecting any ROP in the PHOTO-ROP trial,8 able to detect treatment-warranted ROP (e.g., Type 1 disease: Zone I and Plus OR Zone I Left eye. Multiple near-confl uent white-centered subretinal hemorrhages in the macula, and Stage 3 OR Zone I or II, Stage 3, peri-papillary and extramacular locations. with Plus) in the SUNDROP experience,9 and equivalent to BIO for de- supports the use of RDFI to identify culture of pride about prevention of tecting referral-warranted ROP (simi- patients with clinically signifi cant or re- blindness in this at-risk population. lar to Type 1 disease) in the e-ROP ferral-warranted ROP for ophthalmic trial.10 Basically, remote digital fun- evaluation and management.”12 The Universal Screening of Newborns dus imaging (RDFI) using wide-angle SUNDROP network, which I founded cameras (130 degrees) captured all in 2005 at Stanford University, has the Pediatric vitreoretinal surgery physi- treatment infl ection points for what- longest experience in provision of tele- cians have been looking to expand upon ever ROP severity was present. This medicine screening services for ROP the success of telemedicine screening does not mean it identifi ed all disease; in the United States. This is a commu- for ROP. One potential opportunity in fact, in the SUNDROP experience, nity outreach project, which provides is universal screening of newborn in- it has been shown that oftentimes dis- underserved NICUs with access to fants. In China, Brazil, Hungary and ease exists that is detected on BIO, quaternary ROP experts. Its success Spain, universal screening has been not on camera. However, this disease has been predicated in no small mea- practiced in single-hospital settings is in Zone III and would not trigger a sure on the fact that it has been fi nan- for up to seven years. There has been treatment intervention using current cially sustainable from the beginning remarkable similarity of fi ndings across guidelines. This is an important point: because of the NICU requirements. diverse populations: 10- to 20-percent Telemedicine screening is designed We have developed a partnership with incidence of fundus hemorrhages, and to monitor for treatment inflection our member NICUs to endeavor to 1- to 2-percent incidence of all other points, not capture of all disease. Not- prevent follow-up miscues upon dis- pathology.13 This is of great importance ing the success of these endeavors, charge of the patients. Review of medi- for two reasons: 1) the 2-percent inci- the Joint Statement Screening guide- cal records indicates that most blind- dence of non-hemorrhage pathology lines were updated in 2013 to allow for ness from ROP occurs because of lack meets the 2-percent incidence thresh- telemedicine screening of ROP,11 and of screening for one reason or another, old for a screening program to have the American Academy of Pediatrics as opposed to actual treatment fail- socioeconomic benefi t if performed on recently issued a joint technical report ures. This has placed a greater onus a large scale in a general population; on telemedicine screening for ROP in on expanding the screening to cover and, 2) depending on socio-economic 2015 which concluded “… evidence all eligible patients. The success has of moderate (levels II and III) quality empowered everyone to maintain a (continued on page 80)

March 2015 | Revophth.com | 61

060_rp0315_rtinsider.indd 61 2/20/15 2:11 PM of ers Su t rg s e a r y M Thoughts on Cataract Surgery: 2015

ataract surgery is the most common Preoperative Issues Cprocedure performed by the oph- In the preoperative examination, I thalmic surgeon. This year, 3.6 million do more testing and objective screen- How one cataract procedures will be performed ing, usually at my own expense, since in the United States and more than 20 most third-party payers will not pay for leading surgeon million will be performed worldwide, these tests. Approximately 25 percent according to estimates. In spite of these of my patients opt for a so-called pre- is adjusting his impressive statistics, the number of pa- mium option, which includes a desired tients visually handicapped by cataract refractive outcome to reduce their de- approach to globally increases every year. pendence on glasses. I call this refrac- In the United States, there are tive cataract surgery, and I discuss this cataract surgery to approximately 18,000 ophthalmolo- option with all patients. In order to gists, of whom 9,000 perform cata- properly determine who is a good can- meet today’s new ract surgery regularly. Thus, a typical didate for refractive cataract surgery, surgeon might anticipate a surgical I find screening for hyperosmolarity challenges. volume of about 400 eyes per year. and dry eye with the TearLab device, National statistics in other special- irregular astigmatism, astigmatism axis ties, such as cardiovascular surgery and ectasia with corneal topography, and orthopedics, suggest that a sur- and subtle macular changes with opti- geon who performs more than 50 cal coherence tomography all to be in- procedures per year generates a sig- dispensable. These tests are therefore a nifi cantly lower complication rate; for routine part of my current exam. an institution, the threshold number As a corneal surgeon who also treats is 200. America’s cataract surgeons a lot of glaucoma, my preop testing and the institutions where they work may also frequently include pachyme- almost universally reach these num- try, goniscopy, specular microscopy, vi- bers, which is encouraging for the sual fi elds and OCT of the optic nerve. potential patient. Still, the cataract In summary, I am doing a lot more operation of today is far from perfect, testing, and in the Accountable Care and because vision is so important to Act era with the triple aim of excellent quality of life, everyone engaged in outcomes, highly satisfi ed patients and this marvelous sight-restoring proce- reduced cost, the extra cost is usually dure is highly motivated to seek con- borne by me. The 25 percent of pa- tinuous improvement in outcomes. tients who opt for refractive cataract Here, I will share some thoughts on surgery helps cover these costs, as does By Richard Lindstrom, MD what I am doing in 2015 to enhance the fact that my partners at Minnesota my patient outcomes. Eye Consultants and I perform most of

62 | Review of Ophthalmology | March 2015

062_rp0315_masters.indd 62 2/20/15 12:59 PM Edited by

Taliva D. Martin, MD Sara J. Haug, MD, PhD

our surgery in an owned ambulatory Intraoperative age with only a mild/moderate den- surgery center. As I have suggested In 2013-2014, I worked to incorpo- sity of nucleus. For this reason, I have in several editorials in Ocular Sur- rate femtosecond laser-assisted cata- adopted a supracapsular phacoemul- gery News, the triple aims of the ac- ract surgery (FLACS) into my prac- sifi cation approach I call tilt and tum- countable care act will in large part be tice, but in 2015 it will play a minimal ble for most cases. I hydrodissect the achieved on the backs of the physician role. I like FLACS and fi nd it fun to nucleus with the Chang cannula until provider. Such is the state of modern- do, but simply cannot afford it in my it sits vertical within the capsular bag. day U.S. practice. current practice environment. I am In some cases, viscodissection with my dispersive viscoelastic is helpful. This approach also works extremely well Even after 40 years, it is still a pleasure to in patients with small pupils, intraoperative fl oppy iris syndrome, or IFIS, restore ... and enhance a patient’s vision. and pseudoexfoliation cases, which are very common in my practice. I will also In those patients with evidence passionate about the ocular surface, “push” the iris back in IFIS cases with of significant ocular surface disease, and also advocate for protecting it dur- Viscoat. In this approach, the nucleus I perform what I call ocular surface ing surgery. I therefore treat the cor- itself dilates the pupil and irrigation preparation. Most patients do not want neal epithelium with the same respect is superior to the iris plane, blowing to wait more than two weeks to sched- most surgeons reserve for the corneal the floppy iris posterior rather than ule their surgery. For me, the most endothelium. I fi nd a dispersive visco- anterior. The use of the soft-shell ap- rapidly acting agent for ocular surface elastic on the ocular surface, especially proach, as described by Steve Arshi- preparation is a topical corticosteroid. when warmed in an incubator to 34 to noff, MD, with a dispersive viscoelastic I usually combine it with an antibiotic 37 degrees C, to be extremely effective (the same Viscoat I have used to pro- using one of the combinations drops in protecting the ocular surface during tect the corneal epithelium, viscodis- such as tobramycin/dexamethasone or surgery. In addition, the surgeon view sect and position the iris in IFIS) and a tobramycin/loteprednol 4X daily, along is enhanced and no irrigating with BSS bevel-down, 20-ga. phaco needle with with artificial tears (usually Systane is required during the procedure, free- a hyper-pulse energy profi le generates Balance or Blink), hot packs (Bruder ing the scrub nurse for other tasks. minimal endothelial cell loss. I have Compresses are convenient and effec- After decades of performing and also adopted forced-infusion fl uidics tive), lid hygiene(I Lid Cleanser from teaching corneal relaxing incisions, with the Stellaris and Centurion, set- NovaBay and, in recalcitrant cases, today I manage astigmatism in most ting the intraocular pressure at 55 to 60 Cliradex) and 2 grams a day of a qual- patients with an on-axis incision or mmHg, generating an extremely stable ity omega 3 (PRN or Nordic Natural). a toric IOL. I mark the steeper and anterior chamber. When needed, the I want corneal staining absent before fl atter meridian during surgery using ocular sealant ReSure has replaced surgery whenever possible. I am in- a surgical keratoscope (Mastel). This sutures. Perhaps most controversial, creasingly aware of and aggressive in eliminates issues with globe rotation after three years of intracameral moxi- the preoperative management of ocu- and, for me, is more than accurate fl oxacin, I have adopted the intavitreal lar surface disease. I also pretreat with than preoperative marking. I factor transzonular injection of moxifl oxacin an NSAID for three to seven days, the fi ndings of Doug Koch, MD, on or moxifl oxacin/vancomycin and triam- with duration depending in large part posterior corneal astigmatism into my cinolone (TriMoxi, Imprimis) for in- on a given patient’s risk for postopera- management plan, as, to date, I do not fection prophylaxis and infl ammation tive infl ammation and cystoid macular have an instrument to measure poste- management. edema. If I am using a topical cortico- rior astigmatism accurately. steroid, I prescribe it before surgery I have found intraoperative aber- Postop for use the same number of days. The rometry enhances my refractive out- My preferred postoperative regi- NSAID and corticosteroid are syner- comes (Verifye, WaveTec). The aver- men requires only a single drop when gistic, and no additional cost is gener- age patient in America who presents TriMoxi is injected—ILevro or Pro- ated. for cataract surgery is 69 years of lensa once per day at bedtime. I like

March 2015 | Revophth.com | 45

062_rp0315_masters.indd 63 2/20/15 12:59 PM Cover Cataract

REVIEW Focus

(continued from page 35) laser makes a big difference in getting the effective lens position right. There are still LASIK surgeons using blad- my patients to be on an NSAID for four to six weeks in ed keratomes to make flaps. That’s fine, but it doesn’t routine cases and eight to 12 weeks in high-risk cases such mean that using a laser to make the fl ap adds nothing to as those with diabetes mellitus. I also encourage patients the procedure. to continue with ocular surface treatment as needed. To “Last week I had two pseudoexfoliation patients; one me, there is an ocular surface rehabilitation required after agreed to the laser, the other said no,” he says. “Thank- surgery followed by long-term ocular surface maintenance. fully, nothing bad happened to the patient who elected At a minimum, I encourage the same artifi cial tears pre- to do a standard procedure, but it was a much harder scribed preoperatively 4X daily, along with other adjuncts procedure for me because she didn’t have good zonular as needed. For many patients, ocular surface disease is support in certain areas. The patient who used the laser fi rst diagnosed in a preoperative examination and lifelong had a clear cornea and 20/30 vision at the three-hour visit; therapy is appropriate and to be encouraged, including the other surgery took longer and the patient had corneal adjuncts such as omega 3 nutritional supplements, Restasis, edema and 20/80 vision at the three-hour visit. Using the erythromycin ointment or topical azithromycin and low- laser does make a difference.” dose oral doxyclycline (20 to 40 mg a day), when needed. “I think we’re starting to see more data supporting the In refractive surgery patients, I am aggressive with idea that femtosecond cataract surgery does have advan- enhancements, which for me are usually LASIK or PRK. tages over traditional phacoemulsification using ultra- I will rotate a toric intraocular lens in select cases, using sound,” agrees Dr. Chu. “I agree that traditional cataract the astigmatismfi x.com guidelines of my partner David surgery is excellent; but once you start using the femto- Hardten, MD and former fellow John Berdahl, MD, second laser, you do see some advantages, and those are but I fi nd laser corneal refractive surgery to be more beginning to come out in the studies. Patients get quicker accurate for most patients, as I can fi ne-tune both the visual recovery because there’s less ultrasound energy, and sphere and cylinder. I am very reluctant to exchange there’s less infl ammation in the eye. We’re seeing better multifocal or accommodating IOLs, and stall as long as I refractive outcomes and reduced enhancement rates with can and exhaust all other possibilities—especially ocular our premium IOL patients. So I do believe that over time surface restoration, posterior capsule clarity and residual we’ll see the femtosecond laser become an increasingly refractive error management—before performing IOL important part of cataract surgery.” exchange. Having implanted these lenses for more than Dr. Stonecipher says he believes the femtosecond cata- 20 years, I fi nd an in-focus, well-centered multifocal or ract laser technology is a worthwhile investment. “Most accommodating IOL in a healthy eye is almost always ac- people are paying off the cost of the technology much cepted over time by the patient. Exceptions are patients more quickly than they expected,” he says. “We paid our who likely should have never received a presbyopia- laser off in three years, and we probably could have paid it correcting IOL, such as those with prior radial kera- off faster than that. Also, many people believe that it mat- totomy, signifi cant higher-order aberrations after LASIK ters what part of the country you practice in and who your or even frank keratoconus, Fuch’s dystrophy, glaucoma patient base is. I don’t agree. I think what does matter is with signifi cant damage and macular disease, especially what you feel is the best technology in your hands.” unrecognized epi-retinal membranes and age-related “The hurdle that’s keeping everyone from using fem- macular degeneration. tosecond surgery is the economics and the regulatory Cataract surgery fortunately continues to evolve. This environment,” Dr. Chu concludes. “Right now it has to fi eld of surgery is economically viable and critical to the be used in a refractive cataract situation; it’s an expensive, ophthalmic surgeon, patient and society, which supports premium technology. I think some things need to change continuing innovation. Even after 40 years, it is extreme- before it becomes widely adopted as a good surgical tool ly satisfying to restore and, in many cases, enhance the that’s used for all patients. We’ll have to wait and see how vision of a patient handicapped by cataract. it plays out, both in the marketplace and in the regulatory agencies.” Dr. Lindstrom is the founder and attending surgeon at Minnesota Eye Consultants; he is an Adjunct Professor Dr. Chu is a consultant to Bausch + Lomb. Dr. Stoneci- Emeritus at the University of Minnesota, Department of pher is a consultant for Alcon, Bausch + Lomb and LenSx, Ophthalmology and a visiting professor at the University of and is a speaker for LENSAR and Abbott Medical Optics. California, Irvine, Gavin Herbert Eye Institute. Dr. Singh is a consultant and speaker for Bausch + Lomb.

64 | Review of Ophthalmology | March 2015

0062_rp0315_masters.indd62_rp0315_masters.indd 6464 22/20/15/20/15 12:5912:59 PMPM The Rock ‘em Sock ‘em Glaucoma Instrument

The Octopus 600 Perimeter

It’s working. Thanks to doctors like you and early diagnosis, the risk of blindness due to glaucoma has been cut by 50%. But Octopus can do better. It’s the all-in-one early detection and management device with the most accurate and reproducible data. Take your best shot at one soon.

Call Haag-Streit for an online demo at 800-787-5426.

Tradition & Innovation.

RP0315_Haag Octopus.indd 1 2/18/15 1:52 PM Therapeutic Topics REVIEW

Sampling New Targets For Allergy Therapy Learning more about ocular allergy has revealed a host of potential allergic mediators for researchers to attack. Mark B. Abelson, MD, CM, FRCSC, FARVO, Claire Gelfman, PhD, and James McLaughlin, MD, Andover, Mass.

he hunt for new therapeutics those derived from neighboring tis- signaling compounds. At this point Tis daunting. Beyond the initial sues, have come to our attention only it may seem self-evident that since matchmaking of drug candidate and recently. This month we survey fi nd- mast cells elicit allergic responses, and cellular target comes a string of hur- ings on new potential targets for thera- mast cells release histamine, hista- dles—some sequential and many par- peutic treatment of ocular allergy. mine must be responsible for the al- allel—that include preclinical testing, lergic response. But this hadn’t been formulation, manufacturing, stability, Mast Cells: An Allergic Nexus established when we began looking toxicology and clinical confi rmation. at histamine levels in tears and the As our knowledge of the myriad physi- Mast cells have been the target for association between those levels and ological pathways regulating the ocu- most allergic therapies because of ocular allergic disease.2 While we’ve lar surface has expanded, the number their role in the response to allergen established that antihistamines have of potential targets for therapeutic in- exposure.1 In an atopic response, the a high degree of effi cacy in relieving tervention has grown. But the goal is exposure to antigen involves process- signs and symptoms of AC, there are not simply to accumulate prospects, ing of the offending agent—pollen, still many patients who are not well- but rather to identify and develop new dander or dust mite—by antigen- served by these compounds.3 treatments that address unmet needs. presenting dendritic cells. These cells In addition to histamine, mast cells In ocular allergy, we are well-served signal a stepwise activation of T and B package and secrete proteoglycans, by the currently available cadre of lymphocytes, and eventual production various hydrolases and signaling mol- anti histamines, anti-inflammatories of an allergen-specifi c IgE antibody. ecules, including interleukins, tumor and mast cell stabilizers, yet there re- These steps are part of the adaptive necrosis factor and platelet activating mains a signifi cant need for therapies immune process that’s hijacked in the factor.1 Lipid metabolism triggered by that can alleviate chronic allergy and development of allergic conjunctivitis phospholipase A2 activation generates ocular infl ammation. Most anti-aller- and other allergic conditions. prostaglandins, leukotrienes and other gic drugs target the mast cell and its When mast cells are activated lipid-based signaling molecules. In chief minion histamine, but these cells by binding of the complex of aller- theory, all of these compounds repre- are only one step in the ocular allergic gen, specifi c IgE and IgE receptors sent potential targets for allergy thera- ε cascade, and their activation frees a (Fc Rs) expressed on the mast cell py, and many have been investigated. kaleidoscope of allergic mediators in surface, a cascade of cellular events is addition to histamine. Many of these initiated that includes the release of Mast Cell Targets are molecules that we’ve examined pre-formed allergic mediators and the over the years, while others, including synthesis of additional lipid-derived In previous installments of Thera-

66 | Review of Ophthalmology | March 2015 This article has no commercial sponsorship.

0066_rp0315_ttops.indd66_rp0315_ttops.indd 6666 22/20/15/20/15 2:152:15 PMPM peutic Topics, such as the May 2013 tion and the associated infi ltration of column, we discussed the importance infl ammatory cell types into the ocu- of a number of protein kinases as lar surface environment. Established potential targets for allergic therapy. mast cell pre-formed mediators such ε α Allergen cross-linking of the Fc RIs as TNF- are thought to be involved leads to activation of a series of kinases in this process as either direct chemo- that provides the link between aller- attractants or as instigators of infl am- gen and mast cell degranulation and matory cell recruitment. Recent stud- activation.4 For example, one of the ies of TNF-α in pre-clinical models earliest responses to surface antigen- of ocular inflammation suggest that antibody binding is phosphorylation of topical use of inhibitors can reduce Lyn kinase, an enzyme that responds both inflammatory cell recruitment to this phosphorylation by physically and production of infl ammatory cyto- associating with the antibody-receptor kines such as IL-6.14 Perhaps the one- complex on the intracellular side of two punch of an antihistamine, which the cell membrane, initiating subse- blocks the acute effects of degranula- quent phosphorylation events. Spleen tion, and an anti-allergic, which blocks tyrosine kinase (Syk), phosphoinosit- TNF-α-mediated infl ammation, could ide 3-kinase, and protein kinase C all provide a more comprehensive anti- participate in the activation chain, and Studies suggest that the leaves of allergic response than the presently so all are potential targets for interven- various species of Camellia are a rich available therapeutic compounds, tion. Based upon issues of pharmaco- source of compounds with potential as whose effi cacy against severe ocular kinetics and tissue specifi city, it turns therapeutics for ocular allergy. allergies is lacking. out that Syk appears to be the best Yet another approach to infl amma- of these potential choices. There are hibitors such as montelukast have con- tion involves intervention beyond the small molecule inhibitors of Syk in fi rmed that leukotrienes have little or mast cell. A key cytokine in infl amma- development for a number of disor- no role in the etiology of AC.9 tory signaling is thymic stromal lym- ders, and their future testing in models Studies dating back a decade or phopoietin, an epithelial cell-derived of ocular allergy may not be far off.5 more demonstrated that PAF is che- molecule that acts to shift adaptive Interestingly, a Japanese laboratory motactic for eosinophils, and that this responses toward a sensitized, allergic studying therapeutic effects of plant PAF-mediated chemotaxis has been phenotype.15 In the eye, TSLP ap- glycosides has identified Syk kinase shown to contribute to the chronic pears to enhance allergic responses of inhibition as a potential mechanism phase of allergic rhinitis and conjuncti- antigen-presenting dendritic cells and in the treatment effi cacy of Camellia vitis.10,11 In addition, PAF induces de- mast cells, and it appears to have a role japonica extracts in models of both al- granulation of eosinophils and increas- in the underlying etiology of AKC.16 lergic rhinitis and conjunctivitis.6 es vascular permeability, two effects In a recent clinical trial, treatment of Lipid-derived signaling molecules associated with chronic-phase allergy. asthmatic patients with a monoclonal include prostaglandins, leukotrienes The permeability response is separate antibody to TSLP reduced allergen- and PAF. Compounds that block cy- from that elicited by histamine, as it induced bronchoconstriction and clooxygenase, such as ketorolac or isn’t blocked by antihistamines such indices of airway inflammation both other NSAIDs, have been used in as olopatadine.12 Despite this, most before and after allergen challenge.17 chronic allergy as steroid-sparing com- research efforts on PAF have focused pounds, and they have demonstrated on its role in neuropathic and cancer- Monoclonals as Topicals? some effi cacy, especially in VKC.7 Sev- related pain.13 With renewed interest eral recent clinical studies showed that in fi nding therapies for more chronic Among current therapies, mast cell another NSAID, pranoprofen, com- allergic conditions, it may be time to stabilizers such as pemirolast act at pared favorably with a topical steroid give PAF a second look. one of the earliest points in the al- in patients with AC.8 In contrast to lergic cascade, disrupting the linkage ε these results, our pilot studies testing Tackling Allergic Infl ammation between Fc RI activation and mast the responses to topical leukotrienes cell degranulation.18 While this is an showed little or no allergic responses. A signifi cant part of perennial and attractive strategy, these drugs are lim- More recent trials of leukotriene in- chronic allergy is ocular inflamma- ited by lower effi cacy and a require-

March 2015 | Revophth.com | 67

066_rp0315_ttops.indd 67 2/20/15 2:15 PM Therapeutic

REVIEW Topics

ment for pretreatment, both of which Like the Japanese Camellia leaves 2. Abelson MB, Baird RS, Allansmith MR. Tear histamine levels in vernal conjunctivitis and other ocular infl ammations. reduce their overall utility. An alterna- that are used to make tea (and poten- Ophthalmology 1980;87:812-4. 3. Gomes PJ, Ousler GW, Welch DL, Smith LM, Coderre J, Abelson tive that would also halt the activation tially, Syk inhibitors), another poten- MB. Exacerbation of signs and symptoms of allergic conjunctivitis process before it starts would be an tial anti-allergic comes from an un- by a controlled adverse environment challenge in subjects with a history of dry eye and ocular allergy. Clin Ophthalmol 2013;7:157- inhibitor like omalizumab, a human- likely place: the kitchen. It turns out 165. ized monoclonal antibody that binds that turmeric roots, members of the 4. Gilfi llan AM, Peavy RD, Metcalfe DD. Amplifi cation mechanisms for the enhancement of antigen-mediated mast cell activation. to the CH3 domain near the binding ginger family that are commonly used Immunol Res 2009;43:15-24. site for the high-affi nity type-I IgE F as spices (especially in Indian foods) 5. Coffey G, DeGuzman F, Inagaki M, et al. Specifi c inhibition of c spleen tyrosine kinase suppresses leukocyte immune function receptors of human IgE. Omalizumab are also the source for curcumin, a and infl ammation in animal models of rheumatoid arthritis. J can neutralize free IgE and inhibit the polyphenol compound with multiple Pharmacol Exp Ther 2012;340:2:350-9. 6. Kuba M, Tsuha K, Tsuha K, Matsuzaki G, Yasumoto T. In vivo IgE allergic pathway without sensitiz- therapeutic applications. Among these analysis of the anti-allergic activities of Camellia japonica extract ing mast cells or other cell types with is an ability to suppress responses to and okicamelliaside, a degranulation inhibitor. Journal of Health ε Science 2008;54:5:584-588. surface Fc RI receptors such as those allergen challenge in a mouse model 7. Abelson MB, Butrus SI, Weston JH. Aspirin therapy in vernal found on basophils.19 Although this of allergic conjunctivitis.24 Our own conjunctivitis. Am J Ophthalmol 1983;95:502-5. 8. Li Z, Mu G, Chen W, Gao L, Jhanji V, Wang L. Comparative mechanism requires the mAb to be mouse model has been designed to evaluation of topical pranoprofen and fl uorometholone in cases with chronic allergic conjunctivitis. Cornea 2013;32:579-82. used in an injectable form, a recent test compounds that target both the 9. Gane J, Buckley R. Leukotriene receptor antagonists in allergic report demonstrated its effi cacy as a acute, early phase (antihistamine) re- eye disease: A systematic review and meta-analysis. J Allergy Clin 20 Immunol Pract 2013;1:65-74. treatment for a case of severe VKC. sponse, as well as later stage chronic 10. Zinchuk O, Fukushima A, Zinchuk V, Fukata K, Ueno H. Direct Another potential target for mAb ther- (anti-inflammatory, steroid-like) reaction of platelet activating factor (PAF) induces eosinophil accumulation and enhances expression of PAF receptors in apy, particularly in severe conditions sponses. We know from our own conjunctivitis. Mol Vis 2005;11:114-23. such as AKC or VKC, is the IL-4 mAb studies that this pre-clinical confi rma- 11. Kato M, Imoto K, Miyake H, Oda T, Miyaji S, Nakamura M. Apafant, a potent platelet-activating factor antagonist, blocks Dupilumab (Regeneron), currently in tion of efficacy is an important step eosinophil activation and is effective in the chronic phase of development for atopic dermatitis.21 in the overall process of discovery. experimental allergic conjunctivitis in guinea pigs. J Pharmacol Sci 2004;95:435-42. As in other disorders, use of mAbs (McLaughlin JT, et al. IOVS 2013; 54: 12. Yanni JM, Stephens DJ, Miller ST, et al. The in vitro and targeting other candidates for allergic ARVO E-abstract 2553) In fact, the in vivo ocular pharmacology of olopatadine (AL-4943A), an effective anti-allergic/antihistaminic agent. J Ocul Pharmacol Ther intervention—interleukins or inter- endpoints evaluated in early animal 1996;12:389-400. leukin receptors, for example—will efficacy work mirror those that will 13. Morita K, Shiraishi S, Motoyama N, et al. Palliation of bone cancer pain by antagonists of platelet-activating factor receptors. sink or swim based upon issues of ultimately be evaluated in the clinic, PLoS One 2014;9:e91746. 14. Ji YW, Byun YJ, Choi W, et al. Neutralization of ocular pharmacokinetics. Even monovalent thus increasing the translatability of surface TNF-α reduces ocular surface and lacrimal gland antibody fragments are extremely preclinical effi cacy into success in the infl ammation induced by in vivo dry eye. Invest Ophthalmol Vis Sci 2013;54:7557–7566. large molecules by pharmaceutical fi nal stages of development. 15. Ziegler SF. Thymic stromal lymphopoietin and allergic disease. standards, and wouldn’t be expected It seems that we don’t have to look J Allergy Clin Immunol 2012;130:845-52. 16. Matsuda A, Ebihara N, Yokoi N, et al. Functional role of thymic to appreciably penetrate ocular tis- too far to fi nd many potential targets stromal lymphopoietin in chronic allergic keratoconjunctivitis. sues when applied topically. Despite for new therapies to treat ocular al- Invest Ophthalmol Vis Sci 2010;51:1:151-5. 17. Gauvreau GM, O’Byrne PM, Boulet LP, et al. Effects of an anti- this, a number of published studies lergies, but as always, the real effort TSLP antibody on allergen-induced asthmatic responses. N Engl J have provided encouraging evidence comes in sorting the true contenders Med 2014;370:22:2102-10. 18. Abelson MB, Berdy GJ, Mundorf T, Amdahl LD, Graves AL; that topically applied mAbs can have a from the false pretenders. Still, it’s en- Pemirolast study group. Pemirolast potassium 0.1% ophthalmic therapeutic impact on the ocular sur- couraging to see that many of the new- solution is an effective treatment for allergic conjunctivitis: A pooled analysis of two prospective, randomized, double-masked, face. In several recent trials employing est treatment candidates have shown placebo-controlled, phase III studies. J Ocul Pharmacol Ther 2002; the topical VEGF inhibitors ranibi- the promise of addressing our biggest 18:5:475-88. 19. Yalcin AD. An overview of the effects of anti-IgE therapies. Med zumab or bevacizumab as a treatment current unmet need: chronic allergic Sci Monit 2014;20:1691-9. 20. de Klerk TA, Sharma V, Arkwright PD, Biswas S. Severe vernal for corneal neovascularization, both conjunctivitis. keratoconjunctivitis successfully treated with subcutaneous treatments were able to reduce vas- omalizumab. J AAPOS 2013;17:305-6. 22,23 21. Malajian D, Guttman-Yassky E. New pathogenic and cular proliferation. This finding Dr. Abelson is a clinical professor therapeutic paradigms in atopic dermatitis. Cytokine. 2014;in establishes a proof of principle that of ophthalmology at Harvard Medical press Dec 23 [Epub ahead of print] 22. Ozdemir O, Altintas O, Altintas L, Ozkan B, Akdag C, Yüksel even molecules as large as mAbs can School. Dr. Gelfman is senior director N. Comparison of the effects of subconjunctival and topical be of benefi t when delivered topically. of Pre-Clinical and Translational Ser- anti-VEGF therapy (bevacizumab) on experimental corneal neovascularization. Arq Bras Oftalmol 2014;77:209-13. While their therapeutic utility may be vices at Ora, Inc. Dr. McLaughlin is a 23. Bucher F, Parthasarathy A, Bergua A, et al. Topical limited to the most severe cases of al- medical writer at Ora Inc. Ranibizumab inhibits infl ammatory corneal hemangiogenesis and lymphangiogenesis. Acta Ophthalmol 2014;92:143-148. lergy with epithelial damage, they also 24. Chung SH, Choi SH, Choi JA, Chuck RS, Joo CK. Curcumin can help to establish suitable targets 1. Moon TC, Befus AD, Kulka M. Mast cell mediators: Their suppresses ovalbumin-induced allergic conjunctivitis. Mol Vis differential release and the secretory pathways involved. Front 2012;18:1966-72. for small molecule discovery. Immunol 2014;5:569.

68 | Review of Ophthalmology | March 2015

0066_rp0315_ttops.indd66_rp0315_ttops.indd 6868 22/20/15/20/15 2:152:15 PMPM Go Further—Without Leaving Home

Continue your professional development and sharpen your clinical skills through convenient CME programs online and on your schedule.

Review of Ophthalmology® offers continuing education for physicians and staff, covering the latest in disease diagnosis and treatment, surgical advances and other topics, available any time on our website at CME online.

www.reviewofophthalmology.com/continuing_education/ Download a QR scanner app. Launch app and hold your mobile device over the code to view www.reviewofophthalmology.com/continuing_education/.

2013_cme_housead_ad.indd 1 10/22/14 2:29 PM Glaucoma Management

REVIEW Edited by Kuldev Singh, MD, MPH, and Peter A. Netland, MD, PhD

Are Two MIGS Surgeries Better Than One? Using multiple stents or combining options that affect different pathways may increase their pressure-lowering capacity. L. Jay Katz, MD, Philadelphia

ne of the frontiers in glaucoma by multiplying them. That can be glandins, and some newer drugs O treatment today is a group of done in two ways: in the case of a under investigation like rho kinase surgeries referred to as minimally given device, by implanting more than inhibitors and adenosine agonists invasive glaucoma surgeries, or MIGS. one; and in general, by combining that enhance trabecular outflow. The primary advantage of these different MIGS approaches—in (Another new drug, latanoprostene procedures, which currently include particular those affecting different bunod, has a complex molecule that the iStent, the Trabectome and mechanisms and pathways. affects both trabecular outflow and endoscopic cylcophotocoagulation, uveoscleral outfl ow.) Experience has is that they involve far less risk for Using Multiple Pathways confi rmed that combining drugs that the patient than options such as act on different pathways can increase trabeculectomy and tube shunts. The options we have for maximizing the amount of pressure reduction, so Furthermore, because they are the effectiveness of MIGS procedures acting via multiple mechanisms is a ab interno procedures, they can in many ways parallel what we can do reasonable approach. be performed through a cataract with pharmaceuticals. For example, The idea of combining treatments incision, making them ideal for we can aim to lower IOP by maximiz- is now beginning to show up in combining with cataract surgery. ing a single outflow pathway using the MIGS arena. The early data The perceived drawback to these multiple drugs that affect that pathway, that’s being reported indicates that procedures is that they tend to or by using two aqueous suppressants combining pathways through multiple produce a smaller pressure reduction such as beta-blockers and carbonic MIGS procedures can increase the than the other surgeries mentioned. anhydrase inhibitors. I think this is amount of pressure reduction we can As a result, they’re often thought of as much like placing multiple iStents in achieve. For now, this data is limited, intermediate procedures—kind of a the trabecular meshwork, which the partly because many potential MIGS bridge to more invasive surgeries that data suggests lowers pressure more devices are still awaiting approval by may lower IOP more dramatically. than a single stent. the FDA. For example, the devices Today, however, as surgeons become On the other hand, a lot of what intended to enhance uveoscleral out- more familiar with these options we do with drugs involves lowering fl ow, including Transcend Medical’s and more of them make it through pressure by enhancing multiple CyPass and Glaukos’s iStent Supra, the Food and Drug Administration pathways. We can lower pressure are not currently FDA-approved, and approval process, a new possibility by decreasing aqueous production, the Xen Gel Stent (from AqueSys), is arising: Increase the pressure- but we also have drugs that enhance an ab interno device designed to lowering power of these procedures uveoscleral outflow, such as prosta- allow outfl ow to the subconjunctival

70 | Review of Ophthalmology | March 2015 This article has no commercial sponsorship.

070_rp0315_gm.indd 70 2/20/15 12:35 PM space, is also still in the pipeline. Putting Glaucoma on ICE However, some surgeons are actively combining the currently approved The combination of simultaneous infl ow and outfl ow procedures makes sense for MIGS procedures with good results. many reasons. One need only look at how we treat glaucoma with eye drops (using both In particular, performing ECP and agents that reduce aqueous production and those that enhance its outfl ow) to see that implanting an iStent during cataract combined infl ow and outfl ow strategies can be complementary and synergetic. (There is no existing evidence to suggest that one strategy is better than the other for the pres- surgery—sometimes referred to as ervation of visual function.) The potential disadvantage of combining several strategies the ICE procedure—has surgeons for traditional glaucoma surgery would be a concern that hypotony might become more reporting positive outcomes. (See of an issue. Fortunately, in the microincisional glaucoma surgery space, hypotony is not Putting Glaucoma on ICE, right.) a signifi cant concern because we are not typically performing full-thickness fi ltration And Glaukos, manufacturer of the procedures. iStent, is looking into the possibility Shortly after adopting trabecular micro bypass using the iStent (from Glaukos), some of maximizing pressure reduction colleagues and I began combining cataract extraction, endocyclophotocoagulation and by combining the trabecular and trabecular micro bypass to form the ICE procedure (iStent-cataract-ECP). Mechanisti- uveoscleral pathways. This makes cally, the procedure should provide increased trabecular outfl ow, decreased aqueous production and a likely increase in both trabecular outfl ow from angle widening and sense because they have stents that possibly some reduced aqueous production as a result of the cataract surgery.1-3 address each of those pathways; the In a series of 70 moderate glaucoma patients who underwent the procedure, we current iStent and the (not approved) noted that the procedure was as safe as standard cataract surgery.(Radcliffe N, Noecker iStent Inject are designed to enhance R, Sarkisian S, Parikh P. ICE Surgical Technique Outcomes: MIGS Implantation of Tra- trabecular outflow, while the (not becular Bypass Stent, Cataract Extraction, and Endoscopic Cyclophotocoagulation. 2014 approved) iStent Supra is intended to American Glaucoma Society Annual Meeting, Feb 27-March 2, 2104, Washington, DC.) enhance uveoscleral outfl ow. ECP can create some additional infl ammation, but this does not affect the visual outcome if managed appropriately. From a baseline intraocular pressure of 19.4 mmHg, the pres- Which Combination to Use? sure was reduced to 15.8 mmHg by the three- to six-month visit. While about 60 percent of patients used two or more medications prior to the procedure, only a quarter remained on this many medications after. Note that the procedure did not work for everyone—at One question this raises is whether least 20 percent of patients experienced minimal or no pressure reduction. one particular combination of Currently, I offer this procedure to patients with moderate glaucoma damage who are procedures (and/or outfl ow pathways) on at least one medication; sometimes I offer it to “tough-to-treat” patients with early would be more effective at reducing glaucoma who are on several medications. I avoid using the procedure on patients with IOP than another. Of course, we advanced glaucoma, who would likely require more aggressive and riskier interventions. have no clinical trial data on which In summary, the ICE procedure is important not simply because of the combination of to base such a comparison right now, these specifi c procedures, but because it illustrates the potential of combining future in- but even if clinical trials eventually fl ow and outfl ow MIGS procedures, as well as combining future dual outfl ow procedures that take advantage of different outfl ow pathways. compare different combinations of — Nathan Radcliffe, MD MIGS procedures, the results might not tell us which combination would work best in a specifi c patient. This may determine which combination affect which combination a given is certainly true for drugs; if a trial of procedures will work best for a surgeon might end up using is the compared a fixed combination of given individual. You might choose surgeon’s own preference and comfort a beta blocker and prostaglandin a different combination of MIGS level, as well as which techniques he or to a beta blocker-brimonidine procedures for a patient who has a she happens to learn. If all the options combination, you might get a bigger relatively low IOP but is progressing were approved, some surgeons might average drop in one group than the than for someone with high-tension feel most comfortable combining other, but an individual patient might glaucoma, just because it makes more a Xen Gel implant and a Hydrus. not mirror that finding. So a trial sense based on the pathophysiology Others might prefer combining ECP wouldn’t necessarily tell you which of the disease. With glaucoma drugs and Trabectome, or prefer combining choice is best for the patient seated in (for now, at least) it’s trial and error the iStent Inject and the Supra. So front of you. because of the diffi culty of predicting which procedures a surgeon ends up The nature of the glaucoma, the age the effi cacy of a given treatment. And using will be partly determined by of the patient, the stage of the disease, that will probably also be true when the patient’s condition and partly by how elevated the pressure is—all of combining MIGS procedures. the surgeon’s knowledge and comfort these factors, and possibly others, Of course, another factor that will level.

March 2015 | Revophth.com | 71

0070_rp0315_gm.indd70_rp0315_gm.indd 7171 22/20/15/20/15 12:3512:35 PMPM Glaucoma

REVIEW Management

More of a Burden? Ike Ahmed, MD, suggests that the applying them, perhaps in various success of iStent surgery may be combinations. Future development What about the burden that linked to determining the location of will be guided by people who are performing multiple procedures the most functional collector channels very clever who understand the basic places on the surgeon and the eye? before placing the iStent. science and the pathophysiology of This really is the infancy of our use of We’re also learning about conditions the various diseases that we refer to MIGS procedures, but in comparison that contraindicate specific MIGS as glaucoma. to other traditional procedures for approaches. For example, patients And that’s a reason to be hopeful lowering intraocular pressure these who have Sturge-Weber syndrome about the future. The glaucoma mi- procedures are generally easier on with a facial hemangioma typically crosurgical arena is quite inspiring, both the surgeon and the eye—even have elevated episcleral venous and there are a lot of creative people if we do two of them. Most of these pressure, countering aqueous outfl ow. still in their training or in their early procedures can be done through the If the episcleral venous pressure is years of practice who will make great same single incision; there’s no need 30 mmHg instead of the normal 10 contributions. We haven’t seen a to make a second incision (except mmHg, you’re not going to get a situation like this in a while, where in some ECP cases). You go in with pressure reduction by clearing out the there are so many different possi- one instrument and place one type of resistance in the trabecular meshwork bilities and avenues an individual stent; you come back out and go back with a stent or Trabectome. Instead, can take to make a great idea even in through the same incision and put the surgeon might want to favor other better. It’s a wonderful growth op- a different stent in a different part of pathways, such as using a Xen Gel portunity for bright young people to the anatomy. In the case of ECP, you Stent to generate subconjunctival radically change how we approach use the same incision (and possibly filtration or reducing aqueous pro- surgery for this disease, improving a second one) to put the probe into duction with ECP. techniques and devices and setting the eye and apply the laser. I believe In the meantime, trabeculectomy more specifi c guidelines that better this compares quite favorably to and tube shunts remain valuable individualize care for patients, getting trabeculectomy and tube shunt pro- surgical options. But I believe better outcomes and fi nding ways to cedures in terms of complexity, time MIGS procedures will increasingly minimize the risks. I firmly believe spent and trauma to the eye. be considered in certain patients— that over the next decade there will be The other reality is that the amount whether it’s a single MIGS approach, really important contributions from of foreign material being implanted or a combination approach—to bright young physicians, scientists in the eye in MIGS procedures is eliminate the need for resorting to who are excited about entering this miniscule compared to something like a trabeculectomy, or at least delay fi eld. a tube shunt (or for that matter an that need. The reality is that when intraocular lens), even if you implant managing glaucoma, we’re always Dr. Katz is the director of the multiple stents. Of course, they are trying to postpone progression with Glaucoma Service at Wills Eye Hos- utilized for different purposes and medications, lasers or surgery; we pital in Philadelphia. He is a medical they’re placed in different parts of never cure the disease. So the more monitor and investigator for Glaukos the eye, but the comparison is worth time and options we can offer to and a medical investigator for noting. (The downside of the small patients with safer procedures, the InnFocus. Dr. Radcliffe is director amount of material implanted in better. of the Glaucoma Service and clini- MIGS procedures is that the success cal assistant professor at New York of most of them requires a great deal A Great Opportunity University. He is a consultant for of fi nesse in terms of understanding Glaukos, Transcend, Alcon and the anatomy of the eye and the proper Of course, we’re just beginning to Allergan. placement of these devices.) figure out which MIGS approaches 1. Augustinu CJ, Zeyen T. The effect of phacoemulsifi cation will make the most sense for each and combined phaco/glaucoma procedures on the intraocular Building the Foundation patient. Not all of the devices out pressure in open-angle glaucoma. A review of the literature. Bull there will be approved, but hopefully Soc Belge Ophtalmol 2012;320:51-66. 2. Samuelson TW, et al. Randomized evaluation of the trabecular For now, we’re refi ning the use of many of them will be, and new micro-bypass stent with phacoemulsifi cation in patients with the existing devices to maximize their modifications and options will be glaucoma and cataract. Ophthalmology 2011;118:459-467. 3. Kahook MY, Lathrop KL, Noecker RJ. One-site versus two- individual effectiveness. For example, developed. If we have an arsenal site endoscopic cyclophotocoagulation. J Glaucoma 2007;16: the work done with the iStent by of choices, a lot of surgeons will be 527-530.

72 | Review of Ophthalmology | March 2015

0070_rp0315_gm.indd70_rp0315_gm.indd 7272 22/20/15/20/15 12:3512:35 PMPM Richard Lindstrom, MD Ophthalmologist and noted refractive and cataract surgeon. Minnesota Eye Consultants

“Good lid and lash hygiene is not a sometime event. 2bMPVa^]WP3ZR_VMaWcWbbdŪRaRa͜;dbR2eR]^eMMb_Mac^S\h QMWZhZWQVhUWR]RaRUW\R]͙2]Q;aRP^\\R]Q2eR]^eMc^\h patients.”

Daily lid and lash hygiene.

Hypochlorous Acid in Solution - Kills organisms - Neutralizes toxins from microorganisms ͹BaReR]cbOW^ŬZ\S^a\McW^]

OPHTHALMOLOGIST AND OPTOMETRIST TESTED | RX ONLY AVENOVA.COM | ͻͻͻ

RP0215_Novabay.indd 1 1/21/15 11:25 AM Refractive Surgery

REVIEW Edited by Arturo Chayet, MD

ISRS Members Share Practice Trends Bilateral intraocular procedures, femtosecond cataract surgery and LASIK volumes are highlights of the latest ISRS survey. Walter Bethke, Managing Editor

he most recent survey of the it’s pretty consistent year in and year and PROWL-1 and PROWL-2. So, T U.S. members of the Interna- out,” says Dr. Duffey. “Usually when it with a combination of these things, the tional Society of Refractive Surgery shows something, that trend will show future is looking a bit better.” has revealed some interesting trends, on other indicators, as well. But as a In terms of the procedures chosen including the use of femtosecond la- general rule of thumb, I like to see a for particular patients, 40 percent of sers for refractive cataract surgery, the two-year trend. I think this coming surgeons say they do some sort of laser propensity of some surgeons to per- year will really tell us if we’re truly vision correction even for high myopes form intraocular procedures bilateral- up or not. I know in my practice I’m (-10 D). The other popular option for ly and even signs of life in the LASIK up a little from previous years. I hope those patients is phakic intraocular market. Here’s a look at the survey’s that we’ve possibly reached the val- lenses (43 percent). For the low hyper- highlights with commentary from one ley, if you will, and will start to see an ope (+3 D), 63 percent of respondents of its co-authors, Mobile, Ala., sur- upward trend. Some of the trend may prefer LVC, and 18 percent choose a geon Richard Duffey. Four hundred be related to the economy, and some phakic lens. Fifteen percent say they’d eighty-six of 1,022 members opened may be related to the good press we’re wait. For the high hyperope (+5 D) it the survey and it had a response rate getting from the studies sponsored tips in the lens’s favor, however, with of 15 percent. Here’s a look at what by ASCRS and AAO, as well as the 61 percent preferring to implant a the ISRS members had to say. independent studies such as Frank phakic IOL, 9 percent choosing LVC Price’s contact lenses vs. LASIK study and 19 percent electing to wait. Volume Uptick Volume of Surface Ablation/LASIK Procedures Last year marked the ﬁ rst time in several years that there was an increase 600 570 2011 549 in the average LASIK volume report- 2012 451 451 403 428 ed on the survey. The total number 2013 400 339 of procedures reported was 549,000, 2014 319 which is an increase of 22 percent over

last year’s 451,000. Dr. Duffey notes Thousands 200 167 though, that many sources still find 132 121 volumes to be ﬂ at, so he’d like to see 112 0 more data to declare this a solid trend. Surface ablation LASIK Total LVC “The sample size isn’t huge, but

74 | Review of Ophthalmology | March 2015 This article has no commercial sponsorship.

074_rp0315_rs.indd 74 2/20/15 2:49 PM Bilateral Surgery Preferred Treatment for 1.12 to 2 D of Astigmatism Interestingly, 23 percent of the surgeons say they do bilateral phakic lens 2012 77 76 75 implantation. Also, though 67 percent 2013 of the respondents usually implant 2014 phakic lenses in an ambulatory surgery center and 4 percent operate % at a hospital, a fi fth of them implant 16 15 phakic lenses in an in-office modi- 10 12 10 fied operating room and 9 percent 8 use a LASIK clean room. Dr. Duffey prefers to use his ASC, but explains LRI/AK Femto AK Toric IOL where the in-offi ce modifi ed OR and LASIK room fi t in: “The move to doing intraocular procedures in these lo- say about 19 percent of their cases are a little more diffi cult to open, and cations is done mostly to save money; are done with the femtosecond laser. placing them exactly at the limbus vs. when a phakic lens is done, if you take What was interesting, however, is that a little more anterior or posterior can the patient over to the ASC, a lot of only 54 percent of the respondents use be challenging to accomplish consis- your fee goes to the surgery center. I it to correct astigmatism, which was tently. Sometimes, you get in there think for some to make it fi nancially the main reason put forth for using and you might wish that you’d been viable, they’ll establish an environ- the laser in order to get reimbursed 0.5 mm more anterior or posteri- ment in their offi ce that’s not really in the first place. Eighty-four per- or with the incision; you can work a sterile OR and make it as clean as cent use it for the capsulotomy and 82 around that, however. My biggest is- they can. percent to fragment the nucleus. “It’s sue is that you can’t make a primary or “I used to have a LASIK clean also interesting that only about half secondary incision within 5 degrees of room,” he continues. “It was an ex- use it for the primary and secondary an AK incision. If you try to program tra exam lane that we reserved for incisions,” says Dr. Duffey. “For me, it otherwise, the system won’t allow lasers. We added an air fi lter and de- 100 percent include AK. That was the it. To eliminate that problem, I just humidifi er, and were more conscien- indication that was put out there for it do the capsulorhexis, lens fragmenta- tious about keeping it cleaner than fi rst, yet there are plenty of surgeons tion and AK with the laser. Then, in just a standard exam room. I also use on the current survey using it for the the OR, I’ll place my primary and/or a minor OR in my offi ce in which I do capsulotomy and lens fragmentation secondary incisions manually where minor extraocular procedures such alone.” I want them. If they coincide with as pterygium removals, SFKs and Dr. Duffey posits a reason why the AK, I still go at the same axis, conjunctival cyst excisions. I’ll rarely more corneal entry incisions aren’t only underneath it. I’ve spoken with repair an emergency corneal perfo- being made with the femtosecond Alcon about it and they say a fi x for ration in it for a patient who doesn’t laser. “In my personal experience, the it will possibly be in a future software have insurance, or a gluing procedure primary and secondary laser incisions update.” for a corneal perforation. It’s my own bias, but I wouldn’t want to do an Location of Phakic IOL Surgery elective intraocular procedure in a minor OR where I normally do my 83 76 2011 external disease surgeries.” 71 2012 67 2013 Femtosecond Cataract Surgery 2014 %

The survey has begun to feel out 17 20 surgeons regarding femtosecond la- 16 11 7 9 ser for cataract and correcting astig- 5 2 3 4 4 5 matism in conjunction with cataract surgery. Hospital OR ASC In-ofﬁ ce LASIK clean room Modiﬁ ed OR On the survey, the respondents

March 2015 | Revophth.com | 75

0074_rp0315_rs.indd74_rp0315_rs.indd 7575 22/20/15/20/15 2:492:49 PMPM EVERY MONDAY E-NEWS YOU CAN USE

Have you been receiving and reading custom e-blasts from Review of Ophthalmology? If not, you’re missing out on valuable information!

You’re a busy practitioner and not surprisingly, your e-mail inbox is often full. Fortunately, when you scan through the sender list, determining which messages to delete and which to save or read, you can feel conﬁ dent knowing that e-blasts from Review of Ophthalmology, a Jobson Medical Information LLC publication, contain the most current and comprehensive information available in the ﬁ eld to keep you on the cutting edge. Review of Ophthalmology’s online stable of products includes editorial newsletters and promotional information about new products, treatments and surgical techniques, as well as alerts on continuing education courses for ophthalmologists.

Our FREE weekly e-newsletter, Review of Ophthalmology Online, brings you the latest in ophthalmic research, as well as industry news. In an eff ort to keep eyecare professionals informed, this resource is waiting in your inbox every Monday morning.

Retina Online, our free monthly e-newsletter, is for retina specialists and general ophthalmologists interested in enhancing their knowledge on the topics of retina and related disease diagnosis and treatment, as well as the latest in surgical procedures.

Your time is valuable — and so is your practice. These e-products are the most eff ective way for you to receive updates on breaking news and research — all just a click away. DON’T MISS OUT!

Unfamiliar with our products? Visit www.reviewofophthalmology.com and check out our newsletter archives. Go to www.jobson.com/globalEmail/default.aspx to sign up for the e-newsletters that interest you.

2015_RPonline_house.indd 1 12/10/14 2:38 PM Research Review REVIEW

Cataract Surgery Safe For Outpatient Clinic

esearchers from St. Elizabeth’s mologist performed the procedure Patients who were aged 40 years RHospital in the Netherlands uti- assisted by two registered nurses in and older in the Kaiser Permanente lized a retrospective, observational an independent outpatient clinic op- Northern California health plan from cohort study to determine that cata- erating room within the hospital. The January 1, 2007 through December ract surgery can be safely performed clinical pathway was without dedicat- 31, 2011 with a documented CCT in an outpatient clinic in the absence ed presence of or access to anesthesia (n=81,082) were included in this of the anesthesia service and with lim- service. Perioperative monitoring was cross-sectional study. Patients with ited workup and monitoring. Basic limited to blood pressure and plethys- any cornea-related diagnoses or a his- fi rst aid and life support skills seem to mography preoperatively and intraop- tory of corneal refractive surgery were be suffi cient in the case of an adverse eratively. Patients were offered sup- excluded. Demographic characteris- event, and a medical emergency team portive care and instructed to avoid tics, including age, sex and race/eth- provides a generous failsafe for what fasting and continue all their chronic nicity, as well as clinical information is a low-risk procedure. medication. including glaucoma-related diagnosis, All patients who underwent elec- Three medical emergency team in- diabetic status, CCT and intraocular tive phacoemulsification/intraocular terventions related to the phacoemul- pressure were gathered from the elec- lens surgery under topical anesthesia sifi cation/intraocular lens pathway oc- tronic medical records. in the ophthalmology outpatient unit curred in the study period, resulting Multivariate linear regression between January 1, 2011 and De- in an intervention rate of 0.04 per- analysis indicated that female sex, cember 31, 2012 were included as cent. None of the interventions was increased age and black race were study participants. Within the cataract intraoperative. All three patients were significantly associated with thinner pathway, 6,961 eyes of 4,347 patients diagnosed as vasovagal collapse and corneas. A subgroup analysis among were eligible for analysis. The primary recuperated uneventfully. No hospital Asians revealed that Chinese, Japanese outcome measure was the incidence admittance was required. Eight other and Koreans had corneas 6 to 13 µm of adverse events requiring medi- incidents occurred within the general thicker than South and Southeast cal emergency team interventions ophthalmology outpatient unit popu- Asians, Filipinos and Pacifi c Islanders through the pathway. Secondary out- lation during the study period. for each diagnosis (p<0.001). Within come measures were surgical ocular Ophthalmology 2015;122:281-297. the patient population, 24.5 percent complication rates, use of oral seda- Koolwijk J, Fick M, Selles C, Turgut G, Noordergraaf J, et al. (n=19,878) had some form of tives and reported reasons to perform open-angle glaucoma; 21.9 percent the surgery in the classical operation Central Corneal Thickness (n=17,779) did not have any glaucoma- room complex. Impact on Risk of Glaucoma related diagnosis. Variation in CCT Cataract surgery was performed by ew research supports the recent accounted for only 6.68 percent phacoemulsifi cation under topical an- Nassertion that thin central corneal (95 percent confidence interval, esthesia. The intake process mainly thickness is a predictor of glaucoma 6.14 percent to 7.24 percent) of the embraced ophthalmic evaluation, ob- progression and explains a substantial increased risk of open-angle glaucoma taining a medical history and propos- portion of the increased risk of glauco- seen with increasing age, but explained ing the procedure. A staff ophthal- ma seen among blacks and Hispanics. as much as 29.4 percent (95 percent CI,

This article has no commercial sponsorship. March 2015 | Revophth.com | 77

0077_rp0315_rr.indd77_rp0315_rr.indd 7777 22/20/15/20/15 2:082:08 PMPM Hungry for success?

At Jobson, we have more effective ways for you to reach the optical market than anyone. So our approach to serving clients is unique. First, we develop a thorough understanding of your speciﬁ c goals. This understanding, plus our extensive offering of products and services, enables us to then suggest solutions that will help achieve those goals. This often includes innovative ideas and premium positions. For advertising information contact Michele Barrett (610-492-1014, [email protected]) or Jim Henne (610-492-1017, [email protected]). Let us satisfy your hunger for success.

www.revophth.com

The vision to help you succeed

063_rp0711Reviews_Platter.indd 1 6/14/11 9:35 AM Research

REVIEW Review

27 to 32.6 percent) of the increased vs. deferred laser groups; an improve- keratoplasty in three eyes with recur- risk of glaucoma seen among blacks ment of ≥10 letters in 46 percent of rent Acanthamoeba keratitis resulted and 29.5 percent (95 percent CI, 23.5 the prompt laser group vs. 58 percent in two additional microbiological cures to 37 percent) of the increased risk of of the deferred laser group; and an and one more clear graft. The final glaucoma seen among Hispanics. improvement of ≥15 letters in 27 per- best-corrected visual acuity was ≥20/40 J Glaucoma 2014;23:606-612. cent vs. 38 percent of the prompt vs. in fi ve eyes (62.5 percent) and worse Wang S, Mellex R, Lin S. deferred laser groups. From baseline than 20/200 in three eyes. Overall, the to fi ve years, 56 percent of the par- fi nal vision was improved in six eyes DME, Ranibizumab and Prompt ticipants in the deferred group did not (75 percent), remained the same in vs. Deferred Laser Treatment receive laser treatment. The median one eye (12.5 percent) and was worse ive-year randomized trial results number of injections was 13 vs. 17 in one eye (12.5 percent). Fsuggest focal/grid laser treatment in the prompt and deferred groups, Cornea 2015;34:49-53. at the initiation of intravitreal ranibi- including 54 percent and 45 percent Sacher B, Wagoner M, Goins K, Sutphin J, Greiner M, et al. zumab is no better than deferring la- receiving no injections during year ser treatment for ≥24 weeks in eyes four and 62 percent and 52 percent Three-year Outcomes for AMD with diabetic macular edema involv- receiving no injections during year Treat-and-Extend Regimens ing the central macula with vision im- fi ve, respectively. esearchers from the Wills Eye pairment. Although more than half Ophthalmology 2015;122:375-381. RHospital have determined that a of eyes in which laser treatment is Elman M, Ayala A, Bressler N, Browning D, Flaxel C, et al. treat-and-extend regimen is effective deferred may avoid laser for at least in achieving and maintaining visual five years, such eyes may require IV Pentamidine Before TKP to and anatomic improvements with more injections to achieve these re- Treat Acanthamoeba Keratitis neovascular age-related macular de- sults when following this protocol. esearch from the University of generation for up to three years of Most eyes treated with ranibizumab RIowa Hospitals and Clinics on treatment. and either prompt or deferred laser patients treated with intravenous The Wills Eye Retina Service treat- maintain vision gains obtained by the pentamidine before therapeutic kera- ed 212 eyes from 196 patients diag- fi rst year through fi ve years with little toplasty for Acanthamoeba keratitis nosed with treatment-naïve neovascu- additional treatment after three years. suggests that the adjunctive use of lar AMD between January 2009 and Participants were from a previously IVP before surgery may assist with the March 2013; they were treated with reported three-year trial evaluating achievement of microbiological cure, either ranibizumab or bevacizumab 0.5 mg intravitreal ranibizumab every clear graft and good visual outcome in for a minimum of one year, using a four weeks until no longer improving a majority of cases. treat-and-extend regimen. The main (with resumption if worsening) with A retrospective medical chart re- outcome measures were change from prompt vs. deferred (for ≥24 weeks) view of every patient treated with IVP baseline best-corrected Snellen vi- focal/grid laser treatment; of those before therapeutic keratoplasty for sual acuity, proportion of eyes losing who consented to and completed the Acanthamoeba keratitis at the UIHC <3 BCVA lines, proportion of eyes two-year extension, 124 patients (97 between January 1, 2002 and Decem- gaining ≥3 BCVA lines, change from percent) were from the prompt group ber 31, 2012 found eight eyes of seven baseline central retinal thickness and and 111 (92 percent) were from the patients that met inclusion criteria for mean number of injections at one, deferred group. The main outcome the study. Preoperatively, all eight eyes two and three years of follow-up. measure at the fi ve-year visit was best- had failed traditional antiamoebic ther- The mean follow-up period was corrected visual acuity. apy, including fi ve eyes with recurrent 1.88 years (median, two years). At The mean change in visual acu- infections after previous therapeutic baseline, BCVA was 20/139; it ity letter score from baseline to the keratoplasty. The patients were treated improved to 20/79 (p<0.0001) after fi ve-year visit was +7.2 letters in the with IVP (190 to 400 mg/day) for a one year of treatment and was prompt laser group compared with median of 14 days (r: seven to 26 days). maintained at 20/69 and 20/64 at two +9.8 letters in the deferred laser After eight therapeutic keratoplasties, and three years follow-up (p<0.001). group (mean difference, -2.6 letters; a microbiological cure was achieved At baseline, mean central retinal 95 percent CI, -5.5 to +0.4 letters; and a clear graft maintained in five thickness was 351 µm and signifi cantly p=0.09). At the fi ve-year visit, there eyes (62.5 percent) during a mean fol- decreased to 285 µm, 275 µm and was a vision loss of ≥10 letters in 9 low-up interval of 31.2 months (r: one 276 µm at one, two and three years percent vs. 8 percent of the prompt to 95.7 months). Repeat therapeutic of follow-up (p<0.001). Patients

March 2015| Revophth.com | 79

0077_rp0315_rr.indd77_rp0315_rr.indd 7979 22/20/15/20/15 2:082:08 PMPM Research Retinal

REVIEW Review REVIEW Insider

received, on average, 7.6, 5.7 and 5.8 (continued from page 61) injections over years one, two and three of treatment. At ﬁ nal follow-up, status, there is a 1.8- to 4-percent rate The telemedicine 94 percent of eyes had lost <3 lines of unexplained amblyopia in the Unit- experience in pediatric BCVA and 34.4 percent of eyes had ed States, which may be due to tran- gained ≥3 lines of BCVA. sient phenomena that can temporarily retinal diseases has Am J Ophthalmol 2015;159:3-8. occlude the visual axis (such as retinal, been successful because Rayess N, Houston S, Gupta O, Ho A, Regillo C. optic nerve and foveal hemorrhages). Fortunately, we will have two- and it has avoided the Hydrogel Sealant vs. Sutures to three-year follow-up on development pitfalls of casting too Prevent Postop Fluid Loss of amblyopia in children identified esults from a multicenter study with ocular abnormalities in the New- wide a net. Rindicate that hydrogel sealant is born Eye Screen Testing (NEST) pro- safe and effective, and is better than spective study at Stanford University sutures for the intraoperative man- School of Medicine in the summers of agement of clear corneal incisions 2015 and 2016, respectively. University School of Medicine where with wound leakage as seen on Se- Other strategies that are being em- he is the director of the vitreoretinal idel testing, and for the prevention of ployed are assessment of axial length, surgery fellowship program and direc- postoperative ﬂ uid egress. refraction, optical coherence studies tor of pediatric vitreoretinal surgery as Healthy patients having uneventful of the macula, and, potentially, in- well as director of telemedicine (oph- clear corneal incision cataract surgery traocular pressure assessment in the thalmology). He may be reached at were recruited for this study at 24 oph- near future. While the NEST pro- [email protected].

thalmic clinical practices in the United gram is currently being evaluated as 1. Silva PS, Cavallerano JD, Aiello LM. Ocular telehealth initiatives in States. Spontaneous and provoked a prospective study with longitudinal diabetic retinopathy. Curr Diab Rep 2009;9(4):265-71 2. Kumar S, Giubilato A, Morgan W, Jitskaia L, et al. Glaucoma fl uid egress from wounds was evalu- follow-up with pediatric ophthalmol- screening: Analysis of conventional and telemedicine-friendly devices. Clin Experiment Ophthalmol 2007;35(3):237-43. ated at the time of surgery using a cali- ogy/retina specialists, it is evident from 3. AREDS2-HOME Study Research Group, Chew EY, Clemons TE, brated force gauge. Eyes with leakage early data that commercialization and Bressler SB, Elman MJ, Danis RP, Domalpally A, Heier JS, Kim JE, Garfi nkel R. Randomized trial of a home monitoring system for early were randomized to receive a hydrogel widespread adoption will be offered in detection of choroidal neovascularization home monitoring of the Eye (HOME) study. Ophthalmology 2014;121:535-44. sealant (ReSure) or a nylon suture at the future. 4. Tsui I, Drexler A, Stanton AL, Kageyama J, Ngo E, Straatsma BR. the main incision site. Incision leakage The telemedicine experience in pe- Pilot study using mobile health to coordinate the diabetic patient, diabetologist, and ophthalmologist. J Diabetes Sci Technol 2014 was reevaluated one, three, seven and diatric retinal diseases has been suc- Jul;8(4):845-9. 5. http://www.novartis.com/newsroom/media-releases/en/2014/ 28 days postoperatively. cessful because it has avoided the pit- 1824836.shtml (accessed 1/25/15) Of 500 eyes, 488 had leakage at the falls of casting too wide a net. Instead, 6. http://abc7news.com/health/stanford-implant-could-fi ght-glaucoma/485552/ (accessed 1/25/15) time of cataract surgery. The leak was we have identifi ed niche markets with 7. Schwartz SD, Harrison SA, Ferrone PJ, Trese MT. Telemedical evaluation and management of retinopathy of prematurity using spontaneous in 244 cases (48.8 per- well-defi ned intervention points that a fi beroptic digital fundus camera. Ophthalmology 2000;107:25-8. cent) and 488 (97.6 percent) of all are easily identified using the tech- 8. Photographic Screening for Retinopathy of Prematurity (Photo- ROP) Cooperative Group. The photographic screening for retinopa- incisions leaked with one ounce or nology. These markets, whether in thy of prematurity study (photo-ROP). Primary outcomes. Retina 2008 Mar;28(3 Suppl):S47-54. less of applied force. After random- ROP or congenital ocular pathology, 9. Fijalkowski N, Zheng LL, Henderson MT, Wang SK, Wallenstein ization, 12 (4.1 percent) of 295 eyes have a limited timeframe in which MB, Leng T, Moshfeghi DM. Stanford University Network for Diagno- sis of Retinopathy of Prematurity (SUNDROP): Five years of screen- in the sealant group and 60 (34.1 per- therapy is benefi cial, but can result in ing with telemedicine. Ophthalmic Surg Lasers Imaging Retina 2014;45(2):106-13. cent) of 176 eyes in the suture group life-long benefi t. Therefore, the soci- 10. Quinn GE, Ying GS, Daniel E, Hildebrand PL, Ells A, Baumritter had wound leakage with provocation etal and patient benefi t is large from A, Kemper AR, Schron EB, Wade K; e-ROP Cooperative Group. Va- lidity of a telemedicine system for the evaluation of acute-phase (p<0.0001). The overall incidence of these screening programs. As oph- retinopathy of prematurity. JAMA Ophthalmol 2014;132:1178-84. 11. Fierson WM; American Academy of Pediatrics Section on adverse ocular events was statistically thalmologists, we need to continue to Ophthalmology; American Academy of Ophthalmology; American signifi cantly lower in the sealant group defi ne very narrow ranges of targeted Association for Pediatric Ophthalmology and Strabismus; Ameri- can Association of Certifi ed Orthoptists. Screening examination of than in the suture group (p<0.05). telemedicine screening that will offer premature infants for retinopathy of prematurity. Pediatrics. 2013 Jan;131(1):189-95. Six of this article’s authors are immediate relief and benefit, while 12. Fierson WM, Capone A Jr.; American Academy of Pediatrics consultants to and shareholders of still maintaining economic feasibility. Section on Ophthalmology, American Academy of Ophthalmol- ogy, and American Association of Certifi ed Orthoptists. Telemedi- Ocular Therapeutix. cine for evaluation of retinopathy of prematurity. Pediatrics 2015 Jan;135(1):e238-54. J Cataract Refract Surg 2014;40: 13. Li LH, Li N, Zhao JY, Fei P, Zhang GM, Mao JB, Rychwalski 2057-2066. Dr. Moshfeghi is an associate pro- PJ. Findings of perinatal ocular examination performed on 3573, Masket S, Hovanesian J, Levenson J, Tyson F, et al. healthy full-term newborns. Br J Ophthalmol 2013 May;97(5):588- fessor of ophthalmology at Stanford 91.

80 | Review of Ophthalmology | March 2015

0077_rp0315_rr.indd77_rp0315_rr.indd 8080 22/20/15/20/15 2:082:08 PMPM Product News REVIEW

Confocal Scanning + True-Color Imaging

enterVue announced Food and vice can be used automatically or The cannula is supplied packed C Drug Administration clearance manually, with or without pupil di- and sterile, in boxes of 10 pieces. for its Eidon true-color confocal lation. It is operated via a dedicated Product code M2280. scanner. The company calls Eidon software application as a standalone Sterimedix manufactures a com- the ﬁ rst fully automated retinal im- unit by means of a high-resolution, plete range of single-use products aging system available in the global multi-touch tablet. For information, for ophthalmic surgery. For more eye-care market that combines the visit centervue.com. information, visit sterimedix.com. advantages of confocal scanning with true-color imaging capabilities. Sterimedix: New Transzonular Catalys Laser Goes Mobile White-light, confocal imaging Injection Cannula orTec Medical recently collabo- technology facilitates diagnosis and terimedix has introduced a new Frated with Abbott’s vision-care management of retinal disease, Scannula for transzonular injec- business to mobilize the Catalys while the combination of confocal tions. Designed in conjunction with Precision Laser System for the imaging and white light illumination Jeffrey T. Liegner, MD, the cannula convenience of bringing this preci- provides greater contrast and supe- is designed for the intraoperative in- sion cataract procedure directly to rior image quality over a traditional jection of steroid-antibiotic combi- ophthalmology practices across the fundus camera, says CenterVue. nations at the end of a standard cata- United States. Further, the retinal appearance ract procedure, which may replace ForTec notes the benefits of with Eidon’s white-light source mir- the traditional patient-administered adopting Catalys Laser System in a rors that seen during white-light, prophylaxis of antibiotic eye drops. mobile platform: “If your cataract direct observational techniques. Ei- Available in 27 ga., the new can- surgical volume does not support don’s optics allow imaging of the nula is angled with a 2-mm distal the capital outlay, you can still lever- central retina as well as the periph- segment to facilitate safe and easy age the finest laser cataract tech- ery, over a viewing angle of up to injection of the drug with minimal nology to meet your schedule. And 110 degrees. Multiple imaging mo- risk to the zonules and offers an easy if you do have higher surgical vol- dalities—true-color, red-free and approach to the delivery of medica- umes and want to prove the value of infrared—provide information con- tions to the desired site. the system prior to a purchase, you cerning different layers of can leverage the mobile option the retina. while you ramp up your patient Eidon streamlines im- adoption.” age acquisition and ensures ForTec Medical provides minimum operator in- trained and credentialed tech- volvement by automatically nicians who expertly assist all aligning the patient’s pupil, scheduled procedures. For focusing on the retina and information, call 1 (800) 963- capturing images using a 7101, or visit mobile catalys.com soft light source. The de- or fortecmedical.com.

This article has no commercial sponsorship. March 2015 | Revophth.com | 81

081_rp0315_products.indd 81 2/20/15 3:24 PM REVIEW Classiﬁ eds

Equipment and Supplies

&ç½½^Ùò®½Ù • Classical • ŝĂŐŶŽƐƟĐ • Surgical • ZĞƟŶĂWĂĐŬĂŐĞƐ

VISITçùͬ^½½ͬdÙ US AT THE AAO ^®Äϭϵϴϵ

800-336-0410 ǁǁǁ͘ŇŽƌŝĚĂĞǇĞ͘ĐŽŵ

For classified advertising çù®Ä¦Ä^½½®Ä¦ call 1-888-498-1460 WÙͲÊóÄ or e-mail us at [email protected] KÖ«ã«½Ã®Øç®ÖÃÄã ^/Eϭϵϴϵ

82 | Review of Ophthalmology | March 2015

ROPH0315.indd 82 2/18/15 7:01 PM REVIEW Classiﬁ eds

Merchandise Offered

BUILDING YOU A BETTER BUSINESS SPACE PLANNING INTERIOR DESIGN DISPLAY INNOVATION MANUFACTURING WWW.EYEDESIGNS.COM 800.346.8890

FREE GIFT for the first 25 people to contact us. Ref code OPH0315 exp. 03/31/15

4741

1319

Targeting Ophthalmologists? CLASSIFIED ADVERTISING WORKS

• JOB OPENINGS • CME PROGRAMS • PRODUCTS & SERVICES • AND MORE...

March 2015 | Revophth.com | 83

ROPH0315.indd 83 2/18/15 7:02 PM REVIEW Classiﬁ eds

Merchandise Offered Products and Services

P.M. MEDICAL BILLING AND CONSULTING SPECIALIZING IN OPHTHALMOLOGY THE PATIENT EXPERIENCE BILLING & CONSULTING GOES BEYOND THE OPTICAL t National, full service billing to ophthalmologists t Maximum reimbursement is guaranteed LEARN MORE... GO TO WWW.ORVOSEXAM.COM 800.346.8890 t Staff consists of Ophthalmic techs, expert coders & billers t Increased revenue/low denial rate/complete & unrelenting follow up We specialize in old, outstanding AR, Practice Management & Credentialing Contact us at: [email protected] or call us toll-free at: 1-888-PM-BILLING for a free in-office consultation WWW.PMOPHTHALMOLOGYBILLING.COM

Practice For Sale

4741

1319

PRACTICES FOR SALE NATIONWIDE Visit us on the Web or call us to learn more about our company and the practices we have available. Targeting [email protected] 800-576-6935 Ophthalmologists? www.practiceconsultants.com CLASSIFIED ADVERTISING WORKS

Do You Have Contact us today Positions for classified advertising: Available? Toll free: 888-498-1460 Contact us today for E-mail: [email protected] classified advertising: Toll free: 888-498-1460 E-mail: [email protected]

84 | Review of Ophthalmology | March 2015

ROPH0315.indd 84 2/18/15 7:02 PM 085_rp0315_wills.indd 85 Intraocular pressureswere17mmHgOUbyGoldmanntonometry. color plateswere5/8inbotheyes,andthepatientsaidthiswasnormalforhim. eye withproportionatelyverticalbinoculardiplopiainupgaze.Visual ﬁ elds werefulltoconfrontationinbotheyes.Ishihara A lefthypertropiawaspresentinprimarygaze,andextraocularmotilityrevealedonly50percentsupraductionoftheright or tendernessandnoresistancetoretropulsion. hypoglobus. Hertelexophthalmometryrevealed5mmofright-sidedproptosis chanical andneurogenicrightupperlidptosis,demonstratedbydecreasedlevatorfunction.Therewas2.5mmof plaques onhisfaceandneck.Therewasasoft,non-tender, mobilemassbeneaththerightupperlidwithconsequentme- Examination tobacco, alcoholandintravenousdrugabuse.Hewasnotonanymedications,deniedknownallergies. Medical History symptom resolution. had initiallypresentedtoanoutsidehospitalandcompletedacourseoforalcephalexintopicalbactrobanwithout toms, butdidrevealarecentrashonhisupperandlowerextremitiesforweek,withtwodaysoffacialskininvolvement.He review ofsymptomswasnegativeforjointpain,shortnessbreath,cough,abnormalbowelmovementsorurinarysymp- tearing andcrustingoftheeyelashes.Hedeniedvisionchanges,diplopia,pain,historytraumaorrecentillness.Systemic Presentation Alison Huggins, MD principal presentingsignsforthismiddle-agedpatient. Lid swellingandrecenttearingcrustingoftheeyelashesare What isyourdifferentialdiagnosis? Whatfurtherworkupwouldyoupursue?Please turntop. 86

Anterior slit-lampexaminationandfundoscopicwereunrevealingwithnosignsofinﬂ ammation orinfection. The best-correctedvisualacuitywas20/20OU.Pupillaryexamshowednoanisocoriaorrelativeafferentpupillarydefect. The patientwasafebrilewithstablevitalsigns.Hisexternalexaminationdemonstratedmultiplecrustederythematous The patienthadnosigniﬁ cant medicalhistory, butdidhaveahistoryofdecreasedcolorvisioninbotheyes.Hedenied A 48-year-old African-Americanmalepresentedwithatwo-monthhistoryofrightupperlidswellingrecent-onset REVIEW Wills Eye Wills Eye proptosis andhypoglobus, alongwithdiffusecrusted, skinlesions. erythematous photographyFigure demonstrating 1.External rightorbitalmasswithassociatedptosis, Resident CaseSeries Edited by Alessandra Intili, MD . There was no eyelid erythema (See Figure1).Therewasnoeyeliderythema March 2015 | Revophth.com |

85 2/20/15 3:51 PM 085_rp0315_wills.indd 86 granulomatous inflammation. demonstrating non-caseating superior orbitalmasshistologicspecimen Figure 3.Hematoxylinandeosinstainof pathic infl circumscribed lesions,suchasidio- remained broadandincludedpoorly imaging, thedifferentialdiagnosis ies andconcerningclinicalexam given hisunrevealinglaboratorystud- bitally limiteddiseases.Therefore, with generallypoorsensitivityforor- negative, althoughitconsistedoftests mained stable.Hislabworkupwas fuse rightorbitalmass(SeeFigure2). mass. Imagingrevealedasuperiordif- further characterizetherightorbital contrast wasobtainedto and orbitswithintravenous graph. AnMRIofthebrain had anormalchestradio- 0 to10).Thepatientalso 5) andESRof20(normal protein of6(normal0to the exceptionofC-reactive and allunremarkable,with ferential) werecompleted ESR andCBCwithdif- HIV, RF, C3,C4,CRP, P-ANCA, FTA-Ab, ANA, (Lyme, ACE,C-ANCA, and infiltrativeprocesses autoimmune, infectious Laboratory studiesfor and neoplasticprocesses. cluded bothinfl differential diagnosisin- perior orbitalmass,the a painless,progressivesu- 86 Diagnosis, Workup andTreatment REVIEW On follow-up,thepatient’s examre- Given thepresenceof | ReviewofOphthalmology Resident CaseSeries ammation; specifi ammation; infl c am- ammatory superior extraconal spaceoftherightorbit. Figure 2. A mildlyheterogeneouslyenhancingmassoccupying the | March 2015 Figure 3). mation consistentwithsarcoidosis(See non-caseating granulomatousinfl ever, thehistopathologydemonstrated of lymphoproliferativedisease.How- cytometry, whichshowednoevidence proach. Freshtissuewassentforfl mass debulkingthoughalidcreaseap- ed orbitotomywithlesionbiopsyand etiology anduncleardiagnosisprompt- lesions. Theconcernforaneoplastic phoproliferative disease;andvascular Sjögren’s, etc.);metastaticlesions;lym- matory conditions(sarcoid,Wegener’s, improvement skinlesions. ofpreviously present erythematous Figure 4. Two weekspostop: persistentptosisbutimproved rightproptosis, aswell am- ow ow term immunosuppression. gist todeterminetheneedforlong- awaiting evaluationbyhisrheumatolo- prednisone taperto5mgdaily, andis two monthstime,hetoleratedanoral persistent rightupperlidptosis.Over improved poglobus andextraocularmotilityhad Two weekspostop,hisproptosis,hy- surgical debulkingandcorticosteroids. had signifi cant improvement following on 60mgdailyoforalprednisone.He agnosed withsarcoidosisandstarted put waspending,thepatientdi- (See Figure4).Therewas therapy. rheumatology fordefi patient wasalsoreferredto matous infl dermatitis withoutgranulo- This revealedpsoriasiform of thepatient’s facialrash. ogy referralledtoabiopsy tion testinganddermatol- normal pulmonaryfunc- pulmonology demonstrated tuberculosis. Referralto antibody testingruledout sarcoid. QuantiferonGold concerning forpulmonary interstitial inflammation, lar lymphadenopathyand chest thatdemonstratedhi- tomography scanofthe derwent acomputerized prednisone, thepatientun- While rheumatologyin- Prior totheinitiationof ammation. The The ammation. nitive nitive 2/20/15 3:52 PM Discussion

Sarcoidosis is a multi-system disease mation on biopsy. Specifi c lesions are nary, dermatologic and ocular fi ndings of non-caseating granulomatous in- commonly fi rm, 2- to 5-mm papules simultaneously. Given the reported fl ammation thought to be the result of that are translucent red-brown or yel- frequency of each organ system’s in- immune stimulation by self or non-self low-brown in color; however appear- volvement, the incidence of all three antigens.1 Despite investigation of po- ance is very variable4 and may include occurring likely ranges from 1 to 23 tential etiologies, including a multitude plaques, psoriaform lesions and intra- percent of patients.4 Nonetheless, a of genetic, infectious and environmen- dermal nodules, among others. Lupus large case-control study investigating tal factors, there have been no estab- pernio is a disfiguring form of facial the clinical characteristics of patients lished causative relationships. Regard- sarcoidosis that may be severe enough with newly diagnosed sarcoidosis il- less of the inciting antigen, the final to erode into bone. Interestingly, skin lustrated that it is relatively rare for pa- common pathway of disease is thought lesions have a predilection for involve- tients to present with disease in three to result from an exaggerated immune ment of scars, tattoos, skin piercings organ systems. Among the 736 studied response resulting in a T helper cell 1 and sites of old trauma.4 In this case, patients, only 13 percent had disease immune cascade with the subsequent psoriaform dermatitis was present, but involving three organ systems at the elaboration of chemokines and cyto- there was no evidence of granuloma- time of diagnosis.5 kines, resulting in organ fi brosis and tous infl ammation to suggest this rash On the other hand, 50 percent of dysfunction.1 was a specifi c lesion of sarcoidosis. patients will have single-organ in- Variability in the severity and type of volvement at presentation.5 In fact, disease manifestations has made quan- ocular sarcoid may pose a diagnostic tifying disease frequency challenging, dilemma, as it is not uncommon for as it can have a subclinical course in The most common the systemic and laboratory workup some. Despite this, there is a predilec- ophthalmologic to be unrevealing. Short of biopsy, no tion for certain races and ethnicities; clear diagnostic criteria for defi nitive specifi cally, it is most commonly seen manifestation of sarcoid diagnosis have been established. In among African Americans, as well as is uveitis, present in 70 cases of systemic involvement, chest Caucasians of Scandinavian and Irish radiography demonstrating hilar ad- decent.2 The incidence of sarcoidosis percent of patients with enopathy and an elevated ACE level among African Americans is 35 to 80 ocular involvement. are suggestive of sarcoidosis. However, per 100,000 with a 30-percent higher CT scan of the chest has been found to risk in females and a peak incidence have increased diagnostic sensitivity.4 in the third to fourth decade of life. The mainstay of therapy for sarcoid- Among Northern Europeans, the inci- The most common ophthalmologic osis remains immunosuppression with dence is 15 to 20 in 100,000, they share manifestation of sarcoid is uveitis, pres- corticosteroids.1 However, in the afore- a similar increased risk in females and ent in 70 percent of patients with ocu- mentioned review of patients with or- age of onset to the African-American lar involvement.1 Orbital involvement bital sarcoid, surgical debulking is also population.3 is much rarer; in a review of 379 cases used to supplement systemic therapy Pulmonary involvement is most of ocular sarcoidosis at Henry Ford with good long-term outcomes.6 At common among patients with sarcoid- Hospital, only 30 cases demonstrated present, there are no randomized con- osis, occurring in more than 90 percent orbital and/or adnexal involvement. trolled trials comparing therapeutic of patients with sarcoidosis.1 However, Of these, only nine cases involved the treatment options in systemic sar- this disease also frequently manifests orbit, eyelids and extraocular muscles.4 coidosis; however, steroid-sparing im- in the lymph nodes, skin and eyes.4 A The majority of orbital lesions were munosuppressants are widely used. comprehensive review of the clinical situated in an anterior, superior posi- Monoclonal antibodies used to antago- features of sarcoidosis discusses the tion, as seen in this case. nize tumor-necrosis factor alpha, a key dermatologic disease manifestations Interestingly, in this case the patient player in the sarcoidosis infl ammatory as two discrete classifi cations: nonspe- had disease manifestations in all three cascade, have shown benefi t in refrac- cifi c lesions that are infl ammatory skin of the aforementioned organ systems tory cases. While none of these treat- reactions, most commonly erythema at the time of diagnosis. It is unclear ment modalities are without risk, the nodosum; and specific lesions that from the current literature how fre- question of whether or not to pursue demonstrate granulomatous inflam- quently patients present with pulmo- surgical intervention in this steroid-re-

March 2015 | Revophth.com | 87

0085_rp0315_wills.indd85_rp0315_wills.indd 8877 22/20/15/20/15 3:523:52 PMPM 085_rp0315_wills.indd 88 088_rp0315_varitronics_frac.indd 1 disease. evaluation andtreatmentofsystemic tion ofsteroid-sparingagentsandfor should besoughttoentertaininitia- ther, consultationofarheumatologist systemic immunosuppression.Fur- infectious etiologiespriortotrialof rule outallpossibleneoplasticand therapy, butcaremustbetakento well tosystemicimmunosuppressive than anX-ray. Sarcoidosisresponds be low, asitisamoresensitivetest ing aCTscanofthechestshould Additionally, thethresholdforcheck- negative inophthalmologicdisease. as, inthiscase,thesetestsareoften able ACElevelandchestradiography remain highdespiteinitialunremark- Likewise, clinicalsuspicionshould inﬁ ered incaseswheninﬂ manifestations, andshouldbeconsid- thalmologic diseasegivenitsdiverse remains agreatmasqueraderinoph- suppression. indicated beforeatrialofimmuno- the purposeofdebulkingmaynotbe sic diseasemanifestations,surgeryfor However, forpatientswithmoreclas- this timecertainlyseemsappropriate. diagnosis, asinthiscase,debulkingat For patientsundergoingsurgeryfor sponsive conditionremainsunclear. 014-8450-y. 2014]. ClinRev Allerg Immunol2014doi10.1007/s12016- hensive review[publishedonlineaheadofprintOctober 02 6. JudsonM. The clinical ofsarcoidosis: features A compre- 2001;164(10): 1885-1889. of sarcoidosis.case controlstudy Am JRespirCritCareMed 5. Baughman, RP, etal. ina Clinicalcharacteristics ofpatients in 30cases. Am JOphthalmol2011;151(6):1074-1080. in sarcoidosis: Anaylsis ofclinical andsystemicdisease features 4. DemirciH, ChristiansonMD. OrbitalandadnexalInvolvement 2007;28(1):22-35. advances andfutureprospects. SeminRespirCritCareMed 3. RybickiBA, IannuzziMC. ofsarcoidosis: Epidemiology Recent 2000;84:110-116. 2. Rothova A. Ocularinvolvementinsarcoidosis. BrJOphthalmol 2012;23:447-484. ofsarcoidosis.logic manifestations CurrOpinOphthalmol 1. UmurKA, Tayfun B, OguzhanO. Differentophthalmo- MD, andMichaelP. Rabinowitz,MD. Brian Doyle,MD,RalphC.Eagle, cial thanksandacknowledgementto REVIEW In conclusion,ocularsarcoidosis The authorwouldliketogivespe- ltrative diagnosesareconsidered. Resident CaseSeries ammatory and 2/20/15 3:52 PM 2/9/15 2:23PM Advertising 20TH ANNUAL

REVIEW Index OPHTHALMIC RODUCT Abbott Medical Optics, Inc. (AMO) 15 P Phone (800) 366-6554 Alcon Laboratories 2, 3, 9, 29, 30, 33, 35 UIDE Phone (800) 451-3937 G Fax (817) 551-4352

Allergan, Inc. 90, 92 Phone (800) 347-4500 Innovative products to enhance your practice Bausch + Lomb 17, 18 Phone (800) 323-0000 Fax (813) 975-7762

Bausch + Lomb 41, 42-43 Phone (866) 246-8245 www.bausch.com

Bio-Tissue, Inc. 51 A-F Phone (305) 412-4430 Fax (305) 412-4429

Glaukos 21 Phone (800) 452-8567 www.glaukos.com The future

Haag-Streit 12, 45, 65 Phone (800) 627-6286 is in your Fax (603) 742-7217 Keeler Instruments 7, 91 hands. One Phone (800) 523-5620 Fax (610) 353-7814

Lombart Instruments 57 tap, many Phone (800) 446-8092 Fax (757) 855-1232 possibilities. NovaBay Pharmaceuticals, Inc. 73 Phone (800) 890-0329 [email protected] www.avenova.com Experience the digital edition Ocular Therapeutix, Inc. 53 Phone (877) 628-8998 www.ocutx.com on your handheld device. Omeros 24-25 Use your smart device to Phone (206) 676-5000 Fax (206) 676-5005 scan the code below or visit: Regeneron Pharmaceuticals, Inc. 47, 48 Phone (914) 847-7000 www.regeneron.com

Rhein Medical 5 www.reviewofophthalmology.com/supplements/ Phone (800) 637-4346 Fax (727) 341-8123 Download a QR scanner app. Launch app and hold your TearLab Corporation 11 mobile device over the code to view Phone (888) 677-8327 http://www.reviewofophthalmology.com/supplements/. Fax (858) 812-0540

ThromboGenics Inc. 23 Phone (732) 590-2901 Fax (866) 936-6676

Varitronics 39, 88 Phone (800) 345-1244 Fax (610) 356-1222

This advertiser index is published as a convenience and not as part of the advertising contract. Every care will be taken to index correctly. No allowance will be made for errors due to spelling, incorrect ® page number, or failure to insert.

March 2012 | Revophth.com | 89

089_rp0315_adindex.indd 89 2/20/15 4:34 PM

2015_opg_ad_half_rp.indd 1 2/20/15 3:46 PM ® At doses at least 41 times the maximum intended human exposure based on blood LUMIGAN 0.01% AUC levels, the gestation length was reduced in the dams, the incidence of dead fetuses, late resorptions, peri- and postnatal pup mortality was increased, and pup (bimatoprost ophthalmic solution) body weights were reduced. There are no adequate and well-controlled studies of LUMIGAN® (bimatoprost Brief Summary—Please see the LUMIGAN® 0.01% package insert for full ophthalmic solution) 0.01% administration in pregnant women. Because animal Prescribing Information. reproductive studies are not always predictive of human response LUMIGAN® 0.01% should be administered during pregnancy only if the potential benefit justifies the INDICATIONS AND USAGE potential risk to the fetus. LUMIGAN® (bimatoprost ophthalmic solution) 0.01% is indicated for the reduction Nursing Mothers: It is not known whether LUMIGAN® 0.01% is excreted in human of elevated intraocular pressure in patients with open angle glaucoma or milk, although in animal studies, bimatoprost has been shown to be excreted in ocular hypertension. breast milk. Because many drugs are excreted in human milk, caution should be CONTRAINDICATIONS exercised when LUMIGAN® 0.01% is administered to a nursing woman. None Pediatric Use: Use in pediatric patients below the age of 16 years is not recommended WARNINGS AND PRECAUTIONS because of potential safety concerns related to increased pigmentation following long-term chronic use. Pigmentation: Bimatoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased Geriatric Use: No overall clinical differences in safety or effectiveness have been pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Pigmentation is observed between elderly and other adult patients. expected to increase as long as bimatoprost is administered. The pigmentation Hepatic Impairment: In patients with a history of liver disease or abnormal ALT, change is due to increased melanin content in the melanocytes rather than to AST and/or bilirubin at baseline, bimatoprost 0.03% had no adverse effect on liver an increase in the number of melanocytes. After discontinuation of bimatoprost, function over 48 months. pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital OVERDOSAGE tissue and eyelash changes have been reported to be reversible in some patients. No information is available on overdosage in humans. If overdose with LUMIGAN® Patients who receive treatment should be informed of the possibility of increased (bimatoprost ophthalmic solution) 0.01% occurs, treatment should be symptomatic. pigmentation. The long term effects of increased pigmentation are not known. In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not Iris color change may not be noticeable for several months to years. Typically, the produce any toxicity. This dose expressed as mg/m2 is at least 210 times higher than brown pigmentation around the pupil spreads concentrically towards the periphery the accidental dose of one bottle of LUMIGAN® 0.01% for a 10 kg child. 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 NONCLINICAL TOXICOLOGY LUMIGAN® (bimatoprost ophthalmic solution) 0.01% can be continued in patients Carcinogenesis, Mutagenesis, Impairment of Fertility: Bimatoprost was not who develop noticeably increased iris pigmentation, these patients should be carcinogenic in either mice or rats when administered by oral gavage at doses examined regularly [see Patient Counseling Information (17.1)]]. of up to 2 mg/kg/day and 1 mg/kg/day respectively (at least 192 and 291 times Eyelash Changes: LUMIGAN® 0.01% may gradually change eyelashes and vellus the recommended human exposure based on blood AUC levels respectively) for hair in the treated eye. These changes include increased length, thickness, and 104 weeks. number of lashes. Eyelash changes are usually reversible upon discontinuation Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse of treatment. lymphoma test, or in the in vivoo mouse micronucleus tests. Intraocular Inflammation: Prostaglandin analogs, including bimatoprost, have been Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day reported to cause intraocular inflammation. In addition, because these products may (at least 103 times the recommended human exposure based on blood AUC levels). exacerbate inflammation, caution should be used in patients with active intraocular PATIENT COUNSELING INFORMATION inflammation (e.g., uveitis). Potential for Pigmentation: Advise patients about the potential for increased brown Macular Edema: Macular edema, including cystoid macular edema, has been ® pigmentation of the iris, which may be permanent. Also inform patients about the reported during treatment with bimatoprost ophthalmic solution. LUMIGAN 0.01% possibility of eyelid skin darkening, which may be reversible after discontinuation of should be used with caution in aphakic patients, in pseudophakic patients with a LUMIGAN® (bimatoprost ophthalmic solution) 0.01%. torn posterior lens capsule, or in patients with known risk factors for macular edema. Potential for Eyelash Changes: Inform patients of the possibility of eyelash and Bacterial Keratitis: There have been reports of bacterial keratitis associated with vellus hair changes in the treated eye during treatment with LUMIGAN® 0.01%. the use of multiple-dose containers of topical ophthalmic products. These containers These changes may result in a disparity between eyes in length, thickness, had been inadvertently contaminated by patients who, in most cases, had a pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash concurrent corneal disease or a disruption of the ocular epithelial surface [see Patient growth. Eyelash changes are usually reversible upon discontinuation of treatment. Counseling Information (17.3)]]. Handling the Container: Instruct patients to avoid allowing the tip of the dispensing Use with Contact Lenses: Contact lenses should be removed prior to instillation of ® container to contact the eye, surrounding structures, fingers, or any other surface in LUMIGAN 0.01% and may be reinserted 15 minutes following its administration. order to avoid contamination of the solution by common bacteria known to cause ADVERSE REACTIONS ocular infections. Serious damage to the eye and subsequent loss of vision may Clinical Studies Experience: Because clinical studies are conducted under widely result from using contaminated solutions. varying conditions, adverse reaction rates observed in the clinical studies of a drug When to Seek Physician Advice: Advise patients that if they develop an intercurrent cannot be directly compared to rates in the clinical studies of another drug and may ocular condition (e.g., trauma or infection), have ocular surgery, or develop any ocular not reflect the rates observed in practice. reactions, particularly conjunctivitis and eyelid reactions, they should immediately In a 12-month clinical study with bimatoprost ophthalmic solutions 0.01%, the most seek their physician’s advice concerning the continued use of LUMIGAN® 0.01%. common adverse reaction was conjunctival hyperemia (31%). Approximately 1.6% Use with Contact Lenses: Advise patients that LUMIGAN® 0.01% contains of patients discontinued therapy due to conjunctival hyperemia. Other adverse drug benzalkonium chloride, which may be absorbed by soft contact lenses. Contact reactions (reported in 1 to 4% of patients) with LUMIGAN® 0.01% in this study lenses should be removed prior to instillation of LUMIGAN® 0.01% and may be included conjunctival edema, conjunctival hemorrhage, eye irritation, eye pain, eye reinserted 15 minutes following its administration. pruritus, erythema of eyelid, eyelids pruritus, growth of eyelashes, hypertrichosis, Use with Other Ophthalmic Drugs: Advise patients that if more than one topical instillation site irritation, punctate keratitis, skin hyperpigmentation, vision blurred, ophthalmic drug is being used, the drugs should be administered at least five (5) and visual acuity reduced. minutes between applications. Postmarketing Experience: The following reaction has been identified during postmarketing use of LUMIGAN® 0.01% in clinical practice. Because it was reported © 2014 Allergan, Inc., Irvine, CA 92612 voluntarily from a population of unknown size, estimates of frequency cannot be ® marks owned by Allergan, Inc. made. The reaction, which has been chosen for inclusion due to either its seriousness, Patented. See: www.allergan.com/products/patent_notices frequency of reporting, possible causal connection to LUMIGAN® 0.01%, or a Made in the U.S.A. combination of these factors, includes headache. APC87BO14 based on 71807US14. Rx only In postmarketing use with prostaglandin analogs, periorbital and lid changes including deepening of the eyelid sulcus have been observed. USE IN SPECIFIC POPULATIONS 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 or 97 times, respectively, the maximum intended human exposure based on blood AUC levels.

RRP0115_AllerganP0115_Allergan LLumiganumigan PPI.inddI.indd 1 112/16/142/16/14 12:1812:18 PMPM Great Company

BOS ARB NY CLE PHI

BAL IOW

DUR

STL

LA LA

MIA

Where will you find Keeler’s Vantage Plus? Easy...the top 12 ophthalmology centers in the US*. Keeler Vantage Plus • Intelligent Optics for superior views (US Patent: 8,132,915) • HiMag™ Lens for detailed magnified views • Convertible Illumination LED and Xenon • Lightest Wireless System

Get a Free Keeler Indirect When Yoou Buuy Any 3 KeKeeleeler Inddiirecttss, & TTrade-Inrade-IIn AnyA 3 Indirectsd through March 31, 2015

Learn more at www.keelerusa.com

*Top-ranked hospitals for ophthalmology – Source: U.S. News & World Report

Keeler Instruments, Inc. • 456 Parkway • Broomall, PA 19008 • Tel: (800) 523-5620 • Fax: (610) 353-7814 • email: [email protected]

RP0115_Keeler Indirect.indd 1 12/8/14 2:53 PM RP0115_Allergan Lumigan.indd 1 12/16/14 11:38 AM