REVIEW OF OPTOMETRY ■ EARN 2 CE CREDITS: Don’t Be Stumped by These Lumps and Bumps, Page 70 VOL. 154 NO. 4 ■

April 15, 2017 www.reviewofoptometry.com

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VOL. 154 NO. 4 ■ APRIL 15, 2017

IN THE NEWS Stress and AMD: North Carolina Senator Danny Britt recently introduced a bill requesting $2.1 Recognize the Link million for the creation of a new school of optometry at the University of North New research suggests ODs should be looking at more Carolina at Pembroke. With no other schools of optometry in the state (the than a patient’s visual acuity and ocular anatomy. closest being the University of Alabama at By Rebecca Hepp, Managing Editor Birmingham School of Optometry), Sen. Britt believes the legislative environment ll clinicians know the Photo: Julie Poteet, OD is favorable for such a project, and his importance of moni- district would benefi t from the new Atoring patients with school, according to a press release. age-related macular degen- eration (AMD) for disease Researchers recently discovered progress. What fewer think that using SD-OCT to noninvasively about is keeping an eye on measure the peripapillary retinal patients’ psychological sta- structure may be a better way to tus. One research team at the measure intracranial pressure in children. Ohio State University Col- SD-OCT parameters outperformed lege of Optometry sought to other conventional clinical measures, better understand how stress suggesting it is an effective surrogate levels for patients with AMD for invasive techniques currently could affect their health employed. Detecting elevated intracranial status. But fi rst, they had to AMD patients require education about influences pressure in children helps ensure timely prove the best method for on their ocular status, and that includes stress. intervention and prevent neurocognitive monitoring patient stress in impairment, the study said. this population. from interventions for managing Swanson JW, Aleman TS, Xu W. Evaluation of optical The researchers used the Per- stress,” says Bradley E. Dougherty, coherence tomography to detect elevated intracranial pressure in children. JAMA Ophthalmol. February 23, ceived Stress Scale (PSS) with 137 OD, PhD, assistant professor at 2017. [Epub]. patients with AMD and found it the Ohio State University College New research suggests larger eyes and is a useful method of evaluating of Optometry and study author. better eyesight in air vs. water were key the connection between patient “While it may not be commonly to life’s transition from ocean to land, stress and vision loss associated considered, as it’s not directly and even consciousness, according to with AMD. Using Rasch analy- related to the eye, the identifi ca- a recent study. Eyes tripled in size and sis to discover how well the PSS tion and management of perceived shifted from the sides to the top of the measured perceived stress, the stress should be thought of as head long before fi sh modifi ed their fi ns study authors found nine of the important to the complete care of into limbs, researchers found. The com- 10 questions commonly used for the patient. Stress has a negative bination of the increase in eye size and the PSS performed well with the effect on patients’ overall quality vision through air would have conferred study participants and were able of life.” a one million-fold increase in the amount to differentiate between patients According to the authors, AMD of space within which objects could be seen, according to the researchers. with higher vs. lower levels of patients are known for their perceived stress. increased rates of psychological Maclver MA, Schmitz L, Mugan U, et al. Massive “Understanding a patient’s level symptoms. In addition, previ- increase in visual range preceded the origin of terrestrial vertebrates. PNAS. March 7, 2017. [Epub]. of perceived stress could help ous research shows PSS scores identify those who would benefi t (continued on page 9)

4 REVIEW OF OPTOMETRY APRIL 15, 2017

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Old Drug Shows Promise for Retinal Disease

he breast cancer drug treated mice also demonstrated tients receiving a similar dose,” says tamoxifen appears to protect higher photoreceptor function, Dr. Ferrucci.3,4 against photoreceptor de- compared with controls, according In this case, it may be useful in T 1,2 generation, according scientists at to the study. certain diseases such as AMD and the National Eye Institute (NEI). “What’s interesting is that RP, says Dr. Ferrucci. “Certainly The drug prevented immune tamoxifen, a medication linked to while exciting news, further inves- cells from removing injured retinal toxicity, is now being stud- tigation in both animal and human photoreceptors in an animal ied as a neuroprotective drug for studies is needed before we can model of retinal injury, suggesting the retina in certain degenerative conclude this is a viable treatment tamoxifen might work for treating eye diseases,” says Steven Ferrrucci, option for such diseases.” age-related macular degeneration OD, Chief of the Optometry De- Since the drug dosage in the (AMD) and retinitis pigmentosa partment at the VA Sepulveda Am- animal study was equivalent to (RP).1,2 bulatory Care Center and professor eight times the FDA-approved dose While using tamoxifen in the at the Southern California College for breast cancer, the NEI scientists laboratory to activate specifi c of Optometry at Marshall B. Ket- are currently investigating whether genes in mouse models, research- chum University. Reported ocular lower tamoxifen concentrations ers observed that mice treated toxic reactions consist of crystal- garner the same protective benefi t.1 with tamoxifen gained resistance line retinopathy, corneal deposits The authors say this research to light-induced eye injuries and and optic neuritis, according to Dr. forms the foundation for clinical experienced little to no photorecep- Ferrucci. The reported incidence trials, which are not far off, given tor degeneration.1 of toxic reactions to tamoxifen in the established safety of the drug.1 The team then investigated the literature varies between 0.9% 3,4 1. Breast cancer drug dampens immune response, protecting the effects of tamoxifen on light- and 12%. “For instance, UK light-sensing cells of the eye. National Eye Institute. http://nei. induced photoreceptor degenera- researchers looked prospectively at nih.gov/news/briefs/breast-cancer-drug-dampens-immune- response-protecting-light-sensing-cells-eye. Accessed March tion in normal mice and mice with 65 women receiving the standard 23, 2017. 2 2. Wang X, Zhao L, Zhang Y. Tamoxifen provides structural and a disease similar to RP. Results dose of tamoxifen, 20mg/d, fi nding functional rescue in murine models of photoreceptor degen- showed signifi cantly lower levels of that eight patients (12%) developed eration. Journal of Neuroscience. 2017;37(12):3294-310. 3. Alwitry A, Gardner I. Tamoxifen maculopathy. Arch Ophthal- photoreceptor degeneration com- some form of ocular toxic reaction, mol. 2002;120(10):1402. 4. Lazzaroni F, Scorolli L, Pizzoleo CF. Tamoxifen retinopathy: pared with control mice that did while another study found a 3.1% does it really exist? Graefes Arch Clin Exp Ophthalmol. 1998 not received tamoxifen. Tamoxifen- rate of crystalline retinopathy in pa- Sep;236(9):669-73. Legislative Update: FL and GA in Play ptometrists in Florida the board of optometry, on laser allow optometrists to administer are backing a bill that and non-laser ophthalmic surgery. pharmaceutical agents related Owould expand their scope The bill passed the House Health to the diagnosis or treatment of of practice to include some laser Quality Subcommittee and was diseases and conditions of the eye procedures. HB 1037, if passed, under review by the Health and and adnexa by injection, so long would allow certifi ed optometrists Human Services Committee as of as they complete an injectables in ophthalmic surgery to perform March 20. training program or are enrolled in laser and non-laser ophthalmic a program and under an ophthal- surgery. To become a certifi ed Injections in Georgia mologist’s supervision. Despite optometrist in ophthalmic surgery, Georgia optometrists are wag- pushback from Georgia oph- clinicians would have to success- ing another legislative battle, thalmologists, the bill passed the fully complete a course and subse- this time for the right to perform Senate 34 to 17 on March 3 and is quent examination, approved by injections. Senate bill 221 would now under review in the House.

6 REVIEW OF OPTOMETRY APRIL 15, 2017

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Stem Cells: Handle with Care

recent study reveals a new ception, the NEJM article found.3 stem cell identifi cation To Dr. Thimons, what is most BUSINESS OFFICES 11 CAMPUS BLVD., SUITE 100 Amethod that may eventually concerning about the report is that NEWTOWN SQUARE, PA 19073 allow doctors to restore vision to both eyes of the patients were oper- CEO, INFORMATION SERVICES GROUP patients with damaged corneas. Us- ated on in the same day, which is MARC FERRARA ing a technique that involves highly atypical in clinical trials; even many (212) 274-7062 • [email protected] sensitive atomic force microscopy, routine surgical procedures are not PUBLISHER JAMES HENNE researchers put pressure on certain performed bilaterally same-day. (610) 492-1017 • [email protected]

cells to better understand their abil- These cases highlight the signifi - REGIONAL SALES MANAGER 1 ity to transform into mature cells. cant risk clinics touting the restor- MICHELE BARRETT The researchers were able to ative benefi ts of unproven stem cell (610) 492-1014 • [email protected] differentiate limbal cells as softer therapy pose to the population, as REGIONAL SALES MANAGER MICHAEL HOSTER and more fl exible than other cells well as to future stem cell research. (610) 492-1028 • [email protected]

studied. Because of this, the new “You’d hate to see stem cells as a VICE PRESIDENT, OPERATIONS method shows potential as a quick technology placed into a negative CASEY FOSTER identifi cation system to fi nd trans- public view,” says Dr. Thimons. “It (610) 492-1007 • [email protected] plantable cells in a patient’s own doesn’t take a great leap of faith VICE PRESIDENT, CLINICAL CONTENT PAUL M. KARPECKI, OD, FAAO tissue. Researchers also developed a to believe that a negative headline [email protected]

new microfl uidic cell-sorting device like this could impact the future of PRODUCTION MANAGER that could speed up the existing cell legitimate studies.” SCOTT TOBIN sorting process. To prevent such issues, he stresses (610) 492-1011 • [email protected] “Studies are on track to show the importance of patient-clinician SENIOR CIRCULATION MANAGER HAMILTON MAHER that this could be a very helpful communication when a patient is (212) 219-7870 • [email protected]

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a report recently published in the allowed investigators to not only CIRCULATION New England Journal of Medicine identify transplantable cells but PO BOX 81 CONGERS, NY 10920 (NEJM) highlights the potential also sort them quickly holds huge TEL: (TOLL FREE): (877) 529-1746 dangers of stem cell therapy if not promise for the future—and clini- OUTSIDE US: (845) 267-3065 handled properly. The report details cians shouldn’t let negative reports three women who lost sight after of mishandled therapies stymie undergoing stem cell treatment for enthusiasm. “My hope is that we CEO, INFORMATION SERVICES GROUP macular degeneration at a Florida will look at this as a profession and MARC FERRARA

clinic. Clinic staff extracted stem understand the potential of stem SENIOR VICE PRESIDENT, OPERATIONS cells from the patients’ own belly fat cells, and that incidents like these JEFF LEVITZ

to inject into the eyes, according to are isolated,” says Dr. Thimons. VICE PRESIDENT, HUMAN RESOURCES a New York Times article.2 TAMMY GARCIA 1. Bongiorno T, Chojnowski JL, Lauderdale JD, Sulchek T. Clinicians not associated with the Cellular stiffness as a novel stemness marker in the corneal VICE PRESIDENT, CREATIVE SERVICES & PRODUCTION limbus. Biophysical Journal. 2016;111(8):1761-72. MONICA TETTAMANZI Florida clinic found the patients’ 2. Grady D. Patients lose sight after stem cells are injected entering acuities ranged from 20/30 into their eyes. NYTimes. March 15, 2017. www.nytimes. CORPORATE PRODUCTION DIRECTOR com/2017/03/15/health/eyes-stem-cells-injections.html. JOHN ANTHONY CAGGIANO to 20/200; one year after the injec- Accessed March 20, 2017. tions, the patients’ visual acuities 3. Kuriyan AE, Albini TA, Townsend TH. Vision loss after intravit- VICE PRESIDENT, CIRCULATION real injection of autologous “stem cells” for AMD. N Engl J Med. EMELDA BAREA ranged from 20/200 to no light per- 2017;376:1047-53.

8 REVIEW OF OPTOMETRY APRIL 15, 2017

0004_ro0417_news.indd04_ro0417_news.indd 8 44/3/17/3/17 2:482:48 PMPM Stress & AMD (continued from page 4) are related to increased cortisol levels, susceptibility to infection, increased proinfl ammatory cyto- kines and slow wound healing, to name just a few negative health outcomes. “A fi rst step optometrists could take is using a survey such as the Perceived Stress Scale to formally evaluate perceived stress levels,” AW]¼ZM Dr. Dougherty says. “From there, optometrists could familiarize TMI^QVOUM° themselves with local mental health providers and with other IZMV¼\aW]' strategies that could be effective for patients to manage their own stress.” The authors also note previous research found perceived stress as measured by the PSS can be predictive of infl ammation—and AMD is an infl ammatory disease. “We are investigating the rela- tionships among stress and things such as visual acuity, change in vision with treatment and self- reported visual function,” Dr. Parasol® Dougherty says. “We are also interested in determining whether the increased infl ammation that Trust us. We’re not like the others. can result from high levels of Patients shouldn’t fear their tears will disappear stress may negatively affect AMD treatment results. To accomplish because their plugs up and left. Help them face this, we are measuring C-reactive life with eyes wide open and comfortably moist. protein levels, which are known Trust the Parasol Punctal Occluder; it’s the perfect to be associated with AMD fi t for your patients — and guaranteed to stay put. incidence, and investigating how those might be related to treat- 866-906-8080 ment outcomes.” [email protected] As research digs deeper into beaver-visitec.com the relationship between stress and disease progression, clinicians can treat the whole patient now, and the PSS is a good tool to start with, the study concluded. ■

Dougherty BE, Cooley SL, Davidorf FH. Measurement of perceived stress in age-related macular degeneration. Optom Vis Sci. 2017;94(3):290-6. Beaver-Visitec International, Inc., 411 Waverley Oaks Road, Waltham, MA 02452. BVI, BVI Logo and all other trademarks (unless noted otherwise) are property of Beaver-Visitec International (“BVI”) © 2017 BVI

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RRO0317_BLO0317_BL AAccess.inddccess.indd 1 33/1/17/1/17 2:202:20 PMPM Contents th Review of Optometry April 2017 10 Annual Pharmaceuticals Report How Antibiotics Work 30 —and Why They Sometimes Don’t Before reaching for the Rx pad, know the drug, the patient and the disease. By Bruce Onofrey, OD, RPh

Anti-inflammatories: Sort Out 40 Your Many Steroids and NSAIDs With so many medications out there, treatment can get complicated. Here is a rundown of your options and when to use them. By Laine Higa, OD

Glaucoma Therapy: Finding 46 the Right Combination Understanding the basic pharmacology for each glaucoma medication can help you sort out which ones work well together for combination treatment. By Susan Yee, OD

Dry Eye: Master the Science 56 Beneath the Surface Learn how inflammatory mediators govern the disease course—and provide an avenue to treatment. By Michelle Hessen, OD

Resist the Itch: Managing 64 Allergic Conjunctivitis Flowers may be blooming, but this season leaves many ODs seeing red. By Charissa Young, OD

EARN 2 CE CREDITS 70 Don’t Be Stumped by These Lumps and Bumps Most eyelid lesions are benign, but some can lead to severe clinical outcomes if not caught early. By Rodney Bendure, OD, and Jackie Burress, OD

REVIEW OF OPTOMETRY APRIL 15, 2017 11

011_ro0417_toc.indd 11 4/4/17 5:24 PM Departments On The Web ›› Review of Optometry April 2017 and more

4 News Review Check out our multimedia and continuing education online at: 15 Outlook www.reviewofoptometry.com It’s Like Pulling Teeth JACK PERSICO Digital Edition 16 Through My Eyes Left your copy of Dollars and Sense Review of Optometry at PAUL M. KARPECKI, OD the office? No problem! Access Review on your 18 Chairside computer or mobile device! Haters Gonna Hate Go to www.reviewofoptometry. MONTGOMERY VICKERS, OD 20 com and click on the digimag link 20 Clinical Quandaries for the current issue. Tonometry: To Dye For? Facebook and Twitter PAUL C. AJAMIAN, OD For daily updates, “Like” 22 Urgent Care our page on Facebook or Find the Nerve to Fight Diplopia “Follow” us on Twitter! CECELIA KOETTING, OD, AND • www.facebook.com/revoptom RICHARD MANGAN, OD • http://twitter.com/#!/revoptom 26 Coding Connection Caring for the Chronic Patient JOHN RUMPAKIS, OD, MBA Look for augmented content and special offers from Review and 81 Focus on Refraction our advertisers. Specified pages Low-Tech TBI Rehabilitation 22 work in conjunction with your PAUL HARRIS, OD, AND smartphone or other mobile MARC B. TAUB, OD, MS device to enhance the experience. With Layar, interactive content 84 Neuro Clinic leaps off the page! Imaging for Unilateral Proptosis MICHAEL TROTTINI, OD, AND MICHAEL DELGIODICE, OD

86 Retina Quiz Scrambling For a Diagnosis Step1: Download the free Layar TEA AVDIC, OD, AND app for iPhone or Android. MARK T. DUNBAR, OD

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INTERACTIVE PRINT 91 Surgical Minute Extend Your Patient’s Vision JILLIAN JANES, OD, WALTER WHITLEY, OD, MBA, AND DEREK N. CUNNINGHAM, OD Step 3: Open the Layar app, hold the phone above the page 93 Product Review and tap to scan it. Hold the phone above the page to view 93 Advertisers Index the interactive content. 94 Classifieds The first 150 app downloads and completed forms will be entered into a drawing for a 98 Diagnostic Quiz complimentary registration to one of Review’s Bullseye 98 14-hour CE meetings, valued at $495. ANDREW S. GURWOOD, OD

12 REVIEW OF OPTOMETRY APRIL 15, 2017

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RO0417_Shire.indd 1 3/23/17 1:58 PM CONTRIBUTING EDITORS PAUL C. AJAMIAN, OD, ATLANTA AARON BRONNER, OD, KENNEWICK, WASH. MILE BRUJIC, OD, BOWLING GREEN, OHIO ATTRACT NEW DEREK N. CUNNINGHAM, OD, AUSTIN, TEXAS MARK T. DUNBAR, OD, MIAMI ARTHUR B. EPSTEIN, OD, PHOENIX JAMES L. FANELLI, OD, WILMINGTON, NC PATIENTS FRANK FONTANA, OD, ST. LOUIS GARY S. GERBER, OD, HAWTHORNE, NJ ANDREW S. GURWOOD, OD, PHILADELPHIA ALAN G. KABAT, OD, MEMPHIS, TENN. WITH A WEBSITE THEY WON’T BE DAVID KADING, OD, SEATTLE ABLE TO RESIST. CONTACT US FOR A PAUL M. KARPECKI, OD, LEXINGTON, KY. JEROME A. LEGERTON, OD, MBA, SAN DIEGO FREE EVALUATION AND RECEIVE JASON R. MILLER, OD, MBA, POWELL, OHIO CHERYL G. MURPHY, OD, BABYLON, NY 40% OFF SETUP! CARLO J. PELINO, OD, JENKINTOWN, PA. JOSEPH PIZZIMENTI, OD, FORT LAUDERDALE, FLA. JOHN RUMPAKIS, OD, MBA, PORTLAND, ORE. DIANA L. SHECHTMAN, OD, FORT LAUDERDALE, FLA. JEROME SHERMAN, OD, NEW YORK JOSEPH P. SHOVLIN, OD, SCRANTON, PA. JOSEPH W. SOWKA, OD, FORT LAUDERDALE, FLA. MONTGOMERY VICKERS, OD, ST. ALBANS, W.VA. WALTER O. WHITLEY, OD, MBA, VIRGINIA BEACH, VA.

EDITORIAL REVIEW BOARD L JEFFREY R. ANSHEL, OD, ENCINITAS, CALIF. R JILL AUTRY, OD, RPH, HOUSTON SHERRY J. BASS, OD, NEW YORK EDWARD S. BENNETT, OD, ST. LOUIS MARC R. BLOOMENSTEIN, OD, SCOTTSDALE, ARIZ. CHRIS J. CAKANAC, OD, MURRYSVILLE, PA. JERRY CAVALLERANO, OD, PHD, BOSTON WALTER L. CHOATE, OD, MADISON, TENN. BRIAN CHOU, OD, SAN DIEGO A. PAUL CHOUS, MA, OD, TACOMA, WASH. ROBERT M. COLE, III, OD, BRIDGETON, NJ GLENN S. CORBIN, OD, WYOMISSING, PA. ANTHONY S. DIECIDUE, OD, STROUDSBURG, PA. S. BARRY EIDEN, OD, DEERFIELD, ILL. STEVEN FERRUCCI, OD, SEPULVEDA, CALIF. MURRAY FINGERET, OD, HEWLETT, NY IAN BEN GADDIE, OD, LOUISVILLE, KY. MARC HARRIS, OD, MEMPHIS, TN MILTON HOM, OD, AZUSA, CALIF. BLAIR B. LONSBERRY, MS, OD, MED, PORTLAND, ORE. THOMAS L. LEWIS, OD, PHD, PHILADELPHIA DOMINICK MAINO, OD, MED, CHICAGO KELLY A. MALLOY, OD, PHILADELPHIA RICHARD B. MANGAN, OD, LEXINGTON, KY. RON MELTON, OD, CHARLOTTE, NC PAMELA J. MILLER, OD, JD, HIGHLAND, CALIF. BRUCE MUCHNICK, OD, COATESVILLE, PA. MARC MYERS, OD, COATESVILLE, PA. WILLIAM B. POTTER, OD, FREEHOLD, NJ CHRISTOPHER J. QUINN, OD, ISELIN, NJ MICHAEL C. RADOIU, OD, STAUNTON, VA. MOHAMMAD RAFIEETARY, OD, MEMPHIS, TN JOHN L. SCHACHET, OD, ENGLEWOOD, COLO. JACK SCHAEFFER, OD, BIRMINGHAM, ALA. LEO P. SEMES, OD, BIRMINGHAM, ALA. LEONID SKORIN, JR., OD, DO, ROCHESTER, MINN. JOSEPH W. SOWKA, OD, FORT LAUDERDALE, FLA. SRUTHI SRINIVASAN, PhD, BS OPTOM, WATERLOO, ONT. BRAD M. SUTTON, OD, INDIANAPOLIS LORETTA B. SZCZOTKA, OD, PHD, CLEVELAND 877.716.0927 PAUL TAUB, OD, MEMPHIS, TN TAMMY P. THAN, MS, OD, BIRMINGHAM, ALA. go.imatrix.com/ReviewOptometry RANDALL THOMAS, OD, CONCORD, NC SARA WEIDMAYER, OD, ANN ARBOR, MI KATHY C. WILLIAMS, OD, SEATTLE KAREN YEUNG, OD, LOS ANGELES

011_ro0417_toc.indd 14 4/4/17 5:24 PM Outlook By Jack Persico, Editor-in-Chief PRINTED IN USA

FOUNDING EDITOR, FREDERICK BOGER 1891-1913

EDITORIAL OFFICES It’s Like Pulling Teeth 11 CAMPUS BLVD., SUITE 100 NEWTOWN SQUARE, PA 19073 The dental model of practice has long been touted as an WEBSITE • WWW.REVIEWOFOPTOMETRY.COM

SUBSCRIPTION INQUIRIES inspiration for optometry. Is it finally starting to work? 1-877-529-1746 CONTINUING EDUCATION INQUIRIES ow often do I envy ity as they integrate with Luxottica 1-800-825-4696 the dentist across the and become the biggest conduit to EDITOR-IN-CHIEF • JACK PERSICO corridor?” an optom- the consumer in eye care. Essilor and (610) 492-1006 • [email protected] “H etrist lamented in a prior issue of others have long been supporters MANAGING EDITOR • REBECCA HEPP (610) 492-1005 • [email protected] this magazine. “He has his patients of Think About Your Eyes. Alcon SENIOR EDITOR • BILL KEKEVIAN trained to appear before him every recently pledged to give $5 to the (610) 492-1003 • [email protected] six months to have their teeth exam- program for every annual supply of ASSOCIATE EDITOR • MICHAEL RIVIELLO (610) 492-1021 • [email protected] ined. They come as if they were its daily or monthly contact lenses ASSOCIATE EDITOR • MICHAEL IANNUCCI glad to come. They ought to be. But purchased, to encourage healthy (610) 492-1043 • [email protected] when I send notices to my patients wear schedules and support the cam- SPECIAL PROJECTS EDITOR • JILL HOFFMAN (610) 492-1037 • [email protected] that they should come to me for an paign’s public advocacy goals. ART DIRECTOR • JARED ARAUJO annual examination of their eyes, Sure, these corporate efforts ben- (610) 492-1032 • [email protected] they ignore the notices and I may not efit the bottom lines of manufactur- DIRECTOR OF CE ADMINISTRATION • REGINA COMBS (212) 274-7160 • [email protected] see them for another year. Yet their ers, but they also help people modify

EDITORIAL BOARD eyes are getting older every day.” their lifestyles in ways that promote CHIEF CLINICAL EDITOR • PAUL M. KARPECKI, OD It’s a familiar refrain, and you’ve health and wellness—a too-rare con- ASSOCIATE CLINICAL EDITORS • JOSEPH P. SHOVLIN, OD; likely felt it too. What’s striking fluence of capitalism and altruism. ALAN G. KABAT, OD; CHRISTINE W. SINDT, OD about this quote isn’t the message, But it’s been a long road. “The DIRECTOR OPTOMETRIC PROGRAMS • ARTHUR EPSTEIN, OD CLINICAL & EDUCATION CONFERENCE ADVISOR it’s the vintage. That article appeared public acts in some ways as if it PAUL M. KARPECKI, OD in 1930. Yes, optometry has been doesn’t care a continental about its CASE REPORTS COORDINATOR • ANDREW S. GURWOOD, OD swooning over the much-vaunted eyesight,” our 1930 author wrote. CLINICAL CODING EDITOR • JOHN RUMPAKIS, OD, MBA dental model of practice at least (If you’re unfamiliar with old slang, CONSULTING EDITOR • FRANK FONTANA, OD since Herbert Hoover was president. care a continental = give a damn.) COLUMNISTS Our depression-era author was After literally decades of frustra- CHAIRSIDE • MONTGOMERY VICKERS, OD quick to stress that he wasn’t moti- tion, we’re finally seeing results. The CLINICAL QUANDARIES • PAUL C. AJAMIAN, OD vated by self-interest. “Keep in mind, Vision Council says Think About CODING CONNECTION • JOHN RUMPAKIS, OD CORNEA & CONTACT LENS Q+A • JOSEPH P. SHOVLIN, OD please, that I am not complain- Your Eyes generated 1.15 million eye DIAGNOSTIC QUIZ • ANDREW S. GURWOOD, OD ing of lack of practice on my own exams in 2016, a 38% increase over THE ESSENTIALS • BISANT A. LABIB, OD account,” he wrote. “I am comment- 2015. Even better: exam cycles short- FOCUS ON REFRACTION • MARC TAUB, OD; ing on the common heedlessness of ened from 24 to 14 months. That’s PAUL HARRIS, OD GLAUCOMA GRAND ROUNDS • JAMES L. FANELLI, OD the public in regard to its eyes, the solid progress. But there’s more work NEURO CLINIC • MICHAEL TROTTINI, OD; most useful and the most blessed to do if your practice is still less pop- MICHAEL DELGIODICE, OD part of the human anatomy.” ular than one where someone puts a OCULAR SURFACE REVIEW • PAUL M. KARPECKI, OD In other words, the template for drill in the patient’s mouth. RETINA QUIZ • MARK T. DUNBAR, OD REVIEW OF SYSTEMS • CARLO J. PELINO, OD; today’s Think About Your Eyes pub- At each visit and in your market- JOSEPH J. PIZZIMENTI, OD lic education campaign was written ing, stress that routine care allows SURGICAL MINUTE • DEREK N. CUNNINGHAM, OD; on a Remington typewriter while disease prevention, makes early WALTER O. WHITLEY, OD, MBA THERAPEUTIC REVIEW • JOSEPH W. SOWKA, OD; Louis Armstrong played on the radio. treatment possible, and helps people ALAN G. KABAT, OD I was thinking about the long his- feel and see better. With industry THROUGH MY EYES • PAUL M. KARPECKI, OD tory of this sentiment during a press support reaching mass audiences and URGENT CARE • RICHARD B. MANGAN, OD briefing from Essilor at Vision Expo. ODs personalizing the message in JOBSON MEDICAL INFORMATION LLC The company’s execs mentioned that their communities, public attitudes “giving vision a louder voice” in the can change for the better. Even if it public discourse will be a top prior- sometimes feels like pulling teeth. ■

REVIEW OF OPTOMETRY APRIL 15, 2017 15

015_ro0417_outlook.indd 15 4/4/17 5:28 PM Through My Eyes By Paul M. Karpecki, OD, Chief Clinical Editor Dollars and Sense We need to recognize that our responsibility to patients doesn’t end at the Rx pad.

tudies show that, beginning forward-thinking ophthalmologists are paying high deductibles in the this year and increasing for the as well) have since realized that the first few months of the year. In Sforeseeable future, the supply enormous need for eye care services response, it has created a program of ophthalmologists is no longer simply requires that optometrists that allows patients to pay next to sufficient to meet the demand for provide most routine eye care so nothing for their first three-month cataract removal and other surgi- that ophthalmologists can concen- supply of Restasis. cal procedures. The number of trate on surgery. • Shire has been able to place new ophthalmology graduates has Unfortunately, all this evolution Xiidra on over 80% of commercial remained stagnant for some time, and cooperation can be undone by insurance plans within a year of its while demand for eye care is soar- one inescapable problem: even the approval, which is relatively quick. ing. This leaves an incredible void best medication—prescribed with The company also offers a free and an opportunity we are wise to care and attention by a well-trained 60-vial tray to patients with their embrace: medical eye care. OD—is useless if patients can’t first prescription. Our profession has risen to the afford to get it. That “last mile” of • Sun Pharmaceutical offers a challenge admirably. Optometric getting the drop into their hands is program that essentially provides colleges have been training new often the toughest slog. BromSite free to most first-time grads in medical therapeutics and Restrictive insurance formular- users. clinical procedures since before we ies shouldn’t undo all the care and • Alcon has a program for Pazeo had the laws to perform them, and attention you’ve given your patient for allergic conjunctivitis where our legislative advocates have been in the exam room. Although gener- qualifying patients pay no more tireless in pushing for the freedom to ics are sometimes an option, they than $10. This wouldn’t apply to put those skills to use for the public. can still be expensive in many patients enrolled in Medicare Part Industry has stepped up and cases. For example, various generic D, Medicaid or other government- supported us, too. When I entered steroids cost more than $100 to sponsored healthcare programs with practice in the 1990s, it was still patients paying out of pocket. a pharmacy benefit. somewhat controversial for phar- Drug companies are seeking to • Akorn has an RxAssist program maceutical companies to detail ODs ensure their pharmaceuticals are to help patients afford their antibiot- and advertise their products to us financially obtainable for a broad ic and glaucoma medications. Aller- in journals like this one. Not any swath of patients. Most provide gan, Alcon, Shire, B+L/Valeant and more. Drug manufacturers (and assistance to those in need. Here Sun also have patient assistance pro- are some key programs we can take grams that allow indigent patients Resources For Finding advantage of to help our patients: to access drugs at reduced cost or, in Affordable Meds • Bausch + Lomb offers an option some cases, no charge. whereby patients in need pay no Until healthcare costs are con- goodrx.com more than $35 for their portfolio of trolled in an all-encompassing Finds the best price at local drug stores medications, including Bepreve for way—and none of us should hold and automatically downloads any allergic conjunctivitis at $10. The our breath waiting for that—it will available coupons. caveat: it won’t apply to patients fall to us to “work the system” on ■ needymeds.org who are enrolled in Medicare, and behalf of our patients. Provides downloadable discount cards patients must fill their prescriptions Relevant financial disclosures: and links to patient assistance programs at Walgreens or a participating inde- Akorn, Aerie Pharmaceutical, available from drug manufacturers. pendent pharmacy. Alcon, Allergan, Bausch + Lomb, • Allergan has found that patients Shire, Sun Pharmaceuticals.

16 REVIEW OF OPTOMETRY APRIL 15, 2017

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RCCL0315_Menicon.indd 1 2/23/15 11:15 AM Chair Side

Haters Gonna Hate It’s a complex emotion reserved for rare occasions—you know, no shows, online glasses sales and patients presenting with a complaint. By Montgomery Vickers, OD

ate is such a damaging will no doubt get angry right back; one’s eye except in very rare cases word, isn’t it? Webster’s and since the other person is angry of someone who totally deserves it, Hdefines it as “intense hostil- at you now, you will feel vindicated like a diabetic who is three months ity.” Do you have intense hostility for being angry in the first place. It’s late for their yearly examination, toward something? Could it be the a win-win. for example. election … for chairman of dea- I guess cussing out a no show Sense of injury means you prob- cons at the church? Perhaps free will, nearly 100% of the time, solve ably see it coming in the first place, eye examination advertising? No the problem. They will never, ever so you can clear it up ahead of time shows? People who serve white schedule an appointment again, so by turning them over to collections, wine with beef bourguignon? (OK, you no longer have to fret they will for example (to prevent your hate) that’s one I understand.) no show. Problem solved. or giving them an official office “Intense hostility” turns out to be Anger certainly has some advan- t-shirt (to prevent their hate). Find a the least important part of the defi- tages. If you get a dry eye patient way to smell injury in the air before nition. Webster’s goes on to say why mad enough, their eyes will water the actual injury occurs. That’s why hate occurs: because of “fear, anger and they won’t need punctal occlu- we teach contact lens insertion and and sense of injury.” sion. Raise enough Cain and your removal, check IOPs and ask about receptionist will stop chewing gum their vision plans before they show Fear all day, or at least swallow it when up all crazy and cocksure. Fear produces a rush of adrenaline you appear. I could go on and on. causing our heart rate to increase Get angry and watch your problems Hate is never really appropriate, and our brain to get ready for fight melt away. Maybe. although there are certainly excep- or flight, or maybe explain why we tions. Why else would it be in charge extra for a contact lens fit- Sense of Injury Webster’s? OK, it can get confusing. ting. Sometimes fear is immediate, Hate doesn’t come from actual I hate when that happens. ■ like when a patient says, “Doctor, injury, but from sense of injury. If I have a complaint.” Sometimes it you put peroxide-based contact lens is subtle, slow and debilitating, like cleaning solution in a patient’s eye, when your wife says, “Let’s talk it will cause actual injury. Pain, not about planning a trip tonight.” Or hate, is the final outcome. There your son keeps asking for his Rx to will be plenty of hate later when buy glasses online. their eye isn’t killing them. By the But remember, the body’s way, I would not response to fear is identical to its advise putting response to elation. It’s your choice peroxide how to handle it. For me, moping in any- around the office all day seems to help. It means I am very, very happy, obviously. Anger Does getting angry work? Sure it does! Whoever you are angry with

18 REVIEW OF OPTOMETRY APRIL 15, 2017

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RO0417_MS Technology.indd 1 3/23/17 1:47 PM Clinical Quandaries

Tonometry: To Dye For? Even fundamental techniques deserve skepticism and reinvention. Edited by Paul C. Ajamian, OD Q I would like to streamline my hydrochloride ophthalmic solution, exam in every way possible and USP, 0.25%/0.4%, Akorn) contains heard from a colleague that they don’t too much fluorescein to be of value use fluorescein to obtain Goldmann in tonometry. “Invariably, the mires pressures. What’s your take on this? are huge and distorted, requiring a A Sam Quintero, OD, adjunct delay for the solution to dissipate associate professor at and the mires to thin, rendering it University of Houston College of ineffective and a big waste of time.” Optometry, says he hasn’t used Recent research reveals IOP is fluorescein in years and experiences lower—a mean difference of 1.4mm excellent results when perform- The mires are crystal clear without Hg—when tonometry is used with- ing tonometry—and forgoing it fluorescein, as seen in this photo. out fluorescein.1 Older literature saves him a step in the process. He shows much greater differences—up encourages students to aperform to measure IOP in the first eye; by to 7mm Hg—than anecdotal data.2 Goldmann tonometry without it. He the time they get to the second eye, Andrea Knouff, OD, founder of notes that “students don’t challenge you guessed it, they now have to Eyeclectic Vision Source in Atlanta, the modalities as taught,” but he instill the fluorescein again and, as hasn’t used fluorescein in clini- encourages them to question long- a consequence, it can take as much cal practice for a number of years standing practices. “For instance, as seven to eight extra minutes either. “I find a high correlation the sole purpose of the dye in to complete this procedure—one between results with and without Goldmann tonometry is to enhance that should have lasted approxi- dye, and so have chosen to do the observation of the tear film,” mately one minute total,” says Dr. without it,” eliminating a step and which can be accomplished without Quintero. Another problem he sees saving valuable chair time, says Dr. dye, with practice, he says. with students: On occasion, they Knouff. “If I ever have a question, spill a drop on the patient’s clothing. or the mires are too faint, I can Overcoming Assumptions “And now you have an unhappy always put a dry strip in the eye and When Dr. Quintero presents the patient, no matter what you say or light up the mires a bit,” she says. concept of going without fluorescein how much you reassure them” that Forgoing fluorescein also preserves to students, he tells them I don’t the dye won’t permanently stain the patient’s contact lenses when use fluorescein when I measure IOP Nevertheless, Dr. Quintero tells they are reinserted at exam’s end. with the Goldmann tonometer, and his students to be aware of the Dr. Knouff advises ODs rely on I will have the students look through expectations from other attending our other tried-and-true methods the teaching tube and emphasize ODs and not to engage in quarrels. and tests of detecting glaucoma. that they look for the tear layer. “I However, he also cautions them to “Use careful stereoscopic nerve like to seek out new ways to arrive “do as the National Board requires evaluations, pachymetry, fields at the same answer in a more effi- and perform tonometry as described and OCTs for glaucoma diagnosis, cient manner,” says Dr. Quintero. “I on the skills assessments for this instead of putting too much empha- am an efficiency fanatic and spend technique—one must use the dye or sis on IOP readings alone.” ■ as little time arriving at the correct else you fail this skill on Part III.” 1. Arend N, Hirneiss C, Kernt M. Differences in the measure- answer as possible.” ment results of Goldmann applanation tonometry with and Here is the typical with-dye sce- Flush the Fluress without fluorescein. Ophthalmologe. 2014 Mar;111(3):241-6. 2. Bright DC, Potter JW, Allen DC, Spruance RD. Goldmann nario, according to Dr. Quintero: Dr. Quintero suggests Fluress applanation tonometry without fluorescein. Am J Optom Physiol “Some students take too long (fluorescein sodium and benoxinate Optom. 1981 Dec;58(12):1120-6.

20 REVIEW OF OPTOMETRY APRIL 15, 2017

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Find the Nerve to Fight Diplopia When a patient’s double vision is caused by a cranial nerve palsy, ODs must act quickly. By Cecelia Koetting, OD, and Richard Mangan, OD

ouble vision rent glasses. Red is a com- desaturation and Dplaint that color vision were can bring a dull, sick normal and no feeling to an optom- afferent pupillary etrist’s stomach. defect was noted Diplopia can develop at the exam. Ver- from a host of sions and ductions pathologies including reveal a complete dry eye, cranial nerve loss of abduction (CN) palsies and in the right eye retinal issues.1 We and full range of know these patients motion in the left require a thorough (Figure 1). In pri- case history and mary gaze, prism some quality chair measurement time to diagnose showed a 40PD properly and get to esotropia, OD. the cause of the prob- External examina- lem. When patients tion was normal present with a CN Fig. 1. Note the normal movement of the eyes gazing to the left and straight in each eye, and palsy causing double in the top two photos. The bottom photo shows the patient’s eyes in right dilated fundus vision, optometrists gaze and her inability to fully abduct the right eye. exam revealed no are tasked with abnormalities. isolating which nerve or nerves that the patient self reports was are involved and, ultimately, the normal. How We Handled It underlying cause. The patient had no prior his- We performed a forced duction test tory of strabismus or any ocular on the right eye, which was nega- The Patient surgery, but did have a history of tive. The patient’s blood pressure A 63-year-old woman presented to lung cancer in 2005 and relapse in was checked in office and found to our office for examination with a 2014. When asked in clinic if her be 140/80 using her right arm. chief complaint of new-onset dip- double vision improves with one Based on her presentation, we lopia starting approximately two eye covered, the patient stated determined it was most likely a months earlier. She described it as that it goes away when her right VI CN palsy. The most common “side-by-side images” and even eye is covered. cause of VI CN palsy is ischemia occasional “triple vision.” She also A former smoker, she had quit due to either diabetes or hyperten- reported an increase in headaches approximately 12 years earlier. sion. The next most common are for and that her overall vision had She also had hypertension and tumor or increased intracranial decreased. Also of note, the patient hyperlipidemia, which she was pressure. If the medical history sup- was established with a neurolo- controlling medically. She was ports uncontrolled hypertension or gist and was last seen two months not diabetic or borderline dia- diabetes, imaging at the initial pre- earlier, at which point magnetic betic. Best-corrected visual acuity sentation may not be necessary. In resonance imaging (MRI) was done was 20/20 OU through her cur- this case, the medical history does

22 REVIEW OF OPTOMETRY APRIL 15, 2017

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not support an ischemic and patients will often cause, so we recommended turn their head to avoid imaging. That same day, double vision. the patient underwent MRI This leaves CN III to and magnetic resonance control all the other extra- venography (MRV) of the ocular muscles and, when head and orbit with and affected, tends to be the without contrast. most dramatic, leaving the Blood work including eye in a “down and out” erythrocyte sedimentation position.5 CN III also con- rate, C-reactive protein, trols the innervation of the and a complete blood levator muscle, which, if count with A1c was also paralyzed, may also result ordered. in ptosis.5 The parasympa- The results of her blood thetic pupillary constrict- work were normal, but ing fibers travel along the the MRI and MRV both external portion of the CN had significant findings. III, which may be affected Compared with her MRI during a compressive two months prior, a sizable lesion or aneurysm.3 An (2.1x1.6x2.4cm) peri-sphe- APD can be a sign of an noid lesion abutting the right aneurysm, which is emer- cavernous sinus and involv- gent.3 ing right Meckel’s cave was When any one of these detected (Figure 2). three cranial nerves is Additionally, two small- Fig. 2. This is our patient’s FLAIR MRI with contrast of the palsied it can result in dip- er enhancing brain nodules head. The red arrow is pointing to the 2.1x1.6x2.4cm lopia, and the nerve expe- were found in the left para- peri-sphenoid lesion abutting the right cavernous sinus and riencing the palsy should falcine occipital lobe and involving right Meckel’s cave be identified.2-4,6 With CN in the left frontal lobe. All III palsy, it is extremely were considered suspicious for lung Anatomy important to monitor for pupil- cancer metastases. Cranial nerves III, IV and VI lary involvement at the time of the control our extraocular muscles exam and in the coming weeks Follow-up and each plays a specific role in thereafter. With the cause identified, it was the movement of our eyes. CN time for our patient’s neurolo- IV controls our superior oblique Causes gist and neurosurgeon to take muscles, which control intor- Studies show that the most preva- charge in treatment. But our roles sion, depression and abduction.2,3 lent ocular CN palsy is that of CN as optometrists were not over. Loss of this muscle’s function VI, followed by CN III and then Working closely with neurology causes an upward deviation of the CN IV.7-11 The most common cause during treatment is vital to show- affected eye with a cyclotorsion of acquired palsy in all three is ing improvement in the lesion and that causes the patient to tilt their ischemic changes from vascular dis- its effects. head away from the lesion.2,3 eases including diabetes, hyperten- The patient underwent five This is the most common cause sion and atherosclerosis.2,12 rounds of radiation and came in of acquired vertical diplopia Mass lesions both in the orbit every four weeks for versions/ that is worse on downgaze.4 CN and in the brain are likely causes as duction testing and visual fields. VI controls our lateral rectus well for CN III, IV and VI palsies. While all cases may not need to muscle, which controls abduc- Depending on the location, a lesion be seen this frequently, all CN tion.5 With loss of innervation to or aneurysm on CN III can cause palsies should be monitored for this muscle, we are unable to turn pupillary involvement. improvement. the eye away from the midline Trauma is the third most com-

24 REVIEW OF OPTOMETRY APRIL 15, 2017

022_ro0417_Urgent.indd 24 3/30/17 12:09 PM Finally: Tear Stimulation mon cause of these ocular palsies, with a higher occurrence of CN IV palsies related to the long dis- tance it covers inside the cranial vault.5,9-11 Eye Drops Although not common, research shows a CN VI palsy can occur with giant cell arteritis (GCA).13 Treatment In CN palsy cases involving the III, IV or VI nerve where the likely cause is ischemia, the patient should be monitored for improvement approximately a Dry Eye month after onset to make sure it is resolving. It may take three to six months before it is completely resolved. However, if a patient is appropriately mak- ing changes in blood sugar or blood pressure with their primary care doctor and not showing improve- ment in muscle movement recovery, it may indicate another pathology and warrant imaging. If the cause is indeterminate at the time of diagnosis, or a CN III ProfessionalProfessional Quality Q palsy presents with an afferent pupillary defect, an Only Available Via Doctors MRI and MRV of head and orbit with and without t
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DPOUBDUT your patient caused by a CN palsy is more than just good care. It can be lifesaving. ■ Dr. Koetting practices at Virginia Eye Clinic, where she leads the externship program. Meet us at COVD 1. Gerstenblith A, Rainowitz M. The Wills Eye Manual: Office and Emergency Room in Jacksonville Diagnosis and Treatment of Eye Disease, 6th ed. Philadelphia: Lippincott Williams and Wilkins;2012:2-3. 2. Miller N, Walsh F, Hoyt W. Walsh and Hoyt’s Clinical Neuro-ophthalmology, 6th edition. Philadelphia: Lippincott Williams & Wilkins. 2008. 3. Leigh J, Zee DS. The Neurology of Eye Movements. New York: Oxford University Try a dozen bottles on Press;2015. 4. Marais W, Barrett S. An overview of the third, fourth and sixth cranial nerve palsies. Con- your toughest patients. tinuing Medical Education [Online]. 2013;31(4):147-152. 5. Remington LA. Clinical anatomy of the visual system, 3rd edition. Philadelphia: Elsevier 12 @ $6.39 ea = $76.68 Health Science. 2011. 190-4. 100% money back guarantee 6. Miller N, Newman N. Walsh and Hoyt’s Clinical neuro-ophthalmology 5th edition. Balti- more: Williams & Wilkins;1998:1194-223. 7. Park U, Kim S, Hwang J, Yu Y. Clinical features and natural history of acquired third, fourth and sixth cranial nerve palsy. Eye. 2008:22(5)691-6. Call today 877-220-9710 8. Rucker CW. Paralysis of the third, fourth and sixth cranial nerves. Am J Ophthalmol. 1958;46:787–94. 9. Rush J, Younge B. Paralysis of cranial nerves III, IV and VI. Cause and prognosis in 1,000 cases. Arch Ophthalmol. 1981;99:76–9. 10. Rucker C. The causes of paralysis of the third, fourth and sixth cranial nerves. Am J Ophthalmol. 1966;61:1293–8. 11. Rowe F, and VIS group UK Departments of Orthoptics, Multicentre UK recruiting centers, UK. Prevalence of ocular motor cranial nerve palsy and associations following stroke. Eye. 2011;25(7):881–7. 12. Park U, Kim S, Hwang J, Yu Y. Clinical features and natural history of acquired third, fourth, and sixth cranial nerve palsy. Eye (Lond). 2008 May;22(5):691-6. 13. Wilson CM, D’Ath P. A case of sixth cranial nerve palsy and suspected giant cell arteritis. BAOJ Ophthalmology. 2017;2(1):7.

022_ro0417_Urgent.indd 25 3/30/17 12:09 PM Coding Connection

Caring for the Chronic Patient The changing care model is making these patients more challenging than ever. By John Rumpakis, OD, MBA, Clinical Coding Editor any, if not most, of the Follow-up visits also may be less sees her patient every six months ocular conditions for frequent than you expect. However, and performs one VF and one OCT. Mwhich we prescribe medi- you should always provide the spe- She also achieves a 15% drop in cations are chronic in nature. In cific care that is medically necessary IOP and maintains that IOP level. addition, certain medications often for the individual patient, even if Which physician is going to be create or exacerbate a disease state. it is in conflict with the respective attractive to health insurance car- For example, ocular surface disease guidelines. riers? You may think Dr. Smith is can be caused by chronic use of cer- doing a better job by covering all of tain glaucoma medications.1 Outcome-based Coding the bases, but this testing—trans- To manage these patients, clini- Let’s say two ODs are managing lated into coding patterns when cians need time to not only examine their respective patients who have combined with H40.1132—would the patient but also test to establish the same ICD-10 diagnosis: pri- suggest just the opposite. He is less disease progression. But it’s not as mary open-angle glaucoma, bilat- effective and efficient in getting the simple as it sounds. eral, moderate stage, H40.1132. same outcome as Dr. Jones. Most Outcome-based care—for which Optometrist #1, Dr. Smith, is likely, he will not be as attractive to you need to see the patient less, do not familiar with either the AOA carriers and may be dropped from less testing and still get measurable or AAO guidelines or practice pat- the panel, paid less by the carrier or results—is the reality of our health terns, and has incorporated a lot not even asked to participate at all. care system today. To many, this of new technology into his practice This is the reality and potential mandate creates the paradox of the within the last few years. He has impact of outcome-based care. ages for patients who need more visual evoked potential (VEP), Insurance carriers will grade each specialized care. So, how does this electroretinography (ERG), opti- physician and it’s entirely plau- impact your practice as you learn to cal coherence tomography (OCT), sible that practitioners in the same “re-manage” these disease states? autofluorescence (AF) imaging and practice may have different patient corneal hysteresis, in addition to groups for whom they are able to Efficiency is Important, fundus imaging and visual fields provide care. But Effectiveness More So (VF). He sees this patient four to Caring for patients with chronic Managing these chronic diseases five times each year and performs conditions is a cornerstone of opto- efficiently and effectively is not dif- VEP and ERG at least twice annu- metric practice. We must practice ficult, just different from what you ally, OCT at least three times, AF at the highest level while simultane- are doing, or were taught in school. once and corneal hysteresis once. ously evaluating our effectiveness First, you must become familiar He is able to manage the patient and efficiency. Diligence is crucial with the American Optometric successfully and achieves a 15% to maintaining our position as pri- Association’s Clinical Practice drop in intraocular pressure (IOP) mary eye care providers. ■ Guidelines and the American and maintains that IOP level. Send questions and comments to Academy of Ophthalmology’s In contrast, optometrist #2, [email protected]. Preferred Practice Patterns for the Dr. Jones, is familiar with the guide- 2,3 1. Actis AG, Rolle T. Ocular surface alterations and topical diseases you are managing. These lines and is more effective and effi- antiglaucomatous therapy: a review. Open Ophthalmol J. 2014;8:67-72. guidelines provide a protocol of evi- cient in delivering care. She also has 2. American Optometric Association. AOA Optometric dence-based medicine. You might purchased much of the same tech- Clinical Practice Guidelines. www.aoa.org/optometrists/ tools-and-resources/clinical-care-publications/clinical- be surprised to learn that many nology as Dr. Smith, but employs practice-guidelines?sso=y. Accessed March 9, 2017. 3. American Academy of Ophthalmology. Guidelines. www. of the tests you order don’t neces- it only when the clinical evidence aao.org/guidelines-browse?filter=preferredpracticepatternsgu sarily deliver optimal outcomes. demonstrates the need for it. She ideline. Accessed March 9, 2017.

26 REVIEW OF OPTOMETRY APRIL 15, 2017

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RO0417_BL Biotrue.indd 3 3/23/17 11:28 AM Drug Mechanisms: Antibiotics

How Antibiotics Work —and Why They Sometimes Don’t Before reaching for the Rx pad, know the drug, the patient and the disease. By Bruce Onofrey, OD, RPh Photo: Christine Sindt, OD ince their introduc- First, Know Thine Enemy tion, antibiotics have In adults, several well- revolutionized our recognized gram-positive Sapproach to treating, microbes comprise the controlling and preventing list of the most common human and animal infec- pathogens—including tious diseases. The modern several staphylococcal spe- antibiotic era has markedly cies. They range from the improved survival rates and opportunistic pathogen longevity, as catastrophic Staphylococcus epidermidis, disease outbreaks were con- an organism that commonly trolled and previously fatal Fig. 1. This patient presented with dacryocystitis. colonizes the ocular adnexa infections became clinically as a normal part of the manageable. Overall, these changes response to the selective pressure ocular flora, up to the true patho- greatly improved the quality of created by antibiotic use. Evidence gen Staphylococcus aureus, which human life. is mounting that much of the prob- produces exotoxins that allow it to However, the emergence and lem is rooted in the inappropriate produce significant tissue damage spread of antibiotic resistance has and excessive use of these life-sav- and threaten sight. Regarding resis- become a major problem. This ing therapeutics, and that one of the tance, the most problematic mem- global phenomenon has raised the most effective countermeasures is ber of the staphylococcal family of alarming possibility of subsequent to dole out antibiotics in a prudent pathogens is MRSA—methicillin- generations returning to the pre- and judicious manner.1 resistant S. aureus.3 antibiotic era, when common infec- In light of the evidence, we will Other gram-positive organisms tions were often fatal due to the cover strategies and information include several Streptococcus spe- lack of effective treatments. Medi- to empower clinicians with the cies. For example, Streptococcus cal history and research shows that resources and information they pneumonia can be particularly viru- the prevalence of resistance genes need to make sound decisions per- lent. It produces enzymes including and resistant bacteria increases in taining to antibiotic use. streptokinase and hyaluronidase

30 REVIEW OF OPTOMETRY APRIL 15, 2017

030_ro0417_f1x.indd 30 4/3/17 11:30 AM that allow it to penetrate tissue, when an older antibiotic would Photo: Christine Sindt, OD potentially leading to corneal perfo- have better efficacy. This overuse ration or orbital cellulitis.3 of current-generation antibiotics Common gram-negative patho- for minor infections exposes com- gens include Haemophilus species, mon pathogens to new antibiotics Pseudomonas and Neisseria. See and can hasten the development of Table 1 for the full list of the com- resistant strains. Even worse, many mon ocular pathogens. clinicians prescribe antibiotics for prophylaxis when in many cases no Betting the Farm real need exists. This not only leads Fig. 2. This patient presented with an The worldwide animal industry to an increase in resistance among instance of cellulitis. is estimated to use more tons of common ocular flora, but also tox- antibiotics than does all of human icity from the use of an unnecessary tion of pneumococcal isolates had medicine, a practice that elevates therapeutic agent. intermediate resistance to penicillin the risk of treatment failure for (18.3%), azithromycin (22.4%) us all.4 For the growing antibiotic Bugs and Drugs and trimethoprim (22.4%), resistance problem to be effectively The World Health Organization, whereas no notable resistance was contained or reversed, responsible the Food and Drug Administration reported for H. influenza isolates. antibiotic use in the human medical and the Centers for Disease Control Results of the second and third community must be accompanied and Prevention all monitor antibi- years of the Ocular TRUST study by a corresponding effort among otic resistance trends among bacte- (TRUST 2 and TRUST 3) showed veterinarians, farmers and others rial pathogens. The organisms that methicillin resistance among S. in the food animal and companion produce ocular disease are rarely aureus isolates increased to nearly animal industries. targets of these investigations. It 50% in 2008 and methicillin resis- The overuse of potent antibiot- wasn’t until 2008 that results were tance among coagulase-negative ics for non-bacterial disease is a available from the first multicenter, Staphylococci (CoNS) was as high major reason for resistance.4 Physi- nationwide antibiotic resistance sur- as 62.0%. Results for S. pneu- cians are pressured by patients to veillance program specific to ocular monia and H. influenza appeared prescribe them in spite of evidence pathogens.6 The first of these, the unchanged.6 of non-bacterial signs and symp- Ocular Tracking Resistance in the The Antibiotic Resistance Moni- toms. Patients start treatment and US Today (Ocular TRUST) study, toring in Ocular Microorganisms then stop prematurely when their annually evaluates, in vitro, the (ARMOR) study was initiated in symptoms subside, allowing the less susceptibility of three bacterial spe- 2009 to survey antibiotic resis- susceptible bacteria to survive, thus cies—Staphylococcus aureus, S. tance among S. aureus, CoNS, producing a strain resistant to tra- pneumonia and H. influenza—to S. pneumonia, H. influenza and ditionally effective treatments. Fur- several antibiotics: ciprofloxacin, Pseudomonas aeruginosa isolates thermore, overuse and misuse can gatifloxacin, levofloxacin, moxi- from ocular infections.7 As in the allow bacteria of different species floxacin, penicillin, azithromycin, Ocular TRUST study, ARMOR and even different genus to trans- tobramycin, trimethoprim and was a multicenter, nationwide fer resistance genes. For instance, polymyxin B in national samples of prospective surveillance study and research shows antibiotic resis- ocular isolates.6 provided resistance data to extend tance, once acquired, disseminates The study reported antibiotic the information gleaned from Ocu- throughout Enterococci, via hori- resistance among ocular isolates lar TRUST.7 It presents antibiotic zontal transfer of mobile genetic of the test organisms collected resistance profiles and trends for elements, and confers vancomycin between 2005 and 2006 from 35 more than 3,000 ocular isolates resistance from Enterococci to institutions across the United States. collected during the first five years MRSA.5 The study found that 16.8% of of the ARMOR study. The isolates, In the case of eye disease, S. aureus isolates were methicillin which included 1,169 S. aureus, optometrists often reach for the resistant (MR), with many isolates 992 CoNS, 330 S. pneumoniae, latest and greatest antibiotic for concurrently resistant to other anti- 357 H. influenza and 389 P. aeru- non-sight-threatening conditions biotic classes. A significant propor- ginosa, were collected from 72 eye

REVIEW OF OPTOMETRY APRIL 15, 2017 31

030_ro0417_f1x.indd 31 4/3/17 11:30 AM Drug Mechanisms: Antibiotics

gen in the pediatric population. In in the case of higher risk infections, Table 1. Common Ocular ARMOR, pseudomonal isolates which include bacterial keratitis, Pathogens3 were most common in patients postoperative refractive surgery between 10 to 29 years old.7 infections, periocular infections and I. Gram-positive Organisms As with the TRUST study, prophylaxis prior to procedures, A. Staphylococci Staphylococcus species were found specific protocols are required to 1. S. aureus to be the most antibiotic resistant. ensure we meet the standard of 2. S. epidermidis Both methicillin-resistant S. aureus care. Preseptal cellulitis, dacryo- B. Streptococci 1. alpha-Hemolytic streptococcus (MRSA), methicillin-susceptible S. adenitis, dacryocystitis, internal 2. beta-Hemolytic streptococcus aureus (MSSA) as well as CoNS hordeola and chlamydial infections 3. Streptococcus pneumoniae demonstrated the highest levels of may require both systemic and topi- C. Bacilli (rods) general antibiotic resistance.7 cal therapy (Figures 1, 2 and 3). 1. Bacillus Of the 1,169 S. aureus isolates, A significant risk factor for a. B. anthracis 465 (39.8%) and 743 (63.6%) ocular infectious disease is contact b. B. cereus were resistant to ciprofloxacin lens use. Despite the development c. B. subtilis and azithromycin, respectively. of new materials and lens care 2. Cornybacterium In addition, 227 isolates (19.4%) systems, ODs must deal with the a. C. diphtheria were resistant to tobramycin. All unpredictable human factor. Poor b. C. xerosis S. aureus isolates were susceptible hygiene, dirty, dusty work envi- 3. Listeria 4. Nocardia to vancomycin, and only a small ronments, smoking, overwear of 5. Mycobacterium proportion were resistant to trime- contact lenses and failure to replace thoprim (4.7%) and chlorampheni- lenses according to recommended II. Gram-negative Organisms col (0.4%).7 schedules are all risk factors for A. Neisseria Regarding Streptococcus species, developing potentially serious cor- 1. N. gonorrhea only azithromycin has a significant neal infections. 2. N. meningitidis rate of failure. The resistance was Most non-sight-threatening ocu- B. Bacilli found to be 34%, much higher than lar disease is treated empirically. If 1. Enterobacteriaceae all other drugs tested.7 The gram- the condition is serious enough to a. E. coli negative H. influenza species in threaten visual function, it’s impera- b. Shigella children was found to be susceptible tive to determine the identity and c. Klebsiella 7 d. Serratia to all test drugs. More information susceptibility of the organism. For e. Proteus that can be derived from the Ocular instance, sight-threatening keratitis 2. Moraxella TRUST and ARMOR studies can may require the compounding of 3. Haemophilus be found in Table 2. specific antibiotics for their appro- a. H. Influenza Of greatest importance: the rise priate therapy (Figure 4).3 These b. H. aegyptius of resistant among the most com- include the compounded forms of 4. Brucella mon adult pathogens—coagulase vancomycin, amikacin and azithro- 5. Pseudomonas negative and positive Staphylococ- mycin (Table 3).

a. P. aeruginosa cus species—the high failure rate of E. Oliver,Photo: Gary OD b. P. cepacia fluoroquinolones and the efficacy of older drugs like trimethoprim and care centers, community hospitals tobramycin.7 and university hospitals across 36 states.7 Gram-positive isolates such Disease Factors as Staphylococcus and Streptococ- Selecting an antibiotic therapy cus species came primarily from is highly dependent on the risk adults and, as would be expected, to the patient. We don’t want to H. influenza was primarily iso- undertreat—or overtreat, as low- lated from children younger than risk infections can often be treated Fig. 3. This patient’s chlamydial 10 years.7 H. influenza represents empirically with a host of topical conjunctivitis will likely require topical the most common ocular patho- broad-spectrum agents. However, therapy.

32 REVIEW OF OPTOMETRY APRIL 15, 2017

030_ro0417_f1x.indd 32 4/3/17 11:31 AM A DROP OF PREVENTION FOR YOUR CATARACT SURGERY PATIENTS

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Indications and Usage surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, BromSite™ (bromfenac ophthalmic solution) 0.075% is a or repeat ocular surgeries within a short period of time may be nonsteroidal anti-infl ammatory drug (NSAID) indicated for at increased risk for corneal adverse events which may become the treatment of postoperative infl ammation and prevention sight threatening. Topical NSAIDs should be used with caution in of ocular pain in patients undergoing cataract surgery. these patients. Post-marketing experience with topical NSAIDs Important Safety Information also suggests that use more than 24 hours prior to surgery or • Slow or Delayed Healing: All topical nonsteroidal anti- use beyond 14 days postsurgery may increase patient risk for the infl ammatory drugs (NSAIDs), including BromSite (bromfenac occurrence and severity of corneal adverse events. ophthalmic solution) 0.075%, may slow or delay healing. • BromSite should not be administered while wearing contact Topical corticosteroids are also known to slow or delay healing. lenses. The preservative in BromSite, benzalkonium chloride, Concomitant use of topical NSAIDs and topical steroids may may be absorbed by soft contact lenses. increase the potential for healing problems. • The most commonly reported adverse reactions in 1% to 8% of • Potential for Cross-Sensitivity: There is the potential for patients were anterior chamber infl ammation, headache, vitreous cross-sensitivity to acetylsalicylic acid, phenylacetic acid fl oaters, iritis, eye pain, and ocular hypertension. derivatives, and other NSAIDs, including BromSite (bromfenac You are encouraged to report negative side effects of prescription drugs ophthalmic solution) 0.075%. Therefore, caution should be to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. used when treating individuals who have previously exhibited sensitivities to these drugs. Please see brief summary of full Prescribing Information • Increased Bleeding Time of Ocular Tissue: With some on the adjacent page. NSAIDs, including BromSite (bromfenac ophthalmic solution) NSAID=nonsteroidal anti-infl ammatory drug. 0.075%, there exists the potential for increased bleeding time References: 1. BromSite [package insert]. Cranbury, NJ: Sun Pharmaceutical due to interference with platelet aggregation. There have been Industries, Inc.; 2016. 2. Hosseini K, Hutcheson J, Bowman L. Aqueous humor reports that ocularly applied NSAIDs may cause increased concentration of bromfenac 0.09% (Bromday™) compared with bromfenac in DuraSite® 0.075% (BromSite™) in cataract patients undergoing phacoemulsifi cation bleeding of ocular tissues (including hyphemas) in conjunction after 3 days dosing. Poster presented at: ARVO Annual Meeting; May 5-9, 2013; with ocular surgery. Seattle, Washington. 3. Bowman LM, Si E, Pang J, et al. Development of a It is recommended that BromSite be used with caution in patients topical polymeric mucoadhesive ocular delivery system for azithromycin. J Ocul Pharmacol Ther. 2009;25(2):133-139. 4. ClinicalTrials.gov. Aqueous humor with known bleeding tendencies or who are receiving other concentration of InSite Vision (ISV) 303 (bromfenac in DuraSite) to Bromday once medications which may prolong bleeding time. daily (QD) prior to cataract surgery. https://clinicaltrials.gov/ct2/show/results/ • Use of topical NSAIDs may result in keratitis. Patients with evidence NCT01387464?sect=X70156&term=insite+vision&rank=1. Accessed July 18, 2016. 5. Si EC, Bowman LM, Hosseini K. Pharmacokinetic comparisons of bromfenac in of corneal epithelial breakdown should immediately discontinue DuraSite and Xibrom. J Ocul Pharmacol Ther. 2011;27(1):61-66. use of topical NSAIDs, including BromSite (bromfenac ophthalmic solution) 0.075%, and should be closely monitored for corneal Sun Ophthalmics is a division of Sun Pharmaceutical Industries, Inc. © 2016 Sun Pharmaceutical Industries, Inc. All rights reserved. health. Patients with complicated ocular surgeries, corneal DuraSite® and BromSite™ are trademarks of Sun Pharma Global FZE. denervation, corneal epithelial defects, diabetes mellitus, ocular SUN-OPH-BRO-014 09/2016

RP1116_Sun.indd 1 10/13/16 10:55 AM BromSite™ (bromfenac ophthalmic solution) 0.075% USE IN SPECIFIC POPULATIONS Brief Summary Pregnancy Risk Summary There are no adequate and well-controlled studies in pregnant women to inform any drug associated risks. Treatment of pregnant rats and rabbits with oral bromfenac did INDICATIONS AND USAGE not produce teratogenic effects at clinically relevant doses. BromSite™ (bromfenac ophthalmic solution) 0.075% is a nonsteroidal Clinical Considerations anti-inflammatory drug (NSAID) indicated for the treatment of postoperative Because of the known effects of prostaglandin biosynthesis-inhibiting drugs on the inflammation and prevention of ocular pain in patients undergoing cataract surgery. fetal cardiovascular system (closure of ductus arteriosus), the use of BromSite during DOSAGE AND ADMINISTRATION late pregnancy should be avoided. Recommended Dosing Data One drop of BromSite should be applied to the affected eye twice daily (morning Animal Data and evening) 1 day prior to surgery, the day of surgery, and 14 days postsurgery. Treatment of rats with bromfenac at oral doses up to 0.9 mg/kg/day (195 times a Use with Other Topical Ophthalmic Medications unilateral daily human ophthalmic dose on a mg/m2 basis, assuming 100% absorbed) BromSite should be administered at least 5 minutes after instillation and rabbits at oral doses up to 7.5 mg/kg/day (3243 times a unilateral daily dose of other topical medications. on a mg/m2 basis) produced no structural teratogenicity in reproduction studies. However, embryo-fetal lethality, neonatal mortality and reduced postnatal growth Dosage Forms and Strengths were produced in rats at 0.9 mg/kg/day, and embryo-fetal lethality was produced Topical ophthalmic solution: bromfenac 0.075%. in rabbits at 7.5 mg/kg/day. Because animal reproduction studies are not always CONTRAINDICATIONS predictive of human response, this drug should be used during pregnancy only if None the potential benefit justifies the potential risk to the fetus. WARNINGS AND PRECAUTIONS Lactation Slow or Delayed Healing There are no data on the presence of bromfenac in human milk, the effects on the All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including BromSite breastfed infant, or the effects on milk production; however, systemic exposure to (bromfenac ophthalmic solution) 0.075%, may slow or delay healing. Topical bromfenac from ocular administration is low. The developmental and health benefits corticosteroids are also known to slow or delay healing. Concomitant use of topical of breastfeeding should be considered along with the mother’s clinical need for NSAIDs and topical steroids may increase the potential for healing problems. bromfenac and any potential adverse effects on the breast-fed child from bromfenac or from the underlying maternal condition. Potential for Cross-Sensitivity There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid Pediatric Use derivatives, and other NSAIDs, including BromSite (bromfenac ophthalmic solution) Safety and efficacy in pediatric patients below the age of 18 years 0.075%. Therefore, caution should be used when treating individuals who have have not been established. previously exhibited sensitivities to these drugs. Geriatric Use Increased Bleeding Time of Ocular Tissue There is no evidence that the efficacy or safety profiles for BromSite differ With some NSAIDs, including BromSite (bromfenac ophthalmic solution) 0.075%, in patients 65 years of age and older compared to younger adult patients. there exists the potential for increased bleeding time due to interference with NONCLINICAL TOXICOLOGY platelet aggregation. There have been reports that ocularly applied NSAIDs may Carcinogenesis, Mutagenesis and Impairment of Fertility cause increased bleeding of ocular tissues (including hyphemas) in conjunction Long-term carcinogenicity studies in rats and mice given oral doses of bromfenac up with ocular surgery. to 0.6 mg/kg/day (129 times a unilateral daily dose assuming 100% absorbed, on a It is recommended that BromSite be used with caution in patients with known mg/m2 basis) and 5 mg/kg/day (540 times a unilateral daily dose on a mg/m2 basis), bleeding tendencies or who are receiving other medications which may prolong respectively revealed no significant increases in tumor incidence. bleeding time. Bromfenac did not show mutagenic potential in various mutagenicity studies, including Keratitis and Corneal Reactions the bacterial reverse mutation, chromosomal aberration, and micronucleus tests. Use of topical NSAIDs may result in keratitis. In some susceptible patients, Bromfenac did not impair fertility when administered orally to male and female rats continued use of topical NSAIDs may result in epithelial breakdown, corneal at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, respectively (195 and 65 times a thinning, corneal erosion, corneal ulceration or corneal perforation. These events unilateral daily dose, respectively, on a mg/m2 basis). may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs, including BromSite (bromfenac PATIENT COUNSELING INFORMATION ophthalmic solution) 0.075%, and should be closely monitored for corneal health. Slow or Delayed Healing Post-marketing experience with topical NSAIDs suggests that patients with Advise patients of the possibility that slow or delayed healing may occur complicated ocular surgeries, corneal denervation, corneal epithelial defects, while using NSAIDs. diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid Concomitant Topical Ocular Therapy arthritis, or repeat ocular surgeries within a short period of time may be at increased If more than one topical ophthalmic medication is being used, advise patients to risk for corneal adverse events which may become sight threatening. Topical NSAIDs administer BromSite at least 5 minutes after instillation of other topical medications. should be used with caution in these patients. Concomitant Use of Contact Lenses Post-marketing experience with topical NSAIDs also suggests that use more than Advise patients not to wear contact lenses during administration of BromSite. 24 hours prior to surgery or use beyond 14 days postsurgery may increase patient The preservative in this product, benzalkonium chloride, may be absorbed by risk for the occurrence and severity of corneal adverse events. soft contact lenses. Contact Lens Wear Sterility of Dropper Tip/Product Use BromSite should not be administered while wearing contact lenses. The preservative Advise patients to replace the bottle cap after use and do not touch the dropper in BromSite, benzalkonium chloride, may be absorbed by soft contact lenses. tip to any surface as this may contaminate the contents. ADVERSE REACTIONS Advise patients to thoroughly wash hands prior to using BromSite. Clinical Trial Experience Rx Only Because clinical trials are conducted under widely varying conditions, adverse Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The most commonly reported adverse reactions in 1–8% of patients were: anterior chamber inflammation, headache, vitreous floaters, iritis, eye pain BromSite is a trademark of Sun Pharma Global FZE. and ocular hypertension. SUN-OPH-BRO-017 09/2016

RRP1116_SunP1116_Sun PPI.inddI.indd 1 110/13/160/13/16 10:3810:38 AMAM Drug Mechanisms: Antibiotics

Topical vs. Systemic Therapy most gram-negative bacteria, Ocular infections can be unique in Table 2. Resistance in MRSA including Pseudomonas, without that, in many cases, topical therapy and Pseudomonas7 the toxicity issues and the need to is preferred over systemic. Topical S. aureus – MRSA % Resisitant be compounded. Overall, we don’t therapy allows for a highly con- Ofloxacin 76% see many indications for tobramy- centrated dose of medication to be Ciprofloxacin 76% cin today. Trimethoprim, however, applied directly to the site of infec- Levofloxacin 72% shows high efficacy against MRSA tion. The benefits are obvious: mini- and is less toxic for management Gatifloxacin 68% mal systemic absorption, reduction of non-sight threatening conjunc- Moxifloxacin 57% in systemic toxicity and direct deliv- tivitis.6 Vancomycin is the drug of Besifloxacin NA ery of high drug concentration to choice for sight-threatening resis- avascular tissues (i.e., the cornea). Azithromycin 93% tant Staphylococcus species. Systemic medications are necessary Chloramphenicol 0.7% Trimethoprim is a synthetic when infections involve deeper, Tobramycin 41% anti-infective agent. Like the sul- vascularized structures such as the Trimethoprim 7% fonamides, it is a folic acid inhibi- lids, periorbital area and lacrimal Vancomycin 0% tor, but mediates its effects slightly apparatus. differently; it’s also safe for sulfon- The choice of drug depends on Pseudomonas amide-sensitive patients.10 the pathogen and the patient’s Ofloxacin 6% Its activity is limited to gram- 3 history, which includes allergies, Ciprofloxacin 5% positive bacteria. Therefore, it preexisting medical conditions Levofloxacin 4% is usually combined with a drug and the patient’s current medica- Gatifloxacin NA that has gram-negative activity tions. Another major consideration like polymyxin B. This combina- Moxifloxacin NA for using systemic medications is tion has broad-spectrum activity Besifloxacin NA pregnancy. Doctors must select an and low toxicity, and it is a good Tobramycin 3% effective medication that does not option to empirically treat bacterial pose a risk to the fetus. The FDA’s Polymyxin B 3% conjunctivitis in all age groups. It is classification system can help clini- bacteriostatic, not bactericidal, and cians review the risk of medications Tobramycin is the most com- is a time-dependent antibiotic. This in pregnant patients (Table 4). monly prescribed aminoglycoside, means the concentration in tissues High-risk diseases warrant high-risk a category which also includes two must remain above the organism’s

treatments and discussions with topical drugs—neomycin and genta- MIC90 level (the minimum concen- the patient, family doctor and OB/ micin—and the newest aminoglyco- tration needed to inhibit growth of GYN. Otherwise, clinicians should side, amikacin (no ophthalmic form 90% of the isolates present) for a avoid high-risk treatments in low- is currently available).3 Amikacin specific period of time for it to be benefit situations. is generally compounded to treat effective. Trimethoprim has recently tobramycin-resistant Pseudomonas. made a comeback for managing The Drugs Topical neomycin is highly sensitiz- non-sight-threatening MRSA con- A host of new and old agents are ing, and gentamicin has significant junctivitis.7 It exhibits low toxicity, currently available to help us com- corneal toxicity.9 Tobramycin is high efficacy against gram-positive bat infectious disease. Many have mostly popular for its anti-pseu- bacteria—specifically MRSA—and become obsolete while others that domonal activity.3 The ophthalmic is inexpensive. had fallen out of favor have been form is available as a 0.3% solu- Polymyxin B is a topical peptide resurrected as useful therapies. tion (3mg/cc), but can be com- antibiotic and a bactericidal cell Aminoglycosides. These drugs pounded in a concentration as high wall inhibitor effective against Pseu- are bactericidal and their efficacy as 13.5mg/cc for use in suspected domonas, Escherichia coli, Entero- is concentration dependent, both gram-negative corneal infections. bacter and Klebsiella.3 The more desirable characteristics of a topical Its use is also limited by its effective fluoroquinolone agents anti-infective.8 They inhibit bacte- corneal toxicity—it’s now been have supplanted its use in cases rial ribosomes, the workhorses of replaced by topical fluoroquinolone of serious sight-threatening gram- cellular protein synthesis. agents, which are effective against negative infection.

REVIEW OF OPTOMETRY APRIL 15, 2017 35

030_ro0417_f1x.indd 35 4/3/17 11:31 AM Drug Mechanisms: Antibiotics Photo: Christine Sindt, OD Bacitracin, once a popular fluoroquinolones used are for bactericidal topical antibiotic, is prophylaxis in agricultural rarely used today for several rea- animals.14 Broad exposures of sons. First, it is a narrow-spec- the drugs to the biosphere and trum drug with efficacy only for the food chain has resulted in gram-positive organisms such as a significant reduction in their Staphylococcus and Streptococ- efficacy. This is particularly cus species.3 Second, it frequently problematic because resistance produces contact dermatitis reac- has primarily developed in tions.3 Finally, it is only available gram-positive Staph. species.7 as an ointment, which most In an effort to combat resis- patients dislike due to greasiness tance, new generations of FQs and blurred vision.3 Fig. 4. Keratitis, seen here, requires aggressive have been developed. Erythromycin and azithro- therapy to stave off vision loss. The first drugs approved mycin. These are both available to treat bacterial keratitis in topical and oral dosage forms. Note that azithromycin is not were ciprofloxacin and ofloxacin. These drugs represent the macrolide effective in treating MRSA infec- Improvements in third-generation protein synthesis class of antibiot- tions because of a greater than 90% FQs included a purified version of ics. Topical use of erythromycin resistance seen in the ARMOR ofloxacin, a 50/50 mixture of left- was once quite common. It had study.13 It is commonly used to treat and right-handed stereoisomers, good gram-positive activity and marginal blepharitis due to reported though only the left-handed isomer was effective against Chlamydia anti-inflammatory properties.3 was biologically active. By produc- trachomatis. It also has very low Fluoroquinolones (FQ). This ing a purified left-handed isomer, corneal toxicity. Unfortunately, it is drug class functions by inhibiting levofloxacin, they greatly lowered

only available in ointment form for the enzyme DNA gyrase in both the required MIC90. topical use. And, its ineffectiveness gram-positive and gram-negative The fourth-generation fluoro- against H. influenza and propensity organisms, an enzyme necessary quinolones adds a methoxy func- to irritate the GI tract has caused it during microbial replication.3 tional group to the fluoroquinolone to fall out of favor. The topical formulations of these structure, making it more effective Erythromycin is bacteriostatic, agents revolutionized the topical against resistant gram-positive with limited efficacy against pedi- management of ocular infectious organisms, and decreasing resis- atric Haemophilus.11 Oral erythro- disease. They possessed the ideal tance. The fourth-generation drugs mycin interferes with the hepatic characteristics of an anti-infective include moxifloxacin 0.5% and metabolism of drugs metabolized agent. They are bactericidal, gatifloxacin 0.3% and 0.5%. Both by the cytochrome P-450 system, concentration-dependent, rarely drugs are available in oral formula- whereas azithromycin does not.12 produce sensitization or toxicity tions, but they are rarely used sys- Erythromycin is notorious for and are broad-spectrum agents. temically to treat eye disease. producing GI irritation, while once- Of course, due to these favorable Besifloxacin represents an daily azithromycin rarely does.12 characteristics, they were—and improved version of the FQ drug Because of its marked ability to are still—widely overprescribed. class. In addition to fluorine quickly treat chlamydial infec- Furthermore, the majority of the attached to the quinolone ring, an tions (a single dose of 1,000mg in adults), long half-life, lack of Table 3. Antibiotic Selection for Sight-threatening Pathogens hepatic drug interactions and effi- Vancomycin 50mg/cc MRSA cacy against Haemophilus, azithro- Gatifloxacin or Moxifloxacin 0.5mg/cc Pseudomonas mycin has become one of the most popular oral antibiotics for treating Tobramycin 13.5mg/cc Pseudomonas ocular disease.11 Furthermore, it Amikacin 50mg/cc Pseudomonas can be used safely in both pregnant Solomon R, Donnenfeld ED, Holland EJ, et al. Microbial keratitis trends following refractive surgery: results of the ASCRS patients and those allergic to peni- infectious keratitis survey and comparisons with prior ASCRS surveys of infectious keratitis following keratorefractive pro- cillins.3 cedures. J Cataract Refract Surg. 2011;37(7):1343-50.

36 REVIEW OF OPTOMETRY APRIL 15, 2017

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RO0417_BL Lotemax.indd 1 3/23/17 11:25 AM Drug Mechanisms: Antibiotics

atom of chlorine is attached as well. Disinfectants Table 4. FDA Pregnancy Furthermore, this drug is not used These compounds have the abil- Category of Risk of Selected orally or in agriculture. Current ity to kill bacteria, virus, fungi and Antibiotics3 studies of efficacy are limited, but protozoa. Their use is limited pri- have demonstrated reduced resis- Tobramycin (topical) B marily by their toxicity.22 tance in FQ-resistant bacteria.15 Fluoroquinolones (topical) C Povidone-iodine, a 21-iodine- Trimethoprim/polymyxin B (topical) C Vancomycin. This is a bacteri- based disinfectant, has become Cephalosporins B cidal cell wall inhibitor with speci- quite popular for disinfection of the Azithromycin B ficity for gram-positive bacteria.12 eye and adnexa prior to surgical Amoxicillin-Clavulanate B 22 It is compounded as a 25mg to Chloramphenicol (topical) C procedures. It has also been used 50mg/mL topical form or an intra- in its 5% ophthalmic dosage form ocular injection to treat MRSA to treat adenoviral conjunctivitis.23 endophthalmitis and is the principal Clavulanate’s ability to inhibit A povidone-based product is cur- drug used to treat serious ocular beta-lactamase improves efficacy rently in clinical trials for the treat- MRSA infections.13,16 The ARMOR against organisms traditionally ment of both viral and bacterial eye study showed it was 100% effective resistant to penicillin therapy. This disease. The drug contains a com- against ocular MRSA isolates; how- includes beta-lactamase produc- bination of povidone-iodine 0.4% ever, vancomycin-resistant strains of ing Staphylcoccus, Streptococcus and dexamethasone 0.1%.24 MRSA have surfaced. and Haemophilus bacteria.3 It is Chloramphenicol. This is an not effective against MRSA strains. Non-ophthalmic Topicals extremely potent inhibitor of bacte- The drug is a bactericidal, cell Mupirocin, a combination of pseu- rial ribosomal protein synthesis. It wall-inhibiting antibiotic. It is well domonal acids sold as Bactroban is a bacteriostatic, broad-spectrum tolerated and safe in pregnancy.19 (GlaxoSmithKline), is available as antibiotic.3 Its spectrum of activity The major issue with it and other a topical ointment and cream. It is is impressive. It is effective against penicillins is the significant number profoundly effective against gram- gram-positive and gram-negative of individuals allergic to this class positive bacteria, most importantly bacteria, anerobic and aerobic of therapeutic agent.19 MRSA. It is the topical drug of organisms, tick-borne rikettsiae and Cephalosporins. This group of choice for impetigo and MRSA MRSA.3 It is highly lipid soluble oral agents is very similar to the skin infections and is administered and therefore has excellent tissue aminopenicillins. They inhibit nasally in MRSA carriers to reduce penetration when used topically, cell walls and are bactericidal.3 their contagion potential.25 It is not and can pass through the blood- Compared to the penicillins, they approved for ophthalmic use, but brain barrier and blood-eye barrier exhibit improved resistance to beta certainly could be used off-label on when it is used systemically.3 lactamase, but are not as effective lids and periocular infected skin. Chloramphenicol is widely used as clavulanate-protected amoxicil- to topically treat eye disease in lin.19 Given an approximate 3% When Star Trek’s producers were many parts of the world due to its incidence of cross-sensitivity with asked how the ship’s transporter high efficacy and low cost.17 Its use penicillins, cephalosporin use in works, they responded without in the United States for eye disease penicillin-sensitive patients should pausing, “Very well, thank you.” is limited due to its systemic toxicity be limited.3 Unfortunately, clinicians responsible in both systemic and topical dosage Over time, researchers have for selecting an antibiotic agent forms. It has the potential to pro- developed several generations of don’t have the luxury of such a duce fatal aplastic anemia at a rate cephalosporins. The most com- breezy dismissal of the rigors of of one case in 24,000 of treatment monly prescribed first-generation science. The treating doctor must courses.18 drug, cephalexin, is primarily choose an agent that’s both safe Amoxicillin-clavulanate (Aug- effective against gram-bacteria in and effective for their patient, ide- mentin). This is a combination of adults.20 When treating children ally one with minimal impact on the broad-spectrum aminopenicil- younger than 10 years of age who individual and global resistance pat- lin amoxicillin and clavulanate, a tend to colonize Haemophilus, cli- terns. This is accomplished by being non-anti-infective compound that nicians should use a second-genera- familiar with the pharmacology of binds to the enzyme beta-lactamase. tion cephalosporin.21 all the anti-infective agents we use.

38 REVIEW OF OPTOMETRY APRIL 15, 2017

030_ro0417_f1x.indd 38 4/3/17 11:31 AM 1. Bertino JS. Impact of antibiotic resistance in the manage- Staph. aureus in the United States 2000-2005. J Cat Refract This includes their indications, con- ment of ocular infections: the role of current and future Surg. 2008;34(5):814-18. antibiotics. Clin Ophthalmol. 2009;3:507-21. 14. Gustafson RH, Bowen RE. Antibiotic use in animal agricul- traindications, side effects, adverse 2. Chang VS, Dhaliwal DK, Raju l, Kowalski RP. Antibiotic ture. J App Microbiol. 1997;83(5):531-41. effects, dosages and forms. Most resistance in the treatment of Staphylococcus aureus kerati- 15. Sanders ME, Norcross EN, Moore QC. Efficacy of besiflox- tis: a 20 year revue. Cornea. 2015;34(6):698-703. acin in a rabbit model of methicillin resistant Staphylococcus are prescribed empirically, without 3. Onofrey BE, Skorin, L, Holdeman NR. The Ocular Therapeu- aureus keratitis. Cornea. 2009;10(28):1055-60. tics Handbook. 3rd ed. Lippincott Williams and Wilkins; 2011. 16. Manav K, Pathenga A, Mathai A, et al. Vancomycin resis- identifying the pathogen, then fine- 4. Laxminarayan R, Duse A, Wattal C, et al. Antibiotic tant gram positive bacterial endophthalmitis: epidemiology, tuned based on staining, culturing resistance: The need for global solutions. Lance Infec. Dis. treatment options and outcomes. J Ophthalmol Inflam Infec. 2013;13(12):1057-98. 2013;3:46. and sensitivity testing in sight- 5. Palmer KL, Kos VN, Gilmore MS. Horizontal gene transfer 17. Walker S, Diaper CJ, Bowman R, et al. Lack of evidence and the genomics of enterococcal antibiotic resistance. Curr of systemic toxicity following topical chloramphenicol use. threatening disease. We also must Opin Microbiol. 2010;113(5):632-9. Eye. 1998;12( Pt 5):875-9. give special consideration to issues 6. Asbell PA, Colby KA, Deng S, et al. Ocular trust: Nationwide 18. McWhae JA, CChang J, Lipton JH. Drug induced fatal antibiotics susceptibility patterns in ocular isolates. Amer J aplastic anemia following cataract surgery. Can J Ophthalmol. such as drug allergy, pregnancy, Ophthalmol. 2008;145(6):951-8. 1992;27(6):313-5. 7. Asbell PA, Sanfilippo CM, Pillar CM, et al. Antibiotic resi 19. Nahum GG, Uhl K, Kennedy DL. Antibiotic use in preg- reduced renal or hepatic function stance among ocular pathogens in the United States nancy and lactation: What is and is not known about terato- and special dosing in children. (ARMOR). JAMA Ophthalmol. 2015;133(12):1445-54. genic and toxic risks. Obs Gynec. May 2006;107(5):1120-38. 8. Poole K. Aminoglycoside resistance in Pseudomonas aeru- 20. Dancer SJ. The problem with cephalosporins. J Antibio In short: In an age of flourishing ginosa. Antibiotics Agents Chemother. 2005;49(2):479-87. chemother. 2001;48(4):463-78. 9. Kaye D. Current for old antibacterial agents: Polymyxins, 21. Rathore M. Pediatric Haemophilus infection. Emedicine. bacterial resistance to antibiotics, rifampin and aminoglycosides. Infect Dis Clin North Am. medscape.com/article/964317-overview. MedScape. know the patient, know the drug 2004;18(3):669. Updated April 4, 2016. Accessed March 30, 2017. 10. Chambers HF, Deck DH. Sulfonamides, trimethoprim and 22. Isenberg SJ, Apt L. The ocular application of povidone and know the disease before treat- Quinolones. In: Katzung, BG, Master SB, Trevor AJ. Basic and iodine. Comm Eye Health J. 2003;16(46):30-1. ■ Clinical Pharmacology. 11th ed. 2009; Lange. 23. Abel R, Abel AD. Use of povidone-iodine in the treatment ing any infection. 11. Gilbert DN, Moellering RC, Eliopoulos GM, et al, eds. The of presumptive adenoviral conjunctivitis. Ann Ophthalmol Dr. Onofrey is a clinical profes- Sanford guide to antibiotics therapy. 46th ed. Antimicrobial Glaucom. 1998;30(6):341-3. Therapy; 2016. 24. Pinto RD, Lira RP, Abe RY, et al. Dexamethasone/Povidone sor at the University of Houston 12. Chambers HF, Deck DH. Tetracyclines, macrolides, Eye Drops versus Artificial Tears for Treatment of Presumed clindamycin, chloramphenicol, streptogramins and oxazolidi- Viral Conjunctivitis: A Randomized Clinical Trial. Curr Eye Res. College of Optometry and is an nones. In: Katzung, BG, Master SB, Trevor AJ, eds. Basic and 2015 Sep;40(9):870-7. author of The Ocular Therapeutics Clinicical Pharmacology. 11th ed. McGraw-Hill Medical; 2009. 25. Lewis l. Impetigo treatment and management. Med- 13. Asbell PA, Sahm DF, Shaw M, et al. Increasing prevalence Scape. Emedicine.medscape.com/article/965254-treatment. Handbook. of methicillin resistance in serious ocular infections caused by Updated May 4, 2016. Accessed March 30, 2017.

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030_ro0417_f1x.indd 39 4/3/17 11:29 AM Drug Mechanisms: Anti-Inflammatories

Anti-inflammatories: Sort Out Your Many Steroids and NSAIDs

With so many medications out there, treatment can get complicated. Here is a rundown of your options and when to use them. By Laine Higa, OD

ngoing advances in topical recruit macrophages to remove the Similarly, when AA is metabolized ocular therapeutics have offending stimulus.1 This recruit- via the COX-1/COX-2 isoenzymes, given the eye care provider ment initiates the healing process prostanoids (prostaglandins and more options in the treat- and manifests the cardinal signs of thromboxane A ) are produced.1 O 2 ment of ocular inflammation than inflammation: redness, swelling, Prostanoid formation increases arte- ever. In this article, we review the heat and pain.1 rial dilation and vascular permeabil- various topical corticosteroid and Tissue injury causes degrada- ity, which account for the redness, nonsteroidal anti-inflammatory drug tion and lysis of the cell membrane edema and pain associated with 1 (NSAID) options available. A closer via the phospholipase A2 (PLA2) inflammation. look at when and how to implement enzyme, resulting in arachidonic The two major classes of anti- these medications into your treat- acid (AA) formation. AA medi- inflammatories—corticosteroids and ment regimen will help you care for ates the inflammatory cascade and NSAIDs—each cause different path- all of your patients who present with is metabolized by 5-lipoxygenase way inhibition (Figure 2). ocular inflammation. Additionally, a (LOX) and cyclooxygenase isoen- succinct review of immunomodula- zymes (COX-1/COX-2).1 When Corticosteroids tors for the dry eye patient will hone AA is metabolized via LOX, the The anti-inflammatory properties in on this common cause of inflam- generated leukotrienes recruit white of corticosteroids are mediated at mation. blood cells to the damaged area.1 the genomic level.2 When corticoste- roids bind to receptors in The Inflammatory the cytoplasm, the bound Pathway complex migrates into the The successful treatment nucleus and upregulates the of ocular inflammation expression of anti-inflam- requires a solid founda- matory proteins and down- tion and understanding of regulates the expression of the inflammatory pathway proinflammatory proteins.2 (Figure 1). Inflammation is More specifically, lipocor- the body’s response to repair tins, which are produced tissue to normal structure after corticosteroid cellular

and physiologic function. In modulation, inhibit PLA2 the presence of tissue dam- and histamine synthesis in age or an offending agent, Fig. 1. This illustration demonstrates the inflammatory pathway mast cells.3 Corticosteroids

neutrophils and monocytes of the innate immune system: PLA2, LOX and COX-1/COX-2. also have non-genomic

40 REVIEW OF OPTOMETRY APRIL 15, 2017

040_ro0417_f2.indd 40 4/3/17 12:56 PM modulating effects medi- formulated to increase pene- ated by the corticosteroid- tration into the eye for more receptor binding, which targeted anti-inflammatory include inhibition of action.4 Dermatologic, sur- vasodilation, vascular per- face and corneal diagnoses, meability, decrease in scar however, would benefit from formation and the stabili- lesser-strength corticosteroid zation of intracellular and options.4 extracellular membranes.3 Location-specific therapy Because corticosteroids decreases the risk of side inhibit the inflamma- effects and corticosteroid- tory cascade earlier than related sequelae. Ocular NSAIDs, corticosteroids Fig. 2. The two classes of anti-inflammatory drugs each inhibit hypertension and a hasten- are more effective anti- the inflammatory pathway differently. ing of posterior subcapsular inflammatory agents.4 cataract formation are In my personal clinical experience, Corticosteroids inhibit the resi- well documented in the literature employing topical corticosteroids dent immune system to employ its with prolonged corticosteroid use.2- for many inflammatory (i.e. uve- anti-inflammatory properties. This 4,8,9,11,12 Research suggests roughly itic, ocular surface, atopic) condi- decrease in the immune system 33% of the adult population are tions has yielded positive results. increases the risk for opportunistic moderate responders—IOP increases Although the condition may not infections. When you have concern by 6mm Hg to 15mm Hg.3 Alter- be completely resolved at the first for infectious etiologies, be cautious natively, 4% to 6% of the general follow up, I usually see a dramatic to initiate isolated corticosteroid population are high responders— decrease in symptoms. therapy. IOP elevates above 15mm Hg with If there is no improvement in As red eye presentations can often therapy.3 Family history of glau- patient symptoms or clinical signs, be difficult cases, consider the fol- coma, diabetes, myopia and younger an astute clinician should investigate lowing before initiating therapy: age are all risk factors that preclude medication compliance and instilla- • Take a thorough case history responders to elevations in IOP.11,12 tion. As many of the corticosteroid that may preclude corticosteroid However, more often than not, options are in suspension form, use, at least initially the benefits of corticosteroid treat- failing to shake the bottle prior to • Instill vital dyes that may reveal ment outweigh the potential side instillation tends to be the culprit of an epithelial herpetic etiology effects. Additionally, visual acuity, delayed resolution. Additionally, the IOP assessment and ophthalmo- varying strengths of topical cortico- Initiating Therapy scopic evaluation of the optic nerve steroids allow clinicians the option New drug designs have increased head at subsequent visits will ensure to increase the medication strength corticosteroid potency and metabo- clinicians catch any possible side when little improvement is observed. lism with decreased side effects.7-10 effects before they become vision Before initiating corticosteroid threatening. Indications and Contraindications therapy, clinicians should consider Many of the adnexal and anterior the following baseline factors: Intraocular Inflammation segment inflammatory conditions • Presence of an anterior chamber Intraocular inflammatory conditions can be successfully treated with reaction (cell/flare) require aggressive corticosteroid topical steroid therapy. Additionally, • Significance of hyperemia/injec- therapy to prevent vision-threaten- first-line therapy for post-op retinal tion ing complications and sequelae.4,7 cystoid macular edema (CME) is • Symptomatology (photophobia, An appropriate corticosteroid pen- topical corticosteroids and NSAIDs.5 pain, irritation) level etrates the ocular surface to inhibit Indicated conditions for corticoste- • Targeted location of treatment inflammation at its source. Durezol roid use include steroid-responsive • Presumed diagnosis (difluprednate 0.05%, Alcon) and inflammation of the palpebral and Intraocular inflammation should Pred Forte (prednisolone acetate bulbar conjunctiva, cornea and ante- be treated with maximal efficacy ophthalmic suspension 1%, Aller- rior segment of the globe.6 topical corticosteroids, which are gan) are corticosteroid options for

REVIEW OF OPTOMETRY APRIL 15, 2017 41

040_ro0417_f2.indd 41 4/3/17 12:56 PM Drug Mechanisms: Anti-Inflammatories

The OCT on the left shows a patient with CME. This was successfully resolved with Durezol BID OS and Ilevro QD OS over a nine- week period, as seen in the right OCT.

endogenous inflammations of the Durezol had superior dose unifor- Vexol and prednisolone phosphate eye.4 mity compared with Pred Forte and sodium provide for cost-consci- Approved by the FDA in 2008, its generic counterpart because of its entious prescribing. Additionally, Durezol—a synthetic difluorinated emulsion formulation.13 research found Vexol had equal prednisolone derivative—is the most Historically, Pred Forte has been efficacy in the treatment of anterior recent corticosteroid addition to the the main option for intraocular uveitis with a decreased chance of list of drugs approved for the treat- inflammation treatment.7 Research increasing IOP compared with Pred ment of postoperative inflammation shows Pred Forte has varying anti- Forte.15 This may be a good alterna- and pain.7 In addition to difluorina- inflammatory benefits compared tive for known steroid responders or tion and augmentation with butyr- with the generic formulation. In a glaucoma patients. ate, Durezol has increased corneal comparative analysis of prednisolone penetration due to the substitution acetate suspensions, one study found Ocular Surface of a hydroxyl group with acetate.7 that Pred Forte exhibited greater Retrometabolic drugs are currently This translates into topical dosing homogeneity and bioavailability of used in the treatment of many that is half of what is needed with the drug between doses compared systemic conditions.8 Such agents Pred Forte, which may help improve with EconoPred (Alcon) and generic convert the inactive drug metabo- patient compliance. A study that prednisolone acetate.14 Pred Forte lite into a structurally modified investigated Durezol dosed QID and its generic counterparts are for- analogue. After eliciting therapeu- compared with prednisolone acetate mulated in a suspension and require tic benefit, the analog undergoes 1% dosed at eight times a day found vigorous shaking before instillation. rapid degradation and metabolism, Durezol to be noninferior in a mul- Other maximally effective corti- thereby decreasing the opportunity ticenter randomized double-masked costeroids for treating intraocular for adverse drug reactions.9 Because trial.7 Additionally, Durezol is for- inflammation include Vexol (rimexo- these synthetic analogs possess mulated as an emulsion, which does lone 1%, Alcon) and prednisolone the same therapeutic benefit with not require shaking prior to instilla- phosophate sodium 1%. decreased adverse drug reactions, tion. In one study, researchers found Available in generic formulations, they are known as soft drugs.8,9

42 REVIEW OF OPTOMETRY APRIL 15, 2017

040_ro0417_f2.indd 42 4/3/17 12:56 PM Photos: Sulman Hans, OD

The lower photo shows dramatic improvement over one week of the anterior uveitis (4+cell/4+flare) and posterior synechiae in this patient’s right eye (above) with Durezol six times a day and cyclopentolate BID.

Loteprednol etabonate, for exam- Alrex, and a combination of lotepre- Allergan) or prednisolone acetate ple, is a cortienic acid-based deriva- dnol etabonate 0.5% and tobramy- 0.12%. These alternatives are avail- tive that exhibits highly lipophilic cin 0.3% is branded as Zylet. able in generic formulations and are properties, reported to be 10 times Both Lotemax 0.5% gel and lower in cost compared with their greater than dexamethasone, allow- ointment are FDA-approved for branded counterparts. ing increased penetration into cell the treatment of postoperative membranes.9,10,16 Researchers found inflammation and pain.20 Alrex is Dermatological Inflammation of the C-labelled loteprednol etabonate FDA-approved for the treatment Eyelids/Adnexa 0.5% metabolites in highest concen- of seasonal allergic conjunctivitis.21 Inflammation of the eyelids and tration in the cornea of rabbit eyes Though the literature is divided on adnexa are common presentations, and lower metabolite concentrations its efficacy in treating anterior uveitis and a detailed history and thorough in the iris/ciliary body and aqueous compared with prednisolone, there ophthalmoscopic evaluation should humor, respectively, indicating a is increased safety with loteprednol yield whether it is allergic in nature majority of loteprednol etabonate etabonate use, evidenced with a or of infectious etiology. In cases of metabolism occurs in the cornea.17,18 lower frequency of IOP elevation.3 moderate to significant dermatologic Additionally, researchers increased Other conditions that respond inflammation, topical corticosteroids penetration of loteprednol etabonate well to lesser-strength (compared are warranted. in the cornea and conjunctiva com- with Pred Forte and Durezol) cor- Dermatologic presentations can pared with the aqueous humor levels ticosteroids include keratoconjunc- be treated with ointment formula- due to rapid hydrolysis.19 tivitis sicca, corneal-involving viral tions (an off-label use), such as Lotemax (loteprednol etabonate conjunctivitis, allergic and vernal Lotemax 0.5% and FML 0.1%, as 0.5%, Bausch + Lomb)—available conjunctivitis and to prevent scar- they allow for increased contact time as a gel or ointment—is a useful ring of the cornea.4 at the site of inflammation.4 anti-inflammatory option to have Alternative options for the treat- If the inflammation is secondary in your arsenal. A 0.2% suspension ment of ocular surface inflammation to infectious etiologies, clinicians can formulation of loteprednol eta- include FML (fluorometholone oph- use a combination corticosteroid/ bonate is available under the name thalmic suspension 0.25%, 0.1%, antibiotic ointment such as Tobra-

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040_ro0417_f2.indd 43 4/3/17 12:56 PM Drug Mechanisms: Anti-Inflammatories

Dex (tobramycin 0.3%/dexametha- sone 0.1%, Alcon), TobraDex ST (tobramycin 0.3%/dexamethasone 0.05%, Alcon), Maxitrol (neomy- cin 0.35%/dexamethasone 0.1%, Alcon) or Blephamide (sulfacetamide 10%/prednisolone acetate 0.2%, Allergan), to name a few. These pro- vide good gram-positive coverage for the normal flora of the eyelids/skin. Additionally, consider sulfa allergies prior to prescribing some of these This patient’s neomycin ointment hypersensitivity of the right eyelid (left) was alternatives. resolved (right) with topical FML 0.1% ointment applied BID OU for four weeks.

Ending Treatment Indications Alcon) and Prolensa (bromfenac All corticosteroid therapy should In addition to the synergistic effects 0.07%, Bausch + Lomb). Both Ilevro be tapered to prevent any bouts of NSAID and corticosteroids have on and Prolensa are dosed QD and are repeat inflammation. Unfortunately, postoperative CME formation and FDA-approved for postoperative tapering schedules are more of an treatment, NSAID use primarily inflammation and pain.24,25 Ilevro, art than a science. There is no uni- ameliorates pain on the ocular sur- a prodrug, is highly permeable to versally accepted tapering regimen face. Anecdotally, research suggests the cornea and is rapidly hydro- in the literature other than defined NSAIDs can be used temporarily to lyzed to amfenac in the aqueous.26,27 improvement by the Standard Uve- treat pain and irritation related to Amfenac is a potent inhibitor of itic Nomenclature (SUN) group.22 mechanical or surgical irritation of COX-1/COX-2 isoenzymes.27 Once- With improvement, and thereby the conjunctiva and cornea, pre-post a-day dosing is possible due to the response to the steroid regimen, the 5% betadine wash for viral epidemic increased nepafenac concentration taper can be initiated. Ultimately, the keratoconjunctivitis or in combina- from 0.1% to 0.3%. Almost struc- clinician is responsible for changing tion with a strong corticosteroid for turally identical to amfenac, Prolensa dosing schedules and the start of the recalcitrant cases of uveitis.4 Most contains a bromine atom that makes taper based on clinical improvement indications for NSAID use are off- Prolensa highly lipophilic, increasing and intuition. When a clinician inev- label therapy options. corneal penetration and duration of itability encounters a reoccurrence Generally, topical NSAIDs will action.27 As NSAIDs are intrinsically of inflammation because a steroid be used in combination with maxi- acidic, Prolensa has been buffered to is tapered too quickly, initial dosing mal efficacy corticosteroids in the a pH of 8.3 for additional comfort schedule of the steroid is required. treatment of postoperative CME, with instillation.27 typically in concert with the cataract An NSAID’s formulation is key NSAIDs surgeon. to ensuring the patient is obtain- Topical nonsteroidal anti-inflam- Today’s NSAID options are ing a therapeutic concentration of matory therapy is used sparingly dosed anywhere from QID to QD. drug with each instillation. NSAID in the primary care setting, mostly Clinicians should follow the recom- formulations in suspension require to prevent and treat postoperative mended dosing to limit risk for side shaking to increase the drug’s bio- inflammation. A vast majority of the effects related to prolonged NSAID availability. NSAID options are FDA-approved use. As with corticosteroid use, Other NSAID options available for the treatment of pain and inflam- duration of use should be limited include: Acular LS and Acuvail mation associated with cataract (roughly one month). Chronic use (ketorolac tromethamine, Allergan), surgery.4 retards corneal epithelial healing Bromsite (bromfenac ophthalmic Additionally, NSAID therapy can and corneal melting and perfora- solution, Sun Pharmaceuticals) and be used to maintain mydriasis dur- tion, although extremely rare, are Voltaren (diclofenac sodium, Endo ing cataract surgery and decrease reported in the literature.23 Pharmaceuticals). These options may pain in photorefractive keratectomy Newest to the topical NSAID drug be dictated by the patient’s insurance patients.18 market are Ilevro (nepafenac 0.3%, coverage or budget. They range in

44 REVIEW OF OPTOMETRY APRIL 15, 2017

040_ro0417_f2.indd 44 4/3/17 12:56 PM 6. Allergan. Pred Forte package insert. Irvine, CA, 2013. dosing from BID to QID and may and completed a one-year post- 7. Jamal KN, Callanan DG. The role of difluprednate oph- sacrifice medication compliance, graduate residency in primary care at thalmic emulsion in clinical practice. Clinical Ophthalmology. 2009;3:381. given the increase in dosing com- The Eye Institute. He currently is an 8. Bodor N, Buchwald P. Soft drug design: general principles pared to their QD counterparts. instructor at Salus University-PCO and recent applications. Medicinal Research Reviews. 2000;20(1):58-101. where he works with interns and 9. Bodor N, Buchwald P. Ophthalmic drug design based on the metabolic activity of the eye: soft drugs and chemical delivery Advancement in drug delivery sys- residents. He has a special interest in systems. The AAPS Journal. 2005;7(4):E820-33. tems and drug formulations continue ocular surface disease and anterior 10. Yellepeddi VK, Palakurthi S. Recent advances in topical ocular drug delivery. Journal of Ocular Pharmacology and to equip eye care providers for suc- segment inflammation. Dr. Higa has Therapeutics. 2016;32(2):67-82. cessful treatment of many inflamma- received honoraria from Allergan 11. Chang DF, Tan JJ, Tripodis Y. Risk factors for steroid response among cataract patients. J Cataract Refract Surg. tory conditions. The ever-changing but has no direct financial disclo- 2011;37(4):675-81. 12. Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: field promises future advancements sures for the products mentioned. a review of the literature. Eye. 2006;20(4):407-16. to help patients heal quicker and 13. Stringer W, Bryant R. Dose uniformity of topical corticoste- 1. Ricciotti E, FitzGerald GA. Prostaglandins and inflam- roid preparations: difluprednate ophthalmic emulsion 0.05% decrease vision-threatening con- mation. Arteriosclerosis, thrombosis, and Vascular Biology. versus branded and generic prednisolone acetate ophthalmic ditions. With proper selection, 2011;31(5):986-1000. suspension 1%. Clin Ophthalmol. 2010 Oct 5;4:1119-24. 2. Comstock TL, DeCory HH. Advances in corticosteroid therapy 14. Roberts CW, Nelson PL. Comparative analysis of predniso- evaluation and education, eye care for ocular inflammation: loteprednol etabonate. International lone acetate suspensions. Journal of Ocular Pharmacology and Journal of Inflammation. 2012 Mar 28;2012. Therapeutics. 2007;23(2):182-7. providers have a large repertoire of 3. Sheppard JD, Comstock TL, Cavet ME. Impact of the topical 15. Foster CS, Alter G, DeBarge LR, et al. Efficacy and safety treatment regimens for the successful ophthalmic corticosteroid loteprednol etabonate on intraocular of rimexolone 1% ophthalmic suspension vs 1% predniso- ■ pressure. Advances in Therapy. 2016;33(4):532-52. lone acetate in the treatment of uveitis. Am J ophthalmol. treatment of their patients. 4. Thomas R, Melton R. 2016 Clinical guide to ophthalmic 1996;122(2):171-82. Dr. Higa graduated in 2014 from drugs. Rev Optom. 2016;153(5): 20-5. 16. Alberth M, Wu WM, Winwood D, Bodor N. Lipophilicity, 5. Yonekawa Y, Kim IK. Pseudophakic cystoid macular edema. solubility and permeability of loteprednol etabonate: a novel, soft the Illinois College of Optometry Curr Opin Ophthalmol. 2012;23(1):26-32. anti-inflammatory steroid. J Biopharm Sci. 1991;2(2):115-25. 17. Druzgala P, Wu WM, Bodor N. Ocular absorption and dis- tribution of loteprednol etabonate, a soft steroid, in rabbit eyes. Dry Eye Disease Current Eye Research. 1991;10(10):933-7. 18. Schalnus R. Topical nonsteroidal anti-inflammatory therapy Topical anti-inflammatory drugs provide eye care providers a long-term treatment strategy in ophthalmology. Ophthalmologica. 2003;217(2):89-98. for dry eye disease (DED) with almost no risk of systemic ADR when dosed as approved.28,29 19. Glogowski S, Proksch JW. Ocular pharmacokinetics of loteprednol etabonate following ocular administration of a Both Restasis (cyclosporin A 0.05% emulsion, Allergan) and Xiidra (lifitegrast 5% solution, novel ointment formulation or a suspension (Lotemax) in Shire) act on T-cells in the tear film, conjunctiva and cornea to decrease tissue destruction rabbits with corneal inflammation. Invest Ophthalmol Vis Sci. 2010;51(13):1980. and further inflammation related to DED.30-33 20. Bausch+Lomb. Lotemax package insert. Bridgewater, NJ, 2016. Restasis was FDA-approved in 2003 to increase the eye’s ability to produce tears in patients 21. Bausch+Lomb. Alrex package insert. Tampa, FL, 2013. with inflammation related to keratoconjunctivitis sicca.34 Dosed BID, Restasis is a calcineurin 22. Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting 30 inhibitor that prevents interlukin-2 (IL-2) formulation. IL-2 is secreted by T-helper cells and clinical data. Results of the First International Workshop. Am J stimulates the proliferation of cytotoxic T-cells and additional T-helper cells. Restasis halts the Ophthalmol. 2005;140(3):509-16. 23. Lin JC, Rapuano CJ, Laibson PR, et al. Corneal propagation of additional T-cells, decreasing further damage to the ocular surface. Clinically, melting associated with use of topical nonsteroidal anti- inflammatory drugs after ocular surgery. Arch Ophthalmol. the effects of Restasis will not manifest immediately because of activated T-cells on the ocular 2000;118(8):1129-32. surface prior to its use. To combat this, clinicians should consider using topical corticosteroids 24. Alcon. Ilevro package insert. Ft. Worth, TX, 2013. 32 25. Bausch+Lomb. Prolensa package insert. Tampa, FL, 2013. in conjunction with Restasis for a few weeks. The corticosteroid will help target the inflamma- 26. Chastain JE, Sanders ME, Curtis MA, et al. Distribution of tion, while Restasis will maintain long-term anti-inflammatory effects. topical ocular nepafenac and its active metabolite amfenac to the posterior segment of the eye. Experimental Eye Research. Xiidra, FDA-approved in 2016 to treat the signs and symptoms of dry eye, is the second and 2016 Apr;145:58-67. newest addition to topical immunomodulatory drugs for the treatment of dry eye.35 Xiidra also 27. Ahuja M, Dhake AS, Sharma SK, Majumdar DK. Topical ocu- lar delivery of NSAIDs. The AAPS Journal. 2008;10(2):229-41. inhibits the T-cell mediated inflammatory pathway by preventing the recruitment and activation 28. Gire AI, Karakus S, Ingrodi SM, Akpek EK. Frequent dosing of topical cyclosporine A for severe ocular surface of T-cells to the ocular surface. Xiidra does this by blocking the adhesion of lymphocyte func- disease. Journal of Ocular Pharmacology and Therapeutics. tion-associated antigen-1 (LFA-1) to intracellular adhesion molecule-1 (ICAM-1).31 By blocking 2016;32(3):150-4. 29. Donnenfeld ED, Karpecki PM, Majmudar PA, et al. Safety this interaction, T-cells do not migrate out of the blood vessel and decrease the interaction with of Lifitegrast ophthalmic solution 5.0% in patients with dry eye antigen presenting cells.31 Furthermore, there is a decrease in cytokine release at inflammation disease: a 1-year, multicenter, randomized, placebo-controlled study. Cornea. 2016;35(6):741. sites. Formulated in a solution, Xiidra is dosed BID and is preservative-free. Future studies of 30. Matsuda S, Koyasu S. Mechanisms of action of cyclospo- this new agent will help to educate doctors on its clinical performance and role in the treatment rine. Immunopharmacology. 2000;47(2):119-25. 31. Perez VL, Pflugfelder SC, Zhang S, et al. Lifitegrast, a novel regimen. A topical soft steroid such as Lotemax may also be considered at initiation of Xiidra, integrin antagonist for treatment of dry eye disease. The Ocular Surface. 2016;14(2):207-15. given the pre-existing inflammation likely present on the ocular surface. 32. Pflugfelder SC. Anti-inflammatory therapy for dry eye. Am J Having two therapeutic options available provides perceptive practitioners an alternative Ophthalmol. 2004;137:337-42. 33. Donnenfeld E, Pflugfelder SC. Topical ophthalmic cyclo- drug choice if a patient has failed on prior therapies, thus increasing the likelihood of success sporine: pharmacology and clinical uses. Surv Ophthalmol. in the management of this complicated disease process. 2009;54(3):321-38. 34. Allergan. Restasis package insert. Irvine, CA, 2013. 35. Shire. Xiidra package insert. Lexington, MA, 2016.

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Glaucoma Therapy: Finding the Right Combination

Understanding the basic pharmacology for each glaucoma medication can help you sort out which ones work well together for combination treatment. By Susan Yee, OD

s a progressive eye disease, glaucoma is on every optom- etrist’s radar, especially pri- mary open-angle glaucoma A 1-10 (POAG), the most common form. Research estimates it will affect around 80 million people worldwide by the year 2020.6,7,11 The main therapeutic goal for patients diag- nosed with POAG is slowing disease progression and the rate of visual field loss—accomplished by reduc- tion of intraocular pressure (IOP) with medical therapy.1,3,6,8,10-13 These days, however, medical This 69-year-old white male has no family history of glaucoma. His initial IOP was therapy isn’t as simple as prescrib- 42mm Hg in the right eye and 36mm Hg in the left. With brimonidine BID, dorzolamide ing eye drops and sending patients BID and latanoprost QHS, his IOP is now 15mm Hg in both eyes. on their way. Clinicians mainly prescribe from one of four classes clinicians can add a second or even ciliary body. Aqueous is produced of IOP-lowering medications: beta a third drug, which further compli- by diffusion, ultrafiltration and blockers (B-blockers), carbonic cates the treatment plan. This article active secretion, involving the active

anhydrase inhibitors (CAIs), prosta- discusses the many IOP-lowering transport of Na+, Cl- and HCO3-. glandin analogs (PGAs) and alpha medication options and factors that Aqueous production occurs in the 2-adrenergic agonists.2,7,9,14 can influence treatment choices. posterior chamber and passes out Each class can cause local and of the anterior chamber through the systemic adverse reactions, and Physiology and trabecular meshwork. Most resis- clinicians must take all of them Mechanism of Action tance to aqueous outflow is located into consideration when choosing Aqueous humor, produced at the cil- in the extracellular matrix (ECM) of the right therapy for each patient iary processes, is regulated by neuro the trabecular meshwork. Glycos- (Table 1).4,8,9,15,16 And when patients inputs from both the sympathetic aminoglycans within the ECM influ- don’t see the IOP lowering effects and parasympathetic systems and by ence the hydration of the trabecular they need with one class of drug, vascular contractile-dilation in the meshwork, and the parasympathetic

46 REVIEW OF OPTOMETRY APRIL 15, 2017

046_ro0417_f3.indd 46 4/3/17 2:17 PM cholinergic innervation of the iris Two is Better than One and the ciliary muscle all influence Research has yet to outline aqueous humor outflow. which adjunctive agents are Aqueous outflow is also assisted most effective in achieving IOP by an unconventional route through control. Some monotherapy the uveal meshwork and the cili- clinical trials suggest that ary muscle called the uveoscleral B-blockers and alpha agonists pathway. Prostaglandin F2α within are more effective than CAIs in the ciliary muscle decreases the IOP control. However, a sys- flow resistance of its interstitial temic review and meta-analysis space, thereby increasing aqueous revealed similar mean diurnal outflow through the uveoscleral IOP-lowering efficacy when pathway. B-blockers and alpha a B-blocker, an alpha agonist agonists reduce aqueous production or a CAI agent was combined by their effects on the B2 adrener- with a PGA.21 One study gic and presynaptic α2 receptors, found adding a CAI to a PGA respectively. Alpha agonists also lowered nocturnal IOP more can increase trabecular meshwork than with either a B-blocker or outflow. CAIs inhibit the activities alpha agonist.21 of carbonic anhydrase responsible In lieu of better clinical data, The patient’s RNFL scan shows superior and temporal rim thinning in the right eye. for HCO3- secretion, thus reducing clinicians must take factors the production and active secretion such as efficacy, frequency of of aqueous humor from the ciliary dosing schedule, ocular side body. Prostaglandin analogs increase effects and tolerability into uveoscleral outflow by activating consideration when prescribing prostaglandin F2α receptors, leading an additional medication.8,21 to ECM remodeling in the ciliary Research suggests incidence of muscle, in turn reducing hydraulic eye pain and burning sensation resistance and increasing uveoscleral is higher with alpha agonists outflow.9,16 and CAIs compared with B-blockers, which can affect Where to Begin patient compliance.21 Another PGAs are often first-line treatment major advantage of using a for IOP reduction in POAG and B-blocker as adjunctive ther- ocular hypertension (a condition apy is its FDA-approved once- with elevated IOP but no detectable daily dosing of timolol 0.5% glaucoma damage) and are recom- gel forming solution, although mended by both the American Acad- generally FDA-approved dos- emy of Ophthalmology Preferred ing for B-blockers is BID. Practice Patterns and the UK-based Aqueous production drops National Institute for Health and at night, which may explain Care Excellence guidelines.1,9,12,17-19 why B-blockers are ineffective The patient’s GCA correlates with rim thinning in For some, PGA monotherapy in nocturnal IOP reduction. the right eye and a normal left eye. is enough to achieve and maintain Most research indicates timo- adequate IOP control. For many, lol has the greatest IOP-lowering the dosing frequency to only twice a however, more than one medication efficacy in the morning, while PGAs day. Also, one study found timolol is required to achieve desirable IOP are most effective in the evening. Cli- causes less severe ocular side effects reduction, and clinicians must con- nicians may prescribe a concomitant with higher tolerability, which may sider adding a B-blocker, a CAI and/ therapy of timolol 0.5% gel daily in increase patient compliance with or an alpha agonist to an existing the morning and PGA at night for medication adherence. PGA.3,13,20 optimal IOP reduction—limiting CAIs are good alternative agents

REVIEW OF OPTOMETRY APRIL 15, 2017 47

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approved: Cosopt (dorzolamide/ timolol, Akorn) BID, Combigan (brimonidine/timolol, Allergan) BID and Simbrinza (brinzolamide/brimo- nidine, Alcon) TID.13,24 One of the main advantages of fixed-combination is dosing fre- quency. Concomitant treatment involving a B-blocker (BID) and a CAI (BID or TID) or an alpha ago- nist (BID or TID) requires patients instill two separate medications in the morning and in the evening for a total of four drops per day, five minutes between drops—which can Visual fields show the inferior arcuate in the right eye that correlates with RNFL and be troublesome and time consum- GCA. The fields are clean in the left eye. ing. Fixed-combination therapy can reduce dosing frequency to to add to PGAs for patients who down the progressive loss of retinal two or three drops (when already are contraindicated to B-blockers ganglion cells in glaucoma.3,5,9,13,21 on a PGA) per day. Less daily dos- or if the IOP-lowering effects are ing simplifies a patient’s treatment not satisfactory. Topical CAI agents Third Time’s the Charm plan, avoids medication washout, are FDA-approved for TID dosing, Unfortunately, some patients still do decreases preservative exposure but are often used BID in clinical not achieve adequate IOP control and, in many cases, decreases ocular practice, especially as adjunctive with two adjunctive medications. In effects without affecting IOP-lower- therapy. Another option for therapy these cases, treatment becomes more ing efficacy.3,10,13,20,25 with PGAs is an alpha agonist. Like complicated when a third topical Here is a closer look at the com- CAIs, alpha agonists are also FDA- hypotensive agent is added. bined mechanisms of action for the approved for TID dosing, but are Some of the challenges with available fixed-combination medica- often used BID. Some studies have multiple drug therapy include an tions (Table 2): suggested the alpha agonist brimo- increase in dosing frequency, risk of B-blocker/CAIs work synergisti- nidine in particular provides a neu- drug washout, ocular side effects and cally to reduce overall aqueous pro- roprotective role, which may slow exposure to preservatives, the latter duction.3 causing an increase in ocular surface B-blocker/alpha agonists also Contraindications disease and discomfort. These fac- work synergistically as an aqueous All IOP-lowering medications possess tors can potentially interfere with suppressant. Alpha agonists can also some degree of local and systemic side medication adherence and decrease enhance outflow through the uveo- effect. Some, however, are contraindi- overall efficacy.14,22,23 When patients scleral pathway—perhaps further cated for patients with specific systemic are placed on multiple concomitant reducing IOP.3 conditions. Patients with asthma, chronic hypotensive agents, clinicians should CAI/alpha agonists decrease obstructive pulmonary disease, bradycar- consider fixed-combination medica- aqueous production and increase dia, heart block, congestive heart failure or tions as an alternative to traditional uveoscleral outflow. It is often a those taking an oral beta blocker should concomitant therapy.10,19 good alternative treatment for those not be treated with a topical B-blocker.4,8,9 who cannot take B-blockers or wish PGAs should be avoided by those who are Combinations, Simplified to avoid PGAs due to ocular effects pregnant or have an ophthalmic inflam- Most fixed-combination medications of hyperemia, eyelash growth, iris or matory condition. Alpha agonists are con- contain a B-blocker with a CAI, periorbital hyperpigmentation, espe- traindicated in neonates, children younger an alpha agonist or a PGA—only cially with monocular treatments.13 than two and those who are taking mono- one combines a CAI with an alpha B-blockers/PGA lower IOP by amine oxidase inhibitors.15,16 agonist. In the United States, only decreasing aqueous production and three fixed-combinations are FDA- increasing outflow.3,10,20

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046_ro0417_f3.indd 48 4/3/17 2:17 PM CATHY CATARACTS & ANDY ASTIGMATISM 2 EYE CONDITIONS PROCEDURE

1 TWO BIRDS WITH ONE STONE GET . HELP YOUR PATIENTS CORRECT CATARACTS & ASTIGMATISM WITH ONE PROCEDURE.

Talk to your astigmatic patients about toric IOL options earlier, and help them see cataract surgery as an opportunity to correct two eye conditions at once.

mycataracts.com: online patient resources 1-844-MYCATARACT (1-844-692-2827): cataract counselors

© 2016 Novartis 10/16 US-ODE-16-E-4365

WO0317_Alcon surgical.indd 1 2/27/17 4:54 PM Drug Mechanisms: Glaucoma

Table 1. Glaucoma Drug Options4,7,8,12,15,16 Class Names Mechanism of Ocular Effects Systemic Effects Action: Reduce IOP Beta-blocker • Timolol • Decrease aqueous • Conjunctival allergy • Decrease blood pressure/pulse • Betagan (levobunolol, production • Hyperemia • Bradycardia Allergan) • Corneal epithelial disorders • Worsen asthma/COPD • Ocupress (carteolol, Novartis) • Reduced corneal • Depression • Betoptic (betaxolol, Alcon) sensitivity • Impotence • Optipranolol (metipranolol, • Blurry vision • Lethargy Valeant Pharmaceuticals) Carbonic anhydrase • Trusopt (dorzolamide, Merck) • Decrease aqueous • Same as B-blockers Topical use: inhibitor • Azopt (brinzolamide, Alcon) production • Ocular irritation • Bitter taste • Diamox (acetazolamide oral • Foreign body sensation • Fatigue capsule, Teva Pharmaceuticals) • Diuresis • Neptazane (methazolamide • Gastrointestinal upset oral capsule, Perrigo) Oral use: • Nausea • Unpleasant taste • Dysesthesia of fingers/lips • Anorexia • Metabolic acidosis Prostaglandin analog • Xalatan (latanoprost, Pfizer) • Increase uveoscleral • Same as B-blockers • Rarely, upper respiratory • Travatan (travoprost, Alcon) outflow • Eyelash growth infection • Rescula (unoprostone • Iris/eyelid pigment • Rarely, myalgia isopropyl, Sucampo) • Deepening of upper eyelid • Zioptan (tafluprost, Akorn) sulcus ------• Recurrence of herpes • Lumigan • Increase uveoscleral • Macular edema post (bimatoprost, Allergan) and trabecular cataract surgery meshwork outflow Alpha 2-adrenergic • Alphagan (brimonidine, • Decrease aqueous • Allergic conjunctivitis • Affects blood pressure/pulse agonist Allergan) production • Hyperemia • Drowsiness • Iopidine (apraclonidine, Alcon) • Increase • Mydriasis • Dizziness uveoscleral outflow • Dry eye • Dry mouth • Dysarthria Parasympathomimetic • Pilocar • Increase trabecular • Miosis Direct-acting: /cholinergic agonist (pilocarpine, FDC Limited) meshwork outflow • Visual field constriction • Rare systemic reactions • Night vision loss Indirect-acting: • Myopia • Sweating • Red eye • Tearing • Brow ache • Nausea/vomiting • Retinal detachment • Diarrhea • Cataract • Bradycardia • Stomach ache

Treatments on the Horizon oxide (NO) donor that reduces Rhopressa (netarsudil 0.02%, Because glaucoma is the second IOP by increasing aqueous outflow Aerie Pharmaceuticals) is both a leading cause of blindness world- through both the trabecular mesh- RHO-associated protein kinase wide, researchers are continually work/Schlemm’s canal and uveo- inhibitor and norepinephrine on the hunt for better therapeutic scleral pathways. In phase III trials, transporter inhibitor. It has two options.1,3,7,8,12,14 These new meds once-daily use of this drug per- mechanisms of action aimed at IOP are designed to simplify treatment formed better than both twice-daily reduction: increasing trabecular with a once-daily dosing schedule: timolol and once-daily latanoprost. meshwork outflow and decreasing Vyzulta (latanoprostene bunod Mild punctate keratitis and ocular aqueous production. Rho-kinase 0.024%, Bausch + Lomb) is a com- hyperemia are the most common inhibitors destabilize filamentous pound of latanoprost and a nitric ocular side effects.2,4,9,14,26-28 actin, leading to more empty space

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046_ro0417_f3.indd 50 4/3/17 2:18 PM RO0815_Lombart.indd 1 7/22/15 2:19 PM Drug Mechanisms: Glaucoma

in trabecular meshwork and improv- risk factor—elevated IOP—clini- 8. Inoue K. Managing adverse effects of glaucoma medications. Clinical Ophthalmology. 2014;8:903-913. ing outflow. Norepinephrine trans- cians must be prepared to prescribe 9. Bucolo C, Platania CB, Reibaldi M, et al. Controversies in glau- coma: current medical treatment and drug development. Current porter inhibitors result in reduced any number of IOP-lowering drugs, Pharmaceutical Design. 2015;21(32):4673-81. aqueous production. It has a once- as monotherapy or in combination. 10. Fang Y, Ling Z, Sun X. Fixed-combination treatments for intraocular hypertension in Chinese patients - focus on daily dosing schedule, and the most PGAs have emerged as the gold bimatoprost-timolol. Drug Design, Development and Therapy. common ocular side effect is mild standard initial monotherapy treat- 2015;9:2617-25. 11. Ting NS, Li Yim JF, Ng JY. Different strategies and cost- hyperemia.2,4,9,11,14,28 A phase III clin- ment for POAG; but when mono- effectiveness in the treatment of primary open angle glaucoma. ClinicoEconomics and Outcomes Research. 2014;6:523-30. ical trial was completed in 2016. therapy cannot achieve desirable 12. Li T, Lindsley K, Rouse B, et al. Comparative effectiveness Roclatan (Aerie Pharmaceuti- IOP reduction, additional medica- of first-line medications for primary open-angle glaucoma: a systematic review and network meta-analysis. Ophthalmology. cals), currently in phase III clinical tions, whether through concomitant 2016;123(1):129-40. trials, is a combination of netarsudil therapy or fixed-combination medi- 13. Sharma S, Trikha S, Perera SA, Aung T. Clinical effectiveness of brinzolamide 1%-brimonidine 0.2% fixed combination for 0.02% and latanoprost 0.005%. It cations, can help adequately control primary open-angle glaucoma and ocular hypertension. Clinical Ophthalmology. 2015;9:2201-7. is administered once daily to act on a patient’s IOP. In the future, newer 14. Schehlein EM, Novack GD, Robin AL. New classes of glau- both the trabecular meshwork and treatment modalities may lower coma medications. Curr Opinion Ophthalmoly. November 2016. [Epub ahead of print]. the uveoscleral outflow pathways to IOP and slow glaucoma progression 15. Rhee DJ. Glaucoma: color atlas and synopsis of clinical oph- reduce fluid production.9,14,24,28 with even better dosing regimens. ■ thalmology. Wills Eye Hospital. 2003. 16. Bartlett JD. Clinical ocular pharmacology. Fourth ed. Boston: Trabodenoson (Inotek Pharma- Dr. Yee is a staff optometrist in Butterworth-Heinemann; 2001. 17. Peeters A, Schouten JS, Severens JL, et al. Latanoprost ceuticals) is an adenosine analog the Salisbury VA Health Care Sys- versus timolol as first choice therapy in patients with ocular that targets A1 receptors, resulting in tem, Salisbury, NC. hypertension. A cost-effectiveness analysis. Acta ophthalmologica. 2012;90(2):146-54. the removal of proteins from the tra- 18. Daka Q, Trkulja V. Efficacy and tolerability of mono-compound becular meshwork, lowering outflow 1. Fung DS, Whitson JT. An evidence-based review of unopros- topical treatments for reduction of intraocular pressure in patients tone isopropyl ophthalmic solution 0.15% for glaucoma: place in with primary open angle glaucoma or ocular hypertension: an over- 9,14,29 resistance and IOP. Researchers therapy. Clinical Ophthalmology. 2014;8:543-54. view of reviews. Croatian Medical Journal. 2014;55(5):468-80. 2. Rocha-Sousa A, Rodrigues-Araujo J, Gouveia P, et al. New 19. Singh K, Lee BL, Wilson MR. A panel assessment of glaucoma are working to combine trabodeno- therapeutic targets for intraocular pressure lowering. ISRN oph- management: modification of existing RAND-like methodology for thalmology. 2013;2013:261386. consensus in ophthalmology. Part II: Results and interpretation. son with latanoprost and brimoni- 3. Radcliffe NM. The impact of timolol maleate on the ocular 2,4,9,14,28 Am J Ophthalmol. 2008;145(3):575-81. dine for glaucoma treatment. tolerability of fixed-combination glaucoma therapies. Clinical 20. Barnebey HS, Robin AL. Adherence to fixed-combination Ophthalmology. 2014;8:2541-9. versus unfixed Travoprost 0.004%/timolol 0.5% for glaucoma In January 2017, Inotek announced 4. MK. Present and new treatment strategies in the management or ocular hypertension: a randomized trial. Am J Ophthalmol. of flaucoma. The Open Ophthalmology Journal. 2015;9:89-100. the results of phase III clinical trials, December 2016. [Epub ahead of print]. 5. Doozandeh A, Yazdani S. Neuroprotection in glaucoma. J Oph- 21. Tanna AP, Lin AB. Medical therapy for glaucoma: what to thal Vision Res. 2016;11(2):209-20. which did not achieve superiority to add after a prostaglandin analogs? Curr Opin Ophthalmol. 6. Knight OJ, Lawrence SD. Sustained drug delivery in glaucoma. 30 2015;26(2):116-20. placebo at all 12 time points. Curr Opin Ophthalmol. 2014;25(2):112-7. Because the only way to manage 7. Wojcik-Gryciuk A, Skup M, Waleszczyk WJ. Glaucoma -state of 22. Hollo G, Topouzis F, Fechtner RD. Fixed-combination the art and perspectives on treatment. Restorative Neurology and intraocular pressure-lowering therapy for glaucoma and ocular glaucoma is to reduce the primary Neuroscience. 2015;34(1):107-23. hypertension: advantages in clinical practice. Expert Opinion on Pharmacotherapy. 2014;15(12):1737-47. 23. Friedman DS, Quigley HA, Gelb L, et al. Using pharmacy Table 2. Fixed-combination Medications3,4,8,13,24 claims data to study adherence to glaucoma medications: meth- odology and findings of the Glaucoma Adherence and Persistency Study (GAPS). Invest Ophthalmol Vis Sci. 2007;48(11):5052-7. Effects on aqueous humor (AH) Market availability 24. Fechtner RD, Khouri AS. Fixed combination: a mainstay of glaucoma management today and tomorrow. Glaucoma Today. Cosopt (dorzolamide/ Decrease AH/decrease AH USA/other countries 2016;14(6):33-6. timolol, Akorn) 25. Newman-Casey PA, Robin AL, Blachley T, et al. The most common barriers to glaucoma medication adherence: a cross- Combigan (brimonidine/ Decrease AH, increase outflow/ USA/other countries sectional survey. Ophthalmology. 2015;122(7):1308-16. timolol, Allergan) decrease AH 26. Araie M, Sforzolini BS, Vittitow J, Weinreb RN. Evaluation of the effect of latanoprostene bunod ophthalmic solution, 0.024% in lowering intraocular pressure over 24 h in healthy Japanese Simbrinza (brinzolamide/ Decrease AH/decrease AH, USA/other countries subjects. Advances in Therapy. 2015;32(11):1128-39. brimonidine, Alcon) increase outflow 27. Cavet ME, Vollmer TR, Harrington KL, et al. Regulation of endothelin-1-induced trabecular meshwork cell contractil- Brinzolamide/timolol Decrease AH/decrease AH Other countries ity by latanoprostene bunod. Invest Ophthalmol Vis Sci. 2015;56(6):4108-16. DuoTrav (travoprost/ Increase outflow/decrease AH Canada/other countries 28. Glaucoma Research Foundation. New medical therapies for glaucoma. 2017. www.glaucoma.org/treatment/new-medical- timolol, Alcon) therapies-for-glaucoma.php. Accessed February 17, 2017. 29. Myers JS, Sall KN, DuBiner H, et al. A dose-escalation study to Latanoprost/timolol Increase outflow/decrease AH China/other countries evaluate the safety, tolerability, pharmacokinetics, and efficacy of 2 and 4 weeks of twice-daily ocular trabodenoson in adults with Bimatoprost/timolol Increase outflow (uveoscleral and China/countries ocular hypertension or primary open-angle glaucoma. J Ocular TM)/decrease AH worldwide Pharmacol Therapeutics. 2016;32(8):555-62. 30. Inotek announces top-line results for MATrX-1, first phase PGA/alpha agonist/ Increase outflow/decrease AH Mexico 3 trial of trabodenoson for galucoma. BusinessWire. January 3, 2017. www.businesswire.com/news/home/20170103005518/ B-blocker en/Inotek-Announces-Top-line-Results-MATrX-1-Phase-3. Accessed March 22, 2017.

52 REVIEW OF OPTOMETRY APRIL 15, 2017

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DRY EYE: Master the Science Beneath the Surface Learn how inflammatory mediators govern the disease course—and provide an avenue to treatment. By Michelle Hessen, OD

nflammation plays a significant Photo: Robert Prouty, OD, Paul Ajamian, OD and mature IL-1β) and a decrease role in the etiopathogenesis of in the biologically inactive precur- dry eye.1 It promotes ocular sur- sor IL-1β found in the tear film Iface disruption and symptoms of dry eye patients.5 Investigators of irritation. It is accompanied by recognize that IL-1β, IL-6, IL-8 and increased osmolarity of the tear tumor necrosis factor (TNF)-α also film and inflammation of the ocular play a significant role in SS-related surface.1,2 Once investigators identi- dry eye as compared with healthy fied inflammation’s role in dry eye eyes.6 This explains why treatments development, research could target This patient has severe dry eye due to in development today specifically treatment using anti-inflammatory Sjögren’s syndrome. Identifying the target inflammatory cytokines. agents that inhibit the expression cause of a patient’s dry eye is key to The response of cells to extracel- of inflammatory mediators on the targeting treatment. lular stimuli, such as ocular surface ocular surface. By doing so, these stress due to changes in the tear film agents help restore a healthy tear by T-cell infiltrates and upregulation composition, hyperosmolarity or film and reduce signs and symptoms of CD3, CD4 and CD8, as well ultraviolet (UV) light exposure, is of afflicted patients. as lymphocyte activation mark- partially mediated by a number of This article reviews the inflam- ers CD11a and HLA-DR.4 These intracellular kinase and phosphatase matory process, how different anti- results suggested that clinical symp- enzymes.7 inflammatory drugs can disrupt that toms and signs of dry eye may be According to one study, “mito- process and how to appropriately dependent on T-cell activation and gen-activated protein (MAP) kinases apply that knowledge in your clinic. resultant autoimmune inflamma- are integral components of parallel tion. Multiple other studies demon- MAP kinase cascades activated in Pathophysiology strated the role of proinflammatory response to a number of cellular Growing evidence shows dry eye- cytokines and matrix metallopro- stresses including inflammatory related ocular surface inflammation teinases (MMPs) in the pathogenesis cytokines (e.g., Il-1 and TNF-α), is mediated by lymphocytes.3 Based of dry eye.5-6 heat shock, bacterial endotoxin and on earlier immunohistopathologi- Interleukin (IL)-1 is one of the ischemia.”7 Researchers have identi- cal evaluations, patients with both most widely studied cytokines fied these stress-activated protein Sjögren’s syndrome (SS) related and accompanying dry eye. Researchers kinases in the tear film of patients non-SS dry eye have identical con- point to an increase in the proin- with dry eye and documented that junctival inflammation manifested flammatory forms of IL-1 (IL-1α activation of the stress pathways

56 REVIEW OF OPTOMETRY APRIL 15, 2017

056_ro0417_f4.indd 56 4/3/17 10:43 AM The leading cause of ocular discomfort and contact lens dropout is dryness.

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RO0217_Tear Scient.indd 1 2/2/17 11:12 AM Drug Mechanisms: Dry Eye Photo: Dan Fuller, OD often associated with those prod- ucts, as they contain benzalkonium chloride (BAK). Instead, opt for preservative-free agents for these patients. Before any other treatment, examine the patient for blepharitis. If present, the first step is to dif- ferentiate between bacterial and Demodex infections. In bacte- rial cases, it may be necessary to prescribe topical antibiotic or an antibiotic/steroid combination. If Demodex is at the root of the infec- This Keratograph 5M (Oculus) image shows an assessment of a patient’s noninvasive tion, turn to a product that con- tear break-up time. tains 4-Terpineol, such as Cliradex (Biotissue) or Cliradex Light. results in the transcription of stress- These activated CD4+ effector related genes, including MMPs, T-cells migrate from the lymph Corticosteroids mainly MMP-9.8 nodes to the ocular surface and Topical steroids, through several Another study shows that MAP lacrimal glands, where they exert mechanisms, help reduce ocular kinases stimulate the production of inflammatory effects. Researchers inflammation. Corticosteroids inflammatory cytokines—including suggest that LFA-1/ICAM-1 may function via suppression of cellular IL-β, TNF-α and MMP-9—causing play a role in reactivation of CD4+ infiltration, capillary dilation, pro- ocular surface damage.9 cells at the ocular surface to further liferation of fibroblasts and collagen Lymphocyte function-associated promote release of proinflammatory deposition.19 They stabilize intracel- antigen-1 (LFA-1), with its cog- cytokines from either the T-cells or lular and extracellular membranes.19 nate ligand intercellular adhesion antigen presenting cells.17 Corticosteroids increase the molecule-1 (ICAM-1), plays an Finally, research shows that inhi- synthesis of lipocortins that block

important role in the cell-mediated bition of ICAM-1 and LFA-1 in phospholipase A2 and inhibit his- immune response and inflammation mice reduces the number of inflam- tamine synthesis in the mast cells.19 10 associated with dry eye. LFA-1 is matory infiltrates in the lacrimal Inhibition of phospholipase A2, an expressed on the cell surface of leu- gland.18 Ultimately, it is possible that essential step in the inflammatory kocytes and binds with high affinity LFA-1/ICAM-1 may possibly recruit cascade, prevents the conversion of to ICAM-1 and with lower affin- and retain LFA-1 expressing T-cells phospholipids to arachidonic acid. ity to ICAM-2 and ICAM-3.11,12 to the epithelium and conjunctiva, Corticosteroids also interfere with ICAM-1 is expressed on the cell thus inducing proinflammatory transcription factor NF-kB, which surface of leukocytes, endothelial cytokine release. regulates synthesis of a number of cells, keratinocytes and epithelial All these inflammatory mediators proinflammatory molecules, thereby cells.13 LFA-1 binding to ICAM-1 and pathways relate to the patho- stimulating lymphocyte apoptosis. is involved in dendritic cell migra- genesis of dry eye and play a role in Corticosteroids mediate their tion to regional lymph nodes in the targeting treatment strategies. anti-inflammatory effects primar- afferent arm of the dry eye inflam- ily through the modulation of the matory pathway.14,15 LFA-1 and First-line Therapies cytosolic glucocorticoid receptor at ICAM-1 may be involved in the dry When treating dry eye, over-the- the genomic level.20,21 After cortico- eye immunoinflammatory efferent counter lubricants (e.g., artificial steroids bind to the glucocorticoid pathway as well.14-16 tears, gels, ointments) may be com- receptor in the cytoplasm, the acti- Naïve T-cells are primed in the mon but, for patients who need vated corticosteroid-glucocorticoid lymph nodes through interaction multiple doses per day or who have receptor complex migrates to the with dendritic cells and differentiate a punctal occlusion, your aim will nucleus, where it upregulates the 14-16 to TH1 and TH17 effector cells. be to reduce the cytotoxic effects expression of anti-inflammatory

58 REVIEW OF OPTOMETRY APRIL 15, 2017

056_ro0417_f4.indd 58 4/3/17 10:43 AM LCD Visual Acuity System VVA-1A 1 proteins and represses the expres- formation, glaucoma, corneal thin- sion of proinflammatory pro- ning and infectious keratitis.25 teins.20,21 However, recent work suggests the activated corticoste- NSAIDs roid-glucocorticoid receptor com- Topical nonsteroidal anti-inflam- plex also elicits nongenomic effects, matory drugs (NSAIDs) are used to such as inhibition of vasodilation, manage allergic conjunctivitis, post- vascular permeability and migration operative ocular pain, cystoid macu- of leukocytes.20,22 lar edema after cataract surgery and Several clinical studies demon- several other conditions in addition strate the effectiveness of topical to dry eye. NSAIDs treat inflamma- steroids in treating dry eye.23-25 In a tion by inhibiting the production retrospective clinical series, topical of prostaglandins via the cyclooxy- administration of a 1% solution of genase enzyme.26 However, research ComprehensiveComprehensive nonpreserved methylprednisolone, shows NSAIDs—specifically diclo- Visual Acuity Solution given TID or QID for several weeks fenac—can reduce corneal sensitiv- 27 to patients with SS-related dry eye, ity, too. This may cause insult to Multiple optotype selections provided moderate to complete the disrupted epithelium in dry eye relief of symptoms in all patients.23 patients.28-34 The literature shows All acuity slides presented with In addition, a decrease in corneal several cases of corneal melt associ- ETDRS Spacing fluorescein staining score (2.6 ± 0.5 ated with use of topical NSAIDs, on a 12-point scale) and complete including diclofenac, ketorolac, Contrast sensitivity testing resolution of filamentary kerati- nepafenac and bromfenac.28-34 In all Crowding bars (for pediatrics) tis were seen.23 This therapy was of these cases, preexisting epitheli- effective even for patients suffering opathy was identified.28-34 Although Multimedia system and more! from severe dry eye who had no the exact relationship between cor- improvement from maximum aque- neal melt and topical NSAID use ous tear enhancement/replacement is still not clear, various suggested therapies.23 mechanisms include activation of One pilot study looked at 64 matrix metalloproteinases, impair- patients to evaluate the efficacy of ment of wound healing and neu- Lotemax (loteprednol etabonate rotrophic effect resulting from the 0.5%, Bausch + Lomb) ophthalmic analgesic action of these drugs.28-34 suspension QID vs. placebo to treat Short-term use of NSAIDs can the inflammatory component of dry be useful in ameliorating symptoms eye associated with aqueous tear of ocular discomfort in dry eye. deficiency and delayed tear clear- However, they should be used with ance.24 After two weeks of therapy, caution and under close monitoring, Lotemax-treated patients with mod- and the treatment should be prefer- erate to severe clinical inflamma- ably discontinued if the corneal epi- tion showed a significant decrease thelium becomes damaged. in central corneal staining, nasal bulbar conjunctival hyperemia and Cyclosporin A lid margin injection, compared with The immunomodulating effects the placebo group.24 No patients of cyclosporin A are achieved experienced clinically significant through binding with cyclophilins. increase in intraocular pressure fol- Cyclophilin A, which is found in lowing one month of therapy.24 the cytosol, and the cyclosporin- Patients treated with topical cor- cyclophilin A complex inhibits a ticosteroids should be monitored calcium/calmodulin-dependent closely for known risks of cataract phosphatase, calcineurin, the inhibi-

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056_ro0417_f4.indd 59 4/3/17 10:43 AM Drug Mechanisms: Dry Eye Photo: Robert Prouty, OD, Paul Ajamian, OD tion of which is thought to halt the to be aware of when administering production of the transcription of long-term systemic therapy.54 Topi- T-cell activation by inhibiting IL-2.35 cal tacrolimus is available in 0.03% Cyclophilin D is located in the and 0.1% concentrations as an oint- matrix of mitochondria. Cyclospo- ment (typically applied externally rin A-cyclophilin D complex modu- to eyelids) as well as compounded lates the mitochondrial permeability eye drops. It is a promising off-label transition pore, thereby inducing a treatment of dry eye in the setting of mitochondrial dysfunction and cell chronic GVHD and SS.55-57 death.36 The reduction in inflam- mation, via inhibition of T-cell Tetracycline Derivatives activation and downregulation of Oral tetracycline derivatives possess inflammatory cytokines in the con- Superficial punctate keratitis in a antibacterial as well as anti-inflam- junctiva and lacrimal gland, allows Sjögren’s patient on Restasis therapy. matory properties. Doxycycline has enhanced tear production.37-41 been shown to inhibit c-Jun N-ter- Topical cyclosporine also increases discontinuation because of TEAEs minal kinase and extracellular sig- goblet cell density and decreases were 12.3% (lifitegrast) vs. 9.0% nal-related kinase mitogen-activated epithelial cell apoptosis.42 Com- (placebo).47 The most common protein kinase signaling in epithelial mercially available Restasis (topical (>5%) TEAEs occurring in either cells of the ocular surface exposed cyclosporine 0.05%, Allergan) or a treatment group were instillation to hyperosmolar stress, downregu- 1% compounded preparation is fre- site irritation (burning), instillation lating the expression of CXCL8 and quently used to treat various inflam- site reaction, reduced visual acuity, proinflammatory cytokines IL-1β matory ocular surface disorders.43 dry eye and dysgeusia (change in and TNF.58 Doxycycline inhibits Dosing topical cyclosporine at a taste).47 There was no indication of MMP-9 activity and supports ocu- frequency greater than twice a day systemic toxicity or localized infec- lar surface integrity.59,60 may be more effective for patients tious complications secondary to Additionally studies demon- who do not demonstrate improve- chronic immunosuppression. strated that minocycline inhibits ment of severe dry eye disease with expression of cell-associated pro- the twice-daily regimen.44,45 Tacrolimus inflammatory molecules, including This topical anti-inflammatory major histocompatibility complex Lifitegrast agent (previously known as FK506) class II.61 Doxycycline has been This formulation blocks the binding is a macrolide antibiotic.48 Although reported to be effective in patients of the surface proteins LFA-1 and the mechanism of tacrolimus is with ocular rosacea by reducing ICAM-1, thereby reducing inflam- similar to cyclosporin A, research irritation symptoms, improving mation in dry eye.46 The recom- shows the potency in vitro has been tear film stability and decreasing mended dosing of the commercially shown to be significantly greater.49 the severity of ocular surface dis- available Xiidra (lifitegrast 5%, Only when bound to immunophilin ease.62-64 In addition, doxycycline Shire) is twice daily.47 Research- does it become biologically active, has been useful in the treatment of ers recently completed a one-year thus effectively inhibiting calcineu- corneal erosions.65,66 multicenter, randomized, placebo- rin, and inhibiting T- and B-lym- controlled study of the safety of phocyte activation via reduction Azithromycin lifitegrast ophthalmic solution 5.0% in IL-2 synthesis.48,50,51 Tacrolimus This broad-spectrum macrolide in 331 participants (220 lifitegrast, suppresses the immune response antibiotic has been shown to have 111 placebo) with dry eye.47 There by inhibiting the release of other good tissue penetration to the eyelid were no serious treatment-emergent inflammatory cytokines as well, and favorable pharmacokinetics adverse events (TEAEs). Overall, such as IL-4 and IL-8.50,52,53 for daily dosing. Azasite (topi- 53.6% of participants receiving Systemic tacrolimus has been cal azithromycin, Akorn) is FDA lifitegrast experienced ≥1 ocular reported to be effective for improv- approved to treat bacterial conjunc- TEAEs vs. 34.2% in the placebo ing dry eye associated with graft tivitis, but may be used as off-label group.47 Most TEAEs were mild- vs. host disease (GVHD). However, therapy for clinical control or relief moderate in severity. Rates of there are potential adverse reactions of symptoms and signs of meibo-

60 REVIEW OF OPTOMETRY APRIL 15, 2017

056_ro0417_f4.indd 60 4/3/17 10:43 AM Diagram: Bruce Onofrey, OD, RPh The Dry Eye Cascade Abnormal Tear Film Healthy ocular surface Causes & Contributors Aqueous deficiency • Aging Abnormal or • Dry environment insufficient tears TBUT less than blink rate • Hormonal changes • Contact lenses • Blepharitis Reduced tear Observable occurrence Pathophysiologies • LASIK • Autoimmune disease Increased Ocular osmolarity irritation • Antihistamine • Alcohol Use TBUT less than blink rate • Pollution Increased The • Computer use cytokines Series 3 Mucin abnormalities • Antidepressant use Inflammation RETINOMAX The increased prevalence of dry eye disease can be attributed to a number of factors. HAND-HELD Understanding the mechanism of action behind therapeutic options can help you best target your patients’ treatments. Autorefractor

mian gland dysfunction, as well as Autologous serum Precise measurements improvement in lipid behaviors of Serum contains several anti- Anywhere - Anytime meibomian gland secretion.67 It has inflammatory factors that have also been noted that topical azithro- the capability to inhibit soluble mycin management could lead to mediators of the ocular surface improvement in meibomian gland inflammatory cascade of dry eye. orifice plugging.68 A single oral dose These include inhibitors of inflam- ‘Accurate of 1g has been shown to provide matory cytokines (e.g., IL-1 RA and Fast prolonged high levels after 14 days soluble TNF-receptors) and MMP ‘ in drug-targeted ocular tissues, to inhibitors (e.g., tissue inhibitors of ‘=\_aNOYR decrease inflammatory cytokines metalloproteinases).75-77 Clinical tri- and suppress production of proin- als show autologous serum drops ‘2SSVPVR[a flammatory mediators.69-72 Good improve ocular irritation symptoms intracellular penetration and long and conjunctival and corneal dye half-life of azithromycin can pro- staining in dry eye that occurs in the vide an effective antimicrobial and setting of SS.78-80 Conversely, there favorable immunomodulatory effect is greater risk of microbial growth without compliance issues of long- as autologous serum drops, in addi- term tetracycline use.70,72 Research tion to antimicrobial agents, contain shows the drug could block activa- high protein content and are gener- tion of NF-kB, leading to decreased ally nonpreserved.81 inflammatory cytokine levels such Recent studies have investigated as IL-6 and IL-8.73 Besides, azithro- cord serum drops (prepared from mycin has been shown to suppress donor umbilical cord serum) as well the production of proinflammatory as allogenic serum drops (from a mediators by inhibiting cultured relative donor).82-84 A clinical trial human corneal epithelial cells.74 of 17 patients with GVHD and 13

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056_ro0417_f4.indd 61 4/3/17 10:43 AM Drug Mechanisms: Dry Eye

patients with SS-associated dry eye treatment plan, it is important to 15. Stern M, Schaumburg C, Pflugfelder S. Dry eye as a muco- sal autoimmune disease. Int Rev Immunol. 2013;32:19–41. treated them for one month with consider severity of the condition 16. Perez V, Pflugfelder S, Zhang S, et al. A novel integrin cord blood serum. Patients received based on clinical exam including antagonist for treatment of dry eye disease. Ocul Surf. 2016;14:207–15. cord blood once a day (contain- osmolarity, Schirmer, tear break-up 17. Schaumburg C, Siemasko K, De Paiva C, et al. Ocular ing 0.15ng epithelial growth fac- time and ocular surface staining. surface APCs are necessary for autoreactive T cell-mediated experimental autoimmune lacrimal keratoconjunctivitis. J. tor per drop). Patients reported a It is also necessary to identify con- Immunol. 2011;187:3653–62. decrease in discomfort symptoms as 18. Gao J, Morgan G, Tieu D, et al. ICAM-1 expression predis- current ocular disease as well as poses ocular tissues to immune-based inflammation in dry eye measured with the Ocular Surface possible systemic conditions that patients and Sjögrens syndrome-like MRL/lpr mice. Exp Eye Disease Index score (OSDI) (22.3 ± Res. 2004;78:823–35. may be contributing factors. The 19. Comstock T, DeCory H. Advances in corticosteroid therapy 10.3 vs. 39.3 ± 16.9). Also, clinical treatment goal is to improve patient for ocular inflammation: loteprednol etabonate. Int J Inflam. findings such as impression cytol- 2012;2012:789623. symptoms, restore a healthy tear 20. Rhen T, Cidlowski J. Antiinflammatory action of gluco- ogy score (3.8 ± 1.2 vs. 6.6 ± 2.1), film, prevent further destruction of corticoids - new mechanisms for old drugs. N Engl J Med. 2005;353:1711–23. tear osmolarity (312.5 ± 7 vs. 322 the ocular surface and ultimately 21. Newton R. Molecular mechanisms of glucocorticoid action: ± 9.1mOsm/L), and corneal sensa- reestablish an intact epithelium. ■ what is important? Thorax. 2000;55:603–13. 22. Stahn C, Buttgereit F. Genomic and nongenomic effects of tion (measured with Cochet-Bonnet Dr. Hessen is a clinical instructor glucocorticoids. Nat Clin Pract Rheumatol. 2008;4:525–33. esthesiometers) (48.2 ± 2.1 vs. 49.7 at the Wilmer Eye Institute’s Ocular 23. Marsh P, Pflugfelder S. Topical nonpreserved methylpres- dnisolone therapy of keratoconjunctivits sicca in sjogren’s ± 2.1 nylon/mm/length) improved Surface Diseases and Dry Eye Clinic syndrome. Ophthalmology. 1999;106:811–16. significantly.82 at Johns Hopkins School of Medi- 24. Pflugfelder S, Maskin S, Anderson B, et al. A randomized, double-masked, placebo-controlled, multicenter comparison of Another study, this one involving cine, where she specializes in ocular loteprednol etabonate ophthalmic suspension, 0.5%, and pla- 12 patients with chronic GVHD- surface disease, including autoim- cebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance. Am J Ophthalmol. 2004;138:444–57. associated severe dry eye treated mune disorders. 25. McGhee C, Dean S, Danesh-Meyer H. Locally admin- with cord blood serum for six istered ocular corticosteroids: benefits and risks. Drug Saf. 1. Hessen M, Akpek E. Dry eye: an inflammatory ocular disease. 2002;25:33–55. months, reported statistically sig- J Ophthalmic Vis Res. 2014;9(2):240–50. 26. Vane J, Bakhle Y, Botting R. Cyclooxygenases 1 and 2. Annu nificant improvement (p<0.01) in 2. The definition and classification of dry eye disease: report of Rev Pharmacol Toxicol. 1998;38:97–120. the Definition and Classification Subcommittee of the Interna- 27. Aragona P, Tripodi G, Spinella R, et al. The effects of the symptom score (on a scale of 0-4, tional Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):75-92. topical administration of non-steroidal anti-inflammatory drugs 3.83+/-0.38 vs. 0.83+/-0.57), cor- 3. Stern ME, Schaumburg CS, Pflugfelder SC. Dry eye on corneal epithelium and corneal sensitivity in normal subjects. as a mucosal autoimmune disease. Int Rev Immunol. Eye. 2000;14(2):206-10. neal sensitivity (52.08+/-6.06mm 2013;32(1):19-41. 28. Gokhale NS, Vemuganti GK. Diclofenac-induced acute cor- to 57.50+/-3.00mm), tear film BUT 4. Stern M, Gao J, Schwalb T, et al. Conjunctival T-cell subpopu- neal melt after collagen crosslinking for keratoconus. Cornea. lations in Sjögren’s and non-Sjögren’s patients with dry eye. 2010;29:117–9. (from 2.50+/-0.91 sec. to 5.71+/- Invest Ophthalmol Vis Sci. 2002;43:2609–14. 29. Flach A. Corneal melts associated with topically applied 1.04 sec., P<0.01) and corneal 5. Solomon A, Dursun D, Liu Z, et al. Pro- and anti-inflammatory nonsteroidal anti-inflammatory drugs. Trans Am Ophthalmol forms of interleukin-1 in the tear fluid and conjunctiva of Soc. 2001;99:205–12. fluorescein staining (7.42+/-2.02 to patients with dry-eye disease. Invest Ophthalmol Vis Sci. 30. Khalifa Y, Mifflin M. Keratitis and corneal melt with 1.29+/-0.46).83 2001;42:2283–92. ketorolac tromethamine after conductive keratoplasty. Cornea. 6. Cejková J, Ardan T, Simonová Z, et al. Nitric oxide synthase 2011;30:477–8. Allogenic serum drops are pre- induction and cytotoxic nitrogen-related oxidant formation in 31. di Pascuale M, Whitson J, Mootha V. Corneal melting pared using blood from a family conjunctival epithelium of dry eye (Sjögren’s syndrome). Nitric after use of nepafenac in a patient with chronic cystoid Oxide. 2007;17:10–7. macular edema after cataract surgery. Eye Contact Lens. member rather than the patient’s 7. Paul A, Wilson S, Belham C, et al. Stress-activated protein 2008;34:129–30. own. In one study, allogeneic serum kinases: activation, regulation and function. Cell Signal. 32. Asai T, Nakagami T, Mochizuki M, et al. Three cases of 1997;9:403–10. corneal melting after instillation of a new nonsteroidal anti- tears were used for the treatment of 8. Pflugfelder S, de Paiva C, Tong L, et al. Stress-activated inflammatory drug. Cornea. 2006;25:224–7. dry eye in 16 patients with GVHD. protein kinase signaling pathways in dry eye and ocular surface 33. Isawi H, Dhaliwal D. Corneal melting and perforation in disease. Ocul Surf. 2005;3(Suppl 4):154–7. Stevens Johnson syndrome following topical bromfenac use. J After four weeks of continuous use 9. Luo L, Li D, Doshi A, et al. Experimental dry eye stimulates Cataract Refract Surg. 2007;33:1644–6. the symptom scores (32.5-8.9 OSDI production of inflammatory cytokines and MMP-9 and activates 34. Prasher P. Acute corneal melt associated with topical bromf- MAPK signaling pathways on the ocular surface. Invest Ophthal- enac use. Eye Contact Lens. 2012;38:260–2. score), tear osmolarity (311.1 to mol Vis Sci. 2004;45:4293–301. 35. Matsuda S, Koyasu S. Mechanisms of action of cyclospo- 285.1mOsmL), and corneal stain- 10. Pflugfelder S, Stern M, Zhang S, Shojaei A. LFA-1/ICAM-1 rine. Immunopharmacology. 2000;47:119–25. interaction as a therapeutic target in dry eye disease. J Ocul 36. Stevenson W, Chauhan SK, Dana R. Dry Eye Disease: an ing (2.5 to 1.8) improved as well as Pharmacol Ther. 2017;33(1):5-12. immune-mediated ocular surface disorder. Arch Ophthalmol. increased goblet cell density (90.6 to 11. Evans R, Patzak I, Svensson L, et al. Integrins in immunity. J 2012;130:90–100. 2 Cell Sci. 2009;122:215–25. 37. Pflugfelder S, Wilhelmus K, Osato M, et al. The auto- 122.6 cell/mm ), and tear break-up 12. de Fougerolles A, Springer T. Intercellular adhesion molecule immune nature of aqueous tear deficiency. Ophthalmol. time (2.9 to 4.4 sec.).84 3, a third adhesion counter-receptor for lymphocyte function- 1986;93:1513–7. associated molecule 1 on resting lymphocytes. J Exp Med. 38. Stern M, Gao J, Siemasko K, et al. The role of the lacrimal 1992;175:185–190. gland functional unit in the pathophysiology of dry eye. Exp Eye Dry eye therapy should target 13. Roebuck K, Finnegan A. Regulation of intercellular adhe- Res. 2004;78:409–16. sion molecule-1 (CD54) gene expression. J Leukoc Biol. 39. Stevenson D, Tauber J, Reis BL. Efficacy and safety of the inflammatory cascade, given its 1999;66:876–88. cyclosporine A ophthalmic emulsion in the treatment of moder- significant role in etiopathogenesis. 14. Stern M, Schaumburg C, Dana R, et al. Autoimmunity at the ate to severe dry eye disease: a dose-ranging, randomized ocular surface: pathogenesis and regulation. Mucosal Immunol. trial. The Cyclospoine A Phase 2 Study Group. Ophthalmol. When selecting an appropriate 2010;3:425–42. 2000;107:967–74.

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40. Sall K, Stevenson O, Mundorf T, Reis B. Two multicenter, alpha/betaII. J Biol Chem. 2007;282:15208–16. randomized studies of the efficacy and safety of cyclosporine 62. Frucht-Pery J, Sagi E, Hemo I, Ever-Hadani P. Efficacy of ophthalmic emulsion in moderate to severe dry eye disease. doxycycline and tetracycline in ocular rosacea. Am J Ophthal- CsA Phase 3 Study Group. Ophthalmol. 2000;107:631–9. mol. 1993;116:88–92. 41. Laibovitz R, Solch S, Andriano K, et al. Pilot trial of cyclospo- 63. Zengin N, Tol H, Gündüz K, et al. Meibomian gland rine 1% ophthalmic ointment in the treatment of keratoconjunc- dysfunction and tear film abnormalities in rosacea. Cornea. tivitis sicca. Cornea. 1993;12:315–23. 1995;13:144–14. 42. Kunert K, Tisdale A, Gipson I. Goblet cell numbers and 64. Akpek E, Merchant A, Pinar V, Foster C. Ocular rosa- epithelial proliferation in the conjunctiva of patients with dry cea: patient characteristics and follow-up. Ophthalmol. eye syndrome treated with cyclosporine. Arch Ophthalmol. 1997;104:1863–7. 2002;120:330–7. 65. Dursun D, Kim M, Solomon A, Pflugfelder S. Treatment of 43. Utine C, Stern M, Akpek E. Clinical review: topical recalcitrant corneal epithelial erosions with inhibitors of matrix ophthalmic use of cyclosporin A. Ocul Immunol Inflamm. metalloproteinases-9, doxycycline and corticosteroids. Am J 2010;18:352–61. Ophthalmol. 2001;132:8–13. 44. Gupta A, Sadeghi P, Akpek E. Occult thyroid eye disease 66. Hope-Ross MW, Chell PB, Kervick GN, et al. Oral tetracy- in patients presenting with dry eye symptoms. Am J Ophthal. cline in the treatment of recurrent corneal erosions. Eye (Lond). 2009;147:919–23. 1994;8:384–88. 45. Dastjerdi M, Hamrah P, Dana R. High-frequency topical 67. Foulks GN, Borchman D, Yappert M, et al. Topical azithromy- cyclosporine 0.05% in the treatment of severe dry eye refrac- cin therapy for meibomian gland dysfunction: clinical response tory to twice-daily regimen. Cornea. 2009;28:1091–6. and lipid alterations. Cornea. 2010;29(7):781–8. 46. American Academy of Ophthalmology Cornea/External Dis- 68. Haque R, Torkildsen G, Brubaker K, et al. Multicenter open- ease PPP Panel, Hoskins Center for Quality Eye Care. www.aao. label study evaluating the efficacy of azithromycin ophthalmic org/preferred-practice-pattern/dry-eye-syndrome-ppp–2013. solution 1% on the signs and symptoms of subjects with October 2013. Accessed March 22, 2017. blepharitis. Cornea. 2010;29(8):871–7. Corneal Topography & More! 47. Donnenfeld E, Karpecki P, Majmudar P, et al. Safety of Lifite- 69. Qiao J, Yan X. Emerging treatment options for meibomian grast ophthalmic solution 5.0% in patients with dry eye disease: gland dysfunction. Clin Ophthalmol. 2013;7:1797–803. A 1-year, multicenter, randomized, placebo-controlled study. 70. Kashkouli M, Fazel A, Kiavash V, et al. Oral azithromycin ver- Cornea. 2016;35(6):741–8. sus doxycycline in meibomian gland dysfunction: a randomised 48. Thomson A, Bonham C, Zeevi A. Mode of action of tacroli- double-masked open-label clinical trial. Br J Ophthalmol. mus (FK506): molecular and cellular mechanisms. Ther Drug 2015;99:199–204. Monit. 1995;17:584–91. 71. Greene J, Jeng B, Fintelmann R, Margolis T. Oral azithro- 49. Kino T, Hatanaka H, Hashimoto M, et al. FK-506, a novel mycin for the treatment of meibomitis. JAMA Ophthalmol. immunosuppressant isolated from Streptomyces. I. Fermenta- 2014;132:121–2. tion isolation, and physio-chemical and biological characteris- 72. Igami T, Holzchuh R, Osaki TH, et al. Oral azithromycin for tics. J Antibiot (Tokyo). 1987;40:1249–55. treatment of posterior blepharitis. Cornea. 2011;30:1145–9. 50. Fei W, Chen J, Yuan J, et al. Preliminary study of the 73. Aghai Z, Kode A, Saslow J, et al. Azithromycin suppresses effect of FK506 nanospheric-suspension eye drops on rejec- activation of nuclear factor-kappa B and synthesis of pro- tion of penetrating keratoplasty. J Ocul Pharmacol Ther. inflammatory cytokines in tracheal aspirate cells from prema- 2008;24:235–44. ture infants. Pediatr Res. 2007;62(4):483–8. Meibomian Gland 51. Fujita E, Teramura Y, Mitsugi K, et al. Absorption, distribution, 74. Li D, Zhou N, Zhang L, et al. Suppressive effects of azithro- and excretion of 14C-labeled tacrolimus (FK506) after a single mycin on zymosan-induced production of proinflammatory Imaging & Analysis or repeated ocular instillation in rabbits. J Ocul Pharmacol Ther. mediators by human corneal epithelial cells. Invest Ophthalmol 2008;24:333–43. Vis Sci. 2010;51(11):5623–9. 52. Nishino K, Fukushima A, Okamoto S, et al. Suppression of 75. Liou L. Serum and in vitro production of IL-1 receptor experimental immune-mediated blepharoconjunctivitis in brown antagonist correlate with C-reactive protein levels in newly Norway rats by topical application of FK506. Graefes Arch Clin diagnosed, untreated lupus patients. Clin Exp Rheumatol. Exp Ophthalmol. 2002;240:137–43. 2001;19:515–23. 53. Sasakawa Y, Sakuma S, Higashi Y, et al. FK506 suppresses 76. Ji H, Pettit A, Ohmura K, et al. Critical roles for interleukin 1 neutrophil chemoattractant production by peripheral blood and tumor necrosis factor alpha in antibody-induced arthritis. J mononuclear cells. Eur J Pharmacol. 2000;403:281–8. Exp Med. 2002;196:77–85. 54. Aoki S, Mizote H, Minamoto A, et al. Systemic FK506 77. Paramo J, Orbe J, Fernandez J. Fibrinolysis/proteolysis improved tear secretion in dry eye associated with chronic graft balance instable angina pectoris in relation to angiographic find- versus host disease. Br J Ophthalmol. 2005;89:243–4. ings. Thromb Haemost. 2001;86:636–9. Non-Invasive Tear Film 55. Ryu E, Kim J, Laddha P, et al. Therapeutic effect of 0.03% 78. Fox R, Chan R, Michelson J, et al. Beneficial effect on artifi- Break-up Analysis tacrolimus for ocular graft versus host disease and vernal kera- cial tears made with autologous serum in patients with Kerato- toconjunctivitis. Korean J Ophthalmol. 2012;26:241–7. conjunctivitis sicca. Arthritis Rheum. 1984;27:459–61. 56. Tam P, Young A, Cheng A, Lam P. Topical 0.03% tacrolimus 79. Kono I, Kono K, Narushima K, et al. Beneficial effect of the ointment in the management of ocular surface inflammation in local application of plasma fibronectin and autologous serum in chronic GVHD. Bone Marrow Transplant. 2010;45:957–8. patients with Keratoconjunctivitis sicca of Sjogren’s syndrome. 57. Moscovici B, Holzchuh R, Chiacchio B, et al. Clinical treat- Ryumachi. 1986;26:339–43. ment of dry eye using 0.03% tacrolimus eye drops. Cornea. 80. Tsubota K, Goto E, Fujita H, et al. Treatment of dry eye by 2012;31:945–9. autologous serum application in Sjogren’s syndrome. Br J Oph- 58. Solomon A, Rosenblatt M, Li D, et al. Doxycycline inhibition thamol. 1999;83:390–5. of interleukin-1 in the cornea epithelium. Invest Ophthalmol Vis 81. Tananuvat N, Daniell M, Sullivan L, et al. Controlled study Sci. 2000 Aug;41(9):2544-57. of the use of autologous serum in dry eye patients. Cornea. 59. De Paiva C, Corrales R, Villarreal A, et al. Corticosteroid 2001;20:802–6. and doxycycline suppress MMP-9 and inflammatory cytokine 82. Versura P, Profazio V, Buzzi M, et al. Efficacy in standardized expression, MAPK activation in the corneal epithelium in experi- and quality-controlled cord blood serum eye drop therapy in the mental dry eye. Exp Eye Res. 2006;83:526–35. healing of severe corneal epithelial damage in dry eye. Cornea. 60. De Paiva C, Corrales R, Villarreal A, et al. Apical corneal bar- 2013;32:412–8. Tear Meniscus Height rier disruption in experimental murine dry eye is abrogated by 83. Yoon K, Jeong I, Im S, et al. Therapeutic effect of umbilical methylprednisolone and doxycycline. Invest Ophthalmol Vic Sci. cord serum for the treatment of dry eye associated with graft- 2006;47:2847–56. versus-host disease. Bone Marrow Transplant. 2007;39:231–5. 61. Nikodemova M, Watters J, Jackson S, et al. Minocycline 84. Na K, Kim M. Allogenic serum eye drops for the treatment of downregulates MHC II expression in microglia and macro- dry eye patients with chronic graft-versus-host disease. J Ocul phages through inhibition of IRF-1 and protein kinase C (PKC) Pharmacol Ther. 2012;28:479–83.

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Resist the Itch: Managing Allergic Conjunctivitis Flowers may be blooming, but this season leaves many ODs seeing red. By Charissa Young, OD

hile some enjoy the blooming flora and warm sun of spring, Wothers only see ele- vated pollen levels and a rise in temperature as the dreaded start of allergy season. Their noses will stuff, their throats will itch and their eyes will become itchy and red. Sadly, many patients mismanage ocular allergy by employing over-the-counter (OTC) red eye solutions that neither address the problem nor relieve the symptoms. When it becomes too much, many of these patients will land in our offices seeking relief. The good news is that allergy medication is more targeted than ever, and with the right background optometrists can Above, this patient displays bring patients the relief they’re nasal inferior papillary seeking. Gone are the days conjunctivitis in the right when ODs simply threw a eye. combination antihistamine and mast-cell stabilizer drop at any- At left, if a patient thing that itches. describes the itch as being Over the last decade, an toward the eyelid, there’s explosion of research has a chance they’re dealing focused on the ocular surface, with a Demodex infection, increasing our understanding like the patient in this of how our environment, and photograph.

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064_ro0417_f5.indd 64 4/3/17 2:11 PM its offending allergens, impacts the anterior segment. OCULAR ALLERGY DIAGNOSIS This article provides an update on the state of ocular allergy therapies and how optometrists can use that 4% knowledge to bolster their roles in 7% SAC treatment. Comorbidities 7% PAC Before delving into ocular allergy VKC management, get familiar with your comorbidities. In many cases, man- 9% AKC aging them can reduce the need for 55% directly treating the allergic reaction. CBC Some of my most successful cases have started with first managing 18% GPC the coexisting conditions that were exacerbating the allergy. Demodex: Ask if the patient’s itch is directed toward the conjunctiva or the eyelid. If it’s the former, it’s likely the result of an allergy; if it’s the lat- ter, you should suspect Demodex.1 Percentage of patients with a specific ocular allergy diagnosis: Seasonal allergic con- Look closely at the base of the lash junctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), follicles for protruding tails. If you’re atopic keratoconjunctivitis (AKC), contact blepharoconjunctivitis (CBC) and giant papillary still unsure, try using forceps to conjunctivitis (GPC).3 gently twirl a lash within its follicle to draw out the mite.2 Patients with Demodex blepharitis alone will find to a poor tear film—due to either means less concentration of allergens no relief from topical allergy medi- meibomian gland dysfunction or and allergic mediators on the eye, cations, so eradicating the mites via aqueous deficiency. often serving as an effective treat- mechanical debridement and chemi- Is their ocular itch directed ment for the ocular allergy, which is cal eradication (e.g., ophthalmic- toward the caruncle, where stagnant the exact reason OTC artificial tears grade tea tree oil or hypocholorous tears—loaded with allergens and provide relief as well. However, they acid 0.01%) is necessary to relieve allergic mediators—have collected?5 only provide temporary relief and itchy eyelids.3 A 2016 study in China shows an should be used as adjunctive, not Both patients suffering from alarmingly high incidence of dry eye primary, treatment. allergy and Demodex should be (98%) in young children with aller- Avoid punctal plugs in patients advised to wash their linens weekly gic conjunctivitis.6 More times than with a history of allergy, to allow and to replace makeup containers to not, if I have a patient with both blinking to naturally flush irritants reduce exposure to offending agents. signs of dry eye disease and allergy away through the punctum. If patients are compliant with your and I lead with dry eye treatment, it Demodex treatment regimen and reduces or, in some cases, eliminates Getting a History a papillary reaction is still present the need for allergy treatment. With During the patient’s workup, investi- after several weeks (the life cycle of new dry eye treatments rapidly being gate what symptoms related to aller- Demodex mites is approximately made available, one common prin- gies the patient has. Do they have 14 days) adjunctive topical allergy ciple persists: if you decrease inflam- both ocular and systemic symp- medications are indicated.4 mation on the ocular surface and toms? Patients may inadvertently Dry eye disease. If Demodex improve meibomian gland function, take OTC allergy medications for is ruled out, consider whether the the tear production of most dry eye allergy-related ocular itch, not real- patient has exacerbated allergies due patients will improve.7 More tears izing that they can actually worsen

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Prevalence and Characteristics of Ocular Allergy switching to a daily disposable is In the United States, ocular allergies affect up to 40% of the population. While itching not an option due to the patient’s is reported in 90% of cases, the other most common symptoms—hyperemia (84.6%) prescription, switching to a hydro- and tearing (76.5%)—are also shared complaints in dry eye and other anterior segment gen peroxide cleaner in conjunc- conditions and should be differentiated. Of allergic conjunctivitis cases, 73% are largely tion with manual cleaning (none environmental, 55% are diagnosed as seasonal allergic conjunctivitis (SAC) and 18% are of that “no-rub solution” business perennial allergic conjunctivitis (PAC). Allergy testing for these patients is a cornerstone for for allergy sufferers) optimizes the treatment, as patients can be educated to develop ways to minimize their exposure and modality. receive specific allergen immunotherapy for long-term management. The remaining 27% of ocular allergy sufferers tend to have more severe ocular reactions, from enlargened Allergy Therapeutics papillae to lid edema, requiring specific treatment strategies and more likely necessitate While our arsenal of topical adjunctive topical steroids. allergy medications has remained unchanged since extra-strength 1. Leonardi A, Piliego F, Castegnaro A, et al. Allergic conjunctivitis: a cross-sectional study. Clinical and Experimental Allergy. 2015 May;45:1118-25. Pazeo (olopatadine 0.07%, Alcon) was released three years ago, our the situation. Oral antihistamines utes to prepare and collect patient management of allergic conjunc- reduce aqueous and mucus produc- samples without use of a needle. In tivitis can continue to become tion due to their anticholinergic less than 15 minutes, practitioners more nuanced with each passing activity, which decreases the eye’s will receive the patient’s sensitivity season. I recommend prescrip- ability to dilute allergens on the ocu- results against 58 common allergens. tion medications in place of OTC lar surface.8 Counsel those patients In addition to these, there is also one options, as many patients seem to about the differences and switch to positive and one negative control.5 If have already tried OTC ketotifen a targeted ocular-allergy approach. patients test negative across all aller- without relief (hence, why they are If the patient experiences allergy- gens tested or do not show minimal in your chair in the first place). In related rhinitis and other systemic response to the histamine control, fact, when given both ketotifen symptoms, recommend OTC allergy they are unlikely to benefit from 0.025% and olopatadine 0.1% to orals, emphasizing the benefits of antihistamines or mast-cell stabiliz- try on a twice-daily dose schedule, second-generation histamine H1 ers that inhibit histamine release.4 81% preferred olopatadine, citing antagonists over their more ocular These patients may warrant refer- improved comfort and more reduc- surface-drying first-generation coun- ral to an allergist for longer-term tion in allergy symptoms.7 terparts. management. The mainstays of allergic con- junctivitis therapy are topical Allergen Identification Contact Lenses combination antihistamine and The first rule of allergic conjuncti- Before we discuss therapeutics, mast-cell stabilizer eye drops. This vitis management is to identify and minimizing allergen exposure dual mechanism provides both avoid the allergen whenever possible. on the eye needs to go one step short- and long-term relief for While some patients know their further. Fitting patients in daily its effect on decreasing histamine specific triggers, the majority do not. disposable contact lenses is a release. The two primary once- Some clinics reported up to 80% of foundation of our practice, not daily dosing topical allergy medi- their allergic conjunctivitis patients only due to the improved lens cations are Lastacaft (alcaftadine, had never had an allergy test before.4 wear experience and convenience, Allergan) and Pazeo, Pataday and In-office testing for tear osmolarity, but also decrease in contact lens- Patanol (olopatadine, Alcon). In adenovirus and MMP-9 inflamma- related complications. Of our a head-to-head alcaftadine 0.25% tory biomarkers have been invalu- patients fit in soft contact lenses, vs. olopatadine 0.2% study of 284 able in our viral conjunctivitis and 90% are currently wearing a daily subjects, both topical solutions dry eye management, as their instant disposable modality. The thinking decreased itching severity within results to guide our treatments. is that wearing a new lens daily three minutes of instillation and Now, there’s in-office testing to add will minimize allergen buildup, continued to provide itch relief at to your ocular allergy evaluation. whereas a biweekly or monthly 16 hours. When comparing the The Doctor’s Rx Allergy Formula lens leads to buildup of allergens two, alcaftadine provided more (Bausch + Lomb) takes three min- and irritants over time. When relief.6 That said, due to olopata-

66 REVIEW OF OPTOMETRY APRIL 15, 2017

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Subscribing to Optometric Physician is an effi cient and easy way to stay current with all of the information and events going on in the fi eld. To order your free subscription, e-mail: optometricphysician @jobson.com today. Drug Mechanisms: Allergy

dine’s different available concen- trations, you can customize your treatment regimen to the condition severity. Start at lower concentra- tions and discuss with the patient that, if more frequent dosing pro- vides relief, the stronger formulation may be warranted. Unfortunately, all the major ocular allergy formulations con- tain benzalkonium chloride (BAK) as the preservative. If you’ve ever had a patient in your chair with a laundry list of allergies, it’s not uncommon for them to be sensitive or even allergic to BAK.8 The last thing you want is for your patient to develop allergic conjunctivitis secondary to their topical allergy medication, compounding their When patients suffer from ocular inflammation due to allergy, as seen here, education problem. Palliative ocular allergy about avoidance of triggers is a vital aspect of treatment. therapy includes allergen avoid- ance, cool compresses, regular However, if a patient’s ocular tify the allergen whenever possible linen cleaning, preservative-free allergy is so severe that you’re con- so patients can minimize their artificial tears and, if warranted, sidering those therapies or they’re exposure. ■ short-term fluorometholone 1% experiencing severe systemic symp- Dr. Young specializes in dry eye ointment (non-BAK preserved). toms, comanaging with an allergist and contact lenses at Specialty can help provide the best outcome. Eyecare Group in Seattle.

Systemic Options 1. Kabat A, Sowka J. If it itches, it’s allergy...right? Rev Depending on your state, prescrib- Don’t Wait, Educate Optom. 2011;147(6):107-8. ing systemic medications such as Because we often only see patients 2. Mastrota K. Method to identify Demodex in the eyelash follicle without epilation. Optom Vis Sci. 2013 fluticasone nasal spray and oral once a year for their annual com- Jun;90:e172-4. loratadine for allergy may be prehensive eye exam (and often 3. Kabat A, Sowka J. New blepharitis treatments: a decade ago, we looked at the latest treatment options for additional treatment options. For not during allergy season), take blepharitis. It’s high time we eye them up again. Rev Optom patients who can’t tolerate oral the opportunity during this visit to 2014;152(10):80-1. 4. Rather P, Hassan I. Human Demodex mite: The versatile antihistamines, montelukasts— ask patients if they have a history mite of dermatological importance. Indian J Dermatol. 2014 while less effective—can also pro- of allergy. Begin educating patients Jan-Feb;59(1):60–6. 9 5. Lemp M, Weiler H. How do tears exit? Invest Ophthalmol. vide relief. When topical treatment about preventative measures and Vis Sci. 1983;24(5):619-22. alone is insufficient, consider fluti- the importance of not rubbing their 6. Chen L, Pi L, Fang J, et al. High incidence of dry eye in young children with allergic conjunctivitis in Southwest casone nasal spray or oral lorata- eyes, which further exacerbates the China. Acta Ophthalmologica. 2016;94:e727-30. dine, but proceed with caution. condition due to mast-cell degranu- 7. Management and Therapy Subcommittee. Management and therapy of dry eye disease: report of the management While oral medications can benefit lation and increased histamine and therapy subcommittee of the international dry eye work- both systemic and ocular allergy, release.11 Shop (2007). The Ocular Surface. 2007;5(2):163-78. 8. Baudouin C, Labbé A, Liang H. Preservatives in eye- beware of increased ocular dryness Starting this dialogue early with drops: The good, the bad and the ugly. Prog Retin Eye Res. due to the anticholinergic effects. patients can not only build your 2010;29(4):312–34. If considering a steroid nasal spray, medical practice, but also build 9. Gane J, Buckley R. Leukotriene receptor antagonists in allergic eye disease: A systematic review and meta-analysis educate the patient and monitor patient satisfaction as you preemp- J Allergy Clin Immunol Pract. 2013;1(1):65-74. them more often, as ocular side tively take their eye care beyond 10. Haimovici R, Gragoudas E, Duker J, et al. Central serous chorioretinopathy associated with inhaled or intranasal corti- effects include potential increased the exam chair. Manage co-existing costeroids. Ophthalmol. 1997 Oct;104(10):1653-60. intraocular pressure and higher conditions, prescribe when indi- 11. Greiner J, Peace D, Baird R. Effects of eye rubbing on theconjunctiva as a model of ocular inflammation. Am J 10 risk of central serous retinopathy. cated, and most importantly, iden- Ophthalmol. 1985 Jul;100(1):45-50.

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Don’t Be STUMPED by These LUMPS and BUMPS Most eyelid lesions are benign, but some can lead to severe clinical outcomes if not caught early. By Rodney Bendure, OD, and Jackie Burress, OD

he vast majority of eye- face, eventually losing their melanin lid lesions encountered granules, flattening and producing in the typical optometry keratin. The underlying dermis is practice are benign.1 How- comprised of connective tissue, Tever, it is important clinicians are nerves, blood vessels and lymphat- able to identify lesions capable of ics. Deeper, you will find the orbicu- infiltration, tissue destruction and laris muscle and tarsal plate. Finally, metastasis. To start, clinicians must the palpebral conjunctiva covers the appreciate the basic anatomy of the posterior surface of the eyelid, abut- eyelid. At only 0.7mm to 0.8mm, ting the globe. Adnexal structures, the eyelid is the thinnest skin on the including glands and hair follicles, human body.2 Yet, it contains all the are located in the dermis and tarsal components of skin on other areas Presented here is an advanced infiltrating plate.1 except a layer of subcutaneous fat. eyelid malignancy. Beginning externally and working Physical Characteristics posteriorly, we first encounter the and Merkel cells. Commencing at Specialists use a number of terms epidermis, which contains several the melanin-containing basal cell to describe the presentation of a layers of cells including keratino- layer, epithelial cells differentiate particular lesion. Knowing these cytes, melanocytes, Langerhans cells and migrate toward the skin sur- terms will help clinicians better clas-

Release Date: April 2017 Credit Statement: This course is COPE approved for 2 hours of CE Expiration Date: April 15, 2020 credit. Course ID is 53200-AS. Check with your local state licensing Goal Statement: Although the majority of lesions present on the board to see if this counts toward your CE requirement for relicensure. eyelids are benign, the identification and diagnosis of lesions that are Disclosure Statements: cause for concern are imperative to avoid adverse clinical outcomes. Authors: The authors have no relationships to disclose. This course provides a comprehensive overview of the identification of Peer Reviewers: The reviewers have no relationships to disclose. eyelid lesions and the treatment options for each. Faculty/Editorial Board: Rodney Bendure, OD, and Jackie Burress, Editorial staff: Jack Persico, Rebecca Hepp, William Kekevian, Michael Riviello and Michael Iannucci all have no relationships to disclose. OD

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Learn the Lingo With all the terms used to describe neoplasms, it’s not surprising that a lot of clinicians get lost in the milieu. Brush up on these terms: Neoplasm: A new growth. Essentially, this term grossly defines a mass of tissue that has outgrown the surrounding tissues. Tumor: A general medical term historically used to describe any area of swollen tissue, including those caused by inflammation, hemorrhage or edema. This term is often used interchangeably with neoplasm, though its connotation may be worse. Benign: Neoplasms that have been deemed relatively innocent by clinical and microscopic evaluation, and are unlikely to spread to other sites. These can be excised and carry a good This superior lesion is a typical prognosis, although they can cause local tissue destruction if left untreated. squamous papilloma. The inferior lesion Malignant: All malignancies are cancers. All cancers are malignancies. However, all tumors is a junctional nevus. and neoplasms are not cancers or malignancies. To use the term malignant or cancer means that the lesion has tendency to spread to and undermine neighboring tissues as well sify and more accurately convey as to metastasize (spread to distant sites). Therefore, malignant tumors carry the potential lesion characteristics to the patholo- for early mortality. gist. First, the term tumor does Cancer: A malignant neoplasm. not necessarily describe a cancer. Adenoma: Benign epithelial neoplasm derived from a gland. Rather, it is a general term for an Papilloma: Benign epithelial neoplasm which produces finger-like fronds. area of swollen tissue. Neoplasia, Carcinoma: Malignant neoplasm derived from epithelial cells (any epithelial cell, not just likewise, is a general term describ- skin). ing the abnormal growth of tis- Squamous cell carcinoma: A carcinoma (malignant neoplasm), derived from stratified sue, be it benign (noninvasive) or squamous epithelium. malignant (likely to spread aggres- Adenocarcinoma: A malignant lesion comprised of epithelial cells (carcinoma), which grow sively and metastasize).3 Ulceration in a glandular pattern (adeno). refers to a loss of epithelial tis- Hamartoma: A mass of disorganized tissue comprised of cells native to the host organ. An sue. Hyperkeratosis indicates the example would be an iris Lisch nodule composed of melanocytes. increased production of keratin, Choristoma: A congenital, benign mass of normal tissue located in non-native tissue. often noted clinically as scaling. An example would be a limbal dermoid containing fat, connective tissue and epidermal Induration is seen as redness and appendages. swelling of a lesion. Crusting is dried exudate on the skin surface.1 At the microscopic level, the Clinically, a number of additional A papule is a solid lump less than pathologist may describe atypia, or terms are used to describe the shape a centimeter in size. Nodules are an abnormality of an individual cell, and consistency of a lesion to help essentially just larger papules.1 whereas dysplasia denotes a change differentiate the etiology. A cyst is in the size, shape and organization a nodule lined with epithelial tis- Examination of the cellular structure of a tissue.1 sue and filled with a material that A thorough lesion exam always is fluid to near solid in consistency. begins with a detailed history. The Bullae are large, fluid-filled cysts. patient should be queried regarding Pustules are smaller cysts less than a UV exposure, smoking, immuno- centimeter in size. Vesicles are even suppression and history of cancer smaller fluid-filled cysts, generally and radiation therapy. Lesion- less than half a centimeter in diam- specific questions such as the length eter.1 of symptoms, rate of growth, bleed- Macule refers to an area of flat ing, ulceration, color changes and epidermal tissue, usually less than a alteration of tissue such as loss of centimeter across, with color change lashes should be addressed. only. Examples are freckles and vit- During the exam, clinicians An example of advanced seborrheic iligo. Plaques are similar, but larger should document a detailed descrip- keratosis. (2cm or more) and slightly elevated. tion of each lesion's characteristics.

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nation, as it can wash out the ABCs of Skin Lesions lesion. While no hard and fast rules exist, certain characteristics provide clinicians with Tumor Classification clues as to the nature of skin neoplasms. Eyelid tumors, like neoplasms These rules, easily remembered using the in other areas of the body, are mnemonic ABCDE are described in detail classified by their cell origin. here: Many clinicians find it useful Asymmetry: If you draw a line through to categorize eyelid lesions as a benign lesion, both halves are typically either inflammatory (e.g., symmetrical. chalazion), infectious (e.g., Shown here is an epidermal inclusion cyst. Borders: Benign lesions have regular hordeolum) or neoplastic. borders. Neoplasms can further be Affecting middle-aged and elderly Color: Variations in color in a single described by their oncogenic poten- individuals, these benign lesions are lesion raise suspicion of malignancy. tial, whether benign, premalignant well-demarcated, elevated plaques Diameter: Lesions larger than 6mm or malignant. with variable levels of pigmentation. diameter are suspicious of malignancy. They tend to enlarge and darken Evolution: Growth, bleeding, crusting, Benign Tumors gradually over time. Excision with loss of lashes or changes in color Benign lid lesions are by far the electrocautery or cryotherapy will increase suspicion of malignancy. most prevalent form of neoplasms generally eliminate recurrence. seen in eye care, accounting for Prognosis is excellent.1,10 However, a In particular, record lesion size, more than 80% of lid lesions.8 sudden increase in the size or num- location, pigmentation, ulceration, Epithelial tumors are the most ber of lesions can occur in individu- loss of normal eyelid architecture common type of eyelid neoplasms; als with occult malignancies and and consistency—whether fleshy these include papillomas, seborrheic should therefore raise suspicion.11 or firm, freely mobile or affixed keratoses, inclusion cysts and many Cutaneous horns. These are to underlying tissues. Take time to more.9 A thorough history and somewhat non-specific hyperkera- palpate the lesion to assess these examination of the lid lesion can totic lesions, which may be associ- characteristics. In addition, pho- often result in accurate diagnosis. ated with a variety of both benign tographs are an important part of Squamous papilloma. Far and and malignant eyelid lesions, includ- your documentation. External pho- away the most common benign epi- ing seborrheic keratosis, verruca tography can be accomplished using thelial eyelid tumor, this arises as an vulgaris, basal cell carcinoma (BCC) a slit lamp camera, fundus camera excessive growth of the squamous or squamous cell carcinoma (SCC). with anterior segment features or epithelium. It is characterized as Thus, this is a clinically descriptive even a smart device. It is especially either a sessile (flat) or pedunculated term and not a specific lesion type. helpful to have a metric ruler near (skin tag) growth with an oft-kera- Treatment is excision requiring the lesion for reference. A photogra- tinized surface. This slow-growing pathologic evaluation.10 Because phy tip—don’t use excessive illumi- tumor is common in middle-aged the horn is an extension of an unde-

Photo: Cogan Collection, NEI/NIH and elderly patients and often pres- termined underlying tumor, biopsy ents as multiple lesions. Squamous requires excision of epidermal tissue papilloma is treated by simple exci- beneath the lesion as well.11 sion at the lesion base, cryotherapy, Epidermal inclusion cysts. These or laser or chemical ablation. Prog- arise from entrapment (usually trau- nosis is excellent, though patients matic) of epidermal tissue within often develop additional papillomas the dermis. They appear as discrete with age.1,10 white or light yellow, firm, solid, Seborrheic keratosis. This slow-growing cysts. Treatment is by is another very common slow- excision, though the entire cyst wall growing, benign epithelial tumor. must be removed to prevent recur- This is a typical lesion seen with It is typically described as having rence. Prognosis is excellent.10,11 molluscum contagiosum. a greasy, “stuck-on” appearance. Molluscum contagiosum. A

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070_ro0417_f6(v4).indd 72 3/30/17 12:15 PM Excisional Biopsy Protocols Lesions with clearly benign characteristics (e.g., squamous papilloma, seborrheic keratosis, verruca vulgaris) can be excised in office and should be sent for pathologic confirmation. Benign lesions are characterized by even coloration, well-defined regular borders, lack of ulceration, no indu- ration, a history of slow growth and a maintenance of normal skin structures such as lashes and glands.1 Minor surgical procedures to remove such lesions can be performed by optometrists in Oklahoma, Kentucky, Louisiana and Tennessee.4-7 Here’s how to perform an excisional lesion removal: Benign lesion removal. To excise a benign lesion, you’ll need a 3mL syringe with a one-half inch 27- or 30-gauge needle to inject a small amount of 1% to 2% lidocaine with epinephrine 1:100,000 at the base of the lesion; we often find patients tolerate simple excision without anes- thesia, especially for pedunculated masses. Just prior to anesthetizing the base, the area should be sterilized with an ophthalmic betadine swab. Once the area is numb, the mass is grasped with toothed forceps, pulled slightly away from its base and snipped free. Light pressure for a few minutes with a small gauze pad usually stops any bleeding, but a disposable thermal cautery unit comes in handy in case bleeding continues. Place the specimen in a formalin container suitable for transport to the laboratory for histologic evalua- tion. Prior to releasing the patient, apply a prophylactic antibiotic ointment such as erythromycin or Polysporin and advise the patient to keep the area clean and dry and to apply the ointment three times daily for three days. Malignant lesion removal. Lesions suspicious for malignancy should be promptly referred to an oculoplastics specialist for evaluation, biopsy and reconstruction if needed. Patients may be apprehensive as to what they can expect when referred for lesion removal. It is incumbent upon the referring practitioner to be familiar with the possible treatment techniques to allay any fears the patient may have. A number of alternative methods may be employed for the removal or destruc- Place the specimen in formalin to tion of eyelid tumors, including chemotherapy, radiation or photodynamic therapy.1,10 However, in transport to the laboratory. our experience complete excisional biopsy is far and away the most common treatment method used by our oculoplastics specialists. For large or aggressive lesions, the preferred method for removal is under frozen section, namely Mohs micrographic surgery.19,26,27 This pro- cedure is particularly useful in periocular cutaneous tumor removal because it causes the least collateral tissue damage while ensuring complete tumor excision.19,26-28 In addition, Mohs procedure has a nearly 100% success rate (97.5% overall, 99.4% for primary lesions and 92.4% for recurrent lesions).19,29,30 Mohs surgery works especially well with basal cell carcinoma and squamous cell carcinoma because these types of tumors have a continuous growth pattern as opposed to tumor types with “skip areas” such as sebaceous adenocarcinomas.19 Eyelid repair and reconstruction. Repair of the involved eyelid requires special techniques. If less than one-third of the full thickness of the eyelid is removed, a simple direct closure may be performed. For larger defects, more elaborate lid reconstruction procedures using tissues har- vested from adjacent areas may be needed.1

poxvirus infection, this is charac- often-umbilicated center. These are as a viral wart, this is an epidermal terized by small, typically 1mm to more common in the very young growth caused by the human papil- 2mm, flesh-colored papules with an and the immunocompromised. loma virus, typically types VI or XI.

Photo: Cogan Collection, NEI/NIH Lid margin lesions can cause a fol- Two forms exist: filiform, which licular conjunctivitis. These lesions are also called digitate because are spread by skin-to-skin contact they project in a finger-like fashion and regress spontaneously except from their base, and plana, which in the immunocompromised, where are flat. Beginning as small papules they can develop into disfiguring slightly lighter than the surround- lesions. Molluscum contagiosum ing skin, they tend to darken and can be removed if desired by exci- become hyperkeratotic with time. sion, curettage, electrodesiccation or While benign, eyelid margin warts cryotherapy. The prognosis is good can cause punctate keratitis or even in healthy people, and the risk of corneal pannus.12 Observation is Shown here is an example of an transmission is low.1,10 often adequate, as these lesions tend xanthelasma. Verruca vulgaris. Also known to eventually outgrow their blood

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supply and spontaneously involute, bluish. They may be treated by cyst Photo: Cogan Collection, NEI/NIH but may be removed by excision, drainage, but sometimes require cryotherapy or chemical cautery if removal of the entire cyst wall if eye irritation ensues or for cosmetic recurrent.10,11 reasons.13 Apocrine hydrocystomas. Com- Xanthelasma. This usually pres- monly called cystoadenomas, these ents on the eyelids as yellow plaques resemble sudoriferous cysts except filled with lipid-laden macrophages. their contents are creamy white. These arise after the age of 50 Treatment is by excision.11 and should prompt suspicion of a Pilomatricoma. This arises from lipoprotein disorder when present the germinal matrix of a hair bulb in patients younger than this.1,10 and is thus another adnexal tumor. Seen here are hydrocystomas. Excision, electrodissection, laser This benign tumor is more common treatment and application of trichlo- in young females.1 It presents as a adulthood, darken upon ultraviolet roacetic acid all may be employed hard, indurated nodule. The body light exposure and tend to involute with excellent results. However, the reacts in granulomatous fashion due by the sixth decade.1,10 In adults, lesions tend to recur about 50% of to calcium deposition. Excision is they tend to be asymptomatic the time.1,10 the treatment of choice.1 and stable in appearance. These Syringoma. This benign adnexal Trichoepithelioma. This is note- lesions tend to be one of three main tumor appears in multiple, discrete, worthy because its appearance is types:1,10 skin-colored lesions measuring from sometimes confused with basal cell • Junctional nevi are round, flat 1mm to 2mm on the lower eyelids carcinoma. These lesions are more and less than 1cm in diameter. and cheeks of some females begin- common in males, usually arising Usually, these are tan to brown ning in puberty. Heredity appears to during puberty.10,14,15 These small in color and have regular bor- play some role in the development skin-colored tumors are benign ders. of this condition. These lesions are skin appendage growths. Treatment • Compound nevi are elevated, benign adenomas of eccrine ducts. is by excision. Since these cannot round, dark brown lesions, Prognosis is good, although numer- be clinically differentiated from which often have hair growing ous excisions or electrocautery ses- basal cell carcinoma by physical in them. sions may be required due to the examination alone, pathologic and • Dermal nevi are elevated nod- number of lesions; recurrence is immunohistochemical evaluation is ules with variable pigmenta- common.1,10 warranted.10,14,15 tion, sometimes skin-colored. Eccrine hydrocystomas. Also Freckles or ephelis. These are These do not tend to involute known as sudoriferous cysts, these small, flat brown skin lesions with age.1,10 arise from sweat glands along the appearing most commonly on sun- Nevi carry a relatively good prog- eyelid margin. These fluid-filled exposed skin, including the eyelids. nosis with a low potential for malig- cysts appear translucent, though These are merely a hyperpigmenta- nant transformation.1,16,17 In fact, thicker-skinned lesions may appear tion of the basal cell layer, with no the annual rates of transformation further penetration into the epider- of a melanocytic nevus are only one mis or dermis. These may lighten in 200,000 for younger individuals in the absence of sun exposure and one in 33,000 for the elderly.18 and darken upon re-exposure. The Changes in size, color, irregular bor- prognosis with these lesions is very ders or bleeding are indications for good.1,9 No treatment is necessary, histologic biopsy.1,10 although avoidance of ultravio- Milia. These are small superficial let light and use of sunscreen can white papules 1mm to 4mm in size. reduce pigmentation.11 They represent keratin-filled pilo- Nevi. These are small macules of esebaceous units. Causes include hyperpigmented melanocytic cells idiopathic, trauma, infection, located in the deep epidermis or radiotherapy or bulbous diseases. A hemangioma is present on the upper dermis. These acquired lesions arise Treatment is by expression, electro- eyelid. in childhood and reach full size by dessication or excision.1,11

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070_ro0417_f6(v4).indd 74 3/30/17 12:16 PM Photo: Cogan Collection, NEI/NIH metic reasons.1,10 Pyogenic granuloma. In spite of its name, it is neither pyogenic nor a granuloma and presents in the form of a pinkish red mass that arises after trauma or surgery. These rapidly growing, delicate lesions are comprised of blood vessels and fibroblasts and readily bleed with minor insult. Treatment is by com- plete excision.11 A basal cell carcinoma is depicted here. Seen here is an example of keratoacanthoma. Pre-Malignant Tumors though when they do, they are typi- Some lesions are precursors to cally low-grade (i.e., they have low Hemanigiomas. These are elevat- malignant lesions. These must be mitotic activity).1,10 There is some ed red lesions comprised of blood monitored closely and referred if disagreement in the literature about vessels. Three types of these vascular signs of malignant transformation the likelihood of malignant trans- tumors exist, two being congenital occur. formation, with research suggesting and the other acquired: Keratoacanthoma. This presents risks from 0.1% to 20%, depending • Capillary hemangiomas, often as a dome-shaped nodule with on the literature.10,11 referred to as strawberry nevi, are a keratin-filled core on the sun- Lentigo Maligna. Believed to be one of the most common tumors in exposed skin of individuals over the caused by sun exposure, these flat infancy. These are known to blanch age of 50.10,11 It usually develops brown-to-black macules occur in with pressure and swell with cry- rapidly over weeks, only to regress older individuals, with a median ing.1,10 spontaneously after a few months.10 age of occurrence at 65.1,10 Their • Cavernous hemangiomas, also Those with fair skin, chronic sun appearance has been described as seen in infancy, are located deeper exposure and those undergoing looking like a stain on the skin.10 in dermal tissues. However, these do immunosuppressive therapy are at Slow growth and irregular borders not blanch with pressure or swell risk for keratoacanthoma.1 Some are typical. Nodular thickening and with crying.1,10 Both congenital argument exists as to whether these variations in color suggest malig- forms tend to resolve spontaneously may represent some variation of nant transformation. They should over time. squamous cell carcinoma. These be excised and sent for pathologic • Cherry hemangiomas can tend to be more common in males, laboratory evaluation. Prognosis is arise rapidly in middle age and with a 2:1 predilection. Treatment excellent so long as they are excised older, but are typically associated is by Mohs surgery with pathologic prior to transformation into mela- with similar lesions on other body laboratory evaluation. This lesion noma.1,10 parts. They carry an excellent prog- carries a generally good prognosis.10 nosis and can be excised for cos- Presence of multiple neoplasms may Malignant Tumors signify underlying systemic cancer.11 While malignant tumors are seen Photo: VisualDx Actinic Keratosis. Formerly much less frequently than benign known as solar keratosis, this is a neoplasms, it is imperative to quick- slow growing precancerous cuta- ly recognize the lesions that warrant neous lesion. Occurring on sun- prompt medical intervention. Here exposed areas of the skin, including we discuss the eyelid malignancies the eyelids, these may be caused by clinicians are most likely to encoun- ultraviolet radiation. They are com- ter: mon in fair-skinned individuals and Basal cell carcinoma. This is the are most often noted on the backs most common type of skin cancer of the hands and forehead. These on the eyelid, accounting for 90% solitary or small-grouped, flat, scaly to 95% of all malignant eyelid Pictured above is an example of a lentigo plaques may occasionally transform tumors, and is the most common maligna. into squamous cell carcinoma, human malignancy overall.1,19,20

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Kaposi’s sarcoma. Squamous cell carcinoma. Melanoma of punctum.

Though it rarely metastasizes, BCC cal reconstruction may be required Fortunately, the majority of lesions can be locally invasive, even invad- depending on the size of the are not aggressive and can be treat- ing the orbit. In order of prevalence, lesion. Radiation treatment may ed by surgical excision, preferably BCC most often occurs on the lower be employed only in cases of poor by frozen section or Mohs surgery. lid, followed by the medial can- surgical candidates, while chemical Some may be treated with topical thus, upper eyelid and lateral can- agents such as imiquimod may only imiquimod cream if they are not thus.1,10,21 Variations in UV exposure be used for lesions not located on located on the eyelid margin.10 of the different eyelid locations the eyelid margin.10 Sebaceous adenocarcinomas explains these prevalences.22 In par- Squamous cell carcinoma. This is (SGC). Although rare, these are allel, the highest risk for orbital and far less common than BCC, with an highly malignant and potentially sinus invasion involves lesions of the incidence of 12 per 100,000 white lethal (5% to 10% mortality).1 medial canthal area.1,10,21 Signs of males.10 It is about half as common Arising from the sebaceous glands orbital invasion include a firm mass in white females and about a tenth of the eyelid, they are sometimes that may cause displacement of the as common in blacks. UV light and initially mistaken for chalazia.1 One globe or restrictive strabismus.23 exposure to ionizing radiation cause of the few malignant eyelid tumors These signs warrant urgent diagnos- malignant transformation of epider- more common in females, this lesion tic imaging. Incidence is approxi- mal squamous cells.10,11 SCC most usually arises from a dysplastic mei- mately 500 to 1000 per 100,000, often appears on the lower eyelid, bomian gland or gland of Zeiss in and men are affected more than especially the eyelid margin.1,10 In patients over the age of 50.1,11 SGC women. Those with fair skin and a fact, while far less prevalent than has a predilection for the upper eye- history of chronic sun exposure are BCC, SCC is more common on the lid, likely due to the higher number likely victims.10 upper eyelid and lateral canthus.11 of meibomian glands relative to the These lesions appear as firm, These lesions can take on many rest of the eye.1,11 The Wills Oculo- round-to-oval bumps on the skin forms. Like BCC, SCC appears plastics Manual describes sebaceous surface (i.e., nodular form) that, as in multiple presentations. These adenocarcinoma as “the Great they grow, develop pearly, raised include a nodular presentation with Masquerader.” Thus, any chronic borders with telangiectasia and a a firm hyperkeratotic appearance, blepharitis or recalcitrant chalazion central ulcerated core (i.e., nodu- an ulcerating presentation with dis- in a middle aged or elderly woman loulcerative form). A third subset, tinct, inflamed borders and central should evoke suspicion. sclerosing or morpheaform BCC, crater, and a buried, aggressive form Nodular SGC. This presents as a is less well defined and thus more with a superficial cutaneous horn.1,10 hard mass in the upper eyelid, often difficult to diagnose, as it tends to Though less common than BCC, containing yellowish lipid material, spread beneath the skin surface.1,21 SCC carries more risk as it is more which is highly characteristic.1 Prognosis is good when the lesion aggressive and spreads to regional Spreading SGC. This is less obvi- is completely excised, though any lymph nodes in 20% of cases.1 It ous, infiltrating through the dermis tumor remnants left behind tend has also been known to spread and causing a diffuse thickening to be agressive.1 Mohs surgery or intracranially by growing along of the lid and loss of lashes.1 Sus- frozen sections should be employed nerves, including the trigeminal, picion should prompt referral for to ensure complete excision. Surgi- oculomotor and facial nerves.1,24,25 biopsy, which in and of itself poses

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070_ro0417_f6(v4).indd 76 3/30/17 12:16 PM advanced disease state (AIDS), hence short-term mortality is high.10 Merkel cell carcinomas. These are rare, highly aggressive tumors affect- ing older individuals. They arise from sensory touch receptors within the eyelid. Characteristic appearance is a slightly purplish, well-defined nodule most commonly in the upper eyelid with no ulceration. At the time of presentation, it is estimated that 50% have metastasized. Treat- Pictured here is the reconstruction of an Shown above is the reconstruction of an ment is excision followed by chemo- eyelid after excision and Hughes flap. eyelid with basal cell carcimona. therapy or radiation.1

some concern, as special staining deeper tissues, the lesion appearance Eyelid neoplasms are a common and treatment of samples must be changes, becoming multi-nodular entity encountered in optometric performed, or the diagnosis could and indurated. practice. While the vast majority be incorrect. The surgeon must alert • Acral lentiginous melanoma of these neoplasms are benign, it is the pathologist as to the suspected occurs mostly on nonocular tissues. of the utmost importance to recog- etiology. Wide excision with con- • Nodular melanoma is the most nize any potential malignancy. The trolled margins is necessary because common form affecting the eyelids. management of these malignancies this aggressive tumor sometimes has It presents variably as a darkly pig- requires prompt referral to oculo- skip areas and could recur or spread mented to amelanotic nodule, which plastics for biopsy and reconstruc- without appropriate treatment.9,11 grows rapidly with notable bleeding tion; early intervention minimizes Therefore, vigilant follow-up is and ulceration.11 These dangerous the amount of collateral tissue dam- warranted. If diagnosis of SGC is lesions often spread despite aggres- age, resulting in easier reconstruc- confirmed, the patient will need to sive excision efforts with controlled tion. This allows for retention of be seen by their primary care doctor surgical margins. Sentinel lymph normal eyelid function, preservation immediately to rule out metasta- node (nearest the lesion) biopsy is of the globe, a functional lacrimal ses.9,11 required due to the propensity to system and a pleasing cosmetic Malignant melanoma. This is spread via lymphatics. These malig- outcome.2 Thankfully, a thorough not common. In fact, it comprises nancies have a high rate of distant case history and physical examina- only about 1% of eyelid malignan- metastasis, which may occur years tion can easily help the primary care cies. Despite the lower incidence, after the initial lesion. The eight- optometrist decide when referral is melanoma is the cause of over 60% year survival rate is 33% (greater needed and avert adverse ocular and of deaths from all cutaneous can- than 3.6mm) to 93% (less than systemic outcomes related to malig- cers.11 Whites, especially those with 0.76mm) depending on the tumor nant eyelid neoplasm. ■ a history of severe sunburns, are at depth.10 Careful follow-up care with Dr. Bendure is a staff optom- a higher risk. Many are identified their primary care doctor is needed etrist at the Ernest Childers VA after a patient notices a change in long-term for these patients. Outpatient Clinic in Tulsa, OK, and color or increased size of a long- Kaposi's sarcoma of the eyelid. an adjunct faculty member with standing mole.10 Four subtypes exist: This is rare, but when present likely Oklahoma College of Optometry. • Lentigo malignant melanoma, signifies an immunocompromised Dr. Burress is a staff optometrist which arises from lentigo maligna, state. These vascular tumors appear at Ernest Childers VA Outpatient may exist for a number of years as a as red-to-purple elevations on the Clinic in Tulsa, OK, and an adjunct pigmented macule up to several cen- skin surface. They can be removed faculty member with Oklahoma timeters in diameter with irregular by excision, cryotherapy or intra- College of Optometry. borders. lesional chemotherapeutic agents. 1. Bowling B, Kanski J. Kanski’s clinical ophthalmology: a systematic • Superficial spreading melanoma Large lesions may require radiation. approach. 8th ed. Edinburgh: Elsevier; 2016. Print. 2. Dekmezian M, Cohen P, Sami M, Tschen J. Malignancies of the is smaller and mildly elevated. As The presence of these lesions in an eyelid: a review of primary and metastatic cancers. Int J Dermatol. 2013;52:903-26. it begins to transform and invade HIV-positive patient signifies an 3. Kumar V, Robbins S, Cotran R. Basic Pathology. 6th ed. Philadel-

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phia: Saunders; 1997. Print. ably distinguishes trichoepitheliomas from basal cell carcinomas. Br J Skin Cancer Foundation. December 7, 2012. Accessed February 4. Lubell J. In scope. AOA Focus. Nov/Dec 2014:22-9. Dermatol. 1994;131:28-31. 27, 2017. 5. Eisenberg J. Kentucky expands O.D.s’ scope of practice. Rev 15. Heidarpour M, Rajabi P, Sajadi F, et al. CD10 expression helps to 23. Slutsky J, Jones E. Periocular cutaneous malignancies: A review Optom. 2011;148(3):4-6. differentiate basal cell carcinoma from trichoepithelioma. J Res Med of the literature. Dermatol Surg. 2012;38:552-69. 6. Louisiana Gov Jindal signs expanded scope of practice bill. AOA Sci. 2011;16(7):938-44. 24. Kasenchak J, Notz G. Eyelid lesions: diagnosis and treatment. Rev News. June 2, 2014. www.aoa.org/news/advocacy/louisiana-gov- 16. Hernandez A, Torrelo A. Recent data on the risk of malignancy Ophthalmol. 2016;23(4):71-5. ernor-jindal-signs-expanded-scope-of-practice-bill?sso=y. Accessed in congenital melanocytic nevi: the continuing debate on treatment. 25. Bernardini F. Management of malignant and benign eyelid lesions. March 27, 2017. Actas Dermosifiliogr. 2008;99:185-9. Curr Opin Ophthalmol. 2006;17:480-4. 7. Legislation in Tennessee to allow ODs to use injectable anesthetic. 17. Schwartz R. Congenital nevi treatment and management. emedi- 25. Muller F, Dawe R, Moseley H, Fleming C. Randomized compari- Rev Optom. 2014;151(4):8. cine.medscape.com/article/1118659-treatment. Medscape. June 10, son of Mohs micrographic surgery and surgical excision for small 8. Deprez M, Uffer S. Clinicopathological features of eyelid skin 2016. Accessed February 17, 2017. tumors. A retrospective study of 5504 cases and review of literature. 18. Bauer J, Garbe C. Risk estimation for malignant transformation of nodular basal cell carcinoma: tissue-sparing outcome. Dermatol Sur. Am J Dermatopathol. 2009;31(3):256-2. melanocytic nevi. Arch Dermatol. 2004;140(1):127. 2009;35:1349-54. 9. Pe’er J. Pathology of eyelid tumors. Indian J Ophthalmol. 19. Moul D, Zabielinski M, Choudhary S, Nouri K. Mohs micrographic 27. Tildsley J, Diaper C, Herd R. Mohs surgery vs primary excision for 2016;64(3):177-90. surgery for eyelid and periorbital skin cancer. Int Ophthalmol. Clin. eyelid BCCs. Orbit. 2010;29(3):140-5. 10. Penne R. Oculoplastics. 2nd ed. Philadelphia: Wolters Kluwer 2009:49(4):111-27. 28. Ong L, Lane C. Eyelid contracture may indicate recurrent Health/Lippincott Williams & Wilkins Health; 2012. Print. 20. Madge S, Khine AA, Thaller VT, et al. et al. Globe sparing surgery basal cell carcinoma, even after Mohs micrographic surgery. Orbit. 11. Yanoff M, Duker J. Ophthalmology. 4th ed. Philadelphia: Elsevier for medial canthal basal cell carcinoma with anterior orbital invasion. 2009;28:29-33. Saunders; 2014. Print. Ophthalmol. 2010;111(11):2222-8. 29. Rowe D, Carroll R, Day Jr C. Long term recurrence rates in previ- 12. Proia A, Gayre G, Dutton J. Diagnostic atlas of common eyelid 21. Gündüz K, Esmaeli B. Diagnosis and management of malignant ously untreated (primary) basal cell carcinoma: implications for patient diseases. New York:Informa Healthcare; 2007. Print. tumors of the eyelid, conjunctiva, and orbit. Expert Rev Ophthalmol. follow-up. J Dermatol Surg Oncol. 1989;15:315-8. 13. Casser L, Fingeret M, Woodcome H, et al. Atlas of primary eyec- 2008;3(1):63-75. 30. Rowe D, Carroll R, Day Jr C. Mohs surgery is the treatment of are procedures. 2nd ed, Norwalk:Appleton & Lange; 1997. Print. 22. How Sunlight Damages Your Eyes. www.skincancer.org/preven- choice for recurrent (previously treated) basal cell carcinoma. J Der- 14. Smoller B, Van de Rijn M, Lebrun D, et al. bcl-2 expression reli- tion/sun-protection/for-your-eyes/how-sunlight-damages-the-eyes. matol Surg Oncol. 1989;15:424-31.

OSC QUIZ

ou can obtain transcript-quality c. Lesion diameter less than 6mm. prevalence for: continuing education credit through d. Both a and b. a. Lower eyelid. Ythe Optometric Study Center. Com- b. Medial canthus. plete the test form and return it with the $35 4. Large numbers or rapid growth of these c. Upper eyelid. fee to: Jobson Medical Information, Dept.: typically benign "stuck on" lesions is d. Lateral canthus. Optometric CE, 440 9th Avenue, 14th Floor, suggestive of systemic malignancy: New York, NY 10001. To be eligible, please a. Squamous papilloma. 10. Which basal cell carcinoma location return the card within one year of publication. b. Actinic keratosis. carries the highest risk for orbital and sinus You can also access the test form and c. Seborrheic keratosis. invasion? submit your answers and payment via credit d. Syringoma. a. Lower eyelid. card at Review of Optometry online, www. b. Medial canthus. reviewofoptometry.com/ce. 5. Which of the following is true regarding c. Upper eyelid. You must achieve a score of 70 or higher nevi? d. Lateral canthus. to receive credit. Allow eight to 10 weeks a. Three types exist: junctional, compound for processing. For each Optomet ric Study and bi-directional. 11. Squamous cell carcinoma has a highest Center course you pass, you earn 2 hours of b. Temporary changes in size, color and prevalence for: transcript-quality credit from Pennsyl vania shape are common. a. Upper eyelid. College of Optometry and double credit c. Nevi are not capable of darkening with b. Lateral canthus. toward the AOA Optom et ric Recog nition UV exposure. c. Lower eyelid. Award—Cate gory 1. d. Nevi carry a low risk of malignant d. Medial canthus. Please check with your state licensing transformation. board to see if this approval counts toward 12. Which of the following lesions is your CE requirement for relicensure. 6. Suspicious eyelid lesions should be: considered a low-grade squamous cell a. Excised in office. carcinoma? 1. The average thickness of the human b. Photodocumented. a. Xanthelasma. eyelid is approximately: c. Sent for biopsy and pathologic evaluation. b. Squamous cell papilloma. a. 1.0mm. d. Both b and c. c. Pyogenic granuloma. b. 2.0mm. d. Keratoacanthoma. c. 0.3mm. 7. Signs of orbital invasion include: d. 0.75mm. a. Proptosis. 13. Which of the following lesions, if found b. Strabismus. on a patient younger than 50, should 2. The term cancer: c. Follicular conjunctivitis. prompt laboratory serum lipid evaluation? a. Is a general term for any abnormal skin d. Both a and b. a. Milia. growth. b. Xanthelasma. b. Denotes a malignant lesion. 8. Basal cell carcinoma accounts for c. Epidermal inclusion cyst. c. Is synonymous with the term what percentage of all malignant eyelid d. Pyogenic granuloma. "neoplasm." neoplasms? d. Describes a lesion with low potential for a. 50%. 14. A chronic, hard lump filled with yellow metastasis. b. 75%. material in the upper eyelid of an older c. 20%. female patient should raise suspicion of 3. Signs suggestive of malignancy are: d. 90%. which of the following neoplasms? a. Asymmetry. a. Keratoacanthoma. b. Loss of eyelashes. 9. Basal cell carcinoma has a highest b. Verruca vulgaris.

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0070_ro0417_f6(v4).indd70_ro0417_f6(v4).indd 7878 33/30/17/30/17 12:1712:17 PMPM OSC QUIZ Examination Answer Sheet Don't Be Stumped by These Lumps and Bumps c. Sebaceous cell carcinoma. d. Lentigo maligna. Valid for credit through April 15, 2020 Online: This exam can be taken online at www.reviewofoptometry.com/ce. Upon passing the exam, you can 15. What is the treatment of choice for a view your results immediately and download a real-time CE certificate. You can also view your test history at cutaneous horn? any time from the website. a. Warm compresses and eyelid hygiene. Directions: Select one answer for each question in the exam and completely darken the appropriate circle. A b. Intralesional triamcinolone injection. minimum score of 70% is required to earn credit. c. Application of a gentle ophthalmic Mail to: Jobson Medical Information, Dept.: Optometric CE, 440 9th Avenue, 14th Floor, New York, NY 10001. antibiotic to soften the lesion. Payment: Remit $35 with this exam. Make check payable to Jobson Medical Information LLC. d. Biopsy of the underlying cutaneous Credit: This course is COPE approved for 2 hours of CE credit. Course ID is 53200-AS. tissue. Sponsorship: This course is joint-sponsored by the Pennsylvania College of Optometry. Processing: There is an eight- to 10-week processing time for this exam. 16. Malignant melanoma comprises what percentage of malignant eyelid Answers to CE exam: neoplasms? Post-activity evaluation questions: 1. A B C D a. 1%. Rate how well the activity supported your achievement of these learning objectives: b. 15%. 2. A B C D 1=Poor, 2=Fair, 3=Neutral, 4=Good, 5=Excellent c. 10%. 3. A B C D 21. Improve my clinical ability to differentiate between benign, pre-malignant and malignant eyelid neoplasms 1 2 3 4 5 d. 5%. 4. A B C D 22. Become familiar with the key definitions related to 5. A B C D neoplasms in general, and eyelid neoplasms specifically. 1 2 3 4 5 17. Nodular malignant melanoma presents 6. A B C D 23. Increase skill in my examination and documentation as: 7. A B C D abilities as they pertain to neoplasms of the eyelids. 1 2 3 4 5 a. A darkly pigmented lesion. A B C D 8. 24. Better know the best practices for performing excisional b. A lightly pigmented lesion. 1 2 3 4 5 9. A B C D biopsy of eyelid lesions. c. A variably pigmented lesion. 10. A B C D 25. Increase my knowledge of the types of neoplasms d. Both b and c. within the benign, pre-malignant and malignant categories. 1 2 3 4 5 11. A B C D 26. Improve my ability to communicate with patients about 12. A B C D 18. Malignant melanoma is the cause the nature of their eyelid lesions and any treatment needed. 1 2 3 4 5 13. A B C D of what percentage of deaths due to Rate the quality of the material provided: 14. A B C D cutaneous neoplasms? 1=Strongly disagree, 2=Somewhat disagree, 3=Neutral, 4=Somewhat agree, 5=Strongly agree a. 15%. 15. A B C D 27. The content was evidence-based. 1 2 3 4 5 b. 90%. 16. A B C D 28. The content was balanced and free of bias. 1 2 3 4 5 c. 75%. 17. A B C D 29. The presentation was clear and effective. 1 2 3 4 5 d. 60%. 18. A B C D 30. Additional comments on this course: 19. A B C D

19. Presence of Kaposi's sarcoma 20. A B C D suggests which of the following systemic conditions? Please retain a copy for your records. Please print clearly. a. Immunocompromised state. b. HIV positive status with normal CD4 cell First Name count. Last Name c. Neurofibromatosis type I. d. Both b and c. E-Mail The following is your: Home Address Business Address 20. What is the treatment of choice for Merkel cell carcinoma? Business Name a. Electrocautery. Address b. Excision followed by adjuvant chemotherapy or radiation. City State c. Topical imiquimod. ZIP d. Photodynamic therapy. Telephone # - -

Fax # - -

By submitting this answer sheet, I certify that I have read the lesson in its entirety and completed the self- assessment exam personally based on the material presented. I have not obtained the answers to this exam by any fraudulent or improper means.

TAKE THE TEST ONLINE TODAY! Signature Date www.reviewofoptometry.com/ continuing_education/ Lesson 114271 RO-OSC-0417

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0070_ro0417_f6(v4).indd70_ro0417_f6(v4).indd 7979 33/30/17/30/17 12:1712:17 PMPM Up to 18-28 CE Credits 2017

REVIEW OF OOPTOMETRYPTOMETRY EDUCATIONAL MEETINGS OF CLINICAL EXCELLENCE

2017 MEETINGS Program Chair: Paul Karpecki, OD

San Diego, CA Orlando, FL Philadelphia, PA April 20-23, 2017** June 8-11, 2017** November 3-5, 2017* Joint Meeting: NT&T/OCCRS Disney’s Yacht & Beach Club Loews Philadelphia Hotel San Diego Marriott Del Mar

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See Review website for any meeting schedule changes or updates. Review of Optometry® partners with Salus University Stock Images: ©iStock.com/JobsonHealthcare for those ODs who are licensed in states that require university credit. Focus on Refraction

Low-Tech TBI Rehabilitation Often, binasal occlusion with a small piece of tape can be a huge help for stroke and brain injury patients. By Marc B. Taub, OD, MS, and Paul Harris, OD

his is the fourth year we brain injury many patients have been seeing patients are unable to deal with the Tonsite at several inpa- level of visual information tient rehabilitation facilities. they are receiving. They may We started slowly and, with the complain of balance issues, support of Southern College light sensitivity, a swimming of Optometry, grew the pro- sensation and blurry or funny gram annually. We now have a looking vision, to name only team of four doctors who see a few visual symptoms. patients at several facilities, and Fig. 1. Binasal occlusion helped this patient overcome a Binasal occlusion reduces the we are busier than ever. swimming sensation and get back to her rehabilitation amount of incoming stimula- When we get the call to visit following a stroke. tion, particularly blocking a patient in an inpatient reha- parts of the image seen by bilitation facility, we never know therapy and using base-in prism.3 both eyes. Remember, the visual sys- what we are going to find when Binsasal occlusion is a type of sec- tem receives information from both we walk in the room. Commonly, tor occlusion that blocks the nasal eyes’ nasal visual field. In some TBI we encounter patients with field portion of each lens to some degree. cases, the patient cannot process loss, visual inattention, diplopia or The practitioner can use virtually all of the data in real time, which unexplained decreased vision. Our any kind of tape, but we prefer to results in the failure of the vision mission is to help the patient obtain use Transpore tape (3M), as it is system to keep clear, single binocu- clear, single binocular vision, which not opaque. Some light can pass lar vision. According to one study, not only helps the patient, but also through, which stimulates the retina “when the visual process is labored, allows the doctors, therapists and and helps keep the patient alert and the organization and integration of even other patients to make the best oriented. To account for conver- this portion of visual space may be use of their time while there. gence when viewing at a close dis- the most demanding as far as main- tance, we always tilt the occlusion taining comfortable and clear bin- Go-to Treatment so there is a smaller amount on the ocular, single vision. Modifying the Binasal occlusion is a staple lower portion of the lens. input from the very core of this area treatment for many patients. may serve to relieve stress.”2 The Investigators show it can be ben- Binsasal Occlusion for TBI following two cases demonstrate the eficial for patients with esotropia, Traumatic brain injury (TBI) is a benefit of binasal occlusion in the non-strabismic functional vision major cause of death and disabil- TBI population. problems and amblyopia.1 Research ity worldwide.4 The Centers for highlights binasal occlusion use in a Disease Control estimates that TBIs Case 1 patient with significant visual distur- account for 2.2 million emergency A 62-year-old black female with a bances secondary to cerebral palsy, room visits, 280,000 hospitaliza- history of four strokes in the past but little literature exists regarding tions and 50,000 deaths annually.5 several years presented, following its use for patients suffering a trau- Changes in function following a her most recent stroke, complain- matic brain injury (TBI) or stroke.1 TBI can be widespread and impact ing of swimming vision when she One study demonstrates symptom every single organ system, includ- moved her head. Her occupational and visual function improvements ing the visual system. Aside from therapist was having trouble get- in a TBI patient undergoing vision the obvious ocular injuries, after a ting her to balance well and said the

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patient preferred to be lying down or reclined in a chair. Both postures make rehabilitation problematic. The examination at the patient’s bedside showed slightly decreased visual acuity with her current glasses, an intermittent alternating exotropia of about eight to 10 prism diopters at near and poor fixation, to the extent that she had trouble localizing and touching a target Fig. 2. Although binasal occlusion improved this patient’s vision, he felt it was more using her vision. She knew an issue annoying than helpful. existed and was particularly dis- turbed by the swimming sensation. As this was not a case of double vision, my first inclination was to try binasal occlusion (Figure 1). Upon placement, the patient felt markedly better. When placing the occlusion for the first time, it’s acceptable to guess the best loca- tion. We have the patient fixate on the practitioner’s nose and place the Fig. 3. By reducing occlusion, we were able to eliminate the visual symptom without tape just nasal of the pupillary mar- interrupting the patient’s vision. gin. Then, we have the patient relax and engage with the surroundings. trouble reading and watching TV. formed well on a visual efficiency Some patients need more occlusion, The examination showed excellent and processing evaluation. others less. It’s straightforward to visual acuity, no restriction in eye remove and readjust the tape a few movements and accurate localiza- These cases highlight the immedi- millimeters. tion of hand-eye coordination. ate positive impact of binasal occlu- Since the patient was in the facil- We placed the binasal occlusion sion. This treatment need not be ity a few weeks, I stopped back and observed noticeable relaxation relegated to inpatient use, but can to assess the treatment a few days in the patient’s body (Figure 2). be of value to the patients in your later. While she was still suffering He tried texting on his phone and chair. You will be surprised how with balance issues, she was making looked at the TV’s closed captioning often patients slip below the radar, progress, according to the thera- and said his vision was not perfect, if you ask them about concussion pist. I chose to leave the amount of but more tolerable. We followed or stroke and the most common occlusion in place for the time being up a few days later, and the patient accompanying symptoms. You have and requested a follow up when she felt the occlusion was blocking his a great opportunity to help your was transferred to outpatient care. vision and was more annoying than suffering patients—and all it takes is She started vision therapy several helpful. We reduced the amount of a little piece of tape. ■ weeks later and is showing wonder- occlusion, with positive feedback 1. Tassinari JD. Binasal occlusion. J Behav Optom. 1990;1:16- ful progress every week. The occlu- from the patient (Figure 3). He was 20. sion was successfully removed at the seen several days later at the college 2. Gallop S. A variation in the use of binasal occlsuion. J Behav Optom. 1998;9:31-5. start of the therapy process. and reported the swimming sensa- 3. Proctor A. Traumatic brain injury and binasal occlusion. tion was gone. The occlusion was Optom Vis Devel. 2009;40:45-50. 4. Park E, Bell JD, Baker AJ. Traumatic brain injury: Can Case 2 removed and he was given several the consequences be stopped? Canadian Med Assoc J. A 65-year-old white male presented basic eye movement activities to 2008;178(9):1163-70. 5. Report to Congress on Traumatic Brain Injury Epidemiology with a complaint of swimming perform several times daily. At fol- and Rehabilitation. Centers for Disease Control and Prevention. www.cdc.gov/traumaticbraininjury/pdf/tbi_report_to_con- vision at distance and near follow- low up a month later, he once again gress_epi_and_rehab_snapshot-a.pdf. Accessed March, 24 ing a recent stroke. He was having reported no symptoms and per- 2017.

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RO0417_House TAYE.indd 1 3/23/17 10:55 AM Neuro Clinic

Imaging for Unilateral Proptosis Clinical findings alone won’t always be enough to make the diagnosis. Here’s advice on radiologic testing and what it may reveal. By Michael Trottini, OD, and Michael DelGiodice, OD linical evaluation of trast-enhanced orbital MRI.2 the orbit involves three OIS is associated with autoim- Ccritical steps: (1) taking a mune diseases such as Crohn’s detailed history; (2) conducting a disease, systemic lupus erythema- clinical exam of the extraocular tosus, rheumatoid arthritis, granu- muscles (EOMs), assessing resis- lomatosis with polyangiitis and tance to retropulsion and per- sarcoidosis. The first-line therapy forming exophthalmometry; and for OIS is systemic corticosteroids; (3) performing imaging of the 75% of cases show improvement orbit and brain with computed within 24 to 48 hours. An initial tomography (CT) or magnetic dose of 60mg to 80mg of oral resonance imaging (MRI). Acute prednisone should be started after symptoms of diplopia, vision MRI is used to discount alterna- loss, proptosis and hyperemia are This is a subconjunctival heme from a gunshot tive etiologies such as orbital cel- often associated with inflamma- injury. lulitis and lymphoma.3 tion, infection, vascular anoma- • Orbital cellulitis. The clini- lies and, occasionally, tumors. Each retro-orbital involvement and risk of cal characteristics of this condition of these conditions will be present- optic nerve compression or avulsion. include fever and antecedent ed in a stepwise fashion based on Following the clinical examination, sinusitis, periorbital swelling with presenting factors. urgent emergent non-contrast orbital proptosis, conjunctival hyperemia Scenario 1: Acute painful propto- CT is the most appropriate modality with chemosis and EOM restriction. sis and hemorrhage. A patient with to assess for structural damage. Management involves emergent severe subconjunctival hemorrhage Scenario 2: Acute or subacute referral to the ED for immediate and chemosis can be a diagnostic painful proptosis, chemosis and intravenous broad-spectrum anti- challenge. Although most cases pres- diplopia. The three most common biotics including a third-generation ent in the setting of trauma, post-op conditions that present similarly cephalosporin and the narrow- status and prolonged anticoagula- include orbital inflammatory syn- spectrum penicillin class antibiotic tion therapy are risk factors. drome (OIS), orbital cellulitis and flucloxacillin, which are effective The most important condition arteriovenous malformation (AVM). against Staphylococcus aureus, to consider in this setting is retro- Infectious causes of unilateral pain- Staphylococcus epidermidis, Strepto- bulbar hemorrhage. If a history of ful proptosis are uncommon and cocci and Haemophilus species. trauma exists, the patient should include cellulitis and mucormycosis. Next, order non-contrast CT of be evaluated for an open-globe • OIS. This is a disorder of the the brain and orbits to demonstrate injury. Evidence of rupture war- orbit characterized by a polymor- an infective source in order to obtain rants application of a plastic shield phous lymphoid infiltrate with vary- cultures, evaluate for intracranial to the affected eye and immediate ing degrees of fibrosis.1 In a review, extension and assess the need for transport to the closest emergency the most common orbital compo- surgical drainage. Surgery is indi- department (ED) for surgical repair. nent affected was intraconal fat, fol- cated for significant sinus disease, In the setting of a closed-globe lowed by lacrimal gland enlargement including orbital or subperiosteal injury, measure intraocular pressure and EOM restriction. To determine abscess.4 and evaluate EOMs and posterior the level of soft tissue involvement, • Mucormycosis. This is an segment to determine the extent of it’s best to evaluate OIS with con- aggressive opportunistic fungal

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084_ro0417_neuro.indd 84 3/30/17 12:50 PM infection that enters through the or when congestion from the supe- paranasal sinus mucosa and travels rior ophthalmic vein and cavernous to the orbital apex, where it can sinus places the cerebral venous cir- breach the intracranial space. A culation at risk for thrombosis. patient with acute symptoms should The other CCF form is classified undergo emergent referral to the ED as low-flow. Astute clinical evalu- for non-contrast CT of the head, ation is essential because the signs orbit and sinuses to assess the extent and symptoms are relatively mild of the disease process followed by and often overlooked in favor of biopsies of involved tissues and sinus more benign entities such as ocular mucosal secretions. Those with less surface disease, conjunctivitis or aggressive signs can be managed on episcleritis. Contrast-enhanced MRI Here is a CT image of the gunshot injury. an outpatient basis with contrast- or MRA of the head and orbit is the enhanced MRI of the sinuses, orbit preferred imaging modality. Most cesses are best evaluated with MRI, and brain. Early MRI findings lesions undergo spontaneous occlu- progressive signs of proptosis, optic include lack of enhancement within sion without visual sequelae.8 neuropathy and choroidal folds the sinus mucosa and cavernous Scenario 3: Intermittent Pain and often signal a retro-orbital mass, sinus, a finding consistent with Proptosis. The clinical presentation easily identifiable with non-contrast devitalized tissue. First-line medical of a young adult with complaints of orbital CT.11 Lesions causing signifi- therapy includes amphotericin B and intermittent positional pain and pro- cant proptosis, optic neuropathy or counteracting the potential sequelae ptosis exaggerated during valsalva- visually significant choroidal folds of acidemia and hyperglycemia with type maneuvers should be initially should be surgically removed. IV insulin and fluids.5 evaluated with non-contrast CT, for • Arteriovenous malformations. an enlarged superior ophthalmic Unilateral proptosis often presents These are high-flow or low-flow vein consistent with orbital varices.9 a diagnostic dilemma. However, communications between arteries Varices are venous malformations taking a detailed history, perform- and veins with no interposed capil- that consist of low-pressure and low- ing a comprehensive clinical exam lary bed; the most common are flow plexi that intermingle within and using appropriate neuroimaging carotid-cavernous fistulas (CCF).6 the orbital circulation. If the clinical techniques will help rule out emer- AVM can be classified as traumatic history is suspicious for varices and gent causes and increase the chance vs. spontaneous, high-flow vs. low- CT imaging is normal, magnetic res- of early diagnosis for the patient. ■

flow, and direct vs. dural. onance venography (MRV) should 1. Orbits, Eyelids, and Lacrimal System. Basic Clinical Sci- The clinical scenario of acute be performed to evaluate the orbital ence Course, Section 7. San Francisco: American Academy of Ophthalmology; 2011-2012:59. unilateral proptosis with severe che- and intracranial venule system. 2. Swamy BN, McCluskey P, Nemet A, et al. Idiopathic orbital mosis, pain, orbital bruit, restricted While surgery is reserved for varices inflammatory syndrome: Clinical features and treatment outcomes. Br J Ophthalmol. 2007;91:1667-70. ocular motilities, elevated IOP and that cause significant pain, proptosis 3. Mombaerts I, Goldschmeding R, Schlingemann RO, dilated episcleral veins suggests a and optic nerve compression, small Koornneef L. What is orbital pseudotumor? Surv Ophthal- mol. 1996;41:66-78. high-flow fistula from trauma or an lesions with minimal signs and 4. Chaudhry IA, Shamsi FA, Elzaridi E, et al. Outcome of aneurysmal rupture of the internal symptoms can be observed.10 treated orbital cellulitis in a tertiary eye care center in the Middle East. Ophthalmology. 2007;114:345-54. carotid artery within the cavernous Scenario 4: Painless Progressive 5. Kauh CY, Nelson CC. Diagnosis and management of sinus, necessitating emergent imag- Proptosis. Suspect cavernous heman- orbital mucormycosis. EyeNet Magazine. June 2014. 6. Levy JV, Zemek L. Ophthalmic arteriovenous malforma- ing of the brain and orbits.7 Con- gioma in these circumstances. This tions. Am J Ophthalmol. 1966;62:971-4. 7. Gean AD. Imaging of Head Trauma. New York, NY: Raven trast-enhanced magnetic resonance is the most common orbital tumor Press;1994:349-54,474. angiography (MRA) and CT angi- in adults and typically presents in 8. Flanagan JC. Vascular problems of the orbit. Ophthalmol- ogy. 1979;86:896-913. ography are superior for evaluating middle age with painless, progres- 9. Shields JA, Dolinskas C, Augsburger JJ, et al. Demonstra- venous distention, the lumen of sive proptosis that causes hyperopia tion of orbital varix with computed tomography and valsalva maneuver. Am J Ophthalmol. 1984;97:108-10. aneurysms and increased flow to the and choroidal folds. The differential 10. Islam N, Mireskandari K, Rose GE. Orbital varices and cavernous sinus. Surgical treatment diagnosis includes orbital metastasis, orbital wall defects. Br J Ophthalmol. 2004;88:1092-1093. 11. Thorn-Kany M, Arrue P, Delisle MB, et al. Cavernous with embolization is warranted orbital lymphoma and hemangio- hemangiomas of the orbit: MR imaging. J Neuroradiol. when optic nerve compression exists pericytoma. While most orbital pro- 1999;26(2):79-86.

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084_ro0417_neuro.indd 85 3/30/17 12:50 PM Retina Quiz

Scrambling For a Diagnosis Combining old and new images may explain this patient’s vision loss. By Tea Avdic, OD, and Mark T. Dunbar, OD

57-year-old male presented complaining of mildly Adecreased vision in both eyes. He noted the change a few months prior. His medical, fam- ily and social history is noncon- tributory. Upon examination, his best-corrected visual acuity Figs. 1a and 1b. These two OCT images show two stages of the patient’s condition. was 20/40 OD and 20/30 OS. Can you make the diagnosis? Extraocular motilities showed full range of motion in both eyes. His 2.What does OCT imaging show? show a fairly classic “vitellirup- confrontation fields were full- a. Retinal thickening with cystoid tive” stage of the disease that, to-careful finger counting in the changes of the inner retina. over the ensuing three years, has right and left eye. His pupils were b. Subretinal exudates and progressed to the “atrophic” unremarkable with no afferent intraretinal edema. stage. pupillary defect. Additionally, his c. Macular edema. Adult-onset vitelliform dystro- intraocular pressures (IOP) were d. Retinal atrophy with subretinal phy is an autosomal dominant 17mm Hg OD and 16mm Hg OS. fluid. disorder with variable expres- Anterior segment examina- sion and incomplete penetrance tion was within normal limits. 3. What additional testing is that results in slow, progressive The fundus showed significant warranted? bilateral vision loss. The classic retinal pigment epithelium (RPE) a. Fluorescein angiography. presentation resembles a sunny- atrophic changes in the macula b. Genetic testing. side egg-yolk appearance, which of both eyes. In the right eye, we c. B-scan ultrasonography. can be appreciated in the images; observed some elevation of the d. No additional testing. however, it is apparent from the RPE. A macular optical coher- photos that the disease has pro- ence tomography (OCT) image 4. Which of the following gressed to the next stage—the was obtained and is available for represents the best treatment plan “pseudohypopyon” stage. review (Figures 1a and 1b). for this patient? Further review of the patient’s a. Observation. Discussion medical record showed fundus b. Laser treatment. Adult-onset vitelliform dystrophy, images that were taken three c. Anti-VEGF. initially referred to as “peculiar years prior (Figures 2a and 2b). d. b and c. foveomacular dystrophy,” is divided into five distinct stages. Take the Quiz For answers, see page 98. They are: 1. What is the likely diagnosis? 1. Vitelliform a. Central serous retinopathy. Diagnosis 2. Pseudohypopyon b. Age-related macular Based on the fundus photos that 3. Vitelliruptive degeneration. were reviewed from three years 4. Atrophic c. Adult-onset vitelliform dystrophy. prior, we determined that our 5. Cicatricial d. Polypoidal choroidal patient has adult-onset vitelliform The “egg-yolk” lesion that vasculopathy. dystrophy. The fundus photos presents as a yellow subretinal

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086_ro0417_RQ.indd 86 3/30/17 12:53 PM deposit and does not affect vision characterizes the vitelliform stage. In the pseudo- hypopyon stage, the yellow mate- rial liquefies, set- tling inferiorly and giving the appearance of a hypopyon. Acuity becomes affected once the disease progresses to the vitelliruptive stage, in which the central aspect of Figs 2a and 2b. These fundus photos show our patient from three years prior to the diagnosis. Can this the lesion becomes presentation, combined with the current-day OCT, lead you to a diagnosis? atrophic and the “egg-yolk” takes OCT, fluorescein angiography Amsler grid to monitor for visual on the “scrambled” appear- (FA) and, in some cases, electro- changes at home. Referrals to ance. When we most recently physiological studies. Despite vision rehabilitation should be saw the patient, the disease had variability in visual outcomes and made to enhance quality of life. progressed to the atrophic stage acuity, full-field and multifocal Although rare, complications in which the changes can be non- electroretinograms in patients such as full thickness macular specific. The OCT image shows with adult-onset vitelliform dys- holes, choroidal neovascular disruption at the RPE level with trophy reveal that the disease membranes and retinal detach- loss at the inner segment/outer significantly disrupts macular ment can occur; therefore, annual segment junction as well as in the function.3 Furthermore, the elec- dilated exams and close observa- right eye and area of subretinal tro-oculograms may be slightly tion are warranted.8 ■ fluid. reduced or normal.4 Early in the Dr. Avdic is a resident at Bascom Researchers believe the disease disease, the FA will expectedly Palmer Eye Institute in Miami. develops as a result of genetic reveal a pattern of patchy hypo- 1.Felbor U, Schilling H, Weber B. Adult foveomacular vitel- mutations in the photoreceptor fluorescence at the macula with liform dystrophy is frequenty associated with mutations in the protein-encoding genes, which surrounding hyperfluorescence.5,6 peripherin/RDS gene. Hum Mutat 1997;10:301-9. 2.Chowers I, Tiosano L, Audo I, Grunin M. Adult onset foveo- leads to breakdown of the RPE- OCT can be used to identify the macular vitelliform dystrophy: A fresh perspective. Prog Retin photoreceptor complex causing anatomical location of the lesion Eye Res. 2015:47:64-85. 3. Yamamoto S, Saito W, Ogata K, Hayashi M. Electro- toxic accumulation of cellular and will reveal a linear RPE layer physiologic studies on patinets with adult onset vitelliform debris at the RPE level, result- separated from the photorecep- macular degeneration. Invest. Ophthalmol. Vis. Sci. 2002;43(13):1162. ing in the classic presentation of tor layer by cellular debris, likely 4. Birndorf L, Dawson W. A normal electrooculogram in a bilateral yellow subfoveal depos- to be lipofuscin.7 Note that the patient with a typical vitelliform macular lesion. Invest Oph- 1,2 thalmol. 1973:12(11):830-3. its. The deposits intensify over fluorescein pattern and OCT 5. Parodi M, Iacono P, Campa C, et al. Fundus Autofluores- time, ultimately resulting in RPE findings will change as the lesions cence Patterns in Best vitelliform macular dystrophy. Am J Ophthalmol 2014;158(5):1086-92. 2 atrophy and vision loss. progress. 6. Pierro L, Tremolada G, Introlini U, et al. OCT findings in The age of onset remains vari- As the disease evolves, vision adult onset foveomacular vitelliform dystrophy. Am J Oph- thalmol 2002;134:675-80. able with many patients remain- loss becomes more severe. In 7. Benhamou N, Messas-Kaplan A, Cohen Y, et al. Adult onset foveomacular vitelliform dystrophy with OCT. Am J ing asymptomatic until the fifth the later disease stage, as visual Ophthalmol 2004;138(2):294-6. or sixth decade of life. impairment and loss of central 8. Tiosano L, Grunin M, Hagbi-Levi S, et al. Character- izing the phenotype and progression of sporadic adult Monitoring acuity become a greater concern, onset foveomacular vitelliform dystrophy. Br J Ophthalmol Diagnostic testing often includes patients should be issued an 2016;100:1476-81.

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086_ro0417_RQ.indd 87 3/30/17 12:53 PM Therapeutic Review

The Compliance Conundrum Sustained-release delivery aims to keep patients adherent. By Joseph W. Sowka, OD, and Alan G. Kabat, OD

48-year-old man was bimatoprost SR was 7.2mm referred to our office for Hg, 7.4mm Hg, 8.1mm Hg and urgent glaucoma man- 9.5mm Hg with the 6-µg, 10-µg, agement. He reported 15-µg, and 20-µg dose strengths of thatA his sight had been getting implant, respectively, vs. 8.4mm worse “over some time” and knew Hg in topical bimatoprost-treated that he had poor vision in his right fellow eyes.1 The implant lowered eye. Indeed, his corrected visual IOP in 92% of patients at four acuity was hand motion in the months and 71% at six months.1 right eye and 20/30 OS. No serious adverse ocular events He reported no systemic health were noted, and the most common issues, but said he “didn’t really go adverse events were related to the to the doctor much.” He had no injection procedure.1 biomicroscopic abnormalities, and Similarly used as an intracam- his intraocular pressures (IOP) were eral implant is ENV515 (Envisia), 46mm Hg OD and 38mm Hg OS. an extended release form of tra- He had advanced glaucomatous Researchers are investigating whether voprost. A Phase 2a open-label, damage to both optic discs. glaucoma patients, such as the one 28-day dose-ranging study of 21 After a discussion of the diag- shown in this photo, may be better patients yielded 28% IOP lower- nosis and treatment options (he treated using sustained-release ing at day 25 in one group, which adamantly refused surgery), he medications. was comparable with once-daily was prescribed latanoprost in each Travatan Z (travoprost, Alcon).2 eye and scheduled for a follow-up; with any great effect since the Interim Phase 2 results showed a however, it took several months of 1970s when Ocusert wafers were favorable safety profile and sus- no-shows before he returned. He used to deliver pilocarpine in a tained IOP reduction up to three reported that he used the medica- more-or-less continuous fashion. months.2 Envisia is planning to tion “a bit,” but didn’t really feel It was not readily adapted due to advance to a 12-month study to a difference, never refilled the pre- discomfort and the overall poor evaluate the long-term IOP lower- scription and discontinued after a tolerability of pilocarpine. ing of ENV515.2 month. His IOP hadn’t changed. Today, many innovators are He again refused surgery, was reviving sustained-release options Sustained-release Devices again educated about his prognosis in an attempt to solve the com- Additionally, researchers have and re-prescribed latanoprost. He pliance issue. For instance, considerable work to do on has since been lost to follow up. bimatoprost SR (Allergan), is sustained-release platforms deliv- an intracameral depot implant ered externally. One such device The Compliance Challenge placed in the anterior chamber. is a bimatoprost-laden ring being The greatest challenge in managing Bimatoprost SR is a biodegrad- developed by Allergan. This glaucoma has got to be medication able polymer matrix that releases thin silicone ring suffused with adherence. Great IOP lowering a steady amount of bimatoprost bimatoprost that slowly releases medications don’t work if patients 0.03%.1 One study shows the medication over time is fit under don’t use them. Sustained-release overall mean IOP reduction from the upper and lower eyelids by medications haven’t been used baseline through week 16 using a doctor, so that it rests in the

88 REVIEW OF OPTOMETRY APRIL 15, 2017

088_ro0417_TR.indd 88 3/30/17 12:57 PM conjunctival sulcus. It is designed is exciting and promises to reduce chamber or into a medication-elut- to be replaced every six months. adherence and persistence issues. ing ring. Patients also, obviously, In a Phase 2 randomized, double- However, they carry potential have a limited number of puncta, masked controlled study, the drawbacks. and additional topical therapy may bimatoprost-delivery device was In regards to injectable implants, still be needed. compared with timolol 0.5% BID. a medication cannot be easily dis- Some drugs may work better The bimatoprost ring lowered IOP, continued if there is an adverse in pulsatile form and not so well but less than did topical timolol reaction, whereas a patient can in constant delivery systems. We 0.5% dosed twice daily. Retention simply stop using a topical drop. know that prostaglandin analogs was 90% at six months and was Anterior chamber implants can, are less effective at BID dosing, generally well tolerated by the study theoretically, block parts of the likely due to receptor supersatura- patients.3 There exists a possibility angle or even a trabeculectomy tion and desensitization.7 Likely, to develop the device to contain a site. Invasive options carry the risk the once-a-day dosing of these fixed combination of bimatoprost of infection and even endophthal- medications provides needed and timolol. mitis. Also, a great many patients downtime between drops to pre- Beyond an externally applied are cared for by optometrists. vent receptor desensitization. In medication-eluting conjunctival Should the direction of glaucoma clinical trials, it appears that these ring, punctal plugs may serve as care shift towards invasive options, sustained-release prostaglandins a promising method of delivering access to care will decrease as these are not as effective at lowering IOP sustained-release medications via options may be beyond the scope as they are in topical form.3 punctual plugs.4 Ocular Therapeu- of optometric licensure. Also, it is tix is developing the OTX-TP, a not clear if insurance will pay for Sustained delivery of glaucoma travoprost-eluting intracanalicular these medications and procedures therapy is still several years away. punctal plug designed to slowly simply to increase adherence. Some options will be invasive, deliver the medication. It can be Further, glaucoma patients who which may limit access to care. placed in either the superior or infe- perceive no vision loss may not be Many options will be noninvasive. rior canaliculus. Because it is intra- as accepting of an injection into All offer some benefits combined canalicular, it can only be visualized the eye as those, say, with severely with limitations. We anxiously in place by a fluorescent light, thus deteriorating vision from macular await the results from clinical tri- retention cannot be determined by degeneration. Intravitreal therapy als and the introduction of these the patient. In clinical trials, reten- for macular degeneration has devices to the ophthalmic market- tion of the OTX-TP device was shown great advances in vision place. However, we believe that 91% at 60 days but only 48% at recovery and preservation, but drops, laser and surgery will not 90 days.5 One study noted that IOP those patients who have dropped become obsolete any time soon. ■

with OTX-TP was reduced 23% out of regimented therapy are 1. Lewis RA, Christie WC, Day DG, et al. Bimatroprost SR Study to 28% at day 10.3 However, at 30 mostly doing poorly. Group. Bimatoprost sustained-release implants for glaucoma thera- py: 6-month results from a Phase I/II clinical trial. Am J Ophthalmol. days, plug retention had declined to 2016 March;175:137-47. 42%, and the overall IOP reduction Still a Ways Away 2. Navratil T, Garcia A, Tully J, et al. Preclinical evaluation of ENV515 5 (travoprost) intracemeral implant-clinical candidate for treatment of had decreased to 16%. As for externally delivered sus- glaucoma targeting six-month duration of action. Paper presented at Mati Therapeutics is working tained-release options, patients will ARVO; May 6, 2014; Orlando, FL. 3. Brandt JD, Sall K, DuBiner HB, et al. 6-month IOP-reduction with on its own drug-eluting punctal have to verify if a punctal plug or a single dose of a novel topical bimatroprost ocular insert: a phase plug, the latanoprost-punctal plug ring is still in place. Retention of 2 randomized, double-masked, controlled study. Paper presented at the AAO Annual Meeting; November 17, 2015; Las Vegas. delivery system, which releases external devices may pose a prob- 4. Aref AA. Sustained drug delivery for glaucoma: current data and latanoprost and is grossly visible. lem for patients who are scheduled future trends. Curr Opin Ophthalmol. 2017;28(2):169-174. 5. Perera SA, Ting DS, Nongpiur ME, et al. Feasibility study of sustained- As a superficial punctal plug, it can for replacement at three- or six- release travoprost punctum plug for intraocular pressure reduction in an Asian population. Clin Ophthalmol. 2016;10(4):757-64. be verified present and pulled out month intervals. It may be that 6. Mati Therapeutics. Mati Therapeutics Inc announces initiation of relatively easily.6 patients are not receiving therapy phase II study to compare latanoprost punctal plug delivery system (L-PPDS) to timolol eye drops. bit.ly/1Mdcvwo. October 28, 2013. for a significant period of time Accessed March 9, 2017. Pitfalls between visits. There will be limita- 7. Brandt JD, VanDenburgh AM, Chen K, et al. Comparison of once- or twice-daily bimatoprost with twice-daily timolol in patients The concept of sustained-release tions on the number of drugs that with elevated IOP : a 3-month clinical trial. Ophthalmology. 2001 devices for glaucoma medications can be placed within the anterior Jun;108(6):1023-31.

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RO0417_House AAO.indd 1 3/23/17 11:34 AM Surgical Minute Edited By Derek N. Cunningham, OD, and Walter O. Whitley, OD, MBA Extend Your Patient’s Vision Can the Symfony intraocular lens provide significant benefits for presbyopic patients in need of cataract surgery? Here’s what its proponents anticipate. By Jillian Janes, OD

hen patients first start vision obtained with traditional to develop cataracts, multifocal lenses, and clinicians Wmany look to us to walk must keep this in mind with patients them through the surgical options. whose work or hobbies require Because an intraocular lens (IOL) precise near vision. Some cataract choice is a once-in-a-lifetime deci- surgeons may compensate for this sion, patients must be confident in by using bilateral Symfony lenses that choice—and the more educated and leaving the non-dominant eye our patients are, the more confident slightly myopic, in the -0.75D to they’ll be, resulting in better out- -1.00D range. comes. The Symfony’s refractive echelettes look similar to concentric rings found on Procedure Basics A New Read on Presbyopia traditional multifocal IOLs. Preoperatively, we have to keep in Currently, our options for correcting mind other ocular pathologies (e.g., presbyopia at the time of cataract refractive echelettes, which appear severe ocular surface disease, cor- surgery are traditional multifo- as concentric rings and have a simi- neal dystrophy, retinal pathology) cal IOLs, accommodating IOLs, lar appearance to traditional multi- that would limit patients’ quality of monovision with monofocal IOLs focal lenses at the slit lamp.1 These vision after cataract removal and and now the new Tecnis Symfony echelettes do not split the light into make them less than ideal candi- IOL (Abbott Medical Optics). different foci; rather, they introduce dates for this lens. Traditional multifocal lens implants a pattern of light diffraction that Clinicians must check distance, use diffraction, which allocates light elongates the focus of the eye, pro- intermediate and near vision at all to multiple focal points by creating viding an extended range of vision. post-op visits. To ensure patient zones on the anterior surface of the AMO also says the lens design satisfaction, we need to ask patients lens. This allows for simultaneous corrects for spherical and chromatic how their “new eyes” are function- viewing of images at distance and aberrations, and that the aspheric ing during activities of daily living. near. Accommodating IOLs hinge anterior surface and posterior ach- While most achieve positive out- forward by their haptics as the romatic diffracting surface provide comes, it’s important to reassure natural ciliary muscle contracts and great retinal image quality and con- those with less than ideal outcomes relaxes to provide near vision focus. trast sensitivity.1 The Symfony also that you will work closely with them Independent research on the has a toric version for astigmats. and their surgeon to address any new Symfony lens is limited at this The manufacturer says contrast concerns. Luckily, these conversa- time, but its manufacturer says it sensitivity with Symfony is similar tions, in our experience, are few and was designed with what’s called an to that of monofocal IOLs, which far between. extended range of vision to provide may be better than that obtained Staying up to date on the latest clear vision though a limited depth with a multifocal IOL due to the lat- IOLs allows us to better educate of focus without splitting light or ter’s splitting of light. Instead, AMO patients on this important decision. changing position.1 The lens has says, Symfony images are not out of Often, patients are unaware they focus, causing fewer halos.1 could possibly regain some of the To see a video of this range of vision they used to have. ■ procedure, visit www. Sacrificing Near Vision reviewofoptometry.com, or 1. Abbott Medical Optics. Tecnis Symfony IOL. 2017. Available at www.vision.abbott/us/iols/extended-depth-of- scan the QR code. Despite its advantages, this new lens may not provide the same near focus/tecnis-symfony.html. Accessed March 8, 2017.

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Product Review

Lens Technology The edging system is roughly 50% faster than other HLM-1 Huvitz Lensmaster tabletop edgers, quickly integrates, is intuitive (no vac- Practitioners can now upgrade to Coburn’s uum or compressed air) and interfaces effortlessly with new HLM-1 Lensmaster, which comes laboratory management software, according to Essilor. with the same wavefront analysis as in Visit www.essilorinstrumentsusa.com. older models but with more measure- ment points, according to Coburn. Other Diagnostic Technology features include multifocal measurement, Topcon SL-D301 Slit Lamp with on-screen prompts; enhanced camera Optometrists in need of a new performance; high processing speed and slit lamp can consider Topcon’s frames per second; and newly designed nose cone and SL-D301, which comes with a Gal- lens support for measuring smaller frame styles. ilean-type observation system and Visit www.coburntechnologies.com. 10x, 16x and 25x magnifications. Topcon says it can be easily upgraded to full digital with FastGrind Photochromic FT28 Lens an optional camera attachment, and can be used with Patients can look forward to a new photochromic lens R-900 and 870 model applanation tonometers. from FastGrind. The FT28 lens quickly changes opacity Visit www.topcon.com. while blocking harmful UV rays. You can produce lenses in-office for immediate dispensing, FastGrind says. Icare Home Tonometer Visit www.superoptical.com/fast-grind. This device lets patients self-monitor IOP and gives their doctors access to the data to better track diurnal fluctua- New Edging System tions, according to Icare. The unit is easy to use, per- Essilor’s Pro-E 600 gives high-volume labs something forms automatic OD/OS recognition and uses red and to look forward to. The company says it’s designed green signals to help correctly position the tonometer, the with faster processes and suited for specialty edging and company says. An automated measuring sequence can mountings—from bevel and mini-bevel, to asymmetric take a single measurement or a series of six. and step bevel, groove, mix, drill, chamfer and polish. Visit www.icare-usa.com.

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REVIEW OF OPTOMETRY APRIL 15, 2017 95

ROPT0417.indd 95 3/30/17 8:38 AM Review Classifi eds

Contact Lenses

Continuing Education

Do you have Products and Services to offer?

CLASSIFIED ADVERTISING WORKS

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96 REVIEW OF OPTOMETRY APRIL 15, 2017

ROPT0417.indd 96 3/30/17 8:38 AM Review Classifi eds

Career Opportunities

Here we grow again! KWdKDdZ/^dKWWKZdhE/dz STAFF OPTOMETRIST đ«Êك¦›͕<͘ Bard Optical is a leading Midwest vision care organization in business for over 70 years and DÊã®òƒã›—KÖãÊÛãÙ®ÝãÝ we are still growing. The company is based in ŶĐŚŽƌĂŐĞ͕<͘Ͳ&ƵůůƟŵĞKƉƚŽŵĞƚƌŝƐƚKƉƉŽƌ- />>/EK/^ Peoria, IL with 20 retail offices throughout the ƚƵŶŝƚLJ ǁŝƚŚ ůĂƐŬĂ͛Ɛ WZD/Z LJĞ ,ĞĂůƚŚ ĂƌĞ central Illinois area, as far north as Sterling The largest eye care provider to extended care WƌĂĐƟĐĞʹůĂƐŬĂLJĞĂƌĞĞŶƚĞƌƐ͕WʹǀŽƚĞĚ and as far south as Jacksonville. Once again and assisted living residents in our great state ĞƐƚŽĨůĂƐŬĂƐŝŶĐĞϮϬϬϳ͘A privately owned, two this year we were named to the Top 50 Optical ŽĨ/ůůŝŶŽŝƐŝƐůŽŽŬŝŶŐĨŽƌŵŽƟǀĂƚĞĚŽƉƚŽŵĞƚƌŝƐƚƐ ůŽĐĂƟŽŶƉƌĂĐƟĐĞǁŝƚŚϳĚŽĐƚŽƌƐŝƐƐĞĞŬŝŶŐĂŶĞǁ Retailers in the United States by Vision ƚŽũŽŝŶŽƵƌƉƌĂĐƟĐĞ͘KƵƌĚŽĐƚŽƌƐĂƌĞƉƌŽĮĐŝĞŶƚ ŐƌĂĚƵĂƚĞ Žƌ ĞdžƉĞƌŝĞŶĐĞĚ K͘͘ ĨŽƌ ĞŵƉůŽLJŵĞŶƚ Monday – currently ranking 37th. A progres- ŝŶ ŽŶͲƐŝƚĞ ƌĞĨƌĂĐƟŶŐ͕ ĚŝĂŐŶŽƐŝŶŐ ĂŶĚ ƚƌĞĂƟŶŐ ŽƉƉŽƌƚƵŶŝƚLJ͘ sive optometric staff is vital to the continued ocular pathology and posses a passion for the growth of our organization whose foundation ǁŽƌŬƚŚĞLJĚŽ͘ ĂĐŚ ůŽĐĂƟŽŶ ŚĂƐ ϰͲϱ ĨƵůů ĞdžĂŵ ƌŽŽŵƐ ĂŶĚ ƚŚĞ is based on one-on-one patient service. We ĂƉƉƌŽƉƌŝĂƚĞ ĞƋƵŝƉŵĞŶƚͲ ƐƉĞĐŝĂů ƚĞƐƟŶŐ ĞƋƵŝƉͲ are currently accepting CV/resumes for tĞ ŚĂǀĞ ŇĞdžŝďůĞ ƉŽƐŝƟŽŶƐ ĂǀĂŝůĂďůĞ ŝŶ ďŽƚŚ ŵĞŶƚ͕ ŽƉƚŽŵĞƚƌŝĐ ƉƌĞͲƚĞƐƚĞƌƐ͕ ĂŶĚ ĨƵůů ĂĚŵŝŶŝƐͲ optometrists focused on full scope primary ƚŚĞŚŝĐĂŐŽͲůĂŶĚ͕ĞŶƚƌĂů͕Θ^ŽƵƚŚĞƌŶ/ůůŝŶŽŝƐ ƚƌĂƟǀĞ ƐƵƉƉŽƌƚ͘  dŚĞ ŵĂŝŶ ŽĸĐĞ ŽīĞƌƐ ĨƵůů ůĞŶƐ medical patient care. The candidate must have an Illinois license with therapeutics. The prac- ĂƌĞĂƐ͘ ŵĂŶƵĨĂĐƚƵƌŝŶŐ ĨŽƌ ďŽƚŚ ůŽĐĂƟŽŶƐ͘  ĂĐŚ ŽĸĐĞ ŚĂƐ ŽƉƟĐĂů ĚŝƐƉĞŶƐĂƌŝĞƐ ĐŽŶƐŝƐƟŶŐ ŽĨ ŽǀĞƌ Ϯ͕ϱϬϬ tice includes (but is not limited to) general KƵƌ ƉŚLJƐŝĐŝĂŶƐ ĐĂŶ ĂƩĞƐƚ ƚŽ ƚŚĞ ƐƵďƐƚĂŶƟĂů ĨƌĂŵĞƐ ĂŶĚ ŝƐ ƐĞƌǀŝĐĞĚ ďLJ ůŝĐĞŶƐĞĚ ŽƉƟĐŝĂŶƐ͘  /Ŷ optometry, contact lenses, and geriatric care. Salaried, full-time positions are available with ƉƌŽĨĞƐƐŝŽŶĂůĂŶĚĮŶĂŶĐŝĂůƌĞǁĂƌĚƐƚŽďĞŐĂŝŶĞĚ ĂĚĚŝƟŽŶ͕ĞĂĐŚŽĸĐĞŚĂƐĨƵůůĐŽŶƚĂĐƚůĞŶƐƐĞƌǀŝĐĞƐ͕ excellent growth programs and benefits. Ăƚ KǀŝƚƐŬLJ sŝƐŝŽŶ ĂƌĞ͘ ^ŽŵĞ ŽĨ ƚŚĞ ŵĂŶLJ ŝŶĐůƵĚŝŶŐůŝĐĞŶƐĞĚ>ƚĞĐŚŶŝĐŝĂŶƐ͘ Some part-time opportunities may be avail- ďĞŶĞĮƚƐ ŝŶĐůƵĚĞ͗ džĐĞůůĞŶƚ ƉĂLJ н ŽŶƵƐĞƐ able also. Please email your information to ;сϭϱϬ<нͿ͕ ƚƌĂǀĞů ƌĞŝŵďƵƌƐĞŵĞŶƚ Θ ĐĂƌ ĂůůŽǁ- dŚŝƐ ŽƉĞŶŝŶŐ ŝƐ ĨŽƌ ŽƵƌ tĂƐŝůůĂ ůŽĐĂƟŽŶ ƌŽƚĂƟŶŐ [email protected] or fax to 309-693-9754. ĂŶĐĞ͕ ŶĞǁ ƐƚĂƚĞͲŽĨͲƚŚĞͲĂƌƚ ƉŽƌƚĂďůĞ ĞƋƵŝƉ- ŝŶƚŽ ŶĐŚŽƌĂŐĞ Ăƚ ůĞĂƐƚ ŽŶĐĞ Ă ǁĞĞŬ͘  tĂƐŝůůĂ Mailing address if more convenient is ŵĞŶƚ͕ ĂŶĚ Ă ƉĞƌƐŽŶĂů ĂƐƐŝƐƚĂŶƚ ďƵƚ ŵŽƐƚ ŝƐ Ă ƐĞŵŝͲƌƵƌĂů ƐĞƫŶŐ ĂƉƉƌŽdžŝŵĂƚĞůLJ ϰϬ ŵŝůĞƐ Bard Optical, Attn: HR, 8309 N Knoxville ŝŵƉŽƌƚĂŶƚůLJ͕ ŚĞůƉŝŶŐ ƉĞŽƉůĞ ŝŶ ŶĞĞĚ ŽĨ LJŽƵƌ ĨƌŽŵ ŶĐŚŽƌĂŐĞ͕ ůĂƐŬĂ͘  dŚĞ ƉŽƉƵůĂƟŽŶ ŽĨ ƚŚĞ Avenue, Peoria, IL 61615. Ask about ƐƵƌƌŽƵŶĚŝŶŐ ĂƌĞĂ ŝƐ ĂďŽƵƚ ϵϴ͕ϬϬϬ ĂŶĚ ŚŽƵƐŝŶŐ ƉƌŽĨĞƐƐŝŽŶĂůƐĞƌǀŝĐĞƐ͘ opportunities within Bard Optical. We have ĂŶĚƵƟůŝƟĞƐĐŽƐƚƐĂƌĞĐŽŵƉĂƌĂďůĞƚŽtĞƐƚŽĂƐƚ openings in several existing and new offices /ŶƚĞƌĞƐƚĞĚ?ŽŶƚĂĐƚ^ĂŵĂƚ ůĞǀĞůƐ͘ŶƚĞƌƚĂŝŶŵĞŶƚ͕ĮŶĞĚŝŶŝŶŐĂŶĚƚŚĞĂƌƚƐĂƌĞ opening soon in central Illinois. ĞĂƐŝůLJĂǀĂŝůĂďůĞŝŶŶĐŚŽƌĂŐĞ͕ĂĐŝƚLJŽĨŵŽƌĞƚŚĂŶ ^ĂŵΛKǀŝƚƐŬLJǀŝƐŝŽŶĐĂƌĞ͘ĐŽŵ Bard Optical is a proud ŽƌĂƚϳϳϯͲϱϴϴͲϯϬϵϬ͘ Ϯϵϭ͕ϬϬϬƌĞƐŝĚĞŶƚƐ͘ Associate Member of the Illinois Optometric Association. Only serious inquiries please. We will help ůĂƐŬĂŝƐŽŶĞŽĨƚŚĞŵŽƐƚďĞĂƵƟĨƵůƉůĂĐĞƐƚŽůŝǀĞĂŶĚ ǁŝƚŚƌĞůŽĐĂƟŽŶĞdžƉĞŶƐĞƐ͕ŝĨŶĞĐĞƐƐĂƌLJ͘ ƉƌĂĐƟĐĞ͘&ŽƌĨƵƌƚŚĞƌŝŶĨŽƌŵĂƟŽŶ͕ƉůĞĂƐĞĐŽŶƚĂĐƚ͗ www.bardoptical.com ůĂƐŬĂLJĞĂƌĞĞŶƚĞƌƐ ϭϯϰϱt͘ϵƚŚǀĞŶƵĞ͕ŶĐŚŽƌĂŐĞ͕<͘ϵϵϱϬϭ Contact us today ŽŶƚĂĐƚ͗Ğď&ŽƐƚĞƌ͕ĚŵŝŶŝƐƚƌĂƚŽƌ ODs WANTED ĚĞďΛĂůĂƐŬĂĞLJĞĐĂƌĞ͘ĐŽŵ for classified advertising: West Coast Mobile Eye Care, a well- ;ϵϬϳͿϮϳϮͲϮϱϱϳyϭϲϬϰ Toll free: 888-498-1460 established group practice since 1999, has ;ϵϬϳͿϮϳϰͲϰϵϯϮ;&ĂdžͿ Full/Part-time positions open in our beautiful E-mail: [email protected] tĞďƐŝƚĞ͗ǁǁǁ͘ĂůĂƐŬĂĞLJĞĐĂƌĞ͘ĐŽŵ sunshine state of Florida – Tampa/St. Petersburg, Sarasota/Bradenton, and Ocala/Leesburg. ODs will travel with a team of technicians to nursing homes. No weekends or holidays. High pathology, portable OCT and Fundus camera. Competitive rate per diem with commission. If you are compassionate and Targeting Optometrists? love ocular pathology, this job is for you. CLASSIFIED ADVERTISING WORKS If you have passed all 3 parts of NBEO (and are considering a move to Florida) call Contact us today for classified advertising: Joe Bensaid (813) 732-2750, or email your Toll free: 888-498-1460 resume to [email protected]. E-mail: [email protected] Check out www.floridaoptometry.gov for information on licensure requirements.

Place Your Ad Here!

Toll free: 888-498-1460

E-mail: [email protected]

REVIEW OF OPTOMETRY APRIL 15, 2017 97

ROPT0417.indd 97 3/30/17 8:38 AM Diagnostic Quiz

Bullseye By Andrew S. Gurwood, OD

History A 57-year-old Caucasian male reported to the office emergently following blunt trauma to his left eye caused by a falling 2x4. He was clearly in distress, suffering from pain, photophobia, lacrima- tion, hemolacria (bloody tears) and blurry vision. He had no previous ocular history and his systemic history was remarkable for hyper- tension, for which he was prop- erly controlled with lisinopril. He denied allergies of any kind. Diagnostic Data His best-corrected entering visual acuities were 20/20 OD and 20/100 OS at distance and near with no improvement upon pin- This 57-year-old patient’s left eye shows the result of a blunt trauma. Can you hole. His external examination is diagnose him? demonstrated in the gross pho- tograph. His pupils were normal photograph. No other testing or tests? How would you manage this with no evidence of afferent pupil manipulation was done. patient? What is the likely prog- defect. The biomicroscopic exami- nosis? nation of the anterior segment is Your Diagnosis To find out, please visit www. demonstrated in the magnified Does this case require additional reviewofoptometry.com. ■

Retina Quiz Answers (from page 86): 1) b; 2) d; 3) a; 4) a.

Next Month in the Mag Wipes, Plugs and More (earn 2 CE credits) In May, Review of Optometry will present its Also in this issue: annual dry eye report. • The Online Refraction Threat: Are You Prepared? Topics include: • Collagen Crosslinking: What do Real-World Results Show? • Omega Fatty Acids for Dry Eye: How They Differ and Why it Matters • Is Dropless Cataract Surgery Improving Outcomes? • Managing Severe Dry Eye • Spectacles: How Would You Handle These Tricky Refraction • A Comprehensive Look at Dry Eye Therapy: Tears, Meds, Challenges?

REVIEW OF OPTOMETRY (ISSN 0147-7633) IS PUBLISHED MONTHLY, 12 TIMES A YEAR BY JOBSON MEDICAL INFORMATION LLC, 440 9TH AVENUE, 14TH FLOOR, NEW YORK, NY 10013-1678. PERIODICALS POSTAGE PAID AT NEW YORK, NY AND ADDITIONAL MAILING OFFICES. POSTMASTER: SEND ADDRESS CHANGES TO REVIEW OF OPTOMETRY, PO BOX 81, CONGERS, NY 10920-0081. SUBSCRIPTION PRICES: US: ONE YEAR $56; TWO YEARS $97, CANADA: ONE YEAR $88, TWO YEARS $160, INT’L: ONE YEAR $209, TWO YEARS $299. FOR SUBSCRIPTION INFORMATION CALL TOLL-FREE (877) 529-1746 (USA); OUTSIDE USA, CALL (845) 267-3065. OR EMAIL US AT [email protected]. PUBLICATIONS MAIL AGREEMENT NO: 40612608. CANADA RETURNS TO BE SENT TO BLEUCHIP INTERNATIONAL, P.O. BOX 25542, LONDON, ON N6C 6B2.

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