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REVIEW OF OPTOMETRY ■

Take a Clinical Approach to Anterior Uveitis, p. 72 — EARN 2 CE CREDITS VOL. 156 NO. 2 ■

February 15, 2019 www.reviewofoptometry.comif FEBRUARY 15, 2018 ■

IN EYE CARE

Get a Glimpse of INNOVATIONS IN EYE CARE ■ WORK IN PROGRESS Five research teams share details about their efforts to build new tools for glaucoma, AMD, diabetic

PLAQUENIL SCREENING ■ retinopathy and drug delivery. Page 34

NEURO-OPHTHALMOLOGY ■

ANTERIOR UVEITIS

ALSO: How to Succeed in Plaquenil Screenings, p. 56 Step-by-Step Neuro Exam, p. 64

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REFERENCE: 1. Data on ﬁ le. Bausch & Lomb Incorporated. 3rd Party Industry Report. 2017-2018. Biotrue and inspired by the biology of your eyes are trademarks of Bausch & Lomb Incorporated or its afﬁ liates. All other products/brand names and/or logos are trademarks of the respective owners. ©2019 Bausch & Lomb Incorporated. BOD.0114.USA.19

RRO0219_BLO0219_BL Biotrue.inddBiotrue.indd 3 22/7/19/7/19 111:261:26 AMAM News Review

VOL. 156 NO. 2 ■ FEBRUARY 15, 2019

IN THE NEWS Feeling Stressed?

A study found either a small to moderate benefi t or no benefi t at all to Dry Eye Could Be Next immediately prescribing glasses for Two studies link psychology with physiology. young children with uncorrected moderate hyperopia. Researchers evaluated By Jane Cole, Contributing Editor one- and two-year-olds with hyperopia between +3.00D and +6.00D prescribed tress can put a whammy on the prevalence and risk factors of glasses or observed without correction. your health, including mani- dry eye among medical students in Three years of follow up revealed 11 of Sfesting into physical conditions Korea found a correlation between 53 failed in the glasses group and 18 of such as high blood pressure, obesity increased psychological stress and 53 failed in the observation group. The and cardiovascular issues, to name dry eye symptoms.2 fi ndings are inconclusive, and require a few. But two new studies have The study included 209 students further study, the study concluded. found that stress can also exacer- at a medical school in Korea. Re- 1,2 Kulp MT, Holmes JM, Dean TW, et al. A randomized bate dry eye. searchers assessed dry eye symp- clinical trial of immediate versus delayed spectacles for moderate hyperopia in 1- and 2-year olds. Ophthalmol- A recent study found sleep qual- toms by using a nine-item question- ogy. January 4, 2019. [Epub ahead of print]. ity may play an important role in naire, the Ocular Surface Disease the development of dry eye by infl u- Index (OSDI) and the visual analog Researchers found pigment disper- encing tear secretion and tear fi lm scale (VAS). The subjects also par- sion syndrome (PDS) was diagnosed stability and by indirectly aggravat- ticipated in a survey that included in 25.9% of patients undergoing ing anxiety and depression.1 demographic data, potential risk evaluation for refractive surgery. The Investigators performed tear fi lm factors for dry eye, personal habits study also found that Caucasian patients break-up time (TBUT), corneal and psychological stress.2 with blue eyes were most likely to have fl uorescein staining and Schirmer The study found the dry eye PDS. The researchers suggest this early I tests to evaluate dry eye in 106 prevalence was 27.1%. Participants diagnosis isn’t a reason to cancel surgery patients. Subjects completed a Pitts- with dry eye had signifi cantly higher but could be a reason to follow these burgh Sleep Quality Index, a patient VAS and OSDI scores compared patients more closely to monitor for health questionnaire and a general with those without dry eye symp- conversion to pigmentary glaucoma. anxiety disorder scale survey.1 toms. Subjects who were female, Doane J, Rickstew J, Tuckfi eld J Cauble J. Prevalence The study found patients with wore contact lenses, were on the of pigment dispersion syndrome in patients seeking refractive surgery. J Glaucoma. January 15, 2019. dry eye had higher depression and computer for long periods of time [Epub ahead of print]. anxiety scores compared with the or had higher psychological stress control group. In the dry eye group, scores had a signifi cant association Researchers investigated the valid- patients with poor sleep quality had with dry eye symptoms.2 ity and reliability of retinoscopy in more severe symptoms indicated by The researchers found symptom- screening for keratoconus compared shorter TBUT and lower Schirmer atic dry eye was prevalent among with the rotating Pentacam Scheimpfl ug I fi ndings. Investigators found a medical students, and increased camera. Two independent, masked reti- signifi cant correlation between sleep psychological stress was associated noscopists screened patients for scissor- quality and mood status in patients with higher risk of dry eye.2 ing refl ex and showed that retinoscopy with dry eye. Additionally, severe 1. Wu M, Liu X, Han J, et al. Association between sleep quality, had 97.7% sensitivity, 79.9% specifi c- symptoms of dry eye were signifi - mood status, and ocular surface characteristics in patients with ity and 70.8% positive predictive and dry eye disease. Cornea. December 31, 2018. [Epub ahead cantly associated with a higher level of print]. 98.4% negative predictive values. of anxiety in patients with dry eye.1 2. Hyon JY, Yang HK, Han SB. Dry eye symptoms may have association with psychological stress in medical students. Eye Al-Mahrouqi H, Oraba SB, Al-Habsi S, et al. Retinoscopy A second study that evaluated Contact Lens. January 14, 2019. [Epub ahead of print]. as a screening tool for keratoconus. Cornea. January 9, 2019. [Epub ahead of print]. NEWS STORIES POST EVERY WEEKDAY MORNING AT www.reviewofoptometry.com/news

4 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

0004_ro0219_news.indd04_ro0219_news.indd 4 22/7/19/7/19 11:0711:07 AMAM OCT Sign Predicts LPI Success

atients who present with evidence of previous or current primary angle closure (PAC) need a Pprompt laser peripheral iridotomy (LPI) to avoid sight-threatening outcomes. But what about patients with narrow angles and no other symptoms? A new study suggests patients with a “triple hump” sign on anterior-segment optical coherence tomography (AS-OCT) may achieve signifi cantly lower intraocular pressure (IOP) with an LPI. Researchers studied AS-OCT and IOP measurements in 84 eyes of 84 PAC suspects before LPI. They de- fi ned the positive triple hump group as those with “the characteristic confi guration formed by the angulations between the crystalline lens’s central anterior surface and both sides of the iris pigment epithelium.” Two glaucoma specialists, masked to any other clinical data, separated AS-OCT images into positive and a negative triple hump groups. The one-month post-LPI assessment revealed the positive triple hump group had signifi cantly decreased IOP, with an average of 1.19mm Hg, compared with the negative triple hump group, which had no statistically signifi cant change in IOP. For the positive triple hump group, “signifi cant IOP reduction after one month indicated that the pressure gradient of the anterior and posterior chambers was eliminated, and pupil block resolved, by LPI,” according to the study. The negative triple hump group, however, had no change in IOP post- op, suggesting pupil block didn’t play a role in the angle closure and “a pushing mechanism might be the key contributing factor” that may warrant lens extraction. The triple hump sign was “a useful screening tool for discriminating ‘LPI responder’ cases from ‘LPI non- responder’ cases in PAC suspect eyes,” the researchers conclude. They further speculate the new AS-OCT sign may be a benefi cial screening method for discriminating pupil block and phacomorphic angle-closure in PAC suspect eyes.

KI Na, A Ha, SU Baek, et al. Predicting the therapeutic efﬁ cacy of laser peripheral iridotomy for individuals with asymptomatic narrow angle: the triple hump sign. J Glaucoma. 2019;28(2):125-30.

004_ro0219_news.indd 5 2/7/19 11:07 AM News Review For more, visit www.reviewofoptometry.com/news Multiple Births Increases OAG Risk

esearchers in Photo: Brian Fisher, OD changes during preg- Korea recently nancy and after deliv- Rdiscovered asso- ery, younger age at fi rst ciations between having delivery seems to be more kids and an increased stressful physiologically risk of open-angle glau- and neurophysiologically, coma (OAG), suggesting which could affect the changes during preg- development of OAG,” nancy and delivery affect according to the study. the development of the While the study high- disease. lights the role pregnancy The study, pub- and delivery may play lished in the Journal of in the pathogenesis of Glaucoma, included glaucoma, more work is 1,798 postmenopausal necessary. women from the Korean “The link between National Health and parturition and glaucoma Nutrition Examination in current literature is in- Survey from 2010 to Having more than two kids could put a strain on the mother’s conclusive, and additional 2011. After performing a ocular system, possibly increasing her risk of open-angle longitudinal studies with comprehensive eye exam glaucoma. a more diverse population and gathering informa- are needed to better sup- tion on demographics, comorbidi- delivery causes temporary systemic port the fi ndings in this study,” says ties and health-related behaviors, hypotension and decreased ocu- Brian D. Fisher, OD, student extern- researchers found the prevalence of lar perfusion, thus increasing the ship coordinator at the Villages VA OAG was 6.42%. They also found risk for glaucoma development or Outpatient Clinic. “Despite several patients who had three or more progression. In addition, increased limitations, the results agreed with deliveries were at increased risk of oxytocin levels during labor can the Blue Mountains Eye Study that OAG compared with those who induce capillary constriction and multiple pregnancies (>2) increases had two deliveries; however, two decreases aqueous outfl ow, while risk for glaucoma.” deliveries was not associated with a stress during labor could induce the “As we await further support, higher risk than one. release of large amounts of epi- we can implement these fi ndings in “This might be because the optic nephrine and norepinephrine, also evaluating our glaucoma patients,” disc can overcome small insults increasing IOP. he adds. “The more risk factors below a threshold, but the accumu- The study also found an inde- we can identify, the better we can lation of multiple stressors could pendent association with younger diagnose and manage our patients. create an unfavorable environment age at fi rst childbirth and a higher Moreover, by employing these fi nd- around the optic nerve that crosses risk of OAG. Patients who were ings into clinical practice we can a certain threshold, initiating between the ages of 16 and 20, as better educate our female patients OAG,” according to the study. well as 21 and 23, were at a higher of childbearing age and those with The researchers believe hormonal risk of OAG compared with those other established risk factors.” changes and the effects of the birth ages 24 to 26 at fi rst delivery. JY Lee, JM Kim, SH Kim, et al. Associations among pregnancy, parturition, and open-angle glaucoma: Korea National Health process are both involved in the “Considering the fl uctuations and Nutrition Examination Survey 2010 to 2011. J Glaucoma. increased risk. Blood loss during of hormone levels and physiology 2019;28(1):14-19.

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6 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

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RO0219_Eyefinity.indd 1 1/24/19 11:05 AM News Review For more, visit www.reviewofoptometry.com/news Leukocytes May Cause Scleral Lens Fogging

or scleral contact lens wear- Photo: Jan P.G. Bergmanson, OD, presence of fogging. ers, midday fogging is a “If you think about Ffrequent nuisance. To get to it, leukocytes are white the bottom of this conundrum, blood cells, and the fog- researchers from the University of ging is a white fi lm that Alabama at Birmingham looked happens in the post-lens into the relation between midday tear fi lm. So there seems fogging, ocular surface leukocytes to be a connection,” ex- and lens fi tting characteristics. plains Dr. Nichols. “One of the most common As the lens vaults high- modern complications we see in er and higher, researchers scleral lens wear is midday fog- saw more neutrophils ging. Different estimates suggest and more leukocytes. “So there is somewhere between 30% This scleral lens wearer, a competitive tennis basically, it shows if you and 50% of scleral wearers who player, had daily midday foggings. Particulate increase the vault, you get have midday fogging, and it’s matter is seen in direct light and over the pupil more hypoxia and more really inconvenient,” says study from the iris reflectant light. white blood cells, and this investigator Jason J. Nichols, is possibly why fogging OD, MPH, PhD, associate vice The study enrolled 39 eyes occurs,” he says. president research and professor including 19 fulltime scleral lens While Dr. Nichols believes the at the School of Optometry at the wearers, of which 46% had mid- study results show leukocytes University of Alabama at Birming- day fogging issues. After at least could be a contributor to midday ham. four hours of wear, the lenses were fogging in scleral lens wearers, he Adding to the inconvenience rinsed with phosphate-buffered says there could be other factors factor, these patients have to re- saline, and eyes were treated with as well. move their lenses midway through 5mL of saline per eye. Leukocytes It seems that hypoxia may be the day, which means they must were counted and isolated from the driver for the release of the have solutions on hand and the the wash solutions and assessed leukocytes into the tear fi lm, ability to clean the lenses and put with fl ow cytometry. Investigators investigators noted. If you keep them back in, he adds. then stained the samples from the the vault to a minimum, 200µm or Midday fogging results from post-lens tear fl uid with fl uores- less, you’ll likely get less leuko- particulate matter that is trapped cently labeled antibodies to detect cytes and less fogging, Dr. Nichols between the ocular surface and leukocyte distributions. says. contact lens in the post-lens tear Researchers found a great deal Additional factors to consider fi lm. As such, there’s been a great of leukocytes behind the post-lens would be ways to improve tear deal of speculation about the post- tear fi lm bowl of the scleral lens exchange and peripheral curves lens tear fi lm and scleral lenses, he wearers with fogging. They also or by using more oxygen perme- says. reported scleral lens corneal clear- able material—factors that weren’t With a scleral lens in place, “you ance was 246 ± 61µm for nonfog- part of the study but still relate to have a post-lens tear fi lm behind gers compared with 308 ± 98µm hypoxia, he adds. it, and there’s not much tear ex- for those who had fogging. On Dr. Nichols and his team may change,” Dr. Nichols says. “In fact, average, the number of leukocytes continue the investigation by using there is very little, if any, tear ex- collected from the scleral contact different materials and fi ts to see change from behind the scleral con- lens bowl was greater than the their impacts on white blood cells tact lens, so the tears are trapped. number of leukocytes recovered and midday fogging. ■ The question is, ‘What is it?’ People from the eyewash. Research- Postnikoff CK, Pucker AD, Laurent J, et al. Identifi cation of leukocytes associated with midday fogging in the post-lens have speculated that perhaps it’s a ers noted the scleral lens corneal tear fi lm of scleral contact lens wearers. Invest Ophthalmol lipid or protein or mucin.” clearance was associated with the Vis Sci. 2019;60(1):226-33.

8 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

004_ro0219_news.indd 8 2/7/19 11:08 AM RO0219_Contamac.indd 1 1/23/19 10:19 AM T H E I N T E L L I G E N T T O N O M E T E R T H E A C C U R A T E T O N O M E T E R T H E C O N S I S T E N T T O N O M E T E R T H E O B J E C T I V E TTONOMETERO N O M E T E R TTHEH E RREPEATABLE P E A T A B L E T O N O M E T E R T H E I N T E L L I G E N T T O N O M E T E R T H E A C C U R A T E T O N O M E T E R T H E C O N S I S T E N T T O N O M E T E R T H E O B J E C T I V E T O N O M E T E R T H E R E P E A T A B L E T O N O M E T E R T H E I N T E L L I G E N T T O N O M E T E R T H E A C C U R A T E T O N O M E T E R T H E C O N S I S T E N T T O N O M E T E R T H E O B J E C T I V E T O N O M E T E R T H E R E P E A T A B L E T O N O M E T E R T H E O B J E C T I V E T O N O M E T E R T H E R E P E A T A B L E T O N O M E T E R T H E I N T E L L I G E N T T O N O M E T E R

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RO0219_Icare.indd 1 1/23/19 10:25 AM Contents INNOVATION IN EYE CARE Review of Optometry February 15, 2019 Can We Lower IOP with Glasses? 35 Researchers are finding shocking new ways to employ electro-stimulation. BY TAYLOR LUKASIK, MD, AND IQBAL IKE K. AHMED, MD

A Light in the DARC: Seeing 39 Glaucoma Before it Strikes This cutting-edge technology could give us a window into the disease earlier in its course—shifting treatment ahead and possibly preventing vision loss. BY MELANIE T. ALMONTE,RN, BSN, MSC, AND M. FRANCESCA CORDEIRO, PHD, MRCP, FRCOPHTH Bioengineering the Retinal Pigment 42 Epithelium New stem cell-based therapies are paving the way for age-related macular degeneration treatment. BY AMIR H. KASHANI, MD, PHD, DIANA HONG, BS, AND MARK S. HUMAYUN, MD, PHD

Iontophoresis: Wave of the Future? A low-level electrical current may turbo-charge 46 topical drug delivery to the eye. BY BARBARA WIROSTKO, MD, AND MICHAEL RAIZMAN, MD

While You Were Sleeping 48 A new phototherapeutic contact lens, worn overnight, could effectively address diabetic retinopathy progression. BY MARK DE LEON, ASSOCIATE EDITOR

ALSO INSIDE How to Succeed in Plaquenil Screenings The spectrum of OCT findings associated with the medication can make incorporating the 2016 guidelines harder than you think. Here’s help. BY MARLON DEMERITT, OD, SHERROL REYNOLDS, OD, DIANA SHECHTMAN, OD, AND JENNIFER DAVIDSON, OD PAGE 56

The Neurologic Exam, Step-by-step This case-based review will help you assess beyond each patient’s visual presentation and uncover key clinical signs of neurologic dysfunction. BY ASHLEY KAY MAGLIONE, OD, AND KELLY SEIDLER, OD PAGE 64

Earn 2 CE Credits: Take a Clinical Approach to Anterior Uveitis The ultimate goal is to narrow down symptoms to effective treatment. BY DOMINICK L. OPITZ, OD PAGE 72

REVIEW OF OPTOMETRY FEBRUARY 15, 2019 11

011_ro0219_toc.indd 11 2/7/19 11:11 AM Departments Review of Optometry February 15, 2019

4 News Review 16 Outlook ‘Further Research is Needed’ JACK PERSICO BUSINESS OFFICES 11 CAMPUS BLVD., SUITE 100 18 Through My Eyes NEWTOWN SQUARE, PA 19073 Let’s Get Medical PAUL M. KARPECKI, OD CEO, INFORMATION SERVICES GROUP MARC FERRARA 20 Chairside (212) 274-7062 • [email protected] Summon Some Courage PUBLISHER MONTGOMERY VICKERS, OD JAMES HENNE 22 (610) 492-1017 • [email protected] 22 Clinical Quandaries REGIONAL SALES MANAGER Making the Grade MICHELE BARRETT (610) 492-1014 • [email protected] PAUL C. AJAMIAN, OD REGIONAL SALES MANAGER 24 Coding Connection MICHAEL HOSTER The Telephone is Ringing… (610) 492-1028 • [email protected] JOHN RUMPAKIS, OD, MBA, VICE PRESIDENT, OPERATIONS CLINICAL CODING EDITOR CASEY FOSTER (610) 492-1007 • [email protected]

26 Focus on Refraction VICE PRESIDENT, CLINICAL CONTENT Beyond the Phoroptor PAUL M. KARPECKI, OD, FAAO MARC B. TAUB, OD, MS, [email protected] AND PAUL HARRIS, OD PRODUCTION MANAGER SCOTT TOBIN 28 Retina Dilemmas (610) 492-1011 • [email protected] Serous Problem Business 28 SENIOR CIRCULATION MANAGER JAY HAYNIE, OD, HAMILTON MAHER DIANA SCHECHTMAN, OD, (212) 219-7870 • [email protected] AND RASHID TAHER, MD CLASSIFIED ADVERTISING (888) 498-1460

83 Cornea + Contact Lens Q&A SUBSCRIPTIONS Making the Leap $56 A YEAR, $88 (US) IN CANADA, JOSEPH P. SHOVLIN, OD $209 (US) IN ALL OTHER COUNTRIES.

SUBSCRIPTION INQUIRIES 84 Glaucoma Grand Rounds (877) 529-1746 (US ONLY) If Only They Had Asked OUTSIDE US CALL: (845) 267-3065 JAMES L. FANELLI, OD CIRCULATION PO BOX 81 88 Ocular Surface Review CONGERS, NY 10920 Grow Some Nerve TEL: (TOLL FREE): (877) 529-1746 OUTSIDE US: (845) 267-3065 PAUL M. KARPECKI, OD 88 90 Retina Quiz What’s in Your Head? SHREYA JAYASIMHA, OD, CEO, INFORMATION SERVICES GROUP AND MARK T. DUNBAR, OD MARC FERRARA

SENIOR VICE PRESIDENT, OPERATIONS 94 Classifieds JEFF LEVITZ

VICE PRESIDENT, HUMAN RESOURCES 97 Surgical Minute TAMMY GARCIA Cutting Out Calcifications KYNNDYL GIANNONATTI, BA, AND VICE PRESIDENT, CREATIVE SERVICES & PRODUCTION MONICA TETTAMANZI LEONID SKORIN, JR., DO, OD, MS CORPORATE PRODUCTION DIRECTOR 98 Advertisers Index JOHN ANTHONY CAGGIANO VICE PRESIDENT, CIRCULATION 98 Diagnostic Quiz EMELDA BAREA Headbanger’s Flaw 98 ANDREW S. GURWOOD, OD

12 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

011_ro0219_toc.indd 12 2/7/19 11:12 AM it’s time for patients to love their eyes

(as much as they love their screens)

The face of dry eye is changing. That’s why it’s super important to chat with your patients about things that can trigger their dry eye symptoms—like staring at laptop, phone, and TV screens all day.1 Start with some eyelove. Join us at myeyelove-ecp.com Shire is here to help. We want to make sure you and your patients are feeling the eyelove. And what better way to show it than by encouraging eye health for everyone? Together, we can ensure that eyes are healthy and loved, now and in the future. That’s eyelove.

Reference: 1. TFOS DEWS II Research Subcommittee. Report of the Research Subcommittee of the Tear Film & Ocular Surface Society Dry Eye WorkShop II (2017). Ocul Surf. 2017;15(3):269-649.

©2018 Shire US Inc., Lexington, MA 02421. 1-800-828-2088. All rights reserved. SHIRE and the Shire Logo are trademarks or registered trademarks of Shire Pharmaceutical Holdings Ireland Limited or its afﬁ liates. The EYELOVE logo and marks designated ® and ™ are owned by Shire or an afﬁ liated company. S43693 12/18

RO0219_Shire.indd 1 1/23/19 10:21 AM Earn up to NEWNEEW TTECHNOLOGIES 2019 & TTREATMENTS IN 18-28 CE Credits* 9 EyeEyyeeGVCE CCaCarearearree REVIEW’S COMMITMENT TO CONTINUING EDUCATION Join us for our 2019 MEETINGS

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GVCE **16th Annual Education Symposium REVIEW’S COMMITMENT TO CONTINUING EDUCATION *Approval pending Joint Meeting with NT&T in Eye Care RGVCE partners with Salus University for those ODs who are licensed in states that require university credit. See www.reviewsce.com/events for any meeting schedule changes or updates. CONTRIBUTING EDITORS World Class PAUL C. AJAMIAN, OD, ATLANTA AARON BRONNER, OD, KENNEWICK, WASH. MILE BRUJIC, OD, BOWLING GREEN, OHIO Continuing Education DEREK N. CUNNINGHAM, OD, AUSTIN, TEXAS MARK T. DUNBAR, OD, MIAMI ARTHUR B. EPSTEIN, OD, PHOENIX JAMES L. FANELLI, OD, WILMINGTON, NC GARY S. GERBER, OD, HAWTHORNE, NJ + ANDREW S. GURWOOD, OD, PHILADELPHIA ALAN G. KABAT, OD, MEMPHIS, TENN. Bucket List DAVID KADING, OD, SEATTLE PAUL M. KARPECKI, OD, LEXINGTON, KY. JEROME A. LEGERTON, OD, MBA, SAN DIEGO Travel JASON R. MILLER, OD, MBA, POWELL, OHIO CHERYL G. MURPHY, OD, BABYLON, NY CARLO J. PELINO, OD, JENKINTOWN, PA. JOSEPH PIZZIMENTI, OD, SAN ANTONIO, TEXAS. = JOHN RUMPAKIS, OD, MBA, PORTLAND, ORE. DIANA L. SHECHTMAN, OD, FORT LAUDERDALE, FLA. JEROME SHERMAN, OD, NEW YORK JOSEPH P. SHOVLIN, OD, SCRANTON, PA. Your Host for the Best in Destination CE JOSEPH W. SOWKA, OD, FORT LAUDERDALE, FLA. MONTGOMERY VICKERS, OD, LEWISVILLE, TEXAS. WALTER O. WHITLEY, OD, MBA, VIRGINIA BEACH, VA.

EDITORIAL REVIEW BOARD Join Us for Our JEFFREY R. ANSHEL, OD, ENCINITAS, CALIF. JILL AUTRY, OD, RPH, HOUSTON 2019 - 2020 SHERRY J. BASS, OD, NEW YORK EDWARD S. BENNETT, OD, ST. LOUIS MARC R. BLOOMENSTEIN, OD, SCOTTSDALE, ARIZ. International CE Meetings CHRIS J. CAKANAC, OD, MURRYSVILLE, PA. JERRY CAVALLERANO, OD, PHD, BOSTON Registration Open at www.internationaleye.net WALTER L. CHOATE, OD, MADISON, TENN. 15 Hours Credit at each event - COPE Approval Pending. Accredited BRIAN CHOU, OD, SAN DIEGO by University of Houston School of Optometry. 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. Florence, Italy MURRAY FINGERET, OD, HEWLETT, NY IAN BEN GADDIE, OD, LOUISVILLE, KY. October 19-25, 2019 PAUL HARRIS, OD, MEMPHIS, TN MILTON HOM, OD, AZUSA, CALIF. BLAIR B. LONSBERRY, MS, OD, MED, PORTLAND, ORE. Edinburgh, Scotland THOMAS L. LEWIS, OD, PHD, PHILADELPHIA DOMINICK MAINO, OD, MED, CHICAGO June 13-19, 2020 KELLY A. MALLOY, OD, PHILADELPHIA RICHARD B. MANGAN, OD, LEXINGTON, KY. RON MELTON, OD, CHARLOTTE, NC PAMELA J. MILLER, OD, JD, HIGHLAND, CALIF. Paris, France BRUCE MUCHNICK, OD, COATESVILLE, PA. October 18-25, 2020 MARC MYERS, OD, COATESVILLE, PA. WILLIAM B. POTTER, OD, FREEHOLD, NJ CHRISTOPHER J. QUINN, OD, ISELIN, NJ MICHAEL C. RADOIU, OD, STAUNTON, VA. EXPLORE OUR 2020/2021 MOHAMMAD RAFIEETARY, OD, MEMPHIS, TN DESTIDESTINATIONSESTSTIT T ONS JOHN L. SCHACHET, OD, ENGLEWOOD, COLO. LONDON JACK SCHAEFFER, OD, BIRMINGHAM, ALA. PRAGUE LEO P. SEMES, OD, BIRMINGHAM, ALA. FRENCH RIVIERA LEONID SKORIN, JR., OD, DO, ROCHESTER, MINN. CARTAGENA JOSEPH W. SOWKA, OD, FORT LAUDERDALE, FLA. BRAD M. SUTTON, OD, INDIANAPOLIS LORETTA B. SZCZOTKA, OD, PHD, CLEVELAND Sign up for our mailing list online to get all the latest news about our MARC TAUB, OD, MEMPHIS, TN destinations, speakers and agendas. TAMMY P. THAN, MS, OD, BIRMINGHAM, ALA. RANDALL THOMAS, OD, CONCORD, NC SARA WEIDMAYER, OD, ANN ARBOR, MI KATHY C. WILLIAMS, OD, SEATTLE KAREN YEUNG, OD, LOS ANGELES internationaleye.net

0011_ro0219_toc.indd11_ro0219_toc.indd 1515 22/7/19/7/19 11:1211:12 AMAM Outlook By Jack Persico, Editor-in-Chief PRINTED IN USA

FOUNDING EDITOR, FREDERICK BOGER 1891-1913 EDITORIAL OFFICES ‘Further Research is Needed’ 11 CAMPUS BLVD., SUITE 100 NEWTOWN SQUARE, PA 19073 It’s both a mantra and a cliché—and also an important

SUBSCRIPTION INQUIRIES 1-877-529-1746 reminder to practicing clinicians. CONTINUING EDUCATION INQUIRIES 1-800-825-4696 n our website, we’ve been discussion we had while working

EDITOR-IN-CHIEF • JACK PERSICO publishing news stories on this issue (his work is featured in (610) 492-1006 • [email protected] each weekday for nearly a two of the five projects profiled in MANAGING EDITOR • REBECCA HEPP O (610) 492-1005 • [email protected] year—check ’em out if you hadn’t this month’s cover series). SENIOR EDITOR • BILL KEKEVIAN noticed! Nearly all are summaries of Dr. Humayun was explaining the (610) 492-1003 • [email protected] journal articles we feel have clinical challenges doctors face when col- ASSOCIATE EDITOR • CATHERINE MANTHORP (610) 492-1043 • [email protected] relevance. With so much research laborating with engineers, whose ASSOCIATE EDITOR • MARK DE LEON news churning through our word discipline has been following clearly (610) 492-1021 • [email protected] processors, one phrase shows up predictable rules ever since Newton SPECIAL PROJECTS MANAGER • JILL HOFFMAN (610) 492-1037 • [email protected] again and again without fail: the gave them a systematic concep- ART DIRECTOR • JARED ARAUJO dreaded ‘further research is needed’ tion of the natural world. Medical (610) 492-1032 • [email protected] to close a paper. researchers don’t always have fully DIRECTOR OF CE ADMINISTRATION • REGINA COMBS (212) 274-7160 • [email protected] Well, of course it is. That’s pretty formed, mechanistic laws to rely much the mission statement for all on. As a result, they can’t deliver to EDITORIAL BOARD CHIEF CLINICAL EDITOR • PAUL M. KARPECKI, OD of science. engineers the precise specifications ASSOCIATE CLINICAL EDITORS • JOSEPH P. SHOVLIN, OD; As an editor, that line always irks of what to build. Doctors have a ALAN G. KABAT, OD; CHRISTINE W. SINDT, OD me. It feels trite to keep restating much more provisional and tenta- DIRECTOR OPTOMETRIC PROGRAMS • ARTHUR EPSTEIN, OD CLINICAL & EDUCATION CONFERENCE ADVISOR an obvious, foundational principle. tive understanding of their field, and PAUL M. KARPECKI, OD Authors of journal articles shouldn’t that manifests in what people call CASE REPORTS COORDINATOR • ANDREW S. GURWOOD, OD rely on such an empty phrase; the so-called ‘art’ of medicine. CLINICAL CODING EDITOR • JOHN RUMPAKIS, OD, MBA rather, they should articulate the That interplay of instinct and pre- CONSULTING EDITOR • FRANK FONTANA, OD scope of specific future work they’d cision is showcased in this month’s COLUMNISTS like to see. Who better to say what cover focus on innovation in eye CHAIRSIDE • MONTGOMERY VICKERS, OD deserves to come next than the care. Breaking from our usual for- CLINICAL QUANDARIES • PAUL C. AJAMIAN, OD CODING CONNECTION • JOHN RUMPAKIS, OD people responsible for the original mat, we’ve asked several research CORNEA & CONTACT LENS Q+A • JOSEPH P. SHOVLIN, OD findings? teams to share with us the work DIAGNOSTIC QUIZ • ANDREW S. GURWOOD, OD Still, maybe that cliché has some they’re engaged in now to build new THE ESSENTIALS • BISANT A. LABIB, OD value in reminding everyone that tools for tomorrow. FOCUS ON REFRACTION • MARC TAUB, OD; no question is ever truly answered Why care about research? It’s a PAUL HARRIS, OD GLAUCOMA GRAND ROUNDS • JAMES L. FANELLI, OD with absolute certainty, at least not fair question to ask. In your busy NEURO CLINIC • MICHAEL TROTTINI, OD; in medicine. Although an interest- day, you have to prioritize the here MICHAEL DELGIODICE, OD ing new book, Solving Chemistry, and now. But staying attuned to the OCULAR SURFACE REVIEW • PAUL M. KARPECKI, OD RETINA DILEMMAS • DIANA L. SHECHTMAN, OD; argues that that field has in fact near future helps you do better in JAY M. HAYNIE, OD wrapped up all its big issues, medi- the present. Seeing all the questions RETINA QUIZ • MARK T. DUNBAR, OD cine is far more messy, intellectually being asked allows you to recognize REVIEW OF SYSTEMS • CARLO J. PELINO, OD; JOSEPH J. PIZZIMENTI, OD speaking. Everything you do in the the shortcomings and just plain SURGICAL MINUTE • DEREK N. CUNNINGHAM, OD; clinic can and should be challenged guesswork you sometimes have WALTER O. WHITLEY, OD, MBA periodically, because its foundations to get by with right now. Hope- THERAPEUTIC REVIEW • JOSEPH W. SOWKA, OD; ALAN G. KABAT, OD are surprisingly shaky. fully, that reminds you to approach THROUGH MY EYES • PAUL M. KARPECKI, OD “Most physicians are largely pre- patient care decisions with a dose of URGENT CARE • RICHARD B. MANGAN, OD Newtonian” in their understanding skepticism. Following research also of the processes that govern the gives you the liberty to contemplate JOBSON MEDICAL INFORMATION LLC body, retina specialist Mark Huma- a better future, for you and your yun, MD, PhD, pointed out in a patients, and watch it unfold. ■

16 REVIEW OF OPTOMETRY FEBRUARY 15, 2019 COMING 2019 Open your eyes to what’s on the horizon in dry eye.

TearCare is indicated for the application of localized heat when the current medical community recommends the application of a warm compress to the eyelids. Such applications would include Meibomian Gland Dysfunction (MGD), Dry Eye, or Blepharitis.

RO0119_Sight Sciences.indd 1 1/4/19 12:29 PM Through My Eyes

Let’s Get Medical This is the year to embrace medical optometry or even consider a specialty. By Paul M. Karpecki, OD, Chief Clinical Editor

espite the growing need for medical eye care (Bausch + Lomb) is likely to be available soon. This drug services, more than 70% of the average optome- uses key polymers and a submicron particle size to allow trist’s income still comes from goods and services for higher potency and penetration with a lower concen- D 1 related to glasses and contact lenses. But challenges from tration of drug. online vendors and the advent of virtual or automated • Glaucoma. An estimated 61 million people had vision screenings will make it increasingly difficult to suc- glaucoma as of 2010, and the number may rise to 80 ceed at this model. million by 2020.7 Fortunately, advanced technologies Meanwhile, the demand for medical eye care services and new therapeutics can help with early detection and is expanding at a rate nearly three times that of compre- management. We now have several new drugs as well as hensive eye exams. Someone must care for these patients modified or preservative-free versions of early-generation and, in many cases, this responsibility is ours. drops. Some of these affect outflow in novel ways and show significant promise for improving patient care. Assess the Need In addition, new surgical devices such as MIGS have If you look at the specific areas where medical eye care improved intraocular pressure control and are a good services are growing, several specialties stand out: opportunity at the time of cataract surgery. • Diabetes. Diabetic retinopathy (DR) is a leading • AMD. Clinical AMD is more prevalent than glau- cause of vision loss.2 According to the American Diabetes coma and DR combined—and by the year 2050, it is Association, the annual economic burden of diabetes is estimated to double. Unfortunately, both optometrists about $245 billion.3 Further estimates speculate that the and ophthalmologists are missing AMD about 25% of total cost of diabetes attributable to DR ranges anywhere the time.8 It’s no wonder that as many as 78% of patients from 10% to upwards of 42%.4 Optometrists can play are first diagnosed with AMD after having already suf- a leading role in early detection and appropriate man- fered irreversible vision loss in one eye, and nearly half agement, since many adults living with diabetes remain of them are first diagnosed with an acuity of 20/200 or unaware of their condition until their DR has progressed worse.9 One of the best ways to improve these statistics is to a stage at which treatment is difficult. For example, of to start testing dark adaptation time. This functional test an estimated 285 million people worldwide with diabe- allows you to detect early AMD up to three years before tes, more than a third have signs of DR, and a third of it becomes clinically evident and it takes the guesswork these are afflicted with vision-threatening DR.5 out of AMD diagnostics so you can move forward with a • Cataract. Rising patient expectations and a growing plan to slow or prevent progression. number of surgical options have expanded the cataract • Dry eye. In the United States, managing dry eye costs pre-op evaluation. Patient selection is a primary compo- healthcare $55.4 billion annually—and the demographic nent in achieving satisfactory visual outcomes after cata- most likely to suffer is growing.10 A few decades ago, ract surgery, and the results depend heavily on the quality there wasn’t much we could do to address dry eye in a of the ocular surface. meaningful way. But our options are expanding. Several Ocular surface disease increases the risk of surgical years ago, a better understanding of the inflammatory complications, affects intraocular lens (IOL) measure- process led to the introduction of two modern mainstays ments and impacts comfort and quality of vision. In fact, of dry eye therapy, cyclosporine and lifitegrast. Today, research shows that patients who have osmolarity scores these advanced pharmaceuticals are being joined by more within normal limits are within a half diopter of intent, treatments. Cequa (cyclosporine A 0.09%, Sun Pharma- whereas 17% of those with hyperosmolarity would have ceuticals) is a preservative-free nanomicellar formulation missed their IOL calculation by more than a diopter.6 For of cyclosporine A in a stronger formulation than has post-op care, a new formulation of loteprednol 0.38% been previously available. Klarity-C (cyclosporine 0.1%/

18 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

018_ro0219_TME.indd 18 2/5/19 1:49 PM VisiPlug is the only one for me… No pop-out! chondroitin sulfate ophthalmic emulsion) is another compounded dry eye drop that’s available through Imprimis. KPI-121 (loteprednol etabonate ophthalmic suspension 0.25%, Kala Pharmaceuticals) uses a mucus-penetrating particle technology to increase the penetration of a familiar steroid. P-321 (Shire), an epithelial sodium channel inhibitor for the treatment of tear volume deficiency and the promotion of ocular surface healing, is also under investigation. Beyond pharmaceuticals, we also now have access to other efficacious dry eye and meibomian gland dysfunction treatments, including intense pulsed light, neurostimu- lation and thermal pulsation. Make a Difference If you haven’t embraced medical eye care, this is the year to do it. If you have, maybe consider adding a specialty to your practice. We must take a more active role when treating patients with diabetes, cataract, glaucoma, AMD and dry eye. Beyond our training as diag- nosticians, we can recommend treatments that make a meaningful difference, and we can suggest lifestyle changes, diet and exercise modifications, systemic dis- Lacrimedics’ VisiPlug® has been the ease management, nutritional supplementation, retinal market leading synthetic dissolvable light protection and more careful follow-up. plug for YEARS! Medical optometry will change the lives of your patients, and it will change the course of your practice VisiPlug® was the first FDA approved in meaningful, positive ways. The top 5% of optom- and CE Marked plug to provide etrists receive at least 50% of their income from medi- approximately 180 days of cal services.11 How much of your practice revenue can Occlusion Therapy. you attribute to medical optometry? For most of your colleagues, it’s only about 17%, which leaves plenty of Available for immediate delivery. room to grow in a diverse list of specialties that show Don’t make your Dry Eye patients wait no signs of shrinking.11 ■ Note: Dr. Karpecki consults for a number of manu- for relief. facturers with products relevant to this topic. ® 1. AOA Excel and Jobson Medical Information. The State of the Optometric Profession. 2013. VisiPlug – 2. Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis. 2015;2:17. a visibly better plug 3. American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36:1033-46. 4. Summers KHR, Ryan GJ. The economic impact of diabetic retinopathy and the promise of emerging to treat dry eye! therapies [CE Activity]. International Medical Press; 2007. 5. Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556-64. 6. Epitropoulos AT, Matossian C, Berdy GJ, et al. Effect of tear osmolarity on repeatability of keratom- etry for cataract surgery planning. J Cataract Refract Surg. 2015;41(8):1672-7. 4FFZPVBU4&$0JO#PPUI 7. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262-7. 8. Neely DC, Bray KJ, Huisingh CE, et al. Prevalence of undiagnosed age-related macular degeneration in primary eye care. JAMA Ophthalmol. 2017;135(6):570-5. 9. Cervantes-Castañeda RA, Banin E, Hemo I, et al. Lack of benefit of early awareness to age-related macular degeneration. Eye. 2007;22(6):777-81. (800) 367-8327 10. Yu J, Asche CV, Fairchild CJ. The economic burden of dry eye disease in the United States: a decision tree analysis. Cornea. 2011;30(4):379-87. E-mail: [email protected] 11. Management & Business Academy. Key Metrics: Assessing Optometric Practice Performance. www.lacrimedics.com 2015 Edition.

018_ro0219_TME.indd 19 2/5/19 1:50 PM Chair Side

Summon Some Courage Jury duty isn’t so bad when you can’t weasel out of it—and remember, it could always be worse. By Montgomery Vickers, OD

hen I was born, my dad that might screw up their Christmas than that a day? Hey, don’t blame was an agent in the FBI. plans. me, blame the Magna Carta. It’s a WBut when he took one It turned out fine when 220 good slippery slope when you give rights look at his new little criminal, he Americans showed up and they to the commoners. immediately quit to become a small only needed about 80, so they never All of us civilians should be glad town lawyer. Dad taught us to even called my name. I didn’t have jury duty is all we have to do to always respect our law enforcement to rip off my shirt to reveal my new serve our country. There are many officers and the judicial system. We full-body tattoo of Charles Manson wonderful folks who serve our did and we always will. My dad was and the Family while being vetted country while crazy people try to a wise man. by the attorneys. Hopefully I can hurt them. I certainly understand sit- get the tattoo artist to somehow add ting on a jury to hear a case about a Do What’s Right enough ophthalmoscopes to it so the faulty AC installation isn’t remotely I could never be in law enforcement, grandkids think it’s a salute to the the same. My guess is it is way more but at least when I received my Texas Optometry Board when we go inconvenient to get shot at. Denton County, Texas, jury sum- to the beach. Turns out it’s hard to So, have the courage to make an mons, I knew my duty as a citizen remove tattoos. Who knew? office policy, one that shows you are of this wonderful nation. I knew, in grateful for our country. And when my heart, exactly what to do. That’s Share the Joy of Jury Duty you get called, show up and do your right: I searched the internet for how Luckily, my office has a great policy duty. It’s the least you can do. Also, to get out of it. in place for this; I didn’t even have none of your excuses will work… That, unfortunately, didn’t pan to come in for the afternoon, even trust me, I tried. My understand- out because I couldn’t figure out though the jury selection was over ing is there are very few convicted how to convince the judge that I was before noon. I finally had time to felons who are practicing optometry. an active duty member of the armed finish my Christmas shopping. The Maybe optometrists are just hard to forces, a convicted felon (I couldn’t kids will understand. convict. ■ rob somebody and also get con- What’s your jury duty policy? Do victed in time), a pregnant woman you pay your staff members who are (again, no time, but my understand- called? I mean, why should you? As ing is that this is not impossible in I just found out, sitting on a jury in California), or an employee of the Texas gets you $6 for the first visit Texas state government (God for- and $40 a day while you serve— bid an employee of the Texas state quite generous! government spends a couple of days What, you usu- serving the state of Texas. Against ally pay your union rules, I guess.) staff more So, the best I could do was request a delay until mid-December, which I was granted. It seemed a logical assumption that all the judges in Denton County were completely impartial in every way but one: none of them wanted to try a case

20 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

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RO0119_Partners In Vision.indd 1 1/9/19 2:06 PM Clinical Quandaries

Making the Grade Type A personalities can get an F if their treatment expectations are not kept in check. Edited by Paul C. Ajamian, OD

I have been seeing a patient know the patient best. Q with mild cataracts for routine care, and he has been finicky about Refining the Results every one of his contact lens and The second question, assuming the spectacle prescriptions. I referred patient is a good candidate for a him for a cataract evaluation, and the multifocal, is how to tailor the lens surgeon implanted a multifocal lens. to the individual. “The Restor lens The patient is very unhappy. What (Alcon) allows us to customize the went wrong? visual correction to the patient’s Communication, or the lack Your role in pre-op multifocal IOL counseling lifestyle,” says Dr. Ajamian. If the A thereof, was a big problem in could mean the difference between success patient spends most of their time on this case, says Paul C. Ajamian, OD, and failure. the computer and little time read- Director of Omni Eye Services of ing, Dr. Ajamian suggests the Restor Atlanta, the nation’s oldest coman- ing the patient and then write a Activefocus +2.5D lens. “If the agement center. “I looked back at the referral letter that says more than patient does a lot of reading in addi- chart, and there was no referral let- please do a cataract evaluation.” tion to intermediate computer work, ter that would have given us a heads Your preoperative cataract exam a good way to hedge your bet is to up about our patient’s personality should always include corneal topog- start with the +2.5D Activefocus in and predilection for perfection,” Dr. raphy to determine if the patient the dominant eye for better distance Ajamian notes. All his practice knew needs a toric lens. Irregular astigma- and intermediate vision.” When the was that the patient wanted to go tism usually precludes a toric IOL second eye is done two weeks later, without glasses at distance and near. but also often rules out a multifocal. reassess and determine if you need They informed the patient that he Surface disease, pterygia, Salzmann’s the slightly stronger +3.0D to assist might still need to wear glasses in nodular degeneration, map-dot- them while reading. certain situations, but he didn’t want fingerprint dystrophy and LASIK are to hear it. An initial discussion with all deal-breakers for the multifocal. Final Evaluation his optometrist would have had a Identify Type A personalities if at Our Type A patient got a failing much greater impact. After the sur- all possible. Be careful not to prom- grade with a multifocal lens because geon implanted the Restor (Alcon) ise that the patient that they will be the surgical practice didn’t have lenses, the patient’s vision was 20/25 able to get rid of their glasses. “I tell the information they needed. The and J2 OU, but he was still very everyone that they will be wearing patient can score a better grade if unhappy. glasses for some situations, even if optometrists take the time to counsel the results are perfect,” Dr. Ajamian each patient and then pass the infor- Communication Breakdown adds. Finally, understand that any- mation they learn along to surgeons. There is no one who knows the one who pays upwards of $3,000 It will make you look much better patient better than you. The key is for a premium lens product is going in your patient’s eyes and leave for to share that intel with your sur- to expect perfection, and the current you fewer messy surprises behind to geon! It is unrealistic to expect that technology is not yet there. clean up post-op. the surgeon will get to know your Once your exam and pre-op coun- An A or an F? That depends on patient and assess their needs in the seling is complete, let the surgeon the extra effort you are willing to short period of time they have. Dr. know what you observed, discussed make to “school” the patient on Ajamian advises, “If you want the and recommend. Most will take the options available and what will best outcomes, spend time counsel- your advice, knowing that you work best for them. ■

22 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

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RP0918_Keeler Trade.indd 1 8/22/18 11:28 AM Coding Connection

The Telephone is Ringing… A new year brings new rules—make sure you know what your carriers expect when it comes to telehealth services. By John Rumpakis, OD, MBA, Clinical Coding Editor

n November 2018, CMS final- • Brief communication tech- Clinicians must understand that ized and released the 2019 nology-based service, e.g. virtual CMS restricts the use of the vir- IPhysician Fees Schedule, which check-in (HCPCS code G2012): tual check-in and the pre-recorded contains significant changes aimed This applies to check-in services patient information codes, which at modernizing the healthcare sys- used to evaluate whether or not an can only be used by practitioners tem by using technology, reducing office visit or other service is neces- who furnish E/M codes. administrative burden and improv- sary. The modalities include audio- ing the doctor-patient relation- only real-time phone interaction, in Carrier Considerations ship.1,2 While CMS’s interpretation addition to synchronous, two-way As technology continues to expand and implementation of telehealth audio interactions enhanced with and drives changes in the patient is amongst the most restrictive, this video or other forms of data trans- journey and the quality of clini- latest release expands and clarifies mission. CMS pays approximately cal outcomes, optometrists must things, at least a little. $14 for this service (unless it is the stay abreast of the rule sets and Telehealth-delivered services result of a previous appointment changes that come at a furious under Medicare are regulated in or leads to a face-to-face appoint- pace. Pay attention to the rules of statute by 1834(m) of the Social ment). CMS believes the check-ins each of your contracted medical Security Act, which limits the use will mitigate the need for poten- carriers, as they can differ based of telehealth to certain services, tially unnecessary office visits. on whether the carrier is com- providers, technology (mainly • Remote evaluation of pre- mercial, Medicaid, Medicare Part live video) and patient locations recorded patient information C (Medicare Advantage), or tra- (certain types of healthcare facili- (HCPCS code G2010): CMS final- ditional Medicare Part B. And as ties in rural areas). The CMS rule ized the creation of a specific new always, make sure you are aware expresses concern that these code to describe remote profes- of these rules prior to providing requirements may be limiting the sional evaluation of patient-trans- the care—never assume that meet- coding for new kinds of services mitted information conducted via ing the requirements of telehealth that use communication technol- pre-recorded “store-and-forward” for one carrier means you meet the ogy. video or image technology. These rules for other carriers. services are not subject to the Out-of-office Care Medicare telehealth restrictions Hopefully we will eventu- Luckily, these restrictions only because they could not substitute ally have a universal rule set that apply to professional services speci- for an in-person service currently streamlines the delivery of care by fied in the statutory provisions, separately payable under the PFS. telehealth; but until then, you must such as office visits, professional • Interprofessional internet maintain a separate rule set for consultations and other in-office consultation (CPT codes 99452, each carrier. ■ services. Other services that can be 99451, 99446, 99447, 99448 Send questions and comments to provided remotely using communi- and 99449): These codes cover [email protected]. cations technology are not subject interprofessional consultations 1. Centers for Medicare & Medicaid Services. Final policy, pay- to these restrictions because they performed via communications ment, and quality provisions changes to the Medicare physician fee schedule for calendar year 2019. www.cms.gov/newsroom/ are not considered “Medicare tele- technology such as telephone or fact-sheets/final-policy-payment-and-quality-provisions- health services.” Because of this, internet. This supports a team- changes-medicare-physician-fee-schedule-calendar-year. November 1, 2018. Accessed January 9, 2019. optometrists need to be aware of based approach to care that is often 2. Dizon R. Big changes in 2019 for Medicare telehealth policy. National Telehealth Policy Resource Center Blog. www. three scenarios and the associated facilitated by electronic medical telehealthresourcecenter.org/big-changes-in-2019-for-medicare- new codes: record technology. telehealth-policy. November 6, 2018. Accessed January 9, 2019.

24 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

024_ro0219_coding.indd 24 2/5/19 12:08 PM # Dryness is the #1 problem Biotruth 31 for contact lens wearers1

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Recommend Biotrue®—the #1 multi-purpose solution used in more households.* *Highest household penetration among multi-purpose solutions; IRI Data MULO 52 weeks ending 08/12/18. REFERENCES: 1. The Multi-sponsors Survey’s 2017 study of the US consumer contact lens market. December 2017. 2. In vitro studies evaluated the rate of release of sodium hyaluronate (HA), a conditioning agent in the Biotrue® multi-purpose solution, from both conventional and silicone hydrogel contact lenses over a twenty-hour time period. HA was adsorbed on all traditional and silicone hydrogel contact lenses tested upon soaking in the solution overnight. HA is then released from the lenses throughout at least a twenty-hour time period when rinsed with Hank’s balanced salt solution at a rate mimicking tear secretions. The in-vitro performance of Biotrue® multi-purpose solution suggests that it will provide lens conditioning throughout a twenty-hour time period. 3. Results of an online survey of contact lens wearers with self-reported dryness on a regular basis who completed an evaluation program for Biotrue® multi-purpose solution (n=348). Survey results include patients who strongly agreed, agreed, or slightly agreed (on a 6-point agreement scale). ®/™ are trademarks of Bausch & Lomb Incorporated or its afﬁ liates. Any other products/brand names and/or logos are trademarks of the respective owner. ©2018 Bausch & Lomb Incorporated. BIO.0130.USA.18

RO0219_BL Biotrue.indd 1 1/23/19 10:14 AM Focus on Refraction

Beyond the Phoropter Are glasses always necessary? It takes more than just the numbers to make that call. By Marc B. Taub, OD, MS, and Paul Harris, OD

t’s not a typical day in the office Case #2 Exam Findings without a parent asking, “Does Visual Acuities (unaided) 20/25- OU, 20/20- OU at distance, 20/20 OU at Imy child really need glasses?” near When working with a patient Stereopsis (unaided) 20 seconds with 2.00D of myopia, the answer Cover Test Ortho at distance and at near is obvious, but what about when even you’re not sure if you should Near Point of Convergence Test Break at 7cm, recovery at 11cm prescribe or hold off for another Accommodative Amplitudes 11.00D OD, 9.00D OS year? While there are some guide- First Prescription (three years prior) +2.25 -2.25x180 OD, +1.00 -2.25x180 OS lines to help us make this decision, Previous Prescription (18 months prior) Plano -1.00x180 OU we also have our own clinical VAs of 20/20 OU experience to rely on when making Retinoscopy +1.50 -150x180 OU the final call. We’ve included two VAs of 20/20- OU similar cases that resulted in us tak- Subjective Refraction 1.00 -1.00x180 OU ing two different actions and the VAs of 20/20 OU reasoning behind each decision. Final Prescription +0.50 -1.00x180 OU VAs of 20/15 OU at distance, 20/20 OU at near Case #1 Cover Test Through Final Prescription 6 exophoria at near A nine-year-old female came in for Vergence Ranges Through Final Prescription x/20/18 for base in, x/25/12 for base out her routine exam, stating she had lost her glasses three months prior and had not been seeing well with The patient did well after all developmental milestones. She them. She reported that she actually receiving her first pair of glasses did not report any problems with sees better without them, and her three years earlier and wore squinting or headaches and has mom said her visual behavior them at school and while doing been receiving As and Bs in school. and school performance have not homework. She was born full-term Now, we refer back to the declined since she lost them. with no complications and met question we hear almost daily and ask ourselves whether this child Case #1 Exam Findings needs glasses. Every patient has Visual Acuities (unaided) 20/20 OU at distance and at near different visual needs, even if they Stereopsis (unaided) 25 seconds happen to have similar refractive findings, so we must always be Cover Test Ortho at distance, 4 exophoria at near thoughtful about how we proceed. Quality of Life Test 12 (a score of 20 or higher is a red flag) According to our findings, Accommodative Amplitudes 12.00D OU this patient is a high-functioning Previous Prescription (18 months prior) +1.50 -1.00x180 OU child who is doing well in and Retinoscopy +2.00 -1.00x180 OD, +1.25 -1.00x180 OS out of school. We agreed that, VAs of 20/20 OD and 20/20- OS at distance, 20/20 OU if this were the patient’s first at near examination, we would have made Subjective Refraction +1.50 -1.00x180 OU the straightforward decision to VAs of 20/20 OU hold back from prescribing glasses. Damp Retinoscopy +2.75 -1.00x180 OD, +2.00 -1.00x180 OS This is due to the fact that her

26 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

026_ro0219_FoR.indd 26 2/5/19 4:36 PM 2019

hyperopia and astigmatism are right at the point when prescribing is recommended, her school performance is not a concern and her uncorrected visual function is within expected levels. Given that this was not her first examination, however, we had to look at all of the facts and discuss with the patient and her parent. Since the patient’s behavior and school performance did not worsen after losing her glasses, a new prescription was not issued. If the patient were to return with near-point complaints later on, a near only would then be considered. Case #2 A nine-year-old male presented complaining of slight trouble seeing distant objects, and his mom reported that he squints while reading. She said he has a pair of glasses but often misplaces and has never consistently worn them, even though they were prescribed three years ago. She said his grades THE 2019 SECO SHOW DAILY! in school fluctuate based on how much he can focus The SECO conference, one of the while reading. premier educational events of the year, Upon reviewing this case, we can observe that while our findings are somewhat similar to the first, will take place February 20-24, 2019 — this child presented under different circumstances. and Review of Optometry will be there! He exhibits erratic school performance, poor Review’s on-site editorial staff will behavior and suboptimal visual function data. When his acuity is corrected, we can also see an provide live daily coverage of important improvement in the cover test and vergence ranges show news and events, educational at near, which are close to expected values. Taking highlights, product launches and more. all of this information into account, it is obvious that prescribing in this case is less of a question. The patient’s parents were on board as soon as we explained how glasses could positively impact his academics and behavior. Moving forward, we decided to cut 0.50D off the sphere component to allow Attendees on-site can pick up the SECO for acuities similar to, if not better than, those the Daily each morning for the latest news subjective refraction yielded. and highlights. Those at home can stay When deciding whether to prescribe glasses, in touch, too—a digital edition of the especially for a child, first gather a comprehensive patient history and conduct a complete ocular exam. SECO Daily will be posted online, plus So much more goes into prescribing than just the numbers. an e-newsletter will be sent out each In both of these cases, we looked to the parents morning with the day’s top stories. to provide background information. We also relied on the non-acuity-based examination data to guide us in the decision-making process. Without the combination of parental information and visual function testing, it would have been pretty much Show copies will also be available impossible to see the full picture and decide how to at the Review of Optometry booth proceed accordingly. ■

REVIEW OF OPTOMETRY FEBRUARY 15, 2019 27

026_ro0219_FoR.indd 27 2/5/19 4:36 PM Retina Dilemmas

Serous Business CSR can be treated a number of different ways—but should it be? By Jay M. Haynie OD, Diana Shechtman OD, and Rashid Taher, MD

entral serous retinopathy All photos: Jay M. Haynie, OD (CSR) is thought to be an Cidiopathic disorder typically found in the macula, characterized by a neurosensory detachment from the retinal pigment epithelium (RPE) and a localized pigment epithelial detachment (PED). Symptoms of CSR can include a loss of central vision, a central scotoma, micropsia, metamorphopsia, reduced color vision and reduced contrast sensitivity. Visual acuity may only be Fig. 1. SD-OCT reveals a neurosensory detachment in the patient’s left eye. reduced moderately, and the refraction tends to reveal a hyperopic Risk factors associated with CSR should be considered an associated shift in most cases.1 Enhanced depth include steroid use, increased caf- risk factor, especially in patients imaging optical coherence tomogra- feine consumption, higher stress who suffer from recurrent episodes phy (EDI-OCT), available for both levels (or a type-A personality trait), of CSR or have chronic symptoms.2 spectral-domain (SD) and swept- testosterone supplements, preg- In the clinical setting, CSR is source OCT, has demonstrated that nancy, Helicobacter pylori ulcers, classified as either acute or chronic patients with CSR tend to have Viagra (Pfizer) use and obstructive (recurrent). In acute CSR, the visual thicker, larger diameter choroidal sleep apnea. All of these risk fac- symptoms are often self-limiting for vessels (i.e., pachychoroid). tors can result in increased vascular one to four months; chronic CSR permeability of the cho- may cause more prolonged visual roid, causing a localized symptoms and a risk for permanent PED, an accumulation visual loss. of subretinal fluid or a Although CSR is thought to be neurosensory detach- self-limiting in most cases, treatment. ment should be considered in some When asking patients cases. These include monocular about any possible patients, those that need a more exposure to steroids, rapid recovery in visual acuity to be sure to question perform work or vocational tasks, them on the use of any those that have had a poor visual products that may con- outcome from chronic CSR in the tain steroids, such as fellow eye or persistent subretinal creams, inhalants, nasal fluid beyond three to four months. sprays and joint injec- Treatment options for CSR tions. Research shows include myriad systemic medi- sleep apnea is present cations, such as the diuretics Fig. 2. Fluorescein angiography shows focal leakage in up to two-thirds of acetazolamide, eplerenone and and a well-defined serous PED. patients with CSR and spironolactone; the antibiotic

28 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

028_ro0219_RD.indd 28 2/5/19 1:59 PM rifampin; and the hormone supple- ment melatonin. Focal laser photocoagulation can also help with subretinal fluid absorption. Research also shows photodynamic therapy with the light-activated drug Visudyne (verteporfin, Bausch + Lomb) can be effective for CSR treatment.3 Fig. 3. The patient’s neurosensory detachment was nearly resolved three weeks post- A Hairy Situation treatment. Case by Dr. Haynie A 42-year-old male presented to the clinic with a two-week history of vision loss in the left eye. His medical history included Kenalog (corticosteroid) injections in the scalp for the treatment of alopecia, an autoimmune disease characterized by hair loss. He reported that he developed vision loss three days after his treatment. His left eye’s entering Fig. 4. SD-OCT imaging of the patient’s left eye, pretreated with acetazolamide, one visual acuity measured 20/60 and week after the Kenalog treatments. Note that the CSR remains inactive with no sub- the intraocular pressure was 14mm retinal fluid detected. Hg. Dilated examination revealed a serous macular lesion. OCT con- (Figure 4). permeability in the peripapillary firmed a neurosensory detachment area of the choroid and SD-OCT with a pachychoroid; fluorescein Lighting the Way confirmed a large neurosensory reti- angiography confirmed focal leak- Case by Dr. Haynie nal detachment (Figures 5 and 6). age and a well-defined serous PED A 39-year-old female was referred These findings led to a diagnosis of (Figures 1 and 2). He was diag- for a retinal consultation after not- recurrent CSR. nosed with acute CSR secondary to ing sudden vision loss in the right After discussing her treatment the Kenalog injections. eye. Her history included a similar options, which could include obser- Following a discussion of treat- episode of vision loss the year prior, vation, she elected to be treated ment vs. observation, he elected to although it recovered spontane- with low-fluence photodynamic be treated with oral acetazolamide ously over two months. Her medi- therapy based on the degree of 250mg QHS. At follow-up three cal history includes osteoarthritis, vision loss and the recurrent nature weeks later, he reported some visual gastroesophageal reflux disease and of the condition. Six weeks follow- recovery to a level of 20/20- and migraine syndrome. Her medica- ing treatment, the neurosensory OCT imaging confirmed near com- tions included Topamax (topira- detachment had resolved (Figure 7). plete resolution of the neurosensory mate, Janssen Pharmaceuticals), Fluorescein angiography and ICG detachment (Figure 3). Mobic (meloxicam, Boehringer angiography revealed cessation of As part of the management of Ingelheim) and Protonix (panto- the intense leakage with no evidence CSR, I discussed avoiding any prazole, Pfizer). Her visual acuity of activity (Figure 8). Her visual future Kenalog injections; however, measured 20/50- in the right eye. acuity improved to 20/20-. he wanted to continue the treat- Dilated examination revealed serous ment for alopecia. To avoid another edema in the right eye involving the Therapy Preferences acute CSR episode, I treated him macula. Fluorescein angiography Commentary by Dr. Shechtman with acetazolamide 250mg one confirmed focal intense leakage, Most CSR cases resolve spontane- week prior to his Kenalog treat- indocyanine green (ICG) angiog- ously within three months without ment, which worked well long-term raphy confirmed choroidal hyper- intervention. However, 30% to

REVIEW OF OPTOMETRY FEBRUARY 15, 2019 29

028_ro0219_RD.indd 29 2/5/19 1:59 PM Retina Dilemmas

develop CSR. Thus, the use of an MR antagonist, such as spironolactone, can be an effective treatment option for chronic CSR. A recent study shows 83% of those treated vs. 8% of those observed had complete resolution of the CSR within two months. Given spironolactone’s status as a potassium-sparing diuretic, clinicians should consider evaluating the patient’s potassium level prior to its implementation. In addition to spironolactone, Fig. 5. This patient’s ICG angiography reveals choroidal hyperpermeability. focal laser photocoagulation applied to a “hot spot” seems to also be an effective option for patients with CSR. Fluorescein angiography is used to identify the presence of a hot spot, which shows up as hyperfluorescence at the site of RPE detachment. The focal RPE detachment must not involve the fovea. Although the treatment may lead to more rapid resolution, choroidal neovascularization may develop at the treatment site. CSR can be a challenging condi- Fig. 6. SD-OCT imaging uncovers a large neurosensory retinal detachment. tion to treat. Luckily, clinicians have many options that provide an 50% of patients experience recur- While a variety of treatment opportunity to tailor therapy to the rence, which may be seen as gut- options exist for chronic or recur- needs of each patient. ■

tering on fundus autofluorescence. rent cases of CSR, we find spirono- 1. Wang M, Munch IC, Hasler PW, et al. Central serous cho- Both recurrence and chronicity lactone 50mg QD and focal laser rioretinopathy. Acta Ophthalmol. 2008;86:126-45. may lead to RPE atrophy in these photocoagulation most effective in 2. Yavas GV, Küsbeci T, Ka ikci M, et al. Obstructive sleep apnea in patients with central serous chorioretinopathy. Curr patients, with associated permanent our practice. Studies show a rela- Eye Res. 2014;39(1):88-92. visual disturbance, in addition to tionship between mineralocorticoid 3. Yannuzzi LA, Slakter JS, Gross NE, et al. Indocyanine green angiography-guided photodynamic therapy for treat- increased risk of choroidal neovas- (MR) receptors and choroidal vas- ment of chronic central serous chorioretinopathy: a pilot cularization. cular dilation, which collaborate to study. Retina. 2003;23(3):288-98.

Fig. 7. Six weeks after low-fluence photodynamic therapy, the Fig. 8. Treatment stopped the intense leakage, and no activity patient’s neurosensory retinal detachment had resolved. was noted six weeks after initiating therapy.

30 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

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Get a Glimpse of WORK IN PROGRESS Five research teams share details about their efforts to build new tools for glaucoma, AMD, diabetic retinopathy and drug delivery.

lasses that lower IOP. An eye scan that reveals dying WHAT’S INSIDE cells. Electrically charged drug delivery. A way to regrow Transcorneal stimulation of the ciliary body GRPE. And a contact lens that treats diabetic retinopathy. Can We Lower IOP with Glasses? None are available yet, and perhaps not all will make it Page 35 to market. But each breaks from the conventional wisdom, eschewing the familiar in hopes of creating something Detection of apoptosing retinal cells groundbreakingly new. That’s why we’ve selected these five research projects to A Light in the DARC: highlight in this year’s annual Innovation in Eye Care issue. Seeing Glaucoma Before it Strikes They challenge the norms of today, but might become the Page 39 ones of tomorrow. Research need not always be groundbreaking to be Stem cell implantation for RPE remodeling worthwhile, of course. The field of eye care is sustained and Bioengineering the Retinal Pigment strengthened each day by the release of new research papers Epithelium in the scientific journals. Those are the lifeblood of clinical Page 42 practice, a way to reinforce and refine the techniques you use and decisions you make everyday. But the researchers who “think different” (to use the old Electrically enhanced drug penetration Apple slogan) open up entirely new avenues of investigation— Iontophoresis: Wave of the Future? and that effort may one day change the field of eye care in Page 46 meaningful ways. In the pages to follow, the researchers themselves will Phototherapy for diabetic retinopathy share their thoughts, experiences and hopes for the work they While You Were Sleeping are conducting. We hope you enjoy this glimpse behind the Page 48 curtain.

34 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

034_ro0219_Innovation.indd 34 2/7/19 2:34 PM Can We Lower IOP with Glasses? Researchers are finding shocking new ways to employ electro-stimulation. By Taylor Lukasik, MD, and Iqbal Ike K. Ahmed, MD

s eye care professionals, we Photo: Bionode used this research as the underlying diagnose patients with pri- basis in developing IOPTx, which mary open angle glaucoma uses transcorneal electrical stimula- A(POAG) every day in our tion that targets the aqueous inflow clinics. We tell them about the dis- and outflow structures of the eye in ease and how the pattern of vision an effort to reduce IOP. loss begins with the peripheral The system consists of a light- vision and slowly encroaches cen- weight pair of glasses and custom- trally. We tell them they will need ized contact lenses. The spectacles to begin lifelong treatment with an have embedded electronics in antihypertensive drop and possibly addition to a circuit that delivers laser therapy. The indolent pro- an electromagnetic stimulus that gression of glaucoma often leaves reduces IOP. These glasses are fitted patients understandably surprised This gold coil, affixed to a contact lens, with wound enamel copper wire– by their diagnosis, as the vision loss is triggered by an electromagnetic field coated coils that receive electricity they have experienced is hidden to and delivers a stimulus that, researchers from an external pulse generator them. speculate, could reduce IOP. and battery pack attached to the Patients commonly ask if there coils via a USB cable. When the are other treatment options for seen the rise of minimally invasive device is activated, the pulse gen- their condition. We impress on our glaucoma surgeries (MIGS), which erator in the spectacle coil creates patients that drops are currently the are less invasive and possess greater an electromagnetic field directed first-line treatment for glaucoma. safety profiles than traditional glau- towards the eye and induces a cur- After their initial pressure checks, coma surgery.1 Additional benefits rent in the customized contact lens. patients return to us at their six- include decreasing patients’ medi- The contact lens consists of two month and one-year follow-ups cation burden while maintaining Alcon Air Optix hydrophilic hydro- describing difficulties with their intraocular pressure (IOP) control. gel contact lenses (Alcon) with the drops. “I tried the drops but I However, little progress has been gold coil embedded in an electri- didn’t like them,” “I forgot to take made for patients diagnosed with cally insulating parylene substrate them,” and “they make my eyes milder stages of disease. between the two lenses. The contact uncomfortable” are all common The IOPTx system from Bionode lens acts as a secondary coil that is explanations for non-adherence. is aiming to offer these patients stimulated by the electromagnetic These reasons are always troubling a solution in the form of a con- field emitted from the spectacle coil because for many patients, conven- tact lens and glasses combination inserts. The electricity generated is tional treatments seem unacceptable designed to lower intraocular pres- driven across the physiologic struc- or impractical to incorporate into sure. Our clinicians at the Prism Eye tures of the eye. their daily lives. Institute are evaluating these efforts. Another version of the IOPTx Over the past 15 years, glaucoma system bypasses the use of a contact management has begun to shift. How It Works lens altogether and instead uses the Clinicians are moving away from Previous research has shown trans- electromagnetic field generated by a treating patients with topical drops corneal stimulation is safe for the coil on the glasses as the only neu- to maximum medical therapy then anterior segment and deeper struc- romodulatory source to potentially referring for traditional filtering sur- tures of the globe in the treatment lower IOP. This may be useful in gery, which is traumatic and carries of retinitis pigmentosa and various patients who cannot tolerate con- significant risk. Instead, we have optic neuropathies.2-5 Bionode has tact lenses, although currently this

REVIEW OF OPTOMETRY FEBRUARY 15, 2019 35

034_ro0219_Innovation.indd 35 2/7/19 11:26 AM IN EYE CARE Photo: Bionode version of the device is not included cytotoxic and can destroy normal in any clinical trials. conjunctival epithelial cell mem- Based on animal and biomechan- brane, ultimately releasing proin- ical studies, the purported mecha- flammatory mediators that can lead nism of action is twofold. First, the to inflammation and dryness and primary IOP-reducing effect stems be a precipitating factor for OSD.10 from the electrical current causing Continual use of topical medica- interference with the normal functions can lead to alterations in tear tioning of the ciliary epithelial ion film composition and even damage pumps. This, in turn, decreases the to the ocular surface.10 quantity of aqueous humor actively Preservative-free medications are transported into the posterior available to combat this problem; chamber. The secondary mechanism however, these medications are not of action involves electrical stimu- as readily available and increase the lation of the ciliary body causing cost to patients. They also do not contraction of the muscle and open- The Bionode system uses spectacles address patient compliance issues. ing of the drainage structures of embedded with circuitry to deliver an Neuromodulation may have a role Schelmm’s Canal. Potentially, this electromagnetic stimulus designed to in reducing rates of ocular surface means the device is able to modu- reduce IOP. disease related to topical hypo- late both the outflow and produc- tensive medication in glaucoma tion of aqueous simultaneously. Difficulties with Traditional patients. Glaucoma Treatment Another option is laser trabecu- Multicenter Clinical Trials Non-adherence is a long-standing loplasty. This is an appropriate, Clinical trials of the device are cur- problem in glaucoma management.6 noninvasive option as a primary rently underway in Spain and are Recent research shows that between or secondary treatment for POAG beginning at the Prism Eye Institute 1995 and 2001 in the United States or in patients who have adherence in Mississauga, Canada. The study almost half of patients who filled issues with medication. Selective design is a prospective multicenter one prescription discontinued their laser trabeculoplasty (SLT) can double-masked randomized clinical use after the first bottle and only achieve 20% or greater reduction in trial. At the Mississauga site, we are 37% continued use at three years.7 IOP in 58% to 94% of patients at hoping to enroll 20 to 30 patients Another study—one that used elec- 12 months.11 However, the attrition with POAG or ocular hypertension. tronic monitoring systems—pub- rate is high, with only 38% to 68% After a washout period, patients lished in 2015 compared patients’ of eyes maintaining 20% reduction will be randomized to the Bionode self-reported medication adherence at four years.11 and control groups. Exclusion cri- to medication event monitors at teria will include secondary types 60-day follow-up appointments. Wearables of glaucoma and patients with pre- In this study, 31% overestimated Recent trends in medicine have vious glaucoma surgery. Enrolled their drop use when compared with sought to develop treatment and patients will undergo treatment their monitors.8 In the future, the monitoring modalities personal- using the Bionode IOPTx system IOPTx system could be used to ized to patients’ needs. Some of and IOP will be measured periodi- address patient compliance issues the emerging wearable noninvasive cally over one month. The primary and, hopefully, reduce glaucoma devices aim to monitor and treat objective of the study is to evaluate progression. patients with glaucoma. the safety and IOP-lowering efficacy Ocular surface disease (OSD) is Triggerfish contact lens sensor of the IOPTx system in glaucoma- one of the most frequent comor- (CLS) (Sensimed). This is a non- tous eyes. Secondary outcomes will bidities associated with glaucoma, invasive wireless soft contact lens include the longevity of IOP reduc- as nearly 50% of patients treated that measures IOP over a 24-hour tion. This trial will provide valuable with topical glaucoma medications period. The CLS sends IOP mea- information for the appropriate have OSD.9 Topical medications surements wirelessly to an adhesive use and protocol for the device in often contain preservatives, such as disposable antenna that is placed patients with POAG. benzaklkonium chloride, which is around the periorbital skin. The

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034_ro0219_Innovation.indd 36 2/7/19 11:26 AM RO0618_Menicon.indd 1 5/25/18 10:20 AM antenna is connected to a recorder IOP modulating goggles. Department of Ophthalmology and the patient wears in a pouch, simi- Researchers suggest significant Vision Sciences, Toronto, Canada. lar to 24-hour blood pressure moni- interplay between the pressure of 1. Pillunat LE, Erb C, Jünemann AG, Kimmich F. Micro-invasive tor. The CLS measures changes in the cerebrospinal fluid (CSF) and glaucoma surgery (MIGS): a review of surgical procedures using corneal curvature to estimate IOP the optic nerve.19,20 A correlation stents. Clin Ophthalmol. 2017;11:1583-600. 2. Naycheva L, Schatz A, Röck T, et al. Phosphene thresholds over a 24-hour period. This device also exists between low CSF pres- elicited by transcorneal electrical stimulation in healthy subjects has the potential to capture the sure and the development of glau- and patients with retinal diseases. Invest Ophthalmol Vis Sci. 19,20 2012;53(12):7440-8. variation of a patient’s IOP during coma. Although the theoretical 3. Schatz A, Pach J, Gosheva M, et al. Transcorneal electrical their daily activities, as opposed to basis behind the pathogenesis of stimulation for patients with retinitis pigmentosa: A prospective, randomized, sham-controlled follow-up study over 1 year. Invest merely when they are in the office. glaucoma in this patient population Ophthalmol Vis Sci. 2017;58(1):257–69. This could help identify their true is still under debate, supporters pos- 4. Fujikado T, Morimoto T, Kanda H, et al. Evaluation of phosphenes elicited by extraocular stimulation in normals peak IOP, which is associated with tulate that patients with low CSF and by suprachoroidal-transretinal stimulation in patients long-term progression of their pressure have an abnormally high with retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol. 12 2007;245(10):1411-9. disease. A recent study of this trans–lamina cribrosa pressure dif- 5. Fujikado T, Morimoto T, Matsushita K, et al. Effect of transcor- technology concluded that the CLS ference that leads to glaucomatous neal electrical stimulation in patients with nonarteritic ischemic 20 optic neuropathy or traumatic optic neuropathy. Jpn J Ophthal- appears to be better than mean nerve damage. mol. 2006;50(3):266-73. clinic Goldmann IOP measurements Balance Goggles (Equinox) 6. Bloch S, Rosenthal AR, Friedman L, Caldarolla P. Patient compliance in glaucoma. Br J Ophthalmol. 1977;61(8):531-4. at assessing risk of glaucomatous attempt to balance the pressure 7. Nordstrom BL, Friedman DS, et al. Persistence and adher- visual field deterioration.13 differential by applying a negative ence with topical glaucoma therapy. Am J Ophthalmol. 2005;140(4):598-606. Repetitive transorbital alternat- vacuum around the orbit of the eye. 8. Sayner R, Carpenter DM, Blalock SJ, et al. Accuracy of ing current stimulation (rtACS). The company has received funding patient-reported adherence to glaucoma medications on a visual analog scale compared with electronic monitors. Clinical Alternating current stimulation from NASA’s National Space Bio- Therapeutics. 2015;37(9):1975-85. of the brain has been shown to medical Research institute and are 9. Fechtner RD, Godfrey DG, Budenz D, et al. Prevalence of ocular surface complaints in patients with glaucoma using potentially increase excitability currently conducting research on topical intraocular pressure-lowering medications. Cornea. and synchronicity in patients with up to 50 clinically normal eyes to 2010;29(6):618-21. 14-16 10. Mastropasqua L, Agnifili L, Mastropasqua R, Fasanella V. brain injury. This method of evaluate safety and efficacy of their Conjunctival modifications induced by medical and surgical neuromodulation has recently product. This technology may have therapies in patients with glaucoma. Curr Opin Pharmacol. 2013;13(1):56-64. been applied to the visual system future applications in glaucoma 11. Leahy KE, White AJ. Selective laser trabeculoplasty: current in the context of optic neuropathy. management as well as idiopathic perspectives. Clin Ophthalmol. 2015;9:833-41. 12. Konstas AGP, Quaranta L, Mikropoulos DG, et al. Peak A small study involving patients intracranial hypertension, hypotony intraocular pressure and glaucomatous progression in primary with non-specific optic neuropa- and visual impairment and intra- open-angle glaucoma. J Ocul Pharmacol Ther. 2012;28(1):26- 32. thies showed that rtACS was able ocular pressure. 13. De Moraes CG, Mansouri K, Liebmann JM, Ritch R, Trig- to improve patients’ visual fields gerfish Consortium. Association between 24-Hour intraocular 17 pressure monitored with contact lens sensor and visual field in the treatment arm. This study Innovation is never easy, but it is progression in older adults with glaucoma. JAMA Ophthalmol. was limited by the small number necessary to drive disease manage- 2018;136(7):779-85. 14. Nair DG, Renga V, Lindenberg R, et al. Optimizing recovery of enrolled patients (n=12) in the ment forward and overcome barri- potential through simultaneous occupational therapy and non- treatment group, but its application ers to conventional treatment. New invasive brain-stimulation using tDCS. Restor Neurol Neurosci. 2011;29(6):411-20. in glaucoma management is promis- technology is moving towards less 15. Song S, Sandrini M, Cohen LG. Modifying somatosensory ing. A larger prospective random- invasive and more objective mea- processing with non-invasive brain stimulation. Restor Neurol Neurosci. 2011;29(6):427-37. ized double blind, sham-controlled sures for chronic diseases such as 16. Chrysikou EG, Hamilton RH. Noninvasive brain stimulation trial compared rtACS to placebo glaucoma. While further research is in the treatment of aphasia: exploring interhemispheric relationships and their implications for neurorehabilitation. Restor in partially blind patients with needed, the Bionode IOPTx system Neurol Neurosci. 2011;29(6):375-94. glaucoma (n=33) or other causes has the potential to play a promis- 17. Sabel BA, Fedorov AB, Naue N, et al. Non-invasive alternating current stimulation improves vision in optic neuropathy. of optic nerve damage (n=50) and ing role in the glaucoma manage- Restor Neurol Neurosci. 2011;29(6):493-505. demonstrated a 24% improvement ment algorithm. ■ 18. Gall C, Schmidt S, Schittkowski MP, et al. Alternating current stimulation for vision restoration after optic nerve damage: A in visual fields in the treatment Drs. Lukasik is a research fellow randomized clinical trial. PLoS ONE. 2016;11(6):e0156134. group.18 In the future, this technol- at the Prism Eye Institute. 19. Berdahl JP, Fautsch MP, Stinnett SS, Allingham RR. Intracra- nial pressure in primary open angle glaucoma, normal tension ogy could possibly maximize the Dr. Ahmed practices at the Prism glaucoma, and ocular hypertension: a case-control study. Invest residual visual potential of patients Eye Institute, Mississauga, Canada Ophthalmol Vis Sci. 2008;49(12):5412-8. 20. Ren R, Jonas JB, Tian G, et al. Cerebrospinal fluid pres- with glaucoma who have significant and is a professor of ophthalmol- sure in glaucoma: a prospective study. Ophthalmology. loss of visual field. ogy at the University of Toronto, 2010;117(2):259-66.

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A Light in the DARC: Seeing Glaucoma Before it Strikes This cutting-edge technology could give us a window into the disease earlier in its course—shifting treatment ahead and possibly preventing vision loss. By Melanie T. Almonte, RN, BSN, MSc, and M. Francesca Cordeiro, PhD, MRCP, FRCOphth

pon initial so doing, we hope to diagnosis, a provide the eye care new glaucoma community with tools Upatient typi- to identify clinically cally faces some grim modifiable targets realities. They learn before RNFL loss hap- that their neuro-oph- pens, possibly even thalmic infrastructure allowing us to stave is already damaged— off that previously and irreversibly unavoidable conse- so—because as much quence. as 40% of retinal Apoptosis occurs ganglion cell (RGC) in all multicellular degeneration occurs organisms, permitting before the condition cell death without is even clinically dis- necrosis and subse- tinguishable through Fig. 1. This diagram shows where annexin-5 binds to an apoptosing cell quent inflammation. visual field changes.1,2 compared with a normal cell. However, pathogenic They are also highly altered rates of this vulnerable to further vision loss. coma’s story, our research team has process are implicated in hemato- And not a single treatment in the been working on a promising new logic, cardiovascular, neurodegen- clinician’s arsenal can undo any of diagnostic approach to improve erative (Alzheimer’s, Parkinson’s) the damage. early diagnosis that detects glauco- and retinal (AMD) diseases.6-14 In Population-wide, the prospects matous changes at a cellular level. early apoptosis, the cell membrane are no better. Glaucoma is respon- changes its structure, and phosphati- sible for 15% of all blindness with Detecting Cell Death dylserine, a membrane phospholipid, over 500,000 new cases each year.3,4 Recent advances in OCT technol- moves from within the cell to the In the United States alone, 2.9 mil- ogy have given clinicians the ability outer surface. The protein annexin- lion people are affected, represent- to measure retinal nerve fiber layer A5 has been extensively used in cell ing 2.1% of the population over the (RNFL) and ganglion cell complex biology to assess apoptosis in cancer, age of 40.5 These estimates are only (GCC) thickness, but of course stroke and heart disease.15 It contrib- predicted to worsen as the popula- the process begins earlier than utes to the regulation of membrane tion ages. that, at the cellular level. What we permeability and repair, making it It is common to detect retinal see in RNFL or GCC dropout is an ideal marker of cellular predispo- neurodegeneration only after exten- axonal loss. But, what of the cells sition to apoptosis. sive RGC death and significant themselves? Our approach images We have developed a novel tech- visual loss have already occurred. the process of apoptosis, or “pro- nique called DARC (detection of Given the primacy of RGCs in glau- grammed cell death” as it occurs. In apoptosing retinal cells) to monitor

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this process of retinal cell death in a fluorescein or indocyanine green progression. Results from the Phase vivo. Using a fluorescently labeled angiogram.15 Before and following II study should be reported soon. variant of annexin-A5, a protein injection with ANX776, real-time that binds to the exposed phospha- images using near-infrared confocal Future Practice Implications tidylserine, and because the eye is scanning laser ophthalmoscopy cap- DARC offers a unique imaging transparent, we were able to visual- tured retinal images at zero, 15, 30, technique that is able to use the ize the fluorescence and identify 60, 120, 240 and 360 minutes. To eyes as a ‘window’ into the central individual apoptosing cells (Figure establish dose safety and efficacy, nervous system in order to charac- 1). The eye is unique in this ability we administered ascending doses of terize events at a cellular level. This due to the transparent nature of the 0.1mg, 0.2mg, 0.4mg and 0.5mg in novel technique could potentially optical media. four single-dose groups of patients. provide a powerful new tool to This led to the DARC project, a Retinal imaging and pharmacoki- identify patients with pre-perimetric unique collaboration between Impe- netic studies were performed over glaucoma, enabling early treatment, rial College London and University six hours. The resultant images which may prevent or delay irre- College London, funded through displayed hyperfluorescent spots versible visual loss. the Wellcome Trust. In the Phase I appearing on the retina, thought Just enabling early therapy initia- clinical trial, safety and tolerability to represent individual apoptosing tion by conventional pressure-low- of DARC was assessed; however, retinal cells. ering means would be a benefit we we also wanted to compare whether As far as we are aware, this mile- hope to see DARC bring to light. there was a different signal between stone was the first experiment of But the treatment effect of neuro- healthy controls and those who had its kind to visualize in vivo retinal protective agents, such as brimo- progressing glaucoma. Sixteen sub- apoptosis in humans. Importantly, nidine, memantine and glutamate, jects—eight healthy volunteers and ANX776 was found to be safe and can all be documented via DARC eight with early, progressing glau- well-tolerated with a short half-life imaging. The quest to achieve a coma—were included in the trial. of 30 minutes. viable neuroprotective treatment Annexin-776 (ANX776), espe- A Phase II trial has now been per- is a Herculean task, and we hope cially created for this application, formed in patients with glaucoma, our efforts to develop DARC might was intravenously administered AMD, optic neuritis (multiple assist in the undertaking. similar to the procedure used for sclerosis), Down’s syndrome (who This new technology platform display similar patho- also opens the possibility of directly logical features as in observing the effect of treatments in Alzheimer’s disease) neurodegenerative disease using an and healthy volunteers endpoint based on the direct assess- to further characterize ment of retinal cell death, therefore the differences in spot serving as a surrogate biomarker in count, distribution and clinical trials. morphology between The hope is that with the results diseases (Figure 2). from further work in other condi- These four diseases tions, DARC may also improve all lack techniques to diagnosis and provide treatment achieve early diagnosis options in a variety of neurodegen- and monitor disease erative conditions, for which there activity, a barrier to are no effective cures. developing effective These are early days for sure, neuroprotective treat- but we on the research team are ments. optimistic and excited about where Particular to glau- we’re heading. ■ Fig. 2. This retinal image was acquired using the DARC coma, there is also an Ms. Almonte is the research nurse technique during the DARC Phase II trial. The individual unmet clinical need for at Imperial College Ophthalmic apoptosing retinal nerve cells (bright spots) are clearly a surrogate marker to Research Group, Imperial College distinguishable. predict future disease London.

40 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

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RO0219_Katena.indd 1 1/23/19 10:18 AM glaucoma: a comparison of patients progressing to blindness treatment strategies. Drugs. 1996;51(1):28-44. Dr. Cordeiro is professor of glau- from glaucoma with patients maintaining vision. Am J Oph- 10. Pollard H, Cantagrel S, Charriaut-Marlangue C, et al. coma and retinal neurodegeneration thalmol. 2002;133(6):764-72. Apoptosis associated DNA fragmentation in epileptic brain 4. Congdon N, O’Colmain B, Klaver CC, et al. Causes and damage. Neuroreport. 1994;5(9):1053-55. studies at University College Lon- prevalence of visual impairment among adults in the United 11. Portera-Cailliau C, Sung CH, Nathans J, Adler R. Apoptotic States. Arch Ophthalmol. 2004;122(4):477-85. photoreceptor cell death in mouse models of retinitis pigmen- don, professor of ophthalmology 5. Gupta P, Zhao D, Guallar E, et al. Prevalence of glaucoma tosa. Proc Natl Acad Sci USA. 1994;91(3):974-78. and director of the ophthalmology in the United States: The 2005-2008 National Health and 12. Gschwind M, Huber G. Apoptotic cell death induced by Nutrition Examination survey. Invest Ophthalmol Vis Sci. beta-amyloid 1-42 peptide is cell type dependent. J Neuro- research group at Imperial College 2016;57(6):2905-13. chem. 1995;65(1):292-300. London, and consultant ophthal- 6. Selleri C, Maciejewski JP, Sato T, Young NS. Interferon- 13. Walkinshaw G, Waters CM. Induction of apoptosis in gamma constitutively expressed in the stromal microen- catecholaminergic PC12 cells by L- DOPA. Implications mologist at Western Eye Hospital. vironment of human marrow cultures mediates potent for the treatment of Parkinson’s disease. J Clin Invest. hematopoietic inhibition. Blood. 1996;87(10):4149-57. 1995;95(6):2458-464. 14. Reme CE, Grimm C, Hafezi F, et al. Apoptotic cell death in 1. Kerrigan-Baumrind LA, Quigley HA, Pease ME, et al. Num- 7. Raza A, Mundle S, Iftikhar A, et al. Simultaneous assessment of cell kinetics and programmed cell death in bone mar- retinal degenerations. Prog Retin Eye Res. 1998;17(4):443- ber of ganglion cells in glaucoma eyes compared with thresh- row biopsies of myelodysplastics reveals extensive apoptosis 64. old visual field tests in the same persons. Invest Ophthalmol as the probable basis for ineffective hematopoiesis. Am J 15. Yap TE, Donna P, Almonte MT, Cordeiro MF. Real-time Vis Sci. 2000;41(3):741-8. Hematol. 1995;48(3):143-54. imaging of retinal ganglion cell apoptosis. Cells. 2018;7(6). 2. Zeyen T. Target pressures in glaucoma. Bull Soc Belge 8. Thompson CB. Apoptosis in the pathogenesis and treatment 16. Galvao J, Davis BM, Cordeiro MF. In vivo imaging Ophtalmol. 1999;274:61-5. of disease. Science. 1995;267(5203):1456-62. of retinal ganglion cell apoptosis. Curr Opin Pharmacol. 3. Oliver JE, Hattenhauer MG, Herman D, et al. Blindness and 9. Festoff BW. Amyotrophic lateral sclerosis: current and future 2013;13(1):123-27. Bioengineering the Retinal Pigment Epithelium New stem cell-based therapies are paving the way for age-related macular degeneration treatment. By Amir H. Kashani, MD, PhD, Diana Hong, BS, and Mark S. Humayun, MD, PhD

ver the last several decades, While there are many differences based on the presence or absence advances in stem cell biol- between these two types of cells, one of neovascularization, respectively.2 ogy have opened the door major distinction is that iPSC can be Patients with wet AMD have sev- Oto cutting-edge clinical trials obtained from the same person who eral treatment options, including aimed at treating age-related macu- needs the stem cell-based therapy, intravitreal injection of anti-vascular lar degeneration (AMD), one of the thereby minimizing the chances of endothelial growth factor (VEGF) leading causes of blindness in the an immune response. However, cre- drugs, laser photocoagulation to western world.1 Research focuses on ating iPSC can be a labor-intensive ablate the neovascular membrane, two main categories of stem cells, and expensive process that is not surgical removal of the neovascular human embryonic stem cells (hESC) currently commercially feasible. membrane with or without retinal and induced pluripotent stem cells Nevertheless, both cell types have translocation and photodynamic (iPSC). hESC are derived from the been used to generate replacement therapy.3 Applications of stem cell- early blastocyst stage of a fertilized tissue for subjects with atrophic reti- based therapy in NVAMD are likely human egg that has been donated nal pigment epithelium (RPE) and limited to cases involving RPE tears to research. They have the ability AMD. Here we discuss the current or RPE damage from recurrent sub- to differentiate indefinitely and can research efforts to harness the heal- retinal hemorrhage. become any cell type in the body. ing powers of stem cell therapy for Unlike its neovascular counter- In contrast, iPSC are derived from future AMD treatment. part, dry AMD lacks therapeutic adult human cells, usually skin cells. options and causes debilitating These cells are reprogrammed in the Treatment Needs vision loss, albeit over decades. Pro- lab to revert to the pluripotent state AMD is classified as either neovas- gression and vision loss is character- from which they can be differenti- cular (NVAMD) or non-neovascular ized by focal loss of the RPE and ated into almost any cell type. (NNAMD), also called wet and dry, atrophy of the associated overlying

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034_ro0219_Innovation.indd 42 2/7/19 11:30 AM IN EYE CARE Reprinted from Kashani AH, Lebkowski JS, Rahhal FM, et al. neurosensory layer, a process tomography (SD-OCT) dem- also known as geographic atro- onstrated proper orientation phy (GA).4 In theory, being able and persistence of the RPE to regenerate and replace the layer relative to the surround- damaged RPE through stem cell- ing tissue. The researchers also based treatments could delay or noted evidence of significant even reverse the consequences RPE migration away from the of GA. implantation site, for unclear reasons; but importantly, Research Efforts they saw no indication of Over the past year, three early- transplant rejection. At least phase trials have investigated one subject required further the effects of replacing damaged surgery to repair a retinal RPE in subjects with NVAMD Fig. 1. Above is a 3.5mm × 6.25mm sheet of detachment from proliferative and NNAMD with stem cell- hESC-RPE. Below is the same implant under high- vitreoretinopathy following derived counterparts—each with magnification.6 implantation—a complication exciting results. that illustrates the difficulty of The earliest of the three Further analysis revealed one the surgical procedure. studies, reported in the New Eng- more complication, this time with Most recently, our group land Journal of Medicine in 2017, the biocompatibility of the sheet reported preliminary results in Sci- included one patient with NVAMD itself. Imaging of the postoperative ence Translational Medicine on who had severe vision loss and was anatomy of the sheet showed it did five patients with severe vision loss unresponsive to conventional ther- not automatically conform to the from advanced dry AMD and GA.6 apy.3 As part of the trial, the patient anatomy of the native RPE mono- These patients were implanted with received a transplant consisting layer. Despite these setbacks, the a ~3mm x 6mm sheet of hESC-RPE of iPSC-RPE. A 1.3mm x 3.0mm researchers felt this heroic attempt on a biosynthetic substrate that sheet of iPSC-RPE created using the at replacing damaged RPE dem- mimics the native Bruch’s mem- patient’s skin fibroblasts was surgi- onstrated the successful creation brane in several aspects (Figure 1). cally placed under the fovea. Unfor- and surgical implantation of iPSC- Most importantly, this substrate has tunately, the researchers observed no RPE. The results provided enough permeability properties that allow change in visual acuity during the information to keep investigations nutrients and oxygen to diffuse back postoperative one-year follow-up, moving forward, as there was no and forth between the retina, RPE and retinal sensitivity also remained evidence of transplant rejection or ill and choriocapillaris. The interim unchanged. However, a modest effects of the implant on the subject. results of this phase 1/2a study improvement on the National Eye In April 2018, another study, demonstrated that the procedure Institute Visual Function Question- reported in Nature Biotechnology, was well-tolerated and three of the naire 25 (VFQ-25) and a more included two patients with wet five subjects showed signs of visual foveal-centric fixation point showed AMD and severe vision loss who function improvement. While the some promise. were treated with hESC-RPE cells.5 small sample size hinders our ability Further study with a second In this study, the surgeon used an to determine whether the improve- patient was hampered by several artificial polymer to support the ment is statistically or clinically complications, beginning with RPE monolayer, which helped with significant, one patient maintained the concern for potential medical the surgical delivery of the cells into a 17-letter improvement, as well risk due to genetic alterations. In the area where the RPE had been as improved fixation, over three addition, the cost of the iPSC-RPE damaged or ripped as a result of follow-up visits. differentiation procedure was pro- the NVAMD process. Of the 10 Postoperative OCT imaging dem- hibitive for additional studies, and patients enrolled in this study, two onstrated a monolayer of RPE that despite the sophisticated surgical received the transplantation and is quite similar to the native anat- methods used in the study, the iPSC- were included in published findings omy of the hosts’ RPE, suggesting RPE sheet was difficult to handle to date. At the one-year follow-up, the implant is integrating with or intraoperatively. spectral-domain optical coherence supporting the overlying host retina

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where viable photoreceptor inner to the two previous studies, we have suggests that the cell-based thera- and outer segments are present at noted no evidence of transplant pies, when done correctly, are well- the edge of the GA (Figure 2).7 This rejection or ill effects on the sub- tolerated and a feasible therapeutic preliminary data suggests short-term jects, although we have yet to report modality. safety of the implant, as well as its on the final, long-term results. The efficacy of these treatments potential efficacy. remains to be proven, and several The study is still ongoing, with 16 Surgical Concerns research hurdles remain. Therefore, subjects currently enrolled. Similar The surgical methods involved in follow-up studies will look closely

Reprinted from Kashani AH, Lebkowski JS, Rahhal FM, et al. these studies can be challenging, at the data to determine the correct and proper patient selection is patient selection criteria, as well as critical to their success.4 Subjects what clinical criteria may define with GA have generally had long- efficacy. For example, because GA standing disease and atrophy of patients often have chronic dis- the photoreceptor layer in addi- ease and overlying retinal atrophy, tion to the RPE. This often causes improvements in traditional visual the remaining retina to be highly acuity may be limited in these end- adherent to the underlying aber- stage cases. Despite this limitation, rant Bruch’s membrane, making three subjects in our study still surgical separation of the retina showed signs of improvement. The formidable. Careful surgical plan- favorable outcomes suggest these ning, patient selection and inno- subretinal procedures may be war- vative surgical tools are needed ranted, even in later stages of the dis- to avoid potentially serious ease. Therefore, achievable clinical complications such as prolifera- end-points other than acuity must be tive vitreoretinopathy, which has identified to guarantee a benefit to confounded previous submacular potential prospective patients. surgeries as is described in the Overall, the future of stem cell- submacular surgery trials for based retinal therapy is bright, and a NVAMD.5 great deal of hope exists for patients With the advent of modern, suffering from what is currently an small-gauge vitreoretinal surgery untreatable and blinding disease. ■ and equipment, the success rates Dr. Kashani is an assistant profes- have increased, while complica- sor at the University of Southern tion rates for surgery have dra- California’s (USC) Roski Eye Insti- matically decreased over the past tute and Keck School of Medicine of few decades. In all of the studies USC. He is a member of the Insti- reported here, custom surgical tute for Biomedical Therapeutics. instruments were designed and Ms. Hong, a medical student at implemented for delivery of the the California Northstate University, RPE implants. It is likely that the is interested in purusing ophthal- current challenges facing stem mology and is doing a research cell-derived RPE implantation will year elective at the USC Roski Eye be overcome with the aid of tech- Institute. nological advances. Dr. Humayun is a professor of Fig. 2. Above, the study subject’s pre-op ophthalmology and biomedical fundus photo shows large areas of RPE loss, The results of these exciting engineering at the USC Roski Eye consistent with GA. Middle, the fundus photo studies lay the groundwork for a Institute and Keck School of Medi- 180 days after implantation with a sheet of promising future in AMD treat- cine of USC. He is co-director of the hESC-RPE.6 Bottom, the annotated post-op ment using stem cell-derived USC Roski Eye Institute and direc- image shows the location of GA (white dashed therapies. The lack of serious tor of the Institute for Biomedical line) and the implant (black dashed lines). and unanticipated adverse events Therapeutics.

44 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

034_ro0219_Innovation.indd 44 2/7/19 11:30 AM SERVICE SOLUTIONS

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RO0219_Lombart.indd 1 1/24/19 4:12 PM Cost-Effectiveness Study Group. Forecasting age-related tion. N Engl J Med. 2017;376(11):1038-46. Financial disclosure: The sponsor, macular degeneration through the year 2050—the potential 5. da Cruz L, Fynes K, Georgiadis O, et al. Phase 1 clinical Regenerative Patch Technologies impact of new treatments. Arch Ophthalmol. 2009;127(4):533- study of an embryonic stem cell-derived retinal pigment 40. epithelium patch in age-related macular degeneration. Nat (RPT), and the California Institute 2. Nazari H, Zhang L, Zhu D, et al. Stem cell based therapies Biotechnol. 2018;36(4):328-37. for Regenerative Medicine provided for age-related macular degeneration: The promises and the 6. Kashani AH, Lebkowski JS, Rahhal FM, et al. A bioengi- challenges. Progress in Retinal and Eye Research. 2015;48:1- neered retinal pigment epithelial monolayer for advanced, grant support to USC. Dr. Huma- 39. dry age-related macular degeneration. Science Translational yun has intellectual property related 4. Kashani AH. Stem cell therapy in nonneovascular age- Medicine. 2018;10(435). related macular degeneration. Invest Ophthalmol Vis Sci. 7. Kashani AH, Chen CL, Gahm JK, et al. Optical coherence to this study. 2016;57(5):ORSFm1-9. tomography angiography: A comprehensive review of current 3. Mandai M, Watanabe A, Kurimoto Y, et al. Autologous methods and clinical applications. Progress in Retinal and Eye 1. Rein DB, John S. Wittenborn JS, Zhang X; Vision Health induced stem-cell-derived retinal cells for macular degenera- Research. 2017;60:66-100. Iontophoresis: Wave of the Future? A low-level electrical current may turbo-charge topical drug delivery to the eye. By Barbara Wirostko, MD, and Michael Raizman, MD

or years, researchers looked for frequent dosing, which often results 1900s, only within the last few years ways to maximize the effects of in poor compliance, reduced treat- have controlled clinical studies tested topical treatments for chronic ment effect, local tolerability issues its efficacy.2 Iontophoresis is a non- Focular conditions such as dry and negative outcomes. invasive process that allows a greater eye and uveitis. While eye drops A novel drug delivery system that bioavailability of a drug to reach the are simple in theory, in practice uses a small electrical current— anterior and posterior segments than they come with a host of issues that known as iontophoresis—may soon is normally possible with topical hamper their efficacy. Eye drops reduce these limitations by allow- application.3 It is also safer than sys- deliver a volume of 30µl to 50µl of ing eye care practitioners to achieve temic dosing, which exposes patients medication to the eye, most of which topical delivery of concentrated to a higher risk of system-wide drains into the nasolacrimal system medication through a simple, in- adverse effects, and intravitreal injec- or spills onto the lower lid—mean- office process. tion, which is invasive and increases ing only 1% to 5% of the drug is As the current (Dr. Wirostko) and the risk of infection.3 actually absorbed by the eye upon former (Dr. Raizman) chief medical Ocular drug delivery through instillation.1 This necessitates more officers of EyeGate Pharmaceuti- iontophoresis follows the principle cals—the company that like charges repel and opposite developing this tech- charges attract.4 This allows more nology—we have had effective penetration through ocular the privilege of help- tissues by promoting the move- ing bring this exciting ment of a charged drug across bio- concept closer to real- logical membranes and enabling the ization as a commer- delivery of negatively or positively cially viable product. charged therapeutics through tissues Here, we share what to targeted areas.3,4 we have learned and The amount of the drug that where we anticipate enters the eye can be controlled in the technology going. two ways: the strength of the current and the duration of the treatment. A Shocking By controlling the drug amount, Discovery the clinician can deliver therapeutic The EyeGate II includes an applicator placed on the While the concept of levels of the drug into the eye while conjunctiva and a generator connected to an electrode iontophoresis dates minimizing systemic absorption.3 In attached to the patient’s forehead. back to the early a Phase III trial in anterior uveitis

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patients, iontophoresis drug delivery times over a three-week period reduced application of conventional prior to and following treatment topical drugs by almost 98%—two with the EyeGate II system. iontophoretic treatments were equiv- Although the primary end- alent to 154 eye drops.5 points concerning improvement in signs and symptoms at the Going Electric fifth visit were not achieved, The system developed by EyeGate both therapeutic groups showed Pharmaceuticals, called EyeGate some statistically significant II, uses an electrical field generated gains at various other time by a low-level current to enhance points.6 The low-dose protocol the mobility of charged particles.3 appeared more effective than the The device combines an applicator high-dose regimen; the research- placed on the conjunctiva at the ers proposed that this may be limbus and a generator connected to because the high-dose applica- The drug residing in the applicator is an electrode attached to the patient’s tion drove the therapeutic agent propelled through the conjunctiva and sclera forehead.3 The generator creates too deeply into the globe, reduc- during electrical stimulation. an electric field inside the applica- ing efficacy relative to the lower- tor and an opposite charge on the dose effect. ogy attributable to the medication or electrode. The drug resides in the The low-dose group also exhibited the iontophoresis treatment.7 applicator and is propelled through statistically significant improvements One such circumstance requiring the conjunctiva and sclera during the in corneal staining, ocular protection repeated corticosteroid use that may periods of electrical stimulation.3 index and ocular discomfort dur- benefit from iontophoresis is post- The therapeutic agent, EGP-437, ing follow-up visits.6 Clinical find- cataract surgery. Visual recovery is a 40mg/mL dexamethasone phos- ings show that treatment-emergent after cataract surgery can be delayed phate (DP) formulation specifically adverse events (AEs) were expe- by inflammation, which can be developed for use in iontophoresis to rienced by 87% of patients and caused by topical corticosteroids. In treat inflammatory conditions such were consistent across all treatment an effort to learn whether iontopho- as anterior uveitis.5 This drug and groups.6 Most were mild, and no resis can help, a study presented at the EyeGate II drug delivery system severe AEs were observed.6 ARVO 2017 by Dr. Wirostko sought are under investigation.5 Researchers from EyeGate also to determine the safety and efficacy evaluated the toxicokinetics and of EGP-437 in managing post-surgi- Study Notes tolerability of DP by transscleral cal inflammation and pain.8 Upon assessing the safety and effi- iontophoretic delivery to rabbit eyes The study found that patients cacy of EGP-437 in dry eye treat- in a study that ultimately found receiving the 4.5mA/minute and ment, researchers found that ocular repeated treatments might be safe to the 14mA/minute doses exhibited iontophoresis of the drug demon- treat inflammatory ocular disorders the best results, with 20% to 30% strated statistically and clinically that require prolonged or repeated achieving an anterior chamber cell significant improvements in signs corticosteroid therapy.7 Subjects count of zero at day seven and 70% and symptoms within a controlled received EGP-437 transsclerally once to 80% at day 28, 70% of 4.5mA/ adverse environment model.6 biweekly for 24 consecutive weeks minute patients and 90% of 14mA/ The participants (103 dry eye at doses of 10mA/minute, 14mA/ minute patients reporting no pain patients) were randomly divided into minute and 20mA/minute.7 The on day one and 0% experiencing three groups—low-dose, high-dose regimen was well-tolerated, and side elevated IOP.8 Post-op pain and and placebo arms—with the follow- effects either were expected reac- inflammation were managed as early ing characteristics: 7.5mA/minute tions to the ocular applicator or the as days one and seven, respectively.8 at 2.5mA with DP in the reservoir, iontophoresis process or arose from The study concluded that the ion- 10.5mA/minute at 3.5mA with DP factors unlikely related to the treat- tophoretic delivery of EGP-437 is a in the reservoir and 10.5mA/minute ment.7 They note that there was no safe and effective way to deliver ade- at 3.5mA with no DP in the reser- effect on intraocular pressure (IOP), quate amounts of steroids and has voir.6 Patients were assessed seven electroretinography or histopathol- the potential to eliminate the daily

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need for corticosteroid eye drops in More recently, a team of research- versity of Utah. She practices at the post-cataract surgery patients.8 ers conducted the first-in-human, John A. Moran Eye Center at the EyeGate researchers also looked randomized, double-masked, dose- University of Utah. into iontophoresis for anterior escalating study of iontophoretic Dr. Raizman is a consultant for uveitis to establish safe, effective administration of DP for scleritis, the Ophthalmic Consultants of dose levels of EGP-437 and evalu- suggesting the iontophoretic delivery Boston, the director of the Cornea ate the systemic pharmacokinetic of corticosteroids to be a promis- Fellowship and the Cornea and profile after a single iontophoresis ing, well-tolerated and safe potential Cataract Service at the New England administration of EGP-437 to 40 treatment.10 They found the lowest Eye Center, Tufts Medical Center subjects at four different doses.9 The dose (1.2mA/minute at 0.4mA) to be and a professor at the Tufts Univer- team found that following a single the most efficacious, with five out of sity School of Medicine. He was the treatment with EGP-437, half of seven eyes meeting the primary effi- former chief medical officer of Eye- the patients achieved an anterior cacy outcome within 28 days.10 Gate Pharmaceuticals. chamber cell count of zero within 1. Novack GD. Ophthalmic drug delivery: development and reg- two weeks and the majority by day Commercialization Nears ulatory considerations. Clin Pharmacol Ther. 2009;85(5):539- 9 43. 28, requiring no further treatment. After more than a decade of R&D, 2. Myles ME, Neumann DM, Hill JM. Recent progress in ocular IOP and best-corrected visual acu- some of these efforts are approach- drug delivery for posterior segment disease: emphasis on transscleral iontophoresis. Adv Drug Deliv Rev. 2005;57(14):2063- ities were not affected, and there ing commercialization. EyeGate 79. 3. Than TP, Chaglasian EL. Ocular drug delivery—pressing was actually a lower incidence of completed the second Phase III study forward. RCCL. 2013;150(7):12-3. increased IOP.9 While patients expe- in mid-2018 looking at the appli- 4. Eljarrat-Binstock E, Domb AJ. Iontophoresis: a non-invasive ocular drug delivery. J Control Release. 2006;110(3):479-89. rienced low, short-term systemic cation of the EGP-437 in anterior 5. EyeGate Pharma. www.eyegatepharma.com. Accessed Janu- ary 10, 2019. exposure to dexamethasone follow- uveitis and is continuing to assess the 6. Patane MA, Cohen A, From S, et al. Ocular iontophoresis of EGP-437 (dexamethasone phosphate) in dry eye patients: ing treatment, the researchers did next steps toward approval. Once results of a randomized clinical trial. Clin Ophthalmol. not observe any corticosteroid medi- clinicians have access to the EyeGate 2011;2011(5):633-43. 7. Patane MA, Schubert W, Sanford T, et al. Evaluation of ocular ated effects and add that the major- II system, the eye care community and general safety following repeated dosing of dexamethasone 9 phosphate delivered by transscleral iontophoresis in rabbits. J ity of AEs were mild. will be able to learn more about its Ocul Pharmacol Ther. 2013;29(8). To date, roughly 2,000 EGP-437 real-world performance and, ulti- 8. Wirostko BM, Assang CM, Mann B, et al. Efficacy and safety of an iontophoresis platform to manage post-cataract inflam- iontophoretic treatments have been mately, where it fits in the overall mation and pain. Poster. ARVO. 2017. 9. Patane MA, Cohen A, Assang CM, et al. Randomized, double- delivered to patients with anterior treatment armamentarium. ■ masked study of EGP-437 in subjects with non-infectious anterior segment uveitis. Poster. AAO. 2010. segment inflammation, posterior ret- Dr. Wirostko is the chief medical 10. O’Neil EC, Huang J, Suhler EB, et al. Iontophoretic delivery inal edema or both, demonstrating officer of EyeGate Pharmaceuticals of dexamethasone phosphate for non-infectious, non-necrotis- ing anterior scleritis, dose-finding clinical trial. Br J Ophthalmol. the safety and utility of this product. and an adjunct professor at the Uni- 2018;102(8):1011-3. While You Were Sleeping A new phototherapeutic contact lens, worn overnight, could effectively address diabetic retinopathy progression. By Mark De Leon, Associate Editor

cular involvement in eye care practitioners can expect burning the peripheral retinal with diabetes is a near certainty far more cases.1 As in so many laser photocoagulation to reduce the as time goes on. Already, chronic conditions, therapy is often metabolic demands that give rise to Omore than four million hampered by patient compliance new vessel growth, or injecting anti- Americans experience some form issues, diminished efficacy over time VEGF roughly every six weeks to of visual impairment from diabetic and adverse effects. arrest angiogenesis. Neither of these retinopathy (DR), and with the Right now, the therapies retina therapies are patient-friendly nor rates of diabetes steadily rising, specialists turn to are rather crude: particularly effective long-term. An

48 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

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RO0219_Lacrivera.indd 1 1/23/19 10:16 AM Photo: Caltech interdisciplinary team of ophthal- the CLEOPATRA study assessed mologists and engineers have their the two-year outcomes of using the sights set on reducing this treatment Noctura in non-central diabetic burden and are developing a new macular edema (DME). The results method of phototherapy using con- show that the light mask was tact lenses that could improve out- not an effective option. While it comes and reduce the adverse effect significantly reduced DME and profile of long-term management. visible cysts in outer ETDRS zones “The big problem with diabetes in at 12 months, the effect did not the retina is that the hyperglycemic translate to significant change in state influences the endothelial cells retinal thickness and it was not and pericytes and really starts to sustained, suggesting that any affect blood flow, and this results in This glow-in-the-dark contact lens could positive morphological effects are ischemia,” says Mark A. Humayun, help reduce DR-related damage from transient and minimal.9 The study MD, PhD, professor of ophthalmol- nighttime rod cell metabolism. also found compliance waned over ogy and biomedical engineering at time and 75% reporting adverse the University of Southern Califor- result of decreased retinal circula- effects, primarily related to disturbed nia. His research team is partnering tion, or the relative demand for oxy- sleep.10 with engineers from California Insti- gen increases due to metabolic stress, While the study did note that tute of Technology led by Yu-Chong an imbalance will lead to hypoxia in the light mask was not an effective Tai, professor of electrical engineer- both the inner and outer retina.7 option to treat non-central DME, it ing and medical engineering. The “We wanted to modulate the was still worth evaluating other pho- groups have collaborated to design activity of the retina and therefore totherapeutic techniques of rod sup- and test a glow-in-the-dark contact not outstrip the oxygen supply of the pression in DR and DME, a pursuit lens for patients to wear overnight. retina in a diabetic patient, where in which the interdisciplinary team “The thought came to us—could it is already compromised,” Dr. has taken great lengths to engage. we modulate ischemia? In the retina, Humayun says. you have a wonderful opportunity Research suggests that prevent- See the Light to do so during the nighttime period ing dark adaptation by delivering According to a paper Dr. Tai pre- when it’s very metabolically active 507nm light to the retina during the sented at an engineering conference and requires a lot of oxygen,” says night might reduce the risk of DR (MEMS 2018), a key factor likely Dr. Humayun. progression.2 In 2017, PolyPhotonix contributing to disturbed sleep from Medical introduced the Noctura phototherapy is the amount of time- Gas Guzzlers 400 Sleep Mask for treatment of varying stimuli on the retina that The impaired vision in low light late-stage DR patients and as a pre- inevitably results from trans-eyelid conditions that marks the beginning ventative measure for those at the illumination. Differential transmis- of visual loss in people with diabetes early stages of the condition. The sion of light through the eyelid, suggests that DR affects rod func- mask’s organic light emitting diodes which varies in thickness, results in tion first.2 This has subsequently (OLED) produce wavelengths that a spatially heterogeneous illumina- been linked to increased oxygen interact with the photoreceptors of tion field.11 Since the eye moves with consumption during dark adapta- the rods, but not those of the cones, respect to this field, photoreceptors tion, as well as retinal hypoxia and at night, ensuring that it would not experience a time-varying illumina- metabolic overload.3-6 This hypoxia disturb the user’s sleep. The com- tion, to which the visual system is upregulates VEGF and provokes the pany suggested the OLED sleep highly attuned. microvascular changes associated masks would prevent the extra con- If it were possible to fix the illumi- with the disease. sumption of oxygen in dark adapta- nation field with respect to the eye— In the dark, rods consume more tion while sleeping, which would not the eyelid—the perception of the oxygen than any other cell in the then reduce inner retinal vascular light stimuli would rapidly decay 8 body. When O2 is reduced, rod sen- stress. through a neural adaptation process sitivity decreases.7 If retinal disease Published in The Lancet Diabetes known as the Troxler effect.12 This constrains oxygen availability as a & Endocrinology in early 2018, would likely make phototherapy

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more tolerable to patients. A second nescent gaseous tritium light sources several seconds since the contact major limitation of trans-eyelid (GTLS) to satisfy the design condi- lens was stationary on the eye under phototherapy is the uncertainty of tions. These light sources are com- scotopic conditions; however, the photon dosing to the retina. Eyelid posed of tritium gas encapsulated in patient could discern the light stimuli transmissivity is known to vary a phosphor-coated glass shell, similar if the contact lens was manually across the human population.13 Also, to those used in glow-in-the-dark repositioned on the eye.11 “Given the eye rolls backward during sleep, markers seen on wristwatches. the stability of the lens on the eye, which affects retinal dosage from the The tritium emits a high-energy the speed and completeness of the illumination source. electron that strikes and excites the Troxler effect is remarkable,” Dr. “We believe there are clear phosphor, leading to highly reliable Cook says. benefits to providing phototherapy light emission. The light sources’ Dr. Cook and the rest of Dr. Tai’s from a source under the eyelid minute profile (300µm D × 2000µm team transferred the prototypes and immobilized with respect to L) enables integration into thin over to Dr. Humayun’s group who the eye—and this is where contact contact lens designs. Dr. Tai’s team then investigated the bioactivity of lenses play a key role,” Dr. Tai selected a green emitting phosphor the lens through electroretinogram wrote in his MEMS 2018 paper.11 to maximize stimulation of rod cells (ERG) flash response recordings in So, the team recently constructed at 498nm peak absorbance. The rabbits. The analyzed recordings a phototherapeutic contact lens sources have a 12-year half-life and revealed that both the amplitude that may help to manage DR by do not emit any ionizing radiation and implicit time of the b-wave in suppressing the dark current in the outside the glass shell, making them the treated eye was found to be rod and reducing retinal metabolism. remarkably safe and reliable. How- significantly shorter than in the ever, the team recommends the lens untreated eye, a noted characteristic Making Contact be replaced after one year of use.11 of suppressed dark adaptation.14 Given that retinal hypoxia drives According to Colin Cook, PhD, a Regarding the difference in b-wave VEGF expression, the research team researcher who worked closely with amplitude, the phototherapeutic aimed to create a phototherapeu- the contact lens engineering team contact lens caused an average sup- tic contact lens that increased the in Dr. Tai’s lab during his doctoral pression of rod cell dark adaptation minimum retinal oxygen tension by program, fouling of the lens material to 32 ±2% of full dark adaptation.11 100%. They used a silicone-based due to repeated use is the limiting Adjusting for likely human response contact lens embedded with a ring of factor for the product’s lifetime. would put the expected rod cell gaseous tritium light sources provid- The design has the GTLS suppression in diabetes patients at ing continuous illumination over the arranged in an evenly spaced radial approximately 50%, exceeding the lifetime of the lens. Currently, the pattern starting at a radius of design specification but well within a lens is made up of approved poly- 1.5mm and ending at 3.5mm. “This tunable range.11 mers that give it acceptable wetta- annular arrangement of light sources According to Dr. Humayun, they bilty, comfort and fouling resistance. provides an unobstructed view will need to collect human ERG

Using the 1D retinal model on during photopic vision when the Photo: Erik Hanson, MD theoretical estimation of retinal pupil is constricted, while directing oxygenation during retinal artery the complete phototherapeutic dose occlusion, the team found that sup- through the dilated pupil under pressing rod metabolism to 132mm scotopic vision or sleep,” Dr. Tai Hg/s was necessary to double the explained in his paper.11 minimum value of retinal oxygen Testing the design with a human tension. They then estimated that eye ensured that this annular metabolic suppression required reti- arrangement provided a sufficient nal irradiance of 30 photons/s/µm2.11 artificial pupil under photopic, or When designing the lighting sys- well lit, vision, while the GTLS could tem, the team took into account the pass light through the dilated pupil limitations of a contact lens pack- under scotopic, or low light, vision. A light-emitting contact lens could age size, reliability and safety. They The wearer reported the disap- potentially help slow down pathogenesis ultimately decided to use radiolumi- pearance of the light stimuli within in early proliferative diabetic retinopathy.

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data when possible to confirm or it with ortho-K myopia correction. then can we work with the moderate revise these estimates. He is also Thus, the patient is motivated to and severe forms; in the latter two, it looking forward to verify and vali- wear the lens nightly for their daily would be in combination with exist- date the lens on human test subjects vision correction, but in doing so ing therapies,” Dr. Humayun notes. as a baseline to understand what helps prevents retinopathy from Phototherapy represents a prom- modifications and revisions need developing. Dr. Cook has so far been ising noninvasive preventative to be done in each future step. He able to produce lenses with dual measure for diabetic retinopathy, encourages his colleagues to avoid phototherapy and corneal refractive and likely other hypoxic eye dis- over-engineering a prototype prior therapy functionality. eases such as macular edema and to human trials. “You have to do Since completing his doctoral age-related macular degeneration. it safely, but there is a sense of program at Caltech, Dr. Cook has Incorporating a glow-in-the-dark urgency,” Dr. Humayun explains. founded Retinox Medical to help light source for phototherapy inside “There are patients at the end of the continue his work translating pho- an overnight lens could provide con- day who could benefit from this.” totherapy technology out of the lab stant illumination to the retina while and into the clinic. Currently, he has maintaining sleep quality. The lens Ortho-K to the Rescue built functioning prototypes that rely may also combat patient compliance Oxygen transmissivity of the lens on the same phototherapeutic prin- issues, as it minimally impacts the has emerged as a key requirement ciple but differ in their mechanism patient’s habits and quality of life. ■ to prevent corneal hypoxia during of light generation. There is a light- 1. Klein R, Klein BEK, Moss SE, et al. The Wisconsin epidemiologic sleep. The FDA recommends a trans- emitting diode (LED) variant that study of diabetic retinopathy. Arch Ophthalmol. 1984;102(4):520- missivity of 125Fatt for overnight provides the ability to control light 32. 15 2. Sivaprasad S, Arden G. Spare the rods and spoil the retina: contact lenses. The 500µm thick intensity and allow photon dosage to revisited. Eye (Lond). 2016;30(2):189–192. lens has a transmissivity (Dk/t) of be fine-tuned for patients. Dr. Cook 3. Arden GB, Wolf JE, Tsang Y. Does dark adaptation exacerbate diabetic retinopathy? Evidence and a linking hypothesis. Vision around 130Fatt, satisfying the FDA’s has also built a chemiluminescent Res 1998; 38: 1723–1729. recommendation. version that could provide a dispos- 4. Drasdo N,Chiti Z, Owens DR, North RV. Effect of darkness on inner retinal hypoxia in diabetes. Lancet. 2002;359: 2251–2253. While many wear contact lenses able option similar to daily contact 5. Harris A, Arend O, Danis RP, et al. Hyperoxia improves contrast sensitivity in early diabetic in the daytime, the development lenses. retinopathy. Br J Ophthalmol. 1996;80:209–13. of extended-wear lenses and 6. Kurtenbach A, Mayser HM, Jagle H, Fritsche A, Zrenner E. Hyperoxia, hyperglycemia, and photoreceptor sensitivity in normal orthokeratology (ortho-K) lenses Night Moves and diabetic subjects. Vis Neurosci 2006;23:651–661. has led to a better understanding of Dr. Humayun believes that the 7. Arden GB, Ramsey DJ. Diabetic retinopathy and a novel treatment based on the biophysics of rod photoreceptors and dark the requirements for overnight wear, contact lens, if validated by human adaptation. In: Kolb H, Fernandez E, Nelson R, ed. Webvision: The including oxygen transmission. trials, could most likely be used with Organization of the Retina and Visual System. Salt Lake City, UT: University of Utah Health Sciences Center; 2015. Dr. Cook believes the key to mild nonprolieferative DR patients 8. PolyPhotonix. Noctura 400 media pack:a new approach to the management of diabetic retinopathy.https://noctura. ensuring long-term compliance with to prevent progression. However, com/wp-content/uploads/2017/12/Noctura-400-Media- phototherapy for DR is coupling he says, “if severe nonproliferative, Pack-20171214-01-1.pdf. December 12, 2017. Accessed January 9, 2019. or even patients at the proliferative 9. Sivaprasad S, Vasconcelos JC, Prevost AT, et al. Clinical efficacy Kids These Days stages, can benefit somewhat from and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular The contact lens format in general may not using the contact lens, the patient’s oedema at 24 months (CLEOPATRA): a multicentre, phase be suitable for all DR patients, but is particu- current injection intervals could be 3, randomised controlled trial.Lancet Diabetes Endocrinol. 2018;6:382–91. larly well suited to adolescents and young prolonged and they could reduce the 10. Sahni JN, Czanner G, Gutu T. Safety and acceptability of an adults. Type 1 diabetes specifically affects organic light-emitting diode sleep mask as a potential therapy for number of injections in a year.” retinal disease. Eye. 2017;31(1):97-106. juveniles, who must manage the condition Dr. Humayun sees the contact lens 11. Cook CA,Martinez-Camarillo JC, Yang Q, et al. Photothera- peutic contact lens for diabetic retinopathy. Paper presented at: for the rest of their life. Given the near uni- working in both scenarios, but it is 2018 IEEE Micro Electro Mechanical Systems;January 21-25, versal onset of retinopathy within 15 years too early to tell because they have 2018; Belfast, UK. 12. Troxler IPV, Uber das Verschwinden gegeb- ener Gegen- of diabetes, they represent a particularly vul- yet to demonstrate how much the stande innerhalb unseres Gesichtskreises. Ophthalmologische nerable group. Also, adolescents represent lens can actually modulate metabolic Bibliothek. 1804;2(2). 13. Bierman A, Figueiro MG, Rea MS, Measuring and predicting a unique subpopulation from a compliance function in a severely compromised eyelid spectral transmittance. J. Biomed. Opt. 2011;16(6):67011. perspective, as they are under the supervi- 14. Cameron A, Mahroo O, Lamb T, Dark adaptation of human rod eye. “If we can modulate only a little bipolar cells measured from the b-wave of the scotopic electroret- sion of parents who are likely to enforce bit, then obviously it will work on inogram. J. Physiol. 2006;575(2):507–26. 15. Harvit DM, Bonanno JA. Re-evaluation of the oxygen diffusion adherence to the preventative regimen. the milder form of the disease, but model for predicting minimum contact lens Dk/t values needed to if we can modulate a fair amount, avoid corneal anoxia. Optom Vis Sci. 1999;76(10):712–9.

52 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

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How to Succeed in Plaquenil Screenings The spectrum of OCT findings associated with the medication can make incorporating the 2016 guidelines harder than you think. Here’s help. By Marlon Demeritt, OD, Sherrol Reynolds, OD, Diana Shechtman, OD, and Jennifer Davidson, OD

laquenil (hydroxychloroquine sulfate, Sanofi-Aventis) and the Pless-used chloroquine are antimalarial drugs with anti- inflammatory properties that are used for the management of a spectrum of inflammatory conditions. Plaquenil is less toxic than chloroquine; however, long-term use of either drug can result in macular toxicity, leading to dev- astating irreversible vision loss. The mechanism of this toxicity Fig. 1a and 1b. These fundus photos, of the right and left eyes respectively, reveal is not clearly understood, though parafoveal ring-shaped “bull’s eye” RPE defects. it is believed that the drug mol- ecule binds to melanin in the retinal pigment epithelium even after cessation of the drug.5 Thus preventing and (RPE).1 This leads to disruption and damage to the detecting early effects of retinal toxicity prior to irrevers- photoreceptors and outer nuclear and plexiform layer, ible complications is key.6 sparing the foveal center and resulting in the “bull’s eye” appearance in the late stage of the disease. Binding of the Follow the Guides drug to melanin in the RPE contributes to, or prolongs, The latest screening guidelines were published in 2016 its toxic effects.2 by the American Academy of Ophthalmology (Table 1). Plaquenil toxicity is typically asymptomatic in early The most important risk factors are dosage and duration stages, but over time can lead to severe vision loss and of use. Dosage greater than 5.0mg/kg over five years dra- retinal damage. The risk of retinal toxicity was initially matically increases the risk of retinal toxicity, and high believed to be less than 1% after long-term (or a cumu- doses can be exceedingly dangerous. As opposed to the lative dosage of 1,000mg).3 The toxicity would double 2011 guidelines, “real weight” is now considered a bet- by 10 years, resulting in a 20% prevalence after 20 ter indicator than “ideal weight” for calculating dosage years.4 However, research now shows toxicity continues for most patients. For example, for the maximum safe

56 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

056_ro0219_plaquenil.indd 56 2/5/19 5:03 PM Figs. 2a. and 2b. OCT of the right eye reveals a “flying saucer sign” of the macula with associated loss of the parafoveal IS/OS junction. Displacement of the inner retinal structures with loss of foveal contour unveils the “sinkhole sign” (see white arrows).

dose of 5.0mg/kg, the threshold dose would be 400mg/ Her best-corrected acuities were 20/40+ OD and day for a patient weighing 175 pounds. Other major risk 20/30- OS. All preliminary testing, including pupils, factors include concomitant renal disease, concomitant extraocular motilities and confrontation fields, were retinal disease and the use of tamoxifen (Table 2).7,8 unremarkable. Slit lamp exam only revealed posterior Currently, one of the primary functional screen- chamber IOLs OU. Intraocular pressures were 14mm ing tests recommended for the evaluation of Plaquenil Hg OU. A dilated fundus exam revealed unremarkable retinal toxicity is 10-2 white stimulus automated visual optic discs and normal physiological cupping. Parafoveal fields; however, research shows Asian patients benefited ring-shaped “bull’s eye” RPE defects in the macula of from 24-2 or 30-2 visual fields, given that toxicity often both eyes were also noted (Figures 1a and 1b). The ves- manifests changes beyond the macula in these patients.9 sels and peripheral exam did not reveal any abnormal Because spectral-domain optical coherence tomography findings in either eye. SD-OCT revealed “flying saucer” (SD-OCT) is readily accessible and able to detect early sign of the macula area with associated loss of the para- structural damage prior to clinical funduscopic findings, foveal IS/OS junction in both eyes, but intact subfoveally it is now one of the primary objective screening tests. (Figures 2a and 2b). No associated drusen was noted. However, variable SD-OCT findings related to Plaquenil The findings were suspicious for retinal toxicity, and retinal toxicity can make the screening data challenging the patient did reveal a history of Plaquenil use start- to interpret; thus, it is important that clinicians become ing at age 30 and lasting for 15 years. She also recalled familiar with the spectrum of SD-OCT findings. being asked to discontinue the medication due to an Although multifocal electroretinogram (mfERG) and unspecified “retinal problem.” She was asked to return fundus autofluorescence (FAF) are not currently primary to clinic for 10-2 visual field testing and diagnosis and tests used in the evaluation of Plaquenil retinal toxicity, management were explained. they may be beneficial when the diagnosis or findings are enigmatic or an adjunct test is warranted. Case Two A review of the various OCT and visual field findings A 26-year-old black female presented in office for her associated with retinal toxicity, as well as case presenta- annual comprehensive eye exam. Her medical history tions and illustrations, can help you be prepared when a was significant for Plaquenil therapy spanning 12 years patient on Plaquenil presents for an eye exam. with a daily dose of 200mg twice daily. She presented with a best-corrected visual acuity of 20/20 OD and Case One 20/20 OS. All preliminary testing revealed normal find- An 87-year-old Caucasian female presented complain- ings. Slit lamp examination was unremarkable; however, ing of blurred vision while reading with her current her ancillary testing revealed macular changes compat- prescription. Her medical history revealed age-related ible with early toxicity. Her SD-OCT reflected localized macular degeneration that was diagnosed approximately parafoveal thinning (Figures 3a and 3b). The Humphrey 30 years ago (for which she uses AREDS2 supplements) visual field 10-2 (white stimulus) was reliable, showing and cataract surgery in both eyes with posterior chamber bilateral, although asymmetric, patchy parafoveal visual intraocular lens (IOL) implementation 10 years prior. field defects (Figures 4a and 4b). Her medical history was remarkable for hypertension, She was educated on the ocular effects of Plaquenil hypocholesteremia and rheumatoid arthritis. She was and the continuous monitoring and management. The currently taking an unknown beta-blocker and statin corresponding prescribing physician was also advised QD. on the findings.

REVIEW OF OPTOMETRY FEBRUARY 15, 2019 57

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Table 1. 2016 Risk Factors Associated with Retinal Toxicity Major Dosage: >5.0mg/kg real weight Duration of use: >5 years, assuming no other risk factors Renal disease: Subnormal glomerular filtration rate Concomitant drugs: Tamoxifen use Macular disease: May affect screening and susceptibility to Plaquenil and chloroquine Lesser Age, liver disease and genetic factors can be associated with retinal toxicity

Screening Protocol ability to detect early macular dysfunction, so it should Proper protocol implementation requires knowing when be included as part of baseline screening. A maximum to evaluate patients on Plaquenil and what ancillary tests daily dose of Plaquenil of 5.0mg/kg real weight is recom- to perform. To start, have patients complete a question- mended. Communication with the prescribing physician naire that answers the following: is also key to proper treatment and management of your • Are you currently taking Plaquenil? If yes, when did patient. you start? • What is your current dosage? Signs • What is your current weight? Eyes affected by Plaquenil toxicity can be diagnosed • Have you previously had baseline ophthalmic test- based on one or more of several possible telltale pre- ing? sentations ranging from structural changes visible on • Are you currently under the care of another optom- imaging equipment to functional changes detectable via etrists or ophthalmologist? testing. These include: • How often do you see your rheumatologist? OCT. The classic retinal toxicity has been described • Are you being treated for kidney disease? as “bull’s-eye maculopathy,” with the appearance of a • Are you also taking tamoxifen? ring of parafoveal RPE depigmentation that spares the See page 63 for a sample questionnaire; it is also avail- fovea (see case presented). The presence of bull’s-eye able for download in the online version of this article maculopathy indicates the disease has been progressing at www.reviewofoptometry.com. To properly screen for years, resulting in foveal thinning and likely vision patients for Plaquenil toxicity, you should have SD- loss.8 SD-OCT is a highly sensitive and reproducible OCT and automated visual fields; it is also beneficial imaging modality used in the detection of Plaquenil reti- to include FAF and mfERG. Although the latest guide- nal toxicity. The preferential loss of photoreceptor IS/OS lines suggest that Amsler grid, color vision and fundus junction makes SD-OCT an ideal tool to identify early photography are not considered necessary for screening patients on Plaquenil, they can still provide useful information. What tests do you need to perform during their baseline screening? During their baseline screening, you should perform Humphrey visual field testing 10-2 (white stimulus) for non-Asian patients to detect paracentral and central scotomas.9 For Asian patients, perform a 24-2 or 30-2 visual field to detect extramacu- lar defects with a retest using 10-2 if any defects are detected.9 SD-OCT allows early detection of damage to the IS/OS junction before you observe retinal findings. Because early toxicity changes can be revealed on SD-OCT, it is prudent to perform a baseline screening Figs. 3a. and 3b. High-resolution OCT demonstrating localized of patients taking Plaquenil. Multifocal ERG has the parafoveal thinning in a patient with early Plaquenil toxicity.

58 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

056_ro0219_plaquenil.indd 58 2/5/19 5:04 PM Table 2. 2016 Screening Guidelines for Plaquenil Retinal Toxicity Recommended Tests Newer Tests of Not Possible Value in Recommended Future for Screening Primary tests (do both): • Microperimetry • Fundus • Automated visual • Adaptive optics examination fields retinal imaging • Time-domain •SD-OCT OCT • Fluorescein angiography • Full-field ERG • Amsler grid • Color testing • EOG Other objective tests (as needed): • mfERG • FAF

changes associated with Plaquenil retinal toxicity. Due to the capabilities of SD-OCT to enhance the structural assessment of the retina, it has allowed for the detection of early damage prior to funduscopic clinical findings. Yet, there are variable SD-OCT findings associated with Plaquenil retinal toxicity. The earliest finding is disruption of the parafoveal photoreceptor inner segment/outer segment (IS/OS) junction, also known as ellipsoid zone or photoreceptor integrity line (Figure 5).10 This disruption is considered one of the strongest indications of early retinal toxicity.10 Early loss of the IS/OS parafoveal junction may be denoted as the attenuation of the homogenous IS/OS junction reflectivity line. This loss may also correlate with a localized parafoveal thinning in the topographical map (Figure 6). In addition, this may correlate to the paracentral scotomas often seen in patients with early toxicity. (Figure 4a and 4b) The more moderate stage of toxicity may be followed by diffuse parafoveal outer nuclear layer (ONL) with inner plexiform layer (IPL) changes (Figure 7).10-12 Inner retina damage is often a consequence of outer retinal damage. Disruption and loss of the external limiting membrane (ELM) may also be an early OCT finding (Figure 6).13 The ELM is theorized to play an important role in maintaining homeostasis of the photoreceptors and outer nuclear layer.14 Patients with an intact ELM at diagnosis of toxicity had a better prognosis and were unlikely to progress, whereas those with ELM disruption were more likely to show progressive changes on SD-OCT.

056_ro0219_plaquenil.indd 59 2/5/19 5:04 PM Retina

Fig. 5. Early SD-OCT finding showing Fig. 6. Localized parafoveal thinning disruption of the parafoveal noted in the topographical map often photoreceptor inner segment/outer correlates with IS/OS defects early in the segment junction. disease course.

Figs. 4a. and 4b. Visual fields of the right and left eyes reveal paracentral scotoma Fig. 7. High-definition OCT reveals moderate plaquenil-related damage with diffuse consistent with Plaquenil toxicity. parafoveal ONL and IPL changes.

Increased thickness of the RPE-Bruch’s membrane sic representation of Plaquenil toxicity is a preservation complex in Plaquenil patients has also been reported as of the outer retinal layers subfoveally with perifoveal loss an early sign. As the drug binds to melanin in the RPE, of the IS/OS junction on both sides of the fovea. Peri- it causes degenerative changes, which leads to alteration foveal IS/OS junction loss is associated with perifoveal in RPE metabolism that contributes to the changes in outer retinal thinning, resulting in an ovoid appearance the RPE-Bruch’s complex.15 Investigators believe that in the central retina, creating the flying saucer sign. The thickening of the outer band results from thickening of description of this sign was helpful in identifying retinal Bruch’s membrane. toxicity as presented in our cases. The “Sinkhole” sign (Figure 2a and 2b) shows dis- Ganglion cell complex (GCC) defect and peripap- placement of the inner retinal structures toward the illary NFL defects (Figures 8 and 9). A 2008 report retinal RPE with variable loss of the foveal contour.15 A described anatomical changes associated with GCC loss gap between the ONL (due to ONL thinning) associated within the parafoveal region, in particular within the with an intact external limiting membrane contributes inferior temporal region. Hence, the perifoveal thinning to a sinkhole appearance and preservation of subfoveal noted on GCC may be attributed to selective thinning of outer layer. The subfoveal IS/OS junction is not affected the ganglion cell layer and inner plexiform layer.17 in the late stage of the disease and associated with severe Visual fields. In early cases of Plaquenil toxicity, an loss.16 early indicator of damage is the appearance of a para- The “Flying saucer” sign. (Figure 2a and 2b) this clas- central scotoma seen on automated visual field testing

60 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

056_ro0219_plaquenil.indd 60 2/5/19 5:04 PM Fig. 8. High-definition OCT revealing disruption and loss of the external limiting membrane as early OCT findings.

in the absence of fundus changes.18 Each of the testing strategies can be used to detect early toxicity changes, but the presentation of the visual field effects will vary. Due to the central area being depressed in the 24-2 and 30-2 testing strategies, it is difficult to discern the central 2-degree field of sparing seen in the 10-2 tests. You can conceivably misinterpret the visual field if the 24-2 or 30-2 testing strategies are used, because the scotoma may appear as a small central defect as opposed to a paracentral ring scotoma. When using the larger testing strategies, a strong indication of Plaquenil toxicity is the presentation of a scotoma in the central 4 degrees of fixation. Researchers suggest that one central point in both eyes indicates toxicity and one should have a low threshold with regards to any defects.19 The misinter- preted visual field defect using the larger testing strategies could potentially delay the diagnosis of Plaquenil toxicity resulting in irreversible vision loss. Due to the possibility of missing the scotoma while evaluating the greyscale, observation of the total deviation and pattern deviation could help elucidate if there is early retinal toxicity. Similar to the 24-2 and 30-2 visual fields, where the central 4 degrees are affected by Plaquenil toxicity, the area of risk on a 10-2 is two degrees to six degrees from center.19 Due to the inevitability of missed subtle defects, deviation plots should be reviewed. In the

056_ro0219_plaquenil.indd 61 2/5/19 5:04 PM Retina

literature, it has been suggested that the superior visual Facing page: This questionnaire is designed to field is affected first.20 Those findings were corroborated help identify patients with Plaquenil toxicity. in 2011, when researchers noted the superior visual field Feel free to photocopy it and use it in your own was affected more in seven out of 15 patients.19 Evalu- practice. To download a PDF, read this article ation of the greyscale will reveal a paracentral ring sco- online at www.reviewofoptometry.com or scan the QR code. toma, but a subtle abnormality may be easier to detect on the pattern deviation. The choice of HVF 10-2 with findings associated with Plaquenil retinal toxicity. Of the red stimulus or without the red stimulus is controver- note, SD-OCT, in combination with Humphrey visual sial. The 10-2 HVF field testing, is critical for the early detection of Plaque- with red stimulus was nil retinal toxicity. ■ touted as the testing Dr. Demeritt is an assistant professor at Nova strategy of choice due Southeastern University College of Optometry. to its 91% sensitiv- Dr. Reynolds is an associate professor of optometry at ity for detection of Nova Southeastern University College of Optometry. Plaquenil toxicity; Dr. Shechtman is a professor of optometry at Nova however, there is only Southeastern University College of Optometry. a 57% specificity.18 Dr. Davidson is a locum optometrist and 2016 On the converse, the graduate of Nova Southeastern University.

10-2 white stimulus 1. Sundelin SP, Terman A. Different elements of chloroquine and hydroxychloroquine on lysosomal testing strategy has function in cultured retinal pigment epithelial cells. APMIS. 2002;100:481-9. 2. Gamanu (Panca) A, Popa-Cherecheanu A, Marinescu B, et al. Retinal toxicity associated a lower sensitivity of with chronic exposure to hydroxychloroquine and its ocular screening. Review. J Med Life. 78%, but it has a bet- 2014;7(3):322-6. 3. Bernstein H. Ocular safety of hydroxychloroquine sulfate (Plaquenil). South Med J. ter specificity of 84%. 1992;85(3):274-9. 4. Marmor M, Kellner U, Lai T, et al. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmol. 2011;118(2):415–22. Eye care specialists 5. Melles R, Marmor M. The risk of toxic retinopathy in patients on long-term hydroxychloro- provide a valuable quine therapy. JAMA Ophthalmol. 2014;132(12):1453-60. service when screen- 6. Michaelides M, Niam H, Stover P, et al. Retinal toxicity associated with hydroxychloroquine and chloroquine risk factors, screening, and progression despite cessation of therapy. Arch ing for Plaquenil Ophthalmol. 2011;129(1):30-9. retinal toxicity and 7. Marmor M. Comparison of screening procedures in hydroxychloroquine toxicity. Arch Oph- thalmol. 2012;130(4):461-9. advising the treating 8. Marmor M, Kellner U and Lai T. Recommendations on screening for chloroquine and hydroxy- physician or rheuma- chloroquine retinopathy. Ophthalmol. 2016;123(6):1386-94. 9. Melles R, Michael F, Marmor M. Pericentral retinopathy and racial differences in hydroxychlo- tologist with regards roquine toxicity. Ophthalmol. 2015;122(1):110-6. to the patient’s risk, 10. Lally D, Heier J, Baumal C, et al. Expanded spectral domain-OCT findings in the early detection of hydroxychloroquine retinopathy and changes following drug cessation. Int J Retina safe dosing and Vitreous. 2016;2:18. appropriate screen- 11. Korah S, Kuriakose T. Optical coherence tomography in a patient with chloroquine-induced maculopathy. Indian J Ophthalmol. 2008;56(6):511-3. ing procedures. 12. Kellner S, Weinitz S, Kellner U. Spectral domain optical coherence tomography detects early With the updates of stages of chloroquine retinopathy similar to multifocal electroretinography, fundus autofluorescence and near-infrared autofluorescence. Br J Ophthalmol. 2009;93(11):1444-7. the new guidelines 13. Uslu H, Gurler B, Yildirim A, et al. Effect of hydroxychloroquine on the retinal layers: A regarding screening quantitative evaluation with spectral-domain optical coherence tomography. J Ophthalmol. 2016:2016. for Plaquenil-related 14. Abramoff M, Garvin M, Sonka M. Retinal imaging and image analysis. IEEE Trans Med Imag- retinal toxicity, we ing. 2010;3(7):169-208. 15. Chen E, Brown D, Benz M, Fish R. Spectral domain optical coherence tomography as an must be more vigilant effective screening test for hydroxychloroquine retinopathy (the “flying saucer” sign) Clin Oph- in the aggressive and thalmol. 2010;4:1151–8. 16. Mititelu M, Wong B, Brenner M, Bryar P. Progression of hydroxychloroquine toxic effects thorough imaging after drug therapy cessation: new evidence from multimodal imaging. JAMA Ophthalmol. and interpretation of 2013;131(9):1187-97. 17. Rodriguez-Padilla J, Hedges T, Monson B, et al. High-speed ultra-high resolution opti- such diagnostic tests. cal coherence tomography findings in hydroxychloroquine retinopathy. Arch Ophthalmol. Hence, it is impera- 2007;125(6):775-80. 18. Easterbrook E. Ocular effects and safety of antimalarial agents. Am J Med. 1988;85(4. tive that we become S1):23-9. Fig. 9 Cirrus SD-OCT demonstrating familiar with recog- 19. Anderson C, Blaha GR, Marx JL. Humphrey visual field findings in hydroxychloroquine toxicity. Eye (Lond). 2011;25(12):1535-45. progressive GCC damage within the nizing the spectrum 20. Hart W, Burde R, Johnston G, Drews R. Static perimertry in chloroquine retinopathy: perifo- parafoveal and temporal region. of HVF and SD-OCT veal patterns of visual field depression. Arch Ophthalmol. 1984;102:377-80.

62 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

056_ro0219_plaquenil.indd 62 2/5/19 5:05 PM Today’s Date: ____/____/______

HCQ QUESTIONNAIRE

Name: ______Age: _____ Weight (important for medication dosage): _____ Date of Birth: ____/____/______

Race: □ American Indian or Alaska Native □ Native Hawaiian or Other Pacific Islander □ Asian □ Black or African American □ Caucasian

Primary Care Physician: ______Last seen: ______

Referring /Specialty Dr. ______Last seen: ______

Are you currently under the care of an ophthalmologist or optometrist?

□ Yes □ No If yes, please include name and date last seen ______

Have you ever had ocular baseline testing done?

□ Yes □ No □ Unsure

Which medication are you taking that you are being monitored for ocular toxicity?

□ Chloroquine □ Hydroxychloroquine □ Other: ______

Dosage: ______Duration: ______

Why are you taking this medication?

□ Lupus □ Rheumatoid Arthritis. □ Other: ______

Are you currently being treated or monitored for kidney disease?

□ Yes □ No

Any recent major weight loss?

□ Yes □ No

Are you also using the medication Tamoxifen (commonly used to prevent breast cancer)?

□ Yes □ No

Any changes in your vision or color vision?

□ Yes □ No If yes, please explain: ______

Any changes seen with your at home Amsler grid testing?

□ Yes □ No □ Unsure If yes, please attach Amsler with explanation ______

Signature: ______Date: ______

Signature if other than patient: ______Date: ______

Relationship to patient: ______

REVIEW OF OPTOMETRY FEBRUARY 15, 2019 63

0056_ro0219_plaquenil.indd56_ro0219_plaquenil.indd 6633 22/5/19/5/19 5:055:05 PMPM Neuro

The Neurologic Exam, Step-by-step

This case-based review will help you assess beyond each patient’s visual presentation and uncover key clinical signs of neurologic dysfunction. By Ashley Kay Maglione, OD, and Kelly Seidler, OD

ecause the eye is an exten- ric office. Clinicians can tackle the Cranial nerve testing can provide sion of the brain, a neuro- neurologic examination by breaking strong localizing data for a lesion. logic examination can be a it into five sections: For example, if multiple cranial Bcrucial diagnostic tool. The 1. Mental status. Many practi- nerves are affected, the clinician can neuro exam allows you to assess tioners assess mental status at the consider where cranial nerves share structures neighboring those that beginning of the exam and, for a common space, such as within the are important to vision and can help healthy patents, write “A&Ox3,” cavernous sinus (recall that CN III, determine the level of urgency for representing Alert and Oriented to IV, VI, the ophthalmic division of

a patient’s ocular findings such as (1) person, (2) place and (3) time. If the trigeminal nerve, or V1, and the visual field defects, cranial neuropa- the patient is answering your ques- maxillary division of the trigeminal

thies, double vision, optic neuropa- tions inappropriately and seems nerve, or V2, course here) or the thy, ptosis, pupillary abnormalities confused or disoriented, you may superior orbital fissure (which con- and loss of vision. It may increase choose to perform a mini mental tains CN III, IV, VI and the frontal, your clinical suspicion for underly- status exam (MMSE). This question- lacrimal and nasociliary branches ing etiologies, including stroke, naire is designed to assess different of the trigeminal nerve). Table 1 space-occupying lesion and demy- aspects of cognitive function, includ- reviews CN functions and outlines elinating disease, among others. ing orientation, recall and language. how to test for any dysfunction dur- Incorporating the neurologic The MMSE is quick and requires no ing a neurologic examination. Here exam into your tool box will help training, although it may not detect is a brief review of the clinical appli- you provide exceptional care to your mild cognitive decline.1 cations of testing each cranial nerve:2 patients. Here we show you how 2. Cranial nerve testing. You will CN I: This nerve is often not and provide several case examples. already have tested four of the 12 tested unless a frontal tumor is sus- cranial nerves (CNs) during your pected, such as in Foster-Kennedy The Five-step Exam routine eye exam: II, III, IV and VI. syndrome, which is characterized As important as the neurologic Before you tackle your first neu- by pallor of one optic nerve due exam is, it doesn’t take advanced rologic exam, we recommend you to compression and edema of the technology to perform, and the tools review the anatomical locations and contralateral nerve due to increased are readily available in an optomet- pathways of the cranial nerves. intracranial pressure.

64 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

064_ro0219_neuro.indd 64 2/5/19 11:52 AM CN II: This afferent nerve is VIII in the cerebellopontine angle. loss is rarely due to a central lesion assessed during visual acuity, color A patient with an abduction deficit within the brain due to the extensive vision, pupil testing with the swing- and hearing loss on one side would crossing of the auditory pathway. ing flashlight test for afferent pupil- localize to this region and would be CN VIII is also involved in the lary defect and visual field testing concerning for a lesion such as an vestibular system, which is respon- (see “Beyond Visual Field Testing”). acoustic neuroma. Unilateral hearing sible for balance, proprioception CN III: This is routinely tested with extraocular motility. It inner- Beyond Visual Field Testing vates the levator palpebrae superioris Visual field testing can unmask a number of associated neurologic conditions, given the (elevation of the upper eyelid) as expansive visual pathway. The anatomy of the visual pathway allows defects to be localized to well as four of the six extraocular anterior to the chiasm, the chiasm and posterior to the chiasm. muscles and is involved in elevation, If testing reveals a bitemporal hemianopsia, the lesion can be localized to the chiasm depression and adduction of the due to the anatomical crossing of the nasal retinal fibers. A pituitary adenoma is a common eye. It is also involved in pupillary pathology that causes compression of the chiasm. In these cases, you must pay careful atten- constriction. A pupil-involved CN tion to extraocular motilities, as the cavernous sinus is adjacent to the sella. Recall CN III, IV, III palsy is more concerning for an and VI course through the cavernous sinus and may be affected if there is lateral expansion aneurysm because pupillary fibers of a sellar mass. In addition, by performing a neurologic exam you can assess the remaining

travel on the external surface of the cranial nerves within the cavernous sinus (CN V1 and V2). nerve and are subject to compression A homonymous hemianopia visual field defect suggests pathology posterior to the chiasm. CN IV: This is also routinely Additional neurologic exam findings may help you to localize the lesion to the optic tract, tested with extraocular motility. parietal or temporal radiations, or the occipital lobe. For instance, should you detect weakness It innervates the superior oblique of the extremities on the same side as the patient’s hemianopia, consider an optic tract lesion. muscle involved in depression of the Anatomically, the optic tract runs adjacent to the crus cerebri, which carries the descend- adducted eye, as well as intorsion. ing motor pathway in the midbrain. A lesion in this region is above the crossing of the motor Cover testing in multiple positions of pathway; therefore, weakness will be on the contralateral side. Thus, a patient with a right gaze demonstrates a hyper deviation homonymous hemianopia and right-sided weakness may have a lesion affecting the left optic worse on contralateral gaze and ipsi- tract and left crus cerebri. lateral head tilt. Moving posterior, lesions of the optic radiations within the parietal and temporal lobes often CN V: Reduced sensation in the have neurologic signs. A homonymous hemianopia denser above suggests pathology to the optic radiations that course through the temporal lobe; accompanying cognitive impairment distributions of V1 and V2 may indicate a cavernous sinus lesion, espe- may indicate the need for an MMSE. A homonymous hemianopia denser below accompanied cially in cases of CN III, IV and/or by language deficits may suggest a lesion within the parietal lobe. Conversely, a visual field VI dysfunction. defect in the absence of other neurologic findings often localizes to the occipital lobe.1 CN VI: Routinely tested with 1. Goodwin D. Homonymous hemianopia: challenges and solutions. Clinical Ophthalmol. 2014;8:1919-27. extraocular motility, CN VI innervates the lateral rectus muscle which Visual Field and Neurologic Deficits abducts the eye. Abduction deficits Visual Field Defect Localization Additional Considerations may be found in cases of increased Bitemporal hemianopia Optic chiasm • Pay attention to extraocular motilities intracranial pressure. (functions of CN III, IV and VI) and facial CN VII: This is a helpful test sensation, given the proximity of the when you note facial asymmetry cavernous sinus to the chiasm. or an abduction deficit. An upper Non-congruous Optic tract • Assess motor function due to the motor neuron lesion of CN VII (such homonymous hemianopia proximity between crus cerebri and optic as a stroke) will spare the forehead tract. and indicates damage in the cere- Homonymous hemianopia Temporal lobe • Perform an MMSE. brum. A lower motor neuron will denser above • Check for memory impairment. affect the entire half of the face. Homonymous hemianopia Parietal lobe • Look for language deficits. CN VIII: In a patient with an denser below abduction deficit, it is important to Quadrantanopia Occipital lobe • This would elicit a normal neurologic test hearing due to the close relation- exam. ship of cranial nerves VI, VII and

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and eye movements, including the myasthenia gravis, therefore raising of a lower motor neuron lesion. vestibulo-ocular reflex. Disruption clinical suspicion for disease of the Cranial nerve testing clinical to this system can manifest clinically neuromuscular junction. case. A poorly controlled diabetes as nystagmus which may be seen in CN XI: Upper motor neuron patient presented with diplopia conditions such as Meniere’s disease. lesions will relatively spare the ster- and an abduction deficit (75% of CN IX and X: These are not nocleidomastoid muscle function normal capability) concerning for examined separately; their close and comparatively affect the trape- a CN VI palsy. Neurologic exami- anatomic relationship rarely results zius muscle function more. This is nation revealed a subtle ipsilateral in isolated lesions. Dysfunction of also important to test in cases suspi- facial palsy that we could have eas- these nerves or the structures that cious for myasthenia gravis. ily missed with observation alone. they innervate may be indicated by CN XII: The tongue will deviate All other testing of cranial nerve dysphonia, dysphagia or dyspnea. to the contralateral side of an upper functions was normal. Despite the Pay special attention to CN IX and motor neuron lesion and to the ipsi- patient’s vasculopathic risk factor X in patients with diplopia, ptosis lateral side with a lower motor neu- of poorly controlled diabetes, the or both, as they may be involved in ron lesion. Tongue atrophy is a sign concurrent CN VII palsy raised

Table 1. Cranial Nerve Function and Testing3 Cranial Nerve Function Test I – Olfactory • Sense of smell • Ask patient to occlude one nostril and close their eyes. • Present a stimulus, such as coffee, and ask the patient to identify the smell. II – Optic • Vision • Visual acuity. • Color vision. • Visual fields. • Pupillary response to light to test for an afferent pupillary defect. III – Oculomotor • Ocular motility (superior, • Routinely tested during examination with extraocular motility. inferior and medial recti, inferior • Supraduction. oblique) • Infraduction. • Lid elevation (levator • Adduction. palpebrae superioris) • Pupillary constriction (efferent limb of light pathway) IV – Trochlear • Ocular motility (superior • Routinely tested during examination with extraocular motility. Infraduction upon oblique) adduction. • Intorsion.

V – Trigeminal • Facial sensation • Test the distributions of V1, V2 and V3 separately with a light touch with a cotton wisp • Muscles of mastication to the forehead, upper cheek and jaw, respectively, with the patient’s eyes closed. Ask the patient to compare the sensation from right to left, looking for any asymmetry • Assess the motor function of V by feeling either side of the jaw just inferior and anterior to the ear for muscle contraction while asking the patient to clench their teeth.

• If indicated, test the corneal reflex (afferent limb: ophthalmic, V1 and efferent limb, V2) with a cotton wisp. VI – Abducens • Ocular motility (abduction) • Routinely tested during examination with extraocular motility. • Abduction. VII – Facial • Muscles of facial expression • Ask the patient to smile, raise their eyebrows, frown, puff out their cheeks and • Taste to anterior 2/3 of tongue squeeze their eyelids tightly together while looking for any asymmetry or weakness. VIII – • Auditory and vestibular • Hearing can be grossly checked by rubbing your fingers together near a patient’s Vestibulocochlear systems ear and asking if they can identify which ear hears the sound and if they notice any asymmetry in the volume of the sound. IX – Glosso- • Palate elevation, gag reflex/ • Ask the patient to open their mouth and say “ahh” and look for any asymmetry in the pharyngeal swallowing palate or deviation of the uvula. X – Vagus • Speaking XI – Accessory • Sternocleidomastoid and • Ask the patient to turn their head side-to-side and shrug their shoulders looking for trapezius muscle any asymmetry or weakness. XII – Hypo-glossal • Muscle action of the tongue • Ask the patient to stick their tongue out and note if it deviates to one side.

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0064_ro0219_neuro.indd64_ro0219_neuro.indd 6666 22/5/19/5/19 11:5311:53 AMAM ADDRESS CONTACT By Paul M. Karpecki, LENS PROBLEMS OD, FAAO BEFORE IT’S TOO LATE

n the United States alone, 40.9 million adults wear contact Choose Your Compress Wisely lenses.1 That seems like a lot, but this number would be far As stated earlier, not all compresses are created equal. Com- Igreater if contact lens dropout rates were not so high. Con- presses that contain gel, silica gel beads, or grains can dry out tact lens dropout continues to plague our industry and can and deliver uneven heat, causing hot spots that are dangerous negatively affect our practices and our relationships with our and reduce product performance. Only Bruder compresses patients. contain patented MediBeads® Technology. MediBeads® provide Over the years, lens manufacturers have endeavored to clean, uniform heat. Their unique, honeycomb molecular struc- improve materials and encourage patients to move to daily ture encourages complete absorption of water molecules and, disposable options, yet dropout rates are currently estimated when microwaved, releases moist heat in a controlled and con- to be at around 15.9%.2 In other words, not all of our patients’ sistent manner. These unique benefits helped make the Bruder problems can be overcome by switching lenses. Mask the #1 doctor recommended moist heat eye compress. A broader view of the patient and his or her contact lens But, as we know, contact lens wearers have unique needs that wearing experience is required. Fortunately, we now have better even the Bruder mask was not initially designed to address. tools to achieve this. Bruder Healthcare recently announced the For example, contact lens wearers have three times the usual immediate availability of the EyeleveTM Contact Lens Compress, levels of certain bacteria than the eyes of non-wearers. For the first and only compress clinically proven to increase com- this reason, the Eyeleve Contact Lens Compress utilizes an fortable contact lens wear time by up to 3 hours daily.2 Read on anti-microbial EyeOnic™ fabric material that has anti-microbial for more about why this compress is so effective and for details threads woven into the fabric of the compress to help reduce the on how you can position it in your contact lens practice to help risk of infections. Together with silver ion MediBeads®, this helps drive growth and satisfaction. address eyelid hygiene and further reduces the risk of corneal infection. In addition, Eyeleve features a contoured comfort Compresses Work Well for stitch to alleviate pressure off the eyes and avoid heat to the Contact Lens Wearers cornea. In 2013, the International Workshop on Contact Lens Discom- fort report concluded that the primary reasons for contact lens Support and Grow Your Practice intolerance are discomfort and dryness.3 More recently, a 2017 Thanks to this addition to our armamentarium, we are better study in Contact Lens & Anterior Eye found that end-of-day dis- equipped to prevent patients from dropping out of lens wear. comfort is a primary reason for contact lens dropout. A first step More importantly, we have a compress that was specifically toward resolving these problems is to determine what’s causing designed to address the unique needs and concerns of a popula- them in the first place. tion that is otherwise likely to become disenchanted due to clini- As we’ve seen time and again in our practices, our contact cal challenges that, historically, we’ve been unable to overcome. lens wearers frequently present with dry eye and signs of mei- Fortunately, we can now proactively offer a compress that’s bomian gland disease (MGD). As such, supporting meibomian proven to be clinically beneficial and to offer a meaningful ben- gland function is central to promoting a healthy lens wearing efit to contact lens patients. This can and should become an experience and will ultimately lead to improvements in comfort. integral part of our initial dispensing visit. We can likewise pres- Warm compresses are a mainstay clinical therapy for MGD ent this more complete approach to patients who’ve been wear- generally4 and can be particularly helpful in contact lens wearers ing their contacts for a while—especially as they age and are at specifically.2 However, it is imperative that your patient selects greater risk of developing ocular surface problems. an effective compress. Compresses must maintain the right For new contact lens wearers and for those who may already temperature for 8 to 10 minutes to increase be experiencing discomfort, Eyeleve is a welcome addition. By meibum secretion and result in clinically recommending Eyeleve and suggesting it be part of our patients’ meaningful improvement. Currently, only daily contact lens routine, we are offering something that online Bruder masks can achieve these clinical retailers can’t—a protocol and a partnership. goals. Product information is available at www.eyeleve.com, or con- The Bruder Moist Heat Eye Compress tact Bruder Healthcare at 888-827-8337 to learn more. underwent a clinical study at the School 1. of Optometry at the University of Ala- Cope JR, Collier SA, Rao MM, et al. Contact Lens Wearer Demographics and Risk bama in Birmingham.2 The study found Behaviors for Contact Lens-Related Eye Infections, United States, 2014. 2015; that subjects using the Bruder Com- http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6432a2.htm. Accessed Septem- press daily had significantly improved ber 16, 2015. 2. meibomian gland function and 2018 UAB Study: The Effect of the Bruder Eye Hydrating Compress on Contact Lens experienced steeper declines Discomfort in Contact Lens Wearers 3. in their overall Eye Discomfort 2017 Contact Lens & Anterior Eye. Factors in the Success of New Contact Lens Assessment scores. In fact, they Wearers. 4. ultimately increased comfortable Olson MC, Korb DR, Greiner JV. Increase in tear film lipid layer thickness follow- wear time of their contact lenses ing treatment with warm compresses in patients with meibomian gland dysfunc- by up to 3 hours. tion. Eye Contact Lens. 2003;29(2):96-9.

REVIEW OF OPTOMETRY FEBRUARY 15, 2019 67 63

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suspicion for an alternative etiology. symptoms (cranial neuropathy and Given the close association between weakness) that the patient may or cranial nerves VI and VII within the may not be aware of should prompt pons and as they exit the brainstem, you to pursue a more urgent work- simultaneous dysfunction suggests up. If this patient had been evalu- a lesion in that region. We referred ated from purely an ophthalmic the patient for additional testing, standpoint, the CN VI palsy may including an MRI of the brain, have been presumed ischemic or which resulted in the diagnosis of vasculopathic, given the poor con- metastatic cancer and referral to trol of systemic disease. However, oncology for further evaluation. the discovery of a concurrent new- 3. Motor/reflex examination. Fig. 1. Demonstration of upper extremity onset neurologic symptom raised This begins with observation. You strength assessment. significant concern and warranted should first look for any involuntary immediate neuroimaging. While a movement such as tremors sugges- a right abduction deficit concern- cranial nerve palsy may be second- tive of basal ganglia disease (e.g, Par- ing for a CN VI palsy, but the eye ary to vasculopathic risk factors, it kinson’s) or muscle atrophy. Next, examination was otherwise normal. is important to consider that a diag- check for weakness of the upper A neurologic exam revealed a pre- nosis of exclusion. and lower extremities by asking the viously unknown upper extrem- 4. Coordination/gait. The first patient to flex, extend, abduct and ity, left-sided weakness. All other indication of cerebellar dysfunc- adduct their arms and legs against aspects of the neurologic exam were tion may be observed as the patient resistance. Compare the strength and normal. An abduction deficit with walks to the exam room. Those ability of each muscle group with the contralateral weakness is concern- with the condition may exhibit an contralateral side, looking for any ing for a lesion in the brainstem, ataxic, or clumsy, gait. You can also asymmetry (Figure 1). specifically referred to as Raymond’s ask the patient to walk heel-to-toe Weakness may be subtle and can syndrome. The patient was referred in a straight line. Wheelchair-bound be further elucidated with specific immediately to the hospital where patients can slide their heel along tasks. Ask a patient to hold both neuroimaging revealed an infarction their contralateral shin toward their arms out in front of them with their of the right ventral pons. foot. Inability to perform any of palms facing upward and close These first two cases discussed these tasks indicates potential cer- their eyes. A slow, downward drift highlight the importance of per- ebellar dysfunction or intoxication. and pronation of one arm suggests forming a neurologic examination The presence or absence of ataxia weakness. Additionally, check fine on patients with diplopia. The may also be detected by asking the movements by asking the patient presence of additional neurologic patient to quickly touch their finger to rapidly tap a finger or alternate their hand in a palm-up, palm-down fashion. Deep tendon reflexes may be diminished, such as in patients with Adie’s tonic pupil, or abnormally increased, such as in patients with multiple sclerosis.3 Motor/reflex examination case. A 66-year-old patient presented emergently with complaints of double vision. The patient had poorly controlled diabetes and blood pressure was elevated at the time of the exam. The patient denied any associated neurologic symptoms such as weakness, paresthesia or Fig. 2. Humphrey 10-2 visual fields OS and OD show a more severe visual loss in the headache. Examination revealed left eye compared with the right.

68 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

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cerebellar disease, including stroke affecting the left hand more than the and atrophy. right. Records of recent lab work The classic ocular manifestation demonstrated significant vitamin of cerebellar dysfunction is nystag- B12 and folate deficiencies, which mus, with other potential ocular supported a nutritional optic neu- complications such as abnormal ropathy diagnosis. pursuits and optokinetic response. This case highlights how a neuro However, nystagmus is not only exam helps to refine your differen- caused by cerebellar disease and tial diagnosis of an optic neuropa- can be due to vestibular dysfunc- thy. Potential causes of bitemporal tion as well as other etiologies such pallor include inflammatory, infec- as albinism and medication use tious, nutritional and toxic condi- (such as anti-seizure medications). tions. Anemia is a common early

Therefore, performing a neurologic symptom of vitamin B12 deficiency, exam on patients with nystagmus while neurologic symptoms are typi- Fig. 3. OCT of the optic nerves reveal and paying special attention to cally found later. Neurologic symp- temporal retinal nerve fiber layer thinning their coordination and gait can help toms arise due to demyelination and flagged on the deviation map. increase or decrease your clinical can include cerebellar ataxia and suspicion for a lesion within the limb weakness.4,5 In this case, our from their nose to your fingertip an cerebellum. neurological findings helped narrow arm’s length away. Any hesitation, Coordination/gait case. A our differential and avoid additional overshoot or undershoot, shaking 31-year-old woman presented with tests such as laboratory testing and or difficulty when they are about complaints of glare and reduced neuroimaging. to touch your finger may indicate vision. Her best-corrected visual 5. General sensory exam. Pain, ataxia. Stand far enough away so acuity was 20/25- OD and 20/100 temperature, proprioception, two- that these patients have to fully OS. She demonstrated a 0.3 log unit point touch, light touch, pressure extend their arm to reach your fin- relevant afferent pupillary defect of and vibratory sense are all general ger. You can move your finger to the left eye and reduced color vision sensations. The stimulus travels different areas to increase difficulty. (12/14 Ishihara plates OD, 3/14 from the site of stimulation to the To assess rapid alternating move- Ishihara plates OS) (Figures 2 and cerebral cortex. Depending on the ments, ask the patient to tap the 3). Fundus examination revealed sensation, the pathway decussates, palm of their hand on their leg bilateral temporal pallor OS>OD or crosses, the midline in either the repeatedly and quickly. Then ask (Figure 4). A neurologic exam low medulla or spinal cord. Lesions them to flip their hand from palm revealed tandem gait ataxia and a below the decussation cause ipsi- to the back of the hand on their leg. positive Romberg test, suggestive lateral loss of sensation. In general, Inability to do so is known as dys- of cerebellar dysfunction. She also lesions within the brainstem or the diadokinesia and is often a sign of demonstrated fine motor weakness brain cause contralateral loss of sensation. We recommend integrating tests of sensation with other elements of the neurologic exam. While the patient has their arms outstretched with closed eyes to test for pronator drift, lightly touch the backside of one of their hands and ask them to identify which hand was touched. Touch one hand, then the other and then both simultaneously while asking the patient to note any asym- Fig. 4. Note the pallor of the temporal rim in the patient’s fundus photo of the right metry. You may also touch a cool optic disc and left optic disc (please disregard the pink artifact). transilluminator on each of the

70 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

064_ro0219_neuro.indd 70 2/5/19 11:53 AM patient’s arms to assess for asymme- sory defects and a left-sided facial interpreted quickly and efficiently, try in temperature sensation. palsy that was not grossly evident with significant implication for Proprioception can be assessed by observation alone. By correlating patient care. ■ by asking the patient to stand with our findings with the anatomical Dr. Maglione is an assistant pro- their feet touching, known as the location of the stroke, we attributed fessor at the Pennsylvania College Romberg test. Patients can usually his presentation to the prior stroke of Optometry at Salus University keep their balance with their eyes of the right pons, therefore avoiding and clinical instructor in the primary open due to visual cues; however, any further testing or work-up. His care and neuro-ophthalmic disease if they are unable to maintain their previous MRI report was remark- services at The Eye Institute. balance with their eyes closed—a able for gliosis involving the right Dr. Seidler graduated from the positive test—they may have loss of optic tract, which corresponded Pennsylvania College of Optometry proprioception. This test may also with his visual field defect. at Salus University. She is currently indicate cerebellar dysfunction. completing a two-year advanced res- Sensory exam case. A 62-year-old These cases highlight many idency program at The Eye Institute male presented with tearing affect- important clinical implications of in neuro-ophthalmic disease. ing the left eye more than the right, the neurologic exam, hopefully a left-sided, non-congruous, homon- inspiring you to incorporate it 1. O’Bryant SE, Humphreys JD, Smith GE, et al. Detecting dementia with the mini-mental state examination (MMSE) in ymous hemianopia and intermittent into your practitioner’s toolbox. highly educated individuals. Arch Neurol. 2008;65(7):963-7. diplopia. He reported a history of Ultimately, a neurology consult is 2. Finsterer J, Grisold W. Disorders of the lower cranial nerves. J Neurosciences in Rural Practice. 2015;6(3):377-91. a hemorrhagic stroke affecting the often indicated, but an in-office 3. Campbell W. DeJong’s The Neurologic Examination. 7th ed. Philadelphia: Wolters Kluwer; 2015. right side of his brainstem. Neuro screening may help narrow a list of 4. Ralapanawa DMPUK, Jayawickreme KP, Ekanayake EMM, Jay- exam revealed left-sided weakness of differentials to help develop a sense alath WATA. B12 deficiency with neurological manifestations in the absence of anaemia. BMC Research Notes. 2015;8:458. the left upper and lower extremities. of urgency. With practice, the neu- 5. Ashizawa T, Xia G. Ataxia. Continuum: Lifelong Learning in He also demonstrated notable sen- rologic exam can be performed and Neurology. 2016;22(4):1208-26.

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TAKE A CLINICAL APPROACH TO ANTERIOR UVEITIS The ultimate goal is to narrow down symptoms to effective treatment. By Dominick L. Opitz, OD

nterior uveitis (AU) causes ther add to the frustration. Failure of Clinical Examination frustration for patients and timely diagnosis as well as inefficient Anterior uveitis is inflammation that clinicians alike. The incon- and/or ineffective treatment can have arises in the anterior segment, includ- venient onset and often serious sight-threatening complica- ing the iris and anterior ciliary body. Asevere symptoms result in urgent tions. AU is the most common form of office visits, disrupting the patient’s Following a logical, clinical uveitis, accounting for 50% to 60% daily life as well as the provider’s approach to AU will help the prima- of all uveitis, and is the most com- office and clinic flow. The rigorous ry eye care provider effectively and mon type of ocular inflammation treatment, frequency of follow-up efficiently manage anterior uveitis optometrists will encounter.1-4 visits and risk for recurrence can fur- (Figure 1). An estimated 30% to 52% of AU

Release Date: February 15, 2019 Accreditation Statement: In support of improving patient care, this Expiration Date: February 15, 2022 activity has been planned and implemented by the Postgraduate Estimated Time to Complete Activity: 2 hours Institute for Medicine and RGVCE. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Jointly provided by Postgraduate Institute Medical Education, the Accreditation Council for Pharmacy Education, for Medicine (PIM) and RGVCE and the American Nurses Credentialing Center, to provide continu- Educational Objectives: After completing this activity, the participant ing education for the healthcare team. Postgraduate Institute for should be better able to: Medicine is accredited by COPE to provide continuing education to optometrists. • Demonstrate knowledge of the ocular signs and symptoms, as Faculty/Editorial Board: Dominick L. Opitz, OD, associate professor, well as systemic associations, related to anterior uveitis. the Illinois College of Optometry. • Use common lab tests to help localize the etiology of the uveitis. Credit Statement: This course is COPE approved for 2 hours of CE • Perform a dilated fundus examination for all patients who present credit. Course ID is 60776-AS. Check with your local state licens- with anterior uveitis. ing board to see if this counts toward your CE requirement for • Define the appropriate topical or systemic anti-inflammatories relicensure. and, importantly, the frequency of dosing for managing anterior Disclosure Statements: uveitis. Dr. Opitz: Consulting fees from Valeant/Bausch + Lomb and fees for • Describe the use of cycloplegia to reduce pain, prevent synechiae non-CME/CE services from Valeant/Bausch + Lomb. formation and re-establish the blood-aqueous barrier. Managers and Editorial Staff: The PIM planners and managers have Target Audience: This activity is intended for optometrists engaged nothing to disclose. The RGVCE planners, managers and editorial staff in the care of patients with uveitis. have nothing to disclose.

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cases have an underlying systemic matous or non-granulomatous. History (symptoms) etiology, and the primary eye care Granulomatous KPs are large provider is often the first health Physical exam (signs) with a waxy or “mutton fat” 5 care provider to aid in the systemic Anatomical classification appearance (Figure 2). Their disease.4 Effective treatment and presence is highly suggestive of management of uveitis should Associated factors an underlying infectious etiol- include controlling the signs and Lab studies ogy, but they can also be seen in symptoms of the disease, prevent- chronic autoimmune conditions Etiology ing ophthalmic complications and such as sarcoidosis. In contrast, identifying any systemic underlying non-granulomatous KPs are etiology. Treatment small, fine and white, and found The symptoms of AU include Fig. 1. Following this chart may offer an effective more in non-infectious etiologies. pain, redness, reduced vision approach to the diagnosis and management of The hallmark sign of AU is and photophobia, but these vary anterior uveitis where the ultimate goal is to the presence of anterior segment depending on the clinical course narrow down symptoms to effective treatment. inflammatory cells.5 These are (acute vs. chronic) of the uveitis.5 white blood cells that circulate The Standardization of Uveitis systemic autoimmune conditions. in the aqueous humor. The SUN Nomenclature (SUN) Working Non-granulomatous inflammation Working Group developed a uniform Group developed descriptors of uve- allows protein and white blood cells grading scheme for anterior chamber itis to clarify the onset, duration and to enter into the aqueous humor, cells (Table 1).6 course.6 The onset is described as causing the classic signs of anterior The presence of hypopyon in AU either sudden or insidious, whereas chamber cells and flare. AU resulting is highly suggestive of diseases asso- duration is defined as limited (≤3 from non-granulomatous inflamma- ciated with human lymphocyte anti- months duration) or persistent (≥3 tion is more commonly seen in non- gen B27 (HLA-B27), Behcet’s disease months duration).6 These descriptors infectious underlying etiologies. or infectious endophthalmitis. are then used to define the clinical The clinical signs associated with Anterior chamber flare occurs course—acute, recurrent or chronic. AU—manifested in the conjunctiva, from an influx of protein from the Acute uveitis occurs with sud- cornea, anterior chamber and iris— uveal blood vessels into the ante- den onset and limited duration.6 are a direct result of inflammation in rior chamber, which results from Recurrent uveitis is characterized by the anterior segment that results in increased vascular permeability of repeated episodes separated by peri- a breakdown of the blood-aqueous the uveal vasculature in the anterior ods of inactivity without treatment barrier. Inflammation of the con- chamber.9 Flare is graded according for three or more months.6 Chronic junctiva in anterior uveitis is often to the SUN grading scale: no flare uveitis describes cases in which described as perilimbal injection is grade 0; faint/barely present is relapses occur less than three months or circumlimbal injection.5 If the grade 1+; moderate with iris and lens after discontinuing treatment.6 inflammation is granulomatous, con- details clear is grade 2+; marked with The pathophysiology of uveitis junctival nodules may develop. These iris and lens details hazy is grade 3+; refers to the type of inflammatory nodules are collections of inflamma- intense with formed fibrin or plastic cells produced, either granulomatous tory material within the bulbar and/ aqueous humor is grade 4+.6 or non-granulomatous. or palpebral conjunctiva. Granulomatous inflammation Corneal findings associated with Table 1. Anterior Chamber is characterized by inflammatory anterior uveitis may include cor- and Vitreous Cell Grading* cells of the mononuclear phago- neal edema, but the most common Grade Number of Cells cyte system that take the form of corneal finding is keratic precipi- 0 no cells macrophages, epithelial cells and tates (KPs). These are collections of 0.5+ 1-10 multinuclear giant cells.7 This form inflammatory cells that accumulate 1+ 10-20 of inflammation is commonly a on the endothelium.8 New KPs are 2+ 20-30 manifestation of infectious, toxic, typically white in color with smooth autoimmune or neoplastic origin.7 borders. As KPs become more chron- 3+ 30-100 Granulomatous inflammations can ic, they may appear pigmented with 4+ >100 also be a critical sign of chronic irregular borders. *Using a high-intensity 1mm x 1mm slit beam based on the inflammation as seen with chronic KPs can be classified as granulo- Standardization of Uveitis Nomenclature Working Group.6

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When anterior chamber inflamma- low or high depending on the under- Further, clinical signs, symptoms tion is severe and there is significant lying cause, the clinical course and/ and history should enable classifica- breakdown of the blood-aqueous or the number of inflammatory cells tion of the clinical course (acute, barrier, extensive protein leakage affecting the outflow of aqueous chronic, or recurrent). For instance, occurs, which causes the develop- humor through the trabecular mesh- a patient with acute AU will likely ment of fibrin membrane across the work (TM).5,8 It is more common for complain of sudden onset of redness, pupil when the flare is 4+ (Figure 3). IOP to be low during an acute phase pain and light sensitivity, whereas a With AU, changes to the iris— due to secretory hypotony of the cili- patient with chronic anterior uveitis such as miosis, iris nodule formation ary body. Elevated IOP is more likely may have few to no symptoms. and iris synechia—may occur. Miosis to occur in chronic AU when the TM Based on the clinical course, typically occurs from spasms to the becomes overwhelmed with inflam- clinical signs and pathophysiology of iris sphincter or from distension of matory material or pigment. If the inflammation, narrow your differen- iris blood vessels.10 Iris nodules are underlying etiology is due to herpetic tial underlying etiology to infectious accumulations of inflammatory cells eye disease, trabeculitis frequently vs non-infectious. and may occur at the iris margin occurs, which affects outflow and of the pupil or in the iris stroma. causes elevated IOP. Treatment Nodules at the pupil margin are Although vitreous cells are the In general, the goals for treatment of termed Koeppe nodules and are hallmark sign of intermediate uve- AU are to eliminate ocular inflam- found in both granulomatous and itis, it is possible to have anterior mation to preserve vision, relieve non-granulomatous inflammation chamber cells “spill over” into the pain and prevent ocular complica- whereas Busacca nodules are found anterior vitreous. These vitreous tions, as well as identify any possible in granulomatous inflammation and cells, like anterior vitreous cells, are underlying etiology. are located in the iris stroma.5 Other inflammatory cells that arise from For acute AU, initial treatment iris findings in AU may include irido- a breakdown of the blood-aqueous includes topical corticosteroids and corneal adhesions, termed peripheral barrier. They are best visualized in a cycloplegic agents in an effort to anterior synechia.5,8 dilated eye at the slit lamp. Use the reduce and/or eliminate intraocular Posterior synechia are adhesions SUN grading scheme for vitreous inflammation. The dosing of topical of the iris and anterior lens that gen- cells (Table 1).6 corticosteroids often depends on the erally develop from Koeppe nodules Clinical examination of a patient severity and clinical course of the or a thickened iris due to inflamma- with anterior uveitis should include anterior uveitis as well as the type of tion. Localized diffuse or sectoral iris visual acuity, slit lamp exam, IOP corticosteroid used. atrophy may also occur in AU and is assessment and a dilated fundus Prednisolone acetate 1% is more common in chronic and recur- exam.10 If IOP is elevated, gonios- the most commonly prescribed rent uveitis or when the underlying copy may add valuable clues to the corticosteroid used for treating etiology is viral in nature. clinical course (acute vs chronic). AU, followed by dexamethasone Intraocular pressure (IOP) is his- The purpose of the dilated exam is 0.1%.1,4,11-13 For acute AU, the torically described as low in anterior to ensure the anatomical location typical dosing is one drop every uveitis—but IOP may be normal, of uveitis is confined to the anterior one to two hours while awake for a segment and that there are no pos- minimum of one week. Dosing for terior segment complications such chronic AU may be less. as cystoid macular edema, cataracts Difluprednate 0.05% emulsion is (specifically posterior subcapsular generally dosed QID and has been cataracts) or glaucoma. If posterior found to have similar efficacy to that uveitis or panuveitis is present, suspi- of prednisolone acetate 1% when cion for underlying etiology increases dosed eight times daily.11,14 The and management changes. If you lesser dosing regimen of diflupred- find that the anatomical location of nate 0.05% may offer better patient the uveitis is isolated to the anterior adherence, but has been shown to chamber, determine whether the cause higher risk of steroid-induced Fig. 2. Example of granulomatous or inflammation is granulomatous vs IOP elevation compared with pred- mutton-fat KP on the endothelium of a non-granulomatous based on clinical nisolone acetate 1%.15 patient with sarcoidosis. signs as discussed above. Loteprednol 0.5% is often

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072_ro0219_Uveitis_OSC.indd 74 2/5/19 12:00 PM reserved for patients in whom IOP uveitis responds to treatment. spikes are a concern, but its efficacy If the AU is chronic, recurrent, is less than that of prednisolone ace- bilateral, granulomatous and recal- tate 1% or difluprednate 0.05%.16 citrant to treatment, laboratory test- Cycloplegia is generally used as an ing is indicated; however, lab tests adjunctive therapy to corticosteroids. should be specific to the suspected Cycloplegia decreases pain and pho- underlying etiology (Table 2).10 Once tophobia by paralyzing the ciliary the underlying etiology is identified, body and by preventing posterior ocular management may change synechiae.1,4,11-13 Immobilizing the from topical therapy to disease- ciliary body also helps to re-establish specific systemic treatment, especially the blood-aqueous barrier. The dos- for infectious conditions such as ing of the cycloplegic agent varies Fig. 3. This patient has a fibrin membrane Lyme disease, syphilis, herpes and depending on the medication. Tradi- across the pupil with 4+ flare, 3+ cells tuberculosis. tional treatment included homatro- and endothelial keratic precipitates. pine 5% or scopolamine 0.25% or Non-infectious Etiologies 0.5%, but due to their limited access every two hours, provided patient The most common non-infectious it is becoming common to use atro- symptoms have resolved.1,4,11-13 underlying etiology for AU is caused pine 1.0%. Cyclopentolate 1.0% is Follow-up visits may be extended to by a group of inflammatory disor- another topical cycloplegic option. every two weeks and tapering ste- ders collectively termed the seronega- Although signs and symptoms roids may continue, provided signs tive spondyloarthropathies, which may improve after initiation of topi- and symptoms do not increase. account for up to 50% of acute and cal corticosteroids and cycloplegia, recurrent anterior uveitis.19 continue treatment until inflamma- Underlying Etiologies The seronegative spondyloar- tory anterior chamber cells have Although the majority of uveitis thropathies are negative for rheu- resolved. This may take from one is undifferentiated or idiopathic matoid factor (RF) and anti-nuclear week to one month or more, depend- (48% to 70%), infectious and non- antibodies (ANA), but may be posi- ing on the underlying etiology. In infectious causes occur.17,18 Consider tive for HLA-B27, a class I major rare cases, inflammatory cells may systemic etiologies when the AU histocompatibility complex.19-23 persist for years. is bilateral, recurrent, chronic or The conditions associated with The typical follow-up for acute granulomatous in nature and when HLA-B27 seronegative spondyloar- AU is five to seven days, at which patients are younger than 15 years thropathies include ankylosing spon- time the anterior chamber cells of age. Careful review of systems dylitis, reactive arthritis syndrome, should be reduced by at least 50% and lab testing are required to help psoriatic arthritis and inflammatory since the initial presentation.1,4,11 narrow the differential diagnosis and bowel disease, including Crohn’s and Patients should be re-examined ultimately identify the systemic con- ulcerative colitis. An estimated 50% weekly without altering corticoste- dition.9 Failure to properly diagnose of patients with acute anterior uveitis roid and cycloplegia dosing until and treat systemic disease may there are five or fewer cells per high- result in ophthalmic treatment Tapering Steroids in Anterior Uveitis powered field as viewed by slit lamp. failure, ophthalmic complica- A reasonable tapering schedule of topical corticoste- Visual acuity, slit lamp biomicros- tions, loss of vision, or even loss roids for anterior uveitis is one drop every two hours copy, IOP and fundus examination of life. for two weeks, one drop QID for two weeks, one drop should be performed at each follow- Uveitis-specific question- TID for two weeks, one drop BID for two weeks, one up visit. Additional testing may be naires—such as the Ocular drop a day for two weeks, and then topical therapy indicated if ophthalmic complica- Inflammation Disease Review should be discontinued.1,4,10 This schedule may need tions arise, such as reduced vision or of Systems Questionnaire— to be altered depending on the individual patient, cystoid macular edema. allow for a critical review of past history, underlying etiologies, and complications Once inflammatory cells of five systems that guides the lab and/or adverse events from the steroids. or fewer per high-powered field testing.4 In general, labs are If the disease flares at any time during the follow- are visible in the anterior chamber, withheld for initial acute epi- up process or inflammation increases, the corticoste- prednisolone acetate 1% dosing may sodes that are unilateral and roid dosing may need to be increased, followed by a be reduced from every one hour to non-granulomatous and if the slower taper.10-13

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before the uveitis is detected. The temic treatment may include oral uveitis can become chronic, caus- corticosteroids. ing ocular complications such as • Systemic lupus erythematous. cataracts, posterior synechia, band Like sarcoidosis, SLE is a multisys- keratopathy, glaucoma and macular tem autoimmune disease. While anti- edema in 37.3% of patients with bodies in the normal immune system JIA-related AU.27 protect against pathogens such as Because uveitis in JIA can present viruses and bacteria, ANA—a type in a quiet eye, screening is recom- III hypersensitivity reaction—attack Fig. 4. This patient has erythema migrans mended at three months for high-risk cell nuclei triggering inflammation four days after a tick bite and was treated JIA patients, six months for moder- in patients with SLE.34,35 ANA levels with 100mg doxycycline for 21 days. ate-risk JIA patients, and 12 months are elevated in 97% of SLE patients. for low-risk JIA patients.26,28 Although anterior uveitis can occur test positive for HLA-B27, and half Patients with JIA typically present in SLE, it is most commonly associ- of those patients go on to develop with an acute recurrent unilateral or ated with scleritis, episcleritis, sec- one of the seronegative spondyloar- bilateral non-granulomatous AU.29 ondary Sjögren’s syndrome, lupus thropathies.24 Work-up for children or adolescents retinopathy and choroidopathy.34,35 Uveitis associated with HLA-B27 suspected of JIA-related AU should Anterior uveitis seldom occurs in iso- is typically recurrent unilateral, include ANA, HLA-B27, and RF. A lation and is more commonly associ- bilateral or alternating non-granulo- positive ANA increases the risk for ated with scleritis or posterior uveitis. matous AU and may have fine endo- AU, whereas a positive HLA-B27 • Behcet’s disease. This is a thelial KPs.19-32 Symptoms associated increases the risk for developing chronic, multisystem, relapsing with HLA-B27-positive acute AU ankylosing spondylitis later in life. inflammatory disorder of unknown are typically extreme and include eye JIA-associated uveitis is often etiology, characterized by the classic pain, photophobia and intense injec- chronic, requiring long-term treat- triad of oral and genital ulcers, ocu- tion of the bulbar conjunctiva. ment. Systemic “steroid-sparing” lar inflammation and skin lesions. Treatment includes topical cortico- therapeutic options include antime- It is associated with HLA-B51.36,37 steroids and cycloplegia. For patients tabolites and other biologic agents.25 The uveitis in patients with Behcet’s with non-infectious etiologies who • Sarcoidosis. This is a multisys- disease is typically bilateral, non- don’t respond to topical therapy or tem disease of unknown origin that granulomatous anterior uveitis that for patients with recurrent AU, con- predominantly affects the lungs. may be acute, recurrent or chronic. sider systemic treatment with oral Ocular involvement is present in up Posterior uveitis may occur due to corticosteroids or disease-modifying to 50% of patients.30-33 The hallmark the increased risk of vasculitis associ- antirheumatic drugs such as metho- sign of sarcoidosis is non-caseating ated with Behcet’s. Hypopyon is also trexate or hydroxychloroquine. granulomas caused by granuloma- a common finding, present in 19% Other, less common non-infectious tous inflammation. These are com- to 31% of patients with AU and etiologies of AU include juvenile posed of epithelioid and giant cells Behcet’s disease.38,39 idiopathic arthritis (JIA), sarcoidosis, that secrete angiotensin converting Behcet’s disease and systemic lupus enzyme (ACE). Infectious Etiologies erythematous (SLE). Anterior uveitis in sarcoidosis Consider infectious etiologies in • Juvenile idiopathic arthritis. is typically bilateral, chronic and patients with recurrent, chronic gran- JIA-related uveitis accounts for 20% granulomatous with large mutton-fat ulomatous anterior uveitis that fails to 40% of pediatric uveitis patients.25 KPs, TM inflammation and iris nod- to resolve with topical corticosteroids JIA has many different subcategories, ules.30-33 Up to 25% of patients with and whose review of systems sug- but the majority of JIA-associated ocular sarcoidosis develop posterior gests infection. Further, infectious eti- uveitis patients have oligoarticular segment involvement.30-33 Laboratory ologies should be ruled out prior to onset JIA (78% to 90%), while 7% tests for patients suspected of sar- initiating any systemic corticosteroids to 14% have polyarticular JIA.10,26 coidosis AU may include serum ACE or immunosuppressive agents. The onset of JIA uveitis is typically levels, serum lysozyme, chest X-ray Pathogens commonly causing insidious; many patients are asymp- or CT, tissue biopsy or gallium scan. anterior uveitis include bacteria and tomatic with a white and quiet eye. In addition to topical ophthalmic viruses. Fungal infections such as his- Further, the arthritis often manifests treatment for anterior uveitis, sys- toplasmosis and parasitic infections

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072_ro0219_Uveitis_OSC.indd 76 2/5/19 12:01 PM such as toxoplasmosis typically cause chancre, which may be present from Patients with syphilis may present intermediate and posterior uveitis. two to six weeks. with posterior uveitis such as dif- If left untreated, primary syphilis fuse or focal chorioretinitis, neuro- Bacterial Etiologies leads to secondary syphilis. The lat- retinitis, necrotizing retinitis, retinal Some of the more common bacte- ter occurs four to 10 weeks after vasculitis, intermediate uveitis or rial etiologies of AU include syphilis, infection, and the systemic trepone- panuveitis.43-45 Lyme disease and tuberculosis (TB). mal load is largest in this stage. Sec- The diagnosis of syphilis is con- • Syphilis. This is a multisystem, ondary syphilis is characterized by a firmed through serology testing and chronic bacterial infection caused by disseminated maculopapular rash on includes non-treponemal and trepo- the spirochete bacterium, Treponema the palms of hands and soles of feet nemal tests. The non-treponemal pallidum. Syphilis accounts for 1% and lymphadenopathy. Constitution- tests include RPR and VDRL and to 2% of uveitis cases but is consid- al symptoms may include high fever, treponemal tests include FTA-ABS or ered the “Great Masquerader” due malaise, headache, nausea, anorexia, MHA-TP. to the different stages it may progress hepatitis and meningitis. Approxi- If the non-treponemal tests indi- through if left untreated.40-42 Primary mately 10% of cases with secondary cate active disease, determining the syphilis is the first stage, which ini- syphilis present with uveitis.40-42 stage of syphilis will determine the tially presents as erythematous pap- Following secondary syphilis, systemic treatment protocol. Primary, ules at the inoculation site that later patients progress to latent syphilis in secondary or early latent stage treat- erode to a painless ulceration called a which no systemic disease is appar- ment includes a single intramuscular ent. Early latent (IM) injection of penicillin.46 Late Table 2. Common Laboratory Tests1,3-5,8,10,18 syphilis occurs within latent or tertiary stage requires week- Test Diagnostic Use with Anterior one year of initial ly IM penicillin injections for a total Uveitis infection; late latent of three doses, whereas neurosyphilis Complete Blood Count Underlying bacterial or viral 46 (CBC with diff) etiology syphilis occurs after requires intravenous penicillin. Erythrocyte sedimentary rate Measure of generalized one year of infection. Systemic treatment of syphilis- (ESR) inflammations. Non-specific Most cases have been associated uveitis should occur in to disease reported to remain at conjunction with ocular treatment C-reactive protein (CRP) Marker of inflammation the latent stage, but with topical corticosteroids. Antinuclear antibody (ANA) SLE or JIA 30% will progress to • Tuberculosis. This is a granulo- Rheumatoid Factor (RF) Rheumatoid arthritis tertiary syphilis, the matous infection caused by Myco- Human leukocyte antigen B27 IBD (Crohn’s, ulcerative most common stage bacterium tuberculosis. The classic (HLA-B27) colitis), ankylosing spondylitis, in syphilis for uveitis presentation of an active TB infec- reactive arthritis to develop.43-45 tion includes chronic cough, fever, Human leukocyte antigen B51 Behcet’s disease Tertiary syphilis night sweats and weight loss. Granu- (HLA-B51) may cause cardio- lomatous inflammation in TB causes Fluorescent treponemal Syphilis (current or past antibody absorption (FTA-ABS) infection) vascular-syphilis, granulomas to develop in the lungs, Microhemagglutination assay– Syphilis (current or past neuro-syphilis or but granulomas may also develop on treponema pallidum (MHA-TP) infection) benign-tertiary syphi- the iris, angle or choroid. Rapid plasma regain (RPR) Syphilis (screen for active lis. AU in syphilis Uveitis may present in both active disease) patients can occur TB and in patients without systemic Venereal disease research Syphilis (screening for active in secondary, latent TB symptoms.47 The most common laboratory (VDRL) disease) and tertiary stages uveitis seen in TB is disseminated Lyme Titers Lyme Disease of syphilis, but not chorioretinitis, but it can also pres- Enzyme-linked immunosorbent Lyme Disease present in primary ent as acute anterior uveitis, chronic assay (ELISA) syphilis. The uveitis granulomatous anterior uveitis, Angiotensin-converting enzyme Sarcoidosis may be unilateral or intermediate uveitis, vitritis or endo- (ACE) bilateral, granuloma- phthalmitis.48-52 Serum Lysozyme Sarcoidosis tous or non-granulo- Making the diagnosis of TB Quatiferron gold Tuberculosis matous and with or requires lab tests. The purified pro- Purified protein derivative skin Tuberculosis without iris nodules, tein derivative (PPD) skin test can test (PPD) dilated iris vessels identify past exposure but does not Chest X-ray (CXR) Sarcoidosis; Tuberculosis and iris atrophy. indicate if the disease is active. Chest

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CT/X-ray and sputum cultures are zoster virus (VZV) and cytomegalo- (CMV)—is ubiquitous in humans performed to determine if the infec- virus (CMV). The diagnosis of HSV and can cause major morbidity and tion is active. Blood tests, called anterior uveitis is often made based mortality especially in immuno- interferon-gamma release assays, mainly on clinical features—50% to compromised patients; for instance, indicate TB infection. 90% of cases have elevated IOP, iris CMV retinitis is the most com- • Lyme disease. This is a multi- atrophy, KPs, and unilateral presen- mon ocular manifestation seen in system disorder caused by the spiro- tation.60 patients with HIV/AIDS. CMV has chete Borrelia bergdorferi infection, Herpesvirus 1 (HSV-1) is impli- been recognized as a cause of AU which is transmitted via tick bites. cated in anterior uveitis that is granu- in patients who are HIV negative, There are three stages of Lyme dis- lomatous, unilateral, and often with accounting for 22.8% of cases asso- ease: early, disseminated and persis- increased IOP due to concomitant ciated with AU and raised IOP.69 tent. In the early stage of the disease, trabeculitis.60 Although HSV-associ- CMV-associated AU in immuno- 60% to 80% of patients present ated AU is granulomatous, the KPs competent individuals may present with erythema migrans rash (Figure are usually fine and medium sized vs with unilateral ocular hypertension, 4) that may take a bull’s-eye pattern the mutton-fat appearance of other chronic or recurrent uveitis with at the site of the tick bite within two granulomatous etiologies.60 HSV patchy or diffuse iris atrophy, few to 28 days after the bite.53 Associ- anterior uveitis recurs an estimated fine KPs and mild anterior chamber ated symptoms in the early stage 71% of the time, which increases the cells. CMV-associated AU is thought may include fever, malaise, fatigue, likelihood of iris atrophy.61-63 to be the cause of Posner-Schlossman arthralgia and myalgia. Herpesvirus 3—varicella zoster syndrome.69 Treatment for CMV- All forms of uveitis may be pres- virus (VZV)—causes chickenpox. associated AU includes topical gan- ent in the later stages of the disease Following the initial infection, VZV ciclovir as a first-line treatment due (weeks to months after the initial remains dormant in neural ganglia. to good tolerability and minimal side infection), including AU, intermedi- When VZV is reactivated, it causes effects, in conjunction with topical ate uveitis, posterior uveitis, neuro- herpes zoster (HZV), which typically corticosteroids.60,69,70 retinitis, retinal vasculitis, choroiditis manifests with unilateral pain in a and panuveitis.54-58 dermatomal distribution accompa- Anterior uveitis is a common If Lyme disease is suspected, nied by a maculopapular vesicular condition that all primary eye care immunofluorescence assay (IFA) or rash. When reactivated along the providers encounter. To effectively enzyme immunoassay (EIA) are per- trigeminal nerve, it is termed herpes manage AU, the clinician must formed first. If either test is positive zoster ophthalmicus.63-67 know not just the signs and symp- or equivocal, IgM and IgG Western Treat HSV- or VZV-associated AU toms associated with AU, but also blot series are performed if signs or with topical corticosteroids. Because the underlying etiologies that often symptoms are ≤30 days. IgG Western chronic and/or recurrent AU is com- cause it. Narrowing the etiology blot is performed if signs or symp- mon, concomitant oral antiviral first requires identifying the AU as toms are >30 days.59 medication is often also required. acute, chronic or recurrent. Past and Doxycycline 100mg every 12 Acyclovir 400mg (800mg for VZV) current clinical signs and symptoms hours for 10 to 21 days is the recom- five times per day, valacyclovir often guide this determination. mended treatment for non-pregnant 500mg (1,000mg for VZV) three Further, one must know the differ- adults. Amoxicillin is 500mg TID times per day or famciclovir 500mg ent types of clinical signs associated for 14 to 21 days for pregnant adults three times per day are all acceptable with granulomatous vs non-granu- and in children 50mg/kg divided dosages to effectively treat patients lomatous inflammation. Based on into three doses per day for 14 to 21 with active herpes infection and ocu- laterality (unilateral vs. bilateral vs days.59 Ocular treatment includes lar inflammation.60-68 Antiviral cover- alternating), clinical course (acute, topical steroids in conjunction with age can be reduced to two times per chronic or recurrent), type of systemic treatment. day for acyclovir or one time per day inflammation (granulomatous vs. for valacyclovir or famciclovir once non-granulomatous) and review of Viral Etiologies the ocular inflammation shows signs systems, the clinician should be able The most common infectious under- of reduction and the patient’s corti- to differentiate any underlying etiol- lying etiology of anterior uveitis is costeroid therapy has been tapered to ogy as infectious vs non-infectious. caused by viruses—most commonly one drop three times per day.60-68 This will then allow the clinician to herpes simplex (HSV), varicella Herpesvirus 5—cytomegalovirus obtain any necessary laboratory tests

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0072_ro0219_Uveitis_OSC.indd72_ro0219_Uveitis_OSC.indd 7788 22/5/19/5/19 12:0112:01 PMPM criteria for axial spondyloarthritis (part II): validation and final selection. Testing. Centers for Disease Control and Prevention website. December to help support or confirm the sus- Ann Rheum Dis. 2009;68(6):777-83. 21, 2018. www.cdc.gov/lyme/healthcare/index.html. Accessed Septem- pected underlying etiology. 23. Rosenbaum JT. Characterization of uveitis associated with spondylo- ber 3, 2018. arthritis. J Rheumatol. 1989;16(6):792-6. 60. Jap A, Chee SP. Viral anterior uveitis. Curr Opin Ophthalmol. Once the underlying etiology is 24. Wakefield D, Chang JH, Amjadi S, et al. What is new HLA-B27 acute 2011;22(6):483-8. anterior uveitis? Ocul Immunol Inflamm. 2011;19(2):139-44. 61. North RD, Pavan-Langston D, Geary P. Herpes simplex virus types determined, a more targeted treat- 25. Rabinovich CE. Treatment of juvenile idiopathic arthritis-associated 1 and 2: therapeutic response to antiviral drugs. Arch Ophthalmol. ment of the ocular inflammation can uveitis: challenges and update. Curr Opin Rheumatol. 2011;23(5):432-6. 1976;94(6):1019-21. 26. Hofer M, Southwood TR. Classification of childhood arthritis. Best 62. Pavan-Langston D, Grene B. Herpes simplex ocular disease. Compr be initiated through concomitant Pract Res Clin Rheumatol. 2002;16(3):379-96. Ther. 1984;10(6):30-6. 27. Sabri K, Saurenmann RK, Silverman ED, Levin AV. Course, com- 63. Pavan-Langston D. Herpes simplex and herpes zoster keratouveitis: systemic management. ■ plications, and outcome of juvenile arthritis-related uveitis. J AAPOS. diagnosis and management. Bull N Y Acad Med. 1977;53(8):731-48. 2008;12:539–545. 64. Pavan-Langston D. Varicella-zoster ophthalmicus. Int Ophthalmol Dr. Opitz is an associate profes- 28. Cassidy J, Kivlin J, Lindsley C, Nocton James. Ophthalmic Clin. 1975;15(4):171-85. sor in the Department of Clinical examinations in children with juvenile rheumatoid arthritis. Pediatrics. 65. Pavan-Langston D. Ocular viral infections. Med Clin North Am. 2006;117(5):1843–1845. 1983;67(5):973-90. Education at the Illinois College of 29. Burgos-Vargas R, Pacheco-Tena C, Vázquez-Mellado J. The juvenile- 66. Pavan-Langston D. Herpes zoster ophthalmicus. Neurology. onset spondyloarthritides: rationale for clinical evaluation. Best Pract Res 1995;45(12 Suppl 8):S50-1. Optometry and is the senior direc- Clin Rheumatol. 2002;16(4):551-72. 67. Womack LW, Liesegang TJ. Complications of herpes zoster ophthal- tor of Ophthalmology Services and 30. Birnbaum AD, Oh FS, Chakrabarti A, et al. Clinical features and diag- micus. Arch Ophthalmol. 1983;101(1):42-5. nostic evaluation of biopsy-proven ocular sarcoidosis. Arch Ophthalmol. 68. A controlled trial of oral acyclovir for iridocyclitis caused by herpes Practice Development for the Illinois 2011;129(4):409-13. simplex virus. The Herpetic Eye Disease Study Group. Arch Ophthalmol. 31. Jabs DA, Johns CJ. Ocular involvement in chronic sarcoidosis. Am J 1996;114(9):1065-72. Eye Institute. Ophthalmol. 1986;102(3):297-301. 69. Chee SP, Bacsal K, Jap A, et al. Clinical features of cytomegalovirus 32. Karma A, Huhti E, Poukkula A. Course and outcome of ocular sar- anterior uveitis in immunocompetent patients. Am J Ophthalmol. 1. Huang JJ, Gau PA. Ocular Inflammatory Disease and Uveitis Manual coidosis. Am J Ophthalmol. 1988;106(4):467-72. 2008;145(5):834-40. Diagnosis and Treatment. Philadelphia: Lippincott Williams & Wilkins; 33. Crick RP, Hoyle C, Smellie H. The eyes in sarcoidosis. Br J Ophthal- 70. Chee SP, Jap A. Cytomegalovirus anterior uveitis: outcome of treat- 2010:1-9. mol. 1961;45(7):461-81. ment. Br J Ophthalmol. 2010;94:1648-52. 2. Snell RS, Lemp MA. The eyeball. In: Snell RS, Lemp MA, eds. 34. Gold DH, Morris DA, Henkind P. Ocular findings in systemic lupus Clinical Anatomy of the Eye. 2nd ed. Malden, MA: Blackwell Science; erythematosus. Br J Ophthalmol. 1972;56(11):800-4. 1998:140-156. 35. Silpa-archa S, Lee JJ, Foster CS. Ocular manifestations in OSC QUIZ 3. Rao NA, Forster DJ. Basic principles. In: Podos SM, Yanoff M, editors. systemic lupus erythematosus. Br J Ophthalmol. Br J Ophthalmol. The Uvea, Uveitis, and Intraocular Neoplasms. Vol. 2. New York: Gower 2016;100(1):135-41. Medical Publications; 1992:1-17. 36. Ando K, Fujino Y, Hijikata K, et al. Epidemiological features and visu- ou can obtain continuing educa- 4. Foster CS, Vitale AT. Diagnosis and Treatment of Uveitis. 2nd ed. New al prognosis of Behcet’s disease. Jpn J Ophthalmol. 1999;43(4):312-7. tion credit through the Optometric Delhi: Jaypee Brothers Medical Publishers Ltd; 2013:20-32. 37. Nussenblatt RB. Uveitis in Behcet’s disease. Int Rev Immunol. 5. Agrawal RV, Murthy S, Sangwan V, Biswas J. Current approach in 1997;14(1):67-79. Study Center. Com plete the test 38. Mishima S, Masuda K, Izawa Y, et al. The eighth Frederick H. Verhoeff Y diagnosis and management of anterior uveitis. Indian J Ophthalmol. form and return it with the $35 fee to: 2010;58(1):11-9. Lecture, presented by Saiichi Mishima, MD, Behcet’s disease in Japan: 6. Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis ophthalmologic aspects. Trans Am Ophthalmol Soc. 1979;77:225-279. Jobson Healthcare Information, LLC, Attn.: CE Nomenclature (SUN) Working Group. Standardization of uveitis 39. Baer JC, Raizman MB, Foster CS. Ocular Behçet’s disease in the nomenclature for reporting clinical data. Results of the First International United States. Clinical presentation and visual outcome in 29 patients. In: Processing, 395 Hudson Street, 3rd Floor Workshop. Am J Ophthalmol. 2005;140(3):509-16. Masahiko U, Shigeaki O, Koki A, eds. Proceedings of the Fifth Interna- New York, New York 10014. To be eligible, 7. Williams GT, Williams WJ. Granulomatous inflammation—a review. J tional Symposium on the Immunology and Immunopathology of the Eye; Clin Pathol. 1983;36(7):723-33. Tokyo, New York: Elsevier Science; 1990:383. please return the card within three years of 8. Herbort CP. Appraisal, workup and diagnosis of anterior uveitis: a 40. Barile GR, Flynn TE. Syphilis exposure in patients with uveitis. Oph- publication. You can also access the test practical approach. Middle East Afr J Ophthalmol. 2009;16(4):159-67. thalmology. 1997;104(10):1605-9. 9. Yanoff M, Duker JS. Ophthalmology. 2nd ed. St Louis: Mosby; 2004. 41. Margo CE, Hamed LM. Ocular syphilis. Surv Ophthalmol. form and submit your answers and pay- 10. Harthan JS, Opitz DL, Fromstein SR, Morettin CE. Diagnosis and 1992;37(3):203-20. ment via credit card at RGVCE online, www. treatment of anterior uveitis: optometric management. Clin Optom 42. Deschenes J, Seamone CD, Baines MG. Acquired ocular syphilis: (Auckl). 2016 Mar 31;8:23-35. diagnosis and treatment. Ann Ophthalmol. 1992;24(4):134-8. reviewsce.com. 43. Tamesis RR, Foster CS. Ocular syphilis. Ophthalmology. 11. Foster CS, Davanzo R, Flynn TE, et al. Durezol (difluprednate You must achieve a score of 70 or higher ophthalmic emulsion 0.05%) compared with Pred Forte 1% ophthalmic 1990;97(10):1281-7. suspension in the treatment of endogenous anterior uveitis. J Ocul Phar- 44. Mendelsohn AD, Jampol LM. Syphilitic retinitis. A cause of necrotiz- to receive credit. Allow four weeks for pro- mocol Ther. 2010;26(5):475-83. ing retinitis. Retina. 1984;4(4):221-4. 12. Freeman WR, Green RL, Smith RE. Echographic localization of 45. McLeish WM, Pulido JS, Holland S, et al. The ocular manifestations cessing. For each Optomet ric Study Center corticosteroids after periocular injection. Am J Ophthalmol. 1987;103(3 of syphilis in the human immunodeficiency virus type 1-infected host. course you pass, you earn 2 hours of credit Pt 1):281-8. Ophthalmology. 1990;97(2):196-203. 13. Smith RE, Nozik RA. Uveitis: A Clinical Approach to Diagnosis and 46. 2015 Sexually Transmitted Diseases Treatment Guidelines. Centers from Pennsyl vania College of Optometry and Management. Baltimore: Williams & Wilkins; 1989:51-76. for Disease Control and Prevention website. July 27, 2016. www.cdc. double credit toward the AOA Optom et ric 14. Sheppard JD, Toyos MM, Kempeen JH, Foster CS. Difluprednate gov/std/tg2015/syphilis.htm. Accessed September 3, 2018. 0.05% versus prednisolone acetate 1% for endogenous anterior uveitis: 47. Suzuki J, Oh I, Kezuka T, Sakai J, Goto H. Comparison of patients Recog nition Award—Cate gory 1. a phase III, multicenter, randomized study. Invest Ophthalmol Vis Sci. with ocular tuberculosis in the 1990s and the 2000s. Jpn J Ophthalmol. Please check with your state licensing 2014;55(5):2993-3002. 2018;54(1):19-23. 15. Kusne Y, Kang P, Fintelmann RE. A retrospective analysis of intraocu- 48. Cutrufello NJ, Karakousis PC, Fishler J, Albini TA. Intraocular tuber- board to see if this approval counts toward lar pressure changes after cataract surgery with the use of prednisolone culosis. Ocul Immunol Inflamm. 2010;18(4):281-91. your CE requirement for relicensure. acetate 1% versus difluprednate 0.05%. Clin Ophthalmol. 2016 Nov 49. Gupta A, Bansal R, Gupta V, et al. Ocular signs predictive of tubercu- 23;10:2329-36. lar uveitis. Am J Ophthalmol. 2010;149(4):562-70. 16. Controlled evaluation of loteprednol etabonate and prednisolone 50. Gupta A, Sharma A, Bansal R, Sharma K. Classification of intraocular acetate in the treatment of acute anterior uveitis. Loteprednol Etabonate tuberculosis. Ocul Immunol Inflamm. 2015;23(1):7-13. 1. A patient with new onset pain, redness and US Uveitis Study Group. Am J Ophthalmol. 1999;127(5):537-44. 51. Madge SN, Prabhakaran VC, Shome D, et al. Orbital tuberculosis: a photophobia has anterior uveitis with no past 17. Gutteridge IF, Hall AJ. Acute anterior uveitis in primary care. Clin Exp review of the literature. Orbit. 2008;27(4):267-77. Optom. 2007;90(2):70-82. 52. Rosen PH, Spalton DJ, Graham EM. Intraocular tuberculosis. Eye history of uveitis. What best describes the 18. Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern (Lond) 1990;4(pt 3):486-92. patient’s clinical course? California; the Northern California Epidemiology of Uveitis Study. Oph- 53. Guidelines for laboratory evaluation in the diagnosis of Lyme disease. thalmology. 2004;111(3):491-500. American College of Physicians. Ann Intern Med. 1997;127(12):1106-8. a. Acute anterior uveitis. 19. Rosenbaum JT. Characterization of uveitis associated with spondylo- 54. Isogai E, Isogai H, Kotake S, et al. Detection of antibodies against arthritis. J Rheumatol. 1989;16(6):792-6. Borrelia burgdorferi in patients with uveitis. Am J Ophthalmol. 20. Rudwaleit M, van der Heijde D, Landewé R, et al. The Assessment of 1991;112(1):23-30. SpondyloArthritis International Society classification criteria for periph- 55. Karma A, Viljanen M, Pirttila T, et al. Ocular Lyme borreliosis. Duo- eral spondyloarthritis and for spondyloarthritis in general. Ann Rheum decim. 1993;109(1):35-42. Dis. 2011;70(1):25-31. 56. Karma A, Seppala I, Mikkila H, et al. Diagnosis and clinical character- 21. Rudwaleit M, Landewé R, van der Heijde D, et al. The development istics of ocular Lyme borreliosis. Am J Ophthalmol. 1995;119(2):127-35. of Assessment of SpondyloArthritis International Society classification 57. Mikkila H, Karma A, Viljanen M, Seppala I. The laboratory diagnosis criteria for axial spondyloarthritis (part I): classification of paper patients of ocular Lyme borreliosis. Graefes Arch Clin Exp Ophthalmol. 1999 by expert opinion including uncertainty appraisal. Ann Rheum Dis. Mar;237(3):225-30. 2009;68(6):770-6. 58. Flach AJ, Lavoie PE. Episcleritis, conjunctivitis, and keratitis as ocu- TAKE THE TEST ONLINE TODAY! 22. Rudwaleit M, van der Heijde D, Landewé R, et al. The development lar manifestations of Lyme disease. Ophthalmology. 1990;97(8):973-5. https://www.reviewsce.com of Assessment of SpondyloArthritis International Society classification 59. Lyme Disease – Health Care Providers – Diagnosis, Treatment and

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OSC QUIZ

b. Chronic anterior uveitis. difluprednate 0.05% to treat acute anterior 14. You are treating a 37-year-old white c. Recurrent anterior uveitis. uveitis? male for acute, recurrent, alternating d. Undifferentiated anterior uveitis. a. Every one to two hours. non-granulomatous anterior uveitis. When b. 12 times/day. developing your differential diagnosis, which 2. All of the following are suggestive of an c. Four times/day. underlying etiology is at the top of your list? infectious etiology of anterior uveitis, except: d. Once daily. a. Cytomegalovirus. a. Recurrent granulomatous uveitis. b. HLA-B27. b. Chronic granulomatous uveitis. 8. Which topical corticosteroid should be c. Herpes simplex virus. c. Acute non-granulomatous uveitis. considered first for a patient with steroid- d. Varicella zoster virus. d. Chronic bilateral uveitis. induced IOP spikes? a. Dexamethasone 0.1%. 15. All of the following systemic conditions 3. Which of the following is most suggestive b. Prednisolone acetate 1%. are correctly paired with a matching lab test, of an infectious underlying etiology? c. Loteprednol 0.5%. except: a. 44-year-old white male with chronic d. Difluprednate 0.05%. a. Syphilis – MHA-TP. bilateral anterior uveitis with increased IOP, b. Tuberculosis – Interferon gamma. iris atrophy and large mutton-fat KPs on the 9. When should you begin to taper topical c. Sarcoidosis – ANA. endothelium. corticosteroids? d. Ulcerative colitis – HLA B27. b. 12-year-old white male with acute anterior a. Once fewer than five cells per high- uveitis of the left eye. powered field are visible in the anterior 16. What is the systemic treatment for early c. 49-year-old Hispanic male with recurrent chamber. latent syphilis? alternating anterior uveitis of the left eye and b. After three months of treatment. a. A daily intramuscular injection of penicillin fine KPs on the endothelium. c. After laboratory tests confirm no infection. for three days. d. 34-year-old black male with acute bilateral d. Tapering of corticosteroids is not required b. A weekly intramuscular injection of anterior uveitis. with anterior uveitis. penicillin for three weeks. c. A single intramuscular injection of 4. Which of the following is a clinical sign of 10. A child has anterior uveitis and you penicillin. non-granulomatous inflammation? suspect JIA. All of the following blood tests d. Intravenous penicillin every four hours for a. Bussaca nodules. should be performed, except: 10 days. b. Mutton-fat KPs. a. ANA. c. Fine white KPs. b. HLA-B27. 17. What is the recommended treatment for d. Bulbar conjunctival nodules. c. Rheumatoid factor. an adult with Lyme disease? d. Polymerase chain reaction. a. Amoxicillin 100mg for 21 days. 5. You count 15 anterior chamber cells b. Doxycycline 100mg for 21 days. in a 1mm x 1mm slit beam. Based on 11. All of the following are conditions c. Valacyclovir 1,000mg for 14 days. classification by the SUN Working Group, associated with HLA-B27, except: d. Amoxicillin 500mg for 21 days. what grade of cells does your patient have? a. Ankylosing spondylitis. a. 1+. b. Reactive arthritis. 18. What is the most common infectious b. 2+. c. Psoriatic arthritis. underlying etiology for anterior uveitis? c. 3+. d. Rheumatoid arthritis. a. Bacteria. d. 5+. b. Viruses. 12. What is the most common non-infectious c. Syphilis. 6. A 58-year-old black female presents underlying etiology for anterior uveitis? d. Tuberculosis. with a complaint of a blurry left eye for a. Sarcoidosis. the past two weeks. She also reports b. HLA-B27 spondyloarthropathy. 19. Which underlying etiology condition best redness and seven out of 10 pain that is c. Systemic lupus erythematous. describes a patient with recurrent anterior progressing. Upon clinical exam, you note d. Behcet’s disease. uveitis, elevated IOP and iris atrophy that 3+ anterior chamber cells with 2+ flare. occurs only in one eye? She has posterior synechiae at 2:00 and 13. Which of the following is true of the HLA- a. Herpes simplex virus. 5:00. You diagnose the patient with acute B27 spondylarthropathies? b. Tuberculosis. anterior uveitis. Which treatment is the most a. HLA-B27 uveitis is non-granulomatous c. Juvenile idiopathic arthritis. appropriate for this patient? and non-infectious. d. Psoriatic arthritis. a. Difluprednate q1hr OS. b. Patients with HLA-B27 test positive for b. Prednisolone acetate 1% every two hours rheumatoid factor. 20. Treatment of a patient with acute HSV- and homatropine 5% BID OS. c. Ankylosing spondylitis is caused from past associated uveitis should include: c. Prednisolone acetate 1% QID OS. exposure to certain bacterial infections. a. Doxycycline 100mg. d. Atropine 1% QID OS. d. Psoriatic arthritis has the triad of uveitis, b. Valacyclovir 500mg TID. plaque psoriasis and abdominal cramping. c. Acyclovir 800mg BID. 7. What is the standard dosing frequency of d. Single intramuscular injection of penicillin.

80 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

0072_ro0219_Uveitis_OSC.indd72_ro0219_Uveitis_OSC.indd 8800 22/5/19/5/19 12:0212:02 PMPM Examination Answer Sheet Mail to: Jobson Healthcare Information, LLC, Attn.: CE Processing, 395 Take a Clinical Approach to Anterior Uveitis Hudson Street, 3rd Floor New York, New York 10014 Valid for credit through February 15, 2022 Payment: Remit $35 with this exam. Make check payable to Jobson Healthcare Information, LLC. Online: This exam can be taken online at www.reviewsce.com. Upon passing the Credit: This course is COPE approved for 2 hours of CE credit. Course ID is exam, you can view your results immediately and download a real-time CE certifi- 60776-AS. cate. You can also view your test history at any time from the website. Jointly provided by Postgraduate Institute for Medicine and RGVCE. Directions: Select one answer for each question in the exam and completely darken the appropriate circle. A minimum score of 70% is required to earn credit. Salus University has sponsored the review and approval of this activity. Processing: There is a four-week processing time for this exam. Answers to CE exam: Post-activity evaluation questions: 1. A B C D Rate how well the activity supported your achievement of these learning objectives: 2. A B C D 1=Poor, 2=Fair, 3=Neutral, 4=Good, 5=Excellent 3. A B C D 1 2 3 4 5 4. A B C D 21. Demonstrate knowledge of the ocular signs and symptoms, as well as systemic associations, related to anterior uveitis. 5. A B C D 1 2 3 4 5 6. A B C D 22. Use common laboratory tests to help localize the etiology of the uveitis.

7. A B C D 23. Perform a dilated fundus examination for all patients who present with anterior uveitis. 1 2 3 4 5

8. A B C D 24. Define the appropriate topical or systemic anti-inflammatories and, importantly, the frequency of dosing, for 1 2 3 4 5 9. A B C D managing anterior uveitis.

10. A B C D 25. Describe the use of cycloplegia to reduce pain, prevent synechiae formation and re-establish the blood- 1 2 3 4 5 11. A B C D aqueous barrier. 12. A B C D 26. Based upon your participation in this activity, do you intend to change your practice behavior? 13. A B C D (choose only one of the following options) A 14. A B C D I do plan to implement changes in my practice based on the information presented. B 15. A B C D My current practice has been reinforced by the information presented. C I need more information before I will change my practice. 16. A B C D

17. A B C D 27. Thinking about how your participation in this activity will influence your patient care, how many of your patients are likely to benefit? (please use a number): 18. A B C D

19. A B C D

20. A B C D

28. If you plan to change your practice behavior, what type of changes do you plan to implement? (check all 30. Which of the following do you anticipate will that apply) be the primary barrier to implementing these changes? a Apply latest guidelines b Change in pharmaceutical therapy c Choice of treatment/management approach a Formulary restrictions d Change in current practice for referral e Change in non-pharmaceutical therapy f Change in differential b Time constraints diagnosis g Change in diagnostic testing h Other, please specify: ______c System constraints ______d Insurance/financial issues e Lack of interprofessional team support 29. How confident are you that you will be able to make your intended changes? f Treatment related adverse events g Patient adherence/compliance a Very confident b Somewhat confident c Unsure d Not confident h Other, please specify:

Please retain a copy for your records. Please print clearly.

First Name 31. Additional comments on this course: Last Name ______E-Mail ______The following is your: Home Address Business Address ______Business Name ______

Address Rate the quality of the material provided: 1=Strongly disagree, 2=Somewhat disagree, 3=Neutral, City State 4=Somewhat agree, 5=Strongly agree

ZIP 32. The content was evidence-based. 1 2 3 4 5 Telephone # - - 33. The content was balanced and free of bias.

Fax # - - 1 2 3 4 5 34. The presentation was clear and effective. By submitting this answer sheet, I certify that I have read the lesson in its entirety and completed the self- 1 2 3 4 5 assessment exam personally based on the material presented. I have not obtained the answers to this exam by any fraudulent or improper means. 35. Based upon your participation in this activity, do you intend to change your practice behavior? Signature Date 1 2 3 4 5 Lesson 117642 RO-OSC-0219

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0072_ro0219_Uveitis_OSC.indd72_ro0219_Uveitis_OSC.indd 8811 22/5/19/5/19 12:0212:02 PMPM Earn up to NEWNEW TTECHNOLOGIES

20 CE 2019 Credits* & TTREATMENTS IN 9 EyeEyyeeCeGVCE CareCaC ar Join us in REVIEW’S COMMITMENT TO Orlando, Florida CONTINUING EDUCATION March 7-10, 2019

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Photos Courtesy of Disneyisney GrGroupoup MkMarkMarketingetinti g Cornea+Contact Lens Q+A

Making the Leap Avoiding corneal touch whenever possible when fitting scleral lenses helps minimize the risk of long-term ocular damage. Edited by Joseph P. Shovlin, OD

I struggle with the concept the cornea and still achieve Q of achieving complete cor- good results. The answer, nea clearance in every patient fit he says, is it is possible, with scleral lenses. For years, we’ve but not without taking on accepted some apical touch in kera- some risk. toconus patients who wear corneal “The idea of a fully lenses, especially in those with espe- vaulting, touch-free corneal cially steep apical areas. Should we lens is appealing to special- try to completely avoid touch in these ty lens practitioners who patients or is some touch acceptable? want to prevent scarring, “One of the foundational which leads to vision loss,” A concepts of scleral lens fitting Dr. Jedlicka notes. He adds is complete corneal clearance,” that if a scleral lens were Fig. 1. Epithelial bullae from a scleral lens land and says Jason Jedlicka, OD, associate to touch the corneal apex, bear on the peripheral cornea. professor at the Indiana University over time the same risk School of Optometry and chief of of chronic staining that leads to lead to difficult lens removal, the school’s Cornea and Contact irritation and photophobia—and says Dr. Jedlicka. Adhesion forces Lens Service. He adds that part of eventually scarring and vision between a contact lens and an eye what defines a scleral lens is that loss—would also be present. increase as the lens surface and the all the lens bearing occurs on the eye surface become increasingly sclera, hence the name. Dr. Jedlicka Weighing Your Options close over a larger surface area, notes that some may question Scleral lenses can touch the cornea he adds. When fitted with proper whether it is necessary for scleral anywhere on the surface, increas- vault over the entire cornea and lenses to fully vault the cornea or ing the risk of visual and ocular limbal zone, he notes that a scleral if optometrists can fit these lenses health complications if persistent. lens should not exhibit adhesion— with some bearing of the lens on According to Dr. Jedlicka, this can though it may exhibit “suction”— happen when a scleral lens and, therefore, should not be as is fit too shallow. When this challenging to remove. occurs peripherally, he says epithelial bullae formation While we see many instances in could occur, likely from which scleral lenses end up with mechanical forces on the corneal contact that does not lead epithelial tight junctions to any complications, Dr. Jedlicka (Figure 1).1 On the other says the risks increase when touch hand, when this occurs occurs. He recommends making centrally, he notes that the every attempt to avoid corneal result is similar to what touch when fitting scleral lenses to happens during corneal gas minimize these risks and prevent permeable lens use—stain- long-term damage. ■ ing and potentially scarring Fig. 2. This scleral lens was fit with corneal touch. 1. Nixon AD, Barr JT, VanNasdale DA. Corneal epithelial (Figure 2). bullae after short-term wear of small diameter scleral Note the corneal staining on the apex. Corneal touch can also lenses. Cont Lens Anterior Eye. 2017;40(2):116-26.

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083_ro0219_CLQA.indd 83 2/8/19 11:48 AM Glaucoma Grand Rounds

If Only They Had Asked Complications can and do occur, though some can be averted. By James L. Fanelli, OD

63-year-old Caucasian female presented to the office as a new patient in June seeking a second opinion.A She had presented to an eye clinic earlier in the year with complaints of gradually decreasing vision. The patient attributed this to normal decline in her vision, and felt that her eyeglasses needed to be updated. She was told that she did have a change in her prescription This OCT shows our patient’s left macula, highlighting the ganglion cells. Note the and that new glasses were war- significant loss of ganglion cells superiorly as compared with inferiorly, and the lack ranted, but also that she needed to of change seen as compared with the baseline. This is consistent with chronic phase see a glaucoma specialist for a “laser ganglion cell loss, as opposed to acute loss. procedure.” She ordered new eyeglasses, and sequent follow-up with retina, the the left there were two LPIs, one at shortly thereafter she made her way patient was told the blood work was 3 o’clock and the other at 9 o’clock. to an ophthalmic surgeon who per- normal and the residual effects on Her anterior chambers were quiet formed a laser procedure on both vision to her left eye are permanent. with no cells or flare. Applanation eyes that same day. Approximately She was then sent to my office. tensions at 3:45pm were 23mm Hg two weeks after the procedure, she OD and 24mm Hg OS. Pachymetry developed moderate pain, with pho- Examination readings were 598µm OD and tophobia and a headache lasting a When seen by me for the first time, 594µm OS. couple of days as well as difficulty she was only taking lisinopril, and Threshold visual fields were seeing out of the left eye. She subse- had been so for several years, and entirely normal in the right eye. quently reported back to the surgeon she was taking no topical medica- The left was characterized by a field who performed the laser procedure, tions. Her best-corrected visual defect extending from the blind and was put on drops (the patient acuities were 20/20-1 OD and 20/50 spot to fixation, greater below the did not know which ones specifi- OS. Her pupils were round and horizontal than above. The findings cally, but she remembered she was reactive to light, and there was a 2+ were consistent with an optic nerve to shake the drops vigorously before afferent pupillary defect in her left infarct and with the confrontation instillation) for what was about five eye. Confrontation fields demon- field findings. days, during which time the pain strated an altitudinal defect in the The patient was dilated in the seemed to resolve, but her vision left eye and were normal in the right. usual fashion. Through dilated remained blurry. She reported back A slit lamp examination of her pupils, her crystalline lenses were to the surgeon who then referred her corneas was unremarkable. Both characterized by mild nuclear sclero- to retina. anterior chamber angles appeared sis in both eyes. Apparently when seen at retina, somewhat narrow at the slit lamp The cup-to-disc ratio in her right blood work was ordered and the using the Van Herick technique. eye was 0.3x0.3 and that of the left patient was told that she may have Her right eye had a laser peripheral was 0.4x0.4. The neuroretinal rim had a “stroke” in the eye. In a sub- iridotomy (LPI) at 12 o’clock, and in in the right was plush and well per-

84 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

084_ro0219_GGR.indd 84 2/5/19 12:16 PM COMBO CHAIRS & STANDS fused, whereas that of the left was chamber at that visit, and IOPs were pale and atrophic from 12 o’clock 20mm Hg OD and OS. to 4 o’clock. Both maculae were healthy. Her retinal vascular details Diagnosis were also unremarkable. The periph- The retinologist diagnosed an eral retina was characterized by scat- ischemic optic neuropathy and the tered areas of cystoids degeneration patient was ultimately sent to me. OptimizeOptimize in both eyes. Post dilation pressures As best as I can tell, sometime fol- were 22mm Hg OD and OS, with lowing the LPI, most likely within spacespace anandd open angles. the first few days, the left optic nerve OCT imaging of the optic nerves infarcted. Did the LPI contribute to functionality.functionality. was consistent with a chronic that? Possibly, though we’ll never appearance of non-arteritic ischemic know for certain. But the timeframe optic neuropathy (NAION) in the fits. Could she have experienced an left eye; the OCT imaging of the exaggerated inflammatory response right optic nerve was unremarkable. in the left eye that underwent two Neuro OCT imaging of the left optic LPI procedures? Could she have nerve demonstrated a reduced papil- had a concurrent IOP spike post LPI lomacular bundle, consistent with in the left eye? What did that eye the findings of NAION. look like in the immediate post LPI period? The answers to these ques- History tions are unknown, as no follow-up Much of the history on the initial was performed until after the patient visit was from the patient’s perspec- developed symptoms. tive, and I’ve learned over the years This is an important reminder that, sometimes what actually hap- that, following LPI, the patient must pens is different than what is por- be examined several days later for trayed in the history. Subsequent to some of the common side effects our first visit together, I was able to from the procedure, such as inflam- obtain relevant medical records, and mation and IOP elevation, not to the patient’s interpretation of the mention what effect it has on open- series of events was fairly accurate. ing the angles and reducing the risk One of my initial questions at of angle closure. And therein lies the the first visit centered around what rub in this unfortunate situation. transpired during the laser procedure. It was my interpretation from Imaging the history, and later confirmed Standard protocol in my office when Affordable,Affordable, by review of the medical records, I am examining patients with nar- that the patient was only given two row or slightly narrow angles is to space-savingspace-saving drops in each eye of Iopidine (apra- obtain an ultrasound biomicroscopy clonidine, Novartis) in the office, (UBM) image of the anterior seg- cchairhair & standstand and was discharged on a regimen ment. While the angle itself can of Pred Forte (prednisolone acetate, be visualized in a variety of ways, solutions. Allergan) to use for three days. No namely, at the slit lamp, during goni- follow-up was scheduled. oscopy, and with anterior segment Small footprint On the follow-up visit after the OCT imaging, there are times when 41.2” x 34.2” patient experienced pain and blurred UBM gives us important details. vision, she was again prescribed Pred And one of the situations where Forte QID and was scheduled to UBM gives us more data than the see a retina specialist. There was no aforementioned procedures is in the mention of the status of the anterior case of plateau iris configuration.

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RO0119_House VEE.indd 1 1/4/19 12:14 PM Glaucoma Grand Rounds SLITLAMPS SLIT LAMPS Treatment EXCEPTIONAL OPTICS Because a plateau iris configuration lends itself to a different mechanism of subsequent angle closure, the treatment options are different. The treatment of choice in plateau iris situations is a laser iridoplasty.1 In S4OPTIK’s argon laser peripheral iridoplasty, converging laser energy is applied to the peripheral iris in a circumferential pattern. binoculars The thermal energy applied to the DOORZHƪRUWOHVV Note the relative anterior positioning iris causes contracture of the iris, of the ciliary body posterior to the and a somewhat posterior planar PDLQWHQDQFHRI iris root, and the subsequent anterior movement of the peripheral iris IXVLRQ displacement of the iris root. This can be away from the cornea and trabecu- seen on slit lamp as a narrow angle, but lar meshwork. without the ciliary body being visible on Researchers suggest that, when slit lamp exam, the diagnosis of plateau an LPI is performed and there is no European iris configuration cannot be made. opening of the anterior chamber craftsmanship and angle, plateau iris configuration In plateau iris configuration, the be considered.1 And that is exactly engineering provide ciliary body and ciliary processes what happened in this case; post UHOLDEOHRSWLFVDW are positioned more anteriorly, and LPI, the angle configuration had DOOPDJQLƬFDWLRQV therefore result in the iris being not changed. Of course hindsight positioned more anteriorly, espe- is always 20/20, but pre-surgical IRUFRQƬGHQW cially toward the iris root. The iris evaluation with UBM can facilitate H[DPLQDWLRQV may appear non-bowed on clinical the diagnosis before intervention is examination. The mechanism of performed. angle closure in plateau iris syn- What is doubly unfortunate in drome is different than in normal this case is that the ophthalmic sur- anatomically narrow angles, where geon who performed the LPI does typically pupillary block results in not have a UBM unit. We do, and elevation of IOP in the posterior the surgeon knows that we do. How chamber, which in turn forces the many times has that surgeon sent H-Series Z-Series iris root more anteriorly. a patient to this OD for that pro- The benefit of LPI in cases of cedure? Precisely zero. One of the narrow angles and pupillary block other things I’ve learned throughout glaucoma is well documented. the years is that some ophthalmic However, LPIs have little effect in surgeons give lip service to working reducing the potential closure of the with optometry, when in fact their angle in cases of plateau iris con- actions sometimes speak louder than figuration. words. Someone is still fighting the Plateau iris syndrome is essen- old battles between the professions. tially a form of angle closure And unfortunately, it is the patient glaucoma, but with a mechanism who invariably loses. ■ Vertical and compact different than outlined above, and 1. Stefan C, Iliescu D, Batras M, et al. Plateau iris – diagnosis and treatment. Rom J Ophthalmol. 2015;59(1):14-8. with the appearance of narrow 2. Kumar G, Bali S, Panda A, et al. Prevalence of plateau iris con- FRQƬJXUDWLRQVDYDLODEOH angle glaucoma.1 UBM plays an figuration in primary angle closure glaucoma using ultrasound biomicroscopy in the Indian population. Indian J Ophthalmol. important role in differentiating 2012;60(3):175-8. 3. Parc C, Laloum J, Berges O. Comparison of optical coherence anatomically narrow angles from tomography and ultrasound biomicroscopy for detection of plateau iris configuration.2,3 plateau iris. J Fr Ophthalmol. 2010;33(4):266;e1-3.

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084_ro0219_GGR.indd 87 2/5/19 12:30 PM Ocular Surface Review

Grow Some Nerve A new treatment holds promise for helping patients with neurotrophic keratitis. By Paul M. Karpecki, OD

eurotrophic keratitis (NK) see significant staining or is a corneal degenerative SPK and epithelial defects Ndisease characterized by that don’t heal properly, as reduced corneal sensation, chronic well as rapid tear break-up superficial keratopathy (SPK), time and reduced or fluctuat- persistent epithelial defects and ing visual acuity. However, other corneal changes. Although patients will often be far less an “orphan disease” affecting symptomatic than you would fewer than five people out of every expect due to the reduced 10,000, NK is quite challenging to corneal sensation. As the manage when it presents. Untreated disease progresses, corneal or undertreated, it can have serious thinning, ulceration and even consequences for vision and quality perforation occur. of life.1,2 In patients presenting with Fig. 1. Neurotrophic keratitis in a patient with these signs and symptoms, NK Basics herpes simplex keratitis. optometrists should carefully The cornea and corneal epithelium evaluate the lid anatomy are densely innervated by nerves NK is most commonly associated and function, including closure and originating from the ophthalmic with herpetic keratitis (either herpes blink rate. If you suspect NK, assess branch of the trigeminal (fifth cra- zoster or herpes simplex), post- corneal sensation by using either a nial) nerve. In fact, the cornea has neurosurgical nerve damage and cotton wisp or acrylic dental floss 7,000 nerve receptors per square diabetes (Figure 1).1,4 It may also be applied to the cornea. You could millimeter, making it one of the caused by chemical burns, contact also use an esthesiometer. Stain- most sensitive structures in the lens misuse, long-term exposure to ing with vital dyes is important for body.1 Those nerves are responsible preserved medications, overuse of visualizing ocular surface damage for nociception (pain perception) topical anesthetics and, less com- (Figure 2). Suspicion of underlying and sensation of cold and pressure. monly, with tumors, leprosy and brain pathology or systemic disease They are part of complex feedback certain genetic conditions.1 may warrant a referral to internal loops that signal tear production, medicine or neurology. the blink reflex, the production of Presentation and Examination trophic factors that provide nutri- One study recently proposed a sim- Treatment tion to the cornea and the release of plified classification of NK: mild, NK has always been a challenging immune factors into the tears.1 denoted by epithelium and tear film condition to treat. Until recently, we Infrequent blinking and reduced changes; moderate, accompanied have had few good options, espe- tear production in NK exacer- by a non-healing epithelial defect; cially for patients with moderate bate the condition, leading to an or severe, in which stromal melting disease in particular. inflamed ocular surface and further and perforation occur.1 These three As a first step, clinicians should epithelial damage. When epithelial stages are clinically useful for under- minimize ocular irritants. Eliminate healing is compromised, the exposed standing the severity of disease and all preserved topical drops (if pos- stroma becomes more vulnerable to potential treatments. sible) by reducing medications or enzymatic degradation and, eventu- In patients presenting with early switching to non-preserved forms.5 ally, ulceration or even perforation.3 to mid-stage NK, it is common to Regular use of artificial tears and

88 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

088_ro0219_OSR.indd 88 2/5/19 12:32 PM other lubricants, punctal occlusion, Treatment Advances each day and store in the refrigera- increased humidity and dietary The FDA recently approved a new tor between doses. Instructions will omega fatty acids can all be helpful treatment for NK that is expected to be provided for attaching an adapter as well. Research shows autolo- launch commercially in early 2019. to the vial, cleaning the adapter with gous serum drops (e.g., Vital Tears) Oxervate (cenegermin-bkbj ophthal- a sterile wipe, attaching a special improve signs and symptoms and mic solution 0.002%, Dompé) is a pipette with a plunger mechanism, significantly shorten healing time recombinant form of human nerve and then releasing the drop from for, and recurrences of, corneal growth factor that targets the nerve the plunger to administer one drop defects.6 Clinicians may need to pathology.10 In two randomized every two hours, six times a day.13 debride any thickened or rolled double-masked controlled trials, Although the steps may be cumber- edges of epithelial defects.7 A ban- 151 subjects received cenegermin some, mastering them is worth- dage contact lens can be helpful but or vehicle six times daily for eight while, considering cenegermin holds also increases the risk of infection.2 weeks. Complete corneal healing greater potential than most of the A better option might be amniotic was demonstrated in 70% of the treatment options we have for NK. membrane. One study using Prokera 101 patients treated with Oxervate There are several other biologics (BioTissue) showed a statistically compared with only 28% of those and other therapies in practice and significant improvement in nerve treated with the control drop.1,11,12 in the pipeline, including Xiidra density and sensitivity when analyz- The most common adverse (lifitegrast 5%, Shire), regenerating ing the corneal nerves under confo- reaction was eye pain following matrix therapy agent cacicol-20, cal microscopy.8 These patients also instillation, which was reported in thymosin beta 4, coenzyme Q10, showed improvement in corneal approximately 16% of patients. substance P, netrin-1 and Nexagon staining, symptoms of pain and Other adverse reactions included (CoDa Therapeutics), an antisense SPEED scores.8 corneal deposits, foreign body sen- oligonucleotide. Nonsurgical eyelid closure with sation, ocular hyperemia, ocular With these new therapies, we can tape, pressure patching or tempo- inflammation and tearing.12,13 be far more encouraged than ever rary ptosis with botulinum toxin Oxervate will be somewhat before about our ability to success- can help to protect loose epithelium more challenging for patients to fully manage patients with NK. ■ and while epithelial defects heal. administer than the average topical 1. Dua HS, Said DG, Messmer EM, et al. Neurotropic keratopathy. It is also important to treat con- medication. A week’s supply of the Prog Retin Eye Res. 2018;66:107-31. current infection, inflammation medication, frozen, must be shipped 2. Srinivasan S, Lyall DAM. Neurotrophic keratopathy. In: Ocular Surface Disease: Cornea, Conjunctiva, and Tear Film. Holland EJ, or meibomian gland dysfunction directly to patients, who will thaw Mannis MJ, Lee WB, eds. Philadelphia: Elsevier; 2013. with appropriate therapies, such as one of the seven multidose vials 3. Fini ME, Cook JR, Mohan R. Proteolytic mechanisms in corneal ulceration and repair. Arch Dermtol Res. 1998;290(Suppl antibiotics, cyclosporine, lid 1):S12-23. 4. Allen VD, Malinovsky V. Management of neurotrophic keratopa- expression and lid hygiene. thy. Cont Lens Anterior Eye. 2003;26(3):161-5. In more advanced stages 5. Gomes JAP, Azar DT, Baudouin C, et al. TFOS DEWS II iatra- genic report. Ocul Surf. 2017;15:511-37. of the disease, a number of 6. Guadilla AM, Balado P, Baeza A, Merino M. Effectiveness of strategies can help to restore topical autologous serum treatment in neurotrophic keratopathy. Arch Soc Esp Oftalmol. 2013;88(8):302-6. corneal integrity or, for the 7. Katzman LR, Jeng BH. Management strategies for persistent most extreme stages, pri- epithelial defects of the cornea. Saudi J Ophthalmol. 2014;28:168- 72. oritize globe integrity over 8. John T, Tighe S, Sheha H, et al. Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye vision. These include tem- disease. J Ophthalmol. 2017;2017:6404918. porary or permanent tarsor- 9. Bonini S, Rama P, Olzi D, et al. Neurotrophic keratitis. Eye. 2003;17:989-95. rhaphy, use of corneal tissue 10. Bonini S, Lambiase A, Rama P, et al., REPARO Study Group. glue, amniotic membrane Phase I trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology. 2018;125(9):1468-71. graft, Boston keratoprosthe- 11. Sacchetti M, Bruscolini A, Lambiase A. Cenegermin for the treatment of neurotrophic keratitis. Drugs Today (Barc). sis, lamellar or penetrating 2017;53(11):585-95. keratoplasty and a partial or 12. Bonini S, Lambiase A, Rama P, et al., REPARO Study Group. Phase II randomized, double-masked, vehicle-controlled trial of total conjunctival flap (Fig- recombinanat human nerve growth factor for neurotrophic kerati- ure 2).9 Eyes with NK have Fig. 2. Vital dyes are key diagnostic tools to help tis. Ophthalmology. 2018;125(9):1332-43. 13. Oxervate Prescribing Information (PI). www.accessdata.fda. a higher than usual rate of clinicians visualize ocular surface damage from gov/drugsatfda_docs/label/2018/761094s000lbl.pdf. Accessed failure for corneal surgery.2 neurotrophic keratitis. January 14, 2019.

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088_ro0219_OSR.indd 89 2/5/19 12:32 PM Retina Quiz

What’s in Your Head? How can this patient’s presentation and MRI explain his vision loss? By Shreya Jayasimha, OD, and Mark Dunbar, OD

57-year-old Caucasian male presented with a complaint Aof gradually decreasing vision in his left eye for the past eight to nine months. He denied any ocular pain, headaches, tinnitus or transient visual obscuration associated with his vision loss. His ocular history is positive for a cataract surgery performed three years earlier in both eyes. His medical history is Fig. 1. These are the fundus images of the right and left eyes of our patient. What can positive for hypertension, diabetes they tell you about the cause of the patient’s symptoms? and sleep apnea, which are medically controlled with lisinopril, metformin tively. Anterior segment health was a. Guillain-Barré syndrome. and a continuous positive airway unremarkable for both eyes. The b. Anterior ischemic optic neuropa- pressure machine, respectively. He dilated fundus exam for both eyes thy. denied smoking, alcohol or illicit shows a clear vitreous. Images of the c. Foster Kennedy syndrome. drug use. optic nerve of each eye are available d. Pseudo-Foster Kennedy syn- On examination, his best-correct- for review (Figure 1). The macula drome. ed visual acuities were 20/20 OD and periphery were unremarkable. and counting fingers at three feet Magnetic resonance imaging (MRI) 4. How should this patient be man- in his left eye with a prescription of was performed and is available for aged? -1.25 +0.75 x 035 OD, -2.50 +1.00 review (Figure 2). a. Observation. x 005 OS. Confrontation visual b. IV steroids. fields were full for the right eye, but Take the Retina Quiz c. Neurosurgical consult. revealed a generalized constriction 1. How would you describe the optic d. Optic nerve sheath decompres- for the left eye. Threshold visual nerve appearance in our patient? sion. field testing was performed and a. Normal, distinct margins OU. showed an enlarged blind spot in the b. Optic disc pallor in the left eye. Diagnosis right eye and severe depression in the c. Optic disc edema in the right eye Our patient has subtle grade 1 disc left eye. Extraocular motility was full and optic disc pallor in the left. edema in both eyes. What’s more, for both eyes and pupils were equal, d. Grade 1 disc edema in both eyes the left eye also has as obvious tem- round and minimally reactive to with temporal pallor in the left. poral pallor. This is evident when light with a trace afferent pupillary you compare the coloration of the defect in the left eye. Color vision, 2. What does the MRI reveal? neuroretinal rim in each eye. measured with Ishihara plates, was a. A mass in the frontal lobe. This presentation alone should full for the right eye and completely b. A mass in the parietal lobe. raise a red flag for possible Foster diminished for the left eye (10/10 c. An infarct in the occipital lobe. Kennedy syndrome, which presents OD, 0/10 OS). d. A chiasmal lesion. as disc edema in one eye and optic Intraocular pressures were mea- nerve pallor in the other. sured at 15mm Hg and 17mm Hg 3. Based on the testing and images, Foster Kennedy syndrome is for the right and left eye, respec- which is the correct diagnosis? characterized by a sub-frontal

90 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

090_ro0219_RQ.indd 90 2/5/19 12:34 PM meningioma, resulting in compres- sive optic neuropathy and increased intracranial pressure (ICP).1 This, in turn, causes optic nerve atrophy and pallor ipsilateral to the tumor and optic disc edema contralateral to the tumor as a result of increased ICP.2 Researchers believe Foster Ken- nedy syndrome represents 1% to 2.5% of all intracranial masses.4 The conditions three clinical presenta- tions include: Fig. 2. At left, the coronal view of the MRI. At right, the axial view of the MRI. • Type 1: Optic atrophy on one side with contralateral disc edema. the presence of both an intracranial The most effective and primary • Type 2: Papilledema with unilat- mass and an ischemic event that course of treatment is surgical resec- eral optic atrophy. results in the same clinical picture as tion to reduce the mass effect and • Type 3: Papilledema with bilat- Foster Kennedy syndrome.3 Apart relieve the elevated ICP.5 In cases eral optic atrophy. from visual field testing and OCT where tumors are not resectable or Each presentation is dependent a brain and orbital MRI must be do not benefit from radiotherapy, upon the location of the tumor and performed to correctly differentiate hydroxyurea chemotherapy may be when symptoms are detected. Symp- between these syndromes and make modestly beneficial.5 However, fur- toms include progressive vision loss, an accurate diagnosis. ther studies are required to establish ipsilateral anosmia (loss of smell), The MRI of the brain in our its clinical significance.5 diplopia, headaches, nausea and patient revealed a large left-sided The prognosis for these types of vomiting.1 While its primary location meningioma of the anterior cranial cases is variable, depending on fac- is in the sub-frontal region, it can fossa measuring 7x7x6mm with tors such as the chronicity of the also present in the olfactory groove, diffuse enhancement. There is an condition, the size of the tumor and falx cerebri and sphenoid wing, all extension of this mass to the left the age of the patient. Nevertheless, of which result in a different constel- optic canal as well as to the superior early recognition of the signs and lation of signs and symptoms.4 An portions of the left cavernous sinus symptoms along with an accurate optimal way of diagnosing this con- with no effect on the left extraocular diagnosis of Foster Kennedy syn- dition is through funduscopic exami- muscles of the orbit. In contrast, drome is critical to a patient’s qual- nation coupled with MRI. the right optic nerve and the right ity of life and final visual prognosis. One key differential is pseudo- optic canal appears to be intact with Our patient was immediately Foster Kennedy syndrome, which no mass effect. These findings con- referred to a neurosurgeon and he is defined as optic nerve pallor firmed our suspicion of Foster Ken- had emergent surgery. He continues in one eye and disc edema in the nedy syndrome. to be followed closely. ■ contralateral eye in the absence Dr. Jayasimha is an optometric of an intracranial mass.5 The two Management resident at Bascom Palmer Eye most common causes of this condi- Treatment for patients with Foster Institute in Miami.

tion include, but are not limited Kennedy syndrome can be divided 1. Lai A, Chiu S, Lin I, Sanders M. Foster Kennedy syndrome. J to, a bilateral sequential ischemic into medical and surgical manage- Neuro-Ophthalmol. 2014;34(1):92-4. 3 2. Sadun A. Foster-Kennedy syndrome. Science Direct. www.sci- optic neuropathy or optic neuritis. ment. Initial medical management encedirect.com/topics/medicine-and-dentistry/foster-kennedy- Other, less common causes include a for symptomatic brain tumors syndrome. July 03, 2008. Accessed January 16, 2019. 3. Vickers L, Bhatti T, El-Dairi M. Diagnose and manage prior papillitis or a secondary optic includes oral corticosteroids, which pseudo–Foster Kennedy syndrome. www.aao.org/eyenet/article/ atrophy from trauma, infectious, may help to reduce edema surround- diagnose-manage-pseudofoster-kennedy-syndrome-2. January 3 2014. Accessed January 16, 2019. inflammatory or infiltrative origins. ing the tumor as well as decrease 4. Walia H, Grumbine F, Sawhney G, et al. An aggressive Interestingly, pseudo-Foster Ken- ICP.5 Radiotherapy or radiosurgery sphenoid wing meningioma causing Foster Kennedy syndrome. Hindawi. www.hindawi.com/journals/criopm/2012/102365. May nedy syndrome is another clinical is also a non-surgical way to shrink 17, 2012. Accessed January 16, 2019. possibility to consider in our patient. the tumor and prevent further 5. Zhou Y, Vickers A, Ponce C, et al. Foster Kennedy vs pseudo- Foster Kennedy. eyewiki.aao.org/Foster-Kennedy_vs_Pseudo- This rare occurrence is defined as growth and expansion.1,5 Foster-Kennedy. January 14, 2018. Accessed January 16, 2019.

REVIEW OF OPTOMETRY FEBRUARY 15, 2019 91

090_ro0219_RQ.indd 91 2/5/19 12:35 PM Earn up to NEW TECHNOLOGIES 2019 & TREATMENTS IN 28 CE Eye Care Credits* GVCE OPTOMETRIC CORNEA, CATARACT REVIEW’S COMMITMENT TO CONTINUING EDUCATION AND REFRACTIVE SOCIETY SAN DIEGO APRIL 11-14, 2019

We invite you to attend a unique joint meeting held at the Manchester Grand Hyatt. Review’s New Technologies & Treatments in Eye Care and Optometric Cornea, Cataract and Refractive Society’s annual meetings are combined to provide you with up to 28* COPE CE credits in one weekend.

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RGVCE partners with Salus University for those ODs who are licensed in states that require university credit. See www.reviewsce.com/events for any meeting changes or updates. Program Chairs: Paul M. Karpecki, OD, FAAO David Friess, OD, FAAO Review Program Chair President, OCCRS

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Program Chair: Melissa Barnett, OD, FAAO, FSLS Clark Chang, OD, FAAO Douglas Devries, OD Chris Freeman, OD, FAAO David Geﬀ en, OD, FAAO David Friess, OD, FAAO

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ASSISTANT PROFESSOR POSITIONS: PEDIATRICS, PRIMARY CARE/OPTOMETRIC THEORY AND METHODS &ƵůůͲƟŵĞŶŽŶͲƚĞŶƵƌĞƚƌĂĐŬĨĂĐƵůƚǇƉŽƐŝƟŽŶƐĨŽƌƚŚĞŚŝĐĂŐŽŽůůĞŐĞŽĨKƉƚŽŵĞƚƌǇ RĞƐƉŽŶƐŝďŝůŝƟĞƐ͗ĂŶĚŝĚĂƚĞƐĂƌĞĞǆƉĞĐƚĞĚƚŽďĞŚŝŐŚůǇŬŶŽǁůĞĚŐĞĂďůĞŝŶƚŚĞĮĞůĚŽĨƉĞĚŝĂƚƌŝĐŽƌƉƌŝŵĂƌǇĐĂƌĞĂŶĚŽƉƚŽŵĞƚƌŝĐ ƚŚĞŽƌǇĂŶĚŵĞƚŚŽĚƐĂŶĚĚĞǀĞůŽƉĂŶĚƚĞĂĐŚĐŽƵƌƐĞƐĂŶĚͬŽƌůĂďŽƌĂƚŽƌŝĞƐŝŶƚŚĞƐƵďũĞĐƚĂƌĞĂ͘dŚĞƉƌŝŵĂƌǇĐĂƌĞĐĂŶĚŝĚĂƚĞŵƵƐƚ ĂůƐŽďĞĂďůĞƚŽƉƌŽǀŝĚĞĚŝƌĞĐƚƉĂƟĞŶƚĐĂƌĞĂŶĚĐůŝŶŝĐĂůŝŶƐƚƌƵĐƟŽŶƚŽƉƌŽĨĞƐƐŝŽŶĂůƐƚƵĚĞŶƚƐĂƐǁĞůůĂƐƌĞƐŝĚĞŶƚƐ͕ĂŶĚďĞŝŶǀŽůǀĞĚ ŝŶŝŶƚĞƌĚŝƐĐŝƉůŝŶĂƌǇƉƌĂĐƟĐĞǁŝƚŚŽƚŚĞƌĞĚƵĐĂƟŽŶĂůƉƌŽĨĞƐƐŝŽŶĂůƐ͘ ĂŶĚŝĚĂƚĞƐŵƵƐƚďĞǁŝůůŝŶŐƚŽĂĐƟǀĞůǇƉĂƌƟĐŝƉĂƚĞŝŶĐƵƌƌŝĐƵůĂƌĂƐƐĞƐƐŵĞŶƚ͕ƉƌŽĨĞƐƐŝŽŶĂůĚĞǀĞůŽƉŵĞŶƚ͕ƐƚƵĚĞŶƚĐŽƵŶƐĞůŝŶŐĂŶĚƐĞƌǀŝĐĞĂĐƟǀŝƟĞƐ ǁŝƚŚŝŶƚŚĞĐŽůůĞŐĞ͕ƵŶŝǀĞƌƐŝƚǇ͕ĂŶĚƚŚĞƐĐŝĞŶƟĮĐĐŽŵŵƵŶŝƚǇ͘^ƵĐĐĞƐƐĨƵůĐĂŶĚŝĚĂƚĞƐĂƌĞĞǆƉĞĐƚĞĚƚŽďĞŝŶǀŽůǀĞĚŝŶƌĞƐĞĂƌĐŚĂŶĚƐĐŚŽůĂƌůǇĂĐƟǀŝƟĞƐ͕ ĂŶĚŚĂǀĞĂƐŝŶĐĞƌĞĐŽŵŵŝƚŵĞŶƚƚŽŽƉƚŽŵĞƚƌŝĐĞĚƵĐĂƟŽŶ͕ĐŽŵŵƵŶŝƚǇƐĞƌǀŝĐĞ͕ĂŶĚƉĂƟĞŶƚĐĂƌĞ͘WƌŝŵĂƌǇĚƵƟĞƐŝŶĐůƵĚĞďƵƚĂƌĞŶŽƚůŝŵŝƚĞĚƚŽ͗ a) dĞĂĐŚŝŶŐ b) ^ĞƌǀŝĐĞ • WĂƌƟĐŝƉĂƟŶŐŽŶŽůůĞŐĞĂŶĚhŶŝǀĞƌƐŝƚǇ • Developing and delivering lectures • Helping to maintain and grow the state of ĐŽŵŵŝƩĞĞƐ͕ĂƐĂƐƐŝŐŶĞĚ͖ • and/or laboratories for related areas, as the art optometry program with a strong • WĂƌƟĐŝƉĂƟŶŐŝŶŽůůĞŐĞĂŶĚhŶŝǀĞƌƐŝƚǇ assigned; interdisciplinary focus that meets the ƐĞƌǀŝĐĞĂĐƟǀŝƟĞƐ͘ • ŵďƌĂĐŝŶŐĂŶĚĞŶŚĂŶĐŝŶŐƚŚĞĚŝĚĂĐƟĐ ŶĞĞĚƐŽĨƉĂƟĞŶƚƐŝŶƚŚĞƐƵƌƌŽƵŶĚŝŶŐ philosophies in the O.D. program; ĐŽŵŵƵŶŝƚǇ͖ŝƐĞĸĐŝĞŶƚ͕ƉĂƟĞŶƚĨƌŝĞŶĚůǇ͕ c) ^ĐŚŽůĂƌůǇĂĐƟǀŝƚǇ • Maintaining and expanding the high ĂŶĚĐŽƐƚͲĞīĞĐƟǀĞ͖ Engaging in research and scholarly ƋƵĂůŝƚǇĐůŝŶŝĐĂůƉƌĂĐƟĐĞĞŶǀŝƌŽŶŵĞŶƚĨŽƌ • Working closely together with all ĂĐƟǀŝƚǇ͕ŝŶĐůƵĚŝŶŐƉƌĞƐĞŶƚĂƟŽŶƐ ŽƉƚŽŵĞƚƌǇƐƚƵĚĞŶƚƐŽŶƌŽƚĂƟŽŶ͖ optometry and ophthalmology faculty to ĂƚƐĐŝĞŶƟĮĐŵĞĞƟŶŐƐ͕ƌĞƐĞĂƌĐŚ͕ĂŶĚ • WƌĞĐĞƉƟŶŐƐƚƵĚĞŶƚƐŽŶĐůŝŶŝĐĂůƌŽƚĂƟŽŶĂƚ provide a complete range of eye and ƉƵďůŝĐĂƟŽŶŝŶƉĞĞƌƌĞǀŝĞǁĞĚũŽƵƌŶĂůƐ ƚŚĞDŝĚǁĞƐƚĞƌŶhŶŝǀĞƌƐŝƚǇǇĞ/ŶƐƟƚƵƚĞ vision care services; ƐƵĸĐŝĞŶƚƚŽƋƵĂůŝĨǇĨŽƌĂĐĂĚĞŵŝĐ where applicable; • WĂƌƟĐŝƉĂƟŶŐŝŶůĞĂĚĞƌƐŚŝƉƌŽůĞƐŝŶƐƚĂƚĞ͕ advancement in a non-tenure or tenure ƌĞŐŝŽŶĂů͕ĂŶĚŶĂƟŽŶĂůŽƉƚŽŵĞƚƌǇ ƚƌĂĐŬƉŽƐŝƟŽŶ͘ ŽƌŐĂŶŝǌĂƟŽŶƐ͖

YƵĂůŝĮĐĂƟŽŶƐ͗ĂŶĚŝĚĂƚĞƐŵƵƐƚƉŽƐƐĞƐƐĂŽĐƚŽƌŽĨKƉƚŽŵĞƚƌǇĚĞŐƌĞĞĨƌŽŵĂŶKͲĂĐĐƌĞĚŝƚĞĚŝŶƐƟƚƵƟŽŶ͕ŵƵƐƚŚĂǀĞĐŽŵƉůĞƚĞĚĂŶ KͲĂĐĐƌĞĚŝƚĞĚƌĞƐŝĚĞŶĐǇ͕ĂŶĚŵƵƐƚďĞĞůŝŐŝďůĞĨŽƌĂŶ/ůůŝŶŽŝƐŽƉƚŽŵĞƚƌŝĐƐƚĂƚĞůŝĐĞŶƐĞ͘WƌŝŵĂƌǇĞǇĞĐĂƌĞĐůŝŶŝĐĂůĞǆƉĞƌƟƐĞŝƐĂůƐŽƌĞƋƵŝƌĞĚ͘ ^ĂůĂƌǇǁŝůůďĞĐŽŵŵĞŶƐƵƌĂƚĞǁŝƚŚƋƵĂůŝĮĐĂƟŽŶƐĂŶĚĞǆƉĞƌŝĞŶĐĞ ZĞǀŝĞǁŽĨĂƉƉůŝĐĂƟŽŶƐǁŝůůďĞŐŝŶŝŵŵĞĚŝĂƚĞůǇĂŶĚĐŽŶƟŶƵĞƵŶƟůƚŚĞƉŽƐŝƟŽŶŝƐĮůůĞĚ ŽŶƚĂĐƚŝŶĨŽƌŵĂƟŽŶ͗/ŶƚĞƌĞƐƚĞĚĂƉƉůŝĐĂŶƚƐƐŚŽƵůĚĂƉƉůǇŽŶůŝŶĞĂƚǁǁǁ͘ŵŝĚǁĞƐƚĞƌŶ͘ĞĚƵĂŶĚŝŶĐůƵĚĞĐƵƌƌŝĐƵůƵŵǀŝƚĂĞĂŶĚůĞƩĞƌŽĨŝŶƚĞƌĞƐƚ ƐƉĞĐŝĨǇŝŶŐƚŚĞƉŽƐŝƟŽŶĂŶĚĐŽůůĞŐĞƚŚĂƚŚĞͬƐŚĞǁŝƐŚĞƐƚŽďĞĐŽŶƐŝĚĞƌĞĚĨŽƌ͘ƉƉůŝĐĂƟŽŶƉĂĐŬĞƚƐŚŽƵůĚŝŶĐůƵĚĞĐƵƌƌŝĐƵůƵŵǀŝƚĂĞĂŶĚůĞƩĞƌŽĨ ŝŶƚĞƌĞƐƚ͘/ŶƋƵŝƌŝĞƐŵĂǇďĞĚŝƌĞĐƚĞĚƚŽƌ͘DĞůŝƐƐĂ^ƵĐŬŽǁ͕ĞĂŶ͖DŝĚǁĞƐƚĞƌŶhŶŝǀĞƌƐŝƚǇ͗ŵƐƵĐŬŽΛŵŝĚǁĞƐƚĞƌŶ͘ĞĚƵ͘ DŝĚǁĞƐƚĞƌŶhŶŝǀĞƌƐŝƚǇŝƐĂŶƋƵĂůKƉƉŽƌƚƵŶŝƚǇͬĸƌŵĂƟǀĞĐƟŽŶĞŵƉůŽǇĞƌƚŚĂƚĚŽĞƐŶŽƚĚŝƐĐƌŝŵŝŶĂƚĞĂŐĂŝŶƐƚĂŶĞŵƉůŽǇĞĞŽƌĂƉƉůŝĐĂŶƚďĂƐĞĚƵƉŽŶƌĂĐĞ͕ĐŽůŽƌ͕ ƌĞůŝŐŝŽŶ͕ŐĞŶĚĞƌ͕ŶĂƟŽŶĂůŽƌŝŐŝŶ͕ĚŝƐĂďŝůŝƚǇ͕ŽƌǀĞƚĞƌĂŶƐƐƚĂƚƵƐ͕ŝŶĂĐĐŽƌĚǁŝƚŚϰϭ͘&͘Z͘ϲϬͲϭ͘ϰ;ĂͿ͕ϮϱϬ͘ϱ;ĂͿ͕ϯϬϬ͘ϱ;ĂͿĂŶĚϳϰϭ͘ϱ;ĂͿ͘

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Practice For Sale Career Opportunities ARE YOU IN CONTROL? Staff Optometrist Wanted Bard Optical is a family owned full-service Don’t buy a job…acquire a business. retail optometric practice with 22 offices (and growing) throughout Central Illinois. Bard Optical prides itself on having a progressive Select clients have larger practices optometric staff whose foundation is based on one-on-one patient service. We are currently available for outright purchase. accepting CV/resumes for Optometrists to join Positive cash flow and 100% our medical model optometric practice that includes extended testing. The practice financing available. America’s includes but is not limited to general optometry, leading optometry business contact lenses and geriatric care. Salaried, full-time positions are available with excellent development consultancy base compensation and incentive programs provides support before, and benefits. Some part-time opportunities may also be available. during and after closure. Current positions are available in We’ll help you acquire the Bloomington/Normal, Decatur/Forsyth, Peoria, Sterling and Canton as we continue optometry practice of your to grow with new and established offices. dreams with no cost to you. Please email your information to See our current offerings at: [email protected] or call Mick at 309-693-9540 ext 225. http://www.cleinman.com/buy Mailing address if more convenient is: Bard Optical 800-331-5536 Attn: Mick Hall, Vice President 8309 N Knoxville Avenue PRACTICE FOR SALE Peoria, IL 61615

NORTHEASTERN PA. Bard Optical is a proud Long established busy and very Associate Member of the ƐƵĐĐĞƐƐĨƵůŽƉƚŽŵĞƚƌŝĐƉƌĂĐƟĐĞŐƌŽƐƐŝŶŐ Illinois Optometric Association. ŽǀĞƌΨϱϱϬŬĨŽƌƐĂůĞ͘dŚĞƉƌĂĐƟĐĞ www.bardoptical.com involves all phases of optometry with an emphasis on contact lenses. dŚĞƉƌĂĐƟĐĞŝŶĐůƵĚĞƐĂŶŽƉƟĐĂů Equipment and Supplies ĚŝƐƉĞŶƐĂƌǇĂŶĚĮŶŝƐŚŝŶŐůĂď͘ ϯϬǇĞĂƌƉƌŝǀĂƚĞŽƉƚŽŵĞƚƌǇƉƌĂĐƟĐĞŽƉƉŽƌƚƵŶŝƚǇ Numerous vision plans are accepted including Medicare. in Fairbanks, Alaska. tŽƵůĚďĞǁŝůůŝŶŐƚŽǁŽƌŬŝŶƚŚĞƉƌĂĐƟĐĞ ^ĞĞƉĂƟĞŶƚƐŽĨĂůůĂŐĞƐ͘ ĨŽƌĂƐŵŽŽƚŚƚƌĂŶƐŝƟŽŶ͘ This is a great opportunity for an ǆĐĞůůĞŶƚůĞĂƐĞĚůŽĐĂƟŽŶŽŶďƵƐǇƚŚŽƌŽƵŐŚĨĂƌĞ͘ optometrist looking to earn a great 907-978-7481 income immediately. or email [email protected] Contact [email protected] for more details.

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Continuing Education

Dr. Travel Seminars, LLC American Academy of Optometry In Partnership With The NJ Society of Optometric Physicians TM New Jersey Chapter Dalmatian Coast Cruise 1t7 h Annual Educational Conference Celebrity Constellation - Sailing from Venice to Rome April 3-7, 2019 June 28 - July 8, 2019 (10 Night Cruise) Myrtle Beach, South Carolina Sailing to Slovenia, Croatia, Montenegro, Malta, Sicily & Italy Hilton Embassy Suites at Kingston Plantation Jerome Sherman Dr. , OD, FAAO 16 HOURS Optional Private Optional Pre & Post Cruise COPE CE Group Tours Copenhagen Hotel Stay Dr. James Fanelli, OD, FAAO Registration: $500 One, Two or Three Bedroom Suites Accommodations Include a Daily Breakfast Buffet and Evening Cocktail Reception All Programs Are in Partnership Dr. TRAVEL SEMINARS, LLC PACK YOUR CLUBS! With the New Jersey Society of Golf details to follow. Optometric Phyisicans is a COPE approved provider For Accommodation and Additional Information, contact: Course approved for 16 CE Dennis H. Lyons, OD, F.A.A.O. Phone: (732) 920-0110 E-Mail: [email protected] Choose free: $300 Onboard Credit, Drinks, or Internet

“A Contemporary look at Patient Eye Care” Presented by Randall Thomas, O.D., M.P.H., F.A.A.O. Additional Seminar Cruises (12-16 C E): Baltic Sea Cruise: July 22 - 31, 2019 - Leo Semes, OD, FAAO, Professor Emeritus, UAB Round Trip Copenhagen - Norwegian ‘Getaway’ - Special Free Amenities Christmas Week: December 22-29, 2019 - Royal Caribbean’s ‘Allure of the Seas’ Eastern Caribbean Sailing - Edward Paul, Jr., OD, PhD, FIALVS Place Your Ad Here! Royal Caribbean’s ‘Symphony of the Seas’ President’s Week: Febuary 15 - 22, 2020 - Toll free: 888-498-1460 Western Caribbean Sailing - Whitney Hauser OD, FAAO www.DrTravel.com 800-436-1028 E-mail: [email protected] Professional Opportunities

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dŚĞ/ŶƚĞƌŶĂƟŽŶĂůĐĂĚĞŵǇŽĨ>ŽǁsŝƐŝŽŶ^ƉĞĐŝĂůŝƐƚƐ ŚĂƐƚŚĞĨŽůůŽǁŝŶŐdĞƌƌŝƚŽƌŝĞƐǀĂŝůĂďůĞ͗ Targeting Optometrists? Northern California South Carolina ŽŶŶĞĐƟĐƵƚ Maine CLASSIFIED ADVERTISING WORKS Southern Missouri DĂƐƐĂĐŚƵƐĞƩƐ Oklahoma Iowa ^ŽƵƚŚĞƌŶ'ĞŽƌŐŝĂ Ohio tĞƐƚsŝƌŐŝŶŝĂ ^ĂŶŝĞŐŽ • JOB OPENINGS • CME PROGRAMS • PRODUCTS & SERVICES • AND MORE... Members of dŚĞ/ŶƚĞƌŶĂƟŽŶĂůĐĂĚĞŵǇŽĨ>ŽǁsŝƐŝŽŶ^ƉĞĐŝĂůŝƐƚƐ ŚĂǀĞĂŶϭϴǇĞĂƌƉƌŽǀĞŶŚŝƐƚŽƌǇŽĨƐƵĐĐĞƐƐ Contact us today for classified advertising: ƚŚƌŽƵŐŚŽƵƚƚŚĞh^ĂŶĚĂŶĂĚĂ͘ Toll free: 888-498-1460 E-mail: [email protected] >ĞĂƌŶŚŽǁƚŽƉƌŽĮƚĂďůǇŝŶĐŽƌƉŽƌĂƚĞůŽǁǀŝƐŝŽŶĐĂƌĞ ŝŶƚŽǇŽƵƌƉƌĂĐƟĐĞĂƚ͗ ǁǁǁ͘KƉƚŽŵĞƚƌŝĐWƌĂĐƟĐĞŽŶƐƵůƚĂŶƚƐ͘ĐŽŵ or contact Richard J. Shuldiner, OD, FAAO President, IALVS and Low Vision Diplomate, AAO 888 567 2020 / [email protected]

96 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

ROPT0219.indd 96 1/30/19 11:38 PM Surgical Minute Edited By Derek N. Cunningham, OD, and Walter O. Whitley, OD, MBA Cutting Out Calcifications Concretions don’t often need excision, but here’s what to expect when they do. By Kynndyl Giannonatti, BA, and Leonid Skorin, Jr., DO, OD, MS

oncretions—calcified depos- above the concretion, then scrapes its embedded within the and removes the concretion with a Cpalpebral conjunctiva—are curette. Next, pressure is applied often small and do not cause irrita- over the incision with a sterile tion. However, if they are large or cotton applicator for hemostasis. prominent, they may rub against After hemostasis is achieved, topi- the bulbar conjunctiva or cornea, cal antibiotic ointment is applied resulting in irritation, pain and for prophylaxis. Cauterization and foreign body sensation. For these, suturing of the surgical site are not clinicians should consider surgical usually necessary. The incisions are excision for immediate relief. Palpebral view of concretion near the lid small and will stop bleeding with margin. applied pressure and heal by sec- Presentation ondary intention (deliberately leav- Concretions are often an incidental ing the wound open, allowing the finding during anterior segment body to heal on its own).3 evaluation. They are more prevalent with age and in those with Post-op Considerations chronic inflammation. They appear This procedure is typically well as small yellow or white deposits tolerated, and patients will heal that are usually less than 1mm. Concretion in curette after excision. in a few days without complica- These deposits arise from epithe- tions. The eyelid may be tender lial cells, protein, mucin and other Excision: Step-By-Step with slight swelling. Patients are debris trapped in the fornix that Removal is typically performed given topical antibiotic ointment calcifies over time.1 Concretions are under local anesthesia using no with instructions to apply it to the most commonly located in the infe- sedation. The patient is placed in surgical area two times per day for rior palpebral conjunctiva.1,2 a supine position, and lidocaine a week. A follow-up appointment Patients with concretions are hydrochloride 3.5% gel is placed is usually unnecessary, although often asymptomatic and usually into the superior cul-de-sac. The patients should return if they notice only require observation. But large upper lid is everted and xylocaine discharge, pain, redness, swelling or or elevated concretions, especially 2% with 1 to 100,000 epinephrine other signs of infection. ■ in the upper lid, are more likely is injected adjacent to the concre- Mrs. Giannonatti is a fourth- to rub the bulbar conjunctiva or tion. This is done for local anesthe- year student at Pacific University cornea during the blinking process. sia and vasoconstriction to reduce College of Optometry. These patients may complain of bleeding during the procedure. The Dr. Skorin is a consultant in the irritation and a foreign body sensa- eye is prepped with one drop of Department of Surgery, Community tion. In these cases, the concretions povidone iodine 5% ophthalmic Division of Ophthalmology in should be removed surgically for solution, and the face is covered the Mayo Clinic Health System in patient comfort.2 with a sterile fenestrated drape. Albert Lea, MN. Prior to surgery, the site is tested 1. Bowling B. Kanski’s Clinical Ophthalmology, A Systemic To see a video of this to ensure anesthesia has taken Approach, 8th ed. Philadelphia: Elsevier; 2016:131-66. procedure, visit www. 2. Mannis M, Holland E. Cornea, 4th ed. Philadelphia: effect. Once this is confirmed, the Elsevier; 2017:856-74. reviewofoptometry.com, or 3. Skorin L, Genereux L. Secondary intention healing of graft scan the QR code. surgeon makes a horizontal incision donor site wound dehiscence following ectropion repair with through the palpebral conjunctiva autologous graft. Clin Surg Ophthalmol. 2014;32(4):101-2.

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097_ro0219_sm.indd 97 2/5/19 1:53 PM Diagnostic Quiz

Headbanger’s Flaw By Andrew S. Gurwood, OD

History A 33-year-old white female presented with a chief complaint of blurry vision in her left eye more so than in her right for three months. She reported that the persistent blur developed after an auto accident. She reported that, during the accident, she hit one side of her head on the back of the passenger seat, in a slow-moving vehicle while not wearing a seat belt. Her previous ocular and systemic histories were unremarkable and she denied any known allergies to medications or other substances. This 33-year-old patient experienced blurred vision three Diagnostic Data months after an automobile accident in which she sustained Her best-corrected entering visual acuity was 20/20 OD head trauma. Can you identify the cause? and 20/30 OS at distance and near. Refraction revealed hyperopia of +0.75D OD and +1.50D OS with no Your Diagnosis improvement in vision. The pertinent biomicroscopic Does the case presented require any additional tests, findings are illustrated in the photographs. Her intraocu- history or information? What steps would you take to lar pressures were measured at 15mm Hg OD and 18mm manage this patient? Based on the information provided, Hg OS using Goldmann applanation tonometry. what would be your diagnosis? What is the patient’s The patient’s dilated fundus examination revealed most likely prognosis? To find out, please visit us online no significant posterior pole or peripheral retina find- at www.reviewofoptometry.com. ■ ings: the nerves were distinct with cup-to-disc ratios of 0.3/0.35 OD and OS. Retina Quiz Answers (from page 90): 1) d; 2) a; 3) c; 4) c.

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98 REVIEW OF OPTOMETRY FEBRUARY 15, 2019

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References: 1. Alcon data on fi le, 2010. 2. Wolffsohn JS, Hunt OA, Chowdhury A. Objective clinical performance of ‘comfort-enhanced’ daily disposable soft contact lenses. Contact Lens & Anterior Eye. 2010;33(2):88-92. 3. Laboratory study release profi le; Alcon data on fi le, 2007. 4. Winterton L, Lally J, Sentell K, Chapoy L. The elution of poly (vinyl alcohol) from a contact lens: The realization of a time release moisturizing agent/artifi cial tear. J Biomed Mater Res B Appl Biomater. 2007;80B:424-32. See product instructions for complete wear, care, and safety information. © 2017 Novartis 1/19 US-DAT-17-E-2219(2)

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