Cataract Surgery: Sharpen Your Edge an In-Depth Look at the Tools and Techniques Surgeons Are Using to Hone Their Outcomes

Home , Bromfenac

Review of Ophthalmology Vol. XXV, No. 3 • March 2018 • Drops, Dropless or Less-Drops After Surgery? Whither Toric the Most Out of Your Monofocals? • Get Biometry • Cataract Survey TACKLING PREOP ALLERGY P. 16 • PEEKING INTO THE WET AMD PIPELINE P. 20 TREATING UVEITIC GLAUCOMA P. 48 • AN UPDATE ON THE IRIS REGISTRY P. 53 REVIEWING THE LATEST RESEARCH P. 56 • WILLS RESIDENT CASE REPORT P. 63

MarchMarch 20182018

reviewofophthalmology.comreviewofophthalmology.com

ANNUAL CATARACT SURGERY ISSUE Cataract Surgery: Sharpen Your Edge An in-depth look at the tools and techniques surgeons are using to hone their outcomes.

• After Surgery: Shots, Drops or Both? P. 26

• Is There Still a Place for Monofocal Toric IOLs? P. 32

• How to Make the Most of Today’s Biometry Tech P. 36

• Cataract Surgery Survey: Surgeons Slow to Embrace New Tech P. 44

001_rp0318_fc.indd 1 2/26/18 11:10 AM Indications and Usage BromSite® (bromfenac ophthalmic solution) 0.075% is a nonsteroidal anti-infl ammatory drug (NSAID) indicated for Therefore, caution should be used when treating the treatment of postoperative infl ammation and prevention individuals who have previously exhibited sensitivities of ocular pain in patients undergoing cataract surgery. to these drugs. Recommended Dosing • Increased Bleeding Time of Ocular Tissue: With ® One drop of BromSite® should be applied to the affected some NSAIDs, including BromSite , there exists the eye twice daily (morning and evening) 1 day prior to potential for increased bleeding time due to interference surgery, the day of surgery, and 14 days postsurgery. with platelet aggregation. There have been reports that ocularly applied NSAIDs may cause increased bleeding Important Safety Information of ocular tissues (including hyphemas) in conjunction • Slow or Delayed Healing: All topical nonsteroidal with ocular surgery. It is recommended that BromSite® anti-infl ammatory drugs (NSAIDs), including BromSite®, be used with caution in patients with known bleeding may slow or delay healing. Topical corticosteroids are tendencies or who are receiving other medications also known to slow or delay healing. Concomitant use which may prolong bleeding time. of topical NSAIDs and topical steroids may increase the • Keratitis and Corneal Effects: Use of topical NSAIDs potential for healing problems. may result in keratitis. In some susceptible patients, • Potential for Cross-Sensitivity: There is the potential continued use of topical NSAIDs may result in epithelial for cross-sensitivity to acetylsalicylic acid, phenylacetic breakdown, corneal thinning, corneal erosion, corneal acid derivatives, and other NSAIDs, including BromSite®. ulceration or corneal perforation. Patients with evidence

RP0318_Sun.indd 2 2/22/18 10:28 AM The FIRST and ONLY NSAID indicated to prevent ocular pain in cataract surgery patients1

A DROP OF PREVENTION FOR YOUR CATARACT SURGERY PATIENTS

Defend against ocular pain and combat postoperative infl ammation with the penetrating power of BromSite® formulated with DuraSite®1 • DuraSite® increases ocular surface retention time, resulting in increased bromfenac absorption2-5 • Provides 24-hour coverage with BID dosing1 • Available in 5 mL bottle

Visit bromsite.com to fi nd out more.

Formulated with DELIVERY SYSTEM

• Adverse Reactions: The most commonly reported of corneal epithelial breakdown should immediately adverse reactions in 1% to 8% of patients were anterior ® discontinue use of topical NSAIDs, including BromSite , chamber infl ammation, headache, vitreous fl oaters, iritis, and should be closely monitored for corneal health. eye pain, and ocular hypertension. Patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, Please see brief summary of Full Prescribing ocular surface diseases (e.g., dry eye syndrome), Information on the adjacent page. rheumatoid arthritis, or repeat ocular surgeries within a NSAID=nonsteroidal anti-infl ammatory drug. short period of time may be at increased risk for corneal References: 1. BromSite® [package insert]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2016. 2. Hosseini K, Hutcheson J, Bowman L. Aqueous humor adverse events which may become sight threatening. concentration of bromfenac 0.09% (Bromday™) compared with bromfenac in Topical NSAIDs should be used with caution in these DuraSite® 0.075% (BromSite™) in cataract patients undergoing phacoemulsifi cation after 3 days dosing. Poster presented at: ARVO Annual Meeting; May 5-9, patients. Post-marketing experience with topical 2013; Seattle, Washington. 3. ClinicalTrials.gov. Aqueous humor concentration NSAIDs also suggests that use more than 24 hours of InSite Vision (ISV) 303 (bromfenac in DuraSite) to Bromday once daily (QD) prior to cataract surgery. https://clinicaltrials.gov/ct2/show/results/ prior to surgery or use beyond 14 days postsurgery may NCT01387464?sect=X70156&term=insite+vision&rank=1. Accessed March 2, 2017. 4. Si EC, Bowman LM, Hosseini K. Pharmacokinetic comparisons of bromfenac increase patient risk for the occurrence and severity of in DuraSite and Xibrom. J Ocul Pharmacol Ther. 2011;27(1):61-66. 5. Bowman LM, corneal adverse events. Si E, Pang J, et al. Development of a topical polymeric mucoadhesive ocular delivery system for azithromycin. J Ocul Pharmacol Ther. 2009;25(2):133-139. • Contact Lens Wear: BromSite® should not be Sun Ophthalmics is a division of Sun Pharmaceutical Industries, Inc. administered while wearing contact lenses. The © 2017 Sun Pharmaceutical Industries, Inc. All rights reserved. preservative in BromSite®, benzalkonium chloride, BromSite and DuraSite are registered trademarks of Sun Pharma Global FZE. may be absorbed by soft contact lenses. SUN-OPH-BRO-219 03/2017

RP0318_Sun.indd 3 2/22/18 10:28 AM BromSite® (bromfenac ophthalmic solution) 0.075% Brief Summary

INDICATIONS AND USAGE USE IN SPECIFIC POPULATIONS BromSite® (bromfenac ophthalmic solution) 0.075% is indicated for the Pregnancy treatment of postoperative inflammation and prevention of ocular pain in Risk Summary patients undergoing cataract surgery. There are no adequate and well-controlled studies in pregnant women to inform any drug associated risks. Treatment of pregnant rats and rabbits with oral CONTRAINDICATIONS bromfenac did not produce teratogenic effects at clinically relevant doses. None Clinical Considerations WARNINGS AND PRECAUTIONS Because of the known effects of prostaglandin biosynthesis-inhibiting drugs Slow or Delayed Healing on the fetal cardiovascular system (closure of ductus arteriosus), the use of All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including BromSite® during late pregnancy should be avoided. BromSite® (bromfenac ophthalmic solution) 0.075%, may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Data Animal Data Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. Treatment of rats with bromfenac at oral doses up to 0.9 mg/kg/day (195 times a unilateral daily human ophthalmic dose on a mg/m2 basis, assuming 100% Potential for Cross-Sensitivity absorbed) and rabbits at oral doses up to 7.5 mg/kg/day (3243 times a unilateral There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic daily dose on a mg/m2 basis) produced no structural teratogenicity in reproduction ® acid derivatives, and other NSAIDs, including BromSite (bromfenac ophthalmic studies. However, embryo-fetal lethality, neonatal mortality and reduced postnatal solution) 0.075%. Therefore, caution should be used when treating individuals growth were produced in rats at 0.9 mg/kg/day, and embryo-fetal lethality was who have previously exhibited sensitivities to these drugs. produced in rabbits at 7.5 mg/kg/day. Because animal reproduction studies Increased Bleeding Time of Ocular Tissue are not always predictive of human response, this drug should be used during With some NSAIDs, including BromSite® (bromfenac ophthalmic solution) pregnancy only if the potential benefit justifies the potential risk to the fetus. 0.075%, there exists the potential for increased bleeding time due to Lactation interference with platelet aggregation. There have been reports that There are no data on the presence of bromfenac in human milk, the effects on the ocularly applied NSAIDs may cause increased bleeding of ocular tissues breastfed infant, or the effects on milk production; however, systemic exposure (including hyphemas) in conjunction with ocular surgery. to bromfenac from ocular administration is low. The developmental and health It is recommended that BromSite® be used with caution in patients with benefits of breastfeeding should be considered along with the mother’s clinical known bleeding tendencies or who are receiving other medications which need for bromfenac and any potential adverse effects on the breast-fed child from may prolong bleeding time. bromfenac or from the underlying maternal condition. Keratitis and Corneal Reactions Pediatric Use Use of topical NSAIDs may result in keratitis. In some susceptible patients, Safety and efficacy in pediatric patients below the age of 18 years have not continued use of topical NSAIDs may result in epithelial breakdown, corneal been established. thinning, corneal erosion, corneal ulceration or corneal perforation. These Geriatric Use events may be sight threatening. Patients with evidence of corneal epithelial There is no evidence that the efficacy or safety profiles for BromSite® differ in breakdown should immediately discontinue use of topical NSAIDs, including patients 65 years of age and older compared to younger adult patients. BromSite® (bromfenac ophthalmic solution) 0.075%, and should be closely monitored for corneal health. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis and Impairment of Fertility Post-marketing experience with topical NSAIDs suggests that patients with Long-term carcinogenicity studies in rats and mice given oral doses of bromfenac complicated ocular surgeries, corneal denervation, corneal epithelial defects, up to 0.6 mg/kg/day (129 times a unilateral daily dose assuming 100% absorbed, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid on a mg/m2 basis) and 5 mg/kg/day (540 times a unilateral daily dose on a mg/m2 arthritis, or repeat ocular surgeries within a short period of time may be at basis), respectively revealed no significant increases in tumor incidence. increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Bromfenac did not show mutagenic potential in various mutagenicity studies, including the bacterial reverse mutation, chromosomal aberration, and Post-marketing experience with topical NSAIDs also suggests that use more micronucleus tests. than 24 hours prior to surgery or use beyond 14 days postsurgery may increase patient risk for the occurrence and severity of corneal adverse events. Bromfenac did not impair fertility when administered orally to male and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, respectively (195 and Contact Lens Wear 65 times a unilateral daily dose, respectively, on a mg/m2 basis). BromSite® should not be administered while wearing contact lenses. The ® preservative in BromSite , benzalkonium chloride, may be absorbed by soft Rx Only contact lenses. Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the Brief Summary: • Slow or Delayed Healing • Potential for Cross-Sensitivity • Increased Bleeding Time of Ocular Tissue • Keratitis and Corneal Reactions • Contact Lens Wear Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The most commonly reported adverse reactions in 1–8% of patients were: anterior chamber inflammation, headache, vitreous floaters, iritis, eye pain BromSite is a registered trademark of Sun Pharma Global FZE. and ocular hypertension. SUN-OPH-BRO-017-1 03/2017

RRP0318_SunP0318_Sun PPI.inddI.indd 1 22/22/18/22/18 10:2610:26 AMAM REVIEW NEWS Volume XXV • No. 3 • March 2018 Survey Shows Ophthalmology’s EHR Growing Pains

In February, JAMA Ophthalmology where people monitor these systems, “Some things need to be more intui- published a survey authored by and that obviously takes a lot more tive. For example, why is it so hard to Michele Lim, MD, UC Davis Health, skill. You’re hiring higher-skilled write a letter to a referring doctor? It regarding doctor perceptions of elec- people who are going to cost more. defi nitely takes a lot of stakeholders tronic health records systems. Every practice using a cloud-based to engage in trying to build a better In the population-based, cross-sec- solution needs a network specialist to system, however, so we hope that this tional study,1 researchers looked paper starts that process. at a random sample of ophthal- “Some of that is on us as doc- mologists from the American tors, but there is defi nitely room Academy of Ophthalmology’s for improvement with some of active membership database. these systems,” Dr. Lim adds. They found that the adoption “Programs like meaningful use rate of EHRs among the 348 (the federal incentive) seem to responding ophthalmologists be detrimental in a lot of ways. was 72.1 percent. The study de- On the one hand, it was great termined, however, that despite because there was a clear ex- the EHR adoption rate dou- plosion of EHR use after those bling since a previous survey in incentives and penalties came 2011, ophthalmologists report out. However, I think that when that net revenues and produc- that happened, EHR vendors tivity declined and that practice paid too much attention to sys- costs rose with EHR use. tem design to just satisfy the When asked about these meaningful-use reporting and surprising results, Dr. Lim says, “It’s help them deal with all the intricacies turned their attention away from the interesting because metrics like the of that, so the rising costs aren’t much workfl ow-effi ciency aspect of these number of patients seen and revenues of a surprise. It’s just something you systems. It’s as if we’ve been focusing did not actually seem to change much have to keep in mind when imple- on the wrong thing. So there’s room after implementing EHRs. I think the menting these systems.” for improvement, ideally with feed- most surprising thing is [fi nding out] In terms of suggestions or solu- back from the doctors that are using that both of those changed for the tions to help ophthalmologists bet- these systems.” negative. I would expect that to be a ter use these systems, Dr. Lim offers A representative from a company little more mixed. some advice. “I’m hoping that we, the that engineers these EHR systems— “It’s pretty easy to imagine the ris- Academy and other ophthalmologist who chose to remain anonymous— ing costs that these EHR systems groups, use this paper as a point at weighed in on the results of the bring,” Dr. Lim continues. “You have which we can begin to have a con- study. “It is surprising to see,” he says. to pay for expensive hardware equip- versation, and to realize that there’s “Obviously when you design and sell ment that you previously haven’t had a growing sentiment among ophthal- these programs, you expect them to to. Paper charts are a lot cheaper. mologists that EHRs are not effi cient succeed, so you hate to see something Even though you can downsize peo- because they may not be necessarily like that. But at the same time, we ple in terms of having to curate paper following what physicians would do have standards and incentives that we charts, you have to upsize positions naturally in their practices,” she says. have to meet with these programs. It’s

March 2018 | reviewofophthalmology.com | 5

005_rp0318_news.indd 5 2/23/18 2:23 PM ® REVIEW E DITORIAL STAFF News

Editor in Chief just diffi cult to nail down what’s work- sion Inlay, made great strides to build Walter C. Bethke ing and what isn’t when we don’t tangi- a market for the surgical correction (610) 492-1024 bly see how it affects or betters a prac- of presbyopia, but respectful of our [email protected] tice. But this study is starting to reveal best efforts, it is with regret that we those effects, so there will certainly be have to close our doors. The Raindrop Senior Editor interesting discussions going forward Inlay will not be sold to ophthalmic Christopher Kent as to how we can modify and optimize practices or distributors as of Tuesday, (814) 861-5559 our programs. Hopefully we will be January 30, 2018. As a result, the Rain- [email protected] working closely with physicians to see drop Rebate will not be honored past how to best optimize the programs for this date. To address any questions Senior Associate Editor their practices.” you may have in the near-term, we Kristine Brennan Another representative, also anony- have established a Hotline Number, (610) 492-1008 mous, from a competing company 1-866-934-6592, which will be staffed [email protected] shared his thoughts about the study, through April 30, 2018 ...” saying, “Honestly, we’re not seeing a lot John Hovanesian, MD, a Raindrop Associate Editor of complaints with our system. There user who also participated in the inlay’s Liam Jordan are defi nitely things we can tweak, but FDA trial, says his experience was posi- (610) 492-1025 we try to consistently update our EHR. tive, but that the inlay may have faced [email protected] I think a lot of these surprising results an uphill battle from the start. “The fall to the doctors who are using the decision by ReVision Optics’ board to Chief Medical Editor systems. Maybe they’re just not using close their operation is an unfortunate Mark H. Blecher, MD the systems effi ciently, or don’t have a side effect of too-slow market adoption staff that understands or takes advan- of a new technology,” he says. “From Art Director tage of the systems. We have abso- my perspective as a user of their prod- Jared Araujo lutely seen it work in practices. There’s ucts, an investigator in two of their trials (610) 492-1032 a learning curve, but there’s not much and a close advisor to the company, I [email protected] we can do about that on our end.” have always been impressed with their management, their research and devel- Senior Graphic Designer 1. Lim MC, Boland MV, McCannel CA, et. al. Adoption of electronic health records and perceptions of fi nancial and clinical outcomes opment group, and their commercial Matt Egger among ophthalmologists in the United States. JAMA Ophthalmol operations. The technology itself was a (610) 492-1029 2018;136:2:164-170. good performer—good enough that I [email protected] implanted two inlays in close, personal friends, both of whom were quite hap- International coordinator, Japan py. Personally, I believe the slow adop- Mitz Kaminuma ReVision tion of the Raindrop inlay was attribut- [email protected] able to the ‘competition’ of LASIK and Shuts Down premium IOLs’ great results. While Business Offi ces neither procedure is ideally suited to the 11 Campus Boulevard, Suite 100 In late January, ReVision Optics, maker emmetropic presbyope who was a can- Newtown Square, PA 19073 of the Raindrop corneal inlay for the didate for Raindrop, both have received (610) 492-1000 treatment of presbyopia, closed its wide public acceptance and adoption by Fax: (610) 492-1039 doors. The Raindrop was only the surgeons. In addition, achieving a quiet second such inlay approved in the eye with the Raindrop inlay required Subscription inquiries: United States, and the shuttering more follow-up and diligence after sur- United States — (877) 529-1746 leaves the AcuFocus Kamra inlay gery than other refractive procedures. Outside U.S. — (845) 267-3065 as the only approved corneal device “AcuFocus has an aperture IOL E-mail: available for this indication in the U.S. in the pipeline that, if approved, may [email protected] Patients or physicians who visited pave the way for broader acceptance Website: www.reviewofophthalmology.com the ReVision homepage the day of the of small-aperture inlays,” he continues. closure were met with this message “That may be our best hope of having from the company: “ReVision Optics, broad market acceptance of inlay pro- the maker of the Raindrop Near Vi- cedures.”

6 | Review of Ophthalmology | March 2018

0005_rp0318_news.indd05_rp0318_news.indd 6 22/23/18/23/18 2:252:25 PMPM RP0318_Ian Tech.indd 1 2/23/18 10:09 AM It’s time for Triton.

RP0318_Topcon Triton.indd 2 2/27/18 11:02 AM It’s all about the light source. FDA CLEARED

SS-OCT

Contact your local Topcon Representative today or visit newsgram.topconmedical.com/triton.

DRI OCT Triton™ Series A Multimodal Swept Source OCT

RP0318_Topcon Triton.indd 3 2/27/18 11:02 AM Editorial

REVIEW Board

BUSINESS OFFICES 11 CAMPUS BOULEVARD, SUITE 100 NEWTOWN SQUARE, PA 19073 ONTRIBUTORS SUBSCRIPTION INQUIRIES (877) 529-1746 C (USA ONLY); OUTSIDE USA, CALL (847) 763-9630 CHIEF MEDICAL EDITOR PEDIATRIC PATIENT Mark H. Blecher, MD Wendy Huang, MD BUSINESS STAFF CONTACT LENSES PLASTIC POINTERS PUBLISHER Penny Asbell, MD Ann P. Murchison, MD, MPH JAMES HENNE (610) 492-1017 [email protected] CORNEA / ANTERIOR SEGMENT REFRACTIVE SURGERY Thomas John, MD Arturo S. Chayet, MD REGIONAL SALES MANAGER MICHELE BARRETT (610) 492-1014 [email protected] GLAUCOMA MANAGEMENT RETINAL INSIDER Peter Netland, MD, PHD Carl Regillo, MD, FACS REGIONAL SALES MANAGER Kuldev Singh, MD Emmett T. Cunningham Jr., MD, PHD, MPH MICHAEL HOSTER (610) 492-1028 [email protected] MASTERS OF SURGERY TECHNOLOGY UPDATE Taliva D. Martin, MD Steven T. Charles, MD CLASSIFIED ADVERTISING Sara J. Haug, MD, PhD Michael Colvard, MD (888)-498-1460 MEDICARE Q & A WILLS RESIDENT CASE SERIES VICE PRESIDENT OF OPERATIONS Paul M. Larson, MBA Thomas Jenkins, MD. CASEY FOSTER (610) 492-1007 [email protected]

PRODUCTION MANAGER SCOTT TOBIN ADVISORY BOARD (610) 492-1011 [email protected] PENNY A. ASBELL, MD, NEW YORK CITY MIKE S. MCFARLAND, MD, PINE BLUFF, ARK. SUBSCRIPTIONS $63 A YEAR, $99 (U.S.) IN CANADA, PEKIN, ILL. WILLIAM I. BOND, MD, JEFFREY B. MORRIS, MD, MPH, ENCINITAS, CALIF. $158 (U.S.) IN ALL OTHER COUNTRIES. SUBSCRIPTIONS E-MAIL: ALAN N. CARLSON, MD, DURHAM, N.C. MARLENE R. MOSTER, MD, PHILADELPHIA [email protected] Y. RALPH CHU, MD, EDINA, MINN. ROBERT J. NOECKER, MD, FAIRFIELD, CONN. ADAM J. COHEN, MD, DOWNERS GROVE, ILL. ROBERT OSHER, MD, CINCINNATI CIRCULATION UDAY DEVGAN, MD, FACS, LOS ANGELES MARK PACKER, MD, WEST PALM BEACH, FLA. PO BOX 71, CONGERS, NY 10920-0071 ERIC DONNENFELD, MD, ROCKVILLE CENTRE, N.Y. (877) 529-1746 STEPHEN PASCUCCI, MD, BONITA SPRINGS, FLA. OUTSIDE USA: (845) 267-3065 DANIEL S. DURRIE, MD, KANSAS CITY, MO. PAUL PENDER, MD, BEDFORD, N.H. ROBERT EPSTEIN, MD, MCHENRY, ILL. SENIOR CIRCULATION MANAGER CHRISTOPHER J. RAPUANO, MD, PHILADELPHIA HAMILTON MAHER ROBERT D. FECHTNER, MD, NEWARK, N.J. (212) 219-7870 [email protected] AUGUST READER III, MD, SAN FRANCISCO WILLIAM J. FISHKIND, MD, TUCSON, ARIZ.

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

HARRY GRABOW, MD, SARASOTA, FLA. KENNETH J. ROSENTHAL, MD, GREAT NECK, N.Y. CEO, INFORMATION GROUP SERVICES MARC FERRARA DOUGLAS K. GRAYSON, MD, NEW YORK CITY ERIC ROTHCHILD, MD, DELRAY BEACH, FLA.

THOMAS S. HARBIN, MD, MBA, ATLANTA SHERI ROWEN, MD, BALTIMORE SENIOR VICE PRESIDENT, OPERATIONS JEFF LEVITZ DAVID R. HARDTEN, MD, MINNEAPOLIS JAMES J. SALZ, MD, LOS ANGELES

KENNETH J. HOFFER, MD, SANTA MONICA, CALIF. INGRID U. SCOTT, MD, MPH, HERSHEY, PA. VICE PRESIDENT, HUMAN RESOURCES JACK T. HOLLADAY, MD, MSEE, HOUSTON TAMMY GARCIA JOEL SCHUMAN, MD, PITTSBURGH JOHN D. HUNKELER, MD, KANSAS CITY, MO. VICE PRESIDENT, CREATIVE SERVICES & PRODUCTION GAURAV SHAH, MD, ST. LOUIS THOMAS JOHN, MD, TINLEY PARK, ILL. MONICA TETTAMANZI DAVID R. STAGER JR., MD, DALLAS ROBERT M. KERSHNER, MD, MS, FACS, BOSTON CORPORATE PRODUCTION DIRECTOR KARL STONECIPHER, MD, GREENSBORO, N.C. GUY M. KEZIRIAN, MD, PARADISE VALLEY, ARIZ. JOHN ANTHONY CAGGIANO JAMES C. TSAI, MD, NEW YORK CITY TERRY KIM, MD, DURHAM, N.C. VICE PRESIDENT, CIRCULATION VANCE THOMPSON, MD, SIOUX FALLS, S.D. TOMMY KORN, MD, SAN DIEGO EMELDA BAREA FARRELL C. TYSON, MD, CAPE CORAL, FLA. DAVID A. LEE, MD, HOUSTON

FRANCIS S. MAH, MD, PITTSBURGH R. BRUCE WALLACE III, MD, ALEXANDRIA, LA. 440 Ninth Avenue, 14th Floor NICK MAMALIS, MD, SALT LAKE CITY ROBERT G. WILEY, MD, CLEVELAND New York, N.Y. 10001 WILLIAM G. MARTIN, MD, OREGON, OHIO FRANK WEINSTOCK, MD, CANTON, OHIO

REVIEW OF OPHTHALMOLOGY (ISSN 1081-0226; USPS No. 0012-345) is published monthly, 12 times per year by Jobson Medical Informa- tion. 440 Ninth Avenue, 14th Floor, New York, N.Y. 10001. Periodicals postage paid at New York, NY and additional mailing ofﬁ ces. Postmaster: Send address changes to Review of Ophthalmology, PO Box 71, Congers, NY 10929-0071. Subscription Prices: US One Year $63.00, US Two Year $112.00, Canada One Year $99.00, Canada Two Year $181.00, Int’l One Year $158.00, Int’l Two Year $274.00. For subscription information call (877) 529-1746 (USA only); outside USA, call (845-267-3065. Or email us at [email protected]. Canada Post: Publications Mail Agreement #40612608. Canada Returns to be sent to Bleuchip International, P.O. Box 25542, London, ON N6C 6B2.

10 | Review of Ophthalmology | March 2018

0005_rp0318_news.indd05_rp0318_news.indd 1100 22/23/18/23/18 2:232:23 PMPM VYZULTA NOW AVAILABLE IN PHARMACIES NATIONWIDE

YOU CAN NOW START PRESCRIBING VYZULTA FOR YOUR GLAUCOMA PATIENTS.

> VYZULTA delivers a dual mechanism of action for the reduction of IOP in glaucoma patients1

> VYZULTA coupons are available for eligible patients

> There is no A/B generic equivalent to VYZULTA. Please share this information with your patients in case they experience a switch at the pharmacy

For more information about VYZULTA, visit vyzultanow.com

INDICATION • Macular edema, including cystoid macular VYZULTA™ (latanoprostene bunod ophthalmic edema, has been reported during treatment with solution), 0.024% is indicated for the reduction of prostaglandin analogs. Use with caution in aphakic intraocular pressure (IOP) in patients with open-angle patients, in pseudophakic patients with a torn glaucoma or ocular hypertension. posterior lens capsule, or in patients with known IMPORTANT SAFETY INFORMATION risk factors for macular edema • Increased pigmentation of the iris and periorbital • There have been reports of bacterial keratitis tissue (eyelid) can occur. Iris pigmentation is likely associated with the use of multiple-dose containers of to be permanent topical ophthalmic products that were inadvertently • Gradual changes to eyelashes, including increased contaminated by patients length, increased thickness, and number of • Contact lenses should be removed prior to the eyelashes, may occur. These changes are usually administration of VYZULTA and may be reinserted reversible upon treatment discontinuation 15 minutes after administration • Use with caution in patients with a history of • Most common ocular adverse reactions with intraocular inﬂ ammation (iritis/uveitis). VYZULTA incidence 2% are conjunctival hyperemia (6%), should generally not be used in patients with active eye irritation (4%), eye pain (3%), and instillation intraocular inﬂ ammation site pain (2%)

REFERENCE 1. VYZULTA Prescribing Information. Bausch & Lomb Incorporated. 2017. For more information, please see Brief Summary VYZULTA and the V design are trademarks of Bausch & Lomb Incorporated or its afﬁ liates. ©2017 Bausch & Lomb Incorporated. All rights reserved. VYZ.0351.USA.17 of Prescribing Information on next page.

RP0318_BL Vyzulta.indd 1 2/13/18 2:55 PM BRIEF SUMMARY OF PRESCRIBING INFORMATION Doses ≥ 20 μg/kg/day (23 times the clinical dose) produced 100% embryofetal lethality. Structural abnormalities observed in rabbit fetuses included anomalies of the great This Brief Summary does not include all the information needed to use VYZULTA vessels and aortic arch vessels, domed head, sternebral and vertebral skeletal anomalies, safely and effectively. See full Prescribing Information for VYZULTA. limb hyperextension and malrotation, abdominal distension and edema. Latanoprostene ™ VYZULTA (latanoprostene bunod ophthalmic solution), 0.024%, for topical bunod was not teratogenic in the rat when administered IV at 150 mcg/kg/day (87 times ophthalmic use. the clinical dose) [see Data]. Initial U.S. Approval: 2017 The background risk of major birth defects and miscarriage for the indicated population 1 INDICATIONS AND USAGE is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies. VYZULTA™ (latanoprostene bunod ophthalmic solution) 0.024% is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Data 4 CONTRAINDICATIONS Animal Data None Embryofetal studies were conducted in pregnant rabbits administered latanoprostene bunod daily by intravenous injection on gestation days 7 through 19, to target the period 5 WARNINGS AND PRECAUTIONS of organogenesis. The doses administered ranged from 0.24 to 80 mcg/kg/day. Abortion 5.1 Pigmentation occurred at doses ≥ 0.24 mcg/kg/day latanoprostene bunod (0.28 times the clinical VYZULTA™ (latanoprostene bunod ophthalmic solution), 0.024% may cause changes to dose, on a body surface area basis, assuming 100% absorption). Embryofetal lethality pigmented tissues. The most frequently reported changes with prostaglandin analogs (resorption) was increased in latanoprostene bunod treatment groups, as evidenced have been increased pigmentation of the iris and periorbital tissue (eyelid). by increases in early resorptions at doses ≥ 0.24 mcg/kg/day and late resorptions at doses ≥ 6 mcg/kg/day (approximately 7 times the clinical dose). No fetuses survived Pigmentation is expected to increase as long as latanoprostene bunod ophthalmic in any rabbit pregnancy at doses of 20 mcg/kg/day (23 times the clinical dose) or greater. solution is administered. The pigmentation change is due to increased melanin content Latanoprostene bunod produced structural abnormalities at doses ≥ 0.24 mcg/kg/day in the melanocytes rather than to an increase in the number of melanocytes. After (0.28 times the clinical dose). Malformations included anomalies of sternum, coarctation discontinuation of VYZULTA, pigmentation of the iris is likely to be permanent, while of the aorta with pulmonary trunk dilation, retroesophageal subclavian artery with pigmentation of the periorbital tissue and eyelash changes are likely to be reversible in absent brachiocephalic artery, domed head, forepaw hyperextension and hindlimb most patients. Patients who receive prostaglandin analogs, including VYZULTA, should be malrotation, abdominal distention/edema, and missing/fused caudal vertebrae. informed of the possibility of increased pigmentation, including permanent changes. The long-term effects of increased pigmentation are not known. An embryofetal study was conducted in pregnant rats administered latanoprostene bunod daily by intravenous injection on gestation days 7 through 17, to target the Iris color change may not be noticeable for several months to years. Typically, the period of organogenesis. The doses administered ranged from 150 to 1500 mcg/kg/day. brown pigmentation around the pupil spreads concentrically towards the periphery of Maternal toxicity was produced at 1500 mcg/kg/day (870 times the clinical dose, on the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor a body surface area basis, assuming 100% absorption), as evidenced by reduced freckles of the iris appear to be affected by treatment. While treatment with VYZULTA™ maternal weight gain. Embryofetal lethality (resorption and fetal death) and structural (latanoprostene bunod ophthalmic solution), 0.024% can be continued in patients who anomalies were produced at doses ≥ 300 mcg/kg/day (174 times the clinical dose). develop noticeably increased iris pigmentation, these patients should be examined Malformations included anomalies of the sternum, domed head, forepaw hyperextension regularly [see Patient Counseling Information (17) in full Prescribing Information]. and hindlimb malrotation, vertebral anomalies and delayed ossification of distal limb 5.2 Eyelash Changes bones. A no observed adverse effect level (NOAEL) was established at 150 mcg/kg/day (87 times the clinical dose) in this study. VYZULTA may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and the number of lashes or hairs. Eyelash 8.2 Lactation changes are usually reversible upon discontinuation of treatment. Risk Summary 5.3 Intraocular Inflammation There are no data on the presence of VYZULTA in human milk, the effects on the VYZULTA should be used with caution in patients with a history of intraocular breastfed infant, or the effects on milk production. The developmental and health inflammation (iritis/uveitis) and should generally not be used in patients with active benefits of breastfeeding should be considered, along with the mother’s clinical need intraocular inflammation as it may exacerbate this condition. for VYZULTA, and any potential adverse effects on the breastfed infant from VYZULTA. 5.4 Macular Edema 8.4 Pediatric Use Macular edema, including cystoid macular edema, has been reported during treatment Use in pediatric patients aged 16 years and younger is not recommended because of potential with prostaglandin analogs. VYZULTA should be used with caution in aphakic patients, in safety concerns related to increased pigmentation following long-term chronic use. pseudophakic patients with a torn posterior lens capsule, or in patients with known risk 8.5 Geriatric Use factors for macular edema. No overall clinical differences in safety or effectiveness have been observed between 5.5 Bacterial Keratitis elderly and other adult patients. There have been reports of bacterial keratitis associated with the use of multiple-dose 13 NONCLINICAL TOXICOLOGY containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility disruption of the ocular epithelial surface. Latanoprostene bunod was not mutagenic in bacteria and did not induce micronuclei 5.6 Use with Contact Lens formation in the in vivo rat bone marrow micronucleus assay. Chromosomal aberrations were observed in vitro with human lymphocytes in the absence of metabolic activation. Contact lenses should be removed prior to the administration of VYZULTA because this product contains benzalkonium chloride. Lenses may be reinserted 15 minutes after Latanoprostene bunod has not been tested for carcinogenic activity in long-term animal administration. studies. Latanoprost acid is a main metabolite of latanoprostene bunod. Exposure of rats and mice to latanoprost acid, resulting from oral dosing with latanoprost in lifetime 6 ADVERSE REACTIONS rodent bioassays, was not carcinogenic. The following adverse reactions are described in the Warnings and Precautions section: Fertility studies have not been conducted with latanoprostene bunod. The potential to pigmentation (5.1), eyelash changes (5.2), intraocular inflammation (5.3), macular impact fertility can be partially characterized by exposure to latanoprost acid, a common edema (5.4), bacterial keratitis (5.5), use with contact lens (5.6). metabolite of both latanoprostene bunod and latanoprost. Latanoprost acid has not been 6.1 Clinical Trials Experience found to have any effect on male or female fertility in animal studies. Because clinical trials are conducted under widely varying conditions, adverse reaction 13.2 Animal Toxicology and/or Pharmacology rates observed in the clinical trials of a drug cannot be directly compared to rates in the A 9-month toxicology study administered topical ocular doses of latanoprostene bunod clinical trials of another drug and may not reflect the rates observed in practice. to one eye of cynomolgus monkeys: control (vehicle only), one drop of 0.024% bid, one VYZULTA was evaluated in 811 patients in 2 controlled clinical trials of up to 12 months drop of 0.04% bid and two drops of 0.04% per dose, bid. The systemic exposures are duration. The most common ocular adverse reactions observed in patients treated equivalent to 4.2-fold, 7.9-fold, and 13.5-fold the clinical dose, respectively, on a body with latanoprostene bunod were: conjunctival hyperemia (6%), eye irritation (4%), eye surface area basis (assuming 100% absorption). Microscopic evaluation of the lungs pain (3%), and instillation site pain (2%). Approximately 0.6% of patients discontinued after 9 months observed pleural/subpleural chronic fibrosis/inflammation in the 0.04% therapy due to ocular adverse reactions including ocular hyperemia, conjunctival dose male groups, with increasing incidence and severity compared to controls. Lung irritation, eye irritation, eye pain, conjunctival edema, vision blurred, punctate keratitis toxicity was not observed at the 0.024% dose. and foreign body sensation. Distributed by: 8 USE IN SPECIFIC POPULATIONS Bausch + Lomb, a division of 8.1 Pregnancy Valeant Pharmaceuticals North America LLC Risk Summary Bridgewater, NJ 08807 USA There are no available human data for the use of VYZULTA during pregnancy to inform U.S. Patent Numbers: 6,211,233; 7,273,946; 7,629,345; 7,910,767; 8,058,467. any drug associated risks. VYZULTA is a trademark of Bausch & Lomb Incorporated or its affiliates. Latanoprostene bunod has caused miscarriages, abortion, and fetal harm in rabbits. Latanoprostene bunod was shown to be abortifacient and teratogenic when administered © Bausch & Lomb Incorporated intravenously (IV) to pregnant rabbits at exposures ≥ 0.28 times the clinical dose. Based on 9464800 11/2017 VYZ.0055.USA.16 Issued: 11/2017

RRP0318_BLP0318_BL VVyzultayzulta PPI.inddI.indd 1 22/13/18/13/18 2:532:53 PMPM March 2018 • Volume XXV No. 3 | reviewofophthalmology.com Cover Focus 26 | After Surgery: Shots, Drops or Both? Kristine Brennan, Senior Associate Editor Surgeons share their insights on preventing endophthalmitis and CME.

32 | Whither Toric Monofocal IOLs? Liam Jordan, Associate Editor Where do monofocal toric lenses ﬁ t into an increasingly multifocal-centric market? 36 | Making the Most of Today’s Biometry Tech Christopher Kent, Senior Editor Today’s advanced technology improves outcomes, but caution and training still pay off.

44 | E-Survey on Cataract Surgery: Surgeons Slow to Embrace New Tech Walter Bethke, Editor in Chief Most surgeons use traditional techniques, though femto surgeons are using the laser more often.

March 2018 | reviewofophthalmology.com | 13

013_rp0318_toc2.indd 13 2/26/18 11:52 AM Departments

5 | Review News 16

16 | Refractive/Cataract Rundown Stop the Sneeze to Fight the Haze The “Pittsburgh Protocol” calms local allergy for better cataract and refractive outcomes.

20 | Retinal Insider Addressing the Anti-VEGF Treatment Burden Solutions in the pipeline—both drugs and delivery systems—might help ease the treatment hassle.

48 | Glaucoma Management Treating Uveitic Glaucoma: What Works? Because these patients have two conditions, treatment 48 can be a challenge.

53 | Technology Update An Early-2018 IRIS Registry Update With the seemingly exponential growth of the IRIS Registry, it’s a good time to check its progress.

55 | Product News

56 | Research Review Bevacizumab Injection After MIs 63

60 | Classifieds

63 | Wills Eye Resident Case Series

65 | Ad Index

14 | Review of Ophthalmology | March 2018

013_rp0318_toc2.indd 14 2/26/18 11:12 AM LEAVE A LEGACY OF SEAMLESS BRILLIANCE. Start with ME.

TECNIS Symfony® and TECNIS Symfony® Toric IOLs deliver state-of-the-art presbyopia mitigation and astigmatism correction* while providing a full range of high-quality, continuous vision. I’ve never let anything keep me from seeing the big picture. Why would you? Don’t wait to leave a legacy of seamless brilliance. Start now with TECNIS Symfony® and TECNIS Symfony® Toric Extended Depth of Focus IOLs.

*TECNIS Symƒony® Toric IOLs only

The First and Only Extended Depth of Focus IOL

INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR THE TECNIS SYMFONY® AND TECNIS SYMFONY® TORIC EXTENDED RANGE OF VISION IOLs Rx Only

INDICATIONS: The TECNIS Symƒony® Extended Range of Vision IOL, model ZXR00, is indicated for primary implantation for the visual correction of aphakia, in adult patients with less than 1 diopter of pre-existing corneal astigmatism, in whom a cataractous lens has been removed. The lens mitigates the effects of presbyopia by providing an extended depth of focus. Compared to an aspheric monofocal IOL, the lens provides improved intermediate and near visual acuity, while maintaining comparable distance visual acuity. The model ZXR00 IOL is intended for capsular bag placement only. The TECNIS Symƒony® Toric Extended Range of Vision IOLs, models ZXT150, ZXT225, ZXT300, and ZXT375, are indicated for primary implantation for the visual correction of aphakia and for reduction of residual refractive astigmatism in adult patients with greater than or equal to 1 diopter of preoperative corneal astigmatism, in whom a cataractous lens has been removed. The lens mitigates the effects of presbyopia by providing an extended depth of focus. Compared to an aspheric monofocal IOL, the lens provides improved intermediate and near visual acuity, while maintaining comparable distance visual acuity. The model series ZXT IOLs are intended for capsular bag placement only. WARNINGS: May cause a reduction in contrast sensitivity under certain conditions, compared to an aspheric monofocal IOL. Inform patients to exercise special caution when driving at night or in poor visibility conditions. Some visual effects may be expected due to the lens design, including: perception of halos, glare, or starbursts around lights under nighttime conditions. These will be bothersome or very bothersome in some people, particularly in low-illumination conditions, and on rare occasions, may be signiﬁcant enough that the patient may request removal of the IOL. Rotation of the TECNIS Symƒony® Toric IOLs away from their intended axis can reduce their astigmatic correction, and misalignment greater than 30° may increase postoperative refractive cylinder. If necessary, lens repositioning should occur as early as possible prior to lens encapsulation. ATTENTION: Reference the Directions for Use for a complete listing of Indications and Important Safety Information.

RP0118_J&J.indd 1 12/28/17 1:54 PM Refractive/Cataract

REVIEW Rundown Edited by Arturo Chayet, MD

Stop the Sneeze to Fight the Haze The “Pittsburgh Protocol” calms local allergy symptoms for better cataract and refractive outcomes. Kristine Brennan, Senior Associate Editor

ou’ve taken pains to make sure We know that in PRK, people that to?’ We always ask about allergies, Ythat your patient is a suitable can- are atopic have more haze and re- but a lot of times patients may not didate for LASIK, PRK, or cataract gression. Patients with LASIK and even know the specifi c things they’re surgery, refracting and measuring allergies have a higher chance of allergic to. That’s why it’s really im- with care and setting realistic expec- having DLK. Even in cataract sur- portant to question them and get an tations regarding the visual outcome. gery, if someone’s really atopic, they appropriate history taken. Then, on Surgery goes well. But a subsequent could have more inflammation or the exam, we’ll rule out any dryness,” phone call, or perhaps the postop they could want to rub their eye, she says. follow-up visit, fi rst clues you in that which could result in problems with Itching is the main symptom of something’s amiss. You hear com- wound deposition.” To help ensure allergic conjunctivitis: If it’s absent, plaints of haze and irritation, and ob- good visual outcomes and patient then ocular allergy may not be the serve more infl ammation than you’d well-being, Dr. Dhaliwal has insti- culprit. Dr. Dhaliwal distinguishes reasonably anticipate, or a damaged tuted the “Pittsburgh Protocol” to between seasonal allergic conjunc- fl ap. You begin ticking off boxes on control local allergy symptoms peri- tivitis, which is episodic in nature your mental checklist of what could operatively and to maintain that con- depending on the specifi c allergen possibly have gone wrong. trol after surgery. (airborne pollen from grasses, plants Untreated allergies may be the or trees), and perennial allergic con- culprit, according to Deepinder K. Identifying Problems junctivitis arising from chronic ex- Dhaliwal, MD, L.Ac., professor of posure to dust mites, molds and pet ophthalmology at the University of “For refractive surgery, we do dander. Pittsburgh School of Medicine, di- two evaluations: One is just to see Before tailoring the treatment to rector of refractive surgery and the if you’re a candidate; the other is to the allergy symptom, Dr. Dhaliwal cornea service at UPMC Eye Center dilate your eyes and get the precise also needs to fi nd out what medica- and founder and director of the uni- measurements. So at the fi rst visit, tions patients already take. “We have versity’s Center for Integrative Eye we identify all allergy patients and them write down every single thing Care. “The bottom line is that allergy start them on the correct therapy,” that they take,” she says, noting that promotes inflammation,” she says. says Dr. Dhaliwal. “I will not oper- that’s another way she gets tipped “When you’re an allergic individual ate on anyone who has untreated off to a patient’s underlying allergy and you have untreated allergies, allergies. So at the University of issues. “A lot of people don’t think you have more infl ammatory media- Pittsburgh, what we do now is ask an allergy pill is medication,” she tors circulating and causing damage. everybody, ‘What are you allergic observes. “Because they get it over

16 | Review of Ophthalmology | March 2018 This article has no commercial sponsorship. NOW AVAILABLE FROM AN FDA-REGISTERED 503B OUTSOURCING FACILITY

INJECTABLE

Tri-Moxi® (Triamcinolone and moxifloxacin hydrochloride) 15mg/1mg/mL Dex-Moxi® New! (Dexamethasone and moxifloxacin hydrochloride) 1mg/5mg/mL Dex-Moxi-Ketor™ New! (Dexamethasone, moxifloxacin hydrochloride and ketorolac) 1mg/0.5mg/0.4mg/mL Moxifloxacin 5mg/mL

TOPICAL

Pred-Gati™ (Prednisolone acetate and gatifloxacin ) 1%/0.5% Pred-Brom™ (Prednisolone acetate and bromfenac) 1%/0.075% Pred-Gati-Brom™ (Prednisolone acetate, gatifloxacin and bromfenac) 1%/0.5%/0.075% Gati-Dex New! (Gatifloxacin and dexamethasone) 0.5%/0.1% Prednisolone Acetate Preservative-Free 1% New! Mydriatic 3 New! (Tropicamide/Cyclopentolate/Phenylephrine) 1/1/2.5%

SUBLINGUAL

MKO Melt® Sublingual Lemon New! (Midazolam, ketamine HCl and ondansetron) 3mg/25mg/2mg

IMPRIMIS PROVIDES STERILE COMPOUNDED FORMULATIONS* YOU CAN TRUST

Release and stability testing performed at FDA-registered labs Sterility, endotoxin and potency testing performed on each batch Continuous environmental monitoring to maintain product quality standards

Visit us at ASCRS Booth #2218 Order Today at: www.imprimisrx.com/ReviewofOph2018

*For professional use only. Imprimis Pharmaceuticals specializes in customizing medications to meet unique patient and practitioner needs. No compounded medication is reviewed by the FDA for safety or efficacy. Imprimis Pharmaceuticals does not compound copies of commercially available products. References available upon request.

Tri-Moxi, Dex-Moxi-Ketor, Dex-Moxi, Pred-Gati, Pred-Gati-Brom, Pred-Brom, MKO Melt and ImprimisRx are 844.446.6979 trademarks of Imprimis Pharmaceuticals, Inc. ©2018 Imprimis Pharmaceuticals, Inc. All Rights Reserved. IMPO0126 Rev1 2/18

RP0318_Imprimis.indd 1 2/21/18 3:52 PM Refractive/Cataract

REVIEW Rundown

the counter, they consider it more as a supplement or something like that. The problem is that systemic antihistamines cause drying that’s detrimental to the ocular surface and leads to more problems down the road.” Dr. Dhaliwal seeks alternative therapies for allergic patients taking oral antihistamines. “In the Visx manual, it even says that patients on Claritin had a much longer time to re-epithelialization. I wouldn’t pur- posely have somebody on oral antihistamines if their ocular surface was dry, because I know that they’ll have healing issues,” she says.

Topical Treatment Options

Once she’s confirmed a problem and sussed out medicines that could contribute to ocular dryness, Patients with ocular allergies may benefi t from targeted multisymptom relief, including combination antihistamine/mast-cell-stabilizer eye drops. Dr. Dhaliwal works to fi nd the right treatment or combination of treatments to target a patient’s allergy which is fluticasone, a nasal ste- about a week postoperatively. symptoms. “The most important roid. For patients with more of an It doesn’t necessarily follow that thing is to identify the patient’s is- allergic-asthma component to their patients will discontinue their tar- sues and treat them locally. We treat symptoms, we ask them to try Sin- geted pharmacotherapy once they’re what’s causing their symptoms: Do gulair (Merck). It’s a wonderful pill through the early postop period, they have allergic conjunctivitis? Al- because it helps to curb the allergic however. Dr. Dhaliwal says that lergic rhinitis? Or do they have more response, but it does not cause any some of her refractive and cataract of a pharyngeal asthma? Allergic drying of the eyes. So those types surgery patients with severe allergy conjunctivitis is very well treated of medicines have really been our symptoms seek longer-term relief, with topical combination antihista- mainstay of therapy,” she explains. consulting with allergists for com- mine/mast-cell-inhibitor drops like “Some people do fi ne with just the prehensive testing and the initiation Zaditor (Alcon). Those are really drops; some people need drops and of immunotherapy. “We have people great. There are so many different nasal spray; and some people need get allergy tests, and then allergy varieties, and they’re available over all three—drops, nasal spray and shots if they need them,” she says. the counter now,” she says. Other Singulair. Whatever the problem is, “That’s been very beneficial for a combination mast-cell-inhibitor/ we treat perioperatively.” bunch of patients who have signifi - antihistamine drops include olopa- Dr. Dhaliwal says that this peri- cant allergies. Some people initially tadine HCL (Patanol); ketotifen fu- od of localized treatment dovetails put up a bit of a stink about it and marate (Alaway); azelastine HCl with the approximately three-week say, ‘Allergy shots? I thought that (Optivar); epinastine HCl (Elestat); period when patients must abstain was just for kids!’ Obviously, insti- and bepotastine (Bepreve). Topi- from contact lenses prior to surgery. tuting immunotherapy takes much cal steroid drops include lotepred- “They need to keep their contact longer, and it’s not as though I’d have nol etabonate (Alrex and Lotemax). lenses out for about three weeks, so them start doing allergy shots before Topical drops may have the added typically, we’ll try to optimize them their surgery: That would take too benefi t of helping to wash out some in two to three weeks, and then we long. But we do educate patients, offending allergens.1 do surgery,” she explains, adding telling them, ‘You know, you don’t “If they have more of a rhinitis, that the Pittsburgh Protocol allergy- have to live like this.’ ” there’s Flonase (GlaxoSmithKline), treatment regimen also extends for Dr. Dhaliwal notes that a patient

18 | Review of Ophthalmology | March 2018

016_rp0318_rcr.indd 18 2/26/18 11:18 AM FULL POWERED EXAMINATION seeking the lasting relief immuno- ‘Have at least one room that is going therapy provides may no longer be to be animal-free. After surgery, take CHAIR limited to subcutaneous treatment. your nap there, and that’s your spe-

“What’s really cool is that now they cial place to stay, where you can just 2500-CH have sublingual immunotherapy, so rest and recover without any animal you can take a pill to help you get dander near you to make you itch.’ over your allergy to, say, ragweed.” Obviously, if patients rub their eyes FDA-approved sublingual immuno- after LASIK, it’s a big problem,” she therapies include tablets to combat says, since they might disrupt the allergic reactions to grass pollens, flap or set the stage for epithelial ragweed and dust mites. “I don’t cur- ingrowth. rently have any patients who’ve had “We really don’t want people to experience with that, but I’m looking forward to seeing it work,” she says. be exposed to their allergens,” she “It’s something that could be really stresses, adding that avoidance of beneﬁ cial.” seasonal allergens can dictate the timing of surgery if necessary. “If a Allergen Avoidance patient has a springtime issue, we can always do it later in the year,” Nonpharmacologic options for al- she says. “I just ask them, ‘When are lergic refractive and cataract surgery your allergies the worst?’ and then patients include cold compresses to try to avoid operating during that stop itching and prevent eye rub- time period, if possible.” bing; artiﬁ cial tears; and simple al- Although she has not done any lergen avoidance. Dr. Dhaliwal says comparative studies on the outcomes that this last measure is frequently of her allergic patients since insti- overlooked. “People forget this, but tuting the Pittsburgh Protocol, Dr. if you just avoid going outside when Dhaliwal is convinced of its value. “I the pollen levels are high, for ex- haven’t done any head-to-head stud- ample, you’re going to be okay,” she ies because if I have a patient with says. “When you come inside after a allergies, I treat them,” she says. Lo- high-pollen day, you’ve got to take a calized treatment with rapid onset shower, wash your hair and change of action and extended duration has your clothes immediately upon get- helped her cataract and refractive Powerful, precise, ting in the house. But a lot of people don’t do that: They end up rubbing surgery patients enjoy better visual automated. their eyes. They sleep on a pillow outcomes, and sometimes even long- &KRRVHWKH6237,.&+ that has pollen all over it from their term allergy-symptom relief. hair, and then they wonder why they “Its funny, but very many people ([DPLQDWLRQ&KDLUIRUFRQYHQLHQW wake up with itchy eyes in the morn- are really happy after getting off PRWRUL]HGUHFOLQLQJ ing. We do a lot of basic education. their systemic antihistamines,” Dr. Dhaliwal reports. “I’ve had patients We spend a lot of time with our pa- r KleenTech Lift System® tients talking about allergy avoid- say, ‘I feel better off of them, and ance, whether it’s environmental, I’m going to continue on this local- r Weight bearing armrests triggered by animals or anything ized therapy even though I’m healed r Robust footrest else. If patients are allergic to cats postoperatively.’ ” and dogs, but have pets that sleep r Precision engineered in the same bed with them, we have Dr. Dhaliwal is a consultant for them change the sheets and make Bausch + Lomb and a Visx trainer. sure that the animals are not in the room during the perioperative and 1. McGill JI, Holgate ST, Anderson DF, Bacon A. Allergic eye disase postoperative periods. I tell them, mechanisms. Br J Ophthalmol 1998;82:1203–14. 250 Cooper Ave., Suite 100 Tonawanda NY 14150 ZZZVRSWLNFRP, Sensible equipment. Well made, well priced. )RUWRGD\oVPRGHUQRƯFH

016_rp0318_rcr.indd 19 2/26/18 11:18 AM Retinal Insider

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

Addressing the Anti- VEGF Treatment Burden There are solutions in the research pipeline—both drugs and delivery systems—that might help ease the task of treatment.

Rehan M. Hussain, MD, Miami, and Thomas A. Ciulla, MD, MBA, Indianapolis

ntravitreal injections have be- However, real-world outcomes of an- Given the limitations of anti-VEGF I come an increasingly common ti-VEGF therapy are generally worse therapy, along with the burdensome clinic-based treatment for a variety than those obtained in clinical trials, need for repeated intravitreal injec- of exudative retinal diseases since an- possibly due to undertreatment.3 A tions to sustain effi cacy, long-acting ti-vascular endothelial growth factor large, retrospective analysis of a U.S. formulations of anti-VEGF drugs, as pharmacotherapy was introduced in medical claims database showed that well as topical and oral formulations, the early 2000s. One study regard- 19,000 newly diagnosed nAMD pa- are being developed. Brolucizumab ing the evolution of treatment of dia- tients received a mean of only 4.6 and and abicipar pegol are two novel in- betic macular edema over the past 6.9 injections of bevacizumab and ra- travitreal anti-VEGF treatments that decade reported a linear decrease in nibizumab over 12 months, respec- could potentially be approved for 12- frequency of laser therapy, while anti- tively. A meta-analysis of anti-VEGF week (quarterly) dosing after three VEGF therapy frequency exponen- treatment regimens for nAMD sug- monthly loading doses, which would tially increased, leading to a threefold gests that there is a positive linear result in six injections over the fi rst increase in clinic visits from a mean correlation with visual acuity gains 12 months (fewer than all three cur- of three visits per year to nine.1 This and number of bevacizumab or ra- rently available anti-VEGF agents). increased visit frequency related to nibizumab injections over 12 months, However, a deeper dive into the data anti-VEGF agent administration has although there was a ceiling effect in raises important questions. Some nov- created service pressures on ophthal- which more than nine injections an- el anti-VEGF treatments, currently in mology clinics and also places a sig- nually didn’t result in further gains.4 clinical trials, are summarized below, nifi cant burden on patients and their Theoretically, such a regimen could with a more comprehensive overview caregivers, with barriers to compli- be arranged as three monthly loading in the table. ance including patient anxiety/dis- doses followed by a six-week injection comfort, fi nancial burden, time con- interval thereafter, but this regimen Long-acting Anti-VEGF Agents straints and lack of transportation.2 would represent a departure from the Various treatment regimens, such trend towards personalized medicine Rather than use a sustained-deliv- as treat-and-extend and as-needed and personalized treatment regimens. ery approach, some agents that are administration, have been adopted to Afl ibercept, which is FDA-approved being studied are designed to require minimize treatment burden and po- for three monthly loading doses fol- less-frequent dosing. tentially improve compliance, while lowed by two-month dosing after- • Brolucizumab. Brolucizumab also personalizing treatment regimens ward, can be dosed in as few as eight (Novartis) is a humanized single- away from fixed-dosing regimens. injections over the fi rst 12 months. chain antibody fragment inhibitor of

20 | Review of Ophthalmology | March 2018 This article has no commercial sponsorship.

020_rp0318_retinal.indd 20 2/23/18 2:17 PM Visit us at ASCRS 2018 in Booth #1750 VEGF-A that has a smaller molecular every four weeks for three loading weight (26 kDa) compared to afl iber- doses followed by monthly sham out- cept (115 kDa) and ranibizumab (48 performed ranibizumab 0.5 mg given Achieve superior results with kDa). Its molecular properties allow a every four weeks. At the 20-week fol- AMOILS EPITHELIAL SCRUBBER higher molar concentration to be pre- low-up, the abicipar group gained a pared in a 0.05 ml intravitreal injec- mean of nine letters, while the ranibi- tion, which may allow for an extended zumab group gained only 4.7 letters duration of effect and improved ocu- with continued monthly dosing.7 (It’s lar tissue penetration. worth noting that the ranibizumab The Phase III HAWK and HAR- group underperformed compared to RIER trials (ClinicalTrials.gov identi- previous major trials involving ranibi- fi ers: NCT02307682, NCT02434328) zumab, such as the MARINA, CATT compared afl ibercept 2 mg to broluci- and ANCHOR trials, in which a mean zumab 3 mg and brolucizumab 6 mg. of just over six, 6.5 and 10 letters This study enrolled more than 1,800 were gained at 20-week follow-up, patients across 400 centers world- respectively.8-10) Quarterly dosing of wide. After three monthly loading ranibizumab 0.5 mg was tested in the doses, the brolucizumab groups were EXCITE and PIER trials, and visual treated every 12 weeks, with the op- gains weren’t as favorable as those ob- tion of switching to eight-week dosing tained in treatment arms of monthly in case of recurrent disease activity.5 A ranibizumab treatment, although 18 Uniform epithelium removal Novartis press release from June 2017 percent and 13 percent of patients re- in 5–7 seconds announced that the brolucizumab spectively gained ≥15 ETDRS letters 6-mg group met the primary endpoint on this regimen.11,12 of non-inferiority compared to afl iber- The abicipar Phase III trials Corneal Xlinking cept every eight weeks (measured by (NCT02462486) will compare treat- mean change in BCVA from baseline ment arms of abicipar every eight to week 48). A majority of patients, weeks (duration equal to afl ibercept), Improved clinical outcomes 57 percent (HAWK) and 52 percent abicipar every 12 weeks (duration (HARRIER), were maintained ex- superior to afl ibercept), and ranibi- of CXL and PRK with clusively on a 12-week interval im- zumab every four weeks.13 In May of Amoils Epithelial Scrubber mediately following the three-month 2017, Allergan announced comple- loading phase through week 48. The tion of patient recruitment in these • Minimize total procedure time press release didn’t specify the mean two global AMD Phase III studies. If number of injections that patients re- quarterly dosing of abicipar is found • Avoid alcohol damage to ceived after their three loading doses, to be non-inferior to monthly ranibi- surrounding tissue a key metric for comparison to current zumab and bimonthly afl ibercept, this therapies and regimens. The rate of would represent a major step forward • No neednee for subsequent scraping ocular and non-ocular adverse events in reducing treatment burden. were comparable between afl ibercept In the Phase IIb study, approxi- and brolucizumab.6 mately 10 percent of patients who • Abicipar pegol. Abicipar pegol received abicipar experienced epi- (Allergan and Molecular Partners) is sodes of ocular inflammation.14 Al- a monoDARPin (Designed Ankyrin lergan has worked to improve the Repeat Protein) that blocks all iso- abicipar formulation and purifi cation forms of VEGF-A. The Phase IIb trial process with the goal of reducing the data suggested that it has more potent incidence of inflammation in Phase VEGF-A inhibition, smaller molecu- III trials. Similar problems with in- lar size (34 kDa), and longer dura- flammation were encountered with tion (12 weeks) than the currently ranibizumab during early clinical tri- available anti-VEGF-A agents. In a als, which were successfully resolved 20-week study, Abicipar 2 mg given in later trials. The retina community T.800.T.800.461.120046

020_rp0318_retinal.indd 21 2/23/18 2:17 PM Retinal

REVIEW Insider

Table 1. AMD Therapies in the Research Pipeline

Compound Company Stage of Development Structure/Mechanism of Action small MW humanized single-chain Fab anti- Brolucizumab Novartis Phase III VEGF-A Abicipar pegol Allergan Phase III DARPin antagonist of VEGF-A OPT-302 Ophthea Phase IIb anti-VEGF-C/VEGF-D Pegpleranib (Fovista) Ophthotech Phase III did not meet end point anti-PDGF-B aptamer Rinucumab-afl ibercept Regeneron Phase II did not meet end point anti-PDGF-B/anti-VEGF co-formulation DE-120 Santen Phase II dual TKI of VEGF-A/PDGF Nesvacumab-afl ibercept Regeneron Phase II Ang-2/VEGF-A mAb co-formulation RG7716 Roche Phase II bispecifi c Ang-2/VEGF-A antibody ARP-1536 Aerpio Preclinical Tie-2 receptor activation (via VE-PTP inhibition) X-82 Tyrogenex Phase II oral anti-VEGF-A/PDGFR Pazopanib GlaxoSmithKline Phase IIb did not meet endpoint TKI of VEGF-A/PDGF PAN-90806 PanOptica Phase I/II TKI of VEGF-A/PDGF Regorafenib Bayer Healthcare Phase IIa did not meet endpoint TKI of VEGF-A/PDGF LHA510 Alcon Phase II VEGF-A inhibitor Ranibizumab PDS Genentech Phase II refi llable port of VEGF-A mAb bioerodible nanoparticles encapsulate TKI of GB-102 GrayBug Vision Preclinical VEGFR/PDGFR NT-503 ECT Neurotech Phase II terminated VEGF-A receptor fusion protein Hydrogel depot Ocular Therapeutix Preclinical sustained-release anti-VEGF-A Durasert pSivida Preclinical TKI of VEGF-A/PDGF ENV1305 Envisia Therapeutics Preclinical sustained-release anti-VEGF-A AVA-101 Adverum Biotechnologies Phase IIa results were mixed AAV sFLT AVA-201 Adverum Biotechnologies Preclinical AAV sFLT ADVM-022/ADVM-032 Adverum Biotechnologies Preclinical AAV encoding anti-VEGF-A cDNA AAV2-sFLT01 Genzyme (Sanofi ) Phase I AAV sFLT RGX-314 Regenxbio Preclinical AAV8 encoding anti-VEGF-A Retinostat Oxford Biomedica Phase I EIAV encoding endostatin and angiostatin Abbreviation Key: MW = molecular weight mAb = monoclonal antibody Fab = fragment antibody VE-PTP = vascular endothelial-protein tyrosine phosphatase VEGF = vascular endothelial growth factor PDGFR = platelet-derived growth factor receptor DARPin = designed ankyrin repeat protein bFBF = beta Fibroblast Growth Factor PDGF = platelet-derived growth factor VEGFR = vascular endothelial growth factor receptor TKI = tyrosine kinase inhibitor AAV = adeno-associated virus Ang-2 = angiopoietin-2 sFLT = soluble fms-like tyrosine-kinase 1 PDS = port delivery system cDNA = complementary deoxyribonucleic acid ECT = encapsulated cell therapy

Sustained Delivery Treatments eagerly looks forward to more clini- livery System (PDS), a nonbiodegrad- cal trial information, especially the The need for frequent intravitreal able port fixed to the sclera, has a mean number of injections per year, injections has spurred several com- 0.05-ml reservoir that can be refi lled in order to compare abicipar to the panies to develop sustained-release in the offi ce. Phase I results indicated non-fi xed dosing regimens of our cur- anti-VEGF-A devices. that it improved visual acuity compa- rently used agents. • Ranibizumab Port Delivery rable to monthly ranibizumab injec- System. The ranibizumab Port De- tions as reported in the MARINA and

22 | Review of Ophthalmology | March 2018

0020_rp0318_retinal.indd20_rp0318_retinal.indd 2222 22/23/18/23/18 2:172:17 PMPM ANCHOR studies. The 20 patients in ble to currently available anti-VEGF- the need for rescue ranibizumab in- the trial gained a mean of 10 ETDRS A therapies in half of 50 treatment- jection.18 letters and had received a mean of naïve nAMD patients, according to The Phase II APEX study 4.8 refi lls by the 12-month follow-up. a Phase I/II study (NCT02022540). (NCT02348359) is comparing X-82 Three serious adverse events (related According to a presentation from the with as-needed afl ibercept injections to the implantation procedure) were 2016 meeting of the Ophthalmic In- to aflibercept monotherapy in pa- reported, including endophthalmitis novation Summit, PanOptica planned tients with AMD. and persistent vitreous hemorrhage. to initiate a Phase I/II clinical trial of In 2015, Genentech initiated a an updated formulation for patients Gene Therapy Phase II study, the LADDER trial with nAMD in late 2017 or early 2018. (Long Acting Delivery of Ranibi- This newer suspension was designed Recently, the eye has become a tar- zumab, NCT02510794), to test the to reduce the incidence of punctate get for investigational gene therapy safety and effi cacy of the port delivery keratopathy as a side effect.17 due to the monogenic nature of many system on a larger scale, with a focus • LHA510. Alcon has devel- inherited retinal diseases, its acces- on optimizing the treatment dose and oped a topical anti-VEGF-A medi- sibility, the tight blood-ocular barrier, refi ll intervals.15 cation, LHA510, that’s been tested the ability to non-invasively monitor • GB-102. GB-102 (GrayBug Vi- as maintenance therapy for patients for functional and anatomic outcomes, sion) is sunitinib maleate, a multitar- with nAMD. The Phase II study and its relatively immune-privileged geted tyrosine kinase inhibitor with (NCT02355028) compares initial ra- state. Gene therapy for nAMD offers activity against both VEGF-A and nibizumab plus topical LHA510 for the promise of long-term continuous platelet derived growth factor. It’s an 84 days versus initial ranibizumab expression of anti-VEGF protein with injectable depot designed for twice- plus placebo, with the primary end- a single administration. Viral vectors per-year formulation. The drug is en- point being number of patients re- are conduits for transferring desired capsulated within bioerodible poly- quiring rescue ranibizumab injections genetic information to host cells. mer nanoparticles that slowly degrade before day 84.17 Vectors currently used in ocular over time. The GrayBug formulation gene therapy clinical trials include is designed to avoid the infl ammatory Oral Anti-VEGF Therapy: X-82 adeno-associated virus (small single- response seen with other nanopar- stranded DNA viruses of the parvovi- ticles, and the nanoparticles remain X-82 (Tyrogenex) is an oral anti- rus family) and lentivirus (RNA virus- at the injection site to avoid cloud- PDGF and VEGF-A inhibitor. In es of the retrovirus family). Both can ing the visual axis. In a rabbit laser the Phase I dose-escalation study transduce non-dividing cells, but AAV CNV model, GB-102 was found to be (NCT02348359), 10 of 35 patients (29 are non-integrating, while lentivirus superior to afl ibercept, according to percent) didn’t complete the 24-week integrate their genome into the host data published on the GrayBug web- endpoint, with six (17 percent) with- cell genome and have larger trans- site. Afl ibercept is maximally effective drawing due to adverse events. The gene capacity (approximately 10 kb vs when given at the same time as the most common adverse events were 4.5-5.0 kb for AAV). After successful laser injury, whereas GB-102 demon- diarrhea (n=6), nausea (n=5), fatigue transduction of the genome, the tar- strated equal effi cacy when given 10 (n=5) and elevated transaminase en- get cells transcribe and translate the weeks prior to it. Phase I studies are zymes (n=4) that reversed with cessa- viral genetic material into therapeutic in development.16 tion of X-82. protein, which then modulates the In terms of efficacy, 24 of the 25 pathogenesis of the targeted disease Topical Treatments patients that completed the 24-week process. trial maintained or improved their Gene therapy for AMD is still in Another method for reducing the visual acuity (mean +3.8 letters), and its early phases of development and treatment burden is to eliminate the 15 of 25 (60 percent) did so without has not yet translated to consistently need for an injection, a path taken by the need for rescue ranibizumab in- meaningful visual gains in AMD pa- the following investigational thera- jections (as specified by predefined tients, but nonetheless represents an pies: retreatment criteria). Mean central exciting area for future research.19 • PAN-90806. PAN-90806 (Pan- subfi eld thickness was reduced by a Gene therapies for AMD are summa- Optica) is a VEGF-A inhibitor eye mean of 50 µm, and eight patients (all rized in Table 1 on the opposite page. drop that has been shown to produce receiving at least 100 mg daily) main- When we take stock in the cur- an anti-VEGF-A response compara- tained sustained reductions without rent state of ophthalmology, there are

March 2018 | reviewofophthalmology.com | 23

0020_rp0318_retinal.indd20_rp0318_retinal.indd 2233 22/23/18/23/18 2:182:18 PMPM Retinal

REVIEW Insider

verteporfi n for neovascular age-related macular degeneration. N many experimental anti-VEGF agents 1. Jusufbegovic D, Mugavin MO, Schaal S. Evolution of controlling Engl J Med 2006;355:1432-1444. diabetic retinopathy: Changing trends in the management of 11. Schmidt-Erfurth U, Eldem B, Guymer R, et al. Effi cacy and and drug delivery systems under de- diabetic macular edema at a single institution over the past safety of monthly versus quarterly ranibizumab treatment in velopment that aim to decrease the decade. Retina 2015;35:929-934. neovascular age-related macular degeneration: The EXCITE treatment burden associated with fre- 2. Smith AG, Kaiser PK. Emerging treatments for wet age-related study. Ophthalmology 2011;118:831-839. macular degeneration. Expert Opin Emerg Drugs 2014;19:157- 12. Regillo CD, Brown DM, Abraham P, et al. Randomized, double- quent intravitreal injections. If one or 164. masked, sham-controlled trial of ranibizumab for neovascular more of these becomes a successful 3. Holekamp NM, Liu Y, Yeh WS, et al. Clinical utilization of anti- age-related macular degeneration: PIER study year 1. Am J VEGF agents and disease monitoring in neovascular age-related Ophthalmol 2008;145:239-248. part of our everyday practice, treat- macular degeneration. Am J Ophthalmol 2014;157:825-833 13. Safety and effi cacy of abicipar pegol in patients with ment paradigms could be dramati- e821. neovascular age-related macular degeneration. Available at: 4. Hussain RM, Hariprasad SM, Ciulla TA. Treatment burden in https://clinicaltrials.gov/ct2/show/NCT02462486. Accessed 12 cally disrupted, improving the lives neovascular AMD: Visual acuity outcomes are associated with February 2018. of an expanding population of seniors anti-VEGF injection frequency. Ophthalmic Surg Lasers Imaging 14. Positive top-line data reported from Phase II study for with AMD. Retina 2017;48:780-784. DARPin abicipar pegol in wet AMD. Available at: https://www. 5. Dugel P, Warburton J, Weichselberger A, Sallstig P. A 2-year molecularpartners.com/positive-top-line-data-reported-from- study comparing the effi cacy and safety of brolucizumab vs phase-2-study-for-darpin-abicipar-pegol-in-wet-amd/. Accessed Dr. Hussain is a vitreoretinal sur- afl ibercept in subjects with neovascular age-related macular 12 February 2018. degeneration: Testing an alternative treatment regimen. Presented 15. Study of the effi cacy and safety of the ranibizumab port gery fellow at Bascom Palmer Eye at: Association for Research in Vision and Ophthalmology Annual delivery system (RPDS) for sustained delivery of ranibizumab Institute. Dr. Ciulla is the past co-di- Meeting; 2016 May 1-5; Seattle, WA. in participants with subfoveal neovascular age-related macular 6. Novartis RTH258 (brolucizumab) demonstrates robust visual degeneration (AMD) (LADDER). Available at: https://clinicaltrials. rector of the retina service and ocular gains in nAMD patients with a majority on a 12-week injection gov/ct2/show/NCT02510794. Accessed 31 January 2018. angiogenesis research laboratory at interval. Available at: https://www.novartis.com/news/media- 16. GB-102 for Treatment of nAMD. Available at: http://www. Indiana University School of Medi- releases/novartis-rth258-brolucizumab-demonstrates-robust- graybug.com/pipeline-technology/gb-102/. Accessed 12 Febru- visual-gains-namd-patients. Accessed 12 February 2018. ary 2018. cine, and remains a volunteer clinical 7. Abicipar Pegol (Anti-VEGF DARPin) and Bimatoprost Sustained- 17. LHA510 proof-of-concept study as a maintenance therapy for professor of ophthalmology. He serves Release Implant for Glaucoma. Available at: https://www.allergan. patients with wet AMD. Available at: https://clinicaltrials.gov/ct2/ com/miscellaneous-pages/allergan-pdf-files/rd_investor_ show/NCT02355028. Accessed 12 February 2018. on the board of directors of Midwest presentation_jun30_2014. Accessed 12 February 2018. 18. Jackson TL, Boyer D, Brown DM, et al. Oral tyrosine kinase Eye Institute and is currently the 8. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for inhibitor for neovascular age-related macular degeneration: medical strategy lead in ophthalmol- neovascular age-related macular degeneration. N Engl J Med A Phase 1 dose-escalation study. JAMA Ophthalmol 2017; 2006;355:1419-1431. 135:7:761-767. ogy at Spark Therapeutics. Neither 9. CATT Research Group, Martin DF, Maguire MG, et al. 19. Moore NA, Bracha P, Hussain RM, et al. Gene therapy Dr. Hussain nor Dr. Ciulla have fi nan- Ranibizumab and bevacizumab for neovascular age-related for age-related macular degeneration. Expert Opin Biol Ther macular degeneration. N Engl J Med 2011;364:1897-1908. 2017;17:1235-1244. cial interests in anti-VEGF therapies. 10. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus

25TH ANNUAL OPHTHALMIC Product Guide Innovative products to enhance your practice The future is in your hands. One tap, many possibilities. Experience the digital edition on your handheld device. Use your smart device to scan the code below or visit: www.reviewofophthalmology.com/publications/archive

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

020_rp0318_retinal.indd 24 2/23/18 2:18 PM

2017_opg_half_horz_rp.indd 47 2/23/18 2:14 PM The Keeler 3 Trade In Program

Buy 3 // Trade 3 // Get 1 Free The Power of 3. Purchase any 3 Keeler Slit Lamps and trade in 3 of your old Slit Lamps and we’ll send you a 4th Keeler Slit Lamp absolutely free of charge.

K Series Q Series Z Series

Offer valid until June 30, 2018. Keeler Instruments, Inc. • 3222 Phoenixville Pike, bldg. 50 • Malvern, PA 19355 Tel: (800) 523-5620 • Fax: (610) 353-7814 • email: [email protected] Contact Keeler or one of our authorized dealers for more information.

RP0318_Keeler.indd 1 2/22/18 9:17 AM Cataract REVIEW Cover Focus After Surgery: Shots, Drops Or Both?

Kristine Brennan, Senior Associate Editor

Surgeons share ortunately, endophthalmitis af- of Toronto’s department of ophthal- ter cataract surgery is rare, but mology and vision sciences, employs their insights Fthat matters little to the patient intracameral injections to prevent who develops it. The landmark 2007 endophthalmitis. “I was the fi rst in on preventing ESCRS study, a prospective multi- the world to use intracameral moxi- center study of 16,603 patients ran- fl oxacin in 2004, and I still do,” he endophthalmitis domized into four treatment arms, says. found an approximately fi vefold de- Dr. Arshinoff’s infection-control and CME. crease in the risk of developing post- protocol doesn’t involve any preoperative endophthalmitis in those operative drops before the patient who received 1 mg of intracameral walks into the OR. “I think it is a re- cefuroxime at the close of surgery1 ally bad idea to give patients topical versus patients who did not; adding antibiotics for a few days preop. If postoperative topical drops to the you do that, microbiologically, the intracameral drug didn’t provide any drug kills off all the sensitive bacte- demonstrable benefi t. Some subse- ria, but it leaves the nutrients on the quent retrospective cohort studies2,3 conjunctiva for resistant bacteria to suggest that endophthalmitis cases grow,” he says. “You encourage resis- decrease as a practice pattern incor- tant strains because you’re selecting porates intracameral antibiotic injec- for them by killing off the bacteria tions. While many surgeons view this that are sensitive to the drug. When data as compelling and encouraging, patients come to the operating room, many others await defi nitive proof of they’re not there for long preopera- the effi cacy of intraocular antibiot- tively, so then I give them topical ics. Here, left to their own devices Vigamox (Alcon, Novartis) three times with regard to the drops/less-drops/ over 15 minutes: It kills off all the dropless question, surgeons describe sensitive bacteria that are there, but their endophthalmitis- and infl am- there isn’t enough time to grow re- mation-prevention regimens and the sistant strains to colonize the ocular reasoning behind their choices. surface.” Steven M. Silverstein, MD, FACS, Battling the Bugs in practice at Silverstein Eye Cen- ters, Kansas City, Missouri, who Steve A. Arshinoff MD, FRCSC, takes a drops-only approach, notes associate professor at the University that some causative factors are un-

26 | Review of Ophthalmology | March 2018 This article has no commercial sponsorship.

0026_rp0318_f1.indd26_rp0318_f1.indd 2626 22/26/18/26/18 2:052:05 PMPM Steven M. Silverstein, MD, FACS controllable, regardless of prophylaxis used. “There are some factors beyond our control,” he says. “Even if patients are not asked to take any eye drops, patients can still rub their eyes, go to the bathroom without washing their hands, touch doorknobs, shake hands—all kinds of things we can’t control. People can contaminate their eyes in a way that antibiotics alone may not necessarily prevent, regardless of the route of administration.” Dr. Silverstein also uses fl uoroquinolone drops, but he has patients use them for two days prior, and then ad- ministers them three times right before surgery in the preop area. “They Endophthalmitis with hypoyon. Most infections occur during the early postoperative period, also get a topical NSAID for two days but endophthalmitis can develop many months after cataract surgery. before surgery,” he says. At the close of surgery, Dr. Arshinoff injects Vigamox into the Zachary Zavodni, MD, in practice in-house compounding pharmacy or anterior chamber. “I give my patients at The Eye Institute of Utah and an a national commercial supplier such 600 micrograms diluted into 0.4 cc. adjunct clinical associate professor as Imprimis or JCB Labs. Most of We dilute basically the whole bottle at the John A. Moran Eye Center of the time, I end up using medication of Vigamox—3 cc—and add 7 cc of the University of Utah in Salt Lake compounded for intracameral use.” BSS. The concentration is such that City, also gives his cataract patients Dr. Silverstein will give periocular you inject 0.4 cc—a little less than intracameral Vigamox, but more of- antibiotics at the close of surgery in the volume of the pseudophakic an- ten uses compounded moxifl oxacin. a select few cases. “In high-risk pa- terior chamber (0.5 cc). You get a “Intraoperatively, I have been us- tients, those with vitreous loss, a prior totally safe dilution and a perfectly ing intracameral antibiotics for sev- history of endophthalmitis, or signifi - reasonable concentration to use,” he eral years, as the preponderance of cant lid-margin disease, I will give a says, cautioning that other branded data supporting such a practice is sub-Tenon’s injection of antibiotics, and generic moxifloxacin prepara- compelling,” he says. “Like many a depot injection for slow release, in tions have not been demonstrated to surgeons, I used to use intracam- conjunction with the pre- and post- be safe for intraocular use. “Avelox eral vancomycin because its cover- operative fl uoroquinolone antibiotic (Merck) has a pH of 4.1 to 4.6, which age against gram positive bugs is so drops that they receive, ” he says. is totally intolerable in the eye. I want good. Approximately two years ago, Dr. Silverstein thinks the extant to warn everyone: Don’t use Avelox. however, I stopped because of the evidence for intracameral injections Don’t use Moxeza (Novartis). It’s not possible association between vanco- is exciting, but insuffi cient to change worth trying to save fi ve dollars to get mycin and HORV. I now use 0.1 mL his practice pattern. “The Europe- some other solution that appears to of intracameral moxifl oxacin 0.05%. an study was compelling enough to be the same as Vigamox, but isn’t,” he I inject approximately 0.05 to 0.075 make us engage in serious conversa- stresses. “Vigamox is so safe that it’s mL directly into the anterior cham- tion, and to look toward a new U.S.- the only drug ever approved for sale ber at the conclusion of my case, based study with more consistent as a topical eye drop without a pre- and I use the remainder to hydrate parameters,” he notes, adding that servative: Nothing will grow in the the paracentesis wound. Depend- he has seen robust proposed study bottle. You can take it directly from ing on the setting I’m in (i.e., hos- designs that interest him. He remains the bottle and dilute it. It’s simple to pital vs. private-practice ASC) and skeptical of transzonular injections. dilute, and even if you don’t dilute the supply available, I will use either “When there is posterior capsular it but you inject only 0.1 cc, it’s not an unopened bottle of Vigamox or rupture, or even in an intact cap- dangerous.” compounded moxifloxacin from an sule, where medicine is deliberately

March 2018 | reviewofophthalmology.com | 27

026_rp0318_f1.indd 27 2/26/18 2:05 PM Cover Cataract

REVIEW Focus

squirted into the posterior segment countered any adverse reactions to it received vancomycin for something through the zonular network, the po- in intracameral use in an estimated else before: If they were primed im- tential for macular and retinal toxic- 10,000 patients. “I’ve had patients munologically, then they might get a ity is real, especially for aminogly- tell me they’ve had a bad response to reaction to it. It’s also a drug we want cosides,” he says. “Perhaps it’s not systemic moxifl oxacin, so when they to keep as a last resort,” he explains. as great with the fl uoroquinolones, come into the operating room, I give but we haven’t really had enough them a drop of Vigamox while they’re Postop Protocols experience to comment defi nitively waiting,” Dr. Arshinoff says. “If any- about that. Without concrete data, thing happens to them, then I won’t Ocular and periocular steroid it’s not something that I advocate at give them the intracameral.” injections—alone or together with this time.” Dr. Zavodni makes exceptions to compounded antibiotic—are part of Dr. Arshinoff says that his choice intracameral moxifl oxacin use for pa- the dropless cataract surgery trend. of moxifl oxacin is well supported by tients with suspected fluoroquino- None of the three doctors here cur- research. “We wrote a paper fairly lone sensitivities. “The only scenario rently use them, however. “I think recently that explains why moxifl oxa- in which I may vary my protocol is they’re a bad idea, because I think cin is better.4 In addition, Peter Libre when a patient has a history of al- the risk lies in giving the needle. If published a paper that demonstrated lergic anaphylaxis to either Betadine the patient moves during that injec- that the only drug that really kills off (Mundipharma) or fl uoroquinolones. tion, it can get into their eye. I don’t all the bacteria is moxifl oxacin.5 I’m In these cases I may use topical think there’s enough benefi t to jus- also currently writing a paper com- chlorhexidine to prep the eye before tify doing it,” says Dr. Arshinoff, who paring the abatement rates of the surgery. As an alternative to postop- gives Pred Forte (Allergan) drops different drugs and what happens erative topical fluoroquinolones, I postoperatively. “Because they only to their concentrations, and it turns will typically use polymyxin B sulfate/ get the steroid for fi ve to 10 days, and out moxifl oxacin is by far the best,” trimethoprim,” he says. a pressure spike usually takes around he says. While Dr. Zavodni stopped using fi ve days to develop, I ask the patient Dr. Arshinoff distinguishes docu- intracameral vancomycin because of to come back in fi ve days. “If their mented cases of uveitis-like condi- its relatively recent association with pressure is high, then I will stop the tions with transilluminating iris de- HORV, Dr. Silverstein stopped years Pred Forte, and I will tell them to pigmentation associated with oral ago after he and his colleagues at the take more ketorolac, six times a day moxifl oxacin,6 and “one or two” iritis time determined that it didn’t appear until their 10 mL bottle is fi nished, cases arising from intravitreal deliv- to be effective at preventing endo- and then they’re fi ne.” ery, from his preferred intracameral phthalmitis in their patients. “I was In addition to Pred Forte and ke- administration technique through in a practice around 2000 or so, when torolac, Dr. Arshinoff prescribes top- the side-port incision at a safe con- we did a study with all of the cataract ical Vigamox postoperatively. “Those centration. “As time goes by in medi- surgeons in the group to look at our particular medications are extremely cine, whenever we devise ways to practice’s endophthalmitis rates. We cheap in Canada: It probably costs give a drug directly to the area where were using intracameral vancomy- patients $20 to get enough drops for we want it to work, it’s by far the saf- cin, which was a popular product to both eyes, maybe $40. But in the est way you can do it,” he says. “If use prophylactically at the time,” he U.S., it might cost a few hundred,” he you have a high systemic dose, it tra- recalls. “Looking at 9,000 cases, we says. He adds that he also gives drops verses the iris into the vitreous. It saw no difference in the incidence because he thinks they help curb his actually washes the tissues en route, of endophthalmitis with or without patients’ postoperative behavior. “I where it may cause iritis. But when the vancomycin. We stopped using do 90 percent bilateral cataract sur- we put it into the anterior chamber, it because there was absolutely no gery. Bilateral cataract surgery pa- it’s not washing through to the iris. evidence to support its use.” tients may think that their surgery is It’s just in the anterior chamber and Citing concerns about HORV, Dr. trivial because they sit up and can see the capsular bag. In a lower dose, it’s Arshinoff concurs that vancomycin clearly right away out of both eyes. I very safe,” he says. does not belong at the forefront of don’t want my patients to think that A suspected anaphylactic response endophthalmitis prophylaxis. “The their surgery is trivial: When I give to topical moxifl oxacin before cata- risk of HORV is extremely low, but them drops, they think they’d bet- ract surgery has been documented,7 it’s an immunological condition, and ter be careful for the fi rst few days. but Dr. Arshinoff says he hasn’t en- often you don’t know if a patient has They don’t rub their eyes; they’re

28 | Review of Ophthalmology | March 2018

0026_rp0318_f1.indd26_rp0318_f1.indd 2828 22/26/18/26/18 2:052:05 PMPM Samuel Masket, MD more attentive to how they’re healing This encounter comes after prior and more careful overall. After the interventions to help patients and fi rst three days, I back them off the caregivers get a handle on topical drops from six to three or four times eye drops. “From the preoperative a day until the bottles are fi nished,” counselors, they’ve already gotten a he says. handout with this information on it, Dr. Zavodni doesn’t inject intra- and a life-sized color picture of the cameral or intravitreal steroids at bottles of medicine they’re going to close of surgery, either. Because of be using. And then it’s written down Intracameral injection of an antibiotic their short half-life he says, “These for them again on postop day one, preparation at close of surgery has been medications require either transzo- more widely adopted outside of the United when we review the instructions and nular placement or pars plana injec- States. decide whether or not we want to tion at the end of the case. Poten- increase or decrease the frequency tial drawbacks include: possible IOP of anything. If someone has a sig- rise; rebound infl ammation once the eratively until the bottle runs out, nifi cant amount of infl ammation, we steroid is gone; and some of the in- which will get them two to three may temporarily increase the fre- jected steroids are opaque, causing weeks of additional antibiotics. If it’s quency of the steroid, for example. increased floaters postoperatively.” a high-risk case, I’ll supplement that If there was a capsular rupture, we Dr. Zavodni does prescribe topical with periocular gentamycin or genta- may increase the frequency of the drops postoperatively because they mycin and Kefzol (Lilly) sub-Ten- steroid and the NSAID to help pre- remain the standard of care. “I am on’s,” he explains. “They get a topical vent CME. It really is no issue what- still using topical fluoroquinolones NSAID for two days before surgery, soever,” he states. for the fi rst week after surgery. I am on the day of, and then after surgery. One alternative to the treatment aware that there aren’t any random- If they’re not patched, they continue burden of topical steroids recently ized controlled trials to support such the NSAID till the bottle runs out, received FDA approval. DEXYCU a practice, and that Herrinton’s ret- which could be two to four weeks. It’s (Icon Bioscience Inc.; Newark, rospective study out of Kaiser Per- the same with the steroids: They’ll California) is an extended-release manente in 20162 demonstrated that get the steroid after surgery if they’re dexymethasone suspension intended topical antibiotic used in conjunc- not patched until the bottle runs out, for injection behind the iris and in tion with intracameral was not bet- which will cover them for two to four front of the IOL at close of surgery. ter than intracameral alone,” he ac- weeks.” DEXYCU’s intracameral dose is 5 knowledges. “Nonetheless, the use of To dropless-surgery advocates who µL (equivalent dexamethasone dose: topical antibiotics is still considered claim that keeping patients on topi- 517 µg) “The medication dissolves standard of care across the United cal eye drops is burdensome to staff, over three weeks and removes the States [98 percent of ASCRS sur- Dr. Silverstein says that his practice need for a topical corticosteroid for geons reported postoperative use of has devised patient education that most patients,” says Eric D. Don- topical antibiotics in a 2014 survey], is “streamlined, matter-of-fact, and nenfeld, MD, clinical professor of and I haven’t felt comfortable deviat- easy. ophthalmology, New York Univer- ing until prospective data exists prov- “Really, the only criticism of drop sity and trustee, Dartmouth Medical ing that it’s not providing any benefi t. therapy—until we have a defi nitive School, and lead investigator for the I also use both topical steroids and answer about efficacy—is compli- DEXYCU clinical studies. Dr. Don- NSAIDs following surgery, although ance,” he says. “That’s really the only nenfeld says the manufacturer hopes the effi cacy of NSAIDs is highly de- legitimate argument dropless propo- to make DEXYCU available some- bated.” nents have that that I agree with.” To time in 2018. Dr. Silverstein’s all-drops regi- simplify drop compliance, Dr. Sil- men includes postoperative topical verstein says that a postop nurse sits Until the Verdict Comes in NSAIDs and steroids as well as an with patients and family members antibiotic. “My patients receive pre- to review all post-surgical care and Dr. Zavodni, who uses both intraoperative fl uoroquinolone drops for restrictions, including the drop regi- cameral Vigamox and compounded two days before surgery, and then men. “They’re handed a sheet that preparations, summarizes the dilem- three times prior to surgery in the spells out the drops they should take ma faced by surgeons who want to preop area. They continue postop- and at what frequency,” he explains. proceed with injections to prevent

March 2018 | reviewofophthalmology.com | 29

026_rp0318_f1.indd 29 2/26/18 2:05 PM Cover Cataract

REVIEW Focus

infection. “The use of intracameral Steps Taken to Avoid Infection (in Addition to Iodine) antibiotics in the United States is on the rise (41 percent of ASCRS Topical anti-infl ammatory and antibiotic drops postop: 67% surgeons in 2017 clinical survey Intraocular injection of combined antibiotic/steroid: 7 results),” he observes. “Yet, two Combined topical mixture of antibiotic/anti-infl ammatory: 5 large barriers to ubiquitous adop- Topical antibiotic and a combined mixture of steroid/NSAID: 14 tion remain: First, there is no FDA- Other: 9 approved antibiotic, and as a result there is no uniform/commercially Respondents (n=83) to the e-survey published in this month’s Review of Ophthalmology produced, single-use sterile product showed a strong preference for topical antibiotic and anti-inflammatory drops to available here. Secondly, there are prevent infection and CME after cataract surgery. safety concerns regarding medication toxicity and compounding errors. drop to be just as effective at post- To help ensure the effi cacy of what “Currently, to use intracameral phaco inflammation control as an does go into his patients’ eyes, Dr. antibiotics, one must either tackle intracameral antibiotic/steroid injec- Silverstein uses only branded eye the legal and logistical challenges tion, and no cases of endophthalmitis drops. “One thing that people rarely of preparing a medication packaged occurred in any eyes studied.8 An- discuss is that generic steroids and and approved for topical use in the other compared eyes that received NSAIDS are not as uniformly effec- eye (i.e., Vigamox), or rely on a com- fi xed-combination antibiotic/steroid tive as their branded counterparts,” pounding pharmacy to prepare such drops with eyes receiving the com- he says. “I’ll occasionally see some- medications,” he continues. “Despite ponents of those drops separately one come in with postop uveitis, and 503B status-designation standards after cataract surgery. The fi xed-dose I’ll insist that they get off generics for certain compounding pharma- combination was just as effective as and switch to reliable branded topi- cies, there will always be some level the individual drops in preventing in- cal drops.” of risk of dilution error and con- fection and controlling infl ammation Dr. Arshinoff sticks to a branded tamination, given such a production after surgery.9 One study, funded by agent for intraocular injection. “One model. Concentration errors with a grant from Imprimis Pharmaceu- problem that we have now is that all intracameral cefuroxime have been ticals, compared postop eyes that Vigamox is becoming genericized, associated with toxic anterior seg- got a transzonular injection of the with multiple generic versions being ment syndrome and retinal toxicity. company’s compounded Tri-Moxi- sold in both Canada and the U.S. So Compared to cefuroxime, vancomy- Vanc with eyes receiving topical if I was going to use them—and I cin and moxifl oxacin are technically Pred-Moxi-Ketor drops (one week don’t—I would check with the com- more easily compounded. However, postop) followed by Pred-Ketor (two pany that it was the same formula- there is concern about an association to four weeks postop). Both treat- tion before I’d use it in someone’s between intracameral vancomycin ment modes appeared to have equal eye,” he cautions. “Sandoz is owned and HORV, which has curtailed its therapeutic benefi ts, but patients re- by Alcon (Novartis) and Alcon has use in the U.S. Thus far, intracameral ported greater satisfaction with the assured me that the Sandoz generic moxifl oxacin seems to be relatively injection.10 moxifl oxacin is identical to Vigamox.” safe at standard concentrations rang- Dr. Silverstein says that his con- One generally accepted compo- ing from 0.25% to 0.5%, so it has be- cerns about the sourcing and han- nent of endophthalmitis prophylaxis come the most popular intracameral dling of ingredients deters him from is povidone-iodine.11 “Everyone uses choice of U.S. surgeons,” he says. using compounded drugs. He also Betadine. We all clean the lashes The “less-drops” approach—giving worries about the potential for the and drape them carefully and use patients compounded fixed combi- presence of pharmacologic fillers Betadine 10% to wash the face and nations of topical antibiotic/anti-in- that could trigger rare but serious 5% eye drops for at least fi ve to 10 fl ammatory postoperatively, instead hypersensitivities in some patients. minutes before surgery,” says Dr. Ar- of separate antiobiotic, steroid, and “Especially because we’re talking shinoff. NSAID drops—has been adopted about something that goes into the “The only thing we know to de- by some surgeons attempting to de- eye, I’m not a strong fan of com- crease periocular and periopera- crease costs to patients and increase pounded medicines because of these tive bacterial load—and most likely their compliance. One small study rare but potential complications,” he found a fi xed-dose antibiotic/steroid says. (Continued on page 61)

30 | Review of Ophthalmology | March 2018

0026_rp0318_f1.indd26_rp0318_f1.indd 3030 22/26/18/26/18 2:062:06 PMPM ONLY

RP0318_Akorn Azasite.indd 1 2/23/18 10:11 AM Cataract REVIEW Cover Focus Whither Monofocal Toric IOLs?

Liam Jordan, Associate Editor

Where do ith the Symfony extended- pathologies that would make implant- depth-of-focus lens, Re- ing a toric multifocal inappropriate. monofocal toric WSTOR multifocal torics, and “You’ll see patients with amblyopia, the Trulign IOL, doctors can now com- epiretinal membranes, macular de- lenses ﬁ t into bine the features of multifocality/pres- generation, macular edema, macular byopic correction and toric correction holes, macular schisis, vitreoretinal an increasingly into one lens. Despite these advance- traction, advanced glaucoma, ocular ments, Kevin Miller, MD, a profes- misalignments, loose zonules, dry eye, multifocal-centric sor of clinical ophthalmology, David basement membrane degeneration, Geffen School of Medicine at UCLA, et cetera,” he says. “There are a thou- market? says, “There are quite a few instances sand-different corneal, retinal, optic where we like to use monofocal lenses nerve, and central pathologies that in lieu of multifocals. I probably put in could result in a poor visual outcome if as many toric monofocals as toric multi- you implanted a multifocal lens. These focals. It’s not a small sample size.” comorbidities basically close the lid This leads to the question, when on multifocals, but they don’t close would a patient or doctor prefer to the lid on a monofocal toric to correct implant a monofocal toric lens over the astigmatism.” ostensibly more advanced and multi- Cynthia Matossian, MD, an oph- tasking presbyopic IOL option? In this thalmologist based in Doylestown, article, we’ll delve into some of these Pennsylvania, also weighs in on the reasons. signiﬁ cance of these ocular pathologies. “One group of patients where Mono- vs. Multifocal Torics I wouldn’t recommend a multifocal toric lens is those that have coexist- Despite the popularity of premium ing pathologies that affect the macu- IOL options, experts say that there la, retina and the optic nerve. If they are plenty of reasons to recommend have macular degeneration (typically a monofocal toric rather than its pre- early to moderate) with a strong fam- mium counterpart. ily history, or if they have other kinds • Coexisting conditions. Perhaps of macular diseases, as long as it’s not the largest limiting factor for toric mul- that progressive, I’d go with a mono- tifocal lenses are patients who present focal,” she says. “They could have a with coexisting ocular pathologies. Dr. macular hole or epiretinal membrane. Miller describes some of the many Addressing these preop will absolutely

32 | Review of Ophthalmology | March 2018 This article has no commercial sponsorship.

0032_rp0318_f2.indd32_rp0318_f2.indd 3232 22/26/18/26/18 11:3311:33 AMAM help their astigmatism and outcomes, of their lives to correct astigmatism, but they won’t do well with a multifocal and they would be delighted if all they because their vision is already compro- had to do was wear reading glasses mised; giving them a clearer refractive for near vision,” Dr. Miller continues. option is great but splitting the light or “If they’re fine with reading glasses, adding potential light phenomena like monofocal torics are the way to go.” starburst, halos or spiderwebbing will Dr. Lehmann also shares some of his make things much worse. In this group insights into patients deciding to stick of patients, where a lot of people fall, with a monofocal lens. “The patient a monofocal toric is defi nitely the way that sits there and says, ‘I’m very happy to go. When deciding to implant a monofocal lens, with glasses,’ is a terrible candidate “Glaucoma is also a big issue with take into account patient preference. for these newer multifocal torics. We multifocal toric lenses,” Dr. Matossian hear from some, ‘My grandchildren continues. “These patients have com- level of astigmatism may also dictate wouldn’t know who I was without my promised optic nerves, so, implanting a whether or not a monofocal toric is glasses,’ so they’re not likely to benefi t multifocal toric in patients who are al- more appropriate than a multifocal from a multifocal. ready having issues with depth of fi eld is lens. “There is quite a bit of room for “Occasionally, you’ll see people who asking for trouble. They won’t do as well monofocal implants in our spectrum are in a work environment where they as they would with a monofocal toric.” of patients scheduled for cataract wear glasses all the time and it doesn’t Robert Lehmann, MD, an ophthal- surgery,” Dr. Matossian says. “A sub- bother them. Again, a monofocal to- mologist based in Nacogdoches, Texas, stantial portion of those patients have ric to correct their astigmatism is go- reaffirms the issues that arise when astigmatism of 1 D or greater where ing to be better for their lifestyle,” Dr. implanting a multifocal toric in patients these toric monofocal lenses would be Lehmann says. “What’s interesting is with less-than-healthy eyes. “I don’t a great choice. Unfortunately, we don’t patients oftentimes begin the conver- push multifocality—especially in pa- have low-cylinder IOLs in this country. sation by saying, ‘Well I’ve worn glasses tients who have glaucoma, Fuchs’ dys- They start at 1 or 1.25 D.” for X years,’ and you can’t predict the trophy, severe dry eye, et cetera. There Dr. Miller specifies the issues in- other half of the sentence. Seventy are corneal issues where I wouldn’t volved when a patient’s corneal astig- percent say, ‘I’m content with glasses.’ want to use a multifocal lens because matism exceeds the toric powers The other 30 percent say, ‘I hate them! the results aren’t going to be good. If available. “You wouldn’t implant a mul- There’s a way to eliminate them?’ You you’re dead-set on implanting a multifocal lens in an eye with corneal astig- just need to pay attention to their hab- tifocal toric lens, ideally, the patient matism that exceeds the dioptric cor- its and lifestyles.” would have a virgin cornea. Outside rection available in the marketplace. In addition to the habits of patients, of that, I would be hesitant to implant If you have a patient with 3.75 D of doctors may also need to take into ac- one over a monofocal to correct their corneal astigmatism, industry simply count personalities to see if a patient astigmatism.” doesn’t sell a lens at that toric power in is going to be satisfi ed with a multifo- When discussing where the Bausch the United States. So really there’s no cal toric. When asked about identify- + Lomb Trulign fi ts into this landscape, choice—you would implant a monofo- ing patients whose personalities would Dr. Lehmann says, “Typically, I consid- cal toric instead.” benefi t more from a monofocal toric, er the Trulign in much older patients, • Patient preferences. Despite the Dr. Matossian says it’s hard to pinpoint. usually above 75 years old, because numerous medical reasons to choose a “Some studies or authors say if someone we don’t see as many issues with glare, monofocal toric lens over its multifo- is an extreme perfectionist, they may halos or contrast sensitivity. But if you cal counterpart, sometimes, it’s up to not do well with a multifocal,” she says. implant a multifocal and decrease their the patient. “I see a lot of patients who “They won’t be satisfi ed if they work contrast sensitivity when they’re young- have read things about how bad mul- under dim lighting conditions because er than that, you’re not doing them any tifocals are,” Dr. Miller says.” They’ve a multifocal lens splits the light—about favors because they might be at risk for read about the glare and halos or may- 40 percent to distance, 40 percent to a condition that will later on decrease be they have friends who said, ‘I would near, and the rest is lost. So it’s not ideal their contrast sensitivity on top of that.” never do this again,’ and so they decide for people who work in dim conditions. • Level of astigmatism. Aside from they just don’t want a multifocal. Invariably, they are going to have issues. the obvious red fl ags of ocular history “You also encounter patients who “Say you’re a limo or taxi driver,” she and coexisting conditions, a patient’s have worn glasses or contact lenses all continues. “They’re not ideal multifo-

March 2018 | reviewofophthalmology.com | 33

032_rp0318_f2.indd 33 2/26/18 11:33 AM 032_rp0318_f2.indd 34 select basedonpersonalitytype.” fi tient, heorsheisnotgoingtobesatis- matter howhappy-go-luckythepa- refractive error. Ifit’s significant,no with multifocalimplantsissimple—it’s he says.“Thefi nal wordonhappiness plant pilots,etcetera,’tobeuntrue,” sonalities orwhinypeople,don’t im- engineers, don’t implanttype-Aper- we usedtohear, like‘don’t implant focal lens.“Ifi nd thatthosecautions he implantsamultifocalortoricmono- sonality typesdon’t determinewhether lenses.” developed apsychologyofmultifocal we’re stillfl ailing andfailing,havingnot wind isblowingintheirmind.Ithink psychology topredictwhichwaythe sort—a waytomeasureapatient’s to comeupwithanevaluationofsome based onpersonalityalone.“We tried be abettermonofocaltoriccandidate can bediffi cult topindownwhowould and helpthemseethatmuchbetter.” toric wouldcorrecttheirastigmatism different lensbecausethemonofocal cupations. Theywouldbenefi t froma time drivingthatcomeswiththoseoc- cal candidatesbecauseofallthenight- 34 fi enon.” without inducinganylightphenom- issues. Itstillcorrectstheirastigmatism they won’t havetheassociatedlighting “I’ll gowithamonofocaltoricbecause of theircareers,”Dr. Matossianavers. any kindoflightphenomenonbecause to halos,starbursts,spiderwebbingor people whoareveryproneorsensitive whether tousethem. these lensesinmindwhendeciding still keepthequalitativeissueswith focal toriclenses,patientsanddoctors Qualitative Issues ed withtheresults.You don’t needto cacy ofbothmultifocalandmono- Dr. Miller, however, fi nds thatper- Dr. Lehmannagrees,addingthatit In a2016studyevaluatingthe ef- “I wouldnotimplantamultifocalin Despite theadvancementofmulti- REVIEW |

Focus Cover Review ofOphthalmology

Cataract | March 2018 push patientstoward monofocaltorics. The riskofqualitativevisionissuesmay because theycan’t affordthis particular feel thatthey’regettingsecond-best says. “You wouldn’t wantapatientto tifocal becauseofcost,”Dr. Lehmann mended amonofocallensovermul- cal toriciscost.“I’vecertainlyrecom- patient’s decisiontogowithamonofo- Financing and glare. were significantinstancesofhalos cal lensrelyinglessonglasses,there that despitepatientswithamultifo- ract extraction,researchersfound focal intraocularlensesaftercata- these symptoms. of patientswere“verybothered”by group. Inbothgroups,<10percent 57.4 percent(n=85)inthemonofocal cent (n=62)fortheSymfonyversus cal group,andnoglarein42.8per- 74.3 percent(n=110)inthemonofo- cent (n=62)fortheSymfonyversus cal group,nostarburstsin42.2per- 70.9 percent(n=105)inthemonofo- percent (n=60)ofimplantsversus fony groupreportednohalosin40.8 halos, starburstsandglare,theSym- implant (n=148)lookingspeciﬁ Symfony (n=147)andamonofocal months. Inacomparisonbetweenthe group overthepastsevendaysatsix ined visualsymptomsoftheSymfony to amonofocallens.Thedataexam- FDA trial,researcherscomparedit of-focus lenses,intheSymfony’s Another issuethatmightinforma In therealmofextended-depth- 1

cally at 8 F accessda small subset.” would saythetoricmultifocalsarea of mypractice,”Dr. Millersays.“I half, ormaybecloseto65percent these categoriesaccountforatleast the bestoutcomes.“Alltogether, erence andwhichlenswillgivethem torics duetofi nances, personalpref- are oftenoptingtogowithmonofocal cal toriclenses,doctorsandpatients monofocal inthatcase.” a pricingdifference.Iwouldoptfor ously multifocalIOLbecausethere’s to payforbothatoricandsimultane- says, “theyjustdon’t havethefunds some patientshaveastigmatism,”she ing multifocallenses.“Eventhough perience withfi nancing issuesregard- frankly, that’s justnotthecase.” for somekindofworseoptionbecause, the offi ce feelingthattheyreallysettled pleased. Ialsodon’t wantthemleaving with amonofocalandlikelytobevery to affordwhenhe’s goingtoseewell with amultifocaltheywouldstruggle not ahealthythingtomakepatientgo Lehmann continues.“ButIthinkit’s with fi nancing andotheroptions,”Dr. ously youcantrytomakeitaffordable patient isunabletoaffordthose,obvi- gies thatcostmoremoney, andifa so tospeak. not gettingtheshortendofstick, a reliableandeffectivetreatment, guarantees thatapatientisreceiving The technologywehavenowbasically they’re happywithusingamonofocal. done verywellandgetthemresultsthat technology. You canstillgetthejob 2. 2018. CD003169.pub4/abstract accessed12January extraction. 1. Multifocalversusmonofocal intraocularlensesaftercataract Dr. LehmannisaconsultantforAlcon. sultant forAlconandBausch+Lomb. and J&JVision. Dr. Matossianisacon- Summary of safety and effectiveness data (SSED). ofsafetyand effectivenessdata Summary https://www. ebruary 2018. ebruary Despite theavailabilityofmultifo- Dr. Matossianalsodiscussesherex- “In anyfieldtherearetechnolo- Dr. MillerisaconsultantforAlcon accessed ta.fda.gov/cdrh_docs/pdf/P980040S065B.pdf accessed http://onlinelibrary.wiley.com/doi/10.1002/14651858. 2/26/18 11:34 AM STRIVE TO SEE THE BEST RESULTS POSSIBLE Regular fixed-interval dosing of long-term treatment with anti-VEGFs has been shown to provide better gains and maintenance of vision, compared to PRN or treat-and-extend dosing regimens, in some patients with Wet AMD and DME.1-6

Ask your Regeneron representative what we can do to help ensure patients come in for their scheduled treatment.

anti-VEGF = anti–vascular endothelial growth factor; AMD = Age-related Macular Degeneration; DME = Diabetic Macular Edema. References: 1. Heier JS et al. Ophthalmology. 2016;123(11):2376-2385. 2. Rosenfeld PJ et al. N Engl J Med. 2006;355(14):1419-1431. 3. Ho AC et al. Ophthalmology. 2014;121(11):2181-2192. 4. Nguyen QD et al. Ophthalmology. 2012;119(4):789-801. 5. Kaiser PK et al. Ophthalmol Retina. 2017;1(4):304-313. 6. Peden MC et al. Ophthalmology. 2015;122(4):803-808. © 2018, Regeneron Pharmaceuticals, Inc. All rights reserved. 777 Old Saw Mill River Road, Tarrytown, NY 10591 01/2018 US-OPH-13911

RP0318_Regeneron.indd 1 2/13/18 2:56 PM Cataract REVIEW Cover Focus Making the Most of Today’s Biometry Tech

Christopher Kent, Senior Editor

Today’s advanced ver the past 50 years, biometry portance of using them effectively to has become an essential part create optimal outcomes increases technology Oof cataract surgery, thanks in every year. Here, ophthalmologists part to an ever-increasing desire for with extensive experience in optical improves “perfect” refractive outcomes. In a biometry discuss how the technology kind of feedback loop, better tech- has evolved in recent years, and share outcomes, but nology for making the relevant mea- their advice for making the most of surements has resulted in better out- today’s instruments. caution and comes, raising patient expectations and necessitating even more refi ne- New vs. Old Technology training still pay ment in the technology. That evolu- off. tionary loop continues today. Today’s biometry devices serve to- A key turning point in the evolution day’s ophthalmologists better than the of biometry occurred with the switch older instruments, for a number of from ultrasound measurement to op- reasons. One reason is the increas- tical biometry. “The advent of refrac- ing number of patients who‘ve un- tive cataract surgery really began with dergone previous refractive surgery. the use of optical biometry, starting “It used to be that the person who with the fi rst IOLMaster more than had prior refractive surgery was sort a decade ago,” notes Eric D. Don- of a curiosity—an unusual situation nenfeld, MD, a clinical professor of for a cataract surgeon to encounter,” ophthalmology at New York Univer- says Terrence P. O’Brien, MD, a pro- sity Medical Center and a partner at fessor of ophthalmology and director Ophthalmic Consultants of Long Is- of the Refractive Surgery Service at land. “For the fi rst time, we had the Bascom Palmer Eye Institute of the ability to more accurately predict IOL Palm Beaches. “I can recall when we power in patients having cataract sur- only saw a few cases. They’d throw gery.” Since that development, a host our routine off; we’d have to step back of additional technological improve- and perform a lot of extra calculations ments have pushed the envelope even and try to fi gure everything out. Now, further, steadily increasing the accu- people who’ve had prior refractive racy and reproducibility of modern surgery of one type or another are biometry devices. presenting routinely every week. With ever-more-powerful tools at “This is where some of those bells ophthalmologists’ disposal, the im- and whistles on the new devices are

36 | Review of Ophthalmology | March 2018 This article has no commercial sponsorship.

0036_rp0318_f3.indd36_rp0318_f3.indd 3636 22/23/18/23/18 2:072:07 PMPM All images: Steven C. Schallhorn, MD valuable,” he continues. “Despite all “The latest versions of the IOLMas- of the changes we’ve seen, axial length ter and Lenstar are really terrific,” and keratometry still have to be deter- agrees Dr. O’Brien. “They allow us mined accurately, and thanks to today’s to measure additional parameters, technology, axial-length measurement including lens thickness, corneal has come a long way. That process pachymetry and anterior chamber used to involve a one-dimensional depth. And now several of the latest A-scan ultrasound; it was subject to instruments, like the IOLMaster 700 a lot of variability that could have a and some competitors, have added significant impact on the outcome. swept-source optical coherence to- Today’s biometry devices perform multiple The patient wasn’t obliged to ﬁ xate or functions with minimal technician mography. They acquire the measure- look in one direction, but if the patient management, but technicians still need ments even more quickly, and even wasn’t properly aligned the measure- thorough training to catch warning signs with a very dense cataract we can ob- ment might not represent the actual that a reading isn’t reliable. tain a reliable measurement with a distance to the fovea. That was a big two-dimensional conﬁ guration of the problem. yourself, you weren’t always sure of foveal anatomy.” “Of course, even back then there the quality and accuracy of the data. Steven C. Schallhorn, MD, former were ways to try to determine whether Today, automated keratometry is built director of cornea and refractive sur- the measurement was accurate,” he into the popular optical biometers, so gery at the Naval Medical Center in says. “You could examine the peaks on that process is now systematized into a San Diego, now in private practice in the printout, and with some experi- single device and the data is obtainable San Diego, believes the latest genera- ence you could tell if the patient was with a single click in most cases. That tion of biometers will improve the pre- looking askew, meaning you weren’t increases accuracy and makes it easy to dictability of outcomes. “It’s not that getting reliable data. But today, de- obtain repeat measurements.” outcomes were unsatisfactory with termining the axial length optically earlier-generation biometers,” he says. has revolutionized this, especially with Do You Need the Very Latest? “This is simply an evolutionary step the partial-coherence interferometry forward. The latest-generation devices technology found in the IOLMaster Given the rapid advances in biom- provide measurements for the most and Lenstar. This is now a noncontact, etry technology and frequent addi- advanced power calculation formulas, one-click measurement requiring only tion of new features, surgeons today and they make it easier to ensure the topical anesthesia. What used to be are faced with the question of when accuracy of their measurements. Hav- a very challenging, arduous task with it’s worth upgrading to the “latest and ing more accurate measurements and suboptimal reliability is now much greatest” iteration. added parameters for certain formu- simpler, with several orders of magni- “All of the modern optical biometers las will collectively drive better out- tude better accuracy.” are good when it comes to measuring comes.” Dr. O’Brien adds that these instru- axial length,” says Dr. Donnenfeld. Dr. Schallhorn notes that historical- ments also have improved the reli- “What the newest machines do, par- ly, surgeons relied on simple keratom- ability of keratometry measurements. ticularly the IOLMaster 700, is use etry, which measures only two points “That’s the other key variable for swept-source OCT to verify the loca- on the cornea. “Basic keratometry predicting the optimal lens power,” tion of the macula. That helps prevent makes a number of assumptions about he notes. “It’s a challenge to obtain axial-length measurement errors. In the corneal shape, such as that the these measurements, because the fact, errors in the keratometry, rather cornea is spherical (which it isn’t), and measurement process isn’t the only than the axial-length measurement, it applies a simplistic adjustment for issue; the ocular surface may change have become the number-one reason the power of the posterior cornea,” he over time. That means obtaining good patients have erroneous IOL power points out. “Those assumptions have keratometry may require repeat mea- predictions. But even the keratom- been considered reasonable for the surements to make sure the ocular etry is more reproducible because majority of patients, but they are not surface is stable. Also, when manual the IOLMaster 700 uses telecentric reasonable, for example, in patients keratometry was the gold standard for keratometry. That technology makes who’ve had prior refractive surgery. measuring corneal power, user skill the measurements more reproducible Corneal asphericity and other anoma- and experience were very important. even when the user doesn’t have the lies can significantly impact proper If you didn’t make the measurements keratometry in perfect focus.” IOL power selection. Biometers that

March 2018 | reviewofophthalmology.com | 37

036_rp0318_f3.indd 37 2/23/18 2:07 PM 036_rp0318_f3.indd 38 decision thesurgeonhastomake.” level it’s alwaysacost-effectiveness a reading.However, atthepractical takes lessthan30secondstoperform The newIOLMaster700,forexample, of timerequiredtotakethesetests. has dramaticallyreducedtheamount adds. “Inaddition,thenewtechnology nice tohavethelatesttechnology,” he generally yieldsbetterresults,soit’s A-scan ultrasonography. tor isusingopticalbiometryinsteadof great. Ithinkthemostimportantfac- very good,andthedeltaisnotthat ones. Theoldertechnologiesarestill mental improvements,notdisruptive couple ofyears.Buttheseareincre- technologies getbetteroverthenext see incrementalimprovementsasthe measurements, andwe’llcontinueto tal improvementinthequalityof in technologythere’s anincremen- “Every timeyouhaveanimprovement pendence they’relookingfor,” hesays. chance ofachievingthespectacleinde- technologies givepatientsabetter a qualifi cation. “Themoreadvanced comes.” nea aregoingtohelpimproveout- derive moreinformationfromthecor- 38 cian knowswhatheorsheisdoing and need tobeconfi dent thatthetechni- capable,” saysDr. Schallhorn.“You surements shouldbewell-trainedand trusting tomakethebiometrymea- the datacapture.“Thepersonyou’re astute, well-trainedtechniciandoing them quicklyiftheyoccurishavingan in preventingerrorsandcorrecting (and do)happen.Asignifi of operatorerror, buterrorsstillcan have defi nitely reducedthelikelihood well-trained. geons recommendthesestrategies: and reproduciblebiometrydata,sur- Before Taking theMeasurements “As weallknow, bettertechnology Dr. Donnenfeldagrees,butwith • To helpensurethemostaccurate REVIEW |

Make sure your technicians are Make sureyourtechniciansare Focus Cover Review ofOphthalmology The latest instruments The latestinstruments

Cataract cant factor factor cant | March 2018 before proceedingwithsurgery. warning signsofanunreliable reading datafortell-tale double-check thebiometry Surgeons shouldalways take thetimeto tient wearscontactlenses. more reliable,reproducibledata.” over andagain.Thiswillprovide couple of‘go-to’peoplewhodothis absence, butit’s bettertohavejusta a fewtechniciansincaseofillnessor course, youmightwanttocross-train more variabilityintoyourpractice.Of people sharingthistaskwillintroduce er reproducibility. Havingfi be gettingbetterreliabilityandhigh- validation criteria.Thatmeansyou’ll to misssomethingthatviolatesthe needs toberedone;they’relesslikely ly toknowwhenthemeasurement this overandover, they’remorelike- this repeatedly. Whensomeonedoes individuals inyourpracticewhodo better tohaveoneortwodesignated ens ofpeople,”saysDr. O’Brien.“It’s in whichyouwanttocross-traindoz- surements. to acquireyourbiometrymea- cian todoallofthereadings.” many surgeonsreliedononetechni- technician-dependent, whichiswhy The oldertechnologywasmuchmore less variabilitybetweentechnicians. become, whichmeanstherewillbe ogy, themorereproducibleresults fi hour toanoftrainingwouldsuf- says Dr. Donnenfeld.“I’dsayonehalf- need? “Itdependsonthetechnician,” can obtainapropercapture.” ce. Themoremodernthetechnol- • Besuretoaskwhetherthe pa- • How muchtrainingdotechnicians Rely on just a few technicians Rely onjustafewtechnicians “This isnotasituation ve orsix “Many tear fi will helptoimprovethequality ofthe patient takeanomega-3supplement lifi munomodulation withcyclosporineor artificial tears,andifnecessary, im- culations. To thatend,weliketouse tear fi lm priortoperformingIOLcal- that reasonwewanttooptimizethe etry,” Dr. Donnenfeld pointsout.“For reduced accuracyontheirkeratom- have beenshowntomarkedly on thesemeasurements.” ocular surfaceisstablebeforerelying ed. Somakecertainthatthepatient’s adequately beforebiometryisrepeat- surface diseasethatshouldbetreated patients mayhavesignificantocular notes Dr. O’Brien.“Inreality, some be alittlebitofrushtotheOR,” to expeditethatprocess,theremay cataract surgeryandtheteamistrying patients areeagertocompletetheir and tearfi months afterdiscontinuing.” alter thecornealshapeforweeksor lens wearers,thosecontactlensescan thokeratology. “AswithRGPcontact patient thathasarecenthistoryofor- geon shouldbeonthelookoutforany etry areaccurate.” that boththebiometryandkeratom- normal shape.Thishelpstoensure month sothecorneacanreturntoits have thepatientleavethemoutfora tient wearsgas-permeablelenses,we lenses aretoric,”hesays.“Ifthepa- biometry—a weekaheadifthesoft lenses foratleastthreedayspriorto patients toremovetheirsoftcontact are gaspermeable.” surements, especiallyifthecontacts the accuracyofyourbiometrymea- Schallhorn pointsout.“Thatcanaffect do, andthat’s criticaltonote,”Dr. don’t wearcontactlenses,butsome patients oldenoughtohavecataracts tegrast. We alsobelievehavingthe • “Patients withocularsurfacedisease • Dr. Schallhornaddsthatthesur- Dr. Donnenfeldagrees.“We ask Don’t useeyedrops ofanykind Make suretheocularsurface lm.” lm arestable. “Because 2/23/18 2:07 PM How Biometry Has Changed in the Past 25 Years

Terrence P. O’Brien, MD, a professor of ophthalmology and has come a long way since then.” director of the Refractive Surgery Service at Bascom Palmer Eye Dr. O’Brien notes another thing that’s changed since then: the Institute of the Palm Beaches, recalls that when biometry was far recognition that biometry is an integral part of the procedure. more primitive than it is today, ophthalmologists’ ideas about what “Today, we understand that preoperative preparation—planning outcomes were “acceptable” were very different. “A few decades and careful biometry and lens power calculation—are of pivotal ago, biometry was difﬁ cult to perform and outcomes were much importance to a good clinical outcome,” he says. “Those steps less predictable,” he recalls. “I remember seeing papers discuss- are every bit as important as what takes place during the surgery. ing how many patients would fall within a certain standard devia- They’re especially important today because patient expectations tion that would be considered acceptable if we just implanted the are so high. I often quote an old formula: Patient satisfaction same-power lens in every eye! At that point, having an outcome equals the clinical outcome minus the patient’s expectations. That within 2 D of the target was considered reasonable, and if we means that if the patient comes in with very high expectations, implanted a 20-D ‘standard’ lens in everyone, about 70 percent the clinical outcome has to be very close to the target in order to would be within 2 D of plano. We hoped those patients would be achieve overall satisfaction. Biometry is an essential part of that.” happy wearing glasses postoperatively. Needless to say, biometry —CK

right before taking corneal mea- macula-imaging technology, you can printout. “The IOLMaster, the Len- surements. Jack T. Holladay, MD, check the image of the foveola to con- star and the Pentacam AXL all pro- MSEE, FACS, a clinical professor of firm fixation. However, most units vide a standard deviation reading on ophthalmology at Baylor College of don’t have OCT yet. That means the their printouts, based on the multiple Medicine and the developer of the technician has to be paying particular K-readings they take, usually three,” Holladay I, II and Refractive formu- attention to this issue.” notes Dr. Holladay. “Doctors usually las, notes that although the intention “This may be an especially big prob- see standard deviation expressed in when using drops before taking a mea- lem in patients who are highly myo- diopters, because diopters are mean- surement may be to offset dry eye in pic,” adds Dr. Donnenfeld. “Actually ingful for ophthalmologists at a practi- the interest of obtaining a more accu- visualizing the biometry location with cal level. They know that a standard rate reading, the drops can cause cor- new OCT biometers such as the IOL- deviation greater than 0.2 D indicates neal steepening or punctate epithelial Master 700 gives the surgeon certainty a problematic reading, which gener- keratitis. “A better approach is to sim- that the biometry is focused in the ally happens in about 30 percent of ply ask the patient to blink frequently,” right place.” eyes. In most normal patients with a he says. “The measurement should be • If you perform auto-K, make healthy cornea, that number should taken about one second after the fi nal sure the keratometries agree. “It’s be close to zero. blink, which will allow the tear fi lm to good to verify that the keratometry “However, these printouts pres- stabilize.” found on the optical biometer corre- ent this information in millimeters or • Postpone biometry in patients lates with the keratometry on auto-Ks microns instead of diopters,” he con- with obvious superfi cial punctate or topography, whether you’re using tinues. “It’s the same measurement, keratitis in the visual axis. “Mea- the IOLMaster or the Lenstar,” says just expressed in different units. K- surements taken under these condi- Dr. Donnenfeld. “A lot of people ver- readings take a measurement of the tions will almost certainly be inaccu- ify these results with a different read- anterior corneal radius in millimeters rate,” Dr. Donnenfeld notes. ing. Clinicians in general have stopped and convert it to a diopter power. For using manual keratometry, but many example, a cornea that’s 7.5 mm in ra- When Taking the Measurements doctors still do autokeratometry and dius has 45 D in keratometric power. topography.” So a standard deviation of 0.2 D will These strategies will help prevent Dr. Schallhorn agrees. “If the bi- be presented as the equivalent radi- inaccurate measurements: ometer-derived keratometry is sub- us measurement, which is 0.03 mm, • Make sure your technician is stantially different from manual or or 30 µm. That means that if the stan- paying attention to patient fixa- topographic keratometry, that’s a sign dard deviation on the printout is that tion. “This is a key source of inaccu- of trouble,” he says. amount or greater, it’s exactly the same rate measurements,” says Dr. Schall- • Teach your technician to check as a standard deviation of 0.2 D or horn. “If your unit includes OCT with the standard deviation on the greater. It’s a warning flag that the

March 2018 | reviewofophthalmology.com | 39

0036_rp0318_f3.indd36_rp0318_f3.indd 3939 22/23/18/23/18 2:072:07 PMPM RETINA ONLINE E-NEWSLETTER

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

3 EASY WAYS TO SUBSCRIBE! http://www.jobson.com/globalemail/ Fax: 610.492.103910.492.1039 oorr CCall:all: 6610.492.102910.492.1

2016_Retina Online house Ad.indd 1 2/18/16 1:46 PM Cover Cataract

REVIEW Focus

measurement can’t be trusted because if you have a solid understanding of the entire cornea. That’s where you it’s not repeatable. what the technology is doing. may sometimes encounter problems, “The problem is, if the technician because that index of refraction is doesn’t understand the signifi cance of not the actual refractive index of your this number, he or she will ignore it,” patient’s cornea. It’s a number that’s he says. “So, you need to make sure “To achieve high- based on the anterior and posterior the technician knows about this and quality outcomes, a surfaces in an average eye. checks this number. If the number is “This complicates matters when an high, then the patient should be taken basic understanding eye has had previous refractive sur- to the topographer or tomographer of the technology and gery because of the changes in corneal to confi rm the measurement, and the curvature caused by that surgery,” he technician should try to determine the formulas is essential.” continues. “If the patient had radial reason for the problem. The patient —Terrence O’Brien, MD keratotomy, with radial incisions in may have dry eye, irregular astigma- the periphery to flatten the central tism, keratoconus or other issues. By cornea, both the anterior and poste- the time the doctor sees the report, rior curvatures will have been flat- the IOL calculation is done; it shows “In order to achieve high-quality tened together. In contrast, PRK and the lens and power. So, the technician refractive outcomes, having a ba- LASIK change the anterior curvature needs to be aware of this to catch the sic understanding of the technology while leaving the posterior curvature problem before the IOL calculation is and formulas is essential,” says Dr. relatively unchanged. That means the performed.” O’Brien. “That understanding makes fudge factor for the radius of curva- • Make sure the technician it possible to readily determine the ture is likely to be inaccurate in these checks the signal-to-noise ratio of quality and reliability of your preop- eyes. That’s signifi cant because most the axial-length measurement. “If erative data and formula predictions. of the power formulas calculate the that ratio is less than 2, it’s not a re- Fortunately, it’s become increasingly total corneal power and the effective liable measurement,” says Dr. Hol- simple to obtain reliable, high-quality lens position based on the anterior laday. “The ratio can go as high as measurements using today’s noncon- surface radius of curvature measure- 12, which is good; if it’s 2 or less, you tact optical biometers. These devices ments, so an error in that number can shouldn’t use that axial length mea- also have the advantage that many of lead to myopic or hyperopic surprises surement. The technician should go them come with the most advanced after cataract surgery.” back and redo it. If a good ratio can’t IOL power calculation formulas built Dr. O’Brien notes that the latest be obtained using that instrument, it right into the platform. Nevertheless, formulas are getting better at taking may be necessary to use an ultrasound the better you understand what’s hap- this problem into account. “The latest machine to measure the length of pening, the more likely you are to have devices and formulas are designed to the eye. So, be sure your technicians consistently good outcomes. That’s help determine a more accurate cor- check this number and don’t accept especially true when you’re dealing neal power in these eyes, to account the measurement if the signal-to-noise with complex cases, such as eyes that for the keratometric changes follow- ratio is below 2.” fall outside of the average range, or ing refractive surgery,” he says. “Some • Be on the lookout for dispari- eyes that have had prior surgery—in of our organizations are also working ties between the left and right eyes. particular, prior refractive surgery.” to help streamline this process for cat- “Unless there’s a good reason for the For example, it’s helpful to know aract surgeons. The American Society disparity—and there could be—a that different prior refractive surger- of Cataract and Refractive Surgery has great disparity between the two eyes is ies will affect the corneal radius of a post-refractive IOL calculator that’s another indication that at least one of curvature differently. “Both the front online and accessible, that allows sur- the measurements is inaccurate,” says and back surfaces of the cornea have geons to use many of these formulas Dr. Schallhorn. refractive power, and that has to be ac- in order to compare and select the op- counted for when predicting the opti- timal power for an individual patient.” Knowledge is Power mal lens power to implant,” notes Dr. O’Brien. “For that reason, after you Practical Concerns Although it’s easy to simply rely on acquire your measurements, an index technology to carry the day, the odds of refraction is applied to approximate A few more strategies can help en- of catching an error go up signifi cantly the effective keratometric power of sure optimal refractive outcomes:

March 2018 | reviewofophthalmology.com | 41

0036_rp0318_f3.indd36_rp0318_f3.indd 4141 22/23/18/23/18 2:072:07 PMPM 0036_rp0318_f3.indd 42 3 6 _ r p 0 3 1 8 _ f 3 hyperopic surprise. Doug Koch, MD, hyperopic surprise.DougKoch, MD, Dr. Holladay. “Theresulttendstobea using currentopticalbiometry,” says length measurementswhenmeasured long eyesproduceinaccurateaxial- “Surgeons shouldbeawarethatvery than 25mmwithopticalbiometry. rection iftheeyemeasureslonger care.” tant informationtohelpdriveoptimal decrease invision,that’s veryimpor- is partlyormostlyresponsibleforthe to detect.Ifanepiretinalmembrane cally, butit’s relativelyeasyforanOCT membrane canbehardtodetectclini- an epiretinalmembrane.An malities onthemaculaitself,suchas Dr. Schallhorn.“Itcanrevealabnor- performing inacataractpatient,”says not builtintoyourbiometer, it’s worth ning yoursurgery. checking themaculabeforeplan- an accuratemeasurement.” the calculationisgoingtobebasedon surgeon shouldlookattoconﬁ raphy? Theseareallthingsthatthe tometry reasonablymatchthetopog- atometry? Doesthebiometrykera- between manualandbiometryker- captures? Isthereareasonablematch a goodcorrelationbetweenrepeated tween theleftandrighteyes?Isthere Is thereanunexplaineddisparitybe- double-check thebiometrynumbers. immediately, butthesurgeonshould will pickupaproblemandaddressit planted,” hesays.“Agoodtechnician the correctIOLwasselectedandim- that biometrywasdoneproperlyand is ultimatelyresponsibleforensuring have surgeonveriﬁ “However, it’s alwaysagoodthingto producible,” notesDr. Donnenfeld. make senseandthenumbersarere- to makesurethestandarddeviations deviation oftheaxial-lengthreadings technician shouldlookatthestandard that thereadingsmakesense. 42 . i n d

• • Dr. Schallhornagrees.“Thesurgeon • REVIEW d |

Take timetoverifyforyourself

Focus Cover Be suretousethelatestcor- Review ofOphthalmology

If youhaveOCT, consider 4 2

cation.” Cataract “Even if OCT is “Even ifOCTis rm that | March 2018 “The “The able onlineat laday IandIIformulas.“It’s alsoavail- so thatitcanbeusedwiththeHol- Holladay IOLConsultantsoftware, formula hasbeenimplementedinthe ber 2017thenewnonlinearregression or hyperopicerror.” zero meanerrorratherthanamyopic that thelinearregression.Itresultsin nonlinear regressionismoreaccurate line producesbetterresults;hencethe it withacurveratherthanstraight the longereye,socorrectingfor error becomesprogressivelygreater sion. Asitturnsout,themeasurement allowed ustorunanonlinearregres- worked with,”hecontinues. compared tothe200eyesDougKoch from Kaiser-Permanente’s database, much largerdatabase—20,000eyes this measurementproblemusinga myopic error. ing thehyperopicerrortoasmaller the formulatendstoresultinswitch- produce abetteroutcome.However, sion formulatocorrectfortheerror, to co-developed theWang-Koch regres- fi zation isawaytofi each IOLthatyoumightuse. Optimi- the individualsurgeon’s outcomes,for tion formulasshouldbeoptimizedfor that’s acomponentoftheIOLcalcula- part ofthisprocess.Thelensconstant Dr. O’Brien.“That’s averyimportant tracking clinicaloutcomes,”advises accurate, surgeonsshouldnotstop cess moreuser-friendly, reliableand ogy thathelpmakethewholepro- “Despite theadvancesintechnol- ment aswell.” can modifytheformulaininstru- able totheIOLMasterpeoplesothey made thenonlinearregressionavail- long eyes,too.Inthemeantime,we’ve need tobeaddressingthisproblemin using oursoftware,buttheother9,000 more than1,000surgeonsoutthere calculator tab,”hesays.“Thereare gured thisoutafewyearsagoand Dr. HolladaysaysthatasofNovem- “Recently, Iwasabletoanalyze • Keep tracking your outcomes. Keep trackingyouroutcomes. hicsoap.com ne-tune this process ne-tune thisprocess under the underthe 1 “That this.” generation biometerswilladdress suming, costlyandineffi biometer itself,itcanbetime-con- the measurementisnotmadein in ourcalculations.However, because take theposteriorcorneaintoaccount shape ofthecornea;thatallowsusto devices thatcanmeasuretheposterior says. “Rightnowwehavetopography not yetavailableinbiometers,”he in theIOLpowercalculation. altered. Thatcanplayasignifi and anteriorcornealshapehasbeen the differencebetweenposterior patient hashadlaservisioncorrection, an impactontheoutcome,andif with-the-rule oragainst-the-rulehas ple, whetherposteriorastigmatismis posterior cornealshape.Forexam- nea, weneedtoaccuratelyassessthe estimate theopticalpowerofcor- “We nowunderstandthattobetter power selection,”saysDr. Schallhorn. that theposteriorcorneaplaysinIOL years thatwe’veappreciatedtherole “It’s onlybeenwithinthepastseveral analyze theposteriorcornealsurface. vances willincludetechnologythatcan bring evenmoreadvances.Thosead- stopping, andtheupcomingyearswill biometric technologyshowsnosignof What LiesAhead? higher-quality refractiveoutcomes.” and gainevengreateraccuracy calculation formulas.calculation 2018;125:2:169–178. Ophthalmology 1. MellesRB, HolladayJT, Chang WJ. Accuracy ofintraocularlens tant Software( tributor oftheHolladayIOLConsul- laday Consulting,whichisthedis- Zeiss. Dr. HolladayispresidentofHol- nenfeld isaconsultantforAlconand fi product mentioned. O’Brien hasnofinancialtiestoany consultant toCarlZeissMeditec.Dr. cer forCarlZeissMeditec.Dr. Don- “Unfortunately, that technologyis The trendtowardever-improving Dr. Schallhornischiefmedicalof- hicsoap.com cient. Next- cient. ). Heisa cant role 22/23/18 2:08 PM / 2 3 / 1 8

2 : 0 8

P M Clinicians trust Tono-Pen® most. Tono-Pen AVIA®, the most advanced Tono-Pen® tonometer, fi ts comfortably in your hand. Its calibration-free and technician-friendly operation fi ts your busy practice. Over 30 years of clinician-trusted accuracy and reliability fi ts your highest expectations. Tono-Pen AVIA just fi ts.

Visit us at ASCRS #532 for special show pricing or online at reichert.com/tonopenavia

Genuine brand Ocu-Film® protects your patients and your Tono-Pen.

Advancing Eye Care. American Innovation.

Made in USA · www.reichert.com ·

rp0318_Reichert.indd 1 2/27/18 3:09 PM E-Survey: Cataract Surgery REVIEW Cover Focus Surgeons Slow To Embrace New Tech

Walter Bethke, Editor in Chief

Most surgeons n this year’s cataract surgery opened it (13.2 percent open rate) technique survey, many of the and, of those, 83 fully completed the use traditional Isurgeons’ preferences, such as survey. To compare your practice pat- nucleo-fractis technique and the af- tern with theirs, read on. techniques, finity for femotsecond cataract, are similar to those of previous years. One Friends of Femto though femto thing that has changed, however, is the usage patterns of surgeons who As mentioned earlier, the percent- surgeons say use the femtosecond laser for cata- ages of surgeons who use/don’t use a ract procedures. Though most of their femtosecond laser for some aspect of they’re using the colleagues on the survey are shying their cataract procedures are similar laser more often. away from the technology, these fem- to previous years: Thirty-six percent to surgeons say they are getting more use it and the rest don’t (32 and 36 deeply involved, and are using the percent said they used the technol- laser more frequently for the different ogy for cataract surgery in 2017 and phases of the surgery when compared 2016, respectively). However, while to previous year’s surveys. 88 percent of those using it say they Surgeons’ use of femtosecond la- used it for the capsulorhexis and 81 sers is just one aspect of this month’s percent used it for nuclear fragmenta- e-survey. This month, 997 surgeons tion in 2017, this year, 97 percent and of the 7,564 who received the survey 93 percent, respectively, say they use it

Likelihood of Performing Femto- or Zepto-assisted Cataract Surgery Within a Year

Femto 82 82 Zepto

% 16 10 2 8 Very likely Somewhat likely Unlikely

44 | Review of Ophthalmology | March 2018 This article has no commercial sponsorship.

0044_rp0318_f4.indd44_rp0318_f4.indd 4444 22/26/18/26/18 11:5011:50 AMAM Preferred Phacoemulsiﬁ cation Technique

Quadrant division 48% Phaco chop 17 Sculpting 4 Stop and chop 17 Divide in two 5 Phaco ﬂ ip/tilt 5 Femto-fragmentation 2 Other 2

for these steps. the fact that it requires reliable and to use the femto vs. 10 percent who Chicago surgeon Jonathan B. Ru- expert technical support which is not are somewhat likely to try the Zepto. benstein, MD, says he appreciates always available; the frequent pupil “There’s no significant benefit to what the femto brings to his practice. miosis that makes an otherwise rou- patient outcome but an increased out- “It decreases phaco energy, phaco tine case become unnecessarily more of-pocket cost to the patient,” avers time and turbulence during the phaco complex (or expensive if I then have to Gregory Cox, MD, of Hamilton, New portion,” he says. “It’s especially good add Omidria to the bag); the diffi culty Jersey, in reference to the femtosec- in dense cataracts and patients with in seeing the fl uid wave in hydrodis- ond laser. endothelial compromise.” section when using the ‘waffl e pattern’ Robert Mobley, MD, of Clinton Lisa K. Feulner, MD, PhD, from [for nuclear segmentation]; and it’s Township, Michigan, says he’s un- Bel Air, Maryland says, “I fi nd that the sometimes more diffi cult to remove likely to try the new technology, due femto laser provides clean, accurate, cortex. Frankly, I think it offers mini- to benefit/cost issues. “I don’t find and reliable LRIs, entry wound inci- mal improvement for the added time any real advantage to femto,” he sions and paracenteses. The paracen- burden and increased chances of the says. “Plus, it takes up time and is tesis is well centered in the bag which, above-mentioned issues occurring in- an unnecessary cost to the patient. I I believe, allows for symmetric fi brosis traoperatively in our particular setting also found the integrity of the capsu- of the capsule over time, and there- (a university).” lorhexis to not be as good as manual, fore reduces rotation and tilting of the Though a number of surgeons use in my limited experience. I’m not IOLs. Nucleus fragmentation with the femto, as in previous years, a large familiar with Zepto, however.” the femto reduces the phaco time and proportion, 82 percent, say they’re Some surgeons, however, see some energy and is gentler on the cornea.” unlikely to take up the femto or the potential in the technologies, and are Christian Klein, MD, of Rochester, new Zepto capsulotomy device for use willing to try them down the road. New York, says that using the femto in their surgeries. Eight percent say “Zepto may be safer for white cata- has highlighted some pros and cons they’re “very likely” to use the Zepto racts,” says a surgeon from Wisconsin. for him. “I like the size and centration in the coming year (vs. 2 percent who Another surgeon says he’s somewhat of the capsulorhexis,” he says, “but I say the same for the femto), though 16 likely to try the technology due to a dislike the following: the added time; percent say they’re “somewhat likely” “new practice opportunity coming up.”

Surgeons’ Use of the Femtosecond Laser for Cataract Surgery 97 93 87 % 43 33

Entry wound Paracentesis Capsulorhexis Nucleus Astigmatism fragmentation correction

March 2018 | reviewofophthalmology.com | 45

0044_rp0318_f4.indd44_rp0318_f4.indd 4545 22/26/18/26/18 11:5011:50 AMAM 0044_rp0318_f4.indd 46 4 4 _ r p 0 3 1 8 _ f 4 graph above. range ofoptionschosenappearinthe on thesteepaxis(11percent).The bined withplacingtheentrywound second optionwasatoricIOLcom- popular option,at53percent.The a toricintraocularlenswasthemost matism incataractpatients. preferred methodformanagingastig- Astigmatism Management 46 . i n Preferred Way toPromotePupilDilationIntraop Preferred Anti-infection/infl Preferred MethodforManagingPre-existing Astigmatism tri n SI 14 7 5 67% Other 9 steroid andNSAID Topical antibioticandacombinedtopicalmixtureof Combined topicalmixtureofantibiotic/anti-infl ammatory Intraocular injectionofcombinedantibiotic/steroid Topical anti-infl andantibioticdropsforpostopuse ammatory lcn h la ona nr on nteai fatgaim 2 11 7 4 4 Postop refractiveprocedure Placing theclear woundontheaxisofastigmatism cornealentry keratotomy woundonthesteepaxisplusfemtosecondastigmatic Entry woundonthesteepaxisplusmanuallimbalrelaxingincisions Entry Toric IOLplus wound AK incisionsandanon-axisentry Toric IOLplus AK incisions Glasses orcontactlenses Toric woundonthesteepaxis IOLplusentry Toric IOL d

With regardtotoriclenses,Dr. Mo- Similar topreviousyears,theuseof Surgeons alsoweighedinontheir REVIEW % d |

Focus Cover Review ofOphthalmology

4 6 lidocaine injection intracameral epinephrine/ 58

E-Survey: Surgery Cataract phenylephrine and phenylephrine ketorolac injection (Omidria) | March 2018 10 ammation MethodPostop open. “Ihaveconﬁ most cases,butkeepsheroptions New Jersey, preferstoriclensesin Ligaya Prystowsky, MD,ofNutley, omy forlowerlevelsofastigmatism.” astigmatism. Idoastigmatickeratot- stable overtimefor>1Dofcorneal bley says,“They’reveryreliableand from apreopvalueof-6D.Thepa- residual astigmatismofonly-1.50D she says.“Ihavebeenableto sutures ifneededwithatoricIOL,” tially enterinthesteepaxisandadd lenses buttheyarelimited,soIini- take noadditional steps 24 dence inthetoric other 8 or reduceastigmatisminmyhands.” These arethebestwaystoeliminate astigmatism, IwillputinatoricIOL. those patientswithgreaterthan1Dof 1 Dofastigmatism,”hesays.“For atotomy onpatientswithlessthan axis plusfemtosecondastigmaticker- “I usebothentrywoundonthesteep cataract woundwiththefemtosecond. sidual astigmatismtolessthan0.5D.” where mygoalistoreducethere- says, “especiallywithmultifocallenses for higherdegreesofastimatism,”he combination ofatoriclensandfemto up to1.25Dofastigmatism,butusea approach: “Iusethefemtotoaddress tigmatic keratotomy, anddescribeshis a toricIOLwithfemtosecondlaseras- of Morristown,NewJersey, combines I caretoeliminate.”SeanLalin,MD, healing,” hesays,“whichisavariable able andnotdependentuponpatient the steepaxis.“Thisapproachisreli- toric lensesplustheentryincisionon D maxwithsuturesalone.” astigmatic correctionislimitedto-2 tients arehappy. Ifindthelevelof among respondents,with22 percent IOL isstillrelativelyuncommon to honetheselectionofa patient’s The useofwavefrontsensinginorder other aspectsofsurgery: Other Topics A surgeonfromTexas combinesthe A surgeonfromWest Virginia uses • Intraoperativeaberrometry. Surgeons alsosharedtheirviewson 53% 10 1 8 22/26/18 11:51 AM / 2 6 / 1 8

1 1 : 5 1

A M saying they use it, vs. 28 percent the Kansas City, Missouri, an advocate for do a “primary” chop at the start of year before. The doctors shared their stop and chop, says he uses it mainly phacoemulsifi cation for some cases, views on its pros and cons. because that’s how he was trained. “I I’ve begun to sculpt a bowl more fre- “It helps with long/short eyes and will also change the technique based quently at the start of nuclear dissem- multifocal and torics,” says John on the case, of course,” he says. “We bly,” he says. “This really improves Fitz, MD, of Farmington, Missouri. use femto about 35 percent of the the ability to get the phaco tip deeper “Sometimes, though, it gives results time, and when I don’t stop and chop, I into the nuclear wall and makes get- that do not make sense—and you then will fl ip and tilt.” A surgeon from Utah ting a successful chop much more go with preop plan.” Audrey Rostov, also likes stop and chop, because, he reproducible.” MD, of Seattle feels similarly, saying, says, “The initial groove makes room Dr. Fitz says simplifi cation is one of “It’s helpful but doesn’t capture on for cracking and eventual chopping.” the keys to success. “Try to maintain some difficult cases where it could the KISS principle: keep it simple, benefi t most.” stupid,” he says. “And, don’t over- “It’s great for post-LASIK and ab- promise. Some of these innovations normal eyes but time-consuming,” says Regarding nucleo- are more trouble than they are worth; Dr. Lalin. Ismail A. Shalaby, MD, of I’m frustrated that ORA and femto Baltimore says the technology is useful fracture, the most slow things down, and getting people but can pose some logistical problems. popular option on the to spend extra is hard and raises ex- “Benefi ts: More accurate IOL selec- pectations, so don’t push hard.” tion,” he says. “Shortcomings: It takes survey was quadrant James E. Lusk, MD, Shreveport, extra time, and you need a lot of IOLs division, chosen by 48 Louisiana, advises surgeons to “Re- in stock for it to be useful.” lease fl uid/viscoelastic simultaneously • Managing miosis. When faced percent of the surgeons. using the heel of the angled cannula with a pupil that won’t cooperate, the Tied for second place during hydrodissection to assure ele- option chosen by most surgeons on vation of the lens in the capsule bag to the survey is a homemade combina- are phaco chop, and attain the ability to rotate the nucleus. tion of intracameral epinephrine/lido- stop and chop, each at The rest of the case goes routinely.” caine injection, chosen by 58 percent. Dr. Rubenstein says it can help to Twenty-four percent take no addition- 17 percent. customize your approach. “Use three al steps. The results from this ques- different methods in conventional pha- tion appear in the graph on page 46. co: 1) stop and chop for dense lenses; • Nucleo-fracture preferences. 2) split and swirl for medium lenses; 3) The most popular option on the sur- Surgical Tips bowl and roll for soft lenses.” vey was quadrant division, chosen by Rather than giving nuts-and-bolts 48 percent of the surgeons. Tied for The respondents also took the op- advice, some surgeons gave more second place are phaco chop, and stop portunity to share surgical pearls: qualitative tips to mull over: and chop, each at 17 percent. Keith Skolnick, MD, Plantation, • “Fast is slow; smooth is fast,” says Dr. Prystowsky prefers quadrant di- Florida has advice for proper IOL a surgeon from Dallas. vision. “I combine with initial debulk- injection. “Since the 2.4-mm wound is • “Stay focused,” says a California ing in the center, then quadrant divi- tight, inject the IOL in a planar fash- surgeon. sion, and chopping later as the pieces ion parallel to the iris,” he says. “If you • “Enjoy yourself in the OR,” says come depending on the density of the angle the injector you’re less likely to Ron Glassman, MD, of Teaneck, New lens,” she says. “I have a population be able to go through smaller inci- Jersey with very dense lenses and fear of sur- sions.” • “Perfect is the enemy of good,” gery is prevalent.” John J. Brozetti, MD, Johnstown, says Robert Mahanti, MD, of Flag- A surgeon who prefers to do phaco Pennsylvania, advises, “Don’t proceed staff, Arizona. chop says of the technique: “Phaco with the case unless the pupil is 5 mm Dr. Ketcherside says it’s always good chop is less time-consuming, uses less or larger,” he says. “Use intracameral to learn various pearls, but then, “Find phaco energy, is safer than sculpting shugarcaine +/- pupil stretching for what works for you, and get really good techniques and is better in cases of inadequate pupil size for every case.” at that,” he says. “Know that you’ll have zonular weakness.” Dr. Klein has advice for breaking to refi ne as you go, but also that there’s Christopher Ketcherside, MD, of up the nucleus. “While I will still no ‘one right way.’ ”

March 2018 | reviewofophthalmology.com | 47

0044_rp0318_f4.indd44_rp0318_f4.indd 4747 22/26/18/26/18 11:5111:51 AMAM Glaucoma Management

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

Treating Uveitic Glaucoma: What Works? Because these patients have two conditions, treatment can be a challenge. However, today’s options are improving the prognosis.

Peter A. Netland, MD, PhD, Charlottesville, Virginia

bout 25 percent of patients surprisingly, some options work better • Aqueous suppressants, inclu- A with uveitis will develop elevated than others. ding beta blockers and carbonic intraocular pressure at some time In the case of uveitic glaucoma, anhydrase inhibitors. These are during their clinical course. (Different we’re addressing two conditions at the still the mainstay for therapy in studies have found percentages rang- same time: inflammation and glau- these patients. They can reduce IOP ing from 10 to 39 percent.) In chronic coma. Initially it’s important to try even when conventional outflow is uveitis the percentage is higher, ap- to get control of the inflammation. impaired in uveitic glaucoma. proaching 50 percent. This increase Cycloplegic drugs, corticosteroids, • Alpha-2-agonists. These drugs in pressure often appears to be due to nonsteroidal anti-inﬂ ammatory drugs may reduce IOP effectively despite multiple mechanisms. and immunomodulatory therapy are the impaired outﬂ ow caused by uve- In the past, managing these patients all approaches that may be effective itic glaucoma. was a challenge. Even though the for this purpose. • Hyperosmotic drugs. These can number of patients in this situation Immunomodulatory medications be very useful for marked elevations is limited, treatments often failed to are often the preferred drugs for of IOP, especially at presentation; they produce ideal outcomes. However, long-term management of these have a rapid onset of action and can be with today’s ever-growing set of patients. In fact, a major advance very effective at lowering IOP. Glycerol treatment options, that has changed. in the management of these cases has its peak effect approximately Here, I’d like to discuss the main op- has been having a greater choice of 20 minutes after administration. tions we currently have available for immunomodulatory medications, Mannitol is another option, but it helping these patients, and review along with a better understanding of requires intravenous administration, what the published evidence reveals them. However, most ophthalmolo- while oral administration of glycerol about each option’s effectiveness in gists are not comfortable selecting is easier and probably safer. (Recent this situation. these medications and monitoring evidence indicates that increased patients for any side effects. For that blood sugar is not a major concern Medical Management reason it’s important to work with after administration of glycerol, even a uveitis specialist, rheumatologist, in diabetics.) Nearly all of these patients ulti- internist or other clinician who can • Prostaglandins. These are mately require treatment with glau- help manage these patients. OK to use in this situation, but they coma medications, although about a Once the inflammation is under have a slow onset of action. That’s quarter of them also require glaucoma control we can address the elevated not terribly helpful in a patient who surgery to control their pressures. Not pressure. Options include: has an acute presentation of high

48 | Review of Ophthalmology | March 2018 This article has no commercial sponsorship.

048_rp0318_gm 2.indd 48 2/26/18 11:38 AM glaucoma. This problem responded well to laser iridotomy. Laser trabeculoplasty (argon laser trabeculoplasty or diode laser trabeculoplasty) is, generally speaking, not very effective in these patients. In addition, there’s a greater risk of complications, so we generally skip this option in a patient with glaucoma and uveitis. However, at least one study has shown that if the uveitis is very well controlled and the patient has a chronic elevation of pressure, selective laser trabeculoplasty can have a positive impact.2 Some clinicians have used transscleral cyclo- photocoagulation in these patients, even as primary therapy. However, there is a risk of vision loss and hypotony, so these are usually used with caution or in eyes with low visual potential.

Incisional Surgery

Incisional surgery usually means trabeculectomy or drainage implants, and both work well in these patients. If trabeculectomy is performed using antifibrosis drugs (most commonly mitomycin-C today) the success rate can range up to 80 or 90 percent in these patients, according to several relatively short-term studies—although some have found success rates as low as 50 percent. If trabeculectomy is done without the use of antifibrosis drugs, it has a very poor rate of success—53 percent at Figure 1. This patient with chronic uveitis presented at a follow-up visit with posterior 3 synechiae and pupillary block. The anterior segment OCT image shows the iris bombé five years, according to one study. conﬁ guration prior to laser iridotomy. Ultimately, if the uveitis is very well controlled or inactive and there’s been pressures. However, prostaglandins iridotomy does work and can be very no previous surgery, the success rates can be very helpful for patients over helpful as a means to address pupillary achieved with trabeculectomy are the long term, especially if they have block; however, it has a higher fail- very similar to those seen in patients well-controlled uveitis. ure rate in uveitic glaucomas.1 For with primary open-angle glaucoma.4,5 that reason, surgical iridectomy is Predictably, given the nature of Laser Therapy sometimes done instead of laser iri- trabeculectomy, there are some long- dotomy. Figure 1 (above) shows a pa- term complications and failures. There is a somewhat limited role tient who presented with posterior Nevertheless, trabeculectomy can be for laser therapy when managing a synechiae and pupillary block while a useful option in patients with well- patient with uveitic glaucoma. Laser being followed for chronic uveitic controlled uveitis.

March 2018 | reviewofophthalmology.com | 49

048_rp0318_gm 2.indd 49 2/26/18 11:38 AM Glaucoma

REVIEW Management

to five years of follow-up, with 100 Uveitis some signifi cant 94% success at reductions in 80 four years IOP—up to 40 percent— 60 during that 75% success at period.11 So two years 40 All Diagnoses this can be a promising ap- % Success proach. 20 It’s worth noting that 0 some of the MIGS devices 0 1 2 3 4 that have small lumens may Time (years) experience some blockage Figure 2. A comparison of the outcomes of two studies, one involving uveitis patients with glaucoma7 and another caused by in- involving patients with any glaucoma diagnosis.8 Uveitis patients were well-controlled with immunomodulatory flammatory drugs; they had close pre- and postop monitoring for infl ammation. Compared to the glaucoma patients with any debris. The EX- glaucoma diagnosis, outcomes were favorable in the uveitis patient group. PRESS device, for example, Glaucoma drainage implants study found a 75-percent success rate has a 50-µm lumen at its narrowest are also effective in these patients. (defi ned as an IOP between 5 and 22 point, and we’ve seen a small rate of Currently, this is a popular choice mmHg without additional glaucoma obstruction with infl ammatory debris among clinicians treating uveitic surgery and without loss of light in these patients. This may also be glaucoma. Like trabeculectomy, the perception) at two years.8 Given this an issue in other small-lumen MIGS success rate with drainage implants comparison, implanting a drainage devices, such as the Xen, iStent and seems to be tied to how well the device in a uveitic glaucoma patient is others. Surgeons are currently trying uveitis is controlled. Meta-analysis has a very reasonable option. these in uveitic glaucoma patients, shown that better control of uveitis but we haven’t seen any published is associated with higher success Other Surgical Procedures reports yet. rates, compared with poor control of When it comes to angle surgery for uveitis.6 Nonpenetrating surgery in pa- uveitic glaucoma patients, pediatric Figure 2 compares the outcomes tients with uveitis and glaucoma patients are an interesting niche achieved after implanting drainage has been evaluated in a few studies, group. Sharon Freedman, MD, and devices in two groups (from two but there’s no proven superiority to David Walton, MD, have shown that different studies). The first study trabeculectomy.9,10 In contrast, the goniotomy can be a useful approach evaluated the safety and efficacy of new minimally invasive glaucoma for chronic childhood uveitis. Most Ahmed glaucoma valve implantation procedures, or MIGS, are under of these patients are idiopathic in in 19 patients (21 eyes) with chronic intensive evaluation. Many of these their diagnosis, but the success rate uveitis and glaucoma; it found a 94- surgeries, using tools such as the is reported to be around 75 percent at percent success rate (defined as an Trabectome, the Kahook Dual Blade three years, which is pretty good for a IOP between 5 and 18 mmHg) at four (KDB) or the Trab 360, which can very low-complication procedure.12,13 years follow-up.7 For comparison, a perform a 360-degree trabeculotomy The age of these patients ranged up second study (a retrospective case through a single clear corneal to near 20; the average age was 15. So series) reviewed the data from 159 incision, seem to be effective in adult you can use this procedure in teenage eyes of 144 patients diagnosed with patients. One study involving 24 adult uveitic glaucoma patients. any type of glaucoma that were im- patients treated with the Trabectome Another option for the pediatric planted with Ahmed valves. That found a 74-percent success rate at up group is MIGS. Many of these

50 | Review of Ophthalmology | March 2018

0048_rp0318_gm48_rp0318_gm 2.indd2.indd 5050 22/26/18/26/18 11:3811:38 AMAM VisiPlug is the only one for me… surgeries, using tools such as the Trabectome, the Kahook Dual Blade or the Trab 360, also seem to be effective No pop-out! in pediatric uveitic glaucoma patients. So far, we’ve had positive results with these patients and we’re hearing positive anecdotal reports from others about this as well. We’re awaiting publications, which I’m sure will be forthcoming.

Today, the prognosis for these patients has greatly improved compared to a few years ago.

Outlook: Good

Today, the prognosis for uveitic glaucoma patients has greatly improved compared to a few years ago. This is at least partly the result of our more aggressive and comprehensive medical control of the uveitis, which often involves the use of immunomodulatory medications. In Lacrimedics’ VisiPlug is not like terms of the elevated pressure, most of these patients “other” punctum plugs. We have no are currently treated with glaucoma medications. reported “pop-outs” since VisiPlug’s However, the literature has clearly demonstrated that introduction in 2003… and it’s drainage implants are effective for surgical therapy, and many surgeons now consider this a “go-to” procedure. distributed in over forty countries! Goniotomy-related procedures also appear promising in pediatric patients and even adults. Other glaucoma Don’t let your patients become surgical options—including MIGS—may also be effective a victim of PPP (Punctum Plug in these patients, but those approaches are still under Pop-out) Syndrome in addition evaluation. to their Dry Eye Disease.

1. Spencer NA, Hall AJ, Stawell RJ. Nd:YAG laser iridotomy in uveitic glaucoma. Clin Exp Ophthalmol 2001;29:217-219. 2. Maleki A, Swan RT, Lasave AF, Ma L, Foster CS. Selective laser trabeculoplasty in controlled uveitis with steroid-induced glaucoma. Ophthalmology 2016;123:2630-2. 3. Stavrou P, Murray PI. Long-term follow-up of trabeculectomy without antimetabolites in patients with uveitis. Am J Ophthalmol 1999;128:434-439. ® 4. Kaburaki T, Koshino T, Kawashima H, Numaga J, Tomidokoro A, Shirato S, Araie M. Initial VisiPlug – trabeculectomy with mitomycin C in eyes with uveitic glaucoma with inactive uveitis. Eye 2009;23:1509-1517. a visibly better plug 5. Almobarak FA, Alharbi AH, Morales J, Aljadaan I. Intermediate and long-term outcomes of mitomycin C-enhanced trabeculectomy as a ﬁ rst glaucoma procedure in uveitic glaucoma. J Glaucoma 2017;26:478-485. to treat dry eye! 6. Chaku M, Bajwa A, Hao M, Lee JK, Netland PA. Treatment of uveitis and outcomes of glaucoma drainage implant surgery: a meta-analysis. Clin Ophthalmol, in press, 2018. 7. DaMata A, Burk SE, Netland PA, Baltatzis S, Christen W, Foster CS. Management of uveitic glaucoma with Ahmed Glaucoma Valve implantation. Ophthalmology. 1999;106:2168-2172. 8. Huang MC, Netland PA, Coleman AL, Siegner SW, Moster MR, Hill RA. Intermediate-term clinical experience with the Ahmed Glaucoma Valve Implant. Am J Ophthalmol 1999;127:27-33. 9. Auer C, Mermoud A, Herbort CP. Deep sclerectomy for the management of uncontrolled uveitic glaucoma: preliminary data. Klin Monbl Augenheilkd 2004;221:339-42. 10. Dupas B, Fardeau C, Cassoux N, Bodaghi B, LeHoang P. Deep sclerectomy and trabeculectomy in uveitic glaucoma. Eye 2010;24:310-314. 11. Anton A, Heinzelmann S, Neb T, et al. Trabeculectomy ab interno with the Trabectome (800) 367-8327 as a therapeutic option for uveitic secondary glaucoma. Graefes Arch Clin Exp Ophthalmol E-mail: [email protected] 2015;253:1973-1976. www.lacrimedics.com 12. Freedman SF, Rodrigues-Rosa RE, Rojas MC, Enyedi LB. Goniotomy for glaucoma secondary to chronic childhood uveitis. Am J Ophthalmol 2002;133:617-621. 13. Ho CL, Wong EY, Walton DS. Goniosurgery for glaucoma complicating chronic childhood uveitis. Arch Ophthalmol. 2004;122:838-844. 1Dramatization. Not a real patient. ©2017 Lacrimedics, Inc.

048_rp0318_gm 2.indd 51 2/26/18 11:39 AM A PUBLICATION BY

Retina Specialist focuses on the latest advances in the diagnosis, medical management and surgical treatment of diseases of the retina, along with practical, real-world advice from leading clinicians and other experts on managing the successful retina practice. The new addition to the Review family serves the entire Retina Specialist marketplace. Look for your issues in 2018: » MARCH » JUNE » SEPTEMBER » NOVEMBER

For inquiries contact [email protected] Advertising opportunities JIM HENNE • PUBLISHER • 610-492-1017 • [email protected] MICHELE BARRETT • 215-519-1414 • [email protected] MICHAEL HOSTER • 610-492-1028 • [email protected] www.retina-specialist.com

2017_retinaspecialist_housead.indd 1 1/16/18 4:30 PM Technology Update

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

An Early-2018 IRIS Registry Update With the seemingly exponential growth of the IRIS Registry, it’s a good time to check its progress. Liam Jordan, Associate Editor

n November of 2013, The American physician with diagnosed diabetic mac- you see that your performance is lack- IAcademy of Ophthalmology launched ular edema did not have any treatment ing, you can query the database and its Intelligent Research In Sight registry, in the fi rst 12 months, for example.” see why that is. We’ve seen aggressive and, since then, the registry has shown a Another surprising finding was in improvement through specifi c outcome lot of promise. Given IRIS’s staggering the realm of rare genetic diseases. “If and quality measurements as a result of growth and recent collaboration with it’s a rare disease, there will only be evaluating ourselves on a monthly basis. DigiSight, it’s a good time to take a look a few hundred cases,” says Dr. Rich. I think that’s huge. It was our dream at the registry and some of the opportu- “How do you find them in the mil- that this would be a resource of expand- nities it offers. lions? This registry nails down the rare ing clinical knowledge that would be William Rich III, MD, AAO’s cases that have similar through-lines widely available for analysis, and it’s fi - medical director of health policy and of treatment that physicians can use nally there. It’s happening a lot sooner chairman of the executive commit- for educational purposes or even in- than we anticipated.” tee of the IRIS registry, is excited by formed treatment options.” Another big move for IRIS occurred the success of the program. “We were A lot of the results from IRIS fall in an effort to bring in revenue to help overwhelmed with the rate of growth, right in line with the initial expecta- fund the registry. Allowing ophthalmic initially,” he says. “It’s exciting to have tions of the registry, however. “One companies to conduct studies using the 45.75 million patients and 189.62 mil- of the things we looked at is disparity “Big Data” of IRIS will bring in revenue lion charts in a registry. So, in the last in care—we talk about that a lot now,” and further the growth of IRIS, Dr. quarter of 2017, we decided to take a Dr. Rich continues. “Sometimes there Rich avers. However, the academy re- breath and look at the data. are groups of patients that don’t do quired an entity experienced with “big “Typically, if you have a great, solid well even if they are in the health-care data” and pricing such studies. “Our trial, the number of years it takes for system. With IRIS data, we now have partnership with DigiSight was fi nalized that practice or technique to be adopt- mechanisms through which we can in November,” Dr. Rich says. “Digi- ed by practitioners is around 10 years,” look at similarities or trends across Sight is a contractor for the Academy. he says. “IRIS is actually turning that demographics.” We couldn’t fi gure out a way to price on its head. We’re seeing immediate Dr. Rich says the registry has also or value these studies and trials. That’s improvement. helped physicians improve the qual- where DigiSight comes in. They un- “Within the data, we found some ity of their care. “That’s what this is derstand the signifi cance of big medical really surprising things, the first of all about,” he says. “A basic tenet of data and how to price a study. Because which is a gap in care,” Dr. Rich con- the registry is that if you look at per- of them, the Academy gets some rev- tinues. “Much to our shock, 40 percent formance compared to your partners enue stream and ongoing funds for of patients under the treatment of a or 17,000 other ophthalmologists, and IRIS and clinical research.”

This article has no commercial sponsorship. March 2018 | reviewofophthalmology.com| 53

053_rp0318_tech.indd 53 2/23/18 3:44 PM Left your Review of Ophthalmology magazine at the ofﬁ ce? No problem!

Read Review on the go from any mobile device! Simply go to www.reviewofophthalmology.com and click on the digimag link to get your current issue.

2015 Digimag hous ad_RP.indd 1 9/22/16 2:19 PM REVIEW Product News FDA Clearance for Topcon’s PSLT

opcon Medical Systems recent- SynergEyesCL Line Expands at synergeyes.com. Tly announced that its Pascal laser Duette Progressive received FDA clearance to use Pat- SynergEyes recently announced Topcon’s DRI OCT Triton tern Scanning Laser Trabeculoplasty the expansion of its Duette Pro- Topcon Medical Systems’ DRI Software. The software is used for the gressive hybrid contact lens line OCT Triton Series has received reduction of intraocular pressure asso- with the addition of a customiz- FDA 510(k) clearance. ciated with open-angle glaucoma. able center-distance lens. The new Topcon says that the DRI OCT PSLT is an advanced design comes with center-distance Triton features easy image capture tissue-sparing laser FlexOptics and an adjustable cen- and a 1-µm, 1050-nm light source treatment ter-distance zone size ranging from with a scanning speed of 100,000 A- Topcon says, 1.8 mm to 4 mm. The lens is driven scans/second. The multimodal in- that applies by photopic pupil size. Its add pow- strument also incorporates a built- ers range from +0.75 to +5 D. The in retinal camera and eye tracking center-distance design provides for use during the capture of se- a customized vision solution for lected scans. emerging to advanced presbyopes, According to Topcon, in addition including those with astigmatism, to the anterior segment allowing for the Duette Pro- scanning, the DRI gressive line to cover most pa- OCT Triton can tients with presbyopia, visualize deeper SynergEyes says. pathology, rapidly SynergEyes adds that penetrating ocular a rapid, its Duette Progressive tissues regardless precise and hybrid lenses are cus- of media opacities minimally- tomizable by base curve, or hemorrhages. The traumatic computer-guided treat- add power and center- instrument features ment sequence of patterns onto the distance zone to help cov- widefield OCT trabecular meshwork. The auto- er most presbyopic needs. scanning (12 mm mated rotation of consecutive pat- The hybrid design elimi- x 9 mm) with a terns ensures that treatment steps nates the rotation issues reference data- are placed without overlap or ex- commonly associated with base. In addition, cessive gaps. Topcon says it pro- soft toric lenses, SynergEyes says. it displays high-resolution vides an average IOP reduction of These lenses may be ﬁ t empirically fundus images with clear retinal 24 percent at six months. without the need for diagnostic sets vessel and macular mapping. To learn more about Pascal or ﬂ uorescein. For more information on Top- and PSLT, visit pascalvision.com/ More information on the Duette con’s DRI OCT Triton series, visit science/#pslt. Progressive hybrid line is available topconmedical.com.

This article has no commercial sponsorship. March 2018 | reviewofophthalmology.com | 55

055_rp0318_products.indd 55 2/26/18 11:27 AM Research Review REVIEW

Bevacizumab Injections After MIs

oting that intraocular injec- the following differences in mortality: ed ICP were divided into group one Ntions of anti-vascular endothelial • within three months between MI (200 < LP ≤ 300 mmH O) and group 2

growth factor agents are the main and initiation of bevacizumab treat- two (LP > 300 mmH2O). Individuals therapy in age-related macular de- ment, OR=6.22 (CI, 1.08 to 35.97, underwent follow-up ONSD and LP generation, researchers analyzed the p<0.05); measurements within one month. In- mortality associated with intravitreal • within six months, OR=2.37 (CI, vestigators analyzed correlations be- injections of bevacizumab for AMD 0.93 to 6.02, p=0.071); tween the ONSD and ICP on admis- in individuals previously diagnosed • within 12 months, OR=3 (CI, sion, and between changes in ONSD with acute myocardial infarct. 1.44 to 6.28, p<0.01); and ICP, i.e., respective changes in Using a national database, re- • within 24 months after MI, ONSD and ICP from admissions to searchers identifi ed individuals with OR=2.24 (CI, 1.35 to 3.70, p<0.01); follow-up. Main outcomes and mea- bevacizumab-treated AMD with di- and sures included the ultrasonographic agnosis of MI prior to the fi rst beva- • MI any time prior to fi rst bevaci- ONSD and ICP measured at admis- cizumab injection (delivered between zumab injection, OR=1.71 (CI, 1.53 sion and follow-up, correlations be- September 2008 and October 2014 to 1.92, p<0.001). tween ONSD and ICP on admission, [n=2,100]). They then generated sub- They advised that caution should be and changes in ONSD and ICP using groups treated within three months taken when offering bevacizumab to Pearson correlation analyses. (n=11), six months (n=24), 12 months individuals with AMD after MI. Investigators reported that for 60 (n=52) and 24 months (n=124) after Graefes Arch Clin Exp Ophthalmol individuals (mean age 36.2 ±12.04 MI. Researchers compared those in- 2018; Feb. 10. [Epub ahead of print]. years; 29 [48 percent] female) at dividuals to age- and gender-matched Hanhart J, Comaneshter DS, Freier-Dror Y, et al. admission (group one), ONSD and members who had MI at the same ICP values were strongly correlated, time but were never exposed to anti- Ultrasonography Assessment of with an r of 0.798 (CI, 0.709 to 0.867; VEGF. They performed a survival Optic Nerve Sheath Diameter p<0.001). analysis using propensity score-ad- For 25 individuals with elevated justed Cox regression. Investigators wrote that the stan- ICP who completed the follow-up Bevacizumab-treated individuals dard method for monitoring intracra- (group two): were slightly and insignifi cantly older nial pressure can result in complica- • upon admission, the mean ONSD than controls (mean age, 83.25 vs. tions and pain, making noninvasive, was 4.50 ±0.54 mm, and mean ICP

83.19 year; p=0.75). Gender distribu- repeatable methods a valuable option. was 302.40 ±54.26 mm H2O; tion was similar. Researchers reported They examined how ultrasonographic • upon admission, ONSD and ICP increased mortality rates associated optic nerve sheath diameter correlat- values obtained were strongly corre- with the use of intravitreal bevaci- ed with noninvasive and dynamically lated with an r of 0.724 (CI, 0.470 to zumab in AMD cases after MI, com- monitored ICP changes. 0.876; p<0.001); pared with age- and gender-matched Investigators measured the ONSD • the mean change in ICP was

post-MI cases with no exposure to an- before lumbar puncture in 60 individ- 126.64 ±52.51 mm H2O (range: 20 to

ti-VEGF agents. Researchers found uals on admission. Those with elevat- 210 mm H2O) (CI, 106.24 to 146.07),

56 | Review of Ophthalmology | March 2018 This article has no commercial sponsorship.

0056_rp0318_rr.indd56_rp0318_rr.indd 5656 22/26/18/26/18 11:2011:20 AMAM Monthly MACKOOL ONLINE CME CME SERIES | SURGICAL VIDEOS

MackoolOnlineCME.com MONTHLY Video Series Welcome to the third year of Mackool Online CME! With the generous support of several ophthalmic companies, I am honored to have our viewers join me in the operating room To view CME video as I demonstrate the technology and techniques that I have go to: found to be most valuable, and that I hope are helpful to www.MackoolOnlineCME.com many of my colleagues. We continue to edit the videos only to either change camera perspective or to reduce down time – allowing you to observe every step of the procedure. Richard J. Mackool, MD Episode 27: As before, one new surgical video will be released monthly, “Determination of and physicians may earn CME credits or just observe the case. New viewers IOL Power in are able to obtain additional CME credit by reviewing previous videos that are Keratoconic Eyes” located in our archives. Surgical Video by: I thank the many surgeons who have told us that they have found our CME Richard J. Mackool, MD program to be interesting and instructive; I appreciate your comments, suggestions and questions. Thanks again for joining us on Mackool Online CME. Video Overview: This case demonstrates the use of intraoperative CME Accredited Surgical Training Videos Now aberrometry plus the Aphakic Available Online: www.MackoolOnlineCME.com Refraction Technique to best determine the ﬁ nal IOL power in a keratoconic eye. Richard Mackool, MD, a world renowned anterior segment ophthalmic microsurgeon, has assembled a web-based video collection of surgical Tips for visualization, a cases that encompass both routine and challenging cases, demonstrating both comparison of phaco chop familiar and potentially unfamiliar surgical techniques using a variety and divide and conquer and of instrumentation and settings. the advantages of a high IOP setting round out this very This educational activity aims to present a series of Dr. Mackool’s surgical educational case. videos, carefully selected to address the speciﬁ c learning objectives of this activity, with the goal of making surgical training available as needed online for surgeons motivated to improve or expand their surgical repertoire. Learning Objective: After completion of this educational activity, participants should be able to: • Demonstrate the Divide and Conquer methods of nucleus disassembly, and also a method of calculating IOL power in eyes with keratoconus.

Accreditation Statement - In support of improving patient care, this activity has been planned and implemented by Amedco and Postgraduate Healthcare Education, LLC. Amedco is jointly accredited by the American Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Credit Designation Statement - Amedco designates this live activity for a maximum of .25 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Additionally Supported by: Endorsed by: Jointly Provided by: Supported by an unrestricted independent Review of Ophthalmology® medical educational grant from: Glaukos MST Video and Web Production by: & Crestpoint Management JR Snowdon, Inc Alcon Carl Zeiss Meditec Research

REVIEW Review

and in ONSD was 1 ±0.512 mm Table 1. Outcomes of Trab + MMC in Angle-closure Glaucoma (range: 0.418 to 2.37 mm) (CI, 0.83 to 1.20); and Success Criterion 1-year Follow-up 3-years Follow-up 5-years Follow-up • the change in ONSD was strongly Criterion A: 92 ±2.2 percent 78 ±3.8 percent 72 ±4.3 percent correlated with that in ICP, with an r IOP ≤18 mmHg and of 0.702 (CI, 0.425 to 0.870; p<0.001). IOP reduction of 20 Follow-up evaluations revealed that percent elevated ICP and dilated optic nerve Criterion B: 86 ±3.0 percent 65 ±4.4 percent 59 ±4.7 percent sheath diameters returned to normal, IOP ≤15 mmHg and and no evidence of difference was IOP reduction of 25 found in the mean ONSDs between percent group one (3.49 mm; CI, 3.34 to 3.62 Criterion C: 62 ±4.2 percent 40 ±4.5 percent 32 ±4.4 percent mm) and group two (3.51 mm; CI, IOP ≤12 mmHg and 3.44 to 3.59 mm) (p=0.778) at follow- IOP reduction of 30 up. percent Investigators found that the dilated ONSDs decreased along with the elevated ICP reduction. They concluded of 196 eyes (157 patients) who had achieving long-term IOP levels in the that ultrasonographic ONSD mea- surgery between February 1994 and mid-teens. surements may be a useful, noninva- August 2015 were initially included J Glaucoma 2018;27:2:101-107. sive tool for dynamically evaluating in the study. However, 60 eyes (30.6 Romero P, Hirunpatravong P, Alizadeh R, et al. ICP. percent) were excluded due to having JAMA Ophthalmol 2018;Feb. 1 undergone combined trabeculectomy Outcomes of Cataract Surgery [Epub ahead of print]. with MMC and phacoemulsifica- In Epiretinal Membrane Cases Wang LJ, Chen LM, Chen Y, et al. tion surgery; having less than three months of follow-up; or having previ- A team of researchers from differ- Trabeculectomy with MMC in ously undergone surgery in which the ent countries explored the outcomes Angle-closure Patients conjunctiva was manipulated in some of cataract surgery performed in pa- way. tients with primary epiretinal mem- Researchers from the University of The qualiﬁ ed success rates of the branes. California-Los Angeles’ Jules Stein surgery appear in Table 1. In a retrospective clinical database Eye Institute say that, because there The study also identiﬁ ed risk factors study, the investigators collected data had never been a large study of tra- for failure of the procedure. The re- from July 2003 to March 2015 from beculectomy with the use of adjunc- searchers say that eyes that had their eight centers in the United Kingdom. tive mitomycin-C in patients suffering crystalline lenses before their trab- They drew cataract surgery data from from primary angle-closure glauco- eculectomy procedure had a higher 217,557 eyes from the electronic ma, they undertook a study looking rate of failure for all criteria (hazard medical record of the UK Nation- at the long-term tonometric results in ratio of 1.9 for criterion A; HR of 2.9 al Health Service. After excluding these cases. for criterion B; HR of 3.6 for criterion 57,561 eyes that had combined sur- In a retrospective cohort study, the C). A family history of glaucoma was gery, prior vitrectomy, co-pathology investigators used three criteria to associated with a higher rate of failure and/or complications, the researchers judge the success of the procedure, with criterion A (HR: 2.8). Eyes with analyzed 812 eyes with primary ERM with or without adjunctive drugs: in- no previous laser peripheral iridoto- and 159,184 reference eyes. In the traocular pressure ≤18 mmHg and my had a higher risk of failure when study, the primary outcome measures IOP reduction of 20 percent (criterion criteria B and C were used to judge were visual acuity, the incidence of A); IOP ≤15 mmHg and IOP reduc- success (HR for both: 2.5). Worse cystoid macular edema and the need tion of 25 percent (criterion B); and baseline intraocular pressure was a for ERM surgery. IOP ≤12 mmHg and IOP reduction of risk factor for failure with criterion C Epiretinal membrane eyes assessed 30 percent (criterion C). In total, the (HR: 1.1). at four to 12 weeks postoperatively researchers included 136 eyes (102 Ultimately, the researchers say that gained 0.27 (0.32) logMAR (approxi- patients) with PACG who underwent trabeculectomy combined with MMC mately three Snellen lines), with 200 trabeculectomy with MMC. A total effectively reduces IOP in PACG, of 448 (44.6 percent) improving by

58 | Review of Ophthalmology | March 2018

0056_rp0318_rr.indd56_rp0318_rr.indd 5858 22/26/18/26/18 11:2011:20 AMAM 0.30 logMAR or more (≥3 lines) and Replacing a Failed Ahmed hypotensive agents, from a mean of 32 of 448 (7.1 percent) worsening by Valve with a Baerveldt 4.33 to 2.22 (p=0.02). Visual acuity 0.30 logMAR or more. The reference didn’t show a signifi cant deterioration eyes’ vision gained a mean of 0.44 Investigators analyzed outcomes in (p=0.07). In the fi nal offi ce visit, fi ve ±0.26 logMAR (approximately four eyes that underwent surgery to replace of nine individuals met the success Snellen lines), with 48,583 of 77,408 a failed Ahmed valve with a Baerveldt criteria and two individuals were qual- (62.8 percent) improving by 0.30 log- glaucoma implant in the same quad- ifi ed successes. Two cases failed after MAR or more and 2,125 of 77,408 rant, as part of a retrospective case 69 and 125 months of follow-up, re- (2.7 percent) worsening by 0.30 log- series of nine glaucoma patients. spectively. The cumulative probabil- MAR or more. Although all eyes with The parameters analyzed in the ity of success after six months was 76 preoperative VA of 20/40 or less im- study included age, glaucoma type, percent, and this rate remained stable proved, only reference eyes with pre- prior surgery, complications, intraoc- until the sixth year. One individual operative visual acuity of better than ular pressure, visual acuity, and num- developed bullous keratopathy. Two 20/40 showed improvement. ber of glaucoma medications before individuals had early postoperative Cystoid macular edema developed and after the surgery. Surgical success pressure spikes: The fi rst individual in 57 of 663 eyes that had epireti- was defi ned as an IOP measurement was treated by trabeculectomy and nal membranes (8.6 percent) (95% below 21 mmHg or a 20 percent IOP the second underwent a vitrectomy. CI, 6.69-10.98) and 1,731 of 125,435 reduction, with or without a hypoten- Investigators suggested that replac- reference eyes (1.38 percent) (95% sive agent. ing a failed Ahmed glaucoma valve CI, 1.32-1.45) (p< 0.001). Epiretinal The mean follow-up duration in with a new Baerveldt glaucoma im- membrane surgery was performed in the study was 47 months. After sur- plant in the same quadrant could be 43 of 663 of the eyes with membranes gery, at the time of final follow-up, a reasonable choice to control refrac- (6.5 percent). the mean IOP decreased from 29.9 tory glaucoma. JAMA Ophthalmol 2018;136:2:148- to 16.7 mmHg (36 percent of mean J Glaucoma 2018; Feb.16. [Epub 154. IOP reduction, p=0.008). Investiga- ahead of print]. Romero P, Hirunpatravong P, Alizadeh R, et al. tors found a signifi cant reduction of Zuo W, Lesk MR.

TimecToc Hire?

More Eye Care Professionals Will See Your Job Listing On Local Eye Site Than Anywhere Else.

localeyesite.com

056_rp0318_rr.indd 59 2/26/18 11:21 AM REVIEW Classiﬁ eds

Practice For Sale Career Opportunities

Targeting Ophthalmologists? CLASSIFIED ADVERTISING WORKS

OPHTHALMOLOGISTS Danbury, CT KƉŚƚŚĂůŵŽůŽŐŝƐƚƐƚŽƐŚĂƌĞŽĸĐĞ with long standing Ophthalmolo- gist in Danbury, CT. High quality equipment. $2,250 per month or ĂĚũŽŝŶŝŶŐŽĸĐĞǁŝƚŚŽƵƚ equipment- $1,750 per month.

203-545-3539 or FIND MORE PRACTICES FOR SALE ON email [email protected] opti classiﬁeds

FOR CLASSIFIED ADVERTISING CONTACT US TODAY: CONTACT US TODAYƚŽůŝƐƚǇŽƵƌƉƌĂĐƟĐĞ͗

Toll free: 888-498-1460 888-498-1460 E-mail: [email protected] ŽƉƟĐůĂƐƐŝĮĞĚƐΛŬĞƌŚŐƌŽƵƉ͘ĐŽŵ

ǁǁǁ͘ŽƉƟĐůĂƐƐŝĮĞĚƐ͘ĐŽŵ

60 | Review of Ophthalmology | March 2018

ROPH0318.indd 60 2/25/18 11:04 PM (Continued from page 30) eventually become readily available, they’ll remain off-label for endophthal- Dr. Silverstein has never been com- decrease the risk of endophthalmitis mitis prophylaxis, as there is no eco- pensated and has no other fi nancial and postoperative infection—is the nomic incentive for manufacturers to interest in any of the products dis- Betadine prep around the eye and repurpose an existing generic drug, cussed in this article, although he diluted drops in the eye for a few since they would be barred from minutes before surgery. It’s the only having exclusive rights. “Without a has participated in research on anti- thing we know works,” adds Dr. Sil- foreseeable economic return, there biotics, topical NSAIDs and steroids verstein. has not been any industry incentive throughout his career. “Nothing has proven more effi ca- to push for FDA approval, which is a Dr. Arshinoff is a consultant for Al- cious in preventing endophthalmitis great detriment to our patients,” says con, but not with regard to Vigamox. than the use of topical povidone- Dr. Zavodni. “The ASCRS Research He reports no other fi nancial inter- iodine,” states Dr. Zavodni. “My Council has thankfully begun devel- ests in medications mentioned in this patients receive a drop of Betadine opment of a prospective research tri- directly into the conjunctival sac dur- al, which will hopefully lead to FDA article. ing preop and in the operating room. approval and, ultimately, a product Dr. Zavodni reports no relevant This is, of course, in addition to the that all surgeons can feel confi dent fi nancial interests. prepping of periocular skin and lash- using.” es with Betadine before placing the Dr. Silverstein acknowledges that 1. ESCRS Endophthalmitis Study Group. Prophylaxis of postoperative endophthalmitis following cataract surgery: surgical drapes.” the evidence for intraocular injec- Results of the ESCRS multicenter study and identifi cation of risk As for an FDA-approved, single- tions to prevent endophthalmitis is factors. J Cataract Refract Surg 2007;22:978-88. use injectable intracameral antibi- growing, but he awaits tightly con- 2. Herrinton LJ, Shorstein NH, Paschal JF, et al. Comparative otic preparation indicated for en- trolled, prospective multicenter stud- effectiveness of antibiotic prophylaxis in cataract surgery. Ophthalmology 2016;123:287-94 dophthalmitis prophylaxis, the ies to elevate the certainty of that 3. Haripriya A, Chang DF, Ravindran RD. Endophthalmitis prospects are not so cut and dried. “I evidence.“There are a couple of very reduction with intracameral moxifl oxacin prophylaxis: Analysis don’t really see any company invest- bold and aggressive American studies of 600,000 surgeries. Ophthalmol 2017;124:6:768-75. ing the money needed to have the being proposed now to try to answer 4. Arshinoff SA, Modabber M. Dose and administration of intracameral moxifl oxacin for prophylaxis of postoperative FDA approve it. It’s just not reason- the question defi nitively: Does an in- endophthalmitis. J Cataract Refract Surg 2016;42:1730-41. able from an economic standpoint,” tracameral medication such as moxi- 5. Libre PE, Matthews S. Endophthalmitis prophylaxis by says Dr. Arshinoff. “We have to look floxacin, cefuroxime, etc., decrease intracameral antibiotics: In vitro model comparing vancomycin, at reality, and if I were running the the incidence of endophthalmitis? cefuroxime, and moxifl oxacin. J Cataract Refract Surg 2017; 43:833-38. company, I would not be eager to Of course, the rate-limiting factor to 6. Knape RM, Sayyad FE, Davis JL. Moxifl oxacin and bilateral go to all the expense when my drug these kinds of studies has always been acute iris transillumination. J Ophthahlmic Infl amm Infect will rapidly be genericized and the a large enough n to declare statistical 2013;14;3:1:10. chance of recouping the investment signifi cance. Thankfully, because the 7. Ullman MA, Midgley KJ, Kim J, Ullman S. Anaphylactic is miniscule.” incidence of endophthalmitis is so reaction secondary to topical preoperative moxifl oxacin. J Cataract Refract Surg 2016;42:1830-37. He cites one potential off-label low, you’d have to study many thou- 8. Simaroj P, Sinsawad P. Effects of intracameral triamcinolone alternative, though. “Moxifloxacin sands of patients in order to make and gentamicin injections following cataract surgery. J Med solutions for intracameral injection such a claim,” he says. Assoc Thailand 2011;94:7:819-25. that come in pre-loaded syringes are The daunting expenditures of 9. Cunha PA, Shinzato FA, Tecchio GT, et al. Effi cacy and tolerability of a gatifl oxacin/prednisolone acetate fi xed already available from a company time and money, as well as the vast combination for topical prophylaxis and control of infl ammation in India (Entod Pharma). Unfortu- statistical sample that a probative in phacoemulsifi cation: A 20-day double-blind comparison to its nately, they are not sold in North study would demand, mean that for individual components. Clinics 2013;68:6:834-9. America. I think the company that the foreseeable future, cataract sur- 10. Fisher BL, Potvin R. Transzonular vitreous injection vs a single drop compounded topical pharmaceutical regimen after makes it is opening a branch in the geons will have to continue follow- cataract surgery. Clin Ophth 2016;10:1297-1303. U.K., which may help to get these ing the succinct advice of a recent 11. Speaker M G, Menikoff J A. Prophylaxis of endophthalmitis things available in North America. Cochrane Review when ponder- with topical povidone-iodine. Ophthalmology 1991;98:1769– Hopefully, they will make it in the ing antibiotics for endophthalmitis 1775. 12. Gower EW, Lindsley K, Tulenko SE, Nanji AA, Leyngold I, dilute formulation (to inject 0.4 mL prevention: “Practitioners should McDonnell PJ. Perioperative antibiotics for prevention of acute of 150 µg per 0.1 mL) prepackaged rely on current evidence to make endophthalmitis after cataract surgery. Cochrane Database of for single use,” he says. informed decisions regarding pro- Systematic Reviews 2017, Issue 2. Art. No.: CD006364. DOI: Even if pre-filled moxi syringes phylaxis choices.”12 10.1002/14651858.CD006364.pub3.

March 2018 | reviewofophthalmology.com | 61

0026_rp0318_f1.indd26_rp0318_f1.indd 6161 22/26/18/26/18 2:062:06 PMPM EVERY MONDAY E-NEWS YOU CAN USE

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

You’re a busy practitioner and not surprisingly, your e-mail inbox is often full. Fortunately, when you scan through the sender list, determining which messages to delete and which to save or read, you can feel conﬁ dent knowing that e-blasts from Review of Ophthalmology, a Jobson Medical Information LLC publication, contain the most current and comprehensive information available in the ﬁ eld to keep you on the cutting edge.

Review of Ophthalmology’s online stable of products includes editorial newsletters and promotional information about new products, treatments and surgical techniques, as well as alerts on continuing education courses for ophthalmologists.

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

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

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

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

2015_RPonline_house.indd 1 12/10/14 2:38 PM 063_rp0318_wills.indd 63 What isyourdiagnosis? furtherworkupwouldyoupursue?Thediagnosis appearsonp. 64. 0.5 mgasneeded. armodafi sants andanxiolytics,includingbupropion100mg,risperidone2duloxetine30 an allergytosulfa.Sheneversmoked,usedillicitdrugsordrankalcohol. fl lower quadrantabdominalpainofunclearetiology, anddiverticulosis.Ofnote,noin- Medical History joint painorshortnessofbreath,thoughshedidhavepersistentleftlowerquadrantpain. worsening headaches,lightsensitivityandrednessinherlefteye.Reviewofsystemswasnegativefornewrashes,onset colonoscopy thenextweek,fi ndings ofwhichwerebenign.Overthecoursenextfewweeks,shehadprogressively lower quadrantabdominalpain,whichhadtobeaborteddueincompletebowelpreparation.Sheunderwentasecond sion. Shereportedanabruptonsetofthespotsinherlefteyeuponwakingdayafterincompletecolonoscopyfor Presentation Rebecca RussSoares, MD, MPH, andJamesP. Dunn, MD EyeHospital. Wills A womanwithunilateralfl oaters afteracolonoscopyisevaluatedat rhage. However, therewasfocalchorioretinitisintheposteriorpole. sheathing orvasculitis.Themacularexamshowednoedema, thickeningorhemor- of pearls”appearance(Figure2).Theopticdiscwasnormal.vesselswerewithout back ofthelefteyewith1+vitreouscells,andfl uffy white-yellowlesionswitha“string lens (Figure1).Intraocularpressurewas14mmHgODand7OS. vealed brokenposteriorsynechiaewitharingofpigmenton theanteriorcapsuleof keratic precipitates.Theanteriorchamberhad2+cellwithout hypopyon.Theirisre- haze with1to2+Descemet’s membranefoldsanddiffuseinferiornon-granulomatous were normal. visual fi elds werefullODbutgloballydiminishedOS.Theperiorbitaandadnexae had fullextraocularmovements.Therewasnorelativeafferentpupillarydefect.Her demonstrated abestcorrectedvisualacuityof20/40ODandCFat1footOS.She Examination ammatory boweldisease,cancerorinfectionwasfoundonher colonoscopy. Shehad Her medicationlistincludedlevothyroxine75mcgdailyandmultipleantidepres- Past medicalhistorywassignifi cant fordepression,hypothyroidism,chronicleft A 63-year-old Caucasianfemalewithoutpastocularhistorypresentedwithtwotothreeweeksofblackfloaters inhervi- Fundoscopic examination was normal in the right eye. There was a hazy view to the Fundoscopic examinationwasnormalintherighteye.There wasahazyviewtothe Anterior slitlampexaminationoftherighteyewasnormal. The lefteyehadcorneal The patient’s vitalsignswerestableandwithinnormallimits.Ocularexamination REVIEW nil 150mgandtrazodone50mg,alldoseddailyornightly, andclonazepam Wills Eye Wills Eye Resident CaseSeries Edited by Thomas Jenkins, MD March 2018 chorioretinitis. pearls” vitritisandposteriorpolefocal the lefteye demonstrating “string of Figure 2.Colorfundusphotograph of on theanteriorcapsule. synechiae leaving aringofpigment demonstrating broken posterior photograph ofthelefteye Figure 1. Anterior segment | reviewofophthalmology.com |

63 2/26/18 2:00 PM 063_rp0318_wills.indd 64 fortunately, theculturestakenhad every twohoursinthelefteye.Un- treated withprednisoloneacetate1% twice daily. Her anterior uveitiswas cally startedonvoriconazole200mg 1,000 mcg/0.1ml.Shewasempiri- tap andinjectionwithvoriconazole our patientunderwentintravitreal absence ofeyetraumaorsurgery. foreign bodywereruledoutinthe lens materialandretainedintraocular ophthalmia, postoperativeretained also onourdifferential.Sympathetic dromes likelargecelllymphomawere and Behçetdisease.Masqueradesyn- Vogt-Koyanagi-Harada syndrome, tory conditionssuchassarcoidosis, considerations includedinflamma- berculosis) ortoxoplasmosis.Other bacterial (includingsyphilisandtu- were thoughttobemorelikelythan ologies likeCandidaorAspergillus colonic instrumentation.Fungaleti- likely inlightofthehistoryrecent endophthalmitis thoughttobemore endoph thalmitis, withendogenous cluded infectiousetiologiessuchas Workup, DiagnosisandTreatment 64 with indwellingcatheters,and intravenousdrugusers. instrumentation oftheGItract orabdominalsurgery, those at riskfordevelopingthisinfection,asarethoseundergoing renal failure,malignancy, organtransplantationorHIVare a relativeimmunosuppressionfromdiabetes,liverdisease, cated areCandidaandAspergillusspecies.Patientswith visual outcomes.Thepredominantmicroorganismsimpli- and anteriorsegmentinvolvement,canleadtodevastating togenous seedingofthechoroidwithsubsequentposterior Discussion AB REVIEW As in our case, which was ultimately culture-negative, the As inourcase,whichwasultimately culture-negative,the For furtherdiagnosticclarity, Our differentialdiagnosisin- Fungal endogenousendophthalmitis,causedbyhema- | ReviewofOphthalmology Resident CaseSeries | March 2018

of cystoidmacularedemaintheleft raphy showedintervaldevelopment tomography andfl riorated to20/200.Opticalcoherence her visioninthelefteyehaddete- acetate. However, athernextvisit, quently taperedoffprednisolone mation vitreous andchorioretinalinflam- showed resolvinganteriorchamber, antifungal therapy. Herexamination from countfi visual acuityinthelefteyeimproved no yield. initiation ofantifungaltherapy. antifungal therapy. (B) Wide-field colorfundusphotoofthelefteye three monthsafter Figure 3.(A)Colorfundusphotograph ofthelefteye two monthsafterinitiationof Over thenextthreemonths,her (Figure 3).Shewassubse- 1 ngers to20/80whileon uorescein angiog- uorescein vitrectomy. as isanteriorchamberparacentesis,comparedtodiagnostic ment. Fungalcultureviaintravitrealtapisoftenlow-yield, yellow-white chorioretinitis,andresponsetoempirictreat- nation withclassicfi ndings like“stringofpearls”vitritisand the abruptonsetfollowingcomplicatedcolonoscopy, exami- cornerstone ofdiagnosisremainsclinicalsuspicion,given cin B with or without pars plana vitrectomy was considered cin Bwithorwithoutparsplana vitrectomywasconsidered to thedevelopmentofvoriconazole, intravitrealamphoteri- empiric treatmentwithantifungals shouldbeinitiated.Prior Once fungal endogenous endophthalmitis is suspected, Once fungalendogenousendophthalmitisissuspected, (A) andafter(B)sub-Tenon’s triamcinoloneacetonide. Figure 4.Opticalcoherence tomography ofthelefteye before 2

epiretinal membranepeel. quiring aparsplanavitrectomyand epiretinal membranepersisted,re- fortunately, hermacularedemaand endogenous endophthalmitis.Un- was consistentwithpresumedfungal was discontinued,andherdiagnosis of herpanuveitis,voriconazole zumab 1.25mg.Givenfullresolution next treatedwithintravitrealbevaci- CME persisted,forwhichshewas sion improvedto20/70,thoughher acetonide. Uponfollow-up,hervi- jection ofsub-Tenon’s triamcinolone eye (Figure 4).Sheunderwentin- 2/26/18 2:01 PM Advertising

REVIEW Index

standard-of-care. However, systemic ies evaluating the use of anti-VEGF Akorn Pharmaceuticals 31 voriconazole, introduced in 2002, has agents such as bevacizumab for the Phone (800) 932-5676 www.akorn.com excellent bioavailability and less retinal treatment of uveitic macular edema. toxicity. Thus, systemic treatment with Anti-VEGF agents may prove to be Bausch + Lomb 11, 12 or without intravitreal voriconazole is a successful and safer alternative for Phone (800) 323-0000 more frequently used.3 While no ran- treatment of infectious and non-infec- Fax (813) 975-7762 domized controlled trial has been per- tious uveitic macular edema for those formed regarding the effi cacy of pars at risk of increased intraocular pres- ianTECH 7 plana vitrectomy in fungal endogenous sure and with steroid refractory macu- [email protected] endophthalmitis, common indications lar edema.12-15 Randomized, controlled www.iantechmed.com for vitrectomy include diagnostic vit- trials are underway examining the use Imprimis Pharmaceuticals, Inc. 17 rectomy, non-clearing inflammatory of different approaches, including in- Phone (858) 704-4040 vitreous debris, uncontrolled infection travitreal ranibizumab, periocular ste- Fax (858) 345-1745 despite medical management, and re- roid injections, intravitreal methotrex- www.imprimispharma.com lease of vitreoretinal traction to treat ate and intravitreal steroid injections retinal detachments and other struc- and implants.16-18 Johnson & Johnson Vision tural sequelae.1,3 Some recent case se- (formerly AMO) 15 1. Lingappan A, Wykoff CC, Albini TA, et al. Endogenous fungal en- www.vision.abbott ries suggest improved outcomes with dophthalmitis: Causative organisms, management strategies, and immediate total vitrectomy.4,5 visual acuity outcomes. Am J Ophthalmol 2012;153:1:162-6.e1. Another sequela seen in our patient 2. Liu K, Fang F, Li H. Reliability of vitreous histological detection of Keeler Instruments 25 pathogenic fungi in the diagnosis of fungal endophthalmitis. Eye Phone (800) 523-5620 was the development of epiretinal (Lond) 2015;29:3:424-7. 6 3. Chee YE, Eliott D. The role of vitrectomy in the management of Fax (610) 353-7814 membrane. Though literature sur- fungal endophthalmitis. Semin Ophthalmol 2017;32:1:29-35. rounding the specific treatment of 4. Behera UC, Budhwani M, Das T, et al. Role of early vitrectomy in the treatment of fungal endophthalmitis. Retina 2017; May 23. Lacrimedics, Inc 51 epiretinal membrane after fungal en- [Epub ahead of print] Phone (800) 367-8327 dophthalmitis is sparse, small series 5. Birnbaum FA, Gupta G. The role of early vitrectomy in the treat- Fax (253) 964-2699 ment of fungal endogenous endophthalmitis. Retin Cases Brief of patients with epiretinal membrane- Rep 2016;10:3:232-5. [email protected] 6. Smiddy WE. Treatment outcomes of endogenous fungal endo- www.lacrimedics.com induced tractional retinal detachments phthalmitis. Curr Opin Ophthalmol 1998;9:3:66-70. achieved good structural outcomes 7. Naoi N, Sawada A. Effect of vitrectomy on epiretinal membranes after pars plana vitrecomy and mem- after endogenous fungal endophthalmitis. Jpn J Ophthalmol Regeneron Pharmaceuticals, Inc. 35 1996;40:3:434-8. Phone (914) 847-7000 brane peeling.7,8 8. McDonald HR, De Bustros S, Sipperley JO. Vitrectomy for epiretinal membrane with Candida chorioretinitis. Ophthalmology www.regeneron.com The largest contributor to our pa- 1990;97:4:466-9. tient’s poor visual outcome was cystoid 9. Karim R, Sykakis E, Lightman S, Fraser-Bell S. Interventions for the treatment of uveitic macular edema: A systematic review and Reichert Technologies 43 macular edema. Periocular, intravit- meta-analysis. Clin Ophthalmol 2013;7:1109-44. Phone (888) 849-8955 real, implanted and systemic steroids 10. Majji AB, Jalali S, Das T, Gopinathan U. Role of intravitreal Fax (716) 686-4545 dexamethasone in exogenous fungal endophthalmitis. Eye (Lond) have been shown to be effective in the 1999;13(Pt 5):660-5. www.reichert.com control of uveitic macular edema,9 but 11. Fonollosa A, Llorenc V, Artaraz J, et al. Safety and effi cacy of intravitreal dexamethasone implants in the management of macular S4OPTIK 19, 21 must be used with caution in patients edema secondary to infectious uveitis. Retina 2016;36:9:1778-85. with infectious uveitis and fungal en- 12. Al-Dhibi H, Hamade IH, Al-Halafi A, et al. The effects of intravit- Phone (888) 224-6012 real bevacizumab in infectious and noninfectious uveitic macular dophthalmitis. A case series from L. V. edema. J Ophthalmol 2014;2014:729465. Shire Ophthalmics 67, 68 Prasad Eye Institute in India showed 13. Bae JH, Lee CS, Lee SC. Effi cacy and safety of intravitreal bevacizumab compared with intravitreal and posterior sub-Tenon www.shire.com improvement in infl ammation in pa- triamcinolone acetonide for treatment of uveitic cystoid macular edema. Retina 2011;31:1:111-8. tients with fungal endophthalmitis 14. Cervantes-Castaneda RA, Giuliari GP, Gallagher MJ, et al. Intra- Sun Ophthalmics 2-3, 4 concomitantly given antifungals and vitreal bevacizumab in refractory uveitic macular edema: One-year SunIsOnTheRise.com follow-up. Eur J Ophthalmol 2009;19:4:622-9. steroids, without clear evidence of re- 15. Cordero Coma M, Sobrin L, Onal S, et al. Intravitreal bevaci- activation of the infection.10 Steroids zumab for treatment of uveitic macular edema. Ophthalmology Topcon Medical Systems 8-9 2007;114:8:1574-9.e1. Phone (800) 223-1130 may be benefi cial in infectious uveitic 16. The LIMO study: Lucentis for treatment of uveitic patients with macular edema as well—in a series of refractory cystoid macular oedema. ClinicalTrialsgov Identifi er: Fax (201) 599-5250 NCT01564108: Moorfi elds Eye Hospital NHS Foundation Trust. eight patients, intravitreal dexametha- 17. PeriOcular and INTravitreal Corticosteroids for Uveitic Macular sone implants showed improvement Edema Trial (POINT). ClinicalTrials.gov Identifi er: NCT02374060: This advertiser index is published as a JHSPH Center for Clinical Trials and National Eye Institute (NEI). convenience and not as part of the advertising in visual acuity and resolution of ede- 18. Macular Edema Ranibizumab v. Intravitreal Anti-infl ammatory contract. Every care will be taken to index ma without reactivation of infection.11 Therapy Trial (MERIT). ClinicalTrials.gov Identifi er: NCT02623426: correctly. No allowance will be made for errors JHSPH Center for Clinical Trials and National Eye Institute (NEI). due to spelling, incorrect page number, or failure There have only been a few small stud- to insert.

March 2018 | reviewofophthalmology.com | 65

0063_rp0318_wills.indd63_rp0318_wills.indd 6655 22/26/18/26/18 5:295:29 PMPM ENRICH YOUR PRACTICE

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

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

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

www.reviewofophthalmology.com

Jobson Medical Information LLC The Review Group

2017_rp_tsrad.indd 90 12/21/17 11:37 AM VGUVGFOIMIFC[ HQNFVJGJWOCPRNCUOCGZRQUWTGCV the recommended human ophthalmic dose [RHOD], based on VJGCTGCWPFGTVJGEWTXG=#7%?NGXGN 5KPEGJWOCPU[UVGOKE GZRQUWTGVQNKƂVGITCUVHQNNQYKPIQEWNCTCFOKPKUVTCVKQPQH:KKFTC Rx Only CVVJG4*1&KUNQYVJGCRRNKECDKNKV[QHCPKOCNƂPFKPIUVQVJG risk of Xiidra use in humans during pregnancy is unclear. Animal Data BRIEF SUMMARY: .KƂVGITCUVCFOKPKUVGTGFFCKN[D[KPVTCXGPQWU +8 KPLGEVKQP Consult the Full Prescribing Information for complete product VQTCVUHTQORTGOCVKPIVJTQWIJIGUVCVKQPFC[ECWUGF information. an increase in mean preimplantation loss and an increased INDICATIONS AND USAGE KPEKFGPEGQHUGXGTCNOKPQTUMGNGVCNCPQOCNKGUCVOIMI Xiidra® NKƂVGITCUVQRJVJCNOKEUQNWVKQP KUKPFKECVGFHQTVJG FC[TGRTGUGPVKPIHQNFVJGJWOCPRNCUOCGZRQUWTGCV VTGCVOGPVQHVJGUKIPUCPFU[ORVQOUQHFT[G[GFKUGCUG &'& the RHOD of Xiidra, based on AUC. No teratogenicity was QDUGTXGFKPVJGTCVCVOIMIFC[ HQNFVJGJWOCP DOSAGE AND ADMINISTRATION RNCUOCGZRQUWTGCVVJG4*1&DCUGFQP#7% +PVJGTCDDKV Instill one drop of Xiidra twice daily (approximately 12 hours an increased incidence of omphalocele was observed at the CRCTV KPVQGCEJG[GWUKPICUKPINGWUGEQPVCKPGT&KUECTF NQYGUVFQUGVGUVGFOIMIFC[ HQNFVJGJWOCPRNCUOC VJGUKPINGWUGEQPVCKPGTKOOGFKCVGN[CHVGTWUKPIKPGCEJG[G GZRQUWTGCVVJG4*1&DCUGFQP#7% YJGPCFOKPKUVGTGFD[ Contact lenses should be removed prior to the administration +8KPLGEVKQPFCKN[HTQOIGUVCVKQPFC[UVJTQWIJ#HGVCN0Q QH:KKFTCCPFOC[DGTGKPUGTVGFOKPWVGUHQNNQYKPI 1DUGTXGF#FXGTUG'HHGEV.GXGN 01#'. YCUPQVKFGPVKƂGFKP administration. the rabbit. CONTRAINDICATIONS Lactation 6JGTGCTGPQFCVCQPVJGRTGUGPEGQHNKƂVGITCUVKPJWOCP Xiidra is contraindicated in patients with known hypersensitivity VQNKƂVGITCUVQTVQCP[QHVJGQVJGTKPITGFKGPVUKPVJG milk, the effects on the breastfed infant, or the effects on milk RTQFWEVKQP*QYGXGTU[UVGOKEGZRQUWTGVQNKƂVGITCUVHTQO formulation. ocular administration is low. The developmental and health ADVERSE REACTIONS DGPGƂVUQHDTGCUVHGGFKPIUJQWNFDGEQPUKFGTGFCNQPIYKVJ Clinical Trials Experience the mother’s clinical need for Xiidra and any potential adverse Because clinical studies are conducted under widely varying effects on the breastfed child from Xiidra. conditions, adverse reaction rates observed in clinical studies Pediatric Use of a drug cannot be directly compared to rates in the clinical 5CHGV[CPFGHƂECE[KPRGFKCVTKERCVKGPVUDGNQYVJGCIGQH VTKCNUQHCPQVJGTFTWICPFOC[PQVTGƃGEVVJGTCVGUQDUGTXGF years have not been established. KPRTCEVKEG+PƂXGENKPKECNUVWFKGUQHFT[G[GFKUGCUGEQPFWEVGF YKVJNKƂVGITCUVQRJVJCNOKEUQNWVKQPRCVKGPVUTGEGKXGFCV Geriatric Use NGCUVFQUGQHNKƂVGITCUV QHYJKEJTGEGKXGFNKƂVGITCUV No overall differences in safety or effectiveness have been 6JGOCLQTKV[QHRCVKGPVU JCFŰOQPVJUQHVTGCVOGPV observed between elderly and younger adult patients. GZRQUWTGRCVKGPVUYGTGGZRQUGFVQNKƂVGITCUVHQT NONCLINICAL TOXICOLOGY approximately 12 months. The majority of the treated patients Carcinogenesis, Mutagenesis, Impairment of Fertility YGTGHGOCNG 6JGOQUVEQOOQPCFXGTUGTGCEVKQPU Carcinogenesis: Animal studies have not been conducted TGRQTVGFKPQHRCVKGPVUYGTGKPUVKNNCVKQPUKVGKTTKVCVKQP VQFGVGTOKPGVJGECTEKPQIGPKERQVGPVKCNQHNKƂVGITCUV dysgeusia and reduced visual acuity. Other adverse reactions Mutagenesis: .KƂVGITCUVYCUPQVOWVCIGPKEKPVJGin vitro TGRQTVGFKPVQQHVJGRCVKGPVUYGTGDNWTTGFXKUKQP #OGUCUUC[.KƂVGITCUVYCUPQVENCUVQIGPKEKPVJGin vivo conjunctival hyperemia, eye irritation, headache, increased mouse micronucleus assay. In an in vitro chromosomal lacrimation, eye discharge, eye discomfort, eye pruritus and aberration assay using mammalian cells (Chinese sinusitis. JCOUVGTQXCT[EGNNU NKƂVGITCUVYCURQUKVKXGCVVJGJKIJGUV Postmarketing Experience concentration tested, without metabolic activation. 6JGHQNNQYKPICFXGTUGTGCEVKQPUJCXGDGGPKFGPVKƂGFFWTKPI Impairment of fertility: .KƂVGITCUVCFOKPKUVGTGFCV postapproval use of Xiidra. Because these reactions are KPVTCXGPQWU +8 FQUGUQHWRVQOIMIFC[ reported voluntarily from a population of uncertain size, it is not HQNFVJGJWOCPRNCUOCGZRQUWTGCVVJG always possible to reliably estimate their frequency or establish TGEQOOGPFGFJWOCPQRJVJCNOKEFQUG 4*1& QH a causal relationship to drug exposure. NKƂVGITCUVQRJVJCNOKEUQNWVKQP JCFPQGHHGEVQP Rare cases of hypersensitivity, including anaphylactic reaction, fertility and reproductive performance in male and bronchospasm, respiratory distress, pharyngeal edema, swollen female treated rats. tongue, and urticaria have been reported. Eye swelling and rash have been reported. USE IN SPECIFIC POPULATIONS Pregnancy /CPWHCEVWTGFHQT5JKTG75+PE5JKTG9C[.GZKPIVQP/# There are no available data on Xiidra use in pregnant women to (QTOQTGKPHQTOCVKQPIQVQYYY:KKFTCEQOQTECNN KPHQTOCP[FTWICUUQEKCVGFTKUMU+PVTCXGPQWU +8 CFOKPKUVTCVKQP Marks designated ®CPFvCTGQYPGFD[5JKTGQTCPCHƂNKCVGFEQORCP[ QHNKƂVGITCUVVQRTGIPCPVTCVUHTQORTGOCVKPIVJTQWIJ 5JKTG75+PE5*+4'CPFVJG5JKTG.QIQCTGVTCFGOCTMUQT IGUVCVKQPFC[FKFPQVRTQFWEGVGTCVQIGPKEKV[CVENKPKECNN[ TGIKUVGTGFVTCFGOCTMUQH5JKTG2JCTOCEGWVKECN*QNFKPIU+TGNCPF relevant systemic exposures. Intravenous administration of .KOKVGFQTKVUCHƂNKCVGU NKƂVGITCUVVQRTGIPCPVTCDDKVUFWTKPIQTICPQIGPGUKURTQFWEGF Patented: please see JVVRUYYYUJKTGEQONGICNPQVKEGRTQFWEVRCVGPVU an increased incidence of omphalocele at the lowest dose .CUV/QFKƂGF5

RRP0318_ShireP0318_Shire PPI.inddI.indd 1 22/15/18/15/18 3:533:53 PMPM SIGN & SYMPTOM IIMPROVEMENT The only prescription eye drop FDA-approved to treat both the signs and symptoms of Dry Eye Disease

Indication :KKFTC® NKƂVGITCUVQRJVJCNOKEUQNWVKQP KUKPFKECVGFHQTVJGVTGCVOGPV Xiidra improved patient-reported QHUKIPUCPFU[ORVQOUQHFT[G[GFKUGCUG &'& symptoms of eye dryness and improved Important Safety Information signs of inferior corneal staining. :KKFTCKUEQPVTCKPFKECVGFKPRCVKGPVUYKVJMPQYPJ[RGTUGPUKVKXKV[VQ So help patients get to know Xiidra. NKƂVGITCUVQTVQCP[QHVJGQVJGTKPITGFKGPVU +PENKPKECNVTKCNUVJGOQUVEQOOQPCFXGTUGTGCEVKQPUTGRQTVGFKP Check it out at Xiidra-ECP.com QHRCVKGPVUYGTGKPUVKNNCVKQPUKVGKTTKVCVKQPF[UIGWUKCCPFTGFWEGFXKUWCN Four randomized, double-masked, 12-week trials CEWKV[1VJGTCFXGTUGTGCEVKQPUTGRQTVGFKPVQQHVJGRCVKGPVUYGTG GXCNWCVGFVJGGHƂECE[CPFUCHGV[QH:KKFTCXGTUWU DNWTTGFXKUKQPEQPLWPEVKXCNJ[RGTGOKCG[GKTTKVCVKQPJGCFCEJGKPETGCUGF XGJKENGCUCUUGUUGFD[KORTQXGOGPVKPVJGUKIPU NCETKOCVKQPG[GFKUEJCTIGG[GFKUEQOHQTVG[GRTWTKVWUCPFUKPWUKVKU OGCUWTGFD[+PHGTKQT%QTPGCN5VCKPKPI5EQTG CPFQTU[ORVQOU OGCUWTGFD['[G&T[PGUU5EQTG 6QCXQKFVJGRQVGPVKCNHQTG[GKPLWT[QTEQPVCOKPCVKQPQHVJGUQNWVKQP QH&T['[G&KUGCUG 0 RCVKGPVUUJQWNFPQVVQWEJVJGVKRQHVJGUKPINGWUGEQPVCKPGTVQVJGKT 6JGUCHGV[QHNKƂVGITCUVYCUGXCNWCVGFKPENKPKECN G[GQTVQCP[UWTHCEG UVWFKGURCVKGPVUTGEGKXGFCVNGCUVQPGFQUGQH NKƂVGITCUV QHYJKEJTGEGKXGF:KKFTC 6JGOQUV %QPVCEVNGPUGUUJQWNFDGTGOQXGFRTKQTVQVJGCFOKPKUVTCVKQPQH:KKFTC EQOOQPCFXGTUGTGCEVKQPU YGTGKPUVKNNCVKQP CPFOC[DGTGKPUGTVGFOKPWVGUHQNNQYKPICFOKPKUVTCVKQP UKVGKTTKVCVKQPF[UIGWUKCCPFTGFWEGFXKUWCNCEWKV[ 5CHGV[CPFGHƂECE[KPRGFKCVTKERCVKGPVUDGNQYVJGCIGQH[GCTUJCXG PQVDGGPGUVCDNKUJGF

For additional safety information, see accompanying Brief Summary of Safety Information on the adjacent page and Full Prescribing Information on Xiidra-ECP.com.

© 2018 Shire US Inc., Lexington, MA 02421. 1-800-828-2088. All rights reserved. Marks designated ® and ™ are owned by - ÀiÀ>>vw>Ìi`V«>Þ°-, >`Ì i- Ài}>ÀiÌÀ>`i>ÀÃÀÀi}ÃÌiÀi`ÌÀ>`i>ÀÃv- Ài* >À>ViÕÌV> `}ÃÀi>`Ìi`ÀÌÃ>vw>ÌiÃ°-ÎÎÇÈää£É£n

RP0318_Shire.indd 1 2/15/18 3:51 PM