Dry-Eye Diagnosis and Treatmentreview of Ophthalmology Vol

Review of Ophthalmology Vol. XXVI, No. 9 • September 2019 • Dry-eye Diagnosis and TreatmentReview of Ophthalmology Vol. XXVI, No. 9 • September • New Instruments for Vitrectomy • Epithelial Basement Membrane Dystrophy Treatment NEW APPS FOR IOL CALCULATIONS P. 12 • CMS MIPS UPDATE FOR 2020 P. 20 HOW TO SCREEN LASIK CANDIDATES P. 58 • NEW PRODUCTS P. 62 OPHTHALMIC RESEARCH UPDATE P. 65 • GLAUCOMA: INSIGHTS FROM THE PTVT STUDY P. 66

SeptemberSeptember 20192019

reviewofophthalmology.comreviewofophthalmology.com

DRY-EYE FOCUS Zero In on Dry Eye How to get to the root of the problem precisely (P. 28) and treat it effectively (P. 36).

ALSO INSIDE:

• The Latest in Retinal Surgical Instruments P. 46 • When and How to Treat EBMD P. 52

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RRP0919_Myco.inddP0919_Myco.indd 1 88/29/19/29/19 4:084:08 PMPM REVIEW NEWS Volume XXVI • No. 9 • September 2019 Medicare Proposes Another Cut In Cataract Reimbursement

Cataract surgery reimbursement may Reimbursement for cataract sur- primary care.” be cut by about 15 percent next gery has been progressively decreas- The random sample survey of year, according to the proposed ing because ophthalmologists have AAO and ASCRS members required rule changes to the 2020 Medicare gotten so good at it, says Douglas for RUC code revaluation showed physician fee schedule released in Grayson, MD, FACS, in practice a one-minute reduction in time to July by the Centers for Medicare perform 66984 and one less po- and Medicaid Services. stop visit, which Nancy McCann, Non-complicated cataract sur- ASCRS director of Governmental gery (66984) may see a larger cut Relations, says always equates to in reimbursement than complex some kind of reduction.2 ASCRS cataracts (66982). The proposed and AAO demonstrated to the Work Relative Value Unit (RVU) RUC cataract surgery’s unique in- for complex cataracts is 10.25, tensity to bring the reduction to 15 compared to the current Work percent, as opposed to 50 percent.2 RVU of 11.08, a $47 reduction. The proposed rule has a 60-day For non-complicated cataracts, the comment period. Ms. McCann proposed Work RVU is 7.35, com- says ASCRS will submit compared to the current 8.52, a $97 ments, but will support the rec- reduction.1 ommended values along with the After negotiations and efforts to Academy. E/M values are also retain reasonable reimbursement proposed to increase, a move both If the proposed rule changes go through, cataract for cataract surgery, ASCRS and surgeons may face a 15-percent cut in ASCRS and the surgical commu- 1 AAO agreed to the rate set by the reimbursement. nity oppose. Ms. McCann hopes AMA’s Relative Value Scale Update that if these increases are made Committee (RUC), which is respon- at Omni Eye Services in New York. they will be factored into cataract re- sible for describing the resources re- “Technology improved,” he says. imbursement, which may bring the quired to provide physician services. “Cataracts back in the 1990s used to reduction in 66984 to the $90 range.2 CMS takes RUC into account when be hour-long procedures, and now “The only way we’ve been able to developing RVUs. ASCRS notes that they can vary anywhere from fi ve keep up with progressive cuts over though it is a decrease, the rate is to ten minutes. So basically, they’re the years is by fi nding new sources “equitable relative to payments of paying for the time that it takes to do or new ways to maximize reimburse- other physician services of similar the surgery with some small factor ment,” explains Dr. Grayson. “At the time and intensity.”1 added in for the complexity.” end of the day, some doctors will say “We’re disappointed in the val- Part of the decrease in valuation it’s too bad and take less reimburse- ue that we got, but we’re pleased refl ects the proposed rule’s budget ment and some will try to fi gure out it didn’t go down further,” says neutrality. “If cataract surgery goes ways around it.” Michael Repka, MD, MBA, the down, those dollars get redistributed Dr. Grayson anticipates in- vice chair for clinical practice at to other services in medicine,” says creases in femto laser, multifocal the Wilmer Eye Institute and the Dr. Repka. “Oftentimes, those dol- lens and MIGS procedures such as medical director for Governmental lars end up in evaluation and man- iStent, Hydrus and Kahook gonioto- Affairs of AAO. agement services, or the dollars go to my—glaucoma procedures done in

September 2019 | reviewofophthalmology.com | 3

003_rp0919_news.indd 3 8/23/19 4:51 PM REVIEW News E DITORIAL STAFF 2020 Medicare physician fee schedule proposed rule. ASOA. Editor in Chief conjunction with cataract surgery— August 2019. https://asoa.org/news/ascrs-special-report-key- Walter C. Bethke information-about-2020-medicare-physician-fee-schedule- to make up for the defi cit. proposed-rule (610) 492-1024 “Increased volume in cataract sur- [email protected] gery is another concern, and they may audit more charts to make sure visual Senior Editor criteria are defi ned well enough and Christopher Kent (212) 274-7031 that patients truly need cataract sur- Iodine Safe [email protected] gery,” Dr. Grayson says. “Certainly, they’re going to look at MIGS more vs. Viral Senior Editor closely because that’s an expensive Sean McKinney ticket item for Medicare and for the (610) 492-1025 primary insurers, because not only Conjunctivitis [email protected] do they have to pay for the surgical Researchers recently found that procedure, they also have to pay for Associate Editor 5% povidone-iodine (PVP-I) used as the device.” Dr. Grayson notes that a one-time treatment is safe and well- Christine Leonard the iStent Inject device costs over a (610) 492-1008 tolerated by patients with adenoviral thousand dollars. [email protected] conjunctivitis.1 Dr. Grayson also says that de- A double-masked trial included creased reimbursement may cause Chief Medical Editor 56 participants randomized to a one- surgeons to reevaluate their sched- Mark H. Blecher, MD time administration of PVP-I or ules. “If you’re not that great a sur- preservative-free artifi cial tears. The Art Director geon, it might not be cost-effective team assessed visual acuity, and safe- Jared Araujo to go to the OR and do fi ve cataracts (610) 492-1032 at a decreased reimbursement. You ty using corneal fl uorescein staining, [email protected] could actually do better in the offi ce and tolerability using participant- just seeing a bunch of patients.” rated overall ocular discomfort. Senior Graphic Designer Finding ways to streamline ser- In the PVP-I group, the study au- Matt Egger vices and improve offi ce effi ciency is thors discovered that corneal staining (610) 492-1029 increased immediately post-adminis- [email protected] another way doctors might make up the reimbursement decrease, says tration but returned to baseline levels Graphic Designer Dr. Repka. “I expect that doctors will by day one. They noted no change in Ashley Schmouder diversify and add some other ser- visual acuity between baseline and (610) 492-1048 vices. Just be very careful about not day one in either group. In the povi- [email protected] charging for add-on services to try to done-iodine group, they also found recoup revenues, because those may no change in participant-rated overall International coordinator, Japan or may not be legal, depending upon discomfort immediately post-adminis- Mitz Kaminuma how they’re framed and billed to the tration or on day one, compared with [email protected] patient. baseline. “We could have done more poorly Business Offi ces In the artifi cial tear group, on the than we did, but it’s hard to spin a 11 Campus Boulevard, Suite 100 other hand, they note that participant- loss as a win, and I wouldn’t try to,” Newtown Square, PA 19073 rated overall discomfort was lower (610) 492-1000 concludes Dr. Repka. “The good immediately post-administration but Fax: (610) 492-1039 news is that this proposed rule did returned to baseline levels by day one. Subscription inquiries: not have any other eye services that The investigators add that there was United States — (877) 529-1746 CMS considers possibly misvalued, one adverse event in the povidone- Outside U.S. — (845) 267-3065 which means we don’t have to defend iodine group within the fi rst two days E-mail: anything next year. So that, at least, is following drop adminstration that was [email protected] a good thing.” unrelated to treatment. Website: www.reviewofophthalmology.com 1. 2020 Medicare physician fee schedule (MPFS) proposed rule 1. Shorter E, Whiteside M, Harthan J, et al. Safety and tolerability released. ASCRS. August 2019. http://ascrs.org/about-ascrs/ of a one-time, in-offi ce administration of 5% povidone-iodine news-about/2020-medicare-physician-fee-schedule-mpfs- in the treatment of adenoviral conjunctivitis: The Reducing proposed-rule-released Adenoviral Patient Infected Days (RAPID) study. Ocul Surf. August 2. McCann N. ASCRS special report: Key information about the 8, 2019 [epub ahead of print].

4 | Review of Ophthalmology | September 2019

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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 JAMES HENNE Penny Asbell, MD Ann P. Murchison, MD, MPH (610) 492-1017 [email protected] CORNEA / ANTERIOR SEGMENT REFRACTIVE SURGERY REGIONAL SALES MANAGER Thomas John, MD Arturo S. Chayet, MD 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 Yoshihiro Yonekawa, MD 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 Jason Flamendorf, MD CASEY FOSTER (610) 492-1007 [email protected]

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6 | Review of Ophthalmology | September 2019

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RP0919_Lacrimedics.indd 1 8/13/19 1:17 PM September 2019 • Volume XXVI No. 9 | reviewofophthalmology.com Cover Focus 28 | Diagnosing Ocular Surface Disease Sean McKinney, Senior Editor Take this systematic approach—but prepare to individualize your choices. 36 | Knowledge and Tech: Treating Dry Eye, 2019 Christopher Kent, Senior Editor As our understanding of the problem and options for addressing it increase, patients benefit. Feature Articles 46 | The Latest in Retinal Surgical Instruments Christine Leonard, Associate Editor The design and function of vitrectomy cutters have come a long way. Here’s a look at some of the most recent innovations.

52 | When and How to Treat EBMD Michelle Stephenson, Contributing Editor Expert advice on how to approach a treatment plan for the cases that warrant it.

September 2019 | reviewofophthalmology.com | 9

009_rp0919_toc.indd 9 8/23/19 3:15 PM Departments

3 | Review News 14 12 | Technology Update Smartphone Apps for Cataract Surgery A look at two IOL calculators and an axial marking tool you can use on your smartphone or tablet.

20 | Medicare Q & A What’s New for MIPS in 2020? Some changes have been made to the Merit-based Incentive Payment System. Here’s what you need to know.

58 | Refractive/Cataract Rundown 58 Hone Your Refractive Screening Process Follow these tips to safeguard corneal health while ruling candidates in or out.

62 | Product News New Contact Lens Debuts

65 | Research Review The Risks of Interrupting DR Treatment

66 | Glaucoma Management What We’re Learning from the PTVT Study The Primary Tube vs. Trabeculectomy Study is 62 revealing useful data regarding tubes versus trabs in virgin eyes.

72 | Classifieds

72 | Advertiser Index

10 | Review of Ophthalmology | September 2019

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

Smartphone Apps for Cataract Surgery A look at two IOL calculators and an axial marking tool you can use from your smartphone or tablet. Christine Leonard, Associate Editor David Flikier, MD t should come as no surprise that • “IOL Power and Toric Cal- Imedical technology has found a culator.” This includes calculators platform on our mobile devices. for surgically induced astigmatism, Smartphone use in clinical prac- postop toric calculation, Holla- tice is growing,1 and applications day and SRK/T anterior chamber that can save surgeons time and depth calculation and astigmatic money are also helping improve keratotomy calculation; patient outcomes. Here, we’ll take • “Aphakic/Phakic Calcula- a look at some of the recent ad- tor.” This allows both aphakic and vances. phakic IOL calculation, posterior chamber intraocular phakic lens Panacea IOL Calculator diameter and LASIK and PRK ablation thickness calculators; and The Panacea IOL and Toric Cal- • “Optometric Formulas Calcu- culator is a multi-program ophthal- lator.” This includes calculators for mic application created by David toric contact lenses, prism, vertex Flikier, MD, medical director of distance and abbe value. the Instituto de Cirugía Ocular in “I’m very impressed with the San José, Costa Rica. Panacea con- Panacea software for IOL calcula- siders two new corneal variables, tions,” says Arturo Chayet, MD, the Gullstrand ratio (posterior-to- of the Codet Vision Institute in La anterior corneal ratio) and corneal Jolla, California. “In my opinion Q asphericity, which Dr. Flikier it’s the most complete, effective says increase predictability in nor- but underrated IOL calculator. Figure 1. The Astigmatic Keratotomy Calculator in mal cases and also allow for the I’m using it with great success.” Panacea calculates the toric power of the anterior calculation of abnormal corneas Luis Lu, MD, senior member and posterior corneal surfaces; total corneal astigmatism, including that induced by corneal with objective data. of Eye Consultants of Arizona and incisions; recommended arcuate keratotomy Dr. Flikier says he designed preceptor at Arizona State Univer- with graphs according to age, optic zone, arc and Panacea to be intuitive and sity and Hyatt Medical Education, depth; and estimation of the necessary power at easy to use. The app features 19 International University, agrees. the corneal plane to achieve the desired residual programs, including: “I use the program to compare astigmatism according to patient age.

12 | Review of Ophthalmology | September 2019 This article has no commercial sponsorship.

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RP0319_Focus.indd 1 2/26/19 3:17 PM Technology

REVIEW Update

Predictability of Several IOL Formulas

SN60WF IOL outcomes (n=127) SA60AT IOL outcomes (n=193) CB00 IOL outcomes (n=105)

Filomena Riberiro, MD Filomena Riberiro, Methodology SD MAE Methodology SD MAE Methodology SD MAE

Panacea 0.38268 0.29186* Panacea 0.40922 0.31251 Panacea 0.40732 0.30547* Barrett 0.40479 0.29012** RBF 0.44125 0.33830 Barrett 0.41617 0.31576 Olsen 0.41403 0.31860 SRK-T 0.44421 0.33879 Olsen 0.41885 0.30420 RBF 0.42127 0.32253 Barrett 0.44474 0.33767 RBF 0.44655 0.33738 Haigis 0.42943 0.33471** Haigis 0.45974 0.35492 Haigis 0.45301 0.35125 SRK-T 0.44529 0.33633* Olsen 0.46854 0.33867 SRK-T 0.51346 0.38155*

SD=standard deviation; MAE=Mean Absolute Error *p=0.002; p values from within-group ANOVA with Sidak *p=0.006; **p=0.008; p values from within-group ANOVA correction. with Sidak correction. Figure 2. Comparison of prediction error for SN60WF, SA60AT and PCB00 toric IOLs.3

the calculations done with the oth- measuring the total corneal power the use of Panacea as a comparative er fourth-generation formulas that be directly integrated into the pro- formula, my results are 85 percent are available,” he says. “In normal gram.” He hopes that in the future within 0.5 D.” corneas, in a few cases the calcula- more variables will be taken into ac- The Panacea app is currently avail- tion can change a little, but my main count, such as aqueous index of re- able for iPad, as well as for desktop use is on those with previous corneal fraction, vitreous index of refraction, Macs and PCs. Android and iPhone surgeries. I believe this ‘fifth’-gen- lens tilt and retinal tilt. versions are in the works. For more eration program should be used in A 2017 study comparing method- information, visit panaceaiolan- conjunction with the other formulas ologies using estimated versus mea- dtoriccalculator.com. to improve the outcome of the target sured values of total corneal astigma- refraction. Panacea can calculate the tism for toric IOL power calculations iToric Patwardhan toricity well, perhaps because it in- found that the centroid prediction cludes factors or vectors not included error, the error in the predicted mean The iToric Patwardhan is an axial in other programs.” of residual astigmatism for a series of marking tool that checks the accu- Dr. Lu says the Panacea formula patients, was 0.25 ±0.43 D at 173 racy of toric marking and suggests a works well in all kinds of eyes, so degrees for the Panacea calculator.2 new placement axis to reduce error long as the individual’s posterior cor- The latest results of a 2019 study in IOL placement. There’s no need neal power can be measured. This headed by Filomena Ribeiro, MD, for a slit lamp or bubble marker. All is where the advantage of Panacea PhD, FEBO, director of the Oph- the app requires is an Android smart- lies, says Dr. Flikier. “To really get thalmology Service of the Hospital phone with a good camera. the advantage of Panacea, you need da Luz Lisboa and professor of oph- iToric Patwardhan was developed to introduce the posterior surface thalmology and biomedical engineer- by Sourabh Patwardhan, FRCS, data through the Gullstrand ratio or ing at the University of Lisbon, found MD, medical director at India’s Nan- posterior surface curvature,” he ex- Panacea calculated a mean absolute dadeep Eye Hospital and Institute. plains. error of intended versus achieved Using the smartphone’s built-in While the app features several cal- refraction of 0.291 D for the Alcon gyroscope, which can measure an- culators and variables, “it does re- SN60WF and 0.305 D for the John- gular acceleration, iToric can pin- quire the surgeon to be able to cal- son & Johnson PCB00.3 point the exact orientation of a mark culate the power, radius and axis of Dr. Lu ﬁ nds that his refractive out- in space within 1 degree of precision. the anterior and posterior cornea,” comes have improved with Panacea. After taking a photo of the eye, the Dr. Lu says. One improvement he “Prior to this program, about 70 to 75 surgeon can zoom in and align the suggests is that “the data from the percent of my patients were within cornea within the outer calibration Pentacam, Galilei G4 or G5, IOL- 0.5 D of the target refraction and circle in the app. Once the eye is Master 700 or any device capable of 85 to 90 percent within 1 D. With centered, the user places the marks

14 | Review of Ophthalmology | September 2019

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RP0919_Beaver.indd 1 8/26/19 10:39 PM Technology

REVIEW Update

bubble markers. This even helps polar (r,θ) notation, which describes the patient, as the process is fast a point in terms of distance from and and less cumbersome.” angle of rotation around a point. Zain Khatib, MD, in practice “You can bring it with you to the at the Khatib Eye Clinic, Mum- operating theater to recheck biom-

Sourabh Patwardhan, MD Patwardhan, Sourabh bai, has been using iToric for more etries on the spot,” says Dr. Borasio. than two years. “You can capture “I also often use it in the clinic to a photograph and then align the perform post-laser refractive surgery marks with the calibration circles biometries using BESSt 2 and Bora- later,” he says. “This is much more sio Myopic/Hypermetropic Regres- stable and easier to perform than sions (BMR/BHR),6 or for toric IOL working with real-time apps. calculations and for converting visual “Accuracy-wise, it’s excellent,” acuity notations.” Dr. Khatib adds. “iToric almost Surgeons say that Eye Pro’s abil- matches the accuracy of a digital ity to analyze multiple patient data marking system.” sets at once has helped them see im- A 2018 study supports this con- portant trends in their work. “Being clusion. Compared to manual able to see aggregate plots of pre-, marking methods, preoperative post- and induced astigmatism and marking with smartphone gyro- the centroid calculation was an eye- scope-assisted marking signifi cant- opener that helped me to modify 4 Figure 3. The iToric Patwardhan app suggests a ly improved accuracy. my surgical technique based on my new axis of placement to be used intraoperatively. For a tutorial, watch this vid- results,” says Eduardo Viteri, MD, eo: youtu.be/vHKrFGimkHw. of Centro Oftalmológico Humana Visit play.google.com/store/apps/ Vision, Ecuador. “I changed from on the cornea and enters the place- details?id=com.itoric.app1 to a steeper axis to temporal incisions ment axis. The app will then suggest download the app. and was able to take into consider- a new placement axis to correct any ation the vector effect of my 2.2-mm error in marking. Eye Pro incisions to decide on the IOL axis In Dr. Patwardhan’s experience, alignment.” the iToric resulted in a decrease of Eye Pro is a suite of programs For a series of cases, Dr. Viteri average residual cylinder from 32 for iOS that performs calculations explains, “you can easily obtain the to 22 percent and, in 87 toric IOL such as post-LASIK biometry, vector mean astigmatism and standard de- cases, none of them was more than 5 astigmatism analysis and outcome viation, after conversion to Cartesian degrees away from its intended axis. analysis. Edmondo Borasio, MD, notation; plot two series simultane- The quick workfl ow, high accuracy FEBO, Head of the Ophthalmology ously on the same plot—for example, and opportunity to avoid additional Department at Burjeel Day Surgery pre- and postop; and plot the astig- calculations are the main advantag- Center in Abu Dhabi and creator matism centroid.” The SIA plotter es of the app, says Dr. Patwardhan. of the Borasio Edmondo Smith and produces high-resolution, publica- “Patients are much more comfort- Stevens (BESSt) formula,5 devel- tion-level, double-angle polar plots, able with freehand pen marking,” oped Eye Pro in 2009, and he says says Dr. Borasio. he notes. “Children are also more it was the fi rst ophthalmological app Charles Diaper, MD, an oculo- cooperative with this than with metal released for iOS. The current version plastic surgeon with a general cata- toric marking instruments.” includes standard biometry formu- ract practice in the National Health Vinit Shah, MD, who practices at las like SRK/T and Hoffer Q, the System in Scotland, says Eye Pro’s the Vinit Eye Clinic Retina and Laser BESSt formulas for post-refractive astigmatism plotting and group out- Centre in Mumbai, India, agrees, surgery patients,5 and toric IOL and come analysis came in handy when saying, “iToric is very good in a busy SIA calculators. It also includes an he needed to generate audit output operation theater where it might be aggregate astigmatism plotter, opti- data for his department to show diffi cult for surgeons to come out of cal formulas and converter programs they were matching national audit the OT after every case to perform for visual acuity notation, corneal to benchmarks for surgically induced corneal marking at the slit lamp with spectacle plane and Cartesian (x,y) to (Continued on page 19)

16 | Review of Ophthalmology | September 2019

012_rp0919_tech-2.indd 16 8/23/19 5:10 PM SUBSTITUTEGENERICNO FOR INVELTYS

INVELTYS The ƼVWXERHSRP] corticosteroid FDA approved for &-(XVIEXQIRX of post-operative inflammation and pain following ocular surgery

Indication INVELTYS (loteprednol etabonate ophthalmic suspension) 1% is of topical steroids. The initial prescription and renewal of the medication MRHMGEXIHJSVXLIXVIEXQIRXSJTSWXSTIVEXMZIMRƽEQQEXMSRERHTEMR order should be made by a physician only after examination of the patient following ocular surgery. [MXLXLIEMHSJQEKRMƼGEXMSRWYGLEWWPMXPEQTFMSQMGVSWGST]ERH[LIVI ETTVSTVMEXIƽYSVIWGIMRWXEMRMRK Important Safety Information Prolonged use of corticosteroids may suppress the host response and INVELTYS is contraindicated in most viral diseases of the cornea thus increase the hazard of secondary ocular infections. In acute purulent and conjunctiva including epithelial herpes simplex keratitis (dendritic conditions, steroids may mask infection or enhance existing infection. keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. Use of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Use of ocular steroids may prolong Prolonged use of corticosteroids may result in glaucoma with damage to the course and may exacerbate the severity of many viral infections of the eye XLISTXMGRIVZIHIJIGXWMRZMWYEPEGYMX]ERHƼIPHWSJZMWMSR-JXLMWTVSHYGX (including herpes simplex). is used for 10 days or longer, IOP should be monitored. Fungal infections of the cornea are particularly prone to develop Use of corticosteroids may result in posterior subcapsular coincidentally with long-term local steroid application. Fungus invasion cataract formation. must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. In those diseases causing thinning of In clinical trials, the most common adverse drug reactions were eye pain the cornea or sclera, perforations have been known to occur with the use ERHTSWXIVMSVGETWYPEVSTEGMƼGEXMSR 8LIWIVIEGXMSRWQE]LEZI been the consequence of the surgical procedure. Please see Brief Summary of Prescribing Information for INVELTYS on the next page.

US-INV-1900123

RP0919_Kala.indd 1 8/26/19 10:47 PM INVELTYSTM (loteprednol etabonate ophthalmic suspension) 1%, ADVERSE REACTIONS for topical ophthalmic use Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION infrequent optic nerve damage, visual acuity and ﬁeld defects, posterior subcapsular cataract formation, delayed wound healing INDICATIONS AND USAGE and secondary ocular infection from pathogens including herpes INVELTYS is a corticosteroid indicated for the treatment of simplex, and perforation of the globe where there is thinning of the post-operative inﬂammation and pain following ocular surgery. cornea or sclera.

CONTRAINDICATIONS Clinical Trial Experience—Because clinical trials are conducted INVELTYS is contraindicated in most viral diseases of the cornea and under widely varying conditions, adverse reaction rates observed conjunctiva including epithelial herpes simplex keratitis (dendritic in the clinical trials of a drug cannot be directly compared to rates keratitis), vaccinia, and varicella, and also in mycobacterial infection in the clinical trials of another drug and may not reflect the rates of the eye and fungal diseases of ocular structures. observed in practice. The most common adverse drug reactions in the clinical trials with INVELTYS were eye pain and posterior capsular WARNINGS AND PRECAUTIONS opacification, both reported in 1% of patients. These reactions may Intraocular Pressure (IOP) Increase—Prolonged use of corticosteroids have been the consequence of the surgical procedure. may result in glaucoma with damage to the optic nerve, as well as defects in visual acuity and fields of vision. Steroids should be used USE IN SPECIFIC POPULATIONS with caution in the presence of glaucoma. If this product is used for Pregnancy—Risk Summary: INVELTYS is not absorbed systemically 10 days or longer, intraocular pressure should be monitored. following topical ophthalmic administration and maternal use is not expected to result in fetal exposure to the drug. Cataracts—Use of corticosteroids may result in posterior subcapsular cataract formation. Lactation—Risk Summary: INVELTYS is not absorbed systemically by the mother following topical ophthalmic administration, and Delayed Healing—Use of steroids after cataract surgery may delay breastfeeding is not expected to result in exposure of the child healing and increase the incidence of bleb formation. In those to INVELTYS. diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The Pediatric Use—Safety and effectiveness in pediatric patients have initial prescription and renewal of the medication order should be not been established. made by a physician only after examination of the patient with the aid of magnification such as slit lamp biomicroscopy and, where Geriatric Use—No overall differences in safety and effectiveness appropriate, fluorescein staining. have been observed between elderly and younger patients.

Bacterial Infections—Prolonged use of corticosteroids may suppress NONCLINICAL TOXICOLOGY the host response and thus increase the hazard of secondary ocular Carcinogenesis, Mutagenesis, Impairment of Fertility— infections. In acute purulent conditions of the eye, steroids may Long-term animal studies have not been conducted to evaluate mask infection or enhance existing infection. the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse Viral Infections—Use of corticosteroid medication in the treatment lymphoma thymidine kinase (tk) assay, or in a chromosome of patients with a history of herpes simplex requires great aberration test in human lymphocytes, or in vivo in the single dose caution. Use of ocular steroids may prolong the course and mouse micronucleus assay. may exacerbate the severity of many viral infections of the eye (including herpes simplex). For a copy of the Full Prescribing Information, please visit www.INVELTYS.com. Fungal Infections—Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid Manufactured for: application. Fungus invasion must be considered in any persistent Kala Pharmaceuticals, Inc. Waltham, MA 02453 corneal ulceration where a steroid has been used or is in use. Marks designated by TM and ® are owned by Fungal cultures should be taken when appropriate. Kala Pharmaceuticals, Inc. Patented. See www.kalarx.com/patents Contact Lens Wear—The preservative in INVELTYS may be © 2018 Kala Pharmaceuticals, Inc. All rights reserved. absorbed by soft contact lenses. Contact lenses should be removed US-INV-1800055 December 2018 prior to instillation of INVELTYS and may be reinserted 15 minutes following administration.

RRP0919_KalaP0919_Kala PI.inddPI.indd 1 88/26/19/26/19 10:4810:48 PMPM Technology

REVIEW Update Edmondo Borasio, MD (Continued from page 16) astigmatism. Dr. Diaper says his plots showed a change in incision width from 4.2-mm incisions to 2.2 mm, a decrease linked to a reduction in SIA,7 which helped maintain his department “when management wished to constrain resources.” Both Dr. Viteri and Dr. Diaper fi nd the app easy to use, but point out the ever-present possibility of data input error. “For individual cases, the data input is intuitive,” Dr. Viteri says. “You just have to be careful. I suggest using a positive cylinder notation to avoid confusion.” Figure 5. Screenshot of the EB Toric marking tool after gyroscopic realignment, which Though the app’s portability on automatically rotates the photo an equal and opposite number of degrees in order to iPads and iPhones is convenient, es- maintain a perfectly straight-on view of the eye. The surgeon then aligns the blue dot with the scleral mark and sets the location for the incision, marked by a red arrow. The toric IOL pecially when the surgeon, as Dr. axis is imported directly from the EB Toric IOL Calculator. Data can also be entered manu- Diaper puts it, “is away from biom- ally if another calculator is used. etry machinery,” Dr. Viteri says he’d like to be able to use Eye Pro on but it’s worth the effort,” he says. new method of toric marking. The his computer to make data transfer “Having it on my computer would EB Toric marking tool employs a easier. “It can be a little cumbersome just make data transfer easier for ag- speculum and an ink mark applied to export and import the .cvs fi les to gregate vector analysis in astigmatic anywhere on the sclera to orient the obtain the centroid and polar plots, correction. iPhone. A photo is taken, realigned “It would be great to have Eye Pro by gyroscope, and digital marks can integrated with Pentacam AXL to be added. take the back of the cornea into con- Comparing digital toric marking sideration, avoid data input error and to direct marking, Dr. Borasio says improve efficiency,” continues Dr. it’s fast, inexpensive, convenient and Viteri. “I’d also like to be able to take safe, since there’s no need to unpack Edmondo Borasio, MD Edmondo Borasio, or import anterior segment photo- sterile instruments and there’s no risk graphs for axial marking.” of corneal abrasions. While Dr. Viteri doesn’t use Eye For more information or to down- Pro routinely, instead sticking with load a free trial of the new release, Goniotrans, a virtual angle conveyor visit eb-eye.com. for axial marking, and a Pentacam 1. Karthikeyan SK, Thangarajan R, Theruvedhi N, Srinvasan K. AXL for biometry and IOL calcula- Android mobile applications in eye care. Oman J Ophthalmol tion, he still considers Eye Pro a “must 2019;12:2:73-77. 2. Ferreira TB, Ribeiro P, Ribeiro F, O’Neill JG. Comparison of have” for cataract surgeons looking to methodologies using estimated or measured values of total corneal astigmatism for toric intraocular lens power calculation. improve their refractive results. J Refract Surg 2017;33:12:794-800. The latest release of the app con- 3. Ribeiro F, et al. Hospital da Luz Lisboa. 2019. [Submitted] 4. Khatib Z, Haldipurkar S, Shetty V, Setia M. Verion vs manual tains three new features: a stream- marking and smartphone-assisted manual marking in toric IOL implantation. September 23, 2018. Vienna 2018 36th lined prescription app; a toric IOL cal- Congress of ESCRS. Laxmi Eye Institute, Navi Mumbai. [pending culator that supports posterior corneal publication] 5. Borasio E, Stevens J, Smith GT. Estimation of true corneal astigmatism as well as Naeser/Savini power after keratorefractive surgery in eyes requiring cataract surgery: BESSt formula. J Cataract Refract Surg 2006;32:2004- Figure 4. The new EB Toric IOL Calculator supports Optimized Keratometry regressions 2014. and different options for estimating 6. Borasio E. IOL power calculation accuracy in post-myopic different options for estimating astigmatism at and hyperopic ablations using the Borasio Regression formula. the plane of the IOL, including custom/auto the astigmatism component at the March 2011. ASCRS Annual Meeting. San Diego. toricity ratio, custom/auto ELP, and a fully auto- 7. Masket S, Wang L, Belani S. Induced astigmatism with 2.2- IOL plane, including toricity ratio and 3.0-mm coaxial phacoemulsifi cation incisions. J Refract mated mode, recommended by Dr. Borasio. and effective lens position; and a Surg 2009;25:1:21-24

September 2019 | reviewofophthalmology.com | 19

012_rp0919_tech-2.indd 19 8/23/19 5:10 PM 020_rp0919_mqa.indd 20 MIPS in 2020? in MIPS What’s New for A Q 20 QPP/MIPS program next year? next program QPP/MIPS me if there are changes for the tell you Can Rule. Proposed egory islikelytoimpactanyoph- year” activities.The“Cost”cat- for your2019“performance avoid thepenaltyin2021 minimum of30pointsto this year, you’llneeda exempt fromQPP QPP. If you’renot option under likely theironly (APM), MIPSis payment models vanced alternative gists areinad- few ophthalmolo- individual. Since a grouporan is stillaseither tion inQPP Participa- to nextyear. moving on year (2019)before review whatisneededthis Payment System.Here’s whatyouneedtoknow. Some changeshavebeenmadetotheMerit-basedIncentive REVIEW | ReviewofOphthalmology Paul M. Larson, MBA, MMSc, COMT, COE, CPC, CPMA Medicare Q&A planning isakeypartofthis.Let’s Yes—and theyaresigniﬁ

released the 2020 has Medicare I saw cant, so so cant, | September2019 Part Bdrugs. services exceptoffice-administered the maximum7percentonallPartB APM, youwouldbepenalizedin2021 MIPS, andaren’t partofanadvanced pate aseitheragrouporindividualin If youaren’t exemptanddon’t partici- cataract surgerywithIOLplacement. thalmologist whoperformsroutine

what wastheoreticallypossible. Q hasn’t allowedproviderstoget next year to avoid the the avoid to year next I need do score What The maximum bonus is up to The maximumbonusisupto penalty isnow9percent. Additionally, themaximum ing a100-percentscore points for2020reporting. 9 percenttoo,butit’s bud- ion. The bar is raised to 45 ion. Thebarisraisedto45 maximum penalty maximum penalty get neutral,whichhas A in 2022? each year. Evenearn- significantly affected been abletoget what providershave change, inmyopin- This isthebiggest This articlehasnocommercial sponsorship. A Q Q in 2020? those doingclaims-basedreporting. better chancetoscorehigherthan who reportviaaRegistryhavemuch penalty in2019).Historically, those can avoidthemaximum7-percent likely doable(it’s whymostdoctors and gettingamuchlowerpenaltyis points, althoughreachingthemid-30s may havetoworkhardachieve45 Those doingclaims-basedreporting weighted at30percent. and Qualityareeachanticipatedtobe by the2022performanceyear, Cost at 15percent.Infact,CMSnotesthat cent andImprovementActivitiesstays “PI,” theEMRone)staysat25per- “Program Interoperability”(a.k.a., level, continuingthedownwardtrend. percent fromthecurrent45-percent percent. “Quality”goesdownto40 from thecurrentlevelof15 Yes. “Cost”risesto20percent the Cost category of MIPS MIPS of category Cost the to happen to going What’s re-weighted again in 2020? being categories the Are 8/23/19 6:19 PM BRIMONIDINE TARTRATE OPHTHALMIC SOLUTION 0.025% REDNESS RELIEVER EYE DROPS

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REVIEW Q&A

or direct electronic health records Another big change is possible CMS proposes to survey doctors reporting. For claims-based Ain the category of Cost. Many of Aand groups about changes, reporters, this is 70 percent of you may remember the big change but plans no changes other than to Part B patients, and for those with this year was the implementation require half of the doctors in a group Registries or electronic health of the Episode of Cost for Routine to participate for IA to count (instead records systems it’s 70 percent Cataract with IOL. Those doing of only one doctor, as the rule states of all patients. The Centers for routine, uncomplicated cases coded now). If a provider is hospital-based, Medicare and Medicaid Services as 66984 for patients without certain the threshold will be 75 percent of proposes to remove measures concomitant diagnoses (such as age- providers. 192 (Complications within 90 related macular degeneration) are days of Cataract/IOL that require now scored in the Cost category. additional surgery) and 388 This Cost episode is proposed to (Unplanned rupture of posterior continue for 2020 without change, capsule requiring unplanned but there is a proposal to modify one Other than the Quality vitrectomy). The process for of the two other ways to be scored weight changing to removing Quality measures in this category (TPCC, or Total Per continues so it’s likely there may Capita Cost). While, historically, 40 as mentioned, the be fewer options for providers to this hasn’t affected many eye-care reporting thresholds choose from, or that scoring may providers, it doesn’t mesh well with become more difﬁ cult for those how eye doctors practice and the are increasing to that remain in 2020. proposed change was seen as unfair 70 percent for both to those affected. The last way to get scored here (MPSB, or Medicare claims-based reporters Spending Per Beneﬁ ciary) remains, and those using What other changes but might possibly change in a more Registries or direct Q should ophthalmologists subtle way. be aware of? EHR reporting. Cost and Quality reporting Has there been a Aremains a full year, and PI and Q proposal to change the IA stay at 90 days (no change). EMR area of MIPS? Finally, we haven’t covered The small practice doubling of IA everything. You can see the Again, the answer is yes. This scoring for those practices under 16 proposed 2020 changes for QPP Aarea is now known as Program providers is slated to remain, as well, and MIPS on the QPP Resource Interoperability (PI). When MIPS so you can still score 20 but yield Library page at this link: https:// started, it was known as “Advancing 40 (the maximum) in 2020. CMS qpp.cms.gov/about/resource-library. Care Information.” Before that, we also proposes to begin developing a The downloadable document(s) knew it as “Meaningful Use.” This process for deciding how/when IA that ophthalmologists will need latest change isn’t going to impact measures are removed. for the 2020 billing year are near many ophthalmologists. CMS the top of the page right under proposes to remove the “Verify the menu marked “Regulatory Opioid Treatment Agreement” What changes are afoot Resources.” measure and make the “Query Q for the Quality area of CMS also proposed a new “MIPS of Prescription Drug Monitoring MIPS? Value Pathways” (MVP) system for Program” optional. CMS proposes 2021 but that won’t change your 2020 to keep the small-practice exceptions Other than the Quality reporting. here. Ascoring weight changing to 40 as mentioned, the reporting Mr. Larson is a senior consultant How about Improvement thresholds are increasing to 70 at the Corcoran Consulting Group. Q Activities (IA)? Any percent for both claims-based Contact him at plarson@corcoranc- changes there? reporters and those using Registries cg.com.

22 | Review of Ophthalmology | September 2019

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RP0919_Sight Sciences.indd 1 8/27/19 6:23 PM Hypochlorous Acid

Hypochlorous Acid Re-Imagined for Eye Care

How This Naturally Occurring Substance Can Elevate Eyelid Hygiene and Help Manage Dry Eye Symptoms

By Marguerite McDonald, MD, FACS

yelid hygiene is a crucial compo- acid—a substance generated naturally Hypochlorous nent of ocular health, especially in the body. Hypochlorous acid is pro- acid is a natural for patients with conditions such duced in neutrophils and functions as substance that E H plays an important as dry eye, blepharitis, or meibomian an antimicrobial agent that destroys role in keeping the gland dysfunction. However, some bacteria, serving as an important part body healthy. CI older lid hygiene practices are not of the immune system. Studies are optimally effective, and many patients ﬁ nding that solutions containing hypo- aren’t compliant with their eyelid chlorous acid not only possess power- O cleansing regimens. In fact, studies ful antimicrobial properties, but are have shown that though 93% of eye well-tolerated for continuous use and care professionals recommend eyelid yield minimal cytotoxic effects.4-6 Hypochlorous acid cleansing for this group,1 only 19% of dry eye patients regularly cleanse The Need for Improved lipid byproducts and lipolytic bacteria their eyelids.2 The groundbreaking Lid Cleansing Approaches associated with these conditions.3 The Dry Eye Workshop II (DEWS II) report The importance of appropriate report also noted certain outdated strongly advised that clinicians utilize lid hygiene was emphasized in the lid hygiene practices that should be newer, more efﬁ cacious hygiene solu- DEWS II report, offering foundational updated by eye care professionals, as tions available on the market today to guidance from 150 worldwide experts well as a lack of patient compliance improve patient outcomes and com- in the areas of ocular surface care and with best practices. For example, it pliance when it comes to lid hygiene, disease management. The authors revealed:3 as opposed to more traditional strate- stressed the need to appropriately • Though lid scrubs using diluted gies.3 manage a variety of lid conditions baby shampoo traditionally have been One new way to elevate eyelid hy- that result in dry eye, particularly a widely accepted therapy,7-9 one giene and help increase patient adher- blepharitis. If used correctly, they Level 1 study found that a dedicated ence involves the use of hypochlorous determined, lid hygiene could reduce lid cleanser had reduced ocular surface MMP-9 levels and improved lipid Eyelid Cleansing: layer quality, and was better tolerated Essential, But Often Overlooked than diluted baby shampoo.3,10 Baby shampoo also has been associated ONLY with reduced ocular surface MUC5AC levels, suggesting it might have an 93% 19% adverse effect on goblet cell function.8 of eye care professionals recommend of dry eye sufferers regularly • New, proprietary lid cleans- eyelid cleansing for certain patients1 cleanse their eyelids2 ing products that use a diversity of delivery mechanisms are recommend-

24 | REVIEW OF OPHTHALMOLOGY | SEPTEMBER 15, 2019 Sponsored by

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ed over traditional lid cleansing strategies.3 In recent years, many lid hy- Hypochlorous Acid Reduces Research has revealed the ability of hypochlorous acid to reduce the giene solutions have come to market Ocular Skin Bacterial Load bacterial load on the surface of the as marked advancements over baby periocular skin shortly after application.1 One study demonstrated a shampoo. Some solutions have even removed • Though lid hygiene is widely staphylococcal isolates resistant to multiple antibiotics. considered an effective therapy for 11 >99% MGD and blepharitis, compliance 1. Stroman DW, Mintun K, Epstein AB, et al. Reduction in reduction in the staphylococcal load on bacterial load using hypochlorous acid hygiene solution with provider instructions is periocular skin 20 minutes after a solution on ocular skin. Clin Ophthalmol. 2017;13(11):707-14. 3 “notoriously poor.” containing 0.01% pure hypochlorous acid It’s clear that modern approaches was applied.1 to managing lid hygiene, such as A Diversity of use of hypochlorous acid, are a more Clinical Uses for appropriate way to promote eyelid A Natural Opportunity for Hypochlorous Acid health than older methods using baby Hypochlorous Acid shampoo. In today’s world, many patients Products with hypochlorous acid have actively seek out products with more received many FDA and EPA approvals across a broad range of medical mar- natural characteristics. Embodying Expanding Access to kets including dermatology, ophthal- Rx-Strength Solutions such qualities, hypochlorous acid is mology, dentistry, and wound healing Until recently, two types of eyelid organically produced as part of the care. They are also widely used cleansers were available to patients in cytotoxic myeloperoxidase system in in veterinary and ostomy applications. the following ways, with these traits: neutrophils.12,13 This broad spectrum • Cosmetics: Not fi led with the FDA, antimicrobial mimics the human sys- with large variation in ingredients and tem, and has been shown to cause dermatologic conditions.18 For exam- efficacy. Limited availability in retail rapid oxidation of nucleotides, inac- ple, in atopic dermatitis, hypochlorous stores, with most distribution in physi- tivation of cell enzymes, disruption of acid may decrease protease binding cian’s offi ces and online. cell membranes, and cell lysis when and modulate interleukins involved in • Rx products: Proven effi cacy, but introduced to various microorganisms the infl ammatory cascade.18 inconvenient due to prescription re- in vitro.14-17 quirement and potentially very costly From a clinical perspective, agents Clinically Advancing Lid depending on insurance. containing hypochlorous acid hold Hygiene Practices Realizing the need was great to pro- powerful antimicrobial properties that New products featuring hypochlo- vide patients with greater accessibility appear to be useful for ongoing use, rous acid offer leaps forward in the fol- to prescription-strength daily eyelid exhibiting minimal toxic effects to lowing clinical areas of eyelid hygiene: cleansers, researchers embarked on cells in several studies.4-6 In addition, Antimicrobial & Antifungal Effi cacy: developing such a product. The result hypochlorous acid exerts a broad Research has documented the sig- is TheraTears® SteriLid® Antimicrobial range of anti-infl ammatory and immu- nifi cant ability of antimicrobial agents Eyelid Cleanser and Facial Wash, now nomodulatory activities, such as those such as hypochlorous acid to help available at a variety of retail stores. involved in the pruritic cycle of certain maintain healthy skin—including near the eyelids—and to inhibit growth of » A MAJOR MILESTONE pathogenic bacteria while promoting the proliferation of symbiotic bacteria.19 The fi rst FDA-Accepted antimicrobial eyelid cleanser, TheraTears® SteriLid® It also has determined the swift, broad- Antimicrobial Eyelid Cleanser and Facial Wash (Hypochlorous acid 0.01%), a convenient and affordable over-the-counter solution that is spectrum fungicidal activity of 0.01% as effective as a prescription: hypochlorous acid.20 One literature review, which evaluated cases of fun- • Cleanses away bacteria and irritants • pH-balanced formula which is gentle on eyelids gal keratitis and endophthalmitis after • A rinse free formula to promote patient satisfaction Boston keratoprosthesis implantation • Accessibility at major retail stores during a 14-year period, noted the • Patient-friendly pricing ability of 0.01% hypochlorous acid to • 24-month shelf life open or un-opened reduce medically relevant yeast cells or mold conidia by 99.99% within 60

SEPTEMBER 15, 2019 | REVIEW OF OPHTHALMOLOGY | 25

024_ro00919_TheraTears_RP_v4.indd 25 8/29/19 10:41 AM Hypochlorous Acid

shelf life, opened or unopened. Dr. McDonald practices at Ophthalmic A Powerful Agent: My firsthand experience with Consultants of Long Island, Dry Eye Cen- TheraTears® SteriLid® TheraTears® SteriLid® Antimicrobial ter of Excellence in Lynbrook, New York. Antimicrobial Eyelid Cleanser & Facial Wash is that it Dr. McDonald has received compensa- is easy and quick to use, non-irritating, tion for the preparation of this article from KILLSKILLS and effective. It can be applied long- Akorn Consumer Health, manufacturers of % term without irritation. My patients are TheraTears®SteriLid® Antimicrobial Eyelid 99.9OF pleased with how their eyes and lids Cleanser and Facial Wash. BACTERIABACTERIA look and feel after using the product, 1. Data on fi le Akorn Consumer Health. 2. The 2017 Gallup Study of Dry Eye Sufferers (Conducted by Multi- IN UNDER 30 SECONDS and I see the slit-lamp improvements. sponsor Surveys, Inc.) An eyelid cleanser such as 3. Nelson JD, Craig, JP, Esen A, et al. TFOS DEWS II Report. Ocul Surf 8 TYPES OF BACTERIA TESTED: 2017; 2017 July;15(3):269-650. TheraTears® SteriLid® Antimicrobial is 4. Whitfi eld N. Surgical skills beyond scientifi c management. Med Hist • Pityrosporum Ovale 2015;59:421-2. • Serratia Marcescens especially important for dry eye, pre- 5. Kim HJ, Lee JG, Kang JW, et al. Effects of a low concentration hypochlorous acid nasal irrigation solution on bacteria, fungi, and virus. • Staphylococcus Aureus operative, and MGD patients, patients Laryngoscope 2008;118:1862-7. • Pseudomonas who use eye makeup, and those who 6. Crew JR, Thibodeaux KT, Speyrer MS, et al. Flow-through instillation of hypochlorous acid in the treatment of necrotizing fasciitis. • Moraxella wear artifi cial lashes. The MGD Work- Wounds 2016;28:40-7. 7. McCulley JP, Shine WE. Changing concepts in the diagnosis and • Staphylococcus Epidermidis shop21 recommends eyelid cleansing • Escherichia Coli management of blepharitis. Cornea 2000;19(5):650-8. twice daily as a treatment starting at 8. Key JE. A comparative study of eyelid cleaning regimens in chronic • Methicillin-Resistant blepharitis. CLAO J 1996;22(3):209-12. 9. Romero JM, Biser SA, Perry HD, et al. Conservative treatment of 1 the earliest MGD stages, and men- Staphylococcus Aureus (MRSA) meibomian gland dysfunction. Eye Contact Lens 2004;30(1):14-19. tions the advantages of hypochlorous 10. Craig JP, Sung J, Wang MT, et al. Commercial lid cleanser outper- 1. Results from an in vitro laboratory study. forms baby shampoo for management of blepharitis in randomized, TheraTears® SteriLid® Antimicrobial Eyelid Cleanser acid as an important and effective in- double-masked clinical trial. Invest Ophthalmol Vis Sci 2017;58. E- and Facial Wash showed effi cacy in reduction of gredient in cleansing solutions. abstract 2247–B0014. colony forming units for eight common eyelid organ- 11. Geerling G, Tauber J, Baudouin C, et al. The international work- With the exception of blepharitis/ shop on meibomian gland dysfunction: report of the subcommittee on isms. Data was captured at 30 and 60 seconds. management and treatment of meibomian gland dysfunction. Invest MGD that is graded as trace, or trace Ophthalmol Vis Sci 2011;52(4):2050-64. 12. Anagnostopoulos AG, Rong A, Miller D2, et al. 0.01% Hypochlo- seconds, measured by an in vitro time to 1+, my fi rst-line therapy for grade 2+ rous Acid as an Alternative Skin Antiseptic: An In Vitro Comparison. kill assay.20 or greater starts with lid hygiene twice Dermatol Surg. 2018 Dec;44(12):1489-93. 13. Babior BM. The respiratory burst of phagocytes. J Clin Invest Tolerability: New hypochlorous acid daily with an eyelid cleansing solution 1984;73:599-601. 14. Albrich JM, McCarthy CA, Hurst JK. Biological reactivity of hypo- daily eyelid cleansers designed to have containing hypochlorous acid. In chlorous acid: implications for microbicidal mechanisms of leukocyte low toxicity and pH-balanced formulas addition, I also use a host of other myeloperoxidase. Proc Natl Acad Sci U S A 1981;78:210-4. 15. Clark RA. Modulation of the infl ammatory response by the neu- may prevent irritation of the delicate products mentioned in the DEWS II and trophil myeloperoxidase system. Adv Exp Med Biol 1982;141:207-16. 16. Slivka A, LoBuglio AF, Weiss SJ. A potential role for hypochlo- skin of the eyelids and eyelid margin. MGD Workshop recommendations. rous acid in granulocyte-mediated tumor cell cytotoxicity. Blood I have been very pleased with the 1980;55:347-50. Patient satisfaction: Rx-strength 17. Clark RA, Szot S. The myeloperoxidase-hydrogen peroxide-halide daily eyelid cleansers featuring non- results of new hypochlorous acid system as effector of neutrophil-mediated tumor cell cytotoxicity. J Immunol 1981;126:1295-301. irritating substances that are available products. Not only are they effective, 18. Friedman A, Cash K, Berman, B. (2013, January). Hypochlorous acid is anti-infl ammatory and immunomodulatory. Poster presented at retail stores offer the possibility of but they help improve daily eyelid hy- at the Winter Clinical Dermatology Conference, Kauai, HI. high patient satisfaction and compli- giene compliance because patients 19. Grice EA, Kong HH, Conlan S, et al. Topographical and temporal diversity of the human skin microbiome. Science. 2009 May 29; ance due to greater comfort and easi- look and feel better rapidly. Fortu- 324(5931):1190-92. 20. Odorcic S, Haas W, Gilmore MS, et al. Fungal infections af- er access to effective eyelid cleansers. nately, we have therapeutic options ter Boston type 1 keratoprosthesis implantation: literature review now such as the TheraTears® system, and in vitro antifungal activity of hypochlorous acid. Cornea. 2015 Dec;34(12):1599-605. A First in Daily Eyelid designed to offer more complete re- 21. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: Executive summary. Investigative Cleansing lief of dry eye symptoms for patients. Ophthalmology & Visual Science; March 2011;52:1922-9 An innovation helping eye care professionals to advocate for daily eyelid hygiene, TheraTears® SteriLid® » DEWS II Antimicrobial Eyelid Cleanser and Fa- The groundbreaking Dry Eye Workshop II (DEWS II) report cial Wash containing 0.01% hypochlorous acid is the fi rst eyelid cleanser to strongly advised that clinicians utilize newer, more effi cacious be FDA accepted as a medical device. hygiene solutions available on the market today to improve It has a rinse-free formula, eliminating patient outcomes and compliance when it comes to lid the need to clean away a residue, and hygiene, as opposed to more traditional strategies.3 refl ects patient-friendly pricing. In addition, the cleanser has a 24-month

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Reference: 1. Results from an in vitro laboratory study. TheraTears® SteriLid® Antimicrobial Eyelid Cleanser and Facial Wash showed effi cacy in reduction of colony forming units for eight common eyelid organisms. Data was captured at 30 and 60 seconds. M18-069-00

024_ro00919_TheraTears_RP_v4.indd 27 8/23/19 6:36 PM Dry Eye REVIEW Cover Focus Diagnosing Ocular Surface Disease

Sean McKinney, Senior Editor Elizabeth Yeu, MD Take this uidelines for how to diagnose and characterize ocular sur- systematic Gface disease have been available for years. Yet a 2019 survey by approach— the American Society of Cataract and Refractive Surgery found that many but prepare to surgeons don’t know the guidelines, even though they realize the disease individualize your can affect surgical outcomes.1 Figure 1. Expressing meibum in patients “I think most of us want to diagnose choices. with meibomian gland dysfunction can OSD accurately but, frankly, the dis- help remove bacteria and debris, as well as ease is more complex than a lot of us stimulate the glands. For a video show- realize,” says Kenneth Beckman, MD, ing Dr. Yeu performing meibomian gland a clinical assistant professor of ophthal- expression, visit vimeo.com/3555159648 mology at Ohio State University. Performing cataract surgery on patients with unrecognized OSD can Overview of Disease Subtypes lead to refractive errors, OSD exacer- bations and dissatisfaction with surgi- Dr. Beckman has co-authored two of cal outcomes.1,2 Signifi cant lid destruc- the fi ve major reports offering recom- tion3 can occur in nonsurgical patients, mendations on OSD and dry eye since and the disease can destroy more than 2017, including the ASCRS Cornea half of the meibomian glands of other- Clinical Committee’s 2019 consensus- wise healthy patients in their 20s. based algorithm for the preoperative OSD patients of all ages can develop diagnosis and treatment of OSD1 and photophobia, corneal scarring, inter- a “clinical guide” by the Cornea, Ex- mittent blurred vision, pain, limited ternal Disease, and Refractive Society ability to perform daily activities, re- (CEDARS) that combines the latest duced vitality, poor general health and, evidence-based approaches. Below is in many cases, depression.4,5 an overview of the fi ve key CEDARS’ Do you screen thoroughly enough disease subtypes: to spare patients these problems? Find • Subtype 1: Aqueous defi ciency. out how experts do so by balancing di- This primary manifestation is charac- agnostic protocols against the need to terized by a reduction in lacrimal gland respond to unique patient problems. secretions, which form the bulk of the

28 | Review of Ophthalmology | September 2019 This article has no commercial sponsorship.

028_rp0919_f1.indd 28 8/23/19 5:37 PM aqueous component of the tear fi lm. thalmology at the Bascom Palmer Eye Dr. Beckman says it may be caused Institute. “Individuals may report a va- by dysfunction or destruction of the riety of pain-related symptoms, such as lacrimal gland, or scarring and block- sensations of dryness, burning or ach- Elizabeth Yeu, MD Yeu, Elizabeth age of its ducts, which can prevent ing, or they can have visual complaints, secretions from reaching the ocular Figure 2. Example of moderately severe such as poor or fl uctuating vision. Dif- surface. Injury, surgery, systemic con- MGD with Grade 3 truncation and atrophy ferent disease subtypes may underlie ditions and topical agents can reduce of the meibomian glands in a patient’s right these symptoms.” corneal sensation, causing neurogenic eye. Getting a thorough history is criti- infl ammation that leads to decreased cal for a patient who complains of gland activity, he says.6,7 You’ll see a Syndrome/Co-conspirators. “The dry eyes. Besides using three lead- decreased tear lake, increased tear-fi lm term ‘co-conspirators’ refers to condi- ing questionnaires—SPEED, OSDI osmolarity and/or infl ammation.8,9 tions affecting the tear fi lm and ocular and DEQ5, all available online—ask • Subtype 2: Blepharitis/meibo- surface that may either exacerbate dry patients if their eyes are affected by mian gland dysfunction (evapora- eye or masquerade as dry eye,” says dry-eye symptoms, including pain, eye tive and nonevaporative). MGD can Dr. Beckman. These could include fatigue, light sensitivity, blurred vision, be asymptomatic or symptomatic.10 superior limbic keratoconjunctivitis, poor vision and night-time driving is- Symptomatic cases may be restricted medicamentosa, Thygeson’s superfi- sues. to the lids or be associated with MGD- cial punctate keratitis, mucus fi shing “I have a large dry-eye population, related OSD that includes evaporative syndrome, contact-chemical toxicity, and I fi nd a spectrum of patient com- dry eye, according to the CEDARS re- allergic/atopic conjunctivitis, conjunc- plaints and underlying fi ndings,” says port.11 “Insuffi cient meibum fl ow leads tivochalasis, ocular allergy and glau- Dr. Galor. “A basic clinical exam is still to an abnormal lipid component and coma drops. the most important thing we can do.” excessive tear evaporation,” says Dr. She checks blink rate, lid closure Beckman.6 “However, you may also Overlapping Manifestations of both lids, laxity and lid anatomy. see patients who have inflammation She evaluates TBUT, performs ocu- without tear evaporation.” Although subtyping can lead to an lar staining and probes for comor- • Subtype 3: Goblet cell defi cien- accurate diagnosis, Dr. Beckman and bidities, such as arthritis,13 Sjögren’s cy/mucin defi ciency. “This subtype others note that overlapping manifes- syndrome,14 diabetes,15 ocular aller- is based on goblet cell disease, causing tations will complicate your investiga- gies,16 depression and anxiety.17 Also mucin defi ciency,” says Dr. Beckman. tion. The following symptoms may be important: Ocular and systemic medi- “These patients may have experienced found in all of the subtypes: ocular cations. Antihistamines, beta blockers, a chemical burn, contact lens overwear, discomfort; dryness; burning; sting- antispasmodics, diuretics and some or have Stevens-Johnson Syndrome. ing; grittiness; foreign body sensation; psychotropic drugs reduce lacrimal se- Ocular medications such as glaucoma photophobia; and blurred or fl uctuat- cretion and may increase the potential drops may cause goblet cell loss, de- ing vision. Also, aqueous deficiency for subtypes of dry eye.18 Remember- creasing mucins.” Conjunctival tissue can overlap with blepharitis/MGD and ing that tear secretion rates decrease in can be destroyed. “Tears evaporate exposure-related OSD. Blepharitis/ the elderly is also important. too quickly,” he observes. “Typically, MGD can also overlap with goblet Dr. Yeu listens carefully to patients, evaporating tears make us think of lid cell defi ciency, which can additionally mindful that some experience more margin disease. But not all evaporative overlap with exposure-related disease. than one subtype and can be affected disease is lid margin disease.” “Individualizing your approach to by nerve damage, such as neuropathy • Subtype 4: Exposure. “Exposure every patient is critical,” says Elizabeth of the trigeminal nerve endings asso- affects patients who can’t completely Yeu, MD, a surgeon from Norfolk, Vir- ciated with diabetes or other corneal close their eyes,” says Dr. Beckman. ginia who teamed with Dr. Beckman manifestations.19 “They may be hyper- “They could have an incomplete blink and others to write the CEDARS re- esthetic or hypoesthetic,” she adds. from previous ptosis surgery, or a his- port. “There can be good concordance tory of Bell’s palsy, trauma, scarring of signs and symptoms of dry-eye dis- When To Test Tear Osmolarity and Parkinson’s disease. You may fi nd ease or there can be misalignment.” normal tear production and TBUT, but “Patients don’t always present Many doctors evaluate tear osmo- the tears don’t last between blinks.”12 with the same symptoms,” says Anat larity, a biomarker of ocular surface • Subtype 5: Dysfunctional Tear Galor, MD, associate professor of oph- health. The TearLab Osmolarity Sys-

September 2019 | reviewofophthalmology.com | 29

028_rp0919_f1.indd 29 8/23/19 5:37 PM 028_rp0919_f1.indd 30 30 bography). Dr. Galoralsouses meibomian glandmorphology(mei- LipiScan (Tear Science) toevaluate adjuvant imagingtestssuchasthe found ontheocularsurface. 9 (MMP-9),aninfl for thepresenceofmetalloproteinase relies onInfl ammaDry (Quidel)totest production viaSchirmer’s test.Shealso tear stabilityviaTBUT, andaqueous ticipants. Inherpractice,sheevaluates documents theosmolarityofstudypar- she valuesitinresearch,where testing inclinicalpractice,although for othercausesofOSDsymptoms.” tent normalosmolarityalertsustolook doesn’t ruleoutdiabetes.Butconsis- one-time normalbloodsugarreading ing doesn’t ruleoutdryeye,justasa he notes.“Aone-timenormalread- to treatment.“Osmolarityisvolatile,” molarity canhelpmonitorresponse differentiate bydiseasesubtype,os- ity,” hesays.Eventhoughitdoesn’t eye, osmolarityhelpsusgradesever- patients early. “Besidesidentifyingdry mOsm/L. instability, evenforreadingsbelow300 greater than8mOsm/Lalsoindicates instability). Adifferencebetweeneyes (stable) toabove340mOsm/L(severe range from300mOsm/Lorbelow tem measuresconcentrationsthat nicity ofapatient’s OSD,particularly into thepresenceandpotential chro- raphy. These fi ndings provideinsight sential toevaluateoninfraredmeibog- out, congestionandatrophyarees- Why Advanced Testing? present withinthecornea. and whetherinflammatorycellsare mary useistoevaluatenerveanatomy neal Module(HRT-RCM). Onepri- Retinal Tomograph withRostockCor- foscan CS4(Nidek)andHeidelberg confocal microscopy–boththeCon- In appropriate individuals, she uses Inappropriateindividuals,sheuses Dr. Galordoesn’t useosmolarity Dr. Beckmanusesthetesttotriage Dr. Yeu saysmeibomianglanddrop- REVIEW |

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ammation marker marker ammation Dry Eye Dry | September2019 in vivo vivo in

Kenneth Beckman, MD rescein reveals severe aqueousdeficiency. Figure stainingwithfl 3.Central corneal anti-infl ammatory inchroniccare. for acutecasesandasteroid-sparing infl will respondmorefavorablytoananti- has apositiveInflammaDryfinding tions. Dr. Yeu truststhatapatientwho clarify theetiologyandtreatmentop- often notenough.” one medicationforadiseaseprocessis enough, asisoftenthecase,because treatment they’vebeenreceivingisnot positive forMMP-9,thattellsmethe sis) orlifi tegrast (Xiidra).Ifthey’restill been treatedwithcyclosporine(Resta- MMP-9 ispositive,especiallyifthey’ve follow-up visit. and anInfl osmolarity testduringtheinitialvisit bursement issues,soIperformatear Dry duringthefi rst visitduetoreim- can’t testtearosmolarityandInfl patient tears,”shesays.“Igenerally molarity issues,soweobjectivelytest tients haveinflammatoryortearos- vide limitedinsights. referring primarycarepracticespro- diagnoses suggestiveofOSDbecause of themwithoutthebenefi evaluations. Dr. Yeu examinesmany she seesmanypatientsforsurgical forms 1,800cataractproceduresayear, the cracks.”Asasurgeonwhoper- may haveotherwise“slippedthrough in patientswhoareasymptomaticand Positive andnegativetestresults “It’s betterformetofi nd outiftheir “I needtodetermineifthesepa- ammatory drop, including a steroid ammatory drop, includingasteroid ammaDry testduringthe t ofprior amma amma uo- chalasis.” allergic conjunctivitisandconjunctivo- and comorbidities,includingMGD, can alsooccurinOSDmasqueraders recent study, anegativetearosmolarity demonstrated aftercompletingone Yeu. “AsChrisStarr, MD,andothers tient isnegativeforOSD,”addsDr. doesn’t absolutelymeanthatthepa- of suchapatient,Dr. Yeu checkslid ing effectevenafterfourdays ofuse.” mines, whichcanhaveanextremedry- doses ofBenadrylorotherantihista- have allergiesandmaybetakingdaily their tearfi pressing enoughmeibumtostabilize have MGDbecausethey’renotex- deficiency, whichoftenmeansthey “This symptomoftenhidesaqueous tients whoreportfluctuatingvision. dry eye.” you aregoingtomissawholelotof you’re goingstraighttothedye,then neal staining,”sheobserves.“Butif been toseekoutconjunctivalandcor- dry eye,thenextstephasclassically exam. “Ifpatientssoundliketheyhave performing athoroughocularsurface agnose OSDanddryeye,insteadof surface stainingasthesolewaytodi- ogists stillrelytooheavilyonocular Relying OnStainingToo Much? the MMP-9levelnormalizes.” the patient.You canseeovertimeif matories. Infl ammaDry helpsmonitor treat asaggressivelywithanti-infl of thisinflammatory marker, Imaynot test isnegative,refl ecting lowerlevels condition,” Dr. Beckmansays.“Ifthe going tothinkthisisaninfl no obvioussignsofdisease. on hispatients’status,evenifhesees uses Infl ammaDry togetaquickread patients’ tearosmolarityinitially, then “A negativeosmolaritytestresult Besides takingacarefulhistory As anexample,shedescribespa- Dr. Yeu believesmanyophthalmol- “If you get a positive MMP-9, you’re “If yougetapositiveMMP-9,you’re Dr. Beckmanalsodocumentshis 20

lm,” shesays. “Theymay ammatory ammatory am- 8/23/19 5:37 PM sŝƐŝƚ<ĂƚĞŶĂŝŶŽŽƚŚϱϵϲϰĂƚKϮϬϭϵ THE Shape OF THINGS TO COME

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RP0919_Katena.indd 1 8/13/19 12:07 PM 0028_rp0919_f1.indd 32 2 8 _ r p 0 9 1 9 _ f 1 32 poor sensationduetoaneurotrophic issue. Alternatively, ifapatienthas ity torefreshthetearfi out. “Ifapatientdoesn’t havetheabil- the pre-cornealtearfi mechanical elevationsthatbreakup ules, pterygiumandpingueculaareall membrane dystrophy, Salzmann’s nod- ing abnormalsurfacearchitecture. she adds. symptoms oftencreatesadisconnect,” quality. “Notunderstandingsignsand glands, telangiectasiaandsecretion ity, signsofnotching,cappingthe margin health,includingelastic- . i n Surface Disease Current Tests forDiagnosingandMonitoringOcular • Tear-fi • Corneal topography: Opticalcoherencetomography: • • In vivo • Infl Ocularsurface staining: • • Schirmer’s test: • Osmolarity testing: • Meibography: Either aloneorincombination, withOSD. apatient thesetestshelpdiagnose d

“Conjunctivochalasis,anterior She alsocautionsagainstoverlook- REVIEW d | prove discriminative ability for detecting dry eye. abilityfordetectingdry prove discriminative includebreakup timemeasurements)now the useoftheKeratograph, whichmayim- data. missingmiresorkeratometry phy mayshow orsubtleSalzmann’smembrane dystrophy nodulardystrophy. eyes, dry Invery topogra- refl ect anissuewithtearsorthepresenceofaconditionsuchasepithelialbasement meniscus. you determinewhetherthetearvolumeisreducedbynoninvasivelymeasuring Tomograph withRostockCornealModule(HRT-RCM). eye.and dry CurrentoptionsaretheConfoscanCS4(Nidek)andHeidelbergRetinal andassessgobletcellmucindeficorneal neuropathy ciency withOSD inpatients a cellularlevel. easyidentifiAllows ofconjunctivalgobletcells, cation helpingtodetect and infl cells, ammatory cornealnerves, keratocytes, andmeibomian glandstructureson eye. withOSDanddry inthetearsofpatients is consistentlyelevated disease. bulbar conjunctiva, tissueandcandetectearlysignsof stainsdeadanddegenerating of OSD. tothecornea. Fluoresceincandetectdamage LissamineGreen, tothe applied Offered byanumberofcompanies. oftheeyes. eyesorexcessivewatering dry test isusedwhenapersonexperiencesvery eye. 8 mOsm/Lwhencomparedtointhefellow than sistently above340mOsm/Landwhenanosmolarityreadinginoneeyeisgreater tear fi lm. The tearfi lm isunstablewhenosmolarity, abiomarkerofocularhealth, iscon- non-invasive objectivevisionfl measurements. uctuation 5M (Oculus). Also, theHD Analyzer and Tear Film Analzyer (Visionmetrics), whichprovide iew IIOcularSurfaceInterferometer(Johnson&Johnson Vision) andtheKeratograph mian glands

Focus Cover Review ofOphthalmology

3 2 ammaDry ammaDry (Quidel): lm breakuptime: confocal microscopy: in vivo Imaging study developed to directly visualize the morphology ofmeibo- developedtodirectlyvisualizethemorphology study Imaging Determinesiftheeyeisproducingasufﬁ cient amountoftears. This

. Brandsinclude andLipiV- theLipiScanDynamicMeibomianImager The TearLab OsmolaritySystemmeasuresosmolarityinapatient’s Dry Eye Dry lm,” shepoints Irregular miressuggestanirregularocularsurface, whichcould lm, thatisan Detects elevated levelsofMMP-9,Detects elevated aninfl markerthat ammatory Used with a slit lamp to diagnose andmeasuretheeffects Usedwithaslitlamptodiagnose Options forthistraditionaltest(usingfl uorescein tear-fi lm Helps detectchangesinthecornealepithelium, immune | September2019 Several commercially available OCTdevicescanhelp Several commerciallyavailable ease, Itypicallylookforrapid TBUT, Beckman says.“Forevaporative dis- eye isexposedbetweenthelids,” Dr. interpalpebral zone,whichmeansthe fi OSD suspect.“Ilookforaqueousde- sion, stainstheeyesofnearlyevery meibomian glandsfornormalexpres- checks lidmarginsandteststhe Staining Routinely Staining Routinely bate OSD.” be thesourceofproblemsorexacer- won’t reportanysymptoms.Thiscan component architecturally, thepatient ciency, suggestedbystaininginthe Dr. Beckman,whoalsoclosely camentosa,” he adds. camentosa,” headds. punctum, thepatientmayhavemedi- inferior medialstaining,leadingtothe ing oftenrefl says Dr. Beckman. junctiva butdon’t resultfromdryeye,” can causeinflammationofthecon- co-conspirators, thoseconditionsthat may promptmetothinkofsomethe conjunctivitis. “Superiorstainingalso superior entropion;andatopickerato- toconjunctivitis; infectiouskeratitis; conjunctival concretions;vernalkera- superior limbickeratitis;blepharitis; superior staining:fl chiasis. Otherpossibilitiesrelatedto lid forsignsofaforeignbodyortri- prompt youtolookundertheupper perior staining,forexample,should are worthusingasareference.Su- report showedstainingpatternsthat ting damaged.” the wayandinferiorcorneaisget- nea becausethelidsaren’t closingall shows aroundtheinferiorofcor- it’s acompleteblink.Stainingtypically quickly thepatientisblinkingandif in laterstages.Forexposure,Iseehow monly, we’llseeconjunctivalscarring goblet cell/mucindeficiency. Com- a markerofthatsubset.Icheckfor rent Tests forDiagnosingandMoni- just notonthesameday. (See“Cur- Yeu usesallavailable diagnostictests, and canmakeabigdifference.”Dr. ing orSchirmer’s areeasytodo,cheap Simple testssuchasosmolarity, stain- comfortable withwhatyou’redoing. everything. It’s moreimportanttobe Dr. Beckman.“You don’t havetodo sions. “We nowhavealotoftests,”says sary rigortoreachdefi diagnostics theyuseprovidetheneces- their preferences.Allofthemsaythe choices thatdependonavailabilityand day’s diagnostictechnologies,making Individualizing Diagnostics He notesthatwhileinferiorstain- Dr. BeckmansaystheCEDARS Our expertsusethelatestofto- ects exposure, “if you see ects exposure,“ifyousee oppy lid syndrome; oppylidsyndrome; nitive conclu- nitive 88/23/19 5:37 PM / 2 3 / 1 9

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RP0919_Lombart.indd 1 8/27/19 6:12 PM 028_rp0919_f1.indd 34 fi assessing thehealthofentire tear tion oftheglands.We nowknowthat leads topressureatrophyanddestruc- tion ofthemeibomianglands,which meibum. Pooregressleadstoconges- cess thatresultsfrompooregressof bomian glandisasecondarypro- dysfunction. a patient’s signifi cant meibomian gland gland architectureinthepresenceof But I’vealsoseenhealthymeibomian than halfoftheirmeibomianglands. olds withdestructioninvolvingmore OSD. I’veseen20-something-year- of meibumcontributesignifi congestion thatpreventexpression dropout,” shenotes.“Atrophyand progress foryears,causingsignifi insult tothemeibomianglandcan to befollowedovertime.“Signifi or thepatients’eyeswilldryout.” they canstartproducinghealthieroil, them. Theglandsneedtreatmentso meibomian glands.We trytosalvage almost likeacementcomingoutofthe You seeathickpastyoilthat’s become glands arelost,theydon’t regenerate. says Dr. Beckman.“Often,whenthese phy and,eventually, lossoftheglands,” mian glandovertime,leadingtoatro- young andoldpatients. how extensiveundetecteddiseaseisin offers imagesofglandsthatrevealjust For example,meibography(LipiScan) available topractitionersinthepast. phers thatprovideinsightsweren’t are scans,imagingstudiesandtopogra- went down.” dering treatmenttoseeiftheMMP-9 the patientbacksixmonthsafteror- topography. Whennecessary, Ibring I alsomonitorOSDonceayearwith she says.“I’lldotheInfl include osmolarityandmeibography, isn’t asurgicalreferralshouldalways An initialexamforanewpatientwho toring OcularSurfaceDisease”above.) 34 lm reallyrequiresus tounderstand

In general,destructionofthemei- Dr. Yeu agreesmeibographyneeds “You canseedilationofthe meibo- Among today’s diagnosticchoices REVIEW |

Focus Cover Review ofOphthalmology

Dry Eye Dry ammaDry test. cantly to to cantly | September2019 cant cant cant cant can even be misleading enough to take can evenbemisleadingenough totake present asirregularastigmatism, andit gly.’ An irregulartearfilmcanalso fi stead ofseeingsmoothrings,youmay observes. “Inthekeratometryview, in- map—that aredullormissing,”she as AtlasSimKvaluesonanelevation er miresandkeratometrydata—such mann’s nodulardystrophy.” membrane dystrophyorsubtleSalz- conditions suchasepithelialbasement with thetearfi lm orthepresenceof lar surface,eitherbecauseofanissue lar miressuggestsanirregularocu- good information,”sheadds.“Irregu- just theK-values,shenotes. evaluating themires’appearance,not images. Theviewsareimportantfor pography andfocusesonkeratometry bography, shealsoorderscornealto- Besidesmei- abnormal morphology. rescein toinvestigatethepresenceof may staintheocularsurfacewithfl us uncoverOSD,”saysDr. Yeu. She to completethoroughtestinghelp cataract andrefractivesurgeryneed how dotheexpertsreducerisk? that OSDcancomplicatesurgery. So candidates, managing OSDincataractsurgery Cataract Surgery Candidates Cataract Surgery meibomian glandhealthinparticular.” Kenneth Beckman, MD with pluggingofthemeibomianglands. Figure 4.Patientscandevelopsevere MGD nd miresthatarewarpedor‘squig- “For averydryeye,youmaydiscov- “The appearanceoftheringsyields “Patients whoarecontemplating With therecentASCRSreporton

1 more surgeons appreciate moresurgeonsappreciate uo- aggressively before me thattheywillmanagetheirdisease unless theymakeanagreementwith specifically arefractiveIOLoption, consider thesepatientsforsurgery, as microblepharoexfoliation.“Iwon’t terventional lidhygienetherapy, such omega-3 capsulesandprescribesin- the initialvisit.” preparation intwotofourweeksafter dry-eye treatmentandocularsurface weeks. Thisallowsforafollow-upof postpone thesurgeryforﬁ ve toseven with surgery, Ibegintreatmentand patients. “Iftheywanttoproceed sponse dependsonthegoalsofher on akeratoconus-likeappearance.” extremely satisﬁ ed withonefocalpoint incisions. Iwouldratherpatients be will alsonotdocorneallimbalrelaxing vision ofOSDpatients,”shesays.“I “These characteristicscandisturbthe light amidmultiplepointsofvision. reduce contrastsensitivityandscatter monofocals. PremiumIOLssplitlight, it heruseofIOLstosphericalortoric poorly toaggressivetreatmentwilllim- Meeting RefractiveChallenges treatment beforesurgery.” to seehowpatientswillrespond IOL dissatisfaction.It’s veryimportant of advice:“Prepareforextremepostop sively, Dr. Yeu offersthesebluntwords me toanyissues.” readings andmeibographyhelpalert Symptom questionnaires,topography about anysubtypeofOSDisthekey. counseling patientspreoperatively apy,” saysDr. Yeu. “Identifyingand sparing anti-inflammatoryther- such assteroids,orchronicsteroid- a shortcourseofacutetreatments, their procedures.“Theymayrequire may worsenthreetosixmonthsafter she says,notingthatOSDsymptoms Dr. Yeu oftenstartsthesepatientson After diagnosingOSD,Dr. Yeu’s re- Dr. Yeu saysanyOSDthatresponds If youdon’t treatpreopOSDaggres- (Continued onpage57) and after surgery,” 8/23/19 5:37 PM Patented MediBeads® are why Bruder is the

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RP0919_Bruder.indd 1 8/26/19 10:42 PM Dry Eye REVIEW Cover Focus Knowledge and Tech: Treating Dry Eye, 2019

Christopher Kent, Senior Editor

As our reating patients complaining of proval of Restasis. dry eye used to be a less-than- “In the past fi ve years, the focus has understanding Tsatisfying part of an ophthal- shifted again,” she says. “Now we’re mologist’s job; the problem wasn’t well much more aware of meibomian of the problem understood and treatment options gland problems, and we know that were limited. Today, that has changed pure aqueous tear defi ciency is a lot and options for dramatically. “Dry eye” is now under- less common than meibomian gland stood to be a complex issue with mul- dysfunction. In fact, meibomian gland addressing it tiple etiologies, and treatment options dysfunction and aqueous tear defi cien- for the different aspects of the disease cy occur together in more than 80 per- increase, patients are proliferating. But as the fi eld has cent of patients. The problem usually are benefi ting. expanded, the diffi culty of staying on starts as meibomian gland dysfunction; top of the latest developments has also over a period of decades, that causes increased. an aqueous tear defi ciency as well. Here, experts share the latest think- “Today we know that each compo- ing about the group of concerns com- nent needs to be addressed separate- monly labeled “dry eye” and offer ad- ly,” she adds. “As a result of this, we’re vice for helping these patients achieve trying to come up with better ways to true, long-lasting relief. diagnose meibomian gland dysfunction, and we now have better ideas Spotlight: Meibomian Glands about how to address the problem. Indeed, the majority of new dry-eye “In the old days, treating dry eye was treatments are focused on addressing just about supplementing inadequate meibomian gland dysfunction.” tears using over-the-counter artifi cial Christopher J. Rapuano, MD, direc- tears,” recalls Esen Akpek, MD, a pro- tor of the cornea service at Wills Eye fessor of ophthalmology and rheuma- Hospital and a professor of ophthal- tology at Johns Hopkins University mology at Sidney Kimmel Medical School of Medicine, and director of College at Thomas Jefferson Univer- the Ocular Surface Disease and Dry sity in Philadelphia, agrees. “I think Eye Clinic at the Wilmer Eye Institute about 80 percent of patients with ocu- in Baltimore. “Then came the idea lar surface disease have a component of treating inflammation to improve of meibomian gland dysfunction that the quantity and quality of tears; that should be treated,” he says. “Ignoring approach became popular with the ap- the meibomian gland problem—if it’s

36 | Review of Ophthalmology | September 2019 This article has no commercial sponsorship.

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RP0919_Imprimis.indd 1 8/13/19 1:33 PM Cover Dry Eye

REVIEW Focus Christopher J. Rapuano, MD there—is bad for patients and doc- so, the burning is still too much for tors.” some patients, so they stop.” Mark Milner, MD, FACS, an associ- In terms of adding other treatments, ate clinical professor at Yale University Dr. Milner says the CEDARS algo- School of Medicine, notes that doctors rithm can be helpful. (To learn more have always been aware of meibomian about the CEDARS algorithm, check gland dysfunction. “However, it was out “Three New Algorithms for Treat- underdiagnosed for years,” he says. ing Dry Eye” in the October 2017 is- “No treatments were approved for sue of Review.) “Let’s say you start your blepharitis, and getting insurance to patients on Restasis or Xiidra and they pay for compounded or non-approved Several years after LASIK, superfi cial come back 40 percent better,” he says. punctate keratopathy is present in this eye treatments was always diffi cult. over the central and inferior cornea. “If Schirmer’s is still low, you can plug “Today we have more ways to diag- them. If their meibomian glands are nose it, with devices that can image many ophthalmologists have reported still infl amed, you can do a LipiFlow, the meibomian glands and thermal that their dry-eye patients don’t always or Azasite off-label, or oral doxycy- pulsation devices like LipiFlow, iLux, seem to get relief from these drops. cline. If Schirmer’s is OK but there’s TearCare and eyeXpress that heat the Dr. Milner says he believes that this still an evaporative problem, you might lids and help you express the glands,” is partly because of a misconception need an over-the-counter vitamin A he says. “As a result, we’re starting to about the nature of dry-eye disease. ointment, used off-label, which may embrace this problem.” “Like glaucoma, dry eye often requires improve goblet cell health. Dr. Akpek points out that meibo- more than one treatment to resolve “The reality is, many patients need mian gland dysfunction is actually an the problem,” he says. “If a glaucoma two or three different treatments,” age-related problem. “It’s like wear and patient has a pressure of 27 mmHg he concludes. “When a doctor says a tear on your teeth as you grow older,” and needs to be at 17, one drop might dry-eye treatment wasn’t successful, it she says. “If you don’t take care of your only take him down to 22 mmHg. probably was—it just didn’t solve the teeth, you develop dental plaques and In that case, you wouldn’t stop the entire problem.” caries. Eventually, you lose your teeth drop; you’d add another drop. Another question that arises regard- and need dentures. The same thing is “In contrast, I think most doctors ex- ing Restasis and Xiidra is whether true with the meibomian glands; if you pect these anti-infl ammatory dry-eye they’re useful if the core of a patient’s don’t care for them, they stop func- drops to be a panacea,” he continues. dry-eye problem is meibomian gland tioning correctly and symptoms of dry “If you use Restasis or Xiidra and the dysfunction rather than aqueous defi - eye develop. Eventually the glands un- patient is 50 percent better, the prob- ciency. Dr. Milner says in his experi- dergo permanent atrophy. So patients lem isn’t that the drops aren’t working, ence, Restasis and Xiidra do help to need to be caring for their meibomian it’s that the patient needs more than address meibomian gland dysfunction, glands on a regular basis. one treatment. You might need to add although this use is off-label. “The in- “This idea of proactively taking care punctal plugs, and maybe Azasite for fl ammatory process in the meibomian of your eyes is kind of new,” she notes. the blepharitis, and maybe doxycycline glands is very similar to that in the lac- “In fact, patients should ideally have for the meibomian gland dysfunction. rimal glands,” he notes. “T-cells and home treatment modalities that keep “About 85 percent of my patients infl ammatory cells are part of the mei- the meibomian glands in good shape; have some success with Restasis and bomian gland disease process as well, they shouldn’t have to come to the Xiidra,” he says. “That means anything and recent evidence suggests these offi ce for frequent treatments. Hope- from mild success to ‘This is a miracle drugs can help.1 But since this use is fully, these home treatments will end drug.’ The other 10 to 15 percent will off-label, getting it covered by insur- up being more impactful than just do- say either that they didn’t improve, or ance has been diffi cult.” ing hot compresses with a rag.” that the side effects such as burning Dr. Rapuano has used Restasis to were so bad that they couldn’t tolerate treat meibomian gland dysfunction, Addressing Infl ammation it. We try to get around the burning and he agrees that it helps. “I don’t problem by having the patient refrig- think it works as fast as when it’s used Approved treatments such as Resta- erate the drops and/or use an artifi cial to treat aqueous defi ciency,” he says. sis and Xiidra have raised awareness tear 10 minutes before and after. We “It takes about three months to have of the importance of treating infl am- educate them about the burning, and a reasonable effect on aqueous defi - mation when managing dry eye, but we may use a steroid off-label. Even ciency, but it takes about six months

38 | Review of Ophthalmology | September 2019

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REVIEW Focus

for me to notice an improvement in Christopher J. Rapuano, MD place,” agrees Dr. Milner. “Many new meibomian gland dysfunction.” formulas are coming out, such as Al- lergan’s Refresh Optive Mega-3 tears, Restasis Plus Xiidra? which may help with MGD. Freshkote isn’t new, but it’s now being re-mar- Patients often ask Dr. Rapuano keted by Eyevance. The thing we like for assistance in deciding between a about Freshkote is that it’s preserva- treatment course involving Restasis tive-free, so it’s usable with contacts.” or Xiidra. “I say, ‘Restasis has been The presence of preservatives in around for 14 or 15 years. It has a very Moderate lissamine green dye staining can many of the products is an issue. “Even good track record. It works a little bit be seen on the conjunctiva nasally in this if you try to direct patients to preserva- more slowly, but it works very well. patient complaining of severe dryness, but tive-free drops, 99 percent of the time Xiidra’s the new kid on the block; it’s with minimal corneal fl uorescent staining. what they fi nd and end up using isn’t been around for a couple of years now. preservative-free,” says Dr. Rapuano. It tends to work a little faster, but it a practical concern: getting insurance “That can be a problem, because if has a little taste issue and it can blur to cover both drops. “Many patients they’re using preserved tears more your vision. Both products work very aren’t on both,” he says, “not because than three or four times a day, the pre- well for most patients, but both of the drugs wouldn’t work together, but servatives are probably causing some them can burn a little.’ I haven’t been because they can’t get coverage. Insur- of the ocular surface disease. In that as impressed with Xiidra for treating ance companies have no problem pay- case, the drops won’t help as much as meibomian gland inflammation, but ing for two or three glaucoma drops, the patient wants, and they may make it seems to relieve dry-eye symptoms but they won’t pay for two different the problem worse. faster than Restasis,” he notes. “That’s dry-eye treatments. That shows a lack “Patients with ocular surface issues the main thing going for it.” of understanding. should use preservative-free drops as Dr. Milner says that many dry-eye “We fi ght with the insurance compa- much as possible,” he says. “Likewise, experts have noted that Restasis and nies, using information from our charts if the patient has ocular surface disease Xiidra appear to be synergistic, al- showing that these patients are doing and is on multiple glaucoma medi- though there’s no published data to better on both,” he adds. “But it’s a cations—which many of our patients support this claim. “The drugs work on struggle. The insurance companies say are—you should try to get that patient different parts of the T-cell,” he says. they want to see a clinical trial show- switched to less-toxic glaucoma medi- “Many dry-eye specialists are now using the synergistic effect, and we don’t cations, or, ideally, preservative-free ing them concurrently, the way you have that so far. But in my opinion, glaucoma medications.” might use a steroid and a nonsteroidal these drugs do work together to help Dr. Milner notes that many surgeons together because they work on differ- patients, so we’re doing what we can to wonder why drops with preservatives ent parts of the infl ammatory process. get both medications covered.” should be recommended at all. “The I have hundreds of patients who will ITF guidelines published in 2006 tell you they got partial relief with one Artifi cial Tears proposed recommending preserved of the drops; then, when we added the tears for level-one disease, with non- other one, they got complete relief. Dr. Akpek says artifi cial tears are still preserved tears for levels two to four,” Furthermore, if we then take them off relevant. “For milder episodic cases of he says.2 “When asked, the task force one of the drops, they regress a little dry eye, artifi cial tears are therapeu- said that they included preserved tears bit. So they appear to need both. tic,” she says. “They can even cure the in level one because artifi cial tears are “We have those patients use both problem, as long as the inciting factor a billion-dollar industry, and it’s un- drops twice a day,” he adds. “I tell the has been eliminated. Unfortunately, by realistic to expect people not to use patient to wait 10 or 15 minutes be- the time most patients come to see us, preserved tears when they’re a big part tween the drops. If patients want to, they don’t have a mild case. Patients of that market. So, we just restrict our they can alternate—Restasis in the have already tried over-the-counter recommendation to level-one disease.” morning and at dinner, Xiidra at lunch drops. Some are using them every 10 and bedtime. But most patients just do minutes, which is wrong, because it Devices for Treating MGD them twice a day separated by a few disturbs the normal homeostasis of the minutes.” tear fi lm.” Dr. Akpek says she has a low thresh- Dr. Milner concedes that this raises “Artificial tears will always have a old for recommending an offi ce-based

40 | Review of Ophthalmology | September 2019

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meibomian gland procedure. “If a treatments. LipiFlow kick-starts the patient is already doing warm com- process by cleaning out the glands, but presses, and I’ve tried a combination you have to keep them cleaned out or of omega-3 acids and oral antibiotics they’re just going to clog up again.” for two to three months and the patient Dr. Rapuano notes that the cost of isn’t getting better, then I’d defi nitely LipiFlow has come down over the recommend one,” she says. “Of course years. “When we first got LipiFlow there are different options, and the about eight years ago, we charged treatment should be tailored to the pa- about $1,800 for two eyes,” he says. tient’s needs and the severity of mei- “Now we charge $650 or $700 for two bomian gland dysfunction. We usually eyes, which is less than half of the old combine multiple treatments. cost. I believe that’s mostly been pos- “Ironically, doctors often think that sible because the cost of the disposable these modalities don’t work,” she notes. parts has really come down.” “That’s because they’re using them “I think all of these devices work haphazardly. First of all, these are ex- well,” says Dr. Milner. “It comes down Accurate Autorefraction/Keratometry pensive instruments, so most people to doctor preference. The important will acquire just one. Then they keep thing is that this device does two things. using the same treatment on every sin- First, it has to heat the glands above gle patient, which is wrong. Do we use the temperature required for the solid insulin on every single diabetic patient? secretions to turn to liquid, the phase No. We try different options, in a step- transition temperature. Normally, mei- wise approach. That’s what we should bomian gland secretions are liquid at be doing with these patients. body temperature, but when the secre- “The second reason these modalities tions become abnormal, the secretions may not always work is that we don’t become solid at body temperature. have any guidelines to recommend Once that happens, you have to heat which treatment should be done for the lids up—usually to 108 degrees— which kind of fi nding, and how often to convert it back to liquid. Then, ei- Color LCD Screen they should be done, and what to do ther you or the device need to massage between treatments,” she continues. the glands to get the oils out. “Most dry-eye specialists do the same “The mistake doctors make,” he Focus Assist with Color thing on every single person despite adds, “whether they’re accomplish- Coded Guides different needs, different skin types, ing this with IPL, LipiFlow, iLux, different severity of meibomian gland eyeXpress, MiBo Thermoflo or the Children’s Mode with dysfunction and different etiologies of TearCare system, is that they fail to Melody and Colors meibomian gland dysfunction. Then keep the patient on an anti-infl amma- the treatment fails and gets a bad repu- tory drop so the oil glands can be main- Fast and Accurate tation. It’s not that it doesn’t work— tained at a healthy level with less in- Measurements we’re just using it incorrectly.” fl ammation. That’s important. So don’t Dr. Rapuano says he uses LipiFlow just clean out the glands; keep treating Perfect for Mobile Situations on some of his patients. “LipiFlow is them with the anti-infl ammatories and a safe and easy treatment, although it’s maybe Azasite or doxycycline as well.” somewhat expensive and not covered (Other tools that help address the Ergonomically Balanced by insurance,” he notes. “That’s why signs and symptoms of patients suffer- I put it pretty high up the treatment ing from meibomian gland dysfunction Flexible Positioning- stepladder. However, if a patient asks include devices such as BlephEx and Sitting, Standing, Supine about it, I explain how it works. NuLids that remove debris along the “It’s important to remember that it’s edge of the lashes; Cliridex, which kills More Information: [email protected] not a cure-all,” he continues. “It makes Demodex; and Ocusoft and Sterilid, things better, but it’s not a substitute for which help clean the surface of the hot compresses, ointments and other lids.)

036_rp0919_f2 (1) (1).indd 41 8/23/19 6:00 PM Cover Dry Eye

REVIEW Focus Mark Milner, MD, FACS Additional Factors That Trigger Dysfunctional Tear Syndrome derstand more Treatments than ever that neurotrophic ker- • Environment • Rheumatoid Arthritis Many other op- • Medications • Lupus atitis can play a tions are also avail- • Contact Lenses • Sjögrens signifi cant role in able: • Surgery • Graft vs. Host dry eye,” says Dr. • TrueTear. Dr. Irritation Milner. “In fact, Rapuano says several Infl ammation DEWS II added of his patients like the neurosensory the TrueTear device. component to “It defi nitely creates their definition tears,” he says. “The of dry eye. That Tear Defi ciency/ company also claims • Postmenopause validates the idea Instability that if you use it mul- • Meibomian Gland Disease that we need to tiple times a day it start looking at trains your tear-pro- sensation as well. ducing glands to produce more tears patients who have already tried many “This is actually a two-way street,” he on their own. things on the treatment stepladder. continues. “Dry-eye patients often be- “Not too many patients have taken This is toward the top of that steplad- come neurotrophic because the neural us up on using it,” he notes. “We tell der, but it’s easy and safe and often feedback loop breaks down as a result them about it, but it’s expensive and it successful. There are published papers of lacrimal gland infl ammation. That sounds unusual to some patients. Hav- that say it helps between 50 and 75 infl ammation causes a decrease in the ing said that, patients who have bought percent of patients. quality and amount of tears. Neuro- it and tried it have mostly really liked “In the past serum tears were hard trophic patients, who don’t have as it. Furthermore, if your symptoms are to get, but today, this option seems to much sensation, don’t blink as much, making you miserable, that out-of- be more readily available,” he adds. so they get dry eye. pocket expense may seem reasonable. “Still, it’s not for everybody.” “Now, however, we’re seeing a lot of So it could become more mainstream • Scleral lenses. Dr. Rapuano says new therapies that can help regener- in the future. So far, it’s not.” this is another treatment option he ate nerves,” he says. “One therapy in- • Serum tears. Dr. Rapuano says used to reserve for severe patients. volves placing an amniotic membrane serum tears seems to be gaining a little “The Prose lens is one of the original, on the cornea for several days. Two more traction as a dry-eye treatment. best ones,” he says. “Today there are recent studies [sponsored by Tissue- “You get your blood drawn, and it’s several different Prose lenses, and lots Tech] found an increase in corneal sent to a special compounding phar- of other scleral lens options. nerve density and corneal sensation— macy,” he explains. “They make tears “For patients with pretty advanced i.e., nerve regeneration—after put- out of your serum, freeze it and mail it ocular surface disease, a scleral lens ting [Tissue-Tech’s] Prokera amniotic to you. We think it probably helps with keeps a good tear coating on the eye,” membrane on the cornea for five or aqueous-defi cient blepharitis because he explains. “The tears are captured six days.3,4 That improvement can last it has anti-infl ammatory components, under the lens, all day long. The lens for nine months or more. [Dehydrat- but it’s not likely to do much for con- designs have gotten better and bet- ed amniotic membrane such as Kat- junctivochalasis, fl oppy eyelid or pem- ter, and more optometrists are fi tting ena’s AmbioDisk, is another option to phigoid.” them, so it’s more mainstream now. consider in such cases.] In addition, Dr. Rapuano notes that using se- It’s fairly expensive, including the fi t- Oxervate, from Dompe Pharmaceuti- rum tears requires effort, and it has ting, but it will last for years. Serum cals, was recently approved. It’s a re- to be repeated every several months. tears have to be recreated every sev- combinant nerve growth factor that “We used to save this option for severe eral months, for example, and the Tru- helps regenerate nerves.” patients, but now we’re offering it to eTear device requires the purchase of “Right now these treatments are patients who are simply very unhappy,” single-use components every month.” being used for neurotrophic kerati- he says. “It’s fairly expensive, and many • Nerve regeneration. An- tis patients,” he notes. “In the future, insurances don’t want to cover it, but other aspect of dry eye that’s now though, you might see some of them some patients fi nd it very helpful and possible to treat is loss of cor- become accepted as treatments for thank us for suggesting it. These are neal nerve function. “We un- dry eye.”

42 | Review of Ophthalmology | September 2019

0036_rp0919_f236_rp0919_f2 ((1)1) (1).indd(1).indd 4242 88/23/19/23/19 6:016:01 PMPM COMBO COMBINE WITH OUR UNIQUE STAND A Helpful Dry-Eye Model which causes an unstable tear fi lm; and oral medications that shut down your “In the end, dry eye is a carousel of lacrimal glands. These can cause an inflammation,” notes Dr. Milner. “I unstable tear fi lm, which leads to irrita- think of it as a cycle that has three parts. tion, which leads to infl ammation, and Eff ortless [See illustration, facing page.] Under- the cycle is underway.” standing this cycle leads to a much Dr. Milner explains that treatment instrument clearer understanding of treatment. always requires three key things. “The fi rst part in the cycle is irrita- “First, address the thing that’s trigger- positioning tion,” he explains. “If the eye becomes ing the cycle, if you know what it is,” he irritated, no matter what the cause, the says. “If the trigger is anterior blepha- result is an upregulation of T-cells and ritis, use antibiotics and lid wipes or lid production of cytokines; that leads to sterilizers. If the trigger is contact lens infl ammation, which is the second part wear, limit lens wear or change the fi t. of the cycle. That, in turn, leads to the If the trigger is glaucoma drops, get off third part of the cycle: tear defi ciency the drops or decrease the preservative. and instability. Inflammation shuts If the trigger is rheumatoid arthritis, down your lacrimal glands, and your get systemically treated. meibomian glands become infl amed. “Second, no matter what the trigger Goblet cells are lost. That causes an un- is, treat the infl ammation,” he contin- stable tear fi lm, with a decrease in vol- ues. “You won’t break the cycle until ume and quality. That then leads back you do this. That’s where Restasis, Xi- to the first part of the cycle—more idra, and the new Cequa [Sun Pharma] irritation. That leads to more infl am- come in. The third key thing is to treat mation, and the cycle continues. the problem chronically. Use multiple “The beauty of seeing the process medications if you need to, and treat this way is that a dry-eye problem can it for long periods of time. The CE- begin at any point in the cycle,” he DARS algorithm can help you decide continues. “For example, dry-eye trig- which specifi c tool and/or medication gers that jump onto the carousel at part to use as your treatment.” one by causing irritation could include smoking, contact lenses, pollution, top- A Treatment Stepladder Advanced ical medications like glaucoma drops, refractive surgery such as LASIK or Dr. Rapuano has what he calls ergonomics PRK, and cataract surgery. Irritants like “treatment stepladders” for the two these then lead to infl ammation, the main diagnoses he addresses—aque- next part of the cycle. ous defi ciency and blepharitis. “When “Other triggers can start the dry-eye a patient has aqueous defi ciency, the cycle by causing infl ammation fi rst,” he lowest level of the stepladder is what I continues. “These would include Sjö- call ‘situational dry eye,’ ” he explains. gren’s, graft vs. host disease, Wegener’s, “If a patient says his eyes get dry ev- rheumatoid arthritis, diabetes and so ery time he drives in his convertible, forth. These can cause infl ammation, artifi cial tears are fi ne. If a patient is leading to the next part of the cycle: using artifi cial tears more than three or tear defi ciency and instability. four times a day, I switch the patient to “The dry-eye cycle can also be start- preservative-free tears. If tear usage is ed at the point represented by part more frequent than that, I switch the three: tear instability,” he says. “These patient to a thicker preservative-free triggers can include menopause, be- artificial tear such as Celluvisc, and cause androgens, which are critical to may also start a tear gel at nighttime. tear production and meibomian gland “If the patient still has a problem, secretion, are decreased; rosacea, I’d prescribe Restasis or Xiidra,” he

036_rp0919_f2 (1) (1).indd 43 8/23/19 6:01 PM Cover Dry Eye

REVIEW Focus Christopher J. Rapuano, MD continues. “The next step would be “To make a more accurate assess- punctal plugs. Then I might try a short ment of the patient’s problem, some- course of steroids. Rarely, we use ban- times you can take simple steps to rec- dage lenses. Finally we move to more reate the stressed ocular surface that heavy-duty options, like the TrueTear bothers the patient,” she continues. device, serum tears or scleral lenses. “There are many ways to accomplish “To treat blepharitis we start with this. For example, you can ask the pa- warm compresses and lid scrubs,” tient to stare at something for several he says. “Next, we might try a spray minutes, by asking them to read and cleanser like the product Avenova. I fill out the symptom questionnaire. Lid margin irregularity and moderate also typically have the patient use an Or, you can check the corneal staining crusting can be seen in this eye with antibiotic ointment, such as erythro- chronic blepharitis, which caused corneal after IOP measurement. Numbing the mycin, at bedtime. You can keep mov- staining and foreign body sensation. ocular surface to take that measure- ing up the ladder and try Azasite gel ment will have the side effect of reduc- drops at night, although I’ve found tack that exact problem. ing blinking and tear secretion; that that product diffi cult to get these days. “In addition, we need to do all the will worsen the corneal staining from If that’s still not suffi cient, you can try key tests,” she says, “Schirmer’s, cor- baseline. Once you approximate the doxycycline or minocycline pills for neal staining, osmolarity, conjunctival corneal stress the patient is encounter- about six weeks, sometimes longer. staining and a good slit-lamp exam of ing in daily life, your measurements After that I’d try LipiFlow or IPL. the surface. We need to check for con- will refl ect the level of irritation that “In most cases I treat the patient junctivochalasis. If there really is an triggered the patient’s complaint.” for both types of problem, using op- aqueous deficiency, that can be ad- • Don’t try only one treatment. tions from both stepladders,” he adds. dressed by artifi cial tears, anti-infl am- “It’s easy to offer one treatment to a “Meanwhile, if you fi nd that the symp- matories, or other modalities such as dry-eye patient and then move on to toms are related to another issue such punctal plugs or serum tears. Patients other concerns,” notes Dr. Rapuano. as conjunctivochalasis, I’d treat every- with severe aqueous-defi cient dry eye “I think doctors feel more comfort- thing else first. If the patient is still may have Sjögren’s. Many dry-eye pa- able treating problems for which they symptomatic, I’d excise the chalasis.” tients will have meibomian gland dys- can offer a concrete solution. Further- function that needs attention. more, these are chronic conditions, Strategies for Success “The bottom line is that we have patients are often pretty miserable, to pay attention to what the patient and managing them can take up a lot of These tips can help you end up with is saying, correlate that to our ocular chair time. On the other hand, we have a happy patient: surface and tear-film findings so we a lot of treatment options we didn’t • Treat the right problem. Dr. understand the exact problem, and have even 15 years ago.” Akpek says this comes down to two then attack that,” she concludes. “Then • When deciding how to treat, things: Listening carefully to the pa- we need to try different treatment mo- think outside the box. “Right now tient’s complaint and doing a thorough dalities in a stepwise manner, and be we have Restasis, Xiidra and soon exam. “There are subtle differences creative, based on what we fi nd.” we’ll have Cequa,” notes Dr. Milner. among the different conditions that • Measure signs only after stress- “But when anti-infl ammatories aren’t may present as dry eye,” she notes. ing the ocular surface. “There’s a enough, doctors get frustrated: What “Some patients complain of lid red- myth that patient symptoms and clini- else can I do? Well, for one thing, there ness; some complain of discharge; cal fi ndings don’t correlate,” notes Dr. are a lot of great compounded medica- some complain of foreign body sen- Akpek. “On the contrary, there’s a per- tions you can use off-label. We’ve had sation; some complain of dryness or fect correlation—if you measure the great success with them. For example, burning. Foreign body sensation and signs under conditions similar to those the product Metrogel is a great treat- occasional excessive tearing could inthat are bothering the patient. For ex- ment for facial rosacea dermatitis. We dicate conjunctivochalasis rather than ample, when patients complain that order a compound of its main ingredi- dryness. If the patient complains of they can’t see, it’s not that they can’t see ent, metronidazole, into an ophthalmic itching and redness, the problem to write a check; if you listen, they’ll say preparation for posterior blepharitis might be Demodex, which can easily that they can’t see well long enough to or meibomian gland dysfunction, be- be eradicated. We need to listen care- read a book or do computer work. We cause it reduces infl ammation on the fully to the patient’s complaint and at- don’t test that in the clinic. meibomian glands and the lids just like

44 | Review of Ophthalmology | September 2019

036_rp0919_f2 (1) (1).indd 44 8/23/19 6:01 PM Metrogel does on the face. If a patient can’t tolerate oral doxycycline, we compound doxycycline drops. If you really want to help patients who aren’t getting relief with the obvious treatments, think outside the box.” • Make sure your patients understand that these are chronic conditions. “Some patients will do the ag- gressive treatment you’ve prescribed, but when they get relief they decide that they’re cured and stop the treatment,” says Dr. Rapuano. “You have to drum into your patients that this is a chronic condition that they’ll need to address their whole life.” • Let the patient know you’re in this for the long haul. “We need to let these patients know that we’re not going to throw in the towel if one treatment doesn’t work,” says Dr. Rapua- no. “Tell them that you’re going to try a treatment, and if it doesn’t work you’re going to keep trying options until you’ve improved their symptoms as much as possible. Patients want to know that you’re not going to give up on them just because something doesn’t work.”

Dr. Milner has financial interests with Allergan, Novartis, Shire, B+L, TearScience, Aldeyra, Eleven Bio- therapeutics, Ocular Sciences, Kala, Eyevance and Refocus Group. He’s a speaker and consultant for Allergan, Shire, TearScience, Dompe and Sun. Dr. Akpek has received research support from Allergan and W.L. Gore & Associates and is currently a consultant with Shire, Novaliq and Regeneron. Dr. Rapuano has consulted for Sun, Bio- Tissue and Shire.

1. Donnenfeld ED, Perry HD, Nattis AS, et al. Liﬁ tegrast for the treatment of dry eye disease in adults. Expert Opin Pharmacother 2017;18:14:1517-1524. 2. Behrens A, Doyle JJ, Stern L, Chuck RS, et al. Dysfunctional tear syndrome: A Delphi approach to treatment recommendations. Cornea 2006;25:8:900-907. 3. John T, Tighe S, Sheha H. et al. Corneal nerve regeneration after self-retained amniotic membrane in dry eye disease. J Ophthalmol 2017;6404918:1-10. 4. Morkin MI, Hamrah P. Efﬁ cacy of self-retained cryopreserved amniotic membrane for treatment of neuropathic corneal pain. Ocul Surf 2018;16:1:132-138. :LL\ZH[((6)VV[O

036_rp0919_f2074_rp0415_ttops.indd (1) (1).indd 77 45 000_rp1015_varitronics_half.indd 1 8/23/193/27/158/9/17 10:58 6:01 2:41 PM AM 088_rp0315_varitronics_frac.indd 1 2/9/15 2:23 PM Vitreoretinal Instruments REVIEW Feature The Latest in Retinal Surgical Instruments

Christine Leonard, Associate Editor

The design etina is a rapidly chang- says the Bi-Blade cutters are useful ing field,” says Rahul additions to the surgeon’s toolbox. and function of “RReddy, MD, in practice The Bi-Blade cuts backwards in Phoenix, pointing to the diabetes and forwards to achieve a cut rate vitrectomy cutters pandemic, which has been steadily of 15,000 cpm. With its perma- increasing surgeon caseloads. “As nently open port and 100-percent have come a we look to the future, what we want duty cycle, the Bi-Blade allows for is instrumentation that will allow us continuous aspiration and holding long way. Here’s to get good outcomes and be as ef- force and a consistent fl ow rate, he a look at some of fi cient as possible so we can help as says. Consistent flow is crucial to many patients as possible.” vitrectomy procedures, since fl uid the most recent Here’s a look at some of the newest acceleration is related to pressure offerings available in vitreoretinal sur- variations and stress on the retina.1 innovations. gical instruments and how they may Dr. Reddy says one advantage of improve patient outcomes. the Bi-Blade is its predictability. “When we’re working with instru- Stellaris Elite Bi-Blade mentation in the eye, it has to be very predictable,” he says. “We’re The newest addition to working with delicate tissues and Bausch + Lomb’s Stellaris Elite there’s no room for error. As we Vision Enhancement system is get closer to the retina, we want the 23-gauge Bi-Blade cutter. to know what those fl ow rates are Released in July, the 23-gauge doing, and we don’t want the ret- cutter joins its fellow 25- and ina to get into our port, which 27-gauge Bi-Blade cutters, could cause damage. introduced in March 2018, “When people talk about as the most effi cient option vitrectomy systems,” he in the Bi-Blade portfolio, continues, “they tend to according to the company. concentrate on a few con- Kevin Blinder, MD, profes- cepts such as fl uid effi ciency, sor of clinical ophthalmol- speed of vitreous removal ogy and visual sciences at and illumination. But I The Retina Institute, think what is just as Washington University important—if not School of Medicine, more important

46 | Review of Ophthalmology | September 2019 This article has no commercial sponsorship.

046_rp0919_f3_ija.indd 46 8/23/19 6:09 PM —is the idea of what I call ‘fl uidic a bit of a surprise to me. I wasn’t and pediatrics at the Bascom Palm- predictability.’ For me, that’s the anticipating that.” er Eye Institute. Dr. Berrocal is the biggest advantage of the Stellaris Dr. Blinder’s probe of choice is fi rst surgeon in the United States to Bi-Blade. I know exactly what it’s presently the 25-gauge Bi-Blade. use the 27G Ultra Short kit. “This going to do in every part of the eye. “I like the size, the effi ciency, and instrumentation allows us to move It’s not volatile at the tip like some the wide range of instrumentation around these very small eyes much of the other systems I’ve used, so available,” he says. “I also like the more effi ciently and without caus- I’m confi dent that I can get close to 27-gauge Bi-Blade, but I’m still ing complications.” the retina without complications oc- awaiting a few more additions to the DORC says the Ultra Short com- curring. It’s very predictable.” range of available accessories.” pensates for typical size-related Both Dr. Blinder and Dr. Reddy shortcomings of 27-gauge vitrec- point out that the Bi-Blade is not 27G Ultra Short tomy instruments with increased just for vitreous—it’s multifunction- light output and probe rigidity. “We al. For thick diabetic membranes, The 27G Ultra Short vitrectomy haven’t had instruments that are Dr. Blinder advises backing down kit (from DORC) was released in short and stiff in 27-gauge before,” the cut rate on the Bi-Blade or June of this year. It’s designed to she says. “It’s not only the vitrector dropping to the slow-cut mode so meet the challenges presented by and light pipe, but also the trocars. the cutter can function like a pair smaller eyes and to optimize mini- They’re shorter and valved per- of small-gauge intraocular scissors. mally-invasive procedures, says the fectly for sutureless surgery. The Dr. Reddy agrees, noting that us- company. The kit includes three only other short system out now is ing the cutter as scissors to treat probes, the One-Step cannula sys- 25-gauge, but it doesn’t come with surface pathology in the retina spares the cost of opening up another instrument. “We’ve come a long way with our instrumentation. We’re getting smaller and better and more effi- cient in general,” says Dr. Reddy. Dr. Reddy explains that with smaller-gauge surgery, “you’re less likely to have catch when you remove instruments from port sites. They also don’t leak as much, so there’s less need for sutures, which increases our effi ciency in the operating room and reduces complications.” Smaller gauges also reduce postoperative infl ammation, making for quicker visual recovery.2 He prefers the 27-gauge Bi-Blade for its effi ciency, but says choice of gauge often comes down to surgeon tem, the Shielded TotalView En- short trocars that are valved. One of preference and comfort. The intro- doillumination Probe, and an the greatest advances in vitreoreti- duction of the 23-gauge Bi-Blade 8,000 cpm two-dimensional cutter. nal surgery has been valved trocars. accommodates surgeons who are The probes have a 20- to 26-percent They’ve reduced iatrogenic breaks, used to 23-gauge cutters. shorter working length than stan- retina incarceration and supracho- “My issue with 27-gauge in gener- dard 27-gauge instruments. roidal hemorrhages. They’ve also al is that it takes longer to get rid of “It’s hard to fi t our regular instru- improved teaching, since they main- the vitreous,” says Dr. Reddy. “But ments in small eyes with the current tain intraocular pressure stability out of all the 27-gauge instruments diameters of the non-contact sys- during surgeon changes. And, if all I’ve used, the Bi-blade appears to tems,” says Audina Berrocal, MD, these things are true for adult eyes, be the most effi cient. That has been professor of clinical ophthalmology they are also true for the eyes of

September 2019 | reviewofophthalmology.com | 47

046_rp0919_f3_ija.indd 47 8/23/19 6:10 PM Feature Vitreoretinal Instruments REVIEW

babies and kids with formed vitre- that creates more friction, making “It’s a very powerful instrument,” he ous and thin sclerae that collapse it less likely to come out during sur- says. “Start off the vacuum at 200, easily.” gery. It creates a better chance at 250, 300 and increase proportion- Dr. Berrocal says that with larger- stability. A clever idea.” ally. You can still maintain a rea- gauge instruments in small eyes, sonable duty cycle with the lower closing the sclera can be challeng- Hypervit Dual Blade vacuum rate because the cut rate is ing. “The sclera is so thin that some- so high. times even after suturing, the eyes The Hypervit Dual Blade vitrec- “Be sure to check the intraocu- still leak,” she says. That’s where the tomy probe (Alcon), available in 25- lar pressure when you start using Ultra Short comes into play. and 27-gauge, was introduced in the Hypervit,” Dr. Singh adds. “The “It allows me to do sutureless vit- July for a commercial release that’s duty cycle is strong and you want rectomy and leave patients phakic,” planned for later this year. Its open to make sure you’re not cutting too Dr. Berrocal adds. “With this in- port and dual pneumatic cutting much vitreous too quickly or reduc- strumentation, I can work on babies allow for a cut rate of 20,000 cpm. ing the IOP too rapidly. Watch your and kids too. When I tried the new Rishi Singh, MD, a staff physi- IOP infusion to make sure it’s keep- system, I was able to do a traumat- cian and Medical Director, Clini- ing up with you.” ic retinal detachment repair and a lensectomy retinal detachment Hypersonic Vitesse repair in eyes that measure 24 and 25 mm without a problem. Reach- The Hypersonic Vitesse for the ing the nerve to elevate the hyaloid 23-gauge Stellaris Elite system wasn’t an issue.” (Bausch + Lomb) uses a piezoelec- Stiffer probes are another key tric ultrasound transducer to liquefy to successful small-gauge surgery, the vitreous at the port. The tip of notes Dr. Berrocal. “I didn’t come the hypersonic vitrector vibrates out of the eye with bent instru- at about 1.7 million vibrations per ments, and I was able to do anterior minute, creating smaller particles and posterior work without a prob- and less traction on the retina than lem.” traditional pneumatic cutters, the Dr. Berrocal says the 27G Ultra company says. Short doesn’t come with much of a The fi rst in-human study investi- learning curve. “It’s the same tech- gating the safety and performance nology but smaller,” she explains. “It of the 23-gauge Vitesse concluded fi ts better in these small eyes where that the hypersonic vitrector was there’s little room. It’s also safer, cal Systems Offi ce, at the Cole Eye effective in core vitreous removal especially for trainees.” Institute, says the Hypervit’s high in all tested cases and a “promis- As for the Ultra Short TDC cut rate lowers the “sphere of infl u- ing alternative” to current guillotine probe, whose 8,000 cpm is half that ence” on tissue, which allows sur- cutters.3 of the full-size TDC (16,000 cpm), geons to get close to tissue without Dr. Blinder has tested the new Dr. Berrocal says, “The TDC cutter much vibration or movement. “It’s vitrectomy system. “The Vitesse hy- is so effi cient that even at this small been helpful with dense vitreous personic vitrectomy (HV) technol- gauge I didn’t feel a difference from hemorrhages and tractional retinal ogy represents a new and innova- my usual 25- and 27-gauge surgery. detachments, where you want to tive approach to vitreous removal,” The illumination was also great. No get close to the retinal surface and he says. “HV received U.S. FDA difference.” For the trocar, how- avoid incarcerating tissue,” he says. 510(K) clearance in April, 2017, and ever, Dr. Berrocal notes, “The di- “The beveled tip also allows you to has had a limited release to a few ameter of the head of the trocar get much closer to the tissue. You surgeons in the United States and and the elevation of it could still be can use it like scissors.” other countries during an observa- smaller and fl atter.” Dr. Singh says there isn’t much tional trial period. We recently pub- One other thing she adds is that adjustment needed when fi rst using lished on our initial experience with “the metal of the trocars inserted in the Hypervit, but he recommends 64 patients in the United States.4 the sclera have a nonpolished part starting out at a low vacuum level. “The rationale behind the devel-

48 | Review of Ophthalmology | September 2019

046_rp0919_f3_ija.indd 48 8/23/19 6:10 PM SAVE THESE DATES

2ND YEAR OPHTHALMOLOGY RESIDENT WET LAB PROGRAMS 2019-2020 Residency Year

December 7-8, 2019 February 8-9, 2020 February 15-16, 2020 (Saturday-Sunday) (Saturday-Sunday) (Saturday-Sunday) Fort Worth, TX Fort Worth, TX Fort Worth, TX Course Director: Course Director: Course Director: Zaina Al-Mohtaseb, MD Jonathan Rubenstein, MD Derek DelMonte, MD

Dear Resident Program Director and Coordinator, We would like to invite you to review the upcoming 2nd-Year Ophthalmology Resident Wet Lab Programs for the 2019-2020 Residency Year in Fort Worth. These programs offer a unique educational opportunity for second-year residents. To better familiarize beginning ophthalmologists with cataract surgery, these programs will consist of both didactic lectures and a state-of-the-art, hands-on wet lab experience. Technology and technique will be explained and demonstrated and surgeons will leave better prepared to optimize outcomes and manage complications when they arise. The programs also serve as an opportunity for your residents to network with residents from other programs. After reviewing the material, it is our hope that you will select and encourage your 2nd Year residents to attend one of these educational activities, which are CME accredited to ensure fair balance. Sincerely, Zaina Al-Mohtaseb, MD, Jonathan Rubenstein, MD, and Derek DelMonte, MD

www.reviewsce.com/CSE2ndYr2019-20

For more information: Visit the registration site above or Email: [email protected] • Call: Denette Holmes 866-627-0714

Courses are restricted to 2nd-year residents enrolled in an ophthalmology residency program at the time of the course. There is no registration fee for this activity. Air, ground transportation in Forth Worth, hotel accommodations, and modest meals will be provided through an educational scholarship for qualified participants.

Satisfactory Completion - Learners must complete an evaluation form to receive a certifi cate of completion. Your chosen sessions must be attended in their entirety. Partial credit of individual sessions is not available. If you are seeking continuing education credit for a specialty not listed below, it is your responsibility to contact your licensing/certifi cation board to determine course eligibility for your licensing/certifi cation requirement. Physicians - In support of improving patient care, this activity has been planned and implemented by Amedco LLC and Review Education Group. Amedco LLC is jointly accredited by the Accreditation 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

JOINTLY ACCREDITED PROVIDERTM TM INTERPROFESSIONAL CONTINUING EDUCATION Credit Designation Statement - This activity has been approved for AMA PRA Category 1 Credits .

Endorsed by: Jointly provided by: Supported by an independent medical education grant from:

® REG Review of Ophthalmology (Review Education Group) Alcon Feature Vitreoretinal Instruments REVIEW

the transition from the lab setting Elite system. It offers a 40-percent to the operating room has been a increase of infusion fl ow compared smooth one.” to previous-generation infusion Dr. Blinder feels that HV has lines, says the company. a high potential for innovation. According to Bausch + Lomb, a Changing the port opening or curv- larger inner lumen coupled with ing the probe itself for use in pha- an infusion line going over the top kic eyes are just some of the pos- of the trocar cannula, rather than sibilities. Dr. Reddy explains that inside of it, reduces resistance and a curved vitrectomy probe is only makes the increased infusion fl ow possible with hypersonic technolo- possible. Additionally, the infusion gy, since there are no moving blades line extends off the top of the can- within the needle. He’s currently nula at a 30-degree angle, which working on a prototype for a curved provides better access to the eye probe. and direct infusion with less torque, opment of HV was to replace the “With the Vitesse technology, we says the company. tube-inside-of-a-tube technology don’t know what the limits are yet,” Sunir Garg, MD, professor of of the pneumatic cutters, simplify says Dr. Reddy. “I really think it’s ophthalmology at the Sidney Kim- the technology with a hollow tube going to be one of those stepping mel Medical College at Thomas and an open port, and make the stones in retina where we are able Jefferson University, attending notion of duty cycle obsolete,” he to do things more effi ciently than physician on the Retina Service at explains. “The initial animal model we’ve ever been able to do before, Wills Eye Hospital in Philadelphia, trials went well, and the human tri- so we’ll wait and see what happens and partner at MidAtlantic Retina, als subsequently have been success- with the Vitesse system.” says that having a higher fl ow rate ful.4,5 The low-power hypersonic vit- is great. “The Bi-Blade cutters re- rectomy probe has been utilized in FreeFlow Infusion System move vitreous effi ciently, and as a a wide variety of cases, ranging from result we’ve needed better flow,” a dropped nucleus to a rhegmatog- The FreeFlow infusion system he says. enous retinal detachment and re- for retina surgery (Bausch + Lomb) “The FreeFlow lies flat on the moval of intraocular silicone oil. It’s was launched in July for the Stellaris globe, which is different than what presently only available in 23-gauge, we’re used to,” Dr. Garg adds. “So it but there’s active research on the takes a couple of cases to get the hang smaller gauges of 25 and 27.” of it, but it works really nicely.” Dr. Blinder notes there’s a signifi cant learning curve and plenty Drs. Blinder, Reddy and Garg of new terminology to become ac- are consultants to Bausch + Lomb. customed to. “Stroke length is the Dr. Singh is a researcher for Alcon. amplitude of axial oscillation,” he says. “Varying the stroke length is 1. Rossi T, Querzoli G, Angelini G, et al. Introducing new vitreous cutter blade shapes: A fl uid dynamics study. one way to increase or decrease the Retina 2014;34:1896-1904. rate of vitreous liquefaction in the 2. Thompson JT. Advantages and limitations of eye. At the same time, the vacuum small gauge vitrectomy. Surv Ophthalmol 2011 Jan 14;56:2:162-172. [Epub ahead of print] parameter can also affect the egress 3. Stanga PE, Williams JI, Shaarawy SA, et al. First of vitreous out of the eye. in-human clinical study to investigate the effectiveness “These two parameters are con- and safety of pars plana vitrectomy surgery using a new trolled via the foot pedal in a dual hypersonic technology. Retina 2018 Oct 23:1-8. [PMID 30358763] [Epub ahead of print] yaw setting,” Dr. Blinder continues. 4. Blinder KJ, Awh CC, Tewari A, Garg SJ, Srivastava SK, “This concept is probably the most Kolesnitchenko V. Introduction to hypersonic vitrectomy. difficult one in transitioning from Curr Opin Ophthalmol 2019;30:133-137. 5. Bausch + Lomb announces completion of 100th the pneumatic vitrector. There’s clinical case using Vitesse hypersonic vitrectomy system also a pulse mode that can be used on Stellaris Elite Vision Enhancement System. Bausch + to assist in vitreous removal. Thus, Lomb. Oct 16 2018.

50 | Review of Ophthalmology | September 2019

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RP0919_BL Preservision.indd 1 8/13/19 12:04 PM EBMD REVIEW Feature

When and How to Treat EBMD Michelle Stephenson, Contributing Editor

hough epithelial basement Christopher J. Rapuano, MD Expert advice membrane dystrophy isn’t dif- Tﬁ cult to diagnose, deciding on on how to the proper course of treatment for the cases that warrant it can be a chal- approach a lenge. In this article, cornea experts review their approaches to manag- treatment plan ing these cases, and how the type and severity of symptoms play into their decision-making process. for the cases Figure 1. Signiﬁ cant central epithelial basement membrane dystrophy changes that warrant it. When to Treat can be seen in this eye, causing monocular “shadow vision.” Most patients with epithelial basement membrane dystrophy don’t these two main symptoms will often experience pain or visual symptoms complain of poor vision or ‘double and don’t require treatment, but vision,’” he notes. “The irregularities some cases will require your inter- can cause what I call ‘shadow vision,’ vention. Symptoms range from cor- because patients see an image with a neal erosion to pain and diplopia, shadow next to it, as opposed to two surgeons say. equally distinct images. In addition to “Epithelial basement membrane visual symptoms, this condition can dystrophy can manifest with a few also cause recurrent erosions. Pain different symptoms,” says Toronto’s from irregular, loose epithelium typi- Raymond Stein, MD. “It can interfere cally presents at nighttime or upon with vision when the abnormal epithe- awakening in the morning. This is be- lial basement membrane appears over cause epithelial basement membrane the pupil. The other, probably more dystrophy causes the epithelial layer common, symptom is that patients to not adhere properly. It can be pain- can have recurrent corneal erosions ful for just a few seconds after waking in which the epithelial cells slough off up or it can cause a big scratch on the from the cornea, causing severe pain.” cornea that can be painful for days.” Christopher J. Rapuano, MD, Chief Michael B. Raizman, MD, who is in of Wills Eye Hospital Cornea Service practice in Boston, says there is a third in Philadelphia, agrees. “Patients with reason to treat. “I also treat when the

52 | Review of Ophthalmology | September 2019 This article has no commercial sponsorship.

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References: 1. Medeiros FA, Meira-Freitas D, Lisboa R, Kuang TM, Zangwill LM, Weinreb RN. Corneal hysteresis as a risk factor for glaucoma progression: a prospective longitudinal study. Ophthalmology. 2013 Aug;120(8):1533-40. 2. De Moraes CV, Hill V, Tello C, Liebmann JM, Ritch R. Lower corneal hysteresis is associated with more rapid glaucomatous visual field progression. J Glaucoma. 2012 Apr-May;21(4):209-13. 3. Susanna CN, Diniz-Filho A, Daga FB, Susanna BN, Zhu F, Ogata NG, Medeiros FA. Am J Ophthalmol. A Prospective Longitudinal Study to Investigate Corneal Hysteresis as a Risk Factor for Predicting Development of Glaucoma. 2018 Mar;187:148-152. doi: 10.1016/j.ajo.2017.12.018. 4. Felipe A. Medeiros, MD and Robert N. Weinreb, MD. Evaluation of the Influence of Corneal Biomechanical Properties on Intraocular Pressure Measurements Using the Ocular Response Analyzer. J Glaucoma 2006;15:364–370.

RP0919_Reichert.indd 1 8/26/19 10:31 PM Feature EBMD REVIEW

would suggest that if you suspect an is irregular from a ‘lumpy bumpy’ epithelial basement membrane dys- cornea right in the center, you can trophy problem, but you really can’t try lubrication, which doesn’t usu- see it, put fl uorescein in and look for ally do very much,” he says. “Basi- negative staining. If there’s negative cally, you need to remove it. You can staining in the visual axis, then it do a simple epithelial debridement, Christopher J. Rapuano, MD Rapuano, Christopher J. could be causing visual symptoms. If where you just scrape off all of the there’s negative staining in a patient loose epithelium. This usually works with recurrent erosions, then that well. Sometimes, a microscopic ir- might be an area where they had a regular basement membrane is left Figure 2. Central epithelial basement mem- recent erosion,” he says. underneath the epithelium, and if brane dystrophy changes can be seen in you want to remove that, you can this eye, causing severe visual distortion. How to Treat use a diamond burr polisher. Usu- ally, I remove the epithelium, and basement membrane dystrophy af- Visual complaints can be treated then I sand down the cornea gently fects my ability to calculate a lens im- medically or by removing the af- for fi ve to 10 seconds. This removes plant power prior to surgery,” he adds. fected part of the epithelium. any part of the microscopic base- Dr. Rapuano adds that many pa- Dr. Raizman uses either a round ment membrane that’s there. Then, tients have asymptomatic epithelial blade, a spatula, a diamond burr I treat the patient with a bandage basement membrane dystrophy in or an excimer laser to remove the soft contact lens, antibiotic drops, the corneal periphery. “If they don’t epithelium down to Bowman’s layer. lubrication, ice packs for the pain have painful episodes, you don’t “If I’m removing the epithelium to and pain pills—which may include have to do anything about it,” he improve the quality of vision or to narcotics. Then, I’ll see patients the says. “But, once they have visual create a smoother cornea to allow next day and then a couple of days symptoms or recurrent erosions, more accurate keratometry read- later. Usually I’ll take the contact then we’ve got to go look for it. One ings prior to surgery, I prefer to use lens out on day four or fi ve, and the way to do this is to instill fl uorescein a round metal blade, and I scrape epithelial defect will be healed. But and then look for negative staining, off the epithelium without affect- then they still use ointment every where you put the fl uorescein in and ing Bowman’s layer,” he explains. “I night for three to six months, just to look with the cobalt blue light to see generally remove between 5 and 7 let the epithelium tack down.” where the mild lumpy bumpiness mm of the epithelium centrally. I re- For patients with recurrent cor- is lifting the epithelium up off the move a little bit more when I’m do- neal erosions, Dr. Stein says he tries cornea, and the yellow dye is kind ing this for lens calculations because medical management first. “Typi- of pulled off those areas. It basically the mid-periphery can affect my cally, we use hypertonic salt solu- highlights the epithelial basement keratometry readings. If I’m doing tions,” he explains. “For example, I membrane dystrophy problem. I it simply to let the patient see better, use a medication called Muro 128 then, depending on the size of his or (Bausch + Lomb), which comes in her pupil, sometimes I can get away both drop and ointment forms. It with removing just 4 or 5 mm cen- draws water out of the epithelium trally. Additionally, the basement and decreases epithelial swelling, membrane dystrophy is occasionally which results in a decrease in cor- associated with Salzmann’s nodules, neal erosions. That’s the mainstay of which are in the mid-periphery or treatment.”

Christopher J. Rapuano, MD Rapuano, Christopher J. even the periphery, and despite the Unfortunately, many patients nodules being out of the visual axis, have recurrent corneal erosions that they can disturb the tear ﬁ lm and start to interfere with their daily may affect the vision or the kera- activities. “It’s one thing to have an tometry measurement. So, I some- erosion once every six months, but if Figure 3. Fluorescein dye has been placed in the eye. When viewed with a cobalt times have to also remove nodules the erosions are occurring a number blue light, the negative staining pattern that are more peripheral. I also re- of times each month, and the pain becomes quite apparent, revealing areas of move those with the blade.” is persistent for 15 to 30 minutes or elevated epithelium. Dr. Rapuano agrees. “If the vision (Continued on page 57)

54 | Review of Ophthalmology | September 2019

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RP0819_Akorn.indd 1 7/11/19 11:13 AM Monthly MACKOOL ONLINE CME CME SERIES | SURGICAL VIDEOS

MackoolOnlineCME.com MONTHLY Video Series We are excited to continue into our fourth year of Mackool Online CME. With the generous support of several ophthalmic companies, I am honored to have our To view CME video viewers join me in the operating room as I demonstrate go to: the technology and techniques that I have found to be www.MackoolOnlineCME.com most valuable, and that I hope are helpful to 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. Episode 45: Richard J. Mackool, MD “Pupil Repair in a Patient As before, one new surgical video will be released monthly, with Recurrent Iritis” and physicians may earn CME credits or just observe the case. New viewers are able to obtain additional CME credit by reviewing previous videos that are Surgical Video by: located in our archives. Richard J. Mackool, MD I thank the many surgeons who have told us that they have found our CME program to be interesting and instructive; I appreciate your comments, Video Overview: suggestions and questions. Thanks again for joining us on Mackool Online CME. In this case I perform sutured iridoplasty to reduce the size of an CME Accredited Surgical Training Videos Now enlarged pupil using the Available Online: www.MackoolOnlineCME.com Siepser technique to alleviate debilitating glare in a pseudophakic eye with Richard Mackool, MD, a world renowned anterior segment ophthalmic recurrent iritis. microsurgeon, has assembled a web-based video collection of surgical cases that encompass both routine and challenging cases, demonstrating both familiar and potentially unfamiliar surgical techniques using a variety of instrumentation and settings. This educational activity aims to present a series of Dr. Mackool’s surgical 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: • perform an ab externo technique of iris suturing that can be used to repair iris deformities

Satisfactory Completion - Learners must pass a post-test and complete an evaluation form to receive a certifi cate of completion. You must listen to/view the entire video as partial credit is not available. If you are seeking continuing education credit for a specialty not listed below, it is your responsibility to contact your licensing/certifi cation board to determine course eligibility for your licensing/certifi cation requirement.

Physicians - In support of improving patient care, this activity has been planned and implemented by Amedco LLC and Review Education Group. Amedco LLC is jointly accredited by the Accreditation 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

JOINTLY ACCREDITED PROVIDERTM Credit Designation Statement - Amedco designates this enduring material activity for a maximum of .25 AMA PRA Category 1 INTERPROFESSIONAL CONTINUING EDUCATION 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 Glaukos In Kind Support: Review of Ophthalmology® medical educational grant from: MST Sony Healthcare Video and Web Production by: REG & (Review Education Group) Alcon Crestpoint Management Solutions JR Snowdon, Inc Carl Zeiss Meditec 4. Dry Eye Syndrome Preferred Practice Pattern, American Academy of Ophthalmology, 2018. (Continued from page 34) financial relationships with the fol- 5. Craig JP, Nelson JD, Azar DT3, et al, TFOS DEWS II Report with a monofocal IOL—distance, lowing companies: Allergan, Alcon, Executive Summary. Ocul Surf. 2017;15:4:802-812 6. Fiscella RG. Understanding dry eye disease: A managed care for example—instead of marginally TearLab, Takeda, Sun, Ocular Sci- perspective. Am J Manag Care 2011;17:S432-S439. 7. Stern ME, Schaumberg CS, Pfl ugfelder SC. Dry eye as a mucosal satisfied or unhappy with multiple ence, Eyevance, Kala Pharmaceuti- auto-immune disease. Int Rev Immunol 2013; 32:19-41. 8. Mishima S, Gasset A, Klyce SD, Baum JL. Determination of tear points of vision, especially after they’ve cals, eyeXpress, Johnson & Johnson, volume and tear fl ow. Invest Ophthalmol 1966:5:264-276. 9. Li DQ, Chen Z, Song XJ, et al. Stimulation of matrix invested in an elective upgrade. This Bruder, NovoLog, Bausch+Lomb and metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells. Invest Ophthalmol Vis Sci 2004; is a tough conversation to have, but it’s Dompé. Dr. Galor is a consultant to Al- 45:4302-4311. the most important part of diagnosing lergan, NovoLog and Dompé. Dr. Yeu 10. Donnenfeld ED, Solomon R, Roberts CW, et al. Cyclosporine 0.05% to improve visual outcomes after multifocal intraocular lens and managing these patients.” reports relevant fi nancial relationships implantation. J Cataract Refract Surg 2010;36:1095-1100. 11. Milner MS, Beckman KA, Luchs J. Dysfunctional tear syndrome: with Alcon, Allergan, Bausch+Lomb/ Dry eye and associated tear fi lm disorders–new strategies for diagnosis and treatment. Curr Opin Ophthalmol. 2017;Suppl 1:3-47. Being Prepared Valeant, Bio-Tissue, J & J Vision, Kala 12. Tsubota K, Nakamori K. Effects of ocular surface area and blink rate on tear dynamics. Arch Ophthalmol 1995; 113:155-158. Pharmaceuticals, Merck, Novartis, 13. The defi nition and classifi cation of dry eye disease: report of the Defi nition and Classifi cation Subcommittee of the International Dry By incorporating this sage advice Ocular Science, Ocular Therapeutix, Eye WorkShop (2007). Ocul Surf. 2007;5:2:75-92. 14. Begley CG, Chalmers RL, Abetz L. The relationship between into your practice and adopting new OcuSoft, Oyster Point Pharma, Sci- habitual patient reported symptoms and clinical signs among and old tests appropriately, you can enceBased Health, Shire, Sight Scienc- patients with dry eye of varying severity. Invest Ophthalmol Vis Sci 2003;4411:4753-61 minimize the often undetected but es, Sun Pharma, Surface Pharmaceu- 15. Yoo TK, Oh E.Diabetes mellitus is associated with dry eye syndrome: A meta-analysis. Int Ophthalmol 2019; May 7. [Epub deleterious effects of OSD on your ticals, Topcon, TearLab, TearScience ahead of print]. 16. Bielory L. Allergic conjunctivitis: the evolution of therapeutic patients. Your reward? Knowing that and Zeiss. options. Allergy Asthma Proc 2012;33:2:129-39. you’re following the latest guidelines 17 Wan KH, Chen LJ, Young AL. Depression and anxiety in dry 1. Starr CE, Gupta PK, Farid M, et al. An algorithm for the eye disease: a systematic review and meta-analysis. Eye (Lond). for diagnosing OSD and still retaining preoperative diagnosis and treatment of ocular surface disorders. J 2016;30:2:1558-1567 Cataract Refract Surg 2019;45:5:669-684. 18. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II epidemiology your individual practice style. 2. Epitropoulos AT, Matossian C, Berdy GJ, et al. Effect of tear report. Ocul Surf 2017;15:334-65. osmolarity on repeatability of keratometry for cataract surgery 19. Liu Y, Chou Y, Dong X, et al. Corneal Subbasal nerve analysis planning. J Cataract Refract Surg 2015;41:8:1672-1677. using In vivo confocal microscopy in patients with dry eye: Analysis 3. Rynerson JM, Perry HD. DEBS - a unifi cation theory for dry eye and clinical correlations. Cornea 2019; Jul 10. [Epub ahead of print] Dr. Beckman reports relevant and blepharitis. Clin Ophthalmol 2016;2455-2467. 20. Brissette AR, Drinkwater OJ, Bohm KJ, Starr CE. The utility of

(Continued from page 54) ithelium that’s really loose, and we’ll percent of patients don’t have recur- often use a diamond polisher to pol- rent erosions after that. The remain- longer, then the patients need ad- ish the surface of Bowman’s layer. ing 15 percent could still have some ditional treatment, which is typically This very quick procedure is fol- erosions, but, in most cases, they’re superficial keratectomy,” says Dr. lowed by instilling an antibiotic drop less severe and less frequent.” Stein. “In the operating room, with and a non-steroidal drop and then For recurrent corneal erosions, a lid speculum in place, under topi- fitting the patient with a bandage Dr. Raizman also tries a simple de- cal anesthesia, I use a Merocel spear soft contact lens, which we keep bridement ﬁ rst. “However, in my ex- and just touch the epithelium. If it’s in place typically for a few weeks. perience, that is only effective about loose, it comes off very easily. If the And with that treatment, there’s a 50 percent of the time,” he says. “I epithelium is normal, it’s quite ad- very high probability of permanent like anterior stromal puncture for herent. We basically take off the ep- success. We’ve found that about 85 erosions if the recurrent erosions

Raymond Stein, MD are out of the visual axis. I prefer not to do puncture in the visual axis because the puncture creates scars that can be permanent. While those scars aren’t often visually significant, they can be. Because the results are unpredictable, if there are erosions in the visual axis, I would prefer to use a diamond burr or an excimer laser to treat those. I think the excimer laser is safer because there is a more controlled removal Figure 4. Pseudokeratoconus in a patient with epithelial basement membrane dystrophy. of Bowman’s layer and a more uni- The irregular corneal epithelium induced topographic changes suggestive of keratoconus. form removal. The downside is that Epithelial debridement improved the topographic irregularity. (Continued on page 64)

September 2019 | reviewofophthalmology.com | 57

052_rp0919_f4.indd 57 8/23/19 7:03 PM Refractive/Cataract

REVIEW Rundown Edited by Arturo Chayet, MD

Hone Your Refractive Screening Process Follow these tips to safeguard corneal health while ruling candidates in or out. Sean McKinney, Senior Editor

voiding unexpected and unwanted the actual procedure itself,” asserts begin, however, Stanford University’s Aresults of refractive surgery can Kendall E. Donaldson, MD, MS, pro- Edward E. Manche, MD, prioritizes be just as important as striving to fessor of clinical ophthalmology, cor- the need to optimize the ocular sur- achieve ideal visual outcomes. More nea/external disease/refractive surgery face. “You have to make sure you’re surgeons are coming to appreciate at the Bascom Palmer Eye Institute in imaging an eye that’s healthy,” he says. this today. Miami. “I’m not suggesting that refrac- “The ocular surface needs to be pris- “I haven’t had a postop case of tive surgery, which needs to be care- tine, unaffected by meibomian gland ectasia in seven years,” says Scott fully learned and perfected, is easy. But dysfunction, evaporative tear disorder, MacRae, MD, director of refrac- you have to spend more time on preop punctate epithelial erosions or other tive services in the department of planning, evaluating all of the factors signs and symptoms of dry eye. Per- ophthalmology at the University of that could rule in or rule out surgery. form tomography and topography only Rochester. “This problem is so rare We spend a few hours providing our after you’ve treated any of these condi- because we’ve gotten to be so good fellows with instruction on surgical tions successfully. Sometimes, patients at screening these patients.” technique. But many more hours are are also affected by corneal warpage Dr. MacRae and other leading spent on preop preparation.” related to contact lens wear. If so, in- surgeons have learned that the key to Before preop screening can even struct them to not wear soft contacts steering clear of ectasia and oth- for a week before their screenings. er postop problems lies in how For torics, have them go two weeks they approach the initial preop or a month. For RGPs, defi nitely a visit—specifi cally, how well they month. And for Ortho K, several scrutinize the cornea, using cor- months are needed to get the corneal topography, keratometry, MD Scott MacRae, neas into normal shape.” pachymetry and old-fashioned Dr. Manche’s techs work up a examination techniques. Here, history on the patient to address they share strategies for selecting all issues. “We scan the patients, the right patients for surgery and and I try to correlate abnormali- the right surgical modality. ties with the scans,” he notes. “The way our clinic works, when Getting Involved Figure 1. This case of keratoconus, as shown on an I go in to see the patient, I want to Orbscan scan, is characterized by inferior steeping, do so with all of the data in front “Preparing for refractive surgery a crab claw appearance and a high posterior fl oat of of me. Otherwise, it doesn’t make is much more involved than doing more than 0.055 mm. for good fl ow.”

58 | Review of Ophthalmology | September 2019 This article has no commercial sponsorship.

058_rp0919_rcr.indd 58 8/23/19 3:54 PM Kendall E. Donaldson, MD, MS Custom Fit Screening Validation of Path- Finder II with an in- Dr. MacRae meets the preop chal- dependent data set has lenge by making sure he uses a screen- demonstrated greater ing instrument that best fi ts the needs than 90-percent sen- of each case. He relies frequently on sitivity, specificity and an Orbscan (Bausch + Lomb), which accuracy in detecting works well for many patients. But if normal versus abnor- a patient has astigmatism or presents mal corneas, he says. as a potentially complicated case, he Color-coding of Path- Figure 3. Note the contrast between the anterior topographic switches to a multi-modality Galilei Finder II parameters scan and the posterior scan, which shows signifi cant elevation. The fi ndings raise a red fl ag for a surgeon deciding (Ziemer Ophthalmic Systems), which also shows him when if refractive surgery is appropriate for this patient. he has access to at the Flaum Eye parameters are beyond Institute in Rochester. normal limits and may Dr. MacRae say he values the data contribute to specifi c classifi cations. Dr. MacRae uses the “60-percent from the posterior cornea the Gali- “I’m a data hound, so I will get rule” to ensure he has enough cor- lei provides. “But the most helpful placido disc readings from the At- neal thickness with which to work. part of the Galilei is that it has a to- las and the Pentacam,” he says. “The “At 600 mµ of corneal thickness, ric component, so that allows you to Pentacam tomography map shows for example, 60 percent would be compensate for patients with astig- anterior and posterior elevations. I 360 mµ. So you can do a fl ap that is matism,” he observes. “The posterior may see an indication of risk—that 100 microns deep. That means 140 fl oat on the Orbscan can’t be used to the patient is susceptible to ectasia, mµ would be the deepest ablation accommodate astigmatism, anteriorly for example—based on the fi ndings you could do with LASIK because or posteriorly, because it conducts a in the posterior area. In the Belin/ that would bring you to 360 mµ of best-fi t-sphere analysis. So with the Ambrosio Enhanced Ectasia Display residual tissue, or 60 percent of the Galilei, patients who would otherwise embedded into the tomographer, you corneal thickness. be excluded from consideration for can see the summary data. If there are Knowing this during screening can refractive surgery are now included.” abnormal posterior or anterior fi nd- help you determine whether to per- The Galilei also combines diverse ings, it can help determine if a patient form PRK or LASIK, depending on state-of-the-art technologies—such is not a candidate for surgery. On the refractive needs.” as placido topography, dual Scheimp- difference map, depending on the A high myope, such as -8 D, may flug tomography and optical biom- patient, you’ll see white (proceed), push him toward recommending etry—to offer a complete solution yellow (some posterior deviation) and PRK only, he says. “For a 450-mµ for refractive surgery planning. “All red (extreme risk of ectasia in the pos- cornea that’s perfectly symmetrical, measurements are included in one terior wall.) So the testing allows you patients are usually safe candidates if device,” he notes. “The device has to ensure safety and rule out a patient they need only 1 or 2 D of treatment,” also been found to be highly sensitive based on extreme risk of ectasia.” he notes. “These patients can usually and specifi c in detecting keratoconus do well with PRK. You don’t want to and forme fruste keratoconus.” Screening Principles overreact to the 60-percent rule.” Another basic principle to con- Probabilities and Validation Dr. MacRae recommends applying sider is making sure your corneal some basic principles when screen- topographer is at the right setting. Dr. Manche uses the placido-based ing all patients. “I do about 1,000 Dr. MacRae says some surgeons Atlas 9000 Corneal Topography Sys- refractive surgery cases per year,” choose a setting that’s too sensitive. tem (Zeiss) and Pentacam tomogra- he says. “We screen using the cri- “I set my Orbscan setting at 1 D,” pher (Oculus) when screening po- teria most people use. If the poste- he notes. “Others may put it at a tential refractive surgery candidates. rior fl oat is exceptionally high—more half of a diopter, thinking that’s bet- The Atlas includes PathFinder II cor- than 40 mµ on the Orbscan—that ter. Then, all of a sudden, they’ll see neal analysis software, which provides raises a red fl ag. For marked skew- these colors starting to stand out probabilities for five corneal condi- ing, asymmetry, or marked thinning on the scan. Some experts, such as tions by comparing topography ex- (less than 450 mµ), I’m concerned Steve Klyce, MD, recommend a set- ams to an extensive clinical database. about that from the beginning.” ting as high 1.5 D.”2

September 2019 | reviewofophthalmology.com | 59

058_rp0919_rcr.indd 59 8/23/19 3:55 PM Refractive/Cataract

REVIEW Rundown

so than the typical surgeon would in private practice,” she notes. “My experience can help all surgeons keep in mind what to look for, even if 90 percent of their cases are good candidates, such as a 30-year-old with a -3

Kendall E. Donaldson, MD, MS MD, Kendall E. Donaldson, D sphere. ODs do 75 percent of our screening, so we never see bad patients. But we need to screen further before deciding how to proceed.” Figures 4-A and 4-B. The white sections within the map on the left refl ect signs of dry Dr. Donaldson relies on corneal to- eye, while the map on the right shows an eye with a healthy tear fi lm. Your patient’s eyes should be free of dry eye before screening for refractive surgery. pography, corneal tomography, keratometry, pachymetry and a thorough Kendall E. Donaldson, MD, MS Figure 5. This patient exam when screening her patients. has anterior Here are some important consider- basement membrane ations she recommends keeping in dystrophy, which will mind: need to be resolved • Anterior elevation map. before screening for Con- surgery. The placido sider using keratometry to evaluate rings on the the shape of the cornea, looking for topographic map are astigmatism and symmetry. “The not intact, unlike the corneas should be symmetrical,” she round shapes found in says. “Any elevation steeper than 47.2 healthy eyes. D is a red fl ag. You need to investigate for keratoconus.” She also investigates when the manifest astigmatism in the patient’s ophthalmic lens prescription doesn’t match what she sees in topography. “The cause could be lenticular astigmatism,” she points out. “Or it could involve some other situation that would make us think twice before proceeding with a procedure.” • Posterior elevation map. “Again, we’re looking at the keratometry numbers and the shape—this time from the posterior perspective,” says Dr. Donaldson. “The posterior aspect should match the anterior aspect. Anything that doesn’t match is also a red fl ag for us.” • Pachymetry. “Any measurement of the cornea that is below 470 Figure 6. This map for the Pentacam Belin/Ambrosio Enhanced Ectasia Display shows an microns is a red fl ag,” says Dr. Don- elevated posterior fl oat that’s bowed inward, a sign of corneal weakness not detected on aldson. “We are also looking for thin placido scans that could lead to ectasia. A surgeon should opt for PRK instead LASIK or points. If the center of the cornea is SMILE in these cases. too thin or you fi nd thinness within a radius of 0.5 mm from the center, Tertiary Approaches a tertiary practice that receives many that should also raise a red fl ag.” refractive surgery referrals. “We ben- • Underlying pathology. “We Dr. Donaldson offers pointed preop efi t from insights on the many factors make sure we check for ocular screening advice based on her work in that might rule out surgery—more (Continued on page 73)

60 | Review of Ophthalmology | September 2019

058_rp0919_rcr.indd 60 8/23/19 3:55 PM nurtureTHEIR EYES

Take a fresh approach to treating dry eye symptoms with FRESHKOTE® Preservative Free (PF)

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© 2019 Eyevance Pharmaceuticals LLC. All rights reserved. FRESHKOTE® is a registered trademark of Eyevance Pharmaceuticals LLC. Novelia® is a registered trademark of Nemera Development. FPF-08-19-AD-24

RP0919_EyevanceFresh.indd 1 8/13/19 12:01 PM REVIEW Product News New Precision1 Contact Lens Debuts

n the coming year, you’ll be able to be available in a power range of Help for CyPass Patients Iprescribe a new daily disposable -12 D to +8 D, with a 14.2-mm diam- If you’ve got patients with Alcon Cy- contact lens, Precision1, that its man- eter and an 8.3 base curve. Precision1 Pass glaucoma stents in their eyes that ufacturer, Alcon, says is ideally suited will begin rolling out to select doctors need revision, Microsurgical Tech- to the fi rst-time contact lens wearer. in the United States in September, nologies says its new instrument, the Research cited by the company shows with widespread access anticipated 19g Ahmed Micro Stent Cutter, might that 20 percent of new wearers drop for early 2020. For information, visit be of use. out within the fi rst year, and 57 per- alcon.com. cent don’t inform their eye doctor when they do. New Prefi lled Syringe for To help, Alcon developed Preci- Afl ibercept Approved by FDA sion1 to negate what it identifi es as Regeneron Pharmaceuticals rec- the top three motivators of drop out: netly announced the U.S. Food and poor vision; poor comfort; and even Drug Administration approved the the frustrations that arise from poor Chemistry, Manufacturing and Con- lens handling. trols Prior-Approval Supplement for Precision1 uses a new silicone hy- the Eylea (afl ibercept) Injection pre- drogel mate- fi lled syringe. rial, verofil- The 2 mg, con A, and single-dose, Microsurgical Technologies’ new cutting includes a sterilized pre- instrument is designed to snip already im- permanently filled syringe planted CyPass Micro Shunts in an effort to possibly reduce endothelial damage related adhered ‘mi- provides phy- to the shunts. crothin’ (2 to sicians with 3 µm) layer a new way to of moisture. administer MST says that it developed the Alcon says this feature, which it calls Eylea that requires fewer preparation cutter in collaboration with Toronto SmartSurface, improves comfort and steps compared with vials. The com- surgeon Ike Ahmed, MD, and says supports a stable tear fi lm. The lens pany says that it expects the prefi lled the unique design of the instrument has a water content of 51 percent at syringe to be available to physicians enables surgeons to approach a micr- the core and greater that 80 percent this year. stent coaxially, grasp and trim a stent at the anterior surface. For information on the prefilled in a single step using only one hand The company says the lens will syringe for afl ibercept, visit https://in- and make a clean cut of the stent’s be designed to be a mid-tier op- vestor.regeneron.com/news-releases/ proximal end. tion between its Dailies Aqua Com- news-release-details/fda-approves- For information on the new cutting fort Plus and Dailies Total1 lines eylear-afl ibercept-injection-prefi lled- instrument, visit https://microsurgical. of contact lenses. The lens will syringe. com/.

62 | Review of Ophthalmology | September 2019 This article has no commercial sponsorship.

062_rp0919_products.indd 62 8/23/19 6:13 PM RP0919_Topcon.indd 1 8/21/19 11:12 AM 0052_rp0919_f4.indd 64 5 2 _ r p 0 9 1 9 _ f 4 case, Istriptheepithelium offand totherapeutic keratectomy. Inthat then youcandoexcimerlaser pho- the corneaduetomultipleerosions, some scarringontheanteriorpartof expensive. However, ifyou’vegot faster, easiertoschedule,andless tive astheexcimerlaserandmuch burr, whichIfindtobeaseffec- he says.“Iusuallyusethediamond tectomy, butIdon’t usuallydothat,” cimer laserphototherapeutickera- treatment. “You canperformex- Rapuano prefersadiamondburr laser,” hesays. equally aseffectivetheexcimer the medicalliterature,it’s probably with thediamondburr, butfrom personally haveenoughexperience with asingletreatment.“Idon’t for resolvingtherecurrenterosions laser is90to95percenteffective fective inthesecases,theexcimer bridement isabout50-percentef- can’t affordit.” the excimerlaserorforpatientswho surgeons whodon’t haveaccessto safely, soit’s oftenagoodchoicefor practical, andit’s nothardtouseit should emphasizetheburrisquite patient’s visionsometimes.ButI irregular astigmatismandaffectthe some stroma,andthatcancreate areas thanothersorevenremove more ofBowman’s layerinsome too aggressively, youcanremove ues. “However, iftheburrisused ofﬁ sive, simple,andeasytouseinthe the patient. the laserthathastobepassedon there’s acosttothesurgeonuse patients havetopayoutofpocket; surance usuallywon’t payforit,so the laserismoreexpensive,andin- 64 (Continued frompage57) . i n d

For recurrenterosions,Dr. Dr. Raizmanaddsthatwhilede- “The diamondburrisinexpen- REVIEW ce setting,”DrRaizmancontin- d |

Review ofOphthalmology

6 Feature 4

EBMD | September2019 Often, thebestwayisuse offl terested inlaservisioncorrection. dystrophy inpatientswho arein- of epithelialbasementmembrane So, it’s importanttoruleoutcases and thehealingcanbeverydelayed. slough offduringtheprocedure, have LASIK,theepitheliumcan lium thatgoesundetected,andthey he says.“Iftheyhavelooseepithe- better offhavingPRKthanLASIK,” membrane dystrophy, theyarefar patients haveepithelialbasement outcome ofrefractivesurgery. “If can haveasignifi condition areasymptomatic,butit dystrophy. Most patientswiththis for epithelialbasementmembrane surgeons shouldalwaysbelooking pretty uniformly.” cimer isthatitwillpolishabigarea laser. Thenicethingabouttheex- burr topolishit,Iusetheexcimer then, insteadofusingadiamond Pearls the recurrenterosions debridement isabout effective forresolving According toDr. Stein,refractive that whileepithelial 50-percent effective, the excimerlaseris with asinglelaser 90- to95-percent Dr. Raizmansays treatment. cant impactonthe u- patient’s postopneeds.” on everypatient.Itdependsthe datory, soitdoesn’t havetobedone cornea. Mypointisthatit’s notman- a debridementpriortomeasuringthe outcome, thosepatientsshouldhave are lookingforaspecificrefractive best possibleuncorrectedvisionand lations. Butforpatientswhowantthe debridement priortoyourIOLcalcu- phy, there’s notreallyareasontodo by thebasementmembranedystro- if thevisionisn’t signifi ter cataractsurgery. Andinthatcase, ing forthebestuncorrectedvisionaf- he says.“They’renotnecessarilylook- wearing glassesaftertheirsurgery,” often saythattheydon’t reallymind a littlebitirregular. “Thesepatients because thekeratometryreadingsare treatment priortocataractsurgery basement membranedystrophyfor ferred alotofpatientswithanterior ening.” these patientsdon’t needcornealstiff- of thecorneaistotallynormal,and require cornealcross-linking.Therest trophy,” saysDr. Stein,“andtheydon’t epithelial basementmembranedys- marginal degenerationbutisinfact tify thatit’s notkeratoconusorpellucid very importantthatthesurgeoniden- ectasia orpseudokeratoconus,andit’s tions. “Thesepatientscanhavefalse dystrophy canalsomimicothercondi- tory ofcornealerosions. need toaskaboutpatients’pasthis- He addsthatallLASIKsurgeons basement membranedystrophy.” That’s verysuggestiveofepithelial breakup infocalareasofthecornea. the slitlamptolookforabnormal orescein dyeandabluelightusing mentioned. mentioned. in anyoftheproductsorprocedures the articlehaveafinancial interest Dr. Raizmanadds thatheisre- Epithelial basementmembrane None ofthephysiciansquotedin cantly affected cantlyaffected 88/23/19 5:41 PM / 2 3 / 1 9

5 : 4 1

P M Research Review REVIEW

Interrupting Diabetic Retinopathy Treatment

esearchers report increasing inthat 77 percent of eyes lost ≥3 lines of the fi ndings: Rterest in anti-VEGF therapy for visual acuity on the Snellen chart, with • The EBMD group (26 eyes). treating proliferative diabetic reti- 46 percent of eyes having a fi nal visual The difference in K measurements nopathy, since anti-VEGF therapy acuity of hand motion or worse. before and after intervention showed a has been shown to be noninferior Though studies have shown closely- mean K value increase (p<0.001). For to panretinal photocoagulation, the monitored anti-VEGF therapy is ef- biometry, the predicted IOL spherical heretofore standard treatment for fective, especially for ischemic diabetic power closest to a spherical equiva- achieving regression and stabilization retinopathy and PDR, the study au- lent of zero (p<0.001) changed in 21 of PDR. Their study shows, however, thors conclude that these controlled of 26 eyes (8=0.5 D; 9=1.0 D; 4>1.0 that interruptions in anti-VEGF treat- studies may give false assurance be- D). For toric IOL-eligible eyes, there ment for PDR can result in marked cause anti-VEGF therapy is unable was a mean predicted cylinder power progression of disease and potentially to reverse retinal ischemia or fully ad- change of 1.2 D; recommended toric devastating visual consequences. dress diabetic retinopathy. Addition- power changed for 16 of 24 eyes. In a retrospective, multicenter case ally, the real-world situations faced by • The SND group (13 eyes). The series, researchers analyzed 13 eyes of diabetic patients lead to interruptions difference in K measurements before 12 patients with type 2 diabetes, aged in treatment that negatively affect out- and after intervention showed a mean 57 ±10 years. To refl ect real-world con- comes. K value increase (p=0.023). For biom- ditions in which diabetic patients tend J Ophthalmol 2019;204:13-18. etry, the predicted IOL spherical pow- Wubben TJ and Johnson MW. For the Anti-VEGF Treatment to “underuse eye care services and are Interruption Study Group. er closest to a SE of zero (p<0.041) prone to signifi cant losses to follow-up” changed in 11 of 13 eyes (3=0.5 D; because of illness, fi nancial hardship 3=1.0 D; 5>1.0 D). For toric IOL- or noncompliance, the study sample Impact of EBMD and SND on eligible eyes, there was a mean pre- included only those patients who were Biometry Measurements dicted cylinder power change of 1.5 D; temporarily lost to follow-up and treat- In a retrospective case series, re- recommended toric power changed ed exclusively with anti-VEGF therapy searchers from Duke University for 10 of 11 eyes. for either PDR or nonproliferative dia- analyzed 39 eyes of 30 patients who The researchers conclude that betic retinopathy, with or without dia- were evaluated for cataract surgery EBMD and SND have signifi cant ef- betic macular edema. with documented evidence of Salz- fects on biometry measurements and Baseline disease characteristics, mann’s nodular degeneration (SND) IOL calculations, and that optimizing cause and duration of treatment inter- or epithelial basement membrane dys- the ocular surface and being aware ruption, resulting disease progression, trophy (EBMD) and who were also of the effects of these conditions are complications and outcomes were as- scheduled for surgical intervention for important steps in planning cataract sessed. Reasons for treatment hiatus corneal irregularities before cataract procedures. (median: 12 months) included inter- surgery. The study found that SND J Cataract Refract Surg current illness (31 percent), noncom- and EBMD can adversely affect kera- 2019;45:1119-1123. pliance (31 percent) and fi nancial is- tometry and biometry measurements Goerlitz-Jessen MF, Gupta PK, Kim T. De Salles MC, Amrén U, Kvanta A, and Epstein DL. sues (15 percent). The authors report for IOL selection. Here are some of

This article has no commercial sponsorship. September 2019 | reviewofophthalmology.com | 65

0065_rp0919_rr.indd65_rp0919_rr.indd 6565 88/23/19/23/19 5:005:00 PMPM Glaucoma Management

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

What We’re Learning From the PTVT Study The Primary Tube vs. Trabeculectomy Study is revealing useful data regarding tubes versus trabs in virgin eyes.

Steven J. Gedde, MD, Miami

laucoma surgery is generally Comparing Tubes and Trabs dertaken to provide that data. It’s an G undertaken when medical therapy investigator-initiated trial designed and appropriate laser treatment fail Glaucoma specialists continue to to compare the safety and efﬁ cacy of to produce adequate intraocular have different opinions regarding trabeculectomy with mitomycin-C to pressure reduction. In recent years, the best surgical approach for tube shunt surgery, when performed the options for surgically managing patients with medically uncontrolled as an initial procedure in eyes that glaucoma in that situation have great- glaucoma. Medicare claims data haven’t had previous incisional ocular ly expanded with the introduction of indicate that tube shunts are in- surgery. the new “minimally invasive glaucoma creasingly being used as an alter- surgeries,” or MIGS. But despite be- native to trabeculectomy. Surveys Study Design ing known for their excellent safety of the American Glaucoma Society profile, MIGS haven’t replaced the membership have also demonstrated The design of the PTVT Study is traditional glaucoma surgeries— a growing preference for tube shunts similar to that of the Tube Versus trabeculectomy and tube shunt im- over trabeculectomy in many clinical Trabeculectomy (TVT) Study, an plantation. That’s true because tube scenarios. earlier trial that enrolled patients shunts and trabeculectomies are still One clinical situation that’s part of with prior cataract extraction and/or the most effective ways to achieve the this debate is whether a tube shunt failed filtering surgery. In contrast, very low IOP that’s required for some or trabeculectomy is preferable the PTVT Study recruited patients patients. when operating on a “virgin” eye that without prior incisional ocular sur- However, having two surgical op- hasn’t undergone previous incisional gery. Participants in the PTVT Study tions that are capable of producing surgery. In the most recent AGS were 18 to 85 years old, with IOP very low pressures has caused some survey, trabeculectomy has remained ≥18 mmHg and ≤40 mmHg on max- surgeons to wonder whether one the most popular option as an initial imum tolerated medical therapy. might be superior to the other in procedure for eyes with POAG, but The vast majority of the subjects had different surgical situations. Here, a growing number of glaucoma sur- primary open-angle glaucoma, and I’d like to share some of what the geons prefer the use of tube shunts as there were no signiﬁ cant differences Primary Tube vs. Trabeculectomy an initial glaucoma procedure. Until between baseline demographic and Study is revealing about performing now, however, this surgical choice was ocular characteristics of the groups. these procedures on eyes that have being made with limited data. Reasons for exclusion included not undergone previous incisional The Primary Tube Versus Tra- a narrow anterior chamber angle; ocular surgery. beculectomy (PTVT) Study was un- secondary glaucomas such as neo-

66 | Review of Ophthalmology | September 2019 This article has no commercial sponsorship.

066_rp0919_gm.indd 66 8/23/19 3:44 PM PTVT Study: Summary of Findings at Three Years

IOP reduction IOP reduction was greater in the trabeculectomy group at all time points, and fewer adjunctive medications were required to achieve this. Rate of surgical failure The tube group had a higher failure rate at one year, but no signifi cant difference between the groups was seen at three years. Reasons for failure In both groups the most common reason for treatment failure was insuffi cient IOP reduction. Failure because of a need for additional glaucoma surgery was more common in the tube group, while hypotony failures occurred exclusively in the trabeculectomy group. Risk factors for failure Lower preoperative IOP was predictive of failure, especially in the tube shunt group. Medical therapy The tube group required more adjunctive glaucoma medications postoperatively. Complications Many postoperative complications were observed in both groups, but most were self-limited. More complications occurred in the trabeculectomy group, especially during the fi rst month after surgery. Postoperative interventions Postoperative interventions were performed with similar frequency in both groups. Visual acuity No signifi cant difference in visual outcomes were seen between the groups. Cataract formation Cataract progression occurred at a similar rate in both groups.

vascular, uveitic, iridocorneal en- other parts of the procedure, such recommendations from the World dothelial syndrome, epithelial as having the implant placed in the Glaucoma Association. downgrowth and steroid-induced superotemporal quadrant with the glaucoma; severe posterior blephar- tube in the anterior chamber, and The Data (So Far) itis; conjunctival scarring; a func- a complete restriction of flow at tionally signifi cant cataract; and any the time of surgical implantation. Results from the PTVT Study at anticipated need for additional ocular We standardized aspects of the year three were presented at the 2019 surgery. trabeculectomies as well. An MM-C Annual AGS Meeting. Highlights in- As in the TVT Study, participants in dosage of 0.4 mg/ml for two minutes cluded: the PTVT Study were randomized to a was used in all patients, and the • IOP reduction. The pressure 350-mm2 Baerveldt glaucoma implant surgery was performed superiorly. reduction was greater in the tra- or a trabeculectomy with MM-C, Despite standardization of many beculectomy group at all time points, although the dosage of MM-C was aspects of each procedure, surgeons and that difference was statistically lower than in the TVT Study. During were allowed suffi cient fl exibility to significant—with the exception of the design phase of the study, we perform both operations in a manner the 18-month and two-year time considered letting each glaucoma in which they were comfortable and points. Furthermore, the greater surgeon implant whichever tube proficient. For example, surgeons degree of pressure reduction in the shunt was preferred. However, the were allowed to decide whether a trabeculectomy group was achieved biostatisticians tasked with analyzing limbus- or fornix-based conjunctival with fewer postoperative glaucoma our data advised us to standardize the flap was used. The method of tube medications. This clearly suggests surgeries as much as possible. ligation, the size of the trabeculectomy that trabeculectomy with MM-C It was a consensus opinion among fl ap and the number of fl ap sutures was more effective at reducing IOP the investigators in our study that the were also left to the surgeon’s dis- than tube shunt implantation in this 350-mm2 Baerveldt implant offered cretion. population. the highest effi cacy among available Sixteen clinical centers were in- • Rate of surgical failure. The implants due to its large surface volved in the study. Patients were primary outcome measure for the area, and this has been supported randomly assigned to one of the two study was the rate of surgical failure, by two landmark clinical trials— groups, with follow-up visits scheduled using Kaplan-Meier survival analysis. the Ahmed Baerveldt Comparison for one day, one week, one month, The rate of surgical failure increased (ABC) Study and the Ahmed Versus three months, one year, 18 months over time, which came as no surprise; Baerveldt (AVB) Study. So, a 350- and two, three, four and five years even glaucoma surgeries that are mm2 Baerveldt glaucoma implant was postoperatively. The primary outcome initially successful can eventually fail. used in all patients randomized to measure was the rate of surgical At one year, the tube shunt group the tube group. We also standardized failure, using criteria consistent with had a signifi cantly higher failure rate

September 2019 | reviewofophthalmology.com | 67

0066_rp0919_gm.indd66_rp0919_gm.indd 6767 88/23/19/23/19 3:453:45 PMPM Glaucoma

REVIEW Management

Probability of Surgical Failure Based on Preoperative IOP

Tube group Trabeculectomy group IOP < 21 mmHg IOP 21-25 mmHg IOP >25 mmHg 60.0% 0.6 0.6 0.6 0.5 0.5 0.5 0.4 0.4 0.4 0.3 39.3% 0.3 0.3 29.7% 26.4% 0.2 0.2 0.2 0.1 0.1 0.1 13.8% 10.0% 0.0 0.0 0.0

Cumulative Proportions Failing 0 6 12 18 24 30 36 0 6 12 18 24 30 36 0 6 12 18 24 30 36 Follow-up (months)

than the trabeculectomy group. The tube shunt group. (That’s an im- — Early postoperative comp- cumulative probability of failure in portant consideration when man- lications, defi ned as those occurring the trabeculectomy group continued aging a patient who can’t tolerate in the fi rst month after surgery, were to trend somewhat lower than the medications, or a patient who is poorly more common in the trabeculectomy tube group over time. However, the compliant.) group than in the tube group. difference in failure rate between the • Baseline factors associated — The rate of later postoperative groups was no longer statistically sig- with surgical failure. We performed complications (occurring after a nifi cant at three years. a risk factor analysis to identify month) wasn’t signifi cantly different • Reasons for failure. We found baseline factors that were associated between the two groups. some differences in the reasons for with failure in the study. The only — The rate of serious compli- surgical failure between the two significant predictor of failure was cations, defined as those requiring study groups. The most common preoperative IOP. The patients with a reoperation to manage the com- reason for failure in both groups was lower preoperative pressures had a plication, and/or resulting in a vision insuffi cient pressure reduction; either higher risk of failure, and this was loss of two or more lines of Snellen the pressure was above 21 mmHg especially true in the tube group. (See visual acuity, wasn’t significantly at two consecutive visits, or it wasn’t fi gure, above.) In my opinion, this is different between the treatment reduced 20 percent below baseline one of the study’s most interesting and groups. at two consecutive visits. Other rea- important fi ndings. — Overall, the rate of reoperation sons for failure included needing a • Complications. In terms of for complications trended higher in reoperation for glaucoma or having complications, the PTVT Study’s the trabeculectomy group compared hypotony. Interestingly, all of the fi ndings have been similar to what’s to the tube group. hypotony failures occurred in the been observed in other prospective The complications data suggests trabeculectomy group, while more glaucoma surgical trials, including that tube shunt surgery may have reoperations were seen in the tube the TVT, ABC and AVB studies. a slightly better safety profile than group. Postoperative complications are very trabeculectomy with MM-C, at least • Need for adjunctive medical common after traditional glaucoma during the first three years postop. therapy. Patients who didn’t fail surgery, whether it be a tube shunt or If you combine all complications to- were subdivided into complete or a trabeculectomy. Fortunately, most gether, they were signifi cantly more qualified successes. Complete suc- of these complications are self-limited common in the trabeculectomy group cesses didn’t need postop adjunc- and resolve without any specifi c in- than the tube group. However, the tive medical therapy; qualified suc- tervention. PTVT trial will continue out to five cesses were using glaucoma medica- We did, however, find some dif- years, and the long-term data will be tions. The rate of complete success ferences between the types of com- important for evaluating these two was significantly higher in the plications occurring in the two surgical procedures, in terms of both trabeculectomy group than in the treatment groups: safety and effi cacy.

68 | Review of Ophthalmology | September 2019

0066_rp0919_gm.indd66_rp0919_gm.indd 6868 88/23/19/23/19 3:453:45 PMPM YOU ARE INVITED TO A COMPLIMENTARY DINNER DISCUSSION AT MoMA, SF.

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REVIEW Management

• Number of postoperative the titratability of trabeculectomy; it between safety and effi cacy in glau- interventions. In my experience, allows us to do laser suture lysis or coma surgery. In our study com- postoperative management fol- use releasable sutures to titrate the paring tube shunt implantation and lowing tube shunt surgery tends pressure to lower levels in the early trabeculectomy, the data suggests to be less involved than postoper- postoperative period. I think that’s that trabeculectomy is more effective, ative management following tra- particularly valuable in patients who but more likely to be associated with beculectomy. However, in this study have initial low pressure. complications. A similar dichotomy the number of postop interventions • Both tube shunt surgery and was seen in the ABC and AVB stud- performed in the clinic, such as laser trabeculectomy with MM-C are ies; the Baerveldt implant was more suture lysis or pulling a rip-cord very effective at lowering IOP. effective, while the Ahmed valve suture, wasn’t signifi cantly different was safer. Likewise, when com- whether the patient received a tube paring traditional glaucoma surgeries or a trabeculectomy. to MIGS, we find tube shunts and • Visual acuity. We didn’t find Randomized clinical trabeculectomy are more effi cacious, any signifi cant difference between the trials offer the highest but MIGS are safer. So added effi cacy treatment groups with regard to visual seems to be achieved at the expense acuity outcomes. level of evidence-based of reduced safety—at least with the • Cataract formation. All of the medicine, but caution existing glaucoma surgical options. patients in our study were phakic. This shouldn’t be surprising. After three years of follow-up, about should be used in Many of the complications that we a third of the patients in the study had extrapolating study contend with in glaucoma surgery undergone cataract extraction. are related to hypotony, such as There’s ample evidence in the lit- results to dissimilar anterior chamber shallowing and erature to suggest that glaucoma patients. We now choroidal effusions, and sometimes surgery, whether it be trabeculectomy more serious complications, includ- or tube shunt surgery, accelerates the have two trials that ing suprachoroidal hemorrhage and development of cataract. This data compared tube shunts hypotony maculopathy. (Of course, it’s suggests that cataract progression possible that some future glaucoma occurs at a similar rate among patients and trabeculectomy surgery will be both highly effective undergoing trabeculectomy or tube .... Remember to apply and low-risk.) shunt surgery. • Patient comfort. One of the the lessons learned A Few Final Thoughts complications we specifically asked only to the appropriate patients about was dysesthesia, or The purpose of a trial like the PTVT patient discomfort. We found no patient population. Study is to provide useful information significant difference in patient-re- that will help surgeons select the best ported dysesthesia between the two glaucoma procedure for an individual procedures. patient. Data produced by the trial Mean postoperative pressures were thus far hasn’t demonstrated clear su- Take-home Highlights (So Far) in the low teens in both groups periority of one of these procedures throughout three years of follow- over the other. What useful information can we up; most patients ended up with However, there’s another important take away from this study at the three- pressures of 14 mmHg or less. consideration when choosing a year follow-up mark? MIGS procedures seldom achieve glaucoma surgical procedure, one • Preoperative IOP impacts the this degree of IOP reduction. As pre- that was not addressed in the PTVT likelihood of success. When patients viously noted, traditional glaucoma Study: the surgeon’s experience and have lower levels of preoperative surgeries are still an important part of comfort with each procedure. All IOP—in our post hoc analysis the our armamentarium. of the surgeons in the PTVT Study cutoff was less than 21 mmHg— • Your choice of tube or trabec- were profi cient and experienced with trabeculectomy appears to be a more ulectomy may ultimately come both of the procedures being studied, successful operation than tube shunt down to safety vs. effi cacy. There but this may not be the case with surgery. I suspect this is related to seems to be an inevitable tradeoff (Continued on page 73)

70 | Review of Ophthalmology | September 2019

0066_rp0919_gm.indd66_rp0919_gm.indd 7070 88/23/19/23/19 3:463:46 PMPM ENRICH YOUR PRACTICE

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72 | Review of Ophthalmology | September 2019

ROPH0719.indd 62 6/9/19 9:54 PM 072_rp0919_adindex.indd 72 8/23/19 3:00 PM Glaucoma

REVIEW Management

(Continued from page 70) will add signifi cant new information to the highest level of evidence-based all surgeons. A surgeon’s familiarity help answer this question. However, medicine, but caution should be with each operation is an important we’re waiting for the fi ve-year data to used in extrapolating study results factor when deciding which surgery do a full statistical analysis relating to to dissimilar patients. We now have to perform. this question. two trials that compared tube shunts One interesting question that our As noted earlier, glaucoma surgical and trabeculectomy with MM-C study may eventually help answer is practice patterns appear to be in different populations, and we’re how tube shunt and trabeculectomy shifting away from trabeculectomy seeing somewhat different results. function is impacted by subsequent and toward implanting tube shunts. So remember to apply the lessons cataract surgery. All eyes enrolled in The TVT Study provided data to learned only to the appropriate our study were phakic, but a third of support this trend, as tube shunt patient population. the patients had undergone cataract surgery was found to be more suc- surgery by the three-year time point. cessful, with a lower rate of early Dr. Gedde is a professor of oph- Multiple studies have demonstrated postop complications relative to thalmology and vice chair of educa- that when performing cataract sur- trabeculectomy with MM-C among tion at Bascom Palmer Eye Institute. gery in eyes with preexisting tra- patients with prior cataract and/or He is a study chairman for the PTVT beculectomy filtering blebs, there’s failed glaucoma surgery. Notably, Study. He has no personal fi nancial some risk of bleb failure. However, this effi cacy result wasn’t seen in the ties to any product mentioned, but there’s less information in the medical PTVT Study. However, it’s important notes that the PTVT Study was literature about how tube shunts fare to realize that different patient popu- funded by grants from Johnson & with subsequent cataract removal. lations were studied in the TVT and Johnson Vision, the National Eye I believe the data coming from a PTVT Studies. Institute and Research to Prevent prospective, randomized clinical trial Randomized clinical trials offer Blindness.

(Continued from page 60) He also remains vigilant whenever his underlying conditions cause long- surface disease, anterior basement screening exam turns up two other term distortion? membrane dystrophy, and (as key fi ndings: “We want to keep them in the mentioned previously) keratoconus,” • A steep or a posterior slope that’s normal range of corneal fi tness,” she says Dr. Donaldson. bowed in. “Some people say the continues. “Remember to always earliest sign of keratoconus is a bulge calculate preoperatively what their Guarding Against Risks on the posterior cornea,” he notes. corneas will look like postoperatively. “You might also see the anterior We’re looking at how LASIK will Dr. MacRae offers this advice to cornea bowed forward.” affect patients tomorrow and 10 years avoid surgical risks: “If you see a • A view going from the central from now.” marked red zone inferiorly, nasally to the peripheral cornea that reveals or temporally, that’s another red several suggestive indices, including Dr. Donaldson reports financial flag, another sign of what we call those associated with thinning. relationships with Alcon, Allergan, skewing, where the bow tie is bigger Johnson & Johnson Vision, Sun down below than above,” he says. Pulling It All Together Pharmaceuticals, Shire, Bausch “This represents a clear-cut case of + Lomb, Kala Pharmaceuticals, keratoconus. No surgery can be done In summary, Dr. Donaldson advises EyeVance, Lumenis, Omeros and on this patient.” all refractive surgeons to keep the Carl Zeiss Meditech. In a patient with Salzmann’s potential outcome of every case in Dr. Manche is a consultant for nodular degeneration, a topographical mind. “When you’re screening a Allergan, Avedro, J & J Vision and representation of the cornea will reveal patient for an elective procedure, Carl Zeiss Meditec. He performs significant irregular astigmatism, you want to be extra careful and err sponsored research for Allergan, another concern, he says. on the conservative side,” she says. Alcon, Avedro, Carl Zeiss Meditec and If Dr. Manche encounters a subtle “We have to ask ourselves: How well Presbia. He owns equity in Vacu-Site abnormality, he considers using PRK am I going to make this patient see? and RxSight. Dr. MacRae reports no instead of LASIK. “It’s also possible Am I going to fl atten the tissue too fi nancial relationships with relevant we’ll choose IOL surgery,” he notes. much? Is the cornea too thin? Will companies.

September 2019 | reviewofophthalmology.com | 73

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2017_retinaspecialist_housead.indd 1 11/26/18 10:42 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

RRP0919_ShireP0919_Shire PI.inddPI.indd 1 88/13/19/13/19 1:351:35 PMPM FIIRST IN CLASS Xiidra is the only lymphocyte function-associated antigen-1 (LFA-1) antagonist treatment for Dry Eye Disease1,2

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

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RRP0919_Shire.inddP0919_Shire.indd 1 88/13/19/13/19 1:381:38 PMPM