PHACO: KNOW YOUR FLUIDICS OPTIONS P. 16 • MEDICARE UPDATES FOR 2017 P. 23 SECRETS FOR MANAGING GLAUCOMA WITH OCT P. 50 • A REVIEW OF PORTABLE RETINAL IMAGING P. 60
Review of Ophthalmology Vol. XXIV, No. 2 • February 2017 • Cataract and Refractive Issue Toric Alignment • SMILE IOL T A NEW DAY DAWNS FOR DRY-EYE THERAPY P. 64 • WILLS EYE RESIDENT CASE STUDY P. 71
JanuaryJanuary 20172017
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CATARACT REFRACTIVE ISSUE
Surgeons share their best tips and techniques for helping you ips • Multifocal IOLs in Post-refractiveips • Multifocal IOLs Eyes improve your outcomes.
Toric IOLs: Nailing the Target Meridian P. 26 Tips for a Better SMILE P. 34 Odd Couple: Multifocals in Post-refractive Patients P. 40
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RRP0217_AlconP0217_Alcon AAcrysofcrysof Restor.inddRestor.indd 1 11/9/17/9/17 2:572:57 PMPM IMPORTANT PRODUCT INFORMATION FOR THE ACRYSOF® IQ RESTOR® FAMILY OF IOLs CAUTION: Federal (USA) law restricts this Left your Review device to the sale by or on the order of a physician. INDICATIONS: The AcrySof® IQ ReSTOR® Posterior Chamber Intraocular Lens (IOL) of Ophthalmology is intended for primary implantation for the visual correction of aphakia secondary to removal of a cataractous lens in adult patients with and without presbyopia, who magazine at the offi ce? desire near, intermediate and distance vision with increased spectacle indepen- dence. The lens is intended to be placed in the capsular bag. No problem! WARNINGS/PRECAUTIONS: Careful preoperative evaluation and sound clinical judgment should be used by the surgeon to decide the risk/benefit ratio before implanting a lens in a patient with any of the conditions described in the Directions for Use labeling. Physicians should target emmetropia, and ensure that IOL centra- tion is achieved. Care should be taken to remove viscoelastic from the eye at the close of surgery. Some patients may experience visual dis- turbances and/or discomfort due to multi- focality, especially under dim light condi- tions. As with other multifocal IOLs, visual symptoms may be significant enough that the patient will request explant of the mul- tifocal IOL. Spectacle independence rates vary with all multifocal IOLs; as such, some patients may need glasses when reading small print or looking at small objects. Clinical studies with the AcrySof® ReSTOR® lens indicated that posterior capsule opaci- fication (PCO), when present, developed earlier into clinically significant PCO. Prior to surgery, physicians should provide pro- spective patients with a copy of the Patient Information Brochure available from Alcon for this product informing them of possible risks and benefits associated with the AcrySof® IQ ReSTOR® IOLs. Studies have shown that color vision discrimination is not adversely affected in individuals with the AcrySof® Natural IOL and normal color vision. The effect on vision of the AcrySof® Natural IOL in subjects with hereditary color vision defects and acquired color vision defects secondary to ocular disease (e.g., glauco- ma, diabetic retinopathy, chronic uveitis, and other retinal or optic nerve diseases) has not been studied. Do not resterilize; do not store over 45° C; use only sterile Read Review on the go irrigating solutions such as BSS® or BSS PLUS® Sterile Intraocular Irrigating Solutions. from any mobile device! ATTENTION: Reference the Direc- tions for Use labeling for a complete listing of indications, warnings and precautions. Go to www.reviewofophthalmology.com and click on the digimag link to get your current issue. © 2016 Novartis 10/16 US-RES-16-E-4014
003_rp0217_houseads.indd 3 1/18/17 4:32 PM REVIEW NEWS Volume XXIV • No. 2 • February 2017 Lucentis Approved for Myopic Choroidal Neovascularization
Genentech (South San Francisco, Calif.), ity stabilization guidelines. Group II confi rms my personal experience, and part of Roche (Basel, Switzerland), received Lucentis 0.5 mg injection on the collective experience of retina announced in January that Lucentis day one of the study and as needed specialists, that PDT is vastly inferior (ranibizumab injection) was ap proved thereafter per disease-activity crite- to Lucentis 0.5 mg for the treatment by the Food and Drug Administration ria. Group III received vPDT on day of myopic CNV.” Dr. Wells adds that for the treatment of myopic choroidal one, but were permitted treatment the upswing in ETDRS letters gained neovascularization, a sight-threatening with Lucentis and/or vPDT based by the PDT group once Lucentis was complication of high myopia. MCNV upon disease activity, at investiga- allowed after three months is also im- affects more than 41,000 people in the tors’ discretion, from months three portant in illustrating “that PDT is not United States.1 through 11. Groups I and II showed a good option for myopic CNV if anti- Myopic choroidal neovasculariza- dramatic gains in mean average best- VEGF therapy is available.” tion is a complication of high myopia corrected vision as measured by ET- 1. Willis JR, Vitale S, Morse L et al. The prevalence of (eyes with a refractive error of -6 D or DRS letters at three months (10.5 myopic choroidal neovascularization in the United States. greater, and/or axial length of 26.5 mm and 10.6, respectively), compared to Ophthalmology 2016;123:8:1771-1782. 1 2. Adatia FA, Luong M, Munro M, Tufail A. The other CNVM: A or more) in which the eye progres- Group III (2.2 letters gained). Mean review of myopic choroidal neovascularization treatment in the sively lengthens from front to back BCVA gains from baseline to month age of anti-vascular endothelial growth factor agents. Survey of Ophthalmol, 2015;60:3:204-15. and degenerates, and neovasculariza- 12 were 13.8 letters for Group I: 14.4 3. RADIANCE: A randomized controlled study of ranibizumab tion develops. The condition is most for Group II; and, 9.3 for Group III, in patients with choroidal neovascularization secondary to prevalent in people ages 45 to 64.1 who were able to get Lucentis injec- pathologic myopia. Ophthalmology 2014:121;3;682–692. Until this approval for mCNV, the tions after three months. The results FDA-approved standard of care for show that treatment with Lucentis on mCNV has been verteporfi n photody- either schedule I or II resulted in ReSTOR Toric namic therapy, although anti-VEGF dramatic early gains, and gains injections were previously used off in BCVA continued throughout MF: New label and recommended as fi rst-line the study period. Group I patients treatments.2 Lucentis inhibits choroi- received a median of four injections Options And dal neovascularization by binding to over 12 months; Groups II and and interfering with the vascular en- III underwent a median of Challenges dothelial growth factor VEGF-A, the two. There were no ad- As Alcon begins its protein implicated in the formation of verse safety events. scheduled fi rst-quarter incompetent blood vessels. “I think that having an rollout of the new Re- The fi ndings of the RADIANCE FDA approval for Lu- STOR +3 D Multifocal study form the basis of Genentech’s centis benefi ts patients Toric intraocular lens, approval.3 This Phase III, 12-month, and supports reimburse- which was approved in randomized, active-controlled study ment from payers, as late December of 2016, sur- enrolled mCNV patients from 76 it is clearly superior to geons are understandably inter- centers worldwide. They were ran- the other FDA-approved ested in giving their patients a new domized into three treatment groups: treatment, PDT,” says John alternative for vision correction Group I received Lucentis 0.5 mg A. Wells, III, MD, of the Pal- post-cataract, but say it’s best to injection on day one, month one and metto Retina Center in West Co- thereafter as needed per visual acu- lumbia, S.C. “The RADIANCE study (Continued on page 8)
4 | Review of Ophthalmology | February 2017
004_rp0217_news.indd 4 1/20/17 4:20 PM ®
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004_rp0217_news.indd 5 1/20/17 4:20 PM Ophthalmic Product Development Insights Matthew Chapin, Hiro Matsuda & Takako Kawaba REVIEW
Considerations for Development in Japan similar to a pre-IND meeting with the FDA, in that a more detailed briefi ng document is n prior installments of this column, in order Agency. In many regards, the PMDA is very submitted in advance and written com- to help entrepreneurs in their companies’ similar to the FDA. With some requirements ments are provided by the PMDA following Iearly stages look for creative ways to help having been harmonized across regions the meeting. This meeting does carry a fee, move programs forward or to provide ad- as ICH Guidances (International Council which currently is in the range of $50,000. In ditional value, we’ve discussed how regional for Harmonization), components such as many instances, additional clarifi cations are licensing partnerships are an option for toxicology and manufacturing generally are required after this meeting, and the PMDA non-dilutive fi nancing (fi nancing that doesn’t consistent and many times don’t require has always been very helpful and responsive require the sale of shares of your company). additional work or rework. In some regards, about providing clarifi cations as needed. In this month’s column, we’ll focus in on a interaction with the PMDA is very similar to Again, it’s important to recognize that few considerations related to doing business dealing with the FDA. One main difference maybe several rounds of meetings might be in Japan. Japan is one of the top markets between the two is that, in the initial stages necessary in order to fi nalize plans. Compa- for ophthalmology products in the world of the process, rather than a single pre-IND nies must recognize that everything won’t and, in some cases, is the second-largest meeting with the FDA, working with the be formalized in one meeting during a single market behind the United States. As such, it PMDA involves a multistep process. trip to Japan. The PMDA is very thoughtful should be an important component in your The fi rst interaction with the PMDA is called and data-driven and, in some cases, though early global development planning. In other the jizen mendan (“preliminary meeting”). it may not require preclinical or pharmacol- regions such as Europe, Canada or South ogy studies to be repeated, it may ask for America, for some programs the clinical data to be presented in a different package from the U.S. is suffi cient manner to help support such things for fi ling, but the considerations as drug concentration and dosing for bringing programs to Japan selection. are unique. If you plan to pursue The PMDA also views ethnic a regulatory meeting in Japan, differences as very important for then, it’s helpful to understand the interpretation of clinical data. In nuances related to regulatory interac- cases in which pharmacokinetic or tions there. Here, we’ll cover a couple pharmacodynamic data is being used, of key highlights related to the early part of you have to show how the Japanese popu- the process. lation compares to the original data set. The In the past there’s been a considerable This meeting has no fee associated with it, PMDA typically wants to see dose ranging time lag between development and approval is shorter in length and requires less of a established in the Japanese population spe- in the United States and an ultimate launch briefi ng package. It’s important to recognize cifi cally. This is due to potential differences in Japan. Given the size of the market in the role of this meeting: You won’t leave with in both drug activity and dosing frequency, Japan, a more global follow-on or even formal written comments from the PMDA as well as to differences in practice patterns parallel strategy makes sense, and can add and it isn’t intended to discuss details of the that might relate to whether the drug is used more value to your program as you look for development program or clinical protocols. as primary, secondary or objective therapy. partnerships with global companies. In fact, The intention of this meeting is to confi rm For example, drugs in some indications may Japan is becoming a market of interest ear- the materials that are to be submitted need to be dosed more frequently in Japan lier in products’ lifecycles, and it can be very and the sponsor’s questions that will be than in United States. useful to show investors or global partners discussed at the subsequent taimen jogen One key point to recognize is that the what a development program looks like (“full consultation meeting”). Certainly, many PMDA has been very open to helping clients in Japan—even if actual clinical develop- times it is natural to wish to obtain as much run early studies as effi ciently as pos- ment isn’t initiated yet. We’ve seen many information as possible during regulatory sible, and therefore will generally accept companies and entrepreneurs focus solely interactions, but many times we see clients the Phase I/pharmacokinetics being done on Food and Drug Administration interactions having high expectations for confi rming in the United States, if done in Japanese- through Phases I and II, all the while ignoring details and answering all questions about a American patients. But we do generally see other territories. However, investing just a bridging program at this preliminary meet- that the PMDA wants a traditional Phase I/ small amount of time and resources in these ing. However, it’s important to recognize PK study to be conducted/repeated as a fi rst other regions—including Japan—can yield the PMDA review isn’t formalized at this step, even in cases where a program may valuable information on regulatory interac- stage and they will not have reviewed all the have proceeded directly into Phase II in the tions. A word to the wise, though: If you’re information and data. United States, or Phase I data already exists, going to invest extra time in Japan, start However, this fi rst meeting is still very but with a non-Japanese population. This early, because it may take additional time to important for setting the stage and starting includes situations in which Phase III may gain confi rmed written comments. a working dialogue, relationship and level of already be completed in the United States or In Japan, the FDA’s counterpart is known trust with the PMDA. The second meet- as the Pharmaceutical and Medical Device ing, the full consultation meeting, is more (Continued on page 8)
6 | Review of Ophthalmology | February 2017
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RP0217_Imprimis.indd 1 1/18/17 10:39 AM REVIEW News (Continued from page 6) (Continued from page 4) the product is commercialized. Similarly, many times Phase II dose enter into the combined multifocal/toric world with ranging may also be done in the United States in Japanese-American eyes open, and to be prepared for new idiosyncrasies patients. However, generally speaking, the confi rmatory Phase III is associated with getting the implantation right. required to be done in Japan. In the FDA study, at one year, the mean near acuity The safety requirements are specifi c to the drug’s indication and with the news lens was 20/25, and the mean binocular the amount of data already in hand from other parts of the world. intermediate acuity at 60 cm was 20/25. Mean distance In some cases, the additional safety requirements for a number of vision was 20/20. The lenses had rotated an average of patients may be less than the full safety package already completed around 2.5 degrees at the year mark. In terms of cylin- in the United States, and may even be in the form of an open-label der, at one year 75 percent of the fi rst-implanted eyes study. The key is that the PMDA is looking for effi cacy and safety to were within 0.5 D of the preop target. Eighty percent be established in Japanese patients. It’s open to reviewing data from of the second eyes were within 0.5 D of the target. subgroups of patients that may be of Japanese descent from the Alan Crandall, MD, director of glaucoma and cat- United States to support early data. However, we usually fi nd that the aract at the Moran Eye Center at the University of number of Japanese-American patients included in U.S. studies isn’t Utah, says being able to treat astigmatism adds a new large enough to eliminate the need for repeating Phase I and II. The PMDA is also very conscious of reducing the timeline of development dimension to the multifocal lens that patients respond between the rest of the world and registration in Japan. to. “The increaased acuity, lack of glare and unwant- In many respects the PMDA will view data in a way similar to ed images—be they from straylight or halos—is re- the FDA. In some situations, they do have other thresholds. For ally what most of our patients are excited about when example, in the case of dry eye, PMDA’s requirement for approval you just correct their astigmatism with a toric lens,” is to demonstrate a statistically signifi cant improvement in one sign he says. “But when they also have the ability to have only, specifi cally corneal staining. This is an important nuance, and distance and near vision, that’s a good combination. is slightly different from the FDA in that there are a few products In the past, when working with multifocals where you that are approved in Japan that aren’t approved in the United States, had to try to do limbal relaxing incisions to correct the namely diquafosol and repabamide. There are also areas of emphasis astigmatism, they were never as accurate as what you that the PMDA is keen to address, such as neuroprotection, given the could get with a toric lens. Patients would come back higher incidence of low-tension glaucoma in Japan, and allergies, and still say it wasn’t as sharp.” which are a severe problem there. In these conditions, there may be But Dr. Crandall says these improved outcomes opportunities for parallel development—or even leading develop- come at a price. “When you put these lenses in, you ment—in some cases in which it makes sense. have to be right on target,” he avers. “I wouldn’t say it Naturally, this article isn’t intended to be an exhaustive review of demands it, but you’re better off if you have a topog- regulatory strategy for Japan. However, we hope this discussion at raphy device that images both anterior and posterior least highlights the importance of looking into the Japanese market corneal values. You also have to use multiple formu- for your product, and considering starting an earlier dialogue with las–the Barrett, the ASCRS formula, the Olson—and the PMDA than you may have originally planned. This will help show then it helps to have something like ORA or Holos potential partners your focus on global development, and there may intraoperative aberrometry. I think this is why the be opportunities for building and deriving additional value early. For penetration of toric lenses isn’t high: People are con- example, some companies may see an opportunity for a potential cerned about getting it properly on-axis.” regional partnership in Japan. We’ll use this primer as a springboard for future columns on global development, including development in As for the best patient for the lens, Dr. Crandall says China and other Asian countries. someone with extreme dry eye wouldn’t do well, nor would someone on medication for glaucoma because Mr. Chapin is senior vice president of the Corporate Development the lens will result in a little loss of contrast, which Group at Ora, Dr. Matsuda is general manager of Ora Japan KK, such a patient can’t afford. “Someone with pseudoex- and Ms. Kawaba is a senior director of Ora Japan KK. Ora provides foliation might not do well because the optics of the a comprehensive range of development, clinical-regulatory and lens depend somewhat on the pupil,” he adds. product consulting services for developers, investors and buyers; preclinical and turnkey clinical trial services; assistance with regula- tory submissions; and the integration of assets, business partnering Trabodenoson Fails Phase and fi nancing support in ophthalmology. Ora Japan KK is based in Osaka for local regulatory, clinical operations and business develop- III Trial for Glaucoma ment support. We welcome your product development comments or On January 3, Inotek Pharmaceuticals Corporation questions. Please send correspondence to [email protected] or visit oraclinical.com. (Continued on page 47)
8 | Review of Ophthalmology | February 2017
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10 | Review of Ophthalmology | February 2017
0004_rp0217_news.indd04_rp0217_news.indd 1100 11/20/17/20/17 4:214:21 PMPM Down, Boy. Help Tame Postoperative Ocular Inflammation and Pain With LOTEMAX® GEL Indication LOTEMAX® GEL (loteprednol etabonate ophthalmic gel) 0.5% is indicated for the treatment of post-operative infl ammation and pain following ocular surgery. Important Safety Information about LOTEMAX® GEL • LOTEMAX ® GEL is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. • Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. If this product is used for 10 days or longer, IOP should be monitored. • Use of corticosteroids may result in posterior subcapsular cataract formation. • Use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation and occurrence of perforations in those with diseases causing corneal and scleral thinning. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification, and where appropriate, fluorescein staining. • Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infection. In acute purulent conditions, steroids may mask infection or enhance existing infection. • 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 the course and exacerbate the severity of many viral infections of the eye (including herpes simplex). • Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. • Patients should not wear contact lenses when using LOTEMAX® GEL. • The most common ocular adverse drug reactions reported were anterior chamber inflammation (5%), eye pain (2%) and foreign body sensation (2%). Please see brief summary of Prescribing Information on adjacent page. ®/™ are trademarks of Bausch & Lomb Incorporated or its affi liates. © 2015 Bausch & Lomb Incorporated. All rights reserved. Printed in USA. US/LGX/15/0041(1)
RO1015_BL Lotemax.indd 1 9/15/15 2:24 PM BRIEF SUMMARY OF PRESCRIBING INFORMATION ossification) and teratogenic (increased incidence of meningocele, abnormal This Brief Summary does not include all the information needed to left common carotid artery, and limb flexures) when administered orally prescribe Lotemax Gel safely and effectively. See full prescribing to rabbits during organogenesis at a dose of 3 mg/kg/day (35 times information for Lotemax Gel. the maximum daily clinical dose), a dose which caused no maternal toxicity. The no-observed-effect-level (NOEL) for these effects was 0.5 mg/kg/day (6 times the maximum daily clinical dose). Oral treatment (loteprednol etabonate ophthalmic gel) 0.5% Lotemax of rats during organogenesis resulted in teratogenicity (absent innominate Rx only artery at ≥5 mg/kg/day doses, and cleft palate and umbilical hernia Initial Rx Approval: 1998 at ≥50 mg/kg/day) and embryotoxicity (increased post-implantation losses at 100 mg/kg/day and decreased fetal body weight and skeletal INDICATIONS AND USAGE ossification with ≥50 mg/kg/day). Treatment of rats with 0.5 mg/kg/day LOTEMAX is a corticosteroid indicated for the treatment of post-operative (6 times the maximum clinical dose) during organogenesis did not result inflammation and pain following ocular surgery. in any reproductive toxicity. Loteprednol etabonate was maternally toxic DOSAGE AND ADMINISTRATION (significantly reduced body weight gain during treatment) when administered Invert closed bottle and shake once to fill tip before instilling drops. to pregnant rats during organogenesis at doses of ≥5 mg/kg/day. Apply one to two drops of LOTEMAX into the conjunctival sac of the affected Oral exposure of female rats to 50 mg/kg/day of loteprednol etabonate from eye four times daily beginning the day after surgery and continuing the start of the fetal period through the end of lactation, a maternally toxic throughout the first 2 weeks of the post-operative period. treatment regimen (significantly decreased body weight gain), gave rise to decreased growth and survival, and retarded development in the offspring CONTRAINDICATIONS during lactation; the NOEL for these effects was 5 mg/kg/day. Loteprednol LOTEMAX, as with other ophthalmic corticosteroids, is contraindicated in etabonate had no effect on the duration of gestation or parturition when most viral diseases of the cornea and conjunctiva including epithelial herpes administered orally to pregnant rats at doses up to 50 mg/kg/day during the simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in fetal period. mycobacterial infection of the eye and fungal diseases of ocular structures. There are no adequate and well controlled studies in pregnant women. WARNINGS AND PRECAUTIONS LOTEMAX should be used during pregnancy only if the potential benefit Intraocular Pressure (IOP) Increase justifies the potential risk to the fetus. Prolonged use of corticosteroids may result in glaucoma with damage to the Nursing Mothers optic nerve, defects in visual acuity and fields of vision. Steroids should be It is not known whether topical ophthalmic administration of corticosteroids used with caution in the presence of glaucoma. If this product is used for 10 could result in sufficient systemic absorption to produce detectable quantities days or longer, intraocular pressure should be monitored. in human milk. Systemic steroids appear in human milk and could suppress Cataracts growth, interfere with endogenous corticosteroid production, or cause other Use of corticosteroids may result in posterior subcapsular cataract formation. untoward effects. Caution should be exercised when LOTEMAX is administered Delayed Healing to a nursing woman. The use of steroids after cataract surgery may delay healing and increase the Pediatric Use incidence of bleb formation. In those diseases causing thinning of the cornea Safety and effectiveness in pediatric patients have not been established. or sclera, perforations have been known to occur with the use of topical Geriatric Use steroids. The initial prescription and renewal of the medication order should No overall differences in safety and effectiveness have been observed be made by a physician only after examination of the patient with the aid between elderly and younger patients. of magnification such as slit lamp biomicroscopy and, where appropriate, NONCLINICAL TOXICOLOGY fluorescein staining. Carcinogenesis, Mutagenesis, Impairment Of Fertility Bacterial Infections Long-term animal studies have not been conducted to evaluate the Prolonged use of corticosteroids may suppress the host response and carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was thus increase the hazard of secondary ocular infections. In acute purulent not genotoxic in vitro in the Ames test, the mouse lymphoma tk assay, or in conditions of the eye, steroids may mask infection or enhance existing a chromosome aberration test in human lymphocytes, or in vivo in the single infection. dose mouse micronucleus assay. Treatment of male and female rats with up Viral Infections to 50 mg/kg/day and 25 mg/kg/day of loteprednol etabonate, respectively, Employment of a corticosteroid medication in the treatment of patients with (600 and 300 times the maximum clinical dose, respectively) prior to and a history of herpes simplex requires great caution. Use of ocular steroids may during mating did not impair fertility in either gender. prolong the course and may exacerbate the severity of many viral infections PATIENT COUNSELING INFORMATION of the eye (including herpes simplex). Administration Fungal Infections Invert closed bottle and shake once to fill tip before instilling drops. Fungal infections of the cornea are particularly prone to develop Risk of Contamination coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been Patients should be advised not to allow the dropper tip to touch any surface, used or is in use. Fungal cultures should be taken when appropriate. as this may contaminate the gel. Contact Lens Wear Contact Lens Wear Patients should not wear contact lenses during their course of therapy with Patients should be advised not to wear contact lenses when using LOTEMAX. LOTEMAX. Risk of Secondary Infection ADVERSE REACTIONS If pain develops, redness, itching or inflammation becomes aggravated, the Adverse reactions associated with ophthalmic steroids include elevated patient should be advised to consult a physician. intraocular pressure, which may be associated with infrequent optic nerve damage, visual acuity and field defects, posterior subcapsular cataract Bausch + Lomb, a division of Valeant Pharmaceuticals North America LLC formation, delayed wound healing and secondary ocular infection from Bridgewater, NJ 08807 USA pathogens including herpes simplex, and perforation of the globe where US Patent No. 5,800,807 there is thinning of the cornea or sclera. ©Bausch & Lomb Incorporated The most common adverse drug reactions reported were anterior chamber inflammation (5%), eye pain (2%), and foreign body sensation (2%). Lotemax is a registered trademark of Bausch & Lomb Incorporated or its affiliates. USE IN SPECIFIC POPULATIONS Pregnancy LGX.0114.USA.16 Teratogenic Effects Based on 9269101/9269201 Revised: 08/2016 Loteprednol etabonate has been shown to be embryotoxic (delayed
RRP0217_BLP0217_BL LLotemaxotemax PI.inddPI.indd 1 11/13/17/13/17 10:0110:01 AMAM February 2017 • Volume XXIV No. 2 | reviewofophthalmology.com Cover Focus 26 | Toric IOLs: Nailing the Target Meridian By Christopher Kent, Senior Editor Surgeons explain how to provide patients with outstanding results using these lenses. 34 | Tips for a Better SMILE Jesper Hjortdal, MD An expert SMILE surgeon explains how to get the most from this new procedure.
40 | Odd Couple: Multifocals in Post-refractive Patients Kristine Brennan, Senior Associate Editor A history of refractive surgery doesn’t always mean multifocals are out of reach.
34
Cover image: iStock February 2017 | reviewofophthalmology.com | 13
013_rp0217_toc.indd 13 1/20/17 4:11 PM Departments
4 | Review News 50 16 | Technology Update Phaco: Know Your Fluidics Options The latest cataract systems offer a host of features to aid the surgeon and increase safety.
23 | Medicare Q & A What’s New in 2017? How Medicare’s updates might affect practices.
50 | Glaucoma Management Secrets for Managing Glaucoma with OCT Knowing OCT’s advantages and pitfalls can help you make it an effective disease-monitoring tool. 60 60 | Retinal Insider A Review of Portable Retinal Imaging A guide to using devices such as smartphones as well as more exotic consumer-level cameras.
64 | Therapeutic Topics A New Day Dawns for Dry-eye Therapy A look at the challenges involved in getting new dry-eye therapies approved and how researchers are overcoming them.
68 | Research Review Smartphone Use and Pediatric Dry Eye
70 | Classified Ads 71
71 | Wills Eye Resident Case Series
74 | Advertising Index
14 | Review of Ophthalmology | February 2017
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INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR THE TECNIS SYMFONY® AND TECNIS SYMFONY® TORIC EXTENDED RANGE OF VISION IOLs Rx Only INDICATIONS: The TECNIS Symƒony® Extended Range of Vision IOL, model ZXR00, is indicated for primary implantation for the visual correction of aphakia, in adult patients with less than 1 diopter of pre-existing corneal astigmatism, in whom a cataractous lens has been removed. The lens mitigates the effects of presbyopia by providing an extended depth of focus. Compared to an aspheric monofocal IOL, the lens provides improved intermediate and near visual acuity, while maintaining comparable distance visual acuity. The model ZXR00 IOL is intended for capsular bag placement only. The TECNIS Symƒony® Toric Extended Range of Vision IOLs, models ZXT150, ZXT225, ZXT300, and ZXT375, are indicated for primary implantation for the visual correction of aphakia and for reduction of residual refractive astigmatism in adult patients with greater than or equal to 1 diopter of preoperative corneal astigmatism, in whom a cataractous lens has been removed. The lens mitigates the effects of presbyopia by providing an extended depth of focus. Compared to an aspheric monofocal IOL, the lens provides improved intermediate and near visual acuity, while maintaining comparable distance visual acuity. The model series ZXT IOLs are intended for capsular bag placement only. WARNINGS: May cause a reduction in contrast sensitivity under certain conditions, compared to an aspheric monofocal IOL. Inform patients to exercise special caution when driving at night or in poor visibility conditions. Some visual effects may be expected due to the lens design, including: perception of halos, glare, or starbursts around lights under nighttime conditions. These will be bothersome or very bothersome in some people, particularly in low-illumination conditions, and on rare occasions, may be significant enough that the patient may request removal of the IOL. Rotation of the TECNIS Symƒony® Toric IOLs away from their intended axis can reduce their astigmatic correction, and misalignment greater than 30° may increase postoperative refractive cylinder. If necessary, lens repositioning should occur as early as possible prior to lens encapsulation. ATTENTION: Reference the Directions for Use for a complete listing of Indications and Important Safety Information. TECNIS and TECNIS SYMFONY are trademarks owned by or licensed to Abbott Laboratories, its subsidiaries or affiliates. © 2016 Abbott Medical Optics Inc. | www.AbbottMedicalOptics.com | PP2016CT1710
RO0217_Abbott Tecnis.indd 1 1/11/17 10:39 AM Technology Update
REVIEW Edited by Michael Colvard, MD, and Steven Charles, MD
Phaco: Know Your Fluidics Options The latest cataract removal systems offer a host of features to aid the surgeon and increase safety. Here’s what you need to know. Christopher Kent, Senior Editor
oday’s phacoemulsification sys- to maintain a constant pressure of in the bag very rapidly in response Ttems incorporate plenty of ad- fl uid going into the cassette,” he says. to feedback from sensors in both the vanced technology and clever design “They’re usually gravity-fed; a bottle irrigation and aspiration paths within elements that make cataract surgery of BSS is hung above the patient and the cassette. There’s also a pressure safer, faster and less taxing for the gravity provides the input pressure to sensor on the bag itself. surgeon. A big part of that is fluid- maintain eye volume dur- ics—the way in which fl uid is moved ing the surgery. In contrast, through the eye during surgery, which the Centurion’s Active Flu- impacts how easily broken-up nucleus idics system is designed to fragments are removed from the eye maintain the target pressure and how much the eye is disturbed by inside the eye; it does this events such as occlusion of the aspira- by having a variable, rather tion tip. than static, input pressure. Here, the manufacturers of the To make that possible, the three comprehensive phaco systems bag of fl uid is inserted into available in the United States explain the machine and acted upon what makes their fluidics systems by pressure plates that are unique. Surgeons who use each sys- able to change the pressure tem share their thoughts as well. Alcon’s Centurion Alcon’s Centurion Vision System: system maintains a Active Fluidics target pressure inside the eye (instead of the Alcon’s Centurion Vision System, fl uid pressure going into the follow-up to the Infiniti phaco the cassette). It also features a peristaltic system, features what the company pump (right) that doubles calls Active Fluidics Technology. Gary the available fl ow rate Sorensen, head of cataract instrumen- and eliminates the small tation R&D, explains how Active Flu- pulsations usually idics works. associated with “Most fl uidics systems are designed peristaltic pumps.
16 | Review of Ophthalmology | February 2017 This article has no commercial sponsorship.
016_rp0217_tech update.indd 16 1/18/17 2:11 PM “Another factor that sets the Centu- Abbott Medical Optics’ Whitestar Signature rion apart is its nontraditional peristal- System lets the surgeon switch between a tic-style pump which, in effect, acts as peristaltic pump and a venturi pump during two pumps pulling in parallel from the surgery (see screen below), allowing the same piece of tubing,” he continues. surgeon to take advantage of the different capabilities of each pump at different times. “That has two advantages. First, we can get twice the fl ow rate achievable with a single pump, more than enough to overcome the resistance of the Cen- turion’s smaller tubing (which helps to minimize occlusion-break surge). Sec- ond, the two pumps are confi gured to be out of phase with each other, which cancels out the small pulsations that a peristaltic pump always produces. Those small pulses have traditionally been considered one of the downsides of peristaltic pump technology.” Mr. Sorensen notes another design cal professor of ophthalmology at the feature in the Centurion’s fl uidics: ro- University of Illinois Eye Center, and tary valves. “Standard valves close off director of advanced anterior segment fl ow by pinching the tube,” he says. surgery at Arbor Centers for Eyecare “When you do that, it pushes fl uid in in Chicago, uses the Centurion sys- both directions—one direction being tem. “The Centurion fl uidics control into the eye—so when a valve closes system is so adaptive and adjustable you may see motion in the eye. We that it allows automation of the process now use stopcock-type rotary valves; of cataract removal,” he says. “Once a when open, a rotating gate is aligned surgeon decides how he or she would Active Fluidics system. “The Active with the fl uid path so fl uid can go by. like the phaco machine to behave dur- Fluidics system maintains the intra- When you turn it, it stops the flow ing each phase of the procedure, Cen- ocular pressure, helping to maintain a without causing a change in volume turion can be programmed to create very stable anterior chamber, which is or creating a pulse. This also makes it the desired effects. For example, the important not just in routine cases but possible to open or close the valve just surgeon can adjust the speed at which in fl oppy iris syndrome and pseudoex- a little bit, making the flow propor- the eye pressurizes to prevent sud- foliation cases,” he says. “In concert tional. It allows us to do a number of den overpressurization and reverse with the Intrepid Balanced Tip probe, things that would be impossible with pupillary block. As a result, chamber it becomes a powerful emulsifi cation the old type of valve.” maintenance is so stable that cataract unit that uses less energy.” In terms of being operator-friendly, removal can be performed safely at Mr. Sorensen says the surgeon can near physiologic intraocular pressures AMO’s Whitestar Signature: now step through a series of proce- of 25 to 40 mmHg. Our fl uid use has Fusion Fluidics dures that have default values set up been reduced to 35 to 50 ml per pro- for all the engineering parameters, cedure. In my experience, surgery Abbott Medical Optics’ Whitestar such as fl ow and vacuum. “The system with the Centurion system is elegant, Signature System, and its recent up- can be used very effectively with those making it more comfortable for both grade, Whitestar Signature PRO, fea- default settings, or it can be custom- surgeon and patient.” ture what the company calls Fusion ized with help from Alcon personnel,” Alan Crandall, MD, clinical profes- Fluidics, with the CASE (chamber he says. “We try to keep the primary sor, senior vice chair of ophthalmology stabilization environment) system. screens simple, like modern cameras; and visual sciences, and director of “MK” Raheja, PhD, MBA, global they’re point-and-shoot, but if you glaucoma and cataract at the Moran head of cataract R&D for Abbott, want to control every parameter and Eye Center, University of Utah, says explains what makes the Whitestar setting, you can.” he appreciates a number of features Signature’s Fusion Fluidics system David Lubeck, MD, assistant clini- the Centurion offers, including the unique.
February 2017 | reviewofophthalmology.com | 17
016_rp0217_tech update.indd 17 1/18/17 2:11 PM Technology
REVIEW Update
“There are two different technolo- Bausch + Lomb’s Stellaris allows the gies that can be used to manage the surgeon to control vacuum on the fl y, and fl uids,” explains Dr. Raheja. “One is its dual-linear foot pedal (below) lets the a peristaltic system, which uses roll- surgeon manage two parameters at once, if desired. ers to push the liquid being removed from the eye through the tubing. The other option is a venturi system, which creates a vacuum to move the fl uid. Each system has benefi ts. Peristaltic technology gives you great holdability and intraoperative control, which is advantageous early in the procedure. A venturi system gives the surgeon great followability; broken- up particles of the nucleus come to you, which is a big advantage during the removal part of the surgery. tion. The venturi pump allows me to “Rather than ask the surgeon to keep my phaco needle near the center choose one of these technologies, we of the eye and use the fl uidics to draw made a conscious decision to design the fragments to the tip without hav- our phaco system to have both capa- ing to ‘fi sh’ for fragments.” bilities,” he explains. “That’s at the In terms of managing post-occlu- heart of what we call Fusion Fluidics. sion surge, Dr. Raheja says the Signa- The surgeon can decide which system ture system senses that an occlusion at to use during the different parts of the the tip has occurred and automatically surgery, using the foot pedal on the fl y implements changes to minimize any to engage either peristaltic or venturi surge when the occlusion breaks. Dr. aspiration.” Dr. Raheja notes that hav- Garg agrees that this makes a differ- surgeon to control vacuum at the tip ing such advanced technology in the ence. “The combination of updated of the device during phacoemulsifi - system can seem intimidating. “As the sensing and processing along with cation, as well as irrigation and aspi- system becomes more capable, we’re less-compliant tubing makes for im- ration,” he says. “This is also critical making sure it remains easy for the proved chamber stability,” he says. during vitrectomy surgery, which the surgeon to use,” he says. “If a surgeon Stellaris PC can perform.” He notes wants to alter the settings, he can, but Bausch + Lomb’s Stellaris: that post-occlusion surge is more it works beautifully in basic mode.” Stable Chamber Fluidics of an issue with a peristaltic-pump- Sumit Garg, MD, vice chair of clini- based system. “The Stellaris produces cal ophthalmology, medical director Bausch + Lomb’s Stellaris Vision a very stable intraocular environment and associate professor of cataract, Enhancement System features what because the surgeon is able to gauge corneal and refractive surgery at the company calls Stable Chamber what’s happening in the eye and use the Gavin Herbert Eye Institute at Fluidics, a vacuum-control-based sys- the foot pedal to modulate the vac- the University of California, Irvine, tem. (The Stellaris is also available uum level. If I’m doing phaco and uses the Whitestar Signature System. as the Stellaris PC, which is capable I see an occlusion occurring, I can “I really enjoy operating using dual- of performing vitrectomy surgery reduce the vacuum by lifting up on pump fluidics,” he says. “By using in addition to cataract surgery. The the pedal, effectively preventing the the strong point of each pump I’m Stellaris Elite, featuring more than a big post-occlusion surge you may see able to be more effi cient and I fi nd dozen new innovations, will be intro- with some systems.” that I use less phaco energy. Having a duced later this year.) Chuck Hess, In terms of managing the system’s dual pump lets me use the peristaltic vice president and general manager complexity, Mr. Hess says the de- pump to impale and hold the nucleus of Bausch + Lomb’s U.S. surgical divi- velopment of B+L’s dual-linear foot during my initial chops; subsequently, sion, explains what makes the Stable pedal technology allows surgeons to I transition to venturi fl uidics for frag- Chamber Fluidics system unique. manage multiple factors at once— ment removal and irrigation/aspira- “The Stellaris’s system allows the if they wish. “Most surgeons like
18 | Review of Ophthalmology | February 2017
016_rp0217_tech update.indd 18 1/18/17 2:12 PM to have two or three basic modes es of the nucleus to come to the tip surge,” he says. “It maintains excellent set up for their machines, such as so I can stay in the middle of the eye chamber stability even with vacuum dense-lens, soft-lens and small-pupil and do my usual stop-and-chop ma- settings of 600 mmHg. We performed modes. On the other hand, some sur- neuver with ease, even when dealing a study in which we used an endo- geons also like to have the ability to with moderate-to-hard cataracts. This scope to video the chamber stability modulate their parameters on the has been a big help in many small- during a standard case, and we saw fly. Dual-linear control allows the pupil, Flomax and pseudoexfoliation almost no movement of the iris or surgeon to manage two parameters, cases. Vacuum-based systems also shallowing of the chamber. such as aspiration and power, with maximize effi ciency for femtosecond- Dr. Singh adds that he finds the the foot pedal. Your foot can press laser-assisted cases. In these cases, dual-linear foot pedal very useful. “It down on the pedal as if it were an ac- you don’t need to use as much ultra- gives me separate control of phaco, celerator to control one variable, but sound sculpting; the broken-up lens vacuum and irrigation,” he says. “For you can also move it side to side to pieces come to the tip. This allows example, during epinuclear removal control a second variable.” me to perform single-incision cataract pushing down on the foot pedal con- Inder Paul Singh, MD, who prac- surgery without the creation of a para- trols irrigation and aspiration, but if I tices at The Eye Centers of Racine centesis because there’s no need for a need a pulse of ultrasound, I can yaw & Kenosha in Wisconsin, uses the second instrument to help bring them to the right to get that burst. This gives Stellaris Phaco unit. “The fact that it’s to the tip.” me another level of control.” vacuum-based rather than fl uid-based Dr. Singh says he’s impressed by creates many advantages,” he says. the chamber stability he gets. “The Dr. Singh is a consultant to “First, you don’t have to occlude the Stellaris decouples vacuum and fl ow, Bausch + Lomb; Drs. Lubeck and phaco tip to build vacuum. Vacuum which leads to lower fl ow at high vac- Crandall are consultants for Alcon; occurs instantaneously, allowing piec- uum and a decreased likelihood of Dr. Garg is a consultant to AMO.
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016_rp0217_tech update.indd 19 1/18/17 2:12 PM Indications and Usage • Increased Bleeding Time of Ocular Tissue: BromSite™ (bromfenac ophthalmic solution) 0.075% is a With some NSAIDs, including BromSite (bromfenac nonsteroidal anti-infl ammatory drug (NSAID) indicated for ophthalmic solution) 0.075%, there exists the potential the treatment of postoperative infl ammation and prevention for increased bleeding time due to interference with of ocular pain in patients undergoing cataract surgery. platelet aggregation. There have been reports that Important Safety Information ocularly applied NSAIDs may cause increased bleeding • Slow or Delayed Healing: All topical nonsteroidal of ocular tissues (including hyphemas) in conjunction anti-infl ammatory drugs (NSAIDs), including BromSite with ocular surgery. (bromfenac ophthalmic solution) 0.075%, may slow It is recommended that BromSite be used with caution or delay healing. Topical corticosteroids are also known in patients with known bleeding tendencies or who to slow or delay healing. Concomitant use of topical are receiving other medications which may prolong NSAIDs and topical steroids may increase the potential bleeding time. for healing problems. • Use of topical NSAIDs may result in keratitis. Patients • Potential for Cross-Sensitivity: There is the potential with evidence of corneal epithelial breakdown should for cross-sensitivity to acetylsalicylic acid, phenylacetic immediately discontinue use of topical NSAIDs, including acid derivatives, and other NSAIDs, including BromSite BromSite (bromfenac ophthalmic solution) 0.075%, and (bromfenac ophthalmic solution) 0.075%. Therefore, should be closely monitored for corneal health. Patients caution should be used when treating individuals who with complicated ocular surgeries, corneal denervation, have previously exhibited sensitivities to these drugs. corneal epithelial defects, diabetes mellitus, ocular
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surface diseases (e.g., dry eye syndrome), rheumatoid • The most commonly reported adverse reactions arthritis, or repeat ocular surgeries within a short period in 1% to 8% of patients were anterior chamber of time may be at increased risk for corneal adverse events infl ammation, headache, vitreous fl oaters, iritis, which may become sight threatening. Topical NSAIDs eye pain, and ocular hypertension. should be used with caution in these patients. Post- You are encouraged to report negative side marketing experience with topical NSAIDs also suggests effects of prescription drugs to the FDA. that use more than 24 hours prior to surgery or use Visit www.fda.gov/medwatch or call 1-800-FDA-1088. beyond 14 days postsurgery may increase patient risk for the occurrence and severity of corneal adverse events. Please see brief summary of full Prescribing • BromSite should not be administered while wearing Information on the adjacent page. contact lenses. The preservative in BromSite, benzalkonium NSAID=nonsteroidal anti-infl ammatory drug. chloride, may be absorbed by soft contact lenses.
References: 1. BromSite [package insert]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2016. 2. Hosseini K, Hutcheson J, Bowman L. Aqueous humor concentration of bromfenac 0.09% (Bromday™) compared with bromfenac in DuraSite® 0.075% (BromSite™) in cataract patients undergoing phacoemulsifi cation after 3 days dosing. Poster presented at: ARVO Annual Meeting; May 5-9, 2013; Seattle, Washington. 3. Bowman LM, Si E, Pang J, et al. Development of a topical polymeric mucoadhesive ocular delivery system for azithromycin. J Ocul Pharmacol Ther. 2009;25(2):133-139. 4. ClinicalTrials.gov. Aqueous humor concentration of InSite Vision (ISV) 303 (bromfenac in DuraSite) to Bromday once daily (QD) prior to cataract surgery. https://clinicaltrials.gov/ct2/show/results/NCT01387464?sect=X70156&term=insite+vision&rank=1. Accessed July 18, 2016. 5. Si EC, Bowman LM, Hosseini K. Pharmacokinetic comparisons of bromfenac in DuraSite and Xibrom. J Ocul Pharmacol Ther. 2011;27(1):61-66.
Sun Ophthalmics is a division of Sun Pharmaceutical Industries, Inc. © 2016 Sun Pharmaceutical Industries, Inc. All rights reserved. DuraSite® and BromSite™ are trademarks of Sun Pharma Global FZE. SUN-OPH-BRO-015 09/2016
RP1216_Sun.indd 3 11/16/16 2:56 PM BromSite™ (bromfenac ophthalmic solution) 0.075% USE IN SPECIFIC POPULATIONS Brief Summary Pregnancy Risk Summary There are no adequate and well-controlled studies in pregnant women to inform any drug associated risks. Treatment of pregnant rats and rabbits with oral bromfenac did INDICATIONS AND USAGE not produce teratogenic effects at clinically relevant doses. BromSite™ (bromfenac ophthalmic solution) 0.075% is a nonsteroidal Clinical Considerations anti-inflammatory drug (NSAID) indicated for the treatment of postoperative Because of the known effects of prostaglandin biosynthesis-inhibiting drugs on the inflammation and prevention of ocular pain in patients undergoing cataract surgery. fetal cardiovascular system (closure of ductus arteriosus), the use of BromSite during DOSAGE AND ADMINISTRATION late pregnancy should be avoided. Recommended Dosing Data One drop of BromSite should be applied to the affected eye twice daily (morning Animal Data and evening) 1 day prior to surgery, the day of surgery, and 14 days postsurgery. Treatment of rats with bromfenac at oral doses up to 0.9 mg/kg/day (195 times a Use with Other Topical Ophthalmic Medications unilateral daily human ophthalmic dose on a mg/m2 basis, assuming 100% absorbed) BromSite should be administered at least 5 minutes after instillation and rabbits at oral doses up to 7.5 mg/kg/day (3243 times a unilateral daily dose of other topical medications. on a mg/m2 basis) produced no structural teratogenicity in reproduction studies. However, embryo-fetal lethality, neonatal mortality and reduced postnatal growth Dosage Forms and Strengths were produced in rats at 0.9 mg/kg/day, and embryo-fetal lethality was produced Topical ophthalmic solution: bromfenac 0.075%. in rabbits at 7.5 mg/kg/day. Because animal reproduction studies are not always CONTRAINDICATIONS predictive of human response, this drug should be used during pregnancy only if None the potential benefit justifies the potential risk to the fetus. WARNINGS AND PRECAUTIONS Lactation Slow or Delayed Healing There are no data on the presence of bromfenac in human milk, the effects on the All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including BromSite breastfed infant, or the effects on milk production; however, systemic exposure to (bromfenac ophthalmic solution) 0.075%, may slow or delay healing. Topical bromfenac from ocular administration is low. The developmental and health benefits corticosteroids are also known to slow or delay healing. Concomitant use of topical of breastfeeding should be considered along with the mother’s clinical need for NSAIDs and topical steroids may increase the potential for healing problems. bromfenac and any potential adverse effects on the breast-fed child from bromfenac or from the underlying maternal condition. Potential for Cross-Sensitivity There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid Pediatric Use derivatives, and other NSAIDs, including BromSite (bromfenac ophthalmic solution) Safety and efficacy in pediatric patients below the age of 18 years 0.075%. Therefore, caution should be used when treating individuals who have have not been established. previously exhibited sensitivities to these drugs. Geriatric Use Increased Bleeding Time of Ocular Tissue There is no evidence that the efficacy or safety profiles for BromSite differ With some NSAIDs, including BromSite (bromfenac ophthalmic solution) 0.075%, in patients 65 years of age and older compared to younger adult patients. there exists the potential for increased bleeding time due to interference with NONCLINICAL TOXICOLOGY platelet aggregation. There have been reports that ocularly applied NSAIDs may Carcinogenesis, Mutagenesis and Impairment of Fertility cause increased bleeding of ocular tissues (including hyphemas) in conjunction Long-term carcinogenicity studies in rats and mice given oral doses of bromfenac up with ocular surgery. to 0.6 mg/kg/day (129 times a unilateral daily dose assuming 100% absorbed, on a It is recommended that BromSite be used with caution in patients with known mg/m2 basis) and 5 mg/kg/day (540 times a unilateral daily dose on a mg/m2 basis), bleeding tendencies or who are receiving other medications which may prolong respectively revealed no significant increases in tumor incidence. bleeding time. Bromfenac did not show mutagenic potential in various mutagenicity studies, including Keratitis and Corneal Reactions the bacterial reverse mutation, chromosomal aberration, and micronucleus tests. Use of topical NSAIDs may result in keratitis. In some susceptible patients, Bromfenac did not impair fertility when administered orally to male and female rats continued use of topical NSAIDs may result in epithelial breakdown, corneal at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, respectively (195 and 65 times a thinning, corneal erosion, corneal ulceration or corneal perforation. These events unilateral daily dose, respectively, on a mg/m2 basis). may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs, including BromSite (bromfenac PATIENT COUNSELING INFORMATION ophthalmic solution) 0.075%, and should be closely monitored for corneal health. Slow or Delayed Healing Post-marketing experience with topical NSAIDs suggests that patients with Advise patients of the possibility that slow or delayed healing may occur complicated ocular surgeries, corneal denervation, corneal epithelial defects, while using NSAIDs. diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid Concomitant Topical Ocular Therapy arthritis, or repeat ocular surgeries within a short period of time may be at increased If more than one topical ophthalmic medication is being used, advise patients to risk for corneal adverse events which may become sight threatening. Topical NSAIDs administer BromSite at least 5 minutes after instillation of other topical medications. should be used with caution in these patients. Concomitant Use of Contact Lenses Post-marketing experience with topical NSAIDs also suggests that use more than Advise patients not to wear contact lenses during administration of BromSite. 24 hours prior to surgery or use beyond 14 days postsurgery may increase patient The preservative in this product, benzalkonium chloride, may be absorbed by risk for the occurrence and severity of corneal adverse events. soft contact lenses. Contact Lens Wear Sterility of Dropper Tip/Product Use BromSite should not be administered while wearing contact lenses. The preservative Advise patients to replace the bottle cap after use and do not touch the dropper in BromSite, benzalkonium chloride, may be absorbed by soft contact lenses. tip to any surface as this may contaminate the contents. ADVERSE REACTIONS Advise patients to thoroughly wash hands prior to using BromSite. Clinical Trial Experience Rx Only Because clinical trials are conducted under widely varying conditions, adverse Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The most commonly reported adverse reactions in 1–8% of patients were: anterior chamber inflammation, headache, vitreous floaters, iritis, eye pain BromSite is a trademark of Sun Pharma Global FZE. and ocular hypertension. SUN-OPH-BRO-017 09/2016
RRP1216_SunP1216_Sun PPI.inddI.indd 1 111/16/161/16/16 2:572:57 PMPM 023_rp0217_mqa.indd 23 What’s New in2017? increases inreimbursement; procedures hadsubstantial three percentorless.Nine them changedverylittle:By Medicare program,526of ogy andoptometrywithinthe percent. target adjustmentof-0.18 a misvaluedcodereduction resulting fromMACRAand an increaseof0.5percent adjustment of-0.013percent, includes abudgetneutrality conversion factorof$35.8043.It a slightincreasefromthe2016 sion factoris$35.8887,which by the the SustainableGrowthRateformula 2016 isthesecondsincerepealof Federal RegisteronNovember15, A A ophthalmic services? services? ophthalmic 2015? of Act Reauthorization Medicare Access and CHIP increase included in the 0.5-percent the include Q This articlehasnocommercial sponsorship. Q how theymightaffectyourpractice. This month,wetakealookatMedicare’s updatesfor2017and REVIEW Donna McCune, CCS-P, COE, CPMA Medicare Q&A that applytoophthalmol- Of the553CPTcodes Schedule Rulepublishedinthe Yes. The2017PhysicianFee changes to RVUs for signifi there Are Schedule Fee Physician 2017 Medicare the Did MACRA. The2017conver- cant *In 2017, services. theseprocedures aredefinedasbilateral Table 1. MedicarePayments forOphthalmic Imaging 23 SCODI, optic nerve 92133 24 FA &ICG* 92242 25 udspoorpy$9$67 SCODI, retina $79 92134 SCODI, anterior Fundusphotography 92132 92250 23 loeci nigah*$1 $87 $111 ICGangiography* Fluorescein angiography* 92240 92235 CPT shortened to10days. duced whenthepostopperiodwas reductions in2016.Otherswerere- favorably revaluedaftersignifi glaucoma procedurecodeswere (0.01 percent).Someretinaand ophthalmic servicesisminiscule Medicare reimbursementratesfor reimbursement. Average changein 18 hadsubstantialreductionsin dramatically in 2017? Q
of service that changes changes that service of type aparticular there Is Description February 2017 cant 4 $42 $38 $45 $32 $44 $35 27$1 -20% $230 $211 N/A $257 0621 Change% 2017 2016 angiography was paid per eye. angiography waspaidpereye. magnified thereduction.Formerly, of angiographyasabilateralservice duced (SeeTable 1).Theredefi imaging servicesisdramaticallyre- A A reimbursement in 2017? experience increases in facility centers surgery ambulatory Q bursement forallophthalmic Yes. In2017,Medicarereim- tal reimbursementresultina Various adjustmentstohospi- | departments anddepartments Will outpatient hospital reviewofophthalmology.com -10% -14% -16% -24% -8% N/A nition nition |
23 1/20/17 4:45 PM Medicare
REVIEW Q&A
Hospital Outpatient Department of $10 million annually; performed; cryotherapy. rate increase of 1.65 percent. • can report beginning January 1, Δ 67105 Photocoagulation in- For 2017, the wage adjustment 2017; and cluding drainage of subretinal for budget neutrality in addition • mandatory reporting starting fl uid, when performed. to the multifactor productivity-ad- July 1, 2017. Δ 92235 Fluorescein angiogra- justed update factor increases the The fi nal list of codes will be post- phy (includes multiframe imaging) ASC conversion factor by 1.9 per- ed to the CMS website; there are with interpretation and report, cent for those meeting the quality only 40 CPT codes that might po- unilateral or bilateral. reporting requirements, resulting tentially apply to ophthalmology. Δ 92240 Indocyanine-green an- in small increases in facility reim- giography (includes multiframe bursement. imaging) with interpretation and report, unilateral or bilateral. Are there new quality Deleted in 2017: Q measures for ASCs to Some retina and Δ 92140 Provocative tests for report in 2017? glaucoma, with interpretation and glaucoma procedure report, without tonography. No. No new measures were add- codes were favorably A ed in 2017, which would affect Are there any new payments in 2019. Seven additional revalued after Q Category III codes for measures were finalized for imple- signifi cant reductions 2017? mentation in 2018, which will affect 2020 payments. in 2016. Others were Released semiannually by reduced when the A the American Medical Asso- Did MACRA impose ciation, new Category III codes Q any new reporting postop period was became effective January 1, 2017 requirements for surgeons? shortened to 10 days following the six-month implemen- tation period that began July 1, Yes. As of January 1, 2017, 2016. A MACRA, Section 1848(c)(8) Δ 0444T – Initial placement of (B), requires collection of data to a drug-eluting ocular insert under value global surgical packages in- one or more eyelids, including fit- cluding the number of and level of What CPT code changes ting, training, and insertion, uni- visits in the global period and other Q became effective on lateral or bilateral. items and services related to sur- January 1, 2017? Δ 0445T – Subsequent place- gery. The proposed rule contained ment of a drug-eluting ocular in- onerous reporting requirements Category I CPT code changes sert under one or more eyelids, vehemently opposed by surgeons A are as follows: including re-training, and removal of all specialties. The final rule re- New code: of existing insert, unilateral or bi- vises the reporting to include the Δ 92242 Fluorescein angiography lateral. following: and indocyanine-green angiography Δ 0449T – Insertion of anterior • submit with CPT code 99024; (includes multiframe imaging) per- segment drainage device, without • applies to groups with 10 or formed at the same patient encoun- extraocular reservoir; internal ap- more practitioners; ter with interpretation and report. proach, into the subconjunctival • only applies in certain states The following codes contain lan- space. (Florida, Kentucky, Louisiana, guage changes described by under- Δ +0450T – each additional de- Nevada, New Jersey, North lines and represent clarifications vice (List separately in addition to Dakota, Ohio, Oregon, Rhode and, in some cases, substantive re- code for primary procedure). Island); visions: Use 92499 For removal of aque- • report services annually by Δ 67101 Repair of retinal detach- ous drainage device without extra- more than 100 practitioners ment, one or more sessions; cryo- ocular reservoir, placed into the and more than 10,000 times or therapy or diathermy including subconjunctival space via internal have allowed charges in excess drainage of subretinal fl uid when approach.
24 | Review of Ophthalmology | February 2017
0023_rp0217_mqa.indd23_rp0217_mqa.indd 2424 11/20/17/20/17 4:464:46 PMPM Two new and one revised The Medicare Part B basic pre- Category III codes are effective A mium increases to $109 for most January 1, 2017 and will be pub- benefi ciaries. The Part B deductible lished in the 2018 CPT manual: increases to $183. This is a $17 in- Δ 0464T Visual evoked potential, crease from the 2016 deductible. testing for glaucoma, with inter- pretation and report. What changes occurred For visual evoked potential Q with the Medicare Quality screening for visual acuity, use Programs? 0333T. Δ 0465T Suprachoroidal injec- MACRA consolidates the cur- tion of a pharmacologic agent A rent quality reporting pro- (does not include supply of medi- grams of PQRS, EHR Meaningful cation.) Use and the Value-Based Payment The To report intravitreal injection/ Modifier into a new program: the Series 3 implantation, see 67025, 67027 or Merit-Based Incentive Payment 67028. System. The law stipulates a Janu- Δ 0333T Visual evoked potential, ary 1, 2017 start date, but the first RETINOMAX screening of visual acuity, auto- bonus or penalty occurs in 2019 mated, with report. based on a two-year look-back. Coverage and payment for The penalties associated with the HAND-HELD Category III codes remains at current quality reporting programs the discretion of the Medicare sunset after 2018. Autorefractor Administrative Contractor. Were changes made to the Precise measurements What types of regulatory Q electronic health record Anywhere - Anytime Q issues were identifi ed Meaningful Use reporting? in the Offi ce of Inspector General’s annual work plan Yes. The 2015 Electronic A Health Record Flexibility Rule as areas of concern for •Accurate ophthalmology in 2017? revised the requirements for Mean- ingful Use attestation. For 2015 to •Fast The annual publication of the 2017, all eligible professionals must A Office of Inspector General’s report on 10 mandatory objectives •Portable Work Plan contains a few targets included in the Modified Stage 2 for scrutiny of concern to ophthal- Rule. Failure to attest for 2016 •Efficient mologists and optometrists. The participation results in a 4-percent targets are: penalty in 2018. Providers who • Drug Waste of Single-Vial have already attested to MU in pri- Drugs (new); or years are required to report MU • Management Review: CMS’ for any continuous 90-day period Implementation of the Quality in 2016 and 2017. The reporting Payment Program (new); deadline for 2016 is February 28, • ASC – Quality Oversight; 2017. If a provider has never attest- • Anesthesia services – Payments ed to MU and is attesting for the for personally performed services. fi rst time, attestation by October 1, 2017 avoids a 2018 penalty. What Medicare Part Q B changes affect Ms. McCune is vice pres ident of the benefi ciaries from a cost Cor coran Con sult ing Group. Con tact perspective in 2017? her at [email protected].
250 Cooper Ave., Suite 100 Tonawanda NY 14150 www.s4optik.com I 888-224-6012 Sensible equiptment. Well made, well priced. For today’s modern office.
023_rp0217_mqa.indd 25 1/20/17 4:46 PM Cataract & Refractive Surgery REVIEW Cover Focus Toric IOLs: Nailing the Target Meridian
Christopher Kent, Senior Editor
Surgeons explain ike multifocal intraocular lens- Measuring: The Basics es, toric IOLs are considered how to provide Lto be premium lenses. How- While advanced technology can ever, they have one striking advantage increase the precision of lens align- your patients over multifocal IOLs: They’re not as- ment, the basic equipment found in sociated with many postoperative op- most practices can still do a good job. with outstanding tical complaints. Instead, they correct [For more on this, see “Toric Lenses: a basic problem shared by millions of What’s Holding You Back?” on p. 28.] results using these eyes, improving post-cataract surgery If you don’t have access to the latest vision—in some cases dramatically. advanced instrumentation, Robert H. lenses. However, in order for a toric lens to Osher, MD, a professor in the depart- effectively reduce or eliminate astig- ment of ophthalmology at the Univer- matism, its toric axis must be accu- sity of Cincinnati College of Medicine rately aligned with the target merid- and medical director emeritus at the ian. Every degree of misalignment Cincinnati Eye Institute in Ohio, rec- eliminates about 3.3 percent of the ommends relying on three basic in- astigmatism correction, so a multi- struments. “Everyone can do manual degree misalignment can signifi cantly keratometry,” he notes. “Today, the undercut the value of the lens. majority of cataract surgeons also have To get the best outcome with a toric an automated keratometer—either lens, surgeons say it’s important to do IOLMaster or LenStar. Everybody three things well: measure the astig- should also have a topography unit. matic axis accurately; have an effective That’s important because you need way to visualize the target meridian to see what kind of cylinder you’re when the patient is on the table; and dealing with, so you can differentiate position the lens inside the eye during keratoconus or some irregular contact surgery so the lens is aligned with that lens problem from regular cylinder. target meridian and remains there Of course, the presence of an unusual postoperatively. Here, three surgeons fi nding doesn’t mean you’re not going with extensive experience implanting to offer a toric lens, but it certainly these lenses share their advice on how means that you have to explain the to achieve all of these goals, whether situation to the patient.” you’re using relatively low-tech instru- Stephen S. Lane, MD, medical di- ments or the latest in advanced mea- rector at Associated Eye Care and suring and marking systems. adjunct clinical professor of ophthal-
26 | Review of Ophthalmology | February 2017 This article has no commercial sponsorship.
0026_rp0217_f1.indd26_rp0217_f1.indd 2626 11/18/17/18/17 2:172:17 PMPM Stephen S. Lane, MD mology at the University of Minnesota in Minneapolis, says your axis determi- nation should be reasonably accurate if you use an automated keratometer and topography. “Primarily, you have SMART to begin with good preoperative kera- tometry readings,” he says. “A number COMBO of devices can give you that; even man- The Verion’s toric IOL guidance overlay, with ual keratometry can give you good, the target axis set at 95 degrees. The toric UNITS reproducible data if you have someone IOL would be rotated to align with this 95- who is very good at performing it. But degree guide, with no need for ink marks. today, I think most doctors are using an IOLMaster or LenStar to deter- If you measure with two technologies, mine these measurements.” Topcon’s that drops to 8 to 10 percent. But if Aladdin and Movu’s Argos are other you use three technologies, only about options surgeons can use for biometry. 2 percent of the numbers you end up “Topography is probably the best with are outliers. Everyone does man- technology we have today to measure ual keratometry, and everyone should the axis,” Dr. Lane adds. “The axis do an automated K. In addition, you of astigmatism should correlate quite should get topography, because you nicely with the automated keratome- need to understand what the astigma- try readings that you would get with an tism pattern looks like.” space IOLMaster or LenStar, assuming that Although the basic gear found in you’re measuring a relatively normal, most practices today can do a good & functionality healthy cornea. They won’t necessar- job of determining the target meridian A complete solution ily agree exactly, but they should be and amount of astigmatism, there’s no DWDQDƪRUGDEOHSULFH very close. Then, you can use all of the question that having additional ad- rSmall footprint various readings to hone in on what is vanced technology can increase your the most likely—or at least the aver- accuracy. Dr. Osher has access to mul- rRobust all metal construction age—keratometry reading. The more tiple technologies and takes full advan- built for longevity readings you have, the better your re- tage of them. Focus on patient comfort sult. In most cases I rely on automated “Because I’m somewhat of an ac- r keratometry for magnitude; I believe ademician and I love technology, I rSpectacular engineering topography is probably the most accu- collect additional measurements with Smooth tilt/glide function rate and sensitive in terms of the axis.” other devices,” says Dr. Osher. “I mea- r sure with the iTrace because I want &RQƬJXUDWLRQV More Data = Greater Accuracy to see the aberrometry and those Ks. VROXWLRQVIRUHYHU\RƯFH I use the Pentacam because I want Dr. Osher explains that measur- to measure the posterior cornea. And ing with multiple technologies helps I have the luxury of using both the to eliminate outlier measurements. IOLMaster and the LenStar, so I end “All of the machines measure slightly up with six sets of Ks for every patient. differently,” he notes. “A study we Of course, I would never recommend published looked at the question of that every ophthalmologist do this, how much your accuracy improves because the extra work and expense if you measure with more than one would convince many surgeons not instrument and ‘meld,’ or average, to offer toric lenses. But I want to see the numbers.1 After testing 87 eyes all of those measurements because I of 54 patients we found that if you think they’re important. They improve only measure with one technology, the my understanding and increase my number you end up with will be an confi dence. outlier about 20 percent of the time. “When I average all of these mea- 250 Cooper Ave., Suite 100 Tonawanda NY 14150 ZZZVRSWLNFRP, Sensible equipment. Well made, well priced. )RUWRGD\oVPRGHUQRƯFH
026_rp0217_f1.indd 27 1/18/17 2:17 PM Cover Cataract & Refractive Surgery
REVIEW Focus
Toric Lenses: What’s Holding You Back?
Robert H. Osher, MD, medical director emeritus at the Cincin- Dr. Lane suspects that one of the barriers to wider use of toric nati Eye Institute in Ohio, notes that current use of toric lenses in IOLs in the United States is the belief—held by many surgeons— the United States is about 7.5 percent. “That isn’t changing very that to get good results it’s necessary to use advanced-technology rapidly,” he says. “I can see fi ve concerns that may be holding alignment devices and/or aberrometry. “I think that’s a misunder- surgeons back: the cost to the patient; taking the time to talk to standing,” he says. “The fi rst thing to remember is that the original these patients; having enough technology in your practice; know- clinical trials didn’t use anything more than manual keratometry ing how to interpret the technology; and knowing how to plan and and alignment with ink marks that the surgeon placed manually execute the surgery. In reality, the surgery itself is about the same with the patient sitting upright. In the original FDA clinical trial with as a routine cataract, yet these lenses can give our patients the Alcon toric IOLs, 97 percent of patients were independent of spec- best possible vision.” tacles at distance when both eyes were implanted, using what we Stephen S. Lane, MD, medical director at Associated Eye Care would consider today to be relatively crude tools. So getting good and adjunct clinical professor of ophthalmology at the University results is not predicated upon having high-tech alignment devices of Minnesota in Minneapolis, agrees. “Overall, I think there are and aberrometers. Those tools certainly can improve results, but far fewer toric lenses being placed than should be,” he says. surgeons and practices that are considering offering or starting to “Many patients are good candidates for these lenses. We wouldn’t offer toric IOLs to their patients need to realize they don’t have to prescribe eyeglasses for our patients and leave the cylinder out of have all the toys that are now available in order to do this. You can the prescription, so it makes no sense to do cataract surgery and get very good results with a few basic instruments.” deliberately fail to correct the cylinder.” —CK
surements together, it’s amazing how the Thermodot device, which will nologies can give us greater accuracy.” consistent the numbers are,” he says. fi nally be released this year by Bea- In addition to using Thermodots, “If one measurement is an outlier, ver-Visitec International [Waltham, Dr. Osher currently favors Zeiss’s Cal- I throw it out, but I usually get very Mass.]. It makes a tiny pinpoint cau- listo Eye System for aligning his toric good consistency on both the meridian tery mark that eliminates the need for lenses. “It stores the original IOL- and the amount of cylinder. Further- ink. The mark is so small it isn’t even Master biometry measurements and more, if more than one reading is an felt by the patient, and it’s gone in a memorizes the anatomy,” he explains. outlier, then I check the topography day or two. To become even more ac- “When you’re in the OR, you turn on for warpage or tear-fi lm integrity, or curate, I’d suggest iris fi ngerprinting, the Callisto Eye System monitor and search for some other problem. The which is very inexpensive compared to it registers and links up the preopera- patient may not be an ideal candidate aberrometry or the sophisticated reg- tive and live images. Then, you press for a toric lens, and needs to be told.” istration methods. You use a camera to a button and the axis appears in your take a picture and then very inexpen- ocular. It looks like a two-lane high- Marking, from Ink to High-tech sive software tells you at which degree way, making it very easy to align the each iris landmark is located.” lens. It’s simple, quick and accurate.” Once you’ve decided on the target Dr. Lane notes that you’re likely to [See example on p. 32.] meridian, you have to use some form achieve the greatest accuracy of align- David F. Chang, MD, clinical pro- of guidance that will allow you to align ment with toric IOLs when using a fessor at the University of California, the IOL along that meridian. The least guidance system such as Verion, Cal- San Francisco, and in private practice expensive and most common (and ar- listo or the TrueVision system. “With in Los Altos, Calif., agrees. “We’ve guably least accurate) method is to those technologies, you’re trying to used the Zeiss Callisto markerless place ink marks on the cornea. “We align the lens inside the eye relative to system for nearly two years, and it’s a all know that ink diffuses, and in the a fi ne line, as opposed to an ink mark. no-brainer,” he says. “If you already worst-case scenario it disappears com- [Despite its drawbacks,] an ink mark have an IOLMaster 500, you can add pletely,” says Dr. Osher. “Even with can be fairly accurate—that’s what we an inexpensive camera attachment to accurate marking, ink marks are often used in the initial [toric IOL] clinical the front of the machine. There’s no 5 or 10 degrees off, and every degree trial, producing pretty good results. click fee, and it saves a lot of time for away from the target meridian elimi- But since we’re trying to get as close the surgeon and the nursing staff in nates about 3.3 percent of the effect of as we possibly can to the correct axis, terms of operating room workflow. the toric lens. That’s why I developed there’s no question that guidance tech- The improved accuracy is immediately
28 | Review of Ophthalmology | February 2017
0026_rp0217_f1.indd26_rp0217_f1.indd 2828 11/18/17/18/17 2:172:17 PMPM The PROLENSA® Effect POWERED FOR PENETRATION Advanced Formulation to Facilitate Corneal Penetration1-3
PROLENSA® delivers potency and corneal penetration with QD dosing at a low concentration1-3
INDICATIONS AND USAGE PROLENSA® (bromfenac ophthalmic solution) 0.07% is a • Use of topical NSAIDs may result in keratitis. nonsteroidal anti-infl ammatory drug (NSAID) indicated Patients with evidence of corneal epithelial breakdown for the treatment of postoperative infl ammation and should immediately discontinue use of topical NSAIDs, reduction of ocular pain in patients who have undergone including bromfenac, and should be closely monitored cataract surgery. for corneal health. Patients with complicated ocular IMPORTANT SAFETY INFORMATION ABOUT PROLENSA® surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases • PROLENSA® contains sodium sulfi te, a sulfi te that may (e.g., dry eye syndrome), rheumatoid arthritis, or repeat cause allergic type reactions including anaphylactic ocular surgeries within a short period of time may be symptoms and life-threatening or less severe asthmatic at increased risk for corneal adverse events which may episodes in certain susceptible people. The overall become sight threatening. Topical NSAIDs should be used prevalence of sulfi te sensitivity in the general population is with caution in these patients. Post-marketing experience unknown and probably low. Sulfi te sensitivity is seen more with topical NSAIDs suggests that use more than 24 hours frequently in asthmatic than in non-asthmatic people. prior to surgery or use beyond 14 days post-surgery may • All topical nonsteroidal anti-infl ammatory drugs (NSAIDs), increase patient risk for the occurrence and severity of including bromfenac, may slow or delay healing. corneal adverse events. Concomitant use of topical NSAIDs and topical steroids • PROLENSA® should not be instilled while wearing contact may increase the potential for healing problems. lenses. The preservative in PROLENSA®, benzalkonium • There is the potential for cross-sensitivity to acetylsalicylic chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following acid, phenylacetic acid derivatives, and other NSAIDs, ® including bromfenac. Use with caution in patients who administration of PROLENSA . have previously exhibited sensitivities to these drugs. • The most commonly reported adverse reactions in 3%-8% • There have been reports that ocularly applied NSAIDs of patients were anterior chamber infl ammation, foreign may cause increased bleeding of ocular tissues (including body sensation, eye pain, photophobia, and blurred vision. hyphemas) in conjunction with ocular surgery. Use with Please see brief summary of full Prescribing Information caution in patients with known bleeding tendencies or for PROLENSA® on adjacent page. who are receiving other medications which may prolong References: 1. PROLENSA Prescribing Information, April 2013. 2. Data on fi le, Bausch & Lomb Incorporated. bleeding time. 3. Baklayan GA, Patterson HM, Song CK, Gow JA, McNamara TR. 24-hour evaluation of the ocular distribution of (14)C-labeled bromfenac following topical instillation into the eyes of New Zealand white rabbits. J Ocul Pharmacol Ther. 2008;24(4):392-398.
PROLENSA is a registered trademark of Bausch & Lomb Incorporated or its affi liates. © Bausch & Lomb Incorporated. All rights reserved. Printed in USA. PRA.0188.USA.15
RP0316_BL Prolensa.indd 1 2/16/16 10:37 AM BRIEF SUMMARY OF PRESCRIBING INFORMATION rates in the clinical trials of another drug and may not reflect the rates observed in This Brief Summary does not include all the information needed to prescribe clinical practice. Prolensa safely and effectively. See full prescribing information for Prolensa. The most commonly reported adverse reactions following use of PROLENSA ophthalmic solution following cataract surgery include: anterior chamber PROLENSA (bromfenac opthalmic solution) 0.07% inflammation, foreign body sensation, eye pain, photophobia and vision blurred. These reactions were reported in 3 to 8% of patients. Rx only Initial Rx Approval: 1997 USE IN SPECIFIC POPULATIONS Pregnancy INDICATIONS AND USAGE Treatment of rats at oral doses up to 0.9 mg/kg/day (systemic exposure 90 times the ® PROLENSA (bromfenac ophthalmic solution) 0.07% is indicated for the treatment systemic exposure predicted from the recommended human ophthalmic dose [RHOD] of postoperative inflammation and reduction of pain in patients who have undergone assuming the human systemic concentration is at the limit of quantification) and cataract surgery. rabbits at oral doses up to 7.5 mg/kg/day (150 times the predicted human systemic DOSAGE AND ADMINISTRATION exposure) produced no treatment-related malformations in reproduction studies. However, embryo-fetal lethality and maternal toxicity were produced in rats and Recommended Dosing rabbits at 0.9 mg/kg/day and 7.5 mg/kg/day, respectively. In rats, bromfenac One drop of PROLENSA ophthalmic solution should be applied to the affected eye treatment caused delayed parturition at 0.3 mg/kg/day (30 times the predicted once daily beginning 1 day prior to cataract surgery, continued on the day of surgery, human exposure), and caused dystocia, increased neonatal mortality, and reduced and through the first 14 days of the postoperative period. postnatal growth at 0.9 mg/kg/day. Use with Other Topical Ophthalmic Medications There are no adequate and well-controlled studies in pregnant women. Because PROLENSA ophthalmic solution may be administered in conjunction with other topical animal reproduction studies are not always predictive of human response, this drug ophthalmic medications such as alpha-agonists, beta-blockers, carbonic anhydrase should be used during pregnancy only if the potential benefit justifies the potential inhibitors, cycloplegics, and mydriatics. Drops should be administered at least 5 risk to the fetus. minutes apart. Because of the known effects of prostaglandin biosynthesis-inhibiting drugs on the CONTRAINDICATIONS fetal cardiovascular system (closure of ductus arteriosus), the use of PROLENSA ophthalmic solution during late pregnancy should be avoided. None Nursing Mothers WARNINGS AND PRECAUTIONS Caution should be exercised when PROLENSA is administered to a nursing woman. Sulfite Allergic Reactions Pediatric Use Contains sodium sulfite, a sulfite that may cause allergic-type reactions including Safety and efficacy in pediatric patients below the age of 18 have not been anaphylactic symptoms and life-threatening or less severe asthmatic episodes in established. certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in Geriatric Use asthmatic than in non-asthmatic people. There is no evidence that the efficacy or safety profiles for PROLENSA differ in patients 70 years of age and older compared to younger adult patients. Slow or Delayed Healing All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including bromfenac, may NONCLINICAL TOXICOLOGY slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Carcinogenesis, Mutagenesis and Impairment of Fertility Concomitant use of topical NSAIDs and topical steroids may increase the potential for Long-term carcinogenicity studies in rats and mice given oral doses of bromfenac up healing problems. to 0.6 mg/kg/day (systemic exposure 30 times the systemic exposure predicted from Potential for Cross-Sensitivity the recommended human ophthalmic dose [RHOD] assuming the human systemic There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid concentration is at the limit of quantification) and 5 mg/kg/day (340 times the derivatives, and other NSAIDs, including bromfenac. Therefore, caution should be predicted human systemic exposure), respectively, revealed no significant increases used when treating individuals who have previously exhibited sensitivities to these in tumor incidence. drugs. Bromfenac did not show mutagenic potential in various mutagenicity studies, Increased Bleeding Time including the reverse mutation, chromosomal aberration, and micronucleus tests. With some NSAIDs, including bromfenac, there exists the potential for increased Bromfenac did not impair fertility when administered orally to male and female rats at bleeding time due to interference with platelet aggregation. There have been doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, respectively (systemic exposure 90 reports that ocularly applied NSAIDs may cause increased bleeding of ocular tissues and 30 times the predicted human exposure, respectively). (including hyphemas) in conjunction with ocular surgery. It is recommended that PROLENSA ophthalmic solution be used with caution in PATIENT COUNSELING INFORMATION patients with known bleeding tendencies or who are receiving other medications Slowed or Delayed Healing which may prolong bleeding time. Advise patients of the possibility that slow or delayed healing may occur while using Keratitis and Corneal Reactions NSAIDs. Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued Sterility of Dropper Tip use of topical NSAIDs may result in epithelial breakdown, corneal thinning, Advise patients to replace bottle cap after using and to not touch dropper tip to any corneal erosion, corneal ulceration, or corneal perforation. These events may be surface, as this may contaminate the contents. Advise patients that a single bottle of sight threatening. Patients with evidence of corneal epithelial breakdown should PROLENSA be used to treat only one eye. immediately discontinue use of topical NSAIDs, including bromfenac, and should be Concomitant Use of Contact Lenses closely monitored for corneal health. Advise patients to remove contact lenses prior to instillation of PROLENSA. The Post-marketing experience with topical NSAIDs suggests that patients with preservative in PROLENSA, benzalkonium chloride, may be absorbed by soft contact complicated ocular surgeries, corneal denervation, corneal epithelial defects, lenses. Lenses may be reinserted after 10 minutes following administration of diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid PROLENSA. arthritis, or repeat ocular surgeries within a short period of time may be at increased Concomitant Topical Ocular Therapy risk for corneal adverse events which may become sight threatening. Topical NSAIDs If more than one topical ophthalmic medication is being used, the medicines should should be used with caution in these patients. be administered at least 5 minutes apart. Post-marketing experience with topical NSAIDs also suggests that use more than 24 Rx Only hours prior to surgery or use beyond 14 days post-surgery may increase patient risk for the occurrence and severity of corneal adverse events. Manufactured by: Contact Lens Wear Bausch + Lomb, a division of Valeant Pharmaceuticals PROLENSA should not be instilled while wearing contact lenses. Remove North America LLC, Bridgewater, NJ 08807 USA contact lenses prior to instillation of PROLENSA. The preservative in PROLENSA, Product under license from: benzalkonium chloride may be absorbed by soft contact lenses. Lenses may be Senju Pharmaceutical Co., Ltd., Osaka, Japan 541-0046 reinserted after 10 minutes following administration of PROLENSA. Prolensa is a trademark of Bausch & Lomb Incorporated or its affiliates. © Bausch & Lomb Incorporated ADVERSE REACTIONS Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse Revised: 06/2016 reaction rates observed in the clinical trials of a drug cannot be directly compared to Based on: 9306701/9306801 PRA.0119.USA.16
RRP0217_BLP0217_BL PProlensarolensa PPI.inddI.indd 1 11/13/17/13/17 10:0210:02 AMAM 026_rp0217_f1.indd 31
David F. Chang, MD “no rotationrecommended.” rotation hasresulted of inareduction oftheastigmatismto0.37Dandadetermination recommends counterclockwise rotationofthetoricIOL.Right: Slightcounterclockwise different alignments.)Left: With 1.23Dofmeasured residual astigmatism, thesoftware toric IOL.(Thecolumnontherightsideofscreen shows therefractive cylinder with An example screenshots ofORAintraoperative duringthealignmentofa aberrometry serves asmytie-breakerinthat case.” to cylindricalpowerandaxis. ORA erative diagnosticexamswith respect agreement betweendifferentpreop- fi to theexactalignmentthatwascon- then allowsmetoresetthetoricIOL axis. AfterremovingtheOVD,Callisto Callisto tore-markthenewoptimal is minimized,”henotes.“Ithenuse traoperatively measuredastigmatism wise orcounterclockwiseuntilthein- me torotatethetoricaxiseitherclock- selected axisiscorrect. usually veryquickifthepreoperatively system alignment,theconfi and withtheaccuracyofCallisto OVD tominimizespeculumartifact, lar pressureiselevatedwithenough is moreaccuratewhentheintraocu- alignment,” heexplains.“Thelatter to confi rm theoptimaltoricIOLaxis power andapseudophakicreading the sphericalandcylindricalIOL the ORAsystem(Alcon)toconfirm ment. “Iuseanaphakicreadingwith tion todigitalintraoperativeaxisalign- tive wavefrontaberrometryinaddi- Intraoperative Aberrometry toric IOL.” obvious whenyoufi rst useittoaligna rmed byORAtobeoptimal. REVIEW “Often,” headds,“thereissomedis- “However, sometimes ORAdirects Dr. Changlikestouseintraopera- Focus Cover
Cataract &RefractiveSurgery Cataract rmation is is rmation cost becauseofthesurgicalworkfl says. “It’s easytojustifythecapital your ASCoverthenext10years,” he have theirastigmatismmanagedat it. “Addupallthepatientswhowill pecially ifmultiplesurgeonscanuse additional equipmentisworthit,es- however, believesthatthecostof come atasignifi cant cost.Dr. Chang, nologies, whatevertheiradvantages, this; it’s notpurescience.” again, there’s alittlebitofanartto with mypreoperativeK-readings.But the aberrometryreadingifitdisagrees aberrometry tellsyou. a betterresultbygoingwithwhatthe and hydratedthemalot,youmightget wound. Ifyou’vemadelargeincisions ed andhowmuchyou’vehydratedthe much incisiondistortionyou’vecreat- accurate depends,inpart,onhow erative aberrometryreadingismore you shouldassumethattheintraop- alter theaxisofastigmatism.Whether in thecornea,andthatcouldpossibly the lens,you’vemadesomeincisions the trueaxis?”hesays.“To remove “The questionthenbecomes,whatis a keratometeroreventopography. than you’llgetpreoperativelyusing may produceadifferentaxisreading the tablewhenpatientisaphakic ing intraoperativeaberrometryon Of course,theseadvancedtech- “In general,”hesays,“I’llgowith Dr. Lanehasalsonotedthatus- February 2017 ow ow best outcomes.” premiums thatpatientspaytogetthe effi don’t do—toensurethatthe chamber OVD—something mostsurgeons sion beforeremovingthefi the centration.)“Ihydrateinci- microscope makesiteasytoconfi lumination providedbyhisLumera (He notesthatthestereocoaxialil- lens iscenteredandperfectlycoaxial. ing thelastOVD,hemakessure easy andatraumatic.” placed intheoptic-hapticjunction.It’s the siliconetipofI/Ahandpiece bag, thelensrotatesveryeasilywith is dead-on.Becauseoftheexpanded system confirmsthatthealignment cautery marks,andtheCallistoEye lens tomyThermodots,thetwolittle system,” hecontinues.“Irotatethe OVD leftbehindit. against theposteriorcapsule,withno lowing. Nowthelenswillbepressed be looseandhavethechambershal- more easily;youdon’t wantthebagto expands thebagsolenswillrotate bag infrontofthelens,”hesays.“That terwards itcancausethelenstomove. alignment, becauseifItakeitoutaf- OVD behindthelensbeforefi front ofthelens.Ialwaystakeout lens withoutaffectingtheHealonin can easilyremoveitfrombehindthe like tousebecauseit’s socohesive;I and IremovemyHealon5,which I gobehindtheopticwithI/Atip of thetargetmeridian,”hesays.“Then rotate itclockwiseuntilit’s alittleshort correctly. “OnceIputthelensin,I’ll cess ismanagingyourOVDremoval it. Dr. Oshersaysabigpartofthatpro- remain inthepositionyou’veplaced step istoalignthelensandgetit to displaythetargetmeridian,last Aligning theLens Dr. Oshersaysthatbeforeremov- “Next IturnonmyCallistoEye “Next, IinjectmoreOVDintothe Once you’vesettledonamethod ciency yougainandtherefractive | reviewofophthalmology.com nal bitof nal nal rm rm |
31 1/18/17 2:17 PM 026_rp0217_f1.indd 32 of rotationandmovement,”hesays. lenses arequitestable,withlowrates postoperative rotation.“Today’s toric shouldn’t beputoffbyconcernsabout States.” rics, whichwenowhaveintheUnited ticularly importantwithmultifocalto- as thepupilcomesdown.Thisispar- to confi rm thatI’mperfectlycentered that pointImayputinalittleMiochol dilation untilthesurgeryisover. At dots are,soImaintainmaximumpupil obscure myviewofwheretheguiding don’t wantthepupiltocomedownand wait untilthevery, veryendbecauseI he says.“However, withatoriclensI lets youbesurethelensiscentered,” makes theenlargedpupilsmallerand end oftheprocedure.“Doingthat like toputinalittleMiocholnearthe pressure, andI’mdone.” alignment onemoretime,adjustthe sion iswatertight.ThenIcheckmy I hydrateagainandmakesuretheinci- doesn’t change.OncetheOVDisout, and thelensalignment stays niceanddeep, cannula, thechamber and havingthatsecond incision aheadoftime tween hydratingthe the chamberdeep.Be- injecting fluidtokeep sion throughwhichI’m cannula inthestabinci- always haveasecond optic. AsIcomeout, that’s infrontofthe I takeouttheOVD rotate,” hesays.“Then would allowthelensto won’t shallow, which 32 errors canleadtoincorrecttoric IOL able errors.“Anumberofpotential you getthebestpossibleoutcomes: Measurement Pearls Dr. Laneaddsthatsurgeons Dr. Oshernotesthatsomesurgeons • These strategiescanhelpensurethat REVIEW | Watch outfor simple,avoid-
Focus Cover Review ofOphthalmology
Cataract &RefractiveSurgery Cataract 15-degree target meridian. yellow linemarksthe180-degree axis;thethree parallel bluelinesshow the An example ofaCallistooverlay duringimplantationofatoricIOL. The single | February2017 make suretheheadisn’t tilted andthe Osher. “Experienced technicianswill who takethemeasurements,” saysDr. good asthetalentofindividuals ments. technicians aretakingthemeasure- the operatingtable.” lead toa10-degreemisalignmenton mark maybe5degreeswide.Thiscan upright patient,andthentheinkpen axis maybeabitoffwhilemarkingthe he pointsout.“Forexample,the180 ink marktobleed,fadeorsmudge. ink pen,giventhepropensityfor IOL axisusingadegreegaugeandan ing themarkingofintendedtoric fourth potentialsourceoferrorisdur- upright inthepreoperativearea.The quires markingthepatientwhilesitting ocular cyclotorsion;preventingthisre- axis whenthepatientissupinewith ror ismis-identifyingthe180-degree of 110degrees.Thethirdpotentialer- 10 degreesastheoperativeaxisinstead the operatingroom,suchaswriting ing fromthediagnosticmachineto is atranscriptionerrormadewhengo- ments. Thesecondpotentialproblem keratometry andtopographymeasure- fully levelthepatient’s headduringthe surgeon—is thestafffailingtocare- “The fi rst—and leastapparenttothe axis alignment,”notesDr. Chang. • “Some oftheseerrorsareadditive,” Make surethatexperienced “Your resultswillonlybeas inder.” crystalline lensthat’s creatingthatcyl- 1 D,itmeansnothing;couldbethe lens.” to 0.8D.That’s awholestepontoric by theposteriorsurfaceranges from0 I foundthattheastigmatismcaused the posteriorcorneaoneverypatient. factor, Ispentseveralyearsmeasuring alerted ustotheimportanceofthis the correctaverage,butafterDr. Koch astigmatism,” hecontinues.“Thisis 0.3 Dofposterioragainst-the-rule account simplyuseanaverageof surgeons whowanttotakethisinto Vue alsomeasuretheposteriorcornea. the Pentacam;CassiniandOpto- Ziemer’s Gallilei.Alotofushaveused this factor, didhispioneeringworkon who fi that,” hesays.“DouglasKoch,MD, four technologiesthatcanmeasure by theposteriorcornea.“Thereare into accounttheastigmatismcaused tion ofthetoricmeridianmusttake out thatatrulyaccuratedetermina- or cornealsurface.Dr. Osherpoints strategies areworthkeepinginmind: more advancedtechnologies,these High-tech Pearls “Rather thanmeasuringit,many • If you’reabletoaccesssomeofthe Ifpossible,measuretheposteri-
rst pointed out the importance of rst pointedouttheimportanceof David F. Chang, MD Chang, F. David ever, ifthepatienthas tra measurement.How- would usethatasanex- cylinder in her glasses, I cylinder inherglasses,I the patienthas3Dof inder. Forexample,if the patienthashighcyl- tient’s glasses,unless any cylinderinthepa- Osher. “Also,disregard isn’t reliable,”notesDr. get fromarefraction the axis.“Theaxisyou tive measurementsof among otherthings.” cornea isn’t bone-dry, • Disregard subjec- 1/18/17 2:17 PM Dr. Osher says taking posterior cor- ticular astigmatism. and I lose registration, or fl uid from neal astigmatism into account isn’t “The third scenario is the most inter- I/A gets under the conjunctiva causing diffi cult. “The posterior axis is always esting,” he continues. “That’s a person it to balloon up—I have a simple iris against-the-rule,” he says. “So, if the who has never worn glasses. This indi- fi ngerprint that tells me exactly where patient has against-the-rule cylinder on vidual may have with-the-rule cylinder to put my Thermodots, and the IOL the front of the cornea, with the steep in the cornea that’s been neutralized by will be accurately aligned.” axis at 180 degrees, you add the poste- against-the-rule cylinder in the lens. I Dr. Lane says he no longer makes an rior corneal astigmatism. For example, tell them, ‘After we take out your cata- ink mark, now that he uses the more if the patient has 1 D of cylinder at ract you’re going to have a lot of astig- advanced alignment tools, although he 180 degrees, and the posterior cornea matism, so you’re a good candidate for agrees that there’s nothing wrong with has 0.5 D of cylinder, then you need a toric lens.’ They say, ‘Wait a minute, doing so as a failsafe. “To me, not hav- to correct 1.5 D of cylinder overall. why are you trying to sell me a toric ing to do that is one of the advantages On the other hand, if the patient has lens when I’ve never worn glasses?’ I of using a guidance system,” he says. with-the-rule cylinder, you subtract it. show them the iTrace measurements “If the power went out, I could always For example, if the patient has 1 D of so they understand that once we take sit the patient up, mark the eye and lay with-the-rule cylinder at 90 degrees, away the lens, they’ll suddenly have the patient back down, but that hasn’t and the posterior cornea measures a problem with residual astigmatism. happened to me since I’ve had these 0.5 D, you would subtract the 0.5 D, This situation isn’t common, but it defi - instruments.” meaning the patient actually has 0.5 nitely does happen.” D of astigmatism overall. This patient Dr. Osher notes that this supports The Wave of the Future? is not even a toric candidate. Finally, the value of taking multiple measure- if the anterior astigmatism is oblique, ments. “Multiple measurements help “There’s no question that implant- it’s a vector case, and I pay attention to you eliminate outliers, but they also ing toric lenses adds surgical time, the IOL recommended by the Barrett provide additional information,” he and some pre-surgical discussion has toric calculator. says. “Even though the amount of test- to take place to ensure that patients “Some might say that this is a minor ing I do sounds excessive, the tests all have realistic expectations,” Dr. Lane point—like worrying about your lug- help me gain greater understanding admits. “But current toric lenses are gage when you’re on the Titanic,” he about my refractive cataract patient.” excellent, regardless of which manu- continues. “But the way I look at it, we • Even if you use advanced tech- facturer’s lens you use. Meanwhile, the should always do the very best we can nology to align the lens, consider advanced alignment technology that’s for each of our patients. To accomplish also marking the cornea. “I think it’s available will improve your results. I that, we should always measure both important to use a belt-and-suspenders think the investment is worthwhile, the anterior and posterior cornea.” approach,” says Dr. Osher. “The more especially in groups that have multiple • If possible, measure the entire approaches you use, the better, be- surgeons doing cataract surgery, so that optical system to see where the cause something can always go wrong. the surgeons can share in the expense astigmatism is located. Dr. Osher If lightning hits the surgery center or of these instruments up front. The bot- uses the iTrace for this purpose. “I al- the technology breaks down, you still tom line is that surgeons who are will- ways look at the two possible sources have something to go by.” ing to do toric lenses will be very satis- of the astigmatism—the cornea and Dr. Osher explains how he uses the fi ed with the results, and they’ll have a the lens,” he says. “There are three Thermodot with iris fingerprinting. much larger group of happy patients.” possible scenarios. Usually the astig- “I take a picture of the eye while the Dr. Osher agrees. “I’m convinced matism is in the cornea. Rarely—but patient is at the slit lamp and I’m doing that one day toric lenses will be the it does happen—the astigmatism origi- my dilated exam,” he says. “Inexpen- standard of care,” he says. nates in the lens. The patient may have sive software identifies the location been wearing astigmatic correction of key landmarks on that iris. In the Dr. Osher is a consultant to Zeiss, and been referred in for a toric lens, OR I can put my cursor on whatever Alcon, BVI and Clarity. Dr. Chang is a but in this case you may be able to tell landmark I want and the software tells consultant for Clarity and Zeiss; he has the patient she doesn’t need a toric me what degree it’s at, so I always know no fi nancial interest in Alcon or ORA. lens. Once the cataract is removed the exactly where I am. Then, if all of my Dr. Lane is a consultant for Alcon. astigmatism will be gone. Patients love sophisticated technology stops work- 1. Browne AW, Osher RH. Optimizing precision in toric lens that. I show them the iTrace readout, ing—either because the machinery is selection by combining keratometry techniques. J Refract Surg and they can see the corneal and len- temperamental, or something bleeds 2014;30:1:67-72.
February 2017 | reviewofophthalmology.com | 33
0026_rp0217_f1.indd26_rp0217_f1.indd 3333 11/18/17/18/17 2:182:18 PMPM Cataract & Refractive Surgery REVIEW Cover Focus Tips for a Better SMILE
Jesper Hjortdal, MD, PhD, Aarhus, Denmark
An expert SMILE n all areas of surgery, not just oph- based LASIK, but there are also some thalmology, the trend has been to- limitations to the procedure that will surgeon explains Iward accomplishing the surgery’s reduce the number of potential can- goals internally while minimizing the didates. how to get the disruption to the exterior tissue—often One of SMILE’s current limitations the skin. In the eye, small-incision len- is that the most reliable nomograms most from this ticule extraction—recently approved for it are primarily for myopic correc- in the United States—continues this tion, and it’s only approved in the Unit- new procedure. non-invasive tradition by making its ed States for the correction of myopia major tissue modifications intrastro- up to -8 D with no more than 0.5 D of mally, avoiding the creation of a large astigmatism. Also, there’s a hardware fl ap or extensive ablation with an ex- limitation in that, in order to perform cimer laser. I’ve had great success with it, you need to use the Carl Zeiss Med- SMILE in my refractive practice, and itec Visumax femtosecond laser. now use it for all of my myopes who In terms of safety screening, we are suitable candidates. In this article, won’t perform SMILE on someone I’ll share the knowledge about SMILE with a cornea thinner than 480 µm, or that I’ve amassed over the years and whose refraction hasn’t been stable for help you get the best outcomes pos- at least a year. Also, since we mainly sible. perform SMILE on high myopes at our practice, we’re reluctant to per- Preop Considerations form it on patients younger than 25, because of the potential risk of forme Screening criteria for SMILE are fruste keratoconus that might manifest similar to those used for femto-fl ap- in the postop years. When screening for potential ectasia risks, we look for oblique astigmatism and use the Pen- tacam to look for a difference in power After the femtosecond between the inferior and superior cor- pass, surgeons use an neas. Also, we inquire whether anyone instrument to break in the patient’s family has a history of the tissue connections keratoconus. above the lenticule. We take these precautions dur- (All images: Jesper Hjortdal, MD, PhD, and ing screening because, even though Anders Ivarsen, PhD) SMILE is less invasive than LASIK
34 | Review of Ophthalmology | February 2017 This article has no commercial sponsorship.
034_rp0217_f2.indd 34 1/18/17 1:52 PM and should, theoretically, result in a • The femtosecond step. At this more stable cornea biomechanically, point, it’s important to tell the patient it does loosen the fi bers in the ante- to relax. He’ll be able to see with the rior part of the cornea. This means operative eye because the suction isn’t the post-SMILE cornea may still be that high with SMILE. Again, tell him weakened compared to non-dissected the procedure is about to begin, so he cornea. Also, even though we’ve never shouldn’t move the eye or try to fol- experienced it in our practice, there low the light if it appears to move. Let have been reports about ectasia occur- him know that when the femtosecond ring after SMILE.1 However, it’s worth is operating, his vision may become noting that, when one reviews these Surgeons say it’s easier if you free the blurred due to small bubbles in the reports, it appears that the patients in posterior side of the lenticule after the cornea and that it’s perfectly normal. question had some signs of subclinical anterior side. Keep him calm and apprised of how keratoconus before the SMILE proce- much time remains in the procedure, dure, such as corneal asymmetry. we instill two drops of anesthesia: one which usually takes 20 to 25 seconds, three minutes before the case and an- depending on the spot pattern. Then, The Procedure other one minute before we insert the when the lenticule cut is complete and speculum. During this period, it’s im- the side incision has been made, the la- There are certain measures you can portant to evaluate the situation in a ser will stop and suction will automati- take to help the procedure go more way similar to a LASIK protocol, to cally decrease. Reassure the patient smoothly, and to avoid potential dif- make sure you have good access to the that things went well and that the most fi culties. eye and that the suction device on the diffi cult part is over. You then move the To help understand the specific laser won’t collide with the speculum. patient bed down beneath your surgi- tips for the various steps of SMILE, it Move the patient’s head a few degrees cal microscope. helps to have a general overview of the to the side opposite the eye to be treat- It’s worth noting that, in rare cases procedure. In SMILE, the surgeon ed, then adjust the head so it’s exactly (0.7 percent in a study we performed),2 uses the femtosecond laser to create coaxial with the laser beam. you can lose suction during the pro- a lenticule of stromal tissue within the We then perform a mild cleaning of cedure. To try to avoid this, the most cornea; the laser then makes a small the corneal surface to ensure there’s no important thing is to have the correct side incision through which the tissue debris, such as mucus, in the tears. We amount of hydration on the eye—not is removed with forceps. This removal instill a little BSS to ensure a nice wet too much or too little. Also, you can causes corneal fl attening that treats the surface, and then move the patient’s help prevent it by, again, talking to the myopia. laser bed from the surgical microscope patient and keeping him calm. If suc- First, I’ve found it helps to give the to beneath the laser. When this occurs, tion loss does occur, however, your re- patient a detailed explanation of what’s you’ll notice that the screens on the la- sponse depends on how much tissue going to occur at each phase of the pro- ser have changed, and you’ll then have you’ve cut and where you are in the cedure. We do this both in our offi ce in another view through the microscope procedure, per Carl Zeiss: the days before the procedure as well that’s down the laser path. You then • Stage 1 (posterior lenticule cut is as during the actual SMILE surgery. elevate the patient bed toward the less than 10 percent complete): During the procedure, I’m constantly suction device and make sure to cen- Restart the procedure; telling the patient to keep calm, to look ter the suction head along the visual • Stage 2 (posterior lenticule cut at the blinking green light and to not axis, which you can accomplish by ask- is greater than 10 percent done): follow the light if it appears to move. ing the patient to look at the blinking Switch to LASIK; I keep her looking straight during the green light. The suction device then • Stage 3 (lenticule side cut): Re- docking step. After docking, when the makes contact with the cornea. Make peat the lenticule side cut, and patient is moved under the laser, I then sure you’ve centered the procedure decrease the lenticule diameter explain what’s going to happen in the over the pupil and then elevate the by 0.2 to 0.4 mm; next few seconds. This relaxes the pa- patient bed a little more. Then, just • Stage 4 (anterior lenticule cut): tient and helps her to keep her gaze before you have a full, curved applana- Repeat the anterior lenticule cut; straight. tion, activate the suction. Have a look or • Docking and suction. When the at the pupil to make sure that every- • Stage 5 (anterior lenticule side time comes to perform the procedure, thing is centered. cut): Repeat the anterior lenticule
February 2017 | reviewofophthalmology.com | 35
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REVIEW Focus
side cut and decrease the lenticule go back and see whether the lenticule diameter by 0.2 to 0.4 mm. is actually stuck to the cap, and try to • Completing the dissection. It’s now see if you can get into the plane be- time to complete the dissection and tween the lenticule and the cap at the remove the lenticule. Remind the pa- very edge. tient to keep looking at the light, and If it’s really diffi cult or almost impos- tell him he may experience movement sible to dissect, it’s better to acknowl- of the eye during the dissection. edge that the lenticule wasn’t prop- First, use a Sinskey hook or other erly cut and just stop—don’t make a sharp instrument to identify the plane mess of the middle of the cornea. It’s of the lenticule. Most surgeons do this With both sides free of tissue connections, better to come back in a month or so by going to the left side of the inci- remove the lenticule with forceps and make when you’ve have time to see what sion and making sure that they have a sure it’s complete, with no missing pieces. happened, and consider doing another plane above the lenticule before they procedure such as PRK or LASIK. start dissection. Then you take a dis- the lenticule while it’s sitting on the • Closing the case. After you’ve re- sector, either fl at or curved—we prefer cap. However, most surgeons find it moved the lenticule, fl ush the interface curved—and go to the extreme left to easier to do the anterior cap layer fi rst. with BSS and, using either a sponge a place where you know you’re above • Two-incision technique. You or the head used for docking, push on the lenticule and dissect with smooth can also choose to have two incisions: the cornea to squeeze out any remain- movements from left to right over the one at 12 o’clock and one at 6 o’clock. ing saline. Wait 30 seconds to a min- anterior surface of the lenticule toward Then, if you dissect from the 12 o’clock ute before removing the speculum to the periphery of your cap cut. This will position but realize you’ve started with make sure that everything is in place. break all the tissue connections above the wrong plane before you complete- In some cases, you might notice that the lenticule. Having done that, you go ly dissect the other plane, you’ll have a the operation caused a small epithelial below the lenticule, entering through second chance at success by using the defect or abrasion. If this is the case, the right side of your incision, and do incision down at 6 o’clock. place a bandage contact lens postop. the same type of dissection from right • Low vs. high myopia. The thick- You can typically remove the bandage to left toward the edge of the lenticule, er the lenticule, the easier the dissec- lens on postop day one because the breaking all the connections below. tion. So, in low myopia, you should abrasion is usually healed. Make sure you’ve dissected the full typically add a little to the base thick- We then instill Vigamox and a mild, planes above and below the lenticule. ness to make the lenticule easier to pain-relieving NSAID drop. We pre- You then remove the lenticule with manipulate. In the typical SMILE scribe a mixture of tobramycin and forceps and place it on top of the cor- case, there’s a 15-µm base thickness. dexamethasone q.i.d. for a week, and nea to make sure that it’s complete. So, in low myopes, you should increase then b.i.d. for another week. Visualization can be challenging that to 20 or 25 µm, giving more bulk during the dissection, so here’s some to the lenticule. It’s like a plano abla- Postop Matters advice: If you go in on the left side with tion, so this extra tissue shouldn’t have your Sinskey hook you’ll be outside any refractive effect. Though most of our SMILE cases the actual lenticule. If you then move • Notable differences from go smoothly, it helps to be vigilant for the Sinskey hook—pointed slightly LASIK. The dissection in SMILE is postop problems in order to nip them upward toward the cap—across the more diffi cult than just lifting a LASIK in the bud. Here are the things you actual border of the lenticule, you’ll flap. Also, it’s important to realize if should be looking for. almost certainly be above the lenticule. you really can’t get under the lenti- • Watch for infl ammation. Postop, A good way to gauge your position is cule properly, the most likely reason is we’ll take a look to see if there is any to look for the small air bubbles in the that the lenticule is still attached to the debris or inflammation in the inter- interface: There should be no air bub- cap. So, if you fi nd yourself having to face. Sometimes, you see small fi bers bles above your Sinskey hook for your be very aggressive and digging down like the kind seen after LASIK. If the initial dissection above the lenticule. under the lenticule, your fi rst thought debris is central, or you have a feeling Also, it’s not necessarily a catastrophe if should be that the lenticule may actu- that there’s some epithelium in the in- you go below the lenticule. If you press ally be stuck to the cap. Therefore, in- terface, then fl ush the interface. (This a little with a Sinskey hook, you most stead of just continuing a rough dissec- happens rarely.) Then look for tears often will be able to catch the edge of tion where there’s no dissection plane, around your incision, which typically
36 | Review of Ophthalmology | February 2017
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RP0117_Alcon Acrysof.indd 1 12/14/16 2:56 PM 0034_rp0217_f2.indd 38 3 4 _ r p 0 2 1 7 _ f 2 38 a lineofvision,2percentlostline. Although 32percentofpatientsgained cent ofthecasessaw20/20orbetter. average preoperrorof-7D,86per- study of45eyes35patientswithan vision duringthatperiod. lost twoormorelinesofbest-corrected 0.07 (logMAR),12eyes(1.6percent) preop andthreemonthspostopwas gain inbest-correctedvisionbetween months postop.Thoughtheaverage which improvedto83percentatthree cent saw20/25orbetteratdayone, the targetrefraction.Sixty-threeper- 88 percentofeyeswerewithin0.5D preop errorof-6.8D,atthreemonths included 722caseswithanaverage be fi perfectly clearondayone,butthey’ll prepared thattheirvisionmaynotbe and whowon’t, wetellpatientstobe difficult topredictwhowilldowell first postopday. Sinceit’s somewhat who haveexcellentvisualacuityonthe ever, therearealsoSMILEpatients may see20/25oralittleless.How- ter surgery, atypicalSMILEpatient LASIK patientsees20/20thedayaf- LASIK. If,forexample,theaverage with SMILEisalittleslowerthan only requireobservation. learning curveatwork.It’s important eyes treated,sotheremayhave beena of theseeyeswerewithinour fi energy andwiderspacing).Also,eight spacing) thansetting2(higherspot setting 1(lowerspotenergyandcloser cantly moreweretreatedwithlaser noted, though,thatofthese,signifi- lost twoormorelinesofBCVA. We best-corrected distancevision. the caseshadsameorimproved month follow-upvisit,86percentof treatment of-0.15±0.5D.Atthethree -0.28 ±0.52D,withameanerrorof -7.25 ±1.84D.Postop,theaveragewas tive sphericalequivalentrefractionwas our practice,theaveragepreopera- . i n
d REVIEW In anotherstudyofSMILEthat • Visual results. In ourstudy, 1.5percent(24eyes) In a study of 1,800 SMILE eyes at In astudyof1,800SMILEeyesat d |
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Focus Cover Review ofOphthalmology
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Cataract &RefractiveSurgery Cataract Visual recovery 3 In a smaller Inasmaller 2 |
rst 100 100 rst February2017 4 weren’t associatedwithany sequelae. were smalltearsattheincision and were minorabrasionsand17percent LASIK. However, 59percentofthem to berelativelyhighwhencompared SMILE surgeries,whichmightappear complications in10.8percentofthe surface in4percent(n:75). cent ofcases(n:127)andadryocular corneal haze(grade0.5to1)in7per- main complicationsinourserieswere or alossofBCVA. Postoperatively, the issues resultedinlatevisualsymptoms cap intwo.However, neitherofthese edge oftheincisionnearlydivided and inoneeyeamajortearfromthe perforated duringsurgeryinfoureyes complications. Thecornealcapwas in somecases,acombinationofthose at theincisionsitein1.8percentand, cule in1.8percent(n:34),smalltears (n: 114),diffi the incisionsitein6percentofcases our studywereepithelialabrasionsat line ofpreoplevelsinalleyes. 18 monthspostop,BCVA waswithina to note,however, thatbyanaverageof Table 1. SMILEComplications • Enhancements. Overall, therewereperioperative The mostcommoncomplicationsin (percent); Intraoperative SMILEComplications Infl intheinterface(0.22) ammation (0.27) Monocular ghostimages Infi(0.27) ltrates/keratitis Fibers ininterface (0.3) incisionsite(0.6) Epithelial islandsat ocularsurface,Dry fi rst daypostop(4.2) Haze, grade0.5to1(7) (percent) Postoperative SMILEComplications Lenticule extractionimpossible(0.06) Major tear(0.06) (0.2) perforation Cap Central abrasion(0.2) Suction loss(0.7) theincision(1.8) Minor tearat Lenticule extractiondiffi culties (1.8) theincision(6) Abrasion at culty removingthelenti- (N=1,800) Fortunately, en- 1
2 2 myopes inourpractice. found itaneffectivetreatmentforthe need tolearnnewtechniques,we’ve terms ofnewinstrumentationandthe put somedemandsonthesurgeonin and itsidiosyncrasies.Thoughitdoes learned alotabouttheprocedure cedures underourbeltsnow, we’ve ing apreviousSMILEisstillunclear. for us,thebestprocedureenhanc- surface ablationenhancementworks use anexcimertodoaLASIK.Though terface andcreateafl use ittocutdownintotheSMILEin- with acircleoptionthatallowsyouto SMILE cap.TheVisumax lasercomes pend onhowthickyoumadetheinitial enhancement, thoughthiswouldde- cap intoafl nately, youcouldchangetheSMILE thelial PRKwithmitomycin-C.Alter- hance aSMILE,weperformtransepi- procedure foranenhancement. this, mostsurgeonswilluseanexcimer challenging toworkwith.Becauseof enhancement wouldbeverythinand lenticule you’dneedtoremoveforthe of postoperrorisverysmall,sothe refractive change.Usually, theamount use ofaveryfinelenticuletocause to thenatureofprocedureandits enhancements canbeachallengedue is even-0.75D.Thatsaid,SMILE myopes whoarehappyiftheirresult patients, becausethey’reusuallyhigh hancements arerareinourSMILE High Myopia. Turk JOphthalmol2016;46:5:200-204. 4. Yıldırım Y, C,Alagöz Demir A, etal. Long-termresultsofSMILE in Graefes Arch ClinExpOphthalmol2016;254:2:399-405. formyopiaandmyopicastigmatism. Outcomes of722eyestreated 3. HansenRS, Lyhne N, GrauslundJ, Vestergaard AH. SMILE: than 1500SMILEprocedures. 2014;121:4:822-8. Ophthalmology 2. Ivarsen A, Asp S, HjortdalJ. ofmore Safetyandcomplications Surg 2016;1:32:7:497-500. laser-assisted smallincision lenticuleextraction(SMILE). JRefract 1. JS, Mattila HolopainenJM. ectasiaafterfemtosecond Bilateral Zeiss Meditec. fied researchagreementswithCarl Aarhus UniversityHospitalhasspeci- director oftheDanishCorneaBank. at AarhusUniversity, andismedical With thousandsofSMILEpro- In ourpractice,ifwehavetoen- Dr. Hjortdalisaclinicalprofessor ap andperformaLASIK ap. Then, you can ap. Then,youcan 11/18/17 1:53 PM / 1 8 / 1 7
1 : 5 3
P M RP0815_Lombart.indd 1 7/21/15 10:07 AM Cataract & Refractive Surgery REVIEW Cover Focus Odd Couple: Multifocals And Post-refractive Eyes
Kristine Brennan, Senior Associate Editor
A history of or the right patients, multifocal and medical director of the Eye Cen- IOLs can offer acute near and ter of New York, is more willing to refractive surgery Fdistance vision without sacri- use multifocal IOLs in post-refractive ficing the middle range. Eyes with patients, but still acknowledges that doesn’t always prior refractive surgery have tradition- they are imperfect candidates. “Post- ally been considered poor candidates. refractive patients are some of the mean multifocals Thanks to improving lens, biometry most challenging ones we have,” he and calculation technologies, how- observes. are out of reach. ever, cataract patients who once paid “I have done multifocals in post- out of pocket for refractive surgery to refractive eyes, both post-LASIK and achieve spectacle independence may -PRK, and I’ll do both hyperopic and now have another shot at achieving it. myopic previous refractive surgery,” Here, surgeons outline their own do’s says Daniel H. Chang, MD, of Em- and don’ts regarding the use of multi- pire Eye and Laser Center in Bakers- focal IOLs in post-refractive surgery fi eld, Calif. “The fact that they’ve had patients. previous refractive surgery indicates Post-refractive surgery patients that they obviously do value spec- seeking multifocal IOLs may not tacle independence—or at least at fi nd encouragement from many doc- one point they did.” tors. “I don’t do that many multifocal Since LASIK and its precursors, IOLs, only 2 percent of my patients. RK and PRK, are now decades old, In people who have had previous re- the march of time portends that for- fractive surgery I generally discour- mer patients will return to the operat- age it, since I try to get them the best ing suite with high expectations when quality of distance vision—which usu- cataracts develop. “This is largely an ally was their previous goal—rather anticipatory issue, because of the cer- than the convenience of decreased tainty of aging,” observes Ming Wang, reading-glasses dependency,” says MD, PhD, of Wang Vision Institute James A. Davison, MD, FACS, of the in Nashville, and clinical associate Wolfe Eye Clinic in Des Moines. professor of ophthalmology at the Tal Raviv, MD, FACS, associate University of Tennessee. Dr. Wang clinical professor of ophthalmology at estimates that cataract patients with a the New York Eye and Ear Infi rmary prior refractive history comprise well of Mount Sinai Icahn School of Medi- over 10 percent of his cases, and he cine at Mount Sinai, and the founder predicts that their numbers will soon
40 | Review of Ophthalmology | February 2017 This article has no commercial sponsorship.
0040_rp0217_f3.indd40_rp0217_f3.indd 4040 11/20/17/20/17 3:463:46 PMPM increase nationwide. “The LASIK Tal Raviv, MD, FACS population peaked around 2002, when today’s cataract patients were around 40 years of age. Simple math tells us that a wave of baby-boomer patients is imminent,” he says. “They will make multifocal IOL implanta- tion popular, along with accommoda- tive and extended-range IOLS. There will be a new surge in such proce- dures.” For now, though, post-refractive eyes and multifocal IOLs remain a relatively odd couple; succeeding with them requires taking extra precau- tions during patient screening, work- up and counseling.
Develop Exclusion Criteria The new Tecnis Symfony, the only extended depth-of-focus lens approved in the United States, is a viable option for patients with a history of refractive surgery who don’t want The limited literature on such eyes1 monofocal lenses. looks at small study groups,2 and sug- gests that while excellent outcomes are as an example, Dr. Wang’s calculation tial precision value), the eye’s corneal attainable, getting there often requires of its ST value (the number of microns aberrations clearly exceed the toler- enhancements.3 Despite the shortage of corneal irregularity the lens will tol- ance of the multifocal IOL. Unless of literature on the use of multifocals in erate before its performance suffers) treatment can decrease the patient’s post-refractive eyes, Dr. Wang believes would go as follows: corneal irregularity to less than 76 µm, it’s only fair that patients seeking such the surgeon should use a monofocal or procedures get checked against de- Spatial Tolerance=(diffractive zone other lens with an ST greater than the fi nitive exclusion criteria. To that end, diameter-central diffractive zone cornea’s SP limit. he has developed a rough preliminary diameter)/(2 X the number of rings Dr. Wang stresses that his computa- method that helps him eliminate un- and intervening transition zones). tions represent a rudimentary attempt suitable eyes by measuring their cor- to develop objective exclusion criteria neal aberrations against the amount of The lens in the example has a 6-mm when dealing with this highly variable irregularity that a proposed multifocal diameter optic containing a central dif- patient group. “This post-refractive lens will tolerate.4 fractive button measuring 0.86 mm in calculation is an early attempt to match “Multifocal IOLs are extremely diameter, surrounded a larger diffrac- cornea to lens tolerance. There is much picky regarding corneal irregular- tive zone that’s 3.6 mm in diameter. Its work to be done on this approach. It’s ity, and introduction of a multifocal to distance zone goes from 3.6 mm to the still a crude model,” he emphasizes. such eyes creates higher demand on outer edge of the optic. The lens has The fi t between corneal aberration the cornea,” says Dr. Wang. “The high nine concentric rings with nine tran- and a multifocal IOL is one factor number of rings in their design cor- sition zones between them, creating in visual outcome, infl uenced by the responds with greater demand on the 18 distinct steps. The ST value would type of refractive surgery and degree corneal surface.” represent the average step size for the of dioptric correction patients have To help identify a potential fi t be- lens: undergone. “In my experience with tween a given post-refractive cornea hundreds of eyes, generally cases of and multifocal IOL, he uses a numeri- ST=(3.6 mm-0.86 mm)/ up to 4 D to 6 D of correction with cal computation to determine the spa- (2X18)=.0761 mm, or 76.1 µm. prior myopic LASIK will be suitable tial tolerance (ST) of the IOL. He only for multifocals,” says Dr. Wang. He considers a multifocal if the eye’s spa- If we compare this lens to a cornea notes that he generally doesn’t put tial precision falls within the lens’s tol- with irregularity measured to be on multifocals into eyes with a history of erance parameters. Using a +3 D lens the order of 250 µm (the SP, or spa- RK, early PRK or hyperopic LASIK,
February 2017 | reviewofophthalmology.com | 41
040_rp0217_f3.indd 41 1/20/17 3:46 PM Cover Cataract & Refractive Surgery
REVIEW Focus Ming Wang, MD, PhD although he makes occasion- al exceptions for hyperopic LASIK corrections no greater than 2 D to 3 D. “As a gen- eral concept, most of these cases won’t work with a lens so acutely sensitive to inaccu- racy, but doing the calculation provides greater certainty in this assessment,” he states. Similarly, Dr. Raviv uses multifocal IOLs in select post-refractive patients, the majority with a history of my- opic LASIK. “The fi rst thing that I differentiate is patients who have had myopic LASIK versus hyperopic LASIK and RK,” he says. “Radial keratot- omy is much more challenging and much more diffi cult, due to the variation and fl uctua- tion of the vision and the ker- atometry. I avoid multifocals in those patients at all costs.” Dr. Raviv also considers post- LASIK patients who’ve had a lot of dioptric correction poor candidates for multifocal IOLs. “I would avoid status Preoperative corneal topography is especially important in eyes with prior refractive surgery. This post high myopia treatment, topography shows a decentered ablation zone, a contraindication for multifocal IOLs. he says, “but people who’ve had under 5 D of treatment usually do refractive surgery?’ If they respond, cerned with some of the higher-or- pretty well.” ‘The vision never really cleared up. I der aberrations which are inherent Dr. Chang, who notes that he had night vision problems and never to and created by LASIK, as well as is now trending towards Symfony really liked it,’ that’s a big red fl ag, the dysphotopsias that multifocals can extended-depth-of-focus lenses in because if they had a decentered ab- create,” says Dr. Raviv. “We didn’t post-refractive patients, also avoids lation or some other surgically in- want to combine those in the past, but multifocals in post-RK eyes, but duced problem, I’m not going to be our lenses have gotten better. Most doesn’t have hard limits regarding able to fi x that with a lens surgery,” of our patients who’ve had myopic other types of previous surgery or he says. “If they say, ‘It was great! It LASIK have positive spherical aber- degree of dioptric correction. “With stayed great for 10 years, but it’s got- ration in the cornea. The multifocals post-refractive eyes, it’s a case-by- ten worse recently,’ then that makes we have now have negative spherical case basis. Not all LASIK is the same, me think that their problems are aberration, so we can treat that,” he for example, so you need to consider probably cataract-related. I can be a continues. “Furthermore, we’ve re- each case on an individual basis,” he little bit more fl exible with my IOL cently gained the ability to use toric says. Dr. Chang also says that patient options.” multifocal or toric EDOF lenses. A response to the prior surgery is im- lot of post-LASIK patients have re- portant when selecting suitable mul- Rethink the Multifocal Category sidual astigmatism, so the newer toric tifocal patients. “One of the things EDOF lenses have allowed us to treat I always ask patients is, ‘How did “To be successful with multifocals their residual refractive error.” you do after your initial LASIK or after LASIK, we have to be con- Dr. Raviv has grown more will-
42 | Review of Ophthalmology | February 2017
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2015_RPonline_house.indd 1 12/10/14 2:38 PM Cover Cataract & Refractive Surgery
REVIEW Focus Tal Raviv, MD, FACS ing to implant presbyopia-correcting IOLs into post-refractive eyes with the emergence of low-add multifocals and EDOF lenses. “In 2015, we saw the advent of the low-add multifocal. I put those into post-LASIK patients and they did great, with very few nighttime symptoms and very good distance and near vision,” he says. “Now with the [Symfony] EDOF lens, we have a forgiving lens that is toler- ant of some residual refractive error, something more likely to occur in a post-refractive eye. These lenses are really more suitable for post-LASIK patients.” Dr. Raviv adds that he re- gards EDOF IOLs as a subcategory of multifocal IOLs. “In any discussion about multifocals after LASIK, you’ve Intraoperative aberrometry can aid in multifocal IOL selection in eyes that have undergone also got to include EDOFs, because refractive surgery, which are notorious for unpredictable IOL implantation outcomes. those are the most user-friendly type of multifocal. It’s a subset of multifo- cal, and they are the lenses that I’m done well for a lot of people. You have near vision for reading or other close now primarily using,” he says. to make sure they know what to ex- work, Dr. Raviv will use low-add mul- Dr. Chang also finds the Symfo- pect,” he says. He advises patients that tifocals. “I’ll use the Tecnis ZKB00,” ny’s refractive forgiveness especially in addition to refractive misses, they he says. “It’s one of the lowest adds of helpful in his post-refractive patients. may be at higher risk for quality-of- the multifocals, so there’s a very low “The jury’s still out,” he says, “but in vision issues. “Sometimes, prior hyper- incidence of optic phenomena with my hands I’ve seen excellent results.” opic LASIK may work against them, that lens.” Dr. Chang says that when consider- for example, because most of our mul- ing an IOL in the post-refractive eye, tifocal lenses are negatively aspheric,” Measuring and Operating the avoidance of “splitting light” is he says. not the key factor. “The most impor- Although post-LASIK patients can Dr. Chang’s preop workup of these tant thing to consider is the quality enjoy excellent results with multifocal patients differs from that for typical of the image you’re putting on the IOLs, Dr. Raviv is also careful to give cases mainly in the amount of at- retina,” he says. “When you look at patients a preoperative dose of realism. tention to corneal topography. “I’ll some modeling and benchtop trials, “We don’t promise them complete, always review the topography a lot the lenses that correct spherical aber- 100-percent glasses independence,” more closely in my previous refrac- ration and chromatic aberration actu- he says. “We shouldn’t do that with tive surgery patients. I’m using the ally produce better image quality.” any multifocal patient. I don’t mind Atlas topographer right now, which the super type-A-triple-plus patients, allows me to assess what the refrac- Counsel Carefully because we read them the riot act, and tive surgery did, to make sure that they know what they’re getting into,” the treatment zone size is good, that Dr. Chang intensifies his pre- he continues. “We tell them, ‘This is the centration is good and that there’s operative counseling a little when the best technology we can give you: no irregular astigmatism,” he says. post-refractive surgery patients want This is your eye. We’re going to match His preop presbyopic workup also in- presbyopia-correcting IOLs—in part the two and do what we can. If you cludes a standard eye exam, biometry because their prior results are gener- hate it, we’ll take it out and put in an- with the IOLMaster 700 and macular ally so good. “With any patient, coun- other lens, but you’re limited to this or OCT with the Cirrus SD-OCT. seling is critical, but especially for post- that. That’s all we have. I’m offering Dr. Raviv also doubles down on to- refractive patients; their expectations you the best we’ve invented.’ ” pography. “For those patients, I’m get- may be high from LASIK, which has For patients who insist on sharp ting two sets of topographies,” he says.
February 2017 | reviewofophthalmology.com | 45
040_rp0217_f3.indd 45 1/20/17 3:47 PM Cover Cataract & Refractive Surgery
REVIEW Focus
“One is a standard placido disk topog- edge of the fl ap is. You want to make notes Dr. Chang. His next step “de- rapher and the other is a topographer your incisions away from the fl ap and pends upon how unhappy the patient that helps me measure the posterior just stay out of its way. It’s usually not a is,” he says, adding that he offers en- corneal astigmatism, and therefore the problem, and the surgery is otherwise hancements after waiting three to six total corneal astigmatism, more ac- quite the same as it is for traditional months for the refraction to stabilize. curately.” patients,” he says. Dr. Raviv also watches and waits for He reports good results using the refraction to stabilize in these cases. modern formulas. “I like the Barrett Have a Plan B “For patients who are still unhappy, I’m True-K,” Dr Raviv says. “That formula going to wait three months,” he says. “If seems to be very accurate. But I will In a patient group where both ex- it’s not better, then I’ve got to do some- also run the Shammas and the Haigis- pectations and the potential for subop- thing, whether it’s explantation or some- L. Those are all found on the ASCRS timal outcomes run high, you must also thing else. I’m happy to wait, unless the post-refractive calculator. I used to be prepared to act when multifocal patient is miserable. A lot of these lenses use historical data. Ten years ago, we IOLs prove unsatisfactory. “You need do get better in three months.” hunted down documents, trying fi nd to have the skills, the wherewithal and For a carefully selected group of pa- people’s previous Ks.” He no longer the ability to correct any unhappy pa- tients who have had refractive surgery spends time on records requests to fa- tients, whether it’s because of dyspho- in the past, some surgeons say that mul- cilities around the world, however: “It topsia or because of residual refractive tifocal IOLs can provide customized turns out that the no-history methods error,” stresses Dr. Raviv. “If it’s residu- visual results that monofocals can’t. Al- have gotten so good that we’re using al refractive error, you have to be ready though it takes careful screening, a scru- them exclusively at this point,” he says. to do one of three things: PRK touch- pulous preoperative workup and per- The second pillar of Dr. Raviv’s up or LASIK enhancement; IOL ex- haps extra time in follow-up, such care lens-selection strategy is interopera- change; or toric rotation.” Although can reap rewards in terms of patient tive aberrometry. “You just have to suboptimal outcomes are atypical if pa- satisfaction. “Post refractive surgery check off a box on the ORA indicating tients are carefully selected and worked patients have already invested finan- post-myopic LASIK, or post-hyperopic up, Dr. Raviv acknowledges, “It’s much cially in their vision, and they want to LASIK, so it feels a little bit like cheat- more likely for them to happen in post- continue the good-quality uncorrected ing,” he says. “I fi nd that by combining refractive multifocal patients than in vision they have already achieved when the formulas I use with the ORA, I get traditional cataract cases.” they undergo cataract surgery,” says Dr. very close. I use it with all my post- When unhappy multifocal IOL pa- Raviv. “We’ve come a long way, and we refractive cases and all of my multifocal tients present themselves, Dr. Raviv now have many ways of making these patients; so certainly, with multifocal teases out the cause. “One of the patients happy.” post-refractive cases I’m using ORA.” simplest things to do is make sure While he doesn’t use intraoperative it’s not residual refractive error. The Dr. Davison is a consultant for Alcon. aberrometry, Dr. Chang is another fan post-LASIK eye may be more sensi- Dr. Raviv is a consultant for Abbott, of the ASCRS calculator for post-re- tive to even 0.5 D or 0.75 D of this. Ocular Therapeutics and Glaukos, and fractive eyes for preop measurements. In the unhappy multifocal patient, is is a paid speaker for Bausch + Lomb “Warren Hill, Doug Koch and Li Wang it posterior capsule opacifi cation, or is and Shire. Dr. Chang is a consultant for have done a fantastic, amazing job put- it the lens itself? If it’s PCO, we want Carl Zeiss Meditec AG and Abbott. Dr. ting that out there as a resource,” he to address that early,” he says. “If they Wang reports no fi nancial interest in says. “Typically for presbyopic IOLs, are immediately unhappy early on, I any products or procedures discussed I will look at multiple scans and com- want to address their residual refractive in this article.
pare their consistency. That’s obviously astigmatism. The easiest way to do that 1.Khor WB, Afshari NA. The role of presbyopia-correcting trickier if I’m manually entering data is to put on a trial contact lens that cor- intraocular lenses after laser in situ keratomileusis. Curr Opin Ophthalmol 2013;24:1:35-40. into the ASCRS Web site, but I do use rects them to plano, even if it’s just -0.5 2.Alfonso JF, Madrid-Costa D, Poo-Lopez A, Montes-Mico R. Visual the multiple scans to make sure there’s D. Some people will come back after a quality after diffractive intraocular lens implantation in eyes with previous myopic laser in situ keratomileusis. J Cataract Refract a fair amount of consistency among day or two and say it’s perfect, and then Surg 2008;34:11:1848–1854. them.” I’ll just do a touch-up on their cornea.” 3.Muftuoglu O, Dao L, Mootha VV et al. Apodized diffractive intraocular lens implantation after laser in situ keratomileusis In surgery, Dr. Raviv is careful to “If there’s a postoperative refractive with or without subsequent excimer laser enhancement. J avoid LASIK flaps when implanting error, my patients have been prepped Cataract Refractive Surg 2010;36:11:1815-21. any IOL. “When I’m operating, I’m beforehand to understand that there’s 4.Wang M. Multifocal IOLs for post-LASIK patients: Establishing clinical guidelines for patient selection. Refractive Eyecare always very cognizant of where the a higher-than-normal chance for that,” 2012;16:6:1-4.
46 | Review of Ophthalmology | February 2017
0040_rp0217_f3.indd40_rp0217_f3.indd 4646 11/20/17/20/17 3:473:47 PMPM REVIEW News (Continued from page 8) researchers administered three doses that was 2 to 3 mmHg greater than (Lexington, Mass.), announced that of trabodenoson: 3%/1,000 mcg once previously observed in their Phase II its proposed glaucoma treatment, daily; 4.5%/1,500 mcg twice daily; and trial of the drug. trabodenoson, failed its FDA phase 6%/200 mcg once daily. David Southwell, president and III trial. Specifi cally, the drug didn’t There were no signifi cant safety chief executive offi cer of Inotek, ad- achieve its primary endpoint of sig- or tolerability events reported in the dressed the results in a conference nifi cantly reducing intraocular pres- study. The safety of trabodenoson was call after the news broke. “Phase III sure compared to the placebo at every comparable to the placebo. Just four results always contain unexpected ele- time point. Trabodenoson is designed subjects (2.2 percent) discontinued ments, which teach us about the com- to lower a patient’s IOP by altering the trial because of treatment-related pounds we are developing,” he said. the natural function of the trabecular adverse events. “We clearly need to better understand meshwork. The 6%/2,000 mcg dose of trabode- these results and, particularly, what The MATrX-1 Phase III trial was noson was superior to the placebo drove the placebo response.” a randomized, double-masked, pla- at days 84, 42, 14 and marginally su- However, Mr. Southwell remained cebo-controlled trial, looking at 303 perior at 28. Daily IOP reduction at optimistic. “Trabodenoson has iden- subjects diagnosed with primary three months for this dosage was 4.25 tifi ed itself as a drug with very clean open-angle glaucoma or ocular hy- mmHg compared to the placebo’s safety profi les, with low side effects, pertension and an IOP greater than 2.38 mmHg. This normal response both in the eye—such as hyper- or equal to 24 mmHg and less than or confi rms that the trial was properly emia—and in the systemic compart- equal to 34 mmHg. The trial lasted for conducted, Inotek says. However, the ment,” he said. “This trial, by some three months. The subjects’ IOP was trial didn’t achieve its goal of signifi - measure, showed an even better measured at four time points during cantly reducing IOP compared to the safety and tolerability profi le than the day: 8 a.m.; 10 a.m.; 12 p.m.; and placebo at all time points. Research- previously observed, particularly with 4 p.m. on days 14, 28, 42 and 84. The ers attribute this to a placebo response hyperemia.” 22ND ANNUAL OPHTHALMIC Product Guide Innovative products to enhance your practice The future is in your hands. One tap, many possibilities. Experience the digital edition on your handheld device. Use your smart device to scan the code below or visit: www.reviewofophthalmology.com/supplements/ Download a QR scanner app. Launch app and hold your mobile device over the code to view http://www.reviewofophthalmology.com/supplements/.
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February 2017 | reviewofophthalmology.com | 47
004_rp0217_news.indd 47 1/20/17 4:21 PM FEBRUARY 18-19, 2017 OphthalmologyUpdate
LOCATION Hilton La Jolla Torrey Pines 10950 North Torrey Pines Rd. La Jolla, CA 92037 P: 858-558-1500 UCSD SPEAKERS PROGRAM CHAIRS Natalie Afshari, MD, FACS Don O. Kikkawa, MD, FACS Daniel Chao, MD, PhD Robert N. Weinreb, MD William Freeman, MD Michael Goldbaum, MD DISTINGUISHED Weldon Haw, MD INVITED SPEAKERS Chris Heichel, MD Alex Huang, MD, PhD Bobby Korn, MD, PhD, FACS Lee Jampol, MD Felipe Medeiros, MD Rob Knight, PhD Eric Nudleman, MD, PhD David Serraf, MD Shira Robbins, MD Jeremiah Tao, MD Peter Savino, MD Mandi Conway, MD Karl Wahlin, MD Derek Welsbie, MD, PhD REGISTRATION FEE: $95 FOR MORE INFORMATION www.ReviewofOphthalmology.com/Update2017 Email: [email protected] Phone: 855-306-2474
Accreditation Statement This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Amedco and Postgraduate Health Education, LLC (PHE). Amedco is accredited by the ACCME to provide continuing medical education for physicians. Credit Designation Statement This meeting is approved for AMA PRA Category 1 Credits™
Jointly provided by Shiley Eye Institute Review of Ophthalmology® UC San Diego An interdisciplinary faculty of ophthalmic subspecialists will review the continuing progress in Cataract and Refractive Surgery, Glaucoma, Retina, Neuro-Ophthalmology, Pediatric Ophthalmology, Ocular Surface Disease, Cornea and Oculoplastics.
Discounted room rates EDUCATIONAL OBJECTIVES available at $209/night. Limited number of rooms After participating in this educational activity, attendees should available. See registration be able to: site for more information. • Analyze new research that illustrates the key role that infl ammation plays in the genesis of DME and macular edema secondary to RVO • Engage in discussions related to emerging issues in glaucoma, including risk assessment, imaging, management and progression assessment • Manage glaucoma using newer treatments available: surgical and pharmaceutical • Discuss the newest glaucoma surgical devices, including those used in patients undergoing cataract surgery • Describe outfl ow biology and its relevance to MIGS while citing relevant MIGS studies and trials • Utilize advanced technologies and techniques in refractive cataract surgery, including advanced technology IOLs • Outline current management and treatment of dry eye and keratitis. • Discuss the rationale for anti-VEGF therapy and steroids in posterior segment diseases including age-related macular degeneration and diabetic macular edema • Managing IOP in retina disease state treatments • Navigate issues relating to patient compliance/adherence with eye drop medications • Describe how various imaging technologies, such as OCT and angiography, can assist in diagnosing and monitoring ocular conditions • Discuss options for cosmetic skin procedures
PROGRAM TIMES Saturday, February 18th 8:00am — 5:00pm Reception to follow Sunday, February 19th 8:00am — 12:15pm
Photho os: ©2015 HHiltonlto Hotels &&R Resortts
Jointly provided by Shiley Eye Institute Review of Ophthalmology® UC San Diego Glaucoma Management
REVIEW Edited by Kuldev Singh, MD, MPH, and Peter A. Netland, MD, PhD
Managing Glaucoma with OCT: Secrets to Success Knowing the advantages and potential pitfalls of this technology can help you make it an effective disease-monitoring tool. Brian Francis, MD, MS, and Vikas Chopra, MD, Los Angeles
oday, optical coherence tomog- with a visual fi eld test, the plasticity studies are currently exploring that T raphy has become a standard and overlap inherent in the visual possibility.) In addition, a newer tool for diagnosing and monitoring system tend to compensate for any technology called OCT angiography, glaucoma. As with many advanced early damage. As a result, early dam- or OCTA, which uses OCT to map technologies, there are several ways age may be picked up by an OCT scan the blood vessels in the retina, might we can use OCT and a number of rather than by a visual fi eld test. also turn out to be helpful in advanced potential pitfalls to avoid. Here, we’d On the other hand, late in the dis- disease. like to discuss some of those issues, ease OCT is less useful because of OCT gives us a wealth of data to including the limitations of this the “fl oor effect,” which refers to the work with, because it can provide technology; the pros and cons of event- fact that when the nerve fi ber layer structural information about many based and trend-based progression thickness reaches about 45 to 50 µm, parts of the retina and optic nerve analysis; common mistakes to avoid; it bottoms out and doesn’t decrease head—and now the lamina cribrosa— and ways to improve the accuracy of any further—even though damage while OCTA can look at the retinal your interpretation of OCT data. caused by the disease may continue and peripapillary blood vessels. In to worsen. Once you reach that level, fact, one of our jobs over the next OCT Today there’s really no point in using OCT to five years is to figure out which detect progression; if you do, it may information provided by OCT is For now, OCT is most useful when give you a false sense of security that important at which stage of the a patient is either a glaucoma suspect there’s no change happening when the disease. We may end up focusing on or has early-to-moderate disease, as patient may actually be getting worse. one group of OCT parameters in early a tool for helping to detect damage At that point we usually rely on visual disease and a different group in more and progression (or conversion from fi elds and other functional testing to advanced disease. glaucoma suspect or ocular hyperten- determine whether progression is sive to glaucoma). While there are occurring. Factors Affecting OCT Accuracy many parallels between OCT tech- This limitation of OCT mea- nology and visual fi elds—for example, surements could change in the future, A number of things can undermine being able to use them for either event- because there’s some evidence that the accuracy of an OCT scan. To avoid based analysis or trend-based progres- other OCT parameters such as the basing a medical decision on poor sion analysis—OCT is arguably a thickness of the macular ganglion data, be mindful of these fi ve factors: better tool for use in early disease, cell complex may still reveal change • Signal quality. The quality of the because when we test visual function in more advanced disease. (Some data in an OCT scan depends, among
50 | Review of Ophthalmology | February 2017 This article has no commercial sponsorship.
050_rp0217_gm.indd 50 1/18/17 1:56 PM RETINA ONLINE E-NEWSLETTER
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2016_Retina Online house Ad.indd 1 2/18/16 1:46 PM Glaucoma
REVIEW Management
Potential problems that can undercut the accuracy of your scan. Left: The depth of the scan must be correct. Here, the display is cut off at the top because of inaccurate scan depth. The instrument may interpret the missing data as 0-µm thickness at that location. Center: If the optic nerve is not centered in the scan circle, thickness measurements will be thrown off, giving the impression of a focal defect that doesn’t exist. Right: Opacities such as this fl oater will disrupt the data because the instrument can’t measure through them.
other things, on signal strength. reliable, useful information. (Other circle isn’t centered around the optic Fortunately, OCT systems measure manufacturers also have minimum nerve (see example, above, center), the signal-to-noise ratio of the data signal strength guidelines that are the part of the circle that’s too close to being received and give us a number considered necessary to perform the nerve will measure thicker than it gauging the scan quality after each analysis.) Checking the scan-quality actually is, and the part that’s farther measurement. number before you rely too much away from the center will measure Signal strength can be decreased for on the data is important, because the thinner. As a result, you may think a variety of reasons; the most common OCT will give you an analysis even if there’s a focal defect in the thin area. reasons are cataract, media opacities, the scan had poor signal strength. This problem usually occurs when corneal edema, vitreous fl oaters and If you do fi nd that the scan was of the patient has diffi culty maintaining dry eye. The latter is easy to treat, poor quality, then you need to fi gure fixation. The instrument may be so if you get poor signal strength out the reason. In that situation, centered properly at first, but then and the media appear clear, give the every box on the OCT readout tells the patient moves a little or the eye patient artifi cial tears right before the you something—even the parts that shifts. A good technician will pick this next scan. That often improves signal people don’t pay much attention to, up and instruct the patient to refi xate. strength significantly. Lower signal like the TSNIT graph overlay between This is an error that you won’t pick strengths will often yield lower retinal the two eyes, and the segmentation up by looking at the scan quality and nerve fi ber layer thickness values that section at the bottom. signal strength. The signal strength will improve with re-scanning to yield • Scan alignment. Not only does may be excellent, but if the scan is higher (and probably more accurate) the eye have to be aligned on the not centered properly, you’re going values.1 visual axis, but the depth of the scan to get misleading measurements. Movement and blinking artifacts has to be correct. You can see whether Fortunately, this error is becoming can also be a problem because or not it’s correct in the colored graph less common with the newer-genera- they interrupt the scans. This is where the retinal data is presented tion OCT devices that have an auto- becoming less of a problem as OCT as a sinusoidal pattern. The graph tracking feature to maintain scan instruments scan faster, but it’s still should be aligned centrally in the box. centration. a potential issue. You may observe If it’s too high or too low—too high • Opacities. These are usually these movements if you’re watching is most common—then the scan was fl oaters. (See example, above, right.) the patient, but if not, you may note a cut off, and you’ll be missing data for Floaters will disrupt the scan, because break or a horizontal line in the gray- that section, which the instrument OCT technology can’t measure scale image of the optic nerve and will interpret as 0-µm thickness in through them. This is a problem retina. It may look like the top half that area. (See the sample scan shown that’s often easy to fi x, however; you and bottom half don’t line up. That above, left.) That’s certainly going to can have the patient look away and means the patient moved or blinked. disrupt your data and make values less look back. That will usually move the Using the Zeiss Cirrus spectral- than they should be. This type of scan fl oater out of the fi eld of view, or at domain OCT, we consider a scan- alignment error is quite common in least outside of the scan circle. quality reading of 7 out of 10 (or bet- eyes with high axial myopia. • Segmentation errors. The soft- ter) to mean that the scan contains • Scan centration. When the scan ware will try to segment out the reti-
52 | Review of Ophthalmology | February 2017
050_rp0217_gm.indd 52 1/18/17 1:57 PM The next advancement from the leader in intraoperative aberrometry
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*HWUHDOWLPHGDWDYHULȴFDWLRQZLWK WKH25$™6\VWHPZLWK9HULI(\H™. IMAGE PLAN GUIDE VERIFY OPTIMIZE Cataract procedures using the ORA™ System with ™ ORA System VerifEye™ Technology have been proven to help with VerifEye+™ deliver better outcomes for your astigmatic and post-LASIK patients.1,2 • Provides IOL sphere, cylinder and alignment suggestions Contact your local Alcon rep or • Dynamic variable optimization and robust reporting pow- visit www.GuideandVerify.com for more information. ered by AnalyzOR™ Technology See adjacent page for important product information.
ORA ™ System Advancing WITH VERIFEYE+™ CATARACT SURGERY
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In that case I’ll support cataract surgical procedures. lower my benchmark for progression CONTRAINDICATIONS: The ORA™ System to 8 µm. is contraindicated for patients: who have Note that when doing an event- progressive retinal pathology such as diabetic retinopathy, macular degeneration, or any based comparison, you should other pathology that the physician deems OCT software will try to show the segments compare the current test to the ZRXOG LQWHUIHUH ZLWK SDWLHQW ȴ[DWLRQ ZKR of the retinal nerve fi ber layer, but low scan baseline tests—which should have have corneal pathology such as Fuchs’, EBMD, quality can produce a garbled result. been based on two stable early tests keratoconus, advanced pterygium impairing done within a limited time period— the cornea, or any other pathology that the physician deems would interfere with the nal nerve fi ber layer, but if the scan rather than comparing it to the PHDVXUHPHQW SURFHVV ZKRVH SUHRSHUDWLYH quality isn’t good, the segmentation previous test. If you only compare it regimen includes residual viscous substances will be thrown off and lead to inac- to the previous test, you could miss left on the corneal surface such as lidocaine curate values. (See example, above.) slow progression. JHO RU YLVFRHODVWLFV ZLWK YLVXDOO\ VLJQLȴFDQW The retinal nerve fi ber layer is sup- Event-based analysis has some PHGLD RSDFLW\ VXFK DV SURPLQHQW ȵRDWHUV or asteroid hyalosis) what will either limit or posed to be the area between the two notable limitations: It’s susceptible SURKLELW WKH PHDVXUHPHQW SURFHVV RU ZKR red lines. Anything that affects scan to outliers, and it may identify false have received retro or peribulbar block or quality can cause this type of error. progression. On the other hand, any other treatment that impairs their ability it’s easy. That’s why many doctors WR YLVXDOL]H WKH ȴ[DWLRQ OLJKW ΖQ DGGLWLRQ Event-based or Trend-based? use this kind of analysis in practice, utilization of iris hooks during an ORA™ System image capture is contraindicated, especially if they don’t have glaucoma because the use of iris hooks will yield There are two basic strategies for progression analysis software, which inaccurate measurements. WARNINGS detecting change over a series of features trend-based analysis. AND PRECAUTIONS: 6LJQLȴFDQW FHQWUDO tests: event-based analysis and trend- • Trend-based analysis. This corneal irregularities resulting in higher order based analysis. Each has advantages approach looks at a series of sequential aberrations might yield inaccurate refractive and limitations, so it’s important to tests, including your baseline tests, measurements. Post refractive keratectomy eyes might yield inaccurate refractive understand the difference. and measures the slope of change PHDVXUHPHQW7KHVDIHW\DQGHHFWLYHQHVVRI • Event-based analysis. To over time for whatever parameter using the data from the ORA™ System have not perform event-based analysis, you you’re looking at—overall change, been established for determining treatments simply compare one test to another. change in the superior or inferior involving higher order aberrations of the eye The practical reality is that there’s a segments, or change in the ganglion such as coma and spherical aberrations. The ORA™6\VWHPLVLQWHQGHGIRUXVHE\TXDOLȴHG measurement error in every test we cell complex. It’s primarily concerned KHDOWKSHUVRQQHORQO\ΖPSURSHUXVHRIWKLV do, so in order to decide whether a with the rate of change rather than the device may result in exposure to dangerous change has actually occurred between amount. (This is analogous to visual voltage or hazardous laser-like radiation the two tests, you have to fi rst decide fi eld progression detection.) As you ™ exposure. Do not operate the ORA System what amount of change in the can see in the example on the facing LQWKHSUHVHQFHRIȵDPPDEOHDQHVWKHWLFVRU volatile solvents such as alcohol or benzene, measurements is likely to be greater page, three of four parameters have or in locations that present an explosion than the instrument’s potential error. remained relatively stable in this eye, hazard. ATTENTION: Refer to the ORA™ Some current studies indicate that but one has changed signifi cantly over System Operator’s Manual for a complete spectral-domain-OCT has about a time. The software has highlighted this description of proper use and maintenance of 4-µm intervisit reproducibility.2 So, by turning the circle that represents the ORA™ System, as well as a complete list of contraindications, warnings and precautions. to be sure a change is real, it should that measurement orange. be greater than twice that, or 8 µm The advantage of trend-based (approximately twice the statistical analysis is that it’s less susceptible standard deviation value). to fl uctuation because it’s looking at Advancing In our practice, we’ve chosen to change over a period of time. The CATARACT SURGERY be conservative and look for change disadvantage is that it requires a large greater than 10 µm; if we don’t see a number of tests. In addition to your 10-µm change, we take the result with baseline tests, you usually need at a grain of salt. However, certain things least two or three subsequent tests can lower our threshold for detection. to compare to your baseline to make © 2015 Novartis 12/15 US-ORA-15-E-0947 050_rp0217_gm.indd 54 1/18/17 1:58 PM • Be sure to account for normal aging. There’s a small loss of retinal nerve fiber layer and ganglion cells as we age, even in the healthiest of individuals, so it’s important to take this into account when diagnosing or monitoring progression to avoid Trend-based analysis looks at a series of sequential test results over time. Here, three mistaking normal aging for disease. of four parameters have remained stable, but one has changed signifi cantly, which the To do that, we need to know what software has highlighted by coloring the circle orange. the rate of normal loss is—at least on average. the trend statistically robust. If you sure the scan has good-quality data. Different studies have looked at only get one scan a year, it can take This is part of the reason for the this, both in a cross-sectional manner several years to detect change using problem referred to as “red disease,” (taking a population and dividing it up this type of analysis. Furthermore, to where patients get referred—and into decades or fi ve-year periods and allow valid comparisons, it’s critically sometimes treated—for glaucoma looking at the average NFL thickness important to choose baseline scans because they appear to have an of normal patients in each age group) that were performed with good scan abnormal OCT. When you look at and longitudinal fashion (where parameters. the OCT, you fi nd there’s something individuals are followed over time). In general, trend-based analysis is wrong with the scan, not the patient. One study recruited 100 normal in- preferable to event-based analysis. OCT is a powerful tool, but it’s up to dividuals for cross-sectional analysis However, there are many situations the clinician to use it correctly. and 35 for longitudinal analysis.4 That in which trend-based analysis can’t • Look for focal change, not study found a loss of 0.33 µm per year help—even if it’s available in software just overall change. It’s important using cross-sectional data and 0.52 like Zeiss’s Guided Progression Anal- to remember that retinal nerve fi ber µm per year using longitudinal. The ysis. For example, a new patient may layer thinning can happen in several Advanced Imaging for Glaucoma have had an OCT done on one ma- ways, which will be reflected in Study did both types of analysis with chine and now you’re doing it on different scores. For example, you 192 eyes over fi ve years. The cross- another. Or you may have recently may find a global, overall decrease sectional analysis found a GCC loss of upgraded from one OCT to a newer in average thickness, or you may fi nd 0.17 µm per year and overall retinal one, perhaps from time-domain to a focal decrease in one quadrant. nerve fi ber layer loss of 0.21 µm per Fourier-domain. Those two types of The three most common RNFL year; the longitudinal analysis found OCT data can’t be directly compared. progression patterns are: a loss of 0.25 µm per year in GCC Practical issues like these often force — a new RNFL defect; thickness and 0.14 µm in overall nerve us to resort to event-based analysis. — widening of an existing defect; fiber layer thickness.5 (Obviously, — deepening of an existing RNFL longitudinal data is likely to be more Helpful Strategies defect without widening. robust, but longitudinal studies don’t Studies have looked at these go on long enough to cover the age These strategies will help you get changes, and all of them seem to span that can be covered in a cross- the most from your OCT data: be important as a means to detect sectional study.) • Look at the entire readout, glaucoma.3 In practice, some doctors Many people combine the cross- not just one or two numbers. are in the habit of just looking at the sectional data and longitudinal data Many surgeons pick out one or two overall thickness number; but for and average them. Conservatively, key numbers and only look at those monitoring progression, if there’s you’re looking at about 0.2 µm per when they review a scan. But you already a defect, you want to look year for the NFL thickness. That’s not have to look at the entire scan to at that area for changes. (The pie a lot of loss, but over 10 years that can make sure the quality is good and the charts on the readout will tell you if add up to several microns of change. scan is centered. We try to discipline a focal defect is getting worse.) That’s As a result, that has to be factored ourselves to avoid looking at the nerve important, because if a focal defect into the software designed to analyze fi ber layer thickness—overall, inferior gets worse it may not cause much of these data and taken into account and superior—until after we review a difference in the overall thickness, when you’re looking into progression all of the other parameters, to make leading you to miss the change. without the help of software. So if February 2017 | reviewofophthalmology.com | 55 050_rp0217_gm.indd 55 1/18/17 1:56 PM Monthly MACKOOL ONLINE CME CME SERIES | SURGICAL VIDEOS MackoolOnlineCME.com MONTHLY Video Series Welcome to the second year of Mackool Online CME! With the generous support of several ophthalmic companies, I am honored to have our viewers join me in the operating To view CME video room as I demonstrate the technology and techniques that I go to: have found to be most valuable, and that I hope are helpful www.MackoolOnlineCME.com 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 14: Richard J. Mackool, MD “Restoring Vision to a As before, one new surgical video will be released monthly, Special Young Man” 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: Richard J. Mackool, MD located in our archives. I thank the many surgeons who have told us that they have found our CME Video Overview: program to be interesting and instructive; I appreciate your comments, Tom is a courageous and engaging young man with advanced Duchenne’s Muscular suggestions and questions. Thanks again for joining us on Mackool Online CME. Dystrophy. Years of steroid treatment have caused him to develop extremely dense cataracts and he is now legally CME Accredited Surgical Training Videos Now blind. Severe muscular atrophy has left Available Online: www.MackoolOnlineCME.com him quadriplegic with very signifi cant respiratory problems that do not permit him to lie fl at. Furthermore, even mild Richard Mackool, MD, a world renowned anterior segment ophthalmic sedation could result in life-threatening microsurgeon, has assembled a web-based video collection of surgical oxygenation problems. In this video, our team performs cataract surgery without cases that encompass both routine and challenging cases, demonstrating both any sedation. Signifi cant assistance is familiar and potentially unfamiliar surgical techniques using a variety rendered by his mother, an RN who has essentially dedicated her life to caring of instrumentation and settings. for her severely disabled son. During the procedure, reverse Trendelenburg This educational activity aims to present a series of Dr. Mackool’s surgical positioning, a positive pressure breathing videos, carefully selected to address the specifi c learning objectives of this apparatus and special draping to prevent activity, with the goal of making surgical training available as needed online for claustrophobia enabled us to optimize his comfort and safety. Tom now has 20/20 surgeons motivated to improve or expand their surgical repertoire. distance and near vision in both eyes without glasses. His remarkable bravery in Learning Objective: dealing with this dreaded disease and the After completion of this educational activity, participants should be able to: dedication of his mother are more than • Demonstrate techniques that can be employed during cataract surgery inspirational, and their joy at the recovery of his sight was wonderful to behold. to improve the comfort and safety of patients with respiratory and/or From the vantage point of this surgeon, claustrophobic problems. I can only attest to what my dedicated colleagues already know; this is why we Learn more about Duchenne’s Muscular Dystrophy at www.endduchenne.org became physicians. Accreditation Statement This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Amedco and Postgraduate Healthcare Education, LLC (PHE). Amedco is accredited by the ACCME to provide continuing medical education for physicians. Credit Designation Statement Amedco designates this live activity for a maximum of .25 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Commercially supported by: Endorsed by: Jointly Provided by: Supported by an unrestricted independent Review of Ophthalmology® medical educational grant from: Carl Zeiss Meditec Crestpoint Management Video and Web Production by: Glaukos JR Snowdon, Inc & Alcon MST Glaucoma REVIEW Management you’re not using the GPA software and you’re comparing two scans fi ve years apart, trying to decide whether the patient has progressed or not, you need to be aware of that possible age- related change. Using GPA Zeiss’s GPA is one of the programs commonly used to help analyze OCT results. The printout includes thickness charts at the top, in color; the change graphs for different parameters appear below that; and at the bottom left there’s a chart that overlays the TSNIT pattern from multiple tests so you can identify any focal areas of change or loss. (See example, right) When the printout shows a yellow marker, that means it detects significant progression in that parameter; if it’s red, that means the progression has been confi rmed by multiple tests. In this example, the printout indicates progression of an inferior defect, noted in three different places on the printout: the area is illuminated in yellow on the black and white change map for exam Guided Progression Analysis shows focal areas of change or loss in yellow. #3; it’s also represented by a yellow dot in the inferior segment thickness eye has decreased from 70 µm to conflicting parameters—perhaps change graph; and it’s colored yellow 61 µm. You might say that’s signifi cant; one looks stable while the other in the TSNIT graph in the lower left. it is 9 µm of change. But if you look appears to have progressed—having The GPA also allows you to do at reference baseline exams 1 and a sense of which parameter is known event-based analysis, which is 2, there’s some variability between to be associated more strongly with sometimes useful for comparing to them, meaning the value of 70 µm progression will help you judge which trend-based analysis. The readout should be taken with a grain of salt, parameter should have more impact provides a chart that shows the and the amount of change may be on your decision. scores from different tests. However, less than it appears. Again, these Another issue is that doctors would as with most event-based analyses, examples demonstrate why trend- prefer to look at one or two things you have to be careful. Consider the based analysis is generally preferable rather than a field of information two examples on the following page to event-based analysis—as long as when making a clinical decision. (p.58). In the example on the left, the you have suffi cient data to use trend- Knowing which parameters are most highlighted boxes are parameters that based analysis. associated with progression should appear to be significantly changed. make it possible to create an index However, if you compare this to the Which Parameters Matter Most? that incorporates those particular trend analysis over time (as shown in parameters, allowing doctors to get the images above the boxes), there is This is a challenging question the most reliable information in a no signifi cant change. that’s being looked at by a number single number. Admittedly, it’s always The second example shows that of researchers. One reason this is dangerous to give people a single thing the average RNFL thickness in this important is that if you have two to look at—we might be encouraging February 2017 | reviewofophthalmology.com | 57 050_rp0217_gm.indd 57 1/18/17 1:59 PM Glaucoma REVIEW Management Differences between individual numbers may suggest that signifi cant change has taken place, but a closer examination of the larger picture, including trend analysis, may show that a signifi cant change has not actually occurred. them to ignore something else that’s others’) are still just research; they Dr. Francis is a professor of ophthal- important. But it’s better to have a haven’t been incorporated into any mology in the glaucoma service and composite index that takes different instruments. But based on our own the Rupert and Gertrude Stieger things into account than to only look work, we can at least say that doctors Endowed Chair at the Doheny Eye at one piece of data, such as change in should be monitoring the GCC focal Institute, Stein Eye Institute, David average thickness. loss volume. That parameter was bet- Geffen School of Medicine, University Our group conducted a sub- ter at predicting change than the other of California Los Angeles. Dr. Chopra study under the Advanced Imaging focal loss or overall loss measurements is the medical director of the Doheny for Glaucoma Study in which we your instrument may provide. Eye Centers Pasadena and an asso- identified different parameters that ciate professor of ophthalmology of the appeared to be especially useful for Making the Most of OCT glaucoma service in the department of detecting progression. (We defined ophthalmology at the David Geffen progression as visual fi eld progression, To summarize, there’s no question School of Medicine at UCLA. He is to use a marker not related to nerve that OCT can help us diagnose and also the director of glaucoma research fiber layer change.) For example, monitor our glaucoma patients, at the Doheny Image Reading Center we looked at different retinal nerve especially those with early or at the Doheny Eye Institute. Drs. fi ber layer parameters like focal loss moderate disease. But you’ll get the Francis and Chopra have no fi nancial volume; overall inferior quadrant most out of your OCT scans if you: ties to any product mentioned. volume; and all of the ganglion cell • maintain good quality readings 1. Wu Z, Vazeen M, Varma R, Chopra V, Walsh AC, LaBree LD, complex parameters. We found that by monitoring scan signal quality and Sadda SR. Factors associated with variability in retinal nerve one of the most sensitive predictors of the alignment and centration of the fi ber layer thickness measurements obtained by optical progression is focal loss volume, both scan, and watch out for opacities and coherence tomography. Ophthalmology 114:1505-1512, 2007. 2. Mwanza JC, Chang RT, Budenz DL, et al. Reproducibility in the GCC and RNFL. (This supports segmentation errors; of peripapillary retinal nerve fi ber layer thickness and optic the premise that focal change is able to • look at the entire readout, not just nerve head parameters measured with cirrus HD-OCT in glaucomatous eyes. Invest Ophthalmol Vis Sci 2010;51:5724- detect progression earlier than overall one or two numbers; 5730. average thickness changes.) Using • look for focal change, not just 3. Leung CK, Yu M, Weinreb RN, Lai G, Xu G, Lam DS. Retinal nerve fi ber layer imaging with spectral-domain optical that finding in concert with other overall change; coherence tomography: Patterns of retinal nerve fi ber layer relevant data, we created something • remember to account for the progression. Ophthalmology 2012;119:9:1858-66. 4. Leung CK, Yu M, Weinreb RN, Ye C, Liu S, Lai G, Lam DS. we call the Glaucoma Composite aging effect; and Retinal nerve fi ber layer imaging with spectral-domain optical Progression index. The GCP index • use trend-based analysis whenever coherence tomography: A prospective analysis of age-related combines structural measurements possible. And when you need to use loss. Ophthalmology 2012;119:4:731-7. 5. Zhang X, Francis BA, Dastiridou A, Chopra V, Tan O, Varma such as central corneal thickness and event-based analysis, be aware of its R, Greenfi eld DS, Schuman JS, Huang D; Advanced Imaging GCC focal loss volume with patient potential problems so you get the best for Glaucoma Study Group. Longitudinal and cross-sectional analyses of age effects on retinal nerve fi ber layer and ganglion parameters such as age. possible information from the data cell complex thickness by fourier-domain OCT. Transl Vis Sci So far, our attempts (and many comparison. Technol 2016;4:5:2:1. 58 | Review of Ophthalmology | February 2017 050_rp0217_gm.indd 58 1/18/17 1:59 PM Retinal Insider REVIEW Edited by Carl Regillo, MD, and Emmett T. Cunningham Jr., MD, PhD, MPH A Review of Portable Retinal Imaging A guide to using common devices such as smartphones as well as more exotic consumer-level cameras to capture images. Melissa Sieber, MD, Murtaz Adam, MD and Sunir Garg, MD, Philadelphia ur ability to image the eye en- O hances patient care and counsel- ing, while augmenting medical educa- tion. However, outside the traditional clinical setting, standard ophthalmic cameras can be impractical and costly. Accordingly, there’s been interest in adapting non-ophthalmic imaging de- vices that are readily available, easy to use, and relatively inexpensive for ophthalmic use. Figure 1a (left). Mydriatic fundus photo of cryptococcal meningitis with focus on the Advancements in microfabrica- posterior pole and macula captured with a 20-D lens and smartphone camera. tion, optics, digital sensors and image By capturing video instead of still photos, the best image for highlighting the pathology of 4 processing have led to progressive- interest can be selected. Figure 1b (right). Mydriatic fundus photo of optic-disc edema secondary to cryptococcal ly smaller, more portable and more meningitis, captured with a 20-D lens and smartphone camera. powerful imaging devices. Integrating these devices into wireless networks facilitates secure image transmission In 2013, the iExaminer (Welch- Moorfi elds Eye Hospital. It’s a modu- for tele-ophthalmology applications. Allyn; Skaneateles Falls, N.Y.), an lar adapter created for Android-based As a result, there are now numerous adaptive device used to capture fun- devices that makes the camera’s fl ash ways to image the retina. Here, we’ll dus images with the iPhone became confocal with the optical sensor so it discuss a few of them. available. iExaminer captures images can illuminate the retina and capture through undilated pupils; however, a clear image. A prospective study in Smartphone Ophthalmoscopy the quality and restricted fi eld of view Kenya compared optic disc photos of this device has limited its use. using PEEK Retina with a Samsung The smartphone camera is the most More recently, a non-mydriatic S3 phone to photos taken with a non- ubiquitous technology available for smartphone camera device called mydriatic fundus camera (CentreVue ophthalmic imaging, and it can ap- PEEK Retina (Peek Vision, London) + Digital Retinal System, Haag-Stre- proach the optical quality and res- was created by an interdisciplinary it; Harlow, U.K.). The images were olution of many commercial digital team of ophthalmologists, optics securely transmitted and remotely single-lens refl ex cameras. experts and engineers at London’s graded in the U.K. The authors found 60 | Review of Ophthalmology | February 2017 This article has no commercial sponsorship. 060_rp0217_rtinsider.indd 60 1/20/17 3:52 PM excellent agreement with vertical tiple studies have validated the utility cup-to-disc ratio grading between the and quality of images captured using two devices. This was even more im- this technique,5,6,7 though the need for pressive because the PEEK device dilation and a learning curve similar to was operated by non-clinicians given that of indirect ophthalmoscopy may only a brief training course, while the limit its utility for non-ophthalmolo- fundus camera was operated by an gists. Other investigators have created ophthalmic technician.1 This proof- and tested adapters to perform head- of-concept study demonstrated that mounted indirect ophthalmoscopy a smartphone device can be used in using an iPhone or GoPro camera remote areas, operated by lay examin- Figure 2. A surgeon wearing the Google (GoPro; San Mateo, Calif.).8,9 ers, recharged with mobile units not Glass, which displays the recorded image A group from Stanford University requiring constant electricity and can in front of the user’s eye through a prism. has tried to simplify this indirect tech- 2 Google Glass has a computerized central easily be replaced if lost or damaged. processing unit, touchpad display screen, nique by using a smartphone mount Another device, D-Eye (D-Eye; microphone and high-defi nition camera. It to hold a 28-D lens (Paxos, Digisight Pasadena, Calif.), was developed in records in 720p with 5 MP still shots and is Technologies; San Francisco). This Italy and can also be used to cap- worn like a conventional pair of glasses. might limit the bimanual variability ture non-mydriatic fundus images. that occurs with indirect ophthalmos- A prospective, cross-sectional study video rather than still photos, frames copy. Two studies demonstrated that of dilated eyes demonstrated 55- to that best highlight the pathology of this device is capable of producing 89-percent sensitivity for detection of interest can be selected (Figure 1a high-quality fundus images that can diabetic retinopathy using the D-Eye and 1b, facing page). This technique be useful in screening for moderate device fi tted to an iPhone 5 compared is most useful in resource-poor areas to more advanced diabetic retinopa- to slit lamp biomicroscopy. Differenc- and in inpatient settings. thy.10,11 es in sensitivity rates varied depend- In the Smartphone Ophthalmos- ing on the degree of retinopathy.3 copy and Reliability Trial, images ob- Surgeon POV Recording All three of the above devices tained via smartphone ophthalmos- are bundled with associated secure copy detected 74.3 percent of critical It’s been hard to obtain surgical HIPPA-compliant apps for image fundus fi ndings (like retinal hemor- videos of globe and ocular adnexa transmission; however, only the iEx- rhage, subretinal fl uid and optic disc from the surgeon’s point of view, a aminer and D-Eye are approved by edema) found on binocular indirect perspective that helps teach surgical the Food and Drug Administration. examination.5 This rate was only techniques to others. Operating mi- PEEK Retina is currently seeking slightly less than the 77.1 percent de- croscopes obtain high-quality videos FDA approval. tection rate for critical fundus fi ndings of the anterior and posterior segment, with a standard fundus camera. Mul- but are hampered by a static, top- Taking Pictures down point of view. A videographer can record surgery, but an off-axis With practice, a smartphone cam- perspective and non-optimal lighting era can be used to obtain high-quality limit these videos. Surgical cameras images of the posterior pole through a mounted in the overhead lights work dilated pupil. well but can be cost-prohibitive.12 PEEK Vision’s CEO Andrew Recently, relatively affordable first- Bastawrous, who is also an ophthal- person cameras such as Google Glass mologist, developed a way to cap- and GoPro have been used effectively ture mydriatic fundus images using to record eye surgery from the sur- a smartphone.4 With a smartphone’s geon’s point of view.13,14 Figure 3. A still photo captured with the native camera application set to video Google Glass during a scleral buckle Google Glass (Figure 2), worn like a mode with the fl ash “on,” the photog- surgery. Photo capture is activated with pair of conventional glasses, contains rapher holds the phone in one hand a head tilt and voice command from the a heads-up display with a fi rst-person and a 20- or 28-D lens in the other in surgeon. This is the surgeon’s point of view camera that is turned on with a tilt of a manner analogous to performing in- when scleral quadrants are being examined the head. Voice commands capture direct ophthalmoscopy. By capturing prior to buckle placement. still images (Figure 3) and 10-second February 2017 | reviewofophthalmology.com | 61 060_rp0217_rtinsider.indd 61 1/20/17 3:52 PM Retinal REVIEW Insider video clips. Google Glass has success- to evolve to help us to meet the needs fully recorded scleral buckle surgery.15 of patients and our profession. Unfortunately, there is no commercial version of Google Glass available, but Melissa Sieber, MD, is a second year Google is rumored to be working on a ophthalmology resident at Wills Eye newer version, and there are a num- Hospital. Murtaza Adam, MD, is a ber of companies that support the one second year retina fellow at Wills Eye we’ve used. Hospital. Sunir Garg, MD, is a profes- The GoPro (Figure 4), designed to sor of ophthalmology at MidAtlantic record extreme sports, features a high Retina, the retina service of Wills Eye recording frame rate and dynamic Figure 4. The GoPro Hero4 Silver Edition. Hospital. He can be reached at sgarg@ lighting adaptability; it has been used GoPro is worn on the forehead of the midatlanticretina.com. The authors to record a tap-and-inject procedure surgeon with the camera mounted on a have no fi nancial interest in any of the 16 head strap within a case. The compact for endophthalmitis. The GoPro de- camera is equipped with a touchscreen products discussed. vice can also be used hands-free to display, micro-speaker, and Wi-Fi. It records 1. Bastawrous A, Giardini M, Bolster NM, et al. Clinical validation record photos and videos in the op- in 1080p and takes 12 MP still shots. of a smartphone-based adapter for optic disc imaging in Kenya. erating room (Figure 5). Simultane- JAMA Ophthalmol 2016;134:151–158. 2. Garg SJ. Applicability of smartphone-based screening ous recording with two head-mounted It’s clear that portable ophthalmic programs. JAMA Ophthalmol 2016;134:158–159. GoPro cameras has also been used to imaging will become increasingly im- 3. Russo A, Morescalchi F, Costagliola C, et al. Comparison of smartphone ophthalmoscopy with slit-lamp biomicroscopy for record 3D video for stereoscopic view- portant in the years to come. In ad- grading diabetic retinopathy. Am J Ophthalmol 2015;159:360. ing of scleral buckle surgery.17 dition to using video equipment for 4. Bastawrous A. Smartphone Fundoscopy. Ophthalmology 2012;119:432-433. Each device has some advantages. recording procedures for presenta- 5. Adam MK, Brady CJ, Flowers AM, et al. Quality and diagnostic Google Glass is comfortable to wear tions and lectures, tele-ophthalmology utility of mydriatic smartphone photography: The smartphone ophthalmoscopy reliability trial. Ophthalmic Surg Lasers Imaging and looks like a pair of glasses. The networks are growing both in devel- Retina 2015;46:631-637. surgeon can see what’s being recorded oped and developing countries, and 6. Ryan ME, Rajalakshmi R, Prathiba V, et al. Comparison among methods of retinopathy assessment (CAMRA) study. in real time, so adjustments in camera portable, easy-to-use, low-cost, high- Ophthalmology 2015;122:2038-2043. position are easy to make. However, resolution panophthalmic imaging is 7. Haddock LJ, Kim DY, Mukai S. Simple, Inexpensive technique for high-quality smartphone fundus photography in human and the camera doesn’t have a great dy- critical. Although no current portable animal eyes. J Ophthalmol 2013. doi: 10.1155/2013/518479 namic range, and the spotlights in the device ideally images the anterior and 8. Wang A, Avallone J, Guyton DL. Head mounted digital camera for indirect ophthalmoscopy. Invest Ophthalmol Vis Sci operating room can overexpose the posterior segments, there are several 2014;55:1606-1606. image. The GoPro camera has bet- options currently available, and newer 9. Welch RJ, Nguyen QD. A novel approach to ophthalmic photography using a portable and versatile camera device. Invest ter dynamic range and comes with ones are in development. Additionally, Ophthalmol Vis Sci 2015;56:4102-4102. easy-to-use software that facilitates fi rst-person surgical videography of- 10. Ludwig CA, Murthy SI, Pappuru RR, et al. A novel smartphone ophthalmic imaging adapter: User feasibility studies in Hyderabad, post-production zoom and adjustment fers a new and potentially better way India. Indian J Ophthalmol 2016;64:191-200. of both audio and video quality. With to educate others on surgical tech- 11. Toy BC, Myung DJ, He L, et al. Smartphone-based dilated fundus photography and near visual acuity testing as inexpensive the GoPro, the image can be sent to a nique, and the technology continues screening tools to detect referral warranted diabetic eye disease. smartphone so an assistant can watch Retina 2016;36:1000-1008. 12. Matsumoto S, Sekine K, Yamazaki M, et al. Digital video the live footage. The surgeon, how- recording in trauma surgery using commercially available ever, can’t see what’s being recorded in equipment. Scand J Trauma Resusc Emerg Med 2013;21:27. 13. Hashimoto DA, Phitayakorn R, Fernandez-del Castillo C, real time and, since the surgeon con- Meireles O. A blinded assessment of video quality in wearable tinuously moves, the forehead-mount- technology for telementoring in open surgery: The Google Glass experience. Surg Endosc 2016;30:372-378. ed camera also moves. This means 14. Paro JAM, Nazareli R, Gurjala A, et al. Video-based self-review: that the surgical fi eld is frequently out Comparing Google Glass and GoPro technologies. Ann Plast Surg 2015;74:S71-S74. of the frame. To increase the likeli- 15. Rahimy E, Garg SJ. Google glass for recording scleral buckling hood of capturing useful images with surgery. JAMA Ophthalmol 2015;133:710-711. 16. Calvo CM, Sridhar J, Hong BK, et al. Video recording of GoPro, simultaneous recording with vitreous tap and intravitreal antibiotic injection from the surgeon’s two GoPro cameras, one on the head perspective. Retina 2015;35:2147-2149. Figure 5. Still photo of scleral buckle 17. Birnbaum FA, Wang A, Brady CJ. Stereoscopic surgical and another on the chest, has been surgery captured with GoPro Hero4 Silver. recording using GoPro cameras: A low-cost means for capturing proposed,18 or the assistant viewing external eye surgery. JAMA Ophthalmol 2015;133:1483-1484. GoPro can be controlled via live stream onto 18. Warrian KJ, Ashenhurst M, Gooi A, Gooi P. A novel combination the smartphone with live feed can di- a nearby smartphone or computer. This is point-of-view (POV) action camera recording to capture the rect the surgeon to keep the image the surgeon’s point of view, showing the surgical fi eld and instrument ergonomics in oculoplastic surgery. usable. scleral buckle being placed around the eye. Ophthal Plast Reconstr Surg 2015;31:321–322. 62 | Review of Ophthalmology | February 2017 060_rp0217_rtinsider.indd 62 1/20/17 3:53 PM A PUBLICATION BY Retina Specialist focuses on the latest advances in the diagnosis, medical management and surgical treatment of diseases of the retina, along with practical, real-world advice from leading clinicians and other experts on managing the successful retina practice. The new addition to the Review family serves the entire Retina Specialist marketplace. Look for your issues in 2017: » MARCH » JUNE » SEPTEMBER » NOVEMBER For inquiries contact [email protected] Advertising opportunities JIM HENNE • PUBLISHER • 610-492-1017 • [email protected] MICHELE BARRETT • 215-519-1414 • [email protected] MICHAEL HOSTER • 610-492-1028 • [email protected] www.retina-specialist.com 2017_retinaspecialist_housead.indd 1 12/14/16 3:26 PM Therapeutic Topics REVIEW A New Day Dawns for Dry-eye Therapy A look at the challenges involved in getting new dry-eye therapies approved and how researchers are overcoming them. Mark B. Abelson, MD, CM, FRCSC, FARVO, George Ousler, James McLaughlin, PhD, and David A. Hollander, MD, MBA, Andover, Mass. or many years, dry eye has been assessment.2 Despite this, the report retrospectively. F a tough nut to crack from the did recognize the lack of correlation In the decade that followed, a host standpoint of new therapies, since the between diagnostic measures and of compounds were tested as poten- signs and symptoms often don’t line symptomatic assessments, and pro- tial dry-eye therapies,4-7 but only one up the same way in different patients. moted a general rubric where both treatment was approved, the cyclo- Now, however, with the fi rst FDA ap- signs and symptoms were part of clini- sporine ophthalmic emulsion Restasis proval of a therapeutic in 13 years— cal assessment of new therapies. (Allergan). In this case, the approval Xiidra ophthalmic solution (lifi tegrast, In hindsight, this might be consid- used a narrow indication, improve- Shire)—it appears that researchers ered a case of one step up, two steps ment of tear production, as the clinical and clinicians are finally beginning back: Recognition of the importance endpoint rather than the co-primary to understand how to approach the of the disconnect between signs and endpoints of other trials. It’s for this treatment of this elusive condition, symptoms is a key to understanding reason that the Restasis label indica- and numerous therapies are sure to dry eye, but many of the studies that tion is for increasing tear production follow. In this month’s Therapeutic followed were based upon a near-im- in patients whose tear production is Topics, the authors survey the list of possible hurdle of co-primary end- presumed to be suppressed due to past treatments that didn’t pass mus- points. In addition, the measurement ocular infl ammation associated with ter, discuss refi nements in treatment of symptoms turns out to be much keratoconjunctivitis sicca. approaches and take a look at the ex- more nuanced than was appreciated citing therapies in the pipeline. at the time, and an evaluation of the Progress is Made —Walter Bethke, Editor in Chief McMonnies symptom questionnaire showed that the design of the test Drug developers trying to devise A Tough Road failed a Rasch analysis of univariate treatments for dry eye were stymied assessments.3 This analysis tests the by the unusually large degree of pa- In 1995, the National Eye Institute statistical validity of using summated tient heterogeneity that is character- hosted an industry workshop called scores of a specifi c series of questions istic of the condition. Some patients Clinical Trials in Dry Eye. Looking as a reliable metric of a condition or have severe symptoms but few or back at the meeting report,1 it’s re- variable. Symptom questionnaires none of the physical manifestations markable that so little emphasis was have been refined since then, with of disease, such as increased corneal placed on symptoms of the disease: an emphasis on a few select ques- staining, reduced Schirmer’s scores or There was only a brief mention of a tions focusing on subjects reporting altered tear-fi lm breakup times. In ad- dry-eye questionnaire for symptom symptoms as they occurred instead of dition, signifi cant variability from en- 64 | Review of Ophthalmology | February 2017 This article has no commercial sponsorship. 0064_rp0217_ttops.indd64_rp0217_ttops.indd 6464 11/20/17/20/17 4:234:23 PMPM vironmental factors such as air qual- signs and symptoms of dry eye. The ity and humidity, and lifestyle factors study demonstrated signifi cant, dose- such as computer use and medica- dependent improvements in corneal tions, means that day to day, dry eye staining and in the visual function can be severe, mild or totally absent. subset of the ocular surface disease This kind of variability can be prob- index,12 and thus confi rmed the ben- lematic in the setting of a clinical trial, efi t of CAE-based inclusion criteria. even with large patient populations. A subsequent Phase III trial repli- We can get a clue to the ways this cated the staining results from Phase problem has been addressed by com- II. Collectively, these studies demon- paring clinical trial protocols from strated a remarkable degree of repro- 2004 to those in 2016. For a 2004 The intranasal tear neuro-stimulator from ducibility, a key result that was par- study,4 the inclusion criteria were Allergan is showing potential in trials. ticularly encouraging for an indication “non-Sjögren’s dry eye with symp- such as dry eye, which is infamous for toms for more than six months, and assessed primarily with symptomatic its variable nature. intermittent or regular artifi cial tear criteria. Refi ned scales for both signs use for three months.” The exclusion and symptom assessment, such as the Peering into the Pipeline criteria were equally brief—patients Ora Calibra scales used for staining could not have undergone LASIK, and discomfort,10 improve assessment One drug is rarely the best drug for punctal occlusion or cauterization. reproducibility. Similarly, inclusion everyone, especially with a hetero- Despite this, most patients in early based upon established signs such as geneous condition such as dry eye. studies were the most severe dry-eye corneal staining or Schirmer’s scores Fortunately, several other compounds sufferers, and tended to be those less can be used to assess improvements in are now poised to bring their thera- responsive to any treatment. In con- these measures independent of symp- peutic benefi ts to the market. Many trast, the most recent trials have fo- tomatic improvements. of these treatments are based upon cused on either a sign or a symptom as Another approach to minimizing distinct mechanisms of action, prom- a primary endpoint, and they include variation in dry-eye trials is the use ising a future where ophthalmologists inclusion criteria of a minimal level of adverse environments such as the may be able to provide their patients of current disease severity (such as CAE. The adverse environmental with an individualized selection of corneal fl uorescein staining score of conditions mimic those that exacer- suitable treatments. Different MOAs ≥ 2) to establish a suffi cient level of bate dry eye and provide enhanced ef- for a selection of agents also provide disease for therapeutic assessment. In fi cacy measures by comparing patient the potential of a future combination addition, tools such as the controlled responses to CAE stress before and therapy for patients with severe dry adverse environment, or CAE, have after a treatment regimen. Because eye. As in other diseases, it’s clear that provided an additional inclusion tool dry eye is a result of a combination of dry eye has many phenotypical sub- by identifying those dry-eye patients physiological factors and the environ- sets that have yet to be teased out, and most likely to experience an exacerba- mental milieu, disease variability can widening the choices for treatment is tion of their disease under conditions be reduced if parameters such as tem- the best way to successfully treat the of environmental stress.8,9 perature and humidity are controlled. most patients. Thus, the answer to the problem Other types of visual stress, such as Some new therapies are devices, of patient heterogeneity seems to in- computer work and reading,11 have not topical medications. The intrana- volve several steps. First, it’s essential been incorporated into experimental sal tear neuro-stimulator system (OD- to identify dry-eye patients that share clinical trial designs, and these show 01 Intranasal Device, Allergan) is a similar disease phenotypes using care- promise as a means of establishing device that increases tear production fully designed inclusion criteria; this clinically signifi cant therapeutic ben- with a mild nasal electrical stimulus. allows for an unambiguous assess- efi ts of an intervention. The stimulator has demonstrated in- ment of a therapeutic effect. Since we Recent trial results show how these creased Schirmer’s scores and reduc- know that some experience signifi cant new approaches can impact clinical tions in corneal staining in open-label discomfort, grittiness, burning or oth- success. One recent Phase II study trials,13 and is currently awaiting FDA er symptoms without showing signs used CAE-based inclusion criteria to review. such as elevated corneal staining, it enrich the population with patients Milder forms of dry eye are typi- follows that these patients should be who had measurable, reproducible cally treated with artifi cial tears, and February 2017 | reviewofophthalmology.com | 65 064_rp0217_ttops.indd 65 1/20/17 4:23 PM Therapeutic REVIEW Topics several programs are exploring im- fl uorescein staining when assessed as to find a treatment best-suited to provements in these formulations that the change from pre- to post-exposure them. may provide relief comparable to anti- in the CAE chamber.10 Tavilermide infl ammatories. Many of these com- also showed signifi cant improvements Dr. Abelson is a clinical professor pounds include chemically modifi ed in diary-reported ocular dryness, and of ophthalmology at Harvard Medical versions of hyaluronic acid,14 with the ocular discomfort was significantly School. Mr. Ousler is vice president primary goal of providing a longer last- improved in the high-dose treatment for dry eye at the research and con- ing symptomatic relief that reduces group (p=0.014). These results were sulting fi rm Ora Inc. Dr. McLaughlin the need for frequent dosing. encouraging, and despite missing the is a medical writer at Ora. Dr. Hol- One of the new potential dry-eye primary endpoints, the drug is now in lander is chief medical offi cer at Ora, therapeutics, SkQ1 (Mitotech, Lux- Phase III development. and assistant clinical professor of oph- embourg), has a mechanism quite dif- thalmology at the Jules Stein Eye In- ferent from other therapeutics: It’s a stitute at the University of California, free-radical scavenger that acts by re- Los Angeles. ducing oxidative stress, including the There is an assortment 1. Lemp MA. Report of the National Eye Institute Industry oxidative stress associated with infl am- workshop on Clinical Trials in Dry Eyes. CLAO J 1995;21:4:221. mation. A recently published Phase II of molecular targets 2. McMonnies CW, Ho A. Patient history in screening for dry eye 15 conditions. J Amer Optom Assoc1987;58:296-301. study focused on therapeutic effects that may be able to 3. Gothwal VK, Pesudovs K, Wright TA, McMonnies CW. McMonnies before and after CAE exposure, and questionnaire: Enhancing screening for dry eye syndromes with Rasch analysis. Invest Ophthalmol Vis Sci 2010;51:3:1401-7. showed that the drug provided sig- provide a pathway to 4. ClinicalTrials.gov Identifi er: NCT00037661 “INS365 Ophthalmic Solution in a Controlled AE in Patients with non-Sjogren’s Dry nifi cant improvements in both corneal dry-eye relief for our Eye” Sponsor: Merck Sharp & Dohme Corp. First received: May staining and in multiple measures of 18, 2002. Last updated: October 1, 2015. patients. 5. Sall K, Stevenson OD, Mundorf TK, Reis BL. Two multicenter, ocular discomfort. randomized studies of the effi cacy and safety of cyclosporine A second therapeutic that has com- ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology 2000;107:4:631-9. pleted Phase II is RGN-259 (ReGen- 6. ClinicalTrials.gov Identifi er: NCT00198536 “Effi cacy and Safety Study for Ecabet Ophthalmic Solution for Treating Dry Tree; Princeton, N.J.), an ophthalmic Eye Syndrome,” Sponsor: Bausch & Lomb Incorporated. First solution containing 0.1% thymosin A handful of other compounds un- received: September 13, 2005. Last updated: March 13, 2013. 7. ClinicalTrials.gov Identifi er: NCT00201981 “Study of β4, an endogenous, pleiotropic pep- der development include CyclASol Rebamipide Eye Drops to Treat Dry Eye,” Sponsor: Otsuka tide that acts to resolve infl ammatory (Novaliq, Germany), a cyclosporine Pharmaceutical Development & Commercialization, Inc. First received: September 12, 2005. Last updated: January 4, 2008. events both by acting on cell migration that employs a proprietary formula- 8. Abelson R, Lane KJ, Rodriguez J, Johnston P, Angjeli E, Ousler and on cytokine signaling. The trial tion designed to optimize drug deliv- G, Montgomery D. A single-center study evaluating the effect of the controlled adverse environment (CAE) model on tear fi lm used a CAE challenge to screen and ery; BRM 421 (Brim Biotechnology, stability. Clin Ophthalmol 2012;6:1865-72. 9. González-García MJ, González-Sáiz A, de la Fuente B, et al. enroll an enriched patient population Taiwan), a neurotrophic peptide that Exposure to a controlled adverse environment impairs the ocular and measure a patient’s ability to with- stimulates wound healing and corneal surface of subjects with minimally symptomatic dry eye. Invest Ophthalmol Vis Sci 2007;48:9:4026-32. stand an acute adverse environmental repair; TOP1630 (Topivert, UK), a 10. Meerovitch K, Torkildsen G, Lonsdale J, Goldfarb H, Lama T, challenge to the ocular surface.16 Re- kinase inhibitor that blocks inflam- Cumberlidge G, Ousler GW 3rd. Safety and effi cacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled sults from the study included signifi - matory signaling; and KPI-121 (Kala Phase 2 clinical trial in patients with dry eye. Clin Ophthalmol cant improvement in discomfort and Pharmaceuticals; Waltham, Mass.) a 2013;7:1275-85. 11. Ousler GW 3rd, Rodriguez JD, Smith LM, Lane KJ, Heckley central corneal staining. A Phase III novel formulation of loteprednol eta- C, Angjeli E, Abelson MB. Optimizing Reading Tests for Dry Eye Disease. Cornea 2015;34:8:917-21. study for RGN-259 is in progress. bonate. 12. Semba CP, Torkildsen GL, Lonsdale JD, et al. A Phase II Another new potential treatment These examples of potential dry- randomized, double-masked, placebo-controlled study of a novel integrin antagonist (SAR 1118) for the treatment of dry eye. Am J that has reached the Phase III de- eye therapies demonstrate that there Ophthalmol 2012;153:1050-1060. velopment stage is Tavilermide is an assortment of molecular targets 13. Friedman NJ, Butron K, Robledo N, et al. A nonrandomized, open-label study to evaluate the effect of nasal stimulation on (Mimetogen Pharmaceuticals, Mon- that may provide a pathway to dry- tear production in subjects with dry eye disease. Clin Ophthalmol 2016;4:10:795-804. treal), a TrkA receptor agonist that eye relief. Perhaps one of the most 14. ClinicalTrials.gov Identifi er: NCT02205840 “A Clinical Study can mimic or augment the effects of encouraging aspects of the near future Evaluating the Safety and Effi cacy of SI-614 Ophthalmic Solution in Patients With Dry Eye,” Sponsor: Seikagaku Corporation. First nerve growth factor. NGF is a ma- of dry-eye treatments is that, with a received: July 30, 2014. Last updated: January 19, 2015. jor positive regulator of goblet cell refined roadmap to clinical success 15. Petrov A, Perekhvatova N, Skulachev M, et al. SkQ1 ophthalmic solution for dry eye treatment: Results of a Phase II growth, conjunctival and goblet cell and a growing number of candidate safety and effi cacy clinical study in the environment and during mucin expression, and mucin secre- therapies, each with a unique ap- challenge in the CAE model. Adv Ther 2016;33:1:96-115. 16. Sosne G, Ousler GW. Thymosin beta 4 ophthalmic solution tion. In Phase II trials, Tavilermide proach to dry eye, the odds increase for dry eye: A randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE) significantly improved total corneal that all of our patients will be able model. Clin Ophthalmol 2015;20:9:877-84. 66 | Review of Ophthalmology | February 2017 0064_rp0217_ttops.indd64_rp0217_ttops.indd 6666 11/20/17/20/17 4:244:24 PMPM ENRICH YOUR PRACTICE Review of Ophthalmology delivers current and comprehensive information focusing on topics such as disease diagnosis, surgical techniques and new technologies. The Review Group offers eyecare practitioners quality informational The Review Group’s Ophthalmic Product Guide brings you the latest products and technology on the market. Published every February resources dedicated to the growth and July. and education of the profession. The TheT Review Group also distributes a variety Review Group offers a variety of print ofo supplements, guides and handbooks withw your subscription to Review of and online products to enrich your OphthalmologyO . 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These meetings cover a broad range of topics in the form of educational or promotional roundtables and forums. www.reviewofophthalmology.com Jobson Medical Information LLC The Review Group 2015_rp_tsrad.indd 90 11/12/15 11:42 AM Research Review REVIEW Smartphone Use and Pediatric Dry Eye esearchers from Korea investi- in the DED group than controls (p< in aging eyes. Rgated risks and protective factors 0.001, OR= 13.07), and the mean daily In this cross-sectional study, looking associated with pediatric dry-eye dis- duration of outdoor activities was short- at 38 pre-presbyopic and 42 presby- ease in relation to smartphone use rate, er in the DED group than controls opic eyes, researchers measured pupil categorized by region and age. (p<0.01, OR=0.33). After cessation of diameter, radius of corneal curvature They enrolled 916 children in the smartphone use for four weeks in the values, central corneal thickness, WtW, study and performed an ocular exam DED group, both subjective symptoms ACD, LT and axial length, both before that included a slit lamp exam and and objective signs had improved. and after cycloplegia. Using SRK/T, tear breakup time. Researchers also While smartphone use in children Holladay 2 and Haigis formulas, re- administered a questionnaire to chil- was strongly associated with pediat- searchers performed IOL power calcu- dren and their families, inquiring about ric DED, outdoor activity appeared to lations. To pinpoint the effect of cyclo- video display terminal use and outdoor be protective against it. Older-grade plegia, researchers recorded refractive activity. DED was defined based on students in urban environments had predictions in pre- and post-dilation the International Dry Eye Workshop DED risk factors and a short duration conditions using the same IOL power guidelines, looking specifi cally at punc- of outdoor activity time. Therefore, the calculations, even if post-dilation IOL tate epithelial erosion and short tear researchers say, close observation and power calculations had changed. breakup time. Children were divided caution are needed when older chil- With cycloplegia, pupil diameter into: DED vs. control; urban vs. rural; dren in urban areas use smartphones, changed signifi cantly more in presby- younger grade (1st to 3rd) vs. older as they are more likely to develop pe- opic eyes (p=0.001). Central corneal grade (4th to 6th). diatric DED. thickness decreased in pre-presbyopic A total of 6.6 percent of children BMC Ophthalmol 2016;16:188 eyes (p=0.048), whereas WtW in- were included in the DED group; Moon J, Kim K, Moon N. creased in presbyopic eyes (p=0.02). 8.3 percent of children in the urban In both groups, ACD and LT changed group were diagnosed with DED com- IOL Powers in Aging Eyes significantly (p<0.001). IOL power pared to 2.8 percent in the rural group ecause age-related changes in calculations using the Holladay 2 for- (p=0.03). The rate of smartphone use Blens elasticity and ciliary muscle mula differed in pre-presbyopic eyes was 61.3 percent in the urban group contractility can affect how ocular pa- (p=0.042), and refractive predictions and 51 percent in the rural group rameters respond to cycloplegia and with the Holladay 2 and Haigis for- (p=0.04). In total, 9.1 percent of chil- intraocular lens power measurements mulas differed significantly in pre- dren in the older-grade group were calculated by formulas using anteri- presbyopic eyes (p=0.043 and p=0.022, diagnosed with DED compared to 4 or chamber depth, lens thickness or respectively). percent in the younger-grade group white-to-white for effective lens po- Considering these results, the (p=0.03). The rate of smartphone use sition prediction can therefore vary. investigators recommend that sur- was 65.1 percent in older-grade chil- With that in mind, researchers from geons consider the effect of cyclople- dren and 50.9 percent in younger-grade Turkey sought to investigate changes gia on refractive prediction errors and children (p<0.001). The mean daily in ocular parameters and IOL power IOL power calculations determined duration of smartphone use was longer calculations attributable to cycloplegia with Haigis and Holladay 2 formulas, 68 | Review of Ophthalmology | February 2017 This article has no commercial sponsorship. 0068_rp0217_rr.indd68_rp0217_rr.indd 6868 11/20/17/20/17 4:134:13 PMPM especially in pre-presbyopic eyes. epithelial space, if applicable. eyes with CNV seen by OCTA were Am J Opthalmol 2017;173:76-83 The researchers defi ned clinical ac- clinically active, whereas six eyes with Özyol P, Özyol E, Baldemir E. tivity as the presence of one of the fol- visible CNV on OCTA were clinically lowing: a new diagnosis of neovascular inactive. Of the 17 eyes that didn’t have Clinical Activity of CNV in AMD AMD with active leakage on FA and/or evidence of CNV on OCTA imaging, esearchers from Boston sought to the presence of fl uid on OCT, or a pre- 14 were clinically inactive and three Rcharacterize the features of choroi- vious diagnosis of neovascular AMD; were clinically active. Presence of CNV dal neovascularization in neovascular vision loss greater than or equal to one on OCTA correlated with clinical ac- age-related macular degeneration us- Snellen line; presence of new hemor- tivity, and absence of CNV correlated ing spectral-domain optical coherence rhage on fundus examination; recur- with inactivity (p<0.0001). tomography angiography and to deter- rent intraretinal or subretinal fl uid on OCTA is a noninvasive imaging mine whether OCTA can be used to structural OCT B-scans; persistent or technique that can be used to visual- monitor clinical activity of CNV. increased intraretinal or subretinal fl u- ize blood flow comprising CNV. It In the observational, retrospective, id on structural OCT B-scans despite detects CNV vessels in some, but not consecutive case series, research- treatment; and presence of leakage on all eyes with neovascular age-related ers looked at patients with a clini- FA if performed on the same day as macular degeneration. Although the cal diagnosis of neovascular AMD OCTA. presence or absence of CNV vessels who underwent OCTA imaging. OCTA revealed CNV in 28 eyes on OCTA was highly correlated with The patients were imaged between (62.2 percent) while 17 eyes (37.8 per- clinical activity of CNV, the morpho- August and October 2014 at the cent) didn’t demonstrate CNV vessels. logic appearance of CNV on OCTA New England Eye Center at Tufts The researchers classified the CNV didn’t have significant correlation Medical Center. The investigators as well-circumscribed in 12 eyes (42.8 with clinical activity in this study. used OCTA software to delineate the percent) and poorly circumscribed in Retina 2016;36:2265-2273 outer retina and subretinal pigment 16 eyes (57.2 percent). Twenty-two Liang M, De Carlo T, Baumal C, Reichel E, et al. Is there something missing in your online marketing? We’ll provide the focus your marketing needs. Contact us for a free evaluation and receive 40% off initial setup! 877.716.0927 go.imatrix.com/ReviewOphthalmology 068_rp0217_rr.indd 69 1/20/17 4:13 PM REVIEW Classifi eds Equipment and Supplies / Career Opportunities 237,&$/ ',63(16$5< '(6,*175(1'6 3/86),1$1&,1*)25<($56 )RUZHOOTXDOLILHGDSSOLFDQWVRQO\ 5HVWULFWLRQVDSSO\&DOOIRUGHWDLOV Practice For Sale ĂƐƐĞƩ ,ĞĂůƚŚĐĂƌĞ EĞƚǁŽƌŬ͕ Ă ƉƌŽŐƌĞƐƐŝǀĞ ŚĞĂůƚŚ ĐĂƌĞ ŶĞƚǁŽƌŬ ŝŶ ĐĞŶƚƌĂůEĞǁzŽƌŬĂŶĚŵĂũŽƌƚĞĂĐŚŝŶŐĂĸůŝĂƚĞŽĨŽůƵŵďŝĂhŶŝǀĞƌƐŝƚLJŝƐƐĞĞŬŝŶŐ OPHTHALMOLOGYĂGeneral OphthalmologistƚŽũŽŝŶĂďƵƐLJŽƉŚƚŚĂůŵŽůŽŐLJĚĞƉĂƌƚŵĞŶƚďĂƐĞĚŝŶƚŚĞ ůŽǀĞůLJǀŝůůĂŐĞŽĨŽŽƉĞƌƐƚŽǁŶ͘'ůĂƵĐŽŵĂĞdžƉĞƌŝĞŶĐĞĂƉůƵƐ͊ ĂƐƐĞƩ ,ĞĂůƚŚĐĂƌĞ EĞƚǁŽƌŬ ŝƐ ĂŶ ŝŶƚĞŐƌĂƚĞĚ ŚĞĂůƚŚ ĐĂƌĞ ƐLJƐƚĞŵ ƚŚĂƚ ƉƌŽǀŝĚĞƐ ĐĂƌĞ ĂŶĚ ƐĞƌǀŝĐĞƐƚŽƉĞŽƉůĞůŝǀŝŶŐŝŶĂŶĞŝŐŚƚĐŽƵŶƚLJƌĞŐŝŽŶĐŽǀĞƌŝŶŐϱ͕ϲϬϬƐƋƵĂƌĞŵŝůĞƐŝŶƵƉƐƚĂƚĞEĞǁ zŽƌŬ͘dŚĞŽƌŐĂŶŝnjĂƟŽŶŝŶĐůƵĚĞƐƐŝdžĐŽƌƉŽƌĂƚĞůLJĂĸůŝĂƚĞĚŚŽƐƉŝƚĂůƐ͕ ĂƐ ǁĞůů ĂƐ ƐŬŝůůĞĚ ŶƵƌƐŝŶŐ ĨĂĐŝůŝƟĞƐ͕ĐŽŵŵƵŶŝƚLJĂŶĚƐĐŚŽŽůͲďĂƐĞĚŚĞĂůƚŚĐĞŶƚĞƌƐ͕ĂŶĚŚĞĂůƚŚƉĂƌƚŶĞƌƐŝŶƌĞůĂƚĞĚĮĞůĚƐ͘ <ùÄ¥®ãÝʥ㫮ÝWÊÝ®ã®ÊÄ͗ ͻ KƉƉŽƌƚƵŶŝƟĞƐĞdžŝƐƚĨŽƌďŽƚŚƌĞƐĞĂƌĐŚĂŶĚƚĞĂĐŚŝŶŐŝĨŝŶƚĞƌĞƐƚĞĚ͘ ͻ ƵƌƌĞŶƚůLJƚŚĞƌĞĂƌĞƐƉĞĐŝĂůŝƐƚƐŝŶƌĞƟŶĂ͕ĐŽƌŶĞĂ͕ƉĞĚŝĂƚƌŝĐƐĂŶĚŽĐƵůŽƉůĂƐƟĐƐ͘ ͻ dŚĞƐƵƉƉŽƌƚƐƚĂīŝƐǁĞůůƚƌĂŝŶĞĚĂŶĚĞdžƉĞƌŝĞŶĐĞĚŝŶďŽƚŚƚŚĞĐůŝŶŝĐĂŶĚŽƉĞƌĂƟŶŐƌŽŽŵ͘ ͻ 'ƌŽƵƉĞŵƉůŽLJĞĚŵŽĚĞůǁŝƚŚĐŽŵƉĞƟƟǀĞƐĂůĂƌLJ ͻ ŽŵƉƌĞŚĞŶƐŝǀĞ ďĞŶĞĮƚ ƉĂĐŬĂŐĞ͕ ŝŶĐůƵĚŝŶŐ ďƵƚ ŶŽƚ ůŝŵŝƚĞĚ ƚŽ ŵĞĚŝĐĂů͕ ĚĞŶƚĂů͕ D ͕ ƌĞůŽĐĂƟŽŶĂƐƐŝƐƚĂŶĐĞĂŶĚƉĂŝĚŵĂůƉƌĂĐƟĐĞŝŶƐƵƌĂŶĐĞ ĂƐƐĞƩ DĞĚŝĐĂů ĞŶƚĞƌ ŝƐ ůŽĐĂƚĞĚ ŝŶ ŽŽƉĞƌƐƚŽǁŶ͕ EĞǁ zŽƌŬ͕ Ă ďĞĂƵƟĨƵů ƌĞƐŽƌƚ ǀŝůůĂŐĞ ŽŶ KƚƐĞŐŽ >ĂŬĞ͘ ,ŽŵĞ ƚŽ ƚŚĞ EĂƟŽŶĂů ĂƐĞďĂůů ,Ăůů ŽĨ &ĂŵĞ ĂŶĚ DƵƐĞƵŵ͕ ƚŚĞ 'ůŝŵŵĞƌŐůĂƐƐ KƉĞƌĂŽŵƉĂŶLJ͕ĂŶĚƚŚĞ&ĞŶŝŵŽƌĞƌƚDƵƐĞƵŵ͕ƚŚĞĂƌĞĂĂůƐŽďŽĂƐƚƐŵĂŶLJĐƵůƚƵƌĂůĂŶĚĨŽƵƌƐĞĂͲ ƐŽŶƌĞĐƌĞĂƟŽŶĂůĂĚǀĂŶƚĂŐĞƐŝŶĐůƵĚŝŶŐƚŚĞĂƚĞƌ͕ŵƵƐŝĐ͕ŵƵƐĞƵŵƐ͕ŐŽůĨ͕ƐĂŝůŝŶŐ͕ŚŝŬŝŶŐ͕ĂŶĚƐŬŝŝŶŐ͘ EEO Employer &ÊÙÊÄ¥®Ä㮽ÊÄÝ®Ùã®ÊÄ͕Ö½ÝÊÄãã͗ ĞďƌĂ&ĞƌƌĂƌŝ͕DĂŶĂŐĞƌ͕DĞĚŝĐĂů^ƚĂīZĞĐƌƵŝƚŵĞŶƚ͕ CONTACT US TODAY ĂƐƐĞƩDĞĚŝĐĂůĞŶƚĞƌ͕KŶĞƚǁĞůůZŽĂĚ͕ŽŽƉĞƌƐƚŽǁŶ͕Ez͕ϭϯϯϮϲ FOR CLASSIFIED ADVERTISING ƉŚŽŶĞ͗ϲϬϳͲϱϰϳͲϲϵϴϮ͖ĨĂdž͗ϲϬϳͲϱϰϳͲϯϲϱϭ͗ĞŵĂŝů͗ĚĞďƌĂ͘ĨĞƌƌĂƌŝΛďĂƐƐĞƩ͘ŽƌŐ Toll free: 888-498-1460 ŽƌǀŝƐŝƚŽƵƌǁĞďͲƐŝƚĞĂƚǁǁǁ͘ďĂƐƐĞƩŽƉƉŽƌƚƵŶŝƟĞƐ͘ŽƌŐ E-mail: [email protected] 70 | Review of Ophthalmology | February 2017 ROPH0217.indd 70 1/18/17 8:12 AM 071_rp0217_wills.indd 71 was astrongfamilyhistoryofbreastcancer. Infact,therewas patient didnotspecifythereasonformastectomy, butthere need forchemotherapy, radiationorhormonetherapy. The tional medicalhistoryincludedbilateralmastectomywithout metastases andunderwentGammaKniferadiotherapy. Addi- months followingdiagnosis,shewasfoundtohavebrain with ipilimumab,pembrolizumab,anddabrafenib.Nine site oneyearpriortopresentation.Sheunderwenttreatment nant melanomatotherighthipfromanunknownprimary Medical History tal forasecondopinion. She presentedtotheOncologyServiceofWills EyeHospi- creased thesubretinalfluid, andhervisualacuityfl luprednate dropsfourtimesaday, whichreportedlyde- “retinal pigmentation”bilaterally. Shewasstartedondif- ophthalmic evaluationrevealedsubretinalfl oped blurredvisionassociatedwithahead-to-toerash,and that spontaneouslyresolved.Onemonthprior, shedevel- ed threemonthspriortopresentationwithphotophobia blurred visioninbotheyes.Hersymptomsinitiallystart- Presentation Jason Flamendorf, MD, andCarolL.Shields, MD OncologyService. Wills’ Photophobia anddecreasedvisionbringamiddle-agedwomanto What isyourdifferentialdiagnosis? Whatfurtherworkupwouldyoupursue?Please turntopage72 A Past medicalhistorydisclosedmetastaticcutaneousmalig- A 55-year-old Caucasianfemalenotedphotophobiaand REVIEW Wills Eye Wills Eye uid and slight slight and uid uctuated. uctuated. B Resident CaseSeries Edited by Alison Huggins, MD while shewasoffdabrafenib. cies); temazepamandalprazolam.Hersymptomsstarted reported thatshewastakingitatvaryingdosesandfrequen- pembrolizumab; difl uprednate drops;prednisone(patient melanoma). Hersocialhistorywasunremarkable. carcinoma, prostatebreastcutaneous family historyofmultiplememberswithcancer(lung Examination pseudohypopyon appearance. pseudohypopyon appearance. cumulated atthebottomofsubretinalfl uid, producinga present wasbilateralsubretinalvitelliformdebris,whichac- of fl uid intheextramacularregionaswell(SeeFig.1.).Also fl tion wasonlyremarkableforearlynuclearsclerosisbilaterally. motility werefullbilaterally. Theanteriorsegmentexamina- sion wasnormal.Confrontationvisualfi elds andextraocular declined applanation,butintraocularpressurebyfi light withoutrelativeafferentpupillarydefect.Thepatient OS (PH:20/50).Pupilswereequal,roundandreactiveto acuity of20/50OD(pinhole:noimprovement)and20/60 uid in the macular region of both eyes, with smaller pockets uid inthemacularregionofbotheyes,withsmallerpockets The patient’s currentmedicationsincluded:dabrafenib; Dilated fundus examination revealed shallow subretinal Dilated fundusexaminationrevealedshallowsubretinal Ocular examinationdemonstratedanuncorrectedvisual February 2017 | reviewofophthalmology.com of subretinal fl multifocal pockets associated with lesions vitelliform dependent demonstrating (A) andleft(B)eyes photos oftheright Figure 1.Fundus nger ten- nger uid. | 71 1/20/17 3:23 PM 071_rp0217_wills.indd 72 others. liform maculopathy, paraneoplasticopticneuropathyand nopathy, acuteexudativeparaneoplasticpolymorphousvitel- cancer-associated retinopathy, melanoma-associatedreti- areas. corresponding fl uorescence in trace hypo- eyes revealed and left(D) of theright(C) cein angiography debris. Fluores- of thevitelliform to thelocation corresponding autofl uorescence areas ofhyper- (B) eyes showing right (A)andleft imaging ofthe autofl uorescence Figure 3.Fundus phy cluding opticalcoherencetomogra- Diagnosis andWorkup 72 metastases. remote fromthesiteofamalignantneoplasmorrelated symptoms thatresultfromdamagetoanorganortissue Discussion neoplastic syndromes, and often manifests with symptoms neoplastic syndromes,andoften manifestswithsymptoms shaped” areasofhyperautofl uorescence correspondingto be ofnormalthicknessandvascularity. FAF showed“boat- revealed preservedarchitecture.Thechoroidappearedto RPE. Theinnerretinallayersuptotheellipsoidzone a liningontheinnersurfaceof of thephotoreceptorlayer, aswell appeared asanirregularthickening cular arcades.Thesubretinaldebris nal detachmentnearthesuperiorvas- eyes alsoshowedsmallerareasofreti- the foveaandinferiormacula;both and debriswithapredominancein fi angiography imaging rmed thepresenceofsubretinalfl REVIEW Ancillary imagingwasobtainedin- Paraneoplastic syndromesareacomplexofsignsand | ReviewofOphthalmology Resident CaseSeries (Fig. 2),fundusautofl 2 CARisthemostcommonof theintraocularpara- (Fig. 3A,B),andfl 1 The typical paraneoplastic retinopathies include Thetypicalparaneoplasticretinopathiesinclude (Fig. 3C,D).OCTcon- A C uorescence uorescence uorescein | February2017 uid uid presence ofsubretinal fluid anddebrisisconfi rmed. Figure 2.Foveal opticalcoherence tomography throughtheright(A)andleft(B)eyes. The A B D B testing suchasERG,visualfi amination isfrequentlynormal initially;additionaldiagnostic to alesserdegreethanCAR.Similar toCAR,thefundusex- MAR presentswithrod-mediatedsymptomsandvisualloss carcinoma, followedbygynecologicandbreastcarcinomas. The mostfrequentlyassociatedmalignancyissmall-celllung inogram andvisualfi eld changeshelpestablishthediagnosis. fundus examinationmaybenormal;characteristicelectroret- of rodandconephotoreceptordysfunction.IncasesCAR, hypofluorescence atthe siteofthelipofuscindebris. suggestive oflipofuscinaccumulation.IVFA revealedtrace the vitelliformlesionsobservedonfundusexamination, The differential diagnosis for this patient with a history The differentialdiagnosisforthispatientwithahistory tion wasrendered. roids. Perpatientchoice,observa- immunoglobulin andcorticoste- tion, plasmapheresis,intravenous observation forspontaneousresolu- neoplastic retinopathyincluded tions formanagementofthispara- of AEPPVMwasconsidered.Op- and imagingfindings,adiagnosis tient’s melanomahistoryandclinical macular dystrophy. Giventhepa- zumab andadult-onsetvitelliform related todabrafeniborpembroli- medication-associated retinopathy (AEPPVM), choroidalmetastasis, phous vitelliformmaculopathy exudative paraneoplasticpolymor- vitelliform materialincludedacute and new-onsetsubretinalfl of metastaticcutaneousmelanoma elds andserumanti-retinal uid with with uid 1/20/17 3:23 PM antibody testing support the diagnosis. MAR is most often chose observation, and we anticipate little change in the associated with metastatic cutaneous melanoma but has also fundus appearance over time. Reduction of tumor burden been reported with uveal melanoma.2 has been found successful in a patient with AEPPVM dis- AEPPVM is a paraneoplastic retinopathy demonstrating covered four months before a diagnosis of cutaneous meta- bilateral multifocal pockets of subretinal fl uid and subretinal static melanoma.12 Initially not responding to prednisone, vitelliform deposits documented on fundus examination and the patient received temozolomide, an alkylating agent, for confi rmed with hyperautofl uorescence on FAF. This condi- treatment of the underlying melanoma and regained 20/20 tion is usually found in patients with cutaneous melanoma visual acuity OU following resolution of the subretinal fl uid or choroidal melanoma and can appear before or after at one year follow-up. Reduction of autoimmune factors detection of the primary malignancy and/or metastasis. Ini- is accomplished with plasmapheresis and IVIg, although tially thought to be an unusual presentation of MAR, AEP- evidence for their use is sparse.8 Most important in the PVM seems to demonstrate a different spectrum of fi ndings management of affected patients is a careful and thorough from MAR and is now classifi ed as a separate entity.3,4 AEP- evaluation for systemic metastatic disease performed by an PVM has subsequently been identifi ed in cases of metastatic oncologist, even if the patient is believed to be in remission. lung and breast adenocarcinoma, as well as a single case of Other considerations in the differential diagnosis of our metastatic clear cell sarcoma of the toe.5,6,7 The vitelliform patient included choroidal metastases and medication- fundus lesions are a classic distinction of AEPPVM and associated retinopathies, especially medications for meta- are different from the features of MAR, which typically static melanoma. Subretinal vitelliform debris is not gener- presents with a normal fundus picture but occasionally with ally seen with choroidal metastases, and the OCT did not optic nerve pallor, vascular attenuation and, rarely, retinal demonstrate any choroidal tumor. pigment epithelial changes.8 Regarding medication, this patient was currently taking Researchers reviewed 23 cases of AEPPVM and found or had taken three medications used in the treatment of that the average age of onset was 59 years (range, 33 to 80). metastatic melanoma, including ipilimumab, pembroli- The underlying malignancies included cutaneous melano- zumab and dabrafenib, all of which have been associated ma (44 percent), choroidal melanoma (30 percent), mucosal with retinopathies. Ipilimumab and pembrolizumab are melanoma (4 percent), breast and lung carcinoma (9 per- two monoclonal antibodies that upregulate the immune cent) and clear cell sarcoma of the toe (4 percent); two cases response to tumor cells by inhibiting the checkpoint sites had unknown primary tumors (9 percent). The onset of reti- of CTLA-4 and PD-1, respectively, on the T cell surface. In nal features can occur remotely from the original diagnosis many instances, patients with AEPPVM are on medication and treatment of the primary tumor, and these fi ndings usu- for melanoma control, and it’s challenging to sort out if the ally herald metastatic spread, often within several months.2 features are truly autoimmune or medication related. In the Saad Al-Dahmash, MD, and co-workers published a series literature, there are two reports describing serous retinal of fi ve patients with AEPPVM managed at the Wills Eye detachment with and without vitelliform subretinal material Hospital Ocular Oncology Service.6 The features included suggested to be related to ipilimumab, and both patients blurred vision (n=5), nyctalopia (n=1) and photopsia (n=1). demonstrated reduction in fundus features upon discon- Visual acuity ranged from 20/30 to 20/100, with the majority tinuation of the medication.14,15 Regarding pembrolizumab, of eyes seeing 20/50 or worse. Fundus, OCT and FAF fi nd- there is a single report of a patient with multiple bilateral ings were similar to those seen in our patient; fl uorescein peripheral chorioretinal scars with RPE atrophy and pig- angiography and ERG fi ndings were variable. ment clumping after starting pembrolizumab.16 Our patient The pathogenesis of AEPPVM is poorly understood, didn’t report taking ipilimumab at the time of presentation, but several studies have revealed serum autoantibodies and the lesions on fundus examination didn’t resemble against various retinal and retinal pigment epithelial anti- those reported with pembrolizumab. Finally, dabrafenib is a gens. These include antibodies against bipolar cells,3 rod B-Raf inhibitor, which targets a protein in the MAP Kinase outer segment protein,9 bestrophin 1,10 interphotoreceptor pathway, frequently dysregulated in neoplasms. While dab- retinal-binding protein,11 peroxiredoxin 312 and carbonic rafenib has not been implicated directly in retinopathy, the anhydrase II.6,13 While autoantibody testing by Western blot related family of MEK inhibitors has been associated with and immunohistochemistry is commercially available, the the presence of subretinal fl uid and vitelliform lesions in patient often incurs an out-of-pocket expense, and this may some patients.17 Although our patient was taking dabrafenib not be essential for establishing the diagnosis. when she presented to us, she reports that the symptoms Treatment of AEPPVM includes observation for ill pa- started while she was off the medication, making it unlikely tients, reducing the underlying malignancy burden, or to be the underlying cause. reducing the presumed autoimmune etiology. Our patient In summary, AEPPVM must be considered in the February 2017 | reviewofophthalmology.com | 73 0071_rp0217_wills.indd71_rp0217_wills.indd 7733 11/20/17/20/17 3:233:23 PMPM Advertising Resident Case Series REVIEW Index REVIEW For advertising opportunities contact: Michelle Barrett ...... (610) 492-1014 or [email protected] James Henne ...... (610) 492-1017 or [email protected] differential diagnosis of patients with Michael Hoster ...... (610) 492-1028 or [email protected] subretinal fluid demonstrating vitel- liform lesions, whether or not a known Abbott Medical Optics, Inc. (AMO) 15 history of malignancy exists. When Phone (800) 366-6554 present, close coordination of care with an oncologist must be undertaken to Akorn Consumer Health 43 perform a thorough investigation for Phone (800) 579-8327 metastases. www.akornconsumerhealth.com 1. Darnell RB, Posner JB. Paraneoplastic syndromes involving Alcon Laboratories 2, 3, 37, 53, 54 the nervous system. NEJM 2003;349:1543-1554. Phone (800) 451-3937 2. Rahimy E, Sarraf D. Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: Evaluation and management. Fax (817) 551-4352 Surv Ophthalmol 2013;58:430-458. 3. Borkowski LM, Grover S, Fishman GA, et al. Retinal fi nd- ings in melanoma-associated retinopathy. Am J Ophthalmol Bausch + Lomb 11, 12, 29 ,30 2001;132:273-275. Phone (800) 323-0000 4. Jampol LM, Kim HH, Bryar PJ, et al. Multiple serous retinal detachments and subretinal deposits as the presenting signs of Fax (813) 975-7762 metastatic melanoma. Retina 2004;24:320-322. 5. Grunwald L, Kligman BE, Shields CL. Acute exudative poly- Capital One Bank 9 morphous paraneoplastic vitelliform maculopathy in a patient with carcinoma, not melanoma. Arch Opthalmol 2011;129:1104- www.CapitalOne.com/SmallBusiness 1105. 6. Al-Dahmash SA, Shields CL, Bianciotto CG, et al. Acute exuda- tive paraneoplastic polymorphous vitelliform maculopathy in fi ve Glaukos 75 cases. Ophthalmic Surg Lasers Imaging 2012;43:366-373. Phone (800) 452-8567 7. Suelves AM, García-Delpech S, Gallego R, et al. Diagnostic www.glaukos.com and therapeutic challenges. Retina 2012;32:635-639. 8. Keltner JL, Thirkill CE, Yip PT. Clinical and immunologic characteristics of melanoma-associated retinopathy syndrome: Imprimis Pharmaceuticals, Inc. 7 Eleven new cases and a review of 51 previously published cases. J Neuro-Ophthalmol 2001;21:173-187. Phone (858) 704-4040 9. Sotodeh M, Paridaens D, Keunen J, et al. Paraneoplastic vitel- Fax (858) 345-1745 liform retinopathy associated with cutaneous or uveal melanoma www.imprimispharma.com and metastases. Klin Monatsbl Augenheilkd 2005;222:910-914. 10. Eksandh L, Adamus G, Mosgrove L, et al. Autoantibodies against bestrophin in a patient with vitelliform paraneoplastic Lombart Instruments 39 retinopathy and a metastatic choroidal malignant melanoma. Arch Ophthalmol 2008;126:432-435. Phone (800) 446-8092 11. Bianciotto C, Shields CL, Thirkill CE. Paraneoplastic reti- Fax (757) 855-1232 nopathy with multiple detachments of the neurosensory retina and autoantibodies against interphotoreceptor retinoid binding protein (IRBP) in cutaneous melanoma. Br J Ophthalmol. 2010; Rhein Medical 5 94: 1684-1685. Phone (800) 637-4346 12. Koreen L, He SX, Johnson MW et al. Anti-retinal pigment epithelial antibodies in acute exudative polymorphous vitelliform Fax (727) 341-8123 maculopathy. Arch Ophthalmol 2011;129:23-29. 13. Aronow ME, Adamus G, Abu-Asab M, et al. Paraneoplastic S4OPTIK 25, 27 vitelliform retinopathy: Clinicopathologic correlation and review of the literature. Surv Ophthalmol 2012;57:558-564. Phone (888) 224-6012 14. Crews J, Agarwal A, Jack L, et al. Ipilimumab-associ- ated retinopathy. Ophthalmic Surg Lasers Imaging Retina 2015;46:658-660. Shire Ophthalmics 76 15. Mantopoulos D, Kendra KL, Letson A, et al. Bilateral www.shire.com choroidopathy and serous retinal detachments during ipilim- umab treatment for cutaneous melanoma. JAMA Ophthalmol 2015;133:965-967. Sun Ophthalmics 20-21, 22 16. Roberts P, Fishman GA, Joshi K et al. Chorioretinal lesions SunIsOnTheRise.com in a case of melanoma-associated retinopathy treated with pembrolizumab. JAMA Ophthalmol 2016;134:1184-1188. 17. van Dijk EHC, van Herpen CML, Marinkovic M, et al. Serous retinopathy associated with mitogen-activated protein kinase This advertiser index is published as a convenience and not as part of the advertising contract. Every care will be taken to index correctly. No allowance will be made for errors due to spelling, incorrect inhibition (Binimetinib) for metastatic cutaneous and uveal page number, or failure to insert. melanoma. Ophthalmology 2015;122:1907-1916. 74 | Review of Ophthalmology | February 2017 0071_rp0217_wills.indd71_rp0217_wills.indd 7744 11/20/17/20/17 3:463:46 PMPM START HERE Choose iStent®—First and foremost. Right from the beginning, iStent is designed to restore and maintain conventional physiological outfl ow in the trabecular meshwork, and deliver a favorable benefi t-to-risk ratio. Studied extensively around the world, iStent has been implanted in hundreds of thousands of eyes, and is backed by years of documented effi cacy and safety data. For cataract patients with open-angle glaucoma, start with the MIGS leader—and fi nish with leading performance. + The complete procedure. 800.GLAUKOS (452.8567) Glaukos.com INDICATION FOR USE. The iStent® Trabecular Micro-Bypass Stent (Models GTS100R and GTS100L) is indicated for use in conjunction with cataract surgery for the reduction of intraocular pressure (IOP) in adult patients with mild to moderate open-angle glaucoma currently treated with ocular hypotensive medication. CONTRAINDICATIONS. The iStent® is contraindicated in eyes with primary or secondary angle closure glaucoma, including neovascular glaucoma, as well as in patients with retrobulbar tumor, thyroid eye disease, Sturge-Weber Syndrome or any other type of condition that may cause elevated episcleral venous pressure. WARNINGS. Gonioscopy should be performed prior to surgery to exclude PAS, rubeosis, and other angle abnormalities or conditions that would prohibit adequate visualization of the angle that could lead to improper placement of the stent and pose a hazard. The iStent® is MR-Conditional meaning that the device is safe for use in a specifi ed MR environment under specifi ed conditions, please see label for details. PRECAUTIONS. The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. The safety and effectiveness of the iStent® has not been established as an alternative to the primary treatment of glaucoma with medications, in children, in eyes with signifi cant prior trauma, chronic infl ammation, or an abnormal anterior segment, in pseudophakic patients with glaucoma, in patients with pseudoexfoliative glaucoma, pigmentary, and uveitic glaucoma, in patients with unmedicated IOP less than 22 mmHg or greater than 36 mmHg after “washout” of medications, or in patients with prior glaucoma surgery of any type including argon laser trabeculoplasty, for implantation of more than a single stent, after complications during cataract surgery, and when implantation has been without concomitant cataract surgery with IOL implantation for visually signifi cant cataract. ADVERSE EVENTS. The most common post-operative adverse events reported in the randomized pivotal trial included early post-operative corneal edema (8%), BCVA loss of * 1 line at or after the 3 month visit (7%), posterior capsular opacifi cation (6%), stent obstruction (4%) early post-operative anterior chamber cells (3%), and early post-operative corneal abrasion (3%). Please refer to Directions for Use for additional adverse event information. CAUTION: Federal law restricts this device to sale by, or on the order of, a physician. Please reference the Directions for Use labeling for a complete list of contraindications, warnings, precautions, and adverse events. ©2016 Glaukos Corporation. Glaukos and iStent are registered trademarks of Glaukos Corporation. 400-0370-2016-US Rev. 0 RP0217_Glaukos.indd 1 1/13/17 9:52 AM innovation Eyelove is a celebration of the things we love to do with our eyes. It’s also a commitment from Shire to help educate your patients about Dry Eye Disease. Start with some eyelove. Join us at sharesomeeyelove.com it’s time for some eyelove © 2016 Shire US Inc., Lexington, MA 02421 S12516 06/16 Marks designated ® and ™ are owned by Shire or an affi liated company. RP0217_Shire.indd 1 1/11/17 2:52 PM