How to Choose the Right Lens

TIPS FOR BETTER FILTERING PROCEDURES P. 12 • RLE AND LATE IOL DISLOCATIONS P. 18

Review of Ophthalmology Vol. XXIV, Formulas for Difﬁ Calculators • IOL No. 1 • January 2017 The IOL Best THE CLINICAL UTILITY OF OCT ANGIOGRAPHY P. 51 • THE MANY SHADES OF PINKEYE P. 56 A REVIEW OF THE LATEST RESEARCH P. 60 • WILLS EYE RESIDENT CASE STUDY P. 65

January 2017

reviewofophthalmology.com IOL ISSUE HOW TO CHOOSE THE RIGHT LENS

cult Eyes • Shorten Your Discussion • Tips for Filtration Surgery IOL Expert tips on selecting the best IOL formulas. P. 25

IOL Formulas for Difficult Eyes P. 34 Minimizing Your IOL Chair Time P. 42 E-mail Survey of IOL Preferences P. 46

001_rp0117_fc.indd 1 12/22/16 12:34 PM ALCONNEW ONLINE TORIC IOL CALCULATOR

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RP0117_Alcon Acrysof.indd 1 12/14/16 2:56 PM REVIEW NEWS Volume XXIV • No. 1 • January 2017 The Cures Act Becomes The Law of the Land

The Cures Act, formerly known as 21st for [AAO] members to be success- he says. “The bill potentially lowers Century Cures, became law in mid- ful in the new quality payment pro- the bar for their approval while, at December of 2016 and carries with gram, particularly the [Merit-based the same time, purporting not to. It it a lot of hope for patients suffering Incentive Payment System], it’s re- essentially commands the FDA com- from a range of illnesses, as well as the ally important for us to have access misioner to promulgate new guidance potential for quicker approval of drugs there. So, we hope that will get bet- on the use of the various ways to get and devices. It sets aside funds for ter with this law. Specifi cally, many of a drug approved, which, in this case, the Precision Medicine Initiative for the AAO members who aren’t in the is the use of real-world evidence. This personalized medicine, the “Cancer IRIS registry happen to have one of provides a bit more cover to allow Moonshot” research championed by the large, institutional-based EMR’s drugs with less-clear evidence of ef- Vice President Joe Biden, and the such as EPIC, which, for the most fi cacy to go through. Essentially, it’s BRAIN initiative aimed at studying part, can’t participate in the IRIS reg- saying, ‘How can we use just regu- neurological disease. Some observers, istry. Of course, participating in the lar, observational data to support a though, are a little wary of several of IRIS registry is important because it’s supplemental drug approval?’ That’s the law’s provisions, especially those a relatively painless way to succeed in problematic because that type of that seem to water down the Food MIPS.” evidence can be very misleading, and and Drug Administration’s approval There’s a chance, however, that isn’t subject to the same rigor that a process. the billions in funds might not mate- randomized clinical trial is. One of the law’s key aspects is the rialize. “The biggest promise of the “The second area involves the issue funding it provides to the National law—greater funding for the NIH— of medical devices,” Dr. Sapartwari Institutes of Health, which would is a bit illusory, in that it’s subject to continues. “There’s an existing pilot amount to $4.8 billion over 10 years. the appropriations process each year,” program that would allow so-called “There are a lot of things that sound cautions Ameet Sarpatwari, PhD, JD, breakthrough devices to be approved good about the law,” says Michael Instructor in Medicine at Harvard under a sort of accelerated time Repka, MD, the American Academy Medical School and assistant director frame using, basically, more ques- of Ophthalmology’s medical director of the Program on Regulation, Thera- tionable evidence. What the Cures for government affairs, and a profes- peutics, and Law at Brigham and Act would do is formalize this pro- sor of ophthalmology and pediatrics Women’s Hospital in Boston. “And, gram and expand it to potentially al- at Johns Hopkins in Baltimore. “The as we’ve seen in years past, that sort low more products under it, because $4.8 billion or so would be a terrifi c of set-aside can be raided during that the products that can be classifi ed as improvement in a space that’s been process, so it’s not necessarily a sure ‘breakthrough’ under this pathway somewhat stifl ed in recent years [out thing.” don’t necessarily have to be clinically of] particular concern about too much Dr. Sarpatwari goes on to outline meaningful. So, there’s an inherent spending among members of Con- other aspects of the law that could tension if you speed up the review of gress and even on the executive side. have some negative effects down the products and base it on less-rigorous “[Another] thing that’s probably road depending on how they’re imple- evidence. You’re going to allow more good for us involves lessening EHR- mented. “One concern regards sup- devices through that aren’t, again, blocking regulations,” Dr. Repka plemental approval of drugs, meaning necessarily that effective. And, if they continues. “We have had issues with drugs that are already on the market aren’t that effective, this changes the IRIS registry and data blocking by but are looking to gain another foot- risk/benefi t profi le of these prod- certain large EMR vendors. In order hold in terms of another indication,” ucts, and results in signifi cant waste

January 2017 | reviewofophthalmology.com | 3

0003_rp0117_news.indd03_rp0117_news.indd 3 112/22/162/22/16 12:1312:13 PMPM REVIEW News

for patients and taxpayers who have Peng, MD, PhD, observes, “The re- to pay for them. This is important in sults show that our algorithm’s per- the context that, when you look at the formance is on-par with that of oph- evidence base that supports device ap- thalmologists. For example, on the provals, it is already far less than that fi rst validation set, the algorithm has which supports new drugs.” an F-score [combined sensitivity and The third aspect that concerns some specifi city metric] of 0.95, which is is the law’s use of the limited popula- slightly better than the median F- tion pathway for antibiotic approval. score of 0.91 achieved by the eight “This would allow antibiotics to be ap- ophthalmologists we consulted. The proved on a sliding benefi t/risk scale,” signifi cance here is that deep-learning Dr. Sarpatwari explains. “And so, you algorithms had high sensitivity and can imagine again that it allows the Google’s learning algorithm was able to specifi city for detecting diabetic reti- FDA commissioner to use his or her detect diabetic retinopathy with 90 percent nopathy and diabetic macular edema sensitivity and 98 percent specifi city. discretion to steer through more prod- in retinal fundus photographs.” ucts that previously wouldn’t have With regard to the algorithm’s place gotten through. Then, the law would searchers tested a newly developed in a clinical setting, its practical ap- require the product to indicate that deep learning computer algorithm plication requires further research. it had been approved under this lim- designed to detect diabetic retinopathy “Another open question is whether ited pathway. However, we know that, and diabetic macular edema from the design of the user interface and based on evidence, particularly from retinal fundus photographs. Deep the online setting for grading used by the nutritional supplement industry, learning is a computational method ophthalmologists has any impact on consumers don’t really heed these dis- which allows an algorithm to program their performance relative to a clinical claimers very well.” itself through “learning.” The project’s setting,” says Dr. Peng. “Addressing Dr. Repka says worries over lax ap- system, called DeepMind, “learns” by this will require further experiments. proval standards have always accom- studying a large set of examples that The algorithm has only been trained panied FDA revamps. “That’s always demonstrate the desired behavior and to identify diabetic retinopathy and been the dilemma with the FDA,” he then adapting itself in response. diabetic macular edema. It may miss says. “Where do you put the cut point The algorithm graded 128,175 reti- non-diabetic retinopathy lesions that between safety, aka patient protec- nal images three to seven times each it was not trained to identify. Hence, tions, and technology advancement? for diabetic retinopathy and DME. this algorithm is not a replacement for That’s tough to do. This seems to The images were also examined by a a comprehensive eye exam, as it will lean both ways: improving the sup- panel of 54 U.S.-licensed ophthalmol- ignore components such as visual acu- port of the safety side but also helping ogists. When set for high specifi city, in ity, refraction, eye pressure measure- to promote some innovation. I think two validation sets composed of 9,963 ments, etc. However, with further that anytime the FDA gets pushed images and 1,748 images, the algo- research, the results suggest that the to move things along, this is going to rithm had a 90.3-percent and 87-per- algorithm could lead to improved care be a very appropriate concern. In no cent sensitivity and 98.1-percent and and outcomes compared with the cur- way should we downplay that, and we 98.5-percent specifi city, respective- rent ophthalmologic assessment.” should continue to say that the agency, ly, for detecting referable diabetic Although further research is neces- as it implements the programs as de- retinopathy —which was defi ned as sary, this new deep-learning algorithm signed, shouldn’t pay short shrift to the moderate or worse diabetic retinopa- has potential use in telemedicine, as it approval process.” thy—or referable macular edema by will allow patients to “self-diagnose” in the majority decision of a panel of at the comfort of their own homes, even least seven of the ophthalmologists. if it is only for diabetic retinopathy Google Algorithm When set for high sensitivity, the algo- and diabetic macular edema. “Along rithm had 97.5-percent and 96.1-per- with telemedicine, technologies such Detects Diabetic cent sensitivity and 93.4-percent and as these could increase access to care 93.9-percent specifi city, respectively, and assist in screening for diabetic Retinopathy in the two validation sets. retinopathy in areas with limited re- In reviewing the data, one of the sources,” Dr. Peng claims. In a study sponsored by Google, re- DeepMind researchers, Google’s Lily (Continued on p. 50)

4 | Review of Ophthalmology | December 2016

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6 | Review of Ophthalmology | January 2017

0003_rp0117_news.indd03_rp0117_news.indd 6 112/22/162/22/16 12:1312:13 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.

RP0316_BL Prolensa.indd 1 2/16/16 10:37 AM PROLENSA® (bromfenac ophthalmic solution) 0.07% Brief Summary

INDICATIONS AND USAGE PROLENSA® ophthalmic solution following cataract surgery include: PROLENSA® (bromfenac ophthalmic solution) 0.07% is indicated for the anterior chamber inflammation, foreign body sensation, eye pain, treatment of postoperative inflammation and reduction of ocular pain in photophobia and vision blurred. These reactions were reported in 3 to patients who have undergone cataract surgery. 8% of patients. DOSAGE AND ADMINISTRATION USE IN SPECIFIC POPULATIONS Recommended Dosing Pregnancy One drop of PROLENSA® ophthalmic solution should be applied to Treatment of rats at oral doses up to 0.9 mg/kg/day (systemic the affected eye once daily beginning 1 day prior to cataract surgery, exposure 90 times the systemic exposure predicted from the continued on the day of surgery, and through the first 14 days of the recommended human ophthalmic dose [RHOD] assuming the human postoperative period. systemic concentration is at the limit of quantification) and rabbits Use with Other Topical Ophthalmic Medications at oral doses up to 7.5 mg/kg/day (150 times the predicted human PROLENSA ophthalmic solution may be administered in conjunction systemic exposure) produced no treatment-related malformations in with other topical ophthalmic medications such as alpha-agonists, beta- reproduction studies. However, embryo-fetal lethality and maternal blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics. toxicity were produced in rats and rabbits at 0.9 mg/kg/day and Drops should be administered at least 5 minutes apart. 7.5 mg/kg/day, respectively. In rats, bromfenac treatment caused delayed parturition at 0.3 mg/kg/day (30 times the predicted human CONTRAINDICATIONS exposure), and caused dystocia, increased neonatal mortality and None reduced postnatal growth at 0.9 mg/kg/day. WARNINGS AND PRECAUTIONS There are no adequate and well-controlled studies in pregnant women. Sulfite Allergic Reactions Because animal reproduction studies are not always predictive of Contains sodium sulfite, a sulfite that may cause allergic-type reactions human response, this drug should be used during pregnancy only if including anaphylactic symptoms and life-threatening or less severe the potential benefit justifies the potential risk to the fetus. asthmatic episodes in certain susceptible people. The overall prevalence Because of the known effects of prostaglandin biosynthesis- of sulfite sensitivity in the general population is unknown and probably inhibiting drugs on the fetal cardiovascular system (closure of ductus low. Sulfite sensitivity is seen more frequently in asthmatic than in non- arteriosus), the use of PROLENSA® ophthalmic solution during late asthmatic people. pregnancy should be avoided. Slow or Delayed Healing Nursing Mothers All topical nonsteroidal anti-inflammatory drugs (NSAIDs), including Caution should be exercised when PROLENSA is administered to a bromfenac, may slow or delay healing. Topical corticosteroids are also nursing woman. known to slow or delay healing. Concomitant use of topical NSAIDs and Pediatric Use topical steroids may increase the potential for healing problems. Safety and efficacy in pediatric patients below the age of 18 have not Potential for Cross-Sensitivity been established. There is the potential for cross-sensitivity to acetylsalicylic acid, Geriatric Use phenylacetic acid derivatives, and other NSAIDs, including bromfenac. There is no evidence that the efficacy or safety profiles for Therefore, caution should be used when treating individuals who have PROLENSA differ in patients 70 years of age and older compared to previously exhibited sensitivities to these drugs. younger adult patients. Increased Bleeding Time With some NSAIDs, including bromfenac, there exists the potential for NONCLINICAL TOXICOLOGY increased bleeding time due to interference with platelet aggregation. Carcinogenesis, Mutagenesis and Impairment of Fertility There have been reports that ocularly applied NSAIDs may cause Long-term carcinogenicity studies in rats and mice given oral increased bleeding of ocular tissues (including hyphemas) in conjunction doses of bromfenac up to 0.6 mg/kg/day (systemic exposure 30 with ocular surgery. times the systemic exposure predicted from the recommended It is recommended that PROLENSA® ophthalmic solution be used with human ophthalmic dose [RHOD] assuming the human systemic caution in patients with known bleeding tendencies or who are receiving concentration is at the limit of quantification) and 5 mg/kg/day (340 other medications which may prolong bleeding time. times the predicted human systemic exposure), respectively, revealed Keratitis and Corneal Reactions no significant increases in tumor incidence. Use of topical NSAIDs may result in keratitis. In some susceptible Bromfenac did not show mutagenic potential in various mutagenicity patients, continued use of topical NSAIDs may result in epithelial studies, including the reverse mutation, chromosomal aberration, and breakdown, corneal thinning, corneal erosion, corneal ulceration or micronucleus tests. corneal perforation. These events may be sight threatening. Patients with Bromfenac did not impair fertility when administered orally to male evidence of corneal epithelial breakdown should immediately discontinue and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, use of topical NSAIDs, including bromfenac, and should be closely respectively (systemic exposure 90 and 30 times the predicted human monitored for corneal health. exposure, respectively). Post-marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial PATIENT COUNSELING INFORMATION defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), Slowed or Delayed Healing rheumatoid arthritis, or repeat ocular surgeries within a short period Advise patients of the possibility that slow or delayed healing may of time may be at increased risk for corneal adverse events which may occur while using NSAIDs. become sight threatening. Topical NSAIDs should be used with caution Sterility of Dropper Tip in these patients. Advise patients to replace bottle cap after using and to not touch Post-marketing experience with topical NSAIDs also suggests that use dropper tip to any surface, as this may contaminate the contents. more than 24 hours prior to surgery or use beyond 14 days post-surgery Advise patients that a single bottle of PROLENSA® ophthalmic may increase patient risk for the occurrence and severity of corneal solution, be used to treat only one eye. adverse events. Concomitant Use of Contact Lenses Contact Lens Wear Advise patients to remove contact lenses prior to instillation of PROLENSA should not be instilled while wearing contact lenses. PROLENSA. The preservative in PROLENSA, benzalkonium Remove contact lenses prior to instillation of PROLENSA. The chloride, may be absorbed by soft contact lenses. Lenses may be preservative in PROLENSA, benzalkonium chloride may be absorbed by reinserted after 10 minutes following administration of PROLENSA. soft contact lenses. Lenses may be reinserted after 10 minutes following Concomitant Topical Ocular Therapy administration of PROLENSA. If more than one topical ophthalmic medication is being used, the medicines should be administered at least 5 minutes apart ADVERSE REACTIONS Rx Only Clinical Trial Experience Manufactured by: Bausch & Lomb Incorporated, Tampa, FL 33637 Because clinical trials are conducted under widely varying conditions, Under license from: adverse reaction rates observed in the clinical trials of a drug cannot be Senju Pharmaceuticals Co., Ltd. directly compared to rates in the clinical trials of another drug and may Osaka, Japan 541-0046 not reflect the rates observed in clinical practice. Prolensa is a trademark of Bausch & Lomb Incorporated or its affiliates. The most commonly reported adverse reactions following use of © Bausch & Lomb Incorporated. 9317600 US/PRA/14/0024

RRP0316_BLP0316_BL PProlensarolensa PPI.inddI.indd 1 22/16/16/16/16 10:3810:38 AMAM January 2017 • Volume XXIV No. 1 | reviewofophthalmology.com Cover Focus 25 | In Search of the Perfect IOL Formula By Christopher Kent, Senior Editor Experts offer advice on which formulas to select and how best to use them. 34 | Choosing IOLs for Difficult Eyes By Kristine Brennan, Senior Associate Editor Careful biometry and corneal health are as important as the choice of formula.

42 | Minimizing IOL Chair Time By Jeffrey Eisenberg, Contributing Editor Ways to educate patients about their myriad options—and still have time left over to operate. 46 | E-Survey: Surgeons Tune in to Symfony By Walter Bethke, Editor in Chief New technology may encourage surgeons to give premium IOLs a second look.

Cover image: iStock January 2017 | reviewofophthalmology.com | 9

009_rp0117_toc.indd 9 12/22/16 12:36 PM Departments

3 | Review News 12 12 | Glaucoma Management Keeping Your Trabeculectomy on Track With many factors beyond our control, it behooves us to control the things we can.

18 | Refractive/Cataract Rundown RLE and the Risk of Late Dislocation Are surgeons in for a wave of problems?

20 | Technology Update A Look at the MacBook Pro 2016 A rich display and a speedy processor may offer workstation capabilities in a portable package. 51 51 | Retinal Insider The Clinical Utility of OCT Angiography The strengths and limitations of this promising new technology.

56 | Therapeutic Topics The Many Shades of Pinkeye A discussion of the various causes of conjunctivitis, and new therapeutic approaches on the horizon.

60 | Research Review The Risk Factors for NAION Researchers look at the demographic, systemic and ocular risk factors for the disease. 65

64 | Classified Ads

65 | Wills Eye Resident Case Series

68 | Advertising Index

10 | Review of Ophthalmology | January 2017

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RP0117_Abbott.indd 1 12/14/16 3:02 PM Glaucoma Management

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

Keeping Your Trabeculectomy On Track With so many factors beyond our ability to control, it behooves us to be vigilant about controlling the things we can. Thomas W. Samuelson, MD, Minneapolis

rabeculectomy has been the a lot of advanced disease out there. poor technique. These strategies can T primary go-to operation for sur- Those of us who primarily treat glau- help you avoid trouble. gical glaucoma care for most of my coma see a lot of those patients, so • Before surgery, address any career. However, that’s changed pretty we’re still doing quite a few fi ltering toxicity caused by glaucoma med- signifi cantly in the past fi ve years or so surgeries. ications. Make sure the ocular sur- with the advent of minimally invasive One of the primary reasons fi ltration face is primed for a good surgical glaucoma surgeries, or MIGS. Fil- surgery can produce mixed results is outcome. If the patient has a toxic tration surgery is highly effective, but that there are so many uncontrollable surface because of aggressive medical it isn’t safe enough to justify using it variables in the surgery—factors that therapy for glaucoma, pretreat the to treat mild or moderate glaucoma. we can’t predict or manipulate. For patient with steroids. If someone has The MIGS procedures nicely fi ll that example, we can’t control the integrity follicular conjunctivitis because of an niche, so it’s no surprise that they’re of the conjunctiva-Tenon’s complex, allergy to topical CAIs or brimonidine doing well. Meanwhile, because of especially three, four or five years (the two most common allergies) you MIGS, we’re doing far less fi ltration after the procedure. As a result, some might want to stop the offending agent surgery than we have in the past, blebs will break down; some will leak a few weeks before surgery to try to although admittedly we only have late; and some will fi brose very rapidly minimize infl ammation on the ocular two or three years’ follow-up on and fail. On the other hand, there are surface. Follicular conjunctivitis will the majority of MIGS procedures plenty of things we can control, so doom a fi lter from the outset. completed thus far. it’s important for us to be masters of • Make sure the sclerostomy is Although trabeculectomy is being those things. adequate. A poorly executed scler- performed less frequently, I suspect Here, I’d like to discuss some of the ostomy will result in insuffi cient fl ow or most glaucoma surgeons would agree issues surrounding filtering surgery too much fl ow—the latter making the that when a patient has very advanced, and offer some strategies that will help patient hypotonous and problematic rapidly progressive glaucoma requir- produce the best possible outcomes from the start. Experienced glaucoma ing a dramatic pressure reduction, for these patients. surgeons respect and fear hypotony fi ltering surgery is still the fastest way as much or more than elevated intra- to get that patient out of trouble. Most Optimizing the Surgery ocular pressure. MIGS surgeries simply don’t have • Perform meticulous wound the pressure-lowering efficacy that Intraoperative technique is one closure. This is crucial for preventing a patient with advanced disease may of the things within our control, and perioperative wound leaks. Even need, and unfortunately, there’s still filters do sometimes fail because of with careful wound closure, small,

12 | Review of Ophthalmology | January 2017 This article has no commercial sponsorship.

012_rp0117_gm.indd 12 12/21/16 4:42 PM transient leaks may occasionally occur at the incision site, but significant wound leaks early in the postoperative period should be very uncommon. It’s true that we can’t control late leaks, typically caused by the conjunctiva breaking down. That’s partly because we have a catch-22 in glaucoma surgery: We have to use antimetabolites to prevent aggressive healing. Those antimetabolites may cause the tissue to break down over time, leaving us with problems several years down the road. In the meantime, however, careful wound closure can prevent most immediate leaks.

Postoperative Management

One of the nice things about trabeculectomy is that it’s titratable. We establish an outflow pathway and make sure there’s abundant fl ow; then we control that fl ow by how tightly we suture the scleral fl ap, and by suturing it in such a way that we can release the sutures later to allow additional fl ow as needed. • Think carefully about the tim- ing of suture release. When to cut or release sutures is highly dependent on the severity of the glaucoma. How vascularized is the bleb? How low is your target pressure? How advanced is the glaucoma? Is the eye phakic or pseudophakic? How much does the patient depend on the surgical eye? (For example, if the other eye has no light perception, we have to be very careful not to put central vision at Whether the sclerostomy is created manually with a blade or punch (top) or with a device risk.) All of these things should factor (middle), fi ltration is controlled with sutures (bottom) that can be released or lysed to into how aggressive we are with our individualize care and titrate fl ow postoperatively. surgery and suture releasing. Because of the multiple issues involved, it much of that pharmacologic therapy ciliary body is still under the infl uence takes a lot of experience and surgical was intended to reduce aqueous of pharmacological suppression, the wisdom to time suture lysis and production. In that situation the result can be hypotony. release correctly. ciliary body may have been receiving However, as the ciliary body • You may want less flow at the pharmacologic message to not recovers from the effect of those one day postop than later on. make aqueous for years. Now we’re drugs, it will probably make more Some patients come into glaucoma creating a new outfl ow system. If the aqueous one or two weeks postop surgery on multiple medications, and outfl ow is overly aggressive and the than it was making at postop day one.

January 2017 | reviewofophthalmology.com | 13

012_rp0117_gm.indd 13 12/21/16 4:42 PM Glaucoma

REVIEW Management

An Early Look at the XEN Gel Stent

In late November, 2016, the U.S. Food and Drug Administration effectiveness of the device in neovascular, congenital and infantile approved Allergan’s XEN glaucoma implant system, comprised glaucomas has not been established.) of the XEN45 gel stent and a proprietary injector, for commercial The most common postoperative adverse events included a use. The XEN system had previously received the CE Mark and loss of two or more lines of BCVA (experienced by 15.4 percent been approved in Canada, and more than 10,000 devices have of patients during the fi rst month and 6.2 percent at one year); been implanted worldwide. The stent is made of a soft, fl ex- hypotony, defi ned as an IOP <6 mmHg, at any time (experienced ible collagen-derived gelatin that’s highly biocompatible and by 24.6 percent of patients, although no clinically signifi cant con- noninfl ammatory; it’s 6 mm long and about the width of a human sequences occurred and no surgical intervention was required); an hair. It’s implanted using an ab interno approach, injected through IOP increase greater than 10 mmHg from baseline (experienced by a self-sealing corneal incision using a preloaded injector. Once in 21.5 percent of patients); and a postoperative needling procedure place it reduces intraocular pressure by creating a new drainage (performed in 32.3 percent of patients). channel from the anterior chamber into the subconjunctival space, Davinder S. Grover, MD, MPH, attending surgeon and clinician at resulting in the creation of a bleb. (One advantage of this method Glaucoma Associates of Texas in Dallas, has used the XEN implant of implantation is the preservation of external ocular tissue, allow- for the past several years as part of the U.S. pivotal trial. He notes ing a greater array of future treatment options than might be avail- that, compared to other MIGS procedures, XEN stands out because able following other procedures such as a trabeculectomy or tube of its ability to treat advanced glaucoma. “I think this will be a very shunt.) The pliability of the material allows the stent to conform to safe and effective MIGS procedure for all types of glaucoma,” he the anatomy of the ocular tissue, helping to minimize issues such says. “That’s the most powerful thing about it. I’ve seen the XEN as migration, erosion and corneal-endothelial damage. used successfully on a large spectrum of patients, from mild to According to the approval, XEN is indicated for the manage- moderate to very advanced disease.” ment of refractory glaucoma where previous surgical treatment He notes that the way the implant procedure was done for has failed, and in patients with primary open-angle glaucoma—as the FDA trials is different from the way the procedure is usually well as pseudoexfoliative or pigmentary glaucoma with open performed outside the United States. “Implanting the XEN involves angles—that are unresponsive to maximum tolerated medi- the use of mitomycin-C,” he explains. “The FDA would only allow cal therapy. A clinical trial of the device involving 52 refractory the company to use Mitosol, the only FDA-approved formulation of glaucoma patients found that the stent reduced IOP from a mean MMC. However, Mitosol is only indicated for ab externo use. As a baseline of 25.1 ±3.7 mmHg (on medications) to 15.9 ±5.2 mmHg result, we were required to take down the conjunctiva in order to at 12 months. Use of IOP-lowering medications dropped from 3.5 apply MMC, then insert the device via an ab interno approach, and ±1 medications to an average of 1.7 ±1.5 medications. then close the conjunctiva. In addition, the FDA trials were done According to the company, XEN is contraindicated in angle- with advanced, refractory glaucoma cases. In contrast, the APEX closure glaucoma where the angle has not been surgically trial that was done in Europe used a different study population opened; when the target quadrant has previously had a glaucoma with less-advanced glaucoma and MMC injected through the con- shunt, conjunctival scarring or pathology; and in the presence junctiva. That trial showed even better results. So, I’m optimistic of active iris neovascularization, an anterior chamber intraocular that we’ll see fewer complications and an even higher success lens, intraocular silicone oil or vitreous in the anterior chamber. rate once we can perform the procedure that way over here.” Complications arising from implantation of the XEN stent may For more information about XEN, visit Allergan.com. include choroidal effusion; hyphema; hypotony; implant migration; implant exposure; wound leak; the need for secondary surgical in- Dr. Grover is a speaker and consultant for Allergan. tervention; and intraocular surgery complications. (The safety and —Review Staff

In these patients, the drain needs to because of the steroid use is minimized day one and the pressure is 18, I’ll be smaller immediately after surgery by the bleb.) I suggest a minimum use localized or focal massage to and larger at one or two weeks. Again, of three months for phakic eyes and generate a well-formed bleb to bring this is one of the advantages of doing four months for pseudophakic eyes. the pressure down. You don’t want trabeculectomy; we can titrate it as This is not because pseudophakic eyes the raw surgical surfaces, the Tenon’s the ciliary body recovers from years of have more inﬂ ammation, but because conjunctival complex and the sclera, aqueous suppression. there’s no risk of cataract formation in to be adherent; instead, you want a • Optimize your use of postoper- a pseudophakic eye. cushion of aqueous between them. So ative steroids. I generally use a ste- • Create a good bleb at every I want to generate a bleb each time roid up to four months, sometimes early visit. I like the patient to leave I see the patient. If I ﬁ nd that I still longer, after a typical trabeculectomy. each postoperative visit with a pressure have to do focal massage at each visit (Note that the risk of increased IOP of 6 to 10 mmHg. If it’s postoperative in the second or third week postop, I’ll

14 | Review of Ophthalmology | January 2017

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RP0716_Omeros.indd 1 6/7/16 10:07 AM Glaucoma

REVIEW Management

cut a suture to increase the outfl ow. and it’s not reimbursed. To put it • Be alert for bleb leaks. Leaks another way, the reimbursement is are bleb killers. If it’s a significant the same whether you see the patient leak and the bleb is fl at, do something fi ve times or 20 times. It’s diffi cult to to seal the leak so the bleb is regen- fi ll your clinic up with nonreimbursed erated. If the bleb has been fl at for visits, but it’s important to see these a while postoperatively, it’s going patients regularly to help ensure the to fail because there’s no potential best possible outcome. You just have space there. The conjunctiva will scar to accept that it’s a lot of work. down and when the leak eventually Gonioscopic view of an ExPress implant seals, the potential subconjunctival with an obstructed ostium prior to applying Communication Counts reservoir has scarred down. So, fix YAG laser energy to re-establish fl ow. leaks as quickly as possible to maintain A good outcome often depends on the bleb. it adds one more consideration if getting patients—and in some cases • If all sutures have been cut and the bleb fails, because it’s possible referring doctors—to understand the pressure is still too high, use that the device has become occluded what needs to be done to minimize gonioscopy to see if the scleros- with fi brin or infl ammatory material. postoperative risks. tomy is patent internally. If you For this reason, I tend to not use an • Do what you can to make sure fi nd that the sclerostomy is not patent ExPress shunt in younger individuals patients return in a timely manner. internally, take measures to clear the or those prone to infl ammation. It’s not easy to convince patients that sclerostomy, such as YAG or argon If the bleb does fail after implanting it’s important for them to come back laser iridoplasty. an ExPress shunt, it can be diffi cult to weekly for the fi rst few weeks; they • If all sutures have been cut tell whether an occlusion is the source may, for example, be dependent on a and the pressure’s still too high, of the bleb failure. I’ve had several family member for a ride. It’s worth consider needling the bleb. Need- patients who maintained excellent spending a little time to make sure the ling may help to salvage a bleb that’s pressure with the ExPress for several patient understands how important threatening to fail early on. In many years; then they suddenly came in these visits are. instances needling can prevent the with high pressure. In this situation • Educate patients that they patient from having to go back on my fi rst strategy is to needle the bleb. must always be alert for long- medications. If that has no effect, I take them to term complications, even though Before needling the bleb, pretreat the YAG laser and fi re 2 to 6 mJ of the risk is low. Patients are never with neosynephrine to blanche blood energy up the lumen of the shunt; completely out of the woods with vessels and minimize bleeding. Then, this frequently causes the pressure fi ltration surgery; they can still have take a needle and probe under the to drop dramatically. If that happens, problems fi ve or 10 years later. For that bleb and/or scleral fl ap to see if you I’ll treat the patient with an ongoing reason it’s important to educate them can reestablish flow. If flow is re- topical steroid to keep the blockage about that possibility. I always tell established, I may bring the patient from recurring. patients who have highly functional, back in several days or a week later For some surgeons the possibility pale, ischemic blebs that if aqueous to repeat the needling, this time ad- of an occlusion is reason enough not can get out of the eye, bacteria can get ministering antimetabolites. If I’m to use an ExPress device. They’ll say, in. That makes it critical for patients unable to reestablish fl ow, I’ll have the “I don’t want to add one more thing to take precautions against infection patient resume medical therapy. that could go wrong.” But for some and understand the symptoms of • If you use an ExPress shunt patients the intraoperative control infection. They need to be ready to and the bleb fails, occlusion of the and precision the ExPress offers is take action if their eye gets red or shunt could be the cause. I some- worth the small risk of occlusion. they get a purulent discharge. In that times use Alcon’s ExPress shunt for • Don’t skimp on follow-up situation they should be started on fi ltering surgery; it helps me achieve visits. Make sure you see the patient antibiotics immediately. very reproducible results, since the in a timely manner. This isn’t “cut Some of my patients travel to third outfl ow channel is consistent. I fi nd and forget” surgery; it requires care- world countries or go to Mexico the ExPress especially useful in more ful postoperative monitoring. The for spring break, and they can find elderly patients, or in individuals on reason this can be a challenge is that themselves in situations where they anticoagulants. The downside is that postoperative care is a lot of work, can’t get medical care promptly.

16 | Review of Ophthalmology | January 2017

012_rp0117_gm.indd 16 12/21/16 4:42 PM LCD Visual Acuity When I’m aware of such travel, cut sutures during the ﬁ rst week, but VVAA-11 I make sure these patients take a I would strongly prefer performing System fourth-generation fluoroquinolone suture lysis to putting the patient back along with them on the trip. That way, on medications. Please let me know if if they develop a red eye, they can suture lysis is required.” I even give start the antibiotic empirically. It’s the doctor my cell phone number to really important that these patients make it as easy as possible for him to understand that they’re at risk for contact me. infection, even if it’s a small risk. Unfortunately, what often happens is that despite laying all of this out clearly, the patient comes back six months later with elevated pressure, Make sure that any back on medications, and no sutures communication have been cut. Meanwhile, there’s ComprehensiveComprehensive been no communication from the Visual Acuity Solution breakdown doesn’t other doctor. It may be that the other originate at your end. doctor just didn’t put the energy into Multiple optotype selections trying to make this work; maybe he never even looked at the letter I All acuity slides presented with sent. Then when the pressure rose ETDRS Spacing • Make sure referring doctors are he simply put the patient back on Contrast sensitivity testing on board with your management medications rather than doing the plans. High-quality postoperative suture lysis or release. Crowding bars (for pediatrics) care is time-consuming, and no one This is very frustrating. Multimedia system and more! will work harder than you to salvage One thing that may help—depend- the bleb on a trabeculectomy that isn’t ing on the patient—is explaining the performing. So if you have to leave situation to the patient. That way, postoperative care to another doctor, when the local doctor suggests putting the other doctor may not expend the the patient back on medication, energy needed to get the patient to the patient might say, “Well, Dr. the argon laser and cut a stitch. That’s Samuelson said you might be able especially true if it’s a hard suture to to open up the drain a little bit so I see or remove. won’t have to use drops again.” Of For this reason, as much as possible, course, not all patients will be able we do our own postoperative care for to understand and participate in that our surgical glaucoma patients that way, but some may be up to it. live in our area. When patients come Whatever happens, make sure from the far reaches of the state, that any communication breakdown however, we may have to work with doesn’t originate at your end. If a local doctor. In that situation we do someone drops the ball, make sure it our best to convince the doctor that isn’t you. this is really important. Unfortunately, this can have mixed Dr. Samuelson is a founding partner results. For example, suppose a patient and attending surgeon at Minnesota lives 300 miles away. I do the surgery Eye Consultants in Minneapolis and and then I send the patient back an adjunct associate professor of home with a letter saying something ophthalmology at Hennepin County like this: “I recommend a slow taper Medical Center and the University of steroid over three to four months. of Minnesota. He is a consultant for In addition, there are three scleral Alcon, as well as several competing flap sutures that should be cut as companies in the glaucoma surgical 250 Cooper Ave., Suite 100 Tonawanda NY 14150 needed to augment ﬁ ltration. I rarely space. www.s4optik.com I 888-224-6012 Sensible equipment. Well made, well priced .

012_rp0117_gm.indd 17 12/21/16 4:42 PM 018_rp0117_rcr.indd 18 Brace for Dislocations? Should Surgeons RLE P tion inrecentyears. ed toin-the-bagsubluxationordisloca- increasing numberofspecimensrelat- ed, reportedthatthey’vereceivedan which theIOLssubluxatedordislocat- IOL-capsular bagcomplexesineyes study in2015,designedtoanalyzethe that theirincidencemaybeincreasing. causative factors,andhavementioned the-bag lensdislocationsandtheir Late Dislocations that looked at the possible causes of 86 that lookedatthepossiblecauses of86 previous studytheyperformed in2009 it mightmeanforlong-termresults. the dataonlensdislocationsandwhat surgery techniques,surgeonsdiscuss tion devotedtocataractandrefractive inaugural oneforReview’s newsec- tions withtime.Inthisarticle,the will resultinawaveoflensdisloca- group ofpatients’eyesfor40years however, ifhavingIOLsinalarge formance. Somesurgeonswonder, tion oftenenjoyimprovedvisualper- clear lensextraction/IOLimplanta- Walter Bethke, EditorinChief 18 that inﬂ uence thelong-termstabilityofIOLsincapsularbag. A lookatthedata,andsurgeonexperience,regardingfactors

Researchers in a joint U.S./German Researchers inajointU.S./German Recent studieshavelookedatin- REVIEW | ReviewofOphthalmology late 40s/early50swhoundergo re-cataract presbyopesintheir Rundown Refractive/Cataract 1 They refer to a Theyrefertoa

| January2017 Edited by Arturo Chayet, MD

Nick Mamalis, MD intervention.” in IOLdislocationsneedingsurgical concerns ofapendinglargeincrease with increasingfrequency, leadingto ation ordislocationhasbeen“reported ies foundthatlatein-the-bagsublux- Spain thatlookedatdislocationstud- and 2008. while 84weresubmittedbetween2006 submitted between2000and2003 that justtwoofthespecimenswere subluxations ordislocations,andnote population-based study, theSpanish related tolatedislocationsislow inthe 25 years. with time,a1.7-percentriskafter risk ofIOLdislocationincreasesslowly based studythatfoundthecumulative cite alarge,retrospective,population- a caseofspontaneousIOLdislocation. with exfoliative materialseenanteriorlyin Photomicrograph oftheanteriorcapsule 4 2 Though the rate of surgery Thoughtherateofsurgery A recent meta-analysis from Arecentmeta-analysisfrom 3 The researchersalso This articlehasnocommercial sponsorship. third ofthepatientshaddiagnosed sular bagstoanalyze,eventhough a who sentustheIOLswithin the cap- further withourGermancolleagues syndrome. Butthen,whenweworked had dislocatedsecondarytoexfoliation we foundthathalfofthespecimens did ourfi rst majorlabstudyonthat, reason ispseudoexfoliation.Whenwe lab. Intheselenses,themostcommon ously dislocatedthataresenttoour least inthelensesthathavespontane- that wehaven’t seensignsofthat,at go by?”hemuses.“Thegoodnewsis within thecapsularbagasyears spontaneous dislocationoftheIOL see themhavingmoreofachance younger andpatients,dowe tion is:Aswedocataractsurgeryon Center, isn’t sosure.“Thekeyques- at theUniversityofUtah’s MoranEye the OphthalmicPathologyLaboratory about? NickMamalis,MD,directorof a problemsurgeonsshouldbeworried an increaseinlatedislocations. other factors,andthatthismightmean ments inphaco,longerlifespansand growing quicklyasaresultofimprove- pseudophakes intheWestern worldis researchers saythatthenumberof Given these studies, though, is this Given thesestudies,though,isthis 3 12/22/16 12:27 PM ELITE SLIT exfoliation prior to the dislocation we thelial cell eradication, and to date we LAMP found that actually two-thirds of the don’t have a way to do that,” he says. cases had exfoliation.” Lessons from Younger Eyes The Capsulorhexis Connection Dr. Waring says ophthalmologists’ The H5 ELITE Another factor that some surgeons experiences with the youngest of pa- slit lamp features point to regarding a possible increased tients may help allay some fears of an innovative LED incidence of dislocations is the capsu- long-term dislocation. illumination system lorhexis. In a letter published in Oph- “The best line of reasoning for this is providing brilliant thalmology, Los Altos, Calif., surgeon pediatric cataract surgery,” Dr. Waring light spectrum, David Chang reported on two patients says. “With refractive lens exchange, while increasing who had late dislocations, comment- you’re probably talking about someone patient comfort. ing, “The incidence of this delayed who’s already lived 50 years with his complication appears to have skyrock- natural lens and is getting a lens re- eted after universal adoption of the placement. But if you look at a cohort capsulorhexis technique.”5 of infants or toddlers who are having “I think one of the crucial issues in IOLs implanted, they have their im- spontaneous IOL dislocation within plants for more than 70 or 80 years, the capsular bag is the use of a cap- and we don’t have any evidence that An extensive power sulorhexis,” says Dr. Mamalis. “In the suggests that they’ll have additional range, with Ƭ ve past, when we were doing can-opener zonular issues because they have an magniƬ cation settings capsulotomies and extracapsular sur- implant. I think that we feel secure that from 6x to 40x. Standard geries, we just weren’t seeing it hap- this is still basically a non-concern.” on all ELITE slit lamps. pen. I think there’s something to the Ultimately, Dr. Mamalis says long- idea that a good capsulorhexis, and an term dislocations should be on the implant placed completely in the bag, surgeon’s radar, but maybe not a can somehow, over many years, pos- source of worry. “We haven’t done IMAGING sibly lead to some constriction of the cataract surgery with a capsulorhexis bag, some phymosis and some addi- in people in their 40s and then fol- The S4OPTIK H5 ELITE slit tional stretching of the zonules which lowed them for 40 years because cap- lamp comes digital ready. could, in theory, put the patient at risk sulorhexis hasn’t been around for 40 Combine with the S4OPTIK for a spontaneous dislocation. I say ‘in years,” he says. “We just don’t know all-in-one digital camera to theory’ because we haven’t seen any the answer regarding the risk of dislo- acquire exceptional still and signs of this in the lab at this point.” cation in these patients. I can say we video images. George O. Waring IV, MD, medical haven’t seen signs of it actually occur- director of the Medical University of ring, which is reassuring, but we just South Carolina’s Magill Vision Center don’t know. It’s not a procedure that I and assistant professor of ophthalmol- would say we shouldn’t be doing, but ogy and director of refractive surgery it’s something we should keep an eye at the MUSC’s Storm Eye Institute, on.” was one of the fi rst surgeons to help 1. Liu E, Cole S, Werner L, Hengerer F, Mamalis N, Kohnen T. surgeons and patients understand the Pathologic evidence of pseudoexfoliation in cases of in-the-bag intraocular lens subluxation or dislocation. J Cataract Refract term dysfunctional lens syndrome, and Surg 2015;41:5:929-35. 2. Davis D, Brubaker J, Espandar L, Stringham J, Crandall notes that nothing about the capsu- A, Werner L, Mamalis N. Late in-the-bag spontaneous intraocular lens dislocation: Evaluation of 86 consecutive cases. lorhexis has been defi nitively shown to Ophthalmology 2009;116:4:664-70. cause dislocations down the line. He 3. Ascaso FJ, Huerva V, Grzybowski A. Epidemiology, etiology, and prevention of late IOL-capsular bag complex dislocation: Review says neither femtosecond capsuloto- of the literature. J Ophthalmol 2015;2015:805706. Published online 2015 Dec 21. mies nor manual capsulorhexes will 4. Pueringer S. L., Hodge D. O., Erie J. C. Risk of late intraocular lens dislocation after cataract surgery, 1980–2009: A population- put a lot of stress on the zonules. “As based study. Amer J Ophthalmol 2011;152:4:618–623. 5. Chang D. Letter to the editor: Prevention of bag-fi xated far as capsular contraction goes, this IOL dislocation in pseudoexfoliation. Ophthalmology 2002; would be an opportunity for lens epi- 109:11:1951. 250 Cooper Ave., Suite 100 Tonawanda NY 14150 www.s4optik.com I 888-224-6012 Sensible equipment. Well made, well priced. For today’s modern oƯ ce.

018_rp0117_rcr.indd 19 12/22/16 1:55 PM Technology Update

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

Smaller, Brighter, Faster: The MacBook Pro 2016 A rich display and a speedy processor may be able to offer workstation capabilities in a portable package. Kristine Brennan, Senior Associate Editor

hether you want to run manage- ina display, rendering lines seen on book has a screen resolution of 2560 Wment software for your prac- the monitor at 220 ppi unbroken to x 1600 pixels; the 15-in. model has tice or visual acuity tests for your the eye when viewed at a normal dis- 2,880 x 1,800. Apple claims that the patients, a good notebook comput- tance. Available with a 13-inch or 15- DCI-P3 color space of the Macbook er with brisk processing speed and inch monitor, both sizes are lighter Pro is 25 percent broader than that standout graphics can allow you and than their predecessors: the 15-in. of competitors with a conventional your staff to get the job done with- MacBook Pro 2016 weighs in at four RGB color gamut. The graphics are out being shackled to an in-office pounds (1.83 kg), representing an also 67 percent brighter than before, workstation or testing system. In late eight-ounce slim down, while the 13- according to Apple. October of last year, Apple unveiled in. version is just over three pounds “The 2016 MacBook Pro’s P3 color the MacBook Pro 2016, the fourth (1.37 kg), shedding just under half a gamut helps it show a wider range generation of its MacBook line. This pound compared to the previous ver- of colors, with more realistic hues,” lightweight notebook is now avail- sion. The 15-in. and 13-in. MacBook says Susie Ochs, executive editor of able, and it comes in three versions: Pros are both thinner with smaller Macworld magazine. “Oranges and 13-in. without the new Touch Bar; footprints. The 15-in. version is 15.5 deep greens are the most noticeable 13-in. with Touch Bar; and the 15-in. mm thick (14 percent thinner than difference, but you might have to MacBook Pro 2016 with standard the previous version) and 20 percent view the same images side-by-side Touch Bar. Any of the new MacBooks smaller overall, and its 13-in. coun- with an RGB display to tell. The could accompany you wherever you terpart is 14.9 mm thick (18 percent MacBook Pro is the first laptop to go and provide a high-end work ex- thinner than the previous version) have a P3 display, which Apple pre- perience—but there are some limita- and 23 percent smaller overall. This viously introduced with the 4K and tions. Here’s an initial look at the new translates to considerable portabil- 5K Retina iMac line, and the screen laptop in case you were thinking of ity at either size, making the new is also much brighter.” In terms of working it into your life and/or daily MacBook Pro suitable for running audio, the speakers are also louder practice. software while floating from office and clearer than those on older Mac- to ofﬁ ce, or for running visual acu- Books. Under the Hood ity testing in non-office settings as Apple also says that the new Mac- needed. Book Pro’s graphics are 130 percent Boasting its most thorough revamp The MacBook Pro’s new profile faster than in prior MacBooks in since 2012, the MacBook Pro 2016 doesn’t come at the expense of its the 15-in. laptop, and 103 percent brings back Apple’s proprietary Ret- graphic display. The 13-in. note- faster in the 13-in. version. The disk

20 | Review of Ophthalmology | January 2017 This article has no commercial sponsorship.

020_rp0117_tech update.indd.indd 20 12/22/16 10:31 AM speed is modestly faster than be- some practitioners pause. The ultra- of a dedicated key, such as adjust- fore in both—a consideration when sleek notebooks no longer have SD ing brightness or speaker volume. it comes to copying fi les. “The pro- card slots, and although Apple says Some users may miss having a per- cessor speeds aren’t a huge jump that the new MacBooks have a bat- manent escape key, but the Mac- from the last model, but if you’re tery life of about 10 hours, they no Book Pro 2016 should bring it up on upgrading from a Mac that’s a longer use MagSafe power adapters, the Touch Bar if it thinks an escape couple years old or older, key is needed for the this should feel faster,” task at hand. Simply says Ochs. clicking the desktop screen will also re- Apple The Touch Bar store the escape key to the Touch Bar, The most immediately along with the pri- obvious change in the mary function keys. MacBook Pro, though, The touchpads on all comes standard on the of the new MacBook 15-in. model and is op- Pros have doubled tional on the 13-in. ver- in size, and feature sion: the Touch Bar. Ap- Apple’s Force Touch ple’s Touch Bar is a glass haptics, which allow strip of organic light- users to perform dif- emitting diode (OLED) ferent functions with display that replaces the the touchpad by ap- row of function keys plying varying levels typically found at the of pressure. How- top of the keyboard. Un- ever, this sensitivity, like dedicated keys, the plus the increased Touch Bar’s context-sen- real estate that the sitive, illuminated icons new touchpads take change depending upon The Macbook Pro 2016 features a DCI-P3 color gamut in all three versions. up, means that an The Touch Bar is available on two of them. what the user is doing. errant brush of the For example, a user send- wrist may open un- ing emails, texts or notes in Messages the familiar magnetic adapters that wanted functions, at least until users will fi nd that the Touch Bar lights up break free from the port if enough adapt. with functions to support that—in- tension is applied. Consequently, if For doctors who want a work-wor- cluding emoji options. Users can also someone or something snags a cable thy notebook with premium features, make one-touch online purchases during charging, a broken MacBook the MacBook Pro 2016 may be the using Apple Pay. The Touch Bar is Pro 2016 may result. prescription for a workstation-like customizable with some compatible The new MacBook Pro doesn’t experience in a lightweight package. applications, allowing users to add have any standard USB ports, in- As mentioned previously, however, helpful commands and to eliminate stead featuring Thunderbolt 3 USB- power users who depend on second- others. The MacBook Pro’s Touch C ports (one on each side for the ary monitors and peripherals should ID sensor replaces the traditional smaller model; two on each side for be prepared to invest in Apple’s pro- typed login for added effi ciency and the larger one). Users who rely on prietary adaptors. security. secondary cameras, monitor screens “The biggest snag in integrating it or backup drives for their work- into a practice could be its ports— A Few Caveats fl ow will therefore have to purchase the four [in the 15-inch model] adapters. The Touch Bar itself may Thunderbolt 3 ports support USB-C For all of its enhanced brightness, affect workfl ow, since it takes swip- devices, but you’ll need adapters to processing speed and other bells and ing along the Touch Bar and tap- add USB Type A, Ethernet, HDMI whistles, however, a few changes to ping the selected icon to do many or SD card ports as required,” ob- the latest crop of MacBooks may give things that formerly took just one tap serves Ochs.

January 2017 | reviewofophthalmology.com | 21

020_rp0117_tech update.indd.indd 21 12/22/16 10:32 AM 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 IOL Power Formulas REVIEW Cover Focus In Search of the Perfect IOL Formula

Christopher Kent, Senior Editor

Experts offer s every cataract surgeon Baylor College of Medicine in Hous- knows, there are a number of ton and developer of the Holladay I advice on which Aformulas that can be used to and Holladay II formulas. “That ver- decide what intraocular lens power gence formula was fi rst published by formulas to use should be implanted in a given eye. Stanilov Fyodorov back in 1975.1 The But how do you know which formula only thing that’s different [among the and how best to (or formulas) to use? Is one better current theoretical formulas] is the than another? Can you use a single prediction of the effective lens posi- use them. formula, or should you plug your tion. Prior to about 1970, everybody numbers into several and compare used about 4.5 mm for the axial length the results? How much difference of every eye. Then Richard Binkhorst, does it make to use a formula with MD, suggested that if the axial length seven variables instead of two? These is 10 percent longer than average, we are complex questions, and many should use a value 10 percent greater surgeons disagree about the answers. than 4.5 to calculate the ELP, and if Here, to shed light on this topic, the eye is 10 percent shorter, a value three surgeons with extensive experi- 10 percent smaller. He was the fi rst ence developing and using these for- person to individualize this. mulas share their thoughts. “For many years, most of the formulas, including the Holladay I, SRK/T Formula Evolution and Hoffer Q, just required inputting axial length and K-reading, because As our understanding of the eye’s those were the measurements we anatomy has improved, the complex- had back then,” he continues. “Then ity of the predictive formulas for IOL Thomas Olsen, MD, PhD, came out power has increased. That’s not the re- with a formula using four predic- sult of a change in our understanding tors: axial length; K-reading; anterior of optics; it’s because of refi nement in chamber depth; and lens thickness. In our ability to predict where the IOL 1992 our team created the Holladay II will sit inside the eye. “All the theoret- formula, using seven variables to pre- ical formulas use the same vergence dict the effective lens position. Then formula to relate the cornea, the lens Olsen and Barrett followed with new and the distances between them,” says seven-variable formulas of their own. Jack T. Holladay, MD, MSEE, FACS, These formulas use axial length, K- clinical professor of ophthalmology at reading, anterior chamber depth, lens

January 2017 | reviewofophthalmology.com | 25

0025_rp0117_f1.indd25_rp0117_f1.indd 2525 112/21/162/21/16 4:094:09 PMPM 0025_rp0117_f1.indd 26 2 5 _ r p 0 1 1 7 _ f 1 eyes withashortaxiallength); and with shortereyes(hyperopic, small average eyes;theHofferQworks best duces themostaccurateresultswith formulas: TheHolladayIformulapro- eral consensusabouthowtousethese er. Overtime,surgeonsreachedagen- tions abouthowtocalculateIOLpow- ﬁ laday IandSRK/T. Thosewerethe generation formulas—HofferQ,Hol- were usingwhatarecalledthethird- Formula.) “Foralongtimepeople helped todeveloptheLadasSuper Institute inLosAngeles.(Dr. Devgan ophthalmology attheJulesSteinEye cal Centerandclinicalprofessorof ogy attheOliveView UCLAMedi- in BeverlyHills,chiefofophthalmol- vate practiceatDevganEyeSurgery Devgan, MD,FACS, FRCS, inpri- have comealongway,” agreesUday of thepatient.” and some,liketheHolladayII,age thickness, cornealdiameter, refraction 26 . rst togobeyondthemostbasicno- i n d

“IOLpowercalculationformulas REVIEW d Super Formula at you did. Now, foreachcaseusingtheLadas thepowers calculate surgeons, theoutcomesoflast50or100cataracts lookat theirweaknesses,” formulaswhileavoiding many hesays. “I tell sary. “The LadasSuperFormula bringstogetherthestrengthsof plugging yourmeasurementsintomultipleformulasisunneces- theJulesSteinEyeInstituteinLos at mology Angeles, believes theBarrettformula.”cation—and a littlebitmorewiththeHolladayI—with Wang-Koch modifi - based oncertainfeatures. Ifit’s alongeye, forexample, Imaygo with theothers, tofi Itry nd areason. Also, oneformula Imayfavor of themeasurements. Ifoneofthethreeformulasdoesn’tagree and mayedgeonewayortheother, dependingupontheaccuracy also usetheOlsenandHolladayIIformulas. Ilookforconsensus short eyes, anteriorchamber, particularlythosewithashallow we modifi cation, theBarrettUniversalIIandHill-RBF,” hesays. “In this approach. “I usuallyusetheHolladayIwith Wang-Koch BaylorCollegeofMedicineinHouston, at ophthalmology favors theresults.and/or average DouglasD. Koch, MD, professorof sense toplugtheirnumbersintomultipleformulasandcompare winner intermsofaccuracy, surgeonsbelieveitmakes many have beenbetter.have The proofisinthepudding.” | Should You UseMultipleFormulas?

Uday Devgan, MD, FACS, FRCS, clinical professorofophthal- formulaswithnoclear ofcalculation Given theproliferation Jack T. Holladay, MD, FACS, clinical professorofophthalmology

Focus Cover Review ofOphthalmology

2 6

IOLcalc.com IOL Power Formulas andseeiftheoutcomeswould | January2017 became verycumbersome.” If this,thenthat.that, this.It literally hadafl mulas hadbecomeveryconvoluted.I more than25or26mmlong. ply toyourmeasurementsiftheeyeis [the Wang-Koch modifi myopic eyes.Theyprovidedafactor about axiallengthadjustmentinhighly Medicine publishedaverygoodstudy and LiWang fromBaylorCollegeof outcomes evenfurther. DougKoch suggesting fudgefactorstorefi seven variables.Thenpeoplebegan The HolladayIIformulaincorporates requires theanteriorchamberdepth. reading andtheaxiallength,butalso “The HaigisformularequirestheK- corporate additionaldata,”hesays. fourth-generation formulaswhichin- appropriate fortheeyeinquestion. used whicheverformulaseemedmost results withlongereyes.Sosurgeons the SRK/Tformulaproducesbest “By thispoint,”henotes,“thefor- “Eventually, surgeonsdeveloped ow chartonmydesk: the pooleyeyou’reworkingwithfallsinto.” aboutwhichpartof you’renotgoingtobeaccurate information formissinginformation.of casescan’tcompensate Without that about theeye’s pluggedinto theformula. anatomy A largervolume therightdetails goodifyoudon’thave believe itwon’tdoyouany makesadifference,”size ofthedataset hesays. “However, Istill largedataset.the formulaonavery “It’s the certainlytruethat unique.” Dr. aboutsimplybasing Holladayalsohasreservations makestheeye enough ofthevariablestoreallyunderstandwhat measured you workwiththeolderformulasstillhaven’t dousingasingleformula,”able predictorsalready hesays. “When sorted fordifferentkindsofeyes, butthat’s theseven-vari- what reason. “The SuperFormula ofolderformulas usesacombination muchyou’dgain.” so I’mnotsurehow variable formulas, farapart, aren’tthat buttheirrecommendations eye intoaccount. thethreeseven- Itmightmakesensetoaverage ofthe takesmoreoftheanatomy a seven-variablepredictorthat and asmallanteriorsegment, forexample. It’s alotbettertouse You’re betweenanormalanteriorsegment stillnotdifferentiating produceless-reliableresults. formulasthat doesisaverage that areusingtheolderformulas,”surgeons whodothat hesays. “All measurements intomultipleformulasmakesmuchsense. “Most BaylorCollegeofMedicine,at pluggingyour isalsoskepticalthat Dr. HolladayisskepticaloftheLadasSuperFormula forthesame cation] toap- ne the the ne improves itsaccuracybased onnew from 100,000surgeriesandconstantly erate aresult.Italsoincorporates data the bestresultswithshorteyestogen- Formula usestheequationsthatget dealing withashorteye,theSuper automatically,” heexplains.“Ifyou’re measurements intotherightformula into asingleequationthatshiftsyour incorporates manyexistingformulas for yoursetofmeasurements. using existingdatatopredictresults cifi from thousandsofeyes.It’s notaspe- net-based formula,incorporatingdata basis function;it’s abig-data/neural- he says.“Hill-RBFreferstoaradial la, whichismeanttoworkforalleyes,” created theBarrettUniversalFormu- up anyaccuracy. “GrahamBarretthas the calculationprocesswithoutgiving las aretryingtofi Trying toSimplify “Finally, theLadasSuperFormula Dr. Devgansaysthenewestformu- c equation;instead,it’s amethodof nd waystosimplify —CK 112/21/16 4:10 PM 2 / 2 1 / 1 6

4 : 1 0

P M data that’s coming in. The addition of quite as well as the Holladay I formula ing able to base the result on either crowd-sourced data lets you be pretty combined with our Wang-Koch modi- crowd-sourced data or his own previ- darn accurate. It can also give you an fi cation. In short eyes, we have some ously entered data. “I’ve entered data answer based on data from your own preliminary data that suggests that the from a thousand eyes of my own,” he past results. But any of the latest for- Hill-RBF formula is a little better than notes. “I know that my results with mulas, including the Ladas Super For- some other formulas. It’s also impor- myopic eyes tend to be pretty spot mula, the Barrett Universal II and the tant to point out that both the Hill- on, so I can just use my own previous Hill-RBF, should give surgeons great RBF and Barrett are constantly being results to determine what I should do. results, as long as they’re paying close evaluated for ongoing improvement. When I’m operating on an unusual eye attention to the details.” Overall, they’re all pretty close.” where I don’t have many previous data points to work with, I can use the data Is One Formula the Best? others have turned in when operating on similar eyes. I might see an eye like This is a tricky question to answer, “The more you know that once every five years, but with in part because some formulas seem about the anatomy input from thousands of surgeons, the to give better results in certain types of formula has plenty of data to work eyes (short vs. long eyes, for example), of the eye and the with.” and in part because not much research patient, the better Dr. Devgan points out that surgeons has been done comparing formulas. wanting to try the Ladas Super For- The development of each formula you’ll be able to mula can access it for free at IOLcalc. has been different as well. “Everyone predict the effective com. “An app with the formula is com- who develops a formula says his is the ing soon for both the iPhone and An- best,” notes Dr. Holladay. “It’s not nec- lens position.” droid devices,” he says. “The formula essarily that people are biased; it’s that —Jack Holladay, MD can also be installed on an instrument formulas are developed based on a like the LenStar or IOLMaster.” set of data, and the formula is refi ned until it produces the best outcomes— Why Use Seven Variables? with that dataset. If you develop your Dr. Devgan says he’s had great suc- formula using 300 cases, your formula cess using the Ladas Super Formula “The reason it makes sense to use is always going to be the best with that that he helped to develop. “We’re able a formula with seven variables is that dataset because you’ve tweaked your to get 90-plus percent of eyes within the more you know about the anatomy formula until it produced the best re- half a diopter,” he says. “The older, of the eye and the patient, the better sults. Whether it will produce the best third-generation formulas usually only you’ll be able to predict the effective results with every other set of cases is a get about 70 percent within a half di- lens position,” explains Dr. Holladay. different question.” opter. That’s a big difference. In ad- “Here’s a specific example involving “There aren’t many studies compar- dition, I can now outsource the lens the Holladay II formula. Our group ing recent formulas such as the Bar- calculations to someone else in my was working with James Gills, MD, rett Universal II and Hill-RBF,” notes practice. We just plug the numbers on a group of eyes that needed lens- Douglas D. Koch, MD, professor in and the calculation is done. Right es between 40 and 60 D because the of ophthalmology at Baylor College now we have a Ladas Super Formula eyes were so short—from 15 to 20 mm of Medicine in Houston. (Dr. Koch program that can be installed on your long. The outcomes we achieved were and Li Wang, MD, PhD, created the biometer that will automatically im- mixed. Some we got right; others we Wang-Koch modifi cation.) “The best port the data to eliminate transcription missed by as much as 6 D. data I’ve seen was more than 90 per- errors. We’re also working on adding “To try and figure out the reason cent of eyes within 0.5 D of predicted character recognition technology to for this, we went back and mea- outcome for the Hill-RBF in normal the Ladas Super Formula app we’re sured six anatomic characteristics of eyes. I also still fi nd the Holladay I to developing, so you’ll be able to use these eyes,” he says. “We found that be an excellent formula, and I now your phone to take a photo of the the white-to-white measurement— also routinely use the Barrett Univer- printout from the IOLMaster or Len- the corneal diameter—was the most sal II. I’ve seen data that suggests that Star and it will automatically pick up helpful of the six measurements in the Barrett Universal II formula does all of the data.” terms of explaining the discrepancy. very well in long eyes, but perhaps not Dr. Devgan also appreciates be- We discovered that these very small

January 2017 | reviewofophthalmology.com | 27

0025_rp0117_f1.indd25_rp0117_f1.indd 2727 112/21/162/21/16 4:104:10 PMPM 0025_rp0117_f1.indd 28 2 5 _ r p 0 1 1 7 _ f 1 time, bothtypesofeyeshave anor- the time.Eightyto90percent ofthe only trueinlongeyes10percent of short eyes20percentofthetime,and surements found,that’s onlytrueof anterior segments.Butasourmea- segments andlongeyeshavedeep that shorteyeshaveshallowanterior into theboxesalongdiagonal— traditionally assumedthateyesfall terior segments.Mostpeoplehave segments toshorteyeswithdeepan- from longeyeswithshallowanterior you withninecategories,ranging rior segment,”hesays.“Thatleaves axial lengthandthesizeofante- can divideeyesalongtwoaxes:the that illustratesthispoint that hadasmallanteriorsegment.” much deeperintheeyethanthose corneas endedupwithlensessitting dealing with.Andthosewith12-mm to tellwhichtypeofshorteyewewere white measurementwastheonlyway and somehadﬂ reading; someshorteyeshadsteepK’s which fromtheaxiallengthandK- The problemis,youcan’t tellwhichis opia—but anormalanteriorsegment. short posteriorsegment—axialhyper- (nanopthalmos), andthosethathavea portionally small,likeapygmyeye kinds ofshorteyes:thosethatarepro- dent. We realizedthatthere aretwo surements areindepen- “In fact,thosetwomea- ments,” hecontinues. have shortanteriorseg- sume thatshorteyes 11.8 or12mm. had cornealdiametersof one. Thelattereyesalso ment ratherthanasmall a normalanteriorseg- but othershorteyeshad to-white measurements; ments andsmallwhite- had smallanteriorseg- gories: Someshorteyes eyes fellintotwocate- 28 . i n

d REVIEW Dr. Holladayhascreatedachart “Most surgeonsas- d |

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Review ofOphthalmology

2 8 at K’s. Thewhite-to-

IOL Power Formulas [above]. Holladay, MD, MSEE, FACS andJamesGills, MD, foundthatthisisn’tthecase. segments andlongeyes have deepanteriorsegments, butresearch by Jack Surgeons have traditionally assumedthatshorteyes have shallow anterior Anterior Segment Size Anterior SegmentSizevs. AxialLength | January2017 Small Normal Large “You hr NormalLong Short (20%) Small eyeNanophthalmia normal axial hyperopia(80%) hyperopia (0%) Megalocornea +axial most accurateresults. seven-variable formulasproducethe dent groups,haveconﬁ manufacturers, aswellindepen- In fact,studiesconductedbythelens make abigdifferenceinmanyeyes. having theextrameasurementscan posterior segmentsrightaswell.So had biganteriorsegmentsbutshort tionally smallright,andtheeyesthat “We gottheeyesthatwere propor- making those6-Derrors,”hesays. all ofasuddenwewerenolonger that mistake. seven-variable formulascorrectfor only true20percentofthetime.The shallow anteriorsegments,whichis formulas assumethatshorteyeshave with thetwo-variableformulas;those one ofthemistakessurgeonsmake mal anteriorsegmentdepth.That’s Holladay IversionoftheWang-Koch modifier? “We’ve verifiedthatthe still makesensetousetheWang-Koch Holladay IIismoreaccurate,doesit better thananother.” you tosaythat,overall,oneformulais signiﬁ new datasets,there’s nostatistically were different.Butwhenappliedto the datasetsusedtodevelopthem may notbeexactlythesamebecause the lensesthoseformulasrecommend “Once wetookthisintoaccount, If a seven-variable formula like the If aseven-variableformulalikethe cant difference that would allow cant difference thatwouldallow Axial Length (2%) Microcornea (96%) (2%) Megalocornea rmed thatthe 2-14 Ofcourse, (0%) + axialmyopia Microcornea (90%) axial myopia (10%) + axialmyopia Megalocornea Bupthalmos Large Eye meeting thisyear, Igaveanexample American AcademyofOphthalmology In myJacksonMemoriallecture atthe tive errorsgreaterthanhalfadiopter. sometimes getpostoperativerefrac- ings fromdifferentdevices,butIstill eters andlookatthreesetsofK-read- he says.“Imeasurewithtwobiom- cially trueofcornealmeasurements,” putting intotheformula.“Thisisespe- curacy ofthemeasurementsyou’re uses tocalculatetheELP, andtheac- uncertainty: themethodformula formulas aresubjecttotwosourcesof Accurate InputCounts of yourcaseswithinhalfadiopter.” stant, you’llgetmorethan90percent formula andpersonalizeyourcon- dataset. Ifyouuseaseven-predictor and whichisthebestdependsonyour a slightlydifferentrecommendation, ner amongthem;eachoneproduces best, althoughthere’s noclearwin- the seven-predictorformulasare your resultwillbeoffanyway. Second, to worryabouttheformulabecause constant; otherwisethere’s noreason ber one,”hesays,“personalizeyour two basicpiecesofadvice.“Num- in thissubject,heoffershisstudents being measuredexceed25mm.) Dr. Kochpointsoutthatalmostall When Dr. Holladayteachesclasses need for compensation need forcompensation eyes. Hebelievesthe when dealingwithlong tion increasesaccuracy Wang-Koch modifica- tally, agreesthatthe (Dr. Holladay, inciden- longer,” saysDr. Koch. all eyes25.2mmand Koch modificationfor II, soweusetheWang- well fortheHolladay formula worksequally ments whentheeyes exaggerated measure- biometers producing results fromoptical 112/21/16 4:10 PM 2 / 2 1 / 1 6

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P M 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. Richard J. Mackool, MD As before, one new surgical video will be released monthly, Episode 13: and physicians may earn CME credits or just observe the case. New viewers “Correction of are able to obtain additional CME credit by reviewing previous videos that are located in our archives. Negative Dysphotopsia by Optic Capture I thank the many surgeons who have told us that they have found our CME After Capsulorhexis program to be interesting and instructive; I appreciate your comments, Enlargement” suggestions and questions. Thanks again for joining us on Mackool Online CME. Surgical Video by: Richard J. Mackool, MD CME Accredited Surgical Training Videos Now Available Online: www.MackoolOnlineCME.com

Video Overview: Richard Mackool, MD, a world renowned anterior segment ophthalmic This patient underwent microsurgeon, has assembled a web-based video collection of surgical cataract-implant surgery cases that encompass both routine and challenging cases, demonstrating both 3 weeks ago, has severe familiar and potentially unfamiliar surgical techniques using a variety negative dysphotopsia and, of instrumentation and settings. fortuitously, a mild hyperopic refractive error. However, This educational activity aims to present a series of Dr. Mackool’s surgical the preexisting capsulorhexis videos, carefully selected to address the speciﬁ c learning objectives of this is too small to permit the activity, with the goal of making surgical training available as needed online for optic to be captured. In this surgeons motivated to improve or expand their surgical repertoire. video, I demonstrate rhexis Learning Objective: enlargement prior to successful After completion of this educational activity, participants should be able to: capture of the lens optic. • Demonstrate capsulorhexis capture of the optic of an IOL.

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 the Institute for the Advancement of Human Behavior (IAHB) and Postgraduate Healthcare Education, LLC (PHE). IAHB is accredited by the ACCME to provide continuing medical education for physicians. Credit Designation Statement IAHB 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 0025_rp0117_f1.indd 30 2 5 _ r p 0 1 1 7 _ f 1 30 steep meridians,aswellthe astig- power measurementsofthe fl standard deviationsofitssix corneal With theLenStaryoucanlookat may notbeasaccurateitshouldbe. sharp. Thattellsyouthatthereading the refl LED lights;youmayseethatsomeof the corneafrominstrument’s 18 at theimagesthatarereflectedoff “With theIOLMaster, you canlook consistency ofthedata,”hecontinues. important tolookatthequalityand ASCRS website. and Hill-RBFformulasonlineatthe formulas, youcanusetheBarrett IOLMaster andwanttouseallthree by. Inthemeantime,ifyouhave their formulaoptionsastimegoes I presumetheIOLMasterwillexpand can purchasedirectlyfromDr. Olsen. quite assophisticatedtheoneyou version oftheOlsenformulathat’s not LenStar offersallthree,alongwitha Barrett orHill-RBFformulas.The laday IIformula,itdoesn’t includethe ever, isthatwhileitincludestheHol- racts. Onelimitationofthe700,how- axial lengthineyeswithdensecata- most robustbiometerformeasuring depth. TheIOLMaster700isalsothe when measuringanteriorchamber rior, andthe700hasgreateraccuracy neal powermeasurementsaresupe- to theIOLMaster500;Ifi says. “IdoprefertheIOLMaster700 when usedcorrectly. “Iuseboth,”he and IOLMasterproducegoodresults always bewhatyouexpectittobe.” understand thattheoutcomewon’t your bestandmakesurepatients can stillhappen.You justhavetodo ing andouradvancedtechnology, this the error. Evenwithcarefulmeasur- enough ofadifferencetoaccountfor er andgotareadingof44.6,whichwas remeasured thepatienttwoweekslat- ended upmyopicpostoperatively. I one patientwas44.1,andthe of this.TheK-readingImeasuredfor . i n

d REVIEW “Whichever instrumentyouuse,it’s Dr. KochsaysboththeLenStar d |

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3 0 ections aresmudgy insteadof

IOL Power Formulas nd thecor- | January2017 at and at The majorityofeyes shouldfollow thedecisionpathmarked inred. power ofthelensyoushouldimplanttogetasclosepossibleyourdesired outcome. Jack Holladay, MD, MSEE, FACS, recommends the usingthisdecisiontree todetermine gotten betterresultsusingthe Hol- Holladay IorII? tive adjustment.” IOL, shouldIneedtodoapostopera- the patientafterIputinapremium ly useexcimerlasersurgerytotreat my IOLselectionorabilitytosafe- or otherfactorsthatmightinﬂ curvature, anyirregularastigmatism there areanyabnormalitiesincorneal measurements. Third,ittellsmeif paring totheLenStarandIOLMaster meridian ofanyastigmatismforcom- ond, itgivesmethemagnitudeand before proceedingwithsurgery. Sec- is irregularandthatIneedtoﬁ which meansthatthecornealsurface it tellsmeifthemiresaredistorted, a numberofimportantthings.First, Scheimpflug technology. Ittellsme pher, whichhasbothplacidodiscand he says.“IusetheGallileitopogra- the qualityofcornealsurface,” that givesyouinformationabout “It’s importanttouseatopographer especially intermsofastigmatism. validate topographymeasurements, the qualityofmeasurement.” IOL calculations,youneedtovalidate matic axis.With anymeasurementfor Dr. Holladay’s CornealPower DecisionTree Barrett Formula Some surgeons report that they’ve Some surgeonsreportthatthey’ve Dr. Kochsaysit’s alsoimportantto H2, Olsenor (7 variables) 70% ofcases (blink, blink) No drops No w/ BackSurface Keratometry Exact ToricCalc ATR Adjustment Exact ToricCalc Toric? SD <0.03mm SD <0.20D uence uence x that that x Yes SD >0.03mm SD >0.20D patient’s previousrefractionismore values thatyouhaven’t measured.” number blank.Asarule,neverputin worse answerthanifyoujustleavethe “If theeyeisn’t averageyou’llgeta not abletomeasureit,”hecontinues. something likelensthicknessifyou’re the formulawillthrowyourresultoff. before thecataract,putting-4Dinto right beforethesurgerywasplano formed. Iftheeyeyoumeasureas-4D was emmetropicbeforethecataract ent positionthanitwillinaneyethat implant isgoingtoendupinadiffer- person. Inthosepeople,thelensyou ful crystallinelensthananaverage will haveathickerandmorepower- an adultbeforedevelopingacataract gery. Apersonwhoreallywas-4Das measured rightbeforecataractsur- age 21mightappeartobe-4Dwhen formed. Someonewhowasplanoat adult refractionbeforethecataract the sizeofeye,butonlyifit’s the fraction helpstheformuladetermine by thecataract,”heexplains.“There- visit. “Thatrefractionhasbeenaltered tion theymeasureatthepreoperative cause surgeonsofteninputtherefrac- says thatinhisexperience,thisisbe- seven-variable formula.Dr. Holladay laday IformulathantheHolladayII Dr. Holladay admitsthatgettingthe “Also, don’t useanaveragefor 4.5 mmZonalK No To No Ref Sx, KC, PMD,…? P Dry Eye? Dry ography 4.5 mmZonalK To Treat >6wks M ography Yes Yes 112/21/16 4:10 PM 2 / 2 1 / 1 6

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RP1016_Capital One.indd 1 9/12/16 12:26 PM 0025_rp0117_f1.indd 32 2 5 _ r p 0 1 1 7 _ f 1 back radiusis82percentof that, as- radius ofthecornea,assume thatthe a keratometertomeasurethe front tainly intheK-reading,whereweuse axial lengthmeasurement,andcer- “There willalwaysbevariabilityinthe ments wehavetotake,”heexplains. of thevariabilityallmeasure- curacy inlenscalculationisthesum measurements. “Thelimitofourac- of theaccuracylimitspreoperative rometry willstillbeusefulbecause come, toolslikeintraoperativeaber- how goodlenspowerformulasbe- ing itabitlessthanIusedto.” post-LASIK eyes.ButI’malreadyus- I stillusethistechnologyroutinelyfor particularly trueforastigmatism,and not thereyet,”saysDr. Koch.“That’s intraoperative aberrometry, butwe’re eventually reducetheindicationsfor and preoperativemeasurementswill unnecessary. “Ithinkbetterformulas erating table—mayeventuallybecome fraction whilethepatientisonop- like theORAorHOLOStotakeare- ment—where thesurgeonusesatool that intraoperativeaphakicmeasure- improving, somesurgeonsbelieve Formula vs. Intraop Refraction visit beforethecataractsurgery.” manifest refractionmeasuredonthe cataract refraction.Justdon’t usethe you agoodapproximationofthepre- their 20s.Anyofthesethingscangive to seethemclearlywhentheywerein how farawaythingshadtobeinorder metropic. Manypeoplecantellyou know thepatientwasprobablyem- glasses?’ Ifthepatientsaysyes,you your driver’s licensewithoutwearing questions like:‘Were youabletoget before hehadLASIK.Or, youcanask He maystillhavetheglasseshewore you havetoaskthepatientforhelp. seeing thepatientforﬁ geons don’t doit,”hesays.“Ifyou’re work. “That’s onereasonmanysur- 32 . i n

d REVIEW Dr. Holladaybelievesthatnomatter Given thatcalculationformulaskeep d |

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IOL Power Formulas rst time, rst | January2017 and thatmakesahugedifference in they stillhavetocalculatethe ELP, tell usthevergencecalculation, but tive lensposition.Theaberrometers vergence calculationandtheeffec- “All formulascalculatetwothings:the tion doneonthetable,”heexplains. complicated thanjusttheauto-refrac- “Intraoperative aberrometryismore into theintraoperativeaberrometer. incorporating anadvancedformula seen, however,” hesays. may stillimprove.“Thatremainstobe the accuracyofthesemeasurements the targetoutcome.” cent ofpatientswithinhalfadiopter error limitskeepusatabout90per- tion isdownto0.2or0.3mm.Those ber depthandtheeffectivelensposi- about 0.1mm;andtheanteriorcham- 0.25 D;theerrorforaxiallengthis precision limitforthecorneaisabout able thatgoesintotheformula.Our the squaresoferroreachvari- the errorofanswerissum it fromanengineeringperspective, put intotheformula.Ifyoulookat cision ofthemeasurementsthatwe isn’t theformula;limitispre- of accuracy,” hepointsout.“Thelimit of eyeswithinhalfadiopter, interms reaching aplateauatabout90percent traocular lenscalculationsandwe’re the accuracyofyourprediction.) surface usingtomographywillincrease surface radius,someasuringtheback is nolonger82percentofthefront gery cases,theposteriorsurfaceradius laday notesthatinpost-refractivesur- have anirregularcornea.”(Dr. Hol- ple whohavehadrefractivesurgeryor and assumptions,particularlyforpeo- variability ofallthosecalculations kic refraction.Thateliminatesthe cornea asalenstomeasuretheapha- operative refractionsimplyusesthe calculate thepowerofcornea. sume anindexofrefractionandthen Dr. Devganseesanotherpossibility: Dr. Holladayacknowledges that “We’ve spent50yearsdoingin- “In contrast,”hecontinues,“intra- 2000;11:1:35-46. aftercorneal refractive surgery.status CurrOpinOphthalmol 14. SeitzB, Langenbucher A. Intraocularlenscalculations RefractSurg2001;27:4:571-6. Cataract afterlaserinsitukeratomileusis. calculation lens power J 13. GimbelHV, SunR. Accuracy andpredictabilityofintraocular surgery. RefractSurg2004;30:7:1430-4. JCataract afterincisionalandthermal keratorefractive calculation power 12. Packer M, LK, Brown HoffmanRS, Fine IH. Intraocularlens 2004;111:10:1825-31. Ophthalmology undergoneLASIK. have methodsineyesthat calculation power 11. Wang L, BoothMA, Koch DD. Comparison ofintraocularlens 2004;102:189-96; discussion196-7. laser-assisted in-situkeratomileusis. Trans Am OphthalmolSoc undergone have methodsineyes that calculation lens power 10. Wang L, BoothMA, Koch DD. Comparison ofintraocular Ophthalmol 2006;34:7:640-4. aftercornealrefractivesurgery.lens power ClinExperiment 9. ChanCC, HodgeC, M. Lawless ofintraocular Calculation 2006;32:12:2050-3. 1, Holladay2, andSRK/Tformulas. RefractSurg JCataract predictionusingtheHofferQ,of intraocularlenspower Holladay 8. J, Narváez ZimmermanG, StultingRD, ChangDH. Accuracy Yan KeZaZhi2006;42:10:888-91. Chinese. phacoemulsiﬁcataract afterrefractivesurgery.cation Zhonghua 7. HuBJ, ZhaoSZ, Tseng P. in calculation Intraocularlenspower Ophthalmologica 2008;222:5:302-7. cataracts. inpaediatric chamber intraocularlensimplantation posterior oropticcaptured Holladay IIformulaafterin-the-bag Kohnen T. usingthe Predictabilityofintraocularlenscalculation 6. LüchtenbergM, Kuhli-Hattenbach C, Fronius M, Zubcov AA, 2009l;35:7:1181-9. for highmyopiaandhyperopia. RefractSurg JCataract formulasinrefractivelensexchange calculation lens power 5. Terzi E, Wang L, Kohnen T. Accuracy ofmodernintraocular 2011;118:3:503-6. length andacomparisonofvariousformulas. Ophthalmology usingtheIOLMasterineyeswithlongaxial lens calculations 4. BangS, EdellE, Yu Q, K, Pratzer Stark W. Accuracy ofintraocular inhighmyopia.calculation OmanJOphthalmol2010;3:3:126-30. 3. Ghanem AA, El-SayedHM. Accuracy ofintraocularlenspower 43. refraction.preoperative RefractSurg2011;37:7:1239- JCataract eyesintheabsenceof 2 intraocularlensformulaforpediatric 2. Trivedi RH, Wilson ME, Reardon W. Accuracy oftheHolladay ofintraocularlenses.power InvestOphthalmol1975;14:8:625-8. 1. FyodorovSN, GalinMA, Linksz A. oftheoptical Calculation Formula andthe Solutions whichownstheLadasSuper is aprincipalinAdvancedEuclidean lergan, ZeissandWavetec. Dr. Devgan AMO, NIDEK,Oculus,Acufocus,Al- eyes withinhalfadiopter.” might bepossibletoget99percentof should resultinincreasedaccuracy. It into theintraoperativeaberrometers formula liketheLadasSuperFormula gery. Soincorporatinganadvanced before evenstartingthecataractsur- axial lengthandotherbiometricdata requires youtoinputtheK-reading, the outcome.That’s whytheORA sulted forCarlZeissMeditec. and Holoshaspreviouslycon- site. Dr. KochconsultsforAlcon,AMO Dr. Holladayisaconsultantfor IOLcalc.com web- 112/21/16 4:10 PM 2 / 2 1 / 1 6

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RP1117_Oculus.indd 1 12/16/16 11:04 AM IOLs REVIEW Cover Focus Calculating for Success: IOLs in Difﬁ cult Eyes

Kristine Brennan, Senior Associate Editor

Careful biometry r. Harold Ridley (1906-2001), fundamental to a good refractive out- who implanted the first in- come. “We have a routine that applies and corneal health Dtraocular lens in 1949, lived to all eyes identifi ed as being partic- to see cataract surgery evolve into a ularly exceptional,” he says. “We do are as important true refractive procedure, undergoing a lot of repeat testing. We do partial IOL implantations himself in 1989 and coherence interferometry using the as choice of 1990.1 Today, outcomes within half a IOLMaster for axial length, and we do diopter or less of target are attainable ultrasound. We do both every time, for formula. in most normal eyes, but some cases every patient. For the measurement continue to present challenges. This of the K value, we use at least three article provides insights from seasoned methods. Another thing we do is OCT cataract surgeons about how to maxi- of the retina for all patients. We also do mize your outcomes and includes brief pachymetry on all patients.” discussions of specifi c types of chal- Dr. Sayegh says these measures help lenging eyes. to reveal any pathology ahead of time. “Everybody having cataract surgery Preop Workup is Critical will get OCT, and they will get evaluation of the thickness of the cornea, “I can have a long eye, a short eye so that if there is underlying Fuchs’ or a post-LASIK eye, but the most im- or anything that would be an issue at portant thing I do is give them all the the time of surgery, we can take extra same thorough preoperative workup,” care with the eye. If there’s anything emphasizes P. Dee Stephenson, MD, that would show up later, in the postop FACS, president of the American Col- results, we also want to know ahead of lege of Eye Surgeons, associate profes- time.” sor at University of South Florida Col- “Anybody that comes into our of- lege of Medicine in Tampa and CEO/ fi ce for an exam gets an aberrometry CFO of Stephenson Eye Associates. scan,” says Brock K. Bakewell, MD, “I use the IOLMaster 700, the Cassini FACS, partner at Fishkind, Bakewell and the iTrace on every patient. I also & Maltzman Eye Care in Tucson, do an OCT of the macula to make sure Ariz., and adjunct associate professor there is no pathology.” of ophthalmology at the University Samir Sayegh, MD, PhD, FACS, of Utah. “We do an OPD using the of the Eye Center in Champaign, Ill., Nidek system for aberrometry. I can also considers a meticulous workup look at that and usually tell if they’ve

34 | Review of Ophthalmology | January 2017 This article has no commercial sponsorship.

0034_rp0117_f2.indd34_rp0117_f2.indd 3434 112/22/162/22/16 10:4810:48 AMAM Samir Sayegh, MD, PhD, FACS

The UniversIOL Calculator’s database includes a vast array of lenses. It also allows surgeons to enter spherical and toric data simultaneously and features multiple computation modes, including the Hybrid function, which runs multiple formulas and selects the best one.

had myopic or hyperopic LASIK just ules affect the central cornea at all, the Barrett, the Olsen, and Warren from looking at the aberrometer. You they should be scraped two to three Hill’s new formula, the radial basis know how much spherical aberration months prior to doing your measure- function (RBF).” He says that he runs patients have, and that dictates what ments for cataract surgery,” he says. this trio of formulas on every patient. lens you’re going to put in the eye if Dr. Sayegh adds, “Once you have “If you’re trying to hit zero correction, you’re going to try and balance that for a very good assessment of the state of using those formulas is going to get the best optical outcome. the cornea with regard to astigmatism you within about half a diopter, plus or “The aberrometry is great, but you and any dryness, and you treat and minus, of your target about 90 percent obviously also need a good examina- stabilize it, then there’s no reason to of the time,” Dr. Bakewell estimates. tion at the slit lamp,” continues Dr. measure differently than with other Dr. Sayegh and colleagues have de- Bakewell, who adds that he’s had eyes. Make sure that you have a stable veloped the web-based UniversIOL some patients forget to tell him about K for a consistent reading.” Calculator (2020eyecenter.com/iol- refractive surgery performed 15 or 20 calculator/) to help make searching years ago. Use Modern, Tested Formulas for the single best formula for a given eye a thing of the past. “Everybody Stabilize the Ocular Surface Repeated measurements of a stable and their brother or sister has a for- eye facilitate good IOL power calcula- mula,” he quips. “But there are some “Anybody who’s doing cataract tions. So does the use of modern, yet that have stood the test of time. Some surgery needs to be aware of corneal tested formulas. “I look at all of the prove very effective, very consistently surface disease,” states Dr. Bakewell. data I’ve collected and run calculations over large groups of eyes.” Dr. Sayegh “Dry eye can make your biometry using multiple formulas,” says Dr. Ste- singles out the Haigis-L formula as one measurements very inaccurate. If you phenson of her next step after workup. such example. His calculator incor- get a lot of variability in your measure- She has a repertoire of formulas that porates third- and fourth-generation ments, you should put your patients she uses consistently. “Right now, I use formulas and allows the surgeon to en- on drops and tune up the corneal sur- SRK/T, Barrett, Koch and Haigis,” she ter spherical data and toric data at the face before you take their fi nal mea- says, adding that she notes she’s been same time without switching from one surements prior to cataract surgery.” using more Barrett and less SRK/T calculator to another. It also contains He adds that map-dot-fi ngerprint and Haigis lately. ranked data for every IOL manufac- surface dystrophy (anterior basement “The third- and fourth-generation tured worldwide. membrane corneal dystrophy) and formulas are the ones we should be The UniversIOL Calculator Salzmann’s nodules are two fi ndings using now,” says Dr. Bakewell. “We will guide the selection of correctly that must be addressed before doing used to run Holladay 1 and Holladay powered IOLs for any lens mod- fi nal biometry. “If Salzmann’s nod- 2. Now our standards are pretty much el, but the surgeon can override its

January 2017 | reviewofophthalmology.com | 35

034_rp0117_f2.indd 35 12/22/16 10:48 AM Cover IOLs

REVIEW Focus

recommendations. Users can also run eyes are done for you using the nea can lead to the opposite error: arti- one or multiple formulas simultane- IOLMaster after you plug in the fi cially deeper effective lens placement ously. “My calculator has a function data you have,” she notes. estimate and an overpowered IOL se- called Hybrid, were it calculates all “Hopefully, anybody who has had lection, a causative factor in myopic of them and it selects the one that is RK has already had their cataract out,” outcomes.2 the best for that particular eye,” Dr. says Dr. Sayegh, adding that he hopes “If they’ve had myopic LASIK, I’d Sayegh explains. the procedure is now “a historical aber- rather leave patients slightly myopic He adds that the Hybrid function ration that we don’t have to encounter versus hyperopic. Patients hate hyper- is important because formulas may often.” Faced with such an eye, Dr. opia. The other thing is that it’s easier demonstrate instability when applied Sayegh says he would refract it with a to correct myopia with PRK than hy- to certain diffi cult eyes. “Certain com- contact lens and then target for slight peropia,” says Dr. Bakewell. binations of Ks and axial lengths in myopia. “If you implant something and Of prior hyperopic LASIK patients, the SRK/T, for example, are unstable they’re still -3 D or -2 D and they don’t he says, “Their Ks are a tiny bit steeper. and will not give you a result that you like it, you wouldn’t want to mess with They’re read by the Lenstar or IOL- should rely on,” he explains. “So if the their cornea. What you can do is im- Master as a little bit fl atter than they eye we are looking at is in that region, plant a piggyback IOL. I think we’ll really are. For a patient with previous we exclude the SRK/T from being cal- get a few more of them in the United hyperopic LASIK, you’re going to pick culated. You can override the system States in the next few years.” a lens that suggests a slight hyperopic and say you want to use the SRK/T “We have an Orbscan for topogra- result.” anyway, but our Hybrid algorithm al- phy, and we do total axial power mea- If you do end up with a small refrac- ways chooses one formula that’s con- surements on anybody who’s had myo- tive surprise and an unhappy patient, sistent with all the published literature pic PRK or LASIK or RK,” says Dr. resist intervening too soon, says Dr. and is established to be the best in that Bakewell. “Averaging the four central Bakewell. “If you do a surgery and it parameter set.” keratometry readings from the total comes out just 0.5 D or 0.75 D on the Dr. Sayegh reports encouraging re- axial power measurements gives an farsighted side, I would let the lens refractive outcomes. “People at -15 D, average K that we run in the Barrett side in the eye for approximately three -16 D come very comfortably within formula. Since this average K is usually months, because the refraction can ±0.5 D of target,” he says. “Very often slightly fl atter than the true K readings, change in the right direction. I recently we get within ±0.25 D. The results are one must choose an IOL power that had a patient who was hyperopic after really very good. “ shoots slightly on the hyperopic side, myopic LASIK. She was +0.75 D after approximately 0.25 to 0.5 diopters. The her cataract and IOL surgery. This lady Post-refractive Surgery Eyes ASCRS calculator for post-refractive was very unhappy, and wanted me to surgery is also one of the best things to do something right away. I said, ‘No. Patients with prior refractive pro- use, but still requires some interpola- We need to wait,’ and she ended up cedures may be expecting the same tion due to the range of suggested IOL being -0.5 D three months later. So you dramatic visual improvement after powers.” don’t want to be too quick to do a PRK cataract surgery with IOL implanta- That is thought to be in part because or an IOL exchange. You really want to tion that they enjoyed after LASIK, myopic and hyperopic ablation pro- wait those three months for the lens to PRK or RK. “Prior refractive surgery cedures fl atten or steepen the cornea, settle in and see if it changes position in patients have very high expectations,” respectively, throwing off assumptions the capsular bag with healing.” says Dr. Bakewell. “You always have to about corneal power in IOL formulas tell them that even with all the formu- developed for surgically virgin eyes. Short Axial Length las we run, everything is a best guessti- Also, after myopic LASIK, IOL for- mate, and they still might come out a mulas relying on the relationship be- In eyes with short axial length the diopter wrong. If they do, I tell them tween anterior chamber depth and biggest challenge to a good refractive I won’t make them live with it. I’ll of- the steepness of the cornea to estimate outcome is that the actual implant fer them the option of exchanging the the effective lens position can errone- position may be more anterior in the lens, for example.” ously predict an artifi cially shallow lens eye than the estimated effective lens Dr. Stephenson finds both the position, leading surgeons to select an position indicates, causing calculation ASCRS calculator and the IOLMas- underpowered IOL, which plays a role of an overpowered lens and a myopic ter helpful in these eyes. “Optimiza- in hyperopic surprise. After hyperopic surprise. tions for different post-refractive LASIK, the surgically steepened cor- Dr. Sayegh believes that Hoffer Q

36 | Review of Ophthalmology | January 2017

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RP1111_FCI.indd 1 10/11/11 2:01 PM 0034_rp0117_f2.indd 38 3 4 _ r p 0 1 1 7 _ f 2 38 stants notsuitedtothelongeye. creases; inaccurateELP;andIOLcon- tion errorinformulaeasaxiallengthin- axial length;anincreaseinthepredic- obtaining anaccuratemeasureofthe comes formultiplereasons:diffi underpowered lensandhyperopicout- axial lengthcanleadtoselectionofan Long AxialLength short eyes.” I thinktheOlsenisprobablybestfor outdated. Holladay2isnotbad,but Hoffer formula,butthat’s somewhat short axiallengths.“Iusedtousethe itate towardstheOlsenformulafor this hasbeentestedagainandagain.” sistency there,whereyouknowthat thousands ofeyes,sothere’s somecon- of thosepapershas100,200ormaybe one, butdozensofpapers,andeach dence intheliterature.“There’s not in shorteyes,basedonconsistentevi- is agoodchoiceforIOLcalculation to theHybridfeaturethatwould fi is consideringaddingamini-calculator UniversIOL calculator, butDr. Sayegh Koch modificationsdirectlyintothe Surgeons cancurrentlyenterWang- Haigis andHofferQformulas,aswell. the optimizedaxiallengthusing crete Wang-Koch modifi formula tomodifyit.”Therearedis- fi not thetrueaxiallength,butmodi- ent correctivemodification:You use mulas, theysuggestyoumakeadiffer- for example,buteachofthesefor- can usetheHolladay1orSRK/T, eyes. “Ifyouhaveverylongeyes, Koch modificationoptimalforlong than movethemintofarsightedness.” er patientscomeoutatinybitmyopic -0.5 D,-0.75Doreven-1D. to shootforalensthat’s gotmaybe to givemeazeroresult. “I won’t pickalensthatisprojected eye isreallylong,”saysDr. Bakewell, . ed axiallength,andtheygiveyoua i n

d REVIEW IOL calculations in eyes with long IOL calculationsineyeswithlong Dr. Bakewellsayshetendstograv- Dr. SayeghconsiderstheWang- d |

Focus Cover Review ofOphthalmology

3 8

IOLs cations tofi I’m going | I’d rath- culty in January2017 3 “If the “Ifthe gure gure nd nd out theWang-Koch modifi calculations. calculations. the convertedALintofinalIOL the trueaxiallength,andthenfeed you’re offalittlebitinthatdirection.” -0.75 Dora-1D,becausefrequently to achieveplano,I’mshootingfor folks,” hesays.“EvenifI’mtrying power ofthelenstoputintothese mulas sometimesunderestimatethe he fudgestowardsmyopia.“Your for- AL measurementtothefovea,and Hill formulasfortheseeyesusingan sizes. HerunstheBarrett,Olsen,and in lensimplantpower,” heempha- translates tobeingoffthreediopters off onemillimeterintheaxiallength result inbigrefractiveerrors.“Being trying tomeasurethefoveacan the centerofstaphylomawhile ing evenatinybitlateralornasalto magic formulaforstaphyloma.” length is.You don’t havetouseany tion youdeterminewhatthetrueaxial also doOCT. With allofthatinforma- between thecorneaandfovea.You reliable reading.You wantthe distance yloma isandgetyouamuchmore can helpyouidentifywherethestaph- of theeye.Howsignalisbouncing but alsothewholeshapeofback That willgiveyounotjustthelength, ferent devices,andwedoaBscan. ing multiplemeasurementswithdif- interferometry; weuseultrasound,do- axial length.We usepartialcoherence main problemisgettingthecorrect lem isnotwhichformulatouse:The is,” saysDr. Sayegh.“Your mainprob- ma throwsyouoffastowherefovea ing theALchallenging.“Thestaphylo- Staphyloma tient is a successful contact lens wearer tient isasuccessfulcontactlens wearer plano inkeratoconiceyes.“If thepa- Keratoconus andPK Dr. Bakewellemphasizesthatbe- Staphylomatous eyesmakemeasur- Dr. Bakewell generallydoesn’t target cation using cation using of the cornea is what really limits their of thecorneaiswhatreallylimits their Sometimes, thedistortionat the level before theydevelopedthecataract. at thetimeofcornealtransplant, know whatthepotentialvisionwas “Post cornealtransplant,youwantto them backformeasurements,”hesays. surface ofthecorneaandthenbring tially variable.You havetostabilizethe The problemisthattheirKsareessen- matters isaneffectivereadingoftheK. for keratoconic/PKeyes,either. “What there isanall-purposeIOLformula going tobemuchmoreaccurate.” really needit.Your measurements are the cornealtransplantfi corneal transplantation.It’s bettertodo be four, sixoreightdioptersfl your keratometrymeasurementsmight your measurementscallfor, because put asteeper-powered lens in thanwhat corneal transplant,thenyou’llhaveto you’re doingcataractsurgerypriortoa you’ve alreadyfl going tohavebestronger, assuming from theireye,thenthelensimplantis ter one.Ifyou’retakingpoweraway replacing theirsteepcorneawithafl but ifyoudoacornealtransplant,you’re keratoconics haveverysteepcorneas, he says.“Intermsofcataractsurgery, astigmatism, sothey’rediffi but manytimestheyhaveveryirregular tions youjustuseyourregularformulas, cataract surgery. “Intermsofcalcula- of thesuturestobeoutbeforedoing mately ninemonthstoayearformost plant procedurefi Dr. Bakewellwilldoacornealtrans- and thecataractisnottoodebilitating, shoot forplano.” to seetheirbest.There’s noreasonto ways goingtoneedacontactinorder keratoconus issignifi enough toputtheircontactsin.If -2.5 Dto-3D.Thatletsthemseewell patients onthemyopicside,maybe surgery, Iusuallyshoottoleavethose ning onwearingcontactsaftercataract with gas-permeablelenses,andisplan- Dr. Sayeghdoesnotbelievethat If thekeratoconusissevereenough, attened their cornea. If attened theircornea.If rst, thenwaitapproxi- cant, theyareal- rst ifpatients cult eyes,” eyes,” cult atter after at- 112/22/16 10:48 AM 2 / 2 2 / 1 6

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RO0916_Volk.indd 1 8/23/16 2:42 PM 034_rp0117_f2.indd 40 40 Intraoperative Aberrometry stable refraction. on axiallength,providedthateyehasa an unaffectedfelloweyetohelpzeroin ract cases.Shealsosuggestsmeasuring ments feasibleinmostadvancedcata- 700 makesgoodaxiallengthmeasure- poor visioninthefi for patientswhocometoyouwithvery differences areminimal—especially not alwaysasreproducible,butthe it everytime:Italwaysgetsresults— ultrasound,” hesays.“Ultrasounddoes cataracts, yousometimeshavetogo systems thatpenetratemoredense new partialcoherenceinterferometry the newIOLMasterandsomeof “For theadvancedcataract,evenwith cessing healthcareatearlierstages. abroad becauseoftheirdiffi cataracts bothintheUnitedStatesand sizeable subsetofpatientswithdense Dense Cataracts can dowellwithtoricIOLs.” vision, notthecataract.Thesepatients the EyeCenterofNewYork, describes nai, andfoundermedicaldirector of York Eye&EarInfirmary ofMountSi- cal professorofophthalmologyatNew vice’s predictedoutcome. ORA eyeswerewithin±1Dofthede- error at0.35D,and94percentofthe ORA hadthelowestmedianabsolute that eyesrefractedintraoperativelywith myopic LASIKorPRKdemonstrated eyes of215patientswithahistory Haigis- L,andtheShammas)in246 culation (surgeon’s bestchoice;the with threepreopmethodsofIOLcal- Optiwave RefractiveAnalysis(ORA) challenging eyes.Researchcomparing orate orfi ne-tune IOLpowerchoicesin aberrometry canhelpsurgeonscorrob- any cataractpatients—intraoperative REVIEW Dr. StephensonsaystheIOLMaster Dr. Sayeghreportsthatheseesa Tal Raviv, MD,FACS, associateclini- For patientswithdensecataracts—or |

Focus Cover Review ofOphthalmology

rst place.” IOLs 4 culties ac- culties | January2017 Intraoperative aberrometry canconfiIntraoperative aberrometry orrefirm ne IOLpower estimates. to what ORA recommends in the OR if to whatORArecommendsinthe ORif op calculationsprepared,butwill move results. participation willyieldmoreaccurate slight movementsoftheeye.”Patient surements jumpsignifi cantly withvery explains, “onecanseethecylindermea- ing theVerifeye aphakicreading,”he tient fixation intomeasurements.“Dur- ORA, sincethedeviceincorporatespa- level areimportantconsiderationswith that surgicalapproachandsedation matism withhighaccuracy.” Headds geon toneutralizetherefractiveastig- tism oftheseeyes.ORAallowsthesur- the trueanteriorandposteriorastigma- measurement canperfectlymeasure quire atoricIOL,andnopreoperative uncommon forpost-LASIKeyestore- in somestudies.Furthermore,itisnot has beenshowntobemoreaccurate Raviv continues.“However, usingORA available ontheASCRScalculator,” Dr. ‘no-history’ IOLcalculationmethods keratoconus, andpost-refractiveeyes. very longaxiallength,mildtomoderate able fortoughbiometrycasessuchas intraoperative aberrometryas“invalu- Dr. Stephenson goesinwithherpre- “In 2016wehavesomeverygood refractive surgery. 2014;121:1:56-60. Ophthalmology afterpriormyopic calculation for predictingintraocularlenspower 4.Ianchulev org.10.1155/2016/1917268. Accessed December9, 2016. Ophthalmol 2016(2016):Article ID11917268, 7pages. formulasforhighlymyopiceyes. calculation power Journal 3. Zhang Y, LiangXY, LiuS, etal. Accuracy ofintraocularlens after refractivesurgery. IntOphthalmolClin2016;56:2:171-182. 2.Patel RH, KarpCL, Yoo SH, Amescua G, Galor A. surgery Cataract lens. Ophthalmol1996;40:4:279-292. Surv DJ,1.Apple SimsJ. HaroldRidley and theinventionofintraocular AMO. for AMO.Dr. Ravivisaconsultantfor disclosures. Dr. Bakewellisaconsultant Alcon. Dr. Sayeghreportsnofi speakers’ bureauforCassiniandORA/ will bebestforthepatient.” tion andmakeadecisionthatyouthink have tolookatthegestaltofsitua- sometimes therearesurprises,andyou you want,”saysDr. Stephenson,“but tion andwell-being.“You can planall a moreimmediategoal:patientsatisfac- surgeons implantchallengingeyeswith to thelong-termgoalofemmetropia, operatively,” shesays. err onthesideofwhatittellsmeintra- reference some550,000cases,andI’ll there isadiscrepancy. “TheORAcan Dr. Stephensonisamemberofthe As IOLimplantationinchescloser T, HofferK, Yoo SH, etal. refractivebiometry Intraoperative nancial nancial http://x.doi.

12/22/16 10:48 AM Cynthia Matossian, MD, FACS MD, Matossian, Cynthia A PUBLICATION BY

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2017_retinaspecialist_housead.indd 1 12/14/16 3:26 PM IOLs REVIEW Cover Focus Minimizing Your IOL Chair Time

Jeffrey S. Eisenberg, Contributing Editor

Ways to educate n 2010, an estimated 24.4 million But, how do you accomplish this individuals had cataracts, accord- and still have enough time left over patients about Iing to the National Eye Institute— to actually perform the surgery? Here and the number is expected to rise to are some suggestions. their myriad some 38.7 million by 2030. Market Scope expects intraocular lens pro- In the Mail options—and still cedures to climb from roughly 24.4 million globally in 2015 to nearly 30 You don’t need to wait until the have time left over million in 2020 at a compounded an- patient is in the exam lane—or even nual rate of 3.6 percent. And, accord- in the offi ce—to begin the education to operate. ing to the ASCRS 2016 Clinical Survey, process. You can send the patient and the average annual cataract volume family members introductory letters continues to rise and now stands at 512 and brochures that provide informa- a year per surgeon. tion about your practice and intro- And that’s not counting IOL produce cataract surgery and IOLs to the cedures other than cataract. “We’re patient ahead of time. Don’t forget probably going to see more interest to include some information on your in presbyopic lens exchange because practice’s website as well. surgeons are getting more comfortable “This information gives the patient with newer technology and its avail- and his family the chance to begin un- ability,” says R. Bruce Wallace III, of derstanding what will occur during his Alexandria, La. cataract evaluation and what will be Just as the number of cataract pa- discussed when they come to the of- tients has risen, so too have the IOL fi ce,” says James Loden, MD, of Nash- options you can offer these patients. ville, Tenn. “One of our primary responsibili- Another item to send patients in ties as eye surgeons today is to help advance: a lifestyle survey such as guide patients through a dizzying ar- the Dell questionnaire (developed by ray of new technology,” says Michael Austin, Texas, surgeon Steven Dell Colvard, MD, of Encino, Calif. “Our in 2004). The questionnaire should goal should be to help patients select ask about the patient’s preference for the specifi c technology that best meets achieving distance or near vision with- their needs and expectations, and you out glasses, what activities the patient can’t do this by simply giving patients a engages in and for which he would be mind-boggling laundry list of options.” willing to wear glasses, whether issues

42 | Review of Ophthalmology | January 2017 This article has no commercial sponsorship.

0042_rp0117_f3.indd42_rp0117_f3.indd 4242 112/22/162/22/16 12:3812:38 PMPM such as glare would bother him, and them their options and discuss pricing. even how the patient sees his or her This brings up two additional points. own personality. First, think of the referring optom- “By the time I see patients, they’ve etrist as part of your team. “One of the given some thought as to their desire values of having referring optometrists for spectacle independence,” says is that they know the personality traits Daniel H. Chang, MD, of Bakersfi eld, of the patient better than we do,” Dr. Calif. In his questionnaire, Dr. Chang Wallace says. also asks patients if they would be will- They also know based on their own ing to pay extra if they could poten- Surgeons recommend that you think of the fi ndings who may be a good candidate tially avoid needing glasses. (Medi- referring OD as part of your team. for a premium IOL and any history care requires that you inform patients that might make the patient unsuit- prior to surgery that Medicare will not There are several keys for making able, such as a history of RK or PRK. pay for services specifi c to the inser- the patient evaluation more effi cient— And the referring optometrist can let tion, adjustment and other subsequent starting with clear guidelines and get- the patients know which options you’ll treatments related to premium IOLs ting your staff on board with those likely discuss when the patient is in and vision-correcting technology.) This guidelines. “The staff should be aware your chair. “It helps to use a group ef- gets the discussion started. of all of the lens choices and be able fort to fi nd out which patients are good Once the patient arrives at the of- to recognize potential candidates for candidates,” Dr. Wallace says. fi ce, you can continue the education certain types of lens implants based on Second, consider delegating discus- process right in your waiting room or those guidelines,” says Cory Pickett, an sions of cost to your staff. “Most of the further into the visit as patients dilate. ophthalmlic consultant in the Midland, time I try not to talk about cost,” Dr. For example, software and videos are Texas, area. Chang says. available from such companies as Ren- Mr. Pickett’s advice: Start your in- Instead, he has his surgical coordi- dia (formerly Eyemaginations) and Pa- volvement early on. For example, once nator discuss cost and financing op- tient Education Concepts—some of pretesting is done, you might review tions with the patient—another way of which let you select only those options the initial results and perform a pre- reminding him or her that premium suitable for the patient. liminary slit lamp exam, explain that IOLs aren’t covered by Medicare. Giv- the patient has cataracts and instruct en that some patients will not consider In the Offi ce the staff which follow-up tests to per- options that aren’t covered, this is a form. “It is important the surgeon puts time-saver for the doctor. Once the patient is in the exam lane, his own spin on that so it doesn’t come if you’ve had him fi ll out the Dell ques- off as robotic,” he adds. The Technology Advantage tionnaire or something similar, you’ll For example, Dr. Chang uses an eye know whether he wants distance or model to demonstrate to patients what In addition to your staff’s help, con- near vision without glasses, whether happens during cataract surgery and tinue to take advantage of diagnostic the patient is willing to tolerate a cer- what implant he or she might wish to technology to guide your exam. Just tain amount of glare, and what the pa- consider. He also uses an IOL model as IOL technology has evolved—and tient’s vocations and avocations are. that shows the difference between continues to evolve—so, too, has di- “I ask the patient: ‘In a best-case monofocal and diffractive lenses. agnostic technology. “Another way scenario, what are you hoping to In Dr. Wallace’s practice, two tech- to expedite the evaluation is by using achieve with cataract surgery?’ ” Dr. nicians who serve as IOL counselors this technology to fi nd out information Colvard says. “The answer almost al- meet with patients after he finishes quickly,” Mr. Picket says. ways is, ‘I want to see better.’ So then his examination. These counselors re- For example, Mr. Pickett recom- I ask, ‘How important is it to you to fer prospective candidates to the staff mends the OPD-Scan III Wavefront reduce your dependency on glasses?’ optometrist or perform further testing Aberrometer (Marco), which essential- This introduces the concept that there themselves to determine if any factors ly serves as autorefractor, keratometer, are possibilities beyond just better vi- might make the patients unsuitable pupillometer (up to 9.5 mm), corneal sion with glasses. And it helps me to for premium IOLs. They also review topographer and integrated wavefront understand what the patient is think- the brochures the patient was sent to aberrometer. “You get this information ing or is hoping for as an additional answer any questions the patient or quickly and have a basic idea of what benefi t to cataract surgery.” family members may have, then show the patient may be a candidate for very

January 2017 | reviewofophthalmology.com | 43

042_rp0117_f3.indd 43 12/22/16 12:39 PM Cover IOLs

REVIEW Focus

early in the evaluation,” he says. “This plain the implications, and guide the nology to correct astigmatism and im- can be used to help guide the rest of patient away from IOLs with multifo- prove vision without glasses,” adds Dr. the exam,” he says. cality. Macular degeneration, epireti- Colvard. To narrow down in advance which nal membranes—any kind of macular lenses might be appropriate for the pa- pathology—will reduce the patient’s Invest the time tient, look at the information you have contrast sensitivity.” in hand, including: • Corneal topography. Research Obviously, the IOL selection process • Ocular surface health. Blurred has shown that toric IOLs provide bet- involves a lot of information for the vision postop and ocular surface issues, ter uncorrected vision, greater spec- patient to assimiliate. “It’s sometimes often the result of pre-existing dry eye, tacle independence, and lower residual a lot for doctors to assimilate, too,” Dr. are among the major causes of patient astigmatism than non-toric IOLs, even Loden says. dissatisfaction after an implant with a with relaxing incisions.1 Accept that you’ll need to spend multifocal IOL. “If they have keratitis “If the corneal map shows -2 D of more time than you did 10 years ago, present, with dry eyes, and/or meibo- astigmatism, I’ll only talk toric lens- when there were fewer options. But, mian gland dysfunction, this must be es,” Dr. Loden says. “So it narrows my in those extra minutes, you’ll be able treated before considering a multifocal choices down before I even come in. If to satisfy the patient’s visual needs and IOL,” says Dr. Colvard. “If the fi ndings the eye looks healthy and patient says, grow your practice—more than you persist despite treatment, I try to lead ‘I’m interested in these options,’ then might have been able to do with stan- patients away from multifocal IOLs.” we go into the lenses.” dard monocular IOLs several years • Macular health. “The fi rst thing Dr. Colvard discusses toric IOLs if ago. “You’d have to do five cataracts I consider when I begin to review op- the patient has more than -1 D of astig- minimum to make up that difference,” tions with the patient is the presence matism. “If the patient has an astig- Dr. Loden says. or absence of macular pathology,” Dr. matic error greater than -1 D, I explain 1. Kessel L, Andresen J, Tendal B. Toric intraocular lenses in the Colvard says. “If macular issues ex- the signifi cance of this and explain that correction of astigmatism during cataract surgery: A systematic ist, I show the patient the OCT, ex- we have two options with new tech- review and meta-analysis. Ophthalmology 2016;123:2:275-86.

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042_rp0117_f3.indd 44 12/22/16 12:39 PM RP0815_Lombart.indd 1 7/21/15 10:07 AM IOLs REVIEW Cover Focus Surgeons Tune in To the Symfony

Walter Bethke, Editor in Chief

New technology s recently as last year’s intra- dresses astigmatism as well as depth ocular lens e-survey, cataract of focus. may encourage Asurgeons seemed hesitant to In addition to documenting their embrace presbyopic IOLs whole- outlook on presbyopic lens options, surgeons to give heartedly, and, in their survey com- surgeons responding to this month’s ments, would often say that their IOL survey also shared their opinions premium IOLs a interest in the devices might be high- on topics such as the most important er if some different technology came features for an IOL to have, toric IOLs second look. along. Even though it’s only the re- and managing complications of IOLs sponses from one questionnaire, if this that require a secondary procedure to month’s IOL e-survey is any indication suture-ﬁ xate the lens. This month, the surgeons may have found that differ- e-mail survey was opened by 1,089 of ent technology in the form of the Ab- 8,171 subscribers to Review’s e-mail bott Symfony IOL. The arrival of this service (13.3 percent open rate) and, new lens appears to have rekindled of those, 74 shared their responses. To surgeons’ interest in giving patients a see how your opinions on IOLs com- wider range of vision via an IOL, with pare with theirs, read on. the reasons for their renewed interest ranging from the possibility 0f a lower Growing Interest rate of qualitative vision problems to the simple fact that the Symfony ad- In last year’s IOL survey, surgeons

Surgeons’ Likelihood of Using a Presbyopic IOL in Two Years

2015 48 2016 38 29 24 % 16 24 12 10

Very likely Somewhat likely Unlikely Very unlikely

46 | Review of Ophthalmology | January 2017 This article has no commercial sponsorship.

0046_rp0117_f4.indd46_rp0117_f4.indd 4646 112/22/162/22/16 12:3212:32 PMPM didn’t have high The First Presbyopic IOL Surgeons Are Most Likely to Try might implant hopes for presby- the Symfony. opic lenses: 38 per- 56 “I’d like to try cent characterized this new lens themselves as un- and see if the likely to use a pres- results are satis- byopic IOL within % factory,” he says. 19 two years, and 29 15 “Also, I’d like to percent said they see if the side 7 were very unlikely 4 effects are less.” to do so (for a total As for the of 67 percent in the AMO Tecnis AMO Tecnis Alcon Alcon Crystalens surgeons who negative). Only 24 Symfony Multifocal ReSTOR 2.5 D ReSTOR 3 D AO currently use percent said they presbyopic lens- were somewhat likely to try them, and high risk of vision threatening retinal es, 34 percent are satisfi ed with their just 10 percent were very likely. complications.” lens, and 27 percent are very satis- This year, however, things have Though the overall numerical refi ed. Thirty-seven percent say they’re nearly flipped, with 48 percent of sults were positive, many of the sur- somewhat satisfi ed, while 2 percent surgeons saying they’re somewhat geons who described themselves as are unsatisfi ed. likely to try presbyopic lenses and somewhat likely to use a presbyopic “They’re not great, but they’re all 16 percent saying they’re very likely lens maintained a guarded outlook we have,” says a surgeon from Mary- (putting 64 percent of the respon- on the devices. “There are still un- land who implants the ReSTOR and dents in the positive camp). Twelve answered questions about the night- the Tecnis multifocal. “There is a loss percent describe themselves as un- driving qualities of these lenses,” says of contrast sensitivity, and we must likely to try the lenses, and 24 per- a surgeon from Kansas. screen patients carefully prior to use. cent say they’re very unlikely. “The A surgeon from Ohio is thinking These lenses can only be used in a presently available multifocal IOLs along the same lines. “I hesitate to small percentage of patients. We need have too many problems with visual use a lens that can decrease a patient’s a lens that mimics the natural lens in aberrations and quality of vision,” best potential visual acuity,” he says. “I design.” says Nick Mamalis, MD, director of also hate to risk problems with glare Sid Moore, MD, of Macon, Ga., the Intermountain Ocular Research and halos. If a patient has a high pri- agrees that this sort of lens would be Center at the University of Utah’s ority for being spectacle-free, I will helpful. “A true accommodative lens Moran Eye Center. “The ‘accommo- use them. Otherwise, I hate to leave would be hugely benefi cial,” he says. dating’ IOLs do not really accommo- patients with a lens that could impair “Optical compromises with multifo- date. I’m interested to see how the their best corrected visual acuity and cals make predicting patient satisfac- extended depth of focus IOLs work glare for the rest of their, hopefully, tion diffi cult.” out and will consider using them in many years of future life.” A surgeon from Maryland who’s the future.” A retina surgeon who When asked which lens in particu- begun implanting the Symfony lens chose to remain anonymous says he’s lar they might like to try if they’re says that he’s had a positive experi- very likely to use a presbyopic lens not yet performing presbyopic lens ence so far. “I love the new Symfony in the coming year, but he has reser- surgery, 56 percent of the respon- lens,” he says. “Minimal halos, great vations. “I understand the Symfony dents chose the Symfony. Nineteen optics. Patients say they have never lens may have less effect on contrast percent named the Tecnis multifo- seen like this before. I’d love it to sensitivity; I’ll research this and, if cal and 15 percent said the ReSTOR have a little more reading vision and this is the case, I feel it may be a good 2.5 D. (The rest of the results appear would also like to have better IOL option,” he says. “Additionally, I feel in the graph above.) “The Symfony formulas to improve outcomes.” Jon that surgery for ‘dysfunctional lens has a longer range of focus and a wider Weston, MD, of Roseburg, Ore., says syndrome’ in the presence of clear central zone,” explains a surgeon from he’s developed a way to deal with any lenses should be accompanied by full Oregon who says he most likely would near issues with Symfony. “I’ll mix a and complete disclosure that cata- try the Symfony. “Also, it takes the Tecnis multifocal with a Symfony if ract surgery in young patients—es- patient’s astigmatism into account.” A sharper vision for shorter working pecially males—is associated with a surgeon from Michigan also says he distances is needed,” he says.

January 2017 | reviewofophthalmology.com | 47

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REVIEW Focus

Surgeons Rank the Features of IOLs Complications In another section of the survey, sur- Toric design 4.5 geons say there are times when im- Asphericity/neutral asphericity 4.2 Edge design to decrease PCO 3.8 plantations don’t go as well as hoped, Multifocality/bifocality 3.8 and intraocular lenses need to be Blue-light blocking 2.8 sutured in place in order to remain Pseudo-accommodative motion 2.6 stable. Fifty-four percent of the respondents, though, say that this is rare, Surgeons on the survey ranked IOL features in terms of their usefulness using a numerical and they don’t need to do it in a given scale that ran from 1 (least useful) to 6 (most useful). The average scores are shown. year. Forty-four percent, however, say Lens Design they usually need to suture a lens one cent say it’s good. Fifty-seven percent to three times per year, and 2 percent Surgeons also took a look at the of the surgeons use the AcrySof toric have to do it four to six times. various elements of IOL design, com- for most of their cases, and 33 per- Surgeons also described various sce- menting on which ones they preferred. cent use the Tecnis toric. Eight percent narios that called for suturing. “Su- In terms of monofocal IOLs, 51 use the Symfony. “Toric IOLs provide turing was performed for a dislocated percent of the respondents say they excellent vision and have been a real IOL within the capsular bag or for a use the Alcon IQ Aspheric for most of advance in the treatment of patients case of poor zonular support,” recounts their cases, and a third prefer the AMO with cataracts and astigmatism,” says Dr. Mamalis. A surgeon from Montana Tecnis one-piece lens. The rest of the Dr. Mamalis. Ron Glassman, MD, of says his suturing was a result of “pseu- lenses were chosen by less than 5 per- Teaneck, N.J., agrees, saying, “This is doexfoliation and a dehisced capsular cent of surgeons. Eighty-fi ve percent the way to treat astigmatism.” bag,” for which he sutured the lens to of them think acrylic is the best mate- Some surgeons on the IOL survey, the iris, adding he’ll suture it “rarely to rial, with 7 percent preferring silicone. however, are more reserved in their the sclera.” Surgeons also ranked specifi c IOL praise for toric lenses, noting that, Juan Nieto, MD, of Dubuque, Iowa, features, such as toric correction or though they’re useful in many cata- says his complicated IOL suturing cas- multifocality/bifocality, on a scale of ract cases, they can still have some es usually involve “poor or no capsular one to six, with six being most impor- issues, as well. “Often, there’s astig- support” and that he’s “comfortable su- tant. (A graph of all the rankings ap- matism that’s unaccounted for in the turing to the iris or glueing it to/tucking pears above.) Toric design, with an preop calculations,” says a surgeon it into the sclera.” An ophthalmologist average rank of 4.5, was thought to from Michigan. “Also, the lens often from Kansas says there’s one surgeon at be most important, followed closely rotates at the last second when trying his practice who performs all the chal- by asphericity/neutral asphericity at to remove the viscoelastic.” A surgeon lenging cases requiring IOL suturing. 4.2. Pseudo-accommodative motion, at from Maryland says, “It’s diffi cult for “He uses mostly an intrascleral fi xation 2.6, was thought to be least important. the patient to go back to the OR if I approach for them,” he says. “He does “The optics are the most important need to rotate the lens; we also need fewer cases using either polypropylene part of any lens,” avers Bruce Cohen, a better system to ensure alignment suturing to the iris, or Gore-Tex sutur- MD, of St. Louis. A surgeon from in the OR.” ing to the sclera.” Montana says he doesn’t have a lot of confi dence in multifocality/bifocality, saying, “Premium lens patients are a Surgeons’ Annual Frequency of Suturing an IOL pain if they have the least little com- plaint after paying extra out of pocket.” 56 A surgeon from Maryland also doesn’t think highly of this approach to pres- 44 byopia. “Right now,” he says, “it seems better to correct presbyopia on the % cornea than within the lens.” As the rankings suggest, surgeons are very impressed with toric IOLs. 2 00 Fully 65 percent of surgeons rate toric performance as excellent, and 31 per- Zero times 1-3 times 4-6 times 7-10 times > 10 times

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REVIEW News (Continued from p. 4) In data released by Ophthotech, therapy lost fi ve or more letters from “Despite these exciting fi ndings, patients receiving Fovista combo ther- baseline at one year, compared to 11.2 there are a few limitations to this sys- apy gained a mean of 10.24 letters at percent of patients receiving Lucentis tem,” Dr. Peng notes. “The algorithm 12 months compared to a mean gain alone. In OPH1002, 12 percent of may not perform as well for images of 10.01 letters for patients receiving patients receiving the combination with subtle fi ndings that a majority of Lucentis monotherapy. In OPH1002, lost fi ve or more letters at month ophthalmologists would miss. Another consisting of 619 patients, combo-ther- 12, compared to 12.3 percent of limitation arises from the nature of apy patients gained a mean of 10.74 patients receiving Lucentis. And in deep networks, in which the neural letters at 12 months, compared to a OPH1003, 12.2 percent of patients network was provided with only the mean gain of 9.82 ETDRS letters in receiving the Fovista combination image and associated grade, without Lucentis-only patients. In OPH1003, lost fi ve or more letters at a year, explicit defi nitions of features (micro- consisting of 626 treated patients, sub- compared to 10.2 percent of the Lu- aneurysms, exudates). Because the jects receiving combo therapy gained a centis patients. net work ‘learned’ the features that mean of 9.91 letters at 12 months vs. Samir Patel, president of Oph- were most predictive, it is indeed possi- a mean gain of 10.36 ETDRS letters thotech, expressed his disappointment ble that the algorithm is using features in patients receiving Lucentis mono- in the results in a conference call fol- previously unknown to or ignored by therapy. None of these results of the lowing the release of the data. “We are humans. Understanding which fea- pre-specifi ed primary effi cacy analysis in the process of analyzing the data in tures are used to make predictions will were statistically signifi cant, the re- order to better understand this out- be an important area of investigation searchers say. come,” he said. “We are most disap- for further studies, and is indeed an ac- In a pooled data analysis, 12.1 per- pointed by these results—especially tive area of research within the larger cent of patients receiving combo for patients.” machine-learning community.” News Briefs Fovista Fails to • BromSite now available. Sun Pharma recently made the non-steroidal anti-infl ammatory drop BromSite available for sale. Approved in April 2016 by the FDA, BromSite (brom - Meet Phase III fenac ophthalmic solution) 0.075% has unique labeling: It’s the fi rst NSAID approved for the actual prevention of ocular pain that follows cataract surgery, as well as the postop- Endpoint erative treatment of infl ammation. Sun also notes that it’s the fi rst bromfenac ophthalmic solution formulated in DuraSite, a polymer-based drug delivery system used to improve Hot on the heels of apparently positive drug solubility, absorption, bioavailability and residence time. The product will be marketed data from its Phase IIb trial, the by Sun Ophthalmics. platelet-derived growth factor drug In terms of safety, the company notes that, like other NSAIDs, there is a potential for cross- Fovista (Ophthotech) didn’t provide sensitivity with BromSite, and the potential for increased bleeding time of ocular tissue due the visual acuity benefi t that was aimed to interference with platelet aggregation. In addition, Sun notes that BromSite should not be administered while a contact lens is in the eye, as soft lenses may absorb the drug’s preserva- for in its pivotal Phase III study. tive, benzalkonium chloride. The Phase III Fovista clinical trials, Regarding adverse events, the most commonly reported adverse reactions, occurring in 1 to 8 OPH1002 and OPH1003, were in- percent of patients, were anterior chamber infl ammation, headache, vitreous fl oaters, iritis, eye ternational, multicenter, randomized, pain and ocular hypertension. double-masked, controlled studies For more information on the new NSAID, visit bromsite.com. evaluating 1.5 mg of Fovista adminis- • New swept-source OCT approved. Carl Zeiss Meditech says its newly approved PLEX Elite tered in combination with Lucentis, an 9000 offers swept-source OCT posterior ocular imaging. The company claims that the new OCT approach dubbed “Fovista combina- imaging method will expand the potential for researchers to easily diagnose diseases affecting tion therapy,” compared to Lucentis the retina. ZEISS highlights the wide-fi eld, high-resolution visualization provided by the new imaging of injection alone, for the treatment of the PLEX Elite platform, allowing clinicians to examine microstructures and microvasculature at wet age-related macular degeneration. any depth, from vitreous to sclera. Zeiss says the examination of these microstructures offers In each trial, patients were random- researchers the potential to explore the progression of retinal and choroidal pathology, to study ized to one of two approximately equal choroid physiopathology, and to evaluate how the retina and choroid respond to therapy. sized treatment groups. The two Phase ZEISS notes that the new PLEX Elite 9000 will have a limited release for use as a research III trials enrolled 1,248 patients with tool. wet AMD. For more information on ZEISS’ new OCT, visit zeiss.com.

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

The Clinical Utility of OCT Angiography Retina specialists experienced in OCTA discuss the strengths— and the limitations—of this promising new technology.

Eduardo Novais, MD, Sao Paulo, Brazil, and Caroline Baumal, MD, Boston

he retinal and choroidal vascula- OCTA Explained rately for each sub-spectrum, which T ture can be the site of pathology in improves the signal-to-noise ratio.7 many ocular diseases, and dye-based OCTA is a noninvasive imaging Doppler OCT is a phase-based tech- angiography has been the gold stan- modality that allows for detection of nology from which OCTA has its ori- dard diagnostic test for assessing blood fl ow and three-dimensional re- gins.8,9 It can quantify axial blood fl ow vascular disorders such as choroidal construction of blood vessels using that’s parallel to the direction of the neovascularization, retinal vascular oc- signal decorrelation between consecu- imaging acquisition device.7,10,11 clusion, diabetic retinopathy, macular tive transverse cross-sectional OCT In addition, it’s possible to view telangiectasia and central serous cho- scans. An OCTA image is computed OCTA images in tandem with the rioretinopathy.1,2 Though dye-based by comparing, on a pixel-by-pixel basis, corresponding structural en face and approaches such as fl uorescein angi- repeated B-scans acquired at the same cross-sectional OCT B-scans. This ography and indocyanine green angi- retinal location in rapid succession. allows the correlation of clinical and ography allow for direct visualization The rationale behind OCTA imaging is structural features of retinal and cho- of the dynamic properties of vascular that in non-mobile tissue the refl ected roidal diseases with microvascular fea- fl ow such as leakage, pooling or stain- signal will be stationary, and thus the tures seen on OCTA. ing, they’re not without limitations: repeated B-scans will be identical. Visualization of small vascular details Inside vasculature, however, moving OCTA for Vascular Disease can be difficult, since they may be- erythrocytes cause a time-dependent come obscured due to late-phase dye backscattering of the OCT signal, The retinal capillary network is ar- leakage. Furthermore, dye-based tests which manifests as differences among ranged into morphologically distinct are time-consuming, require intrave- the repeated B-scans.4-6 layers. The superfi cial retinal capillary nous access and have the potential for Basically, OCT angiograms of the plexus is located predominantly within systemic side effects, including rare posterior pole can be obtained by using the ganglion cell layer; and the deep reports of anaphylaxis.3 Optical coher- one or a combination of two method- retinal capillary plexus is located at the ence tomography angiography is a nov- ologies: amplitude decorrelation and outer boundary of the inner nuclear el imaging technique that may be able phase-variance. Amplitude decorrela- layer, with a smaller intermediate reti- to overcome some of the limitations tion analyzes amplitude changes in the nal capillary plexus at the inner margin of dye-based approaches —though it OCT signal. Split-spectrum amplitude of the inner nuclear layer. The vascular has some limitations as well. In this decorrelation partitions the spectrum layers of the retina are connected by article, we’ll discuss the clinical utility into smaller spectra and performs the perpendicularly positioned vessels.12 of OCTA. repeated B-scan decorrelation sepa- With the ability to analyze each vas-

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REVIEW Insider

cular plexus separately, OCTA A B Figure 1. Multimodal imaging of a has become an important tool 65-year-old patient with moderate for studying retinal vascular dis- non-proliferative diabetic retinopathy. eases such as MacTel, RVO, DR (A) Color photograph shows intraretinal blot-dot hemorrhages and and others. For example, OCTA microaneurysms. (B) Yellow-dashed was used to demonstrate that the frame identifi es the corresponding superfi cial and deep retinal cap- 3x3-mm area imaged on OCTA. (C) illary plexuses may be affected OCTA segmented at the superfi cial differently by retinal vascular dis- retinal plexus shows an enlarged eases such as retinal artery and foveal avascular zone (FAZ). vein occlusion.13-15 Microaneurysms can also be easily Another advantage of OCTA identifi ed (yellow arrow). (D) OCTA is its superior ability to precisely segmented at the deep retinal plexus shows further enlargement of the FAZ. delineate the vessels surround- (E) and (F) represent ing the foveal avascular zone (See corresponding OCT B-scan Figure 1). In contrast, perifoveal segmentation of the superfi cial and leakage of fluorescein dye may deep plexuses, respectively, with blur the FAZ margins, and FA is decorrelation signal overlay. limited to primarily delineating the superficial vascular plexus. Increased FAZ size has been cor- related to reduced visual acuity prog- tion of OCTA. Microaneurysms on used to determine the location of the nosis in eyes with retinal vascular dis- FA may also correspond to capillary CNV, its morphology and its response ease.16 A recent study demonstrated loops or preretinal neovascular tufts to anti-VEGF therapy. As a baseline, in that the perifoveal intercapillary area on OCTA.21 a normal eye the “outer retina” OCTA on OCTA appears to increase in size scan segmenting between the outer as the level of diabetic retinopathy pro- OCTA for Chorioretinal Disease plexiform layer and Bruch’s membrane gresses.17 Also, neovascularization of will be devoid of signal, as there’s no the optic nerve, which can occur in Evaluation of CNV using OCTA is vascular flow in this layer. However, proliferative DR and ischemic reti- one of the most important applications this may not be the case in eyes with nopathy, can be easily detected using of this modality.4,22,23 OCTA can be CNV. OCTA by viewing the inner reti- Figure 2. Multimodal imaging of a na/optic nerve surface at the most 60-year-old patient with 18 superfi cial level (See Figure 2). superotemporal branch retinal vein It’s been hypothesized that occlusion. (A) Color photograph shows OCTA may show retinal micro- neovascularization of the disc. (B) circulation impairment in the Late-phase FA shows macula prior to the development hyperfl uorescence of the optic nerve of retinopathy.19 One study dem- due to neovascularization leakage. onstrated that diabetic individuals Optical coherence tomography angiography of the vitreous (C) and without clinical evidence of dia- optic nerve head (D) demonstrates betic retinopathy have larger FAZ some well-delineated, fi ne, abnormal sizes as well as FAZ remodeling vessels. (E) and (F) represent and subtle capillary non-perfu- corresponding OCT B-scan sion compared to normal, non- segmentation of the optic nerve head diabetic control eyes.20 Microan- and vitreous. The yellow arrow points eurysms imaged with FA may not to the presence of the decorrelation always be apparent on OCTA. signal on the vitreous interface, This may result from stagnant indicative of neovascularization fl ow. erythrocytes blocking fl ow, or the fl ow in the microaneurysms may be below the threshold of detec-

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051_rp0117_rtinsider.indd 52 12/21/16 4:35 PM graded it according to the presence or absence of the following features: well-defined CNV; presence of tiny capillaries; presence of anastomoses and loops; morphology of the vessels termini as opposed to a “dead tree” aspect; and presence of a hypo- intense halo surrounding the CNV. They found a 95-percent agreement between OCTA and the traditional multimodal imaging protocol for a “treatment required” decision in eyes with at least three out of the fi ve features. There was a 91-percent agreement for “treatment not required” when patients presented with fewer than three features.24 Depending on the clinical presen- Figure 3. Multimodal imaging of a 63-year-old patient with choroidal neovascularization tation, OCTA’s sensitivity to visualize secondary to central serous chorioretinopathy. (A) Color photograph shows a subretinal abnormal vascular networks may vary. hemorrhage at the center of the macula surrounded by retinal pigment epithelium clumps. When massive hemorrhage, exudate Early (B) and late-phase (C) fl uorescein angiography show leakage from CNV. (D) and (E) or fibrotic tissue is present, OCTA represent corresponding OCT B-scan segmentation of the outer retinal and signals can be blocked, limiting visu- choriocapillaris, respectively. Yellow arrowheads point to the decorrelation signal below the RPE detachment suggestive of CNV. (F) OCT angiogram segmented at the level of the outer alization of CNV. Because CNV sec- retina reveals CNV. (G) OCT angiogram segmented at the level of the choriocapillaris. The ondary to chronic CSCR and myopic yellow arrow highlights the hypo-intense halo surrounding the CNV. CNV are rarely associated with large subretinal hemorrhages that limit penetration of the OCT signal, the There are different CNV morphol- dusa”) (Figure 3). Recently, research- abnormal vascular network may be ogies on OCTA, but the clinical rel- ers analyzed OCTA patterns of CNV identifi ed with a screening OCTA in evance of this is yet to be determined. and their potential correspondence to such cases. CNV can be identified as several quiescent and progressive CNV char- Choroidal neovascularization can small filamentous vessels that form acteristics seen on multimodal imag- be classifi ed according to the abnor- anastomoses (known as “seafan” or ing (FA, IGCA and spectral-domain mal vascular plexus location in various “lacy-wheel”), or as vessels associated OCT). In this study, the investiga- retinal and choroidal layers: below the with a central trunk of vessels (“Me- tors imaged CNV using OCTA and retinal pigment epithelium (type 1 CNV); above the RPE (type 2 CNV); and intraretinal (type 3 CNV). On OCTA, CNV classification depends on where the evidence of a vascular decorrelation signal is located. It can be located immediately above the RPE (type 2 CNV), and between Bruch’s membrane and the RPE (type 1 CNV).24 Since there can be OCT signal attenuation from the RPE- Figure 4. Multimodal imaging of a 54-year-old patient with branch retinal vein occlusion 25,26 of the inferior temporal arcade. (A) Color fundus photography shows non-perfused vessels Bruch’s membrane complex, it’s and hyperpigmented laser scars on the inferior temporal retina. (B) Fluorescein possible that visualization beneath the angiography. Yellow-dashed frame identifi es the corresponding 6x6-mm area imaged on RPE may infl uence the type 1 CNV optical coherence tomography angiography. White asterisks denote an ischemic retina not identification. Thus, differences in captured due to the small-fi eld coverage. (C) En face OCTA segmented at the superfi cial signal penetration may play an impor- retinal plexus shows a non-perfused area of the retina temporal-inferior to the fovea. tant role in this imaging modality.

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REVIEW Insider

SD vs. SS OCTA for CNV peated at least twice at each position periphery of the fundus. OCTA is a in a volumetric raster scan. However, promising technology, however, as it al- There are currently three FDA-ap- since the number of cross-sectional lows simultaneous assessment of both proved OCTA systems. Two of them OCT scans is limited by the scanning structural and vascular fl ow. OCTA is use a spectral-domain platform operat- speed of the instrument, a larger fi eld also safer, faster, more easily repeated ing at ~840-nm wavelength. The third of view will have reduced density and and more comfortable for the patient uses swept-source OCTA technology resolution. than dye-based angiography, and it with a longer ~1050-nm wavelength OCTA is prone to several artifacts may provide more detailed informa- and is in limited commercial release in during acquisition or post-acquisition tion about blood flow in retinal and the United States. It’s possible that SS- image processing. In order to inter- choroidal vasculature. The ability to OCTA may be less affected by ocular pret OCTA images, it’s necessary to be rapidly obtain images of vascular plex- opacity and allow a deeper penetration aware of the potential image artifacts uses and assess the integrity of retinal into the choroid.25-28 that can occur so as not to interpret and choroidal perfusion should prove SS-OCTA also has less variation in these as part of the actual anatomy. invaluable as a screening and diagnos- sensitivity with depth (sensitivity roll- OCTA works by detection of erythro- tic strategy for chorioretinal disorders. off) compared to SD-OCTA. In SD- cyte motion, so any extraneous move- OCTA, the imaging system is most ment during the image-capturing sensitive to signals coming from re- process may result in motion artifacts, Dr. Novais is a retinal specialist in fl ectors close to what is known as the which appear as white or black lines the department of ophthalmology at zero-delay line; as a refl ector is moved in the flow angiograms, and/or mis- the Federal University of São Paulo in away from the zero-delay, the system alignment of the retinal vasculature. Brazil and was, until recently, a post- becomes less sensitive to the back-re- Additionally, superfi cial vessels may er- doctoral research fellow at the New fl ected signals.29 This sensitivity roll-off roneously appear in segmented views England Eye Center at Tufts Medi- is due to the limited spectral resolu- of deeper layers, such as the outer cal Center. Dr. Baumal is an associate tion of the spectrometers that are used retina and choriocapillaris.32 These professor of ophthalmology at Tufts in SD-OCTA systems. In contrast, are termed “projection artifacts,” and University School of Medicine in Bos- SS-OCTA systems don’t use spectrom- may lead to incorrect diagnosis if not ton. She may be reached at the New eter-based detection. Instead, in SS promptly identified (i.e., the retinal England Eye Center at Tufts Medical systems, it’s the instantaneous line- vessels’ projection may be misinter- Center, 800 Washington St, Box 450, width of the swept light source, along preted as CNV). Boston, MA 02116. Email: cbaumal@ with the analog-to-digital acquisition Another issue is that commercially tuftsmedicalcenter.org, phone: 617- rate, that determine the sensitivity available OCTA devices are currently 636-7950 or fax: 617-636-4866. roll-off of the system. This difference expensive, although this may change The authors have no fi nancial inter- enables SS-OCTA systems to have im- as the technology becomes more com- est in any of the products mentioned. proved sensitivity roll-off compared to mon. Also, there is currently no code 30 1. Stanga PE, Lim JI and Hamilton P. Indocyanine green SD-OCTA systems, which improves beyond the standard OCT imaging angiography in chorioretinal diseases: Indications and inter- visualization of the choroid both on code with regards to reimbursement. pretation: An evidence-based update. Ophthalmology 2003; 110:15-21;quiz 22-13. cross-sectional as well as en face OCTA Finally, in terms of utility, while OCTA 2. Spaide RF, Klancnik JM, Cooney MJ. Retinal vascular layers imaged by fl uorescein angiography and optical coherence imaging, and may also improve visual- provides additional clinical information tomography angiography. JAMA ophthalmology 2015;133:45-50. ization of CNV, especially the sub-RPE for the practitioner, such as noninva- 3. Ha SO, Kim DY, Sohn CH, Lim KS. Anaphylaxis caused by 31 intravenous fl uorescein: Clinical characteristics and review of component of the membrane. sive identifi cation of CNV and retinal literature. Intern Emerg Med 2014;9:325-330. 4. de Carlo TE, de Carlo TE, Bonini Filho MA, Chin AT, et al. vascular abnormalities, its usefulness Spectral-domain optical coherence tomography angiography of Limitations of OCTA with regards to therapeutic monitoring choroidal neovascularization. Ophthalmology 2015;122:1228. 5. Jonathan E, Enfi eld J, Leahy MJ. Correlation mapping is unclear. method for generating microcirculation morphology from optical There are some limitations to OCTA FA and ICGA demonstrate the dy- coherence tomography (OCT) intensity images. J Biophotonics 2011;4:583-587. imaging in its current configuration. namic properties of dye within vascular 6. An L, Wang RK. In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography. One drawback is its restricted fi eld of networks, such as leakage in disorders Optics express 2008;16:11438-11452. view (See Figure 4). The automated that produce vascular incompetence 7. Jia Y, O Tan, J Tokayer, et al. Split-spectrum amplitude- decorrelation angiography with optical coherence tomography. scan protocols that are currently avail- and exudation, and dye-based angiog- Optics Express 2012;20:4710-4725. 8. Fingler J, D Schwartz, C Yang, SE Fraser. Mobility and able are 2x2 mm, 3x3 mm, 6x6 mm and raphy is still an important tool for diag- transverse fl ow visualization using phase variance contrast with 8x8 mm. In order to generate an OCT nosis and management of chorioretinal spectral domain optical coherence tomography. Optics express 2007; 15:12636-12653. angiogram, OCT scans need to be re- diseases, especially when assessing the 9. Kim DY, J Fingler, JS Werner. In vivo volumetric imaging of

54 | Review of Ophthalmology | January 2017

0051_rp0117_rtinsider.indd51_rp0117_rtinsider.indd 5544 112/21/162/21/16 4:354:35 PMPM human retinal circulation with phase-variance optical coherence tomography. Biomedical Optics Express 2011;2:1504-1513. 10. White B, Pierce MC, Nassif N, et al. In vivo dynamic human retinal blood fl ow imaging using ultra-high-speed SD-OCT. Optics Express 2003;11:3490-3497. 11. Leitgeb RA, Werkmeister RM, Blatter C, et al. Doppler optical coherence tomography. Prog Retin Eye Res 2014;41:26-43. 12. Snodderly DM, Weinhaus RS, Choi JC. Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis). J Neurosci 1992;12:1169-1193. 13. Sarraf D, Rahimy E, Fawzi AA, et al. Paracentral acute middle maculopathy: a new variant of acute macular neuroretinopathy A safe and effective associated with retinal capillary ischemia. JAMA Ophthalmol 2013;131:1275-1287. solution for intraoperative 14. Freiberg FJ, Pfau M, Wons J, et al. Optical coherence tomography angiography of the foveal avascular zone in diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2016;254:6:1051. small pupil expansion 15. Bonini Filho MA, Adhi M, de Carlo TE, et al. Optical coherence tomography angiography in retinal artery occlusion. Retina 2015;35:2339. 16. Parodi MB, Visintin F, Della Rupe P, et al. Foveal avascular • Gentle on iris and other zone in macular branch retinal vein occlusion. Int Ophthalmol 1995;19:25-28. intraocular tissue 17. Salz DA, de Carlo TE, Adhi M, et al. Select features of diabetic retinopathy on swept-source optical coherence tomographic • Iris quickly returns angiography compared with fl uorescein angiography and normal eyes. JAMA Ophthalmol 2016;134:644-650. to natural shape 18. de Carlo TE, Bonini Filho MA, Baumal CR, et al. Evaluation of preretinal neovascularization in proliferative diabetic retinopathy post surgery using optical coherence tomography angiography. Ophthalmic Surg Lasers Imaging Retina 2016;47:115-119. • Easy insertion 19. Takase N, Nozaki M, Kato A, et al. Enlargement of foveal avascular zone in diabetic eyes evaluated by en face optical and removal coherence tomography angiography. Retina 2015;35:2377. 20. de Carlo TE, Chin AT, Bonini Filho MA, et al. Detection of microvascular changes in eyes of patients with diabetes but not clinical diabetic retinopathy using optical coherence tomography angiography. Retina 2015;35:2364-2370. 21. Hwang TS, Jia Y, Gao SS, et al. Optical coherence tomography angiography features of diabetic retinopathy. Retina 2015;35:11:2371-6. 22. Kuehlewein L, Bansal M, Lenis TL et al. Optical coherence tomography angiography of type 1 neovascularization in age- related macular degeneration. Am J Ophthalmol 2015;160:4:739. “I particularly like the 23. Baumal CR, de Carlo TE, Waheed NK, et al. Sequential optical coherence tomographic angiography for diagnosis and treatment I-Ring because I fi nd it does of choroidal neovascularization in multifocal choroiditis. JAMA Ophthalmol 2015;133:1087-1090. 24. Coscas GJ, Lupidi M, Coscas F, et al. Optical coherence not distort the pupil or tomography angiography versus traditional multimodal imaging in assessing the activity of exudative age-related macular tear the sphincter.” degeneration: A new diagnostic challenge. Retina 2015;35:2219. 25. Saito M, Iida T, Nagayama D. Cross-sectional and en face optical coherence tomographic features of polypoidal choroidal vasculopathy. Retina 2008;28:459-464. Eric Donnenfeld MD, FAAO 26. Ueno C, Gomi F, Sawa M, et al. Correlation of indocyanine green angiography and optical coherence tomography fi ndings Ophthalmic Consultants of Long Island, NY after intravitreal ranibizumab for polypoidal choroidal vasculopathy. Retina 2012;32:2006-2013. 27. Povazay B, Hermann B, Unterhuber A, et al. Three-dimensional optical coherence tomography at 1050 nm versus 800 nm in retinal pathologies: Enhanced performance and choroidal penetration in cataract patients. J Biomed Opt 2007;12:041211. Call your local sales rep or BVI customer service 28. Unterhuber, Povazay B, Hermann B A, et al. In vivo retinal optical coherence tomography at 1040 nm—enhanced penetration into at 1-866-906-8080. www.beaver-visitec.com the choroid. Optics Express 2005;13:3252. 29. Imamura Y, Fujiwara T, Margolis R, Spaide RF, et al. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina 2009;29:1469-1473. 30. Grulkowski I, Liu JJ, Potsaid B, et al. Retinal, anterior segment and full eye imaging using ultrahigh speed swept-source OCT with vertical-cavity surface emitting lasers. Biomedical Optics express 2012;3:2733-2751. 31. Novais EA, Adhi M, Moult EM, et al. Choroidal neovascularization analyzed on ultra high-speed swept-source optical coherence tomography angiography compared to spectral-domain optical coherence tomography angiography. Am J Ophthalmol 2016;164:80-88. 32. de Carlo TE, Romano A, Waheed NK, Duker JS, et al. A review of optical coherence tomography angiography (OCTA). International Beaver-Visitec International, Inc. | 411 Waverley Oaks Road Waltham, MA 02452 Journal of Retina and Vitreous 2015;1:1:1-15. US patent # 8,900,136. Additional US and international patents pending. BVI, BVI Logo and all other trademarks (unless noted otherwise) are property of a Beaver-Visitec International (“BVI”) company © 2016 BVI

051_rp0117_rtinsider.indd 55 12/21/16 4:35 PM Therapeutic Topics REVIEW

The Many Shades Of Pinkeye A discussion of the various causes of conjunctivitis, and new therapeutic approaches on the horizon. Mark B. Abelson, MD, CM, FRCSC, FARVO, Aron Shapiro, Connie Slocum, PhD, and David A. Hollander, MD, MBA, Andover, Mass.

owhere do the practices of pri- wide; it’s estimated to be responsible the importance of rigorous hygiene N mary care medicine and ophthal- for ~2 million cases of blindness or cannot be overemphasized in these mology overlap more than in the diag- visual impairment.3 While rare in the situations. This aspect of the disease nosis and treatment of conjunctivitis, United States, the devastating effects leads to a major impact on productiv- the pathological inﬂ ammation of the of trachoma and other conjunctival ity through losses of time at work and conjunctiva. The condition presents infections serve to remind us that medical visits that represent a signiﬁ - itself in many forms; it can be due to these seemingly innocuous ailments cant economic burden for society. infectious agents, allergens, chemi- can have serious complications. This Patients presenting with infectious cal or irritant exposures, or physical month we examine the current stan- conjunctivitis typically experience a trauma. dard of care and emerging trends in bilateral hyperemia along with other In Western countries, infectious this all-too-common ocular malady, signs such as ocular discharge, tear- conjunctivitis is common, with an in- with a particular focus on viral forms ing, chemosis, itching, pain or irri- cidence of 15 per 1,000 patients per of the disease. tation. Some patients may also ex- year in primary care.1 Although most perience lid edema or photophobia, incidents of conjunctivitis are treated Identifying Infectious Agents petechial hemorrhage, follicles on the in the primary care setting, complica- tarsal or fornix conjunctiva, and pre- tions from viral or bacterial infection Infectious conjunctivitis is particu- auricular lymphadenopathy.6-9 Other can arise and lead to sight-threaten- larly prevalent in the pediatric popu- signs associated with a viral rather ing conditions.2 Conjunctivitis is also lation, where one in eight schoolchil- than bacterial infection are palpa- a major health issue in developing dren is expected to have an episode ble pre-auricular or submandibular countries, especially in areas with each year.4 The contagious nature lymph nodes.7 Viral infections may poor public water supplies. Outside of these infections means that chil- also produce follicles caused by a lym- the United States, cases of conjuncti- dren diagnosed with “pinkeye” are re- phocytic response of the conjunctiva.7 vitis are estimated to affect more than quired to leave school and seek treat- It’s important to note that these folli- 30 million people, due to both the ment. Indeed, cases of conjunctivitis cles are different from papillae, which highly contagious nature of infectious have been shown to be the leading are formed by bunches of conjunctival forms and to poor sanitary conditions cause of day care and school absences, capillaries that become dilated during that lead to cycles of repeated infec- which directly impacts a parent’s time some other ocular diseases such as gi- tion. An example of this is trachoma, a at work.5 Outbreaks tend to be rapid ant papillary conjunctivitis. bacterial conjunctivitis that is the most and pervasive, owing to the extremely While there are many signs and preventable cause of blindness world- contagious nature of the condition; symptoms that overlap between bac-

56 | Review of Ophthalmology | January 2017 This article has no commercial sponsorship.

0056_rp0117_ttops.indd56_rp0117_ttops.indd 5656 112/22/162/22/16 10:2410:24 AMAM terial and viral forms of con- even for a short period of junctivitis, the nature of the time, may actually extend the discharge is typically the key period of viral shedding and/ diagnostic characteristic: To or increase latency of the vi- differentiate between viral rus, consequently prolonging and bacterial forms of con- the course of the infection.7 junctivitis, it’s generally ac- It’s thought that steroids may cepted that a thick, purulent have this effect on the viral discharge is associated with infection due to their interac- bacterial conjunctivitis, while tion with cellular processes a watery discharge is more associated with the immune characteristic of viral conjunc- system, thus preventing the tivitis.7,8 Specifi cally, if the eye immune cells from fully erad- exhibits a sticky, opaque se- icating the virus. Combina- cretion, then a bacterial in- tion products such as FST- fection is most likely; without Steroid treatment in the setting of viral conjunctivitis may 100 (Shire) that include both this, a viral infection is most increase the latency of the virus, prolonging the infection. a steroid and an anti-infective probable. Laboratory tests agent (povidone iodine) may confirming these diagnoses antivirals have been shown to be inef- allow for the benefi ts of ste- are not usually required, but a culture fective in treating viral conjunctivitis; roids without concerns of prolonged swab of the conjunctiva prior to initia- the exception to this is in the case of disease duration. tion of treatment may be useful.10 The herpes simplex viral infections, which use of an in-offi ce rapid antigen test comprise between 1 and 5 percent of Beyond Adenovirus can help prevent the inappropriate all acute conjunctivitis cases. Antivi- use of antibiotics, due to its accuracy rals such as acyclovir, trifl uridine and Although the majority of viral infec- in identifying a viral infection from valacyclovir have all been shown to ef- tions are due to members of the ad- a group of viruses—adenoviruses— fectively treat herpesvirus infections.9 enovirus family, there is a tremendous which comprise 65 to 90 percent of While corticosteroids are often pre- diversity in the types of viruses that in- all viral conjunctivitis cases.10 The scribed to dampen infl ammation asso- fect the eye.13 There are more than 40 in-offi ce antigen test has been shown ciated with a number of ocular disor- types of adenovirus that cause condi- to be highly specific (~95 percent), ders, the use of steroid monotherapy tions including colds, gastrointestinal although the reports of test sensitiv- in the treatment of viral conjunctivi- illness, conjunctivitis or more serious ity have been more variable.11,12 The tis isn’t currently recommended. It’s ocular conditions. Ocular manifesta- value of these tests is that they pre- been shown that steroid treatment, tions of adenoviral infections include vent the unnecessary use of pharyngoconjunctival fever, antibiotics, which have no epidemic keratoconjunctivi- value in our therapies for viral tis, acute nonspecifi c follicu- infections. lar conjunctivitis, and chronic Although many patients vis- kerato-conjunctivitis. Other it a physician with the hopes viruses known to cause con- of receiving a treatment for junctivitis include the human quick recovery, there is cur- immunodefi ciency virus, Vari- rently no specific treatment cella zoster virus and Epstein- for the viral form of infectious Barr virus.12,13 conjunctivitis. Treatment typi- Another virus that has been cally involves the use of cold the subject of much pub- packs, artifi cial tear lubricant lic debate in the past year eye drops, ocular deconges- is the Zika virus.14 Zika is a tants and education on pre- mosquito-borne RNA virus, venting transmission of the Aedes aegypti, the mosquito that carries the Zika virus. Among related to viruses associated virus through frequent hand- its many other signs and symptoms, Zika can also cause with dengue fever, yellow fe- washing.10,13 For the most part, conjunctivitis in infected individuals. ver and West Nile virus. The

January 2017 | reviewofophthalmology.com | 57

056_rp0117_ttops.indd 57 12/22/16 10:25 AM Therapeutic

REVIEW Topics

virus gained public attention during newly-formed viruses are released the experimental fi res, giving a much- the Brazil Olympics because of its as- to infect other cells. This type of life needed boost to research into new sociation with congenital abnormali- cycle means it’s more diffi cult to clear antiviral therapies. Hopefully this re- ties in infants of infected mothers. a viral infection once it has been intro- newed interest will lead to more ef- Most patients infected with Zika are duced; some viruses lay dormant in a fective ways to treat and eliminate all asymptomatic, but those infected in- nonproliferative stage within the host viral conditions, including ocular viral dividuals who display disease features cell, further extending their inhabit- infections. experience a constellation of symp- ance. These host-pathogen interac- toms including conjunctivitis, fever, tions, along with the highly genetically Dr. Abelson is a clinical professor maculopapular rash and joint pain.14 diverse group of viruses that can in- of ophthalmology at Harvard Medi- Although the disease is still rare in duce conjunctivitis, have complicated cal School. Mr. Shapiro is vice presi- the United States, increased Zika in- the discovery of effective therapeutics dent at the ophthalmic consulting fi rm cidence rates in some southern states for viral infections. Ora. Dr. Slocum is a medical writer at suggest that Zika infection may need Ora. Dr. Hollander is chief medical of- to be considered as a possible cause fi cer at Ora, and assistant clinical pro- for cases of conjunctivitis of unknown fessor of ophthalmology at the Jules etiology that occur in those regions. A mouse model of the Stein Eye Institute at the University Beyond its association with con- Zika virus suggested of California, Los Angeles. junctivitis, a mouse model of Zika demonstrated that the virus was pres- that it might be 1. Rietveld RP, G. ter Riet, Bindels PJ et al. The treatment of acute infectious conjunctivitis with fusidic acid: A randomised controlled ent in the tears, suggesting that Zika secreted from the trial. Br J Gen Pract 2015;55:521:924-930. might be secreted from the lacrimal 2. Collin HB, Abelson MB. Herpes simplex virus in human cornea, 15 lacrimal gland or shed retro-corneal fi brous membrane, and vitreous. Arch Ophthalmol. gland or shed from the cornea. Ad- 1976 Oct;94:10:1726-9. ditionally, it was shown that Zika in- from the cornea. 3. http://www.who.int/mediacentre/factsheets/fs382/en/ fected the iris, retina and optic nerve, Accessed 2 Dec 2016. 4. Rose PW, Harnden A, Brueggemann AB, et al. Chloramphenicol leading to panuveitis and neuroretini- treatment for acute infective conjunctivitis in children in primary tis in addition to conjunctivitis. These care: a randomised double-blind placebo-controlled trial. Lancet. 2005;366:9479: 37-43. observations are reminiscent of an- A promising new therapeutic ap- 5. Patel PB, Diaz MC, Bennett JE and Attia MW. Clinical features other recent viral epidemic, the West proach to treatment of viral conjunc- of bacterial conjunctivitis in children. Acad Emerg Med.2007; African Ebola outbreak of 2014. Of tivitis is represented by OKG-0301 14:1:1-5. 6. http://www.aoa.org/documents/CPG-11.pdf. accessed course, Ebola is much different from (Okogen, Encinitas, Calif.). While 18Nov2016 Zika: It is a hemorrhagic fever virus most antiviral drugs act by inhibition 7. Azari AA and Barney NP. Conjunctivitis: A systematic review of diagnosis and treatment. JAMA 2013;310:16:1721-1729. spread without an insect vector, and it of nucleic acid biosynthesis, OKG- 8. Jackson WB. Differentiating conjunctivitis of diverse origins. primarily impacts the gastrointestinal 0301 is a ribonuclease that acts to in- Surv Ophthalmol 1993;38:S91. system, where it is often fatal without hibit viral replication by interfering 9. Morrow GL, Abbot RL. Conjunctivitis. AM Fam Physician 1998;57:4735-46. significant supportive care. Despite with viral protein synthesis. OKG- 10. Jhanji V, Chan TC, Li EY, Agarwal K, Vajpayee RB. Adenoviral these differences, a well-documented 0301 also interferes with the infl am- Keratoconjunctivitis. Surv Ophthalmol. 2015; 60:5:435-43. 11. Kam KY, Ong HS, Bunce C, Ogunbowale L, Verma S. Sensitivity case of an Ebola survivor reported matory response by inhibiting NF- and specifi city of the AdenoPlus point-of-care system in detecting that a convalescing patient presented κB, a transcription regulator that is adenovirus in conjunctivitis patients at an ophthalmic emergency with uveitis;16 subsequent to this, fol- a key signal point in the inflamma- department: A diagnostic accuracy study. Br J Ophthalmol. 2015; 99:9:1186-9. low-up identifi ed 57 Ebola survivors tion process. Another new product 12.https://www.aao.org/preferred-practice-pattern/ with uveitis, suggesting that infectious in development, APD-209 (Adenovir conjunctivitis-ppp--2013 accessed 18 Nov 2016. 13. Newman H and Gooding C. Viral ocular manifestations: A virus or viral RNA in the eye may have Pharma; Helsingborg, Sweden), is de- broad overview. Rev Med Virol 2013;23:281-294. 17 triggered this complication. It may signed to treat epidemic keratocon- 14. Murray JS. Understanding Zika virus. J Spec Pediatr Nurs. be that some aspects of ocular physi- junctivitis by preventing adenoviral 2016 Nov 9. [Epub ahead of print] 15. Miner JJ, Sene A, Richner J et al. Zika virus infection in mice ology leave the eye susceptible to viral binding and entry into cells. These causes panuveitis with shedding of virus in tears. Cell Reports infi ltration and/or retention, and thus examples of new therapies are par- 2016;16:12:3208-3218. 16. Varkey JB, Shantha JG, Crozier I, et al. Persistence of Ebola any viral conjunctivitis may have this ticularly exciting because they repre- Virus in Ocular Fluid during Convalescence. N Engl J Med same risk. sent new mechanistic strategies in the 2015;372:2423–2427. The life cycle of viruses involves design of antiviral drugs. 17. Tiffany A, Vetter P, Mattia J, et al. Ebola virus disease complications as experienced by survivors in Sierra Leone. Clin an intracellular growth and assembly The silver lining of these recent vi- Infect Dis 2016;62:1360–1366. phase and a cell lysis phase where ral epidemics is that they rekindle

58 | Review of Ophthalmology | January 2017

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2015_RPonline_house.indd 1 12/10/14 2:38 PM Research Review REVIEW

Understanding the Risk Factors for NAION

sing the Clinformatic DataMart nos had a 46-percent decreased risk This retrospective, population- Udatabase, researchers sought of developing NAION, whereas Af- based, cohort study identifi ed pa- to understand the risk factors for rican ancestry was not signifi cantly tients newly diagnosed with CRAO nonarteritic anterior ischemic optic associated with NAION. Systemic between 2001 and 2013 in a da- neuropathy, a devastating ocular diseases associated with NAION in- tabase of 1,000,000 patients that disease that causes permanent vi- cluded hypertension and hyperco- were randomly selected from all sion loss. In order to isolate and agulable states. Although diabetes registered benefi ciaries of the Na- explore NAION’s risk factors, re- mellitus was not signifi cantly associ- tional Health Insurance program searchers specifi cally looked at as- ated with NAION when compared in Taiwan. The researchers refer- sociated demographic, systemic with those without DM (p=0.45), enced air pollutant monitoring sta- and ocular factors. patients with end-organ involve- tions located near these patients’ This retrospective, longitudi- ment from DM had a 27-percent residences throughout Taiwan to nal cohort study included patients increased risk of NAION relative determine the recorded concentra- between 40 and 75 years old with- to those with uncomplicated DM. tions of pollutants. Patients without out NAION at baseline who were Ocular diseases associated with corresponding monitoring stations enrolled in a large U.S. managed- NAION were age-related macular were excluded. care network. These enrollees were degeneration and retinal vein oc- Using a time-stratified, case- monitored for at least two years clusion. crossover study design and condi- between 2001 and 2014 to iden- The study identifi ed several mod- tional logistic regression analysis, tify those newly diagnosed with ifi able risk factors that may be asso- researchers assessed associations NAION. All persons were under ciated with NAION. Should future between the risk of CRAO and the ophthalmic surveillance, and all studies confi rm these fi ndings, they air pollutant levels in the days pre- cases had ≥1 confi rmatory ICD-9- may offer opportunities to prevent ceding each increase in those lev- CM code for NAION during fol- or treat this debilitating condition, els. Ninety-six patients with CRAO low-up. the researchers say. were enrolled in this study. The Of the 1,381,477 eligible enroll- Ophthalmology 2016;123:2446- mean age was 65.6 years, and 67.7 ees, 977 (0.1 percent) developed 2455 percent of the patients were male. NAION during a mean ±stan- Cestari D, Gaier E, Bouzika P, Blachley T The risk of CRAO onset was signifi - dard deviation follow-up of 7.8 cantly increased during a five-day ±3.1 years. The ±D mean age for Air Pollution and Central Retinal period following a one-part-per- NAION cases at the index date was Artery Occlusion billion increase in pollutant levels. 64.0 ±9.2 years vs. 58.4 ±9.4 years esearchers investigated whether After multi-pollutant adjustment, for the remainder of the benefi cia- Rdaily changes in ambient air pollu- the increase in risk was most prom- ries. Female subjects had a 36-per- tion were associated with an increased inent after four to five days in dia- cent decreased risk of developing risk of central retinal artery occlusion, betic patients. The risk of CRAO NAION compared with male sub- using the Taiwan National Health In- onset also significantly increased jects. Compared with whites, Lati- surance Research Database. in patients with hypertension and

60 | Review of Ophthalmology | January 2017 This article has no commercial sponsorship.

0061_rp0117_rr.indd61_rp0117_rr.indd 6060 112/22/162/22/16 11:3511:35 AMAM in patients ≥65 years old after just sponse to IVB as a 20-percent reduc- 95 percent-CI: 0.7 to 21) was a statisti- one day of elevated pollutant lev- tion in central macula thickness after cally signifi cant predictor (p=0.025) of els. The results demonstrated a the first course (three injections) of a good response to IVB, while previous positive association between air IVB. macular laser was a statistically sig- pollution and CRAO onset, par- nifi cant (p=0.0005) predictor of a poor ticularly in patients with diabetes response (odds ratio: 0.07; 95-percent or hypertension and those older CI: 0.01 to 0.32). Sixty-eight percent of than 65 years. eyes underwent subsequent treatment Ophthalmology 2016;123:2603- Long-term visual for DME after the fi rst course of IVB. 2609 acuity changes in DME The visual acuity gain at 24 months Cheng HC, Pan RH, Yeh HJ, Lai KR, Yen MY in hypertensive individuals (0.7 ±3.6 weren’t signifi cantly letters) and nonhypertensive individu- Intravitreal Bevacizumab different between eyes als (5.2 ±3.7 letters) was not statisti- for DME cally significantly different (p=0.41). esearchers from the U.K. wrote with and without Researchers concluded that hyperten- Rthat since outcomes of intravitreal systemic hypertension sion was a positive predictor, and previ- anti-vascular endothelial growth factor ous macular laser was a negative pre- injections are variable among individu- dictor of response to IVB. However, als with diabetic macular edema, they they found that long-term visual acuity set out to determine the ocular and changes weren’t signifi cantly different systemic predictors of DME response In 78 eyes of 54 individuals, 28 per- between eyes with or without systemic to intravitreal bevacizumab. The study cent of cases had an anatomical re- hypertension. was a retrospective review over two sponse after the fi rst course of IVB. Sys- Clin Ophthalmol 2016;10:2093-8 years. They defi ned an anatomical re- temic hypertension (odds ratio: 12.1; Joshi L, Bar A, Tomkins-Netzer O, et al.

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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 available at $209/night. EDUCATIONAL OBJECTIVES Limited number of rooms available. See registration After participating in this educational activity, attendees should site for more information. be able to: • 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

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ĂƐƐĞƩ ,ĞĂůƚŚĐĂƌĞ EĞƚǁŽƌŬ͕ Ă ƉƌŽŐƌĞƐƐŝǀĞ ŚĞĂůƚŚ ĐĂƌĞ ŶĞƚǁŽƌŬ ŝŶ Cornea/Anterior Segment ĐĞŶƚƌĂůEĞǁzŽƌŬĂŶĚŵĂũŽƌƚĞĂĐŚŝŶŐĂĸůŝĂƚĞŽĨŽůƵŵďŝĂhŶŝǀĞƌƐŝƚǇŝƐƐĞĞŬŝŶŐ Glaucoma Specialist OPHTHALMOLOGYĂGeneral OphthalmologistƚŽũŽŝŶĂďƵƐǇŽƉŚƚŚĂůŵŽůŽŐǇĚĞƉĂƌƚŵĞŶƚďĂƐĞĚŝŶƚŚĞ ůŽǀĞůǇǀŝůůĂŐĞŽĨŽŽƉĞƌƐƚŽǁŶ͘'ůĂƵĐŽŵĂĞǆƉĞƌŝĞŶĐĞĂƉůƵƐ͊ Oculo-plastics ĂƐƐĞƩ ,ĞĂůƚŚĐĂƌĞ EĞƚǁŽƌŬ ŝƐ ĂŶ ŝŶƚĞŐƌĂƚĞĚ ŚĞĂůƚŚ ĐĂƌĞ ƐǇƐƚĞŵ ƚŚĂƚ ƉƌŽǀŝĚĞƐ ĐĂƌĞ ĂŶĚ Overall practice growth has and will ƐĞƌǀŝĐĞƐƚŽƉĞŽƉůĞůŝǀŝŶŐŝŶĂŶĞŝŐŚƚĐŽƵŶƚǇƌĞŐŝŽŶĐŽǀĞƌŝŶŐϱ͕ϲϬϬƐƋƵĂƌĞŵŝůĞƐŝŶƵƉƐƚĂƚĞEĞǁ continually provide ample opportunities for zŽƌŬ͘dŚĞŽƌŐĂŶŝǌĂƟŽŶŝŶĐůƵĚĞƐƐŝǆĐŽƌƉŽƌĂƚĞůǇĂĸůŝĂƚĞĚŚŽƐƉŝƚĂůƐ͕ ĂƐ ǁĞůů ĂƐ ƐŬŝůůĞĚ ŶƵƌƐŝŶŐ new physicians to grow with the practice. ĨĂĐŝůŝƟĞƐ͕ĐŽŵŵƵŶŝƚǇĂŶĚƐĐŚŽŽůͲďĂƐĞĚŚĞĂůƚŚĐĞŶƚĞƌƐ͕ĂŶĚŚĞĂůƚŚƉĂƌƚŶĞƌƐŝŶƌĞůĂƚĞĚĮĞůĚƐ͘ <ùÄ¥®ãÝÊ¥ã«®ÝWÊÝ®ã®ÊÄ͗ We offer a competitive base salary commensurate with experience, full ͻ KƉƉŽƌƚƵŶŝƟĞƐĞǆŝƐƚĨŽƌďŽƚŚƌĞƐĞĂƌĐŚĂŶĚƚĞĂĐŚŝŶŐŝĨŝŶƚĞƌĞƐƚĞĚ͘ Beneﬁts, k and performance bonus. ͻ ƵƌƌĞŶƚůǇƚŚĞƌĞĂƌĞƐƉĞĐŝĂůŝƐƚƐŝŶƌĞƟŶĂ͕ĐŽƌŶĞĂ͕ƉĞĚŝĂƚƌŝĐƐĂŶĚŽĐƵůŽƉůĂƐƟĐƐ͘ ͻ dŚĞƐƵƉƉŽƌƚƐƚĂīŝƐǁĞůůƚƌĂŝŶĞĚĂŶĚĞǆƉĞƌŝĞŶĐĞĚŝŶďŽƚŚƚŚĞĐůŝŶŝĐĂŶĚŽƉĞƌĂƟŶŐƌŽŽŵ͘

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64 | Review of Ophthalmology | January 2017

ROPH0117.indd 64 12/21/16 8:08 AM 065_rp0117_wills.indd 65 ric casesappearsinTable 1,below.) (The differentialdiagnosisforretinaldetachmentinpediat- the childtoanocularoncologycenterforfurtherevaluation. sician identifi ed aninferiorretinaldetachmentandreferred for theamblyopiaandencouragedpatching.Thethirdphy- Wills. Thefi rst twoophthalmologistsfoundnoorganiccause uated bythreedifferentophthalmologistsbeforecomingto years laterdemonstratedaleftesotropia.Hehadbeeneval- parents. Thechildcontinuedintermittentpatching,buttwo following admittedlypoorcompliancewithpatchingbythe ly thevisualacuityimproved,butitsubsequentlyregressed, and hewasinstructedtobeginpatchinghisrighteye.Initial- was diagnosedwithamblyopiaonophthalmicexamination of thevisionproblematthattime.Later, atage8,thechild screening atage5;however, hisparentswerenotinformed OD, 20/200OS)wasfi rst notedonaroutineschoolvision over thepastfi ve years.His decreasedvisualacuity(20/20 ther evaluationofblurredvisioninhislefteyethatpersisted Presentation Jordan D. Deaner, MD, andCarolL.Shields, MD visioninoneeye. blurry A 10-year-old forhelpwithlong-standing boypresentsatWills Table 1. DiagnosisofPediatric Detachment

A 10-year-old African-Americanboypresentedforfur- REVIEW The mostimportantconditionsinclude: genital, infl ammatory, traumatic, conditions. neoplasticanddegenerative ofretinaldetachmentinachildincludesThe differentialdiagnosis con- • Vascular/degenerative vitreoretinopathy • Vascular/degenerative • Neoplastic • Traumatic • Infl ammatory – Stickler’s syndrome – tractionretinaldetachment retinaldetachment – rhegmatogenous – juvenileX-linkedretinoschisis ofprematurity – retinopathy vitreoretinopathy – familialexudative disease – Coats – choroidalnevus – choroidalmelanoma – choroidalhemangioma – retinalhemangioblastoma – retinoblastoma – retinaldialysis – abusiveheadtraumawithretinaldetachment retinaldetachment – blunttrauma/foreignbody – posteriorscleritis – posterioruveitis Wills Eye Wills Eye Resident CaseSeries Edited by Alison Huggins, MD diffuse choroidal hemangioma. mass withassociatedinferiorretinal detachment, suggestive of affected lefteye demonstrating adiffusered-orange choroidal righteyeFigure and(B) 2.Fundusphotograph of(A)thenormal (Figure 2). hue totheentire fundus, suspiciousforasolidchoroidal mass left eye revealed aninferiorretinal detachment withared-orange flammeus. Fundusexamination oftherighteye was normal. The Hirschberg refl corneal ex andtheabsenceofcutaneousnevus photograph demonstratingFigure leftesotropiaby 1.External cations includedalbuterol,cetirizineandnasalfl tributory andtherewerenoknowndrugallergies.Hismedi- asthma andseasonalallergies.Familyhistorywasnoncon- imaging andelectroencephalogram.Healsohadahistoryof at thattimedemonstratednormalbrainmagneticresonance of alteredmentalstatusattheage2.Medicalevaluation years oflife.Pastmedicalhistoryrevealedanisolatedepisode upper eyelidthatspontaneouslyresolvedduringhisfi history wasonlynotableforafaintredbirthmarkontheleft Medical History defect. Extraoculareyemovementswerefullbilaterally. The round andreactivetolight,withnorelativeafferentpupillary OD and20/400OS(pinholeto20/200).Pupilswereequal, Examination The patienthadnoadditionalpriorocularhistory. Hisbirth Ocular examination demonstrated visual acuity of 20/20 Ocular examinationdemonstratedvisualacuityof20/20 January 2017 | reviewofophthalmology.com uticasone. rst few few rst |

65 12/21/16 4:25 PM 065_rp0117_wills.indd 66 20/20 ODand20/200OS. ure 7).Visual acuityremainedstableat residual subfovealRPEchanges ula wasflatonOCT, buttherewere 3 mminthickness(Figure6).Themac- the hemangiomaregressedfrom5.3to solved the subretinalfl uid wascompletelyre- follow-up, thetumorhadregressedand used forthreeweeks.Atfivemonths and atropineophthalmicdropswere cal antibiotic/corticosteroidointment sutured inplaceforfourdays.Topi- To achievethisdose,theplaquewas tion deliverytoanapexdoseof35Gray. mass posteriorlywithtranscleralradia- plaque waspositioneddirectlyoverthe Iodine-125 plaqueradiotherapy. The Treatment was performed. exposure, localizedplaqueradiotherapy and theconcernforexternalradiation dynamic therapy. Givenhisyoungage beam radiotherapy, protonbeamradiotherapy, plaqueradiotherapyandphoto- choroidal hemangiomawasmade.Optionsformanagementincludedexternal view ofthefoveola(Figure4). demonstrated choroidthickening,andoverlyingsubretinalfl uid wasnotedwithno a diffusechoroidalhemangioma solid echodensechoroidalmassof5.3mminmaximumthickness,consistentwith ultrasonography confi rmed aninferiorretinaldetachmentanddemonstrateda suspicious forthis seen inpatientswithdiffusechoroidalhemangiomas.Thepatient’s leftfunduswas Diagnosis andWorkup What isyourdifferentialdiagnosis?furtherworkupwouldyoupursue? exam demonstratedfewconjunctivalpapillaeandmildconstitutionalmelanosis,bilaterally. sures of10mmHgineacheye.Externalexaminationwasnormalwithoutbirthmarkornevusfl patient demonstrated20prismdioptersofleftesotropiainprimarygaze.Applanationtonometryrevealedintraocularpres- 66 changes. detachment, aflat fovea andresidual RPE demonstrating resolution oftheretinal Figure 7.Postoperative OCTofthemacula REVIEW The patientwastreatedwith With theadditionoffindings onB-scanandOCT, afi nal diagnosisofdiffuse “Tomato catsupfundus”isatermoftenusedtodescribethered-orangechoroid | ReviewofOphthalmology Resident CaseSeries (Figure 5).Byultrasonography, and further diagnostic testing was pursued. B-scan (Figure 2)andfurtherdiagnostictestingwaspursued.B-scan | January2017 . Optical coherence tomography also (Figure 3).Opticalcoherencetomographyalso (Fig- no viewofthefoveola. choroidal thickening surroundingbothsidesofthediscandelevating theretina. There was Figure centrally 4.OCTofthepapillomacularregion andmassive shows theopticnerve subretinal fluid andresidual RPEchanges. showing tumorregression, resolution of Figure 5.Fundusphotograph ofthelefteye 5.3 mminmaximumthickness. echodense choroidal massmeasuring an inferiorretinal detachment andasolid Figure 3.B-scanultrasound demonstrating thickness. the choroidal massto3mminmaximum of theretinal detachment andregression of ultrasonography demonstrating resolution Figure 6.Postoperative B-scan ammeus . Slit lamp (Figure 1).Slitlamp 12/21/16 4:25 PM Discussion a cutaneous capillary malformation Laser photocoagulation has been (nevus flammeus) in combination used in the past, with some effi cacy Choroidal hemangioma is a be- with a vascular anomaly of the brain for the treatment of circumscribed nign vascular hamartoma that can be (leptomeningeal hemangiomatosis), choroidal hemangiomas. In one study, separated into two subtypes: circum- best seen on brain MRI.7,8 Associ- 62 percent of patients had resolution scribed and diffuse.1 The etiology of ated features include seizures (80 per- of subretinal fl uid and 71 percent had vision loss in choroidal hemangioma cent),9 focal neurologic deficits (65 stable or improved VA.14 However, can be attributed to foveal distortion, percent)9,10 and mental retardation subretinal fl uid limits the therapeutic subretinal fl uid, intraretinal edema, (60 percent).10 The frequency and effi cacy of laser therapy and therefore induced hyperopia, amblyopia or a severity of seizures and neurologic may not be a reasonable treatment combination of these factors.2 Dif- defi cits are related to the location and option in patients with large diffuse fuse choroidal hemangioma appears extent of associated capillary venous choroidal hemangiomas associated clinically as a diffuse, red-orange malformations. Seizure control can be with extensive subretinal fluid. In thickening of the posterior choroid, achieved with anti-epileptic medica- these patients, treatment with exter- displaying the appearance of the tions or surgery if the seizures prove nal beam radiotherapy or plaque ra- aforementioned “tomato catsup fun- to be refractory to medical manage- diotherapy has been most effective. dus.”1 ment.11 The primary complications of laser The diagnosis of diffuse choroidal Additional ocular manifestations photocoagulation can include RPE hemangioma is often made on clini- of Sturge-Weber Syndrome include atrophy, scotoma and epiretinal mem- cal fundus examination with indirect glaucoma (30 to 70 percent) as well brane formation.14 ophthalmoscopy, with ancillary test- as capillary venous malformations of Photodynamic therapy, like laser ing generally used for confi rmation. the episclera or conjunctiva (69 per- photocoagulation, is advantageous as In cases complicated by secondary cent).12 The cause of glaucoma associ- it avoids radiation exposure. Photody- total retinal detachment, clinical ex- ated with Sturge-Weber Syndrome is namic therapy also spares the retina amination may be limited, so char- not fully understood and the age of and retinal vasculature, compared to acteristic features of ancillary testing onset may inform the mechanism. In other forms of therapy. Also, like laser play an important role.3 B-scan ul- younger children it may be the result photocoagulation, it has proven effec- trasonography demonstrates an ech- of anterior chamber angle anomalies, tive in the treatment of circumscribed odense dome-shaped mass, often with while in older children it is thought choroidal hemangioma, with 100 per- subretinal fl uid.4 On A-scan ultraso- to result from elevated episcleral cent of patients achieving resolution nography the mass may demonstrate pressure.12 Nonetheless, glaucoma in of subretinal fl uid in one study.15 On high internal refl ectivity.4 Fluorescein these individuals is notoriously dif- the other hand, photodynamic ther- angiography shows diffuse lesion hy- fi cult to control. Medical therapy is apy has had limited success in treat- perfluorescence in the pre-arterial typically only a temporizing agent and ment of diffuse choroidal hemangio- phase and can be useful in determin- surgical correction with gonio tomy, ma, resulting in mixed outcomes, with ing the exact site of leakage in large trabeculotomy or a glaucoma drain- one case report demonstrating reso- tumors.4 Indocyanine green angiogra- age device is often necessary in these lution of subretinal fl uid and tumor phy demonstrates rapid fi lling of the cases.13 regression after a single treatment16 mass by one minute with washout by The management of diffuse cho- and another requiring multiple repeat 10 to 15 minutes, often with a ring of roidal hemangioma depends on the treatments.17 staining.5 extent of the patient’s visual com- External beam radiation therapy Once the diagnosis of diffuse cho- promise, association with subretinal has been used with lens-sparing dos- roidal hemangioma is made, this fl uid, and lesion size. Asymptomatic es, resulting in good outcomes. Res- should prompt a systemic evalua- diffuse choroidal hemangiomas can olution of subretinal fluid occurred tion for the neuro-oculocutaneous be observed by monitoring for sub- in 100 percent of patients in a small Sturge-Weber Syndrome. Choroidal retinal fl uid biannually.4 If the patient study (n=15), tumor regression oc- hemangioma can be present in up to is symptomatic, treatment options in- curred in fi ve patients, and visual acu- 55 percent of cases.6 The diagnosis clude photodynamic therapy, external ity improved in seven. Shortcomings of Sturge-Weber Syndrome is estab- beam radiation therapy, plaque radio- of EBRT include radiation exposure lished clinically with the presence of therapy and propranolol. and the need for patient cooperation

January 2017 | reviewofophthalmology.com | 67

0065_rp0117_wills.indd65_rp0117_wills.indd 6677 112/21/162/21/16 4:264:26 PMPM 0065_rp0117_wills.indd 68 6 5 _ r p 0 1 1 7 _ w of thefivepatients. ity wasstableorimprovedinfourout gioma, ondary todiffusechoroidalheman- of exudativeretinaldetachmentsec- be usedeffectivelyinthetreatment have shownthatoralpropranololcan mixed results.Whiletwocasestudies during treatments. 68 pliance withtreatment. regression isduetopatientnon-com- assuming thatlackofprogress orvisual organic causesofamblyopiapriorto evaluate thepatientforallpossible tance ofathoroughexaminationto stable visualacuity. olution, hemangiomaregressionand ultimately showedsubretinalfl treated withplaqueradiotherapyand angioma. Ourpatientwassuccessfully secondary toadiffusechoroidalhem- result ofaserousretinaldetachment compliance, waslaterfoundtobethe failure, initiallyattributedtonon- amblyopia forfi had beenunsuccessfullytreatedfor radiation exposure. and ourdesiretolimitthepatient’s py forourpatientgivenhisyoungage tion. minimal relianceonpatientcoopera- for ashortduration(fourdays),and plication ofprecise,localizedtherapy therapy isadvantageousgivenitsap- the 32-monthfollow-up. as tumorregression(100percent)at fl onstrated effi patients, plaqueradiotherapydem- fl for patientswithextensivesubretinal tant treatmentoption,particularly nal fl the factthatitmightresolvesubreti- to inducetumorregressiondespite its failure. i l uid. Inaretrospectivereviewoffi uid resolution(100percent)aswell l s

. REVIEW Propranolol has also been used with Propranolol hasalsobeenusedwith This caseunderscorestheimpor- In thecasepresentedhere,boy Plaque radiotherapyisanimpor- i n | d ReviewofOphthalmology uid. uid. d Resident CaseSeries 22

We electedplaqueradiothera-

6 19,20 8 21 anotherhasdemonstrated Propranolol generally fails Propranololgenerallyfails cacy inbothsubretinal ve years. His treatment ve years.Histreatment 18 22 22 Plaqueradio- 22 Visual acu- uidres- | January2017 ve ve Ophthalmology 2013;120:11:2358-2359. Ophthalmology in5cases. withplaqueradiotherapy hemangioma management 22. Arepalli S, ShieldsCL, KalikiS, etal. Diffusechoroidal 2013;131:5:681-683. Sturge-Weber syndrome: A reportof2cases. JAMAOphthalmol forchoroidalhemangiomaof systemic propranololtherapy 21. KremaH, Yousef Y, DurairajP, R. Santiago Failure of 2013;23:6:922-924. hemangioma inSturge-Weber syndrome. EurJOphthalmol retinal detachmentfromdiffusechoroidal ment ofexudative 20. R,Thapa ShieldsC. formanage- Oralpropranololtherapy Ophthalmol 2011;129:1373-1375. tive retinaldetachmentindiffusechoroidalhemangioma. Arch 19. Arevalo JF, Arias JD, SerranoMA. Oralpropranololforexuda- Ophthalmol 1997;81:267-273 forchoroidalhemangioma. doseocularirradiation after low BrJ 18. SchillingH, Sauerwein W, Lommatzsch A. Longtermresults 1469. diffuse choroidalhemangioma. ClinOphthalmol2012;6:1467- 17. Ang M, Shu-Yen L. for therapy Multifocalphotodynamic Ophthalmol 2003;136:4:758-760. withSturge-Weberhemangioma associated syndrome. Am J 16. Anand, R. fordiffusechoroidal therapy Photodynamic 2010;117:8:1630-1637. choroidal hemangioma: Five-year outcomes. Ophthalmology withverteporﬁtherapy circumscribed nforsymptomatic 15. BlasiMA, Tiberti AC, Scupola A, etal. Photodynamic 2001;103:12:2237-2248. mology predictive ofvisualoutcomein200consecutivecases. Ophthal- choroidal hemangioma: andfactors Clinicalmanifestations 14. ShieldsCL, SG, Honavar ShieldsJA, etal. Circumscribed Sturge-Weber syndrome. Journalof AAPOS 1999;3:1:40-45. 13. Awad AH, MullaneyPB, Al-Mesfer S, etal. Glaucomain 1992;29:349-356. tions oftheSturge-Weber syndrome. JPediat OphthStrab 12. Sullivan TJ, ClarkeMP, MorinJD. The ocularmanifesta- The Neurologist2011;17:4:179. ofSturge-Weber oftheneurologicfeatures Syndrome.treatment 11. Comi AM. Presentation, diagnosis, and pathophysiology 1993;9:4:283-288. al. Sturge-Weber syndrome: of40patients. Study Pediatr Neurol 10. Pascual-Castroviejo I, Diaz-GonzalezC, Garcia-MelianRM, et 52 adults. Am JMedGenet1995;57:35-45. 9. SujanskyE, ConradiS. OutcomeofSturge-Weber syndromein 1993;129:2:219-226. tuberous sclerosis, andSturge-Weber syndrome. Arch Dermatol ofneuroﬁrole intheneuroradiologicevaluation bromatosis, 8. Truhan AP, Filipek PA. resonanceimaging: Magnetic Its edition. Sturge-Weber Foundation, 2010: Mt. Freedom, NJ. Bodensteiner JB, RoachES, eds. Sturge-Weber Syndrome, 2nd 7. Sturge-Weber syndrome: Introductionandoverview. In: 1992;29:349-56. tions oftheSturge-Weber syndrome. JPediat OphthStrab 6. Sullivan TJ, ClarkeMP, MorinJD. The ocularmanifesta- 1995;79:237-45. ofchoroidaltumors.green angiography BrJOphthalmol 5. ShieldsCL, ShieldsJA, DePotter P. Patterns ofindocyanine 2010J;17:3:191–200. choroid: andtreatment. Diagnosis MiddleEast Afr JOphthalmol 4. Turell ME, Singh AD. Vascular tumorsoftheretinaand Lippincott,and Wilkins,2008:230-251. Williams JA, ShieldsCL, eds. Atlas ofIntraocular Tumors. Philadelphia: 3. Vascular oftheuvea. tumorsandmalformation In: Shields hemangiomas. Arch Ophthalmol-Chic1989;107:9:1338-1342. 2. Anand R, Augsburger JJ, ShieldsJA. Circumscribedchoroidal 2013;120:Ophthalmology 2358-2359. in5cases. withplaqueradiotherapy hemangioma management 1. Arepalli S, ShieldsCL, KalikiS, etal. Diffusechoroidal number, orfailuretoinsert. will bemadeforerrorsduetospelling, incorrect page care willbetakentoindexcorrectly. Noallowance and notaspartoftheadvertisingcontract. Every This advertiserindexispublishedasa convenience aia n ak 31 www.CapitalOne.com/SmallBusiness 7, 8 Capital OneBank 55 72 www.beaver-visitec.com Fax (866) Phone (866) Beaver-Visitec International, Inc. 2 Fax (813) Phone (800) Bausch +Lomb Phone (800) Allergan, Inc. 906-4304 906-8080 Fax (817) 11 Phone (800) Alcon Laboratories 975-7762 323-0000 Phone (800) Abbott MedicalOptics, Inc. (AMO) 347-4500 551-4352 451-3937 366-6554 okOtcl n. 39 22-23, 24 Fax (440) Phone (800) 5 Volk Optical, Inc. SunIsOnTheRise.com Sun Ophthalmics Phone (888) S4OPTIK 17, 33 Fax (727) 942-2257 345-8655 Phone (800) Rhein Medical Fax (206) Phone (206) 45 Omeros 15 224-6012 Fax (425) Phone (888) 19 Oculus, Inc. 341-8123 637-4346 37 Fax (757) Phone (800) Lombart Instruments 676-5005 676-5000 Fax (603) Phone (800) Haag-Streit 71 867-1881 284-8004 Phone (800) FCI Ophthalmics 855-1232 446-8092 742-7217 627-6286 932-4202 Michael Hoster(610)[email protected] James Henne(610)[email protected] Michelle Barrett(610)[email protected] For advertisingopportunitiescontact: REVIEW Index Advertising 112/21/16 4:26 PM 2 / 2 1 / 1 6

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

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

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

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

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

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