Refractive Surgery Issue • February 2014 • Review of Ophthalmology Vol

$Refractive Surgery Issue • February 2014 • Review of Ophthalmology Vol$

MULTIMODAL IMAGING OF PLACOID DISORDERS P. 42 • WILLS RESIDENT CASE SERIES P. 67 NTG: THE NOCTURNAL BLOOD PRESSURE FACTOR P. 54 • WISE CHOICES FOR OCULAR DIAGNOSES P. 50 eiwo ptamlg o.XI o Fbur 04• ercieSreyIse• omlTninGacm Nwi eaoou eeto The Suite Cataract Surgical New in Keratoconus Detection • Tension Normal Glaucoma • Refractive Surgery Issue • February 2014 • Review of Ophthalmology Vol. XXI, No. 2 • NEW WAYS TO DETECT KERATOCONUS P. 58 • THE INTEGRATED CATARACT SURGICAL SUITE P. 18

February 2014 • revophth.com

Refractive Surgery Issue

Inlays and Presbyopia: On the Horizon P. 24 Crack a SMILE or Raise a Flap? P. 30 LASIK Xtra: Who Should Get It? P. 38

fc_rp0214.indd 1 1/27/14 3:47 PM ILEVRO™ Suspension Designed to put potency precisely where you need it 1,2

ONCE-DAILY POST-OP

One drop should be applied once daily beginning 1 day prior to surgery through 14 days post-surgery, with an additional drop administered 30 to 120 minutes prior to surgery 3 Use of ILEVRO™ Suspension more than 1 day prior to surgery or use beyond 14 days post-surgery may increase patient risk and severity of corneal adverse events3

INDICATIONS AND USAGE ILEVRO™ Suspension is a nonsteroidal, anti-infl ammatory prodrug indicated Patients with complicated ocular surgeries, corneal denervation, corneal for the treatment of pain and infl ammation associated with cataract surgery. epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye Dosage and Administration syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which ™ One drop of ILEVRO Suspension should be applied to the affected eye may become sight threatening. Topical NSAIDs should be used with one-time-daily beginning 1 day prior to cataract surgery, continued on the caution in these patients. day of surgery and through the fi rst 2 weeks of the postoperative period. An additional drop should be administered 30 to 120 minutes prior to surgery. Use more than 1 day prior to surgery or use beyond 14 days post-surgery may increase patient risk and severity of corneal adverse events. IMPORTANT SAFETY INFORMATION • Contact Lens Wear – ILEVRO™ Suspension should not be administered while using contact lenses. Contraindications Adverse Reactions ILEVRO™ Suspension is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formula The most frequently reported ocular adverse reactions following cataract or to other NSAIDs. surgery occurring in approximately 5 to 10% of patients were capsular opacity, decreased visual acuity, foreign body sensation, increased Warnings and Precautions intraocular pressure, and sticky sensation. • Increased Bleeding Time – With some nonsteroidal anti-infl ammatory For additional information about ILEVRO™ Suspension, please refer to the drugs including ILEVRO™ Suspension there exists the potential for brief summary of prescribing information on adjacent page. increased bleeding time. Ocularly applied nonsteroidal anti-infl ammatory drugs may cause increased bleeding of ocular tissues (including hyphema) References: 1. Ke T-L, Graff G, Spellman JM, Yanni JM. Nepafenac, a unique nonsteroidal prodrug in conjunction with ocular surgery. with potential utility in the treatment of trauma-induced ocular infl ammation, II: In vitro bioactivation • Delayed Healing – Topical nonsteroidal anti-infl ammatory drugs (NSAIDs) and permeation of external ocular barriers. Infl ammation. 2000;24(4):371-384. 2. Data on fi le. including ILEVRO™ Suspension may slow or delay healing. Concomitant 3. ILEVRO™ Suspension package insert. use of topical NSAIDs and topical steroids may increase the potential for healing problems. • Corneal Effects – Use of topical NSAIDs may result in keratitis. In some patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use.

RP0114_Alcon Ilevro.indd 1 12/16/13 11:21 AM Non‐Ocular Adverse Reactions Non‐ocular adverse reactions reported at an incidence of 1 to 4% included headache, hypertension, nausea/vomiting, and sinusitis. USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects. Pregnancy Category C: Reproduction studies performed with nepafenac in rabbits and rats at oral doses up to 10 mg/kg/day have revealed no evidence of teratogenicity due to nepafenac, despite the induction of ma- ternal toxicity. At this dose, the animal plasma exposure to nepafenac and amfenac was approximately 70 and 630 times human plasma exposure at the recommended human topical ophthalmic dose for rats and 20 and 180 times human plasma exposure for rabbits, respectively. In rats, maternally BRIEF SUMMARY OF PRESCRIBING INFORMATION toxic doses ≥10 mg/kg were associated with dystocia, increased post- implantation loss, reduced fetal weights and growth, and reduced fetal INDICATIONS AND USAGE survival. ILEVRO™ Suspension is indicated for the treatment of pain and inflammation associated with cataract surgery. Nepafenac has been shown to cross the placental barrier in rats. There are no adequate and well‐controlled studies in pregnant women. Because DOSAGE AND ADMINISTRATION animal reproduction studies are not always predictive of human response, Recommended Dosing ILEVRO™ Suspension should be used during pregnancy only if the potential One drop of ILEVRO™ Suspension should be applied to the affected eye one- benefit justifies the potential risk to the fetus. time-daily beginning 1 day prior to cataract surgery, continued on the day of surgery and through the first 2 weeks of the postoperative period. An Non‐teratogenic Effects. additional drop should be administered 30 to 120 minutes prior to surgery. Because of the known effects of prostaglandin biosynthesis inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the Use with Other Topical Ophthalmic Medications use of ILEVRO™ Suspension during late pregnancy should be avoided. ILEVRO™ Suspension may be administered in conjunction with other topical ophthalmic medications such as beta-blockers, carbonic anhydrase inhibi- Nursing Mothers tors, alpha-agonists, cycloplegics, and mydriatics. If more than one topical ILEVRO™ Suspension is excreted in the milk of lactating rats. It is not ophthalmic medication is being used, the medicines must be administered known whether this drug is excreted in human milk. Because many drugs at least 5 minutes apart. are excreted in human milk, caution should be exercised when ILEVRO™ Suspension is administered to a nursing woman. CONTRAINDICATIONS ILEVRO™ Suspension is contraindicated in patients with previously demon- Pediatric Use strated hypersensitivity to any of the ingredients in the formula or to other The safety and effectiveness of ILEVRO™ Suspension in pediatric patients NSAIDs. below the age of 10 years have not been established. WARNINGS AND PRECAUTIONS Geriatric Use Increased Bleeding Time No overall differences in safety and effectiveness have been observed With some nonsteroidal anti-inflammatory drugs including ILEVRO™ Suspen- between elderly and younger patients. sion, there exists the potential for increased bleeding time due to interfer- NONCLINICAL TOXICOLOGY ence with thrombocyte aggregation. There have been reports that ocularly Carcinogenesis, Mutagenesis, Impairment of Fertility applied nonsteroidal anti-inflammatory drugs may cause increased bleeding Nepafenac has not been evaluated in long‐term carcinogenicity studies. of ocular tissues (including hyphemas) in conjunction with ocular surgery. It Increased chromosomal aberrations were observed in Chinese hamster is recommended that ILEVRO™ Suspension be used with caution in patients ovary cells exposed in vitro to nepafenac suspension. Nepafenac was not with known bleeding tendencies or who are receiving other medications mutagenic in the Ames assay or in the mouse lymphoma forward mutation which may prolong bleeding time. assay. Oral doses up to 5,000 mg/kg did not result in an increase in the for- Delayed Healing mation of micronucleated polychromatic erythrocytes in vivo in the mouse Topical nonsteroidal anti-inflammatory drugs (NSAIDs) including ILEVRO™ micronucleus assay in the bone marrow of mice. Nepafenac did not impair Suspension, may slow or delay healing. Topical corticosteroids are also fertility when administered orally to male and female rats at 3 mg/kg. known to slow or delay healing. Concomitant use of topical NSAIDs and PATIENT COUNSELING INFORMATION topical steroids may increase the potential for healing problems. Slow or Delayed Healing Corneal Effects Patients should be informed of the possibility that slow or delayed healing Use of topical NSAIDs may result in keratitis. In some susceptible patients, may occur while using nonsteroidal anti‐inflammatory drugs (NSAIDs). continued use of topical NSAIDs may result in epithelial breakdown, corneal Avoiding Contamination of the Product thinning, corneal erosion, corneal ulceration or corneal perforation. These Patients should be instructed to avoid allowing the tip of the dispensing events may be sight threatening. Patients with evidence of corneal epithelial container to contact the eye or surrounding structures because this could breakdown should immediately discontinue use of topical NSAIDs including cause the tip to become contaminated by common bacteria known to cause ILEVRO™ Suspension and should be closely monitored for corneal health. ocular infections. Serious damage to the eye and subsequent loss of vision Postmarketing experience with topical NSAIDs suggests that patients may result from using contaminated solutions. with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), Use of the same bottle for both eyes is not recommended with topical eye rheumatoid arthritis, or repeat ocular surgeries within a short period of time drops that are used in association with surgery. may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these Contact Lens Wear patients. ILEVRO™ Suspension should not be administered while wearing contact lenses. Postmarketing experience with topical NSAIDs also suggests that use more than 1 day prior to surgery or use beyond 14 days post surgery may Intercurrent Ocular Conditions increase patient risk and severity of corneal adverse events. Patients should be advised that if they develop an intercurrent ocular condition (e.g., trauma, or infection) or have ocular surgery, they should Contact Lens Wear immediately seek their physician’s advice concerning the continued use of ILEVRO™ Suspension should not be administered while using contact lenses. the multi‐dose container. ADVERSE REACTIONS Concomitant Topical Ocular Therapy Because clinical studies are conducted under widely varying conditions, If more than one topical ophthalmic medication is being used, the medi- adverse reaction rates observed in the clinical studies of a drug cannot be cines must be administered at least 5 minutes apart. directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice. Shake Well Before Use Patients should be instructed to shake well before each use. U.S. Patent Ocular Adverse Reactions Nos. 5,475,034; 6,403,609; and 7,169,767. The most frequently reported ocular adverse reactions following cataract surgery were capsular opacity, decreased visual acuity, foreign body sensation, increased intraocular pressure, and sticky sensation. These events occurred in approximately 5 to 10% of patients. Other ocular adverse reactions occurring at an incidence of approximately 1 to 5% included conjunctival edema, corneal edema, dry eye, lid margin crusting, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, photophobia, tearing and vitreous detachment. Some of these events may be the consequence of the cataract surgical ALCON LABORATORIES, INC. Fort Worth, Texas 76134 USA procedure. © 2013 Novartis 2/13 ILV13030JAD

RP0114_Alcon Ilevro PI.indd 1 12/16/13 11:24 AM REVIEW NEWS Volume XXI • No. 2 • February 2014 Probability of Blindness From Glaucoma Nearly Halved

The probability of blindness due to the incidence of blindness due to OAG in and treatment of most vision loss at- serious eye disease glaucoma has de- at least one eye had decreased from tributed to diabetes, a new study creased by nearly half since 1980, 25.8 percent for subjects diagnosed shows that less than half of Ameri- according to a study published this between 1965 and 1980 to 13.5 per- cans with damage to their eyes from month in Ophthalmology. The recent for those diagnosed between diabetes are aware of the link be- searchers speculate that advances in 1981 and 2000. The population inci- tween the disease and visual impair- diagnosis and therapy are likely causes dence of blindness within 10 years of ment, and only six in 10 had their for the decrease, but caution that a diagnosis also decreased from 8.7 per eyes fully examined in the year lead- signifi cant proportion of patients still 100,000 to 5.5 per 100,000 for those ing up to the study. progress to blindness. groups, respectively. Yet, 15 percent The research, described online on A leading cause of irreversible of the patients diagnosed in the more Dec. 19 in JAMA Ophthalmology, blindness worldwide, glaucoma af- recent timeframe still progressed to also found that nearly half of those fects more than 2.7 million individuals blindness. with diabetes and eye damage had aged 40 and older in the United States “These results are extremely en- not visited a clinician charged with and 60.5 million people globally. Sig- couraging for both those suffering managing their disease in that same nifi cant changes in diagnostic criteria, from glaucoma and the doctors who time period. new therapies and tools as well as im- care for them, and suggest that the “As a nation, we are woefully in- provements in glaucoma management improvements in the diagnosis and adequate as health-care providers techniques have benefi ted individual treatment have played a key role in in explaining to our patients with patients; however their effect on the improving outcomes,” said Arthur J. diabetes that the condition can have rates of visual impairment on a popu- Sit, MD, associate professor of oph- a detrimental effect on their eyes,” lation level has remained unclear. This thalmology at the Mayo Clinic Col- says study leader Neil M. Bressler, study, conducted by a team based at lege of Medicine and lead researcher MD, a professor of ophthalmol- the Mayo Clinic, was the fi rst to assess for the study. “Despite this good news, ogy at the Johns Hopkins University long-term changes in the risk of pro- the rate at which people continue to go School of Medicine and chief of the gression to blindness and the popula- blind due to OAG is still unacceptably retina division at the Johns Hopkins tion incidence of glaucoma-related high. This is likely due to late diagnosis Wilmer Eye Institute. “The earlier blindness. By identifying epidemiolog- and our incomplete understanding of we catch diabetic eye disease, the ic trends in glaucoma, the researchers glaucoma, so it is critical that research greater the likelihood that we can hope to gain insight into best practices into this devastating disease continues, help patients keep their good vision. for the distribution of health and med- and all eye care providers be vigilant Clearly, this research shows how ical resources, as well as management in looking for early signs of glaucoma far we have to go to educate people approaches for entire populations. during routine exams.” about this frequent and feared com- The researchers reviewed every in- plication.” cident case (857 cases total) of open- People with diabetes have at angle glaucoma diagnosed from 1965 Diabetics Losing least a 10-percent risk of develop- to 2009 in Olmsted County, Minn., one ing diabetic macular edema during of the few places in the world where Vision Despite their lifetime, and estimates suggest long-term population-based studies that close to 745,000 of them in the are conducted. They found that the Advances United States have swelling in the 20-year probability and the population Despite recent advances in prevention macula.

4 | Review of Ophthalmology | February 2014

004_rp0214_news.indd 4 1/24/14 10:49 AM Until recently, 15 percent of patients who developed the condition and were treated for it with the standard laser therapy still lost their vision. Dr. Bressler says that ocular in- Phillips* Crosshair Axis Marker jections reduce the swelling and risk of vision loss to less than 5 percent. With treatment, moreover, half of patients ﬁ nd their vision improves, making prompt diagnosis critical. For the study, the Johns Hopkins- led team of researchers used data collected between 2005 and 2008 from Americans enrolled in the Na- tional Health and Nutrition Exami- nation Survey (NHANES). Among the 798 people over the age of 40 with a self-reported diagnosis of type 2 diabetes and who had retinal im- #R T OS EN aging done, 48 had diabetic macular SHAIR!LIGNM edema and were asked in the survey whether a physician had told them about the link between diabetes and vision problems (44.7 percent were). IqUE# They were also asked whether H5N ROS IT SH S7 A they had seen a heath-care provider E IR 08-16160-C: Phillips CrosshairAD Gravity Marker L about their diabetes in the previous " G year (46.7 percent had), and wheth- IN K R er they had received an eye exami- A - nation, including pupil dilation, in L

the previous year (59.7 percent had). S I

Some 30 percent of the individuals $ with diabetic macular edema already had some type of vision loss related to the disease. s 'RAVITY7EIGHTED&OR!CCURATE0LACEMENT7HEN0ATIENT)S While some people fail to see )N4HE5PRIGHT0OSITION eye doctors or diabetes educators s !XIS -ARKS /N "EVEL 4O -ANUALLY 3ET 4O $ESIRED !XIS because they lack insurance, Dr. Bressler says that most of the prob- s #ROSSHAIR &UNCTION !LLOWS 3URGEON 4O!LIGN -ARKS $IRECTLY lem is likely a lack of understanding 7HILE 6IEWING 4OPOGRAPHY !LLOWING &OR ! 3AFETY #HECK about the risks, and most people !ND&INER2EFINEMENT/F!XIS"EFORE-ARKING probably aren’t referred to eye-care s 2EUSABLE !UTOCLAVABLE -ADE)N4HE53! 'UARANTEED&OR specialists who can quickly deter- ,IFE !ND!VAILABLE&OR! $AY3URGICAL%VALUATION7ITHOUT mine retinal vulnerability. /BLIGATION “We can prevent a lot of vision im- #ONTACT2HEIN-EDICALAT pairment or blindness if we can just &OR-ORE)NFORMATION get these people into the medical system,” he says. Now that the extent of the problem is known, strategies can be developed to address issues 3360 Scherer Drive, Suite B, St. Petersburg, FL 33716 of patient education, access to spe- s4EL s&AX cialists and costs. %MAIL)NFO 2HEIN-EDICALCOMs7EBSITEWWW2HEIN-EDICALCOM $EVELOPED)N#OORDINATION7ITH!NDREW&0HILLIPS -$

-ICHAELANGELO ,AMENTATION 1342 Rev.A AHBC

004_rp0214_news.indd 5 1/24/14 10:49 AM REVIEW News

generation. And if it reverses damage plants are performed annually in the Available in the eye, it raises the possibility of United States, making this surgical a cure for other congenital disorders. procedure one of the most common Drug May The challenge is getting it to the right and successful in transplantation. place at the right time.” But out of that total, about 4,000 fail, with the recipient’s body reject- Treat Aniridia ing the corneal graft and requiring a University of British Columbia and Van- Molecule Could second operation. couver Coastal Health scientists A surprising fi nding of the study have developed a potential cure for Be Key to Corneal was learning that IFN-γ can act both a rare eye disease, showing for the as an immune system suppressor or fi rst time that a drug can repair a Transplant Success activator, depending on the context birth defect. For the estimated 10 percent of patients of the histocompatibility antigens They formulated the drug Ata- whose bodies reject a corneal trans- perceived by the immune system, luren into eye drops, and found that plant, the odds of a second transplant Dr. Niederkorn said. Earlier studies it consistently restored normal vision succeeding are poor. All that could indicated that this molecule only ac- in mice who had aniridia, a condi- change, however, based on a UT tivated immune system rejection of tion that severely limits the vision of Southwestern Medical Center study transplants and that disabling IFN-γ about 5,000 people in North Ameri- that has found a way to boost the cor- would improve the acceptance rate. ca. A small clinical trial with children neal transplant acceptance rate. But that was not necessarily the case; and teens is expected to begin next In the study, researchers found researchers found that when there year in Vancouver, the United States that corneal transplants in mice were was no MHC matching between the and the United Kingdom. accepted 90 percent of the time mice and the transplants, and IFN-γ Aniridia is caused by the presence when the action of an immune sys- was disabled, the transplant rejec- of a “nonsense mutation”—an extra tem molecule called interferon-gam- tion rate was 100 percent. “stop sign” on the gene that inter- ma (IFN-γ) was blocked and when “Under those conditions, IFN-γ rupts production of a protein crucial the mice shared the same major was needed to maintain the T regu- for eye development. histocompatibility complex (MHC) latory cells, which suppress the im- Ataluren is believed to have the genotype as the donor cornea. MHC mune response,” Dr. Niederkorn power to override the extra stop matching is not typically done with said. sign, thus allowing the protein to be human corneal transplants because Rather than recommend trans- made. The UBC-VCH scientists ini- of a high acceptance rate. plant matching and inactivation of tially thought the drug would work “Our fi ndings indicate that neither IFN-γ for all fi rst-time corneal trans- only in utero—giving it to a pregnant MHC matching alone nor adminis- plant recipients, Dr. Niederkorn said mother to prevent aniridia from ever tration of anti-IFN-γ antibody alone this strategy would make the most arising in her fetus. But then they enhances graft survival. However, we sense for those who have already re- gave their specially formulated Ata- found that when MHC matching is jected a cornea, or for those individ- luren eye drops, which they call combined with anti-IFN-γ therapy, uals believed to be at risk for a cor- START, to two-week-old mice with long-term corneal transplant sur- neal transplant rejection. But before aniridia, and found that it actually vival is almost guaranteed,” said Dr. a clinical trial can be launched to reversed the damage they had been Jerry Niederkorn, a professor of oph- verify the results obtained in mice, born with. thalmology and microbiology at UT further study is needed. “We were amazed to see how mal- Southwestern and senior author of “We are working to develop an leable the eye is after birth,” said the study. IFN-γ antibody in eye-drop form,” Cheryl Gregory-Evans, PhD, an as- The study fi ndings, reported in Dr. Niederkorn said. “Then we need sociate professor of ophthalmology the December issue of the American to test whether this antibody will and visual sciences and a neurobiolo- Journal of Transplantation, suggest work in animal models.” gist at the Vancouver Coastal Health an option to improve the odds of a The lead author of the study was Research Institute. “This holds subsequent corneal transplant’s suc- Khrishen Cunnusamy, PhD, a former promise for treating other eye condi- cess for those patients whose fi rst postdoctoral researcher in Dr. Nie- tions caused by nonsense mutations, transplant was rejected. derkorn’s lab and current UT South- including some types of macular de- More than 40,000 corneal trans- western medical student.

6 | Review of Ophthalmology | February 2014

004_rp0214_news.indd 6 1/24/14 10:49 AM ReSTOR ® IOLs deliver more.

Recommend AcrySof ® IQ ReSTOR® +3.0 D Multifocal IOLs for the broadest range of vision.† For cataract patients who desire decreased spectacle dependence for the broadest range of vision, the AcrySof® IQ ReSTOR® +3.0 D Multifocal IOL delivers more: • The strength of true performance at all distances 1 • The confidence of the trusted AcrySof® IQ platform • The reassurance of over 93% patient satisfaction2 For information about the lenses that give your patients more, visit AlconSurgical.com or contact your Alcon sales representative today. Please refer to the Important Safety Information on the accompanying page.

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MULTIFOCAL IOLs Deliver More

RP0214_Alcon Restor.indd 1 1/13/14 2:55 PM Review

REVIEW Letters

o the Editor: Spatial and temporal visual impairments are prominent T The review (Pediatric Patient, December 2013) of the features of amblyopia. Judging treatment outcomes with Pediatric Eye Disease Investigator Group’s (PEDIG) article static and isolated optotypes may not be an optimum in- misses some contradictions in the group’s reports. dicator of visual improvement. When reading ability was A PEDIG fi nding was that the acuity of both the amblyo- tested in amblyopic eyes that were successfully treated, a pic and fellow eyes gradually improved with age prior to PEDIG study found that signifi cant limitations were still treatment.1 (Table 3 [Baseline Characteristics According present.5 to Age at Enrollment]). The degree of improvement with PEDIG was formed in 1997 following a review by increasing age was very similar to treatment outcomes. Snowdon and Stewart-Brown. They found “no studies This confi rmed Clarke’s observation that “As in all trials, of natural history of amblyopia, … no randomised con- there is a possibility that those left untreated may suffer, trolled trials of treatment vs. no treatment …”.6 These but the no-treatment group in fact showed a tendency to defi ciencies have still not been addressed by the PEDIG’s spontaneous improvement.”2 reports. These lapses inappropriately elevate hypotheses The lack of untreated controls in most amblyopia that are based on insuffi cient or irrelevant data to dogma. treatment studies makes it impossible to distinguish the We cannot be certain about their conclusions until objec- effects of training and increasing literacy from the pre- tive information is available. sumed benefi ts of treatment. The PEDIG authors agree The clinical environment for amblyopia is complicated that inclusion of an untreated control group would have by the availability of many therapies in addition to oc- been desirable from a scientifi c point of view.3 Since “the clusion and penalization. These include, among others, response to treatment in this study was similar across the forehead massage, suturing eyelids closed, perceptual age range …”4 a delay in including a control group would learning, rotating prisms, neuroadaptation, periauricu- not have incurred appreciable risk. lar acupuncture, vision training, levodopa-carbidopa, colored lenses, Bangerter fi lters, supervised near work, playing computer games and neurologic organization training. The providers of these therapies claim results the AcrySof® ReSTOR® lens indicated that posterior capsule opacification that are equivalent to conventional therapies. Michael (PCO), when present, developed earlier Repka, MD, [of the American Academy of Ophthalmol- into clinically significant PCO. Prior to ogy] warned that the Affordable Care Act may encourage surgery, physicians should provide prospective patients with a copy of the overutilization of amblyopia screening and treatments. Patient Information Brochure available He is correct, and the lack of objective data may encour- from Alcon for this product informing age inappropriate remedies. www.AcrySofReSTOR.com them of possible risks and benefits associated with the AcrySof® IQ ReSTOR® It is important for our profession to develop a sound CAUTION: Federal (USA) law restricts IOLs. basis for the diagnosis and treatment of children pre- this device to the sale by or on the order Studies have shown that color vision sumed to have amblyopia—a basis consistent with proofs of a physician. discrimination is not adversely affected INDICATIONS: The AcrySof® IQ ReSTOR® in individuals with the AcrySof® Natural of effi cacy that are consistent with therapies in other spe- Posterior Chamber Intraocular Lens IOL and normal color vision. The effect cialties, a basis that shows improvement in acuity, read- (IOL) is intended for primary implanta- on vision of the AcrySof® Natural IOL tion for the visual correction of aphakia in subjects with hereditary color vision ing rate, and other visual functions that does not occur secondary to removal of a cataractous defects and acquired color vision de- without that treatment. We are all familiar enough with lens in adult patients with and without fects secondary to ocular disease (e.g., alternative treatment to know what awaits if we fail to presbyopia, who desire near, intermedi- glaucoma, diabetic retinopathy, chronic ate and distance vision with increased uveitis, and other retinal or optic nerve properly address this issue now. spectacle independence. The lens is in- diseases) has not been studied. Do not tended to be placed in the capsular bag. resterilize; do not store over 45° C; use Philip Lempert, MD WARNING/PRECAUTION: Careful pre- only sterile irrigating solutions such as ® ® operative evaluation and sound clinical BSS or BSS PLUS Sterile Intraocular Ithaca, N.Y. judgment should be used by the sur- Irrigating Solutions. geon to decide the risk/benefit ratio be- ATTENTION: Reference the Directions 1. Pediatric Eye Disease Investigator Group. The clinical profi le of moderate amblyopia in children fore implanting a lens in a patient with for Use labeling for a complete listing of younger than 7 years. Arch Ophthalmol 2002;120:281-7. any of the conditions described in the indications, warnings and precautions. 2. Clarke MP, Wright CM, Hrisos S, et al. Randomised controlled trial of treatment of unilateral visual impairment detected at preschool vision screening. BMJ 2003;327:1251. Directions for Use labeling. Physicians 3. The Pediatric Eye Disease Investigator Group. Amblyopia. Ocular Surgery News July 15, 2002 Page should target emmetropia, and ensure 7. that IOL centration is achieved. Care 4. The Pediatric Eye Disease Investigator Group. The course of moderate amblyopia treated with should be taken to remove viscoelastic patching in children: Experience of the amblyopia treatment study. Am J Ophthalmol 2003;136:620-9. from the eye at the close of surgery. 5. Repka MX, Kraker RT, Beck RW, Cotter SA, et al; Pediatric Eye Disease Investigator Group. Monocular Some patients may experience visual oral reading performance after amblyopia treatment in children. Am J Ophthalmol 2008;146:942-7. disturbances and/or discomfort due 6. Snowdon S, Stewart-Brown SL. Preschool vision screening: Results of a systematic review. York: to multifocality, especially under dim NHS centre for reviews, 1997 Report 9. light conditions. Clinical studies with © 2013 Novartis 9/13 RES13076JAD

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RP0114_Keeler PSL.indd 1 12/16/13 2:35 PM Editorial

REVIEW Board

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004_rp0214_news.indd 10 1/24/14 10:49 AM (ocriplasmin) Intravitreal Injection, 2.5mg/mL

The FIRST AND ONLY pharmacologic treatment for symptomatic VMA TAKE IMMEDIATE ACTION WITH JETREA®

Indication JETREA® (ocriplasmin) Intravitreal Injection, 2.5 mg/mL, is a proteolytic enzyme indicated for the treatment of symptomatic vitreomacular adhesion (VMA). IMPORTANT SAFETY INFORMATION Warnings and Precautions • A decrease of ≥3 lines of best-corrected visual acuity (BCVA) was experienced by 5.6% of patients treated with JETREA® and 3.2% of patients treated with vehicle in the controlled trials. The majority of these decreases in vision were due to progression of the condition with traction and many required surgical intervention. Patients should be monitored appropriately. •Intravitreal injections are associated with intraocular inflammation/infection, intraocular hemorrhage, and increased intraocular pressure (IOP). Patients should be monitored and instructed to report any symptoms without delay. In the controlled trials, intraocular inflammation occurred in 7.1% of patients injected with JETREA® vs 3.7% of patients injected with vehicle. Most of the post-injection intraocular inflammation events were mild and transient. If the contralateral eye requires treatment with JETREA®, it is not recommended within 7 days of the initial injection in order to monitor the post-injection course in the injected eye. • Potential for lens subluxation. •In the controlled trials, the incidence of retinal detachment was 0.9% in the JETREA® group and 1.6% in the vehicle group, while the incidence of retinal tear (without detachment) was 1.1% in the JETREA® group and 2.7% in the vehicle group. Most of these events occurred during or after vitrectomy in both groups. • Dyschromatopsia (generally described as yellowish vision) was reported in 2% of all patients injected with JETREA®. In approximately half of these dyschromatopsia cases, there were also electroretinographic (ERG) changes reported (a- and b-wave amplitude decrease). Adverse Reactions • The most commonly reported reactions (≥5%) in patients treated with JETREA® were vitreous floaters, conjunctival hemorrhage, eye pain, photopsia, blurred vision, macular hole, reduced visual acuity, visual impairment, and retinal edema.

Please see Brief Summary of full Prescribing Information on adjacent page. VISIT JETREACARE.COM OR SCAN © 2013 ThromboGenics, Inc. All rights reserved. ThromboGenics, Inc., 101 Wood Avenue South, Suite 610, Iselin, NJ 08830 – USA QR CODE FOR REIMBURSEMENT JETREA and the JETREA logo, JETREA CARE and the JETREA CARE logo and THROMBOGENICS and the THROMBOGENICS logo are trademarks or registered trademarks of ThromboGenics NV. 10/13 OCRVMA0133 AND ORDERING INFORMATION JETREA.COM

RP0214_Thrombogenics.indd 1 1/23/14 3:31 PM 5 WARNINGS AND PRECAUTIONS half of these dyschromatopsia cases there were also The number of patients with at least 3 lines increase in 5.1 Decreased Vision electroretinographic (ERG) changes reported (a- and visual acuity was numerically higher in the ocriplasmin A decrease of ≥ 3 line of best corrected visual acuity (BCVA) b-wave amplitude decrease). group compared to vehicle in both trials, however, the was experienced by 5.6% of patients treated with JETREA number of patients with at least a 3 lines decrease in visual and 3.2% of patients treated with vehicle in the controlled 6.2 Immunogenicity acuity was also higher in the ocriplasmin group in one of the trials [see Clinical Studies]. As with all therapeutic proteins, there is potential for studies (Table 1 and Figure 1). BRIEF SUMMARY OF FULL PRESCRIBING immunogenicity. Immunogenicity for this product has not INFORMATION The majority of these decreases in vision were due to been evaluated. Table 1: Categorical Change from Baseline in progression of the condition with traction and many BCVA at Month 6, Irrespective of Vitrectomy ® 8 USE IN SPECIFIC POPULATIONS Please see the JETREA package insert for full required surgical intervention. Patients should be (Study 1 and Study 2) Prescribing Information. monitored appropriately [see Dosage and Administration]. 8.1 Pregnancy: Teratogenic Effects Pregnancy Category C. Animal reproduction studies 1 INDICATIONS AND USAGE 5.2 Intravitreal Injection Procedure Associated have not been conducted with ocriplasmin. There are no Study 1 JETREA is a proteolytic enzyme indicated for the treatment Effects adequate and well-controlled studies of ocriplasmin in JETREA Vehicle Difference of symptomatic vitreomacular adhesion. Intravitreal injections are associated with intraocular pregnant women. It is not known whether ocriplasmin inflammation / infection, intraocular hemorrhage and increased 2 DOSAGE AND ADMINISTRATION can cause fetal harm when administered to a pregnant N=219 N=107 (95% CI) intraocular pressure (IOP). In the controlled trials, intraocular woman or can affect reproduction capacity. The systemic 2.1 General Dosing Information inflammation occurred in 7.1% of patients injected with ≥ 3 line Improvement in BCVA Must be diluted before use. For single-use ophthalmic exposure to ocriplasmin is expected to be low after JETREA vs. 3.7% of patients injected with vehicle. Most of intravitreal injection of a single 0.125 mg dose. Assuming intravitreal injection only. JETREA must only be the post-injection intraocular inflammation events were Month 6 28 (12.8%) 9 (8.4%) 4.4 (-2.5, 11.2) administered by a qualified physician. mild and transient. Intraocular hemorrhage occurred in 100% systemic absorption (and a plasma volume of 2700 mL), the estimated plasma concentration is > 3 line Worsening in BCVA 2.2 Dosing 2.4% vs. 3.7% of patients injected with JETREA vs. vehicle, respectively. Increased intraocular pressure occurred in 46 ng/mL. JETREA should be given to a pregnant woman The recommended dose is 0.125 mg (0.1 mL of the diluted only if clearly needed. Month 6 16 (7.3%) 2 (1.9%) 5.4 (1.1, 9.7) solution) administered by intravitreal injection to the 4.1% vs. 5.3% of patients injected with JETREA vs. vehicle, affected eye once as a single dose. respectively. 8.3 Nursing Mothers Study 2 5.3 Potential for Lens Subluxation It is not known whether ocriplasmin is excreted in human 2.3 Preparation for Administration milk. Because many drugs are excreted in human milk, JETREA Vehicle Difference Remove the vial (2.5 mg/mL corresponding to 0.5 mg One case of lens subluxation was reported in a patient who ocriplasmin) from the freezer and allow to thaw at room received an intravitreal injection of 0.175 mg (1.4 times and because the potential for absorption and harm to N=245 N=81 (95% CI) temperature (within a few minutes). Once completely higher than the recommended dose). Lens subluxation was infant growth and development exists, caution should thawed, remove the protective polypropylene flip-off cap observed in three animal species (monkey, rabbit, minipig) be exercised when JETREA is administered to a nursing ≥ 3 line Improvement in BCVA from the vial. The top of the vial should be disinfected with following a single intravitreal injection that achieved woman. vitreous concentrations of ocriplasmin 1.4 times higher Month 6 29 (11.8%) 3 (3.8%) 8.1 (2.3, 13.9) an alcohol wipe. Using aseptic technique, add 0.2 mL of 8.4 Pediatric Use 0.9% w/v Sodium Chloride Injection, USP (sterile, than achieved with the recommended treatment dose. > 3 line Worsening in BCVA Administration of a second intravitreal dose in monkeys, Safety and effectiveness in pediatric patients have not been preservative-free) into the JETREA vial and gently swirl the established. vial until the solutions are mixed. 28 days apart, produced lens subluxation in 100% of the Month 6 10 (4.1%) 4 (5.0%) -0.9 (-6.3, 4.5) treated eyes [see Nonclinical Toxicology]. 8.5 Geriatric Use Visually inspect the vial for particulate matter. Only a clear, In the clinical studies, 384 and 145 patients were ≥ 65 years colorless solution without visible particles should be used. 5.4 Retinal Breaks In the controlled trials, the incidence of retinal detachment and of these 192 and 73 patients were ≥ 75 years in the Using aseptic technique, withdraw all of the diluted solution JETREA and vehicle groups respectively. No significant Figure 1: Percentage of Patients with Gain or using a sterile #19 gauge needle (slightly tilt the vial to ease was 0.9% in the JETREA group and 1.6% in the vehicle Loss of ≥ 3 Lines of BCVA at Protocol-Specified group, while the incidence of retinal tear (without differences in efficacy or safety were seen with increasing withdrawal) and discard the needle after withdrawal of age in these studies. Visits the vial contents. Do not use this needle for the intravitreal detachment) was 1.1% in the JETREA group and 2.7% in the vehicle group. Most of these events occurred during injection. 10 OVERDOSAGE 15% or after vitrectomy in both groups. The incidence of retinal The clinical data on the effects of JETREA overdose are 10% Replace the needle with a sterile #30 gauge needle, detachment that occurred pre-vitrectomy was 0.4% in limited. One case of accidental overdose of 0.250 mg carefully expel the air bubbles and excess drug from the the JETREA group and none in the vehicle group, while ocriplasmin (twice the recommended dose) was reported 5% syringe and adjust the dose to the 0.1 mL mark on the the incidence of retinal tear (without detachment) that to be associated with inflammation and a decrease in visual 0% syringe (corresponding to 0.125 mg ocriplasmin). THE occurred pre-vitrectomy was none in the JETREA group and acuity. SOLUTION SHOULD BE USED IMMEDIATELY AS IT CONTAINS 0.5% in the vehicle group. -5%

NO PRESERVATIVES. Discard the vial and any unused 13 NONCLINICAL TOXICOLOGY -10% portion of the diluted solution after single use. 5.5 Dyschromatopsia 13.1 Carcinogenesis, Mutagenesis, Impairment Dyschromatopsia (generally described as yellowish vision) -15% of Fertility 7 14 28 90 180 2.4 Administration and Monitoring was reported in 2% of all patients injected with JETREA. In Days No carcinogenicity, mutagenicity or reproductive and Study 1 Study 1 Study 2 Study 2 The intravitreal injection procedure should be carried out approximately half of these dyschromatopsia cases there JETREA Vehicle JETREA Vehicle under controlled aseptic conditions, which include the use developmental toxicity studies were conducted with were also electroretinographic (ERG) changes reported ocriplasmin. of sterile gloves, a sterile drape and a sterile eyelid speculum (a- and b-wave amplitude decrease). 16 HOW SUPPLIED/STORAGE AND HANDLING (or equivalent). Adequate anesthesia and a broad spectrum 13.2 Animal Toxicology and/or Pharmacology Each vial of JETREA contains 0.5 mg ocriplasmin in 0.2 mL microbiocide should be administered according to standard 6 ADVERSE REACTIONS The ocular toxicity of ocriplasmin after a single citric-buffered solution (2.5 mg/mL). JETREA is supplied in medical practice. The following adverse reactions are described below and elsewhere in the labeling: intravitreal dose has been evaluated in rabbits, a 2 mL glass vial with a latex free rubber stopper. Vials are The injection needle should be inserted 3.5 - 4.0 mm monkeys and minipigs. Ocriplasmin induced an for single use only. Decreased Vision [see Warnings and Precautions] inflammatory response and transient ERG changes in posterior to the limbus aiming towards the • Storage center of the vitreous cavity, avoiding the rabbits and monkeys, which tended to resolve over • Intravitreal Injection Procedure Associated Effects time. Lens subluxation was observed in the 3 species at Store frozen at or below -4˚F ( -20˚C). Protect the vials horizontal meridian. The injection volume of [see Warnings and Precautions and Dosage and from light by storing in the original package until time of 0.1 mL is then delivered into the mid-vitreous. ocriplasmin concentrations in the vitreous at or above Administration] 41 mcg/mL, a concentration 1.4-fold above the intended use. Immediately following the intravitreal injection, patients • Potential for Lens Subluxation [see Warnings clinical concentration in the vitreous of 29 mcg/mL. 17 PATIENT COUNSELING INFORMATION should be monitored for elevation in intraocular pressure. and Precautions] Intraocular hemorrhage was observed in rabbits and In the days following JETREA administration, patients Appropriate monitoring may consist of a check for monkeys. • Retinal Breaks [see Warnings and Precautions and are at risk of developing intraocular inflammation/ perfusion of the optic nerve head or tonometry. If required, infection. Advise patients to seek immediate care from an a sterile paracentesis needle should be available. Dosage and Administration] A second intravitreal administration of ocriplasmin (28 days apart) in monkeys at doses of 75 mcg/eye ophthalmologist if the eye becomes red, sensitive to light, Following intravitreal injection, patients should be 6.1 Clinical Trials Experience (41 mcg/mL vitreous) or 125 mcg/eye (68 mcg/mL painful, or develops a change in vision [see Warnings and instructed to report any symptoms suggestive of Because clinical trials are conducted under widely varying vitreous) was associated with lens subluxation in all Precautions]. endophthalmitis or retinal detachment (e.g., eye pain, conditions, adverse reaction rates in one clinical trial of a ocriplasmin treated eyes. Sustained increases in IOP Patients may experience temporary visual impairment after redness of the eye, photophobia, blurred or decreased drug cannot be directly compared with rates in the clinical occurred in two animals with lens subluxation. receiving an intravitreal injection of JETREA [see Warnings vision) without delay [see Patient Counseling Information]. trials of the same or another drug and may not reflect the Microscopic findings in the eye included vitreous and Precautions]. Advise patients to not drive or operate rates observed in practice. liquefaction, degeneration/disruption of the hyaloideo- heavy machinery until this visual impairment has resolved. Each vial should only be used to provide a single injection capsular ligament (with loss of ciliary zonular fibers), lens for the treatment of a single eye. If the contralateral eye Approximately 800 patients have been treated with an If visual impairment persists or decreases further, advise degeneration, mononuclear cell infiltration of the vitreous, patients to seek care from an ophthalmologist. requires treatment, a new vial should be used and the intravitreal injection of JETREA. Of these, 465 patients and vacuolation of the retinal inner nuclear cell layer. sterile field, syringe, gloves, drapes, eyelid speculum, and received an intravitreal injection of ocriplasmin 0.125 mg These doses are 1.4-fold and 2.3-fold the intended clinical injection needles should be changed before JETREA is (187 patients received vehicle) in the 2 vehicle-controlled concentration in the vitreous of 29 mcg/mL, respectively. administered to the other eye, however, treatment with studies (Study 1 and Study 2). JETREA in the other eye is not recommended within 7 days 14 CLINICAL STUDIES Manufactured for: of the initial injection in order to monitor the post-injection The most common adverse reactions (incidence 5% - 20% The efficacy and safety of JETREA was demonstrated listed in descending order of frequency) in the vehicle- ThromboGenics, Inc. course including the potential for decreased vision in the in two multicenter, randomized, double masked, th controlled clinical studies were: vitreous floaters, 101 Wood Avenue South, 6 Floor injected eye. vehicle-controlled, 6 month studies in patients Iselin, NJ 08830 conjunctival hemorrhage, eye pain, photopsia, blurred with symptomatic vitreomacular adhesion Repeated administration of JETREA in the same eye is not vision, macular hole, reduced visual acuity, visual (VMA). A total of 652 patients (JETREA 464, recommended [see Nonclinical Toxicology]. impairment, and retinal edema. vehicle 188) were randomized in these 2 studies. U.S. License Number: 1866 ©2013, ThromboGenics, Inc. All rights reserved. After injection, any unused product must be discarded. Less common adverse reactions observed in the studies at Randomization was 2:1 (JETREA:vehicle) in Study 1 and 3:1 in Study 2. Version 1.0 No special dosage modification is required for any of the a frequency of 2% - < 5% in patients treated with JETREA Initial U.S. Approval: 2012 included macular edema, increased intraocular pressure, Patients were treated with a single injection of JETREA or populations that have been studied (e.g. gender, elderly). anterior chamber cell, photophobia, vitreous detachment, ThromboGenics U.S. patents: 7,445,775; 7,547,435; 7,914,783 vehicle. In both of the studies, the proportion of patients and other pending patents. 3 DOSAGE FORMS AND STRENGTHS ocular discomfort, iritis, cataract, dry eye, metamorphopsia, who achieved VMA resolution at Day 28 (i.e., achieved Single-use glass vial containing JETREA 0.5 mg in 0.2 mL conjunctival hyperemia, and retinal degeneration. success on the primary endpoint) was significantly higher JETREA and the JETREA logo are trademarks or registered solution for intravitreal injection (2.5 mg/mL). Dyschromatopsia was reported in 2% of patients injected in the ocriplasmin group compared with the vehicle group trademarks of ThromboGenics NV in the United States, 4 CONTRAINDICATIONS with JETREA, with the majority of cases reported from through Month 6. European Union, Japan, and other countries. None two uncontrolled clinical studies. In approximately 05/13 OCRVMA0072 PI G

RP0214_Thrombogenics pi.indd 1 1/23/14 3:33 PM February 2014 • Volume XXI No. 2 | revophth.com Cover Focus 24 | Inlays and Presbyopia: The Next Frontier By Christopher Kent, Senior Editor A look at three leading approaches using inlays to expand presbyopic patients’ range of vision.

30 | Crack a SMILE or Raise a Flap? By Walter Bethke, Managing Editor The benefits and drawbacks of this unique intrastromal refractive surgery procedure. 34 | Refractive Surgeons Embrace Thin Flaps By Walter Bethke, Managing Editor Our survey of refractive surgeons reveals the tools and techniques they like most.

38 | LASIK Xtra: Is It for Everyone? By Michelle Stephenson, Contributing Editor Surgeons have begun combining LASIK and cross-linking to avoid post-LASIK ectasia and to improve refractive outcomes.

February 2014 | Revophth.com | 13

013_rp0214_toc.indd 13 1/24/14 2:41 PM Departments

18 4 | Review News

17 | Editor’s Page 18 | Technology Update The Integrated Cataract Surgical Suite By linking diagnostic and surgical instruments, companies hope to improve safety and efficacy.

42 | Retinal Insider Multimodal Imaging of APMPPE and Related Disorders Recognizing the distinctive features of each placoid disorder is critical for accurate and timely diagnosis and management. 50 50 | Therapeutic Topics Wide Choices for Ocular Diagnoses A look at the value and utility of a range of diagnostic techniques and technology.

54 | Glaucoma Management NTG: The Nocturnal Blood Pressure Factor Evidence indicates that large dips in blood pressure at night correlate with progression in normal-tension glaucoma patients.

58 | Refractive Surgery New Ways to Detect Keratoconus Looking at corneal imaging in different ways can 67 enhance your ability to avoid risky surgeries.

60 | Research Review Effects of BAK on Surgical Outcomes

62 | Product News RPS Office Dry-Eye Test Cleared by FDA

64 | Classified Ads

67 | Wills Eye Resident Case Series 70 | Advertising Index

14 | Review of Ophthalmology | February 2014

013_rp0214_toc.indd 14 1/24/14 2:41 PM The Quintessential

Proven therapeutic utility in blepharitis, conjunctivitis, and other superficial ocular infections

O Profound bactericidal effect against gram-positive pathogens1

O Excellent, continued resistance profile—maintains susceptibility,2,3 even against methicillin-resistant Staphylococcus aureus 4

O Ointment provides long-lasting ocular surface contact time and greater bioavailability5

O Anti-infective efficacy in a lubricating base6

O Unsurpassed safety profile—low incidence of adverse events6

O Convenient dosing—1 to 3 times daily6

O Tier 1 pharmacy benefit status—on most insurance plans7

Bacitracin Ophthalmic Ointment is indicated for the treatment of superficial ocular infections involving the conjunctiva and/or cornea caused by Bacitracin susceptible organisms. Important Safety Information The low incidence of allergenicity exhibited by Bacitracin means that adverse events are practically non-existent. If such reactions do occur, therapy should be discontinued. Bacitracin Ophthalmic Ointment should not be used in deep-seated ocular infections or in those that are likely to become systemic. www.perrigobacitracin.com This product should not be used in patients with a history of hypersensitivity to Bacitracin.

Please see adjacent page for full prescribing information.

References: 1. Kempe CH. The use of antibacterial agents: summary of round table discussion. Pediatrics. 1955;15(2):221-230. 2. Kowalski RP. Is antibiotic resistance a problem in the treatment of ophthalmic infections? Expert Rev Ophthalmol. 2013;8(2):119-126. 3. Recchia FM, Busbee BG, Pearlman RB, Carvalho-Recchia CA, Ho AC. Changing trends in the microbiologic aspects of postcataract endophthalmitis. Arch Ophthalmol. 2005;123(3):341-346. 4. Freidlin J, Acharya N, Lietman TM, Cevallos V, Whitcher JP, Margolis TP. Spectrum of eye disease caused by methicillin-resistant Staphylococcus aureus. Am J Ophthalmol. 2007;144(2):313-315. 5. Hecht G. Ophthalmic preparations. In: Gennaro AR, ed. Remington: the Science and Practice of Pharmacy. 20th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2000. 6. Bacitracin Ophthalmic Ointment [package insert]. Minneapolis, MN: Perrigo Company; August 2013. 7. Data on file. Perrigo Company. Logo is a trademark of Perrigo.

RP0214_Perrigo.indd 1 1/13/14 3:13 PM 19TH ANNUAL Bacitracin Ophthalmic Ointment USP STERILE Rx Only OPHTHALMIC

DESCRIPTION: Each gram of ointment contains 500 units of Bacitracin in a low melting special base containing White Petrolatum and PRODUCT Mineral Oil. CLINICAL PHARMACOLOGY: The antibiotic, Bacitracin, exerts a profound action against many gram-positive pathogens, including the UIDE common Streptococci and Staphylococci. It is G also destructive for certain gram- negative organisms. It is ineffective against fungi. Innovative products to enhance your practice INDICATIONS AND USAGE: For the treatment of superficial ocular infections involving the conjunctiva and/or cornea caused by Bacitracin susceptible organisms. CONTRAINDICATIONS: This product should not be used in patients with a history of hypersensitivity to Bacitracin. PRECAUTIONS: Bacitracin ophthalmic ointment should not be used in deep-seated ocular infections or in those that are likely to The future become systemic. The prolonged use of antibiotic containing preparations may result in overgrowth of nonsusceptible organisms is in your particularly fungi. If new infections develop during treatment appropriate antibiotic or chemotherapy should be instituted. hands. One ADVERSE REACTIONS: Bacitracin has such a low incidence of allergenicity that for all practical purposes side reactions are tap, many practically non-existent. However, if such reaction should occur, therapy should be discontinued. possibilities. To report SUSPECTED ADVERSE REACTIONS, contact Perrigo at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DOSAGE AND ADMINISTRATION: The Experience the digital edition on your ointment should be applied directly into the conjunctival sac 1 to 3 times daily. In handheld device. Use your smart blepharitis all scales and crusts should be carefully removed and the ointment then device to scan the code below or visit: spread uniformly over the lid margins. Patients should be instructed to take appropriate measures to avoid gross contamination of the ointment when applying the ointment directly www.revophth.com/supplements/ to the infected eye. Download a QR scanner app. Launch app and hold your mobile device over the code HOW SUPPLIED: to view http://www.revophth.com/supplements/. NDC 0574-4022-13 3 - 1 g sterile tamper evident tubes with ophthalmic tip. NDC 0574-4022-35 3.5 g (1/8 oz.) sterile tamper evident tubes with ophthalmic tip. Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].

Manufactured For ® ® Minneapolis, MN 55427 0S400 RC J1 Rev 08-13 A

016_ro0214_housead.indd 16 1/27/14 2:54 PM ® Editor’s Page Christopher Glenn, Editor in Chief REVIEW E DITORIAL S TAFF

Editor in Chief Christopher Glenn (610) 492-1008 [email protected]

Managing Editor Making Innovations Walter C. Bethke (610) 492-1024 [email protected] Earn Their Stripes Senior Editor Christopher Kent (814) 861-5559 Every once in a while, one of our au- will be health care-related, accord- [email protected] thors or section editors writes some- ing to Bureau of Labor Statistics es- thing that resonates beyond the timates. Among them: home health Associate Editor topic they’re addressing and seems aides, physician assistants, occupa- Kelly Hills (610) 492-1025 to apply equally well to other issues. tional therapy assistants and dental [email protected] This time, the distinction goes to Dr. hygienists. Abelson and his Therapeutic Topics And it’s not just new levels of per- Chief Medical Editor column, in which he invokes Yogi sonnel that will settle into the space Mark H. Blecher, MD Berra, always a sound policy. In as- formerly reserved for the doctor and sessing new technologies that aim to the patient; as much as anything, Senior Director, Art/Production diagnose and/or follow the progress technology will be occupying that Joe Morris (610) 492-1027 of corneal disease, Dr. Abelson says, space. Patients can sit down today at [email protected] you have to ask (paraphrasing here), a shopping mall and have their blood are they really any better than what pressure, vision and BMI checked Art Director we have now? To be sure, these new by kiosks. Again, the optimist says, a Jared Araujo technologies have a place; but is it better-educated and more involved (610) 492-1023 along side of or in place of current patient can only improve the qual- [email protected] practice? ity of medical care. From telehealth Graphic Designer The squeeze is on in medicine; no to robotic surgery to contact lens- Matt Egger one would deny that. Though costs based detection of disease, or inno- (610) 492-1029 have leveled somewhat in recent vations we haven’t even imagined, [email protected] years, we still spend an unsustain- what another decade of innovation able 20 percent of our budget, $2.79 will bring couldn’t be more exciting. International coordinator, Japan trillion in 2012, or about $8,915 per As long as we stop along the way Mitz Kaminuma person on health care. Combine the and remember to ask of each of [email protected] cost and effi ciency pressure with the these new systems, innovations and Business Offi ces infl ux of new technologies and the improvements: Is it really better 11 Campus Boulevard, Suite 100 swelling ranks of an aging patient than what we have now? Newtown Square, PA 19073 population and it’s likely 10 years (610) 492-1000 from now, we may not even recog- Fax: (610) 492-1039 nize what the health-care system Subscription inquiries: will have evolved into. United States — (877) 529-1746 On the plus side, says the opti- Outside U.S. — (847) 763-9630 mist, a more effi cient new system E-mail: will push activites such as data-col- [email protected] lection and montoring treatment Website: www.revophth.com to lower-level members of the new health-care team, freeing physicians Professional Publications Group and specialists to practice at the Jobson Medical Information LLC highest level of their training. Nearly half of the 30 fastest-grow- ing occupations from 2012 to 2022

February 2014 | Revophth.com | 17

017_rp0214_edit.indd 17 1/27/14 2:51 PM Technology Update

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

The Integrated Cataract Surgical Suite By linking diagnostic instruments with surgical ones, companies hope to improve surgical safety and efﬁ cacy. Walter Bethke, Managing Editor

he drive to integrate and connect OR based on those measurements. The Verion system captures the Ta practice’s equipment is extend- With the Verion, the data is stored globe image and maps out landmarks ing into the cataract suite, as well, digitally on a USB memory stick that such as iris features and blood vessels, with the recent release of integrated is taken to the OR and inserted into explains Dr. Mackool. “That’s how systems from both Alcon and Carl the system. The microscope retrieves it orients the eye in space,” he says. Zeiss Meditec. Users say the beneﬁ ts the data, giving you a digital overlay “When you’re in the OR, you capture can run from simply having all the pa- that’s visible in the microscope oculars another image and the system overlays tient data transferred to the operating and indicates the correct axis at which the original reference image and the microscope to having the microscope to implant the toric IOL. Before this, new image, so that the patient’s eye display digital overlays to aid in the we’d mark the eye with a pen with the under the operating microscope is ori- positioning of toric lenses. Here’s a patient sitting up to indicate the prin- ented in space in the exact position the look at the two new systems and the cipal meridians, then use a toric axis machine expects.” Additionally, the features they bring to the practice. marker to locate the desired merid- Verion gives the surgeon the option of ian. With the Verion, these steps are aligning any IOL, toric or multifocal, Alcon’s Applied Integration eliminated. Instead, you have a digital, on the pupillary axis, the visual axis or real-time overlay as a direct indicator the geometric center of the cornea. A Alcon’s Cataract Refractive Suite of the preop data.” capsulorhexis guide, which can also be connects an imaging/measurement centered where the surgeon chooses, device called the Verion with the Cen- is also available as an overlay, to help turion phaco machine, the LenSx fem- guide the surgeon as he creates it. tosecond cataract laser and the Luxor For lens selection, the Verion has operating microscope. such formulas as the Holladay, Hol- “The goal is to have all of the sur- MD Mackool, Richard laday II, SRK/T and the Hoffer Q. geon’s in-ofﬁ ce data acquisition eas- “More important, after you’ve done ily transferable to the OR suite,’” says a number of cases and entered the Richard J. Mackool Jr., MD, of Asto- results into the system, the Verion will ria, N.Y., who uses the system. “In the optimize your case results in the fu- past, we would do the testing, obtain- ture by retrospectively analyzing the ing the IOL power and astigmatism The Alcon Verion can provide an axis guide data so you can tailor the program results on paper, and then make de- in the microscope to aid in the placement you choose to the cases you perform. cisions about our lens choice in the of a toric intraocular lens. For instance, everyone has a differ-

18 | Review of Ophthalmology | February 2014 This article has no commercial sponsorship.

018_rp0214_tech update.indd 18 1/24/14 10:59 AM ent surgical technique: Some when the patient is selected utilize a larger capsulorhexis from the list, Callisto Basic than others, and the effective will also begin recording high- lens position of the IOL may defi nition video of the case. Carl Zeiss Meditec be different in their patients If the surgeon upgrades to than it would be for surgeons Callisto Eye Assistance, the who make a smaller capsu- Callisto display will show sev- lorhexis.” eral forms of digital overlays If a surgeon uses a to guide the physician dur- LenSx femtosecond laser, ing different phases of the Dr. Mackool says the Verion procedure. If the Integrated data is transferrable to it as Data Injection System is also well. “The same information installed, these overlays will provided to the OR for toric appear right in the micro- lenses can be imported into If a surgeon upgrades to Callisto Eye Assistance, the Zeiss scope. There are currently the LenSx for creating arcu- Callisto will provide intraoperative guidelines on the screen. guides for corneal incisions, ate incisions,” he says. “Some including limbal relaxing inci- surgeons prefer arcuate incisions, or the OPMI Lumera microscope. sions; capsulorhexis creation; Z Align combine them with a toric lens. Ei- Richard Davidson, MD, associate for help in aligning toric IOLs; and K ther way, the axis goes directly to the professor of ophthalmology and medi- Track, which helps visualize corneal LenSx.” cal director for the faculty practice at curvature in combination with a kera- The other part of the equation, the the University of Colorado Hospital toscope. “For now, you have to mark Luxor operating microscope, also has Eye Center, used the Callisto system the eye preoperatively and the system features to aid the surgery. “Regard- in its prototype stage for capsulotomy tracks your marks,” says Dr. David- less of whether the patient is looking creation and the placement of toric son. “But the ultimate goal is to track at the microscope or looking away, lenses, and says he sees the potential based on a preop eye image. When the the red refl ex is extremely well-main- of such integrated systems. He has guides are on, the limbus is marked tained,” says Richard Mackool Sr., also worked with the Alcon system. so you can always see it, and you also MD, who also uses the system. “As “This is the direction cataract surgery have marks for the main axis and the such, areas of the red refl ex never be- is heading—the integrated system,” axis 90 degrees away from it. You get come dark, even in pretty extreme he says. “The main benefits to the a pretty precise idea of where the lens directions of gaze on the patient’s part. surgeon are convenience and patient needs to go.” This comes in handy if you want to safety. If you take the measurements The other eventual goal of the sys- rotate the globe a bit in a certain di- for the IOL in your office and then tem is to be able to transfer the infor- rection to gain access to one area or transfer them to the machine, either mation wirelessly between devices, or another, which happens all the time the femtosecond laser or straight to at least over a network. “When I used during surgery. In fact, the refl ex is so the operating room microscope, you the system, the data was transferred good that we rarely need to use more don’t have to worry about paper charts with a fl ash drive,” says Dr. Davidson. than 50 to 60 percent of maximum il- getting lost, choosing the wrong lens, “Our hospital system here is complex, lumination.” or the lens not matching up correctly so getting access to the network can be For information on the Verion and with the patient.” diffi cult, so we just used a fl ash drive. the integrated system, visit https:// The Callisto system comes in two Eventually it will be networked and, www.myalcon.com/products/surgical/ varieties: Basic and Assistance. With hopefully, wireless as well. The plan is, verion-guided-system/. Callisto Eye Basic, the aim is to sim- if you have a surgery center in your of- plify patient management in the oper- fi ce, to be able to do your IOLMaster The Zeiss Cataract Suite ating room by importing patient lists and then walk into the OR and turn via USB and viewing the microscope on the Callisto machine and see all of The brains of the integrated cata- settings directly in the oculars of the your data right in front of you.” ract suite from Carl Zeiss Meditec is device. The system will also remem- For information on Zeiss’ inte- the new Callisto computer-assisted ber the surgeon’s preferences for the grated cataract system, visit http:// surgery system, which acts as a hub for microscope, allowing the surgeon to meditec.zeiss.com/meditec/en_us/ the company’s IOLMaster device and recall them later. Before the surgery, products.html.

February 2014 | Revophth.com | 19

018_rp0214_tech update.indd 19 1/24/14 12:50 PM 020_rp0214_mqa.indd 20 from 2013,pleaseseeTable 1,below. mation onthepercentageofchange value unit(RVU) changes.Forinfor- ber 2013,containsseveralrelative A ophthalmic CPT codes in 2014? in codes CPT ophthalmic Q as changestofacilityreimbursementsanddoctorbonuses. ofthenewophthalmicCPTcodechanges,aswell An overview Code Changes A New Year Brings New 20 Table 1. RelativeValue UnitChanges Placement ofamniotictissue(65778) Fundus photos(92250) Visual ﬁ eld (92083) Eyeexam(92012) Intermediate 3 level4(99204) E/M newpatient Repair ectropion, tarsalwedge(67916) Fitting ofCL, (92072) keratoconus BCL ﬁ tting (92071) Repair entropion, suture(67921) CPT Code REVIEW | ReviewofOphthalmology Donna McCune, CCS-P, COE, CPMA Medicare Q&A Schedule, publishedinNovem- The to the values of some some of values the to Were there changes made Medicare PhysicianFee | February2014 Percent Change ICD-10 despiterequestsforanother Services expectstomoveforwardwith The CentersforMedicare&Medicaid implementation onOctober1,2014. A that require attention? that require attention? Q

-10 15 -8 -7 -5 -5 4 8 lished, inanticipationofICD-10 No newICD-9codeswerepub- ICD-9 diagnosis codes codes diagnosis ICD-9 Are there any changes to postponement by thepostponement by require fourunitson 0.125 mg). ( monly knownasJetrea for whatismorecom- contains anewcode specialty societies. sociation andvarious American MedicalAs- A manual? manual? Coding Procedural Common Healthcare 2014 the in to ophthalmology codes pertinent Q J7316, Ocriplasmin The J7316 code will The J7316codewill HCPCS manual Yes, the2014 new drug Are there This articlehasnocommercial sponsorship. bursement ofthedrugvial. the claimformforappropriatereim- III codesremainsatcarrierdiscretion. pharmacological agent. posterior extrascleralplacementof I code); proach (replacedwithnewCategory out extraocularreservoir, externalap- ment aqueousdrainagedevice,with- are deletedinthe2014handbook: screening ofvisualacuity, automated. and report; eral orbilateral,withinterpretation tion andreport; lateral orbilateral,withinterpreta- pressure for24hoursorlonger, uni- mented onJuly1,2013: can MedicalAssociation,were imple- released semiannuallybytheAmeri- However, CategoryIIIcodes, these rent ProceduralTechnology A Q Coverage and payment for Category Coverage andpaymentforCategory • • The followingCategoryIIIcodes • • • 0124T Conjunctival incision with 0124T Conjunctivalincisionwith 0330T Tear ﬁ lm imaging,unilat- 0329T Monitoringofintraocular 0192T Insertion ofanterior seg- 0333T Visual evokedpotential, in thehardcopyof2014Cur- anumberofchanges There are code changes for 2014? for changes code III Category any there Are Manual. 1/23/14 11:35 AM

857-0518 855 lacrivera.com ) (

What changes were PERSPECTIVE™ FRESH A Q published with Category I

codes in CPT 2014?

You’ll want to keep an eye on us. on eye an keep to want You’ll Several changes exist in the CPT Lacrivera.

A 2014 manual. There is a new code to replace Category III code months. coming the in products innovative

0192T, which is deleted from the 2014 CPT handbook: several introducing be we’ll it, prove To

•66183 Insertion of anterior segment aqueous drainage device, with- expensive. or painful complicated, be shouldn’t

out extraocular reservoir, external ap-

Treating chronic dry eye eye dry chronic Treating proach. you. hear We

With this change, the 2014

Medicare Physician Fee Schedule will establish RVUs and a payment rate for the surgeon; previously, the re- industry. imbursement was determined by the

Medicare Administrative Contractor.

Revisions were made to the two codes for amniotic membrane placement, and an additional adjustment to eye dry the language of a third:

•65778 Placement of amniotic

membrane on the ocular surface, without sutures; •65779 Placement of amniotic the up membrane on the ocular surface, sin-

gle layer sutured.

The revised text below 65780, Ocular surface reconstruction; amniotic membrane transplantation, mul- shake tiple layers states:

“For placement of amniotic mem-

brane without reconstruction using no sutures or single layer suture technique, see 65778, 65779.” to about Code 13150, Repair, complex, eye-

lids, nose, ears and/or lips; 1.0 cm or

less has been deleted, and the following codes revised to reﬂ ect this change: •13151 Repair, complex, eyelids, We’re nose, ears and/or lips; 1.1 cm to 2.5 cm; •13152 2.6 cm to 7.5 cm; •+13153 each additional 5 cm or less (list separately in addition to code for primary procedure). In the integument section, add-on code +15777, Implantation of biologic implant (e.g., acellular dermal matrix) for soft tissue reinforcement (i..e, breast, trunk), has supplemental

020_rp0214_mqa.indd 21 1/23/14 11:35 AM Medicare

REVIEW Q&A

parenthetical instructions that might a “complex” review, which means that electronic health records, they must apply in oculoplastic surgery with xe- medical records are requested prior start by July 1, 2014 and complete nografts. The new text reads: to any overpayment demand letter. their meaningful use attestation for “For implantation of biologic im- Stage 1 by October 1, 2014 to avoid plants for soft tissue reinforcement in Do any Medicare Part penalties in 2015. The published pen- tissues other than breast and trunk, Q B changes affect alty is 1 percent for 2015, 2 percent for use 17999.” benefi ciaries in 2014 from a 2016 and 3 percent for 2017. Beyond cost perspective? 2017, penalties are up to 5 percent. What types of regulatory Q issues were identifi ed The Medicare Part B premiums Will the Multiple Procedure in the Offi ce of Inspector A remain $104.90 for most benefi - Q Payment Reduction General’s annual work plan ciaries. The Part B deductible also re- continue in 2014? as areas of concern for mains unchanged at $147. These ben- ophthalmology in 2014? efi ciary costs are the same as in 2013. Yes. The MPPR policy reduces A the technical component of the Unfortunately, we don’t know at Are there any bonuses second and subsequent diagnostic A this time. The annual publica- Q for participating in the tests by 20 percent when more than tion of the OIG work plan, usually Physician Quality Reporting one diagnostic test is performed at occurring in the fall, was delayed until System or the Electronic one patient encounter on the same January 2014. According to the OIG Prescribing Incentive Program day by the same physician or group. website, “This change from the usual in 2014? The list of tests includes ultrasounds, October release will better align with imaging and visual fi elds. Tests that do priorities OIG has set for the coming While 2014 is the final year to not have a technical component (i.e., year, a time of continuing fi scal chal- A secure a bonus for successful gonioscopy) are not subject to this lenges.” participation in the PQRS, the fi nal policy. There are no changes to the year for the eRx bonus program was list of affected ophthalmic codes from Is the Recovery Audit 2013. It is expected that all providers 2013 to 2014. Q Contractor program except those that are exempt are using continuing to report successful electronic prescribing systems. If not, What’s happening with recoupment of overpaid penalties exist. For the PQRS, the Q Ambulatory Surgery dollars? bonus remains at 0.5 percent of total Centers’ facility fees in 2014? Medicare allowed dollars for profes- Yes. The RAC program contin- sional services to those who success- ASC facilities realize an increase A ues to thrive. Several states have fully participate in the program. This A in reimbursement. For 2014, the Medicaid RAC programs in place. (2014) is the final year to secure a Consumer Price Index and Multifactor Medicaid RACs operate at the direc- bonus for successful participation. Productivity Adjustment update the tion of the states with the discretion to ASC facility rate conversion factor determine what areas of their Medic- Will the Electronic Health by 1.2 percent. This increase results aid programs to target. Q Record Incentive Program in a very small but positive change to Total corrections since the continue to pay bonuses to facility reimbursement. Medicare Fee-for-Service Recovery eligible providers? Audit Program began in October Did hospital outpatient 2009 stand at $5.7 billion. Between Yes. As of September 2013, the Q department rates increase FY 2011 and 2012, corrected pay- A EHR Incentive Bonus Program similarly to ASC facility rates? ments doubled from $939 million had paid out $3.9 billion to eligible to $2.4 billion. As of June 2013, cor- providers: $115 million paid to oph- Yes. Hospital outpatient depart- rected payments for FY 2013 were thalmologists and $157 million to op- A ment rates increased approxi- already at $2.3 billion. tometrists. Providers who have suc- mately 1.7 percent for 2014. In June 2013, all four RACs added cessfully attested to Stage 1 for two blepharoplasty for review of physi- years, some three years, will be re- Ms. McCune is vice pres ident of the cian services, hospital services and quired to meet Stage 2 requirements Cor coran Con sult ing Group. Con tact ASC services. The review is listed as for 2014. For those not yet utilizing her at [email protected].

22 | Review of Ophthalmology | February 2014

020_rp0214_mqa.indd 22 1/23/14 11:35 AM Peer Pressure. Reichert® 7CR is the tonometer that has everyone talking. Dozens of peer-reviewed articles demonstrate that Corneal-Compensated IOP (IOPcc) may be clinically superior to other methods of tonometry in the evaluation of glaucoma. Made possible by Reichert’s patented Corneal Response Technology.®

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RP0214_Reichert.indd 1 1/23/14 2:16 PM 024_rp0214_f1.indd 24 Christopher Kent, SeniorEditor 24 The Next Frontier Inlays and Presbyopia: REVIEW |

Review ofOphthalmology Cover Focus Cover approaches using patients’ rangeof inlays toexpand three leading presbyopic A lookat vision. | February2014 ecutive medicaldirectorofthe Shina- says MinoruTomita, ex- PhD, MD, been implantedworldwideto date,” tries, andnearly20,000inlayshave is commerciallyavailablein49coun- AcuFocus’s Kamra.“TheKamrainlay and DrugAdministrationapprovalis The AcuFocusKamra P how theymaybeneﬁt yourpatients. what they’velearnedaboutthemand experience withtheseoptionsdiscuss tifocal visionusinganin-cornealens. Presbia inAmsterdam)createsmul- it; andtheFlexivueMicrolens(from the corneamultifocalbyreshaping Optics inLagunaHills,Calif.)makes field; theRaindrop(fromReVision hole principle toincreasedepthof Focus inIrvine,Calif.)usesthepin- process. TheKamrainlay(fromAcu- are indifferentstagesoftheapproval an implantinsidethecornea placing sibly non-emmetropesaswell. in emmetropicpresbyopes—andpos- without compromisingdistancevision lay, intendedtoimprovenearvision The latestapproachisthecornealin- The corneal inlay closesttoFood The cornealinlay Here, four surgeons with extensive Here, foursurgeonswithextensive Three variationsontheconceptof a newsetoftreatmentoptions. “cure” forpresbyopiaproduces eriodically, thesearchfora

Refractive Surgery This articlehasnocommercial sponsorship. visual acuityof20/20 maintain ameanuncorrecteddistance that theKamrainlaycanachieveand He notesthatstudieshaveshown ness andsafetythantheotherinlays. clinical datademonstratingeffective- planted aroundtheworld,ithasmore many Kamrainlayshavebeenim- intermediate andnearimagequality.” distance imagequalitybutimproves stop camera;ithasminimaleffecton of thesmall-apertureeffectinanf- of theinlay’s functionissimilartothat principle size from5to11µm.The 8,400 micro-perforationsthatvaryin and nanoparticlesofcarbon,with It’s madeofpolyvinylidenefluoride ameter and1.6-mmcentralaperture. 5 µmthick;ithasa3.8-mmouterdi- cases wereperformed. “The inlayis where approximately15,000 ofthose gawa LASIKCenterinTokyo, Japan, emmetropia bymakinga100-µm ﬂ LASIK isperformedfirstto target ametropic andpresbyopic, normal explains Dr. Tomita. “Ifbotheyesare mize thefunctionofKamrainlay,” before thesurgeryinordertomaxi- should bebetween-1and0Dright cal equivalentoftheimplantedeye only.refractive spheri- “Themanifest implanted inthenondominanteye intermediate visualacuity. Dr. Tomita saysthatbecauseso Like theotherinlays,Kamrais 1-4 andimproves 3-7 ap ap 1/24/14 10:57 AM Physicians at the Shinagawa LASIK center in Tokyo have implanted thousands of Kamra inlays. The chart above show the refractive results in the inlaid eye for a number of those patients. Left: uncorrected near visual acuity. Right: uncorrected distance visual acuity.

(sub-Bowman’s keratomileusis). A this takes longer as one ages. Some co-medical monitor for the FDA trial month later, a corneal pocket is creat- patients claimed they were hesitant to of the Presbia Flexivue inlay; he has ed in the nondominant eye at a depth drive a car for up to six months after also been an investigator for the Acu- of 200 µm using a femtosecond laser; the surgery, although these conditions Focus Kamra inlay. “The Flexivue is a the inlay is inserted into the pocket.” eventually alleviate over time.” 8,9 crystal clear refractive inlay,” he says. In terms of contraindications, Dr. Dr. Tomita notes that being able “It has an index of refraction different Tomita says patients are excluded if to remove the inlay if the patient is from the cornea. There’s a small hole they’ve had previous ocular surgeries unhappy is a big advantage. “Previous in the center of the inlay that provides or if they have any ocular pathology, papers have reported that patients’ distance vision and allows corneal nu- including keratectasia, corneal de- refractive state returned to within ±1 trients to circulate freely from poste- generation, severe blepharitis, retinal D of the preoperative refractive state rior to anterior. The inlay is designed disease, glaucoma, cataract, marked after inlay removal, with no loss of to sit in the central cornea and create topographic irregularities or severe corrected distance visual acuity,”10 he a multifocal effect so the patient gets dry eyes. “If a patient with severe dry says. “There were also reports of good good close and distance vision.” eye wants to have the inlay, we recom- recovery of corneal topography and Data from outside the United States mend that the condition be treated ag- corneal aberrometry.11 Once the inlay has supported the effectiveness of gressively before the surgery,” he says. has been removed, the patient can be the Flexivue. For example, in a study “It’s also important to provide suf- offered other treatment options. conducted by Ioannis Pallikaris, MD, ficient informed consent to the pa- “The Kamra inlay is at the ﬁ nal stag- PhD, and colleagues, presented at the tient,” he adds. “Preoperatively, risks es of FDA approval,” he adds. “We 2013 European Society of Cataract and precautions should be carefully hope it will be approved by the end and Refractive Surgery Annual Con- explained, especially to those who are of 2014.” gress in Amsterdam, 77 presbyopic professional drivers or drive at night. patients in Italy and Greece ranging Neuroadaptation is required to adjust The Presbia Flexivue Microlens in age from 45 to 60 received the im- to binocular vision with the inlay, and plant. Average monocular UNVC im- The Flexivue is a small, hydrophilic proved from 20/100 preoperatively to acrylic refractive inlay, 3.2 mm wide, 20/25 at one year postop, while bin- with a 1.6-mm hole in the center. The ocular UDVA was unchanged. “The refractive power of the ring ranges European data suggests that the inlay from +1.5 D to +3.5 D. Presbia an- is very safe, and patients have been nounced in November that the FDA very happy,” notes Dr. Maloney. had given conditional approval to be- “The inlay is typically implanted gin a Phase II trial of the inlay. in the nondominant eye of a patient Robert K. Maloney, MD, is a clini- who is emmetropic in both eyes,” he cal professor of ophthalmology at continues. “It creates a slight myopic UCLA-David Geffen School of Medi- shift and a mild multifocal effect in the The Kamra inlay uses thousands of cine and director of the Maloney Vi- implanted eye, thus creating a small tiny pinholes to increase depth of ﬁ eld. sion Institute in Los Angeles. He is the amount of monovision. It’s not an

February 2014 | Revophth.com | 25

024_rp0214_f1.indd 25 1/24/14 10:57 AM Cover Refractive Surgery

REVIEW Focus

extreme multifocal, which the central cornea to the could cause significant peripheral cornea with an glare at night, and it’s not opening in the periphery. a full monovision, which The surgeon grasps the in- could cause binocular dis- lay with a special forceps parity. So it seems to fi t in a and gently slides it into the sweet spot, with a mixture pocket, centers it over the of a little monovision and corneal light refl ex and re- multifocality. That makes leases it, the same way the it very well-tolerated.” Kamra inlay is inserted.” Gustavo E. Tamayo, As far as contraindica- MD, director of the Bogo- tions, Dr. Tamayo says ta Laser Refractive Insti- those would include the tute in Bogota, Colombia patient being unable to cor- says he has implanted the rect to 20/20 at near, what- Flexivue inlay in 75 pa- Presbia’s Flexivue Microlens creates multifocality with a ring that has ever the reason. “Dry eye is tients. “I use it only in pure refractive power surrounding a plano central region. not affected by the inlay, so emmetropes, defined as it’s not an issue,” he adds. those with ±1 D of sphere and ±0.75 like the pinhole mechanism of action Dr. Maloney notes that a full list of D of cylinder,” he says. “It’s mostly be- used by the Kamra inlay, it provides contraindications has not been devel- ing implanted in Europe, where it has an optical correction depending on oped so far. “We don’t have a lot of data the CE Mark, and South America, but the refractive defect present,” he says. yet,” he explains. “But obviously we it’s still not widely used; maybe 1,000 “The other advantage is the fact that it don’t implant the Flexivue in patients have been implanted in total.” does not have any issues regarding the with keratoconus or signifi cant corneal Dr. Maloney notes several differ- distribution of nutrients, which can be dystrophies. Also, signifi cant astigma- ences between the Kamra and Flexi- a factor with the Raindrop and Kamra tism is a contraindication because the vue inlays. “The Kamra inlay improves inlays. Also, the learning curve is very inlay doesn’t correct astigmatism. We reading vision by using pinholes to small; performing the surgery is sim- don’t believe the procedure will wors- increase the eye’s depth of focus,” he ple, fast and easy. Certainly one or two en dry eye because we’re not making a says. “The Flexivue is a refractive in- days of training would be suffi cient.” LASIK fl ap or ablating tissue.” lay; it improves depth of focus by alter- Nevertheless, Dr. Tamayo believes ing the path of light rays to the cornea. Flexivue in Practice that patient selection is critical. “In my It doesn’t block out the peripheral opinion, a monovision test conduct- light rays as the Kamra inlay does. Dr. Maloney says the Flexivue could ed with a +1.5 D contact lens in the “Regarding the reduction of incom- in theory be combined with LASIK. nondominant eye is crucial because ing light caused by the Kamra, one of “You’d make a fl ap, correct the refrac- it gives the patient the opportunity to the interesting things for me has been tive error, place the inlay and then experience the controlled monovision that patients are not complaining that replace the LASIK fl ap,” he says. “Or the inlay produces,” he says. He adds their vision is dark at night,” he adds. it could be used with a SMILE-type that the main limitation of the Flexi- “There may be a couple of reasons for procedure, in which you’d remove a vue may be that monovision effect. that. First, we only implant in one eye, lenticule through a stromal tunnel to “Even though it’s very small, many so the other eye is normal. Second, the correct the refractive error and then patients are sensitive to this approach. Kamra inlay is about 3.8 mm in diam- insert this inlay through the same stro- The rate of rejection after the monovi- eter, so when the pupil dilates at night mal tunnel. But I don’t know if that’s sion trial is almost 70 percent.” light enters the eye around the outer been tried yet. Right now we’re im- Along those lines, some surgeons edge of the inlay. It may be that those planting it in people who are close to have patients try bifocal contact lenses two factors together keep people from emmetropia. We’re not doing simul- before agreeing to implant an inlay, experiencing dim vision at night.” taneous correction of refractive errors. but Dr. Maloney is skeptical about Dr. Tamayo says the main advan- “In the trials, we’re using a pocket, the validity of this approach. “Bifocal tage the Flexivue has compared to the not a fl ap,” he continues. “In a normal contact lenses work in a different way other inlays is its more physiologic ap- emmetrope we make a pocket with than these inlays,” he notes. “The fact proach to correcting near vision. “Un- a femtosecond laser, a channel from that a patient likes the effect of bifocal

26 | Review of Ophthalmology | February 2014

024_rp0214_f1.indd 26 1/24/14 10:58 AM contact lenses is no guarantee that he’s performance improved dramatically going to like the inlay. For example, at all distances in both bright and dim the Kamra reduces the amount of light light. After nine months, all subjects coming in because it’s pinhole-based, were satisfi ed with their vision. and it causes some glare because of • Integrating into a LASIK prac- the 10,000 tiny nutrient holes. A mul- tice. At this year’s ASCRS meeting Ya- tifocal contact lens doesn’t reduce the suda Kazuomi, MD, will report early incoming light, and any glare it causes results from 107 patients implanted would probably be quite different with the Raindrop inlay in the non- from that caused by the pinholes.” dominant eye during standard LASIK In any case, Dr. Maloney says the in Japan. He indicates that he had no procedure isn’t diffi cult. “It’s not like The Raindrop inlay has no refractive power; trouble integrating the procedure, and mastering cataract surgery, but you it reshapes the cornea to create multifocality. patients have achieved good binocular do have to be trained in it,” he notes. vision, stable refraction and had low “For a LASIK surgeon, this will be by the implant produce a refractive rates of complication. relatively easy to learn.” change similar to what you’d achieve • Cataract surgery after an inlay. Dr. Tamayo notes that the FDA- by adding a lens.” Another ESCRS 2013 study reported approved Phase II clinical studies are Recent data indicates that the Rain- a case history in which cataract surgery just starting. drop is effective in a variety of situa- using a femtosecond laser was per- tions, including bilateral implantation: formed three years after the patient ReVision Optics’ Raindrop • Long-term stability. A study by received a Raindrop implant. The sur- Imola Ratkay, MD, PhD, that will be gery was successfully performed with John A. Hovanesian, MD, clini- presented at the 2014 American Soci- no adjustments to accommodate the cal assistant professor at UCLA Jules ety of Cataract and Refractive Surgery implant and no difficulty with mea- Stein Eye Institute in Los Angeles meeting, reports two-year visual out- surements or visualization. The pa- and in private practice at Harvard Eye comes with the Raindrop implant in tient is happy with the outcome and Associates in Laguna Hills, Calif., has 15 presbyopic patients. Binocular un- continues to have a full range of vision. implanted about 40 of the Raindrop corrected near visual acuity improved • Implanting in pseudophakes. inlays as part of the current United from 0.22 preop to 0.9 at two years, a Another ESCRS 2013 presentation States trial. “I’ve had enough experi- gain of six lines; and binocular uncor- reported that implanting the Raindrop ence to get a pretty good sense of how rected distance visual acuity improved in the nondominant eye of pseudo- patients react to it,” he says. “Gener- from 0.77 preop to 1.3 at two years. phakes produced positive results that ally, the reaction is something like the Acuity was stable, tending toward im- compared favorably with the results reaction of patients after LASIK— provement, and at two years there from the multicenter phakic U.S. trial, which makes sense because it’s a very were no complications. signifi cantly improving near, interme- similar procedure. • Bilateral implantation. A pre- diate and distance vision. “The Raindrop inlay is 2 mm in di- sentation at the 2013 ESCRS meeting “The data from outside the U.S. is ameter and 32 µm thick in the center,” reported data from a study in which promising and matches pretty closely Dr. Hovanesian explains. “It’s made 23 hyperopic subjects were implanted what we’re seeing in the U.S. trial,” of hydrogel, which allows nutrients with the Raindrop bilaterally—first adds Dr. Hovanesian. “We’re seeing and oxygen to pass through. It’s cur- in the nondominant eye, then three high levels of satisfaction, high levels rently placed in a fl ap interface in the to six months later in the dominant of spectacle independence and a low cornea, although soon we’ll be placing eye. Mean near vision improved from level of issues with quality of vision. it in a corneal pocket instead. It works 0.54 logMAR to -0.04 logMAR and We’ve seen very few explants or com- by causing central steepening in the remained stable; intermediate and plications.” cornea, producing a variable power distance vision also improved and re- as you move from the center toward mained stable. Compared to a single The Raindrop in Practice the periphery. The result is similar to inlay, bilateral implantation added ap- the effect of a multifocal lens. The im- proximately one line of improved near “Although there’s a little adaptation plant has no power itself; it’s a uniform vision. More than 80 percent of the bi- required, adapting to the Raindrop is disc of hydrogel. But the topographic lateral subjects were 20/20 or better at a lot easier than adapting to monovi- changes in the corneal surface caused all distances at all follow-up visits. Task sion,” notes Dr. Hovanesian. “Many

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patients can see very well up close “We’re optimistic about the results.” of technology. It’s appealing because it and adapt to it right away. Admittedly, serves emmetropic presbyopes—pa- these are patients who have been pre- Closer to a Presbyopia Cure? tients who are not well served by any tested with multifocal contact lenses other modality we have. Many of these to prove that they can deal well with “All of these inlays seem to work,” patients are not willing to try monovi- this type of refractive change. And notes Dr. Hovanesian. “You can make sion, and they’re generally too young that’s an important point: qualifying theoretical arguments as to why one for lens implant surgery. They want a your patients in advance is a real key to might be better than the others, but quick and easy solution, and they like success with an inlay. This is not some- they all seem to achieve a high level the idea of something that’s reversible thing you should generally do without of near vision in the range of J1, while if it doesn’t work out.” trying it fi rst.” only minimally compromising dis- “I think there will defi nitely be a As far as the advantages of this par- tance vision to 20/20 or 20/25.” place for these inlays in our clinical ticular inlay, Dr. Hovanesian points “Overall, the data from the FDA practices,” agrees Dr. Maloney. “It out that the Raindrop is very thin and trial of the Kamra, like the data from looks like the Kamra inlay is the one invisible. “The Kamra inlay is very ef- outside the United States regarding closest to FDA approval, but as a sur- fective, but it’s visible if you look at the the Flexivue, indicates that these in- geon I’d be very happy to add any one eye from the side, particularly if the lays are very safe,” adds Dr. Maloney. of them to my practice.” eye is light-colored, perhaps blue or Of course, they have a few disad- green,” he says. “Some patients might vantages. Dr. Maloney notes that all of Dr. Tomita is a consultant for Acu- see this as a disadvantage compared to them reduce distance vision to some Focus. Dr. Maloney is a paid consul- an implant that’s invisible. Apart from degree. “That’s the trade-off for im- tant for Presbia, but has no equity in- that, it’s difficult to make any com- proved reading vision,” he says. “And terest or fi nancial incentives relating parison, and I don’t think there’s any all of them cause night glare to some to the outcome of the Flexivue trial; head-to-head data. Frankly, I’m hope- degree; that’s the trade-off for chang- he has no fi nancial interest in AcuFo- ful that all three of these technologies ing the way the eye focuses light. So cus or the Kamra inlay. Dr. Tamayo will gain approval so that we can offer if patients aren’t happy, it’s because is a member of the Board of Consul- all of them to our patients.” their night vision isn’t good enough, tants for Presbia. Dr. Hovanesian is Regarding contraindications, Dr. their distance vision isn’t good enough, an investigator, consultant and mem- Hovanesian says anything that might or their reading vision isn’t good ber of the medical advisory board for contraindicate LASIK would also enough—the inlay isn’t strong enough ReVision Optics, but has no equity be an issue here. “I wouldn’t use the to give them the reading vision they interest in the company.

Raindrop in patients with extremely need. Those limitations are probably 1. Tomita M, Kanamori T, et al. Simultaneous corneal inlay dry eyes or who have corneal disorders common to all inlays. But the inlays implantation and laser in situ keratomileusis for presbyopia in patients with hyperopia, myopia, or emmetropia: Six-month that would make creating a corneal can be explanted, and vision returns to results. J Cataract Refract Surg 2012;38:495-506. 2. Tomita M, Kanamori T, et al. Small-aperture corneal inlay fl ap or pocket a poor idea,” he says. being very close to what it was before implantation to treat presbyopia after laser in situ keratomileusis. “These patients need to have good vi- surgery. In addition, we haven’t seen J Cataract Refract Surg 2013;39:898-905. 3. Waring GO 4th. Correction of presbyopia with a small aperture sion in both eyes and be willing to try significant adverse effects with the corneal inlay. J Refract Surg 2011;27:842-5. 4. Seyeddain O, Hohensinn M, et al. Small-aperture corneal inlay to adapt to a new optical system.” current generation of these inlays.” for the correction of presbyopia: 3-year follow-up. J Cataract Refract Surg 2012;38:35-45. Dr. Hovanesian believes the learn- “Using an inlay requires a compro- 5. Chayet A, Garza EB. Combined hydrogel inlay and laser in ing curve will be small for most sur- mise in distance vision,” agrees Dr. situ keratomileusis to compensate for presbyopia in hyperopic patients: One-year safety and effi cacy. J Cataract Refract Surg geons. “Typically it will be LASIK sur- Hovanesian. “That’s the nature of add- 2013;39:1713-21. 6. Garza EB, Gomez S, Chayet A, Dishler J. One-year safety geons doing these procedures,” he ing something to an emmetropic vi- and effi cacy results of a hydrogel inlay to improve near vision says. “As with any new device, there’s sual system. However, you’re usually in patients with emmetropic presbyopia. J Refract Surg 2013;29:166-72. a little bit of learning the right way to doing it in the nondominant eye in 7. Limnopoulou AN, Bouzoukis DI, et al. Visual outcomes and safety of a refractive corneal inlay for presbyopia using handle it, but after a few cases with a a patient who is a good adapter. For femtosecond laser. J Refract Surg 2013;29:12-8. little bit of guidance almost anybody most of these patients, what they sacri- 8. Jackson GR, Owsley C, McGwin G Jr. Aging and dark adaptation. Vision Res 1999;39:3975-82. can do this procedure.” fi ce is well worth it for what they gain. 9. King BR, Fogel SM, et al. Neural correlates of the age-related changes in motor sequence learning and motor adaptation in Dr. Hovanesian adds that the “The Raindrop inlay, and inlays in older adults. Front Hum Neurosci 2013;7:142. Raindrop inlay is currently in an general, are going to serve a very im- 10. Yılmaz OF, Alagöz N, et al. Intracorneal inlay to correct presbyopia:Long-term results. J Cataract Refract Surg expansion of the Phase III study. portant purpose,” he concludes. “As 2011;37:1275-1281. 11. Alió JL, Abbouda A, et al. Removability of a small aperture “We’re continuing to collect data, they become approved, we’re going to intracorneal inlay for presbyopia correction. J Refract Surg and the data looks good,” he says. fi nd that patients really want this kind 2013;29:8:550-6.

28 | Review of Ophthalmology | February 2014

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RP1111_FCI.indd 1 10/11/11 2:01 PM 030_rp0214_f2.indd 30 Walter Bethke, ManagingEditor 30 Or Raise aFlap? Crack aSMILE REVIEW |

Review ofOphthalmology Cover Focus Cover unique intrastromal drawbacks ofthis refractive surgery refractive surgery The beneﬁ ts and procedure. | February2014 varies basedontheamount ofcor- mal lenticule,thethicknessof which tosecond lasertocreateanintrastro- the CarlZeissMeditecVisumax fem- 5 Dofastigmatism. for correctionsupto-10Dwith approved outsideoftheUnitedStates iscurrently Theprocedure tiveness. handle onitspredictabilityandeffec- and SMILEsurgeonshavegottena have beenperformedinternationally, What theDataSays I on howtheycomparetoLASIK. est SMILEresults,andtheirthoughts of theprocedures.Herearetheirlat- the relativestrengthsandweaknesses experts arestartingtogetasenseof study ofLASIKvs.SMILE,refractive controlled, randomizedcomparative the future.Thoughthere’s beenno some surgeonsthinkit’s thewaveof tissue toinduceitsrefractiveeffect, involves anincisiontoremovestromal ticule extraction—orSMILE—still cedure knownassmall-incisionlen- surface. Thoughtheintrastromalpro- ing theneedtodisturbcorneal surgery wouldcometothefore,avoid- In SMILE,thesurgeonprograms Thousands ofSMILEprocedures sioned a time when intrastromal sioned atimewhenintrastromal niques, manysurgeonshaveenvi- n theevolutionofrefractivetech-

Refractive Surgery This articlehasnocommercial sponsorship.

All images: Rupal Shah, MD skill toidentifytheedge. lenticules canbechallenging, sinceittakes thin Some experts sayworking withvery best-corrected vision, with 1.5 percent best-corrected vision,with1.5percent percent hadunchangedorimproved dal reportsthatatthreemonths86 preop refractionof-7.25D,Dr. Hjort- cations of1,800SMILEeyeswitha paper coveringthesafetyandcompli- 80 percentwerewithin±0.5D.Ina ±1 Doftheintendedcorrectionand preop errorof-7.2D)werewithin percent ofhispatients(average of Ophthalmology. With SMILE,95 meeting oftheAmericanAcademy dal discussedtheirresultsatthe2013 SMILE procedures,andDr. Hjort- and histeamhaveperformed2,500 the incisionandremovelenticule. SMILE forcepstogothrough special sion of2.5to3mm.Thesurgeonuses then createsaperipheralcornealinci- rection hewantstoachieve.Thelaser Amsterdam’s JesperHjortdal,MD, 1/24/14 2:49 PM (27 eyes) losing two or more lines.1 The that could pose more diffi culties than average postop refraction was -0.28 in LASIK. “I think suction loss is the ±0.52 D, with a mean treatment error surgeon’s biggest fear when doing this of -0.15 ±0.5 D. By 18 months, how- procedure,” says Dr. Mehta. “You can’t ever, BCVA was within one line of its stop and restart after the movement preop level in all eyes. Intraoperative because the device is actually cutting complications included: the cornea, as opposed to ablating • epithelial abrasions in 108 eyes (6 it—there are cutting planes that need percent); to line up. Last year, though, Zeiss • small tears at the incision site in 32 Separating the small tissue bridges in changed some of the laser program- eyes (1.8 percent); some diffi cult lenticules can result in some ming and decreased the procedure • diffi cult lenticule extraction in 34 postoperative infl ammation, say surgeons. time from 35 to 25 seconds, so patients eyes (1.9 percent); don’t have to stay still under the laser as • perforated cap in four eyes (0.2 thousands of SMILE procedures, long as they had to before. percent) with no visual symptoms; and surgeons say some pros and cons are “Our suction loss rate was about 3.2 • a major cap tear in one eye (0.05 emerging: percent in the fi rst 340 cases we stud- percent) without visual symptoms. • Precision, and the absence of ied,” Dr. Mehta continues. “However, Dr. Hjortdal reports intraoperative fl ap issues. Dr. Hjortdal found that if you handle suction loss correctly the suction loss in 14 eyes (0.8 percent) the procedure is more precise for cer- patients do very well. Eighty-two per- that was remedied by retreatment in tain levels of myopia than LASIK has cent of the suction-loss patients were 13 eyes. The fourteenth eye had ghost been in his hands. “Since the cutting of able to fi nish their procedure on that images and had to be retreated with the lenticule is being done in an intact day with a successful outcome. Two of topography-guided PRK (which isn’t cornea, I think the precision of SMILE them had to be converted to LASIK, available in the United States). is better than that of LASIK for mod- one to LASEK.” Postop complications included: erate and high myopia,” he says. “The To help avoid suction loss from pa- • trace haze in 144 patients (8 per- other advantage is you don’t have a tient movement, Vadodara, India’s Ru- cent); full fl ap, but instead a small opening. pal Shah, MD, says she tries to keep • day-one epithelial dryness in 90 Secondary to this you have, in theory, the patient calm. “It’s important to patients (5 percent); a more stable cornea afterward. Minor keep the patient steady, as the laser • interface infl ammation secondary trauma to the cornea months or even will be operating for 20 to 25 seconds,” to corneal abrasion in five eyes (0.3 years later may have less of a tendency she says. “To keep the patient from percent); and to dislocate the anterior lamellae. You being anxious, so he can focus, keep • minor interface infi ltrates in fi ve may also have less tendency to develop reassuring him with such phrases as, eyes (0.3 percent). ectasia. Since the sensitivity of the cor- “Very little time left now.” The postop complications affected nea is less affected after SMILE than • Low myopia/working with the best-corrected vision at three months it is in LASIK, dry eye may be less.” To lenticule. Paradoxically, some sur- in only one case. The researchers add this point, Singapore ophthalmologist geons have reported anecdotally that, that in 18 eyes (1 percent) the treat- Jod Mehta says he can always pick up while LASIK is easier in lower levels ment resulted in irregularities on to- a difference in the tear fi lm between of myopia, SMILE may get more dif- pography that reduced vision at three LASIK and SMILE eyes in a contra- fi cult since the lenticule is thinner and months (12 eyes) or induced ghost im- lateral eye study he’s currently engaged more challenging to manipulate with ages (six eyes). In the latter, surgeons in. “It’s an obvious sign that you can forceps. Dr. Mehta, however, says it’s performed topo-guided PRK in four of see,” he says. “And when you ask the not the manipulation that’s difficult the eyes, which improved the vision in patients—who are masked as to what in low myopia, it’s fi nding the proper three. Two patients expressed dissat- treatment is in which eye—they almost tissue to manipulate. “When we teach isfaction at the latest follow-up due to always tell you that if they have to put surgeons SMILE, we start with higher blurred vision or residual astigmatism, drops in, it’s in the eye that turns out myopes as patients,” he says. “They are while the rest were satisfi ed. to be the one that had LASIK.” Dr. usually between -5 and -9 D. This is Mehta’s LASIK vs. SMILE study is because the lenticule is thicker in these The Pros and Cons still ongoing. patients. But when you’re doing a low- On the fl ipside, however, there are er-level treatment, such as -3 D as in After accumulating experience with some aspects of the SMILE procedure one of our groups in our current study,

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the difference isn’t in the thickness ence between LASIK and this type of LASIK. “Some surgeons have basically in the lenticule because the edge of surgery in terms of the uncorrected done a LASIK with a 100-µm thin fl ap any SMILE lenticule is always 15 µm. visual acuity on day one being a little on top of the SMILE cap,” he says. Instead, it’s the center thickness of the lower with SMILE than what we’ve “Before doing this, though, you’d need lenticule that differs between low and seen with LASIK,” says Dr. Hjort- to perform an anterior segment OCT high myopia. So, in a -1 myope the dal. “However, it would improve dur- to make sure you have enough stroma center might be 15 µm thick, but in ing the first week. Today, though, I between where your ablation is and a -9 patient it would be around 100 think this has improved, due to the where the lenticule was removed.” µm. It’s easier to see the center thick- experience of the surgeons and the • Hyperopia. The other arena in ness in the higher myopes. It’s just adjustments we’ve made to the laser which SMILE can’t compete with the identifi cation of the edge, and the algorithm.” LASIK, yet, is in hyperopia. SMILE edges above and below the lenticule, Dr. Mehta has noted some differ- is currently only approved outside the that the surgeon must be able to do. ences too, but in favor of SMILE. “Of- United States for myopic corrections. With more experience, you are able to ten LASIK patients get immediately The main challenge is the transition identify the edges a lot more easily.” good vision to start and then, over the zone on the edge of the lenticule. “I Dr. Hjortdal says SMILE can also fi rst year, they get a slight deterioration know the company is studying how to involve some variation in the quality in vision,” he says. “But with SMILE, optimize the lenticule’s shape in order of the lenticule cut, causing issues in they get good vision and then it seems to treat hyperopia,” says Dr. Hjortdal. about 0.5 percent or less of patients. to get better over that fi rst year.” “This is because, when you treat hy- “This is probably related to the ear- • Retreatments. Surgeons have peropia with SMILE, you need to rely stage the SMILE technique is in, been grappling with the question of move a sort of doughnut-shaped piece but there can be a little variation in the best way to perform a retreatment of cornea, and you need smoothing at the completeness of the femtosecond on a previous SMILE patient since the periphery of the doughnut so as laser cut,” he says. “This means that the procedure was introduced. “I not to have an abrupt change in corne- sometimes you may have a slightly dif- don’t think surgeons completely agree al thickness.” Dr. Mehta says regres- fi cult lenticule removal and you might on how to perform retreatments,” says sion has been the main negative effect. induce traces of hazy tissue in the in- Dr. Hjortdal. “If you want to adjust “Walter Sekundo’s group in Germany terface. This may result in day-one a diopter or so, it’s probably not wise has done some hyperopic treatments,” acuity not being as good after SMILE to do a new SMILE surgery, because Dr. Mehta says. “And they’ve found when compared to LASIK, and you you’d need to do that SMILE in a they’re not as stable as myopic treat- can run into problems related to the layer of cornea where you wouldn’t ments. There’s been regression in the completeness of lenticule removal interfere with the fi rst cut. So, you’d hyperopia. They’ve currently changed and smoothness. Specifi cally, you may have to go deeper or more superfi cial. some of the nomogram, so I hope to have a little scar-like tissue in the in- Many surgeons—myself included— be testing that out for them soon.” terface that results from you having to perform a PRK with the excimer to Though SMILE has some areas that be more aggressive in breaking these make minor corrections, if necessary.” could be improved, Dr. Mehta says it’s small tissue bridges. One approach that’s in its early moving in the right direction. “I think “However, even though we’ve ex- stages is a laser software modifica- LASIK is technically easier to do: You perienced such problems in some of tion that allows the Visumax to turn just make a fl ap and the excimer does our 1,800 eyes, when we have a sec- a SMILE into a LASIK by using a the treatment for you,” he says. “With ond look at the patients in whom we circular pattern. “We did the fi rst sev- SMILE, there is defi nitely a learning noted signifi cant problems during sur- en SMILE enhancement eyes with curve with the technique in order to gery, their condition seems to improve the circle software that converted the recognize the planes of the lenticule, with time,” Dr. Hjortdal adds. So, this SMILE cap into a fl ap,” says Dr. Shah. visualization and the like. However, doesn’t end up in a situation of poor “The software works by adding a la- instruments make a huge difference, vision for the patients.” ser separation underneath the exist- and the instrumentation for SMILE is • Early vs. late postop vision. ing SMILE cap. You then lift the fl ap a lot better than it was when I started Surgeons who have done both LASIK and use an excimer to perform the three years ago. That’s been a big im- and SMILE say they’ve noticed a dif- treatment.” She says the downside, of provement.” ference in the procedures’ patterns course, is you lose the benefi ts of fl ap- 1. Ivarsen A, Asp S, Hjortdal J. Safety and complications of more of visual recovery. “At least in the be- less SMILE. Dr. Mehta says one other than 1,500 SMILE procedures. Ophthalmology 2013 Dec 20 pii: S0161-6420(13)01064-6. doi: 10.1016/j.ophtha.2013.11.006. ginning, we felt there was a differ- approach some have used is a thin-fl ap [Epub ahead of print].

32 | Review of Ophthalmology | February 2014

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RP0114_Keeler Indirect.indd 1 12/16/13 2:41 PM 034_rp0214_f3.indd 34 Walter Bethke, ManagingEditor 34 Embrace Flaps Thin Surgeons Refractive REVIEW |

Review ofOphthalmology Cover Focus Cover surgeons reveals techniques they the toolsand of refractive Our survey Our survey like most. | February2014 Here’s whattheyhadtosay. rate), and69surgeonsresponded. open service(15-percent tronic mail 10,000 subscriberstoReview’s elec- survey e-mailwasopenedby1,509of mail surveyonrefractivesurgery. The tackled bysurgeonsinthismonth’s e- fl around 100µmonthesurvey. current averagethicknesshovering thinner andflaps,withthe corrections, haveledsurgeonstoward threat ofectasia,especiallyinhigher in flap-makingtechnologyandthe 145 to160µm.However, advances popular, fl aps werecommonlyaround surgeons. WhenLASIKfi use afemtosecondlaser, withtherest making, two-thirdsofthesurgeons fl 131 and149µm6percentmake percent likeflapsthatarebetween make flapsthinnerthan100µm,6 between 120and130µm.Sixpercent by 24percentwholikeathickness µm formostoftheircases,followed geons saytheyuseflaps of100to119 The Tale oftheTape T ap creationarejustoneofthetopics µm. Forfl aps thickerthan150 Thoughts andopinionsonLASIK On thesurvey, 59percentofsur- month’s surveyofrefractive LASIK fl ap, accordingtothis hin isinwhenitcomestothe rst became became rst

Refractive Surgery ap- This articlehasnocommercial sponsorship. have atendencytotear.” ing,” hesays.“Forme,thinnerfl thickness, withlittletroublelift- him. “Igetconsistentfl flsays these aps alsoworkbetterfor Brown Jr., MD,ofFayetteville,Ark., Ohio. Richard son, MD,ofDayton, handles well,”saysKurtAndrea- stronger flapwithlessstretchthat thickness. “Ipreferitbecause it’s a µm, saytheyneedthatlittleextra a littlethicker, between120and130 sub-epithelial haze,”hesays. sues. “It’s thickenoughtoprevent thinner fl aps mightstartcausingis- may bethethresholdatwhichany from Indianasaysthisthicknessrange striae afterrepositioning.”Asurgeon to ablate,butthickenoughavoid maximum amountofstromaavailable he says.“It’s thinenoughtogetthe agrees. “It’s agoodcompromise,” Devgan. AsurgeonfromMemphis tion,” saysLosAngelessurgeonUday a goodstromalthicknessforabla- a goodbalanceofstableflapand using amicrokeratome. and fortherefractivesurgeons on that hetrustsmorethanthe others, Procedure Volume The surgeonswholiketheirfl “The 100-to119-µmthicknessis Every surgeonhasaprocedure aps withthis aps aps 1/24/14 2:47 PM our survey it’s cus- Best Procedure for a 45-year-old Hyperopic Presbyope tom LASIK, chosen by 43 percent as their procedure of choice. Twenty- eight percent say 24 22 they use conven- % tional LASIK the 15 most, followed by 11 PRK at 15 percent 9 9 and wavefront-op- 7 2 2 timized LASIK at 13 percent. Bifocals Multifocal Contact-lens LASIK LASEK PRK CLE/ CLE/ CLE/ In terms of contacts monovision monovision monovision monovision Crystalens monofocal multifocal IOL lens LASIK volume, monovision surgeons report that things are still sluggish. Forty-eight percent of the extraction/IOL implantation.” to rule out any peripheral retinal pa- surgeons do between fi ve and 20 cases Some surgeons, however, think thology; otherwise, the patient and his per month and 28 percent perform ablation has some benefits in these attorney will point to surgery as the fewer than five. Eleven percent do patients. “Femtosecond wavefront causative factor,” he says. “LASEK al- between 21 and 50 cases and 2 per- LASIK has been excellent for higher lows more residual stromal bed thick- cent perform between 51 and 75. On myopes, with accurate and quicker ness; 250 µm is an arbitrary thickness the high-end of volume, 6 percent of visual recovery and no haze concern,” advised by the FDA that does not surgeons report doing between 76 says Dr. Andreason. “However, cor- guarantee corneal structural integrity and 100 cases, and 6 percent say they neal thickness may limit us to using that would avoid long-term corneal do more than 100 monthly. Surgeons custom PRK—which is good—but ectasia. In addition, LASEK avoids say that they charge an average of not my preference in this case.” Clif- applying a suction ring or Intralase $2,452 per eye for LASIK and $2,404 ford Salinger, MD, of Palm Beach suction to the eye that can induce for PRK. Gardens, Fla., thinks LASEK fi lls the structural changes to the vitreous and The procedures that surgeons favor bill better, and outlines his course of possibly increase the likelihood of ret- change, however, when faced with action and the reasons why he likes inal detachment.” cases that are outliers. For a high- LASEK. “Preoperatively, have the Another challenge that refractive myope (-11 D), about half (51 per- patient screened by a retinal specialist surgeons face is how to approach a cent) say they think a phakic IOL is best; 16 percent like either custom Best Procedure for a -11 D Myope or wavefront-optimized LASIK; 16 percent prefer PRK; 11 percent like using clear-lens extraction/intraocular 51 lens implantation; 4 percent prefer conventional LASIK; and just 2 percent like LASEK. “A -11 correction % is beyond the scope of good LASIK,” says Dr. Devgan. “Phakic IOLs are 16 16 OK, but the best option—and lowest 11 risk—is to stick with contact lenses.” 4 2 A surgeon from Wisconsin thinks a 0 phakic lens is the best option. “Opti- cal aberrations occur with excessive Conventional PRK LASIK Epi-LASIK Custom/ CLE/IOL Phakic corneal fl attening,” he says. “Although LASIK Wavefront- IOL it’s a small risk, retinal detachment is optimized a risk in high myopes with clear-lens LASIK

February 2014 | Revophth.com | 35

034_rp0214_f3.indd 35 1/24/14 3:21 PM Cover Refractive Surgery

REVIEW Focus

45-year-old hyperopic presbyope, wavefront-guided LASIK would be past 23 years since I started LASIK since no clear option has yet emerged. done on the distance eye and possibly I just find it easier to go with the On the survey, the most popular op- PRK on the near eye to minimize the slower healing of PRK for the sake of tions were LASIK monovision (24 risk of late ectasia,” he says. “[For] the predictability of having no prob- percent), bifocals (22 percent), CLE/ 48-year-olds the answer would be a lems with cells. When we used to do multifocal IOL (15 percent) and CLE/ bifocal procedure on the non-dom- LASIK reoperations we did find a accommodative IOL (11) percent. All inant eye, so there are some people lower rate of epithelial cells in the the other options were chosen by less whom I tell to wait until they are old- interface when suturing the fl ap with than 10 percent of the surgeons (the er. But hyperopic presbyopes have a the Barraquer eight-bite, anti-torque results appear in the graph on p. 35). lot to gain from refractive surgery and suture, and cells could be squirted “This is a diffi cult question,” says Ar- are the most appreciative.” from the interface postoperatively, kansas’ Dr. Brown. “While I am not a For the patient in need of an en- but it is just too much trouble. PRK fan of clear-lens extraction and IOL hancement of her LASIK, surgeons is fi ne.” Dr. Salinger, however, thinks implantation in a 45-year-old patient, are divided nearly down the middle: a procedure that involves lifting the for the hyperope, using CLE with a 50 percent will lift the previous fl ap fl ap is better in the end. “I prefer it multifocal IOL and confi rming with and ablate and 45 percent will per- if the available corneal thickness al- [ORA intraoperative aberrometry] form a surface procedure on top of lows for this option,” he says. “If the has, in my experience, produced ex- the fl ap. Five percent will re-cut a fl ap patient chose LASIK for the initial cellent results.” and ablate. For his part, Dr. Epstein procedure, then lifting the fl ap and Robert Epstein, MD, of McHenry, prefers to take the surface ablation performing another LASIK is the fast- Ill., will alter his course of action de- route. “I prefer PRK over the LASIK healing alternative that he is probably pending on the patient. “If the pa- fl ap only,” he says. “After many epi- hoping for in terms of a second vision tient is otherwise a LASIK candidate, sodes of cells in the interface over the correction procedure.”

034_rp0214_f3.indd 36 1/24/14 2:45 PM ANATOMY OF A GREAT EXAM LANE Quality or Value - go ahead you can have both ^ϰKWd/< ƉƌŽĚƵĐƚƐ ĂƌĞ ƚŚĞ ƉĞƌĨĞĐƚ ďůĞŶĚ ŽĨ ĞǆƚƌĂŽƌĚŝŶĂƌǇ sĂůƵĞ ĂŶĚ YƵĂůŝƚǇ͘ /ŶƐƚƌƵŵĞŶƚƐǁŚŝĐŚƐĂƟƐĨǇĞǀĞŶƚŚĞŵŽƐƚĚŝƐĐĞƌŶŝŶŐƉƌĂĐƟƟŽŶĞƌ͘

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RO0913_S4Optik.indd 1 8/26/13 11:22 AM 038_rp0214_f4.indd 38 Michelle Stephenson, ContributingEditor 38 Is It for Everyone? Xtra: LASIK REVIEW |

Review ofOphthalmology Cover Focus Cover improve refractive LASIK andcross- begun combining Surgeons have linking toavoid ectasia andto post-LASIK outcomes. | February2014

Rajesh Rajpal, MD S rigidity may decrease.Dr.rigidity Hershcites structure areweakened,andcorneal tant anterioraspectsofthecorneal ﬂ private practiceinTeaneck, N.J. view,” saysPeterHersh,MD,whoisin corneal ectasiafromasafetypointof andavoidmechanical pointofview ensure cornealstabilityfromabio- LASIK outcomesingeneral,thatisto combination withLASIKistoimprove results. “Thegoalofcross-linkingin ap andremovingtissue,someimpor- He explains that by making a LASIK He explainsthatbymakingaLASIK ing and are achieving promising ing andareachievingpromising in combinationwithcross-link- urgeons areperformingLASIK

Refractive Surgery This articlehasnocommercial sponsorship. procedure, dubbed LASIK Xtra, can procedure, dubbedLASIKXtra,can view isofgreatinterest.” both fromasafetyandeffi cacy pointof concept ofcombiningtheprocedures reliably strengthenthecornea.So, on theotherhand,hasbeenshownto cases,” Dr. Hershsays.“Cross-linking, corneal ectasiainthevastmajorityof lem, anditcertainly doesn’t leadto this doesn’t leadtoanyclinicalprob- cent. “Inthevastmajorityofcases, the corneaby15percentto25per- estimated thatLASIKmayweaken ogist JohnMarshall,PhD,whohas London researcherandophthalmol- Dr. Hershnotesthatthecombined 1/24/14 10:46 AM be viewed as an extra safety element astigmatism when the difference in mal). The differences between the two in patients who may have some theo- astigmatism between the two eyes is groups at the 20/20 and the 20/25 levels retically greater risk: those who have more than 0.75 D. “For example, if were statistically signifi cant (p=0.045 thinner corneas and those who have one eye is 1 D and the other eye is 2 D, and 0.039, respectively). high degrees of correction. “Strength- in my protocol, this is a reason for that When comparing the preopera- ening the cornea with concurrent patient to undergo additive collagen tive corrected distance visual acuity cross-linking may be benefi cial in the cross-linking regardless of age,” Dr. versus postoperative uncorrected dis- longer-term stability of the refractive Kanellopoulos says. tance visual acuity, in the LASIK Xtra result and ultimate predictability of the International studies have shown the group, 35 percent of the eyes were procedure, he says. “Clinical studies benefi ts for patients with high myopia unchanged, 57 percent gained one are showing encouraging results, and and high hyperopia corrections. Dr. Snellen line, and 8 percent gained two further clinical work should continue Kanellopoulos recently concluded a or more Snellen lines. No eye lost any to elucidate the advantages and disad- long-term study comparing LASIK lines. In the LASIK only group, 35 per- vantages of the procedure.” Xtra to standard LASIK for high my- cent of the eyes were unchanged, 59 opia corrections.1 “The results were percent gained one Snellen line, and 5 Who Should Have LASIK Xtra? compelling in favor of the LASIK Xtra percent gained two or more lines. Only cases as far as refraction accuracy and 2 percent (one eye) lost one line. Although LASIK Xtra is not ap- stability,” he says. In the LASIK Xtra group, 85 per- proved in the United States, surgeons In this study, 65 eyes underwent cent of eyes had a postoperative spher- outside of the United States have been LASIK Xtra and 75 eyes underwent ical equivalent refraction between -0.5 performing the procedure, and some LASIK alone. In the LASIK Xtra and 0 D, compared with 83 percent in believe that cross-linking should be group, the mean patient age at the time the LASIK only group. Additionally, performed on all LASIK patients. of the procedure was 27.5 ±6.1 years the LASIK Xtra group had a mean “Internationally, some centers pre- (range: 19 to 39). Preoperatively, the preoperative cylinder of -1.39 D, while fer to treat all LASIK patients, while mean refractive error was -6.60 ±2.02 the LASIK only group had a mean others prefer to only treat high-risk pa- D of sphere (range: -2.50 to -11.50), preoperative cylinder of -0.86 D. De- tients,” says Rajesh Rajpal, MD, who is -1.35 ±1.24 D of cylinder (range: 0 to spite this, postoperatively, 92 percent in private practice in the Washington, -5 D), and -6.75 ±1.75 D of manifest of the eyes in the LASIK Xtra group D.C., area. “These patients generally refractive spherical equivalent (range: had less than 0.25 D of refractive astig- include high myopes, those with thin -2.50 to -11.50). matism, compared with 94 percent in corneas or those with some topograph- In the LASIK only group, the the LASIK only group. ic asymmetry or irregularity. High-risk mean preoperative refractive error The refractive stability is demon- patients might also be very young pa- was -5.14 ±1.74 D of sphere (range: strated by the manifest refractive tients, because their corneas tend to -2.50 to -9.50), -0.85 ±0.75 D of cyl- spherical equivalent correction as change more over time; they may be inder (range: 0.00 to -3.50), and -5.33 seen during the one-, three-, six- and hyperopic or they may have a family ±2.34 D of manifest refractive spheri- 12-month postoperative visits. One- history of keratoconus. Basically, any- cal equivalent (range: -2.50 to -9.50). year postoperative mean manifest re- one who is at greater risk of developing Mean central corneal thickness was fractive spherical equivalent minus the ectasia after refractive surgery would 553.51 ±19.11 µm (range: 503 to 592) one-month baseline was -0.24 ±0.09 be considered a high-risk patient. In- preoperatively and 454.34 ±19.98 µm D in the LASIK Xtra group and -0.27 ternational doctors are approaching it (range: 422 to 515) one year postop- ±0.09 D in the LASIK only group. similarly. Some say there is very little eratively. These results indicate a reduced re- risk to LASIK Xtra, so why not treat In the LASIK Xtra group, 90.8 fractive shift in the LASIK Xtra group everyone? Other doctors would rather percent of eyes had a postoperative compared to the LASIK only group. not add anything to the procedure.” uncorrected distance visual acuity The keratometric stability is demon- A. John Kanellopoulos, MD, who is of 20/20 (1.0 decimal) or better, and strated by the K-fl at and K-steep aver- in private practice in Athens, Greece, 95.4 percent had a UDVA of 20/25 age values up to the 12-month post- and in New York City, employs cross- (0.8 decimal) or better. In the LASIK operative visit. The results indicate an linking in all hyperopic LASIK cases. only group, 85.3 percent of the eyes increased keratometric stability in the He also uses it in all young myopic had a postoperative UDVA of better LASIK Xtra group (one year at +0.03 patients over 6 D and under 30 years than 20/20 (1.0 decimal), and 89.3 per- D in the fl at and +0.05 D in the steep of age and in all patients with myopic cent had better than 20/25 (0.8 deci- in comparison to one month baseline),

February 2014 | Revophth.com | 39

038_rp0214_f4.indd 39 1/24/14 10:46 AM 038_rp0214_f4.indd 40 cm by athree-minuteexposureof10mW/ fl % sodiumphosphateribo- drop of0.1 were randomizedtoreceiveasingle eral topography-guidedLASIKand opic astigmatismelectedtohavebilat- tive patientswithhyperopiaandhyper- astigmatism. patients withhyperopiaandhyperopic Kanellopoulos says. mechanical stabilizationeffect,”Dr. myopia, presumablythroughitsbio- Xtra isarefractivestabilizerinhigh tively). group (+0.57Dand+0.54D,respec- when comparedtotheLASIKonly depth oftheprophylactic cross-linkingeffect. year postoperatively. The intrastromal hyper-reflective sectionsmaycorrelate withthe eye treated withLASIK Xtra for-4.50Dofsphere and-0.25Dofastigmatismobtainedone Anterior-segment opticalcoherence high-resolution cross-sectional(6-mm)imageofan 40 distance visualacuityof0.95 ±0.15 0.76 ±0.72Dandmeanuncorrected mean cylinderof0.65±0.56 Dand -0.20 ±0.56Dand+0.20±0.40with spherical equivalentrefractionwas two yearspostoperatively, themean LASIK onlygroups,respectively. At ±0.25 inthecross-linkingand and 0.1 visual acuity(decimal)of0.1±0.26 D andmeanuncorrecteddistance and 1.40±1.80 inder of1.20±1.18D D and+3.40±1.78withameancyl- spherical equivalentwas+3.15±1.46 follow-up of23months. overmean wereevaluated surements topographic, andtomographicmea- eye. Refractiveerrorandkeratometric, mal cross-linkinginthecontralateral realigned inoneeyeandnointrastro- avin solutionunderthefl REVIEW He has also studied LASIK Xtra in He hasalsostudiedLASIKXtrain “These datasuggestthatLASIK Preoperatively, the meanrefractive | 2

ultravioletAlightwiththeflap Focus Cover Review ofOphthalmology 2 Inthisstudy, 34consecu-

Refractive Surgery ap followed followed ap | February2014 U.S. Trial was adifferenceintherateof ecta- done todetermineonlywhether there rate ofectasiaissolow, ifthestudywas a reasonabletimeperiod.Becausethe ofregressionin or lack strate stability because wemaybeabletodemon- todothat treatments areagoodway and LASIKXtra,”hesays.“Hyperopic a differencebetweenregularLASIK data thatwillshowwhetherthereis proval process,wewillultimatelyhave Food andDrugAdministrationap- “Because wearegoingthroughthe form LASIKXtraintheUnitedStates. was thefi rst refractive surgeontoper- has justgottenunderway. Dr. Rajpal clinical trialevaluatingLASIKXtra says. shape overtime,”Dr. Kanellopoulos to biomechanicalchangesincorneal with hyperopicLASIKmayberelated data suggestthattheregressionseen sion) ineyeswithcross-linking.Our greater long-termefficacy (lessregres- cross-linking issafeandeffective,with LASIK withorwithoutintrastromal sion of+0.72±0.19D(p statistically signifi cant greaterregres- that underwentLASIKonlyshoweda ment of+0.22±0.31D,whereaseyes strated ameanregressionfromtreat- that underwentcross-linkingdemon- LASIK onlygroups,respectively. Eyes ±0.23 inthecross-linkingand and 0.85 In theUnitedStates,afi “Topography-guided hyperopic =0.0001). ve-center ve-center cost, then I think it does make sense cost, thenIthinkitdoesmake sense risk anddoesn’t addriskorsignifi dure forourpatientsthatreduces treat. So,ifwecanprovideaproce- tive surgery, itcanbeverydiffi When ectasiaoccursfollowingrefrac- fect isgreaterwhenthelightpulsed. is evidencethatthecross-linkingef- ing isusingapulsedUVlight,asthere other downside.Thestudywearedo- ment,” hesays.“Costmaybetheonly three tofourminutesthetotaltreat- then theUVlight.“Thataddsabout cedure byapplyingtheribofl adding alittlebitoftimetothepro- downside tothetreatmentotherthan likely tostartofferingitallpatients.” those patients,theywillbemuchmore they feelthatitisprovidingabenefit to off withhigh-riskpatients.Then,if I thinkmostdoctorswillchoosetostart who wanttoofferthistheirpatients. would beausefuloptionforsurgeons LASIK maybethepathwayforit,that in theUnitedStates,andhyperopic feel ifwecangetFDAapprovalforthis to benegativelyaffectedinany way. I the refractiveoutcomedoesnotseem seems tobehavingsomeeffect,and not reallyaneedforadjustment.Soit seen hasdemonstratedthatthereis internationally, thedatathatwehave in thenomogramforsomepatients, may beaneedforsomeadjustment terms ofvisualoutcomes?Whilethere nea changewhatyouareachievingin pal says.“Doesstrengtheningthecor- been oneoftheconcerns,”Dr. Raj- whichhas outcomes, on refractive cross-linking doesn’t haveaneffect nationally showingthatperforming Downsides ofLASIKXtra this country.” why thehyperopicstudywasstartedin dreds ofthousandspatients.That’s cal significance unlesswetreatedhun- sia, itwouldbedifficult toshowstatisti- He notesthatthere islikelyno “We haveverygooddatainter- (continued onp.61) avin and and avin cult to cult cant cant 1/24/14 10:46 AM Ask about optional Slit Lamp & Chart Projector configurations.

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

Multimodal Imaging of APMPPE, Related Disorders Recognizing the distinctive features of each placoid disorder is critical for accurate and timely diagnosis and management. By Meena George, MD, PhD, Pamela Golchet, MD, K. Bailey Freund, MD, and David Sarraf, MD, Los Angeles

cute posterior multifocal plac- syndromes with characteristic plac- and include macular serpiginous A oid pigment epitheliopathy and oid lesions. Variant placoid entities choroiditis, tubercular serpiginoid serpiginous choroiditis are two well- have been described that resemble choroiditis, relentless placoid chorio- deﬁ ned members of the white spot these two better-known disorders retinitis and persistent placoid maculopathy. Although the conditions are rare, recognizing the distinctive features of each is critical for accurate, timely diagnosis and management and, thus, for optimizing visual prognosis. In this review, we summarize the clinical presentation, diagnosis and management as guided by multimodal imaging for these variant placoid white spot syndromes.

APMPPE

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) was fi rst described by J. Donald M. Gass, MD, in 1968.1 It typically presents in young adults with bilateral vision loss and may be preceded by Figure 1. Acute posterior multifocal placoid pigment epitheliopathy. A) Color fundus a viral illness. Presenting symptoms photograph showing placoid lesions in the macula and periphery of the left eye. B and may include photopsia, decreased C) Fluorescein angiogram of the same patient three months prior demonstrating early vision, paracentral scotoma or meta- hypofl uorescence (B) and late staining (C) of the lesions. D) SD-OCT showing lesion with irregular thickening of the retinal pigment epithelium and patchy loss of the ellipsoid zone morphopsia. There is no gender and RPE layers. E) On fundus autofl uorescence, active lesions are hypoautofl uorescent due or ethnic predilection. On fundus to a blocking effect by the outer retinal lesions, but with resolution develop a examination, APMPPE is charac- hyperautofl uorescent rim thought to be secondary to altered RPE metabolism and terized by randomly scattered, flat lipofuscin deposition. multifocal creamy white or yellow

42 | Review of Ophthalmology | February 2014 This article has no commercial sponsorship.

042_rp0214_rtinsider.indd 42 1/24/14 11:06 AM plaques at the level of the retinal pig- RPE cells (See Figure 1E),6 but often In most cases, APMPPE lesions ment epithelium with indistinct mar- the hypoautofluorescence persists. can be observed and will resolve gins. Plaques are typically located Further histological studies are nec- without any intervention. However, in the macula but may also involve essary to determine the true patho- several reports have linked APMPPE the peripheral quadrants (See Figure genesis and whether the primary site to central nervous system vasculi- 1A). New lesions can develop, and as of damage is the outer retina and the tis, with manifestations ranging from such, lesions of differing age may be RPE versus choroidal hypoperfu- headaches to venous sinus thrombo- present at any given time. sion leading to RPE and outer retinal sis.7 This combination of APMPPE On fluorescein angiography, ac- damage. with neurologic manifestations oc- tive lesions demonstrate early hypo- Active plaques resolve spontane- curs more frequently in males and fl uorescence (See Figure 1B) and late ously over a course of approximately very rarely can have dire conse- staining (See Figure 1C). Inactive two to four weeks, often with mottling quences, including death. Treatment lesions show hyperfl uorescence cor- of the RPE but without atrophy of the recommendations in such cases in- responding to window defects from choroid. Visual prognosis is usually ex- clude IV corticosteroids followed by retinal pigment epithelium atrophy. cellent, with most patients recovering a slow oral taper in combination with Indocyanine green angiography their baseline visual acuity, although an immunosuppressant. shows hypofluorescence of active prognosis is less favorable when there and healed lesions. is foveal involvement. There are un- Serpiginous Choroiditis Recent analyses of APMPPE le- common cases of severe vision loss sions using spectral-domain optical from significant RPE alterations in In contrast to the typically short- coherence tomography demonstrate the fovea or due to complications lived course of APMPPE, serpigi- various stages of retinal morphologic from choroidal neovascularization. nous choroiditis is characterized by changes.2,3 At onset, the placoid le- Recurrences are rare. bilateral, progressive and often re- sions appear as prominent, dome- shaped elevations of the ellipsoid zone (EZ) band, with hyper-refl ective material and subretinal fluid accumulation.4 Over the course of the disease, the dome-shaped lesion fl attens, the EZ thickens, the outer nuclear layer shows hyperrefl ectivity followed by thinning, and the RPE thickens (See Figure 1D).5 At three months, there is partial restoration of the outer macula, reconstitution of the EZ band and minimal residual RPE irregularity.2 These fi ndings of outer retinal pathology in the absence of inner retinal abnormalities indicate that the choroid likely plays a role in this disease. Fundus autofluorescence in the acute phase shows hypoautofl uorescence of lesions. This hypoautofl uorescence may be due to a blocking effect by the outer retinal lesions versus RPE edema or direct RPE damage with decreased lipofuscin Figure 2. Classic serpiginous choroiditis. A and B) Color fundus photographs of the right production. After resolution, lesions and left eyes showing yellowish peripapillary serpentine lesions. The right eye (A) displays may demonstrate hyperautofl uores- jigsaw-like chorioretinal atrophy with pigmentary changes that occurs after active lesions cence due to deposition of lipofuscin resolve. The left eye (B) shows active serpiginous choroiditis. On FA, active lesions (left or altered metabolism of affected eye) demonstrate early hypofl uorescence (C) and late staining (d).

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current infl ammation of tive and inactive the choroid and outer inflammation. retina.8 It usually pres- Inactive infl am- ents in healthy, white, mation shows middle-aged adults, dark, hypoauto- with a slight male fluorescent le- predilection.9Although sions with sharp typically a bilateral dis- borders without ease, patients often any hyperauto- present with unilateral MD. Wheatley, Matthew Case and images: fluorescence at activity and decrease in lesion edges. vision once the fovea is With involve- affected. Other common ment of the symptoms include small macula, central scotomas or metamor- vision is often phopsia. Figure 3. Tubercular serpiginoid choroiditis. A) Yellowish choroidal lesion in the significantly On examination, the inferior macula on initial presentation of tubercular serpiginoid choroiditis in a compromised. anterior chamber is gen- 42-year-old Indian male. The lesion demonstrates early hypofl uorescence (B) and An important erally quiet, whereas up late staining (C). Over the course of two to three months, the patient developed complication to 50 percent of patients several new lesions along with extension of existing choroidal lesions in a of serpiginous serpiginoid pattern (D). Wide-fi eld autofl uorescent montage demonstrating the may exhibit fi ne cells in choroiditis is the extension of the old lesion and the presence of new foci of choroidal lesions (E). the vitreous. Peripapil- Wide-fi eld fundus autofl uorescence (F) reveals hypoautofl uorescent inactive lesions development of lary gray-white or yel- as well as lesions with a stippled pattern of hypo- and hyperautofl uorescence, choroidal neo- lowish serpentine lesions suggestive of lesions that are still active but in the early phases of healing. The vascularization, that extend centrifugally patient was treated with a four-drug TB regimen, oral prednisone and ultimately reported to oc- are the classic finding periocular and intraocular steroids in order to prevent further progression. cur in about 13 by ophthalmoscopy (See to 20 percent Figures 2A and 2B). Recurrences are lesions, which appear larger than the of cases.17,18 Other complications contiguous with previous lesions and corresponding lesions on examina- described include cystoid macular often assume a pseudopodal pattern. tion or FA. Recurrences are common edema, pigment epithelial detach- Chorioretinal atrophy in a jigsaw- at the edges of prior atrophic scars ments and branch retinal vein occlu- puzzle confi guration may ensue (See and can occur after long periods of sions.19,20 Figure 2A). Due to the gradual ex- quiescence (even after several years). Various strategies have been at- tension of these geographic (serpigi- In the majority of patients the dis- tempted to treat acute episodes of nous) zones of chorioretinal and RPE ease recurs, often several times.12 serpiginous choroiditis and to pre- infi ltration and then atrophy, serpigi- SD-OCT shows hyperreflectivity vent recurrences. The mainstay of nous choroiditis has previously been of the outer retina13 and RPE with treatment is oral (or periocular) cor- referred to as “geographic helicoid minimal distortion of the inner reti- ticosteroids. Patients may relapse or peripapillary choroidopathy”10 and nal layers.14 Upon healing, lesions recur when tapered to a dose less “geographic choroidopathy,”11 among demonstrate loss of the RPE, pho- than 15 milligrams per day of per other nomenclature. toreceptor outer segments, and EZ oral prednisone.9 Intravitreal cor- On FA, acute serpiginous lesions band with choroidal hyperrefl ectiv- ticosteroid implants may be more demonstrate early hypofl uorescence ity.14 effective in preventing recurrences. (See Figure 2C) likely due to both FAF can be used to follow the Immunomodulatory agents includ- choriocapillaris nonperfusion and course and demarcate the disease.15,16 ing cyclosporine A, azathioprine and blockage from RPE and outer reti- Active infl ammation appears hype- mycophenolate mofetil have been nal edema. Progressive hyperfluo- rautofluorescent, while older inac- employed to prevent recurrences, rescence at lesion margins may rep- tive lesions appear hypoautofl uores- with mixed reports of success. Ad- resent intact choriocapillaris. Over cent. A hypoautofluorescent halo ditional strategies attempted are “tri- time, there is staining of the acute that surrounds all edges of active ple-agent therapy,” which includes lesions (See Figure 2D). ICGA shows hyperautofl uorescent lesions serves cyclosporine A, azathioprine and early and late hypofluorescence of as a transitional stage between ac- prednisolone, as well as alkylating

44 | Review of Ophthalmology | February 2014

042_rp0214_rtinsider.indd 44 1/24/14 11:06 AM agents (e.g., cyclophosphamide or multifocal choroiditis that later be- pole and the periphery. In contrast chlorambucil) in extreme cases, al- comes diffuse and contiguous with to classic serpiginous choroiditis, le- though caution must be used given an active advancing edge resembling sions were usually not contiguous the potentially severe side-effects of classic serpiginous choroiditis (See with the optic disc (>85 percent). these drugs.9,11 Laser photocoagula- Figure 3); or as a diffuse plaque-like Patients treated with antitubercular tion and, recently, anti-VEGF agents choroiditis with amoeboid spread.24,25 therapy (four-drug regimen) and oral have been used to treat CNV associ- Aqueous and vitreous humor aspi- corticosteroids demonstrated good ated with serpiginous choroiditis.18,19,21 rates from two reported cases were responses. The addition of antituber- positive for Mycobacterium tubercular treatment reduced recurrences Macular Serpiginous Choroiditis culosis by polymerase-chain reaction whereas those treated with oral ste- analysis.26 roids alone had a 75 percent recur- A variant of serpiginous choroi- In a retrospective study by Reema rence rate. Lesions were followed ditis termed “macular serpiginous Bansal, MD, and colleagues, of 105 using autofluorescence to monitor choroiditis” was first described by patients with confi rmed TB by posi- response to therapy.24 Active lesions Robert A. Hardy, MD, and showed ill-defi ned hyper- Howard Schatz, MD, in autofluorescence with an 198710 and shares a num- amorphous appearance. ber of features similar to In the early phase of heal- classic peripapillary ser- ing, a thin surrounding rim piginous choroiditis. How- of hypoautofluorescence ever, in the latter entity, with a central stippled pat- lesions begin around the tern developed; on com- nerve and recur centrifu- plete resolution, lesions gally toward the macula, were uniformly hypoau- whereas macular serpigi- tofl uorescent (See Figure nous lesions commence 3F). With treatment, the in the macula and recur fovea was spared in 75 in a pseudopodal pattern percent of patients, in- centripetally towards the cluding those with macu- nerve.22 FA and ICGA lar involvement. Up to 3.5 fi ndings are essentially the Figure 4. Persistent placoid maculopathy. A) Color fundus photograph percent of patients devel- same and treatment strate- showing white plaque-like lesion in the macula of the right eye. The oped CNV. gies are similar.23 Because patient’s best-corrected visual acuity was 20/70 on presentation and Interestingly, 14 percent of its onset in the central declined signifi cantly to 20/400 due to CNV. The white macular lesion of patients were reported becomes fainter over time on serial fundoscopy. B) Early-phase FA macular region, visual to have progression of shows hypofl uorescent plaques with punctate areas of acuity deteriorates early hyperfl uorescence. C) Late-phase FA demonstrates multiple punctate disease after initiation of 24,25 on and permanent vision spots of hyperfl uorescence with partial fi lling of the hypofl uorescent antitubercular therapy. loss is more profound and regions. In this particular case, there is almost complete resolution Some have proposed that diffi cult to treat. Macular of the hypofl uorescent regions. Early hyperfl uorescent spots were tubercular serpiginoid serpiginous choroiditis can associated with leakage and indicate choroidal neovascularization. choroiditis is an immune- also be complicated by D) Persistent hypofl uorescence on indocyanine green angiography. mediated hypersensitivity CNV, further worsening The choroid remained hypofl uorescent in the area of the lesion for a reaction to the acid-fast the visual prognosis.22 period lasting more than 14 months. bacilli sequestrated in the RPE and that dying bacilli Tubercular Serpiginoid Choroiditis tive tuberculin skin testing or Quan- release proteins that can paradoxi- tiFERON-TB gold testing, more cally aggravate the immune-response Included in the differential diagno- than 70 percent of cases were male, and initially worsen the choroiditis, sis of the placoid entities, particularly with a mean age of 33 years. The a type of Jarisch-Herxheimer reac- in areas of endemic tuberculosis, majority (80 percent) of patients pre- tion.24,25 An alternative possibility is such as India, is tubercular serpigi- sented with vitritis and over 60 per- a delayed effect of antitubercular noid choroiditis. It presents in either cent had bilateral disease. Lesions therapy with worsening of the under- of two ways: discrete, noncontiguous were present in both the posterior lying disease by the corticosteroids.

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REVIEW Insider Table 1. Clinical & Angiographic Characteristics of Placoid White Spot Syndromes APMPPE Serpiginous Relentless Placoid Persistent Placoid Choroiditis Chorioretinitis Maculopathy Lesion characteristics Multiple posterior, creamy Classically, serpentine Small (≤1/2 disc area), Geographic central whitish plaques white-yellow lesions of gray or yellow peripapil- creamy white placoid le- at the level of the RPE, centered varying sizes; fade in two lary placoid lesions. In sions at the level of the RPE, around the fovea, not contiguous to three weeks with the macular variant, anterior and posterior to the with the optic disc. Lesions persist subsequent RPE mottling. there is no extension to equator. Pigmented atrophy for months to years but become the disc. may result within weeks, or fainter with time. lesions may persist and grow with new lesions developing over time. May end up with hundreds of lesions. Presenting symptoms Sudden vision loss, Loss of vision, scotomas, Decreased vision, fl oaters, Mild decrease in vision unless CNV photopsias, scotomas. metamorphopsia metamorphopsia present, photopsias, dyschromatopsia Gender, M = F, Slightly more common in Possible male preponder- Possible male preponderance (only Age young males, young to middle ance, young to middle age eight cases), older age (>50 yrs) age Laterality Bilateral, usually Bilateral. Usually one eye Typically bilateral (80%) Bilateral, symmetric symmetric is active at a time. FA characteristics Early hypofl uorescence Early hypofl uorescence Early hypofl uorescence Early hypofl uorescence with late followed by late staining. followed by progressive followed by late staining. partial fi lling; no marked leakage or hyperfl uoresence at staining. lesion margins with late staining. ICG characteristics Hypofl uorescence through- Hypofl uorescence Hypofl uorescence Hypofl uorescence throughout out, less defi ned in late throughout, less pro- throughout phase. nounced in late phase OCT fi ndings Acute: Dome-shaped Acute: Hyperrefl ectivity of Acute: Hyperrefl ectivity of Acute: Retinal thinning with photore- elevations of the EZ band, outer retina and RPE the inner and outer retinal ceptor and RPE disruption hyperrefl ective material, Resolution: Loss of the layers, subretinal fl uid. Stability: Well-defi ned areas of subretinal fl uid. RPE, photoreceptor outer Resolution: Normal anatomy photoreceptor loss, collapse of the Late: EZ thickening, ONL segments, and EZ band; reestablished. outer plexiform layer and thinning of thinning, RPE thickening. normal ONL; choroidal the chorio capillaris. Resolution: reconstitution hyperrefl ectivity. (time-domain OCT fi ndings) of the EZ band, minimal RPE changes. FAF fi ndings Acute lesions demonstrate Active lesions: Hyperau- Extensive confl uent areas Speckled pattern of hyper- and hypoautofl uorescence and tofl uorescent of marked hypoautofl uo- hypoautofl uorescence in the macula. develop hyperautofl oures- Inactive lesions: Hypoau- rescence corresponding cence with resolution. tofl uorescent to areas of chorioretinal Transitional stage: atrophy. Hypoautofl uorescent halo surrounding edges of active hyperautofl uorescent lesion. Complications Rarely signifi cant RPE and CNV and CME in up to Subretinal fi brosis, ERM, High risk for CNV with disciform photoreceptor atrophy or 20%. PED, BRVO also subretinal fl uid reported. scar formation, rare signifi cant RPE CNV resulting in vision loss. reported. atrophy. Treatments Generally none, occasion- Corticosteroids, plus Prolonged corticosteroids; Oral and periocular corticosteroids; ally corticosteroids. other immunosuppres- addition of other immuno- addition of other immunosuppres- sants, reservedly alkylat- suppressants also reported. sants such as cyclosporine. ing agents. Systemic associations Viral prodrome, CNS signs. Increased prevalence of Hashimoto thyroiditis, None systemic autoimmunity; aseptic meningitis, type 1 reports of HLA-B27, diabetes mellitus reported. Crohn’s disease, celiac disease, and also sarcoid. Course Acute decrease in vision Relapsing and progres- Acute loss of vision with Persistent lesions with mild with spontaneous recovery sive nature, often with progression and recurrence decrease in visual acuity and high and good fi nal visual loss of central vision in at and growth of new lesions risk of CNV development, potentially acuity. least one eye. over months to years. Good resulting in loss of central vision. fi nal acuity if no foveal involvement.

46 | Review of Ophthalmology | February 2014

042_rp0214_rtinsider.indd 46 1/24/14 11:06 AM However, this subset of patients re- different case with FAF imaging16 cent plaques that partially fi ll in late sponded to increased oral cortico- have been reported. On time-do- phases of the study (See Figures 4B steroids or the addition of immuno- main OCT, the active stage of the and 4C). ICGA shows hypofl uores- suppressive therapy, supporting the disease demonstrated hyperreflec- cent plaques throughout the study former hypothesis. Thus, identifying tivity of the inner and outer retinal (See Figure 4D). SD-OCT shows ret- the tubercular variant of serpiginous layers with subfoveal fl uid accumu- inal thinning with photoreceptor and choroiditis is critical for initiation of lation and a pigment epithelial de- RPE disruption. Once the disease is appropriate antibiotics in combina- tachment. With quiescence, normal stable, SD-OCT shows well-defi ned tion with oral steroid therapy and foveal anatomy was reestablished.31 areas of photoreceptor loss, collapse one should not terminate antituber- FAF revealed extensive confluent of the outer plexiform layer and thin- cular treatment even in the setting of areas of marked hypoautofluores- ning of the choriocapillaris.34 In the initial paradoxical worsening. cence corresponding to areas of cho- presence of CNV, intraretinal fl uid rioretinal atrophy.16 or neurosensory detachment may Relentless Placoid Chorioretinitis Vision can decrease significantly be present.35 FAF shows a speckled in RPC, especially with foveal in- pattern of hyper- and hypo-autofl uo- Relentless placoid chorioretini- volvement. However, if treated with rescence in the macula.34 tis (RPC) is an entity that has fea- prolonged systemic corticosteroids, Despite macular involvement, vi- tures resembling both APMPPE most patients can recover most of sual acuity is only mildly affected and serpiginous choroiditis, but with their prior vision.27 In the absence in PPM, with good prognosis for vi- an atypical retinal distribution and of treatment with systemic steroids, sual recovery unless RPE atrophy or clinical time course.27 The hallmark fi nal visual acuity tends to be com- CNV develops. While development of this disease is the development promised with prolongation of dis- of RPE atrophy is rare, CNV oc- of numerous new lesions during the ease course.28 Complications of RPC curs at a much higher incidence in disease course, which may span up include CNV, subretinal fibrosis, PPM than any of the previously de- to two years, eventually resulting in subretinal fl uid and epiretinal mem- scribed placoid diseases (only three 50 to hundreds of lesions. Peripheral brane formation. eyes of 16 total eyes reported thus lesions can precede or occur simulta- far did not develop CNV).32-34 Treat- neously with posterior involvement Persistent Placoid Maculopathy ment with oral or periocular cor- and recurrences do not necessarily ticosteroids and cyclosporine have initiate at the edges of prior lesions Persistent placoid maculopathy resulted in improvement in visual (as in serpiginous). Because of its (PPM) was first described by Pa- acuity prior to complications with shared features with APMPPE and mela Golchet, MD, and colleagues CNV.32-35 In one case, chronic im- serpiginous choroiditis, this entity in 2006.32,33 It resembles macular munosuppression was initiated early was termed “ampiginous” by Robert serpiginous choroiditis in its early in the diagnosis of PPM and no CNV B. Nussenblatt, MD.9,28 involvement of the macula and pre- developed in either eye at one-year RPC presents in young patients, dominantly affects middle-aged follow-up.34 Treatment strategies usually with a sudden decrease in Caucasian males. Unlike in macular for PPM-related CNV prior to the vision and/or metamorphopsia with serpiginous choroiditis, patients with age of anti-VEGF agents have inno history of a viral prodrome. An PPM initially present with only mild cluded sub-Tenon’s and intravitreal anterior chamber reaction or vitritis visual symptoms. triamcinolone acetonide, oral pred- may be present.14,29 Patients exhibit Anterior chamber infl ammation or nisone, laser photocoagulation, pho- small, white, placoid lesions at the vitritis is typically absent.32,33 On oph- todynamic therapy and submacular level of the RPE both anterior and thalmoscopy, jigsaw-pattern, whitish surgery, with limited success and posterior to the equator. Some of placoid lesions centered around the subsequent formation of disciform these lesions develop pigmented fovea that are not contiguous with scarring in the majority of cases.32,33 chorioretinal atrophy within weeks the optic disc (See Figure 4A) are There is one reported case of PPM- while others have a drawn out course noted. Unlike serpiginous or macular related CNV treated with intravit- of persistent activity or new growth. serpiginous choroiditis, PPM lesions real bevacizumab with good visual Angiographic fi ndings are similar to have a longer time course and gradu- outcome followed over a period of those of APMPPE and serpiginous ally fade over months to years with- two years.35 choroidopathy.27,28,30 Only one case out the development of new lesions. A summary of the clinical and of RPC with OCT imaging31 and a FA demonstrates early hypofl uores- angiographic characteristics of the

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thy. Arch Ophthalmol 1987;105:1237-42. spectrum of placoid white spot syn- course of months to years; although 11. Hamilton AM, Bird AC. Geographical choroidopathy. Br J Oph- thalmol 1974;58:784-97. dromes is provided in Table 1. In there is only a mild decrease in visu- 12. Christmas NJ, Oh KT, Oh DM, Folk JC. Long-term follow-up 2002, Nadia Bouchenaki, MD, and al acuity, it carries a high risk of cho- of patients with serpinginous choroiditis. Retina 2002;22:550-6. 13. van Velthoven ME, Ongkosuwito JV, Verbraak FD, Schlinge- colleagues described these disorders roidal neovascularization that may mann RO, de Smet MD. Combined en-face optical coherence with characteristic hypofl uorescence result in significant loss of central tomography and confocal ophthalmoscopy fi ndings in active multifocal and serpiginous chorioretinitis. Am J Ophthalmol on ICGA as indicating choriocap- vision. Obtaining imaging studies 2006;141:972-5. illaris nonperfusion and classified including fundus photos, FA, ICG 14. Bansal R, Gupta A, Gupta V. Imaging in the diagnosis and management of serpiginous choroiditis. Int Ophthalmol Clin them as inflammatory choriocapil- angiography, SD-OCT and FAF is 2012;52(4):229-36. laropathies.30 With the aid of newer critical to establishing the correct 15. Carreño E, Portero A, Herreras JM, López MI. Assesment of fundus autofl uorescence in serpiginous and serpiginous-like cho- spectral-domain OCT studies, it ap- diagnosis and guiding management. roidopathy. Eye (Lond) 2012;26:1232-6. pears there is also outer retinal in- Close clinical follow-up and provid- 16. Yeh S, Forooghian F, Wong WT, Faia LJ, et al. Fundus autofl uorescence imaging of the white dot syndromes. Arch Ophthalmol volvement, and exactly where the ing timely treatment when indicated 2010;128:46-56. site of primary insult resides still are paramount in preventing or at 17. Blumenkranz MS, Gass JD, Clarkson JG. Atypical serpiginous choroiditis. Arch Ophthalmol 1982;100:1773-5. remains unclear. Future studies least minimizing permanent vision 18. Lee DK, Suhler EB, Augustin W, Buggage RR. Serpiginous looking at enhanced depth imaging loss. choroidopathy presenting as choroidal neovascularisation. Br J Ophthalmol 2003;87:1184-5. of the choroid may provide greater 19. Jampol LM, Orth D, Daily MJ, Rabb MF. Subretinal neovas- insight and understanding of the Dr. George is in his fi nal year of resi- cularization with geographic (serpiginous) choroiditis. Am J Oph- thalmol 1979;88:683-9. pathogenesis of placoid WSS. The dency at the Jules Stein Eye Institute, 20. Gupta V, Agarwal A, Gupta A, Bambery P, Narang S. Clinical etiology of WSS remains unknown, UCLA, Los Angeles. Contact him at: characteristics of serpiginous choroidopathy in North India. Am J Ophthalmol 2002;134:47-56. although the increased prevalence [email protected]. Dr. Sarraf 21. Song MH, Roh YJ. Intravitreal ranibizumab for choroi- of systemic autoimmunity in patients is a clinical professor of ophthalmology dal neovascularisation in serpiginous choroiditis. Eye (Lond) 2009;23:1873-5. with WSS and their relatives sug- in the Retinal Disorders and Ophthal- 22. Mansour AM, Jampol LM, Packo KH, Hrisomalos NF. Macular gests WSS occurs in families with a mic Genetics Division at Jules Stein. serpiginous choroiditis. Retina 1988;8:125-31. 23. Sahu DK, Rawoof A, Sujatha B. Macular serpiginous choroidi- genetic predisposition toward auto- Contact him at [email protected] or tis. Indian J Ophthalmol 2002;50(3):189-96. immunity.36 (310) 794-9921. Dr. Golchet practices 24. Bansal R, Gupta A, Gupta V, Dogra MR, Sharma A, Bambery P. Tubercular serpiginous-like choroiditis presenting as multifocal Recognizing the different entities at Southern California Permanente serpiginoid choroiditis. Ophthalmology 2012;119:2334-42. among the spectrum of the white- Medical Group in Woodland Hills, Ca- 25. Gupta V, Bansal R, Gupta A. Continuous progression of tubercular serpiginous-like choroiditis after initiating antituberculosis spot syndromes is important for the lif. Dr Freund is a clinical professor of treatment. Am J Ophthalmol 2011;152(5):857-63. general ophthalmologist and espe- ophthalmology at NYU School of Med- 26. Gupta V, Gupta A, Arora S, Bambery P, Dogra MR, Agarwal A. Presumed tubercular serpiginouslike choroiditis: Clinical presen- cially for the retina specialist. Among icine and practices at Vitreous Retina tations and management. Ophthalmology 2003;110:1744-9. the placoid WSS, APMPPE is the Macula Consultants of New York. 27. Jones BE, Jampol LM, Yannuzzi LA, Tittl M, et al. Relentless placoid chorioretinitis: A new entity or an unusual variant of ser- most common and benign with a piginous chorioretinitis? Arch Ophthalmol 2000;118:931-8. 1. Gass JD. Acute Posterior Multifocal Placoid Pigment Epithe- 28. Jyotirmay B, Jafferji SS, Sudharshan S, Kalpana B. Clinical viral prodrome and multiple creamy liopathy. Arch Ophthalmol 1968;80:177-85. profi le, treatment, and visual outcome of ampiginous choroiditis. 2. Goldenberg D, Habot-Wilner Z, Loewenstein A, Goldstein M. lesions that often fade within a few Ocul Immunol Infl amm 2010;18:46-51. Spectral domain optical coherence tomography classifi cation of 29. Biswas J, Narain S, Das D, Ganesh SK. Pattern of uve- weeks as visual acuity recovers. Visu- acute posterior multifocal placoid pigment epitheliopathy. Retina itis in a referral uveitis clinic in India. Int Ophthalmol 1996- 2012;32:1403-10. al prognosis is more ominous in cas- 1997;20(4):223-8. 3. Hirano Y, Yasukawa T, Nagai H, Ogura Y. Spatio-temporal un- 30. Bouchenaki N, Cimino L, Auer C, Tao Tran V, Herbort CP. As- es of serpiginous choroiditis, which derstanding of the pathology of acute posterior multifocal placoid sessment and classifi cation of choroidal vasculitis in posterior pigment epitheliopathy. Jpn J Ophthalmol 2012;56(4):371-4. endangers the fovea and carries a uveitis using indocyanine green angiography. Klin Monbl Augen- 4. Scheufele TA, Witkin AJ, Schocket LS, Rogers AH, et al. Pho- heilkd 2002;219:243-9. high risk of recurrences. The major- toreceptor atrophy in acute posterior multifocal placoid pigment 31. Amer R, Florescu T. Optical coherence tomography in re- epitheliopathy demonstrated by optical coherence tomography. ity of patients with this particular lentless placoid chorioretinitis. Clin Experiment Ophthalmol Retina 2005;25:1109-12. 2008;36(4):388-90. placoid lesion permanently lose cen- 5. Cheung CM, Yeo IY, Koh A. Photoreceptor changes in acute and 32. Golchet PR, Jampol LM, Wilson D, Yannuzzi LA, Ober M, Stroh resolved acute posterior multifocal placoid pigment epitheliopa- tral vision in at least one eye. Relent- E. Persistent placoid maculopathy: A new clinical entity. Trans Am thy documented by spectral-domain optical coherence tomogra- Ophthalmol Soc 2006;104:108-20. less placoid chorioretinitis presents phy. Arch Ophthalmol 2010;128:644-6. 33. Golchet PR, Jampol LM, Wilson D, Yannuzzi LA, Ober M, Stroh 6. Souka AA, Hillenkamp J, Gora F, Gabel VP, Framme C. Corre- with numerous smaller lesions both E. Persistent placoid maculopathy: A new clinical entity. Ophthal- lation between optical coherence tomography and autofl uores- mology 2007;114:1530-40. anterior and posterior to the equa- cence in acute posterior multifocal placoid pigment epitheliopa- 34. Kovach JL. Persistent placoid maculopathy imaged with spec- thy. Graefe’s Arch Clin Exp Ophthalmol 2006;244:1219-23. tor, with a prolonged clinical course tral domain OCT and autofl uorescence. Ophthalmic Surg Lasers 7. O’Halloran HS, Berger JR, Lee WB, Robertson DM, et al. Acute Imaging 2010 Nov-Dec;41 Suppl:S101-3 and frequent relapses over months multifocal placoid pigment epitheliopathy and central nervous 35. Parodi MB, Iacono P, Bandello F. Juxtafoveal choroidal neo- system involvement: nine new cases and a review of the litera- to years. With treatment, there is vascularization secondary to persistent placoid maculopathy ture. Ophthalmology 2001;108:861-8. treated with intravitreal bevacizumab. Ocul Immunol Infl amm often only minimal sustained vision 8. Gass JDM. Stereoscopic atlas of macular diseases: diagnosis 2010;18(5):399-401. and treatment. 3rd ed. vol 1. St Louis: Mosby, 1987. loss. Finally, persistent placoid mac- 36. Pearlman RB, Golchet PR, Feldmann MG, Yannuzzi LA, et al. 9. Lim WK, Buggage RR, Nussenblatt RB. Serpiginous Choroiditis. Increased prevalence of autoimmunity in patients with white ulopathy presents as a placoid lesion Surv Ophthalmol 2005;50(3):231-44. spot syndromes and their family members. Arch Ophthalmol 10. Hardy RA, Schatz H. Macular geographic helicoid choroidopa- in the macula that persists for a time 2009;127:869-74.

48 | Review of Ophthalmology | February 2014

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RP0913_UPMC.indd 1 8/12/13 11:59 AM Therapeutic Topics REVIEW

Wise Choices for Ocular Diagnoses A look at the value and utility of a range of diagnostic techniques and technology for anterior segment disease. Mark B. Abelson, MD, CM, FRCSC, FARVO, and James McLaughlin, PhD, Andover, Mass.

key part of the many debates procedures that are overused, provide Which Conjunctivitis? A over health care is the idea of little clinical benefi t and, in some cas- providing the best possible care with es, may even be obstacles to achieving Acute conjunctivitis presents with increasingly limited resources. This the best possible patient outcomes. a spectrum of features that will often attention to spending has amplified These groups identifi ed fi ve or more provide all the diagnostic data needed the interest in more cost-conscious suggested practices based upon the to determine the underlying etiology.3 medicine. A 2012 report in the Jour- latest in evidence-based assessments. What we like to refer to as “Abelson’s nal of the American Medical Asso- One of the AAO recommendations diagnostic triad” states that if it’s itchy, ciation identifi ed six areas of medical states, “Don’t perform preoperative it’s allergy; if it’s sticky, it’s bacterial; waste and, among these, overtreat- medical tests for eye surgery unless and if it burns it’s dry eye. Clear dis- ment (including superfl uous testing, there are specific medical indica- charge, visual impairment, photopho- treatments or hospitalizations) was tions.” So unless the patient has a bia and ocular pain are other features the biggest of the offenders, with es- history of heart disease, for example, that can be useful in whittling down timates of $150 to $225 billion wasted a preoperative EKG is unnecessary. the diagnosis.4 Viral conjunctivitis can by such activities in the United States Some of the Choose Wisely recom- have a variable presentation, but a annually.1 Lost in these arguments, at mendations run counter to estab- key to remember is that it’s typically times, is that no matter the dollar fi g- lished practices, but in a sense, that’s follicular, so swollen lymph nodes (es- ures involved, such activities are often the point: They are a way of rethink- pecially periauricular nodes) can be bad medicine as well as bad econom- ing standard operating procedures in diagnostic. These initial assessments ics. So perhaps a silver lining that may light of 21st-century economics and, can be followed up by additional test- emerge from the chaos that is health- most importantly, 21st-century medi- ing, exploratory therapeutics or both. care reform is the reaffi rmation that cal evidence. While a test dose of a topical an- in medicine, as in many other avoca- In this month’s column we examine tihistamine is probably the most ef- tions, less is very often more. selected front-of-the-eye diagnostics fi cient way to confi rm a diagnosis of An example of this is the Choose and standard operating procedures allergic conjunctivitis, other forms Wisely campaign,2 an effort spear- and ask how these procedures hold up of conjunctivitis may require further headed by the American Board of to a “choose wisely” inspired evalua- investigation. Another of the AAO Internal Medicine that has recruited tion. Our strong bias in this discussion recommendations in the Choose more than 50 specialty societies, in- is that patient history and examination Wisely campaign is “Don’t order an- cluding the American Academy of remain the most valuable sources of tibiotics for adenoviral conjunctivi- Ophthalmology, to identify tests and information for diagnostic inquiry. tis (pink eye).” Despite this, recent

50 | Review of Ophthalmology | February 2014 This article has no commercial sponsorship.

050_rp0214_ttops.indd 50 1/24/14 11:04 AM estimates suggest that physicians (including ophthalmologists) are not particularly adept at discriminating between bacterial or viral etiologies.4 With the exception of severe cases, culturing of bacteria or viral infections is neither time- nor cost-effective. A simple, rapid test for adenovirus (Ad- enoplus, RPS Inc.) can help defi ne a diagnosis when there is a question of viral vs. bacterial etiology.5,6 It’s worth remembering that about 80 percent of acute conjunctivitis cases are viral, and of these, between 65 to 90 percent are due to one of the adenovirus serotypes (as discussed in Therapeutic Topics, When faced with a case of conjunctivitis, “Abelson’s triad” can help clinch the diagnosis: If March 2010). The Adenoplus test can it itches it’s allergy; if it’s sticky it’s bacterial; and if it burns it’s dry eye. minimize misuse of antibiotics, and also can confi rm the need for patient Review of the evidence behind each tear film, and provide the means to isolation to prevent the spread of virus. of each of these methods indicates monitor the cellular morphology asso- that none alone provides the sensitiv- ciated with dry eye. It’s likely that with Dry-Eye Diagnostics ity and specifi city needed for a reliable additional studies revealing changes diagnostic. Without a diagnostic gold in the epithelium, meibomian glands The diagnosis of dry eye is com- standard, the recommendations of the and corneal nerves associated with plex; the condition can result from any DEWS report leave both practitioners dry eye (both aqueous-defi cient and number of causes (or combinations and clinical researchers to rely on the MG disease), it will be possible to use of causes), each of which contributes “tetrad” of symptom questionnaires, these imaging modalities for objective to the patient’s presentation.7,8 Thus, corneal staining, tear-fi lm breakup and diagnosis and treatment monitoring. patients with an aqueous deficiency Schirmer’s test as the most reliable of the tear fi lm will present different means of dry-eye assessment.8 Re- Analyzing Tear Components symptomology from those with meibo- search at Ora has led to the develop- mian gland disease, but all are likely to ment of a number of refi nements to Efforts at characterizing tear pro- share some degree of discomfort, sur- tear-film assessments, but these are tein components, and the potential face infl ammation and visual impair- generally not suited for routine clini- use of protein profi ling as a diagnostic ment. Diagnosis has traditionally been cal practice.9-11 It seems that none of tool, go back several decades.14 These made using the combination of patient these traditional metrics is a particu- efforts mirror the diffi culty of develop- symptomology, tear assessments using larly wise choice, since none provides ing effi cacious treatments, and there Schirmer’s strips and ocular surface a robust metric from which to derive are still few validated tear biomarkers staining. Lack of a reproducible, con- a therapeutic strategy. Despite this, for dry eye; major candidates include sistent association between signs and new technologies are available or in several pro-inflammatory cytokines, symptoms of dry eye represents the development that attempt to address metalloproteinases or lactoferrin. single biggest impediment to both ac- this unmet need. Several new devices designed for use curate diagnosis and development of Use of imaging techniques is one in clinical practice are available that effective treatments. such area of diagnostic progress. Es- offer the ability to analyze tear con- The diagnostic tests for dry eye tablished technologies such as optical stituents as a diagnostic for dry eye.15 described in the International Dry coherence tomography or confocal One of these, InflammaDry (RPS), Eye Workshop include measures of microscopy are being adapted to ex- measures the concentration of matrix tear volume (Schirmer’s test, phenol amine tear-film properties, corneal metalloproteinase 9 in a simple, one- red thread test and meniscus height), nerve structures, infl ammatory cell in- step device similar to the Adenoplus. physical properties (breakup times, fi ltration and structure of meibomian This protease is involved in the break- osmolarity), composition (lactoferrin) glands.12,13 These methodologies allow down of epithelial integrity associated and tear dynamics (turnover rate).8 for a more precise assessment of the with chronic infl ammation.16 Tearscan

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REVIEW Topics

(ATD), another one-step system to tion for TearLab describes it as an when mapping the course for diag- measure either tear lactoferrin or IgE “aid in the diagnosis of dry-eye disease nosis and management of all ocular levels is also now on the market. It’s in patients suspected of having dry- surface diseases. thought that a comparison of markers eye disease, in conjunction with other of infl ammation (lactoferrin or MMP methods of clinical evaluation.”21 Dr. Abelson is a clinical professor 9) with a primary marker of ocular The value of osmolarity measure- of ophthalmology at Harvard Medical allergy (IgE) will help distinguish be- ments in monitoring treatment is School. Dr. McLaughlin is a medical tween dry eye and chronic allergy, also unclear. In a recent retrospec- writer at Ora Inc. though proof of the utility of these tive study, Francisco Amparo, MD, 1. Berwick DM, Hackbarth AD. Eliminating waste in US health care. devices will only come from clini- and his colleagues at the Schepens JAMA 2012;307:14:1513-6. cal studies that track the biomarkers Eye Research Institute compared os- 2. http://www.choosingwisely.org/doctor-patient-lists/ accessed 6 December 2013. as a function of therapeutic regimes molarity values to other measures of 3. Azari AA, Barney NP. Conjunctivitis. A Systematic Review of Diagnosis and Treatment. JAMA. 2013;310:16:1721-1729. or correlate the biomarkers to other dry eye, including the ocular surface 4. O’Brien TP, Jeng BH, McDonald M, Raizman MB. Acute signs and symptoms. There are prom- disease index survey and Oxford-scale conjunctivitis: Truth and misconceptions. Curr Med Res Opin 22 2009;25:8:1953-1961. ising studies that suggest that elevated rated corneal staining. They report 5. Sambursky R, Tauber S, Schirra F, et al. The RPS adeno detector for diagnosing adenoviral conjunctivitis. Ophthalmology MMP 9 levels in tears are an early that while there was modest correla- 2006;113:10:1758-1764. predictor of dry eye, and that the lev- tion between osmolarity and the more 6. Sambursky R, Trattler W, Tauber S, et al. Sensitivity and Specifi city of the AdenoPlus Test for Diagnosing Adenoviral els of the proteinase in tears show a traditional measures of dry eye, there Conjunctivitis. JAMA Ophthalmol 2013;131:1:17-22. significant correlation to other dry- was no correlation between changes 7. Abelson MB, Ousler GW, Maffei C. Dry eye in 2008. Curr Opin Ophthalmol 2009;20:4:282-6. eye signs and symptoms.16 However, in osmolarity and improvements in 8. Methodologies to diagnose and monitor dry eye disease: Report of the Diagnostic Methodology Subcommittee of the there are several issues with the use of OSDI or staining scores. While an International Dry Eye Work Shop (2007). [No authors listed] Ocul MMP 9 tests for dry eye that clinicians alternative interpretation of this study Surf 2007;5:2:108-52. 9. Ousler GW 3rd, Hagberg KW, Schindelar M, Welch D, Abelson 23 need to be aware of, including the was also recently published, it is MB. The Ocular Protection Index. Cornea 2008;27:5:509-13. 17 10. Walker PM, Lane KJ, Ousler GW 3rd, Abelson MB. Diurnal reported effects of contact lens use nonetheless hard to see how a test variation of visual function and the signs and symptoms of dry and prostaglandin analogues18 on tear with a Food and Drug Administra- eye. Cornea 2010;29:6:607-12. 11. Johnston PR, Rodriguez J, Lane KJ, Ousler G, Abelson MB. The levels of the proteinase. Despite these tion indication to be used in conjunc- inter-blink interval in normal and dry eye subjects. Clin Ophthalmol potentially confounding issues, the tion with other dry-eye metrics can be 2013;7:253-9. 12. Ibrahim OM, Dogru M, Takano Y, et al. Application of MMP 9 test does appear to have value considered a gold standard for either visante optical coherence tomography tear meniscus height measurement in the diagnosis of dry eye disease. Ophthalmology as an objective measure of ocular sur- clinical diagnosis or as an endpoint (or 2010;117:1923-9. face infl ammation. inclusion criteria) for clinical trials. 13. Villani E, Baudouin C, Efron N, et al. In vivo confocal microscopy of the ocular surface: From bench to bedside. Curr Eye Res 2014 in Another tear composition diagnos- Some of these newer technologies press, pub online Nov 14. 14. Bjerrum KB. The ratio of albumin to lactoferrin in tear fl uid as tic that’s now widely available is the may provide value in diagnosis and a diagnostic tool in primary Sjögren’s syndrome. Acta Ophthalmol TearLab Osmolarity Test (TearLab), formulation of the best treatment Scand 1997;75:5:507-11. 15. Sambursky R, Davitt WF 3rd, Latkany R, et al. Sensitivity and a device that measures the concentra- plans. When we consider any new specifi city of a point-of-care matrix metalloproteinase 9 immuno- tion of tear solutes and is described diagnostics, however, remember to assay for diagnosing infl ammation related to dry eye. JAMA Ophthalmol 2013;131:1:24-8. as an objective, reliable measure of consider several key factors: Does the 16. Chotikavanich S, de Paiva CS, Li de Q, et al. Production and 19 activity of matrix metalloproteinase-9 on the ocular surface the severity of dry-eye disease. De- result of the test improve our ability increase in dysfunctional tear syndrome. Invest Ophthalmol Vis spite this claim, there are limitations to render an accurate diagnosis? Can Sci 2009;50:7:3203-9. 17. Markoulli M, Papas E, Cole N, Holden B. Effect of contact lens to the use of osmolarity as a diagnostic the test be used to follow or modify wear on the diurnal profi le of matrix metalloproteinase 9 in tears. Optom Vis Sci 2013;90:5:419-29. for dry eye. For instance, compensa- the course of a patient’s condition? 18. Honda N, Miyai T, Nejima R, et al. Effect of latanoprost on the tory mechanisms, such as more rapid If not, then what is its value? We are expression of matrix metallo-proteinases and tissue inhibitor of metalloproteinase 1 on the ocular surface. Arch Ophthalmol blinking, can significantly alter tear reminded of the Yogi Berra aphorism 2010;128:4:466-71. osmolarity, as can other factors such that, sometimes, “You can observe a 19. Versura P, Profazio V, Campos EC. Performance of tear osmolarity compared to previous diagnostic tests for dry eye as patient hydration, diurnal variation, lot just by watching.” While there are diseases. Curr Eye Res 2010;35:7:553-64. 20. Lemp MA, Bron AJ, Baudouin C, et al. Tear osmolarity in the environmental conditions and other a number of powerful, technologi- diagnosis and management of dry eye disease. Am J Ophthalmol diagnostic procedures. While some cally sophisticated new devices either 2011;151:5:792-798.e1. 21. http://www.accessdata.fda.gov/cdrh_docs/pdf8/k083184.pdf have described osmolarity as the “gold on the market or under development - 69k - 2009-07-02. Accessed 23 December 2013. 20 22. Amparo F, Jin Y, Hamrah P, Schaumberg DA, Dana R. What standard” of dry-eye diagnostics, it’s that will all claim to provide the key is the value of incorporating tear osmolarity measurement in clear that currently available measures to diagnostic success, no machine has assessing patient response to therapy in dry eye disease? Am J Ophthalmol 2014; 157:1:69-77. of osmolarity alone cannot unequivo- been invented that can supplant the 23. Pepose JS, Sullivan BD, Foulks GN, and Lemp MA. The value of tear osmolarity as a metric in evaluating the response to dry cally confi rm or disprove a diagnosis value of a thorough patient history and eye therapy in the clinic and in clinical trials. Am J. Ophthalmol of dry eye. In fact, the FDA indica- exam. So, it’s up to us to choose wisely 2014;157:1:4-6.e1.

52 | Review of Ophthalmology | February 2014

050_rp0214_ttops.indd 52 1/24/14 11:04 AM SAVE THE DATE OPHTHALMOLOGY February 15-16 2014 UPDATE An interdisciplinary faculty of ophthalmic sub-specialties will review the continuing progress in: Cataract and Refractive Surgery, Glaucoma, Retina, Program Chairs: Neuro-Ophthalmology, Oculoplastics, Don O. Kikkawa, MD Ocular Surface Disease, Cornea Robert N. Weinreb, MD and Oncology. Keynote Faculty Gholam Peyman, MD

Featured Faculty Malik Kahook, MD Eytan Blumenthal, MD Sameh Mosaed, MD Sonia Yoo, MD

Invited Faculty Ray Gariano, MD, PhD Francis Mah, MD Tommy Korn, MD, FACS Program Chairs: Baruch Kupperman, MD, PhD UCSD Faculty Don O. Kikkawa, MD Natalie Afshari, MD, FACS William Freeman, MD Robert N. Weinreb, MD Michael Goldbaum, MD Jeffrey Goldberg, MD, PhD Weldon Haw, MD Location Christopher Heichel, MD Bobby Korn, MD, PhD Hilton La Jolla Torrey Pines Jeffrey E. Lee, MD Jonathan Lin, MD, PhD Felipe Medeiros, MD, PhD 10950 North Torrey Pines Rd. Shira Robbins, MD Peter Savino, MD Linda Zangwill, PhD La Jolla, CA 92037 Kang Zhang, MD, PhD Phone: 858-558-1500 Program Times Saturday, February 15, 2014 7:30am-4:30pm Reception to follow 3 WAYS TO REGISTER Sunday, February 16, 2014 Online: www.revophth.com/Update2014 7:30am-12:00pm Email: [email protected] Call: Lois DiDomenico 800-999-0975

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2014weinreb_poster.indd 1 1/22/14 1:38 PM Glaucoma Management

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

NTG: The Nocturnal Blood Pressure Factor Evidence indicates that large dips in blood pressure at night correlate with progression in normal-tension glaucoma patients. Carlos G. De Moraes, MD, New York City

ne of the many challenging are treated for systemic hypertension. pressure and progression, and some O forms that glaucoma may take is The literature indicates that the other epidemiologic studies such as so-called normal-tension glaucoma, deﬁ nition of high blood pressure has the Barbados Eye Study have also in which elevated intraocular pressure been slowly changing, lowering the suggested this association. However, appears to play a less-meaningful cutoff for what is consider elevated these studies either relied on a single part in the equation; these patients pressure, with the result that patients blood pressure measurement or just have IOP measurements within the are sometimes being treated too checked the pressure during the day, statistically normal range. Recently, aggressively. Dr. Charlson’s work is or for 24 hours at most. We know that our group pursued a hypothesis showing that this can have deleterious like IOP, blood pressure varies a lot regarding the possible connection effects on other organs. For example, during the day and from one day to between this type of glaucoma and patients with very low blood pressure the next. So, we decided to monitor blood pressure abnormalities, leading are more likely to have kidney failure, our subjects’ blood pressure every half to the discovery of some previously heart problems and even strokes. hour for 48 hours—on three different undocumented, clinically useful asso- Given the fact that glaucoma is a occasions. ciations. progressive disease with a component In addition, there’s been no con- Here, I’d like to share some of of vascular abnormality—especially sensus regarding what constitutes low what we’ve learned so far, and ways in normal-tension glaucoma—we de- blood pressure, or what parameter which this may help you care for your cided to investigate the possible cor- should be evaluated to determine normal-tension glaucoma patients. relation between glaucoma progres- whether a patient is at risk or not. sion and very low arterial blood So, we not only tested the hypothesis Systemic Hypertension pressure, particularly when it occurs that low blood pressure is associated during sleep, and in some instances with progression, we also proposed a Our group became interested in could be due to excessive treatment of method to measure that. conducting a study after a discussion systemic hypertension. with a group of internists at Cornell Of course, we’re not the first to Designing the Study University, led by Mary E. Charlson, examine such a connection. However, MD, William Foley Professor of most recent research on blood pres- Our hypothesis was that nocturnal Medicine and chief of general internal sure and glaucoma has had a different pressure dips could be an additional medicine. Dr. Charlson is a renowned focus than ours. For example, the risk factor for progression, particularly clinical epidemiologist who has been Early Manifest Glaucoma Trial in patients with normal-tension glau- studying what happens when patients found a relationship between blood coma, who are known to have a strong

54 | Review of Ophthalmology | February 2014 This article has no commercial sponsorship.

054_rp0214_gm.indd 54 1/24/14 11:44 AM IOP-independent component to their Mean Arterial Blood Pressure in an NTG Patient disease. The reason that pressure dips are especially dangerous is the phenomenon of autoregulation, which Arterial pressure while awake (at baseline) is our bodies’ way of maintaining adequate perfusion in key organs such 90 mean arterial as the brain and the heart when blood pressure while pressure drops. The body narrows 80 awake 70

the peripheral blood vessels, causing mmHg vasoconstriction, reducing the blood 60 ﬂ ow to less critical organs—including the eye. Of course, the optic nerve 50 is in a watershed zone in terms of Hours 0 5 10 15 20 25 circulation, so any decrease in blood Arterial pressure during sleep (at baseline) ﬂ ow to the eye can potentially damage the optic nerve. Thus, when blood

90 mean arterial pressure drops below a key level, the pressure while body’s autoregulation kicks in; if the 80 awake insult persists, we see problems such 70 as hypoperfusion, ischemia and nerve mmHg damage. 60

This problem is exacerbated at 50 night, because blood pressure is Hours 0 5 10 15 20 25 normally lower then. Meanwhile, IOP tends to go up at night. Early In this study of normal-tension glaucoma patients, the data revealed a signifi cant in the morning, just before you wake correlation between progression and both the length of time that mean nocturnal blood up, is when your IOP is normally the pressure dropped below the mean diurnal pressure, and the magnitude of the drop. highest—at the same time your blood pressure is usually the lowest, causing enrollment and 77 percent of that pressure monitoring, the patients an imbalance in the blood supply to group were on medications to reduce came back at six months and one year your eye. Healthy people are able to their blood pressure. for visual fi eld testing and repeat 48- compensate for this so that it doesn’t The device we used to measure hour blood pressure monitoring. cause any damage. But in glaucoma blood pressure over a 48-hour period or systemic hypertension, we believe was placed on the arm at the same What the Data Showed this ability is compromised. location at which you would normally To test whether there is a real measure blood pressure; every 30 At the end of that year we analyzed association between nocturnal pres- minutes it automatically inflated the data. From each of the 48-hour sure dips and progression, we decided and recorded the blood pressure. measurements, we got an average to prospectively monitor patients’ The device is very noninvasive and of the mean arterial pressure during nocturnal blood pressure and see reasonably comfortable; I don’t re- the day when the patient was awake. whether those dips correlated with call any patient ever complaining Then we looked at the blood pressure glaucoma progression during the trial about wearing it for the 48 hours. (In profi le when the patient was asleep period. For our study we selected contrast, checking IOP over a 24-hour and calculated how long the nocturnal patients from our office who had period requires waking the patient at mean arterial pressure was below normal-tension glaucoma, defined intervals through the night, which is the awake/ diurnal mean arterial as having all of their untreated IOP not only irritating and disruptive but pressure, and by what amount (See measurements below 21 mmHg. may also affect the legitimacy of the fi gure, above). They also met criteria such as measurements.) This is one of several Comparing this to the rates of pro- having at least fi ve visual fi elds prior such devices that are commercially gression seen in the visual fi elds, we to enrollment. Overall, 32 percent available, and it’s not very expensive. found a significant correlation be- of the subjects had been diagnosed After collecting baseline infor- tween progression and both the length with systemic hypertension prior to mation, including 48-hour blood of time that mean nocturnal blood

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REVIEW Management

pressure dropped below the mean glaucoma with statistically normal glaucoma, but they are statistically diurnal pressure, and the magnitude pressure has a vascular component. connected. For example, Japan has of the drop. For example, if a patient Given the results of our research, a higher proportion of myopes than had a pressure below the mean diurnal we believe that patients with Western countries, and 90 percent arterial pressure for fi ve hours during normal-tension glaucoma should of their open-angle glaucomas are the night, but he was only a few mmHg be considered for evaluation for normal-tension glaucoma. So if below that pressure, he could be at nocturnal dips in pressure—and the other risk factors such as a genetic less risk of progression than another importance of this testing increases predisposition for glaucoma are patient who dropped below the mean if the patient is being treated for present, ophthalmologists should diurnal pressure for only two hours but systemic hypertension. scrutinize myopic patients closely. was 30 or 40 mmHg below the diurnal However, there are other red fl ags • Systemic beta blocker use. pressure. besides being treated for hypertension Plenty of literature has shown that One of our analyses looked to see that should possibly trigger such systemic beta blockers—especially if patients treated for systemic hyper- monitoring: used alone—may not be the best way tension had a different response than • Postural hypotension.If a to treat systemic hypertension. One those not being treated. The data patient says that he feels faint when reason is that their main effect is to showed that for a similar amount standing up too quickly, that’s an lower the heart rate and decrease the of time and magnitude that the indication that he has low blood strength at which the heart pumps nocturnal pressure was below the pressure in general (i.e., systemic blood. When your body senses that average diurnal pressure, those being hypotension) and may have a problem blood pressure is dropping, it attempts treated for systemic hypertension with his autoregulatory mechanisms. to compensate by (among other were more susceptible to progression • Cold hands and feet. This can things) increasing your heart rate than those who were not being indicate insuffi cient blood fl ow to the and the strength of the pumping as treated for systemic hypertension. It extremities. (If this becomes extreme part of autoregulation. Beta blockers was clear that people who don’t have a person may exhibit Raynaud’s phe- can interfere with that protective hypertension also can experience nomenon, in which extremities have mechanism. Other hypertension intense dips, but those who were being an exaggerated response to cold or medications, in contrast, may act treated for systemic hypertension emotional stress. Fingers and hands on the vessels or arteries to prevent were more susceptible to them. can turn pale, even blue, and become excessively high blood pressure, In short, our prospective study cold to the touch; they may eventually allowing the heart to protect key demonstrated that very low blood become tingly or numb, and may organs when pressure drops at night. pressure, particularly at night, is a swell and ache.) significant predictor of progression • Migraines. Patients with mi- Clinical Management in normal-tension glaucoma patients. graines were very common in our sam- Of course, this does leave an imple—another symptom suggesting an For screening purposes, ambulatory portant question unanswered: Is imbalance in the autoregulatory blood blood pressure measurements may be this susceptibility the result of the pressure mechanism. performed on patients with normal- systemic hypertension, or a side effect • Myopia. Myopia is very common tension glaucoma—in particular of the medications being used to treat in normal-tension glaucoma patients. patients who are progressing despite the systemic hypertension? To answer At fi rst, many people thought that this intensive IOP lowering, for no ob- that question we’ll need another study, association was a data fl uke because vious reason. This will allow you to testing the patients after modifying nearsighted people go to the eye doc- tell if signifi cant pressure drops are their medications. But at least we’ve tor more often, so they were being occurring at night. We’ve used the shown that there’s an association diagnosed more often. But research, ambulatory device in our office to between being overtreated for sys- including animal and human research monitor patients for several years; you temic hypertension and being more with in vivo imaging, suggests that just give it to the patient and he comes susceptible to the deleterious effects the optic nerve in myopic eyes is back 48 hours later. You connect the of nocturnal pressure dips. more susceptible to damage because device to a computer and it shows the myopic eye is usually longer, all the blood pressure information. A Red Flags for Clinicians stretching the tissues. Of course, clinician can easily use it. most people with myopia will never If a normal-tension glaucoma pa- As ophthalmologists we know that have a problem with normal-tension tient is being treated for systemic

56 | Review of Ophthalmology | February 2014

054_rp0214_gm.indd 56 1/24/14 11:45 AM hypertension, I highly recommend evidence to support this approach. suspicions were confirmed: Hypo- that you talk to the patient’s internist It’s based on physiology and our best tension during sleep does predict or cardiologist to explain what’s going understanding of what’s happening. progressive visual field loss in nor- on and ask whether the treatment Ultimately, we’ll need clinical trials to mal-tension glaucoma. So, if you might be too aggressive. Does the actually determine whether a given have patients with normal-tension patient really need such a low intervention slows or fails to slow glaucoma—especially those who pressure? Causing the progression to glaucoma progression. keep progressing for no apparent stop may be just a matter of changing reason—it’s very worthwhile to per- a medication, or having the patient Seeing the Whole Picture form ambulatory blood pressure stop taking it at night. monitoring and see if nocturnal Of course, a few individuals will It’s important to remember that dips are occurring. It’s easy and have this problem at night without before being ophthalmologists, we inexpensive to do, and it may not only having a diagnosis of systemic hy- are physicians. We have to look at the explain the reason for the disease and pertension. Unfortunately, there patient as a whole. The eye interacts the progression, it might also help you are no proven treatments to help in with everything else in the body, know what to do to prevent future this situation (that we’re aware of), and factors such as autoregulation, progression. although a clinician could try some blood pressure and IOP may be unproven treatments that might, in interrelated. Don’t forget to consider Dr. De Moraes is an associate pro- theory, be helpful. For example, salt- other ailments the patient may have, fessor of ophthalmology at New loading at night or drinking V8 Juice and don’t hesitate to talk to the York University Medical Center, and before bed might help to raise low patient’s internist or cardiologist if Edith C. Blum Foundation Research blood pressure a little during sleep- blood pressure may be an issue. Scientist at the New York Eye and Ear time. We’ve tried this with moderate The main point I hope clinicians Inﬁ rmary. He has no ﬁ nancial ties to success, but again, there’s no clinical will take from our study is that our any product mentioned.

054_rp0214_gm.indd 57 1/24/14 2:26 PM Refractive Surgery

REVIEW Edited by Arturo Chayet, MD

New Ways to Detect Keratoconus Looking at corneal imaging data in different ways can enhance your ability to avoid risky refractive surgery cases. Walter Bethke, Managing Editor

eing able to identify patients with the cornea that is measured because it our study, when we compared the Birregular corneas is crucial to cor- fi ts closer to the natural corneal shape BFTA to the BFS to screen out the nea specialists in general and refrac- by canceling out its means aspheric- initial stage of keratoconus, we found tive surgeons in particular, since the ity and toricity,” explains Dr. Smadja. the performance of the BFTA to be latter need to avoid removing tissue “What is nice about the BFTA is that much higher than the performance in corneas that are already weak. To comparing a cornea to it is almost like of the BFS in terms of discriminat- this end, researchers and clinicians are comparing the cornea to its perfect ing between normal and forme fruste always devising new ways to detect ir- clone. Therefore, anything that will keratoconus.1 Specifically, when regularities as early as possible. Here, deviate from the reference surface looking at the maximum posterior physicians with a particular interest in will be a sign of irregularity or asym- elevation, BFTA yielded a sensitiv- keratoconus detection share the new metry. This method is important be- ity of 82 percent and a specifi city of methods they’ve developed to identify cause when you’re tracking the initial 80 percent, compared to 51 percent potentially troublesome eyes. signs of asymmetry, if you don’t want and 55 percent, respectively, for the to have the initial bulging hidden by BFS. This sensitivity of 82 percent BFTA vs. BFS the effect of another fi tting method— with the BFTA was then improved to such as with the spherical reference nearly 90 percent when looking at the Bordeaux, France, ophthalmolo- surface, the BFS—it’s important to be AAI [Asphericity Asymmetry Index], gist David Smadja and his research as close as possible to the cornea be- which quantifies the asymmetry of co-workers say that when they fo- ing measured. elevation at the back surface by using cused on the asymmetry of the cor- “Comparing it to the BFS, it’s not the absolute value of the max positive nea’s posterior surface, they were able a matter of one being better or one and max negative elevation within the to achieve excellent sensitivity when being bad,” Dr. Smadja continues. 6-mm central zone. The AAI has a screening patients for keratoconus. “Some people are used to seeing and cutoff value of 21.5.” Dr. Smadja, who used the Ziemer interpreting BFS analyses and some- Though the relative importance of Galilei dual Scheimpfl ug system, says times it’s a matter of subjective inter- the anterior vs. posterior cornea for the key is studying a parameter known pretation of elevation patterns. So if screening out forme fruste keratoco- as the Best-fi t Toric and Aspheric sur- you’re used to using the BFS, it can nus patients has been debated for a face, or BFTA, which seems to be a help screen out suspect corneas— while, Dr. Smadja thinks the evidence better option than the Best-fi t Sphere, but more often with the BFS, the el- is shifting toward the posterior. “It’s or BFS. “The BFTA has a better abil- evation maps can hide crucial early not a matter of the disease starting on ity for screening out the asymmetry of signs of asymmetry in the cornea. In the back or the front of the cornea,”

58 | Review of Ophthalmology | February 2014 This article has no commercial sponsorship.

058_rp0214_rs.indd 58 1/24/14 2:43 PM he says. “Instead, it’s more that some- and it thins over the area of the cone times the epithelial layer can smooth and thickens over the area adjacent out the front surface. This smoothing to the cone in order to ‘mask’ these can hide the ﬁ rst sign of asymmetry in curvature differences and potentially the underlying stroma, and it’s been improve the visual function of the

shown many times that the epithelial MD John Kanellopoulos, cornea,” he says. “So the first thing layer is thinner above a bulging of the that we look at in these spectral do- cornea, whereas it’s thicker above a main anterior segment OCT images is: depression of the underlying stroma. Where is the thinnest location placed So, you can’t see the stromal irregular- by the device in regard to the cornea ity because what you’re imaging from center? When the thinnest part of the the front is the epithelial layer and the cornea is away from the cornea center, epithelium has a large impact on the our index of suspicion for keratoconus topographic image. So, looking at the Researchers have found that patients with increases, as this indicates an eccen- back surface rather than the front is keratoconus appear to have an overall tric thinner part of the cornea, which more sensitive for screening out the increase in epithelial thickness. invariably is due to keratoconus or fi rst signs of bulging.” ectasia. For surgeons who want to use some controls. The mean overall epithelial “Now, what we have reported in the of Dr. Smadja’s fi ndings in their prac- thickness was 55.65 ±1.22 µm in the past with high-frequency ultrasound,” tices, he has some advice. “It’s tough to keratoconus patients and 51.97 ±0.7 Dr. Kanellopoulos adds, “and we con- give a number that would be a red fl ag µm in the controls. The variability in fi rmed with our studies with a spectral with all the various devices, because topographic mapping was ±9.8 ±0.41 domain anterior segment OCT, is that we haven’t tested this approach with µm in keratoconus eyes and ±1.53 is there a very large difference in dif- all of them,” he says. “However, what ±0.21 µm in normals. All the differ- ferent areas and in different aspects should alert the surgeon when inter- ences were statistically significant of the cornea as far as the thickness— preting posterior elevation maps with (p<0.002). The researchers say that so increased variability of the cornea either the Aconic surface (Orbscan) these patients seemed to have an over- epithelial thickness can be related to or the Best-fi t Toric Ellipsoid (BFTE) all epithelial thickness increase. keratoconus. In addition, we’ve found in the Pentacam, which work in a way Athens surgeon John Kanellopoulos that, overall, the epithelial thickness is similar to the BFTA in the Galilei, was a researcher on the study and says increased in keratoconic or pre-kera- is any kind of asymmetric posterior it yielded some insights on irregular toconic eyes, as well. So just looking elevation. Concerning the Galilei Ana- corneas. “We all know that in kerato- at the average corneal epithelial thick- lyzer specifi cally, the AAI was found conus the cornea epithelium remodels ness can be a very helpful tool in pick- to be the most sensitive for screening ing up early keratoconus, because ad- the suspicious cornea. Any AAI value vanced keratoconus is obviously much above 21.5 should make you consider easier to diagnose from the extreme doing PRK rather than LASIK.” irregularities of the epithelial distribution in the cornea.”

Epithelial Analysis MD Smadja, David Whichever method a surgeon uses, Dr. Smadja notes that more informa- Focusing on a different parameter tion is always better. “It’s important to of the cornea, researchers in Greece remember that in our work, we’re still have found that using anterior seg- just talking about one parameter,” he ment optical coherence tomogra- says. “The sensitivity achieved by one phy to image the epithelium showed parameter is never good enough to marked differences between kerato- base your conclusion on. I think that conic and normal eyes. it’s best to consider different param- In a study presented at the 2013 A cornea can prove to be dangerously eters when considering a change to meeting of the American Academy of asymmetric when its posterior aspect the patient’s surgical options.” Ophthalmology, George Chatzilaou, is viewed using the Best-ﬁ t Toric and 1. Smadja D, Santhiago MR, Mello GR, et al. Inﬂ uence of the reference surface shape for discriminating between normal MD, presented results from 55 un- Aspheric surface parameter. This cornea corneas, subclinical keratoconus, and keratoconus. J Refract Surg treated keratoconus patients and 55 has a max posterior elevation of 13 µm. 2013;29:4:274-281.

February 2014 | Revophth.com | 59

058_rp0214_rs.indd 59 1/24/14 2:43 PM Research Review REVIEW

Adverse Effects of BAK On Surgical Outcomes

study from University of Toronto coma as signifi cant confounders of the sion (n=1,068) and miscellaneous di- A researchers extends earlier fi nd- univariate model (p=0.024), although agnosis (n=616). Group B (n=3,063) ings of potential adverse effects of the main effect of BAK exposure was underwent intravitreal injection in ophthalmic preservatives on surgi- maintained, with a hazard ratio of 1.21 the operating room. There were 683 cal outcomes, showing that increased (p=0.032). The number of different ranibizumab injections, 2,364 beva- preoperative exposure to ophthalmic medications used to control intraocu- cizumab injections and 16 triamcino- solutions preserved with benzalko- lar pressure did not signifi cantly af- lone injections. Diagnoses included nium chloride is a risk for earlier tra- fect survival time in a secondary Cox neovascular AMD (n=1,936), DME beculectomy failure, independent of model (p=0.948). (n=771), RVO (n=189) and miscella- the number of medications used. J Glaucoma 2013;22:730-735. neous (n=267). There were fi ve cases A retrospective chart review se- Boimer C, Birt C. (0.043 percent) of clinically suspected lected 128 patients who had under- endophthalmitis in the 11,710 injec- gone a trabeculectomy between 2004 Endophthalmitis Associated tions. Three cases (0.035 percent) and 2006. The number and type of With Intravitreal Injections occurred in Group A and two cases ophthalmic drops used preoperatively retrospective review of patients (0.065 percent) occurred in group B. and relevant demographics were re- A who underwent intravitreal injec- Retina 2014;34:18-23. corded. Surgical failure criteria in- tions in two different settings, offi ce- Tabandeb H, Boscia F, Sborgia A, Cirací L, et al. cluded inadequate pressure lowering based and operating room, between or need for postoperative ocular an- January 2009 and December 2011 Differences in Iris Thickness tihypertensives, laser trabeculoplasty, indicates that the rate of clinically sus- Among Ethnic Groups 5-fluorouracil needling or repeated pected endophthalmitis after intra- alifornia researchers evaluat- surgery. Patients were examined for vitreal injection is low whether the Cing the capability of iris thickness these criteria over a minimum postop- procedure is performed in the offi ce parameters to explain the difference erative period of two years. Data were or operating room setting. in primary angle-closure glaucoma assessed using Kaplan-Meier and Cox A total of 11,710 intravitreal injec- among different ethnic groups sug- regression models. tions were performed by two physi- gest that groups with historically Complete surgical success was cians during the study period. Group higher prevalence of PACG (Chinese achieved in 47.7 percent of the pa- A (n=8,647) underwent intravitreal Americans) possess thicker irides than tients. Patients received between injection in the examination room in other measured groups. one and eight BAK-containing drops an offi ce-based setting. The intravit- In this prospective study, 259 pa- daily, with a median of three. Time real injections performed included tients with open angles and 177 pa- to surgical failure in patients receiv- ranibizumab (n=2,041), bevacizumab tients with narrow angles from five ing higher preoperative daily doses of (n=6,169) and triamcinolone aceton- different ethnicities (African Ameri- BAK was shorter than in patients who ide (437). Diagnoses included neo- can, Caucasian American, Hispanic had less BAK exposure (p=0.008). vascular age-related macular degen- American, Chinese American and Proportional hazard modeling iden- eration (n=5,376), diabetic macular Filipino American) that met the in- tified uveitic and neovascular glau- edema (n=1,587), retinal vein occlu- clusion criteria were consecutively re-

60 | Review of Ophthalmology | February 2014 This article has no commercial sponsorship.

060_rp0214_rr/F4jump.indd 60 1/24/14 10:47 AM cruited from the University of California, San Francisco, (continued from p. 40) general ophthalmology and glaucoma clinics to receive anterior segment optical coherence tomography imag- theoretically, and we are in the process of getting more ing under standardized dark conditions. Images from 11 data to show that.” patients were removed due to poor visibility of the scleral spurs, and the remaining images were analyzed using the Zhongshan Angle Assessment Program to assess the following measurements for the nasal and temporal angle of “Because we are going through the anterior chamber: iris thickness at 750 and 2,000 µm the [FDA] approval process, we from the scleral spurs and the maximum iris thickness at the middle one-third of the iris. will ultimately have data that will In comparing iris parameters among the open-angle show whether there is a difference ethnic groups, significant differences were found for nasal iris thickness at 750 and 2,000 µm from the scleral between regular LASIK and spurs in which Chinese Americans displayed the highest LASIK Xtra.” mean value (p=0.01; p<0.0001). Among the narrow- angle ethnic groups, signifi cant difference was found for —John Kanellopoulos, MD nasal iris thickness at 2,000 µm from the scleral spurs, in which Chinese Americans showed the highest mean value (p<0.0001). A signifi cant difference was also found for temporal maximum iris thickness at the middle one- According to Dr. Kanellopoulos, another downside is third of the iris, with African Americans exhibiting the the possibility of infection, which can result from contami- highest mean value (p=0.021). Iris thickness was modeled nated ribofl avin solution or over cross-linking. “This is the as a function of angle status using linear mixed-effects re- reason we use single-use containers for ribofl avin and use gression, adjusting for age, sex, pupil diameter, spherical a strictly sterile environment in a similar fashion as we do equivalent, ethnicity and the use of both eyes in patients. with a routine LASIK procedure,” he says. “High-fl uence The iris thickness difference between the narrow-angle cross-linking is used to avoid extensive time under the and open-angle groups was signifi cant (p=0.0007). UV source and a possibility for inadvertent contamination J Glaucoma 2013;22:673-678. from the operating room or the health-care staff.” Lee R, Huang G, Porco T, Chen Y, et al. Dr. Kanellopoulos notes that there is no significant learning curve when combining the two procedures. “The Femtosecond Laser-Assisted Cataract Surgery basic principle is to soak the underlying stroma after the Has a Learning Curve, But is Safe and Effi cient end of the ablation with ribofl avin, and we have chosen esearchers from the department of ophthalmology the one that is diluted in saline,” he says. “It is important to Rat Semmelweis University analyzed the intraoperative avoid having the ribofl avin come into contact with the fl ap. complications of the fi rst 100 femtosecond laser-assisted This is why, when I pull the fl ap off the cornea following cataract surgeries, as well as possible complications of the femtosecond laser fl ap creation, I try to fold it onto it- femtosecond capsulotomies. The researchers determined self, thus reducing its dehydration and secondarily protect- that while there is a learning curve, with cautious surgical ing it from any ribofl avin spilled over from its instillation technique these complications can be avoided, and the at the end of the ablation. The soaking takes 60 seconds, femtosecond laser-assisted method is safe and effi cient for and following that, the fl ap is repositioned in place, and cataract surgery. the interface is rinsed copiously in order to remove any re- A retrospective analysis discovered the following com- sidual ribofl avin and to minimize the amount of ribofl avin plications: suction break (2 percent); conjunctival redness that jumps into the fl ap. After repositioning the fl ap, I use or hemorrhage (34 percent); capsule tags and bridges (20 a Johnston applanator to iron out the central part of the percent); anterior tear (4 percent); miosis (32 percent); cornea. I use BSS to lubricate the surface. At the end of and endothelial damage due to a cut within the endothelial the case, I place a bandage contact lens, which I remove layer (3 percent). There were no cases of capsule blockage the next morning.” or posterior capsule tear. During the learning curve, there 1. Kanellopoulos AJ, Asimellis G. Comparative epithelial topography and thickness changes following were no complications that would require vitrectomy. femtosecond-assisted high myopic LASIK with versus without prophylactic higher-fl uence collagen cross-linking. Cornea 2014 (accepted for publication). J Cataract Refract Surg 2014;40:20-28. 2. Kanellopoulos AJ, Kahn J. Topography-guided hyperopic LASIK with and without high irradiance Nagy Z, Takacs A, Filkorn T, Kránitz K, et al. collagen cross-linking: Initial comparative clinical fi ndings in a contralateral eye study of 34 consecutive patients. J Refract Surg 2012;28(11 Suppl):S837-S840.

February 2014 | Revophth.com | 61

060_rp0214_rr/F4jump.indd 61 1/24/14 10:48 AM Product News REVIEW

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66 | Review of Ophthalmology | February 2014

ROPH0214.indd 66 1/13/14 8:03 PM 067_rp0214_wills.indd 67 was fullintherighteyeandlimitedbypoorvisualacuitylefteye.Externalexaminationsignifi cant onlyfor mmHg. Extraocularmovementswerefullinbotheyes, andtherewasnopainwith movement.Confrontationfi eld testing was slightlyirregularandnonreactivewithanafferentpupillarydefect.Goldmannapplanationtonometry10 11 Examination his immunizationswereuptodate. Medical History disease contacts.Thepatienthadvague,non-specific leftlegpainwithoutalimp.Reviewofsystemswasotherwisenegative. normal. Thepatientandfamilydeniedanyoculartrauma,recenttravelor prior toreferralwere and orbitsdoneinthedays tophobia, rednessanddecreasedvisioninhislefteyeforthreedays.Hehadonlymildpain.Two CTscansofthebrain Presentation Michael N. Cohen, MD, SoniaMehta, MD, EuniceM.Kohara, DO, ChristinaM.Ohnsman, MD, Alex V. Levin, MD, ER. consequences forayoungboyreferredtotheWills Failure toadhereaprescribeddrugtreamenthasdire debris, thinvitreous membranes andthickening ofthechoroid. Figure 1.B-scanultrasound ofthelefteye. Notetheintensecellular What isyourdifferentialdiagnosis? Whatfurtherworkupwouldyoupursue?Please turntop. 68

Ocular examination revealed a visual acuity of 20/20 in the right eye and light perception in the left eye. The left pupil Ocular examinationrevealedavisualacuityof20/20in the righteyeandlightperception inthe left eye.Thepupil Past medical,surgical,ocular, familyandsocialhistorywereallnon-contributory. Hewasonnosystemicmedications,and An 11-year-old boypresentedtotheWills EyeHospitalEmergencyRoom,referredfromanoutsidehospital,withpho- REVIEW Wills Eye Wills Eye Resident CaseSeries Edited by David Perlmutter,Edited byDavid MD vitreous membranes. debris inthevitreous,thickeningofchoroidandthin Scan ultrasound(SeeFigure1) view ofthelefteyeduetowhiteretrolentalmaterial.B- examination oftherighteyewasnormal.Thereno Thelenswasclear. thepupil. overlying fundus Dilated chamber cellandadiscofﬁbrin intheanteriorchamber mosis, minimalcornealstromalhaze,moderateanterior eye hadmoderateconjunctivalinjectionwithoutche- examination oftherighteyewasunremarkable.Theleft mild lidedemaanderythemaofthelefteye.Slit-lamp February 2014 showedintensecellular | Revophth.com MHSc |

67 1/24/14 11:46 AM Resident Case Series REVIEW

Diagnosis, Workup and Treatment

Differential diagnosis included remarkable and included CBC; blood blood (See Figure 2). Diagnostic pars inflammatory, infectious, neoplas- cultures; HLA B27; ACE; lysozyme; plana vitrectomy was planned as an tic and traumatic causes. Brain and Toxoplasma antibodies; Toxocara an- outpatient. After three days of intra- orbit MRI demonstrated left-sided tibodies; HSV antibodies; VZV anti- venous steroids, he was discharged reticulation of retrobulbar fat with bodies; RPR, RF; FTA-Abs; cANCA; home on 60 mg of oral prednisone enhancement of the pre-septal tis- pANCA; chest radiograph; and uri- daily. He also continued on topical sues, sclera and choroid. There was nalysis. prednisolone acetate 1% every hour also mild enlargement with enhance- He was admitted with a working while awake, loteprednol ointment at ment of the left lacrimal gland. The diagnosis of panuveitis and started bedtime, and atropine 1% twice daily. brain was normal. The patient had an on topical prednisolone acetate 1% Two days later, he presented for elevated erythrocyte sedimentation every hour and atropine 1% twice follow-up with fevers, eye pain and rate (70) and C-reactive protein (3.3). daily. Skin testing for tuberculosis malaise. We discovered that the pa- Additional laboratory testing was un- was negative at 48 hours, and he was tient was incorrectly taking only 20 started on a 1 mg/kg mg of prednisone daily. His ante- intravenous steroid rior segment exam had regressed to pulse. He quickly felt its initial appearance with new early better with vision im- neovascularization of the iris, and provement to hand his intraocular pressure was now 46 motion. There was mmHg. The patient underwent pars dramatic conden- plana vitrectomy, which revealed sation of the fibrin purulent vitreous aspirate. He was disc in his anterior given intravitreal vancomycin and chamber. Intraocular ceftazidime and admitted for intra- pressure decreased venous antibiotics. Vitreous cultures to 6 mmHg. B-scan revealed heavy growth of methicil- ultrasound showed lin-sensitive Staphylococcus aureus. Figure 2 . Follow-up B-scan ultrasound of the left eye. Note the dense vitreous debris Blood cultures, echocardiogram, increased amount of vitreous debris from the earlier with suprachoroidal dental examination and bone scan ultrasound, as well as the presence of suprachoroidal blood or collections of ﬂ uid or were normal. The infectious disease ﬂ uid (arrows). Ralph Eagle Jr., MD

Figure 3. MRI with contrast, T1-weighted image, coronal slice. Figure 4. Gross specimen of the globe with abscess Note the two areas of globe rupture near the equator (arrows), as encompassing vitreous cavity, along with associated retinal well as contiguous inﬂ ammation consistent with orbital abscess. detachment and choroidal hemorrhage and detachment.

68 | Review of Ophthalmology | February 2014

067_rp0214_wills.indd 68 1/24/14 11:46 AM service was consulted and no system- extraocular movements. MRI dem- Two weeks after enucleation, the ic source for infection was identifi ed. onstrated two areas of globe rup- patient and his mother disclosed that The patient’s condition continued to ture near the equator associated with the step-father had been physical- worsen. Four days after vitrectomy, contiguous orbital abscess. (See Fig- ly abusive to the patient. Although the vision in the patient’s left eye was ure 3) Enucleation was performed. there had been several instances of no light perception. He developed Gross and microscopic examination head trauma, they remained confi - warmth and erythema of the eyelids confi rmed endophthalmitis second- dent that there was never any trauma and started to complain of pain with ary to Staphylococcus (See Figure 4). involving the eyes.

Discussion Infectious endophthalmitis is a rare The majority of cases were due to ex- matory condition. We still lack a clear and potentially devastating condition ogenous causes: either posttraumatic source for his infection but suspect an resulting from either the exogenous or postsurgical.9 Of the two cases with episode of abusive eye trauma. One or endogenous spread of bacteria into endogenous endophthalmitis, the chil- must always suspect physical abuse in the eye.1 Most commonly, this form dren were systemically unwell. One a child when the extent of the injury is of panuveitis presents with reduced patient was an infant with Candida not consistent with the child’s develop- vision, progressive vitritis and hypo- sepsis, and another was immunocom- mental age, or the fi ndings on physical pyon, as well as substantial red eye, promised secondary to leukemia. In exam do not correlate to the history.11 pain and lid swelling.2 Our patient had children, the most commonly associ- Infectious endophthalmitis should a remarkable absence of all of these ated infectious sources for endogenous be considered in the differential diag- signs except for the vitritis and reduced endophthalmitis include wound infec- nosis of pediatric patients presenting vision. Exogenous endophthalmitis is tion, meningitis, endocarditis, urinary with panuveitis, even in the absence more commonly encountered and tract infection, indwelling intravenous of reported trauma or other risk fac- can occur following surgery, trauma, catheters or hemodialysis fi stulas.4 To tors. This may be particularly impor- corneal ulcer or periocular infection our knowledge there has only been tant when evaluation has not otherwise that invades an adjacent ocular wall.3 one reported case of S. aureus in a determined the etiology of the uveitis. Endogenous endophthalmitis oc- child. This was a case of a very low Early diagnostic vitrectomy should be curs through hematogenous spread birth weight neonate with sepsis.10 considered. of micro-organisms that cross the A diagnosis of endophthalmitis is not 1. Kernt M, Kampik A. Endophthalmitis: Pathogenesis, clinical blood-retinal barrier. Risk factors for often suspected in otherwise healthy presentation, management, and perspectives. Clinical Ophthalmol- endogenous endophthalmitis include pediatric patients with no prior eye ogy 2010;4:121-135. 2. Yanoff M, Duker J. Ophthalmology. China: Mosby, 2009. Print. the presence of systemic or local infec- surgery or trauma. Combined with 3. Jackson TL, Eykyn SJ, Graham EM, Stanford M. Endogenous tions, relative states of immunosup- poor communication in pediatric pa- Bacterial Endophthalmitis: A 17-year prospective series and review of 267 reported cases. Surv Ophthalmol 2003;48(4):403- pression or procedures that increase tients or denial of trauma for fear of re- 423. the risk of blood-borne infections. percussion, delay in diagnosis can oc- 4. Chaudhry IA, Shamsi FA, AL-Dhibi H, Khan, AO. Pediatric Endogenous Bacterial Endophthalmitis: Case report and review of Children account for only 0.1 per- cur, resulting in poor visual outcomes. the literature. J AAPOS 2006;10:491-493. cent of all cases of endogenous en- In our patient, initial suspicion for 5. Alfaro DV, Roth DB, Laughlin RM, et al. Paediatric posttraumatic 4 endophthalmitis. Br J Ophthalmol 1995;79:888-891. dophthalmitis in the United States. infectious endophthalmitis was low, 6. Good WV, Hing S, Irvine AR, et al. Postoperative endophthalmitis Reports of pediatric endophthalmitis given the lack of history of trauma, in children following cataract surgery. J Pediatr Ophthalmol Strabismus 1990;27:283-285. are rare in the literature and are either hypopyon, lid swelling or significant 7. Recchia FM, Baumal CR, Sivalingam A, et al. Endophthal- stratifi ed by specifi c etiology5-8 or sin- ocular pain. The patient was other- mitis after pediatric strabismus surgery. Arch Ophthalmol 2000;118:939-944. gle case reports. In a recent retrospec- wise healthy with no other risk factors 8. Waheed US, Ritterband DC, Greenfi eld DS, et al. Bleb-related tive review, over a 10-year period at a for endophthalmitis. Additionally, our ocular infection in children after trabeculectomy with mitomycin C. Ophthalmology 1997;104:2117-2120. tertiary referral center, only 16 cases of patient’s initial excellent response to 9. Thordsen, JR, Harris L, Hubbard GB. Pediatric Endophthalmitis: A pediatric endophthalmitis were identi- both topical and intravenous steroids 10-year consecutive series. Retina 2008;28:S3-S7. 9 10. Basu S, Kumar A, Kapoor K, Bagri NK, Chandra A. Neonatal fied. No child was infected with S. and then subsequent regression on an endogenous endophthalmitis: a report of six cases. Pediatrics aureus and all were obviously symp- incorrectly low dose of oral steroids 2013 Apr;131(4):e1292-7. 11. Waterhous W, Enzenauer RW, Parmley VC. Infl ammatory Orbital tomatic and had clearly identifiable contributed to our thought process Tumor as an Ocular Sign of a Battered Child. Am J Ophthalmol primary sources for their infection. that he had a noninfectious, inflam- 1992;114:510-512.

February 2014 | Revophth.com | 69

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