Expert Views on Medical and Surgical Approaches

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Glaucoma ManagementThe Art and Science of

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Learning Method and MediumThis educational activity consists of a supplement and ten (10) studyquestions. The participant should, in order, read the learning objectivescontained at the beginning of this supplement, read the supplement,answer all questions in the post test, and complete the ActivityEvaluation/Credit Request form. To receive credit for this activity, please follow the instructions provided on the post test and ActivityEvaluation/Credit Request form. This educational activity should take amaximum of 1.5 hours to complete.

Content SourceThis continuing medical education (CME) activity captures content from asymposium held on October 19, 2014, in Chicago, Illinois.

Activity DescriptionGlaucoma continues to be a leading cause of irreversible vision lossworldwide. Recent advances in ophthalmology, including new diagnostictools, novel therapies, and outcomes from clinical trials, allow for theevolution of practice patterns in managing glaucoma. Data from recentstudies have shown the importance of considering 24-hour intraocularpressure in selecting antiglaucoma therapy. Further considerations forantiglaucoma therapy include management of ocular surface health,comorbidities, and options for surgical intervention.

The purpose of this activity is to update ophthalmologists on the optimalclinical evaluation and management of their patients with glaucoma.

Target AudienceThis activity is intended for comprehensive ophthalmologists.

Learning ObjectivesUpon completion of this activity, participants will be better able to:• Assess diurnal IOP and select appropriate ocular antihypertensive

therapy to meet IOP goals throughout the day• Incorporate IOP treatment strategies that consider optimization of ocular

surface health • Select appropriate multitherapy or fixed-combination therapy toindividualize treatment regimens in patients with and without comorbidities

• Incorporate appropriate use of surgical/device options into the effectivemanagement of IOP

Accreditation StatementThis activity has been planned and implemented in accordance with theaccreditation requirements and policies of the Accreditation Council forContinuing Medical Education (ACCME) through the joint providership ofNew York Eye and Ear Infirmary of Mount Sinai and MedEdicus LLC. The New York Eye and Ear Infirmary of Mount Sinai is accredited by theACCME to provide continuing medical education for physicians.

In July 2013, the Accreditation Council for Continuing MedicalEducation (ACCME) awarded New York Eye and Ear Infirmary ofMount Sinai “Accreditation with Commendation,” for six years asa provider of continuing medical education for physicians, thehighest accreditation status awarded by the ACCME.

AMA Credit Designation StatementThe New York Eye and Ear Infirmary of Mount Sinai designates thisenduring material for a maximum of 1.5 AMA PRA Category 1 Credits™.Physicians should claim only the credit commensurate with the extent oftheir participation in the activity.

Grantor StatementThis continuing medical education activity is supported through anunrestricted educational grant from Alcon, Inc.

Disclosure Policy StatementIt is the policy of New York Eye and Ear Infirmary of Mount Sinai that thefaculty and anyone in a position to control activity content disclose anyreal or apparent conflicts of interest relating to the topics of thiseducational activity, and also disclose discussions of unlabeled/unapproved uses of drugs or devices during their presentation(s). New York Eye and Ear Infirmary of Mount Sinai has established policies in place that will identify and resolve all conflicts of interest prior to thiseducational activity. Full disclosure of faculty/planners and theircommercial relationships, if any, follows.

DisclosuresDonald L. Budenz, MD, MPH, had a financial agreement or affiliationduring the past year with the following commercial interests in the form ofConsultant/Advisory Board: Alcon, Inc; Envisia Therapeutics; and SantenPharmaceutical Co, Ltd; Contracted Research: Ivantis Inc.

Shan Lin, MD, has no relevant commercial relationships to disclose.

Marlene R. Moster, MD, had a financial agreement or affiliation during the past year with the following commercial interests in the form ofConsultant/Advisory Board: Alcon, Inc.

Kuldev Singh, MD, MPH, had a financial agreement or affiliation duringthe past year with the following commercial interests in the form ofConsultant/Advisory Board: Alcon, Inc; Allergan, Inc; Bausch + LombIncorporated; Ivantis Inc; Transcend Medical, Inc; and Zeiss.

Peer Review DisclosureJoseph Panarelli, MD, has no relevant commercial relationships to disclose.

Editorial Support DisclosuresCynthia Tornallyay, RD, MBA, CCMEP; Kimberly Corbin, CCMEP; Barbara Aubel; Lisa van Devender, PharmD; Diane McArdle, PhD; andLaura Herold have no relevant commercial relationships to disclose.

Disclosure AttestationThe contributing physicians and instructors listed above have attested tothe following:1) that the relationships/affiliations noted will not bias or otherwise

influence their involvement in this activity;2) that practice recommendations given relevant to the companies with

whom they have relationships/affiliations will be supported by the bestavailable evidence or, absent evidence, will be consistent with generallyaccepted medical practice; and

3) that all reasonable clinical alternatives will be discussed when makingpractice recommendations.

Off-Label DiscussionThis activity includes off-label discussion of dosing for ocularantihypertensives. Participants should consult the official prescribinginformation for indications and administration of all products mentioned.

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This CME activity is copyrighted to MedEdicus LLC ©2015. All rights reserved.

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IntroductionGlaucoma continues to be a leading cause of irreversiblevision loss worldwide. Recent advances in ophthalmology,including new diagnostic tools, novel therapies, andoutcomes from clinical trials, allow for the evolution ofpractice patterns in managing glaucoma. Effectivelymanaging glaucoma requires an individualized approachthat may necessitate the use of multiple therapies toreduce the risk for glaucoma onset or its progression. This educational program features an expert panel ofglaucoma specialists who present patient cases similar tothe ones they have seen in their practices, discuss theirapproach to managing these cases, and review thescience that guides their decisions. Through this process,it is hoped that readers will gain further insight into theoptimal clinical evaluation and management of theirpatients with glaucoma.

Myopia and Normal-Tension GlaucomaDr. Budenz: Our first case involves a 41-year-old Asian male cardiologist who was followed on the comprehensiveophthalmology service as a glaucoma suspect because ofsuspicious-looking optic nerves. His past medical historyincludes hypertension, for which he was taking anangiotensin-converting-enzyme inhibitor (losartanpotassium). He has no family history of glaucoma; however,his father had diabetic retinopathy, and his mother hadcataracts. His visual acuity is 20/20 in both eyes. Thepatient is a –3D myope with a central corneal thickness of575 microns in each eye. His intraocular pressure (IOP)measurements are consistently 14 to 20 mm Hg, and hehas normal slit-lamp examination results with no signs ofpigment dispersion and an open anterior chamber angle.

In 2009, the patient’s initial visual fields were completelynormal and reliable. At that time, optical coherencetomography (OCT) on the right side was normal; on theleft side, there was the possibility of a nerve fiber layerdefect in 1 quadrant. We know that myopes can havenerve fiber layer defects that simulate glaucoma, so wechose to follow this patient. In 2009 and 2011, his visualfield index readings were 99% and 100%, respectively(Figure 1). In 2012, he developed some suspicious butnondiagnostic changes, and on repeat testing there was amore classic superior nerve fiber layer defect. A follow-upexamination in October 2014 showed a field thatconfirmed the glaucomatous changes seen on the prior 2fields, with the visual field index decreasing from 100% to90%, and the mean deviation changing fromapproximately normal to –3 to –4 dB.

CASE 1

Donald L. Budenz, MD, MPHKittner Family Distinguished Professor and ChairmanDepartment of OphthalmologyUniversity of North Carolina School of MedicineChapel Hill, North Carolina

Program Chairman and Moderator

FacultyShan Lin, MDProfessor of Clinical Ophthalmology Director, Glaucoma ServiceDirector, Glaucoma Fellowship Program University of California, San FranciscoSan Francisco, California

Marlene R. Moster, MDProfessor of OphthalmologyThomas Jefferson University School of MedicineGlaucoma ServiceWills Eye InstitutePhiladelphia, Pennsylvania

Kuldev Singh, MD, MPHProfessor of OphthalmologyDirector, Glaucoma ServiceStanford University School of MedicinePalo Alto, California

CME Reviewer for New York Eye and Ear Infirmary of Mount SinaiJoseph Panarelli, MDAssistant Professor of OphthalmologyIcahn School of Medicine at Mount SinaiAssociate Residency Program DirectorNew York Eye and Ear Infirmary of Mount SinaiNew York, New York

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We saw a more convincing change on the OCT, with thoseareas that were in the green shown as red in the same areawhere there was a new nerve fiber layer defect. Accordingto the new macular scans, which were not available in2009, this patient had a large area of thinning of theganglion cell complex in the left eye (Figure 2).

In summary, the patient described above is a 41-year-oldAsian male with myopia who had normal IOPs with central corneal thicknesses that are slightly thick, newlyconfirmed visual field defects in the left eye, and verysuspicious optic discs. What would be your diagnosis forthis patient?

Dr. Lin: I believe that this patienthas normal-tension glaucoma(NTG) with myopia as asignificant risk factor. It can bemisleading to think that the discappearance is due simply tomyopia and that all the testresults are due to myopicchanges to the disc. There canbe rare cases in which myopicchanges to the disc and retinacould slowly worsen over time,but I think this case behoovesyou to treat it as NTG. You haveshown through the visual fieldsand structural tests thatglaucoma progression is likely.

Dr. Singh: I think you shouldtreat the patient with IOP-lowering therapy. Whichdiagnosis you choose is probablyless important than the decisionto treat. If a patient hasprogressive damage that you canmeasure in the clinic over a shortperiod of time, then it makessense to call it glaucoma. It isalways good to keep in mind that even if patients withoutglaucoma have a visual fielddefect, that field defect is goingto get worse with time, because aperson loses 5000 to 10,000retinal ganglion cells a year fromaging. In this case, however, thechange has occurred fast enoughto warrant a glaucoma diagnosis.

Dr. Lin: The initial visual fieldthat is called “normal” istechnically normal according to the algorithm that the SITA (Swedish Interactive

Thresholding Algorithm) standard program uses. However,you can start to see a couple of spots in the superior field.In patients with highly suspicious discs, such as thosewith tilted discs with peripapillary atrophy, it is importantto remember that you cannot just accept machineinterpretation. When you showed the OCT correlation forthe early visual field, I started thinking that this personhad glaucoma early on, because the visual field correlatedwith the OCT even though it was “normal”.

Dr. Budenz: At this point we coded NTG, and startedtreatment. If this was your patient and you came to thesame conclusion, which treatment would you use?

Dr. Moster: I think it is very important to commit toachieving a 30% drop in pressure. I often start with aprostaglandin analogue because it tends to have the best

Figure 2. Optical coherence tomography images from Case 1showing thinning of the retinal nerve fiber layer and ganglioncell/inner plexiform layer in the left eye.

Figure 1. Visual fields showing conversion from normal to glaucomatous visual field defectdescribed in Case 1.

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efficacy and compliance. I think it is also beneficial to putthe maximum pressure reading (Tmax) on the chart so wecan understand what the goal should be moving forward.

Dr. Singh: I would take a slightly different approach andwould not initially commit to a 30% drop, but rather beginwith a prostaglandin, see what kind of IOP lowering isachieved, and then weigh the expected risks and benefitsof the next step. I may hold off on a second agent if 20%IOP lowering is achieved with a prostaglandin, and I wouldfollow the patient for further progression prior tocommitting to additional treatment.

Dr. Budenz: Do you think selective laser trabeculoplasty(SLT) is a valid option at this point?

Dr. Lin: Remember, we classified the patient as NTG. Itdepends on the way you look at it. SLT lowers pressureapproximately 1 to 2 points, so you can look at it as aglass half full or half empty; 1 to 2 points is better thannothing. For NTG, even using medications is not going toget you the 30% drop that we typically expect in standardprimary open-angle glaucoma (POAG). SLT is not going tolower the pressure very much, so you might say it is notworth doing; however, there are also data showing that itseems to flatten out the diurnal curve, which may beimportant in this kind of situation.

Dr. Budenz: Treatment should be directed at IOPreduction over 24 hours and reduction of IOP variability.According to a study of 24-hour IOP patterns, IOP ishighest during sleep (midnight to 6 AM) in most patients(Figure 3).1 In addition to the IOP being higher while in thesupine position, there was a significant decrease in meanblood pressure between the diurnal and nocturnal periodsin the glaucoma group only (99 ± 2 vs 95 ± 3 mm Hg;P<.05), which may cause low ocular perfusion, which maybe related to glaucoma damage.

Antiglaucoma therapies differ in their ability to lower IOP throughout the day and night, and 24-hour IOP isindependent of central corneal thickness, cornealhysteresis, and corneal resistance factors.2 Evidence showsthat beta blockers and alpha agonists do not have ameasurable effect on nocturnal IOP. The proposed

mechanism is that the baseline rate of aqueous flow mightresist any further suppression, although that in itself doesnot explain the beneficial effect of a topical carbonicanhydrase inhibitor (CAI) at night.3 It appears that the CAIsand prostaglandins have the ability to lower IOP more thanbeta blockers over the full 24 hours.4 Brimonidine, analpha agonist, significantly lowered IOP during thediurnal/wake period when taken 3 times a day, but did notsignificantly lower IOP during the nocturnal/sleep period.5

Dr. Budenz: Continuous IOP monitoring shows that IOP ishighest during sleep, even in NTG patients.6 Mean systolicblood pressure is lower during sleep, creating low ocularperfusion pressure and the “perfect storm” for glaucomadamage. The patient’s 24-hour IOP was measured with adevice called the SENSIMED Triggerfish® sensor device(SENSIMED, Lausanne, Switzerland), a 24-hour contactlens sensor that senses eye volume and changes involume, which are assumed to be correlated with IOPchanges. We measured changes in IOP and bloodpressure over 24 hours in this patient and, indeed, his IOP was much higher, and the blood pressure was muchlower, during sleep. Ongoing studies are being conductedto determine whether reduced ocular perfusion pressureis a risk factor for glaucoma and glaucoma progression.

There are other explanations for progressive glaucomadamage at normal IOPs. Other conditions that can causesimilar appearances include intermittent angle-closureglaucoma, nonglaucomatous optic neuropathy, retinalvascular occlusion, and degenerative myopia. Cornealthickness data are important for these patients, and if youfind a very thin cornea, the patient may have artificiallylow pressure measurements and IOP elevation outside of office visits. I do a workup for non-NTG causes forglaucoma in patients who have optic disc pallor; visualfield defects that are out of proportion to cupping;suspicious central nervous system–type defects likebitemporal, homonymous, or vertically aligned defects;early loss of central visual acuity; early dyschromatopsia;and afferent pupillary defect without asymmetric cupping.

To summarize, the IOP is generally highest during sleepbecause of supine positioning. Treatment for this patientshould take into account 24-hour IOP, and preliminaryevidence shows that prostaglandins, topical CAIs, SLT, andsurgical intervention appear to lower IOP at night and toreduce IOP fluctuations throughout the 24-hour period.

Primary Open-Angle Glaucoma With AllergicReaction to Prostaglandin TherapyDr. Singh: The next patient is a 68-year-old white femalewith mild, newly diagnosed, bilateral POAG. She has along history of blepharitis with mild seasonal ocularallergy and is using artificial tears 1 to 3 times daily, asneeded. Her visual acuity on presentation was 20/25 inboth eyes, and IOP was 20 to 24 mm Hg in both eyes on2 visits. On examination, she had mild diffuse punctate

CASE 2

Figure 3. A comparison of 24-hour intraocular pressure patterns.1

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corneal staining, consistent with dry eye syndrome, andmild lenticular opacities. Asymmetric optic nerve cupping(right greater than left) was present, and visual fieldsshowed a corresponding superior arcuate defect in theright eye and inferonasal step in the left eye.

There was a long discussion with the patient regardingtherapeutic choices, including IOP-lowering medicationsand SLT. She was started on prostaglandin therapy anddeveloped severe conjunctival infection in both eyes.Which option would you select next for this patient?

Dr. Moster: At this point, I would add artificial tears, stopthe prostaglandin analogue, and speak to the patientregarding switching the class of medication. Lasertrabeculoplasty is an option that could be considered inthis case. Finally, I would offer her a drop holiday andtreat her blepharitis with warm compresses and a mildsteroid ointment on the lids.

Dr. Lin: I agree with Dr Moster. I would probably leanmore toward switching the medication class, but SLT iscertainly a very good consideration for this patient whohas a relatively high pressure.

Dr. Singh: The patient has a fair amount of ocular surfacedisease (OSD) and ocular allergy. Two studies using theOSDI (Ocular Surface Disease Index) have shown a highprevalence of OSD (48%–59%) in glaucoma patients, andthis clinical scenario is thus fairly common.7,8 She optedto try another prostaglandin analogue, which was not welltolerated, and other classes with or without preservativecaused similar signs and symptoms. Ultimately, she gaveup on medication therapy, opted for SLT, and had 2 SLTsin both eyes over 3 years. During that 3-year period, therewas continued disease progression, with IOP ranging from 17 to 19 mm Hg in both eyes and progressive visual fieldloss. The cup-to-disc ratio increased with correspondingthinning of the neuroretinal rim in both eyes. A corneaconsult revealed moderate-to-severe dry eye, blepharitis,and chronic papillary conjunctivitis.

Which option would you consider next—repeat SLT,canaloplasty, trabeculectomy with mitomycin C, or adrainage device implantation?

Dr. Lin: I do not like any of the choices. After 2 uses of SLT,I do not think it is going to work very well a third time.Canaloplasty is a consideration, especially if you arecomfortable doing this procedure. Trabeculectomy andtube implant would probably be more conventionalchoices.

Dr. Budenz: The patient appears to have significantblepharitis, so some physicians would recommend a tubeimplant because of the infectious risk of trabeculectomyin patients with significant blepharitis, which is due toStaphylococcus aureus. I would aggressively treat thechronic blepharitis before and after trabeculectomy if thisprocedure is chosen.

Dr. Singh: After discussing the risks and benefits oftreatment choices, the patient opted for trabeculectomy

with mitomycin C in the right eye first and then the lefteye. There was initial surgical success in both eyes, withIOP in the low teens without medication, but 4 years later,at age 75 years, she required cataract surgery in botheyes. The IOP was 16 to 20 mm Hg in the right eyefollowing cataract surgery, with further diseaseprogression, and the left eye continued to have an IOP inthe 12 to 15 range. As a result of the cataract surgery, shehad a compromised bleb in the right eye, which wasstarting to scar. This patient still could not tolerate anyglaucoma medications. What is the best treatment optionfor the right eye at this time? Would you repeat the SLT,perform a second trabeculectomy with mitomycin C,implant a drainage device, or choosecyclophotocoagulation?

Dr. Budenz: I typically do not do a second trabeculectomyafter one has failed, and I do not think SLT works aftertrabeculectomy. At this point, I would recommend tubeimplant surgery.

Dr. Moster: I would use a cotton swab with proparacaineto see if the conjunctiva was mobile over the scar oftrabeculectomy after the cataract was removed. If so, Iwould needle this patient's bleb aggressively withmitomycin C to see if I could coax the bleb back to lifeand avoid a tube surgery, if possible.

Dr. Singh: Bleb needling was attempted in the right eye,and after some limited success, the bleb scarringcontinued until the IOP was in the low 20s six months later.After discussing the risks and benefits with the patient, sheultimately opted for a tube implant in the right eye.

Having had prior cataract surgery and prior failedtrabeculectomy, this patient would have been a perfectcandidate for the Tube Versus Trabeculectomy (TVT)Study, which was a multicenter, randomized trial thatprospectively compared the safety and efficacy of tubeshunt surgery vs trabeculectomy in 212 patients withprior ocular surgery.9 The mean IOPs at 5 years weresimilar between the tube and trabeculectomy groups, andthe cumulative probability of failure was 29.8% in thetube group and 46.9% in the trabeculectomy group(P=.002). In the early years after the TVT study, thetrabeculectomy group required fewer medications;however, after 3 years there was no difference in the meannumber of medications between the 2 groups. Seriouscomplications were similar between the 2 groups.

In our patient, a glaucoma drainage device was implantedin the right eye. This was performed inferiorly, because of conjunctival scarring superiorly secondary to priortrabeculectomy in an eye with OSD (Figure 4). TheBaerveldt tube implant was placed posterior to theinferior and medial rectus muscles and anchored to theepisclera with two 9-0 nylon sutures. The sutures wererotated and buried to keep them from protruding. Thetube was ligated with an 8-0 Vicryl suture, which released4 to 6 weeks postoperatively. The tube was coveredexternally with donor sclera. The patient achieved an IOPin the low teens in the right eye and continues to do well.

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In summary, some patients cannot tolerate glaucomamedications and therefore laser and/or surgical optionsmay be necessary. Inferior drainage device implantationcan be successful in eyes that have superior scarringrelated to prior surgery exacerbated by OSD. The TVTstudy has shown that, in eyes with prior failedtrabeculectomy, drainage device implantation is morelikely to be successful than a repeat trabeculectomy.9

Normal-Tension Glaucoma With Significant Field Loss Dr. Lin: The next case is a 46-year-old Chinese femaleengineer whose past medical history includes mitral valveprolapse, systemic hypotension, and sleep apnea. She hasa family history of glaucoma. Her systemic medicationsinclude vitamins and calcium. When she presented, shewas on a prostaglandin analogue and an alpha-agonist inboth eyes. On examination, she was 20/20 in both eyes,and refraction was –6.0D for the right eye and –6.25D forthe left eye. Intraocular pressure was 17 mm Hg for theright eye and 16 mm Hg for the left eye. Tmax was 22 mmHg in both eyes, indicating borderline NTG or high-tension

glaucoma. Corneal thickness was 534 μm for the right eyeand 532 μm for the left eye. Gonioscopy showed wide-openangles. This myopic female had visual loss (left eye greaterthan right eye) and progressive visual field loss in both eyes(Figure 5). What would be your next step?

Dr. Moster: I would take a good history, and would want toknow if she does yoga, stands on her head for any lengthof time, plays a wind instrument, has an unusual historyof migraine and Raynaud disease, or has a family historyof blindness. Indeed, I would want to know if there isanything unusual that would make her progress over time.I doubt she has sleep apnea, but you always have toconsider it. I also would want to know about her sleepingposition, whether she sleeps completely flat or possiblylies on either eye. All these questions help me make adecision on the overall picture moving forward.

Dr. Lin: Those are really good questions, and I will fill in theanswers for some of them. She reports having sleep apnea,she has systemic hypotension, and she does not do yoga orplay a wind instrument. She does not have migraines, butshe has cold hands; there has been some associationbetween NTG and cold hands. If you had to progress intreatment, would you add a beta blocker or a CAI?

Dr. Moster: If more treatment was necessary, I wouldchoose a combination of brimonidine and brinzolamide,because the Low-pressure Glaucoma Treatment Study(LoGTS) showed that over a 5-year period, brimonidinestabilized the visual fields more successfully than didtimolol.10 In another study, the CAI brinzolamide wasshown to lower IOP during sleep.11

Dr. Lin: Dr. Budenz, what would you do?

Dr. Budenz: You could try a topical CAI, which I thinkworks better than beta blockers when combined with a prostaglandin; however, this patient is alreadyprogressing, so brimonidine/brinzolamide and SLT arealso good choices. A lot of physicians will avoid topicalbeta blockers in patients with NTG, so maybe just

consider a topical CAI, brimonidine/brinzolamide, or SLT.

Dr. Singh: I would choose a topical CAI asan adjunct to the prostaglandin. SLT tendsto not work as well in younger individuals,particularly when baseline IOP is in theteens. I think the CAIs, which lower IOPduring the day and night, are a goodchoice in such patients.

Dr. Lin: In this specific case, factors toconsider included systemic bloodpressure, 24-hour efficacy, andcompliance. I replaced brimonidine with the brimonidine/brinzolamidecombination, which resulted in an IOP of 14 mm Hg in both eyes. Nonselectivebeta blockers should be avoided in

CASE 3

Figure 5. Visual fields from the patient described in Case 3.

Figure 4. Implantation of glaucoma drainage device (Case 2).

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persons with systemic hypotension. Patients withhypotension resulting from systemic blood pressure-lowering agents seem to be at particularly high risk forprogression of their glaucoma.

The LoGTS, a randomized study that compared brimonidinewith timolol in 178 patients, showed that statistically fewerbrimonidine-treated patients than timolol-treated patientshad visual field progression (9.1% vs 39.2%; P=.001).10 Thedecrease in IOP was not significantly different between thetreatment groups. The number of patient dropouts wassignificant among those treated with brimonidine, largelydue to side effects. One of the controversies of this study iswhether brimonidine is neuroprotective or whether timololis potentially neurotoxic in terms of lowering blood pressureand decreasing ocular perfusion. In the past, systemichypertension was correlated with elevated IOP and risk forglaucoma; however, the new paradigm is that low bloodpressure and low ocular perfusion pressure are associatedwith increased risk for glaucoma. In a study that evaluatedrisk factors for definite OAG, based on African-descentparticipants of the Barbados Eye Studies, 125 patients (of3222) developed definite OAG over 9 years.12 Lower ocularsystolic, diastolic, and mean perfusion pressures weresignificantly associated with glaucoma incidence. Similarly,in the Early Manifest Glaucoma Trial, which evaluatedpredictors of long-term progression of glaucoma in patientsrandomized to laser trabeculoplasty plus betaxolol or noimmediate treatment, lower systolic perfusion pressure wasa significant predictor of glaucoma.13

We should consider having patients take their bloodpressure medication in the morning rather than at night,since the blood pressure decreases during sleep.

Avoiding topical beta blockers may help preventworsening of ocular perfusion pressure.

Dr. Singh: If a patient’s glaucoma is getting worse and heor she is receiving systemic antihypertensive therapy, youshould communicate with the patient’s internist toascertain whether the patient is being overtreated withblood pressure-lowering medications.

Dr. Lin: The clinical pearls from this case include higherclinical suspicion of glaucoma in high myopes andavoidance of nonspecific beta blockers in subjects withNTG, hypotension, or who are currently taking systemicbeta blockers.

Primary Open-Angle Glaucoma and CataractDr. Moster: The final case is a healthy 61-year-old femalemarketing agent whose sister, mother, and grandmotherall have glaucoma. Her mother had glaucoma surgery forprogressive visual field loss at age 80 years. The patientwas complaining of blurriness and was having troubledriving at night. She was 20/60, with posteriorsubcapsular cataract changes of her lens. Her visual fields

over the years had mild loss that came and went. Her IOPwas 20 to 22 mm Hg on a prostaglandin with a betablocker in the morning. In 2010, her OCT was normal, andwe were following her as a glaucoma suspect. As welooked closely, we observed that the structure of the opticnerve was starting to change. In the right optic nerve, a notch was forming inferiorly at the 6:00 position,compared with the left optic nerve, where the rim wasintact. When the visual field was repeated, we saw that there was a new superior arcuate scotoma thatcorresponded to the structural change that we observedon the right optic nerve (Figure 6).

After these changes were noted, the patient had an SLTwith resulting pressures between 18 and 19 mm Hg. She had difficulty with other medication trials in the past.Because the notch was developing inferiorly and it wastime to operate, we had to make a decision regarding thebest options for her. Should we do cataract surgery alone, cataract plus iStent, cataract plus EX-PRESStrabeculectomy, cataract plus Trabectome, or cataract plus mitomycin C trabeculectomy?

Dr. Lin: The question for me would be whether to add anadjunctive procedure such as an iStent. I would definitelydo the cataract surgery, and I would be 50/50 on whetherto add an iStent or another glaucoma surgery to the mix.

Dr. Budenz: I would try cataract surgery and iStent first,because there is a visually significant cataract.

Dr. Moster: I had a discussion with the patient. Sheunderstood all the options and that there was usuallysome bleeding with the iStent and maybe poor vision the

CASE 4

Figure 6. Visual fields from the patient described in Case 4. There is a new superior arcuate scotoma forming.

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next day. We did not really know what thefuture would bring regarding progression of her visual fields and were especiallyconcerned given her strong family history.

The iStent bypasses the trabecularmeshwork by connecting the anteriorchamber to the Schlemm canal to improvephysiologic outflow. It creates a bypassthrough the trabecular meshwork, and itcan work very well in conjunction withcataract surgery to enhance the naturaloutflow system of the eye. I was planningon using a new technique we haddeveloped of placing an iStent. I use a 25-gauge microvitreoretinal (MVR) blade tobisect the trabecular meshwork, and bydoing so, pull down on the bottom lip tocreate a wide space on the back wall. Thisgives me a landing strip with which to put the iStent rightagainst the wall, pushing it forward as far as it will go intothe trabecular meshwork and then releasing the inserter.This works perfectly every time to assure the correctiStent position.14

The largest, randomized, multicenter trial to date,conducted by the US iStent Study Group, measured theincremental effect from iStent implantation plus cataractsurgery vs cataract surgery alone in 240 eyes with OAGcontrolled on 1 to 3 medications.15 The primary end pointwas an IOP ≤21 mm Hg at 1 year. The resultsdemonstrated a significant IOP and medication reductionin the iStent + surgery group compared with the surgery-only group at 2-year follow-up. The surgery-only grouphad a substantially higher level of glaucoma medicationuse and restarted medications sooner postoperativelycompared with the iStent group, without any increase incomplications. In another prospective, randomized,multicenter trial that assessed long-term safety andefficacy of iStent plus cataract surgery vs cataract surgeryalone, Craven and colleagues showed that mean IOP wasstable between 12 and 24 months in the iStent group butincreased in the surgery-only group.16 At 24 months, theproportion of patients with an IOP ≤21 mm Hg wassignificantly higher in the stent group than in the controlgroup (P=.36), and the mean number of medicationsused was lower in the stent group, although notsignificantly so.

In our patient, the postoperative vision in her right eyewas 20/20, and IOP fell to 17 mm Hg after the phaco-iStent, but she was still getting worse. We increased her brimonidine/timolol to twice a day and used aprostaglandin at night. The patient noticed that thescotoma in her right eye was worsening. On examination,her visual field looked progressive, with the notchappearing to be deeper, and the OCT showed more

thinning (Figure 7). With a goal of lowering her IOP into the low teens, can we consider an EX-PRESS shunt?

Dr. Singh: EX-PRESS shunt is an option, as is a standardtrabeculectomy. I have more experience with the latter.

Dr. Lin: I consider a trabeculectomy and EX-PRESS shuntto be very similar, and there is debate over whether youhave fewer complications, such as hypotony and shallowchamber, after an EX-PRESS shunt, but the EX-PRESSshunt would receive my vote.

Dr. Budenz: I would just do a standard trabeculectomywith an antifibrotic agent.

Dr. Moster: The patient opted for an EX-PRESS shunt. At4-month follow-up, her vision was maintained at 20/20;IOP was 11 mm Hg, no medications, and nice bleb; EX-PRESS was in good position, and all her parametershad been stable. The results of a recent prospective,randomized, multicenter trial that compared the EX-PRESS filtration device with a trabeculectomy in 120eyes showed that the mean IOP at 2 years was nearly thesame between the 2 procedures (EX-PRESS 14.7 mm Hg,trabeculectomy 14.6 mm Hg).17 However, there was lessvariance of IOP in the early postoperative period, fastervisual recovery, and fewer total complications for the EX-PRESS group than for the standard trabeculectomygroup (P=.013).

To summarize, we have to follow our patients closely andreally listen to them. If they suspect they are gettingworse, it is our job to figure out how to stop this process.We are obligated to follow the stability of the visual fields,OCT, and optic nerve. If there is a lack of stability, a moreaggressive approach is indicated.

Figure 7. The superior scotoma was deepening, and the notchwas more defined (Case 4).

10

1. Liu JH, Zhang X, Kripke DF, Weinreb RN. Twenty-four-hour intraocular pressure pattern associated with earlyglaucomatous changes. Invest Ophthalmol Vis Sci.2003;44(4):1586-1590.

2. Bagga H, Liu JH, Weinreb RN. Intraocular pressuremeasurements throughout the 24 h. Curr OpinOphthalmol. 2009;20(2):79-83.

3. Brubaker RF. Flow of aqueous humor in humans [The Friedenwald Lecture]. Invest Ophthalmol Vis Sci.1991;32(13):3145-3166.

4. Liu JH, Medeiros FA, Slight JR, Weinreb RN. Comparingdiurnal and nocturnal effects of brinzolamide andtimolol on intraocular pressure in patients receivinglatanoprost monotherapy. Ophthalmology. 2009;116(3):449-454.

5. Liu JH, Medeiros FA, Slight JR, Weinreb RN. Diurnal andnocturnal effects of brimonidine monotherapy onintraocular pressure. Ophthalmology. 2010; 117(11):2075-2079.

6. Knight OJ, Mwanza J-C, Lawrence SD, Viera AJ, Budenz DL. Diurnal patterns and safety of ambulatoryblood pressure and 24-hour intraocular pressuremonitoring in normal and normotensive glaucomapatients. Poster presented at: 2014 Annual Meeting of the Association for Research in Vision andOphthalmology; May 4-8, 2014; Orlando, FL. Poster A0212.

7. Fechtner RD, Godfrey DG, Budenz D, Stewart JA,Stewart WC, Jasek MC. Prevalence of ocular surfacecomplaints in patients with glaucoma using topicalintraocular pressure-lowering medications. Cornea.2010;29(6):618-621.

8. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17(5):350-355.

9. Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL; Tube Versus TrabeculectomyStudy Group. Treatment outcomes in the Tube VersusTrabeculectomy (TVT) Study after five years of follow-up. Am J Ophthalmol. 2012;153(5):789-803.

10. Krupin T, Liebmann JM, Greenfield DS, Ritch R,Gardiner S; Low-pressure Glaucoma Study Group. A randomized trial of brimonidine versus timolol inpreserving visual function: results from the Low-pressure Glaucoma Treatment Study. Am J Ophthalmol.2011;151(4):671-681.

11. Liu JH, Medeiros FA, Slight JR, Weinreb RN.Comparing diurnal and nocturnal effects ofbrinzolamide and timolol on intraocular pressure inpatients receiving latanoprost monotherapy.Ophthalmology. 2009;116(3):449-454.

12. Leske MC, Wu SY, Hennis A, Honkanen R, Nemesure B;BESs Study Group. Risk factors for incident open-angle glaucoma: the Barbados Eye Studies.Ophthalmology. 2008;115(1):85-93.

13. Leske MC, Heijl A, Hyman L, Bengtsson B, Dong L,Yang Z; EMGT Group. Predictors of long-termprogression in the Early Manifest Glaucoma Trial.Ophthalmology. 2007;114(11):1965-1972.

14. Moster M. New technique for iStent insertion.http://www.eyetube.net/video/new-technique-for-istent-insertion/. Accessed December 21, 2014.

15. Samuelson TW, Katz LJ, Wells JM, Duh YJ,Giamporcaro JE; US iStent Study Group. Randomizedevaluation of the trabecular micro-bypass stent withphacoemulsification in patients with glaucoma andcataract. Ophthalmology. 2011;118(3):459-467.

16. Craven ER, Katz LJ, Wells JM, Giamporcaro JE; iStentStudy Group. Cataract surgery with trabecular micro-bypass stent implantation in patients with mild-to-moderate open-angle glaucoma and cataract:two-year follow-up. J Cataract Refract Surg. 2012;38(8):1339-1345.

17. Netland PA, Sarkisian SR, Moster MR, et al.Randomized, prospective, comparative trial of EX-PRESS glaucoma filtration device versustrabeculectomy (XVT study). Am J Ophthalmol.2014;157(2):433-440.

References

11

1. A field defect in a patient who does not have glaucomawill get progressively worse because retinal ganglioncells decrease by:

a. 2000 to 4000 cells a yearb. 5000 to 8000 cells a yearc. 5000 to 10,000 cells a yeard. 10,000 to 20,000 cells a year

2. Each of the following statements is true regarding alarge multicenter study comparing iStent implantationwith cataract surgery alone, except:

a. At 2-year follow-up, there was a significant IOPreduction in the iStent + surgery group

b. The surgery-only group had a substantially lowerlevel of glaucoma medication use

c. The primary end point was an IOP ≤21 mm Hg at1 year

d. The surgery-only group restarted medicationssooner postoperatively

3. Which of the following medications does not have ameasurable effect on nocturnal IOP?

a. Alpha agonistsb. Beta agonistsc. Beta blockersd. a and c

4. Possible explanations for progressive glaucomadamage at normal IOPs include:

a. Intermittent angle-closure glaucomab. Myopiac. Retinal vascular occlusiond. All the above

5. Which of the following agents significantly lowered IOPduring the diurnal/wake period, but not during thenocturnal/sleep period?

a. Brimonidineb. Timolol gelc. Dorzolamided. Brinzolamide

6. During which of the following periods is IOP highest?a. 6 AM to noonb. Midnight to 6 AM

c. Noon to 6 PM

d. 6 PM to midnight

7. Which of the following is not considered a predictor oflong-term glaucoma progression?

a. Lower systolic blood pressureb. Thinner central corneal thicknessc. History of tube implantsd. Lower systolic perfusion pressure

8. In a diagnostic evaluation of a patient suspected ofhaving glaucoma, each of the following questionsshould be explored, except:

a. Do you have a history of migraines?b. Do you practice yoga?c. Do you experience excessive floaters?d. Do you have a history of sleep apnea?

9. Which of the following combinations during sleep isimplicated in glaucoma damage?

a. Low IOP/High blood pressureb. High IOP/Low blood pressurec. High central perfusion pressure/Low blood

pressured. Low central perfusion pressure/Low blood

pressure

10. Each of the following therapies appears to reduce IOPfluctuations throughout the 24-hour period, except:a. beta blockersb. topical CAIsc. laser trabeculoplastyd. prostaglandins

CME Post Test Questions

To obtain AMA PRA Category 1 Credit™ for this activity, complete the CME Post Test online athttp://tinyurl.com/artandscienceglaucoma. Alternatively, you can complete the CME Post Test by writingthe best answer to each question in the Answer Box located on the Activity Evaluation/Credit Requestform on the following page.

See detailed instructions at To Obtain AMA PRA Category 1 Credit™ on page 2.

Activity Evaluation/Credit Request

The Art and Science of Glaucoma Management: Expert Views on Medical and Surgical Approaches

To receive AMA PRA Category 1 Credit™, you must complete this Evaluation form and the Post Test. Record your answers to the Post Test in the Answer Boxlocated below. Mail or Fax this completed page to New York Eye and Ear Infirmary of Mount Sinai–ICME, 310 East 14th Street, New York, NY 10003 (Fax: 212-353-5703). Your comments help us to determine the extent to which this educational activity has met its stated objectives, assess future educational needs, andcreate timely and pertinent future activities. Please provide all the requested information below. This ensures that your certificate is filled out correctly and is mailedto the proper address. It also enables us to contact you about future CME activities. Please print clearly or type. Illegible submissions cannot be processed.

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Signature Required __________________________________________________________________ Date Completed ______________________________

OUTCOMES MEASUREMENT

oYes o No Did you perceive any commercial bias in any part of this activity? IMPORTANT! If you answered “Yes,” we urge you to be specific about where the bias occurred so we can address the perceived bias with the contributor and/or in the subject matter in future activities.

_________________________________________________________________________________________________________________________________

Circle the number that best reflects your opinion on the degree to which the following learning objectives were met:5 = Strongly Agree 4 = Agree 3 = Neutral 2 = Disagree 1 = Strongly Disagree

Upon completion of this activity, I am better able to:

• Assess diurnal IOP and select appropriate ocular antihypertensive therapy to meet IOP goals throughout the day 5 4 3 2 1

• Incorporate IOP treatment strategies that consider optimization of ocular surface health 5 4 3 2 1

• Select appropriate multitherapy or fixed-combination therapy to individualize treatment regimens in patients with and without comorbidities 5 4 3 2 1

• Incorporate appropriate use of surgical/device options into the effective management of IOP 5 4 3 2 1

1. Please list one or more things, if any, you learned from participating in this educational activity that you did not already know. ____________________________

_________________________________________________________________________________________________________________________________

2. As a result of the knowledge gained in this educational activity, how likely are you to implement changes in your practice?4=definitely will implement changes 3=likely will implement changes 2=likely will not implement any changes 1=definitely will not make any changes

5 4 3 2 1

Please describe the change(s) you plan to make: __________________________________________________________________________________________

_________________________________________________________________________________________________________________________________

3. Related to what you learned in this activity, what barriers to implementing these changes or achieving better patient outcomes do you face?_________________________________________________________________________________________________________________________________

_________________________________________________________________________________________________________________________________

4. Please check the Core Competencies (as defined by the Accreditation Council for Graduate Medical Education) that were enhanced for you through participation inthis activity. o Patient Care o Practice-Based Learning and Improvement o Professionalism

o Medical Knowledge o Interpersonal and Communication Skills o Systems-Based Practice

5. What other topics would you like to see covered in future CME programs? ___________________________________________________________________________

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POST TEST ANSWER BOX

Original Release: March 15, 2015 • Last Review: February 9, 2015Expiration: March 31, 2016