Managing Complex Cases in GlaucomaBased on a CME Symposium held during the AAO/PAAO 2009 Joint Meeting.

Sponsored by The New York Eye and Ear Infirmary

Institute for Continuing Medical Education.

In Association with

This continuing medical education activity is supported through an unrestricted educational grant from Pfizer Inc.

O R I G I N A L R E L E A S E D A T E : M AY 1 5 , 2 0 1 0 • L A S T R E V I E W D A T E : A P R I L 1 1 , 2 0 1 0 • E X P I R A T I O N D A T E : M AY 3 1 , 2 0 1 1

PROGRAM CHAIR AND MODERATOR

Dale K. Heuer, MD

Professor and ChairmanDepartment of OphthalmologyMedical College of WisconsinDirectorFroedtert & Medical College of Wisconsin Eye InstituteMilwaukee, Wisconsin

FACULTY

Richard Lewis, MD

Co-Founder and DirectorCapital City Surgery CenterSacramento, CaliforniaChief Medical EditorGlaucoma TodayChair, Subspecialty Day CommitteeAmerican Academy of Ophthalmology

Richard K. Parrish, II, MD

ProfessorDepartment of OphthalmologyBascom Palmer Eye InstituteAssociate Dean for Graduate Medical EducationUniversity of MiamiMiller School of MedicineMiami, FL

LEARNING METHOD AND MEDIUM

This educational activity consists of a supplement and eight(8) study questions. The participant should, in order, readthe learning objectives contained at the beginning of thissupplement, read the supplement, answer all questions inthe post test, and complete the evaluation form. To receivecredit for this activity, please follow the instructions providedon the post test and evaluation form. This educational activityshould take a maximum of 1 hour to complete.

CONTENT SOURCE

This continuing medical education (CME) activity is basedon a CME symposium held on Monday, October 26, 2009during the AAO/PAAO 2009 Joint Meeting in San Francisco,California.

TARGET AUDIENCE

This educational activity is intended for comprehensive ophthalmologists.

OVERVIEW

Elevated intraocular pressure (IOP), and perhaps its variability,is the only modifiable risk factor for glaucoma progression1

that has also been rigorously proven as a treatment forglaucoma. Given this role of IOP in glaucoma, current therapyand management practices focus on reducing IOP andmaintaining it at acceptable target levels to prevent damageto the optic nerve and visual field. While the number oftreatment options to control IOP has increased, a cure is notyet available. Newer technologies and agents continue to be explored; however, until a cure is discovered, physiciansrely on medical and interventional therapy: topical IOP lowering agents including the mainstay, prostaglandinanalogs, along with carbonic anhydrase inhibitor (CAI) andbeta-blocker topical therapies, and laser (ALT or SLT) or surgical interventions may be employed.

Though the availability of treatments are numerous andeffective, patients still are not free from risk of blindness. Ina retrospective study of treated patients in Olmsted County,Minnesota, the 20-year follow up discovered an incidenceof glaucoma-related blindness of 27% in one eye and 9% inboth eyes.2 Factors impacting a positive outcome of therapyinclude greater severity of disease upon presentation3 anddifficulties with adherence to a treatment regimen.4

Potentially, older age at diagnosis may affect progression.3,4

As the US population ages, the role and challenges of theophthalmologist are bound to increase. Open-angle glaucomanow affects more than 2 million individuals in the UnitedStates and this number is projected to increase to morethan 3 million by 20205.

Surveyed physicians indicated that they often refer these difficult patients yet wish they had the ability andcomfort-level to manage their cases. Many physicians cited a desire for case-based discussion of such patients as a preferred presentation format.

LEARNING OBJECTIVES

After successfully completing this activity, learners will have improved their ability to:• Describe management options for vision preservation

in patients with glaucoma who have advanced disease, concomitant conditions such as retinal disease, ocularsurface disease, and other challenging presentations

• Identify adherence approaches for glaucoma therapy

ACCREDITATION STATEMENT

The New York Eye and Ear Infirmary is accredited by the Accreditation Council for Continuing Medical Educationto provide continuing medical education for physicians.

DESIGNATION STATEMENT

The New York Eye and Ear Infirmary designates this educational activity for a maximum of 1.0 AMA PRACategory 1 Credit ™. Physicians should only claim creditcommensurate with the extent of their participation in the activity.

MISSION STATEMENT

It is The New York Eye and Ear Infirmary Institute forContinuing Medical Education’s stated mission to createmedical education activities that will serve to increase theknowledge, skills, professional performance, and relationshipsthat a physician uses to provide services for patients, thepublic, or the chosen profession.

DISCLOSURE POLICY STATEMENT

The New York Eye and Ear Infirmary requires that eachteacher/contributor or individual in a position to control thecontent of a CME activity accredited by The New York Eyeand Ear Infirmary disclose the existence of any relevantfinancial interests or other relationships (eg, paid speaker,employee, paid consultant on a board and/or committee for a commercial company) that would potentially affect the objectivity of activity content. Teachers/Contributors are also asked to make a disclosure that a product is stillinvestigational when an unlabeled use of a commercialproduct or an investigational use, not yet approved for anypurpose, is discussed during an educational activity. Thedisclosed information in no way presumes to assess thecontributor’s qualifications or suitability. The intention is toprovide full disclosure of any potential conflict of interest,real or apparent, that is related to a specific educationalactivity. Individuals who neglect to provide informationabout relevant financial relationships will be disqualifiedfrom serving as a planning committee member, teacher,speaker, moderator, or author of the educational activity. In addition, such individuals will be prohibited from havingcontrol of, or the responsibility for, the development, management, presentation, or evaluation of the CME activity. Full disclosure of faculty and commercial relationships, if any, follows.

DISCLOSURES

Ted M. Gerzberg, MD, Peer Reviewer has not had a financial agreement or affiliation during the past year with any commercial interest.

Dale K. Heuer, MD: Dr. Heuer had a financial agreement oraffiliation during the past year with the following commercialinterests in the form of Consultant/Advisory Board: Allergan,Inc.; Danube Pharmaceuticals Inc.; NicOx and Pfizer Inc.Interest: Danube Pharmaceuticals Inc. Salary/Honoraria:Allergan, Inc.: Pfizer Inc. and Sirion Therapeutics.

Richard Lewis, MD: Dr. Lewis had a financial agreement oraffiliation during the past year with the following commercialinterests in the form of Consultant/Advisory Board: Alcon, Inc.:AqueSys, Inc.; The Dow Chemical Company; iScienceInternational; Ivantis, Inc. and QLT Inc.; ContractedResearch: iScience International; QLT Inc. and Visiogen, Inc.Salary/Honoraria: Alcon, Inc.; Allergan, Inc. and Pfizer Inc.

Richard K. Parrish, II, MD: Dr. Parrish had a financialagreement or affiliation during the past year with the following commercial interests in the form ofConsultant/Advisory Board: Alimera Sciences and Merck & Co., Inc. Interest: Danube Pharmaceuticals Inc.;Glaukos Corporation; Othera Pharmaceuticals Inc. Sirion Therapeutics and Vitreoretinal Technologies, Inc.Salary/Honoraria: Allergan, Inc.; Bausch & LombIncorporated; Merck & Co., Inc. and Pfizer Inc.

OFF-LABEL DISCUSSION

This activity includes off-label discussion of bevacizumab,doxycycline, 5-fluorouracil, and mitomycin C.

EDITORIAL SUPPORT DISCLOSURES

Deborah Kaplan and Jack McCain have no relevant commercial relationships to disclose.

DISCLOSURE ATTESTATION

The contributing physicians 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 which they have relationships/affiliationswill be supported by the best available evidence or,absent evidence, will be consistent with generallyaccepted medical practice; and

3. that all reasonable clinical alternatives will be discussedwhen making practice recommendations.

GRANTOR STATEMENT

This continuing medical education activity is supportedthrough an unrestricted educational grant from Pfizer Inc.

TO OBTAIN CME CREDITS

To obtain CME credit for this activity, read the material in its entirety and consult referenced sources as necessary.You may access this activity, post test, and evaluation onlineat www.OphthalmologyTimes.com/Glaucoma-CME. Uponsuccessful completion of the post test, your certificate willbe issued immediately. Or, you may complete the evaluationform along with the completed post test answer box withinthis supplement and return via mail to Kim Corbin, Director,ICME, The New York Eye and Ear Infirmary, 310 East 14thStreet, New York, NY 10003 or fax to (212) 353-5703. Yourcertificate will be mailed to the address that you provide onthe evaluation form. Please allow 3 weeks for mailed/faxedforms to process. Note: You must score a 70% or higher toreceive credit for this activity.

References

1 The AGIS Investigators. The Advanced GlaucomaIntervention Study (AGIS): The relationship between control of intraocular pressure and visual field deterioration.Am J Ophthalmol. 2000;130(4):429-440.

2. Hattenhauer MG, et al. The probability of blindness fromopen-angle glaucoma. Ophthalmology. 1998Nov;105(11):2099-104.

3. Oliver JE, et al. Blindness and glaucoma: a comparison of patients progressing to blindness from glaucoma withpatients maintaining vision. Am J Ophthalmol. 2002Jun;133(6):764-72.

4. Chen P. Blindness in patients with treated open-angleglaucoma. Ophthalmology 2003 Apr;110(4):726-33.

5. Friedman DS, et al. Prevalence of open-angle glaucomaamong adults in the United States. Arch Ophthalmol2004; 122:532-538

The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the viewsof The New York Eye and Ear Infirmary, Ophthalmology Times, or Pfizer Inc. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

© 2010 • All rights reserved • USA • 92144B

Managing Complex Cases in Glaucoma 3

Case 1: Advanced Glaucoma D A L E K . H E U E R , M D

A 57-year-old Asian female was referred to my practice in April 2000 with advanced normal-pressure glaucoma(NPG) in both eyes. The glaucoma was worse in the right eye than in the left. Four years earlier, bilateralnasal visual field defects had been noted. Subsequentvisual fields documented progression, such that neuroophthalmology evaluation and MRI were done in 1999. Both were consistent with NPG. The highestintraocular pressure (IOP) of which she was aware was18 mm Hg. She had been treated in both eyes with brinzolamide twice daily for 3 years and levobunolol twice daily for 1 year. Her nonocular medications were levothyroxine and conjugated estrogens.

She had a history of high myopia (spherical equivalent ≈ –12.50 D OD, –12.00 D OS). Her medical historywas remarkable for systemic hypotension. She also reportedthat her extremities become cold on exposure to cold. Her visual acuity was 20/60 in her right eye, 20/25 in the left eye. Color vision was 0/15 in her right eye, 15/15 in the left. Her slit-lamp examination was unremarkable in both eyes. IOP was 14 mm Hg in the right eye, 15 mm Hg in the left. Gonioscopy showedopen grade IV angles in both eyes.

Consistent with her myopia, there were peripapillary crescents in both eyes. Her tilted discs were striking, and this structural change and the peripapillary atrophy may have contributed to the patient’s visualfield defect.

My initial recommendations were to continue levobunololand brinzolamide in the left eye but to discontinue themin the right eye. In that eye, I initiated treatment with

References

1. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol. 2000;130(4):429-40.

Managing Complex Cases in Glaucoma

Elevated intraocular pressure (IOP) is the only modifiable risk factor for glaucoma

progression, such that a reduction in IOP is associated with reduced progression of

visual field defect.1 The medical and surgical interventions employed to reduce IOP in

order to prevent damage to the optic nerve and loss of vision include topical agents

such as prostaglandin analogs, carbonic anhydrase inhibitors, and beta-blockers; laser

surgery, including either argon laser trabeculoplasty (ALT) or selective laser trabeculoplasty

(SLT); and incisional surgery. Treatment of glaucoma with one or more of these

interventions is challenging in its own right, but glaucoma often occurs in combination

with other eye disorders such as dry eye or cataracts. Moreover, patients often complicate

matters by failing to comply with prescribed therapy. Using case studies, this supplement

will help clinicians to better manage the complex cases they inevitably will encounter

in their patients with glaucoma.

4 A Certified CME Supplement to Ophthalmology Times: May 2009

latanoprost every evening and brimonidine twice daily. I advised the patient to wait at least 5 minutes, andpreferably 10 minutes, between administrations of dissimilardrops being used at a similar time.

This treatment regimen was intended to reduce her IOP to 12 or 13 mm Hg, which would constitute a 30% decrease fromher highest known IOP of 18 mm Hg. The decision to attemptto lower her IOP was based on the Collaborative Normal-TensionGlaucoma Study, which showed that after 3 years of treatment,progression was observed in only 20% of treated patientscompared to 40% of controls, and that after 5 years the progression rate remained 20% in treated patients comparedto 60% of controls.1 In a multivariate survival analysis, thisstudy also suggested that women with NPG are nearly twiceas likely to progress as men (male: female risk ratio, 0.54;P =.06).2 In addition, it identified migraine as an independentrisk factor for progression of visual field abnormalities inpatients with NPG (risk ratio, 2.58; P =.006).

In the Collaborative Normal-Tension Glaucoma Study the factors most strongly associated with treatment benefit were lack of a disc hemorrhage, female gender, mild discexcavation, no history of cardiovascular disease, no familyhistory of stroke, and a family history of glaucoma.3

In the future, measuring blood pressure (BP) may become part of the work-up for patients with advanced glaucoma,because as BP approaches IOP, resulting in lower perfusionpressure, the risk of progression increases.4 Many glaucomapatients are being treated for systemic hypertension, and toreduce the risk of light-headedness, they may be instructed by their primary care physician to take their antihypertensivesat bedtime. Because BP is lowest when people are in bedwhile IOP tends to be highest at this time, this practice may be detrimental for eye health.

Over the next few months, the patient’s medications wereincrementally escalated to include latanoprost, fixed-dosetimolol-dorzolamide, and brimonidine in both eyes. InSeptember 2000, her IOP at 13:30 was 15.5 and 17 mmHg in her right and left eye, respectively, while on this regimen. Slit-lamp examination showed moderate follicularconjunctivopathy in both eyes, consistent with a brimonidineallergy, so it was discontinued. In October 2000, IOP at09:40 was 16.5 and 17 mm Hg in the right and left eye,respectively, on latanoprost and timolol/dorzolamide. Thefollicular conjunctivopathy had improved.

Because her IOP still was not at goal, she underwentmultiple surgical procedures: inferior 180° laser

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Figure 1. 57 y/o AF with Advanced NPG OU IOP Profile OU Sep-04 through Oct-09

needle bleb revision w/MMC

no ocularhypotensives

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latanoprost, timolol, & brinzolamide

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Managing Complex Cases in Glaucoma 5

References

1. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma StudyGroup. Am J Ophthalmol. 1998;126(4):498-505.

2. Drance S, Anderson DR, Schulzer M; Collaborative Normal-Tension GlaucomaStudy Group. Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol. 2001;131(6):699-708.

3. Anderson DR, Drance SM, Schulzer M; Collaborative Normal-TensionGlaucoma Study Group. Factors that predict the benefit of lowering intraocularpressure in normal tension glaucoma. Am J Ophthalmol. 2003;136(5):820-9.

4. Tielsch JM, Katz J, Sommer A, et al. Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. Arch Ophthalmol. 1995;113(2):216-21.

trabeculoplasty in both eyes, 1 week apart (October2000); trabeculectomy with 5-fluorouracil (5-FU), righteye (November 2000); trabeculectomy with 5-FU, left eye(January 2001); needle bleb revision with mitomycin C(MMC), left eye (March 2003, July 2003); trabeculectomyrevision with MMC, left eye (September 2003).

Six months postoperatively, she had persistent poor vision in her left eye. I suspected hypotony maculopathy, but optical coherence tomography showed no significant macular thickening. Retinoscopy showed she had developed about +8 diopters of cylinder in the axis of the trabeculoplasty.Because of concern about the risk of bleb-related infection in the presence of relatively a thin, avascular bleb in her better eye, contact lenses were thought too risky. She tried an extended trial of glasses, but because they made her feeldizzy she underwent photorefractive keratectomy (PRK) for high postoperative astigmatism in her left eye in August

2004. After PRK, central corneal thickness was 502-507µm in the left eye and 561-572 µm in the right eye.

Because of IOP fluctuation in her right eye into the mid-teens, I performed needle bleb revision with MMC in 2007,which brought the IOP into the range of 4 to 6 mm Hg(Figure 1). To manage IOP in her left eye, I prescribedtravoprost in 2007, and a few months later I added brinzolamide. I next added timolol to the brinzolamide,and that combination seemed to work on the first visit. Ilater added brinzolamide to the latanoprost and timolol.

In conclusion, PRK for this patient seems to have been the bestchoice, given that the degree of correction was so high that herglasses could not be tolerated and contact lenses were not anoption. A needle bleb revision with MMC or an aqueous shuntmay be the best option for her continued management of herleft eye if progression is documented or her IOP trends higher.

Case 2: Uncontrolled IOPD A L E K . H E U E R , M D

At her visit in September 2009, a 79-year-old whitefemale had IOPs of 35 and 30 mm Hg in her right and left eye, respectively. Her angles were open (grade I superiorly and grade I-II elsewhere in both eyes). Shehad pseudoexfoliation without phacodonesis in both eyes.Her central corneal thickness was 561-566 µm in theright eye and 561-571 µm in the left. Vertical cup:disc(VCD) was 0.75 in the right eye and 0.55 in the left;both rims were indistinct. Her visual fields were normal.

Her previous treatment history was marked by intoleranceor inadequate intraocular pressure (IOP) reduction orboth to multiple medications. Among these were latanoprost,which was discontinued because she complained ofheadache and ocular burning; fixed combination

timolol-dorzolamide, which she reported made her feel as though she was “drinking caffeine all the time”; andtimolol gel, which she tolerated but which resulted inright-eye IOPs ranging from 24 to 30 mm Hg. Wetherefore added latanoprost to timolol gel. This combinationsucceeded in lowering the IOP in her right eye to 20 mmHg, but I discontinued the latanoprost after she expressedconcern about change in the color of her iris. Next Iadded brimonidine to the timolol gel. Both were discontinued after she complained of feeling “sick, tired,and depressed.” At this point I restarted latanoprost,resulting in a right-eye IOP of 29 mm Hg, possibly owingto admitted inadequate adherence to therapy; thelatanoprost therefore was discontinued. Next, I initiatedbrinzolamide, on which her right-eye IOP ranged from 21to 30 mm Hg, again probably contributed to by admittedpoor adherence. Brinzolamide was discontinued andbimatoprost was initiated. The patient discontinued thismedication on her own because she said her eyes werebloodshot and aching, and the skin around her eye turneddark grey to black. She reported that all these signs andsymptoms resolved when she stopped taking bimatoprost.

6 A Certified CME Supplement to Ophthalmology Times: May 2009

At this point, brinzolamide was resumed, but IOPsranged from 18 to 40 mm Hg, owing (at least in part)to admitted poor adherence. Travoprost was added tobrinzolamide, but after the patient complained it madeher eye red and discolored the skin surrounding her eye,the travoprost was discontinued. Brinzolamide 3 timesdaily was continued, but IOPs ranged from 18 to 38 mmHg, again owing (at least in part) to admitted pooradherence. Because of inadequate IOP reduction with brinzolamide, fixed combination timolol-brimonidine wasinitiated. The initial response was good (reduction from 34to 16 mm Hg), but adherence continued to be problematicand subsequent IOPs ranged from 16 to 38 mm Hg.

During her visit in March 2009, I told the patient she needed surgery to reduce her IOP. Despite a lengthyhistory of inadequate adherence with or intolerance of topical medications, her response was to request drops again, but in October 2009 I performed lasertrabeculoplasty on her left eye and she began treatmentwith a topical medication.

Had the Ocular Hypertension Treatment Study Group/EuropeanGlaucoma Prevention Study (OHTS/EGPS) risk calculator1 beenavailable when I first saw this patient, at age 71, her 5-year riskwould have been 20% even though her VCD was 0.45 in botheyes. Although this calculation incorporates untreated IOP, in hercase the measurements probably were essentially untreated,owing to her lack of adherence. While it is possible that sheused her medication in the days immediately prior to her visit,her risk probably was higher than the calculated value. Further,pseudoexfoliation was an exclusion criterion for OHTS, and thefew patients in EGPS who had pseudoexfoliation were removedfrom the database when the calculator was created.

For a patient with high IOP who has difficulty adhering tohypotensive medication, argon laser trabeculoplasty (ALT)might seem to be a reasonable alternative, as it is effectivefor most patients with primary open-angle glaucoma (POAG),pseudoexfoliation glaucoma, or primary glaucoma, and thetreatment effect is independent of patient adherence. It is arelatively noninvasive procedure with a low rate of complications.In medically treated patients with open-angle glaucoma ALThas been shown to reduce mean and peak 24-hour IOP.2

Trabeculoplasty has its limitations, however. In the GlaucomaLaser Trial Follow-up Study, which followed 203 of the 271patients enrolled in the Glaucoma Laser Trial, those eyes inwhich initial ALT had been the treatment for POAG had lower

IOP and better visual field and optic disc status than the eyesin which the initial treatment had been medication, but thedifferences were small after a median follow-up of 7 years(IOP reduction, 1.2 mm Hg; improvement in visual field, 0.6dB).3 Further, ALT was unlikely to eliminate the need for medications, as ALT alone at 7 years’ follow-up was successfulin only 20% of eyes whose initial treatment was ALT.

Likewise, in the Early Manifest Glaucoma Trial (EMGT), inwhich patients with early glaucoma were randomized to ALTand topical betaxolol (n=129) or no initial treatment (n=126),at 4 years’ follow-up 30% of patients in the treatment grouphad progressed (versus 49% of the untreated group), and at 6 years’ follow-up 45% of the treatment group had progressed (versus 62% of the untreated group).4 Thus, in nonadhering patients with manifest glaucoma, performinglaser trabeculoplasty would still allow progression in abouthalf of patients with intermediate follow-up.

The range of this patient’s IOP over 10 years of mostly futiletreatment, owing to her longstanding nonadherence, is depictedin Figure 1. What, if anything, can be done to improvementadherence? Improvements in adherence with ocular hypotensivetherapy have resulted from interventions involving simplifieddosing regimens, reminder devices, patient education, and individualized care planning, but at this point the evidence is not strong enough to advocate any single intervention.5

Even electronic monitoring has been found to be inadequatefor improving adherence: nearly 45% of glaucoma patients(n=196) using an electronic monitoring device for 3 monthsused their drops (travoprost) less than 75% of the time.6

These patients knew they were being monitored and theywere provided free medication. The patients reported farhigher medication use than was demonstrated by their monitored behavior. Further, physicians’ ability to identifypoorly adherent patients through their self-reports or other clues was poor.

In a long-term patient population with open-angle glaucoma,ocular hypertension, or suspected glaucoma (N=181), certain factors were associated with adherence: using fewermedications, use of prostaglandin or beta-blockers instead of carbonic anhydrase inhibitors, living alone, and being widowed. Again, physicians were unable to predict whichpatients were adherent.

As is evident from the figure, this patient’s IOP fluctuated dramatically over the course of 10 years. Some studies have

Managing Complex Cases in Glaucoma 7

References

1. Ocular Hypertension Treatment Study Group; European Glaucoma PreventionStudy Group, Gordon MO, Torri V, Miglior S, et al. Validated prediction modelfor the development of primary open-angle glaucoma in individuals with ocular hypertension. Ophthalmology. 2007;114(1):10-9.

2. Lee AC, Mosaed S, Weinreb RN, et al. Effect of laser trabeculoplasty on nocturnal intraocular pressure in medically treated glaucoma patients.Ophthalmology. 2007;114(4):666-70.

3. The Glaucoma Laser Trial (GLT) and glaucoma laser trial follow-up study: 7.Results. Glaucoma Laser Trial Research Group. Am J Ophthalmol.1995;120(6):718-31.

4. Heijl A, Leske MC, Bengtsson B, et al; Early Manifest Glaucoma Trial Group.Reduction of intraocular pressure and glaucoma progression: results fromthe Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-79.

5. Gray TA, Orton LC, Henson D, et al. Interventions for improving adherence to ocular hypotensive therapy. Cochrane Database Syst Rev.2009;(2):CD006132.

6. Okeke CO, Quigley HA, Jampel HD, et al. Adherence with topical glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology. 2009;116(2):191-9.

7. Djafari F, Lesk MR, Harasymowycz PJ, et al. Determinants of adherence to glaucoma medical therapy in a long-term patient population. J Glaucoma. 2009;18(3):238-43.

8. Nouri-Mahdavi K, Hoffman D, Coleman AL, et al; Advanced GlaucomaIntervention Study. Predictive factors for glaucomatous visual field progressionin the Advanced Glaucoma Intervention Study. Ophthalmology.2004;111(9):1627-35.

9. Caprioli J, Coleman AL. Intraocular pressure fluctuation a risk factor for visual field progression at low intraocular pressures in the advanced glaucomaintervention study. Ophthalmology. 2008;115(7):1123-29.e3.

10. Oliver JE, Hattenhauer MG, Herman D, et al. Blindness and glaucoma: acomparison of patients progressing to blindness from glaucoma withpatients maintaining vision. Am J Ophthalmol. 2002;133(6):764-72.

11. Lewis RA, von Wolff K, Tetz M, et al. Canaloplasty: circumferential viscodilation and tensioning of Schlemm's canal using a flexible microcatheter for the treatment of open-angle glaucoma in adults: interimclinical study analysis. J Cataract Refract Surg. 2007;33(7):1217-26.

shown that IOP fluctuation increases the risk of glaucomatousvisual field progression,8 while a more recent analysis suggeststhat IOP fluctuation doesn’t make much difference in patientswhose IOP is high.9 A retrospective longitudinal study foundthat in patients newly diagnosed with open-angle glaucoma,most patients who progressed to legal blindness had higherIOP variability but pressures that were lower than or similar to those in patients who did not become blind.10

The current unresolved question is how to manage her righteye. Given her age, doing no more than phacoemulsificationof the cataract and implantation of an intraocular lens mightbe prudent, owing to the risk of complications associated withtrabeculectomy. An alternative to trabeculectomy for loweringIOP is canaloplasty, a nonpenetrating surgical procedure thatmay be safer than trabeculectomy.11

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Figure 1. 79 y/o WF w/PXFG OD & PXFG suspect OS IOP Profile Apr-00 through Sep-09

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8 A Certified CME Supplement to Ophthalmology Times: May 2009

Case 3: LASIK, DryEye, and GlaucomaR I C H A R D L E W I S , M D

In 1993, a 46-year-old man was referred to me with a 3-year history of primary open-angle glaucoma (POAG).His highest intraocular pressure ( IOP) during that periodhad been 30 mm Hg. During my initial examination hisIOP was 25 mm Hg in his right eye and 22 mm Hg inhis left eye. His vertical cup-to-disc (VCD) ratio was 0.8.With mild myopic correction his visual acuity was 20/20.Slit-lamp examination was normal. He reported he wastaking timolol and dipivefin twice daily in both eyes(prostaglandin analogs were not yet available). His visual fields showed early glaucomatous changes.

Visual fields are very valuable when the patient is a reliable test-taker. Unfortunately, this patient was unreliable. When patientsare intermediately reliable or unreliable, the reproducibility of their fields deteriorates, forcing the clinician to rely on IOPmeasurements. Having a good perimetrist is one key to generating reliable visual fields. The perimetrist needs to beable to communicate well with patients and help them understand the reason for the test. The perimetrist also cangive the patient a sense of empowerment by explaining thatthey can pause the test by holding the button down when they see the light. Having this power prevents patients fromfeeling out of control and overwhelmed by the testing process.Patients also can be put at ease by explaining that they won’t see the light every time because test has to identify the next-dimmest light that they can’t see in order to identifythe dimmest light that they can see.

I saw this patient again in March 2001, now at age 55, complaining of dry eye in both eyes. He had a trabeculectomy performed in 1995 on the left eye. In1997 he underwent photorefractive keratectomy (PRK) in both eyes (surface ablation). He was using latanoprostand timolol in his right eye, but he admitted to poor compliance with therapy; he was not using any drops in his left eye.

As patients age, glaucoma and dry eye both become morecommon, and glaucoma patients seem to have more dry eyecomplaints than nonglaucomatous patients.1

However, many patients with dry eye don’t have dry eye at all.They have severe posterior blepharitis — meibomian glanddysfunction. Their eyes may be a little dry, but their problem is not fundamentally about the quantity of their tear film butrather its inferior quality. Many such patients have been treatedwith artificial tears and lubricants when the better treatmentwould be doxycycline 2 that could alter the metalloproteinasesin the tear film. It also should be noted that clinical observationin patients with glaucoma and dry eye suggests that someglaucoma medications seem more likely than others to causeredness and irritation.

His visual acuity in March 2001 was 20/20 without correction. His slit-lamp exam was fairly normal in theright eye, but there was a large ischemic bleb on the lefteye. IOP was 22 mm Hg in the right eye, 4 in the left.Visual field showed progressive field loss. VCD was 0.9.Prior to PRK, his corneal thickness was 556 µm in theright eye and 577 in the left; PRK depth was 41 µm and40 µm, respectively. Compared with his visual fields from1998, there had been dramatic progression in the righteye (Figure 1A and 1B).

In October 2009, now age 63, his corrected visual acuitywas 20/25 in each eye. IOP was 17 mm Hg in the righteye, 11 mm Hg in the left without any medications ineither eye. He had well-formed blebs with some earlycataract formation. Corneal thickness was 538 µm in theright eye, 535 µm in the left. C:D ratio is 0.9. In 2002,he had a trabeculectomy in the right eye.

The cataract formation in this patient helps explain why he now is a –2 myope after having PRK less than 10 yearsearlier. Since his cataract is not affecting his activities of dailyliving, cataract surgery is not a consideration at this time. Infact, he is essentially satisfied with his vision.

The real issue is the IOP of 17 mm Hg in the right eye.Interventional options are limited to a needle bleb revision, asecond trabeculoplasty, or an alternative drainage procedure,such as an aqueous shunt. Low-dose methazolamide (25 mgorally twice daily) might be a reasonable short-term medication.

In summary, this patient’s predicament illustrates the problemsthat can emerge when patients who have undergone PRK orLASIK are lost to regular follow-up. Soon after the introductionof LASIK, I noticed a troubling phenomenon: some patientsstopped seeing their ophthalmologist.3 Once they had been

treated, they believed they no longer had eye problems. Thusmany highly myopic patients who were at risk for glaucoma

have become lost to follow-up until such time as they developsome other problem, such as presbyopia or cataract.

Managing Complex Cases in Glaucoma 9

References

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

2. Pflugfelder SC. Anti-inflammatory therapy for dry eye. Am J Ophthalmol.2004:337-342.

3. Lewis RA. Refractive surgery and the glaucoma patient. Customized corneas under pressure. Ophthalmology. 2000;107(9):1621-2.

Case 4: CMG,Cataract and ARMD R I C H A R D K . P A R R I S H , I I , M D

An 87-year-old white male presented with a 30-year history of glaucoma. His recent IOPs ranged from 22 to 27 mm Hg while using bimatoprost at bedtime in botheyes, fixed-combination timolol-dorzolamide twice-daily

in both eyes, and brimonidine twice-daily in both eyes. Healso had cataracts and age-related macular degeneration[ARMD] in both eyes. He has had laser trabeculoplasty 2or 3 times in each eye and iridotomy in the right eye.

His non-ocular surgical history included prostatectomy,vein stripping, hemorrhoidectomy, cholecystectomy, andcystoscopy. His medical history included hypertension,anxiety disorder, urinary difficulties, and postoperativedeep-vein thrombosis. His non-ocular medications were a benzodiazepine, alprazolam, for anxiety; aspirin;

Figure 1A.

Humphrey

Visual Fields

(DH) 1/98

Figure 1B

Humphrey

Visual Fields

(DH) 3/01

10 A Certified CME Supplement to Ophthalmology Times: May 2009

dutasteride for benign prostatic hyperplasia; and an ACEinhibitor, lisinopril, for hypertension.

His visual acuity was 20/50 in his right eye and 20/70 in his left eye. Slit-lamp examination was remarkable formoderate nuclear cataract in both eyes and a patent iridotomy in the right eye. IOP was 21-22 mm Hg in the right eye, 16 mm Hg in the left eye. Central cornealthickness was 605-607 µm in the right eye, 596-600 µmin the left eye. Gonioscopy on the right eye showed anopen angle, while in the left eye there was appositionalclosure in some areas but an open angle in others. Thevertical cup:disc (VCD) ratio in the right eye was 0.7,consistent with glaucoma. Because of the cataract in theleft eye, the view was difficult but the VCD appeared tobe about 0.75. In the right eye RPE changes and drusenwere evident; fundoscopy of the left eye was deferredbecause of the narrow angle.

Given these findings, I continued his current medications and recommended that the referring physician perform laseriridectomy in his left eye, which he did. Consideration ofcataract surgery in this eye was deferred owing to centralvisual field loss, which was more consistent with ARMD than with cataract. I also deferred consideration of glaucomaintervention owing to his relatively normal peripheral visualfield in his left eye.

In the right eye, I continued his current medications and performed selective laser trabeculoplasty (SLT). I deferredconsideration of cataract surgery given his lack of significantfunctional visual impairment and his quasimonocular status(central visual field loss consistent with ARMD in his left eye).

In patients with combined glaucoma and ARMD, visual fieldstend to be less reliable and more variable because of fixationproblems and the effect of macular changes on thresholds.More frequent testing can help mitigate issues with reliabilityand variability, and in a patient with poor central vision theuse of an alternate fixation target can improve the steadinessof “central” fixation.

Disc photographs and optic disc and nerve-fiber layer imaging,or both, can be helpful in patients like this. To improve clarityfor photography or imaging, cataract surgery occasionally iswarranted. Bear in mind, however, that eyes with large areas

of geographic or disciform ARMD have structural alterations ofthe optic disc that resemble glaucomatous optic neuropathy.1

This was confirmed through a study of 31 eyes that hadHeidelberg retinal tomography (HRT) measurements availableand extensive ARMD (6 or more disc areas of ARMD) wereassociated with higher C:D ratios and smaller neuroretinal rim areas.

Three years later, the patient was reevaluated at therequest of his ophthalmologist when IOPs of 32 mm Hgin the right eye and 34 mm Hg in left eye were noted.His vision was worse; visual acuity was 20/100 in theright eye, 20/400 in the left. IOP was 24 mm Hg in the right eye and 20 mm Hg in the left eye. He was using bimatoprost in the evening, fixed combination timolol-dorzolamide twice daily, and brimonidine twicedaily, all in both eyes. He also has had multiple intravitrealanti-VEGF injections in both eyes. VCD then were 0.8 inthe right eye and 0.9 in the left. Fundoscopy showed RPEchanges and drusen in the right eye and geographic RPEatrophy in the left eye. His medical and surgical historieswere unchanged. A week earlier, he had moved into anassisted living facility, but he continued to be vibrant,active, and mentally alert.

In light of his worsening ARMD, I was glad I had not removedthe cataract previously because it is possible that he wouldhave attributed the progression of his ARMD to the cataractsurgery. At this point, it is difficult to say whether cataractsurgery should be performed first on his left or right eye, orperhaps only on his left eye. The argument for removing thecataract from the better eye first is that, given his age and hissevere ARMD, the surgery would give him a better chance ofenjoying improved vision while he still has the opportunity.The argument for performing cataract surgery from his poorereye first would be to assess his IOP (and visual) response tothe procedure as a guide to surgical decision-making in thebetter eye. Prior to removal of the cataract especially fromthe worse eye, the patient should be advised that while hisperipheral vision may improve, his central vision will not getany better.

In this case, I advised the referring physician to manage the patient’s right eye with combined phacoemulsification/intraocular lens implantation and trabeculectomy with MMC or another incisional glaucoma procedure.

References

1. Law SK, Sohn YH, Hoffman D, et al. Optic disk appearance in advanced age-related macular degeneration. Am J Ophthalmol. 2004;138(1):38-45.

Managing Complex Cases in Glaucoma 11

1. In the Collaborative Normal-Tension Glaucoma

Study, which of the following factors was not strongly

associated with treatment benefit?

A. Family history of glaucoma B. Female genderC. Male genderD. No family history of strokeE. No history of cardiovascular disease

2. Compared with open-angle glaucoma patients who did

not become blind, what characteristics distinguished

open-angle glaucoma patients who did progress to

legal blindness?

A. Higher IOP variability and higher intraocular pressuresB. Higher IOP variability and similar or lower intraocular

pressuresC. Lower IOP variability and higher intraocular pressuresD. Lower IOP variability and similar or lower intraocular

pressures

3. What were the progression rates in the Collaborative

Normal-Tension Glaucoma Study after 5 years for treated

patients and controls?

A. Treated, 20%; controls, 40%B. Treated, 20%; controls, 60%C. Treated, 30%; controls, 50%D. Treated, 30%; controls, 70%E. Treated, 30%; controls, 35%

4. Which steps are recommended for patients with

glaucoma and age-related macular degeneration?

A. More frequent testingB. Use of an alternative fixation targetC. Disc photographyD. All the above

5. Which factor was not associated with adherence

in a population with open-angle glaucoma?

A. Use of a beta-blocker instead of a carbonic anhydrase inhibitor

B. Use of a prostaglandin instead of a carbonic anhydrase inhibitor

C. Use of electronic monitoring D. Using fewer medications

6. In Dr. Lewis’s opinion, which skill(s) should a

perimetrist possess to facilitate the generation

of reliable visual fields?

A. Ability to communicate with patientsB. Ability to explain the reason for the test to patientsC. Being able to give patients a sense of empowermentD. All the above

7. Which intervention has been found to be better

than the others for improving adherence to ocular

hypotensive therapy?

A. Individualized care planningB. Patient educationC. Reminder devicesD. Simplified dosing regimensE. None of the above

8. Which troubling phenomenon has Dr. Lewis described

in some patients after they have undergone LASIK?

A. Their post-LASIK vision isn’t as good as they perceive it to be

B. They become lost to regular follow-up because theybelieve they no longer have eye problems

C. They complain of dry eye because their ocular surface disease wasn’t successfully addressed prior to surgery

D. They complain about the cost even though they arepleased with the outcome

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