Managing Complex Cases in Glaucoma

Based on a CME Symposium held during the AAO/PAAO 2009 Joint Meeting.

ORIGINAL RELEASE DATE: MAY 15, 2010 • LAST REVIEW DATE: APRIL 11, 2010 • EXPIRATION DATE: MAY 31, 2011

Sponsored by The New York Eye and Ear Infirmary Institute for Continuing Medical Education.

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This continuing medical education activity is supported through an unrestricted educational grant from Pfizer Inc. PROGRAM CHAIR AND MODERATOR Surveyed physicians indicated that they often refer Richard K. Parrish, II, MD: Dr. Parrish had a financial Dale K. Heuer, MD these difficult patients yet wish they had the ability and agreement or affiliation during the past year with the Professor and Chairman comfort-level to manage their cases. Many physicians following commercial interests in the form of Department of Ophthalmology cited a desire for case-based discussion of such patients Consultant/Advisory Board: Alimera Sciences and Medical College of Wisconsin as a preferred presentation format. Merck & Co., Inc. Interest: Danube Pharmaceuticals Inc.; Director Glaukos Corporation; Othera Pharmaceuticals Inc. Froedtert & Medical College of Wisconsin Eye Institute LEARNING OBJECTIVES Sirion Therapeutics and Vitreoretinal Technologies, Inc. Milwaukee, Wisconsin After successfully completing this activity, learners will Salary/Honoraria: Allergan, Inc.; Bausch & Lomb have improved their ability to: Incorporated; Merck & Co., Inc. and Pfizer Inc. FACULTY • Describe management options for vision preservation Richard Lewis, MD in patients with glaucoma who have advanced disease, OFF-LABEL DISCUSSION Co-Founder and Director concomitant conditions such as retinal disease, ocular This activity includes off-label discussion of bevacizumab, Capital City Surgery Center surface disease, and other challenging presentations doxycycline, 5-fluorouracil, and mitomycin C. Sacramento, California • Identify adherence approaches for glaucoma therapy Chief Medical Editor EDITORIAL SUPPORT DISCLOSURES Glaucoma Today ACCREDITATION STATEMENT Deborah Kaplan and Jack McCain have no relevant Chair, Subspecialty Day Committee The New York Eye and Ear Infirmary is accredited by commercial relationships to disclose. American Academy of Ophthalmology the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. DISCLOSURE ATTESTATION Richard K. Parrish, II, MD The contributing physicians listed above have attested to Professor DESIGNATION STATEMENT the following: Department of Ophthalmology The New York Eye and Ear Infirmary designates this 1. that the relationships/affiliations noted will not bias or Bascom Palmer Eye Institute educational activity for a maximum of 1.0 AMA PRA otherwise influence their involvement in this activity; Associate Dean for Graduate Medical Education Category 1 Credi t ™. Physicians should only claim credit 2. that practice recommendations given relevant to the University of Miami commensurate with the extent of their participation in companies with which they have relationships/affiliations Miller School of Medicine the activity. will be supported by the best available evidence or, Miami, FL absent evidence, will be consistent with generally MISSION STATEMENT accepted medical practice; and LEARNING METHOD AND MEDIUM It is The New York Eye and Ear Infirmary Institute for 3. that all reasonable clinical alternatives will be discussed This educational activity consists of a supplement and eight Continuing Medical Education’s stated mission to create when making practice recommendations. (8) study questions. The participant should, in order, read medical education activities that will serve to increase the the learning objectives contained at the beginning of this knowledge, skills, professional performance, and relationships GRANTOR STATEMENT supplement, read the supplement, answer all questions in that a physician uses to provide services for patients, the This continuing medical education activity is supported the post test, and complete the evaluation form. To receive public, or the chosen profession. through an unrestricted educational grant from Pfizer Inc. credit for this activity, please follow the instructions provided on the post test and evaluation form. This educational activity DISCLOSURE POLICY STATEMENT TO OBTAIN CME CREDITS should take a maximum of 1 hour to complete. The New York Eye and Ear Infirmary requires that each To obtain CME credit for this activity, read the material in teacher/contributor or individual in a position to control the its entirety and consult referenced sources as necessary. CONTENT SOURCE content of a CME activity accredited by The New York Eye You may access this activity, post test, and evaluation online This continuing medical education (CME) activity is based and Ear Infirmary disclose the existence of any relevant at www.OphthalmologyTimes.com/Glaucoma-CME. Upon on a CME symposium held on Monday, October 26, 2009 financial interests or other relationships (eg, paid speaker, successful completion of the post test, your certificate will during the AAO/PAAO 2009 Joint Meeting in San Francisco, employee, paid consultant on a board and/or committee be issued immediately. Or, you may complete the evaluation California. for a commercial company) that would potentially affect form along with the completed post test answer box within the objectivity of activity content. Teachers/Contributors this supplement and return via mail to Kim Corbin, Director, TARGET AUDIENCE are also asked to make a disclosure that a product is still ICME, The New York Eye and Ear Infirmary, 310 East 14th This educational activity is intended for comprehensive investigational when an unlabeled use of a commercial Street, New York, NY 10003 or fax to (212) 353-5703. Your ophthalmologists. product or an investigational use, not yet approved for any certificate will be mailed to the address that you provide on purpose, is discussed during an educational activity. The the evaluation form. Please allow 3 weeks for mailed/faxed OVERVIEW disclosed information in no way presumes to assess the forms to process. Note: You must score a 70% or higher to Elevated intraocular pressure (IOP), and perhaps its variability, contributor’s qualifications or suitability. The intention is to receive credit for this activity. is the only modifiable risk factor for glaucoma progression 1 provide full disclosure of any potential conflict of interest, that has also been rigorously proven as a treatment for real or apparent, that is related to a specific educational References glaucoma. Given this role of IOP in glaucoma, current therapy activity. Individuals who neglect to provide information 1 The AGIS Investigators. The Advanced Glaucoma and management practices focus on reducing IOP and about relevant financial relationships will be disqualified Intervention Study (AGIS): The relationship between maintaining it at acceptable target levels to prevent damage from serving as a planning committee member, teacher, control of intraocular pressure and visual field deterioration. to the optic nerve and visual field. While the number of speaker, moderator, or author of the educational activity. Am J Ophthalmol. 2000;130(4):429-440. treatment options to control IOP has increased, a cure is not In addition, such individuals will be prohibited from having 2. Hattenhauer MG, et al. The probability of blindness from yet available. Newer technologies and agents continue to control of, or the responsibility for, the development, open-angle glaucoma. Ophthalmology. 1998 be explored; however, until a cure is discovered, physicians management, presentation, or evaluation of the CME Nov;105(11):2099-104. rely on medical and interventional therapy: topical IOP activity. Full disclosure of faculty and commercial 3. Oliver JE, et al. Blindness and glaucoma: a comparison lowering agents including the mainstay, prostaglandin relationships, if any, follows. of patients progressing to blindness from glaucoma with analogs, along with carbonic anhydrase inhibitor (CAI) and patients maintaining vision. Am J Ophthalmol. 2002 beta-blocker topical therapies, and laser (ALT or SLT) or DISCLOSURES Jun;133(6):764-72. surgical interventions may be employed. Ted M. Gerzberg, MD, Peer Reviewer has not had a 4. Chen P. Blindness in patients with treated open-angle financial agreement or affiliation during the past year glaucoma. Ophthalmology 2003 Apr;110(4):726-33. Though the availability of treatments are numerous and with any commercial interest. 5. Friedman DS, et al. Prevalence of open-angle glaucoma effective, patients still are not free from risk of blindness. In among adults in the United States. Arch Ophthalmol a retrospective study of treated patients in Olmsted County, Dale K. Heuer, MD: Dr. Heuer had a financial agreement or 2004; 122:532-538 Minnesota, the 20-year follow up discovered an incidence affiliation during the past year with the following commercial of glaucoma-related blindness of 27% in one eye and 9% in interests in the form of Consultant/Advisory Board: Allergan, both eyes. 2 Factors impacting a positive outcome of therapy Inc.; Danube Pharmaceuticals Inc.; NicOx and Pfizer Inc. The views and opinions expressed in this educational activity include greater severity of disease upon presentation 3 and Interest: Danube Pharmaceuticals Inc. Salary/Honoraria: are those of the faculty and do not necessarily represent the views difficulties with adherence to a treatment regimen. 4 Allergan, Inc.: Pfizer Inc. and Sirion Therapeutics. of The New York Eye and Ear Infirmary , Ophthalmology Times , or Pfizer Inc. Please refer to the official prescribing information Potentially, older age at diagnosis may affect progression. 3,4 Richard Lewis, MD: Dr. Lewis had a financial agreement or for each product for discussion of approved indications, As the US population ages, the role and challenges of the affiliation during the past year with the following commercial contraindications, and warnings. ophthalmologist are bound to increase. Open-angle glaucoma interests in the form of Consultant/Advisory Board: Alcon, Inc.: now affects more than 2 million individuals in the United AqueSys, Inc.; The Dow Chemical Company; iScience States and this number is projected to increase to more International; Ivantis, Inc. and QLT Inc.; Contracted than 3 million by 202 05. Research: iScience International; QLT Inc. and Visiogen, Inc. Salary/Honoraria: Alcon, Inc.; Allergan, Inc. and Pfizer Inc.

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.

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.

She had a history of high myopia (spherical equivalent Case 1: ≈ –12.50 D OD, –12.00 D OS). Her medical history was remarkable for systemic hypotension. She also reported Advanced Glaucoma that her extremities become cold on exposure to cold. Her visual acuity was 20/60 in her right eye, 20/25 DALE K. HEUER, MD in the left eye. Color vision was 0/15 in her right eye, 15/15 in the left. Her slit-lamp examination was A 57-year-old Asian female was referred to my practice unremarkable in both eyes. IOP was 14 mm Hg in in April 2000 with advanced normal-pressure glaucoma the right eye, 15 mm Hg in the left. Gonioscopy showed (NPG) in both eyes. The glaucoma was worse in the open grade IV angles in both eyes. right eye than in the left. Four years earlier, bilateral nasal visual field defects had been noted. Subsequent Consistent with her myopia, there were peripapillary visual fields documented progression, such that crescents in both eyes. Her tilted discs were striking, neuroophthalmology evaluation and MRI were done and this structural change and the peripapillary in 1999. Both were consistent with NPG. The highest atrophy may have contributed to the patient’s visual intraocular pressure (IOP) of which she was aware was field defect. 18 mm Hg. She had been treated in both eyes with brinzolamide twice daily for 3 years and levobunolol My initial recommendations were to continue levobunolol twice daily for 1 year. Her nonocular medications and brinzolamide in the left eye but to discontinue them were levothyroxine and conjugated estrogens. in the right eye. In that eye, I initiated treatment with

Managing Complex Cases in Glaucoma 3 latanoprost every evening and brimonidine twice daily. In the future, measuring blood pressure (BP) may become I advised the patient to wait at least 5 minutes, and part of the work-up for patients with advanced glaucoma, preferably 10 minutes, between administrations of dissimilar because as BP approaches IOP, resulting in lower perfusion drops being used at a similar time. pressure, the risk of progression increases. 4 Many glaucoma patients are being treated for systemic hypertension, and to This treatment regimen was intended to reduce her IOP to reduce the risk of light-headedness, they may be instructed 12 or 13 mm Hg, which would constitute a 30% decrease from by their primary care physician to take their antihypertensives her highest known IOP of 18 mm Hg. The decision to attempt at bedtime. Because BP is lowest when people are in bed to lower her IOP was based on the Collaborative Normal-Tension while IOP tends to be highest at this time, this practice may Glaucoma Study, which showed that after 3 years of treatment, be detrimental for eye health. progression was observed in only 20% of treated patients compared to 40% of controls, and that after 5 years the Over the next few months, the patient’s medications were progression rate remained 20% in treated patients compared incrementally escalated to include latanoprost, fixed-dose to 60% of controls. 1 In a multivariate survival analysis, this timolol-dorzolamide, and brimonidine in both eyes. In study also suggested that women with NPG are nearly twice September 2000, her IOP at 13:30 was 15.5 and 17 mm as likely to progress as men (male: female risk ratio, 0.54; Hg in her right and left eye, respectively, while on this P =.06). 2 In addition, it identified migraine as an independent regimen. Slit-lamp examination showed moderate follicular risk factor for progression of visual field abnormalities in conjunctivopathy in both eyes, consistent with a brimonidine patients with NPG (risk ratio, 2.58; P =.006). allergy, so it was discontinued. In October 2000, IOP at 09:40 was 16.5 and 17 mm Hg in the right and left eye, In the Collaborative Normal-Tension Glaucoma Study the respectively, on latanoprost and timolol/dorzolamide. The factors most strongly associated with treatment benefit follicular conjunctivopathy had improved. were lack of a disc hemorrhage, female gender, mild disc excavation, no history of cardiovascular disease, no family Because her IOP still was not at goal, she underwent history of stroke, and a family history of glaucoma. 3 multiple surgical procedures: inferior 180° laser

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

OS OD 16 travoprost & brinzolamide 14 latanoprost, timolol, & brinzolamide 12

10 travoprost 8 timolol & brinzolamide 6 no ocular hypotensives 4 needle bleb revision w/MMC 2

4 4 5 5 5 5 5 6 6 6 7 7 7 7 7 8 8 9 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 -0 - c- - r- l- - v- - l- v- - r- y- l- v- r- v- r- g ep e eb p u ep o eb u o an a a u o p o a u S D F A J S N F J N J M M J N A N M A

4 A Certified CME Supplement to Ophthalmology Times : May 2009 trabeculoplasty in both eyes, 1 week apart (October 2004. After PRK, central corneal thickness was 502-507 2000); trabeculectomy with 5-fluorouracil (5-FU), right µm in the left eye and 561-572 µm in the right eye. eye (November 2000); trabeculectomy with 5-FU, left eye (January 2001); needle bleb revision with mitomycin C Because of IOP fluctuation in her right eye into the mid- (MMC), left eye (March 2003, July 2003); trabeculectomy teens, I performed needle bleb revision with MMC in 2007, revision with MMC, left eye (September 2003). which brought the IOP into the range of 4 to 6 mm Hg (Figure 1) . To manage IOP in her left eye, I prescribed Six months postoperatively, she had persistent poor vision travoprost in 2007, and a few months later I added in her left eye. I suspected hypotony maculopathy, but brinzolamide. I next added timolol to the brinzolamide, optical coherence tomography showed no significant macular and that combination seemed to work on the first visit. I thickening. Retinoscopy showed she had developed about later added brinzolamide to the latanoprost and timolol. +8 diopters of cylinder in the axis of the trabeculoplasty. Beca use of concern about the risk of bleb-related infection In conclusion, PRK for this patient seems to have been the best in the presence of relatively a thin, avascular bleb in her choice, given that the degree of correction was so high that her better eye, contact lenses were thought too risky. She tried glasses could not be tolerated and contact lenses were not an an extended trial of glasses, but because they made her feel option. A needle bleb revision with MMC or an aqueous shunt dizzy she underwent photorefractive keratectomy (PRK) may be the best option for her continued management of her for high postoperative astigmatism in her left eye in August left eye if progression is documented or her IOP trends higher.

References 1. The effectiveness of intraocular pressure reduction in the treatment of 3. Anderson DR, Drance SM, Schulzer M; Collaborative Normal-Tension normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Glaucoma Study Group. Factors that predict the benefit of lowering intraocular Group. Am J Ophthalmol. 1998;126(4):498-505. pressure in normal tension glaucoma. Am J Ophthalmol. 2003;136(5):820-9. 2. Drance S, Anderson DR, Schulzer M; Collaborative Normal-Tension Glaucoma 4. Tielsch JM, Katz J, Sommer A, et al. Hypertension, perfusion pressure, Study Group. Risk factors for progression of visual field abnormalities in and primary open-angle glaucoma. A population-based assessment. normal-tension glaucoma. Am J Ophthalmol. 2001;131(6):699-708. Arch Ophthalmol. 1995;113(2):216- 21.

timolol-dorzolamide, which she reported made her feel Case 2: as though she was “drinking caffeine all the time”; and timolol gel, which she tolerated but which resulted in Uncontrolled IOP right-eye IOPs ranging from 24 to 30 mm Hg. We therefore added latanoprost to timolol gel. This combination DALE K. HEUER, MD succeeded in lowering the IOP in her right eye to 20 mm Hg, but I discontinued the latanoprost after she expressed At her visit in September 2009, a 79-year-old white concern about change in the color of her iris. Next I female had IOPs of 35 and 30 mm Hg in her right added brimonidine to the timolol gel. Both were and left eye, respectively. Her angles were open (grade discontinued after she complained of feeling “sick, tired, I superiorly and grade I-II elsewhere in both eyes). She and depressed .” At this point I restarted latanoprost, had pseudoexfoliation without phacodonesis in both eyes. resulting in a right-eye IOP of 29 mm Hg, possibly owing Her central corneal thickness was 561-566 µm in the to admitted inadequate adherence to therapy; the right eye and 561-571 µm in the left. Vertical cup:disc latanoprost therefore was discontinued. Next, I initiated (VCD) was 0.75 in the right eye and 0.55 in the left; brinzolamide, on which her right-eye IOP ranged from 21 both rims were indistinct. Her visual fields were normal. to 30 mm Hg, again probably contributed to by admitted poor adherence. Brinzolamide was discontinued and Her previous treatment history was marked by intolerance bimatoprost was initiated. The patient discontinued this or inadequate intraocular pressure (IOP) reduction or medication on her own because she said her eyes were both to multiple medications. Among these were latanoprost , bloodshot and aching, and the skin around her eye turned which was discontinued because she complain ed of dark grey to black. She reported that all these signs and headache and ocular burning; fixed combination symptoms resolved when she stopped taking bimatoprost.

Managing Complex Cases in Glaucoma 5 At this point, brinzolamide was resumed, but IOPs IOP and better visual field and optic disc status than the eyes ranged from 18 to 40 mm Hg, owing (at least in part) in which the initial treatment had been medication, but the to admitted poor adherence. Travoprost was added to differences were small after a median follow-up of 7 years brinzolamide, but after the patient complained it made (IOP reduction, 1.2 mm Hg; improvement in visual field, 0.6 her eye red and discolored the skin surrounding her eye, dB). 3 Further, ALT was unlikely to eliminate the need for the travoprost was discontinued. Brinzolamide 3 times medications, as ALT alone at 7 years’ follow-up was successful daily was continued, but IOPs ranged from 18 to 38 mm in only 20% of eyes whose initial treatment was ALT. Hg, again owing (at least in part) to admitted poor adherence. Because of inadequate IOP reduction with Likewise, in the Early Manifest Glaucoma Trial (EMGT), in brinzolamide, fixed combination timolol-brimonidine was which patients with early glaucoma were randomized to ALT initiated. The initial response was good (reduction from 34 and topical betaxolol (n=129) or no initial treatment (n=126), to 16 mm Hg), but adherence continued to be problematic at 4 years’ follow-up 30% of patients in the treatment group and subsequent IOPs ranged from 16 to 38 mm Hg. had progressed (versus 49% of the untreated group), and at 6 years’ follow-up 45% of the treatment group had During her visit in March 2009, I told the patient progressed (versus 62% of the untreated group). 4 Thus, in she needed surgery to reduce her IOP. Despite a lengthy nonadhering patients with manifest glaucoma, performing history of inadequate adherence with or intolerance laser trabeculoplasty would still allow progression in about of topical medications, her response was to request half of patients with intermediate follow-up. drops again, but in October 2009 I performed laser trabeculoplasty on her left eye and she began treatment The range of this patient’s IOP over 10 years of mostly futile with a topical medication. treatment, owing to her longstanding nonadherence, is depicted in Figure 1 . What, if anything, can be done to improvement Had the Ocular Hypertension Treatment Study Group/European adherence? Improvements in adherence with ocular hypotensive Glaucoma Prevention Study (OHTS/EGPS) risk calculato r1 been therapy have resulted from interventions involving simplified available when I first saw this patient, at age 71, her 5-year risk dosing regimens, reminder devices, patient education, and would have been 20% even though her VCD was 0.45 in both individualized care planning, but at this point the evidence is eyes. Although this calculation incorporates untreated IOP, in her not strong enough to advocate any single intervention. 5 ca se the measurements probably were essentially untreated, owing to her lack of adherence. While it is possible that she Even electronic monitoring has been found to be inadequate used her medication in the days immediately prior to her visit, for improving adherence: nearly 45% of glaucoma patients her risk probably was higher than the calculated value. Further, (n=196) using an electronic monitoring device for 3 months pseudoexfoliation was an exclusion criterion for OHTS, and the used their drops (travoprost) less than 75% of the time. 6 few patients in EGPS who had pseudoexfoliation were removed These patients knew they were being monitored and they from the database when the calculator was created. were provided free medication. The patients reported far higher medication use than was demonstrated by their For a patient with high IOP who has difficulty adhering to monitored behavior. Further, physicians’ ability to identify hypotensive medication, argon laser trabeculoplasty (ALT) poorly adherent patients through their self-reports or might seem to be a reasonable alternative, as it is effective other clues was poor. for most patients with primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma, or primary glaucoma, and the In a long-term patient population with open-angle glaucoma, treatment effect is independent of patient adherence. It is a ocular hypertension, or suspected glaucoma (N=181), relatively noninvasive procedure with a low rate of complications. certain factors were associated with adherence: using fewer In medically treated patients with open-angle glaucoma ALT medications, use of prostaglandin or beta-blockers instead has been shown to reduce mean and peak 24-hour IOP. 2 of carbonic anhydrase inhibitors, living alone, and being widowed. Again, physicians were unable to predict which Trabeculoplasty has its limitations, however. In the Glaucoma patients were adherent. Laser Trial Follow-up Study, which followed 203 of the 271 patients enrolled in the Glaucoma Laser Trial, those eyes in As is evident from the figure, this patient’s IOP fluctuated which initial ALT had been the treatment for POAG had lower dramatically over the course of 10 years. Some studies have

6 A Certified CME Supplement to Ophthalmology Times : May 2009 shown that IOP fluctuation increases the risk of glaucomatous The current unresolved question is how to manage her right visual field progression, 8 while a more recent analysis suggests eye. Given her age, doing no more than phacoemulsification that IOP fluctuation doesn’t make much difference in patients of the cataract and implantation of an intraocular lens might whose IOP is high. 9 A retrospective longitudinal study found be prudent, owing to the risk of complications associated with that in patients newly diagnosed with open-angle glaucoma, trabeculectomy. An alternative to trabeculectomy for lowering most patients who progressed to legal blindness had higher IOP is canaloplasty, a nonpenetrating surgical procedure that IOP variability but pressures that were lower than or similar may be safer than trabeculectomy. 11 to those in patients who did not become blind. 10

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

OD OS 40

04 04 05 05 05 05 05 06 06 06 07 07 07 07 07 08 08 09 09 - c- - r- l- - v- - l- v- - r- y- l- v- r- v- r- - ep e eb p u ep o eb u o an a a u o p o a ug S D F A J S N F J N J M M J N A N M A

References 1. Ocular Hypertension Treatment Study Group; European Glaucoma Prevention 7. Djafari F, Lesk MR, Harasymowycz PJ, et al. Determinants of adherence Study Group, Gordon MO, Torri V, Miglior S, et al. Validated prediction model to glaucoma medical therapy in a long-term patient population. for the development of primary open-angle glaucoma in individuals with J Glaucoma. 2009;18(3):238-43. ocular hypertension. Ophthalmology. 2007;114(1):10-9. 8. Nouri-Mahdavi K, Hoffman D, Coleman AL, et al; Advanced Glaucoma 2. Lee AC, Mosaed S, Weinreb RN, et al. Effect of laser trabeculoplasty Intervention Study. Predictive factors for glaucomatous visual field progression on nocturnal intraocular pressure in medically treated glaucoma patients. in the Advanced Glaucoma Intervention Study. Ophthalmology. Ophthalmology. 2007;114(4):666-70. 2004;111(9):1627-35. 3. The Glaucoma Laser Trial (GLT) and glaucoma laser trial follow-up study: 7. 9. Caprioli J, Coleman AL. Intraocular pressure fluctuation a risk factor for Results. Glaucoma Laser Trial Research Group. Am J Ophthalmol. visual field progression at low intraocular pressures in the advanced glaucoma 1995;120(6):718-31. intervention study. Ophthalmology. 2008;115(7):1123-29.e3. 4. Heijl A, Leske MC, Bengtsson B, et al; Early Manifest Glaucoma Trial Group. 10. Oliver JE, Hattenhauer MG, Herman D, et al. Blindness and glaucoma: a Reduction of intraocular pressure and glaucoma progression: results from comparison of patients progressing to blindness from glaucoma with the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-79. patients maintaining vision. Am J Ophthalmol. 2002;133(6):764-72. 5. Gray TA, Orton LC, Henson D, et al. Interventions for improving 11. Lewis RA, von Wolff K, Tetz M, et al. Canaloplasty: circumferential adherence to ocular hypotensive therapy. Cochrane Database Syst Rev. viscodilation and tensioning of Schlemm's canal using a flexible 2009;(2):CD006132. microcatheter for the treatment of open-angle glaucoma in adults: interim 6. Okeke CO, Quigley HA, Jampel HD, et al. Adherence with topical clinical study analysis. J Cataract Refract Surg. 2007;33(7):1217-26. glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology. 2009;116(2):191-9.

Managing Complex Cases in Glaucoma 7 However, many patients with dry eye don’t have dry eye at all. Case 3: LASIK, Dry They have severe posterior blepharitis — meibomian gland dysfunction. Their eyes may be a little dry, but their problem Eye, and Glaucoma is not fundamentally about the quantity of their tear film but rather its inferior quality. Many such patients have been treated RICHARD LEWIS, MD with artificial tears and lubricants when the better treatment would be doxycyclin e 2 that could alter the metalloproteinases In 1993, a 46-year-old man was referred to me with a in the tear film. It also should be noted that clinical observation 3-year history of primary open-angle glaucoma (POAG). in patients with glaucoma and dry eye suggests that some His highest intraocular pressure ( IOP) during that period glaucoma medications seem more likely than others to cause had been 30 mm Hg. During my initial examination his redness and irritation. IOP was 25 mm Hg in his right eye and 22 mm Hg in his left eye. His vertical cup-to-disc (VCD) ratio was 0.8. His visual acuity in March 2001 was 20/20 without With mild myopic correction his visual acuity was 20/20. correction. His slit-lamp exam was fairly normal in the Slit-lamp examination was normal. He reported he was right eye, but there was a large ischemic bleb on the left taking timolol and dipivefin twice daily in both eyes eye. IOP was 22 mm Hg in the right eye, 4 in the left. (prostaglandin analogs were not yet available). His Visual field showed progressive field loss. VCD was 0.9. visual fields showed early glaucomatous changes. Prior to PRK, his corneal thickness was 556 µm in the right eye and 577 in the left; PRK depth was 41 µm and Visual fields are very valuable when the patient is a reliable test- 40 µm, respectively. Compared with his visual fields from taker. Unfortunately, this patient was unreliable. When patients 1998, there had been dramatic progression in the right are intermediately reliable or unreliable, the reproducibility eye (Figure 1A and 1B) . of their fields deteriorates, forcing the clinician to rely on IOP measurements. Having a good perimetrist is one key to In October 2009, now age 63, his corrected visual acuity generating reliable visual fields. The perimetrist needs to be was 20/25 in each eye. IOP was 17 mm Hg in the right able to communicate well with patients and help them eye, 11 mm Hg in the left without any medications in understand the reason for the test. The perimetrist also can either eye. He had well-formed blebs with some early give the patient a sense of empowerment by explaining that cataract formation. Corneal thickness was 538 µm in the they can pause the test by holding the button down when right eye, 535 µm in the left. C:D ratio is 0.9. In 2002, they see the light. Having this power prevents patients from he had a trabeculectomy in the right eye. feeling out of control and overwhelmed by the testing process. Patients also can be put at ease by explaining that they The cataract formation in this patient helps explain why won’t see the light every time because test has to identify he now is a –2 myope after having PRK less than 10 years the next-dimmest light that they can’t see in order to identify earlier. Since his cataract is not affecting his activities of daily the dimmest light that they can see. living, cataract surgery is not a consideration at this time. In fact, he is essentially satisfied with his vision. I saw this patient again in March 2001, now at age 55, complaining of dry eye in both eyes. He had a The real issue is the IOP of 17 mm Hg in the right eye. trabeculectomy performed in 1995 on the left eye. In Interventional options are limited to a needle bleb revision, a 1997 he underwent photorefractive keratectomy (PRK) second trabeculoplasty, or an alternative drainage procedure, in both eyes (surface ablation). He was using latanoprost such as an aqueous shunt. Low-dose methazolamide (25 mg and timolol in his right eye, but he admitted to poor orally twice daily) might be a reasonable short-term medication. compliance with therapy; he was not using any drops in his left eye. In summary, this patient’s predicament illustrates the problems that can emerge when patients who have undergone PRK or As patients age, glaucoma and dry eye both become more LASIK are lost to regular follow-up. Soon after the introduction common, and glaucoma patients seem to have more dry eye of LASIK, I noticed a troubling phenomenon: some patients complaints than nonglaucomatous patients. 1 stopped seeing their ophthalmologist. 3 Once they had been

8 A Certified CME Supplement to Ophthalmology Times : May 2009 treated, they believed they no longer had eye problems. Thus have become lost to follow-up until such time as they develop many highly myopic patients who were at risk for glaucoma some other problem, such as presbyopia or cataract.

Figure 1A.

Humphrey

Visual Fields

(DH) 1/98

Figure 1B

Humphrey

Visual Fields

(DH) 3/01

References 1. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease 3. Lewis RA. Refractive surgery and the glaucoma patient. Customized in glaucoma patients. J Glaucoma 2008;17(5):350-355. corneas under pressure. Ophthalmology. 2000;107(9):1621-2. 2. Pflugfelder SC. Anti-inflammatory therapy for dry eye. Am J Ophthalmol. 2004:337-342.

in both eyes, and brimonidine twice-daily in both eyes. He Case 4: CMG, also had cataracts and age-related macular degeneration [ARMD] in both eyes. He has had laser trabeculoplasty 2 Cataract and ARMD or 3 times in each eye and iridotomy in the right eye.

RICHARD K. PARRISH, II, MD His non-ocular surgical history included prostatectomy, vein stripping, hemorrhoidectomy, cholecystectomy, and An 87-year-old white male presented with a 30-year cystoscopy. His medical history included hypertension, history of glaucoma. His recent IOPs ranged from 22 to anxiety disorder, urinary difficulties, and postoperative 27 mm Hg while using bimatoprost at bedtime in both deep-vein thrombosis. His non-ocular medications were eyes, fixed-combination timolol-dorzolamide twice-daily a benzodiazepine, alprazolam, for anxiety; aspirin;

Managing Complex Cases in Glaucoma 9 dutasteride for benign prostatic hyperplasia; and an ACE of geographic or disciform ARMD have structural alterations of inhibitor, lisinopril, for hypertension. the optic disc that resemble glaucomatous optic neuropathy. 1 This was confirmed through a study of 31 eyes that had His visual acuity was 20/50 in his right eye and 20/70 Heidelberg retinal tomography (HRT) measurements available in his left eye. Slit-lamp examination was remarkable for and extensive ARMD (6 or more disc areas of ARMD) were moderate nuclear cataract in both eyes and a patent associated with higher C:D ratios and smaller neuroretinal iridotomy in the right eye. IOP was 21-22 mm Hg in rim areas. the right eye, 16 mm Hg in the left eye. Central corneal thickness was 605-607 µm in the right eye, 596-600 µm Three years later, the patient was reevaluated at the in the left eye. Gonioscopy on the right eye showed an request of his ophthalmologist when IOPs of 32 mm Hg open angle, while in the left eye there was appositional in the right eye and 34 mm Hg in left eye were noted. closure in some areas but an open angle in others. The His vision was worse; visual acuity was 20/100 in the vertical cup:disc (VCD) ratio in the right eye was 0.7, right eye, 20/400 in the left. IOP was 24 mm Hg in consistent with glaucoma. Because of the cataract in the the right eye and 20 mm Hg in the left eye. He was left eye, the view was difficult but the VCD appeared to using bimatoprost in the evening, fixed combination be about 0.75. In the right eye RPE changes and drusen timolol-dorzolamide twice daily, and brimonidine twice were evident; fundoscopy of the left eye was deferred daily, all in both eyes. He also has had multiple intravitreal because of the narrow angle. anti-VEGF injections in both eyes. VCD then were 0.8 in the right eye and 0.9 in the left. Fundoscopy showed RPE Given these findings, I continued his current medications changes and drusen in the right eye and geographic RPE and recommended that the referring physician perform laser atrophy in the left eye. His medical and surgical histories iridectomy in his left eye, which he did. Consideration of were unchanged. A week earlier, he had moved into an cataract surgery in this eye was deferred owing to central assisted living facility, but he continued to be vibrant, visual field loss, which was more consistent with ARMD active, and mentally alert. than with cataract. I also deferred consideration of glaucoma intervention owing to his relatively normal peripheral visual In light of his worsening ARMD, I was glad I had not removed field in his left eye. the cataract previously because it is possible that he would have attributed the progression of his ARMD to the cataract In the right eye, I continued his current medications and surgery. At this point, it is difficult to say whether cataract performed selective laser trabeculoplasty (SLT). I deferred surgery should be performed first on his left or right eye, or consideration of cataract surgery given his lack of significant perhaps only on his left eye. The argument for removing the functional visual impairment and his quasimonocular status cataract from the better eye first is that, given his age and his (central visual field loss consistent with ARMD in his left eye). severe ARMD, the surgery would give him a better chance of enjoying improved vision while he still has the opportunity. In patients with combined glaucoma and ARMD, visual fields The argument for performing cataract surgery from his poorer tend to be less reliable and more variable because of fixation eye first would be to assess his IOP (and visual) response to problems and the effect of macular changes on thresholds. the procedure as a guide to surgical decision-making in the More frequent testing can help mitigate issues with reliability better eye. Prior to removal of the cataract especially from and variability, and in a patient with poor central vision the the worse eye, the patient should be advised that while his use of an alternate fixation target can improve the steadiness peripheral vision may improve, his central vision will not get of “central” fixation. any better.

Disc photographs and optic disc and nerve-fiber layer imaging, In this case, I advised the referring physician to manage or both, can be helpful in patients like this. To improve clarity the patient’s right eye with combined phacoemulsification/ for photography or imaging, cataract surgery occasionally is intraocular lens implantation and trabeculectomy with MMC warranted. Bear in mind, however, that eyes with large areas 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.

10 A Certified CME Supplement to Ophthalmology Times : May 2009 Activity Post Test Original Release Date: May 15, 2010 • Last Review Date: April 11, 2010 • Expiration Date: May 31, 2011

MANAGING COMPLEX CASES IN GLAUCOMA Credit Request Form: AMA PRA Category 1 Credit s TM are awarded on the basis of the number of hours it took you to complete the supplement. The estimated number of hours to complete this activity is 1. The maximum number of credits that may be claimed for this CME activity is 1. Note: You must score 70% or higher to receive credit for this activity.

Post Test and Answer Key: To obtain a certificate of completion for 1 AMA PRA Category 1 Credi t TM for this activity, you must successfully complete this activity, post test, and evaluation by recording the best answer to each question in the answer key (located on the evaluation page). Complete the post test and evaluation form and mail or fax them to Kim Corbin, Director, ICME, The New York Eye and Ear Infirmary , 310 East 14th Street, New York, NY 10003 (Fax: 212-353-5703). The expiration date for credit is May 31, 2011.

1. In the Collaborative Normal-Tension Glaucoma 5. Which factor was not associated with adherence Study, which of the following factors was not strongly in a population with open-angle glaucoma? associated with treatment benefit? A. Use of a beta-blocker instead of a carbonic A. Family history of glaucoma anhydrase inhibitor B. Female gender B. Use of a prostaglandin instead of a carbonic C. Male gender anhydrase inhibitor D. No family history of stroke C. Use of electronic monitoring E. No history of cardiovascular disease D. Using fewer medications

2. Compared with open-angle glaucoma patients who did 6. In Dr. Lewis’s opinion, which skill(s) should a not become blind, what characteristics distinguished perimetrist possess to facilitate the generation open-angle glaucoma patients who did progress to of reliable visual fields? legal blindness? A. Ability to communicate with patients A. Higher IOP variability and higher intraocular pressures B. Ability to explain the reason for the test to patients B. Higher IOP variability and similar or lower intraocular C. Being able to give patients a sense of empowerment pressures D. All the above C. Lower IOP variability and higher intraocular pressures D. Lower IOP variability and similar or lower intraocular 7. Which intervention has been found to be better pressures than the others for improving adherence to ocular hypotensive therapy? 3. What were the progression rates in the Collaborative A. Individualized care planning Normal-Tension Glaucoma Study after 5 years for treated B. Patient education patients and controls? C. Reminder devices A. Treated, 20%; controls, 40% D. Simplified dosing regimens B. Treated, 20%; controls, 60% E. None of the above C. Treated, 30%; controls, 50% D. Treated, 30%; controls, 70% 8. Which troubling phenomenon has Dr. Lewis described E. Treated, 30%; controls, 35% in some patients after they have undergone LASIK?

A. Their post-LASIK vision isn’t as good as they perceive 4. Which steps are recommended for patients with it to be glaucoma and age-related macular degeneration? B. They become lost to regular follow-up because they A. More frequent testing believe they no longer have eye problems B. Use of an alternative fixation target C. They complain of dry eye because their ocular surface C. Disc photography disease wasn’t successfully addressed prior to surgery D. All the above D. They complain about the cost even though they are pleased with the outcome

Please enter your answers in the answer box on page 12.

Managing Complex Cases in Glaucoma 11 ! Activity Evaluation Original Release Date: May 15, 2010 • Last Review Date: April 11, 2010 • Expiration Date: May 31, 2011

MANAGING COMPLEX CASES IN GLAUCOMA To receive CME credit, please complete this evaluation form and mail or fax it to The New York Eye and Ear Infirmary -ICME, 310 East 14th Street, New York, NY 10003 (Fax: 212-353-5703) . You must complete the post test by recording the best answer to each question in the answer key located below. Your comments help us to determine the extent to which this educational activity has met its stated objectives, assess future educational needs, and create timely and pertinent future activities. Please provide all the requested information below. This ensures that your certificate is filled out correctly and is mailed to 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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r Yes r No Did you perceive any commercial bias in any part of this activity? If yes, please specify content and/or contributor. Post Test Answer Box: To obtain CME ACTIVITY EVALUATION Circle the number that best reflects your opinion on the degree to which the following learning objectives were met: credit for this activity, you Activity Rating: 5 = Strongly Agree 4 = Agree 3 = Neutral 2 = Disagree 1 = Strongly Disagree must complete After successfully completing this activity, I have improved my ability to: the post test by writing the best 1. Describe management options for vision preservation in patients with glaucoma who have advanced disease, answer to each concomitant conditions such as retinal disease, ocular surface disease, and other challenging presentations ...... 543 21 question in the Answer Box 2. Identify adherence approaches for glaucoma therapy ...... 543 21

PERSONAL OBJECTIVES 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

3 2. As a result of this activity, I plan to make the following changes in my practice:

4 3. Please check the Core Competencies (as defined by the Accreditation Council for Graduate Medical Education) that were enhanced for you 5 through participation in this activity. r Patient Care r Practice-Based Learning and Improvement r Professionalism r Medical Knowledge 6 r Interpersonal and Communication Skills r Systems-Based Practice

7 4. What barriers to patient care do you face?

8 ADDITIONAL COMMENTS

92144B !