1. Glaucoma and Ocular Surface Disease: Differentiating Between Disease and Treatment Side Effects Robert D. Fechtner, MD Professor of Ophthalmology Director, Glaucoma Division Institute of Ophthalmology and Visual Science New Jersey Medical School – UMDNJ Newark, New Jersey Clark L. Springs, MD Assistant Professor Director of Cornea and Refractory Surgery Glick Eye Institute Indiana University School of Medicine Indianapolis, Indiana

2. Overall Program Goal The goal of the program is to examine the incidence of and issues involved in accurately identifying and managing ocular surface disease in patients who have glaucoma.

3. Study results showing prevalence of dry eye (overall, in women, in men, and in older individuals): Schaumberg DA, et al. Am J Ophthalmol. 2003;136:318-326. Schaumberg DA, et al. Arch Ophthalmol. 2009;127:763-768. Schein OD, et al. Am J Ophthalmol. 1997:124:723-728. Prevalence of Dry Eye and Ocular Surface Disease

4. Prevalence of Dry Eye Among Women: Study Population 39,876 health professionals Ages 45-84 years Enrolled in the Women’s Health Study, a randomized trial designed to assess the benefits of and risks for aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer in healthy women Participants received mailed questionnaires every year At year 4, included 3 questions about dry eye Schaumberg DA, et al. Am J Ophthalmol. 2003;136:318-326.

5. Prevalence of Dry Eye Among Women: Methods Have you ever been diagnosed by a clinician as having dry eye syndrome? How often do your eyes feel dry (not wet enough)? How often do your eyes feel irritated? Possible answers: –constantly –often –sometimes –never Schaumberg DA, et al. Am J Ophthalmol. 2003;136:318-326.

6. Prevalence of Dry Eye Among Women: Results The prevalence of dry eye syndrome increased with age, from 5.7% among women 75 years old. The age-adjusted prevalence of dry eye syndrome was 7.8%, or 3.23 million women aged > 50 in the United States. Compared with whites, Hispanic (OR 1.81, CI 1.18- 2.80) and Asian (OR 1.77, CI 1.17-2.69) women were more likely to report severe symptoms, but not be clinically diagnosed with dry eye syndrome. Women from the South had the highest prevalence of dry eye syndrome, although the magnitude of geographic differences was modest. Schaumberg DA, et al. Am J Ophthalmol. 2003;136:318-326.

7. Prevalence of Dry Eye Among Women 9.8% among women aged > 75 years old Schaumberg DA, et al. Am J Ophthalmol. 2003;136:318-326.

8. Prevalence of Dry Eye Among Men: Study Population Physicians Health Study (PHS) Randomized period of PHS I and PHS II ended in 1999 25,444 men, including 18,596 original participants in PHS I and 6848 men who did not participate in PHS I but were randomly assigned to PHS II Schaumberg DA, et al. Arch Ophthalmol. 2009;127:763-768.

9. Prevalence of Dry Eye Among Men: Methods Have you ever been diagnosed by a clinician as having dry eye syndrome? How often do your eyes feel dry (not wet enough)? How often do your eyes feel irritated? Possible answers: –constantly –often –sometimes –never Schaumberg DA, et al. Arch Ophthalmol. 2009;127:763-768.

10. Prevalence of Dry Eye Among Men: Results The prevalence of dry eye disease increased with age, from 3.90% among men aged 50-54 years to 7.67% among men 80 years and older (P for trend ≤.001). High blood pressure and benign prostatic hyperplasia were associated with a higher risk for dry eye disease. Use of antidepressants, antihypertensives, and medications to treat benign prostatic hyperplasia were also associated with increased risk for dry eye disease. Schaumberg DA, et al. Arch Ophthalmol. 2009;127:763-768.

11. Prevalence of Dry Eye Among Men 7.67% among men 80 years and older Schaumberg DA, et al. Arch Ophthalmol. 2009;127:763-768.

12. Prevalence of Dry Eye Among the Elderly: Study Population 2520 residents of Salisbury, Maryland 65 years or older as of 1993 Standardized questionnaire (6 questions) Examination –Schirmer’s test –Rose Bengal stain –Assessment of meibomian glands Schein OD, et al. Am J Ophthalmol. 1997:124:723-728.

13. Age Group (yr) Percent Who Have 1 or More Symptoms Often or All the Time 65-6914.2% (774) 70-7414.9% (824) 75-7913.7% (540) 80+16.3% (344) Schein OD, et al. Am J Ophthalmol. 1997:124:723-728. Gender Male13.3% (1052) Female15.6% (1430) Prevalence of Dry Eye Among the Elderly: Results

14. 14.6% reported 1 or more dry eye symptom “often” or “all the time” Schein OD, et al. Am J Ophthalmol. 1997:124:723-728.

15. Approximately what percentage of your patients treated for glaucoma also have ocular surface disease symptoms?  Fewer than 1%  Approximately 10%  Approximately 25%  Approximately 50%  More than half Interactive Poll Question

16. Prevalence of Ocular Surface Disease in Patients With Glaucoma Studies have sought to determine how common ocular surface disease (OSD) is in patients with glaucoma: Leung EW, et al. J Glaucoma. 2008; 17:350-355. Fechtner RD, et al. Cornea. 2010;29:618-621.

17. Prevalence of OSD in Patients With Glaucoma: Study Design 101 patients with glaucoma or ocular hypertension Exclusions: receiving cyclosporine, steroids, topical ocular nonsteroidal anti-inflammatory drugs, or punctal plugs within previous 3 months Testing –Ocular Surface Disease Index (OSDI) –Schirmer’s test –Staining (fluorescein and lissamine green) –Tear break-up time (TBUT) Leung EW, et al. J Glaucoma. 2008;17:350-355.

18. Test Results Lissamine GreenOSDI Schirmer’s TestTBUT Normal79413922 Mild to Moderate 22332713 Severe0273566 Leung EW, et al. J Glaucoma. 2008;17:350-355. Number (%) of Patients With Each Result

19. Symptoms vs Signs of OSD Leung EW, et al. J Glaucoma. 2008;17:350-355. Clinical Tests Patients With Symptoms (%)

20. RankingNormal Mild to ModerateSevere Patients413327 Percentage41%33%27% 59% OSDI Scores in Glaucoma Patients Leung EW, et al. J Glaucoma. 2008;17:350-355. Prevalence of OSD in Patients With Glaucoma: Results

21. Prevalence of OSD in Patients With Glaucoma Treated With Topical Medications: Study Methods Conducted from May 2006 to March 2007 10 sites - geographically distributed 630 glaucoma patients: – > 18 years of age –Primary open-angle, exfoliation, or pigment dispersion glaucoma, or ocular hypertension in both eyes –Treated with 1 or more topical intraocular pressure- lowering medication(s) Patients completed OSDI survey while in the office Fechtner RD, et al. Cornea. 2010;29:618-621.

22. 0102030405060708090100 Normal (0-12) Mild (13-22) Moderate (23-32) Severe (33-100) OSDI Severity Grading Miller KL, et al. 13th Annual Conference of the International Society for Quality of Life Research. 2006. Abstract 1540. Total OSDI Score = (Sum of Score for All Questions Answered) X (25) (Total # of Questions Answered)

23. Prevalence of OSD in Patients With Glaucoma Treated With Topical Medications: Study Results RankingNormalMildModerateSevere Patients3251348487 Percentage51.6%21.3%13.3%13.8% 48.4% OSDI Scores in Glaucoma Patients Fechtner RD, et al. Cornea. 2010;29:618-621.

24. Studies suggest there may be a relationship between the presence of OSD in patients with glaucoma and topical medications for glaucoma: Leung EW, et al. J Glaucoma. 2008;17:350-355. Rossi GC, et al. Eur J Ophthalmol. 2009;19:572-579. Ocular Surface Disease and Topical Medications for Glaucoma

25. OSDI and Number of BAK-Containing Eyedrops BAK = benzalkonium chloride Leung EW, et al. J Glaucoma. 2008;17:350-355. Number of BAK-Containing Eyedrops Patients (Percentage)

26. Quality of Life: Study Methods 61 treated subjects (G1 = 1 drop/day, G2 = 2 drops/day, G3 = 3 drops/day) 20 untreated controls (G0 = no drops) Questionnaires –National Eye Institute Visual Function Questionnaire (NEI-VFQ) –Glaucoma Symptom Scale (GSS) –OSDI Dry eye syndrome was defined as presence of punctate keratitis and decreased TBUT Rossi GC, et al. Eur J Ophthalmol. 2009;19:572-579.

27. Number of Medications Percent With Dry Eye Syndrome 0 medications5 1 medication11 2 medications39 3 medications40 Rossi GC, et al. Eur J Ophthalmol. 2009;19:572-579. Quality of Life: Impact of Multiple Medications

28. Discussion of Answers to Poll Question

29. Case #1: A 55-Year-Old Man 55-year-old psychiatrist Medical History Panic attacks (started 1 month ago) Ocular History Primary open-angle glaucoma (diagnosed 15 years ago) Posterior chamber intraocular lens OU Trabeculectomy OU Presumed ocular histoplasmosis syndrome OU, with central macular scars OU OU = each eye

30. Case #1: Medications Ocular Medications Bimatoprost OU every evening Other Medications Escitalopram (for panic attacks)

31. Chief Complaint “I am uncomfortable driving and I have difficulty reading at work.”

32. Case #1: Examination BCVa 20/400 OD OS vision decreased from 20/50 to 20/100 IOP in mid-teens Moderate rosacea with meibomian gland dysfunction Severe central PEE Normal Schirmer’s test Has to wear SCL to make bioptics work Torn SCL BCVa = best corrected visual acuity; OD = right eye; OS = left eye; IOP = intraocular pressure; PEE = punctate epithelial erosions; SCL = soft contact lens

33. Interactive Poll Question How would you proceed in this patient?  Change to preservative-free artificial tears  Decrease BAK load  Anti-inflammatory therapy  Punctal plugs  All of the above

34. Case #1: Treatment Plan Reduce BAK Load –Travoprost BAK-free substituted for bimatoprost [a-c] Anti-inflammatory therapy –Loteprednol etabonate [d] –4 times a day for 1 week, thrice daily for 1 week, twice daily for 1 week, once daily for 1 week –Cyclosporine OU twice daily [e] –Doxycycline 20 mg orally twice daily [f] a. Baudouin C, et al. Br J Ophthalmol. 1998;82:39-42. b. Pisella PJ, et al. Br J Ophthalmol. 2002;86:418-423. c. Jaenen N, et al. Eur J Ophthalmol. 2007;17:341-351. d. Pavesio CE, Decory HH. Br J Ophthalmol. 2008;92:455-459. e. Perry HD, et al. Cornea. 2006;25:171-175. f. Stone DU, Chodosh J. Cornea. 2004;23:106-109.

35. Case #1: Follow-up 4-week follow-up: BCVa improved to 20/60 left eye 1-year follow-up: BCVa improved to baseline

36. Discussion of Answers to Poll Question

37. Discussion: Approach to Patient

38. 86-year-old white man Medical history –Hypertension –Cerebrovascular disease –Heart disease Ocular history –Primary open-angle glaucoma since 1998 –Cataract extraction with intraocular lens OU 2000 –Branch retinal vein occlusion (BRVO) OD with poor vision 2002 –Steroid responder Family history: sisters with glaucoma Case #2: An 86-Year-Old Man

39. Case #2: Medications Medications: verapamil, lisinopril, propafenone, simvastatin, dronedarone, aspirin Ocular medications: bimatoprost at bedtime OU, brimonidine/timolol twice daily OU, cyclosporine ophthalmic twice daily OU, methazolamide 50 mg thrice daily, artificial tears as needed Allergies: “All glaucoma drops”

40. Chief Complaint “When I use my glaucoma medications and my IOP is controlled, my vision is poor. When I stop my drops, I see much better but my IOP is in the 30s.”

41. Visual acuity: distance OD 20/150, (+0.50-4.00 X 005), OS 20/50 (+1.0-3.50 X 90) ph 20/30-2 External examination –Lids: erythema and meibomian gland dysfunction –Conjunctiva: 2+ injection OU –Cornea: punctate staining –Anterior chamber: quiet –Lens: IOL Extraocular movement: unremarkable Pupils: afferent defect OD Case #2. Ocular Examination

42. Lids: meibomian gland dysfunction Conjunctiva: 2+ injection Cornea: punctate staining OU Anterior chamber: OU, deep, quiet Iris: OU normal IOP: OD, 14 mm Hg, OS 19 mm Hg Pachymetry: 560 OD, 552 OS Gonioscopy: OU, open, ciliary body showing (d-40-q) Case #2. Slit Lamp Examination

43. Interactive Poll Question What are possible contributors to the external signs and symptoms?  Drug allergy  Drug toxicity  Dry eye  Meibomian gland disease  Preservative toxicity

44. Lens: OU, IOL Disc: OD, CDR 0.9 OS, CDR 0.5- (V&H) Retina: OD old BRVO Case #2. Dilated Examination and Diagnostic Testing

45. Optic Nerve >

46. Visual Field: HVF 24-2

48. Discussion of Answers to Poll Question

49. Case #2: Treatment Plan Reduce BAK load [a-c] –Discontinue bimatoprost and brimonidine/timolol –Begin travoprost with sofZia™ preservative and preservative-free timolol –Continue methazolamide Treat meibomian gland disease and ocular surface –Lid hygiene –Add azithromycin ophthalmic [d] –Continue cyclosporine ophthalmic a. Baudouin C, et al. Br J Ophthalmol. 1998;82:39-42. b. Pisella PJ, et al. Br J Ophthalmol. 2002;86:418-423. c. Jaenen N, et al. Eur J Ophthalmol. 2007;17:341-9.15. d. Luchs J. Adv Ther. 2008;25:858-870.

50. Case #2: Follow-up Two weeks later, by telephone call: “I feel a little better” One week after that: –Seen by comprehensive ophthalmologist –Felt fine, felt vision was better –IOP 30s OU –Treated with brimonidine and brimonidine/timolol in the office –Placed on brimonidine 0.15% with Polyquad®

51. Medications Travoprost OU at bedtime Preservative-free timolol OU twice daily Brimonidine 0.15% OU thrice daily Azithromycin ophthalmic OU twice daily Cyclosporine ophthalmic OU twice daily Methazolamide 50 mg orally thrice daily

52. Case #2: Follow-up Examination Visual acuity 20/150 OD, 20/50 OS Lids and eyes red Conjunctiva 2+ injection with follicles Cornea mild punctate staining

53. Case #2: Suspected Brimonidine Allergy Discontinue brimonidine, cyclosporine ophthalmic, azithromycin ophthalmic Continue travoprost, preservative-free timolol, methazolamide Add pilocarpine 1% thrice daily OU, olopatadine once daily OU, doxycyline 20 mg orally once daily Blondeau P, Rousseau JA. Can J Ophthalmol. 2002;37:21-26.

54. Discussion: Approach to Patient

55. Question-and-Answer Session With the Audience

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