Glaucoma and Ocular Surface Disease: Differentiating Between Disease and Treatment Side Effects

Robert D. Fechtner, MDProfessor of OphthalmologyDirector, Glaucoma DivisionInstitute of Ophthalmology and Visual ScienceNew Jersey Medical School – UMDNJNewark, New Jersey

Clark L. Springs, MDAssistant ProfessorDirector of Cornea and Refractory SurgeryGlick Eye InstituteIndiana University School of MedicineIndianapolis, Indiana

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.

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

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.

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.

Prevalence of Dry Eye Among Women: Results

• The prevalence of dry eye syndrome increased with age, from 5.7% among women < 50 years old to 9.8% among women aged > 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.

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.

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.

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.

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.

Prevalence of Dry Eye Among Men

7.67% among men 80 years and older

Schaumberg DA, et al. Arch Ophthalmol. 2009;127:763-768.

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.

Age Group (yr)Percent Who Have 1 or More

Symptoms Often or All the Time 65-69 14.2% (774)

70-74 14.9% (824)

75-79 13.7% (540)

80+ 16.3% (344)

Schein OD, et al. Am J Ophthalmol. 1997:124:723-728.

Gender

Male 13.3% (1052)

Female 15.6% (1430)

Prevalence of Dry Eye Among the Elderly: Results

Prevalence of Dry Eye Among the Elderly: Results

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.

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

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.

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.

Test Results

Lissamine Green OSDI

Schirmer’s Test TBUT

Normal 79 41 39 22

Mild to Moderate 22 33 27 13

Severe 0 27 35 66

Leung EW, et al. J Glaucoma. 2008;17:350-355.

Number (%) of Patients With Each Result

Symptoms vs Signs of OSD

Leung EW, et al. J Glaucoma. 2008;17:350-355.

Clinical Tests

Patie

nts

With

Sym

ptom

s (%

)

Ranking NormalMild to

Moderate Severe

Patients 41 33 27

Percentage 41% 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

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.

0 10 20 30 40 50 60 70 80 90 100

Normal (0-12)

Mild(13-22)

Moderate(23-32)

Severe(33-100)

OSDI Severity Grading

Miller KL, et al. 13th Annual Conference of theInternational 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)

Prevalence of OSD in Patients With Glaucoma Treated With Topical Medications: Study Results

Ranking Normal MildModerat

e Severe

Patients 325 134 84 87

Percentage 51.6% 21.3% 13.3% 13.8%

48.4%

OSDI Scores in Glaucoma Patients

Fechtner RD, et al. Cornea. 2010;29:618-621.

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

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

Patie

nts

(Per

cent

age)

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.

Number of MedicationsPercent With Dry Eye

Syndrome

0 medications 5

1 medication 11

2 medications 39

3 medications 40

Rossi GC, et al. Eur J Ophthalmol. 2009;19:572-579.

Quality of Life: Impact of Multiple Medications

Discussion of Answers to Poll Question

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

Case #1: Medications

Ocular Medications• Bimatoprost OU every evening

Other Medications• Escitalopram (for panic attacks)

Chief Complaint

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

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

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

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.

Case #1: Follow-up

• 4-week follow-up: BCVa improved to 20/60 left eye• 1-year follow-up: BCVa improved to baseline

Discussion of Answers to Poll Question

Discussion: Approach to Patient

• 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

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”

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.”

• 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

• 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

Interactive Poll Question

What are possible contributors to the external signs and symptoms?

Drug allergy Drug toxicity Dry eye Meibomian gland disease Preservative toxicity

• 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

Optic Nerve

<<Hold for photo>>

Visual Field: HVF 24-2

Discussion of Answers to Poll Question

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.

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®

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

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

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.

Discussion: Approach to Patient

Question-and-Answer Session With the Audience

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