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
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.
Prevalence of Dry Eye and Ocular Surface
Disease
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 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 1.182.80) 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.
Prevalence of Dry Eye Among the Elderly:
Results
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)
Gender
Male
13.3% (1052)
Female
15.6% (1430)
Schein OD, et al. Am J Ophthalmol. 1997:124:723-728.
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.
Interactive Poll Question
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
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.
Number (%) of Patients With Each Result
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.
Patients With Symptoms (%)
Symptoms vs Signs of OSD
Clinical Tests
Leung EW, et al. J Glaucoma. 2008;17:350-355.
Prevalence of OSD in Patients With
Glaucoma: Results
OSDI Scores in Glaucoma Patients
Ranking
Normal
Mild to
Moderate
Patients
41
33
27
41%
33%
27%
Percentage
59%
Leung EW, et al. J Glaucoma. 2008;17:350-355.
Severe
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 pressurelowering medication(s)
• Patients completed OSDI survey while in the office
Fechtner RD, et al. Cornea. 2010;29:618-621.
OSDI Severity Grading
Normal Mild Moderate
(0-12) (13-22) (23-32)
0
10
20
30
Severe
(33-100)
40
50
60
70
80
Total OSDI Score =
(Sum of Score for All Questions Answered) X (25)
(Total # of Questions Answered)
Miller KL, et al. 13th Annual Conference of the
International Society for Quality of Life Research. 2006. Abstract 1540.
90
100
Prevalence of OSD in Patients With Glaucoma
Treated With Topical Medications: Study Results
OSDI Scores in Glaucoma Patients
Ranking
Normal
Mild
Moderate
Severe
Patients
325
134
84
87
51.6%
21.3%
13.3%
13.8%
Percentage
48.4%
Fechtner RD, et al. Cornea. 2010;29:618-621.
Ocular Surface Disease and Topical
Medications for Glaucoma
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.
Patients (Percentage)
OSDI and Number of BAK-Containing Eyedrops
Number of BAK-Containing Eyedrops
BAK = benzalkonium chloride
Leung EW, et al. J Glaucoma. 2008;17:350-355.
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.
Quality of Life: Impact of Multiple
Medications
Number of Medications
Percent 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.
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
Case #2: An 86-Year-Old Man
• 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: 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.”
Case #2. Ocular Examination
• 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. Slit Lamp 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)
Interactive Poll Question
What are possible contributors to the external
signs and symptoms?
 Drug allergy
 Drug toxicity
 Dry eye
 Meibomian gland disease
 Preservative toxicity
Case #2. Dilated Examination and
Diagnostic Testing
• Lens: OU, IOL
• Disc: OD, CDR 0.9
OS, CDR 0.5- (V&H)
• Retina: OD old BRVO
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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