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DICAL EDU
G ME
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UIN
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CME
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A CONTINUING
MEDICAL EDUCATION
PUBLICATION
ISSUE 14
Diagnosing Dry Eye
ERIC D. DONNENFELD, MD Dry eye affects tens
of millions of patients and is among the most common
reasons for eye care provider visits. Knowing what to
look for, how, and in whom (hint: everyone) can help
stem the tide of this quiet epidemic.
The exact prevalence of dry eye is difficult to ascertain,
for several reasons, including the absence of a single test (or
universally accepted sequence of tests) for its diagnosis, and
the fact that patient-reported symptoms are often poorly concordant with objective assessments.1 Estimates based on cohort
studies suggest that about 5% to 35% of adults worldwide have
dry eye, a rate that is expected to rise in the upcoming decades
as common risk factors, including advanced age, increase.2,3
Sometimes even higher estimates are cited, as dry eye symptoms are often camouflaged by other ocular surface conditions such as allergic conjunctivitis, surgery, and contact lens
discomfort; in addition, many patients—up to 60% of those
with objective evidence of dry eye—are pre-symptomatic.3
The landmark 2007 International Dry Eye Workshop
(DEWS) report offered the first thorough expert review around
dry eye, including a definition and characterization of two
broad forms—aqueous deficiency and evaporative—with an
emphasis on aqueous deficiency.4
Several years later, as it became clear that meibomian gland
function was critical to ocular surface health, proceedings
from the Meibomian Gland Workshop provided similarly
specific illumination around evaporative dry eye.5 These workshops, along with ongoing efforts in basic science and clinical
research, offer guidance to eye care providers in recognition,
diagnosis, and management of the condition.
FIGURE 1 Lid margin with inspissated meibomian glands and pasty
secretions indicative of MGD.
CATEGORIES AND MECHANISMS
Dry eye is generally divided into two main categories based
on the underlying cause: aqueous deficient and evaporative.4
Aqueous deficiency describes inadequate tear production by
the lacrimal glands. In contrast, evaporative dry eye relates to
impaired production of the lipid component of the tear film,
essential for lubricating the ocular surface and keeping the
aqueous layer from evaporating.3
To obtain CME credit for this activity, go to http://cme.ufl.edu/ed/self-study/toai/
See INSIDE for:
Ocular Surface Disease among Glaucoma Patients:
A Review
by Richard A. Lewis, MD
Topics in
OCULAReducational
ANTIINFLAMMATORIES
1
Supported by an unrestricted
grant from Shire.
Evaporative and mixed forms of
dry eyes are more prevalent than the
pure aqueous-deficient form. 6 This
article is focused on clinical findings
and diagnosis of evaporative dry eye
caused by meibomian gland disease;
disease management will be covered in
a subsequent article.
Evaporative dry eye is almost always
due to chronic disease of the meibomian
glands, often referred to as meibomian
gland disease or dysfunction (MGD).
Characterized by glandular duct obstruction and diminished quality and/or
quantity of sebaceous secretions, MGD
prevents the ocular surface from being
coated with its normal lipid layer, resulting in evaporation of aqueous tears and
a hyperosmolar tear film. MGD is also
associated with increased bacterial lipase activity, which break down meibum
lipids into their substructures, soaps and
fatty acids. A tear film containing soap
and acid certainly explains the common complaints among patients with
evaporative dry eye, namely tearing and
burning! These processes destabilize the
tear film resulting in increased evaporation, hyperosmolarity, bacterial growth
on the lid margin, and increased ocular
surface inflammation.5
MORBIDITY
Dry eye has been associated with reduced quality of life, including negative
effects on psychological, social, workrelated, and physical functioning.7,8
Difficulty with activities of everyday
living—including driving, reading,
working, and leisure activities—are
significantly more common among
patients with dry eye compared with
unaffected persons.7
Dry eye may also contribute to contact lens intolerance and poor outcomes
following ocular surgery.9,10 Moderate to
severe dry eye can compromise vision;
symptoms may include blurring, reduced contrast sensitivity, and impaired
visual acuity.8,11 Pre-symptomatic and
low-grade dry eye can progress and
cause increased symptoms and aggravation over time.
RISK FACTORS
US census data project a more than
2
Topics in OCULAR ANTIINFLAMMATORIES
TOPICS IN OCULAR ANTIINFLAMMATORIES, ISSUE 14
STATEMENT OF NEED
The control of ocular inflammation is a critical aspect of
medical and surgical ophthalmic practice. Despite their side
effects, antiinflammatory drugs are used to treat a very wide
range of conditions throughout the eye, from ocular surface
disease and allergic conjunctivitis to posterior segment
conditions. Use of antiinflammatory agents is also critical in
ocular surgery, contributing greatly to patient comfort and
positive outcomes.
The ocular antiinflammatory landscape is changing as
research reveals more about the role of inflammation in a
range of ocular conditions and as new antiinflammatory
agents enter the market.1,2 Twenty years ago, for example,
the idea of using a topical corticosteroid to treat dry eye and/
or allergic conjunctivitis was viewed with alarm; today, it is
accepted practice.
Although corticosteroids and nonsteroidal antiinflammatory
drugs (NSAIDs) have been the mainstays of the ocular
antiinflammatory armamentarium, a number of new agents
with novel mechanisms of action (and new ocular drug
delivery systems) have come to market or are being made
ready for market.3,4
As indications expand and change, and as new drugs,
formulations, and delivery systems become available, clinicians
require up-to-date protocols for drug selection and use. Such
protocols are also needed for routine (but nevertheless offlabel) uses of corticosteroids and NSAIDs because important
differences in efficacy, safety, and tolerability exist between
these classes and among formulations within each of these
classes.5,6
By putting the latest published evidence into the context of
current clinical practice, Topics in Ocular Antiinflammatories
equips ophthalmologists to maintain competencies and
narrow gaps between their actual and optimal inflammation
management practices, across the range of clinical situations
in which current and novel ocular antiinflammatories may
be used.
REFERENCES
1. Song JS, Hyon JY, Lee D, et al. Current practice pattern for
dry eye patients in South Korea: a multicenter study. Korean
Journal of Ophthalmology. 2014;28(2):115-21.
2. Ciulla TA, Harris A, McIntyre N, Jonescu-Cuypers C.
Treatment of diabetic macular edema with sustained-release
glucocorticoids: intravitreal triamcinolone acetonide,
dexamethasone implant, and fluocinolone acetonide
implant. Expert Opin Pharmacother. 2014;15(7):953-9.
3. Maya JR, Sadiq MA, Zapata LJ, et al. Emerging therapies for
noninfectious uveitis: what may be coming to the clinics. J
Ophthalmol. 2014;2014:310329.
4. Sheppard JD, Torkildsen GL, Lonsdale JD, et al, and the
OPUS-1 Study Group. Lifitegrast ophthalmic solution 5.0%
for treatment of dry eye disease: results of the OPUS-1 phase
3 study. Ophthalmology. 2014 Feb;121(2):475-83.
5. Fong R, Leitritz M, Siou-Mermet R, Erb T. Loteprednol
etabonate gel 0.5% for postoperative pain and inflammation
after cataract surgery: results of a multicenter trial. Clin
Ophthalmol. 2012;6:1113-24.
6. Singer M, Cid MD, Luth J, et al. Incidence of corneal melt in
clinical practice: our experience vs a meta-analysis of the
literature. Clin Exp Ophthalmol. 2012;S1:003.
OFF-LABEL USE STATEMENT This work may discuss off-label
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GENERAL INFORMATION This CME activity is sponsored by
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by an unrestricted educational grant from Shire.
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The University of Florida College of Medicine designates this
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There is no fee to participate in this activity. In order to
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FACULTY AND DISCLOSURE STATEMENTS
Marguerite B. McDonald, MD, FACS, (Faculty Advisor)
practices at Ophthalmic Consultants of Long Island, and is a
clinical professor of ophthalmology at the New York University
School of Medicine. She is also an adjunct clinical professor of
ophthalmology at Tulane University Health Sciences Center.
She’s a consultant to Allergan, Alcon, Abbott Medical Optics,
Bausch + Lomb, FOCUS Laboratories, Shire, OCuSOFT, and
Altaire.
John D. Sheppard, MD, MMSC, (Faculty Advisor) is the
president of Virginia Eye Consultants and is a professor of
ophthalmology, microbiology, and molecular biology at
the Eastern Virginia Medical School. He is also the research
director of the ophthalmology residency program and
clinical director of the Thomas R. Lee Center for Ocular
Pharmacology at Eastern Virginia Medical School. Dr. Sheppard
is on the advisory board for 1-800-DOCTORS, Alcon, Aldexa
Pharmaceuticals, Allergan, Bausch + Lomb, Clearside, EyeGate
Research, EyeRx Research, Imprimis Pharma, Inspire/Merck
Pharmaceuticals, Isis Pharmaceuticals, Kala Pharmaceuticals,
Lacrisciences, Lux Biosciences, Nicox, NovaBay, Novartis/Ciba
Vision, OcuCure Inc., Rapid Pathogen Screening, Santen, Shire,
Stemnion, Synedgen, Talia Technology, TearLab, TearScience,
and Vistakon. He has received grant/clinical research support
from Alcon, Aldexa Pharmaceuticals, Allergan, Bausch +
Lomb, EyeGate Research, EyeRx Research, Insite, Inspire/Merck
Pharmaceuticals, Isis Pharmaceuticals, Kala Pharmaceuticals,
Lux Biosciences, Pfizer, Rapid Pathogen Screening, Rutech,
Santen, Senju, Shire, Topcon, Vistacon, and Xoma/Servier. He
is a consultant for AbbVie, Aldexa Pharmaceuticals, Allergan,
Bio-Tissue, Eleven/Lexitas, Mededicus, NovaBay, Science Based
Health, Stemnion, TearLab, and TearScience. Dr. Sheppard is
on the speakers bureau for Abbvie, Alcon, Allergan, Bausch
+ Lomb, Bio-Tissue, Eleven/Lexitas, EyeGate Research,
Inspire/Merck Pharmaceuticals, Isis Pharmaceuticals, Kala
Pharmaceuticals, Lacrisciences, Lumenis, Mededicus, Nicox,
Novartis/Ciba Vision, Omeros, Pentavision, Pfizer, Rutech,
Santen, Sjo/Nicox, Talia Technology, TearLab, and TearScience.
He is an investor for Rapid Pathogen Screening and has
ownership of stock interest for BioLayer, Clearside, EyeGate
Research, EyeRx Research, Novabay, OccuHub, OcuCure Inc.,
Rapid Pathogen Screening, Stemnion, Strathspey Crowne, and
TearLab. He is a stock shareholder for 1-800-DOCTORS, Eyegate
Research, Lacrisciences, OcuCure Inc., Shire, and TearLab.
Eric Donnenfeld, MD, is a partner at Ophthalmic Consultants
of Long Island and clinical professor of ophthalmology at New
York University in New York, NY. Dr. Donnenfeld is a consultant
for Allergan, Alcon, Bausch + Lomb, Mati Therapeutics, and
Shire. He is also on the speakers’ bureau for Allergan, Alcon,
Bausch + Lomb, and Shire.
Richard A. Lewis, MD, is in private ophthalmology practice
in Sacramento, California. Dr. Lewis is chief medical officer at
Aerie and a consultant for Aerie, Allergan, Glaukos and Ivantis.
He is also on the speakers’ bureau for Carl Zeiss Meditec AG.
DISCLAIMER Participants have an implied responsibility
to use the newly acquired information to enhance patient
outcomes and professional development. The information
presented in this activity is not meant to serve as a guideline
for patient care. Procedures, medications, and other courses
of diagnosis and treatment discussed or suggested in this
activity should not be used by clinicians without evaluation
of their patients’ conditions and possible contraindications or
dangers in use, applicable manufacturer’s product information,
and comparison with recommendations of other authorities.
COMMERCIAL SUPPORTERS This activity is supported by an
unrestricted educational grant from Shire.
To obtain CME credit for this activity, go to http://cme.ufl.edu/ed/self-study/toai/
doubling of the population over the age of 65 years between
2014 (46 million) and 2060 (98 million).12 Advanced age is an
undisputed risk factor for the development of dry eye;13 thus,
unless prevention and early detection improve considerably, a
corresponding rise in dry eye prevalence should be anticipated.
Other dry eye correlates that have surfaced in clinical
studies include female sex; poorer self-reported general health;
certain systemic conditions including arthritis, allergic and
autoimmune conditions, and thyroid disease untreated with
hormonal therapy; and the use of certain medications including antidepressants and antihistamines.13,14
Despite increased risk, dry eye should not be considered
an inevitable consequence of aging; factors within patients’
sphere of influence may play a role.3 For example, lifestyle
and environmental factors—including prolonged computer
use (which decreases blink rate), low humidity environments,
and contact lens wear—have been associated with increased
risk for the development of dry eye.3
Diets deficient in omega-3-fatty acids—found in green
leafy vegetables, nuts, flaxseed oil, organ meats, and fish—may
contribute to dry eye. Omega-3-fatty acid supplementation
has been shown to improve the meibum fatty acid profile and
increase tear breakup time.15
Smoking may be an independent contributor to dry eye,
although data on the benefits of smoking cessation as it pertains to dry eye are lacking.16,17
Lastly, in patients with dry eye associated with an autoimmune disease such as Sjogren’s syndrome or rheumatoid
arthritis, systemic treatments that reduce systemic inflammation will sometimes reduce ocular inflammation and dry
eye as well.
FIGURE 2 Tear film “soapsuds” are a sign of increased bacterial lipase
acting on altered meibum associated with MGD.
DIAGNOSIS
Dry eye is a clinical diagnosis based upon history, physical
examination, and objective assessments of tear film, ocular
surface inflammation, and meibomian gland morphology
and function. Patients with dry eye present with a range of
symptoms that may fluctuate from day to day. Common
complaints include ocular surface irritation, visual fluctuation,
reflex tearing, or difficulty with prolonged visual tasks such as
CORE CONCEPTS
✦ Dry eye is due to aqueous deficiency, MGD, or both; MGD
and mixed forms are most prevalent.
✦ MGD is characterized by gland plugging, reduced quality
and quantity of meibum, hyperosmolar and unstable
tear film, bacterial overgrowth, and ocular surface
inflammation.
✦ Dietary fatty acid intake, reduced blink rate associated
with computer use, and environmental factors may all
contribute to dry eye.
✦ Dry eye may cause mild, moderate, or severe symptoms
including irritation and visual change.
✦ Patients may have reduced quality of life and difficulty
with daily tasks.
✦ Patients may have no symptoms but have objective
evidence of dry eye.
✦ Dry eye symptom questionnaires and point of service
tests improve the chance of detecting dry eye.
computer use or driving. Patients often ascribe the symptoms
they are experiencing to something other than dry eye.
One sensitive and efficient means for improving dry eye
diagnosis is to screen all patients with a brief questionnaire
that can be completed in the waiting room. A written symptom screen is more efficient (and possibly more precise) than
inquiring in an interview. In my practice, every patient who
comes to the office is asked to fill out a modified Ocular Surface
Disease Index (OSDI) questionnaire before I see them; three
or more positive answers raise concern for dry eye and, via
the protocol we use, empower my technician to order more
definitive testing including tear osmolarity, matrix metalloproteinase-9 (MMP9), and sometimes meibomian gland
imaging. Rapid point-of-care determination of tear osmolarity
and ocular surface inflammation biomarker MMP9 greatly
enhances the chance of detecting dry eye and increase efficiency in the office.18,19
A thorough external examination starts with the skin,
looking for evidence of systemic or local risk factors such as
psoriasis, rosacea, or other dermatologic conditions. The lid
margins should be examined for erythema and blood vessel
dilation that can accompany acute inflammatory MGD and
telangiectasia, which is present in chronic MGD.
The meibomian gland orifices should be examined for
plugging and inspissation of secretions and expressed to
evaluate the consistency of secretions; olive oil-looking secretions indicate normal function, whereas thick toothpaste-like
secretions indicate MGD (Figure 1). This is a technique that has
fallen off somewhat in clinical practice, which is unfortunate,
as it is a quick, immediate way to get actionable information
about meibomian gland health. The presence of a chalazion,
or plugged meibomian gland, is a red flag for more widespread
MGD.
My practice is to then examine the tear film, looking at
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Topics in OCULAR ANTIINFLAMMATORIES
3
meniscus height, lid apposition, and evidence of any debris.
I look carefully for a “soapsuds” appearance in the tear film,
a sign of increased lipase activity associated with MGD
(Figure 2). In addition, I often perform a test of tear fi lm
breakup time to assess tear film stability.
Lissamine green staining is useful to assess the extent of
ocular surface damage and to rule out disorders that can mimic
dry eye such as entropion, ectropion, floppy eye syndrome,
and conjunctival chalasis. With the exception of assessing
aqueous deficiency dry eye severity, I generally do not rely on
Schirmer testing.
The questionnaire, exam, and selected tests can be administered in surprisingly little time, leaving me plenty of time to
discuss therapy with patients who have positive results.
CONCLUSION
Dry eye, especially due to meibomian gland disease, is very
common and likely affects more of our patients than those
who carry the diagnosis. Developing an in-office protocol
for diagnosing dry eye, including a screening process for all
patients, will lead to better care for patients and improved
outcomes following ocular surgery.
Eric Donnenfeld, MD, is a partner at Ophthalmic Consultants of Long Island
and clinical professor of ophthalmology at New York University in New York,
NY. Dr. Donnenfeld is a consultant for Allergan, Alcon, Bausch + Lomb, Mati
Therapeutics, and Shire. He is also on the speakers’ bureau for Allergan, Alcon,
Bausch + Lomb, and Shire. Medical writer Noelle Lake, MD, assisted in the
preparation of this manuscript.
REFERENCES
1. Nichols KK, Nichols JJ, Mitchell GL. The lack of association between signs
and symptoms in patients with dry eye disease. Cornea. 2004;23:762-70.
2. The epidemiology of dry eye disease: report of the Epidemiology Subcom-
4
Topics in OCULAR ANTIINFLAMMATORIES
mittee of the International Dry Eye WorkShop. Ocul Surf. 2007;5:93-107.
3. Bron AJ, Tomlinson A, Foulks GN, et al. Rethinking Dry Eye Disease: A
Perspective on Clinical Implications. Ocul Surf. 2014;12(2S):S1-31.
4. The definition and classification of dry eye disease: report of the Definition
and Classification Subcommittee of the International Dry Eye WorkShop
(2007). Ocul Surf. 2007;5(2):75-92.
5. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on
meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis
Sci. 2011;52:1922-9.
6. Lemp MA, Crews LA, Bron AJ, et al. Distribution of aqueous-deficient and
evaporative dry eye in a clinic-based patient cohort: A retrospective study.
Cornea. 2012;31(5):472-8.
7. Miljanovic B, Dana R, Sullivan DA, et al. Impact of dry eye syndrome on
vision-related quality of life. Am J Ophthalmol. 2007;143:409-15.
8. Uchino M, Schaumberg DA. Dry eye disease: impact on quality of life and
vision. Curr Ophthalmol Rep. 2013;1:51-7.
9. Li XM, Hu L, Hu J, et al. Investigation of dry eye disease and analysis of the
pathogenic factors in patients after cataract surgery. Cornea. 2007;26(9 Suppl
1):S16-20.
10. Konomi K, Chen LL, Tarko RS, et al. Preoperative characteristics and a
potential mechanism of chronic dry eye after LASIK. Invest Ophthalmol Vis
Sci. 2008;49:168-74.
11. Montés-Micó R. Role of the tear film in the optical quality of the human eye.
J Cataract Refract Surg. 2007;33:1631-5.
12. 2014 National Population Projections: Publications. http://www.census.
gov/population/projections/data/national/2014/publications.html. Accessed
April 7, 2016.
13. Moss SE, Klein R, Klein BE. Long-term incidence of dry eye in an older
population. Optom Vis Sci. 2008;85:668-74.
14. Paulsen AJ, Cruickshanks KJ, Fischer ME, et al. Dry eye in the beaver dam
offspring study: prevalence, risk factors, and health-related quality of life. Am
J Ophthalmol. 2014;157:799-806.
15. Macsai MS. The role of omega-3 dietary supplementation in blepharitis and
meibomian gland dysfunction (an AOS thesis). Trans Am Ophthalmol Soc.
2008;106:336-56.
16. Moss SE, Klein R, Klein BE. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol. 2000;118:1264-8.
17. Klein BE, Klein R. Lifestyle exposures and eye diseases in adults. Am J
Ophthalmol. 2007;144:961-9.
18. Lemp MA, Bron AJ, Baudouin C, et al. Tear osmolarity in the diagnosis and
management of dry eye disease. Am J Ophthalmol. 2011;151(5):792-8.
19. Sambursky R, Davitt WF 3rd, Latkany R, et al. Sensitivity and specificity
of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing
inflammation related to dry eye. JAMA Ophthalmol. 2013;131(1):24-8.
To obtain CME credit for this activity, go to http://cme.ufl.edu/ed/self-study/toai/
Ocular Surface Disease among
Glaucoma Patients: A Review
RICHARD A. LEWIS, MD Chronic topical
hypotensive exposure can exacerbate ocular surface
disease. Detecting and addressing ocular surface issues
in glaucoma patients is one important way that eye care
providers can enhance their care as they simultaneously
work to maintain IOP.
The state of the ocular surface has always taken a back seat
to the chief consideration in the management of glaucoma:
maintaining good health of the optic nerve and preserving
vision. However, ocular surface disease is not trivial; it has
been implicated in reducing quality of life, contact lens tolerability, and ocular surgical outcomes.1-4 Importantly, ocular
surface disorders can have a deleterious impact on visual
function and acuity.2,5
Ocular surface disease is widespread in the glaucoma
population, and while awareness is increasing, it is almost
certainly underdiagnosed. Among medically treated glaucoma
patients, one study showed that 80% also had meibomian
gland disease.6 Other estimates show ocular surface disease
prevalence of between 40% to 85%—many cases of which are
severe—within the glaucoma population.7 Advancing age
predisposes to both conditions; in addition, long-term topical
medications may induce ocular surface changes via inflammatory, allergic, and/or toxic mechanisms.8
MEDICATIONS
The glaucoma population—indeed, any group of patients
dependent on chronic application of topical ocular medication—is at risk for medication-induced ocular surface damage.
The extent of medication exposure (eg, number of therapies,
number of drops, and treatment duration) has been shown to
correlate with the effect on the ocular surface.9,10 In a prospective controlled trial, greater exposure to topical medications
for lowering intraocular pressure (IOP), quantified as number
of drops per week multiplied by treatment years, was associated with significantly worse ocular surface disease compared
with lesser exposed glaucoma patients.9 In a separate study,
patients on multiple topical anti-glaucoma medications had
more severe ocular surface symptoms compared with patients
on monotherapy.10
The most commonly cited cytotoxic agent in ocular
medication is benzalkonium chloride (BAK), a quaternary
ammonium compound that serves as a preservative and antibacterial agent in many ophthalmic preparations.11 In vitro
studies show that BAK contributes to corneal and conjunctival
cell apoptosis and ocular surface inflammation in a dosedependent fashion.8 Animal studies reveal that BAK induces
CORE CONCEPTS
✦ Ocular surface disruption is common among glaucoma
patients; it may stem from age-related ocular surface
disorders or chronic medication use.
✦ Most glaucoma eye drops, especially ones containing
BAK, can cause minor disruptions in the ocular surface
and exacerbate dry eye signs and symptoms.
✦ Treating pre-existing dry eye and other ocular surface
conditions may help improve tolerability and prevent
noncompliance.
corneal neurotoxicity, inflammation, and reduced aqueous
tear production.12 And clinical studies reveal that dry eye
signs and symptoms improve when patients are switched from
BAK-preserved medications to BAK-free formulations.13 BAK
may be a contributing factor to conjunctival allergy, dry eye
disease, and failure of glaucoma surgery in patients on longterm topical ocular therapy. Preservative-free anti-glaucoma
medications are available; however lack of coverage by insurance providers makes them more expensive for patients and
thus infrequently prescribed. Patients who can afford the additional, out of pocket expense may find BAK-free therapies
less irritating to the ocular surface.
Ocular surface related side effects vary within each class
of agent, which may relate to the active molecule, the type and
concentration of preservative, or due to any component of the
medication vehicle. A study compared the effect of four commercially available prostaglandin analog (PGA) agents—bimatoprost, tafluprost, travoprost, and latanoprost—on normal
human conjunctival cell culture in vitro and found that all four
induced some level of concentration-dependent cytotoxicity,
with preservative-free tafluprost inducing the least damage.14
Among BAK-containing PGA agents, latanoprost was the
least cytotoxic.
The ocular surface may also be susceptible to the active
ingredient of antihypotensive agents, many of which are vasodilatory.7,15 To a varying degree, PGAs cause conjunctival
hyperemia as a side effect in some patients; similarly, alpha
agonists can cause rebound conjunctival redness following an
initial blanching phase.15,16 Redness and other ocular surface
manifestations have a negative influence on quality of life and
can interfere with medication adherence. The long-term effect
on the tear film and ocular surface is unknown.8
COMPLIANCE
Ocular surface conditions present in a variety of ways,
including ocular irritation, redness, discharge, visual
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Topics in OCULAR ANTIINFLAMMATORIES
5
complaints, and related behaviors such as repeatedly rubbing the eye. Symptoms may start within the first few days of
taking a new therapy or present after months to years on the
same therapy.
In some patients, ocular surface symptoms play a role in
medication nonadherence, a multifactorial and vexing problem within the glaucoma population.17 Research has shown
that only 33% to 39% of patients persist in taking ocular
hypotensive medication as prescribed by 12 months after
initiation.18 It not hard to imagine how a patient with daily
medication-related symptoms such as stinging or burning—
or other disincentive such as cost, denial, difficulty instilling
drops, or erroneous belief in the inevitability of blindness—
might struggle with adherence to a treatment prescribed in
perpetuity for a symptomless disease. Although no studies
have proven that decreased hypotensive medication adherence
leads to vision loss, one would logically assume that patients
who discontinue treatment can expect outcomes similar to
untreated patients.
MANAGEMENT
Maintaining ocular surface health should be part and
parcel of glaucoma management for the reasons mentioned:
ocular comfort and quality of life, surface-related visual clarity,
and optimal anti-glaucoma medication adherence and success.
In addition to routine IOP-related testing and management,
every clinic visit for patients with glaucoma should include
a thorough physical examination of the ocular surface and
questions about ocular surface symptoms and medication
tolerance. It is also useful to inquire to the patient, family, or
caregiver about medication adherence; suboptimal adherence,
if uncovered, may be a tip off for tolerability issues related to
the ocular surface.
Patients with signs or symptoms of ocular surface disease
should be assessed for treatable underlying disorders whether
related or unrelated to glaucoma management. In particular,
look carefully for evidence of blepharitis and dry eye disease
which are common comorbidities among older patients. Also
consider less common culprits such as seasonal and perennial allergies and exposure to products such as makeup that
may contact the eye. As discussed, consider the possibility of
medication-induced ocular surface disruption.
For treatment, choose the simplest, most definitive method
that targets the underlying cause or causes. Blepharitis treatment is dictated by the subtype and should always include lid
hygiene. Also, patients should be advised to avoid rubbing
eyes, as fingers can be a source of infection. Patients with
blepharitis who wear eye makeup may need to temporarily
stop or at least replace any products which might have become
contaminated. Dry eye disease must also be treated according to its particular type. It may respond to topical moisturizers or anti-inflammatory medication; punctal plugs may be
preferable when administering drops is problematic.19 There
is some data to support prescribing oral omega-3-fatty acid
supplementation (with flaxseed or fish oil) to reduce ocular
6
Topics in OCULAR ANTIINFLAMMATORIES
surface inflammation in patients with meibomian gland disease and/or blepharitis.20
For some patients, switching anti-glaucoma medication
may help; for example, a patient with redness and irritation
on brimonidine may benefit from switching to a PGA. Some
patients benefit from laser trabeculoplasty or glaucoma surgery to reduce or eliminate topical medication dependency.
Patients with cataract, glaucoma, and medication-related
ocular surface disease may make excellent candidates for a
combination cataract surgery/minimally invasive glaucoma
surgery (MIGS) which can reduce dependence on ocular
hypotensive medication.21 Clearing up the ocular surface preoperatively using antiinflammatory medication is important
for accurate preoperative calculations and best postoperative
visual outcomes.22 In the future, improved MIGS methods
and delivery of anti-glaucoma medication via intracameral
injection (or other sustained delivery system that bypasses
the ocular surface) could be instrumental in reducing ocular
surface stress and adherence issues that accompany today’s
daily drop regimens.
CONCLUSION
Ocular surface disease is multifactorial and variable in its
presentation in glaucoma patients. Physicians must remember
to keep the front of the eye in mind though their focus is on
the back.
Richard A. Lewis, MD, is in private ophthalmology practice in Sacramento,
California. Dr. Lewis is chief medical officer at Aerie and a consultant for Aerie,
Allergan, Glaukos and Ivantis. He is also on the speakers’ bureau for Carl Zeiss
Meditec AG. Medical writer Noelle Lake, MD, assisted in the preparation of
this manuscript.
REFERENCES
1. Miljanovic B, Dana R, Sullivan DA, et al. Impact of dry eye syndrome on
vision-related quality of life. Am J Ophthalmol. 2007;143:409-15.
2. Uchino M, Schaumberg DA. Dry eye disease: impact on quality of life and
vision. Curr Ophthalmol Rep. 2013;1:51-7.
3. Li XM, Hu L, Hu J, Wang W. Investigation of dry eye disease and analysis
of the pathogenic factors in patients after cataract surgery. Cornea. 2007;26(9
Suppl 1):S16-20.
4. Konomi K, Chen LL, Tarko RS, et al. Preoperative characteristics and a
potential mechanism of chronic dry eye after LASIK. Invest Ophthalmol Vis
Sci. 2008;49:168-74.
5. Montés-Micó R. Role of the tear film in the optical quality of the human eye.
J Cataract Refract Surg. 2007;33:1631-5.
6. Uzunosmanoglu E, Mocan MC, Kocabeyoglu S, et al. Meibomian Gland
Dysfunction in Patients Receiving Long-Term Glaucoma Medications.
Cornea. 2016 Apr 6. Epub ahead of print.
7. Bron AJ, Tomlinson A, Foulks GN, et al. Rethinking dry eye disease: A
perspective on clinical implications. Ocul Surf. 2014;12(2S):S1-31.
8. Baudouin C, Labbé A, Liang H, et al. Preservatives in eyedrops: the good,
the bad and the ugly. Prog Retin Eye Res. 2010;29:312-34.
9. Saade CE, Lari HB, Berezina TL, et al. Topical glaucoma therapy and ocular
surface disease: a prospective, controlled cohort study. Can J Ophthalmol.
2015;50:132-6.
10. Fechtner RD, Godfrey DG, Budenz D, et al. Prevalence of ocular surface
complaints in patients with glaucoma using topical intraocular pressurelowering medications. Cornea. 2010;29:618-21.
11. Yee RW, Norcom EG, Zhao XC. Comparison of the relative toxicity of
To obtain CME credit for this activity, go to http://cme.ufl.edu/ed/self-study/toai/
travoprost 0.004% without benzalkonium chloride and latanoprost 0.005%
in an immortalized human cornea epithelial cell culture system. Adv Ther.
2006;23:511-9.
12. Sarkar J, Chaudhary S, Namavari A, et al. Corneal neurotoxicity due to topical
benzalkonium chloride. Invest Ophthalmol Vis Sci. 2012;53:1792-802.
13. Horsely MB, Kahook MY. Effects of prostaglandin analog therapy on the
ocular surface of glaucoma patients. Clin Ophthalmol. 2009:3;291-5.
14. Pérez-Roca F, Rodrigo-Morales E, Garzón I, et al. Effects of four formulations
of prostaglandin analogs on eye surface cells: a comparative study. PLoS One.
2015;10:e0129419.
15. Stewart WC, Kolker AE, Stewart JA, et al. Conjunctival hyperemia in
healthy subjects after short-term dosing with latanoprost, bimatoprost, and
travoprost. Am J Ophthalmol. 2003;135:314-20.
16. Honrubia F, García-Sánchez J, Polo V, et al. Conjunctival hyperaemia with
the use of latanoprost versus other prostaglandin analogues in patients with
ocular hypertension or glaucoma: a meta-analysis of randomised clinical
trials. Br J Ophthalmol. 2009;93:316-21.
17. Reardon G, Kotak S, Schwartz GF. Objective assessment of compliance and
persistence among patients treated for glaucoma and ocular hypertension: a
systematic review. Patient Prefer Adherence. 2011;5:441-63.
18. Schwartz GF, Quigley HA. Adherence and persistence with glaucoma
therapy. Surv Ophthalmol. 2008;53 Suppl1:S57-68.
19. Ervin AM, Wojciechowski R, Schein O. Punctal occlusion for dry eye syndrome. Cochrane Database Syst Rev. 2010;(9):CD006775.
20. Macsai MS. The role of omega-3 dietary supplementation in blepharitis and
meibomian gland dysfunction (an AOS thesis). Trans Am Ophthalmol Soc.
2008;106:336-56.
21. Brandão LM, Grieshaber MC. Update on Minimally Invasive Glaucoma
Surgery (MIGS) and New Implants. J Ophthalmol. 2013;2013:705915.
22. Kim P, Plugfelder S, Slomovic AR. Top 5 pearls to consider when implanting advanced-technology IOLs in patients with ocular surface disease. Int
Ophthalmol Clin. 2012;52:51-8.
To obtain CME credit for this activity, go to http://cme.ufl.edu/ed/self-study/toai/
Topics in OCULAR ANTIINFLAMMATORIES
7
EXAMINATION QUESTIONS TOPICS IN OCULAR ANTIINFLAMMATORIES | ISSUE 14
This CME program is sponsored by the University of Florida College of Medicine and supported by an unrestricted educational
grant from Shire. Directions: Select the one best answer to each question in the exam (Questions 1–10) and in the evaluation
(Questions 11–16) below by circling one letter for each answer. Participants must score at least 80% on the questions and
complete the entire Evaluation section on the form below. The University of Florida College of Medicine designates this
enduring material for a maximum of 1.0 AMA PRA Category 1 Credit™. There is no fee to participate in this activity. You can
take the test online at http://cme.ufl.edu/ed/self-study/toai/.
1. Which of the following
procedures can reduce the
need for ocular hypotensive
medication?
A. MIGS with
phacoemulsification
B. MIGS without
phacoemulsification
C. Both A and B
D. Neither A nor B
2. Pathognomonic signs of
MGD include which of the
following?
A. “Soap suds” appearance
to the tear film
B. Chalazion
C. Conjunctival chalasis
D. Both A and B
3. Which of the following
is NOT a component of
meibomian gland disease
pathophysiology?
A. Ocular surface
inflammation
B. Hypoosmolarity
C. Bacterial growth on lid
margins
D. Altered meibum
4. Managing ocular surface
disease in glaucoma patients
may improve:
A. Quality of life
B. Anti-glaucoma
medication adherence
C. Surgical outcomes
D. All of the above
5. Which of the following
has NOT been shown to
correlate with degree of
ocular surface disease in
glaucoma patients?
A. Number of topical
medications
B. Intensity of treatment
(drops per week times
years of treatment)
C. Weeks of therapy missed
D. None of the above
6. Which of the following
forms of dry eye is caused by
inadequate tear production?
A. Meibomian gland disease
B. Evaporative
C. Aqueous deficiency
D. None of the above
EXAMINATION ANSWER SHEET 8. Which of the following
would likely NOT benefit
patients with ocular surface
disease related to antiglaucoma medication?
A. Sustained anti-glaucoma
drug delivery via punctal
plug
B. Sustained anti-glaucoma
drug delivery via
intracameral injection
C. Improved MIGS
procedures
D. All of the above
9. Which of the following is
NOT a risk factor for the
development of dry eye?
A. Advanced age
B. Autoimmune disease
C. Antidepressant use
D. Male sex
EVALUATION:
1=Poor 2=Fair 3=Satisfactory 4=Good 5=Outstanding
11. Extent to which the activity met the identified
Objective 1: 1 2 3 4 5
Objective 2: 1 2 3 4 5
Objective 3: 1 2 3 4 5
Objective 4: 1 2 3 4 5
1.A B C D
6.A B C D
12. Rate the overall effectiveness of how the activity:
Related to my practice: 1 2 3 4 5
Will influence how I practice: 1 2 3 4 5
Will help me improve patient care: 1 2 3 4 5
Stimulated my intellectual curiosity: 1 2 3 4 5
Overall quality of material: 1 2 3 4 5
Overall met my expectations: 1 2 3 4 5
Avoided commercial bias/influence: 12345
2.A B C D
7.A B C D
13. Will the information presented cause you to make any
changes in your practice? Yes No
3.A B C D
8.A B C D
14. If yes, please describe: __________________________
4.A B C D
9.A B C D
5.A B C D
10.A B C D
15. How committed are you to making these changes?
12345
ANSWERS:
Topics in OCULAR ANTIINFLAMMATORIES
10. Ocular surface disruption
among patients taking
topical hypotensive
medication may:
A. Be caused by exposure to
the preservative
B. Be caused by exposure to
the active moiety
C. Occur within any time
frame
D. All of the above
TOPICS IN OCULAR ANTIINFLAMMATORIES | ISSUE 14
This CME activity is jointly sponsored by the University
of Florida and Candeo Clinical/Science Communications,
LLC, and supported by an unrestricted educational grant
from Shire. Mail to: University of Florida CME Office, PO
Box 100233, Gainesville, FL 32610-0233. DIRECTIONS:
Select the one best answer for each question in the
exam above (Questions 1–10). Participants must score
at least 80% on the questions and complete the entire
Evaluation (Questions 11–16) to receive CME credit.
CME exam expires August 31, 2017.
8 7. Which of the following
is a common presenting
complaint among patients
with dry eye?
A. Burning
B. Blurry vision
C. No symptoms
D. All of the above are
common dry eye
presentations
________________________________________________
16.Are future activities on this topic important to you?
Yes No
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