Dry Eye
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1Learning Objectives
At the end of this class the students shall be able to :
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?Define dry eye disease.
? Understand predisposing and aetiological factors
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responsible for dry eye disease? Comprehend clinical features and tests for the above
condition
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? Understand fundamentals of managing dry eye
depending on the severity of disease
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2
What is Dry Eye Disease?
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?Dry eye disease (DED) is a condition causedby many factors that result in inflammation of
the eye and tear-producing glands.
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?Inflammation can decrease the ability of the
eye to produce normal tears that protect the
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surface of the eye and keep it moist andlubricated.
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3
Definition
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qDry eye is not a trivial complaint. It can cause significantdiscomfort and affect quality of life significantly.
q In 1995 the National Eye Institute defined dry eye
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disease (DED) as " a disorder of the tear film due to tear
deficiency or excessive tear evaporation which causes
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damage to the interpalpebral ocular surface and isassociated with symptoms of ocular discomfort".
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DefinitionqIn 2007 the International Dry Eye Workshop
defined it as
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" a multifactorial disease of the tears and ocular surfacethat results in symptoms of discomfort, visual disturbance,
and tear film instability with potential damage to the ocular
surface. It is accompanied by increased osmolarity of the
tear film and inflammation of the ocular surface."
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5
Dry Eye is more than a red eye.
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Dry Eye
Affects Quality of Life
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7The Healthy Eye
Normal tearing
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depends on a
neuronal feedback loop Secretomotor
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Nerve ImpulsesLacrimal
Glands
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Tears Support and Maintain
Ocular Surface
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Ocular SurfaceNeural Stimulation
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Dry Eye Disease: An Immune-Mediated
Inflammatory Disorder
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Inflammation disrupts
normal neuronal
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Lacrimal Glands:control of tearing
? Neurogenic
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Inflammation
Interrupted Secretomotor
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? T-cell ActivationNerve Impulses
? Cytokine Secretion into
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Tears
Tears Inflame Ocular Surface
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CytokinesDisrupt Neural Arc
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Multiple Factors in Dry Eye
?Transient discomfort
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?May be stimulated byenvironmental conditions
?Inflammation and ocular
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surface damage
?Altered tear film composition
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1de Paiva and Pflugfelder. In: Dry Eye and Ocular Surface Disorders.1 02004;2Pflugfelder et al. In: Dry Eye and Ocular Surface Disorders. 2004.
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Role of Inflammationin Chronic Dry Eye
?Inflammation may be present but not clinically apparent
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?Cycle of inflammation and dysfunction?If untreated, inflammation can damage lacrimal gland and
ocular surface
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? Consequences:
?Lower tear production
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?Altered corneal barrier function11
Pflugfelder. Am J Ophthalmol. 2004.
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Healthy Tears
? A complex mixture of
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proteins, mucin, andelectrolytes
?Antimicrobial proteins:
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Lysozyme, lactoferrin
?Growth factors &
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suppressors ofinflammation: EGF, IL-1RA
?Soluble mucin secreted by
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goblet cells for viscosity
?Electrolytes for proper
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osmolarityStern et al. In: Dry Eye and Ocular Surface Disorders. 2004.
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Image adapted from: Dry Eye and Ocular Surface Disorders. 2004.
Tears in Chronic Dry Eye
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? Decrease in many proteins
? Decreased growth factor
concentrations
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? Altered cytokine balance
promotes inflammation
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? Soluble mucin 5AC greatlydecreased
? Due to goblet cel loss
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? Impacts viscosity oftear film
? Proteases activated
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? Increased electrolytesSolomon et al. Invest Ophthalmol Vis Sci. 2001.
Zhao et al. Cornea. 2001.
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Ogasawara et al. Graefes Arch Clin Exp Ophthalmol. 1996.
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Image adapted from: Dry Eye and Ocular Surface Disorders. 2004.Who Is Likely to Have Dry Eye?
How Do We Diagnose It?
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Dry Eye: Multifactorial nature
Elderly woman
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TakingPost
glaucoma
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menopausal
medications Contact lens
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userWorking for long
Air-conditioned
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hours in front of
environment
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computer15
Patient Types with High Incidence of
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Dry Eye Disease
?Women aged 50 or older
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?Women using postmenopausal hormonereplacement therapy
?Those with ocular co-morbidities ?
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xerophthalmia, cicatrical pemphigoid,
atopic keratoconjunctivitis, ocular rosacea
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?Contact lens wearers?Smokers
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Dry Eye Disease: Predisposing Factors?Ageing
?Menopause - Decreased Androgens
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?Al ergy Response
?Environmental Stresses
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? Contact Lens Wear? Low Humidity: Heating/AC
? Wind
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? Lack of Sleep
? Air Pol ution
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? Use of Computer Terminals?Ocular Surgery (LASIK, Corneal Transplant)
?Medications
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Medications That May Contribute
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to Dry Eye Disease?Systemic
Topical
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?Anti-hypertensives
? Preservatives in
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?Anti-androgensTears
?Anti-cholinergics
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?Antidepressants?Cardiac Anti-arrhythmic Drugs
?Parkinson's Disease Agents
?Antihistamines
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Dry Eye Disease:
Autoimmune Triggers
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?Systemic Autoimmunity
?Rheumatoid Arthritis
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?Lupus?Sj?gren's Syndrome
?Graft vs. Host Disease
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?All can result in immune-mediated inflammation in the eye.
?Inflammatory mediators secreted into tears.
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?Promote inflammation of ocular surface.19
Current Triggers of Dry Eye Disease
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Environment
Rheumatoid
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MedicationsArthritis
Contact Lens
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Irritation
Inflammation
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LupusSurgery
Sj?gren's
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Graft vs Host
Tear
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Deficiency/Postmenopause
Meibomian
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Instability
Gland Disease
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Symptoms of Ocular Surface Disease20
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Dry Eye Disease Symptoms
?Discomfort
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?Dryness?Burning, Stinging
?Foreign-Body Sensation
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?Gritty Feeling, Stickiness
?Blurry Vision
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?Photophobia, Itching,?Redness
Note: Symptoms seldom correlate with clinical signs
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Clinical Presentation Can Vary in Severity
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MildSevere
Slitlamp
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Fluorescein
Dye Stain
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24Slit lamp examination
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?Increased debris/mucin strands in tear film?Inspection of tear meniscus at lid margin.
?Normal thickness ? 1mm, convex.
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? < 0.5mm ? tear deficiency.
?In severe cases ? Marginal tear meniscus is
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concave, small & absent.25
Filaments ( comma shaped) over corneal surface which move
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on blinking
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Mucous plaques ? semi-transparent, white to grey, slightly
elevated lesions
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Stain with rose bengal.27
?Bulbar conjunctival vessels may be dilated Red Eye
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?Corneal surface ? irregularity/ dry areas.
?Blinking ? incomplete/infrequent.
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?Meibomian gland dysfunction/ blepharitis.28
Diagnostic Tests
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?Appropriate choice of test helps the clinician toarrive at an accurate diagnosis as well as for
individualization of therapy.
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1. Basic Secretion Test
?Purpose ? to measure basal secretion by eliminating
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reflex tearing.?< 5mm hyposecretion.
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2. Schirmer's Test I
?Purpose ? measurement of the total (reflex + basal) tear
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secretion.?Eyes should not be manipulated before starting this test.
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Schirmer Test
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?Normal wetting 10-15 mm
?Dry Eye
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?Mild9-14 mm
?Moderate
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4-8 mm
?Severe
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< 4 mm34
Schirmer Test II
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?Purpose ? to ascertain reflex secretion.?Measured after 2 minutes.
?After Strips are placed in eye un-anaeasthetized
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nasal mucosa is irritated.
?Less than 15 mm failure of reflex secretion.
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35Rose Bengal staining
?Purpose - to ascertain indirectly, the presence
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of reduced tear volume by the detection of
damaged epithelial cells.
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?Useful in early stages of conjunctivitis siccaand keratoconjunctivitis sicca syndrome.
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Rose Bengal Staining
? Positive test ? show triangular stipple staining of nasal and temporal
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bulbar conjunctiva in the interpalpebral area & possible punctate
staining of the cornea (esp. lower 2/3rd).
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37Rose Bengal Staining
?False positive ?
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?Chronic conjunctivitis
?Acute chemical conjunctivitis, secondary to hair spray
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use and drugs such as tetracaine & cocaine?Exposure keratitis
?Superficial punctate keratitis, secondary to toxic or
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idiopathic phenomena.
?Foreign bodies in conjunctiva.
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38Modified van Bijsterveld conjunctival rose bengal grading map.
The density of rose bengal staining is recorded on a scale of 0-3 for
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each of 6 areas of the conjunctiva, and then summed for each eye.
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Fluoroscein Dye Test40
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Tear film Break-up time (BUT)? Time of appearance of first dry spot from the last
blink.
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? Tests for stability of tear film.
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42Tear film Break-up time (BUT)
?Wetting time > 20 s Normal Tear film stability.
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?BUT Averages b/w 25-30 s in Normal individuals.?Women < Men
?Less in elderly
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?BUT < 10 s significant tear film instability.
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NEI Workshop gradingEfron Scale
? Grade 0 = no staining
? Grade 1 = trace staining
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? Grade 2 = mild staining? Grade 3 = moderate
staining
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? Grade 4 = severestaining
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Other tests
? Practical Double Vital Staining for Ocular Examination
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? Corneal Residence Time Test or Tear Clearance Rate (TCR)? Tear Function Index
? Tear Film Osmolarity Test
? Tear Lactofer in Test
? Tear Lysozyme Test
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? Impression Cytology? Biopsy of Labial Accessory Salivary Glands
? Ocular Ferning Test
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Tear Film Osmolarity Test
?Tear Samples are collected with hand-drawn micropippete
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from inferior marginal tear strip, without disturbing theocular surface.
?Tear osmolarity is determined by a freezing point
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depression osmometer.
?Normal ? 295 to 309 mOsm/litre
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?Elevated in Dry Eyes.46
Impression Cytology
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?To determine the goblet cell density of bulbar & palpebralconjunctiva.
?A strip of filter paper is gently pressed against the bulbar &
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palpebral conjunctiva with a glass end.
?Staining with Schiff's agent & counter staining with
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haemotoxylin graded with microscope.?Dry Eyes goblet cell counts.
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DEWS Dry eye severity grading scheme
Dry Eye Severity
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Level1
2
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3
4
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Discomfort,Mild and/or
Moderate
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Severe frequent Severe and/or
severity
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episodic;episodic or
or constant
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disabling
& frequency
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occurs underchronic, stress or without stress
and constant
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environmental
no
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stressstress
Visual symptoms None or episodic Annoying and/or Annoying,
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Constant and/or
mild fatigue
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activity-limitingchronic
possibly disabling
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episodic
and/or constant,
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limiting activityConjunctival
None to mild
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None to mild
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+/++injection
Conjunctival
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None to mildVariable
Moderate to
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Marked
staining
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markedCorneal staining
None to mild
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Variable
Marked central
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Severe punctuateseverity/location
erosions
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Dry Eye Severity
Level
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1
2
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Corneal/tear
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None to mild
Mild debris,
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FilamentaryFilamentary
signs
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meniscus
keratitis,
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keratitis,mucus clumping, mucus clumping,
increased tear
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increased tear
debris
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debris, ulcerationLid/meibomian
MGD variably
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MGD variably
Frequent
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Trichiasis,glands
present
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present
keratinization,
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symblepharonTBUT (sec)
Variable
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10
5
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ImmediateSchirmer score
Variable
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10
5
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2(mm/5 min)
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Left Untreated, Chronic Dry Eye
May Become a Progressive Disorder
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?Patients suffering from dry eye disease may movebetween severity levels and can become worse, if
untreated.
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?Disease management options can be adjusted for
individual patients depending on disease severity
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501Nelson et al. Adv Ther. 2000.
Management
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51Aims of Treatment
?Relieve discomfort
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?Provide smooth optical surface
?Prevent structural ocular surface damage
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52Modalities of treatment
?Preservation of existing tears
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?Reduction of tear drainage?Tear substitutes
?Treat any other associated eye disease which
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predisposes to dry eye
?Other options
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53Preservation of existing tears
? Environmental modifications such as humidification,
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avoidance of wind/dusty or smoky environment, avoid
central heating
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? Lifestyle/workplace modifications? taking regular breaks from reading or computer use
? lowering computer monitor below eye level
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? increasing blink/fast blinking exercise
? discontinuing medications that exacerbate DED
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?A small lateral tarsorrhaphy ? useful in incomplete lidclosure.
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Reduction of tear drainage
Done by punctual occlusion
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?Preserves natural tears & prolongs effect of
artificial tears
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?Greatest value in severe KCS who have notresponded to frequent use of topical treatment.
?May be ?
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o Short term occlusion
o Permanent occlusion
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55Temporary occlusion
?Collagen plugs are used.
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?Dissolve in 1-2 weeks time.
?Initially all four puncta are
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occluded?If epiphora occurs, then upper
two plugs removed
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If patient is asymptomatic, then
lower puncta are permanently
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occluded56
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Reversible occlusion?Reversible prolonged occlusion with silicone/ long
acting collagen plugs (that dissolve in 2-6 wks).
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?Problems ?
?Extrusion
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?Granuloma formation?Distal migration.
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Permanent occlusion
?
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Done in severe KCS &repeated Schirmer < 2mm
?
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Should not be done in ?
?
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Patients who developepiphora fol owing
temporary occlusion of
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lower puncta
?
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Young patients as theirtear production tends
to fluctuate
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?
Done by cautery
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58Tear substitutes
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?Artificial Tear Drops used.?Stabilize & thicken pre-corneal tear film .
?Prolongs tear film B.U.T.
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?Keeps ocular surface wet & lubricated .
?Helps to repair ocular surface damage
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?Keeps ocular surface smooth59
Tear substitutes
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?
Drops - Frequent instil ation is required
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Preservative free drops are bet er?
Gels ? Consists of carbomers
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Less frequent instil ation required
?
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Ointments ? Contains petroleum mineral oil & used at bedtimeMucolytic agents ? 5 % acetylcysteine drops QID to disperse
corneal filaments & mucous plaques.
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60Eye Drops
?
Cel ulose derivatives ?
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o Hydroxypropyl methylcellulose
o Carboxymethylcel ulose [more useful in lipid or mucous
deficiency]
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o
Appropriate for mild cases.
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?Polyvinyl alcohol ? Bet er in aqueous deficiency
o Dose
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?
QID in mild cases
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?? hrly ? 2 hrly in severe cases
?
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Povidone
?
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Sodium chloride?
Hypromel ose
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?
Sodium hyaluronate
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?Polyethylene and propylene glycol
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Treatment of associated diseases
?Meibomian gland disease/ Blepharitis ?
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?Lid hygiene ? warm compresses, lid massage?Lid scrubs
?Systemic Doxycycline/ Azithromycin/ Roxitromycin
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?Correction of eyelid abnormalities ? blepharoptosis,
lagophthalmos
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Other options
? Topical cyclosporine [0.05%, 0.1%]
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? Reduces cell-mediated inflammation of lacrimal tissue
increase in goblet cells, reversal of squamous metaplasia
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of conjunctiva.? Oral cholinergic agents (M3) like pilocarpine , cevimeline
? Effective in xerostomia & about 40% of KCS patients
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also obtain relief
? Botulinum toxin injection to orbicularis muscle ? controls
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blepharospasm in severe dry eye.? Sub-mandibular gland transplantation ? for extreme dry eye.
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The DEWS treatment recommendations were based on themodified severity grading (based on severity level)
Level 1:
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Education and counselling
Environmental management
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Elimination of offending systemic medicationsPreserved tear substitutes, allergy eye drops
Level 2:
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If Level 1 treatments are inadequate, add:
Unpreserved tears, gels, ointments
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SteroidsCyclosporine A
Secretagogues
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Nutritional supplements
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Level 3:
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If Level 2 treatments are inadequate, add:
Tetracyclines
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Autologous serum tearsPunctal plugs (after control of inflammation)
Level 4:
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If Level 3 treatments are inadequate, add:
Topical vitamin A
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Contact lensesAcetylcysteine
Moisture goggles
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Surgery-Amniotic Membrane Transplanatation
Limbal stem cell graft
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Keratoplasty65
Thank You
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