Download Dry Eye Hypothesis by Mathers

What is Dry Eye?
Subjective Test
Definition
“Dry eye is a disorder of the tear film due to tear deficiency or excessive tear
evaporation which causes damage to the interpalpebral ocular surface and is
associated with symptoms of ocular discomfort.” (NEI / Industry Workshop on Clinical
Trials in Dry Eyes, 1995)
Prevalence
Recent figures come from largest epidemiological survey of dry eye ever (Schaumberg
DA et al. Prevalence of dry eye syndrome among US women. Am J Ophthalmol 2003)
Studied 40,000 women to estimate prevalence of dry eye among females
Conclusion: dry eye syndrome (DES) affects 3.2 million American women middle-aged
and older alone. Overall prevalence likely higher.
In the literature, prevalence ranges from 5-28% worldwide.
DES is the most common treatable eye condition.
Paradigm Shift:
Dry Eye Yesterday
Limited understanding of DES
Classical Tear Film Model
Lipid
Aqueous
Mucin
3 distinct layers
Palliative treatment of symptoms
Dry Eye Today
Current Concepts
The Lacrimal Functional Unit
The Inflammatory Cycle
Ocular Protection Index (OPI)
Hormonal influences
Nutrition
Updated Tear Film Model
Targeted Treatment
Viscosity Agents
Hypotonic Agents
Anti-evaporants
Mucomimetics
Secretagogues
Anti-inflammatory Agents
Immunomodulators
Cytokine Inhibitors
Androgens
Dry Eye Hypothesis by Mathers
The Lacrimal Functional Unit
The Inflammatory Cycle
Low-grade subclinical inflammation caused by disruption of Lacrimal Functional Unit
homeostasis in DES
Release of inflammatory cytokines IL-1, IL-6, TNFα
Cyclical nature of inflammatory process
Applications in clinical practice
Ocular Protection Index (OPI)
TBUT / IBI
TBUT = Tear Break-up Time (sec)
IBI = Inter-blink Interval (sec)
>1.0 is functional, <1.0 is dysfunctional
NIBUT Subjective Test used
NIBUT is within 1 sec TBUT
Updated Tear Film Model
Bilayer:
Lipid topcoat
Aqueous emulsion with varying gelled concentrations of mucins (MUCs), thicker near cornea
Hormonal Influences
Nutrition
DES Classification
Simple classification
Aqueous-deficient
Evaporative
Combination
Other classification theories exist
Risk Factors
Age
Gender
Associated Systemic Diseases
Sjögren’s Syndrome
Acne Rosacea
Arthritis
Concomitant allergies
Diabetes
Fibromyalgia
Immune disorders
Leukemia
Lupus
Thyroid disease
Viral disease (HZO)
Anterior Segment Pathology
Blepharitis
Meibomian gland dysfunction (MGD)
Lid / Blink Abnormalities
Cicatricial disease
Ectropion / entropion
Facial nerve palsy (Bell’s)
Incomplete blink / lagophthalmos
Nocturnal lagophthalmos
Parkinson’s
Proptosis
Pterygium / Pinguecula
Contact Lens Wear
Refractive Surgery
Medications
Acne medications (isoretinoin and Accutane)
Anti-anxiety medications
Anti-emetics
Antihistamines, sedating / non-sedating
Antipsychotics
Birth control pills
Beta-blockers
Diuretics
HRT
OTC cold remedies
Tricyclic antidepressants
Foods
Alcohol
Artificial sweeteners
Caffeine
Hydrogenated and trans fats
Red meat
Refined sugars
Vitamin A deficiency
Hormonal Imbalance
Menopause
Pregnancy
Environmental
Air pollution
Air travel
Altitude
Central heat / air
Dry environment
Hairdryer
“Office Eye Syndrome”
Pollen areas
Saunas
Smoking
Visual tasking
Windy environment
The Dry Eye Examination
History / Questionnaire
Classical dry eye symptom questionnaires:
Key Questions in a Dry Eye History (The McMonnies Questionnaire)
The Ocular Surface Disease Index (OSDI)
The Dry Eye Questionnaire (DEQ) (Indiana University)
The Contact Lens Dry Eye Questionnaire (CLDEQ)
Symptoms more important than signs in dry eye grading
Diurnal trends
Correlate poorly with signs
Neuro-paralytic cornea
Pain thresholds
Sample DES Questionnaire for Clinical Practice
Adapted from McMonnies’ and Indiana University Questionnaires
Schirmer / Phenol Red Thread (Zone-Quick)
Assessment of lacrimal gland function / tear volume
Schirmer
DES: <10 mm wetting / 5 min
Performed without anesthetic (NEI Dry Eye Workshop), possibly multiple times
Phenol Red Thread (Zone-Quick)
DES: <10 mm wetting / 15 sec
Tear Lake Assessment
Tear meniscus height
DES: <0.3 mm tear prism height
Tear lake quality
Look for tear debris / frothing / filaments / oils
Evaluate viscosity
Topographical / wavefront surface irregularities
Seen on Orbscan or wavefront analysis
Mimic higher-order aberrations
New topographic modeling systems for tear film stability analysis
Tear Break-up Time (TBUT)
Assessment of tear film stability / tear quality
DES: TBUT<=10 sec
Fluorescein Break-up Time (FBUT)
Non-Invasive Break-up Time (NIBUT)
More useful when combined with blink rate / Inter-blink Interval in OPI
DET (Dry Eye Test)
Laboratory Tests
Limited usefulness in clinical practice
Fluorescein Staining
Assessment of epithelial damage
Fluorescein Staining
DES: >3/15 on NEI grid
Test with highest sensitivity for detecting ocular surface disease
Stain pattern more significant than degree
Technique:
Wait 1-2 min before assessment
Wratten #12 yellow filter / cobalt blue
NEI grids
Rose Bengal / Lissamine Green Staining
Assessment of dryness / mucin deficiency of ocular surface
Stain pattern more significant than degree
Rose Bengal 1%
Lissamine Green
Technique:
Wait 2 - 3 min before assessment
Low diffuse white illumination, gradually increased
Lid Examination
Assesses presence of associated lid disease
Inspect lids for:
Blepharitis
Scaling
Collarettes
Lash inflammation
Oily / greasy flakes
Rosacea-associated telangiectasias
Meibomian gland evaluation
Express meibomian glands
Assess gland viability
Ocular Examination
Assesses presence of associated ocular or systemic disease
May elucidate etiology
Acne Rosacea must be first rule-out
Look for MGD, staphylococcal lid disease, recurrent chalazia, chronic
conjunctivitis, peripheral corneal neovascularization, marginal corneal
infiltrates, ulceration, episclerits, irits
Examination:
Lids
Cornea
Conjunctiva
Gross Physical Examination
Assesses presence of associated systemic disease
Acne Rosacea
Look for: subtle rosacea facies, ocular rosacea, acne
Sjögren’s Triad
Look for: dry eyes, dry mouth, arthritis
Rheumatoid Arthritis (RA)
Look for: spindling of fingers, ulnar drift, subluxation
More severe than osteoarthritis
Treatment
Mild DES
Occasional symptoms
Minimal staining
Lubricating therapy as needed
Artificial tears TID-QID
Low to moderate viscosity agents
Active Lid Disease
Treat active lid disease first
Blepharitis / Meibomian Gland Dysfunction (MGD)
Lid hygiene / hot compresses / antibiotic ointment
Preservative-free artificial tears if DES present
Anti-evaporants (Refresh Endura)
Nutritional supplements
Omega-3 fish oil / flaxseed oil
Oral management with tetracyclines if non-responsive
Anti-inflammatory activity, rearrange fatty acids in meibomian glands,
improving lipid function
Oral doxycycline, 100 mg BID x 6 weeks, then taper to QD x few mos
Contraindicated in pregnancy / nursing; phototoxicity, gastritis side
effects
Ocular Rosacea / Acne Rosacea:
Patient education: avoid sun, spicy foods, alcohol
If limited improvement on above regimen
Reduce to periostat (anti-gingivitis) 20 mg BID or QD
Metronidazole cream once stable
Diet / Water Intake
Tear dysfunction caused by excess dietary fats, cholesterol, salt, sucrose, protein,
alcohol
Fluids / water
Consume half one’s body weight in oz water/day, ex 50 oz/100 lbs, not with
meals
Water-containing fruits and vegetables
Omega-3 fatty acids
Anti-inflammatory properties, may improve tear lipid layer
Cold-water fish, ex. salmon, cod, sardines, herring, eel, trout
Flaxseed oil
Similar benefits to fish oils, may be substituted
Flaxseed meal added to food / cereals
Nutritional supplements
Research in this area is limited
Always check with Primary Care Physician first
Omega-3 fish oil pills, 1000mg TID with food, contraindicated in pts on blood
thinners
Flaxseed oil 1000 mg BID
TheraTears Nutrition (Advanced Vision Research) claims to suppress
meibomitis, improve lipid layer, stimulate tear secretion, contains omega-3
supplement, enriched flaxseed oil and Vitamin E
Hydrate Essential (Cynacon/Ocusoft) conatins flaxseed oil, evening primrose
oil and bilberry extract
Vitamin A 10,000 IU in beta-carotene form, regulates proliferation /
differentiation epithelial and goblet cells
Vitamin E 400 IU, protect fish oil fatty acids from oxidative damage in body,
can have negative effect on cholesterol-lowering agents
Avoidance
Alcohol
Caffeine
Common food allergens / processed foods
ex. milk, pasteurized dairy products, corn, wheat, refined sugars, red meat
Benefits reported after 30 days’ use
Environmental Modification
“Office Eye Syndrome”
Increasing in prevalence
Poor blink
Eyestrain / fatigue
Low humidity
Poor ventilation
Humidifier
Blinking exercises
Recommended for DES caused by visual tasking, incomplete blink,
lagophthalmos
Limited Patient compliance
Avoidance
Dry environments
Nature’s Tears Moisturizing Mist, facial spray made of tissue-culture
grade, pH-correct water, claims to replenish tear film
Dust
Smoke / smoking
Ventilation
Turn AC / fans / vents away from face
Wind
Modify Contact Lens Care
Symptoms worse at end of day
Material modification
Switch to non-ionic, low water, higher center thickness materials
Silicone hydrogels
Non-ionic lenses
Daily disposable lenses
Gas-permeable (GP)
Solution modification
New solutions eliminate or contain milder preservatives and / or contain
wetting agents and lubricant additives to provide longer, more comfortable
wear
For severe DES preservative-free agents are indicated
Rewetting agents
New agents decoat the contact lens during wear, add to tear viscosity
Lifestyle modification
Decreasing wear time
Midday soaks
Therapeutic lenses in DES
Custom large-diameter hydrogels (up to 22 mm diameter)
Custom high Dk GP scleral shell (15-24 mm diameter)
Medication Review / Modification
Lubricating Therapy
Mainstay of DES treatment
Low-viscosity, unit-dose
Low-viscosity, multi-dose
Moderate viscosity
High-viscosity
Gels
Ointments
Current concepts:
Preservative-free / disappearing / “gentle” preservatives
Muco-adhesive and viscosity agents
Electrolyte and hypotonic agents
Ointments supplanted by gels
Punctal Occlusion
Indications
Failure / noncompliance with maximal lubricating therapy
Non-responsive Patients with low tear volume, Schirmer <5 mm
Contraindications
Inflammatory dry eye, ex Sjogren’s
Younger Patients with Schirmer >10 mm
New Products
Cauterization
Indicated for Schirmer <3mm
Heat / Electrocautery or argon laser ablation
Cautions
Patient awareness
Dislodging
Continued supplementation with prior treatments necessary
Collagen plug trial
Informed consent
Moisture Chambers
Enclose eye to prevent evaporative tear loss
Reduce wind current / increase humidity at eye level
Modify Patient’s own eyewear or use wraparound shields
Surgery
Tarsorraphy
Ectropion / Entropion Repair
Modern Therapy
Viscosity Agents
Systane (Alcon)
Useful in moderate-severe DES with surface damage
BID dosage
HP Guar, polypropylene glycol, polyethylene glycol 400, borate, essential ions:
K, Ca, Mg, Na
3 mechanisms of action:
Ocular shield / bandage effect
HP guar combines with glycolcalyx slowing TBUT, creates
microenvironment for corneal / conjunctival epithelial cell
repair
Viscosity increases from bottle to eye, with pH change
Longer dwell time, 30-75 min
Essential ions for healing
Dosing QHS makes a.m. dryness less severe
51% reduction in corneal staining from baseline in clinical trials
Hypotonic Agents
TheraTears (Advanced Vision Research)
Useful in moderate-severe DES with surface damage
Hypotonic formulation containing K decreases tear film osmolarity,
restores homeostasis, improves epithelial cell health
Anti-Evaporants
Refresh Endura (Allergan)
Useful in lipid-anomalous DES
Castor-oil emulsion (was vehicle in Restasis trials)
Polar oils increase lipid stability, prevent evaporation of aqueous layer
beneath
Claims to enhance all 3 tear film layers
Mucomimetics
Milcin (Vista Scientific)
Currently under investigation
Agent becomes incorporated into mucin layer and mimics its function
Secretagogues
Mucin Secretagogues
Stimulate mucin production by mucosal surfaces
Goal is to increase mucin production by ocular surface and decrease ocular
surface damage
15 (S) – HETE (hydroxy-eicosatetraenoic acid) (Alcon)
INS365 / diquafosol tetrasodium (Inspire Pharmaceuticals / Allergan)
Tear Secretagogues
Salagen (MGI /Global Pharmaceutics)
Others
Anti-Inflammatory Agents
Useful in severe DES for short-term aggressive inflammation control
Site-specific Steroids
Alrex (loteprednol 0.2%, Bausch & Lomb)
Lotemax (loteprednol 0.5%, Bausch & Lomb)
Vexol (rimexolone 1%, Alcon)
rimexolone 0.1% in development for DES
QID x 1 mo, BID x 1 mo, repeat Q4-6 mos PRN
Safety Profile
Excellent but monitor IOP / cataract formation
<1% IOP rise vs >7% for ketone steroids
Immunomodulators
Restasis Ophtahalmic Emulsion (Allergan)
Useful in long-term management of inflammatory DES
BID dosage
Cyclosporine A (CsA) 0.05% in castor oil vehicle
Mechanism of action:
Inhibits activation of inflammatory T-lymphocytes, stimulating
lacrimal gland tear production
3-4 months to achieve clinically significant effect, 6 months for full
therapeutic potential
59% Patients achieved improvement from baseline Schirmer scores at
6 months
FK-506 / Tacrolimus (Sucampo Pharmaceuticals Inc)
Potent immnosuppressive, in clinical trials
Cytokine Inhibitors
Under investigation
Androgens
Androgen receptors in lacrimal and meibomian glands
Regulate lacrimal secretory function and meibomian gland oils
Testosterone creams
In development
Applied to eyelid skin for pulsed delivery
Androgen supplements
Under investigation
Patient Education
Chronic nature of DES
Prescribing treatments improves compliance
Exit form
Follow-up
RTC 1 month to monitor:
Compliance
Preservative toxicity / medicamentosa
Treatment efficacy
Re-appoint and follow-up
Chronic nature of disease
Provide encouragement
Clinical Pearls
Diagnosis: proper staining techniques
Treatment:
Treat signs OR symptoms and treat aggressively
Look for / treat active lid disease first
Re-appoint / follow-up
Patient empathy
Conclusion
DES is complex disease entity
Understanding of DES evolving
Controversies
Entering era of potentially curative treatments