dry eye 04b

Dry Eye Management
Primary Goals
Improve symptoms, reduce tear osmolarity,
improve tear film stability & reverse ocular
surface damage
Treatment Modalities
• Artificial tears and new selective tear agents
• Immunomodulatory agents: cyclosporin &
steroids
• Oral therapies: Tetracyclines & Omega Fatty
acids
• Punctal plugs
Artificial Tears- you must
decided upon
• Low, medium, or high viscosity
• Preserved , non-preserved or transiently
preserved
• Solution, emulsion, gel, or ointment
• Bottled tears vs unit dose
• What dose?
• What a mess!
Traditional Therapy- Artificial
Tears
• Palliative therapies that hydrate & lubricate the
ocular surface with tear augmentation &
preservation of tears are not often enough to
alleviate the signs & symptoms
• Results are often transient, lasting only 10-15
mins
• Frequent instillation is often necessary for reliefoften poor compliance
• Doesn’t address the underlining problem ie:
inflammation
Your Ideal Dry Eye Drop?
• Long lasting
• Allows epithelial healing
• Maintains healthy ocular surface
• Significant reduction in signs and symptoms
• Lubrication of a gel without blurring or caking
• Multi-dose container
• Preservative free in the eye
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Artificial Tears
Artificial Tears
• Method of preservation
– Many preserved with BAK
• Increase TBUT and corneal staining
– Non-preserved, unit dose
– Preservative that rapidly broken down on eye
Current OTC Therapy – Tears, Gels,
Ointments- At least 30 different OTC
formulas
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Moisture Eyes™ Eye Drops
Moisture Eyes™ Protect
Moisture Eyes™ PM
Bion® Tears
HypoTears® Lubricant Eye
Drops
Visine® Tears™
Akwa Tears®
Celluvisc®
Murine Tears® Lubricant Eye
Drops
All Clear™
Theratears™
Moderate RB staining
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Genteal® Eye Drops
Genteal® Gel
Tears Naturale®
Tears Naturale® Forte
Tears Naturale Free®
Systane ™
Refresh Tears®
Refresh PM®
Refresh Plus®
Refresh Liquigel™
Refresh Endura™
• Action
– Coverage of ocular surface
– Wash out of inflammatory substances
• Also soothing if chilled before use
– Replaces electrolytes
– Largely palliative
Low Viscosity Artificial Tears
• Gen Teal Mild & Moderate (Novartis Ophth) – multi-dose
• HypoTears PF (Novartis Ophth) – unit-dose
• HypoTears Select (Novartis Ophth)- multi- dose
• Moisture Eyes (B & L) – unit-dose
• Refresh Plus (Allergan)- unit- dose
• Refresh Tears ( Allergan) – multi-dose
• Tears Naturale II Free (new) (Alcon) – unit-dose &
multidose
• Thera Tears (Advance Vision Research) – unit-dose &
multi-dose
• Nature’s Tears EyeMist- Mist of pure water
Comments:
• Commonly used preservative-free or non-toxically
preserved or transiently preserved tears in mild to moderate
dry eye syndromes.
• Unit dose solutions difficult to use.
• Multi-dose, non-toxically preserved systems becoming
more popular.
• Gen Teal – uses sodium perborate to generate very low
bactericidal levels of hydrogen peroxide.
• Refresh Tears – uses sodium chlorite (Purite) which rapidly
degrades to chloride ions and water.
• Thera Tears- Foiled packed, hypotonic, sodium
carboxymethylcellulose with multiple electrolytes:
multidose preserved similar to Gen Teal
• Possible problems with transiently preserved tears in severe
dry eye conditions- may not have enough tears to dissolve
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Other uses:
Moderate Viscosity Artificial Tears
• Corneal abrasions
• Recurrent erosions
• U.V. keratitis
• Herpes simplex and zoster keratitis
• Marginal infiltrates or ulcers
• SLK
• Adenoviral infections
• Contact lens rewetting drop
Comments:
• Bion Tears (Alcon) – PF
• OcuCoat PF (B & L) – PF
High Viscosity Artificial Tears
• Aqua Site (Novartis)
• OcuCoat PF preferred over Celluvisc.
• Celluvisc (Allergan) – PF
• Moderate to advance dry eye or epithelial disruption
• Refresh Liquigel (Allergan)- celluvisc in a multidose
• Murocel (B & L)
Bell’s Palsy
Comments:
• Helpful in replacing bedtime ointments – ie. Bell’s
Palsy.
• Helpful in severe dry eye syndrome.
• Transient blurring of vision and crusting of eyelid
margin.
• Used in gonioscopy.
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Recurrent Erosion
Gel Formulations
•Gen Teal Gel (Novartis Ophth)
•Thera Tears Liquid gel
•Refresh liquigel
•Tears Again (OcuSoft)
Comments:
• New delivery system for sustaining lubrication
• Initial blur of about a minute.
• Sustain lubrication for 2-5 hours?
• Tube delivery system for some
• Gel is highly viscous and can be a challenge to
instill.
• Replace high viscosity products and
ointments.
• Not to be used with contact lenses.
Lubricating Ointments (PreservativeFree)
•Hypotears (Ciba Vision)
•Moisture Eyes (B & L)
•Refresh PM (Allergan)
•Duratears Natural (Alcon)
Exposure keratitis
Comments:
•Uncommonly used – blurs vision.
•May help patients with incomplete
closure, absence of positive Bell’s
reflex or significant epithelial
compromise.
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What’s New In Tear Supplements
• Refresh Endura (Allergan)
– castor oil like additive to Refresh
– maintains tear film longer, reduces
tear evaporation
– similar to the vehicle (is the vehicle??)
for Restasis
New Pharmacuetical Products
• Systane (Alcon) - Rx drops
• Contains Hp guar, which helps mix oil & water,
bind to epithelium/glycocalyx
• Soft gel matrix
• pH of 7.0
• Rehabilitates the cornea, not just rewets
– Helps protect the epithelium, keep it moist
while it repairs itself
SYSTANE® Free
• Long lasting relief
SYSTANE® Free Attributes
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SYSTANE® Free is the only liquid gel that
patients are free to use throughout the day (and
night) for maximum dry eye relief.
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This is true because SYSTANE® Free provides:
• Comfort and protection of a
gel with less blur
• Use during day and night
• No traditional preservatives in
the bottle
• Preservative free in the eye,
safe and gentle on the eye
Clinical Profile
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The long lasting comfort of a gel
Has proven minimal blurring
Is safe and gentle because it is preservative free in the
eye
SYSTANE® Free Liquid Gel
• Superior efficacy
– Significant reductions in corneal staining from
baseline
– Significant reductions in corneal staining at 6
weeks vs. Refresh* Tears
– Significant reductions from baseline in burning,
stinging and scratchiness
– Significantly less blur than older generation gels
Acts Like A Drop.
Protects Like A Gel.
* Trademark of another company
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What’s New In Tear Supplements
SUMMARY
• SYSTANE® is a unique ocular surface restorative and
protectant
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SYSTANE®
promotes ocular surface healing
• SYSTANE® decreases the coefficient of friction between the
lid and cornea
• SYSTANE® is compatible with and augments the effects of
Restasis
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Aquify by CIBA Vision
Sodium hyaluronate
For use with all CL
More lasting effect reported
• SYSTANE® effects are evident for weeks even after cessation
of treatment
• SYSTANE® Free - all the benefits of SYSTANE® in
comfortable liquid gel formulation
What’s New In Tear Supplements
What’s New In Tear Supplements
Patented by an optometrist: Donald Korb
• Blink Contacts by AMO
• Contains hyaluronate
• AMO acquired the viscoelastic
products from Pfizer
• Approved for all contact lenses
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Emerging Treatment Strategies
Systemic Dry Eye Treatments
Mucomimetics
Soothe by Alimera Sciences
Emollient based tear product
Contains Restoryl, a lipid restorative
Improves the tear lipid layer to reduce tear
evaporation
• Saligen - 1% Pilocarpine
Secretagogues
Hormonal
Improved Polymers
Anti-evaporatives
Anti-evaporatives
Nutritional
Supplements
– a parasympathomimetic
– 5mg tablet form, QID dosage,
– Build up dose weekly
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5mg QID x 7 days
10mg QID x 7 days
15mg QID x 7 days
– Most need 10-15mg QID; can go up to 20mg
Anti-Inflammatories
Anti-Inflammatories
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Saligen - continued
Systemic Therapies- Evaporative DES
• Oral doxycycline, 50-100 mg bid by 2-4 weeks, then 50-100
mg. q d for 3-6 months plus eyelid hygiene.
• Other effective treatments for Acne rosacea: Metro Gel or
creams (Metronidazole) to the skin
• Avoid triggers: ie. Spicy foods, alcohol, excessive heat
• Note: More recently tetracycline have been observed to have
numerous ant-inflammatory properties
• Improve irritation symptoms, increase tear film stability
and decrease the severity of OSD
• Also effective for treatment of recurrent erosions &
phlyctenular keratoconjunctivitis
• Can cause GI stimulation and irritation
• Contra-indicated in asthmatics
• Increases saliva secretion probably more than
tears
• Generally reserved for severe Sjogrens patients
Comments:
• Aqueous deficiency or rapid evaporation or
both from a deficient lipid, oily layer.
• Meibomian gland dysfunction.
• Rearranges the fatty acid metabolism of
meibomian glands.
• Side effects: C/I pregnancy & breastfeeding,
children under 8 yrs., vaginal yeast infections,
decrease effectiveness of BC pills, skin
photosensitive, diarrhea & cramping, breast
cancer?
Supplemental Flax Seed Oil
• Omega-3 fatty acids
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Essential fatty acids not produced by body
83% of Americans are deficient
Salmon, cold water fish, fish oils, flaxseed, evening primrose
2,000 mg of flaxseed oil per day
Slow onset of their action 3-4 mos.
• Appears to reduce T-cell lymphocyte proliferation and
inflammation
• Side effect- transient facial acne and some GI upset
• Hydroeyes, Hydrate Essential, Thera Tears Nutrition
– Thera Tears 4 caps taken in AM
Theratears Nutrition
HydroEye
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• Science Based Health
• Capsule
• Black currant seed oil, mucin complex, Vit c,
Vit A, cod liver oil, magnesium, Vit B6
Flaxseed
Fish oils
Vitamin E
Eicosapentaenoic acid
Docasahexaenoic acid
2 caps bid
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Other Systemic Non-Rx
Hydrate Essential
• Hydro Eyes Plus Lutein (Science Based
Health)
• Cynacon/OcuSoft
• Luquid
• Contains flaxed seed oil, evening primrose &
bilberry extract
• Once or twice a day
– Omega 3 and 6 fatty acids
– Vitamin A, C, and B6
– Magnesium
Other Systemic Non-Rx
• BioTears (Biosyntrx)
– Omega 3 fatty acid
– “Nutrient co-factors”
– Will introduce a second product
BioTears Plus in Fall 2003 for
more severe dry eye (especially
androgen deficiency)
– www.biosyntrx.com
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Restasis (anti-inflammatory &
immunomodulating agent)
Restasis
• Cyclosporin A, fungal origin, used for
immunosuppression in organ transplants
• Anti-inflammatory action targets lymphocytic
infiltration during inflammation
• Proposed mechanism: block cellular infiltrate
to reduce inflammatory response
• Increased tear secretion in experimental
studies (dogs) and dry eye patients
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Restasis 0.05%
Use of Topical Steroids in Severely
Symptomatic Dry Eye Patients
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Dosing: bid (q12 h): one vial per day?
Formulation: 32 single use vials- cost $85.00
Take CLs out & allow 15 mins
Major side effect: transient burning upon instillation
Expectations: 1 month-reduced symptoms; 3 monthssigns start to improve, peak improvement in signs &
symptoms in 6 months
• After improvement taper to qd? or D/C
Moderately to severe dry eye syndromes
LASIK dry eye
Allergic Diseases: VKC, Atopic, Seasonal
MGD
Thygeson’s SPK & SLK
•Marsh P, et al. Topical nonpreserved
mythprednisolone. Therapy for
keratoconjunctivitis sicca in Sjogren
syndrome. Ophthalmology 1999,
06(4): 811-6.
•Short-term steroid “pulsed” treatment
Comments:
• Selected highly symptomatic KCS
unresponsive to aggressive artificial tears and
punctal occlusion; may act faster than restasis
• An inflammatory response seen in chronic dry
eyes.
• Steroids may decrease or eliminate the factors
that cause irritation in KCS.
• May try soft steroids - loteprednol (Alrex or
Lotemax) qid x 3-4 weeks then bid for 3
weeks.- Lotemax preferred
• Undesirable side effects: increased risk of
cataract, IOP & ocular infection- less of
problem with soft steroids
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Punctal Occlusion:
Review video tape
• Collagen (3-7 days) & silicone plugs
(punctal/intracanilicular)- lower first, then upper
• Great option in those moderate to severe dry eyes where
frequent lubrication is too complicated or inadequate
• May exacerbate problem if used early in the course of
treatment because the abundance of inflammatory cells
on ocular surface accumulate when punctal plugs are
inserted
• Doesn’t always produce long-term symptomatic relief
• Often need to continue with artificial tears.
• Some problems- spontaneously expelled, exposed head
of plug irritating cornea
Punctal Occlusion
• Permanent: Thermal cauterization, laser,
electrodesiccation
• Tarsorrhaphy (suturing eyelids):
Treatment Considerations
• Punctal occlusion
For severe dry eyes that are at risk for ulceration or
melting: neurotrophic
Cosmetic problem
New Tear Occlusion Products
New Tear Occlusion Products
• Smart Plug
• IntelliPort (marketed by Alcon)
– Thin rod of rigid like material
– Insert nearly all the way into the puncta
– Swells at body temperature, and molds and
occludes the tear duct
– Company says it can be irrigated out
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Liquid at 105 degrees is injected into puncta
Solidifies at body temperature, and occludes
May conform to cannula, occlude better
Company says it can be irrigated out using very
warm water
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Fundamental Advancements – Rx
Therapies
Tear Occlusion Success ??
• Virtanen (1996); Tomlinson, et al (1998);
Pearce, et al (1998)
• All showed short-term improvement with
punctal plugs, but no sustainable effect after 14 months
• Lowther has reported similar effect
Future therapies aimed to
TREAT dry eye, not just
‘manage’ it
LIPID LAYER
~0.1 µm
AQUEOUS LAYER
7 µm
All 3 layers of the tear
film have been targeted.
MUCIN LAYER
~0.5 µm
OCULAR SURFACE
Secretagogues – On the Horizon
Secretagogues
Stimulate the production of
essential tear components:
15 (S) – HETE
stimulates mucin production
LIPID LAYER
Muc 1
Aqueous
INS – 365 (P2Y2 agonist)
stimulates aqueous, mucin and lipid production
Mucin
AQUEOUS LAYER
Lipid
Muc 5AC
Combinations
Others: IFN – , EGF , Garfornate
MUCIN LAYER
OCULAR SURFACE
Anti-Evaporatives
Stimulate lipid secretion
Anti-Evaporatives – On the Horizon
• Topical Androgens
LIPID LAYER
Androgens help regulate quality and / or quantity of lipid
secretions
Optimize / enhance barrier
function of the lipid layer.
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AQUEOUS LAYER
Lipid Component Replacement
Lipocalin, Phosphatidylcholine, Caster oil
Evaporation
MUCIN LAYER
OCULAR SURFACE
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Mucomimetics
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Mucomimetics are
designed to mimic the
functions of naturally
occurring mucins
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Stabilizing the tear film,
resulting in a healthier
ocular surface
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On the horizon –
MILCIN™
Therapeutic Options
• Mild therapy: AT alone and/or punctal plugs alone or
Omega-3 fatty acids
• Moderate: preservative free AT used frequently, gel
formulations at night, punctal plugs, Omega3 fatty
acids supplementation, Restasis trial for 3-6 mos
• Severe: AT & gels, Lotemax qid for 1 week, then bid
for a month, long-term Restasis, oral doxycycline
100mg/day for 2-4 wks, then 50mg /day for 6 mos,
punctal plugs after the above have been in effect,
moisture goggles or tarsorrhaphy
LIPID LAYER
AQUEOUS LAYER
MUCIN LAYER
OCULAR SURFACE
Levels of Dry Eye Severity and
Management- the Delphi Panel
• Level 1: mild to moderate symptoms and signs =
preserved tears, allergy drops, lifestyle and
environmental changes
• Level 2: moderate symptoms, mild corneal staining,
conjunctival staining, visual signs = non preserved
tears and gels, steroids &/or Restasis
• Level 3: severe symptoms, marked corneal staining,
central staining & filamentary keratitis = Restasis,
punctal plugs, tetracyclines & topical steriods
• Level 4: severe symptoms, severe corneal staining
erosions, conjunctival scarring = surgery, punctal
cautery, acetylcysteine or bandage cls
Summary
• Managing dry eye as a chronic eye condition
that requires careful patient education and
long term care.
• If using tears more than three instillations use
non-preserved.
• Discontinue OTC meds such as
antihistamines.
• Discuss environmental concerns.
• More aggressive treatment with Restasis,
topical steroids, oral meds, & punctal plugs
Meet Murphy
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Meet Libbey
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