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 • • • • • • • • • • •
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
• • • • • • • • • • •
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 •
SYSTANE® Free is the only liquid gel that patients are free to use throughout the day (and night) for maximum dry eye relief.
•
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
– – –
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 •
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
• • • •
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
• • • •
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 • • •
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 – – – – –
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
• • • • • •
• 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
• • • • •
Restasis 0.05%
Use of Topical Steroids in Severely Symptomatic Dry Eye Patients
• • • • •
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
– – – –
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.
•
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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