Ocular Surface Disease Practical Applications

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1       Ocular Surface Disease: Practical Applications
        DAVID C ELDRIDGE OD FAAO

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2       Ocular Surface Disease
    1   •  Discuss the associated pathology of dry eye including the
           importance of osmolarity

        •  Discuss modalities of etiology and new diagnostic tests
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        •  Latest research of dry eye pathology treatments
3       Ocular Surface Disease

5          – Irregular and Poorly Lubricated Corneal Surface
           – Altered Barrier Function
4       Predisposing factors
    1   •  Gender
        •  Environment
        •  Anterior Segment Disease
        •  Age
6   2   •  CL Wear
7       •  Refractive surgery
        •  Systemic Disease
        •  Medications
5       Environment
        •  Air conditioners or heaters
        •  Airline travel
        •  Winter months, allergy season
        •  Ceiling fan
        •  Exogenous irritants
        •  Reading time/Computer
6       Patient CCF
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7       Environment
        •  Top 5 intake causes of dry eye (no specific order):
        •  Smoking
        •  Caffeine (more than moderate)
        •  Diet
        •  Alcohol

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         •  Alcohol
         •  Systemic Medications
9        Anterior Segment Disease
         •  Blepharitis/Meibomitis

         •  Patients are 2 x more likely to have dry eye symptoms

         •  Could be related to systemic conditions such as acne rosacea
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12       Tear Osmolarity and Lid Disease
         •  Dry eye can be a result of insufficient tear production or excessive
            tear evaporation
         •  Both of which lead to tear hyperosmolarity*
         •  Decreased lipid layer (e.g. MGD) resulting in evaporation is now
            recognized as one of the top causes of hyperosmolarity

         * Foulks GN. The correlations between tear film lipid layer and dry
            eye disease. Surv Ophthalmology. 2007 Jul-Aug;52(4):369-74
13       Tear Osmolarity and DED
         •  The two hallmarks of dry eye disease are increased tear osmolarity
            and instability of the tear film

         •  As DED develops there is a decrease in lacrimal gland secretion
            and/or a decrease in meibomian gland secretion

         •  Compensatory mechanisms are called into play & result in
            variability of tear osmolarity in response to normal environmental
            stress resulting in persistently abnormally high tear osmolarity


14       DTS: Clinical Categories
         •  Most common presentation: “No lid margin disease”
         •  Treatment decision based on severity level

15       Symptoms of Dry Eye
     1   •  Burning
         •  Stinging
         •  Transient blur


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16       •  Stinging
         •  Transient blur
         •  Dry eye sensation
         •  Photophobia
         •  Epiphora
     2   •  Contact lens intolerance
         •  Injection
17       •  Increased blink rate
         •  Foreign body sensation

16       Systemic Disease
         •  Diabetes
         •  Rheumatoid Arthritis
            – Sjogren’s syndrome
         •  Thyroid Eye Disease
         •  Rosacea
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17       Latest Treatment of MGD
         •  TOPICAL AZITHROMYCIN 1% ophthal. Sol (Azasite): safe & well-
            tolerated and highly effectvive
             – Azasite approved for children bacterial conj w/ ≥ 1 y/o Tx bid 5
               day
         •  Significantly greater clinical benefit for both ant/posterior blepheritits
19          than warm compress alone
         •  Azith was better than erythromycin

18       Diagnostic Tests
         •  Pt questionnaire
         •  Tear meniscus height
         •  Tear break-up
         •  NAFL dye
         •  Lissamine Green or Rose Bengal dye
              [Epub ahead phenol
         •  Schirmer test - of print]thread test
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19       Need for a of Diagnostic Test
         CorrelationObjective Tear Tests
         •  The importance of osmolarity
         •  The trend in point-of-care diagnostics
         •  Needs to be quick
         •  Needs to allow for minimal tear volume patients
         •  Needs to be easy for staff and patients
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     •  Needs to allow for minimal tear volume patients
     •  Needs to be easy for staff and patients
21   Tear Osmolarity and Dry Eye
     •  Study to determine if tear osmolarity was valuable in diagnosing
        keratoconjunctivitis sicca (KCS)

     •  Tear samples were taken from 31 normal eyes and 30 eyes
        diagnosed with KCS

     •  Normal eyes showed an average of 302 +/- 6.3 mOsmol/L and KCS
        eyes showed an average of
        343 +/-32.3 mOsmol/L


     Gillbard JP, Farris RL, Santamaria J. Osmolarity of tear
        microvolumes in keratoconjucntivitis sicca. Archives of
        Ophthalmology 1978 Apr;96(4):677-81
22   Tear Osmolarity and Dry Eye
     •  The Tests showed 94.7% sensitivity and 93.7% specificity

     •  Concluded that hyperosmolarity plays a key role in diagnosing dry
        eye


     Gillbard JP, Farris RL, Santamaria J. Osmolarity of tear
        microvolumes in keratoconjucntivitis sicca. Archives of
        Ophthalmology 1978 Apr;96(4):677-81
23   Point of Care Diagnostics
     •  Cholesterol and diabetes measuring is now performed via point of
        care diagnostics

     •  Numerous systemic diseases diagnostics have or are moving to
        point of care systems

     •  Needed in the diagnosis and management of dry eye
24   OcuSense TearLab
25   TearLab Disposable Chip
26   TearLab digital readout
27   Advanced Tear Osmometer

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26   TearLab digital readout
27   Advanced Tear Osmometer
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28   Treatment
     •  Emphasis chronic nature of the condition

     •  Eliminate exacerbating factors
        -caffeine, air conditioner, meds

     •  Increase water intake

     •  Tear replacements


29   Tear Osmolarity and Artificial Tears
     •  Tear osmolarity was studied before and after the use of artificial
        tears*

     •  Tear osmolarity dropped from 365 mOsmol/L to 329

     •  The TearLab Osmolarity System is valuable for monitoring success
        with artificial tears

     •  Artificial tears are a good first line of therapy

     Gilbard JS, Farris RL. Tear osmolarity and ocular surface disease in
        KCS. Archives of Ophthalmology 1979 Sep;97(9)
30   Artificial Tears
     •  Soothe XP & Soothe Alginate
     •  Optive
     •  Systane
     •  Blink Tears and Oasis tears
     •  FreshKote
     •  Genteal
     •  Refresh
     •  TheraTears
     •  Etc.
31   Nutritional Supplements: Essential fatty acids



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31   Nutritional Supplements: Essential fatty acids
     •  Fish oil
     •  Flaxseed oil
     •  Evening primrose oil
     •  Castor oil

     •  Omega-3 fatty acids - alpha linoleic acid
          (Avoid in patients on coumadin as blood thinning can occur with
        the use of omega-3 supplements)
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33   Punctal Occlusion
     •  May worsen certain conditions
         – Allergies
         – MGD
         – EPIPHORA!!!
     •  Ideal as final treatment option and in LASIK dry eye management
     •  Very effective treatment after tear composition is healthy and
        osmolarity is appropriate
34   Rx Targeted Treatments
     •  Treatments aimed at local inflammatory processes
         – Topical corticosteroids (Lotemax)
            • Effective anti-inflammatory agents
            • Site specific Steroids
         – Cyclosporin A (Restasis)
35   Steroids and Dry Eye
        Symptomatic improvement of irritation symptoms in 83% &
        objective improvement ( redness, dye staining and tarsal
        papillae,  FTC) in 80% of 70 patients treated for 2 weeks with
        non-preserved methylprednisolone

        Prabhasawat & Tseng BJO 1998
36   Ester vs. Ketone Steroids
     •  Ketone Steroids are not inactivated and have propensity to remain
        in anterior chamber post breakdown as active metabolites
     •  Ester Steroids are inactivated by naturally occurring esterases
         – less side effects: IOP increase & cataract

37   Ester vs Ketone Steroids
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37       Ester vs Ketone Steroids
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41       Topical Cyclosporine
         Restasis Ophthalmic Emulsion (Allergan)

           – Useful in long-term management of inflammatory DES

           – BID dosage & Excellent safety profile

           – Cyclosporine A (CsA) 0.05% in castor oil vehicle

           – 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

42       How Does Restasis™ Work?
         •  Restasis™ prevents T-cell activation
            (Kunert et al, Arch Ophthalmol. 2000;118:1489)

            – Activated T cells produce inflammatory cytokines that result in:
               • Recruitment of more T cells (Stern et al, IOVS. 2002;43:2609)
               • More cytokine production (Pflugfelder et al, Curr Eye Res.
                 1999;19:201)
43       Topical Loteprednol Improves Patient Compliance and Restasis
         Efficacy
         • Corticosteroids have been shown to improve tear production by
           controlling inflammation1
         • Corticosteroids decreases irritation associated with use of Restasis
           by 75%2
         • Recommend loteprednol qid for two weeks and then bid for 2 weeks
           for patients who complain of irritation with Restasis, high
           maintenance patients, and patient who want more rapid relief
44       Topical Cyclosporine
         •  70% of chronic dry eye Patients reported relief within 3 weeks of
            starting treatment
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         •  70% of chronic dry eye Patients reported relief within 3 weeks of
         0 starting treatment
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45       Burning and stinging are the reasons patients discontinue
         Restasis
         • 20% of patients receiving Restasis experienced burning or stinging
     1      – Patients with dry eye have chronic ocular disease and are more
47            sensitive to ocular insults
48          – Patients with dry eye disease have anesthetic corneas
               • with return of tear function there is a return of corneal sensation,
                 burning and stinging
            – Patients with dry eye are accustomed to treatment failure and are
              not willing to continue therapy which may make them feel
49            temporarily worse
            (Sall et al, Ophthalmol 2000;107: 631)
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48   2   Topical Cyclosporine Disease
         Progression of Dry Eye

         •  Dry eye is a progressive, potentially irreversible disease
         •  Left untreated, the cycle of inflammation and dysfunction may
            punctal occlusion
            cause permanent damage to the lacrimal gland
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49       Delphi Panel: DTS Treatment Algorithm
         Monitoring Progress
51       Effect of Lataprost vs Timolol on Histopathology of Conj
         •  Conj. Biopsies from inf. fornix POAG during cataract Sx
48       •  The number of collagen fibers was sig. decreased in latanoprost
46          pats. (p<0.01)
         •  Latanoprost conj. specimens had less pronuounced inflammatory
            inflitration
50       •  Consideration may be beneficial w/ filtration procedures
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51                              Brit Journal of Ophth. Mar. 2009
52       FreshKote Rx Lubricant Drop
         2% Polyvinyl pyrrolidone

         .9% Polyvinyl alcohol (87% hydrolyzed)

         1.8% Polyvinyl alcohol (99% hydrolyzed)
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47       Also contains Amisol® CLEAR
53       FreshKote Rx
         •  Advantages of Polymer Blending:



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     •  Advantages of Polymer Blending:

         – Assists in healing of ocular surface
         – Provides high oncotic pressure
         – Enhances weeability of ocular surface
         – Stabilization of tear film
54   Request for Phase 3 trial
     •  Inspire Pharmaceuticals, Inc. (Allergan partner), requested Special
        Protocol Assessment to the FDA for a Phase 3 trial diquafosol
        tetrasodium ophth sol for the treatment of DED

     •  Prolacriaz: P2Y(2) receptor agonist that stimulates release of -
        mucin, lipids and fluid. Inspire estimates that DED affects over 30
        million people; 9 million in N.A.


55   Tx Regimen:
     •  Manage contributing factors
     •  Artificial Tears & water intake
     •  Omega-3’s
     •  Lotemax qid for 2 weeks then bid for 6 weeks then PRN
     •  Restasis bid to 6 months
     •  Punctal Plugs
     •  Monitor each treatment with a TearLab Osmolarity assessment

56   Dry Eye Disease Conclusion:
     •  Numerous new treatment options that now allow us to treat dry eye

     •  New diagnostic tests will make management significantly more
        effective

     •  The TearLab Osmolarity System allows for both making a diagnosis
        and monitoring treatment success vs. progression of the disease

     •  Ocular Surface Disease is likely the most common condition we will
        see over the next two decades




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