Ocular Surface Disease. Advanced Treatment in Ocular Surface Disease. Disclosures. Revenue Potential. Chronic Dry Eye Should I Treat It

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1 Advanced Treatment in Ocular Surface Disease Douglas K. Devries, O.D. Eye Care Associates of Nevada Douglas K. Devries Consultant or Speakers Bureau for Allergan AMO TearLab NicOx BVI B&L Disclosures Chronic Dry Eye Should I Treat It Higher Level of Care to Your Patient Expense vs Revenue Center Revenue per Patient Patients Decide Cost vs Benefit Re-Appointment Level II $38.19 Re-Appointment Level III $60.94 Re-Appointment Level IV $91.56 Will be at least 2 visits and upwards to 8 visits Punctal Occlusion OU (one set) $ *Medicare Rates in Nevada Net Revenue $ to $ Plus Per Patient with repeat visits in future years Revenue Potential Dry Eye Greatest Opportunity is Yet to Come 2010 Ocular Surface Disease Greatest Opportunity is Yet to Come Company Compound Status Diquafosol/Prolacria Inspire Phase III Alcon 15-s-HETE/Procaylx Phase III Vista Milcrin Early ISTA Ecabet Phase II Otsuka Rebamipide Phase III Lantiobio Mole-1901 Phase III Daichii Cevelamine Phase III Novartis Pimecrolimus Phase III Alcon Rimexolone Phase III Novagali Nova22007 Phase II Debiopharma SA CsA pro-drug Early Allergan Androgen Tears Phase II Singularis PRG4 Early Nascent Estradiol Phase III Solvay Estratest Phase III Alacrity Alty 0501 Phase II Can-Fite CF-101 Phase II Santen Rivoglitazone Early Fovea Calcineur Early SCIL prongf Early

2 Sept Update What s New In Ocular Surface Disease Possible Paradigm Shift In Methods of Evaluation Clinical Lab Testing Osmolarity Inflammation What Happens When a Patient Doesn t Respond to Conventional Therapy Frustration Sets In Patient Doctor Recalcitrant Cases of OSD Where do you go from here? Compounding Pharmaceuticals Mechanical Therapy Multiple Goals

3 Clinical Presentation Can Vary in Severity Symptom Driven Questionnaire Slitlamp Fluorescein Dye Stain Mild Severe Ocular Surface Disease Index (OSDI) Allergan Create Your Own Questions on Your Letterhead Ask Common Dry Eye Rank Never Slight Moderate - Severe Lemp, 1995; Marsh et al, 1999 Tear Function Screening Questionnaire Gritty or sandy sensation? Pain or soreness? Fluctuating vision? Occasional Tearing? Blurred vision while reading? Discomfort in windy conditions? Discomfort in air conditioned areas? Itching? Standard Patient Evaluation of Eye Dryness (SPEED) Questionnaire Evaluates the frequency and severity of symptoms Easy to use Fast screening tool for Dry Eye disease May be used to identify candidates for LipiView Lipid, aqueous and mucin components Outer lipid layer prevents evaporation Secreted by meibomian glands Aqueous component a complex mixture of proteins, mucins, electrolytes Secreted by main & accessory lacrimal glands Mucins provide viscosity and stability during the blink cycle Mucin gel decreases in density toward tear film surface The Healthy Tear Film A Delicate Balance 17 Image from Dry Eye and Ocular Surface Disorders, 2004

4 Consequences of Tear Composition Changes in CDE Altered environment for ocular surface tissues Increased osmolarity Imbalanced growth factors and cytokines fail to promote normal epithelial growth Poor viscosity can cause thin spots in tear film and tear breakup Lubrication compromised Ocular surface damage Loss of corneal epithelial integrity Squamous metaplasia of conjunctival epithelium Summary: Pathophysiology of OSD Immune-mediated inflammation of lacrimal glands and ocular surface Cytokines in tears, altered tear composition Inflammation disrupts normal neuronal control of tearing Multiple triggers and predisposing factors Age Conjunctivo-chalasis Other autoimmune diseases Sjogren syndrome Blepharitis/MGD Systemic drugs Ocular surgery Computer work Low blink rate Eyelid inflammation Lipid changes Flora changes TEAR FILM INSTABILITY / EVAPORATION Goblet cell loss Improper lipid spreading Cytokine release Tear hyperosmolarity MMP activation Epithelial cell damage INFLAMMATION Corneal damage Apoptosis conjunctival metaplasia Neurogenic inflammation Neurostimulation Systemic diseases Exposure Toxic drugs/ preservatives Allergy Neurotrophic Contact lens Environment Chronic inflammation Ocular Surface Disease Testing Ø Evaluate Tear Meniscus Ø NaFl Staining & Tear Break Up Time Ø Lissamine Green Staining Ø Meibomian Gland Expression Ø Schirmers With Anesthetic or Quick Zone Refractive surgery Viral/bacterial infection Baudoin and Rolando 2007 Menopause Hormonal changes Lid margin irregularities Dry Eye Overview ITF Recommendations: Severity Levels Signs of Dry Eye Dry Eye Severity Level General Mild Moderate Diagnosis Conjunctival staining Corneal staining Mild punctate Tear film Visual signs Other Example staining Severe Extremely Severe Mild Moderate Marked Scarring Marked punctate central Filamentary keratitis Severe punctate erosions TBUT (sec) * <12 >2 to <7 <3 <3 Schirmer score (mm/5 min) * >10 >5 to <10 <5 <2 * Not mandated in the ITF guidelines, but used by many physicians Photos courtesy of M. W. Belin, MD. McDonnell PJ et al, for The Dysfunctional Tear Syndrome Group. Presented at: 76th Annual Meeting of the Association for Research in Vision and Ophthalmology; April 25-29, 2004; Fort Lauderdale, Fla. Abstract B370. ITF Recommendations: Severity Levels of Dry Eye Dry Eye Severity Level General : itchy, sandy, gritty, dry Discomfort: stinging, burning, pain Vision: blurring, interrupted Use of artificial tears Mild Never to Seldom Moderate Severe Extremely Severe Sometimes Frequent Always No Yes Yes Yes No No Sometimes Usually Less than 3 times per day Several times per day Several times per day Dry Eye Overview Several times per day McDonnell PJ et al, for The Dysfunctional Tear Syndrome Group. Presented at: 76th Annual Meeting of the Association for Research in Vision and Ophthalmology; April 25-29, 2004; Fort Lauderdale, Fla. Abstract B370.

5 Progression of DTS Severity Levels Mild to moderate symptoms, no signs LEVEL 1 Mild to moderate conjunctival signs Official Definition: What is Dry Eye Disease? LEVEL 2 LEVEL 3 LEVEL 4 Moderate to severe symptoms Tear film signs, Visual signs Mild corneal punctate staining Conjunctival staining Severe symptoms Marked corneal punctate staining Central corneal staining Filamentary keratitis Extremely severe symptoms/altered lifestyle Severe corneal staining, erosions Conjunctival scarring Dry eye is a multifactorial disease of the tears and ocular surface that 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. Behrens et al, submitted DEWS Report, Ocular Surface April 2007 Vol 5 No 2 The importance of osmolarity Need for a More Objective Dry Eye Test 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 Possible Paradigm Shift Objective Lab Measurements of Ocular Surface Disease Osmolarity as a Gold Standard Hyperosmolarity in Dry Eye Diagnosis The measurement of tear film osmolarity arguably offers the best means of capturing, in a single parameter, the balance of input and output of the lacrimal system. It is clear from the comparison of the diagnostic efficiency of various tests for DED, used singly or in combination, that osmolarity provides a powerful tool in the diagnosis of DED and has the potential to be accepted as a gold standard for the disease. Alan Tomlinson - Glasgow Caledonian University, UK

6 Hyperosmolarity & Ocular Surface Damage Hyperosmolarity as a Proinflammatory Stress Liu H. Invest Ophthalmol Vis Sci. 2009;50: Osmolarity Severity Analysis Osmolarity is the only sign to become stable a6er R x Sullivan BD, Crews LA, Sönmez B, de la Paz MF, et al. Cornea 2012 Osmolarity & Tear Film Instability in DED Osmolarity in the Diagnosis of Dry Clinical Test PPV Eye Disease Osmolarity 87% Schirmers 31% TBUT 25% Staining 31% Meniscus Height 33% Osmolarity is the gold standard test for Dry Eye 45 years peer reviewed research Osmolarity has been added to definition of Dry Eye Global marker of Dry Eye, indicating a concentrated tear film Source: DEWS Report, Ocular Surface April 2007 Vol 5 No 2, & Tomlinson A, et. al., IOVS 47(10) 2006

7 Osmolarity Testing Tear Film Instability in DED Utility of TearLab in Clincal Trials & Disease Management Osmolarity is a compelling choice for primary efficacy endpoint Quantitative Operator independent Noninvasive (done at beginning of test sequence) Inclusion Criteria are Critical One eye > 328 mosms/l, Opposite eye > 316 mosms/l Different signs don t correlate in the general population Test TearLab Osmolarity before any other test Perform daily quality control Discontinue use of artificial tears at least 2 hours before testing Testing for Inflammation What is MMP-9? Matrix metalloproteinases (MMP) are proteolytic enzymes that are produced by stressed epithelial cells on the ocular surface 1 Non-specific inflammatory marker More sensitive diagnostic marker than clinical signs 1 Correlates with clinical exam findings 1 Normal range between 3-41 ng/ml Ocular surface disease (i.e. dry eye) demonstrates elevated levels of MMP-9 in tears 1 Detecting Elevated Levels of MMP-9 Identifying elevated levels of MMP-9 facilitates better management of: Patients who present with signs or symptoms of dry eye Patients having ocular surgery such as LASIK or cataract surgery [1] Chotikavanich S, de Paiva CS, Li de Quan, et al. Invest Ophthalmol Vis Sci 2009; 50(7):

8 InflammaDry Detects elevated levels of MMP-9 in tear fluid 10 minute in-office results Easy to use can be performed by technicians or nurses Disposable no additional equipment required Limit of Detection: the normal level of MMP-9 in human tears ranges from 3-41 ng/ml Positive test result = MMP-9 40 ng/ml Negative test result = MMP-9 <40 ng/ml InflammaDry is CE Marked and commercially available in Europe. At this time InflammaDry is pending 510(k) review by FDA and is not commercially available in the U.S. How to Use InflammaDry: Four-step Process 1. Gently dab the Sample Collector in 6-8 locatons on the palpebral conjunctva (lower eyelid) to collect a tear sample. Do not use a dragging moton. 2. Snap the sample collector into the test cassette and press firmly where indicated. 3. Dip the test cassette into the provided buffer vial for 20 seconds. Replace the cap. 4. Read the results: 2 lines (1 red, 1 blue) = positive, 1 line (blue) = negative Place for Conventional Testing???? Value of Educational Testing Chronic and Progressive Disease Process Multiple Etiologies Multiple Modalities in Treatment Place for Conventional Testing???? Value of Educational Testing Chronic and Progressive Disease Process Multiple Etiologies Multiple Modalities in Treatment Evaluate Tear Meniscus