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Advanced Treatment in Ocular Surface Disease Disclosures • Douglas K. Devries – Consultant or Speakers Bureau for • Allergan Douglas K. Devries, O.D. Eye Care Associates of Nevada • AMO • TearLab • NicOx • BVI • B&L Chronic Dry Eye – Should I Treat It Revenue Potential • Higher Level of Care to Your Patient Re-Appointment Level II $38.19 Re-Appointment Level III $60.94 • Expense vs Revenue Center Re-Appointment Level IV $91.56 • Revenue per Patient • Patients Decide “Cost vs Benefit” Will be at least 2 visits and upwards to 8 visits Punctal Occlusion OU(one set) $194.84 *Medicare Rates in Nevada Net Revenue $341.00 to $800.00 Plus Per Patient with repeat visits in future years Dry Eye – “Greatest Opportunity is Yet to Come” 2010 Company Ocular Surface Disease Greatest Opportunity is Yet to Come Compound Status Inspire Diquafosol/Prolacria Phase III Alcon 15-s-HETE/Procaylx Phase III Vista Milcrin Early ISTA Ecabet Phase II Otsuka Rebamipide Lantiobio Mole-1901 Phase III Daichii Cevelamine Phase III 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 Solvay Estratest Alacrity Alty 0501 Phase II Can-Fite CF-101 Phase II Phase III Santen Rivoglitazone Early Fovea Calcineur Early SCIL proNGF Early Phase III Sept. 2012 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 Multiple Goals • Recalcitrant Cases of OSD – Where do you go from here? • Compounding Pharmaceuticals • Mechanical Therapy Clinical Presentation Can Vary in Severity Mild Severe Symptom Driven Questionnaire • Ocular Surface Disease Index (OSDI) Allergan • Create Your Own Questions on Your Letterhead Slitlamp • Ask Common Dry Eye Symptoms • Rank Symptoms • Never – Slight – Moderate - Severe Fluorescein Dye Stain 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 The Healthy Tear Film A Delicate Balance • Lipid, aqueous and mucin components • Outer lipid layer prevents evaporation – Secreted by meibomian glands • 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® • 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 17 Image from Dry Eye and Ocular Surface Disorders, 2004 Summary: Pathophysiology of OSD Consequences of Tear Composition Changes in CDE • Immune-mediated inflammation of lacrimal glands and ocular surface • Altered environment for ocular surface tissues – Increased osmolarity – Cytokines in tears, altered tear composition – 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 • Inflammation disrupts normal neuronal control of tearing • Multiple triggers and predisposing factors • Ocular surface damage – Loss of corneal epithelial integrity – Squamous metaplasia of conjunctival epithelium Low blink rate Systemic diseases Age Exposure Conjunctivo-chalasis Toxic drugs/ preservatives Other autoimmune diseases Ocular Surface Disease Testing Eyelid inflammation Allergy Flora changes Sjogren syndrome Lipid changes Ø Evaluate Tear Meniscus TEAR FILM INSTABILITY / EVAPORATION Goblet cell loss Blepharitis/MGD Tear hyperosmolarity Epithelial cell damage Contact lens Environment Neurogenic inflammation Neurostimulation Computer work Ø Lissamine Green Staining Ø Meibomian Gland Expression Apoptosis Corneal damage conjunctival metaplasia INFLAMMATION Ocular surgery Ø NaFl Staining & Tear Break Up Time Improper lipid spreading Cytokine release MMP activation Systemic drugs Neurotrophic Ø Schirmers With Anesthetic or Quick Zone Chronic inflammation Refractive surgery Viral/bacterial infection Menopause Lid margin irregularities Hormonal changes Baudoin and Rolando 2007 ITF Recommendations: Severity Levels —Signs of Dry Eye Dry Eye Overview Dry Eye Severity Level 1 2 3 4 General Symptoms Mild Symptoms Moderate Symptoms Severe Symptoms Extremely Severe Symptoms Diagnosis Conjunctival staining Mild Corneal staining Tear film Moderate Marked Scarring Mild punctate Marked punctate central Severe punctate erosions Visual signs Other Filamentary keratitis Example staining TBUT (sec)* Schirmer score (mm/5 min)* *Not <12 >2 to <7 <3 <3 >10 >5 to <10 <5 <2 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 —Symptoms of Dry Eye Dry Eye Overview Dry Eye Severity Level 1 2 3 4 General Symptoms Mild Symptoms Moderate Symptoms Severe Symptoms Extremely Severe Symptoms Symptoms: itchy, sandy, gritty, dry Always Never to Seldom Sometimes Frequent Discomfort: stinging, burning, pain No Yes Yes Yes Vision: blurring, interrupted No No Sometimes Usually Less than 3 times per day Several times per day Several times per day Several times per day Use of artificial tears 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. What is Dry Eye Disease? Progression of DTS Severity Levels Mild to moderate symptoms, no signs LEVEL 1 Official Definition: Mild to moderate conjunctival signs LEVEL 2 Moderate to severe symptoms Tear film signs, Visual signs Mild corneal punctate staining Conjunctival staining LEVEL 3 Severe symptoms Marked corneal punctate staining Central corneal staining Filamentary keratitis LEVEL 4 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. DEWS Report, Ocular Surface April 2007 Vol 5 No 2 Behrens et al, submitted Need for a More Objective Dry Eye Test • The importance of osmolarity • The trend in point-of-care diagnostics Possible Paradigm Shift • Objective Lab Measurements of Ocular Surface Disease • Needs to be quick • Needs to allow for minimal tear volume patients • Needs to be easy for staff and patients Osmolarity as a Gold Standard 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 Hyperosmolarity in Dry Eye Diagnosis Hyperosmolarity & Ocular Surface Damage Hyperosmolarity as a Proinflammatory Stress Liu H. Invest Ophthalmol Vis Sci. 2009;50:3671–3679 Osmolarity Severity Analysis Osmolarity is the only sign to become stable a6er Rx 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 Schirmers TBUT Staining Meniscus Height 87% 31% 25% 31% 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 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 Testing for Inflammation – 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 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 findings1 § Normal range between 3-41 ng/ml § Ocular surface disease (i.e. dry eye) demonstrates elevated levels of MMP-9 in tears1 [1] Chotikavanich S, de Paiva CS, Li de Quan, et al. Invest Ophthalmol Vis Sci 2009; 50(7): 3203-3209. 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 InflammaDry How to Use InflammaDry: Four-step Process § 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 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. Limit of Detection: the normal level of MMP-9 in human tears ranges from 3-41 ng/ml 3. Dip the test cassette into the provided buffer vial for 20 seconds. Replace the cap. § Positive test result = MMP-9 ≥ 40 ng/ml § Negative test result = MMP-9 <40 ng/ml 4. Read the results: 2 lines (1 red, 1 blue) = positive, 1 line (blue) = negative 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. Place for Conventional Testing???? Place for Conventional Testing???? • Value of Educational Testing • Value of Educational Testing • Chronic and Progressive Disease Process • Chronic and Progressive Disease Process • Multiple Etiologies • Multiple Etiologies • Multiple Modalities in Treatment • Multiple Modalities in Treatment Evaluate Tear Meniscus
