Meibomian Gland Dysfunction: Expert Perspectives
Transcription
Meibomian Gland Dysfunction: Expert Perspectives
8/1/2014 Disclosures Meibomian Gland Dysfunction: Expert Perspectives on Diagnostic and Therapeutic Considerations of One of the Most Common Pathologies in Eye Care Caroline A. Blackie, OD, PhD Barry Eiden, OD, FAAO Amber Gaume Giannoni, OD, FAAO Donald Korb, OD Walter O. Whitey, OD, MBA, FAAO Anterior Segment Section Symposium November 12, 2014 Please silence all mobile devices. Unauthorized recording of this session is prohibited. Please complete your session evaluation using EyeMAP™ online at http://eyemap.cistems.net Tweet about this session using the official meeting hashtag #aaoptom14 Interest Continues to Grow: Dry Eye Studies/Year 2003-2012 1000 900 800 700 600 500 400 300 200 100 0 Meibomian Gland Dysfunction is One of the Hottest Topics in Eye Care Dry Eye Market Overview • >25 Million Americans suffer from dry eye disease 2003 2004 2005 2006 2007 • $3.8 Billion spent on dry eye symptom relief annually in the U.S. alone • Most frequently encountered disease state by eye care professionals 2008 Opportunity 2009 2010 2011 2012 STUDIES 1 Prevent Blindness America 2013 & Marketscope 2 GlobalData, Inc. • Caroline Blackie, OD, PhD, FAAO - Co-founder & stockholder of TearScience Research funding personal and TearScience • Donald Korb, OD, FAAO - Co-founder & stockholder of TearScience Research funding personal and TearScience • Barry Eiden, OD, FAAO • Amber Gaume Giannoni, OD, FAAO – Alcon Advisory Board • Walter Whitley, OD, MBA, FAAO has received honorarium or research funding from Alcon (Advisory Board, Research, Speaker), Allergan (Advisory Board, Research, Speaker), Bausch and Lomb (Advisory Board, Speaker), Biotissue (Advisory Board), Nicox (Advisory Board), TearLab (Advisory Board), Tearscience (Speaker) Better clinical outcomes for patients Patient Retention Practice & Referrals Growth Market Scope 2013 Comprehensive Report on the Global Dry Eye Products Market 6 1 8/1/2014 Dry Eye Supplements Fail to Address the Underlying Cause Dry Eye Centers Opening Across US Beard B. Boston Foundation for Sight Survey. Report Back to the Community. Boston Foundation for Sight. July 15, 2010. www.bostonsight.org. Why Treat Ocular Surface Disease? Better Quality of Vision • Address signs/symptoms • Provide relief to patients for which there are limited treatment options • Improve CL intolerance • Improve outcomes in surgical procedures --- 20/20 --- • Stress of surgery on the visual system and even the mildest tear film abnormality result in a significant reduction in quality of vision and patient satisfaction. • Due to this, proper ocular surface treatment is critical to outcomes. • To grow your practice What is Dry Eye Disease? Definition: 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. Dry Eye: Increased Clinical Focus An Important Opportunity • Mounting patient awareness • Progresses with age and lack of effective treatment • Driven by tear instability • Exacerbated by intense, prolonged visual tasks • Impacts vision as well as comfort DEWS Report, Ocular Surface April 2007 Vol 5 No 2 2 8/1/2014 Growing Awareness of MGD ESTABLISHING THE PROBLEM EPIDEMIOLGY OF MGD Caroline A. Blackie, OD, PhD Korb Associates, Boston, MA Senior Scientist TearScience, Inc., Morrisville, NC Donald R. Korb, OD Korb Associates, Boston, MA Co-founder, TearScience, Inc., Morrisville, NC Anterior Segment Section Symposium November 12, 2014 DISLOSURE STATEMENT Founding member of TearScience Inc. Financial interest in TearScience Inc. EPIDEMIOLOGY? • Literally: The study of what is upon the people • The incidence, distribution, and control of disease in a population • The sum of the factors controlling the presence or absence of a disease • Prevalence: the percentage of a population that is affected with a particular disease at a given time HOW DO WE GATHER THE DATA? WHY? We use epidemiological data to: • Understand the significance of the MGD within our local, national and international communities; • Assess the ocular surface health states and health needs of our clinical populations; • Implement and evaluate interventions that are designed to treat MGD; • Efficiently and effectively provide screening and treatment for MGD to all members of our population in a way that is consistent with our policy and health resource values. • Make decisions regarding reimbursement and other policy recommendations for the management of MGD. HOW DO WE GATHER THE DATA? EPIDEMIOLOGICAL STUDIES COHORT STUDIES CASE STUDIES RETROSPECTIVE EPIDEMIOLOGICAL STUDIES EXPERIMENTAL OBSERVATIONAL PROSPECTIVE Please silence all mobile devices. Unauthorized recording of this session is prohibited. RANDOMIZED CONTROLLED TRIAL EXPERIMENTAL OBSERVATIONAL COHORT STUDIES CASE STUDIES RETROSPECTIVE RANDOMIZED CONTROLLED TRIAL PROSPECTIVE Challenge: 1. Clear Definition 2. Metrics to gather high quality data 3 8/1/2014 MEIBOMIAN GLAND DYSFUNCTION Do we know what it is? PRE 1977, 80: INFECTED/INFLAMED, HYPERSECRETORY STATE TWO LANDMARK PAPERS MEIBOMIAN GLAND DYSFUNCTION The MGD workshop executive summary (2011): • • “MGD may well be the leading cause of Dry Eye through out the world” “Although this condition affects the health and well-being of millions of people, there is no global consensus on the definition, classification, diagnosis, or therapy for MGD.” McCulley and Sciallis, 1977: Identified ‘Meibomian Dysfunction’ that resulted in: – – – – – Stagnation of the gland secretions Minimal signs lid inflammation Ocular surface inflammation (SPK) Tear film instability due to a compromised lipid layer Symptoms of discomfort Korb and Henriquez 1980: DEFINITION • Meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. It may result in alteration of • – – – – Introduced the term ‘Meibomian Gland Dysfunction’. – – – – – Gland obstruction: Unexplained contact lens discomfort Dry eye symptoms Reduced MG secretion Pathophysiological evidence for obstruction Consequences of obstruction: Duct dilation, atrophy, drop out the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease. RISK FACTORS • Systemic: – • • Aqueous Deficiency Dry Eye Aging, Hypertension, Menopause, Complexion, Rosacea, Atopy, Androgen deficiency, Prostate hyperplasia, Lupus, Parkinson’s, Polycystic ovary syndrome, Sjögren’s, etc. • Contact Lens Wear • Glaucoma Medications Medications: – • OPHTHALMIC RISK FACTORS • Other Lid Margin Disease Anti-depressants, Antihistamines, Acne (Isortretinoin Tx), Antiandrogens, Prostate Medications, etc. – Anterior blepharitis Environment: – Rosacea – – Demodex Humidity, Visual task, Geography, Temperature, etc. AQUEOUS DEFICIENT DRY EYE & MGD CONTACT LENS WEAR & MGD The mere presence of a contact lens on the eye induces evaporative stress. • MGD Workshop report on Epidemiology 2011: – MGD is more likely to be present with ADDE and with Sjögrens syndrome compared to controls • Bron et al. 2009: – The phenotypes of ADDE and EDE can be difficult to separate particularly in advanced disease • Suhalim et al. 2014: – Evaporative stress results in MGD (even when the evaporative stress does not originate with the glands) • Korb et al. 1986: • Suhalim et al. 2014: • Korb and Henriquez 1980: • Ong and Larke 1990: – – – – This alteration of the normal tear film results in abnormal, unstable (or, in some cases, undetectable) lipid layer and increased rates of evaporation Any form of evaporative stress results in MGD Contact lens wearers with unexplainable reduced wearing time had very high likelihood of MGD After 6 months of CL wear 30% of wearers showed increase in MGD where as only 20% on controls did. CL wear accelerates MGD • Paugh et al. 1990: • Arita et al. 2009: – – Treatment for MGD (lid margin scrubs and lid massage) was effective in improving tear film stability and reducing ocular surface inflammation in contact lens wearers with MGD Contact lens wearers (mean age ~30) demonstrated the same degree of MGD and drop out as the 60+ age group of normals. CL wear accelerates MGD 4 8/1/2014 ROSACEA, ANTERIOR BLEPHARITIS, DEMODEX & MGD GLAUCOMA MEDICATION & MGD ALL STRONGLY ASSOCIATED WITH MGD • Arita et al. 2012a and b, Bahtra et al. 2012, Cunniffe et al. 2011: • - Glaucoma medications significantly elevate the risk and progression of MGD. - – 87% of patients with anterior blepharitis evidenced abnormal gland secretions compared to 6% of controls The preservatives in glaucoma medications are known to destabilize the tear film, cause evaporative stress and result in dry eye. • • Suhalim et al. 2014: - McCann and Tomlinson 2009: – 80% of patients with anterior blepharitis evidenced meibomian gland drop out compared to 30% of controls • Baudouin et al. 2004 and 2008: MGD Workshop Epidemiology Report 2011: – 74% of patients with mixed blepharitis evidenced MG drop out compared to only 20% in controls Evaporative stress has been shown to cause MGD through a cascade of events starting with up-regulation of the glands, depletion of meibocyte stem cells and early aging of the glands. This results in gland obstruction, gland atrophy and drop out. • Soboleskwa et al. 2014: • Bahtia and Del Rosso 2006: • Liu et al. 2010: – One of the most common ocular findings with rosacea is MGD Glaucoma patients are at very high risk – Demodex is more prevalent and more active in patients with rosacea for developing MGD and dry eye due to the glaucoma therapy itself. – Demodex causes meibomian gland dysfunction GENERAL PREVALENCE DATA BURDEN ON SOCIETY THE DATA IS ALL OVER THE MAP (3.5-70%) No consistent metrics, varying definitions Society is causing the problem and we are paying the price Impossible to answer due to poor prevalence data. • The Shihpai Eye Study 2003: DE in general (this means a symptomatic mixed population): – 61.7% of the symptomatic population had MGD • Ong 1996: – 49% of contact lens wearers and 43% of general population • Miljanovic et al 2012, Tong et al 2010: • Yu et al 2011: • Galor et al 2012: • Wadhuthantri et al 2012: – Patients struggle with everyday tasks (reading, working, etc.) • Ong and Larke 1991: – 39% of general population – Direct healthcare costs ~ $3.84 billion (~$783 per patient per year) • Beijing study 2009: – 4 X increase in expenditure on DE between 2001 and 2006 – 69.3% of general population • Foulks et al 2012: – Per patient expenditure on pharmaceuticals including OTC drops and ointments was up by ~ 7% from 2008-2009 – True prevalence of MGD is not known: studies show 20-60% GOING FORWARD WHAT NOW? METRICS FOR: DEFINITION • Meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/ quantitative changes in the glandular secretion. • It may result in alteration of – – – – the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease. • Functional State of the Glands Sequelae DRY EYE MGD is MUCH bigger than the symptomatic dry eye population. Screen everyone for MGD. Secretion quality - Currently a qualitative measure. Assign a number to the appearance. Quantify pressure. - Functional volume (what is expressed with blinking) - MGE (developed by TS) • Gland structure • Secretion volume - Gland imaging: Meibography/ Transillumination) - Assess for gland truncation/ or drop out and duct dilation. - Typically a qualitative measure. Assign a number for the estimated volume. Quantify pressure. - Meibometry - Interferometry - Qualitative e.g. TearScope - Quantitative e.g. LipiView (cut off value diagnostic for MGD) SCREEN FOR MGD NOT DRY EYE 5 8/1/2014 FUTURE is PREVENTION Thank you! Stop only looking for Dry Eye. START LOOKING FOR MGD. • Learn to how to identify and diagnose MGD to - Establish true prevalence data - Educate clinics and patients about MGD - Embrace a culture of prevention by offering cutting edge treatments and ongoing lid margin health maintenance Pathophysiology Defined Webster Medical Dictionary, 2014 PATHOPHYSIOLOGY OF MEIBOMIAN GLAND DYSFUNCTION The physiology of abnormal states, Donald R. Korb, OD Korb Associates, Boston, MA Co-founder, TearScience, Inc., Morrisville, NC Affiliated Clinical Professor School of Optometry, University of CA, Berkeley Anterior Segment Section Symposium November 12, 2014 DISCLOSURE STATEMENT Co-founder & stockholder of TearScience Research funding personal and TearScience Please silence all mobile devices. Unauthorized recording of this session is prohibited. Pathophysiology Defined Webster Medical Dictionary, 2014 What is MGD ? Classical Ophthalmology = Infective ̶ inflammation The physiology of abnormal states, and specifically: the functional changes that accompany a particular syndrome or disease Meibomitis ̶ Meibomianitis Inflammation of the meibomian (tarsal) glands Can discuss anatomy without function, but not function without anatomy Dorland’s Illustrated Medical Dictionary, 2011 MGD ̶ Term coined in1980 Korb and Henriquez 6 8/1/2014 MGD Defined 2011 International Workshop on MGD MGD is the leading cause of dry eye "Meibomian gland dysfunction is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by NOT aqueous deficiency terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. This may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease.” Contemporary Understanding of MGD ̶ 2014 Contemporary Understanding of MGD ̶ 2014 Obstruction of duct Meibomitis ̶ Meibomianitis • Not a primary bacterial disease • Often associated with blepharitis Dilation of duct Autoimmune • RA • Sjögrens • Lupus FUNCTION and STRUCTURE Obstruction of duct McCulley 1977 • Stagnant MG secretions and sequelae Dilation of duct Korb and Henriquez 1980 • Obstruction of duct • Pathophysiology – obstruction Jester 1982 • MG obstruction = duct • Dilation and cystic changes Meibomian Gland Dysfunction • Obstructive • Obvious • Non Obvious Obvious MGD Normal appearing lids (Does not rule out non-obvious MGD) Pathophysiology of Ductal Obstruction Obvious MGD Norn 1987 • Active or inactive glands Blackie and Korb 2006 - 2014 • Developed function • Non obvious MGD • Morphology-function – no correlation Normal appearing lids (Does not rule out non-obvious MGD) Pathophysiology of Ductal Obstruction Korb and Henriquez – 1980 (humans) Korb and Henriquez – 1980 (humans) Obstruction of the Meibomian gland orifices by desquamated epithelial cells in keratotic clusters Obstruction of the Meibomian gland orifices by desquamated epithelial cells in keratotic clusters Jester – 1982 (rabbits) • Used epinephrine to block orifices • Led to duct dilation and cystic changes 7 8/1/2014 Pathophysiology of Ductal Obstruction Korb and Henriquez – 1980 (humans) Obstruction of the Meibomian gland orifices by desquamated epithelial cells in keratotic clusters Pathophysiology of Ductal Obstruction 2014 – Irrefutable Conclusion Obstruction of the Meibomian glands leads to: • Loss of function Jester – 1982 (rabbits) • Used epinephrine to block orifices • Led to duct dilation and cystic changes Nichols et al – 2014 (mice) • Cauterized orifices • At 12 weeks morphological changes • Atrophy and gland drop out • Morphological changes • Atrophy • Gland drop out Treatment must deal with obstruction Etiology ̶ Evaporative Stress Etiology ̶ Evaporative Stress Effect of desiccating stress on mouse meibomian gland function Effect of desiccating stress on mouse meibomian gland function Suhalim JL, Jester JV. Ocul Surf, 2014 Suhalim JL, Jester JV. Ocul Surf, 2014 Mice placed in low humidity Mice placed in low humidity Evaporative stress Evaporative stress Increased meibocyte production – oil production Increased meibocyte production – oil production Dilation of ducts extensive and possible obstruction Dilation of ducts extensive and possible obstruction Short maturation time = increase in protein/lipid ratio Short maturation time = increase in protein/lipid ratio Tear film stability impaired = > evaporative stress Tear film stability impaired = > evaporative stress Chronic exposure to evaporative stress depletes the meibocyte stem cells resulting in early aging of the glands, gland atrophy and drop out Etiology of MG Obstruction Evaporative stress Blinking inhibition Age Drugs Epithelial overgrowth Hormones Eczema Lipid Profiles Seborrhea Surfactants - Phospholipids Dry Eye Cascade Korb & Blackie - 2008 Stasis – Obstruction Decrease in lipid secretions and LLT Evaporation increases – 4 - 16 x Decrease in aqueous layer thickness Unstable tear film and evaporative stress Stare Test Is inflammation the cause or a sequelae ? 8 8/1/2014 Pathophysiology MGD Obstruction – many causes including evaporative stress SYMPTOMS START Loss of MG function Evaporative stress ̶ tear film compromise Lubricity compromised LWE Ocular surface compromise Atrophy Gland dropout Anatomical changes Notching Line of Marx Inflammation Corneal hyperalgesia Fulminant Disease Definition: Coming on suddenly with great severity S Y M P T O M S I N C R E A S E • Occurs, but rarely • Triggers not known • Many anecdotes suggest an acute situation triggers neuropathic pain Neuropathic pain Summary – Pathogenesis of MGD Summary – Pathogenesis of MGD • Evaporative stress results in a broad spectrum of sequelae, and is the single most frequent cause of MGD • Evaporative stress results in a broad spectrum of sequelae, and is the single most frequent cause of MGD Contact lens considerations Contact lens considerations • Blink inhibition and partial blinking also result in MGD Summary – Pathogenesis of MGD Summary – Pathogenesis of MGD • Evaporative stress results in a broad spectrum of sequelae, and is the single most frequent cause of MGD • Evaporative stress results in a broad spectrum of sequelae, and is the single most frequent cause of MGD • Blink inhibition and partial blinking also result in MGD • Blink inhibition and partial blinking also result in MGD • Terminal duct obstruction is the mechanism which initiates the pathophysiology of MGD • Terminal duct obstruction is the mechanism which initiates the pathophysiology of MGD Contact lens considerations Contact lens considerations • The cascade results in ocular surface compromise, lack of lubricity, lid changes, MG atrophy and drop out, inflammation, corneal hyperalgesia and neuropathic pain. 9 8/1/2014 Summary – Pathogenesis of MGD Thank you to the over 400 • Evaporative stress results in a broad spectrum of sequelae, and is the single most frequent cause of MGD Contact lens considerations Scientists • Blink inhibition and partial blinking also result in MGD Optometrists Ophthalmologists • Terminal duct obstruction is the mechanism which initiates the pathophysiology of MGD Residents & Fellows And all those in industry • The cascade results in ocular surface compromise, lack of lubricity, lid changes, MG atrophy and drop out, inflammation, corneal hyperalgesia and neuropathic pain. Who have taught me unselfishly • Treatment must be directed to the prevention and resolution of MG obstruction & worked with me for the past 40 years Disclosures: AAO Anterior Section Symposium • Paid Advisory Board Member for Alcon Meibomian Gland Dysfunction: Clinical Diagnosis and Technology Amber Gaume Giannoni, OD, FAAO, Diplomate (ABO) [email protected] Goals: After this lecture, the attendee will: • Be able to identify lid margin, gland and meibum changes associated with MGD • Understand the latest tools, techniques and technology in diagnosing MGD • Become familiar with MGD classification I do not have any financial or proprietary interests relative to this presentation Outline: I. Who should you assess? Why is it important? Identifying patients II. Clinical Assessment and New Technology in MGD: Tear film quality and blink assessment TBUT and staining Lid margin changes and inflammation Meibum quantity and quality Meibomian gland imaging III. Staging/Classification of MGD 10 8/1/2014 Why Is It Important? Ocular surface wellness is imperative for: Successful surgical outcomes Minimizing post-surgical complications Successful contact lens wear (any type) Quality of Life Identifying patients: Who should we evaluate? Symptomatic Screening failures: OSDI, SPEED, other questionnaire Point-of-care diagnostic tests (i.e. TearLab, InflammaDry etc.) Every pre-CL fit Dry-eye inducing systemic disease Dry-eye inducing medications Clinical Assessment: Tear Stability/TBUT: Tear-Film: General Appearance: Clinical Assessment: Debris? Oily? Foamy (saponification)? Meniscus height? Blink assessment (partial blinks)? Stability: Interferometry Tear break-up time (TBUT) NaFl BUT: > 2ul of NaFl destabilizes the tear film* No volume control with conventional strip Micropipette? Dry Eye Test (DET) strip: <1ul of NaFl Non-invasive BUT: Manual keratometer, placido topography, keratograph How many readings? * Marquardt et. al., 1986 NEW TECHNOLOGY: NEW TECHNOLOGY: Keratograph 5M (Oculus, Inc) with Dry Eye Suite Keratograph 5M (Oculus, Inc) with Dry Eye Suite Computerized Non-Invasive Keratograph Break Up Time (NIKBUT) • Tear meniscus height • Computerized redness classification • Qualitative tear interferometry • • • • Placido disk topography Anterior segment photography/video Noninvasive break-up (NIK-BUT) Infrared meibography 11 8/1/2014 Clinical Assessment: Lid Margin Evaluation: Tear Film Photo/Video Discussion Increased thickness? Posterior lid margin redness? Telangiectasia? Scalloping/serration? Epithelial ridging? Conjunctivalization? Lid wiper epitheliopathy? Clinical Assessment: Meibomian Gland Evaluation: General Appearance: Caps? Focal injection? Distended or pouting gland orifices? Migration of gland line? Narrowing of ducts/loss of cuffing? Opaque glands/scarring? Lid and Meibomian Gland Photo/Video Discussion Clinical Assessment: Diagnostic expression should evaluate: What if the lids and glands look normal? Are we done? MUST express to properly assess! 1. Ease of expression: • Mimic normal blink force 2. Secretion quality: • Thin and clear vs. turbid, thickened or none 3. Number of expressible glands: • 20-70% of glands are expressible at any given time* * Norn. Acta Ophthal. 1987; Blackie, Korb. Cornea, 2009 12 8/1/2014 Clinical Assessment: Meibomian Gland Evaluation: Diagnostic Gland Expression Photo/Video Discussion Imaging: Contact transillumination Infrared meibography (great for patient education!) What do I look for? Gland distention Partial glands Missing glands GRADE PARTIAL GLANDS 1 No partial glands 2 <25% partial glands 3 25%-75% partial glands 4 >75% partial glands GRADE GLAND DROPOUT 0 No dropout 1 <25% 2 < 50% 3 >75% 4 < 100% Staging/Classification of MGD: Importance of Disease Staging: Meibography Photo/Video Discussion Foundation for diagnosis, especially if unfamiliar with MGD Monitor response to treatment, especially when symptoms aren’t improving Foundation for stepped therapy instead of “shooting in-the-dark” 13 8/1/2014 Staging and of MGD (Outlined from the MGD Workshop Staging Chart) STAGE DRY EYE SYMPTOMS 1 None •Oil quality score: >2 to <4 •Expressibility score:1 •No lid changes or gland dropout 2 Mild •Oil quality score: Grade <4 to <8 •Expressibility score: 1 •Mild lid changes, no gland dropout 3 Moderate 4 Severe CLINICAL SIGNS OF MGD CORNEAL/CONJ STAINING None None to mild •Oil quality score: >8 to < 13 •Expressibility score: 2 •Moderate lid changes, plugging, vascularity Mild to Moderate conjunctiva and periph cornea •Oil quality score: >13 •Expressibility score: 3 •Severe lid changes, dropout, displacement, inflammation Severe conjunctiva, periph and central cornea GRADE MEIBUM QUALITY* MEIBUM EXPRESSIBILITY (central 8 glands) (central 8 glands) 0 Clear fluid All expressible 1 Cloudy fluid 3-4 expressible 2 Particulate fluid 1-2 expressible 3 Toothpaste None express *Each expressed gland is assigned a grade for a cumulative meibum quality score OK, we diagnosed MGD, Now what do we do about it??? S.Barry Eiden, OD, FAAO North Suburban Vision Consultants, Ltd. Keratoconus Specialists of Illinois Assistant Clinical Professor, University of Illinois Medical Center, Dpt. of Ophthalmology Adjunct Faculty: Indiana, Illinois, Salus and UMSL Colleges of Optometry 14 8/1/2014 General Dry Eye Therapy… it should be based on the cause • • • • • • Is it due to exogenous causes? Is it due to anatomical issues? Is it assoc. w/ blepharitis / MGD? Is there an inflammatory component? Is there an aqueous deficiency (ADDE)? Is there a lipid deficiency – evaporative component (EDE)? Key: Target your therapy Therapeutic Approaches for MGD & Evaporative Dry Eye • OTC, Mechanical and Adjunctive Therapy – – – – – – Heat application Tear film “stabilizers” (reduce evaporation) Lid Hygiene MG Expression MG orifice exfoliation MG Probing • Medical Therapy – Topical (anti-inflammatory, combination agents) – Oral (Omega-3, Doxy) • Advanced Therapeutic Technologies – – – – LipiFlow MiBo Thermaflow ILP BlephEx Heat Application to MGs Lid Hygiene • M.O.A.: Liquification and loosening of the meibum • Traditional Approaches: • Home Remedy: “Baby Shampoo Systems” • Heat Masks: • Prepared Tx: “Medicated Lid Wipes” – Warm/hot washcloth compresses – Heated “Rice Baggy” – Others – Bruder Heat Mask – TranquilEyes – Others Tear Film “Stabilizers” • Use range: BID to QID • Purpose: to reduce tear film evaporation by stabilizing the lipid layer • Egs: – Systane Balance – Oasis Tears (+) – Liposome Spray – Ocusoft Retaine MGD – Others – Wash cloths – Q-Tips – Others – Types (pads, foam, “+” w/antibacterial preservative ) – Compliance based on perception Therapeutic Approaches & EDE for MGD “Tear Film Stabilizers” –Blink Tears line: low to high viscocity (tears, tearsPF, gel tears), contains “HA” but low MW. • Systane Balance: combination elements of Systane Ultra and Soothe XP, the “guar” complex – anionic phospholipids acts like velcro and attaches the aqueous layer to the lipid layer. – Designed for MGD and EDE 15 8/1/2014 HA*: Eye’s Natural Lubricant General Properties of HA: • One of the body’s natural lubricants: found in synovial fluid in the joints and in the eye Therapeutic Approaches MGD & EDE for “Tear Film Stabilizer” • Oasis Tears / Tears Plus 1 – naturally occurring glycosaminoglycan (a mucopolysaccharide)1 – shown to have anti-inflammatory properties,2 play a role in wound healing,3 and have a protective effect against oxidative damage 4 • Each molecule can hold up to 1000x its weight in water 1,5 • Stabilizes pre-corneal tear film HA HA 6 H 2O 3 *Hyaluronan is the salt form of hyaluronic acid. Figure reproduced from Winter WT, Arnott S. J Mol Biol. 1977;117:761-784. 1. Lapcik L Jr et al. Chem Rev. 1998;98:2663. 2. Pauloin T et al. Mol Vis. 2009;15:577. 3. Lerner L et al. Exp Eye Res. 1998;67:481. 4. Presti D, Scott JE. Cell Biochem Func. 1994;12:281. 5. Winter WT, Arnott S. J Mol Biol. 1997;117:761. Oasis Tears / Tears Plus • Hyaluronic Acid (HA) High M.W. • Glycerin (holds water molecules to the ocular surface) • Prolonged activity (8+hrs.) • Preservative free • One re-capable vial per day *Aragona A, et al, BJO 2002 86: 181-184. OCUSOFT RETAINE MGD Delivers phospholipids to the tear film via the LIPOSOME SPRAY surface of closed eyelids. Single-Dose. Light Mineral Oil 0.5%, Mineral Oil 0.5% - Provides long-lasting relief for moderate to severe dry eyes utilizing Novasorb, a proprietary cationic oil emulsion technology (microemulsification) Patented liposome technology to deliver water, lipids and vitamins A, C and E 16 8/1/2014 Meibomian Gland Expression Meibomian Orifice Exfoliation Devitalized epithelial cells accumulate on the lid margin, over the meibomian gland orifices. Significant accrual of this material can obscure the MG orifices and significantly impact MG function Mastrota Meibomian Paddle Tx: application of 1 drop topical anesthetic followed by mechanical debridement of the keratinized lower lid margin. MG Expressor Gulden, inc. Korb DR, Blackie CA Debridement-scaling: a new procedure that increases Meibomian gland function and reduces dry eye symptoms Cornea 2013 Dec;32(12):1554-7 CONCLUSIONS: The debridement-scaling of the LOM and lower lid margin provides statistically significant symptom relief and improvement in the MG function. The novel procedure should be considered in the management of MGD and evaporative dry eye Collins dual side MG Expressor ***Pre-MGE - Lid heating Maskin MG Probing Procedure • 2 & 4mm MG probes developed by distributed by Rhein Medical Steven Maksin, MD, • http://www.rheinmedical.com/search/index.php?method=details&id=1546&cl ass_id= Maskin Procedure – • • • • • • • • • • • • • • • Therapeutic Approaches MGD & EDE Modified Method by D. Seibel, OD, FAAO 1. Perform baseline Tear Osmolarity and then instill Proparacaine 2. Insert soft bandage contact lens 3. Apply topical ointment to lashes & lid margin - C-Lidocane 8%, 25% Jojoba Oil in petroleum base order in 45 GM quantity from Leiter's pharmacy 800-292-6773 - Ask for "Maskin Oinment". 4. After a few minutes wipe off ointment with tissue or gauze pads. 5. Glove up 6. Express meibomian glands with Qtip or Mastrota paddle 7. Use Maskin Aluminum Handle (Ref 91-1004 from Rhein Medical) and load Maskin 2mm probe (Ref 07-6040-2 from Rhein Medical - 800-637-4346 or www.RheinMedical.com). 8. Use Qtip or gauze pad in fingertips to slightly evert upper eyelid and expose MGs some hopefully pouted but not open and insert probe parallel to ductal tract until you feel a "pop". Some MGs are too atrophied to pop. Attempt to fully insert 2mm probe even in partially open ducts. Some small bleeding is normal but pt will not notice but will notice some discomfort. If probe bends you can bend in back straight with your finger no more than 4 times before it breaks off. I can usually get one probe to last for both upper lids. 9. Re-express MG with Qtip or Mastrota Paddle on upper lid. 10. Repeat Steps 6,8 & 9 on opposite upper lid. 11. Remove Bandage CLs, apply topical antibiotic sol and Pred Forte sol in-office. Tell pt that lids maybe puffy & red for 1 or 2 days. 12. Rx Doxycycline 100 mg p.o. BID x 2 wks 13, RTO in 2 wks and re-express upper MD and ductal probe lower MGs with another 2 wk round of Doxy. RTO 2 wks 14. Perform Tear Osmolarity to compare and then re-express all 4 lids. Usually find an approximately 15 point improvement in Tear Osmolarity after Tx. for Medical Therapy (anti-inflammatory): – Azithromycin topical (Azasite) – off label use – Topical steroids (Loteprednol – Lotemax ung) or Combo agents (Tobradex gtts vs. ung) – Cyclosporine (Restasis) – off label use – Oral Doxy ( maint. low dose – 20 to 50 mg) – Omega – 3 Fatty Acids (2g/day) Tobradex ST • Tx of acute posterior blepharitis: apply directly to lid margins BID for 1 to 2 weeks • Lower Dexamethasone concentration vs. Tobradex (0.05% vs. 0.1%) yet: • “Bioequivalent” due to increased retention time on the ocular surface (Xanthan Gum vehicle) • Alternative: Tobradex ung to lid margins BID 17 8/1/2014 Azithromycin (Azasite – Akorn) AzaSite® (azithromycin 1% solution) Treatment of blepharitis(off label use) • Both antibiotic and anti-inflammatory activity • High tissue penetration into lids • Extended duration w/ “DuraSite” vehicle • R’xd: 1 gtt QHS for 1 month for treatment of blepharitis • PM application to lids or drop • Duration & Frequency of Tx for chronic condition? – Recently: “new bottle!” 2wk Tx effect on lid redness (apply as drop or directly to lid margins) IN DEVELOPMENT: “AzaSite Plus” 1% azithromycin + 0.1% dexamethasone Durasite vehicle Doxycycline Issues: • GI issues, photosensitivity • Cost Issues – Eg low dose tx: – Periostat (20mg tabs): 100 tabs apx. $110. – Orecea (40mg SR caps): 30 capsults apx. $400! – Generic Doxy. (50mg tabs can be “pill cut” to 25mg): 60 tabs apx. $13! a 2wk Tx effect on MG plugging Luchs J, Advanced Ocular Care May/June 2010 Oral Management of Blepharitis and MGD • Doxyclycline – dosed 100 mg. BID 1mo, 50mg BID 1mo, 50 mg. QD 1mo – reduced to a maintenance dose of 25 mg. QD (cut 50mg tab) – Other lower doses: (Alodox kit 20mg/Periostat 20mg/Oracea 40 mg SR) • Omega 3 “Nutraceuticals” – – – – – HydroEyes TheraTears Nutrition PRN Omega EZ Tear Desire 2gm/day dose How to Minimize Stomach Problems with Tetracycline 1. Do not take the second pill (bid) before going to bed 2. Do not take pills with acidic beverages 3. Take pills with food (except a high dairy meal) 4. Prescribe the lowest dose available Courtesy Paul Karpecki, OD, FAAO 18 8/1/2014 Advanced Therapeutic Technologies for Tx of MGD/EDE LipiFlow® (Tear Thermal Science) Pulsation System • LipiFlo (Tear Science) • MiBo Thermaflow (Pain Point) • Intense Light Pulse Tx • BlephEx (Rysurg) LipiFlow Thermal Pulsation by TearScience, Inc. Intense Pulsed Light Treatment (IPL) *dev. by R. Toyos, MD – Memphis, Tn. LipiFlow safely and effectively treats Meibomian Gland Obstruction in both upper and lower eyelids simultaneously, in an in-office procedure, taking only 12 minutes per eye MiBo Thermaflow (Pain Point Medical) Intense Pulsed Light Treatment (IPL) • Originally developed for Dermatology (Rosacea Tx) • Short bursts of wavelength specific light (500-800nm) • Treat “ear to ear” (better effect vs. only lid tx) • + Effect via: – Increase in temperature (“worlds best hot compress!”) – should express glands after tx – Direct closure of superficial vessels reduces release of inflammatory mediators assoc. w/ MGD – Anti infective : kills pathogenic flora (bacteria and demodex) • Year 1: 3-4 Tx’s monthly then maintenance Tx Q 6-12mo. 19 8/1/2014 BlephEx Treatment Eiden’s Tx Protocols for MGD/EDE: • Mild Cases: Tear film stabilizers 3-4/d (pre & w/ CL if wearers), heat mask 2/d 2weeks then QD ongoing, Omega-3, lid wipes2/d 2 weeks then QD • Moderate Cases: above + In office Txs (MGE, Exfoliation, MTF / LipiFlow) + consider oral Doxy therapy • Obvious Inflammation Cases: above + Topical Tobradex ST BID to lids 2 weeks, Azasite QHS 1 mo. Practitioner Survey Outcomes • • • • • • • • • Do you use tear stabilizer OTC agents? Do you use Omega 3’s? Do you use heat treatment? Do you express MGs? Do you exfoliate MG orifices? Do you probe MGs? Do you use topical Rx Tx? Do you use oral Rx Tx? Do you use any advanced technology Tx? (Survey being taken from a group of 14 prominent anterior seg/CL specialty OD practices – will have results prior to AAO) 20