M G D Meibomian Gland Disease Meibomian Gland Dysfunction
Transcription
M G D Meibomian Gland Disease Meibomian Gland Dysfunction
6/6/2016 MGD Meibomian Gland Disease Meibomian Gland Dysfunction and Management Jack Schaeffer OD FAAO Schaeffer Eye Center Birimingham , Alabama Kelly K. Nichols, OD, MPH, PhD FERV Professor University of Houston College of Optometry Chair, TFOS International Meibomian Gland Workshop Disclosures • K. Nichols • Research support – Paid consultant to: • Alcon • Allergan • Celtic/ Resolvyx • Eleven Biotherapeutics • InSite • Ista • SARcode • TearLab – CL Tear Film Lab (OSU) • Alcon • CIBA • Inspire • TearLab • Pfizer • Vistakon – National Eye Institute • R01 EY015519 (PI) • R01 EY017951 (Co-I) • R34 EY017626 (Co-I) ©KNichols 2012 Meibomian Gland Dysfunction • The TFOS Report of the International Meibomian Gland Dysfunction Workshop – Etiologies – Definition/ Classification – Epidemiology – Clinical characteristics – Diagnosis/ Management – Contact lenses, surgical implications ©KNichols 2012 Current Dry Eye Definition DEWS—Classification of Dry Eye “Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.” ©KNichols 2012 20% 5% 65% 35%80% ©KNichols 2012 1 6/6/2016 MGD Contributes to Dry Eye DEWS Definition and classification report. Ocular Surface 2007 ©KNichols 2012 Dry Eye and MGD MGD is the most common cause of evaporative dry eye. ©KNichols 2012 ©KNichols 2012 TFOS International MGD Workshop • Over 65 International clinicians, scientists, and industry participants • 2+ year process • Published in March 2011, IOVS • #1 Most downloaded IOVS article for the last 12 months • Downloaded over 5500 times • All MGD workshop reports are in the “top 10” • Translation into 12 languages ©KNichols 2012 • www.tearfilm.org www.tearfilm.org Lecture Description Anatomy, Physiology and Pathophysiology of the Meibomian Gland Erich Knop, M.D., Ph.D. (Chair) Nadja Knop, M.D., Ph.D. Thomas J. Millar, Ph.D. Hiroto Obata, M.D. David A. Sullivan, Ph.D. ©KNichols 2012 ©KNichols 2012 2 6/6/2016 Meibomian Gland ‐ ANATOMY • Large sebaceous glands • No direct contact to hair follicles • Located in the tarsal plates • Upper and lower eye lids Meibomian Gland ‐ ANATOMY • Length • Follows the tarsus • Number • More in upper lid (30‐40) • Less in lower lid (20‐30) • Volume • Higher in upper lid (26µl vs. 13µl) • Relative functional contribution (upper vs. lower) to the tear film lipid layer is unknown Modified from Sobotta Atlas der Anatomie des Menschen. Urban & Schwarzenberg Verlag 1982, (reproduced from Knop N & Knop E. Ophthalmologe 2009; 106:872–883) Modified and colored from Krstic H. Human microscopic anatomy. Springer Medizin Verlag 1991, (reproduced from Knop N & Knop E Ophthalmologe 2009; 106:872–883) ©KNichols 2012 Meibomian Gland – PATHOLOGY ©KNichols 2012 Interacting Pathways in MGD • Obstructive MGD leads to a progressive ductal DILATATION and acinar ATROPHY Fom Knop E & Knop N. Meibom-Drüsen Teil IV. Funktionelle Interaktionen in der Pathogenese der Dysfunktion (MGD). Ophthalmologe.2009;106:980–987 Modified from Knop E & Knop N. Meibom-Drüsen Teil IV. Funktionelle Interaktionen in der Pathogenese der Dysfunktion (MGD). Ophthalmologe.2009;106:980–987 ©KNichols 2012 ©KNichols 2012 Meibomian Gland Dysfunction Definition & Classification J. Daniel Nelson, M.D. (Co‐Chair) Jun Shimazaki, M.D., Ph.D. (Co‐Chair) Jose M. Benitez‐del‐Castillo, M.D., Ph.D. Jennifer Craig, Ph.D., MCOptom James P. McCulley, M.D. Seika Den, M.D., Ph.D. Gary N. Foulks, M.D. ©KNichols 2012 ©KNichols 2012 3 6/6/2016 Classification of MGD Epidemiology and Associated Risk Factors of Meibomian Gland Dysfunction Debra A. Schaumberg, Sc.D., O.D., M.P.H. (Chair) Jason J. Nichols, O.D., M.P.H., Ph.D. Eric B. Papas, M.Sc., O.D., Ph.D. Louis Tong, F.R.C.S., M.B.B.S. Miki Uchino, M.D. Kelly K. Nichols, O.D., M.P.H., Ph.D. ©KNichols 2012 Prevalence of MGD * † ©KNichols 2012 Factors Associated with MGD ‡ § ¶ £ * Telangiectasia or Meibomian gland orifice plugging † Telangiectasia ‡ Gland dropout, expressibility and nature of Meibum secre on § Telangiectasia or Meibomian gland orifice plugging OR collarettes ¶ Tear break up time < 1SD (10 sec) £ Meibomian gland plugging OR collarettes (grade 2‐3) ©KNichols 2012 ©KNichols 2012 Factors Associated with MGD Factors Associated with MGD ©KNichols 2012 ©KNichols 2012 4 6/6/2016 Overlap of DED Symptoms and Clinical Signs of MGD Study Symptoms Assessed (all frequency) Shihpai Eye Study (Lin, 2003) Eye dryness Gritty/sandy Burning Sticky Watery/tearing Redness Lash crusting Eyes stuck shut (am) Bangkok Study (Lekhanont, 2006)* Eye dryness Foreign body sensation Burning Discomfort Sticky Tearing Clinical Evaluations/ MGD Definition Evaluation, Diagnosis and Grading of Severity of Meibomian Gland Dysfunction % with Dry Eye Symptoms who also had MGD Telangiectasis or gland plugging ≥ G1 61.7% (p = NR) Telangiectasis, Collarettes, and Plugging 63.6% (p = 0.006) Alan Tomlinson, MCOpt, Ph.D. (Chair) Anthony J. Bron, F.R.C.S. Donald R. Korb, O.D. Shiro Amano, M.D., Ph.D. Jerry R. Paugh, O.D. E. Ian Pearce, Ph.D. Richard Yee, M.D. Norihiko Yokoi, M.D., Ph.D. Reiko Arita, M.D., Ph.D. Murat Dogru, M.D. Stages of MGD Testing Summary • Symptoms (no validated survey) • Expression (not widely accepted) – Quality/ Quantity • Lid assessment – Redness (difficult to grade) – Irregularity – MG location • Staining (fluorescein) – Photography • Aq. Production (© 1903) ©KNichols 2012 Management and Therapy of Meibomian Gland Dysfunction Current Practice Patterns* • Lid hygiene, warm compresses and lid massage • Cleaning of the lid margin with baby shampoo, cotton buds or wet towels, daily for 5‐15 minutes • • • • Gerd Geerling, M.D. (Chair) Joseph Tauber, M.D. Christophe Baudouin, M.D., Ph.D. Eiki Goto, M.D. Yukihiro Matsumoto, M.D. Terrence O’Brien, M.D. Maurizio Rolando, M.D. Kazuo Tsubota, M.D. Kelly K. Nichols, O.D., M.P.H., Ph.D. Lubricants in cases with additional dry eye Topical antibiotic oint (moderate to severe) Systemic tetracyclines/ derivatives in recurrence Incision and curettage with optional steroid injection in chalazion *Excerpted from Moorfields Manual, Wills Eye Manual (Guidelines for posterior blepharitis and meibomitis) ©KNichols 2012 ©KNichols 2012 5 6/6/2016 Current Practice Patterns DISEASE STAGING Stage MGD grade • World‐wide variation • Underreporting difficult to assess patterns • Underdiagnosis common, clinical follow‐up irregular • Lid warming and hygiene common • Many use artificial lubricants • Most Common Rx: Systemic tetracycline or derivatives (less frequent in EU/Japan) – 2nd most common Rx: topical antibiotic or antibiotic‐ steroid combination + (minimally altered expressibility and secretion quality) 1 ++ (mildly altered expressibility and secretion quality) 2 +++ (moderately altered expressibility and secretion quality) 3 ++++ (severely altered expressibility and secretion quality) 4 “PLUS DISEASE” Symptoms Corneal Staining Asymptomatic None Minimal to Mild None to limited Moderate Mild to moderate; mainly peripheral Marked Marked; central in addition Co‐existing or accompanying disorders of the ocular surface and/ or eyelids ©KNichols 2012 Stages of MGD ©KNichols 2012 Recommended Staged Therapy Stage = I 2 3 4 Plus‐Disease +Inform patient (about dietary / environmental / medication effects) ± Eyelid hygiene (warming / expression) +Eyelid hygiene (warming / expression), Advise re: potential benefits of ambient humidity / n‐3 fatty acid, ± Lubricant/lipid, topical azithromycin, tetracycl. derivatives + Oral tetracyclines ± Ointment (pm), cyclosporine/steroid for DE + Anti‐inflammatory therapy for DE + Steroids, CL, Surgery ©KNichols 2012 ©KNichols 2012 Existing Clinical Trials Design and Conduct of Clinical Trials Penny A. Asbell, M.D.(Chair) Fiona Stapleton, M.Sc., O.D., Ph.D. Kerstin Wickström, Ph.D. Esen Akpek, M.D. Pasquale Aragona, M.D., Ph.D. Reza Dana, M.D., M.Sc., M.P.H. Michael A.Lemp, M.D. Kelly K. Nichols, O.D., M.P.H., Ph.D. Key Issues Findings Trial objective Majority interventional treatment trials. 1/3 comparative (hot compresses or artificial tears). Trial design /Methodology Primarily small trials (<40 subjects) of short (<3 months) duration. Most prospective, 3 randomized controlled design, & 2 were double masked. Study population Chronic disease but selection criteria not uniformly defined; lid changes & symptoms most common clinical characteristics. Inclusion criteria No specific and consistent criteria; most common are lid margin signs (80%), dry eye findings (50%), symptoms of discomfort/foreign body sensation (46%). Exclusion criteria Classification of exclusion criteria in three different categories: 1) Ocular disease related/CL wear (most common); 2) Iatrogenic ( e.g surgery, 1/3 studies); 3) Systemic disease related/pregnancy (15%). n = 26 ©KNichols 2012 6 6/6/2016 Summary Existing Clinical Trials Priorities for future clinical trials: Issue Findings Outcome measures 1. 2. 3. 4. 5. 6. 7. 8. Treatment Most lacked washout period & did not check for relapse; 50% allowed concurrent use of other treatment & 30% treatment in the control group; large variability between Tx duration but pharmacological trials tended to be longer with follow up. Statistics Limited number of RCTs available; difficult to calculate effect size, power or required sample size. Limited information on how missing data e.g. loss to follow up, exclusion due to non‐compliance, were handled. n = 26 Symptoms TBUT MG secretion/expression Schirmer Corneal staining MG obstruction Eyelids Lipid layer • Additional randomized, controlled, double‐ masked treatment trials with clearly defined objectives, relevant outcome measures based on pathophysiology, and refined inclusion & exclusion criteria • Determination of the natural history of MGD • Further understanding of the association with dry eye disease (and risk factors) • Development and validation of a symptom questionnaire specific to MGD. ©KNichols 2012 Definition J. Daniel Nelson, M.D. (Co‐Chair) Jun Shimazaki, M.D., Ph.D. (Co‐Chair) Jose M. Benitez‐del‐Castillo, M.D., Ph.D. Jennifer P. Craig, Ph.D., MCOptom James P. McCulley, M.D. Seika Den, M.D., Ph.D. Gary Foulks, M.D. Clinical Trials Penny A. Asbell, M.D.(Chair) Fiona Stapleton, MScOD, Ph.D. Kerstin Wickström, Ph.D. Esen Akpek, M.D. Pasquale Aragona, M.D., Ph.D. Reza Dana, M.D., M.Sc., M.P.H. Michael A. Lemp, M.D. Kelly K. Nichols, O.D., M.P.H., Ph.D. Diagnosis AlanTomlinson, MCOpt, Ph.D. (Chair) Anthony J. Bron, F.R.C.S. Donald R. Korb, O.D. Shiro Amano, M.D., Ph.D. Jerry R. Paugh, O.D. E. Ian Pearce, Ph.D. Richard Yee, M.D. Norihiko Yokoi, M.D., Ph.D. Reiko Arita, M.D., Ph.D. Murat Dogru , M.D. Anatomy Erich Knop, M.D., Ph.D. (Chair) Nadja Knop, M.D., Ph.D. Thomas J. Millar, Ph.D. Hiroto Obata, M.D. David A. Sullivan, Ph.D. Team Michelle Dalton Cathy Frey Amy Gallant Sullivan Rose M. Sullivan, R.N. Sabrina Zappia Questions? Thank You! Industry Liaison David A. Sullivan, Ph.D. (Chair) Marco Betancourt Kim Brazzell, Ph.D. Amy Brill Michael J. Brubaker, Ph.D. Timothy L. Comstock, O.D., M.S. Neil D. Donnenfeld, M.B.A. Marie Laure Dupuy Perard, Pharm.D. David Eveleth, Ph.D. Fulvio Foschini Sherryl Frisch, M.S., M.B.A. Manal Gabriel, D.D.S., Ph.D. Kazuto Masuda, M.Sc. Katsuhiko Nakata, Ph.D. ©KNichols 2012 Dr Donald Korb Epidemiology Debra A. Schaumberg, Sc.D., O.D., M.P.H. (Chair) Jason J. Nichols, O.D., M.P.H., Ph.D. Eric B. Papas, M.Sc., O.D., Ph.D. Louis Tong, F.R.C.S., M.B.B.S. Miki Uchino, M.D. Kelly K. Nichols, O.D., M.P.H., Ph.D. Management Gerd Geerling, M.D. (Chair) Joseph Tauber, M.D. Christophe Baudouin, M.D., Ph.D. Eiki Goto, M.D. Yukihiro Matsumoto, M.D. Terrence O’Brien, M.D. Maurizio Rolando, M.D. Kazuo Tsubota, M.D. Kelly K. Nichols, O.D., M.P.H., Ph.D. Lipid Kari B. Green‐Church, Ph.D. (Chair) Igor Butovich, Ph.D. Mark Willcox, Ph.D. Douglas Borchman, Ph.D. Friedrich P. Paulsen, M.D., Ph.D. Stefano Barabino, M.D., Ph.D. Ben J. Glasgow, M.D. ©KNichols 2012 DISRUPTIVE CONCEPTS WHY A NEW PARADIGM? Meibomian gland dysfunction may be the leading cause of dry eye syndrome throughout the world Dry Eye has remained an enigma (Tear Film and Ocular Surface Society (TFOS), 2008 – 2010) Aqueous and lipid deficient dry eye may not be distinguishable: Low Schirmer score and thin-low lipid layer thicknesses coexist “As anomalous results build up, science reaches a crisis, at which point a new paradigm, which subsumes the old results along with the anomalous results into one framework, is accepted.” Isreb et al. Correlation of lipid layer thickness measurements with fluorescein tear film break-up time and Schirmer's test. Eye (Lond). 2005 Apr;19(4):484-5 The phenotypes of evaporative dry eye and aqueous dry eye take on the form of each other Bron et al. Predicted phenotypes of dry eye: proposed consequences of its natural history. Ocul Surf. 2009 Apr;7(2):78-92. Review. Thomas S. Kuhn, 1962 The Structure of Scientific Revolutions The most frequent form of MGD, obstructive MGD, frequently presents without obvious signs (Nonobvious MGD (NOMGD)) Blackie et al. Nonobvious Obstructive Meibomian Gland Dysfunction. Cornea: E-Pub ICO201681 41 42 7 6/6/2016 Structure of a Stable Tear Film Stable Tear Film Maintenance Lacrimal Gland Nonpolar Lipid layer - complex - over 100 Amphiphilic Lipid Layer different species of lipid Aqueous Anatomical Meibomian Gland Lipid Mucin Aqueous/Mucin complex -mucins are distributed throughout this layer, rather than in distinct aqueous and mucin layers Goblet Cells Stable Tear Film Sensory Motor Lid Blinking Tear Clearance & Spread Lid Closure Evaporation Glycocalyx -mucin bound complex responsible for the integration of aqueous layer Corneal with corneal epithelium Epithelium 43 44 Structure of the Lipid Layer Meibomian Glands Two-Phase Lipid Layer Model Modified sebaceous gland HC-Hydrocarbon WE- Wax Ester CE-Cholesterol Ester TG- Triglyceride F-Free Fatty Acid C-Cerebroside P-Phospholipid McCulley et al. A Compositional Based Model for the Tear Film Lipid Layer. Tr Am Ophthal. Sci., 1997 30-40 glands exist in upper tarsus 20-40 glands exist in the lower tarsus Secretion stimulus not fully understood Secretion of meibomian oil increases with testosterone; decreases with estrogen Oil expelled by mechanical force on gland during blinking Not all glands secreting simultaneously 46 45 Meibomian Gland Dysfunction MGD Classification Normal Most common form of lid disease Normal – glands open, secreting clear oil Non Obvious MGD No inflammation or signs Ophthalmologists and optometrists report that blepharitis is commonly seen in clinical practice in 37% and 47% of their patients, respectively, and it is widely agreed that meibomian gland dysfunction (MGD) is the most common cause of evaporative dry eye disease1 Classical & Obvious MGD Hypersecretion (seborrheic) Inflammatory (pouting & plugging) Infective (glands and/or lids) Diffuse inflammation of the lids/ blepharitis Inspissated material, blocked glands 1) Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence and treatment. Ocul Surf. 2009 Apr;7(2 Suppl):S1-S14 2) 2) Hom MM et al. Prevalence of meibomian gland dysfunction. Optom Vis Sci. 1990;67:710-712. 47 Korb and Henriquez, 1980; Mathers et al., 1991. 48 8 6/6/2016 Non-Obvious MGD (NOMGD) MGD may be nonobvious without inflammation and without other obvious signs (NOMGD) NOMGD may be precursor to obvious MGD Highly prevalent and under-diagnosed – may be most common cause of evaporative eye disease In a recent dry eye study of the 52 subjects that had MGD, 48% of them had NOMGD. Non-Obvious MGD Obvious MGD with evidence of inflammation and telangectasia Non-Obvious MGD with no overt inflammation or pathology Healthy Lid Secreting Oil Blackie et al. Nonobvious Obstructive Meibomian Gland Dysfunction. Cornea: E-Pub ICO201681 49 Non-Obvious MGD 50 Treatment of MGD/NOMGD At Home Therapy – Warm compresses – Eyelid Scrubs – Self expression Non-Obvious MGD with no overt inflammation or pathology but no clear oil with normal pressure expression In-Office Therapy White filamentous secretions upon max force manual expression indicating narrowing of the distal portion of the ducts Manual Expression Off-Label Pharmacotherapy Oral tetracycline/doxycycline Topical Antibiotics – erythromycin, tobramycin Topical Steroids – dexamethasone Healthy Lid Secreting Oil Blackie et al. Nonobvious Obstructive Meibomian Gland Dysfunction. Cornea: 2010 Dec;29(12):1333-45 52 51 TearScience® Solution MGD TREATMENT LipiView® OSI LipiFlow® Auto Meibomian Gland Evaluator Warm compresses Meibomian gland scrubs Home expression Blinking Office expression Secretagogues – Androgens Disposable Caution: Investigational device. The LipiFlow Auto Console pictured is not approved for use in the U.S. Limited by United States law to investigational use. 53 9 6/6/2016 New! Ophthalmic Surgical Instruments Collins Expressor Forceps (Item 98610) For aggressive expression of the Meibomian gland. Livengood Expressor Paddles Angled (Item 98620) & Flat (Item 98630) For mild or gentle expression of the Meibomian gland. You can use the BIO to get a lighted slightly magnified view of the lids Maskin Expressor WARNING BRUDER EYE COMPRESSES Microwave Activated Bruder Eye Hydrating Compress and Stye Compress conveniently provide an effective yet natural and drug-free way to help provide and maintain proper eye moisture. BENEFITS • • • • Replenishes Moisture Naturally Relieves Dryness Refreshes Tired Eyes Provides Drug Free Relief FEATURES • • • • • • • $ 575 Rhein Medical Ready in Minutes from the Microwave Naturally Hydrating Washable & Reusable Clean Moist Heat Soft Conforming Design Non-Allergenic Dust-Free BRUDER STYE COMPRESS Item #34170 Hot compresses can change the corneal tissues and structure Possible Link to Keratoconus Evidence Based Medicine BRUDER EYE HYDRATING COMPRESS Item #34160 08.10 10 6/6/2016 Meibomian Gland Expression MGD EXPRESSION Schaeffer Eye Protocol 1) OSD Evaluation Fees: 1) 2) 2) Includes test expression All staining RTC expression At home heat with eye medibeads 2) 15-20 minutes in waiting room with Bruden’s heat pack ( or rear wait) 3) Expression 1 of 3 4) RTC 2 weeks $189 / $25 Out of pocket Covers 3 Office visits $68.00 Per visit after initial three visits 1) 99213 / 99212 Dry eye progress check before expression MGD Maskin Expressor Maskin Probe 1)$ 158 box ( 10) 2) 1,2,4,6 MM intraductals 3) Aluminum Handle $104 11 6/6/2016 Maskin Tube Meibomian gland Drug delivery system Maskin Probe Leiter Pharmacy 8% lidocaine with 25% Jojoba in ung base 12 6/6/2016 OBSTRUCTIVE MGD Warm Compress Treatment Increase in LLT Following Treatment with Warm Compresses in Patients with MGD Olson, Korb, Greiner, Eye & CL, 2003 Baseline LLT 5 minutes 15 minutes 30 minutes = 60 nm = 105 nm = 117 nm = 122 nm Not published: 1 to 2 mins – minimal or no improvement Warm Compresses: Olson et al., 2003: Matsumoto et al., 2006 Warming devices : Goto et al., 2002; Mori et al., 2003; Nagymihalyi et al., 2004; Mitra et al., 2005; Di Pascuale et al., 2005; Spiteri et al., 2007 [email protected] Warm Compresses/Shower Managing Lid Disease Lid hygiene and scrubs for blepharitis Hot compresses, lid massage and meibomian gland expression for MGD Antibiotics to control bacterial overgrowth Steroids for inflammation Systemic medications Treatment must be reinforced repeatedly Regular follow-up Lid Scrub First line of treatment Traditional Approach Artificial Tears / Lubricants Azasite Doxycycline Warm Compresses/Lid Scrubs Second line of treatment Artificial tears / lubricants qid Artificial Tears / Lubricants Topical Loteprednol qid for 2 weeks, then bid for 60 days, then prn Azasite (Doxycycline) Current Approach Current Approach Dry Eyes Restasis BID Oral Nutrition Omega 3’s, Flax Seed Oil In 2 weeks, start and continue with topical Cyclosporin bid Evaluate co‐existing lid margin disease Anti‐inflammatory Second line of treatment Loteprednol? Lipiflow First line of treatment First line of treatment Second line of treatment Punctal occlusion, tarsorraphy, scleral contact lens trial 13 6/6/2016 Warm Compresses/Lid Scrubs Medications for Lid Disease Artificial Tears / Lubricants Replenish the lipid layer Oral Nutrition Current Approach Blepharitis Omega 3’s, Flax Seed Oil To control bacterial over population Must be combined with lid hygiene Antibiotic selection First line of treatment Azithromycin bid 2 days then qd for 1 month Loteprednol prn Cyclosporine prn AzaSite Dosing for Chronic Blepharitis Zithromax 250, 500, 600 mg tabs Tri-Pack 3 x 500 mg tabs Z Pack 6 x 250 mg tabs 500 mg x 1 day 250 mg x 4 days AzaSite ( 1% topical) Bid x 2 day, then qd x 5 days Bact Conj, “MK” , trachoma Adult Chlamydial 1 g po x 1 day/week TX for 4 weeks PEDS: 10 mg/kg/day (max 500) Followed by 5 mg/kg/day x 4 days 1% Azithromycin Ophthalmic solution Indication: bacterial conjunctivitis >age 1 1 drop BID x 2 days 1 drop QD x 5 days DOXYCYCLINE THERAPY to Reduce Inflammation in MGD AZITHROMYCIN Doxycycline Minocycline AzaSite 1 drop bid X 2 days 1 drop per day X 30 days Re-evaluate in 1 month Some recommend 1 month on – 1 month off for more severe cases Tobrex or Tobradex ST Zylet Azasite Systane Balance Soothe XP Lotemax UNG Systemic Medications Second line of treatment Lipiflow Drops much preferred to ointments Antibiotics – Minocycline 50mg/day Topical anti‐inflammatory agents Warm compresses and lid massage An abnormal production of esters &/or bacterial colonies cause the oils to become acidic leading to burning The AB inhibits staph lipase from converting lipids to fatty acids thereby reducing inflammation Dose: 50 mg BID x 1-2 mos Maintenance: 50-20mg qd- bid 14 6/6/2016 DOXYCYCLINE A tetracycline antibiotic that inhibits bacterial protein synthesis by binding to ribosomes Bacteriostatic Broad Gram +/Anti-inflammatory Anticollagenase activity IL-1 and MMP-9 inhibitor Inhibits conversion of staph lipase to fatty acids MGD Acne rosacea RCE prevention Prevent stromal melt Staph marginal dx Ocular Chlamydia DOXYCYCLINE Contra-indications: Category D < 8 years old, hypersensitivity to tetracyclines or sulfites, severe hepatic dysfunction, last ½ pregnancy** Safe for Kidney dx since it is excreted in GI tract DOXYCYCLINE SIDE EFFECTS NVD, anorexia, dysphagia, severe photosensitivity, superinfection (fungus, vaginal candidiasis) benign IC-HTN, hepatoxicity, pancreatitis WARNINGS drink fluids to prevent esophagitis, use sun block, simultaneous ingestion of food OK. Link to Breast CA? ALTERNATIVES Tetracycline qid Minocycline $$ ALODOX Great for long term usage once controlled Blepharitis, dry eye, rosacea Brand Name Oracea® 40mg Long term –cycline therapy associated with pseudotumor cerebri Drug interactions: Antacids (Al,Ca,Mg),Laxatives (Mg), Fe, and some barbiturates may reduce absorption of doxycycline Alodox 20 mg Doxycyline Hyclate Sub-antimicrobial dosage ONCE DAILY DOXYCYCLINE (<50mg) Enzyme modulation of inflammation By OCuSOFT Kit comes with lid scrub foam Claims to be a more potent collagenase inhibitor than minocycline and therefore less SE Long term use Contraindications Pregnant or child bearing age Children TCN, Doxycycline, Minocycline 15 6/6/2016 How to Minimize Stomach Problems with Tetracycline Cautions Photosensitivity with dairy products, antacids etc. Minocycline may cause vestibular toxicity 1. Chelates 2. 3. 4. Omega-3s and Omega-6s: Essential Fatty Acids Essential fatty acids Optimum Omega-6:Omega-3 ratio for good health varies from 3:1 up to 1:1: Ratio in current American Diet is about 1:10 American diet too high in Omega-6s from dairy products, beef, vegetable oils, shortening American diet too low in Omega-3’s from salmon, cold-water fish, krill oil, flaxseed, walnuts, dark green leafy vegetable, beans Do not take the second pill (bid) before going to bed Do not take pills with acidic beverages Take pills with food (except a high dairy meal) Prescribe the lowest dose available Omega-3 Essential Fatty Acids Omega-3’s American diet has undergone a 6-fold reduction in Omega-3’s since 1850 Increases “good” prostaglandins Inhibits “bad” prostaglandins Omega 6’s US consumption of this fatty acid has doubled from what it was in 1940. Excess intake can increase water retention, raise blood pressure and increase blood clotting. How Omega-3s Treat Dry Eye Conclusions Most Americans not willing to change diet to acquire needed levels of Omega-3s Logical choice is via dietary supplementation Omega-3s hold promise as treatment for dry eye by: Suppressing meibomitis Augmenting the oil layer Stimulating tear production? TearScience® How LipiFlow® Addresses Meibomian Gland Dysfunction (MGD), the Leading Cause of Dry Eye 96 16 6/6/2016 Evaporative Dry Eye Is the Most Common Cause of Dry Eye Meibomian Gland Dysfunction: Revised Definition 2011 In a recent study by Lemp et al, 86% of patients evaluated had Evaporative Dry Eye “…a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative and quantitative changes in the glandular secretion. It may result in alteration of the tear film, eye irritation, clinically apparent inflammation, and ocular surface disease.” 159 patients —The International Workshop on Meibomian Gland Dysfunction: Executive Summary Nichols KK, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011;52(4):1922-1929. 97 MGD May Lead to a Downspiraling Cycle of Inflammation 23/159 aqueous deficient 79/159 MGD 57/159 MGD and aqueous deficient 14% 50% 36% Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012;31(5):472-478. 98 MGD is Progressive if Untreated Meibomian gland obstruction Decrease in Meibomian secretions ( Lipid layer thickness) S Y M P T O M S I N C R E A S E Stasis & Inspissation Increase in evaporation ( Aqueous layer thickness) Partial obstruction Unstable tear film SYMPTOMS START Critical intervention point Ocular surface and lubricity compromised Ocular surface exposure (between blinks) and microtrauma (during blinking) INFLAMMATION OCULAR SURFACE CHANGES Visible/nonvisible Decreased availability of Meibomian lipids at the lid margin and tear film Total obstruction Potential long-term damage 99 100 Because Not All MGD Is Obvious, Active Disease Identification Is Crucial • MGD may be present without obvious signs (nonobvious MGD [NOMGD]) Meibomian Gland Dysfunction • NOMGD may be a precursor to obvious MGD, is highly prevalent and underdiagnosed Disease Identification NOMGD with recalcitrant obstruction despite forceful expression 101 NOMGD yielding secretion with forceful expression Blackie CA, et al. Nonobvious obstructive meibomian gland dysfunction. Cornea. 2010;29:1333-1345. 102 17 6/6/2016 Standard Patient Evaluation of Eye Dryness (SPEED) Questionnaire Assess the Tear Film With LipiView® LipiView uses advanced interferometric technology and captures detailed digital images of the eye’s tear film to capture, archive, manipulate, and store the oily lipid layer of tear • Evaluates the frequency and severity of symptoms • Developed as an easy to use fast screening tool for dry eye disease • SPEED questionnaire is one of the tools used to identify candidates for LipiView® Light source: the illuminator Touch-screen control panel Chin rest Camera, computer and drivers are housed by the device LipiView® Report Measurement time: 20 seconds per eye Device dimensions: 28” x 17” x 17” 104 Meibomian Gland Evaluator™ (MGE) Provides a relative measure of the thickness of the lipid layer of the tear film • The TearScience® Meibomian Gland Evaluator – Applies consistent, moderate pressure • Between 0.8 g/mm2 and 1.2 g/mm2 • Produces a measurement called the Ocular Index of Lipid Interferometric Color Unit (ICU) • Calculated on a frame-byframe basis and plotted for ~1 billion data points per eye • The results are then displayed and are available for printout – Allows evaluation of secretions from Meibomian gland orifices through a slit lamp biomicroscope Grade Secretion Characteristics 3 Clear liquid oil 2 Colored/cloudy liquid 1 Inspissated (toothpaste consistency) 0 No secretion (includes capped orifices) 105 106 Indications for Use Meibomian Gland EvaluatorTM LipiView® Ocular Surface Interferometer • Intended for use by a clinician to evaluate meibomian gland secretions. Used to apply consistent light pressure to the outer eyelid skin of a patient while visualizing secretions from meibomian gland orifices through a slit lamp biomicroscope. • An ophthalmic imaging device intended for use in adult patients by a clinician to capture, archive, manipulate and store digital images of specular (interferometric) observations of the tear film, which can be visually monitored and photographically documented. Meibomian Glands Number of Meibomian Glands Yielding Liquid Secretion (MGYLS) By Symptom Categories With Symptoms1 (n=133) Severe Symptoms Symptom Score, SPEED questionnaire (0-28) Number of MGYLS for entire lower eyelid Minimal Symptoms ≥10 6–9 ≤5 (14.39 ± 0.69) (7.26 ± 0.17) (2.30 ± 0.23) 4.14 ± 0.56 0-4 DRY • NO KNOWN CONTRADICTIONS Moderate Symptoms 5.14 6.25 ± 0.35 ± 0.41 5 6 7 Asymptomatic healthy eyes2 (n = 24) 0 10.6 ± 2.6 8 – 10+ NOT DRY • NO KNOWN CONTRADICTIONS 107 1. Korb DR, Blackie CA. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and gland location. Cornea. 2008;27(10):1142-1147. 2. Blackie CA, Korb DR. Recovery time of an optimally secreting meibomian gland. Cornea. 2009;28(3):293-297. 108 18 6/6/2016 Challenges of Current MGD Therapies Therapy • Warm compresses • Eyelid scrubs • Manual gland expression Meibomian Gland Dysfunction Traditional Treatments Challenges • External heat application is inadequate • Significant discomfort • Limited compliance • Only the upper portion of the glands are treated or expressed 109 110 Patient Frustration With Existing Treatments Warm Compresses Have Limited Efficacy • Anterior lid is highly vascular; therefore, difficult for heat application to reach gland contents Survey including ~550 patients diagnosed with Dry Eye: • Those using artificial tears, lubricants, or punctal plugs report little to no success • Adequate temperatures cannot easily and safely be achieved by the use of external warm compresses Huang HW, et al. Predicting effects of blood flow rate and size of vessels in a vasculature on hyperthermia treatments using computer simulation. Biomed Eng Online. 2010 ;26;9:18. Lane SS, et al. A new system, the LipiFlow, for the treatment of meibomian gland dysfunction. Cornea. 2012;31(4):396-404. Beard B. Boston Foundation for Sight Survey. Report Back to the Community. Boston Foundation for Sight. July 15, 2010. www.bostonsight.org. 111 112 Summary Lipid/Oil‐Based Lubricant Eye Drops • Evaporative Dry Eye is the most common cause of Dry Eye • Not all MGD is obvious • Appropriate diagnosis is important • Tools available to aid in making the right diagnosis include: o o o Palliative – None treat the cause Downside can be blurring & stinging with castor oil emulsions SPEED score questionnaire Meibomian Gland EvaluatorTM LipiView® Ocular Surface Interferometer • Most patients are frustrated with the ineffectiveness of current dry eye therapies 114 19 6/6/2016 LipiFlow® Thermal Pulsation System Advanced Treatment of MGD LipiFlow® Thermal Pulsation System 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 115 LipiFlow® Offers a Solution for Patients With MGD In both upper and lower eyelids simultaneously Lid warmer Applies directional heat to inner eyelid Activator Applies intermittent pressure to the outer eyelid Insulated lid warmer shields eye from heat and vaults above the cornea to prevent corneal contact Heats comfortably to liquefy the Meibomian gland contents 116 Therapeutic Goal of Pulsation Lid warmer Applies directional heat to inner eyelid Facilitates release of secretions from the Meibomian glands Activator Applies intermittent pressure to the outer eyelid Insulated lid warmer shields eye from heat and vaults above the cornea to prevent corneal contact Heats comfortably to liquefy the Meibomian gland contents Inflatable air bladder During the heating phase of the treatment (as opposed to after) Increase heat transfer efficiency Inflatable air bladder Allow the natural flow of lipids to resume Enable patient to experience little to no discomfort during treatment as compared to manual expression 117 LipiFlow® Provides Heat and Pressure to Liquefy and Evacuate Obstructed Glands 118 Gland Expression A sterile disposable eyepiece connects to a console used by the physician to control the application of heat and pressure to the eyelids • Obstructed glands should be monitored for gland atrophy Lid warmer Composed of a heater, eye insulation, and vaulted shape Heat is applied to the palpebral surfaces of the upper and lower eyelids directly over the Meibomian glands • LipiFlow® offers relief through evacuation of gland contents LipiFlow® treatment provides improved quality and quantity of gland secretions Activator Composed of an inflatable air bladder and a rigid activator Graded pulsatile pressure is delivered to the outer eyelid 119 120 20 6/6/2016 Pressure and Pulsation for MGD Meibomian Gland Dysfunction Clinical Results With LipiFlow® Korb, DR, Blackie, CA. Meibomian gland therapeutic expression: quantifying the applied pressure and the limitation of resulting pain. Eye Contact Lens. 2011 Sep;37(5):298-301. 121 122 Study Design: Nonsignificant Risk, Open-label Study With Crossover Design 9 Investigational Centers All eligible patients Single 12-minute therapy session N=278 Eyes in 139 Patients Treatment randomization 1:1 by patient n=138 eyes of 69 patients 2 weeks control crossover 4 weeks 1-day safety evaluation Arm LipiFlow® A treatment arm Full exam Full exam Warm compress therapy control arm Full exam Stop warm compress crossover LipiFlow® treatment Full exam Baseline exam Daily warm compress therapy for 2 weeks n=140 eyes of 70 patients 1-day safety evaluation 123 21
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