Embed Size (px)
Citation preview
6/6/2016
1
M G D
Meibomian Gland Disease
Jack Schaeffer OD FAAO
Schaeffer Eye Center
Birimingham , Alabama
Meibomian Gland Dysfunction and Management
Kelly K. Nichols, OD, MPH, PhD
FERV ProfessorUniversity of Houston College of Optometry
Chair, TFOS International Meibomian Gland Workshop
©KNichols 2012
Disclosures
• K. Nichols– Paid consultant to:
• Alcon
• Allergan
• Celtic/ Resolvyx
• Eleven Biotherapeutics
• InSite
• Ista
• SARcode
• TearLab
• Research support– 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 “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
DEWS—Classification of Dry Eye
80%20% 5% 65% 35%
6/6/2016
2
©KNichols 2012
MGD Contributes to Dry Eye
DEWS Definition and classification report. Ocular Surface 2007 ©KNichols 2012
©KNichols 2012
Dry Eye and MGD
MGD is the most common cause of evaporative dry eye.
©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
• www.tearfilm.org
©KNichols 2012
Lecture Descriptionwww.tearfilm.org
©KNichols 2012
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.
6/6/2016
3
©KNichols 2012
• Large sebaceous glands
• No direct contact to hair follicles
• Located in the tarsal plates
• Upper and lower eye lids
Meibomian Gland ‐ ANATOMY
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
• 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
Meibomian Gland ‐ ANATOMY
Modified from Sobotta Atlas der Anatomie des Menschen. Urban & Schwarzenberg Verlag 1982, (reproduced from Knop N & Knop E. Ophthalmologe 2009; 106:872–883)
©KNichols 2012
Meibomian Gland – PATHOLOGY• 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
©KNichols 2012
Interacting Pathways in MGD
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
Meibomian Gland DysfunctionDefinition & 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
6/6/2016
4
©KNichols 2012
Classification of MGD
©KNichols 2012
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
* 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
Factors Associated with MGD
©KNichols 2012
Factors Associated with
MGD
©KNichols 2012
Factors Associated with MGD
6/6/2016
5
Overlap of DED Symptoms and Clinical Signs of MGD
Study Symptoms Assessed(all frequency)
Clinical Evaluations/ MGD Definition
% with Dry Eye Symptoms who also
had MGD
Shihpai Eye Study
(Lin, 2003)
Eye drynessGritty/sandyBurningStickyWatery/tearingRednessLash crustingEyes stuck shut
(am)
Telangiectasis or gland plugging ≥ G1
61.7%(p = NR)
Bangkok Study(Lekhanont,
2006)*
Eye drynessForeign body
sensationBurningDiscomfortStickyTearing
Telangiectasis, Collarettes, and Plugging
63.6% (p = 0.006)
Evaluation, Diagnosis and Grading of Severity of
Meibomian Gland Dysfunction
Alan Tomlinson, MCOpt, Ph.D. (Chair) E. Ian Pearce, Ph.D. Anthony J. Bron, F.R.C.S. Richard Yee, M.D.Donald R. Korb, O.D. Norihiko Yokoi, M.D., Ph.D.Shiro Amano, M.D., Ph.D. Reiko Arita, M.D., Ph.D. Jerry R. Paugh, O.D. Murat Dogru, M.D.
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
Stages of MGD
©KNichols 2012
Management and Therapy of Meibomian Gland
Dysfunction
Gerd Geerling, M.D. (Chair) Terrence O’Brien, M.D. Joseph Tauber, M.D. Maurizio Rolando, M.D.Christophe Baudouin, M.D., Ph.D. Kazuo Tsubota, M.D.Eiki Goto, M.D. Kelly K. Nichols, O.D., M.P.H., Ph.D.Yukihiro Matsumoto, M.D.
©KNichols 2012
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
• 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)
6/6/2016
6
©KNichols 2012
Current Practice Patterns
• 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
©KNichols 2012
DISEASE STAGINGStage MGD grade Symptoms Corneal
Staining
1
+ (minimally altered expressibility and secretion quality)
Asymptomatic None
2
++ (mildly altered expressibility and secretion quality)
Minimal to Mild None to limited
3
+++ (moderately altered expressibility and secretion quality)
ModerateMild to moderate; mainly peripheral
4
++++ (severely altered expressibility and secretion quality)
MarkedMarked; central in
addition
“PLUS DISEASE” Co‐existing or accompanying disorders of the ocular surface and/ or eyelids
©KNichols 2012
Stages of MGD
©KNichols 2012
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
Recommended Staged Therapy
+ Steroids, CL, Surgery
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. ©KNichols 2012
Existing Clinical TrialsKey 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
6/6/2016
7
©KNichols 2012
Issue Findings
Outcome measures
1. Symptoms 2. TBUT 3. MG secretion/expression 4. Schirmer 5. Corneal staining 6. MG obstruction 7. Eyelids 8. Lipid layer
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 Txduration 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.
Existing Clinical Trialsn = 26
©KNichols 2012
SummaryPriorities for future clinical trials:
• 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
Questions?Thank You!
Clinical TrialsPenny 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.
DiagnosisAlanTomlinson, 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.
DefinitionJ. 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., MCOptomJames P. McCulley, M.D.Seika Den, M.D., Ph.D. Gary Foulks, M.D.
EpidemiologyDebra 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.
AnatomyErich 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.
LipidKari 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.
ManagementGerd 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. Industry Liaison
David A. Sullivan, Ph.D. (Chair)Marco BetancourtKim Brazzell, Ph.D.
Amy BrillMichael 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 FoschiniSherryl Frisch, M.S., M.B.A.Manal Gabriel, D.D.S., Ph.D.
Kazuto Masuda, M.Sc.Katsuhiko Nakata, Ph.D.
TeamMichelle Dalton
Cathy FreyAmy Gallant SullivanRose M. Sullivan, R.N.
Sabrina Zappia
Dr Donald Korb
“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.”
Thomas S. Kuhn, 1962The Structure of Scientific Revolutions
WHY A NEW PARADIGM?
Dry Eye has remained an enigma
41
DISRUPTIVE CONCEPTS
42
Meibomian gland dysfunction may be the leading cause of dry eye syndrome throughout the world (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 coexistIsreb et al. Correlation of lipid layer thickness measurements with fluorescein tear film break-up time and Schirmer'stest. Eye (Lond). 2005 Apr;19(4):484-5
The phenotypes of evaporative dry eye and aqueous dry eye take on the form of each otherBron et al. Predicted phenotypes of dry eye: proposed consequences of its natural history. Ocul Surf. 2009 Apr;7(2):78-92. Review.
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
6/6/2016
8
Goblet Cells
Lid Blinking
Lid Closure
Meibomian Gland
Lacrimal Gland
Stable Tear Film
Aqueous
Lipid
Mucin
TearClearance & Spread
Evaporation
Stable Tear Film Maintenance
43
Anatomical
Sensory Motor
Structure of a Stable Tear Film
44
Aqueous/Mucin complex
Corneal Epithelium
Glycocalyx
Amphiphilic Lipid Layer
Nonpolar Lipid layer
-mucin bound complex responsible for the integration of aqueous layer with corneal epithelium
-mucins are distributed throughout this layer, rather than in distinct aqueous and mucin layers
- complex - over 100 different species of lipid
Structure of the Lipid Layer
Two-Phase Lipid Layer
Model
HC-HydrocarbonWE- Wax EsterCE-Cholesterol EsterTG- TriglycerideF-Free Fatty AcidC-CerebrosideP-Phospholipid
McCulley et al. A Compositional Based Model for the Tear Film Lipid Layer. Tr Am Ophthal. Sci., 1997 45
Meibomian Glands
Modified sebaceous gland
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
Meibomian Gland Dysfunction
Most common form of lid disease
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
47
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.
MGD Classification
48
Normal – glands open, secreting clear oil
Hypersecretion (seborrheic)
Inflammatory (pouting & plugging)
Infective (glands and/or lids)
Diffuse inflammation of the lids/ blepharitis
Inspissated material, blocked glands
Classical & Obvious MGD
Normal
Non Obvious MGDNo inflammation or signs
Korb and Henriquez, 1980; Mathers et al., 1991.
6/6/2016
9
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.
49
Non-Obvious MGD
50
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
Non-Obvious MGD
Non-Obvious MGD with no overt inflammation or pathology but no
clear oil with normal pressure expression
White filamentous secretions upon max force manual expression indicating
narrowing of the distal portion of the ducts
51
Healthy Lid Secreting Oil
Blackie et al. Nonobvious Obstructive Meibomian Gland Dysfunction. Cornea: 2010 Dec;29(12):1333-45
Treatment of MGD/NOMGD
In-Office Therapy Manual Expression Off-Label Pharmacotherapy
Oral tetracycline/doxycycline Topical Antibiotics – erythromycin, tobramycin Topical Steroids – dexamethasone
52
At Home Therapy– Warm compresses– Eyelid Scrubs
– Self expression
TearScience® Solution
53
LipiView® OSILipiFlow® Auto
DisposableMeibomian Gland Evaluator
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.
MGD TREATMENT
Warm compresses
Meibomian gland scrubs
Home expression
Blinking
Office expression
Secretagogues – Androgens
6/6/2016
10
You can use the BIO to get a lighted slightly magnified view of the lids
Collins Expressor Forceps (Item 98610)For aggressive expression of the Meibomian gland.
Livengood Expressor PaddlesAngled (Item 98620) & Flat (Item 98630)
For mild or gentle expression of the Meibomian gland.
New! Ophthalmic Surgical Instruments
Maskin Expressor
$ 575
Rhein Medical
BRUDER EYE COMPRESSESMicrowave 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 FEATURES• Replenishes Moisture Naturally• Relieves Dryness• Refreshes Tired Eyes• Provides Drug Free Relief
• Ready in Minutes from the Microwave• Naturally Hydrating• Washable & Reusable• Clean Moist Heat• Soft Conforming Design• Non-Allergenic• Dust-Free
08.10
BRUDER STYE COMPRESSItem #34170
BRUDER EYE HYDRATING COMPRESSItem #34160
WARNING
Hot compresses can change the corneal tissues and structure
Possible Link to Keratoconus
Evidence Based Medicine
6/6/2016
11
Schaeffer Eye Protocol1) OSD Evaluation
1) Includes test expression2) All staining
2) RTC expression1) At home heat with eye medibeads2) 15-20 minutes in waiting room with Bruden’sheat pack ( or rear wait) 3) Expression 1 of 34) RTC 2 weeks
Meibomian Gland Expression
Fees: $189 / $25
Out of pocket
Covers 3 Office visits
$68.00 Per visit after initial three visits
99213 / 99212
Dry eye progress check before expression
MGD EXPRESSION
MGD
Maskin Expressor
Maskin Probe
1)$ 158 box ( 10)
2) 1,2,4,6 MM intraductals
3) Aluminum Handle $104
6/6/2016
12
Maskin Tube
Meibomian gland Drug delivery system
Maskin Probe
Leiter Pharmacy8% lidocaine with 25% Jojoba in
ung base
6/6/2016
13
OBSTRUCTIVE MGDWarm Compress Treatment
Increase in LLT Following Treatment with Warm Compresses in Patients with MGD
Olson, Korb, Greiner, Eye & CL, 2003
Baseline LLT = 60 nm5 minutes = 105 nm15 minutes = 117 nm30 minutes = 122 nm
Not published: 1 to 2 mins – minimal or no improvement
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
Warm Compresses: Olson et al., 2003: Matsumoto et al., 2006
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
Warm Compresses/Shower
Lid Scrub
Artificial Tears / Lubricants
Azasite
Doxycycline
First line of treatment
Second line of treatment
Traditional Approach
Warm Compresses/Lid Scrubs
Artificial Tears / Lubricants
Azasite (Doxycycline)
Restasis BID
Oral Nutrition
Omega 3’s, Flax Seed Oil
Anti‐inflammatory
Loteprednol?
Lipiflow
First line of treatment
Second line of treatment
Current Approach
Artificial tears / lubricants qid
Topical Loteprednol qid for 2 weeks, then bid for 60 days, then prn
In 2 weeks, start and continue with topical Cyclosporin bid
Evaluate co‐existing lid margin disease
Punctal occlusion, tarsorraphy,
scleral contact lens trial
First line of treatment
Second line of treatment
Current ApproachDry Eyes
6/6/2016
14
Warm Compresses/Lid Scrubs
Artificial Tears / Lubricants
Replenish the lipid layer
Oral Nutrition
Omega 3’s, Flax Seed Oil
Antibiotics – Minocycline 50mg/day
Azithromycin bid 2 days then qd for 1 month
Topical anti‐inflammatory agents
Loteprednol prn
Cyclosporine prn
Lipiflow
First line of treatment
Second line of treatment
Current ApproachBlepharitis
Medications for Lid Disease
To control bacterial over population Must be combined with lid hygiene
Warm compresses and lid massage Antibiotic selection
Drops much preferred to ointments Tobrex or Tobradex ST Zylet Azasite Systane Balance Soothe XP Lotemax UNG
Systemic Medications Doxycycline Minocycline
AzaSite Dosing for Chronic Blepharitis
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
AzaSite
1% Azithromycin Ophthalmic solution
Indication: bacterial conjunctivitis >age 1
1 drop BID x 2 days
1 drop QD x 5 days
AZITHROMYCIN
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 daysBact Conj, “MK” , trachoma
Adult Chlamydial 1 g po x 1 day/weekTX for 4 weeks
PEDS: 10 mg/kg/day (max 500)Followed by5 mg/kg/day x 4 days
DOXYCYCLINE THERAPYto Reduce Inflammation in
MGD 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
6/6/2016
15
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
Drug interactions: Antacids (Al,Ca,Mg),Laxatives (Mg), Fe, and some barbiturates may reduce absorption of doxycycline
DOXYCYCLINE
SIDE EFFECTSNVD, anorexia, dysphagia, severe photosensitivity, superinfection (fungus, vaginal candidiasis) benign IC-HTN, hepatoxicity, pancreatitis
WARNINGSdrink fluids to prevent esophagitis, use sun block, simultaneous ingestion of food OK.
Link to Breast CA?
ALTERNATIVES Tetracycline qid Minocycline $$ ALODOX
Alodox
20 mg Doxycyline Hyclate
Sub-antimicrobial dosage (<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
ONCE DAILY DOXYCYCLINE
Great for long term usage once controlled
Blepharitis, dry eye, rosacea
Brand Name Oracea® 40mg
Long term –cycline therapy associated with pseudotumor cerebri TCN, Doxycycline, Minocycline
Contraindications
Pregnant or child bearing age
Children
6/6/2016
16
Cautions
PhotosensitivityChelates with dairy products,
antacids etc.Minocycline may cause
vestibular toxicity
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
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
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 EyeConclusions
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
6/6/2016
17
Meibomian Gland Dysfunction: Revised Definition 2011
97
“…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.”
—The International Workshop on Meibomian Gland Dysfunction: Executive Summary
97Nichols KK, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011;52(4):1922-1929.
Evaporative Dry Eye Is the Most Common Cause of Dry Eye
98
159 patients
23/159 aqueous deficient
57/159 MGD and
aqueous deficient
79/159 MGD
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.
In a recent study by Lemp et al, 86% of patients evaluated had Evaporative Dry Eye
14% 50% 36%
MGD May Lead to a Downspiraling Cycle of Inflammation
Meibomian gland obstruction
Decrease in Meibomian secretions ( Lipid layer thickness)
Increase in evaporation ( Aqueous layer thickness)
Unstable tear film
Critical intervention point
99
OCULAR SURFACE CHANGES Visible/nonvisible
SYMPTOMS
INCREASE
SYMPTOMS START
Ocular surface and lubricity compromised
Ocular surface exposure (between blinks)
and microtrauma (during blinking)
INFLAMMATION
Stasis & Inspissation
Potential long-term damage
MGD is Progressive if Untreated
100
Total obstruction
Decreased availability of Meibomian lipids at the lid margin and tear film
Partial obstruction
Disease Identification
Meibomian Gland Dysfunction
101
Because Not All MGD Is Obvious, Active Disease Identification Is Crucial
102102
• MGD may be present without obvious signs (nonobvious MGD [NOMGD])
• NOMGD may be a precursor to obvious MGD, is highly prevalent and underdiagnosed
NOMGD with recalcitrant obstruction despite forceful expression
NOMGD yielding secretion with forceful expression
Blackie CA, et al. Nonobvious obstructive meibomian gland dysfunction. Cornea. 2010;29:1333-1345.
6/6/2016
18
Standard Patient Evaluation of Eye Dryness (SPEED) Questionnaire
• 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®
Chin rest
Light source:the illuminator Touch-screen
control panel
Camera, computer and drivers are housed by the device
Device dimensions:28” x 17” x 17”
Measurement time:20 seconds per eye
Assess the Tear Film With LipiView®
104
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
LipiView® Report
• Produces a measurement called the Ocular Index of Lipid Interferometric Color Unit (ICU)
• Calculated on a frame-by-frame basis and plotted for ~1 billion data points per eye
• The results are then displayed and are available for printout
105
Provides a relative measure of the thickness of the lipid layer
of the tear film
Meibomian Gland Evaluator™ (MGE)
• The TearScience® Meibomian Gland Evaluator– Applies consistent, moderate pressure
• Between 0.8 g/mm2 and 1.2 g/mm2
– Allows evaluation of secretions from Meibomian gland orifices through a slit lamp biomicroscope
106
Grade Secretion Characteristics
3 Clear liquid oil
2 Colored/cloudy liquid
1 Inspissated (toothpaste consistency)
0 No secretion (includes capped orifices)
Indications for Use
Meibomian Gland EvaluatorTM
• 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.
• NO KNOWN CONTRADICTIONS
LipiView® Ocular Surface Interferometer
• 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.
• NO KNOWN CONTRADICTIONS
107
Meibomian Glands
108
Number of Meibomian Glands Yielding Liquid Secretion (MGYLS)By Symptom Categories
With Symptoms1
(n=133) Asymptomatic healthy eyes2
(n = 24)Severe Symptoms
Moderate Symptoms
Minimal Symptoms
Symptom Score, SPEED questionnaire(0-28)
≥10(14.39 ± 0.69)
6–9(7.26 ± 0.17)
≤5(2.30 ± 0.23)
0
Number of MGYLS for entire lower eyelid
4.14 ± 0.56 5.14 ± 0.41 6.25 ± 0.35 10.6 ± 2.6
DRY NOT DRY
0 - 4 5 6 7 8 – 10+
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.
6/6/2016
19
Traditional Treatments
Meibomian Gland Dysfunction
109
Challenges of Current MGD Therapies
110110
Therapy• Warm compresses• Eyelid scrubs• Manual gland expression
Challenges
• External heat application is inadequate
• Significant discomfort • Limited compliance• Only the upper portion of the
glands are treated or expressed
Warm Compresses Have Limited Efficacy
• Anterior lid is highly vascular; therefore, difficult for heat application to reach gland contents
• Adequate temperatures cannot easily and safely be achieved by the use of external warm compresses
111
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.
Patient Frustration With Existing Treatments
112Beard B. Boston Foundation for Sight Survey. Report Back to the Community. Boston Foundation for Sight. July 15,
2010. www.bostonsight.org.
Survey including ~550 patients diagnosed with Dry Eye:
• Those using artificial tears, lubricants, or punctal plugs report little to no success
Lipid/Oil‐Based Lubricant Eye Drops
Palliative – None treat the cause
Downside can be blurring & stinging with castor oil emulsions
Summary
• 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 SPEED score questionnaireo Meibomian Gland EvaluatorTM
o LipiView® Ocular Surface Interferometer
• Most patients are frustrated with the ineffectiveness of current dry eye therapies
114
6/6/2016
20
LipiFlow® Thermal Pulsation System
Advanced Treatment of MGD
115
LipiFlow® Thermal Pulsation System
116116
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
LipiFlow® Offers a Solution for Patients With MGD
117
In both upper and lower eyelids simultaneously
Facilitates release of secretions from the Meibomian glands
ActivatorApplies intermittent pressure to the outer eyelid
Inflatable air bladder
Insulated lidwarmer shields eye from heat andvaults above thecornea to preventcorneal contact
Heats comfortably toliquefy the Meibomian gland contents
Lid warmerApplies directionalheat to inner eyelid
Therapeutic Goal of Pulsation
118
ActivatorApplies intermittent pressure to the outer eyelid
Inflatable air bladder
Insulated lidwarmer shields eye from heat andvaults above thecornea to preventcorneal contact
Heats comfortably toliquefy the Meibomian gland contents
Lid warmerApplies directionalheat to inner eyelid
Increase heat transfer efficiency
During the heating phase of the treatment (as opposed to after)
Allow the natural flow of lipids to resume
Enable patient to experience little to no discomfort during treatment as compared to manual expression
LipiFlow® Provides Heat and Pressure to Liquefy and Evacuate Obstructed Glands
Lid warmerComposed of a heater, eye insulation, and vaulted shapeHeat is applied to the palpebral surfaces of the upper and lower eyelids directly over the Meibomian glands
A sterile disposable eyepiece connects to a console used by the physician to control the application of heat and pressure to the eyelids
ActivatorComposed of an inflatable air bladder and a rigid activatorGraded pulsatile pressure is delivered to the outer eyelid
119
Gland Expression
• Obstructed glands should be monitored for gland atrophy
• LipiFlow® offers relief through evacuation of gland contents
120
LipiFlow® treatment provides improved quality and quantity of gland secretions
6/6/2016
21
Pressure and Pulsation for MGD
121
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.
Clinical Results With LipiFlow®
Meibomian Gland Dysfunction
122
Study Design: Nonsignificant Risk, Open-label Study With Crossover Design
Arm A
All eligible patients
Treatment randomization 1:1 by patient
2 weeks control crossover
4 weeks
Baseline exam
LipiFlow® treatment
armFull exam
Full examWarm
compress therapy
control arm
Full exam
Full examStop warm compresscrossover LipiFlow®
treatment
Single 12-minute therapy session
Daily warm compress therapy for 2 weeks
1-day safety evaluation
1-day safety evaluation
n=138 eyes of 69 patients
n=140 eyes of 70 patients
9 Investigational Centers N=278 Eyes in 139 Patients
123
