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
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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
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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
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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
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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
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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
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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
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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.
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



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
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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.
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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.
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•
•
•
•
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Relieves Dryness
Refreshes Tired Eyes
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
FEATURES
•
•
•
•
•
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$ 575
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Naturally Hydrating
Washable & Reusable
Clean Moist Heat
Soft Conforming Design
Non-Allergenic
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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
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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
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Maskin Tube
Meibomian gland Drug delivery
system
Maskin Probe
Leiter Pharmacy
8% lidocaine with 25% Jojoba in
ung base
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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
drbilltownsend@gmail.com
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
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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
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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
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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
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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
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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
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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
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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