Ben Gaddie, OD - Vision Institute of Canada

10/26/14
Financial Disclosures:
Ben Gaddie, OD
•  Consultant
MGD and Marginal Creatures: A Look at Life On the Edge-­‐Of The Lid
Ben Gaddie, OD
Marc Bloomenstein, OD
What Percentage of Dry Eye Is
Evaporative?
•  I think most dry eye has an evaporative
component
–  Sometimes from faulty lipid layer
–  Sometimes from faulty mucin layer
–  Or Both
•  I think most dry eye has an inflammatory
component
–  Via InflammaDry
–  Steroid and Restasis clinical experiences
–  Osmolarity experience
–  Allergan
–  Alcon
–  Sucampo
–  Marco
–  Reichert
–  Bausch and Lomb
Dry Eye Disease Cycle of Inflamma.on1 •  Dry eye is o+en hidden un0l pa0ents have progressed and experienced symptoms •  Dry eye symptoms overlap with other ocular surface diseases, complica0ng diagnosis •  Numerous clinical diagnos0cs exist, with no single method preferred •  Most ECPs use one or mul0ple tests, symptom assessment and pa0ent history to diagnose [1] Definition and Classification of Dry Eye. Report of the Diagnosis and
Classification Subcommittee of the Dry Eye Work Shop (DEWS). Ocular Surface
2007;5:75-92.
Terminology of Blephari1s/ MGD IOVS, 2011 Classifica1ons of MGD IOVS, 2011 1
10/26/14
What Types of MGD Exist? • 
• 
• 
• 
• 
• 
• 
Anterior Posterior Mixed Seborrhea Psoria0c Atopic Rosacea • Erythema • Telangiectasia • Pustules • Prominent sebaceous glands • Rhinophyma • 58% of all rosacea pa0ents • Presen0ng sign in : • 20%! MANAGEMENT OF MGD • Meibomian gland dysfunc0on • Dry eye • Blephari0s 2
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Liposomal Spray •  Tetracyclines: Doxycycline 20-­‐50mg bid x 1-­‐2 months •  Taper to qd for 1-­‐6 months depending on response •  Periostat long term (20mg doxycycline) can also be pulsed if seasonal •  Managing Side Effects…. Other Off Label Treatments •  AzaSite® pairs DuraSite® drug delivery technology with azithromycin (1.0%) •  Azithromycin has not been previously used in eye care •  Steroid/An0bio0c combina0on medicines applied to lids( Tobradex ST, Zylet, generic combos) •  Topical an0bio0cs (azithromycin, emycin. Gmycin •  Therapeu0c gland manipula0on (automated of manual) •  In progressive states, I try to seek a dermatologist and/or rheumatologist consult as well –  A stable aqueous formula0on is difficult to produce •  AzaSite®: A stable, easily delivered formula0on of azithromycin –  All the advantages of topical ophthalmic delivery –  All the advantages of the an0-­‐
microbial proper0es of azithromycin • 
• 
Broad-­‐spectrum, an0-­‐inflammatory ophthalmic products1 Mechanism of ac0on spans virtually every aspect of the inflammatory response1 –  Nuclear •  Decreases produc0on of inflammatory precursor proteins –  Cellular •  Suppresses prolifera0on of mast cells and lymphocytes1 –  Biochemical •  Inhibits synthesis and enhances breakdown of histamine1 1. Slonim CB, Boone R. Formulary. 2004;39:213-222.
2. McDonald MB. Refract Eyecare. 2005;9(suppl):3-6.
•  14 to 22 million people who are steroid responders1,2 •  3 to 6 million people with ocular hypertension3 •  3 million people with glaucoma3,4 1. EyeMDLink.com. Steroid induced glaucoma. Available at: http://www.eyemedlink.com/Condition.asp?ConditionID=419. Accessed November 16, 2004.
2. U.S. Census Bureau. U.S. POPClock projection. Available at: http://www.census.gov/cgi-bin/ popclock. Accessed November 16, 2004.
3. E-medicine Consumer Health. Ocular Hypertension. Available at:www.emdicinehealth.com/articles/37513-1.asp. Accessed November 16, 2004.
4. Lee J, Bailey G. Glaucoma: The second-leading cause of blindness in the US. Available at: http://www.allaboutvision.com/conditions/glaucoma.htm. Accessed November 16, 2004.
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®
Lubricant Eye Drops
Refresh Op0ve Advanced •  Tetracyclines: Doxycycline 20-­‐50mg bid x 1-­‐2 months •  Taper to qd for 1-­‐6 months depending on response •  Periostat long term (20mg doxycycline) can also be pulsed if seasonal •  Managing Side Effects…. •  Should be hifng distribu0on in spring and sampling •  Lipid based tear TearScience
Treatment of MGD/NOMGD
At Home Therapy
–  Warm compresses
–  Eyelid Scrubs
–  Self expression
Low
Compliance
In-Office Therapy
–  Manual Expression
–  Off-Label Pharmacotherapy
–  Oral tetracycline/doxycycline -systemic
side effects
LipiView® OSI
LipiFlow® Auto
–  Topical Antibiotics – erythro., tobra. -antibiotic
resistance,
poor gland penetrance
Disposable
–  Topical Steroids – dexamethasone -risk
of cataract, glaucoma,
poor gland penetrance
Meibomian Gland Evaluator
69
70 LipiFlow Auto Console pictured is not approved for use in
Caution: Investigational device. The
the U.S. Limited by United States law to investigational use.
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10/26/14
LipiFlow® Thermal Pulsation
System
LipiView
•  ICU statistics are
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.
The Lid Warmer:
Comprised of a precision
heater, eye insulation &
vaulted shape
The Eye Cup:
Comprised of an
inflatable bladder &
rigid eye cup
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Therapeutic Goal of Heat
Therapy
Therapeutic Goal of Pulsation
•  Liquefy the
meibomain gland
contents
•  Facilitates release of
secretion from the
meibomian gland
Lid Warmer
Applies directional
heat to inner eyelid
Eye Cup
Applies
intermittent
pressure to the
outer eyelid
Insulated lid
warmer shields
eye from heat and
vaults above the
cornea to prevent
corneal contact
•  Increase likelihood
that the glands can
resume normal
function
Heat facilitates release of
secretion from obstructed
meibomian glands
Inflatable
air
bladder
•  Transiently increase
blood flow to the tissue
surrounding the glands,
thus increasing heat
transfer efficiency
•  Evacuate heated and
liquefied gland contents
thus alleviating the
obstruction
•  Less eyelid pain/
discomfort as compared
to manual expression.
73
Eye Cup
Applies
intermittent
pressure to the
outer eyelid
Insulated lid
warmer shields eye
from heat and
vaults above the
cornea to prevent
corneal contact
Heat facilitates release of
secretion from obstructed
meibomian glands
Inflatable air
bladder
74
What Do We Know?
•  Blepharitis and MGD are extremely common
•  Demodex is extremely common
•  Lid disease is a common cause of
evaporative dry eye
•  Rosacea is a common cause of MGD
•  Demodex is a common cause of Rosacea
•  What we thought was anterior blepharitis is
probably Demodex
•  Ocular allergy symptoms overlap dry eye and
MGD symptoms
Lid Warmer
Applies directional
heat to inner eyelid
What We Really DON’T Know:
• 
• 
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• 
What is the true prevalence of Demodex?
How much Demodex results in symptoms
How much “symptom” is needed to treat
Which percentage of dry eye is really lipid
layer evaporation vs. mucin deficiency
•  What is an effective and enduring treatment
for MGD?
•  What is an effective and enduring treatment
for Demodex?
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10/26/14
Demodex
Demodex
•  Mites of the genus Demodex were
described as parasites of hair follicles and
sebaceous glands in man 150 years ago.
•  The hair follicle mite Demodex folliculorum
(detected by Henle,1841 (1), and described
by Simon 1842) (2) and Demodex brevis
(separated in 1963 by Akubulatova) (3) are
the most common ectoparasites of man.
(Fig.1)
Kingdom:Animalia
Phylum:Arthropoda
Class:Arachnida
Subclass:Acarina
Order:Trombidiformes
Family:Demodicidae
Genus: Demodex
HANDBOOK OF MEDICAL
ENTOMOLOGY
Dr. WM. A. RILEY, Professor of
Insect Morphology and
Parasitology, Cornell
University
Dr. O. A. JOHANNSEN,
Professor of Biology, Cornell
University
1915
Demodex folliculorum
Slide courtesy of
Scheffer Tseng, MD
Ocular Surface Center
Miami Florida
Demodex folliculorum
Epilated lash with attached
Demodex folliculorum
•  pictured here three mites
buried “head-down” into
a hair follicle with conical
opisthosomas (tail ends/
caudal portion) visible
•  up to 25 mites per follicle
have been demonstrated
Demodex folliculorum
(5)
•  there is no consensus on
what denotes
“demidicosis” (overinfestation of the
organism)
Demodex
Brevis
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Description of the Mite
Mite Mouthparts
(Fig.2)
Fig. 5
•  Demodex folliculorum =.3-.
4mm long (5)
•  Demodex brevis=.15-.2 mm
long (6)
•  eight segmented legs
(podosoma)
•  two-three tined claws on
each leg and “spurs”
•  locomote at 8-16 mm/hr (7)
•  male and female of the
species
•  more active in the darkness
•  complex gnathosoma
(mouthparts)
•  clawed palpus (feeler
attached to mouthparts)
•  round oral opening
(1211nm)
•  sharp oral needle
(300nm) which pierces
cells to extract cytoplasm
(8)
Demodex
•  Demodex infestation is age dependent,
increasing with age and reaching up to 100% in
elderly patients. (9)
•  Demodex folliculorum is found in hair and
eyelash follicles and elsewhere on the face and
body.
•  Demodex brevis is generally found in sebaceous
glands of the body and in the meibomian and
Zeiss glands of the eyelid.(10)
Making More
The Anatomy of Hair
•  Demodex folliculorum will
nestle “head down” into a lash
follicle (near the infundibulum)
to feed.
•  the bulge is the site of hair
follicle stem cells; pluripotent
stem cells proliferate and then
elaborate the various portions
of the hair shaft
•  hair follicle stem cells are
important contributors to the
wound-healing process (11)
•  Demodex infestation may
interfere with bulge stem cells
Demodex Life Cycle
•  copulation occurs at
the mouth of the hair
follicle (in darkness)
•  the female burrows
into the follicle and
lays eggs
•  life span = 14.5 days
with 120 adult hours
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Demodex Clinical Diagnosis
•  Slit lamp exam
•  Lash epilation and microscopic exam
•  Grinding technique
equence
Clinical s
1. Clinical history: blepharitis, dry
eyes or ocular allergy
2. Slit-lamp examination: cylindrical
dandruff
3.Microscopic confirmation: counting of
Demodex eggs, lavae and adults.
Hom MM, Mastrota KM, Schachter SE. Demodex. Optom Vis Sci. 2013 Jul;90(7):e198-­‐205. Clinical h
1. Clinical history
istory
Symptoms:
Itch, burning, foreign body sensation,
crusting, redness, blurry vision
Hom MM, Mastrota KM, Schachter SE. Demodex. Optom Vis Sci. 2013 Jul;90(7):e198-­‐205. Symptoms of Demodex
itis
Blephar
•  Currently I am only trea0ng symptoma0c pa0ents! –  I could spend my career trea0ng this disease if I treated all the cases I see • 
• 
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Eyelid itching Ocular itching Facial itching Thickened, red lids seen • 
• 
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Watering, o+en chronic Eyelash loss Chronic redness of conjunc0va Coexists with OSD and MGD symptoms –  Personal observa0on: Exacerbated in PGA pts Blephari0s & demodex Meta-­‐analysis of 11 studies Sta0s0cally significant associa0on Zhao YE,Wu LP,Hu L,Xu JR. Associa0on of blephari0s with Demodex: a meta-­‐analysis. Ophthalmic Epidemiol 2012;19:95Y102. 8
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Cylindri
2. Slit lamp evaluation
cal dan
druff
“Cylindrical dandruff was
pathognomonic for the presence of
demodex infestation.”
Gao YY. Di Pascuale MA. Li W. et.al. High Prevalence of
Demodex in Eyelashes with Cylindrical Dandruff. Invest.
Ophthalmol. Vis. Sci. 2005;46(9):3089-3094.
pe
Microsco
3. Epilate and microscope
Celestron 44340 LCD Microscope Amazon $200 approx don’t forget cover slips and slides Microsco
pe
Celestron 44341 LCD Digital Microscope II (Black) Celestron 5 MP LCD Deluxe Amazon $200 approx Have not tried 9
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ex
Demod
Tip sheet Drop cover slip first, then add emulsion drop at the side Show and tell Destruc0ve Mechanisms of Demodex in the Eyelid •  Causes 0ssue edema and inflamma0on of the lash follicle •  Causes disten0on of follicle opening •  Poten0ally act as a vector to transmit viral or bacterial disease to other areas of the eye or head •  Britle and easily lost eyelashes •  Lash cuffing or cylindrical dandruff •  Suspect involvement with Meibomian Gland Dysfunc0on itis
Blephar
Molt
“demodex will molt its shell once
and molt its skin thrice.”
http://www.facedoctor.ca/research/research01.html
Mite/Claw Induced Lid/Lash Changes
•  interrupts tissue integrity
•  causes tissue damage/edema/inflammation/distention of
the lash follicle
•  perifollicular lympocytic inflammation exists(5)
•  mites serve as a vector for infective elements (12)
•  easier lash epilation (13)
•  brittle cilia (13)
•  epithelial hyperplasia = “cuff” formation (10)
•  follicular plugging/lash cuffing, “sleeves” and “cylindrical
dandruff” (14)
•  implicated in meibomian gland granulomas and
meibomian gland dysfunction (10)
Distentio
n
Blephari0s with demodex 62.9% Sumer et. al. 88% Alejo et.al. 97% De Venecia and Siong Sumer Z, Arıcı MK,Topalkara A,Ozçelik S, Yıldırım S.[Incidence of Demodex folliculorum in chronic blephari0s pa0ents]. Cumhuriyet Univ Tıp Fak Dergisi 2000;22:69Y72. Alejo RL, Valenton MJ, Abendanio R. Demodex folliculorum infesta0on of the lids in Filipinos. Philipp J Ophthalmol 1972;4:110Y3. De Venecia AB, Siong RL. Demodes sp. infesta0on in anterior blephari0s, meibomian gland dysfunc0on, and mixed blephari0s. Philipp J Ophthalmol 2011;36:15Y22. 10
10/26/14
n
Distentio
Distention caused by waste products
Half of mites are follicle opening are
dead
Bacteria
n
Distentio
Demodex have no anus, and stores
its waste in large cells within its gut.
When the mite dies, its body
disintegrates and an explosion of
waste can be released.
Rosace
a
Bacillus oleronius has also been detected
inside the digestive tract mites.
Significant correlation serum
immunoreactivity to :bacillus, demodex
infestation and facial rosacea.
Rosacea and demodex
Meta-analysis of 48 studies
10 different countries
28,527 subjects
Rosacea patients 7-8x chance have
Demodex
Liu J. Sheh H. Tseng SCG. Pathogenic role of Demodex mites
in blepharitis. Curr Opin Allergy Clin Immunol. 2010; 10(5): 505–
510.
Zhao YE, Wu LP, Peng Y, Cheng H. Retrospective analysis of
the association between Demodex infestation and rosacea. Arch
Dermatol 2010;146:896Y902.
Allergy
Demodex mites
Link to allergic conjunctivitis
Increase secretion cytokine (IL-17)
Stimulates inflammatory or allergic
reactions
Resulting ocular surface damage.
Koo H, Kim TH, Kim KW. et.al. Ocular surface discomfort and demodex: effect of tea tree oil
eyelid scrub in demodex blepharitis. J Korean Med Sci. 2012 Dec;27(12):1574-9.
Kim JT, Lee SH, Chun YS, Kim JC. Tear cytokines and chemokines in patients with Demodex
blepharitis. Cytokine. 2011;53:94–99.
Demod
ex
Tip sheet Mites in children -­‐ Poster Friday Scot Schachter Mites mistaken for allergy Look for lots of cuff dandruff to epilate. Look for distended bases. Waste products & dead mites. Go for “juicy” or “sick” lashes (short, discolored, mis-­‐
directed, etc) 11
10/26/14
Demodex Has Been Linked to
Rosacea and Blepharitis
Demodex Infestation is Associated
with Floppy Eyelid Syndrome (4)
Slide courtesy of Scheffer Tseng, MD
The Ocular Surface Center, Miami Florida
• 
• 
• 
• 
• 
• 
• 
Skin Rosacea
Ocular Rosacea, Blepharitis
Coston, 1967, English, 1971, English & Nutting, 1981, Heacock,1986, Fulk &
Clifford, 1990, Fulk et al, 1996, Kamoun et al. 1999, Morfin, 2003
In Office Treatment
•  I find about 50% of pa0ents find some symptoma0c relief with one month use of Cliradex at home •  Pa0ents with heavy scruff really need an in office treatment to remove scruff or TTO will never get to the target. •  Typically doing 2 different in office TTO, rarely third •  Maintenance on Cliradex; range QD to Q 1-­‐3 x week Terpinol-4
•  The active ingredient of Tea Tree Oil
• 
• 
floppy, rubbery and easily
everted upper eyelids
lacrimal gland prolapse
ptosis/lash ptosis
dematochalasis
eye lid hyperpigmentation.
papillary conjunctivitis.
squamous metaplasia and
keratinization in meibomian
glands/gland dysfunction
lax lids have diminished lipid
production
associated with obstructive
sleep apnea
Treatment of Demodex
•  Topical Ivermectin
•  Topical Tea Tree Oil
–  Ocusoft Demodex kit
–  Cliradex premedicated towelettes
•  Bland ointments/Erythromycin?
•  Other homemade concoctions?
–  Macadamia Nut oil
In Office Treatments
•  Get an informed consent
•  My protocol:
–  Topical proparicaine and NSAID
–  Very light application of Mac/TTO
•  Followed by q tip or blephabrush removal of scruff
–  Rinse with Ocusoft Plus Scrubs
–  Use Ocusoft TTO with brush to apply into
follicles
–  Rinse and repeat
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eatmen
tr
In-office
ts
1. Clean lids with lid scrub (Ocuso+, etc) 2. Ins0ll proparacaine/tetravisc/NSAID as drop in eyes and along lid margins with coton swab. 3. Apply TTO (Ocuso+ or mix) with coton swab along lid margins. Use a fresh swab for each lid margin. ts
redaetxmen
o
t
m
e
e
ic
D
ff
o
In4. Clean lashes with the short “Bleph” brush (Ocuso+ demodex kit) removing all collaretes and debris that remain. Op0onal: coton swab 5. A+er 5 or more minutes, irrigate. I prefer CL solu0on with PHMB (“acaricide”) 6. Clean again with lid cleaning pads. 7. Repeat TTO, irrigate and scrub again Modified from Cliff Silverman, OD
nts
toredaetxme
In-offDiceem
8. Send home with Cliradex 2x day if moderate/severe, 1x day if mild/moderate 9. Return in about 2 weeks for 2nd treatment Demod
ex
Tip sheet Space 1-­‐2 weeks apart, lifecycle of the mite Minimum 2 treatments, some0mes more is needed Use Cliradex pads 2 x day or 1x day evenings Squeeze pads before opening to spread TTO, some0mes pads are dry Use pads on eyebrows and rest of face Demod
ex
Tip sheet If you see rosacea and see no demodex, you are missing it Everyone has it, normal 1000-­‐2000 mites; like bacteria Q: infesta0on or not In-­‐office will not get rid all of them We only try to control the numbers Add Tea tree oil shampoo Add Tea tree oil soaps Demod
ex
Tip sheet “Squeeze and fan” Lay pads on lids without scrubbing for most sensi0ve pa0ents Q: Do your own mix or not? Use at own risk TTO:Macadamian nut oil; 50:50 mix Be careful of too much TTO with Bleph brush Caraway oil can be used, but $$ Emulsion drops with oil ac0vates the mites 13
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Treatment Goal:
Ointments
•  NOT to eradicate 100%
•  Want to knock down the “load” and reduce
symptoms
•  Like to see some visible reduction in
cylindrical dandruff
•  Improve redness profile of eye, lid and
face
•  Do ointments have any efficacy in treating
demodex?
•  Erythromycin
•  Gentamycin
•  Tobradex Ung
•  Lotemax Ung
•  Pilo ung?
Last thoughts…
Formication
Although their pathogenic
potential remains unclear, the
ubiquitous pilosebaceous mite
Demodex (generally
considered a saprophryte)
overpopulation should be
considered as cause in
recalcitrant cases of
blepharitis/conjuctivitis/corneal
pathology.
Demodex brevis induced
pathological changes in the
meibomian gland function/lipid
layer is implicated in
evaporative dry eye/ocular
surface disease.
Delusional Parasitosis
•  “I am very sick with mites in my hair, and
everywhere..I shaved my eyebrows
yesterday, but my eyelashes are fun of
eggs, I can't get them off. The mites are
biting me everywhere. My hair, and scalp
is full of them..Can you see me? Can you
help me?I looked you up, and you are in
Brooklyn. Please call .”
•  a sensation of insects crawing on or under
the skin
•  “pins and needles”
•  In rare cases, individuals become
convinced that the sensation is due to the
presence of real insects on or under the
skin. In these cases, patients have what is
known as delusional parasitosis
Delusional Parasitosis
•  “The ferrets started scratching, and I took
them to 2 vets, and they were diagnoised
with Demodex mites.”
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Delusional Parasitosis
•  “You could see them in the bright light if
you look really hard in there food bowls, as
they float to the top of the left over water.
They are a half the size of a sesame
seed. I bought a magnifying glass, and
you could see them.”
Delusional Parasitosis
•  “I was not happy with the doctors that I
saw. They did not help me. I am still
infested. I am taking baths with borax
which is helping, and going under water
with my head. The internet says to do
that.”
Delusional Parasitosis
•  “I am 54 years old. My boyfriend left me
when he found out. I am all alone.”
Delusional Parasitosis
•  “I keep shaving my eyebrows because if I
don't they get infested with a lot of mites.”
•  “The mites are in my eyes, eye lids, and
eye lashes. They are also coming out of
my nose. They are in my personal places,
and I am not feeling well.”
Delusional Parasitosis
•  “I have them in my hair, scalp then they
went into my eyebrows, eyelashes, ears,
and nose, and they are biting me all
over.Some are black, and some have no
color. They are breeding on my eye
brows.I have gone to 3 doctors, and the
last one saw the black mites. The gave me
shampoos, and creams that did nothing.”
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