Download Tear Film

Ocular Surface Diagnosis and
Treatments
Richard W. Yee, M.D
Joe M. Green Endowed Chair
Clinical Professor of Ophthalmology
Department of Ophthalmology and Visual Science
Hermann Eye Center/University of Texas Health Science Center @
Houston
Disclosures
 Allergan Speaker’s Board
 B and L Speaker’s Board
 SeeFit
Keep your Eye on the BALL
TAKE A CLOSER LOOK
SIX LAYERS
 Tear Film and Epithelium
 The Ocular Surface
 Basement Membrane (biological role)
 Why Lasek Works
 Bowman’s Layer
 Stroma
 Descemet’s
 Endothelium
What is the Ocular Surface
Microenvironment
• Epithelial cells
Tear Film
• Goblet cells
 Mucin
• Glycocalyx
 Aqueous
• Transmembrane
glycoproteins,
mucin, and
associated
molecules
 Lipid
Tear Film
 Lipid
 Aqueous
 Mucin
Tear Film
(Zeis 20x true non contact lens)
•Mixed Pattern
•Smooth Wave Pattern
•Granular with Holes
•Granular Pattern
Tear Film Structure
Traditional Tear Film
Model
Updated Tear Film Model
(Aqueous phases with differing concentrations of mucins throughout)
(3 Distinct Layers)
MUC 7
MUC
5AC
MUC 1
MUC 4
The Role of Epithelial Glycocalyx
MUCOUS LAYER
 0.02 - 0.05 µ Thick
 Secreted by Goblet
Cells/lacrimal Gland
 Average Goblet Cell
Count - 8.8
Glands/sq mm
 Maintains Stability of
Tear Film
Dry Eye Epithelial Microenvironment
Putting it all together
Lipid Layer
Aqueous Layer
Mucin Layer
Glycocalyx
Ocular Surface Cells
Transmembrane mucins, anchored to epithelial cell membrane and
contributing to glycocalyx structure, help achieve the spread of
secreted mucins across the entire ocular surface.
This is crucial to the integrity of the rest of the tear film (aqueous and
lipid layers), as it relies on the foundation of an intact mucin coating.
What is
Ocular
Surface
Disease?
The Cornea Is
Like a Car
Windshield!
Tears are like the
Wiper Fluid!
Lids are like Windshield Wipers
Eyelid Margin Anatomy
(Riolan’s Muscle)
 Gray line-isolated section
of pretarsal orbicularis
(Riolan’s) between lash
line(ant) and meibomian
gland orifices(post)
 Mucocutaneous junctionposterior to MG orifices
 Meibomian Gland:
 Holocrine glands.
 First described by
Henrich Meibom
in 1666
 Meibum:
 Plays an integral
role in tear film
stability
 Prevents the
premature
evaporation of
the aqueous tear
component.
Meibomian Glands (MG)
Ocular Surface Disesase is associated with heighten
cytokine inflammatory response in glands and on the
ocular surface
Disrupt epithelial cell function
Reduce corneal sensitivity
Decrease sensory input to gland
Destabilize tear film
Ocular surface irritation increases and dry eye becomes
self-perpetuating
The Pathological States
Ocular Surface Disease
Diagnosis
History (symptoms)
Ocular surface exam (signs)
Aqueous Tear Insufficiency
Lid Margin Disease
Computer Vision Syndrome
Dry Eye Cascade
CLINICAL FEATURES
Early Symptoms
None
Fatigue
Tearing (reflex)
Irritation
Scratchiness
Contact lens intolerance
CLINICAL FEATURES
Later Symptoms
Heaviness of Eyelids
Blurred and Fluctuating Vision
Improves with blink
Excess Ropy Mucus
Burning
Itching (clinical study #1)
Photophobia (keratitis, non uveal)
Foreign Body Sensation
Signs & Symptoms Don’t Always
Correlate
LACRIMAL GLAND
SIGNS
OCULAR SURFACE
OCULAR SURFACE
ALTERATION
CNS
SYMPTOMS
Schirmer
Tear Test
Nerve Traffic to Lacrimal Gland
-- Neural Accommodation
Fluorescein
Staining
Compromise of Corneal
Neural/Epithelial Environment
Photophobia
TBUT
Dry Spot Form
Meibomian Gland Dysfunction
Possible Mucin Deficiency
Dryness
Rose Bengal
Staining
Conjunctival Epithelial
Proliferation/Keratin
Expression
Fluctuating Vision
Burning and Stinging
Foreign Body
Decrease Haze Intraoperatively
•
•
•
•
•
Cold BSS (Stein)
Frozen Weck cells (Durrie)
Amniotic Membrane (Tseng)
Mitomycin C (Raviv)
Smoother is Better (Thomas/Vinciguerra/Wilson)
•
Autologous Serum (Lin and Yee)
Make a Great Flap!
•KEY is longer ETOH
durations (45 -90
seconds)
•NOT viable
epithelium
•The flap should come
off this easily, if not
use longer alcohol
times (45-90 secs)
•Risk of Haze
increased if the flap is
not made properly
Case Report
• 30 yr old Asian computer technologist
• Wants LVC because he cannot wear his
SCL
• Spends >8 hrs/day on the computer
• Denies any dry complaints and uses no
eye drops
Case Report
Eye Exam
•
•
•
•
•
-7 D myope
Topography: Unremarkable
SLE: Unremarkable
Basal Tear Test: 15 mm OU
No Staining with Lissamine Green
What Causes Haze?
Endogenous BM prevents TGFB2 release
into the stroma (Fini et al ARVO) 2002
Clinical Implications of Haze
• Haze is  ocular surface disease  stimulating
aggressive wound healing
• Hyperplastic response  ^ stromal thickness 
^ corneal refractive power  myopic regression
• Can cause loss in:
– BCVA (1-3% of overall cases after PRK)
– Contrast sensitivity
(maximal loss of CS correlates with greatest degree)
Timeline of HAZE formation
after excimer photoablation
• Variable due to differences in targeted
refraction, postop gtts, diagnostic
criteria
• Transient, initial peak during first week
(epithelial)
• Onset 1-2 m, peak 1-6 m, resolution 324 m
• Late-onset (LOCH) b/w 4-12 m
Risk Factors for Haze
– Targeted refraction > 6 D or > 80 microns
– Delayed epithelial closure
– Ocular/systemic inflammatory disease
– Postop UV exposure:
– (JCRS 2001;27(13).404.410)
• Sun, Sailing, Snow, Swimming
• CVS = MGD
– Environmental Irritants
• Triathletes
– ? Age
Pathology of Haze
Surgical Treatment: Two Stages
•Scrape Scar and paint with MMC .02%~ 30-60 secs or less
•Approx 4-6 wks: once Rx is stabilize laser
•Agressively tx with SCL, MMC, punctal plugs, cylosporine, steroids,
islolation glasses, IPL and autologous serum, omega 3, and any
environmental control (islolation techniques).
Optimizing the Ocular Surface
•
•
-Ocular Surface Disease Index
(OSDI)
Evaluate the Ocular Surface
– Schirmer’s Test
– Punctal Plugs
– Restasis and Optive Artificial
Tears
•
Computer Vision Syndrome
(CVS~MGD)
– Blinking
– Additional Tears
•
•
•
•
Ocular Surface Abnormalities i.e.
MGD, even borderline dry eyesdelays Wound Healing
Difficult flap creation and any
delay in Healing=Haze
Topical agents: tear preparations,
antibiotics glaucoma meds, may
be more toxic than others and
delay healing
Isolation techniques
Was it the eye drops he was using???
Epithelial Wound Healing After
PRK
Gatifloxacin
Moxifloxacin
Day 0
Day 1
Day 2
Day 3
Day 4
Was it the eye drops he was using??? Maybe, but probably NOT!!!
Was it the Lids???
Association of dyslipidemia
in moderate to severe meibomian gland dysfunction
•Dao AH, Spindle JD, Harp BA, Jacob A, Chuang AZ, Yee RW
•Am J Ophthalmol. 2010 Sep;150(3):371-375.e1. Epub 2010 Jul 8.
YOU HAVE TO PUSH!!!
The Ocular Surface Exam
1. Assess Anterior Blepharitis
2. Assess Posterior Blephartitis
a.
Increased Lid Margin Vascularization
b.
Decreased Meibomian Gland Expression
c.
Decreased Quality of Secretions
d.
Decreased Quantity of Secretions
3. Perform Staining Tests
4. Perform Basal Tear Test
5. Find Tear Breakup Time
Ocular Surface Exam Sheet
Upper Lid
0 1 2 3 4 Anterior Blepharitis
0 1 2 3 4 Vascularization
0 1 2 3 4 Obstruction
0 1 2 3 4 Turbidity
01234
01234
01234
01234
Lower Lid
0 1 2 3 4 Anterior Blepharitis
0 1 2 3 4 Vascularization
0 1 2 3 4 Obstruction
0 1 2 3 4 Turbidity
01234
01234
01234
01234
•Standardization
of Clinical Signs
•Advantages of
following patient
condition
•Lowers your
threshold for
detecting
disease
Scoring a Lissamine Green Stain
1
2
1
3
Example:
3
2
2
3
3
2
2
Shading indicates punctal plugs which may
cause irritation and staining.
How to perform an Ocular Surface Exam
Scoring Anterior Blepharitis
1
2
3
4
Cylindrical Dandruff
Clinical Features

Anterior Blepharitis
caused by ocular
Demodex folliculorum
 Demodex folliculorum is
a mite part of the
arachnid class, normally
found in hair follicles and
sebaceous glands.
 Featured as cylindrical
dandruff at the base of
the eyelash.
 Symptoms include
itchiness, burning, foreign
body sensation.
 Can be present on
asymptomatic patients.
Eyelash Follicle:
Location of Demodex
Cylindrical dandruff
•Demodex Folliculorum
•Demodex
Brevis
Tea Tree Oil (TTO)

TTO, a natural essential
oil steam-distilled from
the leaf of Melaleuca
alternifolia

TTO has long been used
as an aboriginal
traditional medicine in
Australia for wounds
and cutaneous infection

TTO has antibacterial,
anti-fungal, antiinflammatory and
acaricidal effects
•Skin Manifestation
•Demodex has been implicated in rosacea, pityriasis folliculorum,
•perioral dermatitis, pustular folliculitis and basal cell carcinoma
Coston, 1967, English, 1971, English & Nutting, 1981, Heacock,1986, Fulk &
Clifford, 1990, Fulk et al, 1996, Kamoun et al. 1999, Morfin, 2003
•Conjunctival Inflammation Is Reduced
•after TTO Lid Scrub
•Before
•After
•Gao et al
Cornea2006
Ocular Surface Exam Sheet
Upper Lid
0 1 2 3 4 Anterior Blepharitis
0 1 2 3 4 Vascularization
0 1 2 3 4 Obstruction
0 1 2 3 4 Turbidity
01234
01234
01234
01234
Lower Lid
0 1 2 3 4 Anterior Blepharitis
0 1 2 3 4 Vascularization
0 1 2 3 4 Obstruction
0 1 2 3 4 Turbidity
01234
01234
01234
01234
•Standardization
of Clinical Signs
•Advantages of
following patient
condition
•Lowers your
threshold for
detecting
disease
Scoring Lid Margin Vascularization (V)
Grade 1
Grade 2
Grade 3
Grade 4
Lid margin neovascularization=MGD and MG atrophy
Not aqueous deficient
PUSH! Before Ms Smith says OW!!!!
(O)
Scoring the Turbidity of Meibum (T)
Grade 0
Clear
Grade 1
Slight
opacity
observe tear film debris
Yellow
meibum
Grade 3
Grade 4
Toothpaste
Grade 2
Was it the Lids??? YES!!!
Was it the COMPUTER???
Computer Vision Syndrome
Characteristics of CVS Patients
Experiences symptoms such as
 Itchiness, fatigue, burning, dryness, tearing and itchiness
 Inflammation, severe pain and decreased vision
Primarily present in patients diagnosed with Dry
Eye Syndrome, Blepharitis and other eye surface
diseases.
Lifestyle (people who stare and or exposed)




Frequent computer users (>3 hours)
Frequent travelers
Research and Medical Professionals
Students
Blink Rate (Tsubota et al
IOVS Suppl 34:1471, 1993)
Relaxed conditions
Book reading
VDT text reading
22.4+8.9/min
10.5+6.5/min
7.6+6.7/min
11,000 – 12,000 blinks/day
7.5 sec between blinks
Creating a Pathologic Condition???
Blink decreases by 66%
Chronically, the blink decreases and
MGD is exacerbated
Blinking Hypothesis
Tear film
break up
starts
Blink
Tear Protected
Ocular Surface
0
1
2
Time (seconds)
3
4
Cycle Repeats
Unprotected
Ocular
Surface
5
6
Staining of
desiccated cells on
ocular surface
Blink
7
=CVS
Bottom line: decreased blinking  decreased tear layer
 damage to ocular surface increase inflammation
Eyelid Margin Anatomy
(Riolan’s Muscle)
 Gray line-isolated section
of pretarsal orbicularis
(Riolan’s) between lash
line(ant) and meibomian
gland orifices(post)
 Mucocutaneous junctionposterior to MG orifices
Meibomian Glands : Lipid Secretion
•Transillumination of
meibomian glands
•Meibomian gland dysfunction
Þ The lipid layer restricts evaporation to 5-10% of
tear flow
ã Also helps lubricate
Þ Obstruction of meibomian gland ducts reduces
lipid secretion
ã Causes increased evaporation of the aqueous component
Meibomian Gland Histology
Tarsal plate with
meibomian gland
Pretarsal orbicularis
PS
Pars ciliaris
Pars fascicularis
PC
Lipham et al. A Histologic analysis and Three-Dimensional
Reconstruction of the Muscle of Riolan. Ophth Plas and Recon Surg
2002;18:93-98
Pars subtarsalis
Watch the eyelashs
Note the result of the Blink!!!
Baseline Assessment of Meibomian Glands
3.5
3
control
symptomatic
2
1.5
1
0.5
M
G
O
bs
t
R
LM
G
V
LL
LV
U
M
G
R
U
Q
ua
l
ru
ct
io
n
ity
0
M
G
Score
2.5
MG = Meibomian
Gland
ULV = Upper Lid
Vascularization
LLV = Lower Lid
Vascularization
UMGR = Upper Lid
Meibomian Gland
Rounding
LMGR = Lower Lid
Meibomian Gland
Rounding
Association of dyslipidemia
in moderate to severe meibomian gland dysfunction
•Dao AH, Spindle JD, Harp BA, Jacob A, Chuang AZ, Yee RW
•Am J Ophthalmol. 2010 Sep;150(3):371-375.e1. Epub 2010 Jul 8.
CVS Effects: Exposure to the Environment
Side and overhead
Air drafts
Air conditioning
Airborne allergens
Stray light
Synthetic light
Hot or Dry Air
High Altitudes
Smog, Exhaust, or
Smoke
All factors
compromise the
refractive ability of
the tear film layer.
Symptomatic Treatment of CVS
using Isolation Techniques

Increase Humidity 70-90%

Protects from Chronic
Irritation

Wind

Hot or Dry Air

Smog, Exhaust, Smoke

Allergens

CVS

Decreased exposure to light
of various spectral
frequencies

Increase Temperature
 Decreases Lipid Viscosity and
Coefficient of Friction
(increases lubricity)
 Increases Comfort
 Korb: “It cures all dry eyes”
 Improves BUT and staining
Benefits of Isolation
Techniques
MEGs®
Blink
Tear Protected
Ocular Surface
0
Blink
TFBUT
1
Time (seconds)
2
MEGS
Unprotected
Ocular
Surface
3
Normal
4
5
6
CVS
7
Isolation
ADDITIONAL APPROACHES
Intense Pulsed Light
•Current Uses of IPL:
•
-smoothing of wrinkles
•
-treatment of acne vulgaris
•
-treatment of rosacea
•
-treatment of varicose veins
•
-removal of port wine stains
•
-hair removal
Hair Removal
Pigmented Lesions
Acne Vulgaris
IPL for MGD
Incidental observation made by Dr. Rolando Toyos in
an article that appeared in Cataract & Refractive
Surgery Today, April 2009 entitled “Intense Pulsed
Light in Dry Eye Syndrome:
Rosacea patients with various ocular disorders who
were treated with IPL in his aesthetics clinic
“returned reporting improvements in their skin, but
they also said that their eyes felt better and their
vision had improved.”
(Matrix Metalloproteinase MP-9)
 -MMP-9 is a protein that breaks down molecules that hold cells
together which include: collagens, gelatin, elastin and laminin
 -Researchers have found that levels of MMP-9 are higher on the
ocular surface of patients with meibomian gland dysfunction when
compared to people with healthy eyes
 -Researchers have also noticed that levels of MMP-9 in the skin
decrease after treatment with Intense Pulsed Light (IPL)
PREPARING 20% AUTOLOGOUS
SERUM EYEDROPS IN 10 EASY
STEPS
1. Maintain aseptic technique during
preparation
2. Draw the patient’s own blood
(20cc) into 2 red top Vacutainer™
tubes.
3. Centrifuge the blood at 4000 rpm for 4 minutes
.
4. Using a 10 cc syringe, draw off only the serum.
5. Dilute the serum (typically 5 cc) with the
appropriate amount of balanced salt solution
(in the plasma bag).
6. Mix serum and
BSS in plasma bag
to create
“autologous
serum.eyedrops.
7.Allow the serum
solution to flow
from the plasma
bag into sterile IV
tubing.
8. Using a tube sealer, pinch the IV tubing into
1-1 ½ inch ampules.
9. Store at - 80º F (up to 3 months)
10.Stored by patient in refrigerator -40º F or
lower (up to 1 month).
Thanks for taking a closer LOOK!