Lid disease is the MOST underdiagnosed, misdiagnosed, mistreated

4/28/2015
Ocular Surface
and
Lid Margin Diseases
Financial Disclosures
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Thomas P. Kislan, OD, Medical Director
Hazleton Eye Specialists
Stroudsburg Eye Specialists
The Dry Eye Clinic of Northeast PA
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Lid disease is the MOST
underdiagnosed, misdiagnosed,
mistreated and mismanaged
condition among ALL eye care
providers!
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Alcon
Allergan
B+L
Mentholatum
MiBoMedical
PRN
RPS
Tear Lab
Tear Science
Perspective on Dry Eye Disease –
Consumer
Consumers Have a Limited Understanding of Dry Eye as a Disease
79% Self Classify Their Dry Eye as Moderate or Severe
Moderate
Mild
Yet Only About Half View Dry Eye as a Disease
Consumer Experience – Typical
Journey
Gfk 2014 Chronic Dry Eye Patient A&U May 2014.
Perceived Effectiveness of HCPs in Treating Dry Eye
Years Since Diagnosis (Median)
56-Age
Diagnosed with
Dry Eye by
HCP
90%
38%
Omega 3 Supplements
29%
Followed by Ointments, Rx Eye Drops, and
Punctal Plugs
Not at all
Effective
60.5Age Started
Rx Treatment
0
(≈4.5
years)
years)
Importance of Decreasing Use of AT’s
Top 3 Products Currently Using
Gels/Liquigels
Not at All
Minority
• Use drops 1-3 times per day
• Perceive they provide
substantial relief
Very Important
Most
Very
Effective
• Using drops 3–5+ times per day
• Drops are insufficient – do not last
a long time
• Inconvenient to use
PCPs*
Ophthalmologist
Optometrist
*Caution: Small Base Size
Dropping AT’s 3–4 times per day triggers
desire for new treatment
Gfk Chronic Dry Eye Patient A&U July 2013 & May 2014.
CDE Patient Qual. August 2014
Only 45% are Aware of Screening Tests for Dry Eye
Consumer Experience – HCP
Satisfaction
Dry Eye Patient Journey
Artificial Tear Drops
28%
negatively
impacts
way
I look/feel
about
myself
65%
DE is more
of a
nuisance
than
disease
©
(≈3.6
53%
DE
interferes
with daily
activities
Severe
Uncomfortable-unhappy patients
Fluctuating vision-unhappy patients
Poor surgical outcomes-unhappy patients
Contact lens dropouts-unhappy patients
Loss of income-unhappy doctors
52Age First
Experienced Dry
Eye
52.4Symptoms
Impact on Their Quality of Life
Not Sure
Satisfaction with HCPs treating DE is broad across specialty, however both
OPH and OD are perceived to be more effective in treating the disease
©
©
Gfk 2014 Chronic Dry Eye Patient A&U May 2014.
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4/28/2015
Differential Diagnosis of Ocular Surface
and Lid Margin Diseases
THE DRY EYE
SUMMIT 2014
Dallas, TX
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Common Signs and Symptoms:
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Foreign body sensation
Dry, gritty ocular surface
Itchy eyes
Photosensitivity
Hyperemia
Chemosis
Tearing
Lid swelling
FLUCUATING VISION
Why Do We Need
Recommendations
for Dry Eye Disease?
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Improving The
Screening,
Management, and
Diagnosis Of Dry
Eye Disease
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PROGRAM CHAIRS
Bloomenstein
Cunningham
Gaddie
Karpecki
Morris
Nichols
ATTENDEES
Cafferey
Devries
Epstein
Hom
Jones
Kabat
Mastrota
Melton
Opitz
Owen
Quinn
Rumpakis
Schaeffer
Thomas
Wesley Whitley
Dunbar Eiden
Geffen Hauswith
KISLAN Lonsberry
Miller
Nichols
Prokopich
Shovlin Smick
Townsend
The Dry Eye Summit 2014:
How Did We Develop
Recommendations?
• Current guidelines (eg, DEWS, AOA) are
perceived as being too complex or inaccessible
• Discussed clinical data on dry eye disease and the
role of ocular surface wellness
• Limited awareness of guidelines
• Identified current gaps in management through
survey sent to “experts” and >1000 ECPs
• Recommendations from “the experts” are not
being incorporated into everyday practice by
community ECPs for multiple reasons
• Need to SIMPLIFY by setting minimum
recommendations that all ECPs can commit to
Recommendations from the Dry Eye Summit 2014
Identifying Gaps in Care:
“Expert” vs Community ECP
Practices
For What Percentage of Your Dry Eye Disease Patients
Do You Recommend Any Treatment?
• 1.5-day discussion and debate (ECPs and industry)
on best practices for screening, diagnosing, and
managing dry dye disease
• Used interactive polling system to establish
consensus
(minimum 2/3 agreement needed)
Recommendations from the Dry Eye Summit 2014
Know the Risk Factors
• Disease
– Diabetes
– Allergies
• Contact lens wear
• Medications
– Antihistamines/Decongestants
• Age
• Digital device use
– Cell phones
– Tablets
– Computers
Experts are much more likely to recommend treatment for dry eye disease.
Recommendations from the Dry Eye Summit 2014
Recommendations from the Dry Eye Summit 2014
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4/28/2015
Consensus on Baseline
Diagnostic Options for Entry
Level Dry Eye Disease
Consensus on Screening
Questions
1. Do you think your eyes look
healthy?
1. Detailed patient history
2. Do your eyes feel healthy?
2. Staining
3. Are there times when your vision
is not as clear as you want it to be?
3. Osmolarity levels
4. Do your eyes ever feel dry or
uncomfortable?
Recommendations from the Dry Eye Summit 2014
Recommendations from the Dry Eye Summit 2014
Consensus on Baseline
Management
Eyelid Anatomy
1. For all patients:
A. Ocular lubrication
B. Lid hygiene
C. Nutrition
2. Topical anti-inflammatories
Recommendations from the Dry Eye Summit 2014
Prevalence of MGD and Lipid
Deficiency1
Meibomian Gland Dysfunction:
A Prevalent Condition with Consequences
“Meibomian gland dysfunction (MGD) may well
be the leading cause of dry eye disease
throughout the world.”1
-The International Workshop on Meibomian Gland Dysfunction: Executive Summary
MGD is present in ~37% of entire ophthalmic practice
patients and ~47% of optometric practice patients.2
1. Shimazaki J, et al, Ocular surface changes and discomfort in patients with meibomian
gland dysfunction. Arch Ophthalmol. 1995 Oct;113(10):1266-70.
17
1. Nichols KK, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011;52(4):1922‐1929. 2. Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence and
treatment. Ocul Surf. 2009;7(2 Suppl):S1‐S14. 18
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4/28/2015
Posterior Blepharitis (MGD):
Etiology
Tear Composition
1.
Prevents evaporation of tears
and is the final optical
interface
2.
Hydrates and provides optical
interface
Change in composition of meibomian gland
secretions that leads to inflammation, irritation
and an altered tear film
Normal secretions convert from unsaturated
lipids (that melt at body temperature) to
saturated fats
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Adheres to cornea and binds
aqueous
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Posterior Blepharitis (MGD):
Etiology
3. The mono- and diglycerides are more solid in
composition, leading to obstruction/plugging of
the meibomian gland
4. The mono- and diglycerides are proinflammatory, leading to the inflammation
associated with MGD
Consequences of MGD
Obstruction of the gland leads to phases of downstream
consequences, resulting in decreased availability of meibomian
lipids at the lid margin and tear film
Partial obstruction
Initial phases of MGD
• Partial obstruction
• Primary consequence of low delivery
of oil
Progression towards total obstruction
• Stasis of meibum inside the glands
increases with increased pressure
• Resultant dilatation
• Acinar atrophy
Total obstruction
As total obstruction is approached, all
factors are exacerbated, leading to
glandular atrophy and loss of function
1. Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction:
report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest 23
Ophthalmol Vis Sci. 2011;52(4):1938-1978.
Involves degradation of triglycerides to
mono- and diglycerides
Lipases appear to be involved in the
degradation
Pathophysiology
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Irregular oil pattern disrupts tears
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Allows increased exposure of the aqueous layer
to the atmosphere
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Increased evaporation of the aqueous results in
the remaining fluid becoming hyperosmolar
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Obstructed glands lead to ……………
Untreated MGD Leads to the
Dry Eye Cascade
Decrease in lipid secretions and LLT
Evaporation increases (4x to 16x)
Decrease in aqueous layer thickness
Unstable tear film
SYMPTOMS START
LLT indicates lipid layer thickness
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4/28/2015
Ocular Surface and Lid Margin
Diseases
Potential Chronic Changes
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Telangiectasia
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Dislocation of meibomian
glands/ gland atrophy
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Scarring
Why Measure Tear Osmolarity?
Measuring osmolarity allows us to evaluate an actual physiologic marker rather than a “sign” of the disease such as staining or tear break up time.
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Differential diagnosis tests
 Tear Break Up Time
 Corneal FL Stain
 Lissamine Green Staining
 Schirmer
 Meibomian Gland Expression
 Trans-illumination
 Osmolarity
 Inflammadry
 Ant seg photography
 Topography
Osmolarity Testing is Easy to Perform
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Characteristics of Osmolarity
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Lab‐on‐a‐chip technology
Hyperosmolarity Upregulates
EMMPRIN/MMP‐9
Normal
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Wait only 15 minutes after topical anesthetic and/or dilating drops
Wait at least 2 hours after any other topically applied drops including artificial tears
Within seconds, the TearLab Test Card collects 50 nanoliters of fluid from the tear meniscus
Results are displayed within seconds
The test can easily be performed by a technician
Healthy eyes are normal and stable
Tears in proper homeostasis should be equivalent to blood osmolarity which is between 280‐295 mOsml/L
Hyperosmolar
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Is the central pathophysiologic mechanism for all forms of DED
Causes inflammation and apoptosis
Leads to a breakdown of homeostatic control causing tear film instability
Reduces the ability of mucins to lubricate
Unstable tear film leading to inter‐eye differences1
1Lemp MA et al., Am J Ophthalmol. 2011 May;151(5):792‐798
Huet E et al. Am J Pathol. 2011;179.
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4/28/2015
Dry Eye Disease Can Decrease Visual Acuity
and/or Quality of Vision
Two Numbers Crucial to Understand Osmolarity The MAXIMUM of the two eyes:
The DIFFERENCE b/w two eyes:
Tears higher than 300 mOsm/L This shows the stability of the tear demonstrate loss of homeostasis film. Normal tears are stable and and likely become pathogenic > 308. < 300 mOsm/L bilaterally. A difference of > 8 mOsm/L is a hallmark of tear instability.
What if TO is elevated but the ocular surface is quiet and/or the patient is asymptomatic?
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Hyperosmolarity is a hallmark sign of DED as stated in dozens of peer review publications over the past 5 years and even decades of research prior to the development of TearLab (> 250 publications)
The patient may not have reached a point where visible evidence is present e.g. corneal staining which is typically a late sign for DED and can also be present in other OSD conditions
We now are seeing many publications showing hyperosmolarity can cause damage to corneal nerves leaving a neurotrophic condition with poor symptom recognition
What if TO is normal but the ocular surface and/or symptoms indicate dry eye? 
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The Role of Osmolarity in Differential Diagnosis
Osmolarity Clinical Pearls
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Normal osmolarity but ocular surface irritation/complaints
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Partially treated DED
CL and/or solution irritation
Mild allergic conjunctivitis
Epithelial Basement Membrane Dystrophy
Pinguecula/early pterygia
Infection
Anterior blepharitis
Demodex
Elevated >308 or inter‐eye difference of >8 mOsm/L
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Meibomian Gland Dysfunction
Lacrimal Gland Insufficiency
Contact Lens Induced Dry Eye (CLIDE)
Androgen deficiency
Post Refractive/Cataract surgery
SjÖgren’s Syndrome
Signs and symptoms do not correlate with each other and this also includes osmolarity There is significant overlap with other OSD conditions such as ocular allergy, conjunctival chalasis, etc. It is highly unlikely that the TearLab system will show a false positive reading
Subjectivity of patient symptoms (e.g. stoic vs. whiner)
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Hyperosmolarity is a central pathogenic factor in DED
Hyperosmolarity is more prevalent than previously thought
 About 25% with moderately elevated levels
Many symptomatic patients do not actually have DED and thus don’t respond to therapy
Elevated osmolarity and tear film instability define DED:
 Low and stable osmolarity indicates the ABSENCE of DED
 Elevated osmolarity and/or an inter‐eye difference of >8 mOsm/L indicates tear film instability and early manifestation of DED
Osmolarity is the best single predictor of DED severity
Tear osmolarity is a leading indicator of response to therapy
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Billable test
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CLIA waiver needed
Billed/eye 83861
Nets appx $22/pt
FORM-MKT-243.1
MMP-9 in Tears
Matrix metalloproteinases (MMP) are proteolytic enzymes that are produced
by stressed epithelial cells on the ocular surface.1
MMP-9 is a non-specific inflammatory marker that plays a critical role in
wound healing. 1
Normal, healthy range is between 3-41 ng/ml
Dry eye (ocular surface disease) demonstrates elevated levels of MMP-9 in
tears1
MMP-9 is a more sensitive diagnostic marker than clinical signs and
correlates with clinical exam findings1
Increased MMP-9 in dry eye leads to visual morbidity2
Deranged corneal epithelial barrier function
Increased corneal desquamation
 Corneal surface irregularity
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[1] Chotiakavanich S, de Paiva CS, Li de Quan, et al. Invest Ophthalmol Vis Sci 2009; 50(7): 3203-3209. [2] Sambursky R, O’Brien TP. MMP-9 and the perioperative management of LASIK surgery. Curr Opin Ophthalmol. 2011
Jul;22(4):294-303.
MMP-9 Meta-analysis Overview
Normal levels of MMP-9 (ng/ml) in human controls range from 3-41 ng/ml
Importance of Detecting MMP-9
Identifying elevated levels of MMP-9 facilitates better
management of:
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Patients who present with signs or symptoms of dry eye
Patients having ocular surgery such as LASIK or cataract surgery
When elevated levels of MMP-9 are not identified,
confirmed, and treated prior to ocular surgery, the following
complications may occur:
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Less accurate pre-surgical measurements lead to worse visual acuity
outcomes1
Inflammatory
Mild dry eye becomes
severe dry Dry
eye2
Disease
Asymptomatic dry eyeEye
becomes
symptomatic, chronic dry eye2
Epithelial ingrowth or LASIK flap slippage3
[1] Trattler W, Goldberg D, Reilly C. Incidence of concomitant cataract and dry eye: prospective health assessment of cataract patients. Presented at: World Cornea Congress; April 8,2010;Boston,MA. [2] Ambrosio R. J Refract
Surg 2008; 24:396-407. [3] Fournie PR, Gordon GM, Dawson DG, et al. Arch Ophthalmol 2010; 128:426-436.
MMP-9 and Dry Eye Severity
Dry eye may have intermittent, episodic presentation where external forces
generate symptoms that completely resolve when stimulus is removed.1
2
[1] Acera A, Rocha G, Vecino E, et al. Inflammatory markers in the tears of patients with ocular surface disease. Ophthalmic Res. 2008 Oct; 40(6):315-21. [2] Chotikavanich S, de Paiva CS, Li de Q, et al. Production and activity of
matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome. Invest Ophthalmol Vis Sci. 2009 Jul; 50(7):3203-9. [3] Solomon A, Dursun D, Liu Z, et al. Pro- and anti-inflammatory forms of interleukin1 in the tear fluid and conjunctiva of patients with dry-eye disease. Invest Ophthalmol Vis Sci. 2001;42(10):2283-92. [4] Leonardi A, Brun P, Abatangelo G, et al. Tear levels and activity of matrix metalloproteinase (MMP)-1 and
MMP-9 in vernal keratoconjunctivitis. Invest Ophthalmol Vis Sci. 2003;44(7):3052-8. [5] Lema I, Sobrino T, Durán JA, et al. Subclinical keratoconus and inflammatory molecules from tears. Br J Ophthalmol. 2009;93(6):820-4. [6]
Honda N, Miyai T, Nejima R, et al. Effect of latanoprost on the expression of matrix metalloproteinases and tissue inhibitor of metalloproteinase 1 on the ocular surface. Arch Ophthalmol. 2010;128(4):466-71. [7] Markoulli M,
Papas E, Cole N, et al. The effect of contact lens wear on the diurnal profile of matrix metalloproteinase-9 and its inhibitor in the tear film. Poster presented at the 6th International Conference on the Tear Film and Ocular
Surface: Basic Science and Clinical Relevance. Florence, Italy. 24 Sept 2010.
[1] Iyer JV, Lee SY, Tong L. The dry eye disease activity log study. ScientificWorldJournal. 2012:589875. [2] Chotiakavanich S, de Paiva CS, Li de Quan, et al. Invest Ophthalmol Vis Sci 2009; 50(7): 3203-3209.
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4/28/2015
InflammaDry Product Overview
Identifies elevated levels of MMP-9 in tear fluid
CLIA-waived
Rapid: results as soon as 10 minutes
Easy to use: can be performed by a nurse or
technician
In-office: point-of-care immunoassay test aids
in diagnosis at the time of office visit
Low cost: no additional equipment required
InflammaDry Intended Use
The Only Way to Test for MMP9
4,5
3
[1] Schiffman RM, Walt JG, Jacobsen G, et al. Utility assessment among patients with dry eye disease. Ophthalmology 2003;110:1412-1419. [2] Shtein RM. Post-LASIK dry eye. Expert Rev Ophthalmol. 2011 Oct;6(5):575-582. [3]
Sambursky R, O’Brien TP. MMP-9 and the perioperative management of LASIK surgery. Curr Opin Ophthalmol. 2011 Jul;22(4):294-303.[4] Marsh P, Pflugfelder SC. Topical nonpreserved methylprednisolone therapy for
keratoconjunctivitis sicca in Sjögren syndrome. Ophthalmology. 1999 Apr;106(4):811-6. [5] Kaufman HE. The practical detection of MMP-9 diagnoses ocular surface disease and may help prevent its complications. Cornea. 2013
Feb;32(2):211-6.
InflammaDry Limit of Detection
InflammaDry is a rapid, immunoassay
test for the visual, qualitative in vitro
detection of elevated levels of the
MMP-9 protein in human tears from
patients suspected of having dry eye.
InflammaDry is to be used to aid in
the diagnosis of dry eye, in
conjunction with other methods of
clinical evaluation. This test is
intended for prescription use at pointof-care sites.
Normal levels of MMP-9 in
human tears ranges from 341 ng/ml
POSITIVE TEST
RESULT
MMP-9 ≥ 40 ng/ml
InflammaDry Packaging
InflammaDry 20 Pack Contents
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20 InflammaDry tests
•
•
•
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20 foil pouches containing a test cassette
20 foil pouches containing a sample collector
20 buffer vials
NEGATIVE TEST
RESULT
MMP-9 < 40 ng/ml
InflammaDry Test
Test includes
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1 foil pouch containing a sterile sample collector
1 foil pouch containing a test cassette
1 buffer vial
Shelf life = 24 months
Store InflammaDry between 77°F/25°C and 39°F/4°C
1 Package Insert
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4/28/2015
InflammaDry 4-Step Process
Using 4 simple steps, InflammaDry® test results can be achieved in
just 10 minutes, aiding in the diagnosis of dry eye before the patient
leaves the office.
Step 1: Collect the Tear Sample
Instruct the patient to look up (A) and gently lower the eyelid to expose
the palpebral conjunctiva (B).
Dab the sampling fleece in multiple locations along the conjunctiva
(C), releasing the lid after every 2-3 dabs to allow the patient to blink
(D).
After completing a minimum of 6-8 dabs along the conjunctiva, allow
the sampling fleece to rest along the conjunctiva for an additional 5
seconds to ensure saturation (E).
Inspect the sampling fleece; when a sufficient tear sample is collected,
the fleece will glisten (F). The fleece may be white or patchy pink in
color, depending on the patient’s tear composition. If the fleece is not
glistening, repeat the process.
*
Step 2: Assemble the Test
Gently place the sampling fleece of the sample collector
into the sample transfer window of the test cassette.
Press firmly where indicated.
A double-click means the test is properly assembled.
Step 4: Read the Results
Wait a minimum of 10 minutes
before reading test results.
The control line appears in the
control zone and must appear
for the test to be valid.
If the test is negative after 10
minutes, allow an additional 510 minutes before reading test
results.
Read any form of a red line,
whether faint, broken, or
shadow, as a positive test result.
Step 3: Run the Test
Immerse the absorbent tip into
the buffer vial for a minimum of
20 seconds, until a purple fluid
wave is observed moving across
the result window.
Remove the absorbent tip from
the buffer vial, replace the
protective cap, and lay the test
flat on a horizontal surface for 10
minutes.
Internal Procedural Controls
InflammaDry
has built-in
procedural
controls.
Check these
controls for
the first
sample tested
each day.
Two faint orange lines
appear on an unused test
When the test is activated
a purple fluid wave runs
through the window
The presence of a blue
control line indicates that
the test is valid.
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4/28/2015
Tips for Success
Tips for Success
InflammaDry should be performed PRIOR to instilling
ocular anesthetic, topical dyes, or performing Schirmer
testing.
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Reduce false negatives by:
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If drops are used, wait 2 hours before collecting a tear
sample.
InflammaDry should not be used within 20 minutes of
performing a Schirmer tear test.

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The opened test cassette should be used within 1 hour.
Wait the entire 10 minutes of development time before
reading test results.

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If the test is negative after 10 minutes, allow an additional 510 minutes before reading test results.
Reduce false positives by:

Read any form of a red line, whether light or broken, as a positive result.
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$15.74
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Aqueous Deficient Treatments
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Lotemax
Restasis
TG Omega 3s
Plugs-collagen, permanent, semi-perm,
upper/lower
Amniotic Membranes
Lacriserts
Autologous Serum
Not scraping the conjunctiva; gently dab
Our Dry Eye Center Of Excellence
Protocol For Osmo and ID testing
Reimbursement
CPT Code 83516 – “Immunoassay
for analyte other than infectious
agent antibody or infectious agent
antigen; qualitative or
semiquantitative, multiple step
method”
Dabbing in multiple locations along the
conjunctiva
Releasing the lid after every 2-3 dabs
Collect a sufficient tear sample (fleece
should glisten)
Pressing to double-click to allow specimen
transfer
Reconnecting the protective cap while the
test is developing
Waiting at least 2 hours after any topical
therapies are applied to the eye, as this may
dilute MMP-9
EVERY patient with previous dx of DED, MGD,
Ocular allergy, RCE or previous refractive or cataract
surgery
EVERY pre-op refractive/cataract sx patient
EVERY female CL wearer over 30yo
EVERY CL wearer over 40 yo
EVERY patient over 50
EVERY patient on ocular surface drying meds
EVERY patient with autoimmune/vascular disease
TEST AT EVERY VISIT
Lipid Deficient Treatments
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Clean up any ant bleph-tobradex st, lid scrubs
Lotemax
Restasis
TG Omega 3s
Doxy
Miboflo
Lipiflow
Plugs
Amniotic Membranes if cornea still compromised
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What is Human Amniotic
Membrane?
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A unique, avascular
membrane separating
the mother from the
fetus.
Provides an incubating
environment promoting
cellular differentiation.
Provides an
immunological barrier to
prevent “foreign body”
rejection.
The Amniotic Membrane
The amniotic membrane is the innermost lining of the placenta
(amnion)
Amniotic membrane shares the same cell origin as the fetus
•
•
•
Stem cell behavior
Structural similarity to all human tissue
•
Photo: Courtesy of Juan Batlle, M.D.
CONFIDENTIAL AND PRIVILEGED Property of Bio-Tissue, Inc.
Do not reproduce or distribute.
Anatomical Profile: AM
History of AM in
Ophthalmology
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Surgical Indications: AM
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Pterygium Excision
Corneal Ulcerations/Perforations
Chemical/Thermal Burns
Bullous Keratopathy
Ocular Dermoids/Tumors
Fornix Reconstruction/Symblepharon
Stem Cell Transplants
De Rotth. conjunctival defects (1940).
Lavery. lime burn of conjunctiva and cornea (1946).
Sorsby et al. caustic soda burns (1947).
ALLOTRANSPLANTAT [late 80’s USSR>Venezuela, DR]

Batlle and Perdomo. Conjunctival substitute with
placental allotransplant. Scientific Poster 25.
American Academy of Ophthalmology meeting.
Chicago, IL USA. October 1993.
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Kim and Tseng. Transplantation of preserved human
amniotic membrane for surface reconstruction in
severely damaged rabbit corneas. Cornea 14:47384, 1995. [
Surgical Indications: AM
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Pterygium Excision
Corneal Ulcerations/Perforations
Chemical/Thermal Burns
Bullous Keratopathy
Ocular Dermoids/Tumors
Fornix Reconstruction/Symblepharon
Stem Cell Transplants
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4/28/2015
AmbioDry2 Overview
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AmbioDry: Safe & Viable
Tested & Safe
Dehydrated
Terminally
Sterilized
Strict, qualitycontrolled
protocols
Device-like
quality
• Intact epithelial
cell layer
•Intact dense
connective,
basement
membrane
• Presence of loose
fibroblast network
AmbioDry: Logistical Features
• Storage: Roomtemp
• No freezer required
• No dry ice shipments
• Simple prep: No
soaks or rinses
• IOP Customer
Service: 24 Hrs/7
Days
Indications: AmbioDisk™


Sutureless, overlay
amniotic
membrane graft
for non-surgical
treatment of the
ocular surface




Neurotrophic Ulcers
Corneal Erosions
Keratisis (post infectious)
Chemical/Thermal Burns
Stevens Johnson Syndrome
Persistent Epi Defects
12
4/28/2015
Step 2: Placement of Lens
Step 1: Placement of AmbioDisk






Maintain dry ocular surface
Center graft on cornea
Gently smooth using
traction, counter traction
1-2 mm over peripheral conj
Disregard small creases
and bubbles
NOTE: Discuss orientation

18 or 16mm Kontur CL –
other sizes
 Non tooth forceps
 Center lens over AD2
 Maintain centration of AD2
disk over cornea
Step 3: Finish
AmbioDisk™: Management

Follow up: Variable
AD2 dissolves during
healing
 Absorption: 7-10 days
 Rx: OD discretion,
judgment


Gently remove speculum
 Request several blinks
 Disregard small bubbles,
creases
 Apply appropriate meds

< 10 minute procedure
Clinical Case: AmbioDisk™
Clinical Case: AmbioDisk™
Pre-op
10-min Post
•Large, superior persistent
•Placement of 15mm AD2
and 18mm Kontur CL
•Small bubbles @ 10 o’clock
•Small dog-ear @ 4 o’clock
•Light haze indicates presence
of AM
•Patient comfortable w. acuity
•Non-steroidal drops
epithelial defect
•Secondary to previous melanoma
excision and topical MMC
•Treatment w. bandage contact
lens yielded insignificant healing
Compliments of John Hovanesian, M.D.
Compliments of John Hovanesian, M.D.
13
4/28/2015
Clinical Case: AmbioDisk™
Clinical Case: AmbioDisk™
2-day Post
9-day Post
•AD2
•AD2 disk present on slit
lamp
•Fragmented globules of AD2
in place - at the interface
between the CL and the
cornea
•Defect appears healed.
Patient is comfortable,
functional
disk present on slit lamp
•Bubbles, creases resolved
•Patient is pain free, functional
Compliments of John Hovanesian, M.D.
Clinical Case: AmbioDisk™
30-day Post
•Spherical
particles of
retained amnion between
lens and corneal surface.
•Fluorescein stain and
cobalt blue filter shows
pooling but no staining.
•Epithelium has healed.
Compliments of John Hovanesian, M.D.
Ambio AM vs. Frozen AM
Feature
Ambio AM
Frozen AM
Thickeness (options)
Ambio2 and Ambio5
Single layer only
Surgical Handling
Easier/More pliant
No substrate
More difficult/Less pliant
With substrate
Storage
Room Temp
-80° freezer
Side orientation
Embossment/Watermark None
Sterilization
Yes. Device-like
No
Nominal Cost
$600
$800 + $80 freight
Compliments of John Hovanesian, M.D.
Reimbursement Codes
CPT Code: 65778: Ocular surface
reconstruction; amniotic membrane
transplantation
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4/28/2015
Passive vs. Active Therapies
Passive is a single-action therapy that may reduce inflammation but may delay healing
• Therapeutic Contact Lenses are a Passive Therapies
•
•
Provide mechanical protection
May induce infection
• Steroids/ NSAIDs are Passive Therapies
PROKERA®
•
•
Biologic Corneal Bandage
Reduce inflammation
Delay healing/ flare-up infection
Active is a dual action therapy that controls inflammation & promotes scarless healing
•
PROKERA® is an Active Therapy (Biologic Corneal Bandage)
•
•
•
•
Controls inflammation
Prevents additional damage
Promotes and accelerates wound healing
Prevents / reduces scar formation
Active vs. Passive: The Difference Is Clear
EM-014: Rev A 9-26-13
CONFIDENTIAL AND PRIVILEGED Property of Bio-Tissue, Inc.
Do not reproduce or distribute.
PROKERA®:
BIOLOGIC CORNEAL
BANDAGE



Product
Specifications
PROKERA® utilizes the proprietary
CryoTek™ cryopreservation process
that maintains the active extracellular
matrix of the amniotic membrane
which uniquely allows for regenerative
healing.
PROKERA® is the only FDA-cleared
therapeutic device that both reduces
inflammation and promotes scar less
healing
Outer Diameter:
21.6
21.6
21.6
Inner Diameter:
17.9
15.5
15.5
Device Height
0.7
1.1
1.1
Tissue Thickness
100
microns
100
Microns
200
microns
Ring Description
Ring & elastomeric
band system
(polycarbonate)
Dual ring system
(polycarbonate)
Dual ring system
(polycarbonate)
PROKERA® can be used for a wide
number of ocular surface diseases with
severity ranging from mild, moderate,
to severe
PROKERA® SLIM
PROKERA® Insertion
Incorporates New ComfortRING™
Technology for an optimal patient
experience
 Slim profile designed to contour to
the ocular surface
 Elegantly designed to move with
the eye
 Maximizes amniotic membrane
contact with the cornea, limbus,
and limbal stem cells
 Set patient expectations! Inform
the patient they may experience
some foreign body sensation
 Apply topical anesthesia
 Rinse the PROKERA® a with a
sterile solution (saline, BSS etc…)
 Hold the upper eyelid
 Ask the patient to look down
 Insert the PROKERA® into the
superior fornix
 Slide the PROKERA® under the
lower eyelid
“The Sooner the Better”
CONFIDENTIAL AND PRIVILEGED
Property of Bio-Tissue, Inc. Do not
reproduce or distribute.
15
4/28/2015
Post-Treatment Protocol
Continue
medications
Tegaderm/Tapesorrhaphy
Apply Temporary
Tarsorrhaphy (PRN)
- Tape
- Tegaderm
- “Breathe-Right”
nasal strips
CONFIDENTIAL AND PRIVILEGED Property of Bio-Tissue, Inc.
Do not reproduce or distribute.
Lower Lid Tightening for Entropion
CONFIDENTIAL AND PRIVILEGED Property of Bio-Tissue, Inc.
Do not reproduce or distribute.
How do I know when to remove
PROKERA®?
• Determining when to remove PROKERA® is patient and
case dependent
• Follow your usual protocol for follow ups
• Fluorescein staining can be used while PROKERA®
remains on the eye to determine healing progression
• Expect to see the amniotic membrane in PROKERA® to
Lower Lid Tightening for Ectropion
thin when
• Significant inflammation is present
• There has been over exposure to air
CONFIDENTIAL AND PRIVILEGED Property of Bio-Tissue, Inc.
Do not reproduce or distribute.
*
PROKERA® Removal
 Topical Anesthetic
 Pull the lower eyelid
 Lift the lower edge of
PROKERA® using a Q-tip or
forceps
Case Study Review
 Ask the patient to look down
 Slide the PROKERA® out with
gentle pressure on the upper
eyelid
CONFIDENTIAL AND PRIVILEGED
Property of Bio-Tissue, Inc. Do not
reproduce or distribute.
16
4/28/2015
Case Study 1:
Recurrent Corneal Erosion
52 year-old female presented with ocular pain and blurred vision (20/200) for
2 weeks. She had a history of similar attacks & diagnosed as RCE. Epithelial
debridement, lubricants, and BCL failed to relieve pain and halt recurrence.
Treatment Strategy
 Epithelial debridement to remove
loose epithelium (Fig. A, B) followed
by placement of PROKERA® SLIM
 On the 2nd day, the patient had no
pain. Complete healing occurred
within 3 days, resulting in clear
cornea, 20/20 vision. A smooth
surface remained stable with no
recurrence for 13 months follow-up
(Fig. C, D)
PROKERA® Summary

Active Amniotic membrane modulates healing towards regeneration,
away from inflammation /scarring

CRYOTEK™ maintains tissue structure and healing biological properties

PROKERA® when used early reduces inflammation and minimizes
scarring to prevent sight threatening complications

PROKERA® is the only FDA-cleared therapeutic devices that
simultaneously reduce inflammation and promoting “regenerative/scarless
healing”

PROKERA® is a self retaining biologic corneal bandage that can be easily
inserted in your office

Use CPT Code 65778 for in-office reimbursement of PROKERA®
PROKERA® should be considered after lubricants have failed.
LipiFlow® Thermal Pulsation
System
LipiFlow
LipiFlow safely and effectively treats Meibomian
gland obstruction in both upper and lower eyelids
simultaneously
• In-office procedure
• 12 minutes per eye
100
100
MiBoFLo






New technology
The newest best treatment for MGD
No disposables
Cost effective for practice and patient
Easy for staff to perform
Great ROI
17
4/28/2015
Treatment Protocol







3 treatments
First treatment 10 min/lid
Second treatment one week later 18 min/lid
Third treatment 2 weeks later 8 min/lid
$450 out of pocket for all 3 treatments
Can treat q2 months to PRN
Direct treatment to hordeolum 12 min-$75
Study Data







51 patients
4 months post final treatment
Schirmer +4.2
TBUT +9.2
Osmo +15
OSDI +15
SPEED Score +12
www.painpointmedical.com
$24,900
18
4/28/2015
Clinical Case
My Mother-In-Law
8 year history of MGD




Progressive corneal changes
Cataracts and cornea has decreased vision
leading negative effect on life style
BCVA OD 20/70 OS 20/60
Will not do cataract surgery until cornea healthy
Past Treatments Tried






Doxy-severe GI upset and IBS
Azasite-allergic rxn after long term use
Lotemax qtts
Lotemax ung
Various tears
HC/massage/moisture goggles
19
4/28/2015
Present Treatments







Wrap Up Pearls!
PF bid
Restasis bid
Alternating optive adv/blink tears hourly
2 tbsp liquid omega daily (5g)
Lipiflow 12 months ago
2 rounds of MiBo
Last VA OD 20/30-2 OS 20/25-2
Test Aggressively-Protocol










History
Osmo-EVERY VISIT
Inflammadry-EVERY VISIT
Lissamine and Fluorescein
TBUT
Schirmer
Lid expression
Ant seg photography
Topography
Work ups yield $240
Pre Treat Cataract, Refractive
Cataract and LASIK patients

Ophthalmology Management-September 2013”Tear film can be the most important part of the
eye, and instability diminishes performance of a
multifocal lens. In fact, reports have shown that
patients without dry eyes placed on cyclosporine
two weeks pre op and three months post op had
better vision and more ocular comfort”
according to two studies by Dr. Donnenfeld
presented and ASCRS and ARVO
Treat Aggressively
If You Don’t….Someone Else Will!!
When Using Omega 3s
Use A TG Form
PRN has a great business model!
20
4/28/2015
Hang In There!!!!
So you diagnose MGDnow what??
MiBoThermoFLo
Discuss with every MGD patient
Thank You!
[email protected]
21