This document discusses new technologies for managing ocular surface inflammation. It begins by defining ocular surface disease and noting its prevalence. Various causes of ocular surface disease are described, including infectious, immune-related, traumatic/systemic, and iatrogenic factors. Current treatment paradigms focus on passive therapies to reduce inflammation like bandage contact lenses and topical steroids, but these can delay healing. Emerging options aim to control inflammation, prevent tissue damage, and stimulate regenerative healing using amniotic membrane biologics which promote healing and reduce inflammation. Cryopreserved amniotic membrane is presented as a safe and effective option to treat various ocular surface conditions.

1. New Technologies
for Successfully Managing
Ocular Surface Inflammation
Sponsored by:
Property of Bio-Tissue™, Inc.
Do not reproduce or distribute

2.  May be defined as “Any disorder affecting the integrated
functional structures of the ocular surface… ”1
 Accounts for approximately 20% of visits to eye care
practitioners annually2,3
 Etiology/Diagnosis can be difficult due to the similarities
of various disease entities – inflammation being the
hallmark sign
Ocular Surface Disease
1. Pensyl CD. Preparations for dry eye and ocular surface disease. In: Bartlett JD, Jaanus SD, eds. Clinical ocular pharmacology, 5th ed., St. Louis: Elsevier, 2008:263-78.
2. American Optometric Association. Care of the patient with ocular surface disorders. St. Louis (MO): American Optometric Association; 2002 Nov. 59 p.
3. Lemp MA, Marquardt R. Introduction. In: Lemp MA, Marquardt R, eds. The dry eye. A comprehensive guide. Berlin: SpringerVerlag, 1992:1-2.
4. http://www.ncbi.nlm.nih.gov/pubmed/14669026

3. Ocular Surface Disease
Infectious
• Bacterial
• Viral - HSV/HZO/EKC
• Fungal/Amoebic/Parasitic
Immune
• Severe aqueous deficiency
• Filamentary keratitis
• Neurotrophic keratitis
• Chronic allergic (vernal)
keratoconjunctivitis
• Limbal stem cell deficiency
Traumatic/Systemic
• Corneal abrasion PED
• Exposure – TED, injury, palsy
• Recurrent corneal erosion
• Chemical burn
Iatrogenic
• Stevens-Johnson syndrome
• Post cataract / DSEK / B’plasty
• Cl induced LSC deficiency

4. Treat Underlying
Pathology
Address
Inflammation
Await Healing
Current Treatment Paradigm
Passive Therapies to Reduce Inflammation:
• Bandage Contact Lens
o Pro: Mechanical barrier to external irritants, helps with pain
o Con: Potential to induce infection
• Topical Medications—Steroids/NSAIDs
o Pro: Reduce inflammation, helps with pain
o Con: Delay healing and increase potential for infection

5. Emerging Treatment Paradigm
Treat Underlying
Pathology
CONTROL
INFLAMMATION
Prevent Progressive
Tissue Damage
Stimulate
REGENERATIVE
HEALING
Key to minimizing a sight-threatening
scar is limiting inflammatory response
and promoting healing

6. • Amniotic membrane is the innermost lining of the
placenta and shares the same cell origin as the fetus
• Amniotic membrane biologic therapy:
o Promotes regenerative healing
o Reduces inflammation
o Minimizes scar formation
o Inhibits angiogenesis
o Minimizes pain
Amniotic Membrane:
An Emerging Clinical Option

7. Extracellular matrix (ECM) components promote regenerative tissue
processes1,2,3
Key components
• Heavy chain hyaluronic acid
• Proteoglycans
• Growth factors
• Collagens (types I, III, IV, V and VI)
• Fibronectin
• Laminin, MMP inhibitors
Key Amniotic Membrane
Components
1. Rinastiti M, et al. Int J Oral Maxillofac Surg. 2006;35:247-251. 2. Jin CZ, et al. Tissue Eng. 2007;13:693-702. 3. Niknejad H, et al.
Eur Cell Mater. 2008;15:88-99. 4. He H, et al. J Biol Chem. 2009;284:20136-20146. 5. Data on file, Bio-Tissue, Inc., 2012. 6.
Hopkinson A, et al. Invest Ophthalmol Vis Sci. 2006;47:4316-4322.
Direct inhibition of pro-inflammatory cells 4,5
• Suppresses T-cell activation
• Dose-dependently inhibits giant cell
formation
Biological scaffolding
Regenerative healing 6

8. • Bio-Tissue™ Cryopreservation method ensures retention of key active
components of the Extracellular Matrix to promote healing and integrity
of tissue structure
• Cryopreserved Amniotic Membrane is safe and effective
o Extensive number of peer reviewed articles / publications
o Bio-Tissue™ Cryopreserved Amniotic Membrane is the only Amniotic
Membrane granted wound healing indication by the FDA
• Available as Amniograft (typically thick, multilayered, sutured or glued)
and Prokera (self retaining)
Why Cryopreservation vs dry?
1. Rinastiti M, et al. Int J Oral Maxillofac Surg. 2006;35:247-251.
2. Jin CZ, et al. Tissue Eng. 2007;13:693-702.
3. Niknejad H, et al. Eur Cell Mater. 2008;15:88-99.

9. Product
Specifications
Outer Ring
Diameter:
21.6 mm 21.6 mm 21.6 mm
Inner Ring
Diameter:
17.9 mm 15.5 mm 15.5 mm
Device Height 0.7 mm 1.1 mm 1.1 mm
Tissue
Thickness
Single Layer Single Layer Multiple Layers
Ring
Description
Ring & Elastomeric
Band System
(polycarbonate)
Dual Ring System
(polycarbonate)
Dual Ring System
(polycarbonate)

10. • Band keratopathy
• Post PRK/PTK haze
• Chemical burns
• Corneal epithelial defects- RCE, EBMD
• Corneal ulcers, acute and non-healing
• Superficial keratectomy/debridement for Saltzmann’s,
bullous keratopathy post DSEK
• Keratitis - k. sicca, infectious, exposure, filamentary,
LCSD, neurotrophic PED (DM, aging, post HSV, post sx)
• Pterygium sx, conjunctival tumor resection
• Stevens-Johnson Syndrome
CONFIDENTIAL AND PRIVILEGED Property of Bio-Tissue, Inc..
Do not reproduce or distribute.
Indications Overview

11. 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
• Complete healing within 3 days,
resulting in clear cornea and 20/20
vision. A smooth surface remained
stable with no recurrence for 13
months follow-up
Recurrent Corneal Erosion

12. 61 year-old female with long history of severe dry eye and exposure
keratopathy (OD>OS) due to incomplete blinking and lagophthalmos
(blepharoplasty). No response to (Restasis®), copious NPATs and punctal plugs.
Treatment Strategy
• PROKERA®
SLIM was
inserted OD for one week
• After removal of
PROKERA®
SLIM
o Patient comfortable
o The eye was quiet, with a
crystal clear cornea
Dry Eye with Exposure

13. PROKERA Treatment Tips
• Insert only after rinsing well with
saline or CL solution and
installation of topical anesthetic
• PROKERA SLIM most common
• Topical medications may be
used while in place
• Temporary Tarsorrhaphy (PRN)
o TransporeTape
o Nasal Strips
• Follow-up within 3-7 days (10
day global period)
• During the healing process the
membrane will thin or dissolve
– time dependent based on
inflammation
• Easily removed in the office
once the healing is completed
use topical anesthetic and
blunt forceps

14. • Not for severe LSC loss
• May need repeated applications
• Not indicated for major structural damage,
tissue loss or deep stromal defects.
Amniograft or dry AM (Ambiodry) surgical
placement more effective for perforations and
deep wounds
PROKERA limitations

15. • Code 65778, most insurers include materials
and pay $1250-1600
• Prokera cost $800-900 net $400-800
• Include materials code v2790 (with invoice)
and may also get paid from commercial
carriers for materials net $1200-1600
• Can bill multiple times as clinically indicated
CONFIDENTIAL AND PRIVILEGED Property of Bio-Tissue, Inc..
Do not reproduce or distribute.
Billing

16. • Same day billing with other procedures: Bill as
primary procedure, use -59 modifier for
others and see lower reimbursements
• Next day or subsequent billing , staged
procedures, within global period – 58 mod
• If unrelated to a prior procedure (DSEK, PTK,
cataract) but within global period, -79 mod
• Can be repeated as needed – 10 day global
CONFIDENTIAL AND PRIVILEGED Property of Bio-Tissue, Inc..
Do not reproduce or distribute.
Billing

17. Managing Demodex Blepharitis
and Keratoconjunctivitis

18. Demodex Mites1,2
An Often Overlooked Link to Blepharitis
• Demodex blepharitis is the
most common but often
overlooked external disease
problem, causing ocular
surface inflammation
• Ocular Demodex infestation
has been difficult to
eradicate
• Demodex can exacerbate
many other conditions such
as dry eye, MGD, pterygium
and rosacea
1. Rufli et al (1981) dermatologica; 162: 1-11
2. Liu et al (2010) Curr Opin Allergy Clin Immunol; 10:505-10
Demodex BrevisDemodex Folliculorum

19. OD (Normal Eye) OS (Demodicosis)(Same Patient)
Structural damage due to mites digesting and
destroying the Meibomian glands.
Meibography: MGD Linked to Demodex

20. 1. Coston, 1967, English, 1971, English & Nutting, 1981, Heacock,1986, Fulk & Clifford, 1990,
2. Fulk et al, 1996, Kamoun et al. 1999, Morfin, 2003
Skin Manifestation
Demodex has been linked to rosacea, pityriasis folliculorum,
perioral dermatitis, pustular folliculitis, and basal cell carcinoma.1,2

21. 1. Coston 1967; Gao et al, IOVS 46:3089, 2005
Diffuse CD Sporadic CD
CleanGreasy Scales
• Cylindrical dandruff (CD) is
diagnostic for Demodex, but its
absence does not denote a
negative diagnosis1
• Eyelash manifestation
• Trichiasis, malalignment,
madarosis
• Lash epilation may be necessary to
confirm dx
• Supplies
• Forceps
• Microscope
Diagnosing Demodex

22. Approach Targets
Warm compresses Oil glands
Baby shampoo lid scrubs Lid margin, lashes
Commercial lid scrubs Lid margin, lashes
Topical antibiotic Microbes
Omega-3 fatty acids Inflammation, oil glands
Oral Tetracycline/Doxycycline Inflammation, oil glands
Past Approaches to Blepharitis and
Lid Margin Diseases

23. Studies Report that TTO Lid Scrub Helps Manage
Cylindrical Dandruff and Conj. Inflammation1
Before
After
1. Kheirkhah et al, AJO, 143:743, 2007

24. Authors: Sean Tighe, Ying-Ying Gao, Scheffer C. G. Tseng
Published in: Translational Vision Science & Technology Journal, 2013
Purpose: To determine the active ingredient in tea tree oil (TTO) responsible
for its reported killing effect on Demodex mites
Method: Using an in vitro killing assay screened concentrations of 13 out of
the 15 known ingredients of TTO
Results: 4-Terpineol…
1. Was the most potent ingredient to exhibit killing effects
2. Was more potent than TTO at equivalent concentrations
3. Was effective in killing mites at a concentration of 1%
4-Terpinenol is the Most Active Ingredient of
Tea Tree Oil (TTO) to Kill Demodex Mites
1. Tighe Sean, et al, Terpinen-4-ol is the Most Active Ingredient of Tea Tree Oil to Kill Demodex Mites, Translational Vision Science and
Technology, August 2013, Vol. 2, No. 7

25. • Allergic reactions were observed when TTO was used as
a topical formulation1
• Oxidation products formed during prolonged storage of
TTO generate ρ-cymene (an ineffective ingredient), as
well as peroxides and epoxides1
• Some of these TTO ingredients relationships are
clinically antagonistic
Why is 4-Terpineol Isolation Important
1. Carson, C.F., et al, Melaleuca alternifolia (Tea Tree) Oil: a Review of Antimicrobial and Other Medicinal Properties, Clinical Microbiology Reviews, Jan. 2006, p50-62 Vol. 19,
No.1
2. Tighe Sean, et al, Terpinen-4-ol is the Most Active Ingredient of Tea Tree Oil to Kill Demodex Mites, Translational Vision Science and Technology, August 2013, Vol. 2, No. 7

26. Beyond Tea Tree Oil…
• Cliradex™ contains 4-Terpineol
without preservatives for allergy and
toxin-free treatment
• Indicated for lids, lashes and face
• Useful for Demodex and rosacea
associated blepharitis and
keratoconjunctivitis, MGD and peri-
ocular dermatitis
1. Tighe Sean, et al, Terpinen-4-ol is the Most Active Ingredient of Tea Tree Oil to Kill Demodex Mites, Translational Vision Science and Technology, August 2013, Vol. 2,
No. 7

27. • Male,17
• Cylindrical dandruff, redness,
irritation in OS for 6 months
• Didn’t respond well to antibiotics
and steroids
• Signs & symptoms subsided
dramatically after 10 days of
Cliradex™ use. No recurrence
during 3 months follow up
Case Study
OS Before OS After

28. Before & After Cliradex™ Use
Before Before
After 6 weeks

29. • Rx towelette use qd to bid for 4-6 wks,
• 2 cartons typically rx’d
• Place lightly over closed eyelid and rub
side to side for 10-15 seconds, then
wait one minute before opening
• Repeat for fellow eye
• Can use separate wipe for facial
rosacea
• Follow-up in 4-6 wks
• Rarely needs re-treatment, but may rx a
maintenance program as needed
Components:
• Water
• 4-Terpineol
• Glycerin
• Polysorbate 20
• Polysorbate 80
• Carbomer
• Triethanolamine
Patient instructions

30. Thank you!
drthib@msn.com
Sponsored by: