3/17/2017 1 Ocular Surface Disease: The Medical Business of Dry Eye: A Comprehensive Course on OSD Evaluation, Diagnosis, and Treatmetn Strategies Jack Schaeffer OD FAAO Doug Devries OD FAAO Milton Hom OD FAAO Dr Jack L. Schaeffer financial disclosure form Alcon Allergan AMO / Abbott Bausch and Lomb Ciba Vision Cooper Vision Essilor Hoya Inspire Optos Optovue Zeis Vision Disclosures Last 12 months: Dr Milton Hom Allergan Bausch/Valeant Shire Sun Disclosures Douglas K. Devries Consultant or Speakers Bureau for Allergan AMO TearLab NicOx BVI B&L DEWS Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Dry eye is not just a disease, it’s a complex, multi- factorial disorder. Dry Eye Evaluation Vision care Exam CONVERSION Medical Exam
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3/17/2017
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Ocular Surface Disease: The Medical Business of Dry Eye: A Comprehensive Course on OSD Evaluation, Diagnosis, and Treatmetn Strategies
Jack Schaeffer OD FAAO
Doug Devries OD FAAO
Milton Hom OD FAAO
Dr Jack L. Schaeffer
financial disclosure form
Alcon
Allergan AMO / Abbott
Bausch and Lomb Ciba Vision
Cooper Vision Essilor Hoya
Inspire Optos
Optovue Zeis Vision
Disclosures
Last 12 months: Dr Milton Hom
Allergan
Bausch/Valeant
Shire
Sun
Disclosures
Douglas K. Devries
Consultant or Speakers Bureau for
Allergan
AMO
TearLab
NicOx
BVI
B&L
DEWS
Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.
Dry eye is not just a
disease,
it’s a complex, multi-
factorial disorder.
Dry Eye Evaluation
Vision care Exam
CONVERSION
Medical Exam
3/17/2017
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DIAGNOSTIC TESTS
TEAR EVALUATION
Tear Meniscus
TFBUT
Osmolarity
Evidence of Fluorescein Staining
Tear Consistency-i.e. thickness, debris, evidence of meibomian gland oil and sebaceous secretions
Shirmers
DIAGNOSTIC TESTS
Schirmer--w/ or w/o anesthetic
Phenol Red Thread Test
Zone Quick-represents fluid present in the conjunctival sac
Fluorescein Staining
Rose Bengal Staining
Lissamine Green Staining
Tear Osmolarity
Collagen Plugs
Schaeffer Shirmer
Always do this as the last test
Place strip in any part of the eye
Count to three
remove
Tear Osmolarity
Osmolarity Provides
Improved Standard of Care Tear osmolarity is the most accurate diagnostic test for dry
eye disease
Elevated osmolarity is the central mechanism causing
ocular surface damage
Allows a physician to rapidly diagnose & classify patients with
a global assessment
In combination with a slit lamp exam, physicians can select
therapies based on mechanism of disease and severity
Modulate therapy using a quantitative endpoint
Tomlinson A, IOVS 2006. DEWS Ocular Surf 2007
Dry Eye Disease and MMP-9
Matrix metalloproteinases (MMP) are proteolytic enzymes that are produced by stressed epithelial cells on the ocular surface1
MMP-9 in Tears Non-specific inflammatory marker Normal range between 3-41 ng/ml More sensitive diagnostic marker than clinical
Aizawa, A., Ito, A., Masui, Y., & Ito, M. (2014). Case of allergic contact dermatitis due to 1, 3‐butylene glycol. The Journal of dermatology, 41(9), 815-816.
SUGIURA, Mariko, et al. "Results of patch testing with 1, 3-butylene glycol from 1994 to 1999." Environmental
dermatology: the official journal of the Japanese Society for Contact Dermatitis 8.1 (2001): 1-5.
IKEZAWA, Yuko, et al. "Two cases of contact dermatitis due to 1, 3-butylene glycol." Journal of environmental
dermatology: the official journal of the Japanese Society for Contact Dermatitis 11.3 (2002): 59-64.
Oiso, Naoki, Kazuyoshi Fukai, and Masamitsu Ishii. "Allergic contact dermatitis due to 1, 3‐butylene glycol in
YASHIRO, Kyoko, and Masayoshi NISHIMOTO. "A case of contact dermatitis due to 1, 3-butylene glycol and trisodium hydroxyethyl ethylenediamine triacetate." Environmental dermatology: the official journal of the Japanese Society for
Contact Dermatitis 10.1 (2003): 14-20.
Matsunaga, K., et al. "Allergic contact dermatitis from 1, 3-butylene glycol." Allergy Pract 14 (1994): 492-495.
Blackie, Caroline A., and Donald R. Korb. "MGD: getting to the root cause of dry eye: Review of Optometry
149.6 (2012): 30-37. Nelson JD, Shimazaki J, Benitez-del-Castillo JM, et al. The international workshop on meibomian gland
dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7.
“MGD is currently thought to
be the leading cause of dry
eye.” Caroline Blackie
Donald Korb
Blackie, Caroline A., and Donald R. Korb. "MGD: getting to the root cause of dry eye: Review of Optometry
149.6 (2012): 30-37. Nelson JD, Shimazaki J, Benitez-del-Castillo JM, et al. The international workshop on meibomian gland
dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7.
“MGD is currently thought to
be the leading cause of dry
eye.” Caroline Blackie
Donald Korb
Lemp, Michael A., et al. "Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient
cohort: a retrospective study." Cornea 31.5 (2012): 472-478.
299 normal
DED patients (M:81 F:218)
10 sites European Union & US
Lemp, Michael A., et al. "Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient
cohort: a retrospective study." Cornea 31.5 (2012): 472-478.
“Overall, 86% of these qualified
DED patients demonstrated
signs of MGD.” Michael Lemp
What triggers you to perform a
dry eye evaluation?
A. Symptoms
B. Signs
C. Both
Schachter A. Schachter S. Hom MM. Asymptomatic Meibomian Gland
Dysfunction Invest Ophthalmol Vis Sci 2016;57:ARVO E-Abstract:5672.
DOI: 10.13140/RG.2.1.2032.2161
“Of patients with meibomian
gland atrophy…60%…were
asymptomatic”
Schachter S. Schachter A. O’Dell LE. Hom MM. A Dry Eye Survey of
Practicing Optometrists. Optom Vis Sci 2016 American Academy of
Optometry, Anaheim, CA, DOI: 10.13140/RG.2.2.22026.26565
“Only 30% of respondents
routinely test for MGD in
their comprehensive
examinations”
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Obstruction vs inflammation Two camps: Obstruction
Inflammatory
Obstruction
Blackie, Caroline A., and Donald R. Korb. "MGD: getting to the root cause of dry eye: Review of Optometry
149.6 (2012): 30-37. Nelson JD, Shimazaki J, Benitez-del-Castillo JM, et al. The international workshop on meibomian gland
dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7.
“Obstructive MGD is the
most common form of MGD
resulting in dry eye.” Caroline Blackie
Donald Korb
Knop, Erich, et al. "The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland." Investigative ophthalmology & visual
science 52.4 (2011): 1938.
“hyperkeratinization is one
of the primary
components…of obstructive
MGD.”
Hyperkeratinization…disord
er of the cells lining the
inside of a hair follicle.”
Knop, Erich, et al. "The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland." Investigative ophthalmology & visual
science 52.4 (2011): 1938.
“normal function of these cells [is] to..slough off (desquamate)…this process is interrupted…dead skin cells do not leave the follicle…[due to] excess of keratin”
Knop, Erich, et al. "The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland." Investigative ophthalmology & visual
science 52.4 (2011): 1938.
“cohesion of cells
will block or
“cap”…or clog
the sebaceous/oil
duct.”
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Knop, Erich, et al. "The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland." Investigative ophthalmology & visual
science 52.4 (2011): 1938.
“changes in the composition of
meibum…increase its viscosity or…can
reinforce keratinization.”
Inflammation
Obata H, et al. IOVS 2002;43:ARVO E-Abstract 60.
Knop, Erich, et al. "The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland." Investigative ophthalmology & visual
science 52.4 (2011): 1938.
“The definition and involvement
of inflammation in MGD have
been unclear in the past for
several reasons.”
Obata H, et al. IOVS 2002;43:ARVO E-Abstract 60.
Knop, Erich, et al. "The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland." Investigative ophthalmology & visual
science 52.4 (2011): 1938.
“Inflammatory leukocytes
are not apparent [in
atrophied glands]”
Obata H, et al. IOVS 2002;43:ARVO E-Abstract 60.
Knop, Erich, et al. "The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland." Investigative ophthalmology & visual
science 52.4 (2011): 1938.
“inflammation…does not
represent a major etiologic
factor in obstructive MGD”
Knop, Erich, et al. "The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland." Investigative ophthalmology & visual
science 52.4 (2011): 1938.
“inflammatory events [promoted] inside
the gland, in the periglandular
conjunctiva, on the lid margin, and on the ocular surface”
The 65 Most-Frequently Read Articles in Invest. Ophthalmol. Vis. Sci. during October 2010 thru September 2011 -- updated monthly
Most-read rankings are recalculated at the beginning of the month and are based on full-text and pdf views.
1. Kelly K. Nichols, Gary N. Foulks, Anthony J. Bron, Ben J. Glasgow, Murat Dogru, Kazuo Tsubota, Michael A. Lemp, David A. Sullivan
The International Workshop on Meibomian Gland Dysfunction: Executive Summary
Invest Ophthalmol Vis Sci Mar 30, 2011; 52: 1922-1929. (In "Special Issue") [Full Text] [PDF]
(Read 5554 times)
2. Kelly K. Nichols
The International Workshop on Meibomian Gland Dysfunction: Introduction
Invest Ophthalmol Vis Sci Mar 30, 2011; 52: 1917-1921. (In "Special Issue") [Full Text] [PDF]
(Read 5318 times)
3. Erich Knop, Nadja Knop, Thomas Millar, Hiroto Obata, David A. Sullivan
The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Anatomy, Physiology, and Pathophysiology of the Meibomian Gland
Invest Ophthalmol Vis Sci Mar 30, 2011; 52: 1938-1978. (In "Special Issue") [Full Text] [PDF]
(Read 4663 times)
4. Alan Tomlinson, Anthony J. Bron, Donald R. Korb, Shiro Amano, Jerry R. Paugh, E. Ian Pearce, Richard Yee, Norihiko Yokoi, Reiko Arita,
Murat Dogru
The International Workshop on Meibomian Gland Dysfunction: Report of the Diagnosis Subcommittee
Invest Ophthalmol Vis Sci Mar 30, 2011; 52: 2006-2049. (In "Special Issue") [Full Text] [PDF]
(Read 4074 times)
5. Gerd Geerling, Joseph Tauber, Christophe Baudouin, Eiki Goto, Yukihiro Matsumoto, Terrence O''Brien, Maurizio Rolando, Kazuo Tsubota, Kelly K. Nichols
The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Management and Treatment of Meibomian Gland Dysfunction
Invest Ophthalmol Vis Sci Mar 30, 2011; 52: 2050-2064. (In "Special Issue") [Full Text] [PDF]
(Read 4027 times)
6. J. Daniel Nelson, Jun Shimazaki, Jose M. Benitez-del-Castillo, Jennifer P. Craig, James P. McCulley, Seika Den, Gary N. Foulks
The International Workshop on Meibomian Gland Dysfunction: Report of the Definition and Classification Subcommittee
Invest Ophthalmol Vis Sci Mar 30, 2011; 52: 1930-1937. (In "Special Issue") [Full Text] [PDF]
(Read 3221 times)
7. Penny A. Asbell, Fiona J. Stapleton, Kerstin Wickström, Esen K. Akpek, Pasquale Aragona, Reza Dana, Michael A. Lemp, Kelly K. Nichols
The International Workshop on Meibomian Gland Dysfunction: Report of the Clinical Trials Subcommittee
Invest Ophthalmol Vis Sci Mar 30, 2011; 52: 2065-2085. (In "Special Issue") [Full Text] [PDF]
(Read 2580 times)
8. Kari B. Green-Church, Igor Butovich, Mark Willcox, Douglas Borchman, Friedrich Paulsen, Stefano Barabino, Ben J. Glasgow
The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Tear Film Lipids and Lipid–Protein Interactions in Health and Disease
Invest Ophthalmol Vis Sci Mar 30, 2011; 52: 1979-1993.
(In "Special Issue") [Full Text] [PDF]
(Read 2546 times)
9. Debra A. Schaumberg, Jason J. Nichols, Eric B. Papas, Louis Tong, Miki Uchino, Kelly K. Nichols
The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on the Epidemiology of, and
Associated Risk Factors for, MGD
Invest Ophthalmol Vis Sci Mar 30, 2011; 52: 1994-2005. (In "Special Issue") [Full Text] [PDF]
Modified and colored from Krstic H. Human microscopic anatomy. Springer Medizin Verlag 1991, (reproduced from Knop N & Knop E Ophthalmologe 2009; 106:872–883)
• 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
Meibomian Gland - ANATOMY
Modified from Sobotta Atlas der Anatomie des Menschen. Urban & Schwarzenberg Verlag 1982, (reproduced from Knop N & Knop E. Ophthalmologe 2009; 106:872–883)
Alan Tomlinson, MCOpt, Ph.D. (Chair) E. Ian Pearce, Ph.D. Anthony J. Bron, F.R.C.S. Richard Yee, M.D. Donald R. Korb, O.D. Norihiko Yokoi, M.D., Ph.D. Shiro Amano, M.D., Ph.D. Reiko Arita, M.D., Ph.D. Jerry R. Paugh, O.D. Murat Dogru, M.D.
1. Foulks GN1, Nichols KK, Bron AJ, Holland EJ, et al. Improving awareness, ident ificat ion, and management of meibomian gland dy sfunct ion. Ophthalmology. 2012 Oct ;119(10 S uppl):S1-12.
2. M urakami DK, Blackie CA and Korb DR. The Prevalence of M eibomian Gland Dysfunct ion in a Caucasian Clinical Populat ion. ARV O abstract 2015
3. Blackie et al. Nonobvious M GD. Cornea. 2010 Dec;29(12):1333-45.
4. M udgil P. Ant imicrobial role of human meibomian lipids at the ocular surface. Invest Ophthalmol V is S ci. 2014 Oct 14;55(11):7272-7.
5. Napoli PE, Coronella F, S at ta GM, et al. Evaluat ion of the adhesive propert ies of the cornea by means of opt ical coherence t omography in pat ients with meibomian gland dysfunct ion and lacrimal tear deficiency., PLoS One. 2014 Dec 23;9(12):e115762.
6. Jackson et al. Evaluat ion of Thermal Pulsat ion Treatment for M eibomian Gland Dysfunct ion in Cataract S urgery Pat ients AS CRS 2015
7. S uhalim JL, Parfit t GJ, X ie Y, et al. Effect of desiccat ing st ress on mouse meibomian gland funct ion. Ocul S urf. 2014 Jan;12(1):59-68.
8. Holland et al. Pat ient Characterist ics Associated with Improved M eibomian Gland Funct ion after Thermal Pulsat ion Treatment for M eibomian Gland Dysfunct ion. AS CRS 2015
9. Grenon, Liddle and Grenon et al. A Novel M eibographer with Dual M ode S tandard Noncontact S urface Infrared Illuminat ion and Infrared Transilluminat ion. ARV O 2014
The prevalence of MGD is as high as 60-70%1,2
MGD is frequently nonobvious and therefore missed3
Meibomian lipids are critical for innate tear film host defense4
MGD decreases corneal adhesiveness5
Pretreatment optimizes post-cataract surgery ocular comfort6
Evaporative stress causes MGD7 (Modern lifestyle, Contact lens wear and
Chronic use of topical medications all induce evaporative stress)
MGD is progressive: Early intervention optimizes outcomes8
Identify early compromise to MG function and structure with the MGE
and DMI9
An Unstable Tear Film Negatively Impacts Premium
Quality Vision Care
Fluctuating Vision
Ocular Discomfort
Compromised Barrier to Infection1
63%+ of Cataract Patients (PHACO study results)
Contact Lens Intolerance and LASIK
Candidates
Glaucoma and Retinal Patients
108
1Antimicrobial role of human meibomian lipids at the ocular surface. Mudgil P. Invest Ophthalmol Vis
Sci. 2014 Oct 14;55(11):7272-7.
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Focus on the Gland
“Meibomian Gland Dysfunction (MGD) is a
chronic, diffuse abnormality of the Meibomian
Glands, commonly characterized by terminal
duct obstruction and/or
qualitative/quantitative changes in the
glandular secretion.”
109
Notes: The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction. Geerling G, Tauber J,
Baudouin C, et al. Invest Ophthalmol Vis Sc i. 2011 Mar 30;52(4):2050-64
Function Structure
Normal Function Normal Structure
Meibomian Gland Function
110
Notes: Evaluation of lipid layer thickness measurement of the tear film as a diagnostic tool for Meibomian gland dysfunction. Finis D, Pischel N, Schrader S, Geerling G. Cornea. 2013
Dec;32(12):1549-53.
Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and gland location. Korb DR, Blackie CA. Cornea. 2008 Dec;27(10):1142-7.
DRY NOT DRY
0 - 4 5 6 7 8 9 10+
FUNCTIONAL MGs in the Lower Lid
≤ 4, treatment necessary, (if glands present)
5-6, intervention highly advised
7-9, preventive treatment (PRN)
• A functional Meibomian Gland is a gland that releases its liquid
contents during a deliberate blink.
• The number of functional MGs along the lower eyelid can be used to
diagnose MGD and to direct therapeutic intervention
When the total number of functional glands is 10 or higher, but there is evidence of
compromise to gland function and/or structure, therapy should still be considered.
Meibomian Gland Structure
Visualization Prioritizes Therapy
Now MGD is detected and managed with ability to also visualize structure
Any compromise to gland structure is an indication to consider therapeutic intervention
111
MGD is Progressive
Examples of Compromised Function and Structure
Function
Structure
Normal Function Nonobvious MGD Obvious MGD Obvious MGD
Normal Structure Gland Duct
Dilation
& Drop Out
Gland Truncation
& Drop Out
Gland Duct Dilation,
Truncation & Drop Out
112
Notes: Siak JJ, et al. Prev alence and risk factors of meibomian gland dy sfunction: the Singapore Malay Ey e Study . Cornea. 2012;31(11):1223-1228.
Viso E, et al. Prev alence of asy mptomatic and sy mptomatic meibomian gland dy sfunction in the general population of Spain. Inv est Ophthalmol Vis Sci. 2012;53(6):2601-2606.
Hom MM, et al. Prev alence of meibomian gland dy sfunction. Optom Vis Sci. 1990;67(9):710-712.
The Cycle of Inflammation
Sy
mp
to
ms In
crease
Potential Long-term Damage Inflammation
Stasis, inspissation and obstruction of the Meibomian Glands
Meibomian Gland Dysfunction (MGD)
Tissue Changes
Decrease in Meibomian secretions
Decrease in tear film stability, increased aqueous tearing1
1. Arita R, et al. Increased Tear Fluid Production as a Compensatory Response to Meibomian Gland Loss: A
Multicenter Cross-sectional Study. Ophthalmology. 2015 Jan 24. pii: S0161-6420(14)01195-6. doi:
10.1016/j.ophtha.2014.12.018. [Epub ahead of print]
• Wait for the onset of sequelae: The patient
tells you there is a problem
• Measure and manage dry eye sequelae
• Lead with palliative artificial tears
• Gradually advance treatment as sequelae
increase in severity1,2
A Change in Philosophy – MGD First
Dry Eye Approach MGD First/Root Cause Approach
• Evaluate everyone for MGD: Identify MGD at its
earliest stages
• Educate patients about the front line of defense
of the tear film – the lipid layer
• Offer the most efficacious MGD treatment as
early as possible
• Rehabilitate the ocular surface and manage
sequelae with adjunctive therapy
Goal: Restore and optimize gland
function/intervene in progression
• Root cause is not identified: Promotes
confusion, and patient despair
• Promotes patient and physician confidence
in MGD management.
114
Notes: 1. Management and Therapy of Dry Ey e Disease: Report of the Management and Therapy Subcommittee of the International Dry Ey e WorkShop. Geerling G et al. Ocular Surface. 2007 Apr;5(2) 163-
178,
2. The international workshop on meibomian gland dy sfunction: report of the subcommittee on management and treatment of meibomian gland dy sfunction. Geerling G, Tauber J, Baudouin C, et al. Inv est
Ophthalmol Vis Sci. 2011 Mar 30;52(4):2050-64
Goal: Treat Sequelae (primarily
symptoms)
MGD First: If the etiology is not treated, the Dry
Eye will not resolve
MGD First does not mean that the sequelae of dry eye should be ignored.
115
SYMPTOMS
VISION
TEAR INSTABILITY
OCULAR SURFACE DAMAGE
HYPEROSMOLARITY
INFLAMMATION
Compromised
Lacrimal Function
MGD
LipiFlow/ Manual Expression,
Warm Compress, lid hygiene, Blinking,
Lipid Drops Topical & Systemic
Medications
MEASURE AND MANAGE DRY EYE
SEQUELAE IDENTIFY AND TREAT THE CAUSE
MOST COMMON
Allergy,
Autoimmune Treat Accordingly
TREATMENT
Treat Accordingly
+
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.
116
Obstruction Inflammatory
Anti-inflammatories: Steroid
Loteprednol AzaSite
Doxycycline Omegas Restasis
Mechanical therapy:
Lid therapy Masks
In office manual expression Lid margin scraping MiBoFlo, LipiFlow
Mechanical therapy:
Lid therapy Masks
In office manual expression Lid margin scraping MiBoFlo, LipiFlow
Anti-inflammatories: Steroid
Loteprednol AzaSite
Doxycycline Omegas Restasis
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Obstruction Inflammatory Obstruction and inflammatory