Making Friends with Ocular Surface

Dr. Zia.ul.Mazhry
FRCS(Edin), FRCS(Glasgow),

FCPS(Pak), CICOphth- (UK)

Life Member OSP Member American Academy of Ophthalmology Member ESCRS Member Executive Council OSP Lahore Branch

Assistant Professor Central Park medical college Lahore Consultant Surgeon & Head of Ophthalmology Department WAPDA Teaching Hospital Complex Lahore

Ocular Surface-Overview

http://www.virtualcancercentre.com

Conception
Corneal epithelium Conjunctival epithelium Tear film Clinical ocular surface consist of conjunctiva cornea eyelids lacrimal gland lacrimal passages

Origin of Epithelium
Stem cells, SC
Corneal epithelium derived from the Limbal stem cells. Conjunctival epithelium derived from forniceal and palpebral regions.

Ocular Surface Disorders

The ocular surface is a complex biological continuum responsible for the maintenance of corneal clarity, elaboration of a stable tear film for clear vision, as well as protection of the eye against microbial and mechanical insults. Comprising a variety of disorders on cornea, eyelid, conjunctiva, lacrimal apparatus and tear film.

Ocular Surface Disorders Classification

Corneal, conjunctival lesion
Squamous epithelization type Limbal stem cell deficiency type

Tear film disorders

Aqueous tear deficiency Lipid tear deficiency Mucoprotein deficiency Kinetic disorders of lacrimal fluid

Dry Eye Ocular Surface Issues

Lipid Deficiency Evaporative
Meibomian Gland Dysfunction Blepharitis

Aqueous Insufficiency
Inflammation CTDs, Sjogrens Trauma, neurological, congenital

Mucin Abnormalities
Stevens-Johnson, pemphigoid, radiation, vitamin A deficiency, trachoma

> Dry eye is a multifactorial condition, not a single disease entity.

Conditions Associated with Dry Eye

Chronic Systemic Inflammation
Sjogrens syndrome, rheumatoid arthritis, lupus

Ocular surface inflammation

Meibomian Gland Disease, keratitis, infection

Hormonal changes
menopause, oral contraceptives, pregnancy, lactation

Aging Systemic diseases

diabetes, thyroid

Medications
antidepressants, decongestants, antihistamines, antihypertensives, diuretics

Environmental
smoke, air pollution, wind, heat/AC, VDT, light, dry climate, air travel

Blink disorder
anatomical, surgical (LASIK)

Current Triggers of Dry Eye Disease

Environment Medications Contact Lens Surgery

Irritation

Inflammation

Rheumatoid Arthritis Lupus Sjgrens Graft vs Host

Tear Deficiency/ Instability

Postmenopause Meibomian Gland Disease

Symptoms of Ocular Surface Disease

Dry Eye Classification

Dry Eye
Inflamed Non-Inflamed

Lacrimal Gland Non-Sjogens Sjogrens

Ocular Surface

Mechanical

ATD

Blepharospasm

Blepharitis

Toxic

Allergic

1o OSD

Conjunctivochals is Dermatochalasis

With ATD Without ATD

ATD = Aqueous Tear Deficiency

Prevalence of Dry Eye

Epidemiology of Dry Eye Syndrome Schaumberg et. a.l. Lacrimal Gland, Tear Film and Dry Eye Syndromes 3 2002
Prevalence of Dry Eye Salisbury Study = 14.4% Melbourne Study = 5.5% Beaver Dam Study = 14.4% WHS Study = 6.7%

Although, percent of individuals who experience signs and symptoms of dry eye at one time or another due to environmental factors = 100%

Factors Influencing Dry Eye

Age Gender Rheumatoid arthritis Osteoporosis Gout Lens Surgery Contact Lens Wear Blink Disorders Disorders of Lid aperture Nutritional Problems Endocrine status Thyroid Problems Time of Day LASIK Surgery Cosmetic Surgery Mechanical disturbances Exposure Keratitis Entropion Ectropion Symblepheron Large lid notches Lagophthalmos Concomitant meds Dellen Formation Illumination PC use Temperature Humidity Air movement Allergies Change in environment Reading Watching Movies Sleep Environmental pollutants Alcohol Conjunctivochalasis Lid Disease

Prause JU, Norn M. Relation Between Blink Frequency and Break-Up Time. Acta Ophthalmol. 1983 61: 108-116. Cho P, Cheung P, Leung K, Ma V, Lee V. Effect of Reading on Non-Invasive Tear Break-Up Time and Inter-Blink Interval. Clin. Exp. Optom. 1997 80: 62-8. Tsubota K, Seiichiro H, Okusawa Y, Egami F, Ohtsuki T, Nakamori K. Quantitative Videographic Analysis of Blinking in Normal Subjects and Patients with Dry Eye. Arch. Ophthalmol. 1996 114(6): 715-720. Nally L, Ousler GW, Abelson MB. Ocular discomfort and tear film break-up time in dry eye patients: a correlation. IOVS 2000 41(4): 1436. Collins M, Seeto R, Campbell L, Ross M. Blinking and Corneal Sensitivity. Acta Ophthalmologica 1989 67(5): 525-531. Abelson MB, Holly FJ. A tentative mechanism for inferior punctate keratopathy. Am. J. Ophthalmol. 1977 83: 866-869. Doane MG. Dynamics of the Human Blink. Ber. Disch. Ophthalmol. Ges. 1980 77: 13-17. Kaneko K, Sakamoto K. Spontaneous Blinks as a Criterion of Visual Fatigue During Prolonged Work on Visual Display Terminals. Perceptual and Motor Skills 2001 92(1): 234-250..

Tear Film Structure

Traditional Tear Film Model
(3 Distinct Layers)

Updated Tear Film Model

1977 - <8g

1997 30-40g

The Role of Epithelial Glycocalyx

How Tear Film Instability Occurs

Desiccation of the corneal epithelial cells due to varied causes Mucins cannot attach and the water repellant corneal surface is exposed Tear film destabilizes, increasing evaporation and diffusion, exposing the cornea

Damaged corneal cells show up as dry spots during corneal staining.

Consequences of Tear Composition Changes in CDE

Altered environment for ocular surface tissues
Increased osmolarity Imbalanced growth factors and cytokines fail to promote normal epithelial growth Poor viscosity can cause thin spots in tear film and tear break-up Lubrication compromised

Ocular surface damage

Loss of corneal epithelial integrity Squamous metaplasia of conjunctival epithelium corneal filamentary keratitis; marked corneal punctate staining; central corneal staining, conjunctival scarring; corneal erosions; severe corneal staining

Altered lifestyle

Ocular Manifestations of Dry Eye

PATIENT SYMPTOMS
Dryness Itchiness or scratchiness Photophobia Contact lens intolerance Burning or stinging Foreign body sensation Grittiness Fluctuating visual acuity Tired eyes General discomfort

CLINICAL SIGNS
Hyperemia Low tear meniscus Tear debris Abnormal tear osmolarity Fast tear break up time Conjunctival staining Blepharitis Increased cytokines Corneal surface damage

Diagnosing Dry Eye

Dont underestimate prevalence
Easy to overlook because its so common

Symptoms
May be confusing (i.e. reduced VA)

Clinical history
Critical for the diagnosis! Helps pinpoint the cause and the effect

Clinical tests

Dry Eye Questionare

How Frequently Do Your Eyes Water? How Often Do Your Eyes Feel Dry? Is the Dryness Worse Late in the Day? How Often Do You Experience Ocular Discomfort? Is the Discomfort Worse Late in the Day?

ITF: Clinical Symptoms

Symptoms
Itching Sandy Feeling Gritty Feeling Dry Feeling

Vision
Fluctuation Blurring

Artificial Tears
Frequency of Use

Discomfort
Stinging Burning Painful

Dry Eye Diagnosis

Test Schirmer's I cutoff value for dry eye diagnosis

less than or equal to 5 mm wetting over 5 minutes Tear Breakup time less than or equal to 10seconds Tear Meniscus height less than or equal to 0.2 mm Fluorescein staining more than 3 out of 15 Rose Bengal staining more than 3 out of 18 Tear film osmolarity more than 316 mOsm/L Impression cytology more than 1 Brush cytology more than 1 Tear lactoferrin less than or equal to 0.9 ug/mL

Non Invasive Break up time (NIBUT)

clinician focuses and views the crisp keratometric mires, and then records the time taken for the mire image to distort (TTT) and/or break up (NIBUT). NIBUT measurements are longer than fluorescein break up time.

Symptomatic Tear BreakUp Time (SBUT) test

Dry Eye Syndrome test at Systane_com.htm
Obtain a stopwatch or clock. Blink 2 times, then stare straight ahead, taking care to start timing immediately after your second blink. Avoid blinking for as long as possible. Note the time on the clock when you begin to feel eye discomfort (burning, grittiness, dryness, etc.) The SBUT is the amount of time (in seconds) that passes between your last complete blink and the moment you experience eye discomfort.
SBUT is 5 seconds or less, you may have dry eye

Lacrimal river width

Schirmer Test
Normal 10mm/5min

Tear break-up time, BUT

Staining
Using special dyes to highlight areas of possible damage to the eye surface.

N.E.I. Grid Corneal Staining

0 3 for each of 5 zones: 15 points possible

S T C I
OD

S N N C I
OS

N.E.I. Conjunctival Grid

Lissamine Green or Rose Bengal: (0 3 for each zone)
T 2 1 3 5 4 6 N 6 3 5 2 4 1 T

18 Points Possible

Statistically Significant Findings

Signs Less Temporal Corneal Staining Less Conjunctival Staining Corneal Staining Reduction from Baseline

Symptoms Less Morning Dryness Less End of Day Dryness Eyes Felt Refreshed Longer Less Frequent Foreign Body Sensation

Contact Lens Induced Dry Eye

Pathological (Real) Dry Eye Associated with local or systemic disease Marginal (Contact Lens) Dry Eye Usually apparent only when contact lenses are worn

Pseudo-Dry Eye Dry eye symptoms in contact lens wearers that are not due to a true dry eye state

Dry Eye Diagnostic Tools Signs

Tear Film Break-Up Time

Injection

Rose Bengal Staining

Lissamine Green Staining

Fluorescein Staining

Blink Rate

Flourophotometry

Osmolarity

Which dry eye diagnostic tools are you using currently and in which order?
thorough slit-lamp examination Uneven or scanty tear meniscus Vital staining Tear film break-up time Schirmer lacrimation test Lack of goblet cells The lid functioning, Mucous shreds and strings Lid parallel folds

Making Dry Eyes Wet

ITF: Clinical Signs of Dry Eye Syndrome

Staining
Conjunctival Corneal

Tear Film Instability Abnormal TBUT Abnormal Schirmers

Differential Diagnoses - Other External Diseases

Allergy Blepharitis Viral Chlamydia Pemphigoid Bacterial
Contact lens related (irritant conjunctivitis, infiltrates) Ocular Rosacea Medicamentosa

Differential Diagnoses - Other External Diseases

Acute Bacterial Conjunctivitis
Common, can affect any age Causative agents vary, Staphylococcus aureus typically most common Mucopurulent Patches of subconjunctival hemorrhage (rarely) Periorbital edema may also be present, especially in young children

Differential Diagnoses - Other External Diseases

Blepharitis
Lid Swelling, vasodilation of lid margin, lid thickening, lid notches, loss of lashes, blurring of vision, mucous discharge, and crusts

Differential Diagnoses - Other External Diseases

Medicamentosa Rosacea

Toxic reaction due to antibiotics, antivirals, sympathomimetics, miotics, beta-blockers, topical anesthetics, etc. with no underlying immune dysfunction Persistent burning and feeling of grittiness in the eyes, inflamed and swollen eyelids with small inflamed bumps, bloodshot eyes. Pain and photophobia may be present. It is instructive to ask rosacea patients how their eyes react to bright sunlight

Many patients after cataract surgery tell us they () are having real problems with dry eye syndrome
Juan Duran De la Colina; EuroTimes, dec 2005

Cataract surgery
Clear cornea incision

Post operative medication

Increase ocular irritation and tear film disruption

Post surgery ocular inflammation

Cut the corneal nerves

Limit eye stability to create a proper tear film

Affects tear film production and stability

A XLIV-a Reuniune Anuala a Oftalmologilor Iasi, mai2008

Clinical Management Of Dry Eye

How to Treat
Ask for symptoms Determine the primary source of symptoms Avoid drying situations and drugs Local therapy is preferred No toxic preservatives Do not hurt Use the agent most effective and safe Combinations Depending on severity Time: no cure but usually mild

Severity Level
Level 1: Mild to moderate symptoms; mild to moderate conjunctival signs; no staining Level 2: Moderate to severe symptoms; tear film signs; visual signs; mild corneal punctate staining; conjunctival staining Level 3: Severe symptoms; corneal filamentary keratitis; marked corneal punctate staining; central corneal staining Level 4: Extremely severe symptoms/altered lifestyle; conjunctival scarring; corneal Making erosions; severe corneal Dry Eyes Wet staining

Principles of treatment
Treat the Symptoms Treat the Cause Treat the complications

Making Dry Eyes Wet

Treatment Algorithm (ITF)

Level One
Patient education Environmental modification Control systemic medications Control allergy Preserved tears

Level Two
Unpreserved tears Gels and nighttime ointments Nutritional support Cyclosporine Topical steroids Secretagogues

Making Dry Eyes Wet

Treatment Algorithm (ITF)

Level Three
Oral tetracyclines Punctal plugs after inflammation controlled

Level Four
Systemic antiinflammatory therapy Acetylcysteine Moisture goggles Punctal cautery

Making Dry Eyes Wet

Main stay of Current dry eye management is :

TEAR REPLACEMENT THERAPY

Making Dry Eyes Wet

Ideal Tear substitute

Viscosity Exit time increased Vision decreased Hypoosmolar

Ph Value around 7
Thixotropy The property of becoming fluid when shaken and then becoming semisolid again Preservatives/preservative free/disappearing BAK, Polyquad Gen Aqua Sodium Perborate

Patient satisfaction

Contact lens Tolerance Newtonian vs Nonnewtonian Liquids

Is an Ideal tear substitute currently available?

NO

A tear drop

Optimal Artificial Tear

Goals
Dwell Time Long Lasting Protection

Requirements
Minimal Blurring

Minimal Lid Caking

Improved Comfort Non-irritating Preservatives

 SYSTANE
Demulcents

Lubricant Eye Drops

Polyethylene Glycol 400 (PEG 400) Propylene Glycol (PG)

HP-Guar
Large gel-forming polysaccharide

Essential Ions (K, Ca, Mg, Na, Zinc) At pH 7.0 it is fluid in the bottle but in the eye @ ~7.5 7.8
Forms chemical x-links w/ borate Soft gel forming matrix Bioadhesive properties Very lubricous

Mechanism of Action

Systane - Preservative
Polyquaternium-1 (Polyquad) Quaternary ammonium Used in contact lens care solutions Less corneal damage Corneal uptake of carboxyfluorescein:
BAK: 9-99 fold increase Polyquad: 0-4 fold increase

Viscosity As A Function Of pH For SYSTANE Lubricant Eye Drops

Increasing Viscosity
7

7.1

7.2

7.3

7.4

7.5

7.6

7.7

pH of Tear Film

In-vitro Gelation Of SYSTANE Lubricant Eye Drops As It Occurs In The Eye

100.000
Thicker

Shear Thinning with increased Shear Stress

pH 7.0

10.000

pH 7.4

VISCOSITY, cp x10-3

pH 7.8
1.000

0.100

0.010
Thinner

0.001 0.001 0.010 0.100 1.000

SHEAR STRESS, Pa

Systane effects:
in-eye gelling effect adjust pH tear creates an ocular shield decrease the evaporation on tear film increase the stability of tear film allow the epithelial repair in a healthy environment

What Is Restasis?
Ophthalmic emulsion of cyclosporine 0.05%.
Prescription therapy for dry eye disease. Restasis is FDA approved to increase tear production in patients whose tear production may be reduced by inflammation of the eye associated with keratoconjunctivitis sicca.

Immuno-Modulatory Therapy Autologous Serum Administration

40 cc of whole blood drawn by venipuncture spun down at 1,500 rpm for five minutes Diluted in sterile technique to 20% solution Divided into four equal quantities and stored in dark bottles. Three in the freezer, one in the fridge Administered T.I.D. for one month Efficacy Improved With Higher Concentrations,
(Swobota, et al)

Likert Acceptability Questionnaire

Eyes Less Dry in Morning* Eyes Less Dry at End of Day* Eyes Refreshed Longer*

Scale Strongly Disagree Disagree Undecided Agree Strongly Agree

* p<0.05 = In favor of SYSTANE Lubricant Eye Drops

Acceptability Summary
Question My eyes feel dry in the morning. My eyes feel dry at the end of the day. My eyes feel comfortable upon instillation of drops. My eyes feel refreshed when I use the drops. My eyes feel refreshed longer than expected when I use the drops. I frequently forgot my symptoms during the use of the drops. Delta % Change -0.8* 19% -0.9* +0.5* +0.6* 22% 13% 17%

+0.8*
+0.7*

28%
26%

* p<0.0001

Message
Subjective Symptoms and objective signs are both important in the diagnosis and management of dry eye, with the patients symptoms and history playing a critical role. Most clinicians use objective signs in dry eye management. However, currently available diagnostic tests do not correlate reliably with symptom severity. Research aimed at developing accurate, objective, responsive measures of dry eye severity is needed.
Smith, Nichols, and Baldwin, 2008

THANK YOU!