Dry eye: A Multifactorial Disease

1. Dry EyEDry EyE
A MultifActoriAl DisEAsEA MultifActoriAl DisEAsE
Dr sAMArth MishrADr sAMArth MishrA
11

2. Prevalence of Dry EyePrevalence of Dry Eye
DiseaseDisease
• 60 million affected worldwide.60 million affected worldwide.
• 1 to 2 million suffer from severe, chronic1 to 2 million suffer from severe, chronic
symptoms.symptoms.
• 7 to 10 million Americans have some form7 to 10 million Americans have some form
of dry eye needing artificial tears.of dry eye needing artificial tears.
• 33 million adults may be undiagnosed.33 million adults may be undiagnosed.
• Sjögren’s - associated dry effects 1% toSjögren’s - associated dry effects 1% to
2% of the population.2% of the population.
22

3. Prevalence of Dry Eye DiseasePrevalence of Dry Eye Disease
• Average age of a dry eye patient isAverage age of a dry eye patient is
54; most are women.54; most are women.
• Dry Eye Syndrome affects 75% ofDry Eye Syndrome affects 75% of
people over age 65.people over age 65.
• Common reason for ophthalmologistCommon reason for ophthalmologist
visits.visits.
33

4. Prevalence of Dry Eye Disease inPrevalence of Dry Eye Disease in
IndiaIndia
Study N Age Creteria Prevalence Reference
Wisconsin 3,722 48-91 Self-reported 14.4% Moss SE et al. Arch
Ophthalmol.
2000;118(9):1264-
1268.
Shihpai
(Taiwan)
2,038 >65 One of 6 symptoms 33.7% Lin PY et al.
Ophthalmology.
2003;110(6):1096-
1101.
Maryland 2,520 65-84 Symptoms + 1 sign 3.5% Schein OD et al. Am. J.
Ophthalmol.
1997;124(6):723-728.
Women’s
Health
Study
39,876 49-84
(female)
Severe symptoms
or clinical diagnosis
7.8% Schaumberg DA et al.
Am. J. Ophthalmol.
2003;136(2):318-326.
44

5. Contd..Contd..
Study N Age Creteria Prevalence Reference
Dry Eye
Prevalence
(India)
500 >20 Symptoms + Tests 18.4% Sahai A et al Indian J
Ophthalmol
2005;53:87-91
Dry Eye
Study
(Thailand)
550 >550 Symptoms 34% Lekhanont et al
cornea2006;25:1162-
67
55

6. ‘‘Dry eye is a disorder of the tear film due to tear deficiencyDry eye is a disorder of the tear film due to tear deficiency
or excessive tear evaporation, which causes damage to theor excessive tear evaporation, which causes damage to the
interpalpebral ocular surface and is associated withinterpalpebral ocular surface and is associated with
symptoms of ocular discomfort.’symptoms of ocular discomfort.’
Global Definition of Dry Eye
Lemp MA. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J 1995 Oct;21(4):221-32. 66

7. DEWS Dry Eye Definition (2007)
‘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.’
The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007 Apr;5(2):75-92.
77

8. Classification SystemsClassification Systems
88

9. Behrens A, Doyle JJ, Stern L, Chuck RS, McDonnell PJ, Azar DT, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea 2006Sep;25(8):900-7.
Delphi Panel Report − Dysfunctional Tear
Syndrome Classification
Panel Delphi Panel Approach to Dry Eye Disease
Year 2006
Key highlights  A new term proposed for Dry Eye disease: Dysfunctional
Tear Syndrome (DTS)
 Treatment recommendations based primarily on patient
symptoms and signs
Basis of classification  Primary – symptoms and signs
 Secondary – staining and other diagnostic tests
Major categories  With lid margin disease
 Without lid margin disease
 Altered tear distribution and clearance
99

10. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007 Apr;5(2):75-92.
DEWS: Dry Eye Classification
Panel Definition and Classification Subcommittee of DEWS
Year 2007
Key highlights  Classification is more comprehensive, as it includes various tests in
addition to symptoms and signs
 Adopted and modified the Delphi Panel Dry Eye severity grading
Basis of
classification
 Symptoms and signs
 Staining
 Tear Film BreakUp Time (TFBUT)
 Schirmer’s test values
 Lid/meibomian gland disease
Major
categories
 Aetiopathogenic
 Causative mechanisms
 Severity
1010

11. DEWS: Classification
DEWS Dry Eye classification
Aetiopathogenic
Tear
hyperosmolarity
Tear film
instability
Level 4Level 3Level 2Level 1
Causative
mechanisms
Severity of
disease
Details on next
slide
The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007 Apr;5(2):75-92.
1111

12. DEWS: Subset 1 − Aetiopathogenic
Classification
Sjögren Syndrome
Dry Eye
Non-Sjögren Dry
Eye
Primary Secondary
Lacrimal gland
duct obstruction
Reflex sensory
block
Reflex motor
block
Lacrimal
deficiency
Reflex
hyposecretion
Intrinsic
Vitamin A
deficiency
Topical drugs
preservatives
Contact lens
wear
Ocular surface
disease, for
example: allergy
Meibomian
gland
dysfunction
Disorder of lid
aperture
Low blink
rate
Drug action
accutane
Aetiopathogenic
Classification
EvaporativeAqueous deficient
Extrinsic
Primary Secondary
The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007 Apr;5(2):75-92.
1212

13. Dry Eye Severity Level 1 Level 2 Level 3 Level 4*
Discomfort, severity
and frequency
Mild and/or episodic;
occurs under
environmental stress
Moderate episodic or
chronic, stress or no
stress
Severe frequent or
constant without
stress
Severe and/or
disabling and constant
Visual symptoms None or episodic mild
fatigue
Annoying and/or
activity-limiting
episodic
Annoying, chronic
and/or constant,
limiting activity
Constant and/or
possibly disabling
Conjunctival injection None to mild None to mild + /− + /++
Conjunctival staining None to mild Variable Moderate to marked Marked
Corneal staining
(severity/location)
None to mild Variable Marked central Severe punctate
erosions
Corneal/tear signs None to mild Mild debris,
decreased meniscus
Filamentary keratitis,
mucous clumping,
increased tear debris
Filamentary keratitis,
mucous clumping,
increased tear debris,
ulceration
Lid/meibomian glands MGD variably present MGD variably present Frequent Trichiasis, keratinisation,
symblepharon
TFBUT (sec) Variable ≤10 ≤5 Immediate
Schirmer’s score (mm/5 min) Variable ≤10 ≤5 ≤2
*
Must have signs and symptoms; MGD: Meibomian Gland Dysfunction;
TFBUT: Tear Film BreakUp Time
DEWS: Subset 3 − Dry Eye Severity
Grading System
 The basic scheme of the Delphi Panel report was adopted and modified to
produce the third component of the recommendation
The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007 Apr;5(2):75-92.
1313

14. Dry Eye Is a Continuum ofDry Eye Is a Continuum of
DiseaseDisease
1414

15. LacrimalLacrimal
GlandsGlands
SecretomotorSecretomotor
Nerve ImpulsesNerve Impulses
Tears Support and MaintainTears Support and Maintain
Ocular SurfaceOcular Surface
Ocular SurfaceOcular Surface
Neural StimulationNeural Stimulation
The Healthy EyeThe Healthy Eye
Stern et al, Cornea. 1998:17:584
Normal tearingNormal tearing
depends on adepends on a
neuronal feedback loopneuronal feedback loop
1515

16. Lacrimal Glands:Lacrimal Glands:
• NeurogenicNeurogenic
InflammationInflammation
• T-cell ActivationT-cell Activation
• Cytokine Secretion intoCytokine Secretion into
TearsTears
Interrupted SecretomotorInterrupted Secretomotor
Nerve ImpulsesNerve Impulses
Tears Inflame Ocular SurfaceTears Inflame Ocular Surface
CytokinesCytokines
Disrupt Neural ArcDisrupt Neural Arc
Inflammation disruptsInflammation disrupts
normal neuronalnormal neuronal
control of tearing.control of tearing.
Stern et al, Cornea. 1998:17:584
Dry Eye Disease: An Immune-Dry Eye Disease: An Immune-
Mediated Inflammatory DisorderMediated Inflammatory Disorder
1616

17. Multiple Factors in Dry EyeMultiple Factors in Dry Eye
• Transient discomfortTransient discomfort
• May be stimulated by environmentalMay be stimulated by environmental
conditionsconditions11
• Inflammation and ocular surface damageInflammation and ocular surface damage
• Altered tear film compositionAltered tear film composition22
• Few other conditions like Ocular allergy, &Few other conditions like Ocular allergy, & Allergic Conjunctivitis, Blepharitis, Contact lensAllergic Conjunctivitis, Blepharitis, Contact lens
usage etc.usage etc.
1
de Paiva and Pflugfelder. In: Dry Eye and Ocular Surface Disorders. 2004;
2
Pflugfelder et al. In: Dry Eye and Ocular Surface Disorders. 2004.1717

18. ConjunctivitisConjunctivitis
• InflammationInflammation
• ErythemaErythema
• Several causes:Several causes:
– BacterialBacterial
– ViralViral
– AllergicAllergic
– ChemicalChemical
1818

19. ConjunctivitisConjunctivitis
Christopher Baudouin Survey of Ophthalmol 2001;45(2):S211-S2201919

20. Chronic cicatrizing conjunctivitisChronic cicatrizing conjunctivitis
• Stevens-Johnson syndrome (SJS)Stevens-Johnson syndrome (SJS)
• Toxic epidermal necrolysis (TEN)Toxic epidermal necrolysis (TEN)
• TrachomaTrachoma
• Epidemic keratoconjunctivitis (EKC)Epidemic keratoconjunctivitis (EKC)
• Atopic keratoconjunctivitisAtopic keratoconjunctivitis
• Sjogren’s syndromeSjogren’s syndrome
• Progressive systemic sclerosisProgressive systemic sclerosis
• SarcoidosisSarcoidosis
2020

21. Chronic Ocular AllergyChronic Ocular Allergy
• Dry eye is commonly associated with chronicDry eye is commonly associated with chronic
allergic conjunctivitis.allergic conjunctivitis.
• An allergic history has been reported by 36% ofAn allergic history has been reported by 36% of
dry eye patients.dry eye patients.
• Chronic allergy results in loss of goblet cells,Chronic allergy results in loss of goblet cells,
destabilization of the tear film & damage to oculardestabilization of the tear film & damage to ocular
surface.surface.
• VKC is associated with 38% incidence of dry eye.VKC is associated with 38% incidence of dry eye.
Surv Oph 2001, 45(2), S211-202121

22. AllergyAllergy
36% of dry eye patients have a history of36% of dry eye patients have a history of
allergyallergy
Stimulation of the local immune system
Destabilization of tear film
Increased rate of tear evaporation
J.M. Albietz Clin Exp Optom.2001;84(1):4-18
Christopher Baudouin Survey of Ophthalmol 2001;45(2):S211-S2202222

23. Dry Eyes and BlepharitisDry Eyes and Blepharitis
• Very common in older patientsVery common in older patients
• Chronic remitting problemChronic remitting problem
• Not usually serious but constant nuisanceNot usually serious but constant nuisance
• Patient EducationPatient Education
– LifestyleLifestyle
– Regular hygiene/instillation of drops/gelsRegular hygiene/instillation of drops/gels
– Realistic expectations of treatment!Realistic expectations of treatment!
2323

24. BlepharitisBlepharitis
2424

25. Blepharitis is an extremely frequent cause ofBlepharitis is an extremely frequent cause of
Dry EyeDry Eye
Loss of meibomian gland
function
Impairment in the lipid
phase of tear film
Increased rate of tear
evaporation
Destabilization of tear film
Deficient mucin secretion
Loss of goblet cells
Christopher Baudouin Survey of Ophthalmol 2001;45(2):S211-S220 2525

26. Lid anatomyLid anatomy
Meibomian/tarsal glands
Glands of Zeiss and Moll
2626

27. Blepharitis-SymptomsBlepharitis-Symptoms
• Sore burning itching irritation of lidsSore burning itching irritation of lids
• Grittiness and wateringGrittiness and watering
• Mild stickiness particularly on wakingMild stickiness particularly on waking
• Red lid marginsRed lid margins
• Dry eyesDry eyes
2727

28. Contact Lens usage and Dry eye
A survey of 310 practitioners found that:
-18% to 30% of CL patients had dry eye
problems
-12 to 21% had reduced wearing time due to
dryness
-6% to 9% discontinued wear due to dryness
(Orsborn & Zantos, CL Spectrum, 1989) 2828

29. DRYNESS SYMPTOMS WITH CONTACT LENS WEAR
A survey of 214 hydrogel patients found:
21% of males and 26% of females had reduced
wearing time due to dryness symptoms.
(Orsborn & Robboy, J Brit CL J. 1989)
2929

30. 3030

31. 3131

32. DRYNESS SYMPTOMS WITH CONTACT LENS WEAR
Numerous factors effect the dehydration of
hydrogel lenses:
Water content: higher water lenses lose more water
Thickness: Thin lenses dehydrate more
Humidity: Lenses dehydrate more in low humidity
environments
Temperature: less water at higher temperatures.
-less water in lens on eye than in solution
3232

33. 3333
Computer vision syndromeComputer vision syndrome
• Excessive use of visual display unitsExcessive use of visual display units
• Insufficient tear flowInsufficient tear flow
• Glare and reflection on monitorGlare and reflection on monitor
• Need for glassesNeed for glasses
• SymptomsSymptoms
– eyestrain/fatigueeyestrain/fatigue
– itching/burningitching/burning
– photophobiaphotophobia
– blurred visionblurred vision
– irritation and heaviness of lidsirritation and heaviness of lids
www.allaboutvision.com

34. WHAT IS CVS ?WHAT IS CVS ?
Computer Vision Syndrome affects 60% of computer usersComputer Vision Syndrome affects 60% of computer users
Causes Symptoms
• Low Blink Rate • Narrowing eye lid-slits
• Screen Flicker • Eye irritation/pain
• Incorrect viewing Angles • Redness - Burning
• Headaches
3434

35. STARTING AT MONITORSSTARTING AT MONITORS
REDUCED RATE OF BLINKINGREDUCED RATE OF BLINKING
FASTER TEAR FILM EVAPORATIONFASTER TEAR FILM EVAPORATION
DEPRIVATION OF LUBRICATIONDEPRIVATION OF LUBRICATION
& NOURISHMENT& NOURISHMENT
CVS
CONSULT YOUR
DOCTOR TODAY,
TO FIND RELIEF
3535

36. BLINKING TIME PER MINUTEBLINKING TIME PER MINUTE
Average:
22 times per
minute
While
reading:
10 times per
minute
While
looking at
computer/
TV screen:
7 times per
minute
3636

37. WHO IS AT RISK?WHO IS AT RISK?
• Computer users - programmers,Computer users - programmers,
data entry operatorsdata entry operators
• Additionally, those in air-conditionedAdditionally, those in air-conditioned
officesoffices
3737

38. WHAT IS THE SOLUTION?WHAT IS THE SOLUTION?
• Regular use of tear substitutes / ocularRegular use of tear substitutes / ocular
lubricantslubricants
• Acts like real tears to soothe and relieveActs like real tears to soothe and relieve
ocular discomfortocular discomfort
3838

39. Diagnosing Dry Eye DiseaseDiagnosing Dry Eye Disease
1
Nichols et al. Cornea. 2000.
3939

40. Lemp, 1995; Marsh et al, 1999Lemp, 1995; Marsh et al, 1999
SlitlampSlitlamp
FluoresceinFluorescein
Dye StainDye Stain
MildMild SevereSevere
Clinical Presentation Can Vary inClinical Presentation Can Vary in
SeveritySeverity
4040

41. Schirmer TestSchirmer Test
WithoutWithout
AnesthesiaAnesthesia
• Measures reflexMeasures reflex
tear secretion.tear secretion.
With AnesthesiaWith Anesthesia
• EliminatesEliminates
stimulatedstimulated
tearing.tearing.
4141

42. Sterile Melting Bacterial Keratitis
Potential Severe ConsequencesPotential Severe Consequences
of Untreated Dry Eye Diseaseof Untreated Dry Eye Disease
4242

43. Left Untreated, Chronic Dry EyeLeft Untreated, Chronic Dry Eye
May Become a ProgressiveMay Become a Progressive
DisorderDisorder
• Patients suffering from dry eye diseasePatients suffering from dry eye disease
may move between severity levels andmay move between severity levels and
can become worse, if untreatedcan become worse, if untreated11
– Disease management options can beDisease management options can be
adjusted for individual patients depending onadjusted for individual patients depending on
disease severitydisease severity
1
Nelson et al. Adv Ther. 2000.
4343

44. Treatment Options for DETreatment Options for DE
conditionsconditions
4444

45. 4545
Dry Eye TreatmentDry Eye Treatment
Tear-SubstitutesTear-Substitutes
PunctalPunctal OcclusionOcclusion
Moist-chamber gogglesMoist-chamber goggles
Immuno Suppressants – CyclosporineImmuno Suppressants – Cyclosporine

46. DEWS Review: Available Treatment Options
Treatment Option Group/subgroup
Tear supplementation  Lubricants
Tear retention  Punctal occlusion
 Moisture chamber spectacles
 Contact lenses
Tear stimulation  Secretagogues
Biological tear substitutes  Serum
 Salivary gland autotransplantation
Anti-inflammatory therapy  Cyclosporine
 Corticosteroids
 Tetracyclines
Essential fatty acids  Omega-3 fatty acids
Environmental strategies  Avoid low humidity and air conditioning drafts
 Video display terminal should be lowered below eye level
Management and therapy of dry eye disease: report of the management and therapy subcommittee of the international dry eye workshop (2007). Ocul Surf 2007 Apr;5(2):163-78.

47. 4747
Lubricant ComponentsLubricant Components
• Match characteristics of normal tearMatch characteristics of normal tear
• Lubricants contain:Lubricants contain:
– polymers which affect viscosity/surface tensionpolymers which affect viscosity/surface tension
– buffers which affect pHbuffers which affect pH
– salts which affect tonicitysalts which affect tonicity
– preservativepreservative
• Preservatives can reduce tear film stabilityPreservatives can reduce tear film stability
• Preservative-free products preferredPreservative-free products preferred

48. 4848
Ideal lubricantIdeal lubricant
• The ideal ocular lubricant should:The ideal ocular lubricant should:
– create a stable tear filmcreate a stable tear film
– be comfortablebe comfortable
– be sterilebe sterile
– be free from adverse effectsbe free from adverse effects
– be non-toxicbe non-toxic
– have a pH of 7.0-7.4have a pH of 7.0-7.4
– have a long retention timehave a long retention time
– not impair ocular tissue regenerationnot impair ocular tissue regeneration

49. 4949
Lubricant propertiesLubricant properties
• Key physical properties of a lubricant are:Key physical properties of a lubricant are:
– Surface tension - as close to normal tears as possibleSurface tension - as close to normal tears as possible
(46 dynes/cm2)(46 dynes/cm2)
– pH - around 7.4pH - around 7.4
– Tonicity/ Osmolarity - hypo, hyper or isotonic (asTonicity/ Osmolarity - hypo, hyper or isotonic (as
required)required)
– Viscosity - not so high as to blur vision or causeViscosity - not so high as to blur vision or cause
crustingcrusting

50. 5050
PolymersPolymers
• Long chain moleculesLong chain molecules
• Can increase viscosity of tear filmCan increase viscosity of tear film
• Viscosity increases ocular retention andViscosity increases ocular retention and
increases tear B.U.T.increases tear B.U.T.
• Can affect surface tension of TFCan affect surface tension of TF
• Prolong ocular retention by retardingProlong ocular retention by retarding
evaporationevaporation
• Increased B.U.T. reduces dry spots andIncreased B.U.T. reduces dry spots and
associated discomfortassociated discomfort

51. 5151
PolymersPolymers
• Mimic role of mucinMimic role of mucin
– are surfactants that reduce surface tension of aqueous layerare surfactants that reduce surface tension of aqueous layer
– some polymers adhere to ocular surfacesome polymers adhere to ocular surface
– make corneal surface hydrophilicmake corneal surface hydrophilic
– help spread tearshelp spread tears
• Key considerations - the impact of lubricant componentsKey considerations - the impact of lubricant components
on lipid layeron lipid layer
• Can stabilise or destabilise lipid layerCan stabilise or destabilise lipid layer
• Destabilised lipid layer increases evap’nDestabilised lipid layer increases evap’n
• Some can slow epithelium regeneration time (eg: saline,Some can slow epithelium regeneration time (eg: saline,
methylcellulose 0.5%)methylcellulose 0.5%)

52. 5252
Polyvinyl AlcoholPolyvinyl Alcohol
• Synthetic alcoholSynthetic alcohol
• Commonly used in eye dropsCommonly used in eye drops
• Excellent surface contact timeExcellent surface contact time
• 1.4% PVA has same surface tension as tears - optimises1.4% PVA has same surface tension as tears - optimises
wettingwetting
• 3.0% has longer retention time but higher viscosity can3.0% has longer retention time but higher viscosity can
blur vision (more severe OSD cases)blur vision (more severe OSD cases)
• Does not destabilise lipid layerDoes not destabilise lipid layer
• Does not retard epithelium regenerationDoes not retard epithelium regeneration

53. 5353
Polyvinyl AlcoholPolyvinyl Alcohol
• PVA advantages:-PVA advantages:-
• 1.4% ST is 46 dynes/cm2 - same as tears1.4% ST is 46 dynes/cm2 - same as tears
• water-dragging ability leads to thicker tear filmwater-dragging ability leads to thicker tear film
than HPMCthan HPMC
• promotes corneal health (does not slowpromotes corneal health (does not slow
regeneration as does MC and saline)regeneration as does MC and saline)
• 1.4% does not blur vision1.4% does not blur vision
• does not destabilise tear film (unlikedoes not destabilise tear film (unlike
polysorbate)polysorbate)

54. 5454
MethylcelluloseMethylcellulose
• Non-irritating synthetic compoundsNon-irritating synthetic compounds
• Excellent surface contact timesExcellent surface contact times
• Suitable for more advances OSDSuitable for more advances OSD
• Most useful in treatment of aqueous and lipidMost useful in treatment of aqueous and lipid
deficienciesdeficiencies
• The higher viscosity can produce some blurringThe higher viscosity can produce some blurring
of vision and crusting on lids and lashesof vision and crusting on lids and lashes
• Methylcellulose has been shown to slow cornealMethylcellulose has been shown to slow corneal
regenerationregeneration

55. 5555
CarboxymethylcelluloseCarboxymethylcellulose
• Also known as carmellose sodiumAlso known as carmellose sodium
• From group of synthetic cellulosesFrom group of synthetic celluloses
– carboxymethylcellulosecarboxymethylcellulose
– methylcellulosemethylcellulose
– hydroxypropylmethylcellulosehydroxypropylmethylcellulose
• Excellent surface contact timesExcellent surface contact times
• Carmellose also has negative chargeCarmellose also has negative charge
– promotes adhesion to cornea and prolongs lubricationpromotes adhesion to cornea and prolongs lubrication
and comfortand comfort

56. Cyclosporine OphthalmicCyclosporine Ophthalmic
Emulsion 0.05%Emulsion 0.05%

57. What Is RestasisWhat Is Restasis®®
??
• Ophthalmic Cyclosporine 0.05% emulsion
• Cyclosporine: Immunomodulator
• Cyclosporine inhibits T-cell activation thus
restoring natural tear production
• Restasis®
ophthalmic emulsion increases tear
production in patients whose tear production is
presumed to be suppressed due to ocular
inflammation associated with
Keratoconjunctivitis Sicca (KCS)

58. How Does RestasisHow Does Restasis®®
Work?Work?
(Cyclosporine 0.05% Ophthalmic Emulsion)(Cyclosporine 0.05% Ophthalmic Emulsion)
• Restasis®
is believed to inhibit T-cell activation
(Kunert et al, Arch Ophthalmol. 2000;118:1489)
– Activated T-cells produce cytokines that may result in
• Recruitment of additional T cells (Stern et al, IOVS.
2002;43:2609)
• Increased cytokine production (Pflugfelder et al, Curr Eye Res.
1999;19:201)
• Neural signal to lacrimal gland that disrupts
production of natural tears
– Leads to a decrease in quality and quantity of tears
– Tissue damage in lacrimal glands and ocular surface
(Yeh et al, IOVS. 2003;44:124)

59. Cyclosporine Is EffectivelyCyclosporine Is Effectively
Delivered to Target TissueDelivered to Target Tissue
• Cyclosporine 0.05% ophthalmic emulsion
– Instilled BID in rabbits
• Cyclosporine in surface tissues
– Cornea—1550 ng/g- half life 40 hours
– Conjunctiva—713 ng/g
– Lacrimal gland—12 ng/g
• Intraocular cyclosporine
– Aqueous humor—1.4 ng/mL
– Retina—<0.7 ng/g

60. Pre CsA Post CsA
CD3
Dry Eye Dog Conjunctiva

61. Omega 3 Fatty AcidsOmega 3 Fatty Acids

62. Improvement in Meibum Scores with
ω-3 Fatty Acids
6363
 ω-3 fatty acids aid in clearing and thinning of meibomian
gland secretions.
 ω-3 fatty acids alter fatty acid saturation in meibum gland.

63. 6464
Effect Of ω-3 Fatty Acids on
the Dry Eye Network

64. 6565
Lubricants:-Eye dropsLubricants:-Eye drops
Eye DropsEye Drops
• Most widely used lubricant modalityMost widely used lubricant modality
• Used in the first instance by most Px’sUsed in the first instance by most Px’s
suffering with OSDsuffering with OSD
• Available in unit or multi-dose formatsAvailable in unit or multi-dose formats

65. Thank You.Thank You.
6666