This document provides an overview of dry eye disease. It defines dry eye as a multifactorial disease resulting from tear deficiency or excess evaporation, causing symptoms like eye discomfort. Diagnostic tests evaluate tear secretion, stability, and damage to the ocular surface. Clinical features include irritation, redness, blurred vision, and staining of the cornea or conjunctiva. Dry eye exists on a spectrum of severity and has many predisposing factors like age, gender, medication use, contact lens wear, surgery, and autoimmune diseases.

1. Pavankumar

2. INTRODUCTION
• Dry eye is a multifactorial disease of the tears and ocular
surface due to tear deficiency or excessive evaporation 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.*
*2007 Report of the Dry Eye Work Shop (Ocul Surf 2007;5[2]:65-204)

3. SOME RELATED TERMS ...
• Keratoconjunctivitis Sicca
Any eye with some degree of dryness
• Xerophthalmia
Dry eye associated with Vitamin A deficiency
• Xerosis
Extreme ocular dryness and keratinization associated with
severe conjunctival cicatrisation

4. Dry eye is a disturbance of Lacrimal Function Unit
(LFU)
• Tearing apparatus
– Production- lacrimal gland
– Clearance- lacrimal passages
• Ocular surface
– Conjunctiva
– Cornea
• Eyelids
• Sensory and motor
nerves

5. Tear secretion
• Lacrimal gland
– Producing the watery part of the tear film called
the aqueous.
• Meibomian glands
– Producing lipids which keep the tear film from
evaporating.
• Goblet cells of the conjunctiva
– Producing mucin which allows the wetting of the
ocular surface as well as stabilizes the tear film.

6. Tear and the Tear Film
• Function :
– Maintain a smooth corneal surface
– Moistens cornea and conjunctiva
– Lubrication of pre-ocular surface and lids
– Transfer of oxygen to cornea from ambient air
– Prevents infection

7. Healthy Tears
• A complex mixture of proteins,
mucin, and electrolytes:
• Antimicrobial proteins:
• Lysozyme, lactoferrin
• Growth factors & suppressors of
inflammation:
• EGF, IL-1RA
• Soluble mucin 5AC secreted by
goblet cells for viscosity
• Electrolytes for proper osmolarity
Stern et al. In: Dry Eye and Ocular Surface Disorders. 2004., Image adapted from: Dry Eye and Ocular Surface Disorders. 2004

8. Tears in Chronic Dry Eye
• Decrease in many proteins
• Decreased growth factor
concentrations
• Altered cytokine balance
promotes inflammation
• Soluble mucin 5AC greatly
decreased
• Due to goblet cell loss
• Impacts viscosity of
tear film
• Proteases activated
• Increased electrolytesSolomon et al. Invest Ophthalmol Vis Sci. 2001.Zhao et al. Cornea. 2001.Ogasawara et al. Graefes Arch Clin Exp Ophthalmol. 1996.
Image adapted from: Dry Eye and Ocular Surface Disorders. 2004.

9. •Tear film disorders
–Aqueous tear deficiency
–Lipid tear deficiency
–Mucoprotein deficiency
–Kinetic disorders of lacrimal fluid

10. • DRY EYE IS A CONTINUUM OF DISEASE

11. THE HEALTHY EYE
Stern et al, Cornea. 1998:17:584
NORMAL TEARING
DEPENDS ON A
NEURONAL FEEDBACK LOOP
Secretomotor
Nerve Impulses
Tears Support and Maintain
Ocular Surface
Lacrimal
Glands Ocular Surface
Neural Stimulation

12. DRY EYE DISEASE: An Immune-Mediated
Inflammatory Disorder
INFLAMMATION DISRUPTS
NORMAL NEURONAL
CONTROL OF TEARING.
Lacrimal Glands:
• Neurogenic
Inflammation
• T-cell Activation
• Cytokine Secretion into
Tears
Interrupted
Secretomotor
Nerve Impulses
Tears Inflame Ocular
Surface
Cytokines
Disrupt Neural Arc
Stern et al, Cornea. 1998:17:584

13. PREDISPOSING FACTORS

14. CLASSIFICATION
• International Dry Eye Workshop (DEWS):
– 3-part classification
• Etiology
• Mechanism
• Severity
• Updated by National Eye Institute on basis of
etiopathogenesis:
– Aqueous deficiency state
– Evaporative state

16. Aqueous deficiency state

17. • Non-Sjögren syndrome
– Primary lacrimal gland deficiencies
• Age related
• Congenital alacrima
• Familial dysautonomia
– Secondary lacrimal gland deficiencies
• Lacrimal gland infiltrations
– Sarcoidosis
– Amyloidosis
– Tuberculosis
– Lymphoma
– Hemochromatosis
• Graft vs host disease (GVHD)
• Lacrimal gland ablation/denervation

18. – Lacrimal obstructive disease
• Trachoma
• Ocular cicatricial pemphigoid
• Stevens- Johnson syndrome
• Chemical/thermal injuries
• Post-radiation fibrosis

19. – Medications
• Antihypertensives
• Antiandrogens
• Antidepressants
• Cardiac Antiarrhythmic Drugs
• Parkinson’s Disease Agents
• Antihistamines
• Anticholinergics
• Beta-blockers
• Preservatives in Tears
• Topical anesthetics

20. – Reflex hyposecretion
• Reflex sensory block
– Neurotrophic keratitis
– Post-infective, eg: HSV, HZO
– Chronic contact lens wear
– Corneal surgeries, eg: limbal incisions, refractive surgeries,
keratoplasty
• Reflex motor block
– Neuroparalytic keratitis

21. – Low blink rate
• Parkinson’s disease
– Disorder of eye lids and lid/globe congruity
• Lid palsy
• Exophthalmos

22. • Dry eye in contact lens users:
– Contact lens dynamics:
• Alterations in the pre corneal tear film (PCTF)
• Reduction in corneal sensations
• Corneal hypoxia
• Reduced blinking
• Thermal destabilisation.

24. Dry eye severity
level
1 2 3 4
Discomfort,
severity
& 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
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, ↓
meniscus
Filamentary
keratitis,
mucus clumping,
↑ tear debris
Filamentary
keratitis,
mucus clumping,
↑ tear debris,
ulceration
Lid/meibomian
gland
MGD variably
present
MGD variably
present
Frequent Trichiasis,
keratinization,
Symblepharon
TFBUT (sec) Variable ≤ 10 ≤ 5 Immediate
Schirmer’s score
(mm/5 min)
Variable ≤ 10 ≤ 5 ≤ 2

25. Environment,
Medications,
Contact Lens,
Surgery
Rheumatoid Arthritis
Lupus,
Sjögren’s,
Graft vs Host Disease
Menopause,
Meibomian Gland
Disease
Symptoms of Ocular Surface Disease
Inflammation
Tear
Deficiency/
Instability
Irritation
Triggers of Dry Eye Disease

26. Increases significantly with age
Prevalence of dry eye symptoms by age
0
5
10
15
20
Age 48-59 Age 60-69 Age 70-79 Age 80-91
Prevalence(%)
Beaver Dam study Arch Oph 2000, 118:1264-1268

27. More in women
Prevalence of dry eye symptoms by age and sex
0
10
20
30
Age 48-
59
Age 60-
69
Age 70-
79
Age 80-
91
Prevalence(%)
Women
Men
Beaver Dam study Arch Oph 2000, 118:1264-1268

28. CLINICAL MANIFESTATION
 Irritation
 Redness
 Burning/ Stinging
 Tearing
 Contact lens intolerance
 Increased frequency of blinking
 Itchy eyes
 foreign body sensation
 Blurred vision
 Photophobia (less frequent symptom)
 Thick sticky mucous discharge

29. – Worsening of symptoms:
 As day progresses
 After prolonged reading, working on computers
 In windy or air-conditioned environments
 many symptoms are similar to those seen in more common
conditions - mild blepharitis, conjunctival infections, allergies &
refractive errors

30. • Ocular history details about the following:
• Topical medications used, their frequency, and their effect on
symptoms: e.g., anti-histaminic, glaucoma medications,
vasoconstrictors, corticosteroids
• Contact lens wear: type of CL, wearing schedule, and care
• Allergic blepharo-conjunctivitis or other type of chronic allergic
eye disease
• Ocular surgical history: e.g., prior keratoplasty, cataract surgery
and its type, keratorefractive surgery
• Ocular surface disease: e.g., herpes simplex virus, varicella zoster
virus, OCP, SJS, aniridia, GVHD

31. Chemical injury: e.g., lime burn or any other
• Chronic viral infections: e.g., hepatitis C, HIV
• Non-ocular surgery: e.g., bone marrow transplant, head
and neck surgery, trigeminal neuralgia surgery
• Radiation of the orbit or nearby area
• Neurological conditions: e.g., Parkinson disease, Bell’s
palsy, trigeminal neuralgia
• Smoking or exposure to passive smoking
• Technique and frequency of facial washing including
eyelid hygiene

32. ON EXAMINATION
• Eye lids:
 Lid margin
 Eye lashes
 Infections
 Crusting/keratinisation
 Lid closure
• Conjunctival sac:
 Decreased tear meniscus
 Increased debris in the tear film
 Mucous discharge
• Bulbar conjunctiva:
 dry lustreless
 Muddy
 Bitot’s spots
 hyperaemia

33. • Cornea:
– Dry lustreless, hazy look
– Irregular surface
– Superficial punctuate keratitis (Fluorescein staining may be
helpful)
– filaments
– Ulcers/scars in severe cases

34. • Clinical presentation can vary in severity
MildMild SevereSevere
Fluorescein
Dye Stain
Slitlamp

35. DIAGNOSTIC TESTS
• Aims :
– Tear secretion assessment
– Tear volume assessment
– Tear clearance assessment
– Evaluation of tear film stability
– Ocular surface damage assessment

36. • Tear break-up time (TBUT) test – to evaluate tear-film stability;
• Ocular surface dye staining(Fluorescein/rose Bengal/Lissamine
green) test:
to evaluate ocular surface disease (KCS);
• Schirmer test: to evaluate aqueous tear production
• These tests should be performed in this sequence because the
Schirmer test can disrupt tear film stability and cause false-positive
ocular-surface dye staining.

37. • Tear secretion assessment
• Schirmer’s test
– Schirmer’s I : Conjunctival stimulation
– Schirmer’s II : Nasal stimulation
– Schirmer’s III : Retinal stimulation

38. Schirmer Test
Upto 30 years : 20 mm/5 min
31-50 years : 13 mm/5 min
51 and above : 10mm/5 min
< 5 mm/5 min- dry eye
<3 mm/5 min- if topical anesthesia is used.
Zappia RJ, Am.J.Ophthol 1972; 74: 160-162

39. • Evaluation of tear film stability
– Tear film break-up time (TBUT)
• Fluorescein TBUT
• Non-invasive TBUT
– Lipid layer assessment
• Ocular surface damage assessment
– Staining
– Corneal sensitivity
– Impression cytology
– Tear osmolarity
– Tear protein assays
0 1
2 3

40. T-BUT
• Procedure
• Apply flourescene strip
• Frequent blink
• Examine in SLE with cobalt blue filter
• Inference: Recurrent tear break-up in the same area may
indicate localized anterior basement-membrane abnormalities.
• Break-up times less than 10 seconds are considered abnormal.
• A rapid tear break-up time is observed in both aqueous tear
deficiency and meibomian gland disease
• Precaution : The tear break-up time should be evaluated before
the instillation of any eye drops and before the eyelids are
manipulated in any way…

41. • STAINING:
– Fluorescein dye
– Rose-bengal dye
– Lissamine green
• Grading:
– Location
– Intensity

42. ROSE BENGAL
• Rose Bengal staining is more intense on the
conjunctiva than the cornea.
• The dye stains ocular surface cells that lack a
mucous coating as well as debris in the tear film,
• red-free filter
• Concentrion is 1 % of 25 ul is used
• Dis advantage :
• causes more Irritation than flourescene & lissamine

43. • Grading :
• 0-absent
• 1-just present
• 2-moderate staining
• 3gross staining
• -NEI workshop grading:
– Cornea (Fluorescein) >3/15
– Conjunctiva (Rose-bengal) >3/18
2
4
5 31
5
4
3
2
61

44. • Interpretations:
• Diffuse corneal and conjunctival staining is
commonly seen in viral keratoconjunctivitis and
medicamentosa.
• Staining of the inferior cornea and bulbar
conjunctiva is typically observed in patients with
staphylococcal blepharitis, MGD, lagophthalmos,
and exposure,
• Staining of the superior bulbar conjunctiva is
typically seen in SLK.

45. • Corneal sensitivity with wisp of
cotton/anaesthesiometry
• Tear osmolarity is measured with occusense
volume independent tear osmometer
• Procedure: small nano litre of tear is taken from
lower eye lid with micropippet with cappilary
action
• & transferred to a chip where it measures
osmolarity of tear
• Normal is 203-300,
• In dry eye it will go upto 316

46. IMPRESSION CYTOLOGY
• Used for grading the severity
• Has also been used as a prognostic indicator in
evaluating efficacy of therapeutic measures
• Mainly it is for superficial epi cells to see any inlamatory
mediators/markers
• Procedure:
• Topical anaesthesia
• Filter paper(poly ether sulfone filters)
• Transferred to paraldehyde solution 0.05%
• Keep it in at 4*c
• Centrifuge & cells are immunostained & analysed by flow
cytometry

47. Impression Cytology
• Features:
– Relatively larger cell size
– squamous metaplasia
– inflammatory cells
– decrease in goblet cell densities

48. • BUSH CYTOLOGY TECHNIQUE:
• ANOTHER METHOD OF CYTOLOGY , BUT
FOR BOTH SUP & DEEP EPI CELLS

49. FERNING TEST
• To see quality of tears, electrolyte concentration,
hyperosmolarity
• Procedure:
• Tear from meniscus (1ul) is transferred to slide , allowed for
evaporation at 20* c +/- 3*c for ten minutes
• & see for crystalisation or ferning pattern
• Various patterns:
• Type 1:uniform large arborisation
• Type 2:ferning adequate but lesser size
• Type 3:partially present, incompletelly ferning
• Type 4: no ferning
• Inference
• Type 1 & 2 are normal
• 3 & 4 are abnormal

50. • Tear volume assessment
– Tear meniscus height
• Tear clearance assessment
– Fluorescein clearance test
• Basal tear secretion
• Reflex tear secretion
• Tear clearance
– Fluorophotometry
– Tear function index

51. • Tear meniscus examination:
• Radius , height, cross cectional area has to be
seen
• Slit lamp
• Through a light of alternating white & black band
each measuring about 4 mm in size with the help
of rotatable projector system
• Take images & analysed with help of computer
• Inference:
• if <0.18 mm then it is abnormal

52. Tear function index
• To evaluate tear dynamics
• That is production & drainage
• Strip is left in place for 3 minutes& eye lid closed
• See the distance between notch of strip & wetted
area
• Also intensity is compared

53. Sequence of testing
• Clinical tests
– NIBUTS
– FBUT
– Schirmer’s
– Staining
• Lab tests
– Impression cytology
– Tear osmolarity
– Tear protein assays

54. Potential Severe Consequences of Untreated
Dry Eye Disease
Sterile Melting Bacterial Keratitis

55. MANAGEMENT
• Goals of management:
– Establish the diagnosis.
– Differentiate from other causes of similar symptoms.
– Establish presence/absence of limbal cell deficiency.
– Decide appropriate therapy.
• To relieve symptoms
• To prevent complications
– Educate patient / relatives about nature of disease and its
management.

56. • A. Tear
supplementation:
lubricants
• 1. General characteristics
and effects
• 2. Preservatives
• 3. Electrolyte composition
• 4. Osmolarity
• 5. Viscosity agents
• B. Tear Retention
• 1. Punctal occlusion
• b. Types
• d. Indications and
contraindications
• e. Complications
• 2. Moisture chamber
spectacles
• 3. Contact lenses

57. • C. Tear stimulation:
secretagogues
• D. Biological tear
substitutes
• 1. Serum
• 2. Salivary gland
autotransplantation
• E. Anti-inflammatory therapy
• 1. Cyclosporine
• 2. Corticosteroids
• 3. Tetracyclines
• F. Essential fatty acids
• G. Environmental strategies

58. • Elimination/avoidance of exacerbating factors which
• Decrease tear production
• Increase tear evaporation
– Humidification of rooms
– Avoidance of dusty/smoky rooms
– Breaks between prolonged computer use
– Lowering the computer monitor below eye level
– Low water content contact lenses for Shorter duration at a time.
– Blinking exercises*
• *Wolkoff P et al. Occup Environ Med 2005;62:4-12

59. • Tear supplementation
– Ideal tear supplement should
• Be preservative free
• Contain K+
, HCO3
-
and other electrolytes
• Have a polymeric system to increase its viscosity, hence
retention time
• Have neutral to slightly alkaline pH
• Have osmolarity- 181-354 mOsm/L

60. • Tear retention
– Punctal occlusion: Temporary and Permanent.
• Absorbable
– collagen or polymers
– Duration- 1 week- 6 months
• Nonabsorbable
– Silicone or acrylic
– Moisture chamber spectacles
– Contact lenses
• Severe dry eye
– Retain tear film
– Promote ocular surface healing
– Tarsorrhaphy

62. • Biological tear substitutes
– Autologous serum tears1
– Can be stored frozen for 3-6 months
– Autologous platelet rich plasma2
– Salivary gland autotransplantation3
• 1. Geerling G et al. Br J Ophthalmol 2004;88:1467-74.
• 2. Alio JL. Journal of Refractive Surgery 2007;23.
• 3. Geerling G et al. Ophthalmology1998;105:327-35.

63. • Anti-inflammatory therapy
– Topical cyclosporine
• Only pharmacological agent approved by FDA for treatment of dry eye
• Reduces conjunctival IL-6 levels, activated lymphocytes, inflammatory and
apoptotic markers
• Increases conjunctival goblet cell number
– Corticosteroids
• Recommended only for short-term use
– Systemic medications
• Oral tetracyclines (used for anti-inflammatory action)
– Decrease matrix metalloproteinase activity and production of cytokines such as IL-1 and
TNF-ɑ

64. • Eyelid hygiene
– Hot fomentation
– Topical/systemic antibiotics
– Topical steroids
– Artificial tear substitutes

65. • Essential fatty acids
– Reduce inflammation(inhibit the synthesis of lipid mediators &
block IL-1 & TNF.
– Alter the composition of meibomian lipids
• Omega-3 fatty acids
– Inhibit the synthesis of proinflammatory mediators (PGs and LTs)
– Block the production of IL-1 and TNF-ɑ
• Omega-6 fatty acids
– Precursors of proinflammatory mediators (PGE2 and LTB4)
• High Ω-6: Ω- 3 ratio is associated with greater risk for dry eye disease*

66. • Surgical options
– Reserved for severe-very severe dry eyes
• Tarsorrhaphy
• Mucous membrane grafting
• Salivary gland transposition
• Amniotic membrane transplantation

67. NEWER DRUGS ON THE BLOCK
– Tear stimulation: secretogogues
• Diquafosol (P2y2 receptor agonist)
• Ecabet sodium (mucous secretion stimulant)
• Rebamipide
• Gefarnate
– N-acetyl-cystine eye drops.
– Chloroquine Phosphate eye drops (0.3mg/ml).
– Lacriserts, collagen shields.
– Androgen ointment.

68. • Treatment recommendations by severity level
• Level 1:
• Education and environmental/dietary modifications
• Elimination of offending systemic medications
• Artificial tear substitutes, gels/ointments
• Eye lid therapy
• Level 2:
• If Level 1 treatments are inadequate, add:
• Anti-inflammatories
• Tetracyclines (for meibomianitis, rosacea)
• Punctal plugs
• Secretogogues
• Moisture chamber spectacles

69. • Level 3:
• If Level 2 treatments are inadequate, add:
• Serum
• Contact lenses
• Permanent punctal occlusion
• Level 4:
• If Level 3 treatments are inadequate, add:
• Systemic anti-inflammatory agents
• Surgery (lid surgery, tarsorrhaphy; mucus
• membrane, salivary gland, amniotic
• membrane transplantation)

70. SUMMARY
• Eliminating the etiological factors
• Tears replacement therapy
• Maintain moisture in the eyes
• Increasing the tear secretion
• Immune inhibition therapy
• Re-establish the tear film
• Other supporting treatment

71. CARRY HOME MESSAGE…
• Methodical approach to diagnosis.
• Do not miss subtle clinical signs.
• Carefully plan the line of treatment.
• Irrespective of cause of dry eye- immunomodulation + tear replacement.
• Educate the patient and family members about the dilemmas in
management.

72. THANK YOUTHANK YOU