1. • Aj ay Kumar Singh
• Ar t i Elhence Agar wal
• Depar t ment of Opht halmology
• King Geor ge‘s Medical Univer sit y,

2. INTRODUCTION
• 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. *
*2007 Report of the Dry Eye Work Shop (Ocul Surf 2007;5[2]:65-204)

3. • According to the International task force guidelines for diagnosis
and treatment of dry eye1
X
Dry eye disease Dysfunctional Tear Syndrome (DTS)
1. Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome. A Delphi approach to treatment recommendations. Cornea. 2006;25:
90-97.

4. 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

5. 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

6. 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.

7. 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

8. 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

9. 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
• Increasedet electrolytes Vis Sci. 2001.Zhao et al. Cornea. 2001.Ogasawara et al. Graefes Arch Clin Exp Ophthalmol. 1996.
Solomon al. Invest Ophthalmol
Image adapted from: Dry Eye and Ocular Surface Disorders. 2004.

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

11. Ocular surface disorders
•Corneal and conjunctival lesions:
–Squamous epithelization type
–Limbal stem cell deficiency type

12. • DRY EYE IS A CONTINUUM OF DISEASE

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

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

15. PREDISPOSING FACTORS

16. 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

17. Aqueous deficiency state

18. • 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

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

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

21. – 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

23. – Meibomian gland disease
• Reduced number- congenital deficiency
• Meibomian gland dysfunction
– Hypersecretory- seborrhea
– Hyposecretory- retinoid therapy
– Obstructive
» Simple- blepharitis, atopy, ichthyosis etc.
» Cicatricial- trachoma, pemphigoid, burns

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

25. • 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.

27. Dry eye severity 1 2 3 4
level
Discomfort, severity Mild and/or episodic; Moderate episodic or Severe frequent or Severe and/or
& frequency occurs under chronic, stress or no constant without disabling and
environmental stress stress stress constant
Visual symptom None or episodic Annoying and/or Annoying, chronic Constant and/or
mild activity-limiting and/or constant, possibly disabling
fatigue episodic limiting activity
Conjunctival None to mild None to mild +/– +/++
injection
Conjunctival None to mild Variable Moderate to marked Marked
staining
Corneal staining None to mild Variable Marked central Severe punctate
(severity/location) Erosions
Corneal/tear signs None to mild Mild debris, ↓ Filamentary keratitis, Filamentary keratitis,
meniscus mucus clumping, mucus clumping,
↑ tear debris ↑ tear debris,

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

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

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

31. 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

32. – 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

33. • Coexisting connective tissue disease, rheumatoid arthritis,
thyroid abnormalities
• History of prolonged medication
– topical
– systemic
• History of prolonged dryness of oral cavity, repeated
mucosal ulcers

34. 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

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

36. • Clinical presentation can vary in severity
Mild Severe
Slitlamp
Fluorescein
Dye Stain

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

38. • Tear secretion assessment
• Schirmer’s test
– Schirmer’s I : Conjunctival stimulation
– Schirmer’s II : Nasal stimulation
– Schirmer’s III : Retinal stimulation
– Jones’ modification : Basal secretion
(2mts. After LA)
• Phenol red thread test- more reliable than Schirmer’s test

39. 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

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

41. • 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 0 1
– Tear protein assays
2 3

42. • STAINING: 2
– Fluorescein dye 5 1 3
– Rose-bengal dye
– Lissamine green 4
• Grading:
– Location
– Intensity
• NEI workshop grading: 2 4
– Cornea (Fluorescein) >3/15
1 6
– Conjunctiva (Rose-bengal) >3/18 3 5

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

44. Impression Cytology
• Used for grading the severity
• Has also been used as a prognostic indicator in
evaluating efficacy of therapeutic measures
• Features:
– Relatively larger cell size
– squamous metaplasia
– inflammatory cells
– decrease in goblet cell densities

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

46. 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.

47. • 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

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

49. • 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

50. • 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

51. • 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.

52. • 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

53. • Essential fatty acids
– Reduce inflammation
– 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*
• *Miljanovic B et al. Am J Clin Nutr 2005;82:887-93.

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

55. 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.

56. 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

57. 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.

58. THANK YOU