1. Understanding and Clinical Management of Dry Eye FatmaAsyari AINI Eye Hospital Klinik Mata Mayestik RSPI

2. Ocular Surface ( cornea & conjunctiva ) Very sensitive Should be clear and moist Tears : support and maintain integrity Blinking reflex : 4x / min Dry spot  pain  reflex stimulation  lacrimation

3. Dry eye Extremely common in our daily practice Any age , female , male , even children Can be mild to severe Devastating and frustrating “ Long life treatment “ ?

4. Lacrimation PONS N.VII Secreto-motor Nerve Impulses Lacrimal Glands Tears Support and Maintain Ocular Surface Ocular Surface Neural Stimulation N.V dry spot  pain  reflex stimulation  lacrimation

5. Tear film composition Lipid :0.1 um esters, glycerol , fatty acids product of palpebralmeibomian glands prevents excessive evaporation

7. electrolytes, protein, antibody, oxygen , CO2, mineral , glucose Epithelium

8. Mucin : 0,02 - 0,05 um Product of conjunctival Goblet cells present in bulbar conjunctiva , caruncula Maintain tear film stability Glycocalyx produced by epithelial cells help bind mucins onto the epithelial surface

9. Tear outflow / each blink ( 4 x / min )

10. Tear film function Maintain integrity of cornea & conjunctiva Smoothes ocular surface , improve vision Wash away all the dirty materials coming onto the eye Moisturizing, lubricating for comfort , eye movements Media transport for O2 , CO2 ( 40% from atmosphere ) Nutrition ( glucose, electrolytes, enzymes , protein ) Defense : Anti bacterial, antibodies, lisozyme

12. Definition NEI-Industry Workshop 1995 Dry eye is a disorder of the tear film due to tear deficiency or excessive tear evaporation which causes damage to the interpalpebral ocular surface and is associated with symptoms of ocular discomfort DEWS Report 2007 Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbances, and tear instability with potential damage to ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface

14. Dry Eye – Inflammation Model

15. Dry Eye Etiology Tear Deficient Evaporative Sjogrens Non-Sjogrens Oil Deficient Lid Related Surface Change Contact Lens Lacrimal Deficiency Lacrimal Obstruction Reflex Auto-antibodies NEI Workshop - Classification of Dry Eye

16. Dry Eye – Tear Film Deficiencies Lipid Layer Deficiency alterations in meibomian gland secretion (e.g. blepharitis, hordeolum, chalazion ) Aqueous Layer Deficiency aqueous deficient dry eye (e.g. inflammation, neurological defects, trauma, congenital absence, etc ) Mucin Layer Deficiency mucindeficient dry eye (e.g. Stevens-Johnson syndrome, pemphigoid, vitamin A deficiency, trachoma, radiation, etc.)

18. Gender

19. Arthritis

20. Osteoporosis

21. Gout

22. Lens Surgery

23. Contact Lens Wear

24. Blink Disorders

25. Disorders of Lid Aperture

26. Nutritional Problems

27. Rheumatoid Arthritis

28. Thyroid Problems

29. Time of Day

30. LASIK Surgery

31. Cosmetic Surgery

32. Gender

33. Mechanical Disturbances

34. Exposure Keratitis

35. Entropion

36. Ectropion

38. Lagophthalmos

39. Incomplete Blinking

40. Dellen Formation

41. Illumination

42. Temperature

43. Humidity

44. Air movement

45. Allergies

46. Change in environment

47. Reading

48. Watching Movies

49. SleepPrause 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.

50. Conditions associated with dry eye Chronic Systemic inflammation Sjogren’s Syndrome, rheumatroid arthritis, lupus Ocular surface inflammation Meibomian gland disease, keratitis, infection Hormonal changes Menopause, oral contraceptives, pregnancy, lactation Systemic disease Diabetes, thyroid Stevens Johnson’s syndrome : severe dry eye

51. Environment Smoke, air pollution, wind, heat, air-conditioning, air travel, light, dry climate staring at TV , computer reading , SMS etc ( Less blinking reflexes ) Medications Blink disorder Anatomical surgical (LASIK)

52. Dry eye is not just adisease, It is a complex, multi-factorial disorder

53. Diagnosis of dry eye Obtaining patient history Physical examination Staining of the corneal surface Tests of tear production Tests of tear film stability (TBUT)

54. Commonest symptoms : “eye discomfort “ irritating burning / stinging easily fatigue itchy foreign body sensation photophobia fluctuating vision contact lens intolerance sticky dryness / watering sleepy discharge redness blurred vision

55. Patient History Ocular symptoms Redness, dryness, itching, burning, constant tearing, etc. Current illnesses Sinus or ear trouble, hay fever, skin disorders, asthma, etc. Medications Antihistamines, beta blockers, oral contraceptives, etc. Duration of the present problem Recent or ongoing...weeks, months, etc. Family history of a similar problem Parents, siblings, Any present refractive condition Glaucoma, cataracts, contact lenses, etc.

56. Physical examination Five main components of a clinical examination involve: The lids The blink mechanism The tear film The ocular surface General physical assessment

57. Signs conjunctival staining blepharitis increased cytokines corneal staining /damage : epitheliopathy, filaments, ulcers hyperemia low tear meniscus Increase tear debris fast tear break up time conjunctival pleating

58. Lid Wiper Epitheliopathy

59. Slit-Lamp BiomicroscopyCorneal Staining Types of corneal staining include: Fluorescein – Discloses epithelial breaks, erosions and filaments Rose Bengal – Assesses degenerated tissue; indirectly measures tear volume deficiencies Lissamine Green – similar to rose bengal but more comfortable to the patient Carboxyfluorescein – shows the extent of any damage to the corneal epithelium

60. Tear Film Break-Up Time ( TBUT ) Time required for a dry spot to appear on the corneal surface after blinking Dry spots will appear as part of normal evaporation and diffusion of tears Normal healthy eye : dry spots start occuring between blinks at about 10-12 seconds, and an urge to blink is triggered

61. Blink Blink TFBUT Tear Protected Ocular Surface Unprotected Ocular Surface Cycle Repeats 0 1 2 3 4 5 6 7 Time (seconds) Staining Ocular Discomfort Dry Eye - Consequences of an ‘Unprotected Ocular Surface’

62. Tests of tear production standard diagnostic tests for aqueous tear production Schirmer test I : the filter paper strip is placed in the unanesthetized eye and is left in place for 5 minutes. no dry eye : enough tears to wet 20 to 25 mm of the paper strip Wetting of < 10 mm is suggestive of dry eye Schirmer Tear Test II : with topical anesthesia .

63. Ferning test : quality and stability of tear film I II III IV

64. How to treat ... Are artificial tears enough?

65. Treatment : supportiveGoals : Alleviate symptoms Reduce ocular morbidity Prevent complications Improve quality of life Improve productivity Maximise benefit and relief Minimise cost Consultations rheumatologist , internal medicine, dermatologis

67. Anatomy of an artificial tear

68. Qualities of an ideal Dry Eye Product Ability to spread evenly over the cornea quickly and efficiently (Long Lasting) Prolonged retention time for extended efficacy (Long Lasting) Objective and subjective improvement in patient signs and symptoms (Efficacy) *Report of the Definition and Classification Subcommittee of the International Dry Eye Workshop (2007). Ocular Surface 2007;5:165.

69. Varieties of Artificial Tears / Lubricants HydroxypropylMethylellulose ( TNII ,Genteal ) Carboxy Methylcellulose ( Refresh ) Polyvinyl Alcohol ( Hypotears ) Dextran Glycerin Eye Gels ( vit.Apalmitate) Polyethylene glycol : Systane Sodium hyaluronates 0.1 – 0.3%

70. HYALUBSodium hyaluronates 0.1% Lubricating , protecting Powerful wetting agent Long lasting Reduce ocular surface damage Accelerate wound healing Safe , well tolerated for long term use Non preservative

71. Treatment should be based on disease severity The ideal artificial lubricant should be preservative-free, contain potassium, bicarbonate, and other electrolytes, and have a polymeric system to increase its retention time. The goals of pharmacotherapy To reduce morbidity and to prevent complications

73. Report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007 Apr;5(2):75-92

74. Surgical treatments( reserved for severe disease poor/non-compliance ) Punctum Plug Surgical / thermal / laser occlusion

75. Punctal plugs Absorbable - Made of collagen or polymers - occlusion duration ranges from 7-180 days - plugs dissolve by themselves or may be removed by saline irrigation Non-absorbable - Made of silicone - punctum plugs and intracanalicular plugs. ( Cylindrical Smartplug )

77. spontaneous loss into the canaliculus

78. canalicular or NLD obstruction

79. extrusion of plug

80. scarring of punctum

81. ocular surface irritation, epiphora

83. Infection / discomfort (Plugs)

85. Future causal therapy of dry eye Cyclosporine A 0.05% drops in moderate and severe ocular surface inflammation essential fatty acids omega-3 in reducing ocular surface irritation Secretion stimulation, mucin stabilizing ,mucolytic agents ,local androgenic complexes systemic immunomodulation / immunosuppressive in severe cases topical anti-CD4 monoclonal antibody to suppress the activation of CD4+ T cells

86. Dry eye is not just adisease, It is a complex, multi-factorial disorder Regardless of the cause, all dry eye patients have in common an abnormal tear film or abnormal tear function individuals who experience signs and symptoms of dry eye at one time or another due to environmental factors = 100%

87. Thank you