Investigations and Management of Dry Eye.pptx

Dry eye disease

1. Dry Eye Disease (Investigations and management) Dr. Fashola Maryam B.

2. Outline Introduction Epidemiology Applied anatomy Aetiology/Classification Pathophysiology Clinical features Investigations Management Conclusion References

3. Introduction “A disorder of the tear film due to tear deficiency or excess tear evaporation which causes damage to the interpalpebral ocular surface and is associated with symptoms of ocular discomfort”. [National Eye Institute, 1995] “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, and accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.” [TFOS DEWS, 2007]

4. Introduction.. “A multifactorial disease of the ocular surface characterized by a loss of tear film homeostasis, and accompanied by ocular symptoms, in which tear film instability & hyperosmolarity, ocular inflammation & damage, and neurosensory abnormalities play aetiological roles.” [TFOS DEWS II, 2017] DED leads to problems with reading, computer use & work performance, and is associated with role limitations, lower vitality & poorer general well being.

5. Introduction… Impact of moderate to severe dry eye on quality of life has been found comparable to the impact of dialysis and severe angina.

6. Epidemiology Dry eye is one of the most common reasons for ophthalmic consultation. Has a global prevalence of 5-50%. The TFOS DEWS II found that DED affects over 30 million people in the United States alone, at least 344 million people worldwide. It becomes increasingly prevalent with age, affecting 10% of people 30–60 years of age and 15% of adults older than 65 years. Commoner in women, from 50years above. Affects all racial and ethnic groups equally.

7. Epidemiology S.I. Olaniyan et al, Dry Eye Disease in an adult population in South-West, Nigeria. 363 patients between 45-72years, 32.5% had dry eye, age was a significant risk factor. (BAK medications, previous ocular surgery, menopause and pterygium were not significant risk factors). S.N. Onwubiko et al, Dry Eye Disease: Prevalence, Distribution and Determinants in a Hospital-Based population, 2014 402 patients between 18-94years, 19.2% had dry eye, age was a significant risk factor.

8. Epidemiology.. S.D. Akojenu et al, Dry Eye Disease in diabetics and non-diabetics at LASUTH . DED prevalence of 81.5% (Diabetics= 78%; Non-diabetics= 85%). Non-diabetics had more severe disease (30.3%) compared with diabetics (14.1%).

9. Applied Anatomy Lacrimal functional unit: lacrimal glands (main and accessory); ocular surface (cornea & conjunctiva); Eyelids & meibomian glands; Interconnecting nerves.

10. Applied anatomy Conjunctiva : translucent mucous membrane, with 2-5 layered non-keratinized epithelium, within which are the Goblet cells . Gland of Manz in limbal conjunctiva. Accessory lacrimal glands: Krause opens into upper & lower fornix; Wolfring into upper border of sup. Tarsus and lower border of inferior tarsus.

11. Applied anatomy Cornea : multi-layered transparent, avascular and densely innervated structure. Epithelium has 5-6 layers, the 2-most superficial layers made up of flattened cells with microvilli. Nerve supply is by anterior ciliary nvs ., which become unmyelinated and form plexuses with nerve endings in the stroma & epithelium.

12. Tear film Healthy tears preserves smooth optical surface, provides comfort, maintains epithelial cell health, and protects from environmental and microbial insults. Lipid layer (0.1um): Maintains smooth optical surface, prevents evaporation. Aqueous layer (7.0um): Complex mixture of water, proteins, mucins, electrolytes, lysozyme, lactoferrin, IgA. Mucous/mucin layer (0.2um): Provides viscosity and stability during the blink cycle.

13. Tear film Regulation of tear film components Hormonal Androgens regulate lipid production; Oestrogen and Progesterone receptors in the conjunctiva and lacrimal gland are essential for normal function. Neural fibres adjacent to lacrimal glands and goblet cells control aqueous and mucous secretion.

14. Applied anatomy… Tears enter the canaliculi by capillarity. 70% lower punctum, 30% upper punctum. The blink reflex eliminates the tears and debris via the lacrimal pump mechanism, and helps spread lipid layer over the eye.

15. Aetiology/Classification

16. Risk factors (TFOS DEWS report) Consistent Probable Inconclusive Age Diabetes Hispanic ethnicity Sex Rosacea Menopause Environment (Low humidity, pollution) Viral infection Acne MGD Thyroid disease Sarcoidosis CTD Psychiatric conditions Smoking Sjogren syndrome Pterygium Alcohol Hormones (Androgen, Estrogen ) Diet (low fatty acid intake) Pregnancy Computer use Refractive surgery Demodex infestation Contact lens wear Allergic conjunctivitis Medication (Botox injection, Multivitamins, OCPs) Medication (Antihistamine, Antidepressants) Medication (anticholinergics, Diuretics, Beta blockers, BAK)

17. Pathophysiology

18. Pathophysiology Tear hyperosmolarity stresses the surface epithelium, leading to release of inflammatory mediators, which.. Disrupt the junctions between superficial epithelial cells, following which.. T-cells infiltrate the epithelium and release pro-inflammatory cytokines (TNF-a, IL-1 etc), which.. Promotes accelerated detachment of epithelial cells & apoptosis, leading to.. Further disruption of cellular junctions and further influx of inflammatory cells and pro-inflammatory cytokines. [VICIOUS CYCLE]. Essentially, inflammation perpetuates the disease.

19. Clinical presentation Soreness Dry sensation Burning Discharge (from accumulated debris in the tear film) Conjunctival hyperaemia Lid hyperaemia FB sensation/Grittiness Blurred vision Non-specific discomfort

20. Clinical presentation Meibomian gland dysfunction Spouting, obstructed land openings. +/-Features of blepharitis. Scarring/Ectropion Lagophthalmos

21. Clinical presentation Conjunctiva: Lustreless Hyperaemia Bitot’s spots Keratinization Scarring Stains with rose Bengal or Lissamin green

22. Clinical presentation… Tear film Tear meniscus height: crude measure of aqueous volume in tear film. [1mm] Foamy/frothy tear film on eyelid margin. Mucous debris/discharge.

23. Clinical presentation Cornea Lustreless Punctate epithelial erosions Filamentary keratopathy Mucous plaques

24. Clinical presentation Sjogren syndrome: autoimmune destruction of lacrimal and salivary gland 1 : Dry eye and Dry mouth in isolation 2 : In association with connective tissue diseases (SLE, RhA, Scleroderma); Autoimmune diseases (GVHD, Immune reaction to head & neck radiation); Infiltrative diseases (Lymphoma, Amyloidosis) Additional features: Arthralgia, myalgia, dry vagina, caries. Histology: lymphocytic infiltration.

25. Sjogren

26. Investigations Aim To assess symptoms. To assess tear secretion. To assess tear volume. To assess tear clearance. To assess tear film stability. To assess presence of ocular damage.

27. Ocular Surface Disease Index (OSDI) Severity Scale

28. Ocular Surface Disease Index (OSDI) Severity Scale

29. Dry Eye Questionnaires Others: Standard Patient’s Evaluation of Eye Dryness (SPEED) Dry Eye Questionnaire-5 (DEQ-5) Contact lens DEQ McConnies Questionnaire Impact of Dry Eye in Everyday Life (IDEEL) Ocular Comfort Index (OCI)

30. Investigations Tear break-up time (TBUT): 2% fluorescein/fluorescein strip is instilled into lower fornix. Patient is asked to blink severally, and then stop. Eye examined with broad slit lamp beam under cobalt blue light, and observed for appearance of first black (dry) spot or line. TBUT <10secs is abnormal.

31. Investigations The basic secretion test is performed after instillation of a topical anaesthetic and light blotting of residual fluid from the inferior fornix. A thin filter-paper strip (5 mm wide, 30 mm long) is placed at the junction of the middle and lateral thirds of the lower eyelid. Repeated measurements of less than 3 mm of wetting after 5 minutes, with anaesthetic, are suggestive of aqueous tear deficiency (ATD).

32. Investigations… The Schirmer I test done without topical anaesthetic measures both basic and reflex tearing. Less than 5.5 mm of wetting after 5 minutes is diagnostic of ATD. It is relatively specific, poorly sensitivity. Whatmann 41 filter paper

33. Investigations The Schirmer II test Measures reflex secretion Done with topical anaesthetic. After the filter-paper strips have been inserted into the inferior fornices , a cotton-tipped applicator is used to irritate the nasal mucosa. Wetting of less than 15 mm after 2 minutes is consistent with a defect in reflex secretion. Serially consistent results are highly suggestive of ATD.

34. Investigations… Conjunctival & corneal staining Fluorescein (2% soln/strip) Rose Bengal (1% soln/strip) Lissamine green. N.B.: Rose Bengal can cause intense stinging, use topical anaesthetic and wash out with saline.

35. Staining..

36. Investigations.. Fluorescein clearance test : 5uL of fluorescein is placed on ocular surface. Schirmer’s strip is place in the lower lateral lid margin at 1, 10, 20 and 30minutes. Strip is examined under blue light and compared to a standard. Delayed clearance (not 0 at >20minutes) is seen in all dry eye states.

37. Investigations Assays Tear Lactoferrin assay : Radial immunodiffusion assay (Normal: 2.2mg/ml) Immunoglobulin E assay Matrix Metalloproteinase-9 assay

38. Investigations… Phenol red thread test: pH indicator The ends of a phenol red thread is inserted into the lower fornix. The dye changes from yellow to orange/red It is removed and measured after 15seconds. <6mm is abnormal.

39. Investigations Tear meniscometry : measures tear meniscus height. Optical coherence tomography TMH<1.64mm TMD<1.82mm

40. Investigations Impression cytology : Cellulose acetate filter applied to ocular surface to remove the superficial layers of the ocular surface. Air dried and stained with periodic acid Schiff (PAS) and haematoxylin. Examined under light microscopy.

41. Investigations… Meibography : Uses a slit lamp, Infrared filter and infrared video camera.

42. Investigations… Tear film interferometry : Assesses the lipid layer of tear film, by using a tear interference camera.

43. Diagnostic algorithm (TFOS DEWS II)

44. Dry Eye Severity Grading Scheme

45. Management The aim of management in dry eye disease is: Provide comfort; Break the vicious cycle of the disease; Restore ocular surface homeostasis as much as possible; Improve quality of life. Manage underlying diseases. Modify the environment.

46. Management…

47. Management… Tear substitutes (preferably non-preserved) Drops and gels Cellulose derivatives (Hypromellose} – in mild cases. Carbomers ( Viscotears )- viscosity improves duration of action. Polyvinyl alcohol ( Hypotears )- useful in mucin deficiency. Sodium hyaluronate ( Vismed ) –promotes ocular surface healing. Autologous serum – contains Vit. A, lysozyme, fibronectin & TGF-B. Supports proliferation, differentiation and maturation of normal ocular surface Ointments – night-time use.

48. Management… Mucolytic agents Acetylcysteine 5% drops qds – to eliminate corneal filaments and plaques. Debridement can also be done. Secretagogues Oral Pilocarpine 5mg qds /1% topical qds – improves lacrimal gland secretion. Causes blurred vision and excess sweating. Anti-inflammatory agents Cyclosporine A (0.05%, 0.1%) twice daily – prevents T-cell activation, increases density of goblet cells, reverses conjunctival squamous metaplasia.

49. Management… Anti-inflammatory agents (cont’d) Steroids – low potency steroids e.g. fluorometholone qds Tetracyclines – decreases MGD & rosacea, treats recurrent corneal erosion (inhibits MMP-9), anti-inflammatory (inhibits IL-1B). Azithromycin –useful in anterior blepharitis. Dietary change – diets rich in Omega-3 fatty acids/ fish oil capsules 3000mg/day. Decrease inflammation, stimulates tear production and alters the lipid profile in meibomian glands.

50. Management… Contact lenses – e.g.: PROSE (Prosthetic Replacement of Ocular System Ecosystem) Fluid-filled reservoir – hydrates cornea Shields cornea from blink trauma, noxious stimuli and inflammatory mediators in tears.

51. Management… Punctal occlusion – reduces drainage and prolongs the exposure of natural tears or artificial tears Temporary: collagen plugs inserted into canaliculus for 1-2weeks. Prolonged Reversible: Silicone or long acting collagen plugs (2-6months). Can migrate distally, be extruded, or form granuloma. Permanent: cauterization of punctum. Surgery: Lateral tarsorrhaphy, Submandibular gland transplantation.

52. Management : Recommendations for the staged management and treatment of DED. Step 1: Education regarding the condition, its management, treatment and prognosis Modification of local environment Education regarding potential dietary modifications (including oral essential fatty acid supplementation) Identification and potential modification/elimination of offending systemic and topical medications Ocular lubricants of various types (if MGD is present, then consider lipid-containing supplements) Lid hygiene and warm compresses .

53. Management : Recommendations for the staged management and treatment of DED. Step 2: If above options are inadequate consider: Non-preserved ocular lubricants to minimize preservative-induced toxicity . Tea tree oil treatment for Demodex (if present) Tear conservation Punctal occlusion Moisture chamber spectacles/goggles Overnight treatments (such as ointment or moisture chamber devices) In-office, physical heating and expression of the meibomian glands (including device-assisted therapies, such as LipiFlow )

54. Management : Recommendations for the staged management and treatment of DED. In-office intense pulsed light therapy for MGD . Prescription drugs to manage DED Topical antibiotic or antibiotic/steroid combination applied to the lid margins for anterior blepharitis (if present) Topical corticosteroid (limited-duration) Topical secretagogues Topical non-glucocorticoid immunomodulatory drugs (such as cyclosporine) Topical LFA-1 antagonist drugs (such as lifitegrast ) Oral macrolide or tetracycline antibiotics .

55. Management : Recommendations for the staged management and treatment of DED. Step 3: If above options are inadequate consider: Oral secretagogues Autologous/allogeneic serum eye drops Therapeutic contact lens options Soft bandage lenses Rigid scleral lenses

56. Management : Recommendations for the staged management and treatment of DED. Step 4: If above options are inadequate consider: Topical corticosteroid for longer duration Amniotic membrane grafts Surgical punctal occlusion Other surgical approaches T arsorrhaphy S alivary gland transplantation) .

57. Conclusion Dry eye Disease is a common ocular inflammatory disease, it is associated with significant ocular morbidity and can have a substantial effect on quality of life. Early diagnosis and prompt treatment is therefore essential.

58. Refrences Lemp 1995 ; Lemp 1998 ; Pflugfelder 2000 S.I. Olaniyan et al, Dry Eye Disease in an adult population in South-West, Nigeria. S.N. Onwubiko et al, Dry Eye Disease: Prevalence, Distribution and Determinants in a Hospital-Based population, 2014 S.D. Akojenu et al, Dry Eye Disease in diabetics and non-diabetics at LASUTH, 2019 . TFOS DEWS II report, 2017. S.D. Wood & S.I. Main, Diagnostic tools for Dry Eye Disease, American Academy of Ophthalmology (AAO), External Disease and Cornea, 2019-2020. JJ Kanski. Clinical Ophthalmology. A Systematic Approach. Eighth Edition Elsevier Butterworth Heinemann. London 2007 AK Khurana. Comprehensive Ophthalmology. Fifth Edition. New Age Publisher. New Delhi 2007.

59. Thank you!