Evaluation of a patient of Dry Eye .pptx

Dry Eye is a multifactorial & complex disease. Proper patient evaluation according to the protocol is a must for adequate treatment.

1. EVALUATION OF A PATIENT OF DRY EYE By:- Dr. Rachit Rastogi PG2 OPHTHALMOLOGY GMC, Haldwani, Nainital.

2. Definition The NEI (National Eye Institute) definition of dry eye is: “Dry eye is a disorder of the tear film due to tear deficiency or E xcessive tear evaporation, which causes damage to the interpalpebral ocular surface and is associated with symptoms of discomfort.” The newer Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS II) definition of dry eye is “Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability, and hyperosmolarity, ocular surface inflammation and damage and neurosensory abnormalities play etiological roles.”

3. Lacrimal Functional Unit: Anatomy and Physiology Ocular surface (C ornea, conjunctiva, accessory lacrimal and meibomian glands) The main lacrimal glands The blink mechanism that spreads tears, the sensory and motor nerves that connect them

4. According to this model , A queous tear production by the lacrimal gland is largely due to a reflex initiated by subconscious stimulation of the ocular surface and nasal mucosa. This stimulation initiates a sensory afferent signal from the conjunctiva and cornea that travels via the trigeminal nerve to the central nervous system in the superior salivary nucleus in the pons area, from whe r e efferent parasympathetic fibers in the facial nerve pass, in the nervus intermedius, to the pterygopalatine ganglion . Here, postganglionic parasympathetic fibers arise and terminate in the main and accessory lacrimal glands , conjunctival goblet cells, and meibomian glands, where they will stimulate tear production and secretion in response to the efferent signal.

5. Another neural pathway controls the Blink reflex , via trigeminal afferents and the somatic efferent fibers of the seventh cranial nerve. This entire functional unit responds to environmental, endocrinologic, and cortical influences and controls the major components of the tear film in a regulated fashion.

6. Tear Film :- 3 layers, innermost mucinous, middle aqueous, outermost lipid. 2 - 5.5 um OCT has recently resolved the debate over the tear film thickness. Now regarded as a complex blended two-layer structure comprising of an outer lipid layer and an inner muco-aqueous layer.

7. Mucinous Layer- 0.5mm 2 layers : the glycocalyx and mucous layers most significant of the mucin is MUC5-AC To test the integrity of the mucinous layer, the Tear Break-up Time (TBUT) test can be done. Other Abnormalities- Vitamin A deficiency, Ocular Cicatricial Pemphigoid Stevens-Johnsons Syndrome Alkali burns These all lead to destruction of Goblet cells with loss of mucin production.

8. Aqueous Layer :- 2-6um Reflex secretions - main lacrimal gland Basal secretion- accessory lacrimal glands of Krause and Wolfring . Lipid Layer :- Most significant layer in terms of DED. Prevent the rapid evaporation of tears. Prevention of spillage from lid margins. Deficiency occurs in MGD. Non-invasive tests- interferometry, meibography , and meibometry Carried out to detect abnormalities in the lipid layer and meibomian gland.

9. Pathogenesis 2 mechanism:- Tear hyperosmolarity Tear film instability

10. Etiopathogenic Classification

11. Aqueous tear-deficient dry eye (ADDE) Sjögren syndrome dry eye :- Exocrinopathy 2 nd M/C auto-immune disease. F>M (95%) 4 TH – 5 TH Decade. There are two forms of SS: P rimary SS - no other associated systemic connective tissue disease. Secondary SS - primary SS together with the features of another overt autoimmune disease { e.g. RA (M/C), SLE, etc.

12. High risk triggers ( leading to autoimmune acinar damage):- MHC gene[ HLA- DQ1 and DQ2 ] or non-MHC [e.g. apolipoprotein-E, carbonic anhydrase-2]) A ndrogen status ( low androgen favors an inflammatory environment within the target tissues), E xposure to environmental agents ranging from polluted environments to viral infections with lacrimal gland tropism (efficacious by triggering inflammatory states [herpesvirus, Coxsackieviruses] M imicry of SS symptoms due to chronic viral infections [HCV, HIV, HTLV-1])

13. Non- Sjögren syndrome dry eye:- Primary lacrimal gland deficiencies- Age-related dry eye (ARDE): primary increase in ductal pathology with age lacrimal gland dysfunction through its obstructive effect These age-related ductal alterations include inflammation, periductal fibrosis, interacinar fibrosis, paraductal blood vessel loss, and acinar cell atrophy. Congenital alacrima : absent or hypoplastic lacrimal gland, or abnormal innervation of the gland's lacrimal stimulation. M/C :- familial dysautonomia or Riley–Day syndrome - decreased tear production due to abnormal parasympathetic innervation of the lacrimal gland. R educed amount of tears when crying, an absent reflex lacrimation in response to irritants. Histologically, the lacrimal glands appear to be normal.

14. Secondary lacrimal gland deficiencies:- Lacrimal gland infiltration : S arcoidosis (by sarcoid granulomata) L ymphoma (by lymphomatous cells), H emochromatosis, A myloidosis GVHD HIV Obstruction of the lacrimal gland ducts:- Any cause of Cicatrizing Conjunctivitis :- T rachoma M ucous Membrane P emphigoid Stevens–Johnson syndrome Ch emical and Thermal injuries.

15. Reflex Hyposecretion:- Reflex sensory block- A reduction in this sensory drive may lead to DED in two ways: Reducing reflex-induced lacrimal secretio n R educing the blink rate, thus increasing evaporative loss. Seen in: DM Neurotropic Keratitis Reflex Motor Block- d/t reduced lacrimal secretion, d/t certain drugs Antihistamines Beta-blockers, Antispasmodics Diuretics TCA’s and SSRI’s(less common)

16. Evaporative Dry Eye Intrinsic causes:- Meibomian Gland Dysfunction :- diminished delivery of protective lipids to the tear film tear film instability, increased evaporation, and ocular surface alterations . M/C cause of evaporative dry eye. Increased Tear Film Exposure :- Thyroid Eye Disease & other form of proptosis. Reduced Blink Rate :- E xtrapyramidal disorder, such as Parkinson Disease C omputer V ision S yndrome

17. Extrinsic causes:- Ocular Surface Disease- Allergic conjunctivitis Vit A def.- disruption of mucin production Benzalkonium chloride (BAC or BAK)- surface epithelial cell damage and punctate epithelial keratitis, resulting in poor surface wettability. Contact Lens Wear- thinned lipid layer, poor lens wettability, causes higher evaporative loss during lens wear.

18. Diagnosis of DRY EYE History Symptoms- foreign body sensation, burning itching dryness soreness lid heaviness photophobia ocular fatigue Blurred or fluctuating visual acuity are also hallmark DED symptoms O ther visual disturbances - decreased contrast sensitivity and increased forward scatter and Gl are. Exacerbating factors:- reading, watching television, using computer- Decrease blink rate. Intolerance of the draft from air conditioners, smoky environments, and the low humidity of airplane cabins.

19. Pt. with ADDE- worsen as day progresses. Pt. with MGD- worse in morning. Symptomatic response to artificial tears- supports dry eye diag. Past Ocular & medical history. Use of over-the-counter artificial tears asked. Thorough review of systemic disease, e.g. dry mouth (xerostomia).

20. Questionnaires:- for diagnosis and quantification of DED, to study epidemiology of the disease, to assess effects of the treatment and its impact on the quality of life. Ocular Surface Disease Index (OSDI) Dry Eye Questionnaire (DEQ-5) Impact of Dry Eye on Everyday Living (IDEEL) National Eye Institute’s Visual Function Questionnaire (NEI VFQ-25) Dry Eye-Related Quality-of-Life Score (DEQS) Computer-vision symptom scale (CVSS17) McMonnies ’ Questionnaire (MQ) Ocular ComfortIndex (OCI and OCI-C) Symptoms Assessmentin Dry Eye (SANDE) Standard Patient Evaluation of Eye Dryness (SPEED) Contact Lens Dry Eye Questionnaire (CLDEQ) 8-Item Contact Lens Dry Eye Questionnaire (CLDEQ-8) Contactlens impact on Quality oflife (CLIQ )

21. Physical Examination:- evaluating the face and eyelids for signs of rosacea or floppy lids. The Dynamics of blinking a ) frequency of blinking (roughly every four seconds on average); b) variation of blink intervals c) size of palpebral aperture d) adequacy of lid closure . L id position . Entropion; b) Ectropion c) eversion of the lacrimal puncta d) Cicatricial malposition e) Dermatochalasis f) Swelling of the temporal aspect of the upper lid (which may imply enlargement of the lacrimal gland) g) Lid retraction with or without proptosis.

22. Slit Lamp Findings:- a) Lid margins : hyperemia , telangiectasia, thickening, scarring, keratinization, ulceration, tear debris, abnormalities of the meibomian orifices, including metaplasia, and the character of expressed meibomian secretions b) Eyelashes : trichiasis, malposition, encrustations, collarettes, sheathing, mite infestations (demodex), and staphylococcal blepharitis; c) Conjunctiva : erythema, swelling, keratinization, papillary/follicular reaction, pinguecula, lid parallel conjunctival folds (conjunctival chalasis ), superior limbickeratoconjunctivitis (SLK); d) Cornea : infiltrates, scars, punctate staining or ulcers, vascularization, pannus, nodules, filaments and pterygium. E) Tear Film- examined for mucus & cellular debris.

23. Diagnostic Tests To test the tear secretion and tear volume Schirmer’s test - Whatman Filter Paper No. 41- Blotting paper size 5*35mm. Procedure - Folded 5 mm from the inner end which is rounded In lower fornix, at the junction of middle and outer one-third 5 minutes. Touching the cornea or lashes should be avoided. Eyes gently closed. N ormal tear production - 0.5- 0.6 ml of tears/day W ets more than 15 mm of the strip NORMALLY. Lacks repeatability. Series of abnormal result raise DED suspicion. Low cost, M/c performed test clinically. Sensitivity- 77-85% /// Specificity- 70-83%

24. Schirmer’s test I – without the use of topical anesthesia Measures maximum basal plus reflex tear secretion. • Schirmer’s test II – with the help of anesthesia. It measures only the basal tear secretion. • Schirmer’s test III – The patient is advised to look directly in the sun R eflex tear secretion. D angerous, no diagnostic value, so not used . <5 mm- Extremely Dry Eye 5-10 mm- Moderately Dry Eye 10-15 mm – Severe Dry Eye

25. Variation Of Schirmer’s test:- Strip Meniscometry- Strip- 25 mm Polyethylene Terephthalate covered with Urethane-based material. Dip in tear meniscus for 5 sec. <4mm – suspicion of DED{SENS- 84 /// SPEC – 58} When combined with TBUT- {Sens – 81 /// Spec - 99} 1 min Schirmers test- Done to decrease ocular discomfort & save time. Bawazeer and Hodge et al. (2003) concluded that the 5 -minute Schirmer test with anesthesia highly correlates with the 1-minute Schirmer test with anesthesia. Severe < 5.5mm in 5 min test = 2mm in 1 min test Mild – mod. 5-10 mm = 3- 6 mm in 1 min test.

26. Phenol Red Thread Test- Cotton thread impregnated with Phenol Red ( YELLOW ) Folded end hooked over lower eyelid margin in temporal 1/3 rd * 15 sec. Turns Red (Tear- alkaline ph ) No diff. if eyes are open/ closed Less reflex tearing (small size) Costly ( Manufactured in few countries) Cut Off 20 mm - for ADDE.

27. To test Tear Clearance- Fluorescein Clearance test- 5 uL of 2% Dye One set of schirmers paper inserted for each 10 min interval for 30 min. Amount of strip being wet & disapp . Of dye noted. Nasal stimulation with cotton at last strip done to induce reflex tear secretion. Cut off > 3mm @ 10 min interval – Normal Tear Secretion If dye not detected after 20 min - CLEARANCE Tear Function Index - Same as Schirmers with anaesthesia, 10 uL of 0.5% dye. TCR (Tear Clearance Rate) – Rate at which color of FL Dye fades on schirmers strip.

28. Fluorophotometry - measurements of the penetration of fluorescein across the corneal epithelium used in diagnosing or monitoring dry eye disease. To Test Tear Volume- Tear Meniscus Assessment by Meniscometry OCT Meniscometry can measure TMH, TMR, TMA & TMD To test Tear film stability- Tear Fim Break Up Time tes t (TBUT)- last complete blink ------------------first randomly distributed dry spot. Can be done +/- fluorescein 2% (decrease stability) <10sec – DED diagnosed Non Invasive Tear Break up time- Placido- disk

29. Keratography High Speed video Keratography Interferometry Thermography Tear evaporation Rate

30. To test the ocular surface damage Ocular Surface staining- various dyes used are Fluorescein 1% or 2%- stains cornea better then c onj. Stains the surface at area of disrupted cell junctions Highly water soluble---doesn’t penetrate lipid bilayer---- doesn’t stain Normal cornea . various types of fluorescein staining patterns seen in dry eye disease as explained It ranges from mild superficial punctate erosions to involving the whole corneal surface.

31. Rose Bengal 1% Topical anaesthesia used, irritant to eye Staining – dose dependent Stains ocular surface epithelial cells unprotected by mucin + dead or degenerated cells. Mainly used for conjunctival staining Note :- FL & RB can be used concurrently Ex:- in Geographic herpetic lesion, FL stain Base of ulcer & RB stains damaged surrounding virus infected cells. Lissamine Green- Acidic dye Similar to RB, but not an irritant. Checked between 1-4 min after staining

32. Scoring System:- to grade ocular surface staining Van Bijsterveld staining NEI/ Industry workshop guideline

33. Oxford scheme-

34. Recently, Miyata & coauthors gave grading for SPK using Fluoroscein staining. Area & density of SPK is graded. A0- A3 D0-D3 Both are combined in a single index.

35. Impression Cytology- Study Sq. metaplasia & goblet cell density of conjunctiva for diag. & monitoring. Cells from 1 st -3 rd most sup. Layer removed. By applying cellulose acetate filters or bio-pore membrane . Cells analyzed by microscopy, IHC, Immunoblotting analysis, PCR, flow cytometry depending on aim Of inv. Indication- DED LSCD OSN Specific viral inf.

36. Lid Parallel Conjunctival folds (LIPCOF )- Fold in bulbar conjunctiva in lateral & lower quad. Represents Conjunctivochalasis (mild stage). TMH maybe underestimated d/t this In Vivo Confocal Microscopy (IVCM)- Non invasive tech. to evaluate sign of ocular damage Signs:- Decreased Corneal & Conjunctival Epi. Cell density Conjunctival Sq. Metaplasia. Corneal Nerve changes\ To test Lipid Layer Of Tear film - Tear Film Interferometry

37. To test chemical properties of Tear Film Tear Fim Osmolarity- Positive corelation b/w severity of DED & Tear osmolarity. Gold Std. method- Freezing Point Depressiom [FDP]- 0.1 ML tear required. Others- Vapor Pressure & Electrical Conductivity. TearLab System( Tearlan INC., CA, USA) – ex of electrical Impedence Require 0.05 ml tear Result in 30 sec.

38. Tear Film Ferning - Tear film when dried on glass plate- cause ferning . Pre-requisite- Slow Crystal Growth Rate, Low solution viscosity, Low impurity Level. 7-10 min of Normal Room temp. ( 20-26 degree) Room hiumidity (RH upto 50%) Healthy Tear samples - Compact, dense , ferning patterns DED - Fragmented or absent pattern

39. How to DIAGNOSE

40. ASK QUESTIONS :- Presence of eye discomfort & its severity Duration of Symptpoms & aggrevating factors If DOV +/- & effect of blinking on vision H/o itching, crusting, swelling & +/- Discharge Dryness of mouth or presence of swollen glands H/o wearing CL’s (Duration & type) Asso. Systemic health conditions/ smoking/ long term systemic meds Lid, Adnexa & Ant segment Evaluation Questionnare DEQ-5 OSDI >6 = Dry Eye >13 = Dry Eye + Dry Eye Tests TBUT< 10 sec Tear Osmolarity > 308 mosmol /L Inter- oculat osmol diff. >8 mosmol /l Ocular Surface Staining

41. RESULT EVAPORATIVE DRY EYE AQUEOUS DEFICIENT DRY EYE MIXED MILD MODERATE SEVERE Depending on severity of MGD MILD MODERATE SEVERE 0.2mm 0.1mm 0.00mm TEAR FILM HEIGHT (TFH)

42. Treatment Objective:- Improve ocular comfort & quality of life. return the ocular surface and tear film to the normal homeostatic state. Tear Supplementation : Lubricant Mainstay of therapy in all stages of DED. Action:- Lubricant Replacement of deficient tear constituents Dilution of pro-inflammatory substances Reduction of tear osmolarity Protection against Osmotic stress

43. Glycerin , Polyethylene Glycol, Sodium Hyaluronate - Compatible solute provide protection against Osmotic stress. Small non-ionic molecules taken up by cells to increase intracellular osmolarity without disturbing cellular metabolism. Lipid Containing artificial tear products- Restore lipid layer & reduce tear evaporeation . Useful in MGD pt. Preservative free lubricant to be used in Moderate- Severe cases, when more than 4-6 times daily dosage is required. Ocular Ointments/gels- Higher viscosity, longer contact time. Used in night, when aqueous tear production in decreased Ointments – doesn’t promote bacterial growth, no preservative required. Mineral oil & petroleum, sometimes Lanolin- irritation & delay corneal wound healing.

44. Sustained release Hydroxypropyl Cellulose inserts (LACRISERT)- Severe DED Placed in inf. Fornix Gradual dissolution over 24 hrs. Day long relief Tear Retention :- Punctal Occlusion- Used in ADDE . Punctal & Intracanalicular pugs- temporary & reversible Electrocautery & Laser- Irreversible (Not used) 2 types of Punctal Plugs Absorbable- Collagen / Polymer, 3 day s- 6 mnths Non-absorbable- Silicon/ hydrophilic acrylic, Freeman style with surface collar resting on punctal opening, a neck & a base. Indication :- symptoms of DED + Schirmer’s <5mm + ocular surface dye staining. Contraindication :- signs of ocular inflammation +

45. M/C complication- Spontaneous Plug extrusion. Others:- Epiphora Internal migration Biofilm formation Infection Pyogenic granuloma formation Intra-canalicular plug - less risk of extrusion & conjunctival extrusion. Moisture chamber spectacles - Reduce tear evaporation by increasing humidity around eyes.

46. Contact Lens- protect and hydrate the corneal surface in severe dry eye can also exacerbate DED Ex:- Silicone rubber lenses G as-permeable scleral-bearing hard contact lenses (with or without fenestration) Boston scleral prosthetic device (Prosthetic Replacement of the Ocular Surface Ecosystem, PROSE ; Boston, MA, USA). Risk of bacterial Keratitis- reserved for mod- severe DED Avoid risk- regular changing of lens, stop steroids, Prophylactic Antibiotics. Extreme ADDE- Not good candidates. Tarsorapphy - reduces the area of exposed ocular surface . Severe or refractory DED .

47. Tear Stimulation secretagogues:- Diquafosol (P2Y2 Receptor agonist) – stimulate aqueous & mucus secretion. Oral Pilocarpine- Severe ADDE. FDA Approved for Dry mouth in Sjogrens but off-label for ADDE. 5-7 mg , 2-4 times/day S/E:- Sweating, increased urinary freq flushing , hypersalivation Oral Cevimeline- 15-20mg TDS Less S/E (M/C S/E- GI Symptoms & increased sweating)

48. Biological Tear substitutes:- Serum - From pt. own serum Conc. Between 20 & 100 % is used Severe DED. Unpreserved, but can be stored frozen for 3-6 mnths Salivary Gland Autotransplantation - Indication :- End stage DED with absolute Tear deficiency [Schirmer’s - <1 mm] Replace mucin & aqueous tear Ophthalmologist + Maxillofacial surgeon needed. Risk of Microcystic corneal edema ( hyposmolarity of saliva).

49. Anti-inflammatory therapy- Topical Cyclosporin A( CsA )- Calcineurin inhibitor Reduce pro-inflammatory cytokine, activated lymphocytes, inflammatory & apoptotic markers. S/E:- Ocular Burning & stinging Lifitegrast - Integrin antagonist Inhibit T-cell mediated inflammation Corticosteroids:- Inhibit inflammatory response non specifically Short term use(4 weeks)- very effective. RCT with KCS and delayed tear clearance showed that loteprednol etabonate 0.5% ophthalmic suspension 4 times/day * 4 weeks was effective at improving some signs and symptoms and also caused significant improvement in corneal smoothness

50. Sjögren syndrome- Short pulse of sysyemic steroid is effective. Alternate-day oral prednisone (40 mg)- improved aqueous tear production. NOT suitable therapy for the long-term treatment of KCS:- Risk of infection Raised IOP PSC Recommendation- Pulse therapy to control exacerbations f/b taper to low dose (once or twice daily) or to a weaker agent (Loteprednol or Florometholone ) Androgenic steroids- Topical prep. are evaluated in RCT

51. Tetracyclines :- antibacterial, anti- inflammatory and protease inhibitory properties minocycline, doxycycline Macrolides- Topical Azithromycin 1% (4 weeks) - Improve (off-label) meibomian gland plugging, eyelid margin redness, palpebral conjunctival redness, and ocular discharge. antibacterial and antI - inflammatory effect Essential Fatty Acids- Omega-3 fatty acids (e.g. EPA found in fish oil) - inhibit the synthesis of lipid mediators and block the production of proinflammatory IL-1 and TNF-alpha. Reduce inflammation Alter composition of meibomian lipids

52. Topical Vit A (Retinol)- DED may be associated with local retinol deficiency at the ocular surface. Mucolytics- Topical acetylcysteine dense mucus accumulation or filamentary keratitis.

53. CORNEA- fundementals , diagnosis and management By Mark J. Mannis & Edward J. Holland , Elsevier publication Peyman's Principles & Practice of Ophthalmology 1 & 2 Dry Eye Syndrome Modern Diagnostic Techniques and Advanced Treatments by Felicia. M. Ferreri Refrences