Dry eye diagnosis and management

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Introduction : Dry eye disease (DED) is one of the most prevalent ophthalmic disorders, which is influenced by geographic location, climatic conditions, life style of the people and ranges from 5% to 35% [1][2][3]. It may have an adverse impact on the quality of life and on the results of corneal, cataract, and refractive surgical procedures. Due to a wide variety of presentations , multi factorial and elusive etiology, it is often challenging to treat.

Recent studies have given insights into inflammation and hyperosmolarity in etiology of dry eye[4] , which go hand in hand in a vicious cycle . The conventional approach to the treatment of dry eye is providing lubricating eye drops or tear substitutes. However we have a variety of components available in the market making it difficult which to choose for which patient . However, the newer treatment approach is to target the underlying cause rather than symptomatic relief alone.

In light of the above knowledge, this article focuses on simple clinical examination techniques and newer diagnostic modalities used for differential diagnosis of DED which includes Aqueous-Deficiency Dry Eye(ADDE) , Evaporative Dry Eye (EDE) and highlights the various molecules which help in supplementation of the insufficient components of tear film and maintain homeostasis.


DIAGNOSIS  : After a dry eye suspect in identified, a complete medical history including drug history should be taken , patient should be made to fill the OSDI (Ocular Surface Disease Index) questionnaire and then patient undergoes the following tests [5].

1. SCHIRMER TEST (ST): Filter paper marked 0-30 mm is placed at the lateral 1/3rd of lower fornix of both eyes for 5 mins,wetting of less than 10 mm indicates ADDE . 0-3 mm severe dry eye , 3-5 moderate dry eye and 5-10 mild dry eye .ST- 1 is without instilling paracaine i.e topical anesthetic ( reflex tear secretion) ,ST- 2 after instilling paracaine ( basic tear secretion )

2. NON INVASIVE TEAR BREAK UP TIME[5] : One drop of fluorescein is placed in the lower fornix and patient is made to blink multiple times and then asked to stop blinking .The stained cornea is examined under the slit lamp in cobalt blue filter " .APPEARANCE OF 1ST DRY SPOT ON CORNEA IN LESS THAN 10 SEC " indicative of EDE .

3.OCULAR SURFACE PUNCTATE STAINING [5]: Of Cornea with fluorescein sodium and conjunctiva with lissamine green .Appearance of > 5 CORNEAL SPOTS >9 CONJUNCIVAL SPOTS & LID MARGIN (2mm length & 25% width) seen under cobal blue light is indicative of dry eye .


4.TEAR FILM ORIENTED DIAGNOSIS(TFOR), FLUORESCEIN BREAK UP PATTERN [6] : TFOD is the method used for the differential diagnosis of DE, which includes aqueous-deficiency DE (ADDE), decreased wettability DE (DWDE), and increased evaporation DE (IEDE), through the dynamics of tear film (TF) and breakup patterns (BUPs) after the eye is opened. BUPs and/or each diagnosed DE subtype are/is able to distinguish the insufficient components of the ocular surface that are responsible for each BUP in a layer-by-layer fashion. Aqueous fluid, membrane-associated mucins (especially MUC16), and the lipid layer and/or secretory mucins must be insufficient in ADDE, DWDE, and IEDE, respectively, and this allows for a layer-by-layer treatment to be proposed for each BUP via the supplementation of the insufficient components, using the topical therapy currently available.


NEWER DIAGNOSTIC MODALITIES

1.QUANTIFY HYPEROSMOLARITY AND IDENTIFY INFLAMMATORY MARKERS IN DRY EYE.

A .HAND HELD DEVICES LIKE IPEN AND TEAR LAB OSMOMETER : Diagnosing dry eye is challenging as the patient symptoms often don’t match clinical signs.Hence objective diagnostic method is essential .Osmolarity testing has been declared the “gold standard” of objective dry eye diagnosis.

B .INFLAMMADRY: InflammaDry is a rapid , in-office test that detects elevated levels of MMP-9, an inflammatory marker which is consistently elevated in the tears of patients with DED.

2.LIPID LAYER INTERFEROMETRY - Measures lipid layer thickness and accurately diagnoses and monitors lipid-deficient EDE.

3. MEIBOGRAPHY : Specialized imaging study developed exclusively for the purpose of directly visualizing the morphology of meibomian gland,they play a significant role in tear production by contributing lipids to the superficial tear film and hence dysfunction of the meibomian glands results EDE.

MANAGEMENT OPTIONS :

After carrying out these test the root cause of dry eye can be identified ( ADDE / EDE , ASSOCIATED WITH/WITHOUT SIGNIFICANT INFLAMMATION AND HYPEROSMOLARITY , and then the choice of lubricant can be made .

1.AQUEOUS DEFICIENCY : When the root cause of dry eye is insufficient tear production aim of treatment is tear replacement and reversing the hyperosmolar state with osmoregulators .Following are the lubricants of choice ;

A.Carboxy methylcellulose(CMC) 0.2-2.5% - Increases viscosity of tear film.

B.) Hydroxypropyl methyl cellulose(HPMC ) 0.2-0.5% - Cross links on contact with tear film .

C. Sodium Hyaluronate (HA)0.1-0.2% - Mucoadhesive ,Mucomimetic [8] Viscoelastic [9] and CD44 receptor binder [10].


2.MUCIN DEFICIENCY : Mucin is thought to contribute to stabilization of tear film because of its ability to promote water retention on the ocular surface for long periods by binding to large number of water molecules. Secretagogues increase mucin secretion from goblet cells on the conjunctiva .Can be used in both ADDE and IEDD.

A . Rebamipide 2% [7]  : Rebamipide is a novel quinolinone derivative earlier used for gastric ulcer therapy. However later studied and found Rebamipide increases the secretion of both membrane-associated and secreted-type mucins through mucin production in the conjunctival goblet cells, and in the corneal epithelial cells.

B.Diquafosol tetrasodium:It is a P2Y2 Receptor agonist and stimulates fluid and mucin secretion on ocular surface.


3.LIPID LAYER DEFICIENT-EVAPORATIVE DRY EYE: PG:Propylene glycol 0.2-1% , PEG: Polyethylene glycol 0.2-1% , HP GUAR: Hydroxypropyl Guar These when in contact with tear film increase in viscosity forming a protective layer preventing evaporation of tears.


4.OSMOPROTECTANTS: They suppress the production and activity of MMP induced hyperosmolarity in human corneal epithelial cells[13] and protect the cells under extreme osmotic stress by balancing the osmotic pressure without disturbing cell metabolism. Osmoprotective agents used are :

A. Trehalose [11][12] : It is a natural alpha linked disaccharide which provides protection from oxidative & osmotic stress and apoptosis induced cell death.

B. L-carnnitine [13] , GlycerolL ,Erythritol : Their osmoprotectant action is directly proportional to the amount of time they are retained in the cell .L-carnnitine is retained longer hence more effective. These work best when used in combination.[13]


5.ANTI-INFLAMMATORY AGENTS : Severe aqueous deficiency results in increase of inflammatory cytokines which worsen the ocular surface damage and cause tear film instability .Mainly useful for aqueous deficiency dry eye with Sjogren syndrome or autoimmune diseases. topical steroids improve subjective symptoms and ocular surface damage and Cyclosporine improves subjective symptoms.

In order to increase the efficacy of tear substitutes , use them in combination , add antioxidants like Vit B12 , Vit A and use preservative free drugs .


References 1]The epidemiology of dry eye disease: Report of the Epidemiology Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf 2007;5:93-107. 2] McCarty CA, Bansal AK, Livingston PM, Stanislavsky YL, Taylor HR. The epidemiology of dry eye in Melbourne, Australia. Ophthalmology 1998;105:1114-9. [PUBMED] 3] Lin PY, Tsai SY, Cheng CY, Liu JH, Chou P, Hsu WM, et al. Prevalence of dry eye among an elderly Chinese population in Taiwan: The Shihpai eye study. Ophthalmology 2003;110:1096-101. 4] Jacobi C, Jacobi A, Kruse FE, Cursiefen C. Tear film osmolarity measurements in dry eye disease using electrical impedance technology. Cornea. 2011;30(12):1289‐1292. doi:10.1097/ICO.0b013e31821de383 5] Wolffsohn JS, Arita R, Chalmers R, et al. TFOS DEWS II Diagnostic Methodology report. Ocul Surf. 2017;15(3):539‐574. doi:10.1016/j.jtos.2017.05.001 6] Norihiko Yokoi; Georgi As Georgiev 7] Tomoyuki Kashima, Clin Ophthalmol. 2014; 8: 1003–1010 8] J. Necas1 , L. Bartosikova1 , P. Brauner2 , J. Kolar2 . Veterinarni Medicina, 53, 2008 (8): 397–411 9]American Journal of Ophthalmology.2010 apr 1; 149(4):594-601. 10] Lesley J, Hascall VC, Tammi M, Hyman R. Hyaluronan binding by cell surface CD44. J Biol Chem. 2000;275(35):26967‐26975. doi:10.1074/jbc.M002527200 11]Br J Ophthalmol 2001; 885;610-612 12]Int Ophthalmol. 2018; 38(2): 875-895; 13] Deng R, Su Z, Hua X, Zhang Z, Li DQ, Pflugfelder SC. Osmoprotectants suppress the production and activity of matrix metalloproteinases induced by hyperosmolarity in primary human corneal epithelial cells. Mol Vis. 2014;20:1243‐1252. Published 2014 Sep 12.