Dry eye syndrome (DES), as defined by

Signs and Symptoms in Dry Eye Confirm the diagnosis of dry eye before beginning treatment. BY GIANCARLO MONTANI, OPTOM FIACLE, FBCLA; AND UMBERTO BENELLI, MD, PHD Dry eye syndrome (DES), as defined by the Subcommittee of the International Dry Eye WorkShop (DEWS), 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. 1 This condition, which can be caused by deficient tear secretion or excessive evaporation of tears (Figure 1), is often associated with inflammation of the ocular surface, lacrimal glands, or conjunctiva. The term dry eye syndrome is also used to denote any disease process that alters the components of the tears or increases the surface area of the eye, as in thyroid disease when the eye protrudes forward, or certain conditions after cosmetic surgery, such as if the eyelids are opened too widely. DES becomes more prevalent with increasing age, affecting approximately 8.4% of the adult population younger than 60 years and 19% of adults above age 85 years. 2 In addition to age, the risk factors for development of dry eye include female sex (women report dry eye twice as often men) and race or ethnicity; greater incidence is seen in patients of Chinese, Hispanic, Asian, and Pacific Islands descent. 3 The prevalence of dry eye is higher in the presence of ocular conditions such as blepharitis, meibomian gland dysfunction (MGD), and conjunctival disease; in the presence of systemic conditions including arthritis, osteoporosis, gout, and thyroid disorders; and after corneal (LASIK, keratoplasty), Figure 1. Major causes of dry eye. retinal, or ocular oncologic surgery. Additionally, dry eye may be associated with the use of topical or systemic drugs, contact lenses, and cigarette smoking. It may also be triggered by environmental factors such as the use of video display terminals, air conditions associated with heating and cooling systems or air pollution, and airline travel. 4 SYMPTOMS AND DIAGNOSTIC TESTING Many clinicians assume that symptoms are the hallmark of DES; however, symptoms often do not correlate with diagnostic test results, except in severe cases. The symptoms that patients describe with dry eye are the same ocular sensations patients feel with other ocular surface disorders. Several questionnaires are available for dry eye evaluation in 34 I CATARACT & REFRACTIVE SURGERY TODAY EUROPE I NOVEMBER/DECEMBER 2011

Questionnaire Dry Eye Epidemiology Project McMonnies Dry Eye Questionnaire Ocular Surface Disease Index Dry Eye Questionnaire Contact Lens Dry Eye Questionnaire TABLE 1. DRY EYE QUESTIONNAIRES Summary 19 questions: survey of symptoms and associated factors 14 questions: survey of symptoms and associated factors 12 questions: survey of vision-related function, ocular symptoms, and environmental triggers 23 questions: survey of symptoms, associated factors, and self-diagnosis 23 questions: survey of symptoms, associated factors, and self-diagnosis Contact Lens Dry Eye Questionnaire 8 eight questions: survey of symptoms, associated factors, and self-diagnosis clinical practice (Table 1), but only two use a dry eye index score: the McMonnies Dry Eye Questionnaire, which has a range from 0 to 45, 5 and the Ocular Surface Disease Index, which has a range from 0 to 100. 6 In both indexes, higher scores are more indicative of DES. Questionnaires and dry eye index scores can be useful to detect the presence of dry eye and to evaluate the effects of therapeutic treatment. The Dry Eye Investigation and Study Group developed the Dry Eye Questionnaire and the Contact Lens Dry Eye Questionnaire to characterize ocular surface disease symptoms including prevalence, frequency, and diurnal severity and to collect other information related to dry eye. 7 If a physician does not care to use a preoperative questionnaire and a patient presents symptoms normally associated with DES (Table 2), the patient s history should include a series of questions (Table 3) that are helpful in determining ocular health. Clinical examination of the anterior segment and objective tests should be performed after the patient s medical history is obtained and questionnaires are administered to confirm the diagnosis of dry eye. Additionally, slit-lamp biomicroscopy reveals numerous signs of dry eye. For instance, an increase in tear film debris and a lost of luster of the cornea and conjunctiva may be noted. Additionally, conjunctival hyperemia is common and, as with acne rosacea, the lid margin may indicate blepharitis and MGD. It is also important to observe the tear meniscus. OBJECTIVE TESTING Objective tests for dry eye can be categorized as those that examine the tears and those that examine the integrity of the ocular surface. The former can be subdivided into tests that investigate the quantity and the quality or functional properties of tears. Most tests used to assess tears or the ocular surface do not correlate well. Tear quality. Today, tear osmolarity may be considered the gold standard diagnostic test. Tear film osmolarity can be measured using an osmolarity microchip system based on electrical conductivity measurement (TearLab; TearLab, Corp., San Diego). A 50 nl sample is taken from the external lower tear meniscus; this procedure does not cause reflex lacrimation (Figure 2). Tear quantity. The most popular test to evaluate tear quantity is the Schirmer 1 (without anesthesia). In this test, a 5 X 35 mm strip of filter paper that is bent 5 mm from the end is placed under the lower eyelid on the temporal side. The strip is kept in place for 5 minutes, at which point the examiner measures the length of moistened strip that proceeds from the bend. A result less than 5 mm is accepted as diagnostic for aqueous tear deficiency. Insertion of the strip for 5 minutes may cause discomfort with reflex tears, and therefore some practitioners keep the paper in place for 1 minute and multiply the results by three. Another measurement that noninvasively evaluates the quantity of tears is the tear meniscus height on the lower eyelid. A height lower than 0.2 mm is associated with tear deficiency. In dry eye patients, the tear meniscus is reduced and usually has an irregular edge along the lid margin. STAINS AND DYES Fluorescein is useful in assessing dry eye; instillation of this vital stain can determine the integrity of the corneal and conjunctival epithelium. The normal epithelium does not stain with fluorescein; however, when the mucous layer is absent, the dye penetrates and stains the epithelium. It is better to evaluate the anterior segment 2 minutes after instillation of the dye because premature examination of the surface may underestimate the degree of epitheliopathy. Lissamine green is another dye used to evaluate the anterior segment. This dye stains dead or degenerated cells and produces less irritation and stinging compared with rose bengal dye. Grading ocular surface staining after instillation of vital dyes is a crucial component of dry eye diagnosis. The Oxford grading schema can be used to quantify the amount of epithelial surface damage in patients with dry NOVEMBER/DECEMBER 2011 I CATARACT & REFRACTIVE SURGERY TODAY EUROPE I 35

TABLE 2. DRY EYE SEVERITY GRADING SCHEME 1 Dry eye severity level 1 2 3 4* Discomfort, severity, and frequency Visual symptoms Mild and/or episodic; occurs under environmental stress None or episodic with mild fatigue Moderate, episodic, or chronic; stress or no stress Annoying and/or activity-limiting; episodic Severe and/or Severe and/or disabling and frequent or constant; constant without stress Annoying, chronic, and/or constant; limiting activity Constant and/or possibly disabling Conjunctival injection None to mild None to mild None to mild Mild to severe* Conjunctival staining None to mild Variable Moderate to severe Severe Corneal staining (severity/location) Corneal/tear signs None to mild Mild debris, reduced meniscus height None to mild Variable Severe central Severe punctate erosions Filamentary keratitis, mucus clumping, tear debris Filamentary keratitis, mucus clumping, increased tear debris, ulceration Lid/meibomian glands MGD variably present MGD variably present Frequent Trichiasis, keratinization, symblepharon TBUT (sec) Variable 10 5 Immediate Schirmer score (mm/5 min) Variable 10 5 2 * Must have signs and symptoms TBUT = fluorescein tear break-up time; MGD = meibomian gland dysfunction 1.Behrens A, Doyle JJ, Stern L, et al.dysfunctional tear syndrome:a Delphi approach to treatment recommendations. Cornea.2006;25(8):900-907. eye (Figure 3). Staining is represented by punctate dots, and the number of dots increases by 1 log unit between panels A and B and by 0.5 log units between each panel from B to E. Staining ranges from 0 to 5 for each panel and 0 to 15 for the total exposed interpalpebral conjunctiva and cornea. 8 Fluorescein is also used for classic tear film stability tests. Fluorescein is instilled into the lower fornix, and the patient is first asked to blink several times and then to refrain from blinking. The tear film is scanned with a broad slit-lamp beam with cobalt blue filter. The presence of black spots or lines indicates the appearance of dry spots in the tear film. Tear film break-up time (TBUT) is the interval between the blink and the appearance of the first randomly distributed dry spot. Ideally, an average of three measurements is taken. A TBUT of less than 10 seconds is considered abnormal. Tear film stability can also be assessed noninvasively. In these methods, a grid or other pattern is projected onto the cornea, and the amount of time to distortion is measured. TABLE 3. CONSIDERATIONS FOR PATIENTS WHO SCREEN POSITIVE FOR DRY EYE SYNDROME Frequency and severity of symptoms Time of day symptoms occur (generally afternoon and evening symptoms are worse) Interference with daily activities (eg, stopping work to close eyes) Patient perception of dry eye Previous dry eye diagnosis Artificial tear use External factors (eg, contact lens wear, medication use, work environment) Internal factors (eg, systemic disease, refractive surgery) ADDITIONAL TESTS Patients with keratoconjunctivitis sicca often have a decreased eyelid blink rate as result of diminished corneal sensation. In these patients, the decrease in corneal sensation is due to ocular surface inflammation; however, diminished corneal sensation is also seen after refractive surgery and with normal aging. The ocular protection index (OPI) was designed in an attempt to provide a composite measurement of tear film instability and the interblink interval (IBI). IBI is calculated by dividing the number of eyelid blinks in 1 minute by 60. The normal IBI is between 10 and 12 sec- 36 I CATARACT & REFRACTIVE SURGERY TODAY EUROPE I NOVEMBER/DECEMBER 2011

Figure 2. Distribution of osmolarity in normal, mild to moderate, and severe dry eye. The recommended cutoff between normal and mild to moderate DES is 308 mosm/l. onds. To obtain the OPI, divide the TBUT by the IBI. OPI values less than 1 suggest that the tear film destabilizes between blinks. OPI values of 1 or higher seem to correlate with patient symptoms. 9 Additional useful tests include conjunctival impression cytology (to evaluate the goblet cells), brush cytology (to analyze the inflammatory condition of the ocular surface), and measuring the quantities of lysozyme and lactofferin in the tears. Decreases in the concentration of these two major lacrimal proteins secreted by the lacrimal glands in tear film is a relevant indicator of lacrimal gland dysfunction. In Table 4, we list all tests and the cutoff values at which they are considered abnormal and indicative of dry eye syndrome. COMPLICATIONS OF UNTREATED DRY EYE Tears protect the ocular surface from infection. In severe cases of untreated DES, the associated inflammation can damage the conjunctiva and the corneal surface, and, without adequate tears, the patient may have an increased risk of eye infection. Fortunately, most cases of DES-related conjunctivitis are mild and do not need specific treatment. If conjunctivitis becomes severe and chronic, however, adequate therapy must be initiated before associated inflammation damages the corneal surface and leads to ulceration or scarring. These complications can produce more severe symptoms such as extreme sensitivity to light, TAKE-HOME MESSAGE Symptoms of DES often do not correlate with diagnostic test results. Grading ocular surface staining after instillation of dyes is a crucial component of dry eye diagnosis. Treatment approaches include avoidance of exacerbating factors, stimulating and supplementing tears, increasing tear retention, cleansing the eyelids, and treating inflammation. Figure 3. Grading schema for corneal and conjunctival staining. pain, red eyes, and loss of vision. Because corneal damage can be permanent, it is important to prevent and treat these complications. LEVELS OF TREATMENT A variety of treatment approaches can be taken, including avoidance of exacerbating factors, stimulating and supplementing tears, increasing tear retention, and cleansing the eyelids and treating eye inflammation. The recommendations of the DEWS, based on disease severity, consist of four levels of treatment: Level 1 (dry sensation, burning). Education and environmental/dietary modifications; elimination of offending systemic medications; use of preserved artificial tear substitutes, gels, and ointments; and eyelid therapy. Level 2 (itching, pain, photophobia). Use of nonpreserved artificial tear substitutes; antiinflammatory agents (topical corticosteroids, topical cyclosporine A, topical or systemic omega-3 fatty acids); tetracyclines (for meibomianitis or rosacea); punctal plugs (after control of inflammation); secretagogues; and moisture chamber spectacles. Level 3 (red eyes, foreign body sensation, pain, blurred vision). Instillation of autologous serum or umbilical cord serum; prescription of contact lenses; or permanent punctal occlusion. Level 4 (blepharospasm, risk of corneal perforation). Prescription of systemic antiinflammatory agents and surgery (lid surgery, tarsorrhaphy, mucous membrane grafting, salivary gland duct transposition, amniotic membrane transplantation). CONCLUSION Dry eye is a multifactorial disease of the tears and ocu- 38 I CATARACT & REFRACTIVE SURGERY TODAY EUROPE I NOVEMBER/DECEMBER 2011

A spectrum of trusted brands. A single, reliable source. TABLE 4. CLINICAL AND LABORATORY TESTS TO DIAGNOSE DRY EYE Test Abnormal cutoff value for dry eye diagnosis Schirmer 1 5 mm wetting over 5 minutes Tear break-up time 10 seconds Tear meniscus height 0.2 mm Fluorescein staining >3 on scale of 0 to 15 Lissamine green staining >3 on scale of 0 to 18 Tear film osmolarity >308 mosm/l Impression cytology >1 Brush cytology >1 Tear lactoferrin 0.9 ug/ml When performing delicate ophthalmic and microsurgical procedures, using products from brands you trust is crucial. With Beaver-Visitec International, you have a single, reliable source for a suite of products from the most trusted brands, together with exceptional service and support. For quality, precision, innovation, and a commitment to patient and clinician safety, there s just one name to remember: Beaver-Visitec International. lar surface, with symptoms that often do not correlate with diagnostic testing. If left untreated, the patient may experience not only discomfort and visual disturbances but also ocular inflammation and scarring of the corneal surface. The physician must be vigilant in his or her approach to testing for and identifying DES. Today, tests including tear osmolarity, Schimer 1, conjunctival cytology, and brush cytology can help determine the presence of dry eye, and many treatment approaches can be helpful in managing patient comfort and ocular surface health. It is up to the individual surgeon to find the best approach for each patient; however, following the DEWS guidelines is highly recommended. Merocel Fluid Control Products CustomEyes Custom Procedure Packs Beaver and Atomic Edge Safety Knives Visitec Cannulae and Instruments Umberto Benelli, MD, PhD, is a Professor of Ophthalmology at the University of Pisa, Italy. Dr. Benelli states that he has no financial interest in the products or companies mentioned. He may be reached at email: oculista@tin.it. Giancarlo Montani, Optom FIACLE, FBCLA, is in private practice and is a Professor of Clinical Contact Lens Application at the University of Salento, Italy, and Cofounder of the Centre for Contact Lens Research of the University of Salento. Dr. Montani states that he no financial interest in the products or companies mentioned. He may be reached at email: montani.gc@libero.it. 1.[No authors listed].the definition and classification of dry eye disease:report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007).Ocul Surf.2007;5(2):75-92. 2.Moss SE,Klein R,Klein BEK.Prevalence of and risk factors for dry eye syndrome.arch Ophthalmol. 2000;118(9):1264-1268. 3.Gayton JL.Etiology,prevalence,and treatment of dry eye disease.clin Ophthalmol.2009;3:405-412. 4.Tomlinson A.Epidemiology of dry eye.in:asbell PA,Lemp MA,eds.Dry eye disease.1st ed.new York:Thieme;2006;1-15. 5.McMonnies C,Ho A.Patient history in screening for dry eye conditions.j Am Optom Assoc.1987;58(4):296-301. 6.Schiffman R,Christianson MD,Jacobsen G,Hirsch JD,Reis BL.Reliability and validity of the Ocular Surface Disease Index.Arch Ophthalmol. 2000;118:615-621. 7.Begley C,Caffery B,Chalmers RL,Mitchell GL,for the Dry Eye Investigation (DREI) Study Group.Use of the dry eye questionnaire to measure symptoms of ocular irritation in patients with aqueous tear deficiency.cornea.2002;21(7):664-670. 8.Bron A,Evans VE,Smith JA.Grading of corneal and conjunctival staining in the context of other dry eye tests.cornea. 2003;22(7):640-650. 9.Ousler GW,Emory TB,Welch D,Abelson MB.Factors that influence the inter-blink interval (IBI) as measured by the ocular protection index (OPI).Poster presented at:the Association of Research in Vision and Ophthalmology (ARVO) Annual Meeting; Fort Lauderdale,Florida;May 2002. OcuSeal Liquid Ocular Bandage For more information, call +44 1865 601 256 (option 2) or visit us at www.beaver-visitec.com Beaver-Visitec International Sales Ltd, Centurion Court, 85c Milton Park, Abingdon, Oxfordshire, OX14 4RY, UK - Tel: +44 1865 601 256 www.beaver-visitec.com BVI, BVI Logo and all other trademarks (unless noted otherwise) are property of a Beaver-Visitec International ( BVI ) company 2011 BVI