Dry Eye
`Syndrome
`Limited Revision
`
`MYLAN - EXHIBIT 1048
`Mylan Pharmaceuticals Inc. et al. v. Allergan, Inc.
`IPR2016-01127, -01128, -01129, -01130, -01131, & -01132
`
`

`

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`
`As a service to its members and the public, the American Academy of
`Ophthalmology has developed a series of clinical practice guidelines called
`Preferred Practice Patterns that identify characteristics and components of
`quality eye care. Appendix 1 describes the core criteria of quality eye care.
`The Preferred Practice Pattern® (PPP) guidelines are based on the best
`available scientific data as interpreted by panels of knowledgeable health
`professionals. In some instances, such as when results of carefully conducted
`clinical trials are available, the data are particularly persuasive and provide
`clear guidance. In other instances, the panels have to rely on their collective
`judgment and evaluation of available evidence.
`Preferred Practice Pattern guidelines provide the pattern of practice, not
`the care of a particular individual. While they should generally meet the
`needs of most patients, they cannot possibly best meet the needs of all patients.
`Adherence to these PPPs will not ensure a successful outcome in every
`situation. These practice patterns should not be deemed inclusive of all proper
`methods of care or exclusive of other methods of care reasonably directed at
`B4G3<A<A9 G;7 47FG E7FH?GF% ,G @3L 47 A757FF3EL GB 3CCEB35; 6<887E7AG C3G<7AGFR
`needs in different ways. The physician must make the ultimate judgment about
`the propriety of the care of a particular patient in light of all of the
`circumstances presented by that patient. The American Academy of
`Ophthalmology is available to assist members in resolving ethical dilemmas
`that arise in the course of ophthalmic practice.
`Preferred Practice Pattern guidelines are not medical standards to be
`adhered to in all individual situations. The Academy specifically disclaims
`any and all liability for injury or other damages of any kind, from negligence
`or otherwise, for any and all claims that may arise out of the use of any
`recommendations or other information contained herein.
`References to certain drugs, instruments, and other products are made for
`illustrative purposes only and are not intended to constitute an endorsement of
`such. Such material may include information on applications that are not
`considered community standard, that reflect indications not included in
`approved U.S. Food and Drug Administration (FDA) labeling, or that are
`approved for use only in restricted research settings. The FDA has stated that
`it is the responsibility of the physician to determine the FDA status of each
`drug or device he or she wishes to use, and to use them with appropriate
`patient consent in compliance with applicable law.
`Innovation in medicine is essential to assure the future health of the American
`public, and the Academy encourages the development of new diagnostic and
`therapeutic methods that will improve eye care. It is essential to recognize that
`GEH7 @76<53? 7K57??7A57 <F 35;<7I76 BA?L J;7A G;7 C3G<7AGFR A776F 3E7 G;7
`foremost consideration.
`All PPPs are reviewed by their parent panel annually or earlier if
`developments warrant and updated accordingly. To ensure that all PPPs are
`5HEE7AG$ 735; <F I3?<6 8BE & L73EF 8EB@ G;7 P3CCEBI76 4LQ 63G7 HA?7FF
`superseded by a revision. Preferred Practice Pattern guidelines are funded by
`the Academy without commercial support. Authors and reviewers of PPPs are
`volunteers and do not receive any financial compensation for their
`contributions to the documents. The PPPs are externally reviewed by experts
`and stakeholders before publication.
`The intended users of the Dry Eye Syndrome Preferred Practice Pattern
`guideline are ophthalmologists.
`
`

`

`FINANCIAL DISCLOSURES
`
`,A 5B@C?<3A57 J<G; G;7 )BHA5<? B8 -76<53? .C75<3?GL .B5<7G<7FR )B67 8BE ,AG7E35G<BAF J<G; )B@Canies
`(available at www.cmss.org/codeforinteractions.aspx), relevant relationships with industry occurring
`from January 2011 to September 2011 are listed. The Academy has Relationship with Industry
`Procedures to comply with the Code (available at http://one.aao.org/CE/PracticeGuidelines/ppp.aspx).
`
`David F. Chang, MD: Alcon Laboratories, Inc. O Consultant/Advisor; Allergan, Inc. O Lecture fees
`Emily Y. Chew, MD: No financial relationships to disclose
`Steven P. Dunn, MD: No financial relationships to disclose
`Robert S. Feder, MD: No financial relationships to disclose
`Matthew R. Jones, MD: No financial relationships to disclose
`Francis S. Mah, MD: Alcon Laboratories, Inc. O Consultant/Advisor; Allergan, Inc. O
`Consultant/Advisor
`Stephen D. McLeod, MD: No financial relationships to disclose
`David C. Musch, PhD, MPH: No financial relationships to disclose
`Leslie A. Olsakovsky, MD: No financial relationships to disclose
`Bruce E. Prum, Jr., MD: Allergan, Inc. O Consultant/Advisor
`Christopher J. Rapuano, MD: Alcon Laboratories, Inc. O Lecture fees; Allergan, Inc. O
`Consultant/Advisor, Lecture fees; EyeGate Pharma O Consultant/Advisor
`C. Gail Summers, MD: No financial relationships to disclose
`Audrey R. Talley-Rostov, MD: No financial relationships to disclose
`Andrew J. Velazquez, MD: No financial relationships to disclose
`
`

`

`TABLE OF CONTENTS
`
`INTRODUCTION .........................................................................................................................2
`ORIENTATION ............................................................................................................................3
`Entity............................................................................................................................................3
`Disease Definition........................................................................................................................3
`Activity..........................................................................................................................................3
`Patient Population........................................................................................................................3
`Purpose........................................................................................................................................3
`Goals............................................................................................................................................3
`BACKGROUND ..........................................................................................................................3
`Epidemiology ...............................................................................................................................3
`Pathogenesis ...............................................................................................................................5
`Associated Conditions .................................................................................................................5
`Natural History .............................................................................................................................6
`CARE PROCESS ........................................................................................................................6
`Patient Outcome Criteria .............................................................................................................6
`Diagnosis .....................................................................................................................................6
`Patient History .................................................................................................................................7
`Examination..........................................................................................................................8
`Diagnostic Tests...................................................................................................................9
`Classification of Dry Eye Syndrome ............................................................................................9
`Treatment ....................................................................................................................................9
`Mild Dry Eye ..................................................................................................................................11
`Moderate Dry Eye .........................................................................................................................12
`Severe Dry Eye .............................................................................................................................13
`Follow-up ...................................................................................................................................13
`Provider and Setting ..................................................................................................................14
`Counseling/Referral...................................................................................................................14
`APPENDIX 1. QUALITY OF OPHTHALMIC CARE CORE CRITERIA ..................................15
`APPENDIX 2. SUMMARY OF MAJOR RECOMMENDATIONS FOR CARE .........................17
`APPENDIX 3. ASSOCIATED DISEASES ................................................................................19
`APPENDIX 4. DIAGNOSTIC TESTS........................................................................................20
`APPENDIX 5. DRY EYE SEVERITY SCALES.........................................................................22
`RELATED ACADEMY MATERIALS ........................................................................................23
`REFERENCES ..........................................................................................................................23
`
`1
`
`

`

`INTRODUCTION
`
`The Preferred Practice Pattern® (PPP) guidelines have been written on the basis of three principles.
`# Each Preferred Practice Pattern should be clinically relevant and specific enough to provide useful
`information to practitioners.
`# Each recommendation that is made should be given an explicit rating that shows its importance to the care
`process.
`# Each recommendation should also be given an explicit rating that shows the strength of evidence that
`supports the recommendation and reflects the best evidence available.
`In the process of revising this document, a detailed literature search of articles in the English language was
`conducted in December 2007 in PubMed and the Cochrane Library on the subject of dry eye for the years
`2002 to 2007. To complete this limited revision, PubMed and the Cochrane Library were searched on
`January 27, 28, February 4, 11, and 15, 2011 on the subject of dry eye, limited to English language and
`publication date from 2008 to the date of the search. Details of the literature search are available at
`www.aao.org/ppp. The results were reviewed by the Cornea/External Disease Panel and used to prepare
`the recommendations, which they rated in two ways.
`The panel first rated each recommendation according to its importance to the care process. This
`P<@CBEG3A57 GB G;7 53E7 CEB57FFQ E3G<A9 E7CE7F7AGF 53E7 G;3G G;7 C3A7? G;BH9;G JBH?6 <@CEBI7 G;7 DH3?<GL B8
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`# Level A, defined as most important
`# Level B, defined as moderately important
`# Level C, defined as relevant but not critical
`The panel also rated each recommendation on the strength of evidence in the available literature to support
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`# Level I includes evidence obtained from at least one properly conducted, well-designed, randomized
`controlled trial. It could include meta-analyses of randomized controlled trials.
`# Level II includes evidence obtained from the following:
`# Well-designed controlled trials without randomization
`# Well-designed cohort or case-control analytic studies, preferably from more than one center
`# Multiple-time series with or without the intervention
`# Level III includes evidence obtained from one of the following:
`# Descriptive studies
`# Case reports
`# Reports of expert committees/organizations (e.g., PPP panel consensus with external peer review)
`The evidence cited is that which supports the value of the recommendation as something that should be
`performed to improve the quality of care. The panel believes that it is important to make available the
`strength of the evidence underlying the recommendation. In this way, readers can appreciate the degree of
`importance the panel attached to each recommendation and they can understand what type of evidence
`supports the recommendation.
`The ratings of importance and the ratings of strength of evidence are given in bracketed superscripts after
`735; E75B@@7A63G<BA% *BE <AFG3A57$ P1(',,2Q <A6<53G7F 3 E75B@@7A63G<BA J<G; ;<9; <@Cortance to clinical
`care [A], supported by sufficiently rigorous published evidence, though not by a randomized controlled
`trial [II].
`The sections entitled Orientation and Background do not include recommendations; rather, they are
`designed to educate and provide summary background information and rationale for the recommendations
`that are presented in the Care Process section. A summary of the major recommendations for care is
`included in Appendix 2.
`
`2
`
`

`

`ORIENTATION
`
`ENTI
`
`3
`
`

`

`percentages is used, extrapolating to the U.S. population aged 65 to 84 years yields estimates of
`approximately 1 million to 4.3 million people who have dry eye. A population-
`
`4
`
`

`

`A study of dry eye and quality of life found decreased quality of life for all severity levels of dry eye
`syndrome, with an effect on quality of life for severe dry eye comparable with that reported for
`moderate angina.13 A study of anxiety and depression among patients found a high correlation in
`dry eye patients.14 Another study found that patients with dry eye syndrome of any severity level
`reported more limitations due to physical problems and more pain when compared with general
`population norms for the Medical Outcomes Study Short Form-36 (SF-36) Health Survey.15,16
`Patients with severe dry eye reported lower scores than the norms across all scales of the SF-36.15 In
`11
`a study of patients with glaucoma, dry eye syndrome negatively influenced patientRF DH3?<GL B8 ?<87%
`
`PATHOGENESIS
`It is now recognized that the ocular surface and tear-secreting glands function as an integrated unit to
`maintain the tear supply and to clear used tears.17 Disease or dysfunction of this functional unit
`results in an unstable and poorly maintained tear film that causes ocular irritation symptoms and the
`epithelial disease called keratoconjunctivitis sicca (KCS). Dysfunction of this integrated unit may
`develop from aging, a decrease in supportive factors (such as androgen hormones), systemic
`inflammatory diseases (such as rheumatoid arthritis), ocular surface diseases (such as herpes simplex
`virus keratitis) or surgeries that disrupt the trigeminal afferent sensory nerves (e.g., LASIK), and
`systemic diseases or medications that disrupt the efferent cholinergic nerves that stimulate tear
`secretion.18 Decreased tear secretion and clearance initiates an inflammatory response on the ocular
`surface that involves both soluble and cellular mediators.19,20 Clinical and basic research suggests
`that this inflammation plays a role in the pathogenesis of KCS (see Figure 1).21,22
`
`Rheumatoid Arthritis
`#'.&+%)0, #-)$+*(%
`
`Secretory Dysfunction
`Lacrimal Gland
`Meibomian Gland
`
`Hyperosmolar
`Tears
`
`Ocular Surface Epithelial Disease
`(Keratoconjunctivitis Sicca)
`
`Ocular Surface Inflammation
`
`Female Gender
`Androgen Deficiency
`
`Adhesion
`Molecules
`
`T Cell
`Infiltration
`
`MMPs
`
`Apoptosis
`
`Cytokines
`Chemokines
`
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`
`ASSOCIATED CONDITIONS
`Symptoms caused by dry eye may be exacerbated by the use of systemic medications such as
`diuretics, antihistamines, anticholinergics, antidepressants, and systemic retinoids (e.g.,
`isotretinoin).4,8,10,23-27 Instillation of any eye medications, especially when they are instilled
`frequently (e.g., more than four drops a day), may prevent the normal maintenance of the tear film
`and cause dry eye symptoms. In addition, environmental factors, such as reduced humidity and
`increased wind, drafts, air conditioning, or heating may exacerbate the ocular discomfort of patients
`with dry eye. Exogenous irritants and allergens, although not believed to be causative of dry eye,
`may exacerbate the symptoms.
`Blepharitis associated with meibomitis was noted in 3.6% of 2520 subjects aged 65 years and older
`in the population-based study of residents of Salisbury, Maryland.1 Those patients were twice as
`likely to have dry eye symptoms as those without signs of meibomitis. A recent study in Spain
`indicated that nearly half of patients with dry eye have meibomian gland dysfunction.28 In addition,
`
`5
`
`

`

`hyposecretory meibomian gland dysfunction may be a precursor to obstructive meibomian gland
`dysfunction and may play a role in the pathogenesis of dry eye disease.29
`Associated systemic diseases include Sjögren syndrome, in which an inflammatory cellular
`infiltration of the lacrimal gland leads to tear-production deficiency, and rosacea, which is
`associated with posterior blepharitis with increased tear evaporation (see Appendix 3). Aqueous tear
`deficiency may develop in conditions that result in infiltration of the lacrimal gland and replacement
`of the secretory acini such as lymphoma, sarcoidosis,30,31 hemochromatosis, and amyloidosis.32 Dry
`eye may develop in patients with systemic viral infections; it has been reported in patients infected
`by the retroviruses, human T-cell lymphotropic virus type 1, and human immunodeficiency virus
`(HIV).33 Dry eye was diagnosed in 21% of a group of patients with AIDS34 and a condition known
`as diffuse infiltrative lymphadenopathy syndrome has been reported in patients with HIV infection,
`most of whom were children.33 Decreased tear secretion, reduced tear volume, and reduced tear
`concentrations of lactoferrin have been reported in patients with hepatitis C.35,36 Lacrimal gland
`swelling, dry eye, and Sjögren syndrome have been associated with primary and persistent Epstein-
`Barr virus infections.37-40 Severe dry eye has been reported to occur in recipients of allogenic bone
`marrow or stem cell transplants with or without the development of graft-versus-host disease
`(GVHD).41,42 In chronic GVHD, there is infiltration and fibrosis of the lacrimal glands as a result of
`T-cell interaction with fibroblasts.41,43,44 Diseases such as ocular mucous membrane pemphigoid and
`Stevens-Johnson syndrome produce tear deficiency due to inflammation, scarring, and destruction
`of the conjunctival goblet cells. Atopy may produce dry eye due to blepharitis, conjunctival
`scarring, or antihistamine use.
`Local conditions associated with dry eye include eyelid malposition, lagophthalmos, and blepharitis
`as well as neuromuscular disorders that affect blinking (e.g., Parkinson disease, Bell palsy).45 Local
`trauma, including orbital surgery, radiation, and injury, may also cause dry eye.
`
`NATURAL HISTORY
`Dry eye syndrome varies in severity, duration, and etiology.46 In the majority of patients, the
`condition is not sight-threatening and is characterized by troublesome symptoms of irritation and
`intermittently blurred vision. In some individuals, exacerbating factors such as systemic medications
`that decrease tear production or environmental conditions that increase tear evaporation may lead to
`an acute increase in the severity of symptoms. Elimination of such factors often leads to marked
`improvement and may even be curative. In other patients in whom the dry eye condition is caused
`by a nonreversible deficiency of tear production or a chronic condition leading to increased
`evaporation such as blepharitis, the disease may exhibit chronicity, characterized by fluctuating
`severity of symptoms and/or a gradual increase in symptom severity with time.
`Reversible conjunctival squamous metaplasia and punctate epithelial erosions of the conjunctiva and
`cornea develop in many patients who have moderate to severe dry eye. Rarely, patients with severe
`dry eye will develop complications such as ocular surface keratinization; corneal scarring, thinning,
`or neovascularization; microbial or sterile corneal ulceration with possible perforation; and severe
`visual loss.47
`
`CARE PROCESS
`
`PATIENT OUTCOME CRITERIA
`Outcome criteria for treating dry eye include the following:
`# Reducing or alleviating signs and symptoms of dry eye
`# Maintaining and improving visual function
`# Reducing or preventing structural damage
`
`DIAGNOSIS
`Many ocular surface diseases produce symptoms that are similar to those associated with dry eye,
`including foreign body sensation, mild itching, irritation, and soreness. Identifying characteristics of
`
`6
`
`

`

`the causative factors, such as adverse environments (e.g., air travel, sitting near an air conditioner
`vent, low humidity), prolonged visual efforts (e.g., reading, computer use), or ameliorating
`circumstances (symptomatic relief with the use of artificial tears) is helpful in diagnosing dry eye.
`Supporting clinical observations and tests are used to confirm the diagnosis. A diagnostic
`classification scheme adapted from the 2007 Report of the International Dry Eye Workshop is
`shown in Figure 2. Participants in the workshop agreed that the two major factors, deficient aqueous
`tear production and increased evaporative loss, may cause dry eyes independently, but they may also
`be present together and both contribute to dry eye symptoms and signs. Most patients have multiple
`factors contributing to dry eye. Many conditions, such as neurotrophic keratitis after herpes simplex
`virus infection or LASIK, include aspects of decreased tear production and increased evaporative
`loss.
`All patients should have a comprehensive adult medical eye evaluation at the recommended
`intervals.48 [A:III] The initial evaluation of a patient who presents with symptoms suggestive of dry
`eye should include those features of the comprehensive adult medical eye evaluation relevant to dry
`eye.48 [A:III]
`
`DRY EYE
`
`Aqueous-deficient
`
`Combination
`
`Evaporative
`
`Sjögren Syndrome
`Dry Eye
`
`Non-Sjögren
`Dry Eye
`
`Intrinsic
`
`Extrinsic
`
`Primary
`
`Lacrimal
`Deficiency
`
`Meibomian Oil
`Deficiency
`
`Secondary
`
`Lacrimal
`Gland Duct
`Obstruction
`
`Reflex Block
`
`Systemic
`Drugs
`
`Disorders of
`Lid Aperture
`
`Low Blink
`Rate
`
`Drug Action
`e.g., isotretinoin
`
`Vitamin A-
`Deficiency
`
`Topical Drugs
`Preservatives
`
`Contact Lens
`Wear
`
`Ocular Surface
`Disease
`e.g., allergy
`
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`
`Patient History
`Questions about the following elements of the patient history may elicit helpful information:
`# Symptoms and signs:[A:III] e.g., irritation, tearing, burning, stinging, dry or foreign body sensation,
`mild itching, photophobia, blurry vision, contact lens intolerance, redness, mucous discharge,
`increased frequency of blinking, eye fatigue, diurnal fluctuation, symptoms that worsen later in the
`day
`# Exacerbating conditions:[B:III] e.g., wind, air travel, decreased humidity, prolonged visual efforts
`associated with decreased blink rate such as reading and computer use
`# Duration of symptoms[A:III]
`The ocular history may include details about the following:
`# Topical medications used, their frequency, and their effect on symptoms:[A:III] e.g., artificial tears,
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`# Contact lens wear, schedule, and care[A:III]
`
`7
`
`

`

`# Allergic conjunctivitis[B:III]
`# Ocular surgical history:[A:III] e.g., prior keratoplasty, cataract surgery, keratorefractive surgery
`# Ocular surface disease:[A:III] e.g., herpes simplex virus, varicella zoster virus, ocular mucous
`membrane pemphigoid, Stevens-Johnson syndrome, aniridia, GVHD
`# Punctal surgery[A:III]
`# Eyelid surgery:[A:III] e.g., prior ptosis repair, blepharoplasty, entropion/ectropion repair
`# Bell palsy[A:III]
`The medical history may take into account the following elements:
`# Smoking or exposure to second-hand smoke[A:III]
`# Dermatological diseases:[A:III] e.g., rosacea
`# Technique and frequency of facial washing including eyelid and eyelash hygiene[A:III]
`# Atopy[A:III]
`# Menopause[A:III]
`# Systemic inflammatory diseases:[A:III] e.g., Sjögren syndrome, GVHD, rheumatoid arthritis, systemic
`lupus erythematosus, scleroderma
`# Other systemic conditions:[A:III] e.g., lymphoma, sarcoidosis
`# Systemic medications:[A:III] e.g., antihistamines, diuretics, hormones and hormonal antagonists,
`antidepressants, cardiac antiarrhythmic drugs, isotretinoin, diphenoxylate/atropine, beta-adrenergic
`antagonists, chemotherapy agents, any other drug with anticholinergic effects
`# Trauma:[B:III] e.g., chemical
`# Chronic viral infections: [B:III] e.g., hepatitis C, HIV
`# Nonocular surgery:[B:III] e.g., bone marrow transplant, head and neck surgery, trigeminal neuralgia
`surgery
`# Radiation of orbit[B:III]
`# Neurological conditions:[B:III] e.g., Parkinson disease, Bell palsy, Riley-Day syndrome, trigeminal
`neuralgia
`# Dry mouth, dental cavities, oral ulcers[B:III]
`
`Examination
`The physical examination includes a visual acuity measurement,[A:III] an external examination,[A:III]
`and slit-lamp biomicroscopy.[A:III] The purpose of the external examination and the slit-lamp
`biomicroscopy is to do the following:
`# Document the signs of dry eye
`# Assess the presence and severity of deficient aqueous tear production and/or increased evaporative
`loss
`# Determine other causes of ocular irritation
`The external examination should pay particular attention to the following:
`# Skin:[A:III] e.g., scleroderma, facial changes consistent with rosacea
`# Eyelids:[A:III] incomplete closure/malposition, incomplete or infrequent blink, eyelid lag, erythema of
`eyelid margins, abnormal deposits or secretions, entropion, ectropion
`# Adnexa:[A:III] enlargement of the lacrimal glands
`# Proptosis[B:III]
`# Cranial nerve function:[A:III] e.g., cranial nerve V (trigeminal), cranial nerve VII (facial)
`# Hands:[B:III] joint deformities characteristic of rheumatoid arthritis
`The slit-lamp biomicroscopy should focus on the following:
`# Tear film:[A:III] height of the meniscus, debris, increased viscosity, mucus strands, and foam
`# Eyelashes:[A:III] trichiasis, distichiasis, deposits
`# Anterior and posterior eyelid margins:[A:III] abnormalities of meibomian glands (e.g., orifice
`metaplasia, reduced expressible meibum, atrophy), character of meibomian gland secretions (e.g.,
`turbid, thickened, foamy, deficient), vascularization crossing the mucocutaneous junction,
`keratinization, scarring
`# Puncta:[A:III] patency, position, presence, and position of plugs
`
`8
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`

`

`#
`
`# Conjunctiva:
`Inferior fornix and tarsal conjunctiva:[A:III] e.g., mucous threads, scarring, erythema, papillary
`reaction, follicle enlargement, keratinization, foreshortening, symblepharon
`# Bulbar conjunctiva:[A:III] e.g., punctate staining with rose bengal or fluorescein dyes; hyperemia;
`localized drying; keratinization
`# Cornea:[A:III] localized interpalpebral drying, punctate epithelial erosions, punctate staining with rose
`bengal or fluorescein dyes, filaments, epithelial defects, mucous plaques, keratinization, pannus
`formation, thinning, infiltrates, ulceration, scarring, neovascularization, evidence of corneal or
`refractive surgery
`
`Diagnostic Tests
`For patients with mild irritation symptoms, a rapid tear break-up time may indicate an unstable tear
`film with normal aqueous tear production, and there may be minimal or no dye staining of the
`ocular surface.49
`For patients with moderate to severe aqueous tear deficiency, the diagnosis can be made by using
`one or more of the following tests: tear break-up time test, ocular surface dye staining (rose bengal,
`fluorescein, or lissamine green), and the Schirmer test. These tests should be performed in this
`sequence because the Schirmer test can disrupt tear film stability and cause false-positive ocular-
`surface dye staining. (See Appendix 4 for detailed descriptions of these tests.) Corneal sensation
`should be assessed when trigeminal nerve dysfunction is suspected.50 [A:III] A laboratory and clinical
`evaluation for autoimmune disorders should be considered for patients with significant dry eye,
`other signs and symptoms of an autoimmune disorder (e.g., dry mouth), or a family history of an
`autoimmune disorder.[A:III]
`
`CLASSIFICATION OF DRY EYE SYNDROME
`Specific systems to classify dry eye severity have been developed (see Appendix 5); however, these
`are primarily for research purposes and have not been widely used in clinical care.
`Dry eye is generally classified according to a combination of symptoms and signs. In this PPP, dry
`eye has been classified as mild, moderate, and severe based on both symptoms and signs, but with
`an emphasis on symptoms over signs.51 Due to the nature of dry eye disease, this classification is
`imprecise because characteristics at each level overlap.
`Patients with mild dry eye syndrome may have symptoms of irritation, itching, soreness, burning, or
`intermittent blurred vision. It is often difficult to diagnose dry eye definitively in its mild form
`because of the inconsistent correlation between reported symptoms and clinical signs52 as well as the
`relatively poor specificity and/or sensitivity of clinical tests.53,54 Because most dry eye conditions
`have a chronic course, repeated observation and reporting of symptoms over time will allow clinical
`diagnosis of dry eye in most cases.
`Patients with moderate dry eye syndrome have increased discomfort and frequency of symptoms,
`and the negative effect on visual function may become more consistent.
`Patients with severe dry eye syndrome have increasing frequency of symptoms which may become
`constant, as well as potentially disabling visual symptoms.
`Dry eye syndrome is also loosely categorized into one of two forms, aqueous tear deficiency and
`evaporative tear deficiency, and both of these conditions may be present in patients with the disease.
`Table 2 lists characteristic findings for each diagnostic test for each condition.
`
`TREATMENT
`Patients with dry eye symptoms often have many contributory factors. It is imperative to treat any
`causative factors that are amenable to treatment. Tear replacement is frequently unsuccessful when
`used as the sole treatment if additional causative factors are not concomitantly addressed.
`For patients with irreversible tear deficiency or evaporative increase associated with chronic
`condi