Dry Eye Disease - Nordic Guidelines 2016

 

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Dry Eye Disease - Nordic Guidelines 2016

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Nordic Guidelines 2016 Dry Eye Disease Introductory Background Diagnosis and monitoring Management and therapy Tear supplementation: Lubricants Steffen Heegaard Lars Loumann Knudsen Gysbert van Setten Gabor Koranyi Juha Holopainen Kai Kaarniranta Per Klyve Sten Ræder

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Colofon Steffen Heegaard Professor, Consultant, MD DMSc Department of Ophthalmology University Hospital Rigshospitalet Glostrup Nordre Ringvej 57 2600 Glostrup, Denmark Eye Pathology Section, University of Copenhagen Teilum-bygningen, Frederik V’s Vej 11, 1.sal, 2100 København Ø, Denmark, Lars Loumann Knudsen Øjenlæge, dr. med., ph.h. Lektor i oftalmologi (Aarhus Universitet) HH Seedorffs Stræde 3-5, 5 8000 Aarhus C, Denmark Gabor Koranyi MD PhD, Director Eye department Växjö Central Hospital, Sweden Gysbert van Setten MD PhD Ass Prof Clin Ophthalmology St Eriks Eye Hospital / Karolinska Institutet Polhemsgatan 50 11282 Stockholm, Sweden Per Klyve Øyelege Asker og Bærum Øyelegesenter Knud Askers veg 28b 1383 Asker, Norway Sten Ræder M.D. Ph.D., Øyelege Tørreøyneklinikken AS, SynsLaser Kirurgi, Oslo Norway Juha Holopainen Professor, Chief Physician Helsinki Eye Lab Ophthalmology, University of Helsinki and Helsinki University Hospital Haartmaninkatu 4C 00290 Helsinki, Finland Kai Kaarniranta Professor, Chief Physician University of Eastern Finland and Kuopio University Hospital Institute of Clinical Medicine Department of Ophthalmology P.O.BOX 1627 70211 Kuopio, Finland

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Dry Eye Disease Nordic Guidelines Steffen Heegaard Lars Loumann Knudsen Gysbert van Setten Gabor Koranyi Juha Holopainen Kai Kaarniranta Per Klyve Sten Ræder Conflict of interest: T he authors have not received any compensation from any party for the production of this script and have no commercial interest in it’s publication.

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Contents Foreword 7 Introductory Background 8 Introduction 9 Tear glands and glands important for maintaining the tear film 9 Tears 10 The tear film consists of three layers 12 Oil / Lipid Layer: 12 Water (Aqueous) Layer: 12 Mucin (Mucous) Layer: 12 Definition 13 Characterisation of Dry Eye Disease 13 Dry eye disease 13 1. Quantitative DED (Aqueous deficient) causes can be 14 Aqueous Tear-defect 14 2. Qualitative Dry Eye Disease = Evaporative 16 The causative mechanisms of dry eye 18 a. Tear hyperosmolarity 18 b. Tear film instability 18 Classification based on severity 18 References 19 The Epidemiology of Dry Eye Disease 20 Introduction 20 Prevalence and incidence 21 Prevalence 22 Incidence 24 Quality of life (QoL) in Dry Eye Disease (DED) 24 Impact on Visual Function 24 Risk Factors for DED 25 Dry Eye Questionnaires 26 Summary 27 References 28 Introduction 29 Primary methods to diagnose and monitor dry eye disease 29 Symptom questionnaires 29 Diagnosis and monitoring dry eye disease 29 Tear film break up time (BUT) 30 Vital staining 30 Schirmer test 31 Meibomian gland evaluation 32 Advanced methods to diagnose and monitor dry eye disease 32 Tear film osmolarity 32 Meibography in the diagnosis of MGD 33 Corneal imaging 34 Inflammatory markers 34 Impression cytology 35 References 35 Table 2. Treatment algorithm for dry eye disease 36 Introduction 37 Tear supplementation: Lubricants 37 General considerations 37 Viscosity agents 37

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Contents Management and therapy of dry eye disease 37 Electrolyte composition 38 Osmolarity 38 Preservatives 38 Punctal occlusion 38 Moisture chamber spectacles 38 Contact lenses 38 Tear stimulation: Secretagogues 39 Biological tear substitutes 39 Serum 39 Salivary gland autotransplantation 3 9 Anti-inflammatory therapy 40 Cyclosporine 40 Corticosteroids 40 Tetracyclines 40 Essential fatty acids 40 Environmental strategies 41 External factors that increase tear evaporation 41 Medication that may decrease tear production 41 Meibomian Gland Dysfunction Meibomian gland dysfunction Eyelid treatment Lipid-containing artificial tears Tetracyclines and azithromycin Table 3. Treatment algorithm for MGD Future perspectives References 42 42 42 42 42 43 44 45 Tear supplementation: Lubricants 46

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Foreword Dear colleagues ! Dry eye disease is a very common disease in the world and with the increase of the elder population all over the world there is a huge demand for treating the disease as optimal as possible. Many different health care persons treat dry eye disease patients and many patients try different drops before seeking professional help. We wished by writing the Nordic Guidelines 2016 to present an easy going pamphlet usable for health care persons dealing with this patient category. Many different ocular conditions may lead to dryness, burning and a sandy/gritty sensation of the eye. Therefore, the correct diagnosis is essential and it is important to perform the tests described in the Guidelines 2016. The field is developing fast and many new treatment strategies and ointments have been introduced to the market. In order to help the reader we have put all the different lubricants in the Nordic market in one table and dependent on the cause of the dry eye disease in your patient, a treatment strategy should be made. We all hope the reader find the Nordic Guidelines 2016 for Dry Eye Disease valuable. Steffen Heegaard Lars Loumann Knudsen Gysbert van Setten Gabor Koranyi Juha Holopainen Kai Kaarniranta Per Klyve Sten Ræder Tear Film Cornea Mucin Layer Water Layer Oil Layer 7

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Introductory Background 8

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Introductory Background Introduction Millions of people suffer from dry eye. This condition can be caused by many different internal and external factors and it is therefore mandatory to find out what causes the dry eye in order to give the correct treatment. Dry eye disease (DED) may lead to ocular surface discomfort, often described as feelings of dryness, burning, a sandy/gritty sensation, or itchiness and thus causes ocular discomfort for many, many people. This may lead to decreased visual acuity, sensitivity to light, and blurred vision for patients suffering from dry eye disease. Tear glands and glands important for maintaining the tear film The tear volume is mainly produced in the lacrimal gland which is a tubuloacinar gland. It consists of two parts: The smaller palpebral portion that lies along the inner surface of the eyelid and the orbital portion. The lacrimal gland is innervated by the lacrimal nerve (sensory) afferent pathway, the facial nerve (parasympathetic) efferent pathway for reflex secretion, and the sympathetic nervous system. The tear gland secretes the aqueous layer of the tear film. The accessory lacrimal exocrine glands of Wolfring and Krause structurally resemble the main lacrimal gland. The glands of Krause are located in the superior and inferior conjunctival fornices. The glands of Wolfring can be found along the upper border of the superior tarsus, below the lower tarsus and an occasional gland in the caruncle and in the plica semilunaris. The meibomian glands are found closely packed within the tarsal plate and are arranged in a parallel fashion, extending the entire height of the tarsal plate. They are taller and more numerous in the larger superior tarsus than in the smaller inferior tarsus. The glands of Zeis are found along the roots of the eyelashes, to which their contribution is less significant. Conjunctival goblet cells are found in greatest concentration along the eyelid margins, conjunctival fornices, antimarginal tarsal borders (crypts of Henle), and corneal-scleral limbus (glands of Manz). The accessory lacrimal glands have been called the basal secretors because they do not possess direct secretory motor fibres. The other basal secretors are the sebaceous glands (meibomian 9

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Introductory Background and Zeis) and the mucous glands in the conjunctiva (goblet cells). The reflex secretor is the lacrimal gland. Reflex secretion provides additional secretion by peripheral sensory (fifth nerve efferent, seventh nerve afferent), retinal or psychogenic stimulation. Tears Each time we blink, a protective coating of tears is spread like a film on top of the cornea. The tear film serves four important purposes: 1. Protects and lubricates the eyes. 2. Provide nutrients and supports the health of cells in the cornea. 3. Protects the exposed surface of the eye from infections. 4. Washes away foreign particles. Fig. 1. Normal healthy tears C C C C 10 C C C C C C C C C C C C C Electrolytes Na K C1 Ca Proteins Lysozyme Fe Lactoferrin Lipocalin Albumin EGF Cytokines IL-1B TNF-a C C C IL - 1RA TGF-B Mucin 1, Mucin 4 Mucin 5AC Latent Proteases Active Proteases IgA IgG IgM

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Introductory Background Normal healthy tears contain a complex mixture of proteins and other components that are essential for ocular health and comfort (Figure 1). Clear vision depends on homogenous composition and even distribution of tears over the ocular surface. For Sjögren’s syndrome patients, inflammation of tear-secreting glands reduces tear production, resulting in chronic dry eye. In addition, changes in the composition of tears contribute to dry eye (Figure 2). Fig. 2. Alteration in tear composition in dry eye Electrolytes Na K C1 Ca Proteins Lysozyme Fe Lactoferrin Lipocalin Albumin EGF Cytokines IL-1B TNF-a C IL - 1RA TGF-B Mucin 1, Mucin 4 Mucin 5AC Active Proteases IgA IgG IgM 11

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Introductory Background The tear film consists of three layers The tear film is made up of three layers – an oil (lipid) layer, a water (aqueous) layer and a mucin layer. When any part of the tear film is not functioning properly, you may start to experience dry eye symptoms. Oil / Lipid Layer: The outer layer of the tear film is an oil or lipidbased layer. Its main purpose is to seal the tear film which reduces evaporation of the tears. The lipid layer is derived primarily from the meibomian glands in the lids as well as some secretion from the glands of Zeis. The oily layer prevents escape of aqueous tears over the edge of the eyelid margin and retards evaporation of the watery layer. It also provides a lubrication effect between the lid and cornea. Tear Film Water (Aqueous) Layer: The middle layer is mostly comprised of water and is the thickest layer of the precorneal tear film. It is produced by the main lacrimal gland and the accessory lacrimal glands (Wolfring and Krause). It lubricates the eye, washes away particles and prevents infection as it contains most of the bactericidal lysozymes and other proteins. Mucin (Mucous) Layer: The inner and densest layer is the mucin layer and is produced by the conjunctival goblet cells and the conjunctival epithelial cells. The mucin layer allows the watery layer to spread evenly over the surface of the eye and helps the eye remain moist and lubricated. It also provides the underlying cornea epithelium with nourishment. This layer helps the tears adhere to the surface of the eye, but also to clear debirs and pathogens. Lipid layer Hydrophobic active Aqueous layer Hydrophobic active Cornea Mucin Layer Water Layer Oil Layer 12 Mucin strands Mucin layer

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Dry eye disease Definition “Dry eyes are a multifactor disease of the tears and the 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 Dry eye is recognised as a disturbance in the lacrimal functional unit, which is an integrated system comprising the lacrimal gland, the ocular surface, the lids and the sensory and motor nerves that connect them. The functional unit controls the major components of the tear film in a regulated fashion and responds to environmental, endocrinological, and cortical influences. Its overall function is to preserve the integrity of the tear film, the transparency of the cornea and the quality of the image projected to the retina. Characterisation of Dry Eye Disease Dry eye disease can be divided into (figure 3): 1. Quantitative Dry Eye Disease = Aqueous deficient 2. Qualitative Dry Eye Disease = Evaporative Either the tear quantity or tear quality can be compromised. If there is decreased secretion of tears by the lacrimal and the other tear producing glands the quantity of the tears are diminished. If the condition is caused by excess evaporation due to a diseased lipid layer, the quality of the tears is compromised. . Fig. 3 OCULAR SURFACE DISEASE DRY EYE DISEASE NON-DRY EYE DISEASE Quantitative DED Aqueous-deficient Qualitative DED Evaporative Sjögren Non-Sjögren Syndrome Syndrome Intrinsic Extrinsic Blepharitis Other MGD Allergy infection 13

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Dry eye disease 1. Quantitative DED (Aqueous deficient) causes can be i. Sjögren 1. Primary Sjögren 2. Secondary Sjögren ii. Non Sjögren 1. Primary lacrimal gland deficiency 2. Secondary lacrimal gland deficiency 3. Obstructed lacrimal gland ducts 4. Reflex hyposecretion 5. Pharmacological agents Aqueous Tear-defect Aqueous tear-deficient dry eye implies dry eye as a result of a failure of the lacrimal tear secretion. Sjögren Syndrome dry eye (SSDE) is an exocrinopathy in which the lacrimal and salivary glands are targeted by an autoimmune process. The ocular dryness in SSDE is due to lacrimal hyposecretion and the accompanying characteristic inflammatory changes in the lacrimal gland and the presence of inflammatory mediators in the tears and within the conjunctiva. SSDE can be subdivided into primary form SSDE with the occurrence of aqueous tear defect dry eye in combination with symptoms of dry mouth, in the presence of auto antibodies, evidenced of reduced salivary secretion and a positive score on minor salivary gland biopsy. A secondary form of SSDE consists of the symptoms from primary SS together with the features of an overt autoimmune disease (rheumatoid arthritis, SLE, polyarteritis nodosa, Wegener’s granulomatosis, systemic sclerosis, primary biliary sclerosis and mixed connective tissue disease). Non-Sjögren syndrome dry eye is a form of aqueous defect dry eye due to lacrimal dysfunction, where the systemic autoimmune features characteristic of SSDE have been excluded. It can be the result of a number of various conditions and classified in accordance hereby. a. Primary lacrimal gland deficiency can be the result of age related changes, congenital alacrima (rare) or familial dysautonomia. It represents primary changes in the lacrimal gland without underlying more generalised disease. 14

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Dry eye disease b. Secondary lacrimal gland deficiency is the result of changes in the lacrimal gland as lacrimal gland infiltration, sarcoidotic inflammation in the gland, gland lymphoma, T-cell infiltration in the gland in AIDS patients, lacrimal gland fibrosis following graft vs host disease, lacrimal gland ablation and lacrimal gland denervation. c. Obstruction of the lacrimal ducts as the result of any form of conjunctival cicatrising as in trachoma, cicatricial pemphigoid and mucous membrane pemphigoid, erythema multiforma and following chemical and thermal burns. d. Reflex hyposecretion can be the result of a sensory block. It can be initiated from an altered sensory drive from the ocular surface, by decreased reflex-induced lacrimal secretion and increased evaporation due to a lowered blinking rate. It can also represent a motor block from damage of the VII cranial nerve. e. The use of various pharmacological agents can decrease the tear secretion. It includes antihistamines, beta blockers, antispasmodics, diuretics tricyclic antidepressants, selective serotonin uptake inhibitors, calcium channel blockers and cholesterol-lowering drugs. 15

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