AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Dry eye is a multifactorial 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.¹ Dry eye is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.¹

The tear layer covers the normal ocular surface. Generally, it is accepted that the tear film is made up of 3 intertwined layers, as follows:

1. A superficial thin lipid layer (0.11 µm) is produced by the meibomian glands, and its principal function is to retard tear evaporation and to assist in uniform tear spreading.
2. A middle thick aqueous layer (7 µm) is produced by the main lacrimal glands (reflex tearing), as well as the accessory lacrimal glands of Krause and Wolfring (basic tearing).
3. An innermost hydrophilic mucin layer (0.02-0.05 µm) is produced by both the conjunctiva goblet cells and the ocular surface epithelium and associates itself with the ocular surface via its loose attachments to the glycocalyx of the microplicae of the epithelium. It is the hydrophilic quality of the mucin that allows the aqueous to spread over the corneal epithelium.

Pathophysiology

A genetic predisposition in SS associated KCS exists as evident by the high prevalence of human leukocyte antigen B8 (HLA-B8) haplotype in these patients. This condition leads to a chronic inflammatory state, with the production of autoantibodies, including antinuclear antibody (ANA), rheumatoid factor, fodrin (a cytoskeletal protein), the muscarinic M3 receptor, or SS-specific antibodies (eg, anti-RO [SS-A], anti-LA [SS-B]), inflammatory cytokine release, and focal lymphocytic infiltration (ie, mainly CD4⁺ T cells but also B cells) of the lacrimal and salivary gland, with glandular degeneration and induction of apoptosis in the conjunctiva and lacrimal glands. This results in dysfunction of the lacrimal gland, with reduced tear production, and loss of response to nerve stimulation and less reflex tearing. Active T lymphocytic infiltrate in the conjunctiva also has been reported in non-SS associated KCS.

Both androgen and estrogen receptors are located in the lacrimal and meibomian glands. SS is more common in postmenopausal women. At menopause, a decrease in circulating sex hormones (ie, estrogen, androgen) occurs, possibly affecting the functional and secretory aspect of the lacrimal gland. Forty years ago, initial interest in this area centered on estrogen and/or progesterone deficiency to explain the link between KCS and menopause. However, recent research has focused on androgens, specifically testosterone, and/or metabolized androgens.

It has been shown that in meibomian gland dysfunction, a deficiency in androgens results in loss of the lipid layer, specifically triglycerides, cholesterol, monounsaturated essential fatty acids (eg, oleic acid), and polar lipids (eg, phosphatidylethanolamine, sphingomyelin). The loss of polar lipids (present at the aqueous-tear interface) exacerbates the evaporative tear loss, and the decrease in unsaturated fatty acids raises the melting point of meibum, leading to thicker, more viscous secretions that obstruct ductules and cause stagnation of secretions. Patients on antiandrogenic therapy for prostate disease also have increased viscosity of meibum, decreased tear break-up time, and increased tear film debris, all indicative of a deficient or abnormal tear film.

Various proinflammatory cytokines that may cause cellular destruction, including interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 8 (IL-8), TGF-beta, TNF-alpha, and RANTES, are altered in patients with KCS. IL-1 beta and TNF-alpha, which are present in the tears of patients with KCS, cause the release of opioids that bind to opioid receptors on neural membranes and inhibit neurotransmitter release through NF-K b production. IL-2 also binds to the delta opioid receptor and inhibits cAMP production and neuronal function. This loss of neuronal function diminishes normal neuronal tone, leading to sensory isolation of the lacrimal gland and eventual atrophy.

Proinflammatory neurotransmitters, such as substance P and calcitonin gene related peptide (CGRP), are released, which recruit and activate local lymphocytes. Substance P also acts via the NF-AT and NF-K b signaling pathway leading to ICAM-1 and VCAM-1 expression, adhesions molecules that promote lymphocyte homing and chemotaxis to sites of inflammation. Cyclosporin A is an NK-1 and NK-2 receptor inhibitor that can downregulate these signaling molecules and is a novel addition to the therapeutic armamentarium for dry eye, being used to treat both aqueous tear deficiency and meibomian gland dysfunction. It has been shown to improve the goblet cell counts and to reduce the numbers of inflammatory cells and cytokines in the conjunctiva.

These cytokines, in addition to inhibiting neural function, may also convert androgens into estrogens, resulting in meibomian gland dysfunction, as discussed above. An increased rate of apoptosis is also seen in conjunctival and lacrimal acinar cells, perhaps due to the cytokine cascade. Elevated levels of tissue-degrading enzymes called matrix metalloproteinases (MMPs) are also present in the epithelial cells.

Mucin synthesizing genes, designated MUC1-MUC17, representing both transmembrane and goblet-cell secreted, soluble mucins, have been isolated, and their role in hydration and stability of the tear film are being investigated in patients with dry eye syndrome. Particularly significant is MUC5AC, expressed by stratified squamous cells of the conjunctiva and whose product is the predominant component of the mucous layer of tears. A defect in this and other mucin genes may be a factor in dry eye syndrome development. In addition to dry eye, other conditions, such as ocular cicatricial pemphigoid, Stevens-Johnson syndrome, and vitamin A deficiency, which lead to drying or keratinization of the ocular epithelium, eventually lead to goblet cell loss. Both classes of mucins are decreased in these diseases, and, on a molecular level, mucin gene expression, translation, and posttranslational processing are altered.

Normal production of tear proteins, such as lysozyme, lactoferrin, lipocalin, and phospholipase A2, is decreased in KCS.

Frequency

United States

Dry eye is a very common disorder affecting a significant percentage (approximately 10-30%) of the population, especially those older than 40 years. 

In the United States, an estimated 3.23 million women and 1.68 million men, a total of 4.91 million people, aged 50 years and older are affected.

International

The frequency of dry eye in other countries closely parallels that of the United States.

Mortality/Morbidity

Dry eye may be complicated by sterile or infectious corneal ulceration, particularly in patients with SS. Ulcers are typically oval or circular, less than 3 mm in diameter, and located in the central or paracentral cornea. Occasionally, corneal perforation may occur. In rare cases, sterile or infectious corneal ulceration in dry eye syndrome can cause blindness. Other complications include punctate epithelial defects (PEDs), corneal neovascularization, and corneal scarring.

Race

The frequency and the clinical diagnosis of dry eye are greater in the Hispanic and Asian populations than in the Caucasian population.

Sex

Dry eye may be slightly more common in women. KCS associated with SS (a type of dry eye) is believed to affect 1-2% of the population, and 90% of those affected are women.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Ocular irritation of dry sensation, burning, itching, pain, foreign body sensation, photophobia, and blurred vision are common in patients with dry eye. These symptoms are often exacerbated in smoky or dry environments, by indoor heating, or by excessive reading or computer use. These symptoms are quantified objectively in the Ocular Surface Disease Index (OSDI) questionnaire, which lists 12 symptoms and grades each on a scale of 1-4.
• In KCS, symptoms tend to be worse toward the end of the day, with prolonged use of the eyes, or with exposure to extreme environmental conditions. Patients with meibomian gland dysfunction may complain of redness of the eyelids and conjunctiva, but, in these patients, the symptoms are worse on awakening in the morning.
• Paradoxically, some patients with dry eye syndrome complain of too much tearing. When evidence of dry eye syndrome exists, this symptom often is explained by excessive reflex tearing due to severe corneal surface disease from the dryness.
• Certain systemic medications also decrease tear production, such as antihistamines, beta-blockers, and oral contraceptives.
• Past medical history may be significant for coexisting connective tissue disease, rheumatoid arthritis, or thyroid abnormalities. A thorough review of systems should be obtained, asking specifically about dry mouth.

Physical

• Signs of a dry eye include the following:
• • Bulbar conjunctival vascular dilation
  • Decreased tear meniscus
  • Irregular corneal surface
  • Decreased tear break-up time
  • Punctate epithelial keratopathy
  • Corneal filaments
  • Increased debris in the tear film
  • Conjunctival pleating
  • Superficial punctuate keratitis, with positive fluorescein staining
  • Mucous discharge
  • Corneal ulcers in severe cases
• Symptoms often do not correlate with signs.
• In severe cases, there may be an epithelial defect or a sterile corneal infiltrate or ulcer. Secondary infectious keratitis also can develop. Both sterile and infectious corneal perforations can occur.

Causes

The International Dry Eye WorkShop (DEWS) recently developed a 3-part classification of dry eye, based on etiology, mechanisms, and disease stage.¹

The classification system, which is updated as an etiopathogenic classification by the DEWS Subcommittees, formulated by the National Eye Institute (NEI)/Industry Dry Eye Workshop Report in 1995, distinguishes 2 main categories (or causes) of dry eye states, as follows: an aqueous deficiency state and an evaporative state.

• Deficient aqueous production
• • Sjogren syndrome dry eye
  • • Primary
    • Secondary
  • Non-Sjogren syndrome dry eye
  • • Lacrimal gland deficiency
    • Lacrimal gland duct obstruction
    • Reflex hyposecretion
    • Systemic drugs
• Evaporative
• • Intrinsic causes
  • • Meibomian gland dysfunction
    • Disorders of lid aperture
    • Low blink rate
    • Drug action (eg, Accutane)
  • Extrinsic causes
  • • Vitamin A deficiency
    • Topical drugs and preservatives
    • Contact lens wear
    • Ocular surface disease (eg, allergy)

Deficient aqueous production

• Non-Sjögren syndrome
• • Primary lacrimal gland deficiencies
  • •  Idiopathic
    • Age-related dry eye
    • Congenital alacrima (eg, Riley-Day syndrome)
    • Familial dysautonomia
  • Secondary lacrimal gland deficiencies
  • • Lacrimal gland infiltration
    • Sarcoidosis
    • Lymphoma
    • AIDS
    • Graft vs host disease
    • Amyloidosis
    • Hemochromatosis
    • Lacrimal gland infectious diseases
    • HIV diffuse infiltrative lymphadenopathy syndrome
    • Trachoma
    • Systemic vitamin A deficiency (xerophthalmia) – Malnutrition, fat-free diets, intestinal malabsorption from inflammatory bowel disease, bowel resection, or chronic alcoholism
    • Lacrimal gland ablation
    • Lacrimal gland denervation
  •  Lacrimal obstructive disease 
  • • Trachoma
    • Ocular cicatricial pemphigoid
    • Erythema multiforme and Stevens-Johnson syndrome
    • Chemical and thermal burns
    • Endocrine imbalance
    • Postradiation fibrosis
  • Medications – Antihistamines, beta-blockers, phenothiazines, atropine, oral contraceptives, anxiolytics, antiparkinsonian agents, diuretics, anticholinergics, antiarrhythmics, topical preservatives in eye drops, topical anesthetics, and isotretinoin
  • Reflex hyposecretion – Reflex sensory block and reflex motor block 
  • • Neurotrophic keratitis - Fifth nerve/ganglion section/injection/compression
    • Corneal surgery - Limbal incision (eg, extracapsular cataract extraction), keratoplasty, refractive surgery (eg, PRK, LASIK, RK)
    • Infective - Herpes simplex keratitis, herpes zoster ophthalmicus
    • Topical agents - Topical anesthesia
    • Systemic medications – Beta blockers, atropine-like drugs
    • Chronic contact lens wear
    • Diabetes
    • Aging
    • Trichloroethylene toxicity
    • Cranial nerve VII (CN VII) damage
    • Multiple neuromatosis
• Sjögren syndrome 
• • Primary (no associated connective tissue disease [CTD])
  • Secondary (associated CTD) 
  • • Rheumatoid arthritis
    • Systemic lupus erythematosus
    • Progressive systemic sclerosis (scleredema)
    • Primary biliary cirrhosis
    • Interstitial nephritis
    • Polymyositis and dermatomyositis
    • Polyarteritis nodosa
    • Hashimoto thyroiditis
    • Lymphocytic interstitial pneumonitis
    • Idiopathic thrombocytopenic purpura
    • Hypergammaglobulinemia
    • Waldenstrom macroglobulinemia
    • Wegener granulomatosis

Evaporative loss

• Intrinsic causes
• • Meibomian gland disease
  • • Reduced number - Congenital deficiency, acquired meibomian gland dysfunction
    • Replacement - Distichiasis, distichiasis lymphedema syndrome, metaplasia
    • Meibomian gland dysfunction
    • • Hypersecretory - Meibomian seborrhea
      • Hyposecretory - Retinoid therapy
      • Obstructive – Simple, primary or secondary to local disease (eg, anterior blepharitis), systemic disease (eg, acne rosacea, seborrheic dermatitis, atopy, ichthyosis, psoriasis), syndromes (eg, anhidrotic ectodermal dysplasia, ectrodactyly syndrome, Turner syndrome), and systemic toxicity (eg, 13-cis retinoic acid, polychlorinated biphenyls); or cicatricial, primary or secondary to local disease (eg, chemical burns, trachoma, pemphigoid, erythema multiforme, acne rosacea, VKC, AKC) 
  • Low blink rate
  • • Physiological phenomenon, such as during performance of tasks that require concentration (eg, working at a computer or a microscope)
    • Extrapyramidal disorder, such as Parkinson disease (decreasing dopaminergic neuron pool)
  • Disorders of eyelid aperture and eyelid/globe congruity
  • • Exposure (eg, craniostenosis, proptosis, exophthalmos, high myopia)
    • Lid palsy
    • Ectropion
    • Lid coloboma
  •  Drug action (eg, Accutane)
•  Extrinsic causes
• • Vitamin A deficiency
  • • Development disorder of goblet cells
    • Lacrimal acinar damage
  • Topical drugs and preservatives (surface epithelial cell damage)
  • Contact lens wear
  • Ocular surface disease (eg, allergy) 

Dry Eye Severity Levels^{1, 2} 

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Cranial nerve V trauma or corneal surgery
Medicamentosa
Nocturnal lagophthalmos
Thygeson superficial punctate keratopathy

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Conjunctival impression cytology can be used to monitor the progression of ocular surface changes. 
• Serology for circulating autoantibodies, including ANA or SS antibodies (ie, SS-A, SS-B), anti-Ro, anti-La, anti-M3 receptor, and anti-fodrin, as well as ANCA and Rh-F, may be indicated.

Other Tests

• Dry eye is essentially a clinical diagnosis, combining information obtained from both the history and the examination and performing 1 or more tests to lend some objectivity to the diagnosis. No one test is sufficiently specific to permit an absolute diagnosis of dry eye.
• Symptom questionnaires can be used to help establish a diagnosis of dry eye and to assess the effects of treatments or to grade disease severity. Fourteen ideal questionnaires are available in Pubmed. 
• Tear break-up test (TBUT) is determined by measuring the time lapse between instillation of fluorescein and appearance of the first dry spots on the cornea. Measure it prior to instillation of any anesthetic eye drops. A fluorescein strip is moistened with saline and applied to the inferior cul-de-sac. After several blinks, the tear film is examined using a broad-beam of slit lamp with a blue filter for the appearance of the first dry spots on the cornea. Decreased TBUT of less than 10 seconds is considered abnormal, indicative of tear instability.
• Use rose bengal and fluorescein staining to evaluate epitheliopathy. Rose bengal stains not only dead and devitalized cells but also healthy cells that are protected inadequately by a mucin coating. Fluorescein pools in epithelial erosions and stains exposed basement membrane. Generally, it stains the cornea more than the conjunctiva. Lissamine green B and sulforhodamine also have been used as staining agents.
• • Early or mild cases of KCS are detected more easily with rose bengal than with fluorescein staining, and the conjunctiva usually is stained more intensely than the cornea. Interpalpebral staining of the nasal and/or inferior paracentral cornea is seen in KCS. A linear pattern of inferior conjunctiva and corneal staining by rose bengal is characteristic of meibomian gland dysfunction.
  • Van Bijsterveld developed a scoring system for rose bengal that evaluates the intensity of staining based on a scale of 0-3 in 3 areas: nasal conjunctiva, temporal conjunctiva, and cornea. With this system, the maximum possible score is 9. According to this system, a score of 3.5 or greater is considered positive for KCS.
  • Lissamine green staining combines the advantages of fluorescein and rose bengal staining; it stains healthy epithelial cells that are not protected by a mucin layer (similar to rose bengal) and also stains degenerating or dead cells (similar to fluorescein). It avoids the pain, discomfort, and corneal toxicity associated with rose bengal but is somewhat less sensitive and more transient, so it is more difficult to appreciate on slit lamp examination.
• Use the Schirmer test to test aqueous tear production. It is performed by placing a thin strip of filter paper in the inferior cul-de-sac; then, the eyes are closed for 5 minutes, and the amount of wetting of the paper strip is measured. Traditionally, the basic secretion test is performed following the instillation of topical anesthetic and the placement of a thin strip of filter paper in the inferior cul-de-sac. The authors prefer this technique and use the corners of soft tissue to wick, by capillary attraction (without any wiping action), all liquid from the inferior fornix prior to placement of the Schirmer paper. Measurement of less than 5 mm is abnormal; 5-10 mm is equivocal.
• • The Schirmer I test, which measures both basic and reflex tearing, consists of the same test without the use of a topical anesthetic agent. Less than 10 mm of wetting after 5 minutes is diagnostic of aqueous tear deficiency. The test is relatively specific, but it is poorly sensitive.
  • The Schirmer II test measures reflex tearing. It is performed similar to the basic secretion test, with the addition of nasal mucosal irritation with a cotton tip applicator. Wetting of less than 15 mm after 5 minutes is consistent with abnormalities of reflex secretion.
• Absence of nasal lacrimal reflex tearing, presence of serum autoantibodies, and severe ocular surface disease demonstrated by rose bengal or fluorescein staining argues strongly in favor of a diagnosis of SS associated KCS.
• Additional tests may be performed to quantify each individual tear component.
• • Lipids may be tested for by collecting meibum, either by squeezing the eyelid margin to encourage expression from the meibomian glands or by using sterile curettes to suck meibum from individual gland orifices. They may be analyzed by high pressure liquid chromatography (HPLC) or gas chromatography with mass spectroscopy (GC-MS).
  • The aqueous/protein component may be tested for by measuring the tear film osmolarity, tear lysozyme, tear lactoferrin, EGF, aquaporin 5, lipocalin, and IgA concentrations with ELISA. Tear film osmolarity has been shown to be elevated in patients with dry eyes. It is a very sensitive test for identifying a dry eye but lacks specificity in meibomitis, herpes simplex keratitis, and bacterial conjunctivitis. The test often is not used because of the lack of commercially available equipment for its measurement.
  • Mucins may be analyzed by using impression cytology or brush cytology techniques, which obtain epithelial and goblet cells that can then be tested for mucin mRNA expression. Immunofluorescence, flow cytometry, ELISA, or immunoblotting techniques may also be used.
  • Conjunctival biopsy for in situ hybridization and immunohistochemistry may also be used.
  • The tear stability analysis system (TSAS) is a noninvasive and objective test that is used to help diagnose tear film instability.
  • Tear evaporation is tested by evaporimetry.
  • The tear function index (TFI) (Liverpool modification) evaluates the tear dynamics of production and drainage and helps detect subjects suffering from dry eye. The test depends on using prepared filter paper strips containing fluorescein, and it has been designed to allow the direct measurement of the TFI using the prepared tear strips.
  • The tear ferning test (TFT) can be used to help diagnose the quality of tears (electrolyte concentration), KCS, and hyperosmolarity. A drop of tears is collected from the lower meniscus and then placed onto a microscope slide and allowed to dry by evaporation. Different forms of branching crystallization patterns can be observed and classified. This test permits the separation of healthy eyes from dry eyes on the basis of the ferning patterns.
• Impression cytology: In mucin layer deficiency, the epithelium may undergo squamous metaplasia, resulting in a loss of goblet cells. This method is very sensitive but requires proper staining and expert analysis of the slide.
• Meibography/meiboscopy: Meibomian gland morphology and density and dropout may be analyzed by using meibography/meiboscopy to help diagnose meibomian gland dysfunction.  Meiboscopy is the visualization of the meibomian gland by transillumination of the eyelid. Meibography implies photographic documentation.
• Meibometry: Meibomian gland dysfunction may be diagnosed by meibometry. Lipid on the lower central lid margin is blotted onto a plastic tape, and the amount taken up is read by optical densitometry. This provides an indirect measure of the steady state level of the meibomian lipid.
• Meniscometry (tear meniscus radius, height, and cross-sectional area): Meniscometry is used to help diagnose aqueous tear deficiency. A rotatable projection system with a target comprising black and white stripes is projected onto the lower central tear film meniscus. Images are recorded and then transferred to a computer to calculate the radius of curvature.
• Patients with dry eye have reduced central corneal thickness values. This is thought to somehow result from the hypertonicity of the tear film in these patients. The corneal thickness increases after therapy with artificial tears, and this has been suggested as a new diagnostic and follow-up criterion for dry eye. Visual acuity and corneal topography and keratometry readings have been shown to improve after the use of artificial tears.
• The tear turnover rate, defined as the percentage decrease of the fluorescein concentration in tears per minute after instillation, is also reduced in patients with symptomatic dry eye. It is tested by using fluorophotometry.

Procedures

• Lacrimal gland or minor (salivary) gland biopsy may be performed to aid in diagnosing SS.

Histologic Findings

Histopathologically, squamous metaplasia with loss of goblet cells, cellular enlargement, and increase in cytoplasmic/nuclear ratio of the superficial conjunctival epithelial cells are present in patients with KCS. The lacrimal gland and the conjunctiva are also heavily infiltrated by CD4⁺ T cell (and B cell) lymphocytes.

In meibomian gland dysfunction, loss of glandular architecture, dilation of the ductules, ductal occlusion, and hyperkeratinization of the ductal epithelium are seen.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The DEWS Subcommittee members reviewed the Delphi Panel approach to the treatment of dry eye and modified it.¹ Treatment recommendations are based on disease severity.

• Level 1
• • Education and environmental/dietary modifications
  • Elimination of offending systemic medications
  • Preserved artificial tear substitutes, gels, and ointments
  • Eyelid therapy
• Level 2 – If level 1 treatment is inadequate, add the following: 
• • Nonpreserved artificial tear substitutes
  • Anti-inflammatory agents
  • • Topical corticosteroids
    • Topical cyclosporine A
    • Topical/systemic omega-3 fatty acids
  • Tetracyclines (for meibomianitis, rosacea)
  • Punctal plugs  (after control of inflammation)
  • Secretagogues
  • Moisture chamber spectacles
• Level 3 - If level 2 treatment is inadequate, add the following: 
• • Autologous serum, umbilical cord serum
  • Contact lenses
  • Permanent punctal occlusion
• Level 4 – If level 3 treatment is inadequate, add the following:
• • Systemic anti-inflammatory agents
  • Surgery
  • • Lid surgery
    • Tarsorrhaphy
    • Mucous membrane grafting
    • Salivary gland duct transposition
    • Amniotic membrane transplantation
• See related CME at Topical Cyclosporine May Be Helpful for Dry Eye Disease.

Consultations

A rheumatologist can be consulted if a systemic collagen vascular disease is suspected.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Treatments of dry eye syndrome include the following:

• Artificial tear substitutes
• Gel/ointments
• Moisture chamber spectacles
• Anti-inflammatory agents
• • Topical cyclosporine A
  • Topical corticosteroids
  • Topical/systemic omega-3 fatty acids: Omega-3 fatty acids inhibit the synthesis of these lipid mediators and block the production of IL-1 and TNF-alpha.
• Topical/systemic tetracyclines
• Punctal plugs
• • Absorbable - Made of collagen or polymers. The occlusion duration ranges from 7-180 days. The plugs dissolve by themselves or may be removed by saline irrigation.
  • Nonabsorbable - Made of silicone. Two main categories of silicone plugs are available for dry eye: punctum plugs and intracanalicular plugs.  
  • Cylindrical Smartplug® - Made of a thermosensitive, hydrophobic acrylic polymer that changes from a rigid solid to a soft, cohesive gel when its temperature changes from room temperature to body temperature.
• Secretagogues - Diquafosol (INS365, DE-089) – P2Y2 receptor agonist
• Autologous/umbilical cord serum
• Contact lenses  
• • Silicone rubber lenses
  • Gas permeable scleral-bearing hard contact lenses with or without fenestration
  • Highly oxygen-permeable lenses (overnight wear)
• Systemic immunosuppressives
• Surgery  
• • Amniotic membrane transplantation
  • Lid surgery
  • Tarsorrhaphy
  • Mucous membrane/salivary gland transplant

Drug Category: Ophthalmic agents and lubricants

Act as humectants in the eye. The ideal artificial lubricant should be preservative-free, contain potassium, bicarbonate, and other electrolytes, and have a polymeric system to increase its retention time.

Drug Category: Ocular inserts

Reduce symptoms resulting from moderate-to-severe dry eye syndromes.

Drug Category: Mucolytic agents

Lower mucous viscosity by digesting mucoproteins. Use when mucous discharge or plaques are present.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive, covering all likely pathogens in the context of the clinical setting.

Tetracycline analogues, such as doxycycline and minocycline, have been shown to be effective on meibomian gland dysfunction. The effects of these antibiotics occur via 4 ways: (1) Antibacterial effects by causing a reduction in the bacterial load on the eyelid; (2) antiangiogenic effects; (3) anti-inflammatory effects resulting from a decrease in activity of collagenase, phospholipase A2, and several matrix metalloproteinases, and from a decrease in the production of IL-1 and TNF-alpha; and (4) inhibition of lipase production, which decreases production of diglycerides and free fatty acid (FFA) in meibomian secretions. (FFA can destabilize the tear film and can cause inflammation.)

Drug Category: Immunomodulators

Cyclosporine may act as a partial immunomodulator. The exact mechanism of action is not known.

Drug Category: Autologous serum eye drops

Are unpreserved, are nonantigenic by nature, and contain growth factors, fibronectin, immunoglobulins, and vitamins at similar (or higher) concentrations than in tears. Used for severe dry eye with punctate epithelial defects and corneal damage to promote reepithelialization.

Drug Category: Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli. Inflammation is the key component of the pathogenesis of dry eye. Topical corticosteroid agents can be used to reduce the inflammation.

Drug Category: Dietary supplements

Certain dietary supplements may have beneficial effects.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Follow-up care is based on the severity of symptoms.

In/Out Patient Meds

• Artificial tears with and without preservatives depending on severity
• Doxycycline 100 mg qd/bid if indicated for meibomian gland dysfunction

Complications

• Decreased visual acuity
• Blindness

Prognosis

• In general, the prognosis for visual acuity in patients with dry eye syndrome is good.

Patient Education

• For excellent patient education resources, visit eMedicine's Eye and Vision Center. Also, see eMedicine's patient education articles How to Instill Your Eyedrops and Dry Eye Syndrome.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Early detection and aggressive therapy will reduce the incidence of corneal ulcer.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Dry Eye Workshop (DEWS) Committee. 2007 Report of the Dry Eye Workshop (DEWS). Ocul Surf. April 2007;5(2):65-204. [Full Text].
2. Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. Sep 2006;25(8):900-7. [Medline].
3. Abelson MB. Dry eye, today and tomorrow. Review in Ophthalmology. 2000;11:132-34.
4. American Academy of Ophthalmology. External disease and cornea. In: Section Seven: Basic & Clinical Science Course. American Academy of Ophthalmology; 2007-2008.
5. Barabino S, Rolando M, Camicione P, et al. Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component. Cornea. Mar 2003;22(2):97-101. [Medline].
6. Bron AJ, Tiffany JM, Gouveia SM, et al. Functional aspects of the tear film lipid layer. Exp Eye Res. Mar 2004;78(3):347-60. [Medline].
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Article Last Updated: Sep 26, 2008