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 common disorder of the tear film that results from decreased tear production, excessive tear evaporation, or abnormality in mucin or lipid components of the tear film. 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.

The lipid layer produced by the meibomian glands acts as a surfactant, as well as an aqueous barrier (retarding evaporation of the underlying aqueous layer), and provides a smooth optical surface. It may also act as a barrier against foreign particles and may also have some antimicrobial properties. The glands are holocrine in nature, and so the secretions contain both polar lipids (aqueous-lipid interface) and nonpolar lipids (air-tear interface) as well as proteinaceous material. All of these are held together by ionic bonds, hydrogen bonds, and van der Waals forces. The secretions are subject to neuronal (parasympathetic, sympathetic, and sensory sources), hormonal (androgen and estrogen receptors), and vascular regulation. Evaporative loss is predominantly due to meibomian gland dysfunction (MGD).

The aqueous component is produced by the lacrimal glands. This component includes about 60 different proteins, electrolytes, and water. Lysozyme is the most abundant (20-40% of total protein) and also the most alkaline protein present in tears. It is a glycolytic enzyme that is capable of breaking down bacterial cell walls. Lactoferrin has antibacterial and antioxidant functions, and the epidermal growth factor (EGF) plays a role in maintaining the normal ocular surface and in promoting corneal wound healing. Albumin, transferrin, immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) are also present.

Aqueous tear deficiency (ATD) is the most common cause of dry eye, and it is due to insufficient tear production. The secretion of the lacrimal gland is controlled by a neural reflex arc, with afferent nerves (trigeminal) in the cornea and the conjunctiva passing to the pons and efferent sympathetic and parasympathetic nerves terminating in the lacrimal glands.

Keratoconjunctivitis sicca (KCS) is the name given to this ocular surface disorder. KCS is subdivided into Sjögren syndrome (SS) associated KCS and non-SS associated KCS. Patients with ATD have SS if they have associated xerostomia and/or connective tissue disease. Patients with primary SS have evidence of a systemic autoimmune disease as manifested by the presence of serum autoantibodies and very severe ATD and ocular surface disease. These patients, mostly women, do not have a separate, identifiable connective tissue disease. Subsets of patients with primary SS lack evidence of systemic immune dysfunction, but they have similar clinical ocular presentation. Secondary SS is defined as KCS associated with a diagnosable connective tissue disease, most commonly rheumatoid arthritis but also SLE and systemic sclerosis.

Non-SS KCS is mostly found in postmenopausal women, in women who are pregnant, in women who are taking oral contraceptives, or in women who are on hormone replacement therapy (especially estrogen only pills). The common denominator here is a decrease in androgens, either from reduced ovarian function in the postmenopausal female or from increased levels of the sex hormone binding globulin in pregnancy and birth control pill use. Androgens are believed to be trophic for the lacrimal and meibomian glands. They also exert potent anti-inflammatory activity through the production of transforming growth factor beta (TGF-beta), suppressing lymphocytic infiltration.

Lipocalins (previously known as tear-specific prealbumin), which are present in the mucous layer, are inducible lipid-binding proteins produced by the lacrimal glands that lower the surface tension of normal tears. This provides stability to the tear film and also explains the increase in surface tension that is seen in dry eye syndromes characterized by lacrimal gland deficiency. Lipocalin deficiency can lead to the precipitation in the tear film, forming the characteristic mucous strands seen in patients with dry eye symptomatology.

The glycocalyx of the corneal epithelium contains the transmembrane mucins (glycosylated glycoproteins present in the glycocalyx) MUC1, MUC4, and MUC16. These membrane mucins interact with soluble, secreted, gel-forming mucins produced by the goblet cells (MUC5AC) and also with others like MUC2. The lacrimal gland also secretes MUC7 into the tear film.

These soluble mucins move about freely in the tear film (a process facilitated by blinking and electrostatic repulsion from the negatively charged transmembrane mucins), functioning as clean-up proteins (picking up dirt, debris, and pathogens), holding fluids because of their hydrophilic nature, and harboring defense molecules produced by the lacrimal gland. Transmembrane mucins prevent pathogen adherence (and entrance) and provide a smooth lubricating surface, allowing lid epithelia to glide over corneal epithelia with minimal friction during blinking and other eye movements. Recently, it has been suggested that the mucins are mixed throughout the aqueous layer of tears (owing to their hydrophilic nature) and, being soluble, move freely within this layer.

Mucin deficiency (caused by damage to the goblet cells or the epithelial glycocalyx), as seen in Stevens-Johnson syndrome or after a chemical burn, leads to poor wetting of the corneal surface with subsequent desiccation and epithelial damage, even in the presence of adequate aqueous tear production.

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 MGD, 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 MGD, 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 10-14 million people are affected.

International

The frequency of dry eye in other countries closely parallels that of the United States. Prevalence of SS is approximately 0.4% in Sweden.

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

No known racial predilection exists.

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 MGD 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

A classification system formulated by the National Eye Institute distinguishes 2 main categories (or causes) of dry eye states, an aqueous deficiency state and an evaporative state, as outlined below.

• Deficient aqueous production
• Non-Sjögren syndrome
• • Lacrimal disease (primary or secondary)
  • • Idiopathic
    • Systemic vitamin A deficiency (xerophthalmia) – Malnutrition, fat-free diets, intestinal malabsorption from inflammatory bowel disease, bowel resection, or chronic alcoholism
    • Lacrimal ablation
    • Congenital alacrima (Riley-Day syndrome)
    • Primary lacrimal deficiency
    • Graft-versus-host disease
  • Infiltrative processes
  • • Lymphoma
    • Amyloidosis
    • Hemachromatosis
    • Sarcoidosis
  • Infectious diseases
  • • HIV diffuse infiltrative lymphadenopathy syndrome
    • Trachoma
  • Lacrimal obstructive disease
  • • Trachoma
    • Ocular cicatricial pemphigoid
    • Erythema multiforme and Stevens-Johnson syndrome
    • Chemical 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
  • Decreased corneal sensation
  • • Neurotrophic keratitis
    • Corneal surgery
    • Herpes simplex
    • Contact lens wear
    • Cranial nerve VII (CN VII) palsy
    • Diabetes
    • Aging
• 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
• • Blepharitis-associated - Obstructive meibomian gland disease, rosacea
  • Blink disorders
  • Disorders of eyelid aperture and eyelid/globe congruity – Exposure, lid palsy, ectropion, or lid coloboma
  • Contact lenses
• Other classification systems are also used. The Madrid Triple Classification of Dry Eye was proposed in 2003 and modified in 2005. This system includes 3 classes.
• • The first class is based on the affected tissues, called the ALMEN classification (Aqueo-serous deficiency, Lipid deficiency, Mucin deficiency, Epithelial deficiency, and Non-dacryologic deficiencies), as outlined briefly in the beginning of this article.
  • The second class is based on the etiopathogenesis (age related, hormonal, pharmacologic, immunopathic, hyponutritional, dysgenic, infectious/inflammatory, traumatic, neurologic, and tantalic).
  • The third class is based on the clinical severity (grade 1, symptoms without signs; grade 2, symptoms with reversible signs; and grade 3, symptoms with permanent signs).

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), 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.
• 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 MGD.
  • 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 ATD. 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.
  • Lastly, conjunctival biopsy for in situ hybridization and immunohistochemistry may also be used.
• 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.
• 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

• Mild
• • Artificial tears with preservatives up to 4 times daily
  • Lubricating ointment at bedtime
  • Hot compresses and eyelid massage, especially if associated with MGD, which is usually the case
  • Oral supplementation with the essential fatty acids, linoleic acid, and gamma-linolenic acid. Patients showed significant improvement in lissamine green staining, symptoms, and ocular surface inflammation (HLA DR marker expression). The fatty acids are eventually converted to PGE-1, which inhibits superoxide, TNF-alpha, IL-1 beta, and IL-6.
• Moderate
  • Artificial tears without preservatives 4 times daily to hourly
  • Lubricating ointment at bedtime
  • If mucous strands are present, remove and prescribe 10-20% acetylcysteine drops 4 times a day.
  • Doxycycline 100 mg qd/bid if indicated for MGD
  • Lower punctal occlusions
  • Topical cyclosporine (0.05%) twice daily
• Severe
  • Perform all of the above treatments
  • Punctal occlusions (lower and upper), with collagen (dissolvable) or silicone (permanent) plugs. Electric cauterization of puncti (hyfrecation) may be done if the plugs have been effective. Plugs often become dislodged.
  • Moist environment (humidifier, moisture shield)
  • Lateral tarsorrhaphy
  • If perforation is impending, proceed to surgery and perform corneoscleral patch grafting. If perforation has already occurred, seal with corneal cyanoacrylate tissue adhesive.
  • Autologous serum eye drops
• Emerging therapy
  • Topical androgens
  • Secretagogues (substance that increases acinar cell activity and protein synthesis, eg, oral pilocarpine and cevimeline)
  • Cytokine-blocking agents
  • P2Y2 receptor agonist – Diquafosol, increases water flow through cells and also increases lacrimal gland tear production as well as mucin production from goblet cells

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 goal of pharmacotherapy is to reduce morbidity and to prevent complications.

Drug Category: Ophthalmic agents and lubricants

Act as humectants in the eye.

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.

Drug Category: Immunomodulators

Cyclosporine ophthalmic drops are thought to 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 PEDs and corneal damage to promote reepithelialization.

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 MGD

Complications

• Decreased visual acuity
• Blindness

Prognosis

• In general, 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

• Abelson MB. Dry eye, today and tomorrow. Review in Ophthalmology. Vol 11. 2000:132-34.
• American Academy of Ophthalmology. External Disease and Cornea: Section Seven, Basic & Clinical Science Course. American Academy of Ophthalmology;1989-90.
• 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].
• 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].
• Geerling G, Maclennan S, Hartwig D. Autologous serum eye drops for ocular surface disorders. Br J Ophthalmol. Nov 2004;88(11):1467-74. [Medline].
• Gilbard JP. Dry eye disorders. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. Vol 2. WB Saunders Co;2000:982-1000.
• Karadayi K, Ciftci F, Akin T. Increase in central corneal thickness in dry and normal eyes with application of artificial tears: a new diagnostic and follow-up criterion for dry eye. Ophthalmic Physiol Opt. Nov 2005;25(6):485-91. [Medline].
• Krachmer P, Holland. Dry eye. In: Cornea. Mosby Inc;1997:663-686.
• Lemp MA. The 1998 Castroviejo Lecture. New strategies in the treatment of dry- eye states. Cornea. Nov 1999;18(6):625-32. [Medline].
• McCulley JP, Shine WE. The lipid layer of tears: dependent on meibomian gland function. Exp Eye Res. Mar 2004;78(3):361-5. [Medline].
• Murube J, Nemeth J, Hoh H. The triple classification of dry eye for practical clinical use. Eur J Ophthalmol. Nov-Dec 2005;15(6):660-7. [Medline].
• Ohashi Y, Dogru M, Tsubota K. Laboratory findings in tear fluid analysis. Clin Chim Acta. Jul 2006;369(1):17-28. [Medline].
• Perry HD, Donnenfeld ED. Dry eye diagnosis and management in 2004. Curr Opin Ophthalmol. Aug 2004;15(4):299-304. [Medline].
• Pflugfelder SC. Advances in the diagnosis and management of keratoconjunctivitis sicca. Curr Opin Ophthalmol. Aug 1998;9(4):50-3. [Medline].
• Stern ME, Gao J, Siemasko KF, Plugfelder SC. The role of the lacrimal functional unit in the pathophysiology of dry eye. Exp Eye Res. Mar 2004;78(3):409-16. [Medline].
• Tatlipinar S, Akpek EK. Topical ciclosporin in the treatment of ocular surface disorders. Br J Ophthalmol. Oct 2005;89(10):1363-7. [Medline].
• Zoukhri D. Effect of inflammation on lacrimal gland function. Exp Eye Res. May 2006;82(5):885-98. [Medline].

Article Last Updated: Aug 25, 2006