DRY EYE SYNDROME

DRY EYE SYNDROME

Current Diagnosis

• Signs and symptoms of dry eye syndrome are nonspecific.

• There are many potential causes of dry eye syndrome. There is no definitive diagnostic test for dry eye syndrome.

Current Therapy

• Artificial tears may help to palliate symptoms, but preservatives in artificial tears may complicate dry eye syndrome.

• Cyclosporine (Restasis) topical medication should be administered under the care of an ophthalmologist.

• Patients with severe symptoms (especially visual disturbance or eye pain) should be referred to an ophthalmologist.

Introduction

Dry eye syndrome, also known as dry eye, chronic dry eye, dry eye disease, and keratoconjunctivitis sicca, is a condition in which reduced tear secretion and/or increased evaporation of tears causes inflammation of the corneal and conjunctival (ocular) surface.

Epidemiology

An estimated 15% to 20% of patients over 65 years of age have dry eye syndrome, with a higher prevalence in females. Dry eye syndrome is common in a mild form in many patients over the age of 40. The prevalence of dry eye syndrome is believed to be rising as patients live longer and a greater proportion of the population is over 65.

Risk factors

Aging is believed to be the most common cause of dry eye syndrome. Decreases in sex hormone concentration, particularly androgens, play a significant role in lacrimal dysfunction. As patients age, they tend to lose function of many of the accessory lacrimal glands, and experience relatively less secretion from the major lacrimal glands.1  In many cases, the cause of tear deficiency is not apparent. Box 1 lists many of the common causes of dry eye syndrome.

Box 1
Causes of Dry Eye  Syndrome
Aging

Congenital disorders (e.g., congenital alacrima and familial dysautonomia)

Evaporative dry eye:

Meibomian gland dysfunction: posterior blepharitis

Entropion and ectropion

Low blink rate: Parkinson disease, prolonged computer or microscope use

Low-humidity environment

Smoking (direct irritant)

High estrogen levels

Lacrimal duct obstruction: trachoma, pemphigoid, erythema multiforme, chemical and thermal burns

Lacrimal gland denervation

Lacrimal gland infiltration: sarcoidosis, lymphoma, AIDS, graft-vs- host disease

Low androgen levels

Ocular surface disorders: topical anesthetic drops, vitamin A deficiency, preservatives in artificial tears and other ophthalmic medications, contact lens wear, allergic conjunctivitis

Other autoimmune disorders (rheumatoid arthritis [RA], scleritis, episcleritis)

Reflex hyposecretion:

Reflex motor block: damage to the VII nerve, systemic drugs (antihistamines, beta-blockers, antispasmodics, diuretics, tricyclic antidepressants, selective serotonin reuptake inhibitors [SSRIs], psychotropic medications, isotretinoin)

Reflex sensory block: topical anesthetic drops, contact lens wear, laser-assisted in situ keratomileusis (LASIK) surgery, diabetes, keratitis from herpes zoster or ulcerative colitis

Pregnancy

Sjogren syndrome

Pathophysiology

Desiccation of the ocular surface results in symptoms of discomfort, blurry vision, and instability of tear film. Tears are vital for the protection of the ocular surface, which is constantly challenged by the shearing force of blinking, various microbes, and environmental factors such as dust, smoke, wind, and low humidity. In order to maintain a healthy film of tears, the patient must have synergistic interaction of lacrimal glands, eyelids, ocular surface, afferent and efferent neural pathways, and meibomian glands. Each component works together with all other components; not in isolation. If there is dysfunction of any of these components or any combination of them, the patient is likely to develop dry eye syndrome.

Healthy tear film consists of an outer oily (lipid) layer, a middle aqueous layer, and an inner mucin layer. The oily layer is secreted by meibomian glands in the posterior portion of the upper and lower eyelids. The aqueous portion of tear film is secreted by the exocrine lacrimal gland located superior and slightly lateral to the eye, as well as smaller accessory lacrimal glands (Figure 1). The mucinous layer of tears is secreted by goblet cells on the corneal surface as well as the conjunctivae. The oily outer surface of tear film functions to prevent evaporation of tears. The inner mucin layer of tear film helps to lubricate the ocular surface as it constantly undergoes healing. In dry eye syndrome, tears become hyperosmolar as a result of water evaporation from the exposed ocular surface. Hyperosmolarity stimulates a cascade of inflammatory events in corneal epithelial cells resulting in mast cell release of cytokines, leading to damage. When normal ocular surface defense mechanisms are compromised, the cornea is more susceptible to infections.

FIGURE 1    Anatomy of the major lacrimal gland and drainage  system.

Prevention

There is no known prevention for dry eye syndrome.

Clinical Manifestations

Symptoms of dry eye syndrome are listed in Box 2. Excessive tearing is a paradoxical sign of dry eye syndrome. Ocular surface damage or irritation activates the neural reflex that stimulates the lacrimal gland to secrete more aqueous tears. As time goes on, this compensatory ability is often gradually lost. Signs of dry eye from examination are listed in Box 3.

Box 2
Symptoms of Dry Eye  Syndrome
•   Dryness

•   Redness

•   General irritation of eyes

•   Gritty sensation in eyes (especially later in the day)

•   Burning sensation in eyes

•   Foreign body sensation in eyes

•   Excessive tearing

•   Light sensitivity

•   Blurred vision

Box 3
Signs from Physical Examination suggesting Dry Eye Syndrome
•   Conjunctival injection, usually symmetric

•   Excessive tearing

•   Blepharitis (erythematous or irritated eyelid edges)

•   Malposition of eyelids (entropion/ectropion)

•   Reduced blink rate

•   Visual impairment

•   Scant, white, stringy discharge

Diagnosis

The presence of symptoms alone is not sufficient to make a diagnosis of dry eye syndrome, because they are often nonspecific and may not be accompanied by ocular changes.

Diagnostic tests for dry eye syndrome include (1) testing for abnormally rapid corneal tear film break-up time (TFBUT), the Schirmer test (can give quite variable results), and fluorescein or rose Bengal staining of the cornea and conjunctiva (usually positive in more advanced cases). There is no single definitive test in the identification of dry eye syndrome or to measure the severity of disease. Several validated patient questionnaires have been developed that may also be useful.

Differential Diagnosis

The differential diagnosis of dry eye includes blepharitis (which may co-exist with dry eye), ocular allergies, viral conjunctivitis (usually a shorter course), and other infections.

Treatment

Treatment of dry eye syndrome is aimed at increasing tear production, decreasing tear evaporation, or reducing tear resorption. Patients usually need to treat dry eye indefinitely. If patients are taking medications (see Box 1) that cause dry eye, they should stop them if at all possible.

Many forms of artificial tears are available commercially over the counter. Most preparations of artificial tears contain cellulose to increase viscosity, polyethylene glycol or polyvinyl alcohol to help spread the tears across the ocular surface, and a preservative (benzalkonium chloride or cetrimide). Some patients develop sensitivity to preservatives in artificial tears, especially with more frequent or prolonged use. The usual starting dose for artificial tears is one drop in both eyes four times a day. If artificial tears are needed more than four to six times per day, it is best to use preparations without preservatives. Preservative-free artificial tear preparations often range in price from $16 to $22 per month, compared to $4 to $10 per month for preparations containing preservatives. Examples of preservative-free products include Refresh (Allergan), TheraTears, Soothe (Bausch and Lomb), and Systane (Alcon).

Environmental factors can increase the rate of evaporation of tears. People who do not blink frequently enough (e.g., reading, microscope, and computer use) may need to make a conscious effort to blink more. Patients who work very close to heating and air conditioning ducts need to distance themselves from ducts when possible, and should use a humidifier in areas with low humidity. Swim goggles and moisture chambers for glasses may be helpful as well to conserve moisture around the eyes. Lowering computer screens below eye level will decrease exposure of the ocular surface between eyelids. Patients who work at computer terminals should take periodic breaks.

Ophthalmologists may insert silicone plugs to obstruct the puncta and decrease resorption of tears from the surface of the eye.

Sodium hyaluronate (over the counter product) is a lipid-like substance that slows the evaporation of tears.

Topical cyclosporine (Restasis) is a second line agent used in moderate-to-severe disease. It is expensive (about $400 per month) and should not be used if infection is present since cyclosporine is an immunosuppressive agent. It is probably judicious to leave the decision to use cyclosporine to an ophthalmologist primarily because of cost and possibility of adverse effects. Cyclosporine is usually administered one drop in both eyes twice daily, and may take several weeks for symptom reduction. It may cause a temporary burning sensation in the eyes. Lifitegrast (Xiidra) was approved for dry eye by the FDA in 2016. It is from a new class of drugs known as lymphocyte function-associated antigen-1 agents. Like cyclosporine, it is typically prescribed by ophthalmologists.

Topical glucocorticoids may cause symptom reduction in the short term, but are not a good option for long term use as they can cause cataracts and glaucoma.

Dietary supplements containing omega-3 and omega-6 fatty acids are under investigation.7

Surgical correction of eyelid abnormalities such as entropion and ectropion may be helpful to prevent or lessen ocular surface damage.

Several new drugs are under investigation for treatment of Dry Eye Syndrome. They are immunomodulators that suppress inflammatory response on the corneal surface.

Complications

Inflammation and damage to the ocular surface can lead to visual disturbance.

Monitoring

Patients using cyclosporine drops should be under the care of an ophthalmologist.

Conclusions

Dry eye syndrome is a multifactorial disease of tears and the ocular surface that can result in discomfort and visual impairment. There is considerable variability in patient-reported symptoms over time.

There is no single definitive diagnostic test for dry eye syndrome.

Artificial tears should be used for initial management, but this treatment is only palliative. Environmental strategies should also be considered.

References

1.     Gaddie B. Whet Your Appetite for New Dry Eye Drugs. Review of Optometry. 2015. Available at www.reviewofoptometry.com/content/d/dry_eye/c/54628/. Accessed February 2, 2016.

2.    Harper R.A. Basic Ophthalmology. ed 9 San Francisco: American Academy of Ophthalmology; 2010.

3.     Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5:163–178.

4.    O’Brien P.D., Collum L. Dry eye: diagnosis and current treatment strategies. Curr Allergy Asthma Rep. 2004;4:314–319.

5.     The definition and classification of dry eye disease: report of the definition and Classification Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf. 2007;5:75– 92.

6.      Trobe J.D. The physician’s guide to eye care. ed 4 San Francisco: The Foundation of the American Academy of Ophthalmology; 2012.

7.    Wojtowicz J.C., Butovich I., Uchiyama E., et al. Pilot, prospective, randomized, doublemasked, placebo-controlled clinical trial of an omega-3 supplement for dry eye. Cornea. 2011;39:308–314.

1  Not FDA approved for this  indication.

7  Available as a dietary  supplement.

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