Is it Dry Eye, Allergy or Both?

The symptoms are similar, yet the treatments are very different. How do we distinguish between the two?

By Ernie L. Bowling, O.D., M.S.

Release Date: SEPTEMBER 2012
Expiration Date: SEPTEMBER 1, 2015

Goal Statement:

This article will discuss the symptoms of dry eye and ocular allergy and review the distingishing factors between the two diseases.

Faculty/Editorial Board:

Ernie L. Bowling, O.D., M.S.

Credit Statement:

This course is COPE approved for 1 hour of CE credit. COPE ID 35359-AS. Check with your local state licensing board to see if this counts toward your CE requirements for relicensure.

Joint-Sponsorship Statement:

This continuing education course is joint-sponsored by the Pennsylvania College of Optometry.

Disclosure Statement:

The author has no financial relationships to disclose.


Dry eye and ocular allergy, both very common clinical presentations, are responsible for a large number of patient visits. Research and surveys over the past 20 years have estimated that the prevalence of dry eye disease (DED) is between 5% and 30% across various age groups.1 Several large studies have estimated that just fewer than five million Americans, 50 years and older, have moderate to severe DED.2

About 15% to 20% of the U.S. population have atopy--a genetic predisposition toward developing certain allergic hypersensitivity to environmental substances, such as pollens, molds and dust mites.3 More recent, studies indicate that up to 40% of the U.S. population may have ocular symptoms related to allergy.3

Clinical experience suggests that both dry eye and ocular allergy present very frequently in our clinics. To make the diagnosis more complicat ed, both conditions have very similar symptoms. Our job is to distinguish between the two and prescribe the appropriate therapy.

Etiology and Pathophysiology

Fifty million Americans are affected by allergy each year, and 30 million of these individuals suffer from seasonal allergies.4 And 70% to 80% of these patients report that their allergies include ocular symptoms.5,6

Meanwhile, ocular surface disease (OSD) affects approximately 20.7 million people in the U.S. every year.7 Nearly 4.25 million of these individuals have chronic ocular surface disease.8

Dry Eye

Ocular burning is the primary symptom of dry eye; the ocular signs and symptoms include corneal and conjunctival staining, a reduced tear meniscus, sandy and gritty foreign body sensation, keratitis and, albeit rarely, photophobia.

One of the most significant and compelling outcomes from the Dry Eye WorkShop (DEWS) was a new definition of dry eye disease that, for the first time, included terms like "hyperosmolarity" and "inflammation." Dry eye is now defined as "a multifactorial disease of the tears and 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

The core mechanisms of dry eye are driven by tear hyperos-molarity, which activates a cascade of inflammatory events that cause epithelial damage. Meibo-mian gland dysfunction (MGD) is one of the major causes of evaporative dry eye and tear hyperosmolarity.

The International Workshop on Meibomian Gland Dysfunction (MGDW) describes MGD as: "A chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative and quantitative changes in glandular secretion. It may result in alteration of the tear film, eye irritation, clinically apparent inflammation, and ocular surface disease."9

Note that, as with dry eye, this new definition of MGD also includes the term "inflammation."

Allergic Conjunctivitis

The key symptoms of allergic conjunctivitis include itching, tearing, burning, foreign-body sensation and ocular dryness. Itching is the hallmark symptom. If it is absent, the diagnosis of allergic conjunctivitis should be questioned. It is important to inform patients that vigorous eye rubbing will lead to mast cell degranulation and exacerbation of itch. The key clinical signs of allergic conjunctivitis are hyperemia of the conjunctiva and the eyelids, conjunc- tival chemosis and papillae, eyelid edema and a clear, watery discharge.

Ocular surface inflammation plays a key role in the pathogenesis and symptomatology of allergic conjunctivitis. Both seasonal and perennial allergic conjunctivitis are type 1 hypersensitivity reactions that involve sensitization of the immune system upon first exposure of the antigen. After repeated exposure, the antigen-specific IgE binds to mast cells in the conjunctiva, triggering their degranulation.

This, in turn, releases intracellular-stored mediators including histamine, tryptase, chymase, heparin, chondroitin sulfate, prostaglandins, thromboxanes and leukotrienes; this cascade represents the acute phase of the allergic response.10

Depending on the geographic area, the signs and symptoms of allergic conjunctivitis often overlap with other forms of OSD, including aqueous deficient dry eye and MGD. Seasonal allergic conjunctivitis is most often triggered by pollen and typically spikes during the spring and summer months. Perennial allergic conjunctivitis is often caused by dust mites, pet dander and mold, and these symptoms can last throughout the year.

The lack of an adequate tear film and the presence of ocular surface inflammation aggravate the irritation caused by allergens and mast cell products such as histamine. The tear film serves as a barrier to allergens and dilutes them, as well as washes away inflammatory mediators. If eyes are dry, more allergens reach the conjunctiva and mast cells. In addition, inflammatory mediators have an increased residence time and enhanced concentration in the tear film.

Delphi Panel Consensus for Dry Eye Management18
Severity Signs and Symptoms Recommended Treatment
1 Mild to moderate symptoms,
no signs, mild to moderate
conjunctival.
Patient counseling, preserved
tears, environmental
management, use of hypoallergenic
products, water.
2 Moderate to severe symptoms, tear
film signs, mild corneal punctate
staining, corneal staining, visual
signs.
Unpreserved tears, gels,
ointments, cyclosporine
A, secretagogues, topical
steroids, nutritional support
(flaxseed oil).
3 Severe symptoms, marked cornea
punctate staining, central corneal
staining.
Tetracyclines, punctal plugs.
4 Severe symptoms, severe corneal
staining, erosions, conjunctival
scarring.
PO anti-inflammatory therapy,
PO cyclosporine, moisture
goggles, acetylcysteine,
punctal cautery, surgery.

 

Making the Diagnosis

Reviewing past and present medical history can be an important step in the diagnostic process (see "Itching vs. Burning"). Once a complete history is obtained, a thorough eye examination is necessary to confirm the diagnosis. Carefully examine the eye for evidence of eyelid involvement, including blepharitis, dermatitis, swelling, discoloration, ptosis or blepharo-spasm. Conjunctival involvement may present with chemosis, hyperemia, cicatrization, or papillae formation on the palpebral and bulbar membranes. Patients will reveal the characteristic signs of ocular allergies, such as diffuse injection of the bulbar conjunctiva and papillary hypertrophy of the palpebral conjunctiva. The presence of Dennie's lines (crease-like wrinkles that form below the lower eyelid margin), allergic shiners (dark circles under the eye due to swelling and discoloration from congestion of small blood vessels beneath the skin) or increased or abnormal secretions, also should be noted.11

In moderate to severe cases, dry eye disease can be diagnosed based on subjective symptoms and slit-lamp findings. Tear film break-up time is the time interval measured between the last blink and the appearance of the first dry spot.12 Fluorescein break-up time is a widely used method for determining the stability of precorneal tear film and identifying patients with evaporative dry eye. Tear meniscus characteristics (meniscus height, depth and radius of curvature) have been reported to be useful in identifying patients with aqueous-deficient dry eye.13

Itching vs. Burning
Before the physical examination, ask your
patient if it itches more than it burns or
if it burns more than it itches. Patients
who complain of itching without other
symptoms of ocular irritation, such as
burning or gritty sensation, generally have
a primary ocular allergy with an adequate
tear film. However, patients who include
itching among other ocular irritation
symptoms often have a dry eye-induced
ocular allergy

 

The Schirmer tear test is the most commonly used and easily performed test for the evaluation of dry eye. Vital staining is a widely used method for studying the integrity and viability of corneal and conjunctival epithelial cells. Fluorescein staining has been the standard clinical means of diagnosing the presence of corneal epithelial surface defects.

Historically, rose bengal (a derivative of fluorescein) has been the vital dye used for ocular testing as it provides an excellent staining of the ocular surface. It differs significantly from fluorescein because it does not stain the precorneal tear film, but rather the dead and degenerating (not denuded) epithelium of the conjunctiva and cornea. Rose bengal also stains mucous particles, strands, filaments and plaques more vividly than fluorescein, making it a better diagnostic aid in the evaluation of the conjunctiva and tear film. However, rose bengal rarely is used today due to stinging.

Another dye, lissamine green, has the advantage over rose bengal in that it fades relatively quickly and is less irritating. For that reason, it has become more widely used both clinically and in drug studies.

DEWS Dry Eye Severity Grading Scheme1
Dry Eye Severity Level 1 2 3 4*
Discomfort, severity and frequency Mild and/or episodic occurs under environmental stress Moderate episodic or chronic stress or no stress Severe frequent or constant without stress Severe and/or disabling and constant
Visual symptoms None or episodic mild fatigue Annoying and/or activity limiting episodic Annoying, chronic and/or limiting activity Constant and/or possibly disabling
Conjunctival injection None to mild None to mild +/- +/++
Corneal staining None to mild Variable Moderate to marked Moderate to marked
Corneal staining (severity/location) None to mild Variable Marked/central Severe punctate erosions
Corneal/tear signs None to mild Mild debris, meniscus Filamentary keratitis, mucus clumping, tear debris Filamentary keratits, mucus clumping, tear debris, ulceration
Lid/meibomian glands Meibomian gland dysfunction (MGD) variably present MGD variably present Frequent Trichiasis, keratinization, symblepharon
Fluorescein tear break-up time Variable ≤ 10 seconds ≤ 5 seconds Immediate
Schirmer score Variable ≤ 10mm/5 min ≤ 5mm/5 min ≤ 2mm/5 min
*Must have signs and symptoms.

 

A Treatment Plan

Many individuals with multiple ocular surface disorders require polytherapy to address a host of ocular issues. Inflammation is a key etiologic factor in the pathogenesis of OSD. Thus, anti-inflammatory medications are crucial to successful treatment. In all forms of dry eye, primary tear supplementation is recommended by differently acting artificial teardrops and ophthalmic ointments.

Each patient must be treated individually based on subjective complaints and clinical signs along with systemic diseases. Long-lasting application of drugs with preservatives may cause disruption of the epithelial cell-to-cell contacts, allergic reaction, decreased goblet cell density or inflammation.12 Benzalkonium chloride, chlorobutanol and cetrimide are the most common preservatives in artificial tears that can induce toxic epitheliopathy after prolonged usage.14 Therefore, in moderate stage 2 dry eye (see "DEWS Dry Eye Severity Grading Scheme" above), changing to preservative-free artificial tears is reasonable and recommended.15 Most preservative-free tear drops may be used together with contact lenses.

The following medications currently are used for treating OSD (both on and off label):

  • Topical cyclosporine. The only anti-inflammatory agent approved by the FDA for treating dry eye. The Delphi panel recommends its use at stage 2 dry eye.
  • Topical corticosteroids. This is an additional therapy to be used in stage 2 dry eye.
  • Oral or topical antibiotics with anti-inflammatory activity. These include tetracyclines, such as doxycycline and minocycline, and macrolides, such as azithromycin. The Delphi panel recommends their use in stage 3 dry eye, and the MGDW recommends their incorporation for the treatment of stage 3 MGD.
  • Omega-3 fatty acids. Nutritional supplementation is an early recommendation of the Delphi panel, the DEWS report and the MGDW. This treatment has been advocated as an oral therapy to reduce inflammation.16

A key take-away message from the DEWS treatment grid is that topical anti-inflammatory medications are recommended at stage 2 severities.

Several potent eye drops are available for treating allergic conjunctivitis. Convenience is one factor that may influence whether or not a medication produces the desired result, and can often drive a patient's adherence to a regimen. Combination antihistamine/mast-cell stabilizer drops approved for once-a-day dosing are helpful here. All of the available allergy drops are generally safe and patients may use them as needed, up to three times a day when their symptoms are especially bad.

Advise patients to use their drops every day throughout the allergy season--not just when their symptoms are at their worst. If patients are on oral antihistamines, their ocular dryness may be even worse. Stopping the oral antihistamine and substituting a nasal spray can reverse the negative effects of the oral product on lacrimal gland production.

Steroid eye drops are appropriate in recalcitrant cases of OSD. Because the risk of intraocular side effects is small, loteprednol is often favored in these situations. Loteprednol comes in two concentrations: the 0.2% ophthalmic suspension (Alrex, Bausch + Lomb) or 0.5% ophthalmic suspension (Lotemax, Bausch + Lomb). Weak steroids, such as fluorometholone or prednisolone acetate 0.125%, also can be effective and reasonably safe. Keep in mind the potential adverse effects of any steroid when used for many months (notably, IOP elevation). Use these agents in the short-term as a way to break a cycle of inflammation while safer, long-term strategies take effect.

Although lid scrubs often are recommended for blepharitis, avoid them when patients have concomitant ocular allergy, because the scrubbing worsens symptoms and can lead to eyelid eczema. Expressing the meibomian glands and applying dry heat to the eyelids may be helpful. At home, patients can place a hot washcloth inside a dry cloth or a plastic bag to use as a compress. Avoid applying wet compresses directly to the skin because wetting the eyelid skin can dry it and lead to eczema. For patients with severe posterior blepharitis, consider prescribing one of the tetracycline derivatives, either doxycycline or minocycline. Topical antibiotics can be helpful, but must be used chronically.

The underlying message from the MGDW is that topical azithromycin (AzaSite, Merck) and/or oral tetracycline are recommended as early as stage 2, and anti-inflammatory dry eye treatments are recommended adjunctively in stages 3 and 4 (see "Treatment Algorithm for MGD").17

Treatment Algorithm for MGD17
Stage Clinical Description Treatment
1 • No symptoms o f ocular discomfort, itching or photophobia.
• Clinical signs of MGD based on gland expression.
• Minimally altered secretions: grade 2-4.
• Expressibility: 1.
• No ocular surface staining.
Inform patient about MGD, the potential impact of diet, and the effect of work/home environments on tear evaporation, and the possible drying effect of certain systemic medications.
• Consider eyelid hygiene including warming/expression.
2 • Minimal to mild symptoms of ocular discomfort, itching or photophobia.
• Minimal to mild MGD clinical signs.
• Scattered lid margin features.
• Mildly altered secretions: grade 4-8.
• Expressibility: 1.
• None to limited ocular surface staining:
DEWS grade 0-7; Oxford grade 0-3.
Advise patient on improving ambient humidity; optimizing workstations and increasing dietary omega-3 fatty acid intake (+/-).
• Institute eyelid hygiene with eyelid warming (a minimum of four minutes, once or twice daily) followed by moderate to firm massage and expression of MG secretions (+).

All the above, plus (+/-)
• Artificial lubricants (for frequent use, nonpreserved preferred)
• Topical azithromycin
• Topical emollient lubricant or liposomal spray
• Consider oral tetracycline derivatives.
3 • Moderate symptoms of ocular discomfort, itching or photophobia with limitations of activities.
• Moderate MGD clinical signs.
• Lid margin features: plugging, vascularity.
• Moderately altered secretions: grade >8 to <13.
• Expressibility: 2.
• Mild to moderate conjunctival and peripheral corneal staining, often inferior: DEWS grade 8-23; Oxford grade 4-10.
All the above, plus
• Oral tetracycline derivatives (+).
• Lubricant ointment at bedtime (+/-).
• Anti-inflammatory therapy for dry eye as indicated (+/-).
4 • Marked symptoms of ocular discomfort, itching or photophobia with definite limitation of activities.
• Severe MGD clinical signs
• Lid margin features: dropout, displacement.
• Severely altered secretions: grade 13 or greater.
• Expressibility: 3.
• Increased conjunctival and corneal staining, including central staining: DEWS grade 24-33; Oxford grade 11-15.
• Increased signs of inflammation: >moderate conjunctival hyperemia, phlyctenules.
All the above, plus
• Anti-inflammatory therapy for dry eye (+).

 

Allergy, dry eye and blepharitis can be present in any combination in any patient. Inflammation is a key pathophysiologic mechanism in most cases of OSD, including aqueous deficient dry eye, MGD and allergic conjunctivitis. If the inflammation is not treated, the recurring cycles will lead to chronic disease, worsening symptoms and significant ocular surface damage.

By recognizing and treating concurrent components of ocular surface dysfunction and educating patients about their conditions, you can aid in their relief.

References

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