Allergic Eye Disease

Featured News // News // May 05 2016

Allergic eye disease is a bilateral immune mediated process of the ocular surface that occurs in up to 25% of the population of developed countries. Five entities are described as having at least in part some portion of their pathogenesis emanating from mast cell activation: Allergic Conjunctivitis, as seasonal (SAC), or Perennial Allergic Conjunctivitis (PAC), Atopic Keratoconjunctivitis (AKC), Vernal Keratoconjunctivitis (VKC), and Giant Papillary Conjunctivitis (GPC). SAC, PAC, and GPC are non-vision threatening where as AKC and VKC may lead to vision loss. The severe forms of allergic disease, AKC and VKC have an immune mediated pathogenesis as well as mast cell activation. GPC is considered iatrogenic due to the presence of an ocular surface foreign body such as contact lens or an exposed suture. Treatment of allergic eye disease may be as simple as administration of artificial tears or topical antihistamines through to as complex as the need for topical or oral steroids as well as immunomodulatory therapy. Contact dermatitis may occur in the periocular region. The periocular form of contact dermatitis is most commonly associated with topical ophthalmic pharmaceutical agents. Antiviral and glaucoma medications are some of the more common medications implicated. In-vivo conjunctival provocation testing is an ocular equivalent of skin testing to determine sensitivity to specific antigens. This may be used experimentally to develop a reproducible human model of allergic eye disease and has been utilized to test new pharmaceutical agents. This article focuses on Allergic Conjunctivitis.

Allergic Conjunctivitis – Seasonal/Perennial

Introduction

Allergic conjunctivitis (AC) is a bilateral, self-limiting conjunctival inflammatory process. It occurs in sensitized individuals (no gender difference) and is initiated by allergen binding to IgE antibody on resident mast cells contained within the conjunctiva. The importance of this process is related more to its frequency rather than its severity of symptoms. The two forms of AC are defined by whether the inflammation and symptoms occur seasonally (spring, fall) or perennially (year-round). While the inflammatory signs and symptoms are similar for both entities, seasonal allergic conjunctivitis (“hay fever conjunctivitis”) is more common. It accounts for the majority of cases of AC and is related to pollens (e.g. grass, trees, ragweed) that appear during specific seasons. Perennial allergic conjunctivitis is often related to animal dander, dust mites, or other allergens that are present in the environment year-round. Both SAC and PAC must be differentiated from the sight-threatening allergic diseases of the eye, namely AKC and VKC.

Historical Perspective

Hypersensitivity reaction description of the ocular surface dates to the earliest descriptions of hayfever or rhinitis. Some of the earliest allergy provocation testing was performed in the conjunctiva.

Epidemiology

Prevalence estimates for allergic conjunctivitis are difficult because allergies in general tend to be considerably underreported. As high as 40% of the population may suffer from symptoms of allergic conjunctivitis. Importantly, 46% of all allergic conjunctivitis sufferers have associated allergic rhinitis. The distribution of SAC depends largely on the climate. For example, in the United States grass pollen – induced SAC generally occurs in the Gulf Coast and southwestern areas of the country from March to October and from May to August, in most of the rest of the country. Conversely, ragweed pollen – induced SAC occurs in most of the country during August through October, but in the southern-most states it can begin as early as July and stretch out through November. Tree pollens can become a problem as early as January in the south, and March in the north. Race and gender predilection follows that of rhinitis sufferers. Clinical Features (Figure 1) The dominant symptom reported in allergic conjunctivitis is ocular itching (Table 1). Itching can range from mild to severe. Other symptoms include tearing (watery discharge), redness, swelling, burning, a sensation of fullness in the eyes or eyelids, an urge to rub the eyes, sensitivity to light, and occasionally blurred vision. As stated previously, allergic conjunctivitis is often associated with symptoms of allergic rhinitis. Conjunctival hyperemia and chemosis with palpebral edema are typical. A rapid test for tear IgE level has correlated the objective sign of giant papillae with the total IgE tear level. (Mimura et al. 2012) Hyperemia is the result of vascular dilatation while edema (chemosis) occurs because of altered permeability of post-capillary venules. “Allergic shiners” (periorbital darkening), due to an increase of periorbital pigmentation resulting from the decreased venous return in the skin and subcutaneous tissue, are also common.

Patient evaluation, diagnosis, and differential diagnosis

An individual suspected of having allergic conjunctivitis should have a thorough ocular, medical and medication history. This will help greatly in differentiating AC from other ocular processes (Table 1). This history should establish whether the process is acute, subacute, chronic or recurrent. It should further delineate whether the symptoms/signs are unilateral or bilateral, and whether they are associated with any specific environmental or work-related exposure. Ocular symptoms such as tearing, irritation, stinging and burning are nonspecific. A history of significant ocular itching and a personal or family history of “hay fever”, allergic rhinitis, asthma or atopic dermatitis are suggestive of ocular allergy. Because AC is secondary to environmental allergens as opposed to transmission by eye-hand contact (infectious etiology), unless occurring in the context of petting an animal then rubbing one’s eye, SAC and PAC usually present with bilateral symptoms. This is in contrast to transmissible infections caused by viruses and bacteria that in general initially present in one eye, with the second eye becoming involved a few days later. Itch is an uncommon complaint during infectious conjunctivitis episodes. Furthermore, viral conjunctivitis may cause subepithelial corneal infiltrates not seen in AC. Palpable pre-auricular nodes would also signify infectious etiology for the ocular symptoms.

The type of ocular discharge, (watery, mucoid, or grossly purulent), can also be helpful in determining the underlying cause of conjunctival inflammation. A watery discharge is most commonly associated with viral or allergic ocular conditions. A mucoid or purulent discharge, with morning crusting and difficulty opening the eyelids, would strongly suggest a bacterial infection. In allergic inflammation, the eye appears red. Vision, pupil shape, ocular movement, light reactivity, and the red retinal reflex remain normal in allergic conjunctivitis. Dry eye (secondary to a decrease of the aqueous portion of the tear film) gives symptoms suggestive of foreign body in the eye and may result in conjunctiva redness. Similar symptoms are possible from anticholinergic side effects of systemic medications. Typically, itch is not reported with dry eye. Medication history should include questions concerning the patient’s use of over-the-counter topical ocular medications, cosmetics, contact lenses, and systemic medications. Any of these can produce acute or chronic conjunctivitis. This inquiry should include direct questions and should not rely on the patient to volunteer information. Many individuals do not appreciate the potential for nonprescription topical ocular medications to cause eye symptoms or partially treat AC. Differentiation of AC from the more chronic and sight threatening forms of allergic eye disease is discussed below in the context of the specific conditions.

Treatment

Medications approved for use in allergic eye disease are found in Table 2. Allergic conjunctivitis can be debilitating and may cause the individuals affected to seek any type of help for relief of symptoms. Itching and tearing may be unbearable and sleepless nights frequent. Allergic conjunctivitis symptoms may be worse than the nasal symptoms in those suffering from rhinoconjunctivitis. Furthermore, treatment of the nasal symptoms with topical nasal steroids may help the rhinitis, but not be effective for relieving ocular symptoms. Management of allergic conjunctivitis is, therefore, primarily aimed at alleviating symptoms. The best treatment is avoidance of the specific allergen, which, unfortunately, is usually not possible. Avoidance of scratching or rubbing, application of cool compresses, artificial tears and refrigeration of topical ocular medications are practical interventions to alleviate discomfort. While oral antihistamines may help to relieve eye itch, first generation drugs may also decrease tear production, causing more ocular symptoms. Topical medications are generally considered more effective to relieve ocular itching than oral medications and may be additive to relief gained from oral antihistamines. The treatment of choice for mild to moderate AC is a dual acting topical ocular medication. The mast cell stabilizing component of these drugs benefits patients most if treatment is started before the height of symptom onset. Patients usually note rapid onset of relief of itch upon drop instillation, as most dual action medications have high H1 receptor affinity. Drug dosing varies from one to four times per day and efficacy is judged best by symptom relief.

Symptoms of allergic eye disease

Symptoms of allergic eye disease

In summary, Allergic conjunctivitis is a bilateral allergic response of the conjunctiva to airborne allergens to which an individual is sensitized. The symptoms may be seasonal or year round, the signs mild without threat to vision, and the treatment with topical antihistamine drops quite effective as treatment. Loss of vision from the disease would be rare.

Table 1: Allergic Diseases of the Eye:

Disease

Clinical Parameters

Signs/Symptoms

Differential Diagnosis

Seasonal Allergic Conjunctivitis (SAC) Sensitized individuals
Both females and males
Bilateral involvement
Seasonal allergens
Self limiting
Ocular itching
Tearing (watery discharge)
Chemosis, redness
Often associated with rhinitis
Not sight threatening
Infective Conjunctivitis
Preservative Toxicity
Medicamentosa
Dry Eye
PAC/AKC/VKC
Perennial Allergic Conjunctivitis (PAC) Sensitized individuals
Both females and males
Bilateral involvement
Year-round allergens
Self limiting
Ocular itching
Tearing (watery discharge)
Chemosis, redness
Often associated with rhinitis
Not sight threatening
Infective Conjunctivitis
Preservative Toxicity
Medicamentosa
Dry Eye
SAC/AKC/VKC
Atopic Keratoconjunctivitis (AKC) Sensitized individuals
Peak incidence 20-50 years of age
Both females and males
Bilateral involvement
Seasonal/Perennial Allergens Atopic Dermatitis
Chronic symptoms
Severe ocular itching
Red flaking periocular skin
Mucoid discharge, photophobia
Corneal erosions
Scaring of conjunctiva
Cataract (anterior subcapsular)
Sight-Threatening
Contact Dermatitis
Infective Conjunctivitis Blepharitis
Pemphigoid
VKC/SAC/PAC/GPC
Vernal Keratoconjunctivitis (VKC) Some sensitized individuals
Peak incidence 3-20 years of age
Males predominate 3:1
Bilateral involvement
Warm, Dry Climate Seasonal/Perennial Allergens
Chronic symptoms
Severe ocular itching
Severe photophobia
Thick, ropy discharge
Cobblestone papillae
Corneal ulceration and scaring
Sight-Threatening
Infective Conjunctivitis Blepharitis
AKC/SAC/PAC/GPC
Giant Papillary Conjunctivitis (GPC) Sensitization not necessary
Both females and males
Bilateral involvement Prosthetic Exposure
Occurs Anytime
Chronic symptoms
Mild ocular itching
Mild mucoid discharge
Giant papillae
Contact lens intolerance Foreign body sensation
Protein buildup on contact lens
Not sight threatening
Infective Conjunctivitis
Preservative Toxicity
SAC/PAC/AKC/VKC

Table 2

Drug and Classification

Inhibition of Mediator Release From Human Conjunctival Mast Cells

Inhibitory Effects on Other Cells

Antazoline

H1 Receptor Antagonist

No Effect Inhibits IL-6, IL-8 release from on conjunctival
epithelial cells in vitro
Pheniramine

H1 Receptor Antagonist

No Effect Inhibits IL-6, IL-8 release from on conjunctival
epithelial cells in vitro
Emedastine

H1 Receptor Antagonist

No Effect Inhibits IL-6, IL-8 release from on conjunctival
epithelial cells in vitro
Levocabastine

H1 Receptor Antagonist

No Effect Inhibits IL-6, IL-8 release, ICAM-1 expression on
conjunctival epithelial cells in vitro
Olopatadine

H1 Receptor Antagonist
Mast cell stabilizer

histamine, tryptase, PGD2,
TNFα in vitro
Conjunctival mast cell TNFa-mediated
upregulation of ICAM-1 on conjunctival epithelial
cells in vitro
Ketotifen

H1 Receptor Antagonist
Mast cell stabilizer

histamine
in vitro
Chemotaxis and activation of
eosinophils in vitro
Azelastine

H1 Receptor Antagonist
Mast cell stabilizer

in vitro data not
available
Eosinophils and neutrophils in tears
ICAM-1 expression in vivo
Cromolyn

Mast cell stabilizer

not inhibitory for
histmaine release in
vitro
tryptase in tears
Chemotaxis and activation of
eosinophils, neutrophils, monocytes in
vitro
Lodoxamide

Mast cell stabilizer

in vitro data not
available
histamine and tryptase
in tears
Chemotaxis and activation of
eosinophils in vitro
Eosinophils, neutrophils, T cells in
tears
ICAM-1 expression on conjunctival
epithelial cells in vitro
Nedocromil

Mast cell stabilizer

not inhibitory for
histamine release in
vitro
Activation of eosinophils and
neutrophils in vitro
Pemirolast

Mast cell stabilizer

not inhibitory for
histamine release in
vitro
Activation of eosinophils and neutrophils
in vitro
Antazoline

H1 Receptor
Antagonist

No effect Inhibits IL-6, IL-8 release
from an conjunctival epithelial cells in vitro
Alcaftadine

H1 Receptor
Antagonist
Mast Cell stabilizer

histamine in vitro Chemotaxis and activation of
eosinophils in vitro
Bepotastine

Mast Cell stabilizer

histamine in vitro Chemotaxis and eosinophils in vitro