Seasonal allergies typically produce a thin, watery discharge and do not involve the cornea. If the patient exhibits thick, ropy discharge with severe itching and corneal involvement, it is most likely VKC rather than a seasonal allergy. VKC’s prevalence is higher in the warmer climates. Onset is typically between the ages of three and 25 years. Males are typically more affected than females.

The important clinical signs of VKC include large conjunctival papillae on the back of the superior tarsus, Horner-Trantas dots (gelatinous, white clumps of degenerated eosinophils at the superior limbus), areas of superficial punctate keratitis (SPK) and, in severe cases, well demarcated, sterile, superiorly located corneal shield ulcers.

PATHOPHYSIOLOGY
An allergic response is an unwarranted over-reaction of the body’s immune system to foreign substances known as allergens, which the body wrongly perceives as a potential threat. The response can be innate or acquired. The presence of an allergen on the conjunctiva initiates two simultaneous immune responses, one caused by the release of so-called “pre-formed” inflammatory mediators such as histamine from mast cells, and the other by the production of arachidonic acid and its conversion into so-called “newly-formed” mediators such as prostaglandins (see “Tracing the Complex Path of Allergic Reactions,” on next page). Pre-formed mediators are released immediately upon exposure; newly-formed mediators are delayed roughly eight to 24 hours.

In mast cell degranulation, the allergen attracts and binds to an antibody known as immunoglobulin E (abbreviated as “IgE”), then adheres to mast cells and causes them to degranulate, like a key opening a lock. This discharges the pre-formed mediators. Their effects can be either direct, indirect or a combination of the two.

Two important mediators released from mast cells, histamine and bradykinin, immediately begin to stimulate nerve endings called nociceptors, creating the sensation of itching. Both also increase vascular permeability and vasodilation; this causes the clinical signs of redness and conjunctival injection.

Meanwhile, other mediators released from mast cells send out chemical signals that attract both red and white blood cells to the area. Once these cells arrive, they easily reach the conjunctival surface by moving through the dilated and highly permeable capillaries.

The body’s other defense mechanism, referred to as the arachidonic acid cascade, produces three newly-formed inflammatory mediators—prostaglandins, thromboxanes and leukotrienes—which are collectively known as eicosanoids.

Virtually all cells contain a phospholipid layer within their cell walls. Any disruption or threat signals the cell to convert phospholipids into arachidonic acid. When arachidonic acid interacts with two enzymes known as cyclooxygenase and lipoxygenase, it is metabolized into eicosanoids. An allergen’s presence initiates the arachidonic acid cascade both within conjunctival epithelial cells and also within mast cells as they degranulate.

Much like histamine and bradykinin, prostaglandins directly stimulate nerve endings to produce sensations of itching and pain, and also increase vascular permeability and vasodilation. Leukotrienes primarily attract macrophages (white blood cells).

MANAGEMENT
Management of both allergic conjunctivitis and VKC is primarily aimed at alleviating symptoms. The most effective but least practical treatment is to prevent exposure to the allergen. Since this is not usually possible, instruct patients to frequently use cold compresses, artificial tears and ointments to soothe, lubricate and wash away the allergens. Also recommend that patients use a topical decongestant such as naphazoline or phenylephrine as needed. These drugs cause vasoconstriction, retarding the release of the chemical mediators into the tissues from the blood stream. This reduces hyperemia, chemosis and other symptoms.

Mast cell stabilizers such as Alomide and Crolom help prevent the onset of allergic reactions by blocking the adherence of the IgE-allergen compound to the mast cell. Treat patients with a history of recurrent seasonal allergies using a mast cell stabilizer q.i.d. for four weeks in advance of allergy season. Patanol (olopatadine 0.1%) combines mast cell stabilization with an antihistamine to offer therapy that is for both acute and chronic symptoms. The effects last eight hours, allowing for b.i.d. rather than q.i.d. dosing.

In moderate to severe cases, recommend one or more of the following, used from two to four times per day as needed: a topical medication such as Patanol or Livostin, oral antihistamines such as Benadryl, or a topical non-steroidal anti-inflammatory drug (Acular, Voltaren or Profenal). In extremely symptomatic cases, use a topical steroid such as Vexol, Flarex or Alrex q.i.d.

Only prostaglandins and thromboxanes are produced when cyclooxygenase interacts with arachidonic acid. Leukotrienes, by contrast, are produced from the break-down of arachidonic by lipoxygenase. This leads to an interesting distinction in anti-inflammatory treatment. Non-steroidal drugs prevent the formation of cyclooxygenase but not lipoxygenase, thus they have virtually no effect on the production of leukotrienes. As a result, non-steroidals are useful in reducing itching and conjunctival injection but not very helpful in ridding the eye of excess immune cells. But because steroids inhibit the production of arachidonic acid itself, they reduce the production of all three eicosanoids. This is why we must use steroids to treat any inflammatory conditions characterized by a build-up of immune cells, such as chalazia, uveitis or corneal infiltrates.

VKC patients who present with shield ulcers also need aggressive cycloplegia (atropine 1%, homatropine 5% or scopolamine 0.25%, b.i.d.) and a topical antibiotic (Tobrex, Ciloxan Ocuflox or Polytrim) q4-6h. To reduce the interaction between the lid and cornea, provide a low-water content soft lens as a bandage lens. When the corneal lesion has re-epithelialized, begin topical steroid therapy.

Newer anti-histamines, such as dual-action olopatadine hydrochloride 0.1% (Patanol) b.i.d. as well as emedastine difumarate 0.5% (Emadine) q.i.d. have been seen to be very effective. A recently developed steroid, loteprednol etabonate (Alrex) q.i.d. is specifically marketed for the management of allergic conjunctivitis.

CLINICAL PEARLS

• Educate patients with a history of seasonal allergic conjunctivitis about how to avoid exposure to substances that precipitate symptoms, and recommend prophylactic treatment with a mast cell stabilizer. If effective, maintain this therapy for the duration of the season.
• Follow-up with patients on non-steroidal medicines in one to two weeks after the start of therapy. See patients on topical steroids no later than one week after the start of therapy, and monitor their IOP routinely for the duration of the therapy. Re-examine patients treated for shield ulceration every one to three days.
• Mast cell degranulation only occurs in allergic reactions, but the arachidonic acid cascade occurs after any threatening event, such as bacterial infection, surgery or accidental trauma.
• Follow up with patients placed on topical medications after one week, with close monitoring thereafter.

Other reports in this section

• Allergic Conjunctivitis &Vernal Keratoconjunctivitis
• Viral Conjunctivitis
• Bacterial Conjunctivitis
• Chlamydial & Gonococcal Conjunctivitis
• Conjunctival Laceration
• Episcleritis
• Scleritis
• Pingueculitis
• Pterygium
• Superior Limbic Keratoconjunctivitis (SLK of Theodore)
• Toxic Conjunctivitis
• Conjunctivitis with Pseudomembrane
• Giant Papillary Conjunctivitis