Taking Another Look at Ocular Allergy

A refresher to help you prepare for the seasonal spike in cases.

By Robert Murphy, Contributing Editor

To everything there is a season. Nowhere is this more true than with ocular allergies. Early spring notoriously marks the coming-out season for grass and tree pollen, when the outdoors in which the non-allergic population enjoy their picnics and woodsy strolls becomes, for the sensitized, a minefield of unbearable ocular itching.

You hardly need to look at a calendar these days, as your schedule fills up with patients complaining of itching, tearing, redness, and swelling—the hallmark signs of allergic conjunctivitis. They will tell you it gets so bad it disrupts work, leisure, sleep, you name it. In the worst cases, people become virtual prisoners of their own homes. Heretofore beloved pets may be sent packing. Golf clubs may end up on Craigslist once the links become a jinx. Compulsive ocular itching only worsens matters, rupturing conjunctival mast cells, which then spill more histamine—the chief culprit for the eye's allergic signs and symptoms—and other inflammatory mediators.

Here's where your skills as a clinical historian come into play. In the face of ocular allergies, a good history may be your most valuable diagnostic exercise. Before you even get behind the slit lamp, a well-targeted interview will carry you through a differential diagnosis in which you rule out vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis. Also be on the lookout for dry eye, which often partners in confounding ways with ocular allergy. Remember, too, that the offending antigen may come not just from tree or grass pollen—or ragweed in the fall—but also from pet dander, dust mites, mold, allergenic foods or medicines, or even a work environment contaminated with airborne antigens.

Figure 1. Cobblestone papilla in vernal keratoconjunctivitis. Palpebral VKC has large excrescences on the underside of the upper lid. These may be large and seem as only a few, or may appear as many. The apices of the lesions are usually flat-topped.

All ophthalmologists have seen numerous cases of allergic conjunctivitis. Yet, as allergy season comes rushing at us once again, maybe the time is right for a clinical review of allergic conjunctivitis. In this first part, external ocular disease specialists describe how to make an efficient and accurate diagnosis. In the article that follows, they offer clinical pearls on how to bring the condition under control quickly and without complications. That's important, because a patient who comes to you suffering from seemingly unendurable ocular itching wants effective relief now.

Death Knell for a Mast Cell

Isn't it remarkable that with so many varied inciting environmental etiologies—everything from a weeping willow to a tubby tabby cat—the pathophysiology of allergic conjunctivitis and its assault on the mast cell remain strikingly consistent? Sit back and let an expert explain how it works.

“Allergic conjunctivitis falls into a category of conditions known as type-1 IgE-mediated hypersensitivity reactions,” says cornea specialist Jodi Luchs, MD, of North Shore Jewish Medical Center in New Hyde Park, NY, and a private practitioner from Wantagh, NY. “What that means is that an antigen to which a person has previously been sensitized bonds to IgE receptors on the surface of mast cells in the tissue somewhere in the body. And in the case of the eyes, the mast cells are in the conjunctiva.”

Here is where the trouble starts. “That binding to the IgE receptor on the mast cell initiates a whole series of intra-cellular events, including calcium influx and phosphorylations, all of which result in the release of preformed cytoplasmic granules from the mast cell cytoplasm,” Dr. Luchs says.

It gets worse. “These preformed granules contain a variety of inflammatory mediators, the most notable of which of course is histamine,” Dr. Luchs says. “They also contain a host of other inflammatory mediators. At the same time, the mast cell is stimulated to synthesize new mediators of inflammation: prostaglandins, prostacylcins, tumor necrosis factor and others.”

But histamine is the major culprit. “Now, of all of these inflammatory mediators, it's primarily the histamine that's responsible for initiating the classic signs and symptoms of ocular allergy that we're familiar with—the itch, the redness and the swelling,” Dr. Luchs says. “The histamine binds to the H1 receptors in the conjunctival nerve endings, and that's what causes itch. The histamine also binds to the H1 receptors and the H2 receptors in the conjunctival vasculature, which is responsible for vasodilation and increases in vascular permeability.”

This inflammatory cascade concludes with the late-phase allergic response. “All these inflammatory mediators attract other inflammatory cells into the conjunctiva,” Dr. Luchs says. “These inflammatory cells include the eosinophils, neutrophils, macrophages, monocytes, lymphocytes and so forth. Once these cells arrive in the conjunctiva, they also become activated and start secreting their own sets of inflammatory mediators that prolong and propagate this entire allergic inflammatory cascade.”

And it all happens so fast. The preformed mediators—histamine, tryptase, bradykinin—are liberated from the mast cell immediately following allergen exposure.¹ The newly formed mediators, meanwhile—leukotrienes and prostaglandins—burst upon the scene within eight to 24 hours.¹ All of these mediators conspire to trigger the hallmark signs of ocular allergy.

The History Solves the Mystery

In Henry James's novel Washington Square, there's a doctor who has earned a reputation in early-19th-century New York City as a master diagnostician based almost entirely on the skill with which he obtains and analyzes a patient's history. Even with today's sophisticated diagnostic instruments, the history remains an instrumental vehicle on the path to a diagnosis. That is certainly the case with allergic conjunctivitis. “History really is the key when it comes to diagnosing ocular allergy,” Dr. Luchs says. “Because in many situations, findings on the examination are few and far between.”

What makes a good history when a patient presents with complaints consistent with allergic conjuncitivitis? Ask detailed questions about the symptomatology, almost like a detective grilling a suspect or a journalist interviewing a key source. Move from the general to the specific. Like anything else, it's something at which you get more adept over time.

“I always ask patients to describe their symptoms,” says Barry Schechter, MD, director of Cornea and External Diseases and the Cataract Service at Florida Eye Microsurgical Institute in Boynton Beach and Boca Raton, Fla. “When do they occur? When are their symptoms worse? Is there anything that can make it better? Is there anything that makes it worse? Is there any history of sensitivity in the family of allergies? Are there pets in the home? What type of vocation does the patient have? Where do they work? Where do they spend most of their time?”

Family history can be particularly telling. Why? “The family history is important because if you have two parents that have both had allergies, a child has a greater than 50% chance of having an allergy,” says Neal Barney, MD, associate professor of ophthalmology at the University of Wisconsin, who specializes in cornea and external disease as well as ocular immunology.

And don't forget to ask whether the symptoms are unilateral or bilateral. Allergic conjunctivitis usually affects both eyes—after all, an environmental antigen does not discriminate between one eye or the other—whereas infectious conjuncitivitis typically presents unilaterally. But there is one exception to this observation. Sometimes a patient will develop allergic conjunctivitis in just one eye because he touched that eye with a hand which had been colonized by an allergen. If that's the case, suspect a possible ocular allergy in the eye corresponding to the patient's dominant hand.

Figure 2. Commonly in VKC there is a thick, ropy or stringy mucous discharge intervening between the polygonal shaped papillae. The papillae have a single, central blood vessel seen in the center. Follicular reactions are not seen.

Rule Out the Imposters

On the one hand, ocular itching is a necessary condition for a diagnosis of allergic conjunctivitis. But it isn't sufficient. In fact, none of the findings that you see with ocular allergy is pathognonomic, not even itching, which occurs with other ocular disorders. So as you take the patient's history and gather your clinical findings, keep in mind other ocular inflammatory conditions which involve itching.

■ Atopic keratoconjunctivitis. This bilateral chronic inflammation of the conjunctiva and lids is associated with atopic dermatitis.¹ Itching, sometimes quite pronounced and nearly intolerable, is the major symptom. Patients may also report watering, mucous discharge, redness, blurred vision, photophobia and pain. The periocular skin may show a scaling, flaking dermatitis. The lids may develop ectropion and lagophthalmos. Look for lateral canthal ulceration, cracking and madarosis. The conjunctiva of the tarsal surfaces will exhibit a papillary reaction and follicles. The bulbar conjunctriva may show little else besides redness and swelling. Punctate epithelial keratopathy may result in significant vision loss.
■ Vernal keratoconjunctivitis. This disease affects mostly the young, beginning before age 10 and lasting two to 10 years.¹ Its main symptoms are severe itching and photophobia. Patients may also experience a foreign body sensation, ptosis, mucous discharge and blepharospasm. Look for a papillary conjunctival response, mostly at the limbus and upper tarsus. Thick and ropy mucus often accompanies the tarsal papillae. Here too, the corneal changes may be sight-threatening. If a punctate epithelial keratitis goes untreated, a shield ulcer may develop on the upper half of the visual axis, leaving a scar when it heals.
■ Giant papillary conjunctivitis. This condition is characterized by giant papillae on the tarsal conjunctiva lining the upper eyelids.¹ It develops mostly in soft contact lens wearers, although rigid lenses, sutures and ocular prostheses have been implicated as well. GPC may affect up to 20% of soft contact lens wearers. Those who wear disposable lenses overnight are said to be three times more likely to have GPC than those who remove them. Once again, itching after lens removal is a hallmark symptom of GPC, along with redness, burning, mucous discharge in the morning, photophobia and lens intolerance. Blurred vision may develop secondary to deposit build-up on the lenses.

The Season of the Itch

Allergic conjunctivitis—whether it's seasonal from pollen or ragweed, or perennial from animal dander, dust mites, mold, foods or medicines—is estimated to affect upwards of 40 million Americans each year. Is it any wonder the pharmacy shelves groan under the weight of countless OTC remedies? And yet, many find those insufficient.

Figure 3. In VKC, the papillae may be most prominent at the at the limbus. This is said to more likely occur in dark skinned patients.

Allergic conjunctivitis may be a self-limiting condition, but it is anything but benign. That's why patients come to you for immediate relief rather than tough it out for the six-or-so weeks when environmental allergies are at their peak. Many know from past history that you've got just what they need to ease their suffering so they can get back to enjoying spring rather than hiding from it. OM

Reference

1. Yanni J, Barney N. Allergic conjunctivitis. In: Yorio T, Clark AF, Wax MB (eds.): Ocular Therapeutics: Eye on New Discoveries. Elsevier: 2008.