OCULAR ALLERGY AND DRY EYE

Nexus of Misery: Ocular Allergy Meets Dry Eye

Separately, ocular allergy and dry eye are irritating and uncomfortable for patients. What happens when they occur together?

By Arthur B. Epstein, OD, FAAO

Allergy is among the very first diseases to be well understood. It is also among the most disruptive and, in severe cases, it can be debilitating and even life threatening. Ocular allergy, while not life threatening, consistently ranks high as a disrupter in quality of life surveys. The eye is typically near the top of the list as a site of active allergic response; an array of associated functional and cosmetic sequelae involve the eye and surrounding tissue.

In contrast, what has traditionally been called dry eye remains largely unexplored territory. Recent and ongoing advances in our understanding of the ocular surface environment have called into question much of the dogma that continues to guide diagnosis and treatment of ocular surface disease and tear dysfunction.

Clinically, allergy and dry eye co-exist on a continuum of ocular surface disease. At their intersection, each can exacerbate or, in some cases, mitigate the other. Understanding both is critical to effective disease management.

A Practice Growth Opportunity

From the clinicians’ perspective, all forms of ocular surface disease represent a tremendous patient management opportunity. This is especially true in managing allergy. While the U.S. Food and Drug Administration (FDA) currently limits dual-action claims, modern topical ocular allergy medications can effectively block histamine receptors and stabilize mast cell membranes to provide unprecedented relief.

Incremental improvements in drug design and formulation have increased efficacy, with several available topical products indicated for once-daily dosing. Modern ocular allergy medications work so quickly that most patients are still holding the bottle when they start to experience symptomatic relief. This rapid, effective therapy reinforces prescriptive authority.

Advances in our understanding of ocular surface disease and a rethinking of dry eye pathophysiology have also created increased opportunity for more successful patient management and practice growth. Recently, Korb and Blackie (2015) have proposed that dry eye is more often than not the wrong diagnosis for many patients. Regardless of perspective or approach, both “dry eye” and ocular allergy are frequent, albeit sometimes subtle, contributors to the overall surface disease clinical picture. While allergy is clearly recognized as a very specific and narrowly focused form of ocular surface inflammatory disease, its contribution to “dry eye,” as well as to contact lens intolerance and dropout, is less well delineated and, most likely, frequently underestimated. Likewise, the contribution of existing surface disease to the misery of allergy in clinical practice is often overlooked.

The Fundamentals of Ocular Allergy

Although the clinical presentation is usually classical and easily recognized, there is nothing typical about ocular allergy. Allergy by definition is an atypical reaction to otherwise commonplace elements within a patient’s normal environment. The allergic response describes a hypersensitivity reaction triggered by the most ordinary of things, ranging from foods to plants to animal proteins. Indeed, the allergic response is thought to initially derive from the body’s zealous defense against invasion of potentially life-threatening parasites. That helps explain the serious nature and the power of allergy’s more severe systemic presentations, such as asthma and anaphylaxis.

Allergy typically manifests primarily as a localized response, but it is important to recognize that it is a disease that involves the entire body. Inflammation caused by allergy can range from transient, mild, and barely noticeable to devastatingly severe, with resultant tissue destruction and scarring.

In the eye, the allergic response is prototypical, with sensitization to the offending allergen initiating a programmed immune response. Sensitization produces and populates allergen-specific IgE on the surfaces of mast cells. The mast cell is aptly named. It is a stationary inflammatory cell uniquely tethered in place by a “mast,” allowing it to stand at the ready to launch a nearly instantaneous burst of mediators and chemicals that defend and protect critically important tissues.

Histamine is well recognized as the primary actor in the allergic response, but it is not the only mediator of allergy. A variety of preformed inflammatory and pro-inflammatory substances are released as the mast cell degranulates. These include proteases, prostaglandins, leukotrienes, cytokines, and chemokines. A secondary response by the activated mast cell results in the synthesis of additional mediators; this mobilizes a larger-scale and more aggressive cellular response involving eosinophils, basophils, and other inflammatory actors.

Allergy takes a variety of forms based on the triggering allergen and its presence in the environment. Seasonal allergy is typically associated with plant pollens, which wax and wane depending upon the time of year. Perennial allergies are more often associated with indoor environments and are driven by insect or animal detritus. Chronic allergies such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are less common, but far more disruptive and potentially destructive clinical variants of ocular allergy.

The allergic response characteristically occurs in two phases: early and late. The early phase response is localized and driven by mast cell interaction with an allergen, while the late phase describes subsequent infiltration by eosinophils and basophils. While still an issue of debate, the ocular surface response in seasonal and perennial allergy is primarily early phase, as reflex tears help wash away allergens, pro-inflammatory mediators, and signaling molecules. Late-phase response is often associated with more severe disease and can result in permanent tissue damage, such as the scarring caused by shield ulcers in VKC or, systemically, the airway damage seen in asthma.

Dry Eye: New Perspectives

Our understanding of the ocular environment has advanced tremendously in recent years. We now understand that what was labeled as basal tears are structural in nature. At the surface, glycocalyx and surface mucins create a stable foundation for the tear structure. Gel-forming mucins and aqueous components form the bulk of the tears and act as a viscoelastic cushion. Complex lipids expressed by the meibomian glands produce an outermost thin film structural layer—one that serves as a moisture barrier and contributes to tear stability.

The tears are dynamic; they have a structure that collapses and reforms with each blink, yet remains intrinsically protective. As a complement to the structural basal tears, reflex tearing provides an “emergency eyewash” function that flushes away irritants and other potentially harmful elements. Unsurprisingly, reflex tearing had inspired most of the thinking regarding tears and tear dysfunction until the modern era of the last decade.

From a clinical perspective, dry eye continues to be viewed by many as primarily a disorder of aqueous deficiency; however, a more contemporary view suggests that much of what has traditionally been placed in the dry eye bucket is actually tear instability and dysfunction due to meibomian gland disease and evaporative dry eye.

Meibomian gland dysfunction (MGD) is a complex chronic and progressive disorder that not only targets the meibomian glands, but also disrupts tear structure and function. MGD precipitates an inflammatory cascade within the glands and throughout the ocular surface environment. As the disease progresses, the glands become increasingly obstructed, function is compromised, and, over time, inflammation, tissue damage, and gland destruction and loss occurs. In this environment, staphylococcal species flourish and significantly overpopulate the lid margins.

Lid margin flora produce bacterial exotoxins, which can be sensitizing. Flora also produce destructive enzymes designed to compromise barriers and thus facilitate infection. Bacterial lipase entering the tears enzymatically degrades lipids and, in combination with other tear components, causes saponification or soap-making. Often described as “frothing,” these soaps further break down and destabilize the tears. Saponification also contributes to the burning often described by patients who suffer from bacterial overpopulation of the lids. All of these elements combine to produce an upsurge in surface inflammation, which can drive both dry eye and allergy.

How Ocular Allergy and Dry Eye Interact

Allergy, dry eye, MGD­­—in fact, most forms of ocular surface disease—show significant overlap. Environmental factors play a key role in the expression of both ocular allergy and dry eye. While most clinicians’ attention is focused on the external environment, the microenvironment of the ocular surface is equally important in both conditions.

The reduced dilutional reserve present in both the aqueous deficient and evaporative forms of dry eye can potentiate allergy. In addition, prolonged contact time between allergens and conjunctival tissue within a diminished tear lake also increases the concentration of inflammatory and pro-inflammatory mediators.

Tears play an important role in allergic disease. Reactive tearing—one of the hallmark signs of ocular allergy—flushes allergens from the ocular surface, diminishes allergen contact time, and effectively quashes the allergic response. Normal tear production and drainage also reduces allergen contact time and can minimize the severity of the ocular allergic reaction in patients who have normal tear function.

Although symptoms can overlap and be confusing, dry eye can be worsened by the presence of allergens and allergic surface disease. Likewise, the constellation of symptoms caused by tear deficiency or tear instability can sometimes overshadow allergic signs and symptoms. Paradoxically, excessive lacrimation due to chronic dry eye can wash away allergens, reducing the severity of ocular allergy.

Meibomian gland disease injects highly saturated dysfunctional lipids into the tear film, which can cause surface inflammation. As previously described, overgrowth of staph on the lid margins, and their production of exotoxins, contributes to the inflammatory mix within the tears. Delayed clearance potentiates tear contamination, especially in patients who have undergone punctal occlusion.

Adding to the complexity of surface disorder interplay, immune diseases that contribute to dry eye—such as Sjögren’s syndrome, rheumatoid arthritis, lupus, and thyroid disease—all have inflammatory potential, which can worsen ocular surface disease.

Summary

Considering all of these overlapping elements, it is clear that regardless of the presenting complaint or clinical signs or symptoms, all forms of ocular surface disease must be viewed with an open mind and managed with a methodical approach. Determining primary and contributing factors, as well as a thorough understanding of contributing elements, will often result in more successful outcomes for patients. CLS

To obtain references for this article, please visit http://www.clspectrum.com/references and click on document #246.

Dr. Epstein is an internationally recognized expert in complex contact lens management and medical complications of contact lenses, dry eye, and anterior segment disease. He co-founded Phoenix Eye Care and The Dry Eye Center of Arizona and serves as the Director of Cornea - External Disease. Dr. Epstein also heads Ophthalmic Research Consultants of Arizona. He is a stock shareholder of Novartis and NovaBay Pharmaceuticals and has received honoraria for consulting, performing research, speaking, and/or writing from Alcon, B+L, NovaBay, PRN, Oculus, Novartis, Bio-Tissue, BioD, RySurg, and Shire.