Combination a complication

In the world of the ocular surface, allergic disease and dry eye syndromes are the dominant therapeutic challenges. The contrast between these two disorders is that while treatments for allergy are plentiful, the choices for treating dry eye are limited.

A further complication that hasn’t had much attention to date is the co-morbidity of ocular allergy and dry eye. As we look closer at each condition we find a complex relationship that involves important aspects of etiology and therapy. And with both allergies and dry eye disease on the rise, it is becoming increasingly common for patients to present with a combination of the two conditions.

Ocular allergies, including both seasonal and perennial varieties, affect an estimated 60 million people in the United States, and a similar percentage (between 20% and 30%) of individuals in Europe, Australia, Japan, and Korea.Friedlaender MH. Curr Opin Allergy Clin Immunol. 2011;11:477-482. A combination of pollution and a growing urban lifestyle have contributed to the trend of increased prevalence of allergic disease over the past half-century.

In that same time span, the increased lifespan and the aging of populations worldwide are contributing to increased dry eye prevalence. Dry eye is primarily seen in patients aged more than 50 years, as well as those who have undergone ocular surgical procedures.2 Dry eye differs from ocular allergies, however, in that it has an extremely heterogeneous etiology that includes Sjögren’s syndrome, meibomian gland disorders, and the keratitis that often occurs following LASIK surgery.

Despite the close association of these two ocular disorders and the inclusion of allergic conjunctivitis as an “extrinsic factor” in dry eye etiology,Report of the international Dry Eye Workshop (DEWS). Ocul Surf. 2007;5:69-204. there has been little focus on the causal relationships and the potential for overlapping, synergistic therapies to date.

Population demographics of the two disorders suggest that there is likely to be a high degree of co-morbidity, but there are few direct studies that address this issue. Two large-cohort, longitudinal studies indicate that these are not simply two separate, independent conditions.Schaumberg DA. Am J Ophth. 2003;136:318-326.,Moss SE. Arch Ophthal. 2004;122:369-373. Both of these studies provide evidence that patients who suffer from allergic conjunctivitis are significantly more likely to experience signs and symptoms of dry eye disease, especially as they reach middle age. In order to treat these conditions properly when they occur together, it’s useful first to consider the features of each.

Take-Home Message

Patients who suffer from allergic conjunctivitis are significantly more likely to experience signs and symptoms of dry eye disease. Studies of the tear film in allergic conjunctivitis demonstrate the shared pathology between dry eye and ocular allergy: the inflammation of the corneal and conjunctival surface. Perhaps a therapy of the future will be one that any practitioner will think of as the treatment of choice for both ocular allergy and dry eye.

Allergy

The etiology of allergy is relatively straightforward; individuals with atopy have a reaction to specific environmental allergens according to the duration and quantity of allergen exposure. Layered on this is the impact of seasonal versus perennial allergens and environmental factors (such as air pollution) that all act to promote a more persistent type of allergy that may include corneal and/or conjunctival inflammation.

As patients progress toward this continual type of ocular allergy, they may begin to resemble symptomatically the dry eye patient. Patients with allergy can also develop dry eye symptoms due to adverse effects of medications. For example, some oral antihistamines have a tendency to cause symptoms of dry eye. A number of studies have shown that drugs such as loratadine or cetirizine can reduce aqueous tear production and exacerbate the ocular burning, grittiness, and corneal staining in patients who suffer from dry eye.Ousler GW, Wilcox KA, Gupta G, Abelson MB. Ann Allergy Asthma Immunol. 2004;93:460-464.,Wong J, Lan W, Ong LM, Tong L. Ocul Surf. 2011;9 212-226.

Another recent study examined tear composition in patients with allergic conjunctivitis and found that the observed changes could contribute to tear film instability.Li K, Liu X, Chen Z, Huang Q, Wu K. Molecular Vision. 2010;16:2084-2091. Thus, it appears that allergies may predispose patients to developing dry eye disease in a number of ways.

Future studies are likely to consider a history of ocular allergy as an equally important factor in the underlying etiology of dry eye.

To help in understanding the patients’ perspective, we recently conducted a survey of patients in whom both allergic conjunctivitis and dry eye disease had been diagnosed. The surveyed group included slightly more women than men (55% versus 45%), two-thirds of whom were between 50 and 65 years of age.

As shown in Figure 1, the most striking aspect of the survey was that the seasonal nature of both disorders is diminished, and a larger proportion of patients experience symptoms year-round. By comparison, the majority of patients who suffer only from allergies are symptomatic in spring or fall, depending upon the specific allergens to which they respond.1 Dry eye also has a seasonality, with patients experiencing more severe symptoms in winter months when humidity is lower and people typically spend more time indoors.

Inflammation

Figure 1 Survey results of patients with both dry eye disease and ocular allergy. Responses suggest that the combination can exacerbate symptoms of both conditions, shifting them from primarily seasonal to year-round disorders.

While patients with ocular allergies experience an increased risk for dry eye, the converse is also true: dry eye can exacerbate allergic signs and symptoms. At this year’s Tear Film and Ocular Surface in Asia conference, we presented results of a study that showed when patients are exposed to the controlled adverse environment (Ora CAE) their allergic responses are significantly worsened. Our results, together with studies of the tear film in allergic conjunctivitis, demonstrate the shared pathology between dry eye and ocular allergy: the inflammation of the corneal and conjunctival surface.

Several recent reports documenting damage to the conjunctival and corneal epithelium associated with prolonged allergen exposureOno SJ, Lane KJ. Drug Design, Development and Therapy. 2011;5:77–84.,Contreras-Ruiz L, Schulze U, García-Posadas L, et al. Curr Eye Res. 2012:early online 1-11. describe an ocular surface disease that is remarkably similar to that seen in dry eye. Future efforts in therapeutic development may well be designed to treat both conditions by addressing the underlying inflammatory nature.

A key to addressing the needs of this growing population of patients is establishing viable metrics and efficacy standards for therapeutic development. Future studies are likely to consider a history of ocular allergy as an equally important factor in the underlying etiology of dry eye, and this should only enhance development of new therapies.

Ideally, this will provide relief to sufferers of both dry eye and allergy, so symptoms of either disease need not be overlooked. Perhaps a therapy of the future will be one that any practitioner—ophthalmologist, optometrist, allergist, or primary-care provider—will think of as the treatment of choice for ocular allergy and dry eye.