Diagnosing and managing ocular allergy

January 16, 2014

Ocular allergy is one of the most common ocular surface diseases seen in a primary eyecare practice. Allergic conjunctivitis (AC) often exists concurrently with rhinitis and asthma, and patients with allergic rhinitis frequently present with symptoms of AC. AC is often linked to allergic rhinitis and requires co-treatment.

Ocular allergy is one of the most common ocular surface diseases seen in a primary eyecare practice. Allergic conjunctivitis (AC) often exists concurrently with rhinitis and asthma,1 and patients with allergic rhinitis frequently present with symptoms of AC. AC is often linked to allergic rhinitis and requires co-treatment. The major symptoms of conjunctivitis, such as burning and itching and watery eyes, are the same as for allergic rhinitis.

Ocular allergy is often underdiagnosed2 and subsequently undertreated, even though the prevalence of allergic diseases has increased in the last decades.3,4 The cause of this increase cannot be pinpointed, and numerous factors have been considered, including genetics, air pollution in urban areas, pets, and early childhood exposure.5 The costs associated with allergic eye disease have increased substantially as more people require treatment for allergies.6 Studies have estimated the prevalence of allergic conjunctivitis to range between 15%-40% of the population.2 Mild cases of ocular allergy can produce irritating symptoms, and severe forms of the presentation, such as atopic keratoconjunctivitis, could lead to vision loss.7

AC is an inclusive term that encompasses seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), and atopic keratoconjunctivitis (AKC).8 Contact lenses or ocular prosthesis-associated giant papillary conjunctivitis (GPC) are historically included as ocular allergic conditions, yet they should not be considered true allergic diseases, but chronic ocular micro-trauma related disorders.8 SAC and PAC comprise about 95% of the allergic conjunctivitis cases in the United States.9

Diagnosis

It can be difficult to differentiate AC from other ocular surface disorders because they may share signs and symptoms. A wide array of disorders can mimic or mask the condition, including:

• Bacterial conjunctivitis

• Rhinitis

• Dry eye

• Meibomian gland disease (resulting in tear film abnormality or insufficiency)

• Blepharitis10

A diagnosis can usually be made based on the patient history and examination. Slit-lamp examination should focus primarily on the conjunctiva because it is an active immunologic tissue that responds to allergic stimuli. When the signs and symptoms are consistent with SAC and patient history does not indicate other disease, allergy testing is usually not required.11

Pathogenesis

The presentation of allergic signs and symptoms results from a cascade of immune responses through a process called sensitization following the initial exposure of an allergen. The pathogenesis of AC is predominantly an IgE-mediated hypersensitivity reaction in which allergens interact with IgE bound to sensitized mast cells, causing histamine release and resulting in the clinical initial ocular allergic expression. Newly synthesized prostaglandins, leukotrienes, and other inflammatory mediators cause a separate, secondary inflammatory cascade known as the late-phase allergic response. The presence of pro-inflammatory mediators, prostaglandins, and leukotrienes in the tear fluid is associated with the itching, redness, watering, and mucous discharge. AC is characterized by the infiltration of inflammatory cells into the conjunctiva in approximately 25%–43% of patients with the condition.12

AC management

Numerous classes of agents, both systemic and topical, have been used to manage the signs and symptoms of AC. The initial treatment involves artificial tears to physically irrigate and remove the offending allergens as well as prevent these allergens from reaching the ocular surface. These products are available over-the-counter but do not have direct effect on allergic mediators. They may also contain preservatives that can add insult to an already irritated ocular surface.

Many treatment options for allergic rhinitis (intranasal antihistamine sprays, intranasal cromolyn, intranasal anticholinergic sprays, and short courses of oral corticosteroids (reserved for severe, acute episodes) may also provide a benefit.

Topical decongestants (e.g., tetrahydrozoline [Visine, McNeil], naphazoline [Naphcon-A, Alcon) reduce some SAC signs and symptoms by vasoconstriction. Their action reduces hyperemia, chemosis, and ocular redness through the constriction of blood vessels supplying the eye. There is also some reduction of ocular itching. Keep their use to short term-stopping these agents following prolonged use can lead to rebound hyperemia.13

Antihistamines block the inflammatory effects of histamine and prevent or relieve the signs and symptoms of SAC that are associated with histamine. These are often combined with decongestants. Systemic antihistamines may be used to control the symptoms of rhinoconjunctivitis but may have only partial effect on ocular symptoms.14

Mast cell stabilizers (e.g., lodoxamide tromethamine [Alomide, Alcon], pemirolast [Alamast, Santen], cromolyn sodium [Crolom, Bausch + Lomb]) address both the early and late phases of the allergic response. Mast cell stabilizers prevent the degranulation of mast cells and the release of preformed inflammatory mediators, as well as the production of more inflammatory mediators. They are most effective when administered before the allergic reaction and should be used prophylactically,9 but patients may notice improvements in signs and symptoms within 1 to 2 days if the drops are used following allergen exposure.14

The dual action antihistamine⁄mast cell stabilizer agents are currently the most commonly prescribed group of agents for ocular allergy.13 Members of this class include olopatadine (Pataday, Alcon), alcaftadine (Lastacaft, Allergan), and bepotastine besilate (Bepreve, Bausch + Lomb), among others. They provide relief from AC by inhibiting mast cell degranulation as well as competitive H1 receptor binding to block histamine binding.15 These agents have a rapid onset of action, usually within minutes following instillation, and improve patient compliance compared with pure mast cell stabilizers. Several of these agents require only once-a-day or twice-a-day dosing. They are well tolerated and can be used for longer-term treatment. Side effects are generally mild and include headache, cold-like symptoms, ocular burning and stinging, and possible transient bitter taste.15

Nonsteroidal anti-inflammatory (NSAIDs) drugs reduce mucus secretion, cellular infiltration, redness, and swelling, which results in the relief of ocular itching, although improvement in conjunctival hyperemia, inflammation, and swollen eyes may also be seen. Ketorolac tromethamine (Acular, Allergan) has a Food and Drug Administration (FDA)-approved indication for the treatment of SAC.16 In general, NSAIDs are used in the management of postoperative pain and inflammation after cataract surgery but not as a first-line therapy for ocular allergies. NSAIDs may cause stinging and burning upon instillation.

The most effective therapeutic agents in the treatment of AC and allergic rhinitis are corticosteroids because they manage all the facets of allergic symptoms. Topical ophthalmic corticosteroids can be prescribed in lower doses with negligible systemic adverse events, although there is the potential for ocular side effects.17 Loteprednol etabonate (LE) (e.g., Alrex, Lotemax; Bausch + Lomb) was specifically studied in patients with signs and symptoms of SAC prior to obtaining marketing approval.18 Topical steroids can be added to the treatment regimen in a brief pulse fashion during the acute phase of an allergic attack. Avoid certain ophthalmic preservatives (i.e., benzalkonium chloride [BAK]) for patients who appear to be sensitive, particularly those suffering from chronic dry eye because their ocular surface may already be compromised.

Allergic rhinitis treatment with allergen-specific immunotherapy (SIT) has prevented progression of other atopic conditions.19 Immunotherapy has been shown to have an important role in the long-term control of rhinoconjunctivitis, although it has not been proven for AC. SIT can be effective for patients with severe AC/rhinoconjunctivitis. Increasing doses of the allergen are administered via subcutaneous immunotherapy (SCIT) or sublingual immunotherapy route to achieve hyposensitization.11 Side effects, including anaphylaxis, are known to occur with this form of therapy.

The predicted increase in pollen count because of climate change over the next several years20 may create a concomitant increase in ocular allergies. As a result, SAC may become chronic and persistent in more patients and may require treatments over longer periods of time. Anticipate the spring and fall seasonal spikes in pollen counts and be prepared to treat the signs and symptoms that accompany them. The majority of patients with AC will self-diagnose and self-medicate.21 Practitioners must educate patients about their condition, prescribe the appropriate medication, and schedule appropriate follow-up visits to monitor the effects of therapy. Controlling and managing allergic eye disease includes patient education, lifestyle modifications if necessary, and the appropriate medication regimen that is tailored to the severity of the disease.

References

1. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008 Apr; 63 (Suppl 86):8–160.

2. Rosario N, Bielory L. Epidemiology of allergic conjunctivitis. Curr Opin Allergy Clin Immunol. 2011 Oct; 11(5): 471–6.

3. Maziak W, Behrens T, Brasky TM, et al. Are asthma and allergies in children and adolescents increasing? Results from ISAAC phase I and phase III surveys in Munster, Germany. Allergy. 2003 Jul; 58(7): 572–9.

4. Verlato G, Corsico A, Villani S, et al. Is the prevalence of adult asthma and allergic rhinitis still increasing? Results of an Italian study. J Allergy Clin Immunol. 2003 Jun; 111(6): 1232-8.

5. Leonardi S, del Giudice Miraglia M, La Rosa M, et al. Atopic disease, immune system, and the environment. Allergy Asthma Proc. 2007 Jul-Aug;28(4):410–7.

6. Friedlander MH. Ocular Allergy. Curr Opin Allergy Clin Immunol. 2011 Oct;11(5):477–82.

7. Leonardi A, Bonini S. Is visual function affected in severe ocular allergies? Curr Opin Allergy Clin Immunol. 2013 Oct;13(5):558-62.

8. La Rosa M, Lionetti E, Reibaldi M, et al. Allergic conjunctivitis: a comprehensive review of the literature. Ital J Pediatr. 2013 Mar 14;39: 18.

9. Butrus S, Portela R. Ocular allergy: diagnosis and treatment. Ophthalmol Clin North Am. 2005 Dec;18(4):485–92.

10. O’Brien TP. Allergic conjunctivitis: an update on diagnosis and management. Curr Opin Allergy Clin Immunol. 2013 Oct;13(5): 543-9.

11. Kari O, Saari KM. Updates in the treatment of ocular allergies. J Asthma Allergy. 2010 Nov 24; 3:149–58.

12. Bielory L, Goodman PE, Fisher EM. Allergic ocular disease. A review of pathophysiology and clinical presentations. Clin Rev Allergy Immunol. 2001 Apr;20(2): 183–200.

13. Barney NP, Graziano FM. Allergic and immunologic diseases of the eye. In: Adkinson NFJ, Yunginger JW, Busse WW, Bochner BS, Holgate ST & Simons FE (eds). Middleton’s allergy: principles & practice, vol. 2. St. Louis, MO: 2003 Mosby, 1599– 1617.

14. Bielory L, Friedlaender M. Allergic conjunctivitis. Immunol Allergy Clin North Am. 2008 Feb;28(1): 43–58.

15. Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol. 2008 Aug; 122(2 Suppl):S1–84.

16. Raizman MB, Luchs JI, Shovlin JP, et al. Ocular allergy: a scientific review and expert case debate. Rev Optom. 2012. http://www.revoptom.com/continuing_education/tabviewtest/lessonid/108286/. Accessed 01-06-2014.

17. Carnahan MC, Goldstein DA. Ocular complications of topical, periocular, and systemic corticosteroids. Curr Opin Ophthalmol. 2000 Dec;11(6): 478–83.

18. Bielory L. Ocular allergy treatment. Immunol Allergy Clin North Am. 2008 Feb;28(1):189–224.

19. Bielory L, Mongia A. Current opinion of immunotherapy for ocular allergy. Curr Opin Allergy Clin Immunol. 2002 Oct;2(5):447–52.

20. Bielory BP, O’Brien TP, Bielory L. Management of seasonal allergic conjunctivitis: guide to therapy. Acta Ophthalmol. 2012 Aug;90(5):399-407.

21. Palmares J, Delgado L, Cidade M, Quadrado MJ, et al. Allergic conjunctivitis: a national cross-sectional study of clinical characteristics and quality of life. Eur J Ophthalmol. 2010 Mar-Apr;20(2):257-64.