Ocular Allergies: Therapeutic Management

During allergy season, patients presenting with symptoms of itchy, swollen and red eyes are commonly encountered in clinical practice. Primary eye care practitioners should thus be well versed in the effective management of different presentations of ocular allergy. Thankfully, serious complications associated with ocular allergy are uncommon to rare, but the disease can have a significant adverse effect on quality of life.

A complication is that antihistamines can adversely affect tear secretion…

The key to understanding effective treatment for allergy is to recognise that the signs and symptoms of the disease represent aspects of the inflammatory cascade. Sensitisation of the immune system to some type of allergen leads to an inflammatory mediated allergic response upon re-exposure.¹

Recognising the inflammatory and immune mediated nature of an allergic ocular response is key to managing patients in a logical, stepwise, escalating approach as needed.

STEP 1: ALLERGEN IDENTIFICATION, AVOIDANCE AND PALLIATIVE THERAPIES

Ocular allergy requires the exposure of the eye to an allergen, such as pollen, dust mites or animal dander. In theory, overall management of allergy can be obtained by complete avoidance of the inciting allergen. In practice this may not be possible, particularly if the identified allergen is common within the patient’s environment. Regardless, patients with significant allergy signs or symptoms should be encouraged to identify the cause(s) of their allergy and implement strategies to minimise exposure as much as reasonably possible.

Non-pharmaceutical recommendations to lower signs and symptoms of ocular allergy centre on the use of cool compresses and/or artificial tears. Cool compresses provide symptomatic relief by countering some of the heat related aspects of the inflammatory cascade, as well as decreasing signalling of pain or itch. Similarly, the use of artificial tears has a cooling effect on the ocular surface, as well as a diluting effect, reducing and flushing away the allergen and the released allergic mediators such as histamine. Interestingly, these palliative therapies have been shown to be effective in clinical trial settings at lowering signs and symptoms of allergy, although not as effectively as pharmaceutical agents.²

STEP 2: PHARMACEUTICALS DESIGNED FOR ALLERGY

The majority of topical ocular antiallergy therapies in Australia are classified as S2 poisons and thus are available through a pharmacy without the need for a consultation or prescription. In classifying these agents as S2 poisons, the Therapeutics Goods Administration is suggesting that the medicines are relatively safe to use without supervision and that users should generally be able to identify signs and symptoms of the conditions that could be managed with these treatments. Clinical experience and post marketing surveillance have supported the safety of these medicines when used unsupervised by the general public.³

There are four general types of antiallergy medication. Vasoconstrictors, also known as ocular decongestants, include active ingredients such as phenylephrine, tetrahydrozaline or naphazoline. They are typically marketed to the public to “get the red out” of the appearance for hyperaemic allergic eyes. This is achieved through adrenergic stimulation of anterior segment blood vessels leading to vasoconstriction.³ They unfortunately do not contribute appreciably to improving other signs or symptoms of allergy when used alone and are associated with rebound hyperemia if used for longer periods.³ These agents are thus generally not recommended, except for very short term cosmetic use.

Ocular antihistamines, such as azelastine and levocabastine, lower the effects of allergy by mitigating the signalling effects of antigen induced histamine release. They either directly compete with histamine receptors or down regulate their activity, leading to improved redness, chemosis and a decrease in allergy symptoms. An increasing dosing regimen, depending on response and symptoms, is usually recommended, with two drops a day to start and increasing to three or four per day if necessary.

Mast cell stabilisers work to stabilise the membrane of mast cells, lowering the probability of degranulation and release of allergic mediators from these immune cells upon allergen exposure. Cromolyn is the prototypical molecule of this class, with newer variants such as lodoxamide being much more potent in performing these actions, and therefore is available at comparatively lower concentrations.⁴ Lodoxamide in particular has been highlighted to be more effective than cromolyn in managing vernal keratoconjunctivitis.³ Mast cell stabilisers should be considered as anticipatory and maintenance therapy as they do not decrease the effect of already released allergic mediators. Patients are recommended to use these agents one or two times a day, at least one or two weeks prior to allergy season, and to maintain this dosage throughout the season, to give the greatest chance of sustained allergic suppression.

Dual acting antihistamine/mast cell stabiliser drugs are the most commonly recommended/prescribed agents by eye care professionals for the management of allergy. These agents are able to simultaneously lower the effects of allergy through antihistamine activity, and decrease further mast cell degranulation due to their mast cell stabiliser effects.³ There are two agents currently available in Australia. Ketotifen fumarate is classified as an S2 poison available over the counter, while olopatadine hydrochloride is classified as an S4 poison and thus requires a prescription from a medical practitioner or endorsed optometrist. The evidence from the literature is mixed regarding which of these agents is more effective, an issue which is common for the majority of these anti-allergy medications where little to no head-to-head comparisons are typically done.^5-7 They are both dosed at the same frequency of two times a day, although formulations available in other parts of the world for olopatadine are able to reduce this to once a day only. From a practitioner’s point of view, perhaps the recommendation should be to consider whether you wish for your patient to have a prescription for a specific agent which can only be dispensed by the pharmacist for compliance reasons, or whether it is more convenient, cost effective or available to recommend an over the counter option.

STEP 3: ANTI-INFLAMMATORIES

Anti-inflammatory therapies are effective against presentations of allergy due to their actions lowering inflammatory responses associated with allergy. They are generally reserved for severe presentations of allergy due to their potential adverse effects. NSAID formulations such as 0.5% ketorolac tromethamine (Acular) have seasonal allergic conjunctivitis as a labelled indication, with a recommended dosing schedule of one drop four times a day, for up to four weeks, for this use. However, considering the frequency of dosage, as well as the stinging sensation upon instillation, NSAIDs are uncommonly used for allergy, even with this labelled indication.⁴ 

Corticosteroids, in contrast, are used more commonly to acutely quell severe signs and symptoms of allergy. Any of the topically available ophthalmic corticosteroids can potentially be used for this purpose. In selecting the agent and dosing regimen, factors to consider include the severity of the presentation, the structures involved in the allergic presentation, and the ocular and systemic health of the patient. In practice, prescribed corticosteroids are often concurrently paired with a dual acting anti-allergy agent, in the hopes of asserting control before tapering the corticosteroids while the anti-allergy medication is continued long term. In the event where a dual acting agent, such as olopatadine, is insufficient in the chronic management of the disease, clinicians have reported long term success and safety with the immunomodulator cyclosporine as an alternative, best known for its application in dry eye.^8,9 

OTHER OPTIONS AND CONSIDERATIONS

Systemic antihistamine therapy is common, with many agents available over the counter.¹⁰ Earlier generations of systemic antihistamines had a greater propensity to cross the blood-brain barrier and exert anticholinergic effects resulting in drowsiness. Newer generations are much less likely to do this and are, therefore, recommended over earlier generations. Systemic therapy should be considered when there is more than just ocular allergy, whether this be presentations in the nose, skin or other body systems. A complication is that antihistamines can adversely affect tear secretion, leading to issues of ocular surface dryness.¹⁰ Patients may also consider allergen specific immunotherapy, where the body is repeatedly exposed to increasing concentrations of the inciting allergen, either sublingually or through subcutaneous injections, to generate immune tolerance.¹¹ This option should be discussed with the patient’s general practitioner and a potential referral to an allergist may be required.

CONCLUSION

Allergic eye disease is a common presentation in optometric practices. The management of this condition should follow a stepwise approach to mitigate the signs, symptoms and impact on quality of life for patients. Treatments span from palliative to pharmaceutical, and from topical to oral to systemic immunomodulatory therapies.

Dr Alex Hui, OD, PhD, GradCertOcTher, FAAO graduated in optometry and achieved a PhD in vision science at the School of Optometry & Vision Science, University of Waterloo, in Canada. He completed his graduate certificate in ocular therapeutics at the School of Optometry and Vision Science, UNSW Sydney. As a researcher with UNSW, Dr Hui’s work centres around developing and testing novel ways to treat ocular diseases, with a focus on using contact lenses to deliver pharmaceuticals to the eye including antibiotics, anti-allergy, antimyopia and anti-inflammatory agents. The author would like to thank Lily Ho for her contributions to this article. 

References 

1. Bielory BP, O’Brien TP, Bielory L. Management of seasonal allergic conjunctivitis: guide to therapy. Acta Ophthalmol 2012;90(5):399-407. 
2. Bilkhu PS, Wolffsohn JS, Naroo SA, et al. Effectiveness of nonpharmacologic treatments for acute seasonal allergic conjunctivitis. Ophthalmology 2014;121(1):72-8. 
3. Abelson MB, Shetty S, Korchak M, et al. Advances in pharmacotherapy for allergic conjunctivitis. Expert Opin Pharmacother 2015;16(8):1219-31. 
4. Bartlett JD, Jaanus SD. Clinical ocular pharmacology, 5th ed. St. Louis, Mo.: Butterworth-Heinemann/Elsevier, 2008; xvi, 793 p. 
5. Ganz M, Koll E, Gausche J, et al. Ketotifen fumarate and olopatadine hydrochloride in the treatment of allergic conjunctivitis: a real-world comparison of efficacy and ocular comfort. Adv Ther 2003;20(2):79-91. 
6. Patel D, Sarala N, Datti NP. Topical Olopatadine Hydrochloride versus Ketotifen Fumarate for Allergic Conjunctivitis. J Ophthalmic Vis Res 2018;13(2):119-23. 
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8. Pucci N, Caputo R, Mori F, et al. Long-term safety and efficacy of topical cyclosporine in 156 children with vernal keratoconjunctivitis. Int J Immunopathol Pharmacol 2010;23(3):865-71. 
9. Wan KH, Chen LJ, Rong SS, et al. Topical cyclosporine in the treatment of allergic conjunctivitis: a meta-analysis. Ophthalmology 2013;120(11):2197-203. 
10. Bilkhu PS, Wolffsohn JS, Naroo SA. A review of nonpharmacological and pharmacological management of seasonal and perennial allergic conjunctivitis. Cont Lens Anterior Eye 2012;35(1):9-16. 
11. Moote W, Kim H, Ellis AK. Allergen-specific immunotherapy. Allergy Asthma Clin Immunol 2018;14(Suppl 2):53.