Dr. Shawn Moore owns a full scope primary care practice including contact lens care, dry eye, and vision therapy. He is passionate in providing an unparalleled experience for all his patients and he has spoken at multiple conferences to both doctors and staff on how to use knowledge, great products and services to differentiate their practices.
It is important for health care professionals to have an understanding of the tools available to them as we enter into the spring and summer allergy season, where up to 40% of the North American population will suffer from allergic eye disease, and that number is increasing.1-3 This patient population, who may suffer from seasonal or perennial allergic conjunctivitis, may not seek out care or verbalize their symptoms, and they may reach only for self-medicated options, which can lead to poorly controlled disease, prolonged symptoms, and decreased productivity.1,4 Patients with allergic conjunctivitis also report a decreased quality of life, including negative emotions (irritability, frustration, anger, embarrassment), decreased productivity, decreased concentration, fatigue and absenteeism from work.
A detailed case history and examination of the eye and adnexa by slit-lamp biomicroscopy are paramount in the evaluation of allergic conjunctivitis, both to confirm the diagnosis and rule-out other ocular diseases that may require different treatment considerations. A broad differential diagnosis is essential, including the more severe forms of ocular allergy (atopic keratoconjunctivitis, vernal keratoconjunctivitis, atopic dermatitis), contact-lens associated papillary conjunctivitis, infectious causes, dry eye disease, ocular toxicity from preservatives, ocular rosacea as well as blepharitis.
Patients with allergic conjunctivitis will frequently suffer from other allergies and an understanding of the complete clinical picture will be helpful in managing the patient with their team of health care providers. An allergy assessment may be sought when considering the diagnosis of allergic conjunctivitis, with consideration to the management of patient signs, symptoms, severity, and chronicity. Below is a summary of the review paper by Dupuis et al. “A contemporary look at allergic conjunctivitis”,5 which presents a detailed look at allergic conjunctivitis, the most common form of allergic eye disease.
Dupuis, P et al. A contemporary look at allergic conjunctivitis. Allergy Asthma Clin Immunol. 2020;16:5 https://aacijournal.biomedcentral.com/articles/10.1186/s13223-020-0403-9
Allergic conjunctivitis is a type I allergic reaction where Th2 cells release pro-inflammatory cytokines (IL-3, IL-4, IL-5, IL-13) that stimulate immunoglobulin E (IgE) production by the B cells that become bound to mast cells, which in turn triggers mast cell degranulation and the release of preformed (histamine, tryptase) and newly formed (leukotrienes, prostaglandins) mediators.6
The early phase of the allergic cascade begins within seconds to minutes after exposure and typically lasts 20–30 minutes,7 with symptoms such as mild to severe itching (the most common symptom), tearing, redness, conjunctival injection, chemosis, a papillary reaction and eyelid swelling.8 The late phase begins a few hours later and is characterized by epithelial infiltration of inflammatory cells like neutrophils, lymphocytes, basophils and eosinophils, which lead to continued inflammation, persistent symptoms and increased likelihood of tissue damage.6,7 Increased tear secretion and drainage through the lacrimal ducts also carry allergens directly into the nasal passage.8
Patients with allergic conjunctivitis may have unremarkable physical findings if seen outside of exacerbations. The eyelids may be hyperemic and edematous and this can be more marked in the lower eyelid due to gravity. An allergic ‘shiner’, a bluish discoloration below the eyes, may be present in acute disease as a result of venous congestion.9 Watery discharge may be noted, but a mucous discharge may also be present.10 Bilateral conjunctival injection is the most obvious general sign, while the most common symptom of allergic conjunctivitis is pruritus, which can range from mild to severely debilitating,11 accompanied by symptoms of dryness, discomfort, burning, stinging and foreign body sensation.12 Chemosis may be present and can be moderate to severe in acute episodes and, when severe, the conjunctiva appears gelatinous and may be thickened to the point that the cornea appears to be recessed. Signs such as giant papillae, corneal infiltration, pannus, neovascularization and ulceration indicates an alternate diagnosis to allergic conjunctivitis.
Non‐pharmacological treatments include allergen avoidance, cold compresses to minimize itching, hyperaemia, and edema,13 as well as lubricating eye drops to dilute and flush allergens and inflammatory cells from the tear film. However, these methods typically will provide variable or inadequate control of signs and symptoms.
The aim in treating allergic conjunctivitis is to stop or minimize the inflammatory cascade in order to provide relief of symptoms, and to prevent complications associated with prolonged inflammation.
Pharmacologic treatments include:
Topical vasoconstrictors reduce erythema but have a limited effect on itching;14 they can cause rebound hyperemia when discontinued and should only be considered as a short term solution.
Topical mast‐cell stabilizers
Topical mast‐cell stabilizers are best utilized on a prophylactic basis as they require a loading period of a few weeks in order to prevent mast cell degranulation. Due to the availability of more effective therapies, including dual-activity agents, mast cell stabilizers are rarely used as monotherapy.
Antihistamines: topical and oral
Oral antihistamines are easily accessible by patients and available by prescription and over-the-counter (OTC). Oral second-generation antihistamines do not readily cross the blood–brain barrier and produce fewer anticholinergic effects and are therefore preferred over first-generation antihistamines.
Topical antihistamines target the ocular tissues directly and have a faster onset of action (3–15 min), a better safety profile and are generally better tolerated due to less systemic absorption.15 However, topical agents relieve itching and erythema for only a short period of time, and need to be used up to four times per day. Topical antihistamines have no effect on other mediators of the allergic response like leukotrienes and prostaglandins and are best used in the acute phase reaction, are rarely sufficient as monotherapy, and have generally been replaced by the topical dual-activity agents.
Topical dual‐activity agents (antihistamine/mast‐cell stabilizing activity)
Compared with either antihistamines or mast cell stabilizers on their own, topical dual-activity agents are generally clinically superior due the relief of both signs and symptoms that comes from the immediate action of antihistamines and the prophylactic benefit of mast cell stabilizers.14 These are now considered first-line treatment in allergic conjunctivitis.
Examples of topical dual-activity agents include ketotifen 0.025% (Zaditor, Novartis), olopatadine 0.1% (Patanol, Novartis), olopatadine 0.2% (Pataday, Novartis) and olopatadine 0.7% (Pazeo, Novartis), as well as bepotastine besilate 1.5% (Bepreve, Bausch & Lomb).
Steroids: topical ophthalmic and nasal
Steroids may be used to treat allergic conjunctivitis by reducing inflammatory cytokine production, mast cell proliferation and cell mediated immune responses. Caution must always be given when reaching for steroids due to the risk of cataract development, elevated intra-ocular pressure and central serous retinopathy,10,16,17 and they are therefore used for short term treatment only. Ophthalmic steroids are often prescribed along with one of the above dual-activity agents when there is a significant presentation of both signs and symptoms.
The ester-based steroid loteprednol etabonate (0.2% Alrex, 0.5% Lotemax suspension or gel, Bausch & Lomb), is the preferred agent for allergic conjunctivitis due to its decreased risk of cataracts or IOP elevation.18 For severe cases of allergic conjunctivitis the more potent ketone-based topical steroids such as prednisolone acetate 1% (Pred Forte, Allergan), prednisolone phosphate 1%, and dexamethasone 0.1% can be prescribed. However, they carry an increased risk of ocular adverse effects and are generally not necessary.
Intranasal steroids have also been shown to decrease ocular symptoms,19,20 and are often used as first line treatment in allergic rhinoconjunctivitis. Although the risk of ocular adverse events is low, careful monitoring of the IOP is advised with any steroid use.
NSAIDs are not often used in allergic conjunctivitis but may be useful when symptoms continue to be inadequately controlled, despite the use of dual-activity agents or when steroid use is not indicated. NSAIDs inhibit production of prostaglandins which results in the temporary reduction of severe symptoms of discomfort. Topical NSAID use for allergic conjunctivitis is off label (in Canada) and they are generally used short-term only and as an add-on to a dual-activity agent.
Examples of NSAIDs used in ocular allergies are ketorolac tromethamine 0.4% (Acular LS, Allergan) and ketorolac tromethamine 0.5% (Acular, Allergan), diclofenac sodium 0.1% (Voltaren Ophtha, Novartis) and nepafenac 0.1% (Nevanac, Novartis).
Immunotherapy is the only therapy that can provide prolonged benefits after a course of treatment.9 Immunologic changes involve downregulation of the Th2 response and upregulation of regulatory T cells that produce inhibitory cytokines. This ultimately leads to a reduced end-organ response to allergen exposure.21 Two forms of immunotherapy are approved in Canada: sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT). Studies on immunotherapy have assessed allergic rhinoconjunctivitis and have shown mixed results on ocular symptoms, so topical medications may still be required.
Simplified Treatment Algorithm
Dupuis et al provide an excellent and practical algorithm for the treatment of allergic conjunctivitis (Fig. 5 in their open access paper and below, used with permission). Topical dual-activity agents are the first line treatment, with consideration of topical short-term steroids as needed, and while the patient is monitored for ocular side effects. Then consideration is given to nasal steroids, oral antihistamines, topical NSAIDs, or immunotherapy which can be used in any order and used concurrently.
When maximal medical therapy is insufficient at relieving the signs and symptoms of allergic conjunctivitis a referral to an allergist to determine sensitization (skin prick testing or serum specific IgE) is required to determine the course of treatment and to consider whether immunotherapy is indicated. The allergist and eye care specialist may refer back to the primary care provider when signs and symptoms are well controlled, but the patient may require chronic management. Interprofessional collaboration and communication may be essential for optimal patient care.
Eye health professionals are in a unique position to use the diagnostic tools and many treatment options are available to help manage and treat allergic conjunctivitis. It is important to consider the systemic context of the ocular disease to appropriately manage the patient and the entirety of their allergic disease, along with consideration of the need for an allergist and involvement of their primary care physician where required to provide the best outcome for the patient.
- Rosario N, Bielory L. Epidemiology of allergic conjunctivitis. Curr Opin Allergy Clin Immunol 2011;11:471-6.
- Singh K, Axelrod S, Bielory L. The epidemiology of ocular and nasal allergy in the United States, 1988-1994. J Allergy Clin Immunol 2010;126:778-83.e6.
- Brozek G, Lawson J, Szumilas D, et al. Increasing prevalence of asthma, respiratory symptoms, and allergic diseases: Four repeated surveys from 1993-2014. Respiratory medicine 2015;109:982-90.
- Pitt AD, Smith AF, Lindsell L, et al. Economic and quality-of-life impact of seasonal allergic conjunctivitis in Oxfordshire. Ophthalmic epidemiology 2004;11:17-33.
- Dupuis P, Prokopich CL, Hynes A, et al. A contemporary look at allergic conjunctivitis. Allergy, Asthma & Clinical Immunology 2020;16:5.
- Small P, Kim H. Allergic rhinitis. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 2011;7 Suppl 1:S3.
- Leonardi A, De Dominicis C, Motterle L. Immunopathogenesis of ocular allergy: a schematic approach to different clinical entities. Curr Opin Allergy Clin Immunol 2007;7:429-35.
- Prokopich CL, Lee-Poy M, Kim H. Interprofessional Management of Allergic Conjunctivitis. Canadian Journal of Optometry 2018;80:11-27.
- Bielory L, Meltzer EO, Nichols KK, et al. An algorithm for the management of allergic conjunctivitis. Allergy and asthma proceedings 2013;34:408-20.
- Varu DM, Rhee MK, Akpek EK, et al. Conjunctivitis Preferred Practice Pattern®. Ophthalmology 2019;126:P94-p169.
- La Rosa M, Lionetti E, Reibaldi M, et al. Allergic conjunctivitis: a comprehensive review of the literature. Italian journal of pediatrics 2013;39:18.
- Butrus S, Portela R. Ocular allergy: diagnosis and treatment. Ophthalmology clinics of North America 2005;18:485-92, v.
- Sánchez-Hernández MC, Montero J, Rondon C, et al. Consensus document on allergic conjunctivitis (DECA). J Investig Allergol Clin Immunol 2015;25:94-106.
- Leonardi A, Silva D, Perez Formigo D, et al. Management of ocular allergy. Allergy 2019;74:1611-30.
- Simons FE, Simons KJ. Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol 2011;128:1139-50.e4.
- Chan LY, Adam RS, Adam DN. Localized topical steroid use and central serous retinopathy. J Dermatolog Treat 2016;27:425-6.
- Renfro L, Snow JS. Ocular Effects of Topical and Systemic Steroids. Dermatologic Clinics 1992;10:505-12.
- Ilyas H, Slonim CB, Braswell GR, et al. Long-term safety of loteprednol etabonate 0.2% in the treatment of seasonal and perennial allergic conjunctivitis. Eye & contact lens 2004;30:10-3.
- Anolik R, Pearlman D, Teper A, et al. Mometasone furoate improves nasal and ocular symptoms of seasonal allergic rhinitis in adolescents. Allergy & rhinology (Providence, RI) 2010;1:5.
- Andrews CP, Martin BG, Jacobs RL, et al. Fluticasone furoate nasal spray is more effective than fexofenadine for nighttime symptoms of seasonal allergy. Allergy and asthma proceedings 2009;30:128-38.
- Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011;127:S1-55.