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Differentiating ocular allergy


On the surface, eyecare providers may not fully appreciate the prevalence and complexity of ocular allergy and its clinical management; we learn that it is a relatively simple disease defined by ocular itch.

On the surface, eyecare providers may not fully appreciate the prevalence and complexity of ocular allergy and its clinical management; we learn that it is a relatively simple disease defined by ocular itch.

Beyond the surface, however, allergic conjunctivitis is not a simple disease but a group of complex diseases that merits better understanding and more precise and effective management.1 Additionally, we may not know nuances among available ocular allergic medications for judicious prescribing.

Let’s examine current knowledge of the different ocular allergic diseases, drugs, and their clinical management. I will include ICD-10 codes for conditions mentioned for ease of coding.

Related: How to improve diagnosis and treatment of allergy

Acute and chronic allergy

Ocular allergy can be broken down into acute and chronic diseases (see Table 1).

Acute diseases include:

• Seasonal allergic conjunctivitis (SAC; H10.403)

• Perennial allergic conjunctivitis (PAC; H10.403)

Chronic forms include:

• Vernal keratoconjunctivitis (VKC; H16.263)

• Atopic keratoconjunctivitis (AKC; H10.13)

• Giant papillary conjunctivitis (GPC; H10.413)

Related: How to identify and treat allergic eye disease


Although acute allergic conditions may present with severe signs and symptoms, they are milder and easier to manage because they are more responsive to therapy.

Chronic allergic diseases tend to associate with confounding atopic predisposition and require more regimented therapy and closer monitoring. Remodeling of the ocular surface tissues can lead to irreversible cornea damage and vision loss in chronic cases.1

Allergic conjunctivitis (AC) is a very common ocular disease that affects more than one third of the U.S. population. It can occur in isolation but is more often associated with allergic rhinitis.2,3 The prevalence of oculonasal symptoms increased 3.3-fold in the U.S from 1980 to 1984.4

In a recent study, 187 consecutive patients with allergic rhinitis were directly questioned using standard questions relating to red, itchy, and watery eyes. Almost all (95 percent) of the patients had positive symptoms of AC.5

It may not be surprising that AC is so highly linked to allergic rhinitis because the ocular surface, including the conjunctiva, can be viewed as an upper end of the respiratory system. It consists of an area of several hundred square millimeters where allergens can enter and drain into the nose through the nasolacrimal duct. This pathway also explains the effectiveness of ocular allergy medication in alleviating allergic nasal symptoms.6

Related: What's trending in ocular allergy treatment

Incidence of AC is likely underreported because many patients are merely diagnosed with allergic rhinitis; thus, many patients with AC may be undiagnosed and untreated. We can play a proactive role in asking our patients about allergic rhinitis and AC symptoms of red, itchy, puffy, and watery eyes.

Operationally, a total ocular symptom score (TOSS) questionnaire can be implemented as part of the prefilled intake forms, similar to ocular surface disease index (OSDI) questionnaire for dry eyes.7

Allergy in general tends to arise seasonally, so seasonal emphasis on AC is warranted because the overall impact of AC on quality of life is comparable to the nasal symptoms of allergic rhinitis.8

Ocular itching is the pathognomonic symptom of AC, but other comorbid symptoms of lacrimation, burning, photophobia, vasodilation, and chemosis are often present. Itching is predominantly a bilateral manifestation but can be asymmetrical.9


Defining allergy

Although AC shares overlapping ocular signs and symptoms, each type has different underlying pathophysiology and may require distinct therapeutic regimen.

SAC is the most common form of ocular allergy, accounting for more than half of the patients, followed by PAC with frequency of about 20 percent. VKC accounts for less than 10 percent, and AKC is the least common of all ocular allergies.10

Allergic reaction is mainly immunologically mediated, manifesting in two temporal components: early phase and late phase.

The early phase is driven predominantly by the activation of mast cells and the release of histamine and associated inflammatory mediators. Histamine release peaks at five minutes after exposure but can last 30 to 40 minutes. The late phase of the allergic reaction can arise six to 72 hours after initial allergen exposure, culminating in accumulation of inflammatory cells, such as basophils, eosinophils, T cells, and neutrophils within the conjunctiva.11

Related: Diagnosing and managing ocular allergy


SAC is the result of a classic type I hypersensitivity reaction in which allergens from trees, grasses, or ragweed get into the eyes and bind to the immunoglobulin E (IgE) receptors on the surface of mast cells.

The activated mast cells degranulate and release inflammatory mediators, particularly histamine, which cause ocular itching, hyperemia, tearing, and chemosis, culminating in a glassy appearance of the eye.12 The seasonality of SAC corresponds to the tree pollens in early spring, grasses in May through July, and weed pollens and outdoor molds from August through October.13

Although PAC is also mediated by type I hypersensitivity reaction, it differs from SAC by its persistent allergen exposures and chronic activation of mast cells, which trigger the recruitment of eosinophils that can secrete cytotoxic proteins and cytokines and can lead to structural damage and fibrosis.13

Multiple indoor allergens, such as animal dander, molds, and dust mites, account for the perennial exposures.14 Similar symptoms of bilateral ocular itching, tearing, and chemosis are felt in PAC as in SAC, but they can occur at any time throughout the year.

To manage clinically, I perform anterior segment photography of the condition and work with the patient to understand the source of allergens and possible avoidance. I recommend eyewashes and cold compresses as initial support therapy.

I also write a prescription of dual-action antihistamine-mast cell stabilizers such as Pazeo (0.7% olopatadine, Alcon), Pataday (0.2% olopatadine, Alcon), or Patanol (0.1% olopatadine, Alcon), Lastacaft (Alcaftadine, Allergan) or over-the-counter Zaditor (ketotifen, Alcon). I follow the patient in two weeks or sooner.

Alcaftadine is the latest dual-action drug with 10 times greater affinity to histamine H1-receptor than that of olopatadine. Additionally, alcaftadine is the only ocular anti-allergic drop with pregnancy category B and approved for kids as young as age of 2.15

If the patient does not have insurance and prefers the over-the-counter option, ketotifen is recommended with the caution that a prescription strength may be needed. Concurrently, many patients may already take oral antihistamines or fluticasone (Flonase, GlaxoSmithKline) for their allergic rhinitis but still need ophthalmic treatment for ocular manifestations.

Dry eyes are a common comorbidity, so dry eye management is also warranted (see Table 2).



GPC is often seen in patients who wear contact lens which repeatedly rub on the upper palpebral conjunctiva. It is an allergic reaction secondary to chronic mechanical irritations.

These patients complain of mild to intense itching, a foreign body sensation, photophobia, and mucous discharge. Giant papillae (>1 mm) on the upper palpebral conjunctiva are the hallmarks of GPC.13

I recommend patients discontinue their contact lens wear for two to four weeks while the acute allergic reaction is treated with Lotemax (loteprednol, Bausch + Lomb) or Pred Forte (prednisolone acetate, Allergan) qid for the same duration. Lastacaft or Pazeo is prescribed concurrently to quell the symptoms immediately and used for long term as needed in the future.

Patients are followed up at one- to two-week intervals and intraocular pressures (IOPs) are monitored.

Once the acute episodes subside, patients can be refitted with daily disposable hydrogel contact lenses with peroxide disinfecting solutions such as Clear Care (Alcon). Enzymatic cleaning may be considered for recurrent GPC. Examples include Opti-Free SupraClens (Alcon) for soft and gas permeable contact lenses and Boston one-step liquid enzymatic cleaner (Bausch + Lomb) for gas permeable contact lenses.

Related: An allergist talks allergy


Vernal, as the name indicated, is a misnomer because the majority of VKC patients have severe symptoms throughout the year, not only in the spring.16

VKC has a predilection towards children and adolescents in hot and dry climates. Boys are three times more likely to have VKC than girls. Additionally, half of VKC patients have prior history of atopy, including asthma, allergic rhinitis, and eczema.17

Intense itching, severe photophobia, tearing, and stringy mucous discharge are common symptoms of VKC. Tarsal cobblestone-like papillae (Figure 1) are often seen in the upper lids and can rub on the cornea, resulting in a shield ulcer. Limbal gelatinous nodules with neovascularization or Trantas’ dots are other possible signs of severe VKC.18

AKC tends to affect men between the ages of 30 to 50 years with family history of allergies and asthma; however, it can show up in pediatric patients in the first decade.19 Moreover, many patients have eczema since childhood without ocular symptoms until adulthood. Therefore, AKC is a severe form of allergic conjunctivitis with atopic dermatitis that can cause corneal complications.20

Intense itching is felt not only in the eyes but in the periorbital lid skin. Tearing, burning, photophobia, and rope-like mucus discharge are similar to symptoms of VKC. Atopic blepharitis, tylosis (dry thickened skin), and Dennie-Morgan folds (infraorbital skin folds) are often present on the lower lids.19

There appears to be overlap in the history, signs, and symptoms of VKC and AKC. Bremond-Gignac and colleagues suggested that VKC generally ends at puberty but may evolve into AKC.19

Patients with VKC and AKC require aggressive treatment and close monitoring because the conditions can cause shield ulcer and increased risk of developing keratoconus secondary to chronic eye rubbing. Furthermore, chronic inflammation can lead to limbal stem cell deficiency, limbal pannus, and neovascularization (Figure 2) with ultimate loss of vision.21

Clinical management of VKC and AKC are similar to the management of GPC. I prescribe Pred Forte qid to the affected eye and Lastacaft or Pazeo qd for two to four weeks with weekly follow-ups. I also consider Restasis (cyclosporine, Allergan) bid or Xiidra (lifitegrast, Shire) as a continued option for a few months after the initial short pulse of steroid to decrease the inflammatory cytokines and relieve the symptoms.22 Oral corticosteroids can be considered in severe cases with shield ulcer.17

If VKC is a seasonal recurrence, I recommend a mast-cell stabilizer such as Alomide (lodoxamide, Alcon) qid or Alocril (nodocromil, Allergan) bid a few weeks before the season begins and continue throughout the season. Omalizumab (Xolair, Genentech), an anti-IgE monoclonal antibody, may be an effective option for recalcitrant cases.23

Related: How palynology and aldehydes affect allergy treatment


Allergy drug pipeline

As advances are made in understanding the pathophysiology of ocular allergy, novel drug therapies are being investigated in various clinical trials. For example, mapracorat, a new topical corticosteroid, showed similar potency as dexamethasone with a more favorable safety profile on intraocular pressure.24 Other immunomodulatory agents and immunotherapy are being investigated for ocular surface disease.25

The pipeline for new anti-allergy drugs is strong and will add to the multiple effective approaches we have to quell itchy eyes.

Thanks to Dr. Ernie Bowling for his editing inputs.

Related: Nasal sprays for allergies


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2. Singh K, Axelrod S, Bielory L. The epidemiology of ocular and nasal allergy in the United States, 1988-1994. J Allergy Clin Immunol. 2010 Oct;126(4):778-783.e6.

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5. Williams DC, Edney G, Maiden B, Smith PK. Recognition of allergic conjunctivitis in patients with allergic rhinitis. World Allergy Organ J. 2013 Feb 12;6(1):4.

6. Abelson MB, Turner D. A randomized, double blind, parallel group comparison of olopatadine 0.1% ophthalmic solution versus placebo for controlling the signs and symptoms of seasonal allergic conjunctivitis and rhinoconjunctivitis. Clin Ther. 2003 Mar; 25(3):931-47.

7. Bielory, L, Hom MM, Nguyen A. Total ocular symptom score (TOSS) and dry eyes. J Allergy Clin Immunol. 2013;131(2): AB189.   

8. Bielory L, Skoner DP, Blaiss MS, Leatherman B, Dykewicz MS, Smith N, Ortiz G, Hadley JA, Walstein N, Craig TJ, Allen-Ramey F. Ocular and nasal allergy symptom burden in America: the Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys. Allergy Asthma Proc. 2014 May-Jun;35(3):211-8.

9. Abelson M, Smith L, Chapin M. Ocular allergic disease: mechanisms, disease sub-types, treatment. Ocul Surf. 2003 Jul;1(3) 127-149.

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11. Saban DR, Calder V, Kuo CH, Reyes NJ, Dartt DA, Ono SJ, Niederkorn JY. New twists to an old story: novel concepts in the pathogenesis of allergic eye disease. Curr Eye Res. 2013 Mar;38(3):317-30.

12. Akdis CA, Blaser K. Histamine in the immune regulation of allergic inflammation. J Allergy Clin Immunol. 2003 Jul;112(1):15-22.

13. Leonardi A. Allergy and allergic mediators in tears. Exp Eye Res. 2013 Dec;117:106-117.

14. Miraldi Utz V, Kaufman AR. Allergic eye disease. Pediatr Clin North Am. 2014 Jun;61(3):607-620.

15. Gallois-Bernos A, Thurmond RL. Alcaftadine, a new antihistamine with combined antagonist activity at histamine H1, H2, and H4 receptors. J Recept Ligand Channel Res. 2012 Dec 20;5:9-20.

16. Pattnaik L, Acharya L. A comprehensive review on vernal keratoconjunctivitis with emphasis on proteomics. Life Sci. 2015 May 1;128:47-54.

17. De Smedt S, Wildner G, Kestelyn P. Vernal keratoconjunctivitis: an update. Br J Ophthalmol. 2013 Jan;97(1): 9-14.

18. Ackerman S, Smith LM, Gomes PJ. Ocular itch associated with allergic conjunctivitis: latest evidence and clinical management. Ther Adv Chronic Dis. 2016 Jan;7(1):52-67.

19. Brémond-Gignac D, Nischal KK, Mortemousque B, Gajdosova E, Granet DB, Chiambaretta F. Atopic Keratoconjunctivitis in Children: Clinical Features and Diagnosis. Ophthalmology. 2016 Feb;123(2):435-7.

20. Sy H, Bielory L. Atopic keratoconjunctivitis. Allergy Asthma Proc. 2013 Jan-Feb;34(1):33-41.

21. Solomon A. Corneal complications of vernal keratoconjunctivitis. Curr Opin Allergy Clin Immunol. 2015 Oct;15(5):489-494.

22. Vichyanond P, Kosrirukvongs P. Use of cyclosporine A and tacrolimus in treatment of vernal keratoconjunctivitis. Curr Allergy Asthma Rep. 2013 Jun;13(3):308-14.

23. de Klerk, T.A., et al., Severe vernal keratoconjunctivitis successfully treated with subcutaneous omalizumab. J aapos, 2013. 17(3): p. 305-6.

24. Baiula M, Spampinato S. Mapracorat, a novel non-steroidal selective glucocorticoid receptor agonist for the treatment of allergic conjunctivitis. Inflamm Allergy Drug Targets 2014; 13:289-298.

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