Spring is Here: Is it Allergy, Dry Eye or Both?

Hay fever, also known as allergic rhinitis,¹ can be perennial/seasonal (PAC, SAC) and allergic conjunctivitis can occur with it, or independently. Symptoms can include a runny nose; irritated or burning eyes, nose and throat; a post-nasal drip; congestion; sneezing and sinus pressure.² Ocular signs and symptoms may include red, watery, burning, itchy eyes and an oedematous or velvety conjunctiva, as well as lid swelling. Superficial punctate keratopathy (SPK) is often present as is an unstable tear film. Unfortunately for many patients who suffer with dry eye, allergies can mimic and even exacerbate their symptoms, causing confusion for clinicians as to whether the signs are disease progression or the onset of hay fever. Causes can include pollens and grasses, dust mites, dander from pets and mould spores, as well as chemicals and food.

it is always a balance as to whether the inflammatory response caused by allergy in dry eye outweighs the drying effect of these oral antihistamines

While hay fever is common and frequently annoying, it is rarely sight threatening. But care should be taken to observe more severe forms of ocular allergy that can potentially affect vision, such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).

VKC is seasonal, as the name suggests (vernal = spring), and typically affects younger populations aged five to 25-years, with the average age of onset being 10 to 12-years-of-age. It is often seen more in males and in hot, dry climates, and may be associated with a personal or family history of atopy and with keratoconus. Signs, aside from those seen in SAC and PAC, can present as two different forms – tarsal, involving giant papillae on the upper tarsal conjunctiva; and limbal, with thickening of the limbal conjunctiva and the presence of Trantas dots on the perilimbal area (small white dots containing eosinophils and degenerated epithelial cells). Corneal signs can include chronic SPK, which can cause photophobia and create scarring shield ulcers and neovascularisation.³ 

The main differential diagnosis is AKC, which more commonly occurs in the second to fifth decades, is more chronic in nature, and involves more of the lower tarsal plate. This can lead to corneal scarring and cicatrisation of the tarsal conjunctiva. Vision can be affected with the presence of mucoid strands and discharge. Patients with AKC often suffer with atopy, including facial and peri-ocular eczema, which can also occur in the flexures, such as wrists or neck.⁴ The involvement of an immunologist or allergist in both these conditions can be important to manage the patient’s concurrent multiple allergic diseases.

Antihistamines have limited application in both VKC and AKC, but treatment with a topical steroid for acute presentations can be very effective. Ongoing management should comprise a combined topical antihistamine/mast cell stabiliser (MCS) and/or non-steroidal anti-inflammatories (NSAIDs), or the use of topical cyclosporin.

Other differentials are giant papillary conjunctivitis from prolonged contact lens wear and allergic blepharoconjunctivitis from eye drop allergy and blepharitis.

MINIMISING ALLERGEN EXPOSURE

While many people self-diagnose their condition, consultation with a GP, allergy clinic or clinical immunologist can determine specific allergen triggers and differentiate between environmental or food triggers through blood allergen specific IgE and/or skin prick tests.⁵

To minimise their exposure, patients should be advised to avoid known allergens, wear wraparound sunglasses, wash their face or shower after exposure, use a barrier cream around the nostrils, close windows and dry clothes indoors on high pollen count days, and use recycled air (not fresh) when in the car. Encourage patients to check their local pollen counter daily.

SYMPTOM MANAGEMENT

If irritated by allergens, patients should, in the first instance, irrigate the eyes and use cold compresses for relief.

Allergen-specific immunotherapy, also known as ‘desensitisation’, aims to reduce the intensity of the body’s reaction to an allergen. It works by gradually exposing someone to increasing doses of allergen extracts via injection or sublingually. This is a long-term treatment option and should only be initiated by a medical specialist such as a clinical immunologist.⁶ 

Oral Antihistamines 

Many people find relief with oral antihistamines. The so-called ‘first generation’ antihistamines, such as promethazine (Phenergan) and dexchlorpheniramine (Polaramine), can cause drowsiness that can severely impact tasks such as operating machinery and driving. Additionally, they can disrupt REM sleep patterns and impact attention in schoolaged children.⁷ Interestingly, this generation of antihistamines are recommended for pregnant and breastfeeding women as they have been taken by a large number of women and show the greatest evidence of safety – although very high dose promethazine in animals has shown adverse side effects.

Drowsiness is less of a problem with newer ‘second generation’ antihistamines, such as loratadine (Claratyne) and cetirizine (Zyrtec). There is no issue with the use of ‘third generation’ antihistamines such as fexofenadine (Telfast).

Oral antihistamines and nasal irrigation with saline sprays can help with nasal itching, sneezing and rhinorrhoea, but are less effective for nasal obstruction – corticosteroid nasal sprays can best help with this. Decongestant sprays can unblock and dry the nose, but they can cause stimulant side effects such as tremors, difficulty sleeping, anxiety or increased blood pressure. They can also cause rebound congestion with prolonged use.⁸ 

Hay fever can be severe and result in sleeplessness, headaches, fatigue and poor concentration. It may also trigger asthma and ear infections in children, and sinusitis in adults.⁹ Antihistamines are often the answer for hay fever, however the antimuscarinic effects of medications, such as Claratyne and Zyrtec, can cause a decrease in aqueous production,¹⁰ exacerbating dry eye disease as well as causing dry mouth, tachycardia and mucous thickening. From my personal viewpoint, it is always a balance as to whether the inflammatory response caused by allergy in dry eye outweighs the drying effect of these oral antihistamines, however the severity of the patient’s hay fever symptoms is usually the deciding factor in whether to use them or not.

Topical Antihistamines 

Topical treatments often offer more relief in ocular allergy than their oral counterparts. Over the counter red eye/allergy preparations are typically based on sympathomimetic agents with marked alpha adrenergic activity that cause vasoconstriction like naphazoline (Systane Red Eyes, Murine Clear eyes). They can also be combined with antihistamines, such as antazoline (Albalon A) or pheniramine (Naphcone A). Sideeffects can be pupil dilation and blur, and they are contraindicated in narrow angle glaucoma and heart disease, hypertension and overactive thyroid. Prolonged use can cause rebound redness, and many reusable bottles use benzalkonium chloride (BAK) as the preservative, which can disrupt corneal and conjunctival epithelium and exacerbate dry eye.¹¹ Non-preserved topical drops are the preferred option for the dry eye patient or those with ocular surface disease.

More commonly, patients find relief with dedicated topical antihistamine agents such as levocabastine (Zytrec), MCSs like sodium cromoglycate (Chromofresh) and lodoxamide (Lomide) or a combination of the two – olopatadine (Patanol) or ketotifen (Zatiden). Like oral antihistamines, patients may need to experiment with different preparations to find the one that works best for them.

NSAIDs 

NSAIDs inhibit the production of prostaglandins by blocking the enzyme cyclooxygenase, thereby reducing inflammation.¹² They are commonly used in ocular allergy and rhinitis to control symptoms of itching, pain and inflammation. However, they can also reduce corneal sensitivity and disrupt an already compromised epithelium in the dry eye.¹³ Typically, ketorolac (Acular) is used in ocular allergy over diclofenac (Volaren), the latter which is often used to prevent miosis during cataract surgery, control post-operative pain and cystoid macula oedema, and provide pain relief following some post-refractive surgery procedures.14 Unfortunately, there have been many cases of corneal melt associated with the use of NSAIDs.^15,16

While topical NSAIDs can be effective against the ocular irritation caused by allergy, careful assessment of the cornea, particularly in the patient with known ocular surface disease such as dry eye, is an important step in assessing whether this course of treatment is the best. Regular observance of the vulnerable patient is recommended.

Cyclosporin 

Cyclosporin A is a peptide that inhibits T-cell activation and consequently inhibits the inflammatory cytokine production, as well as inhibiting apoptosis by blocking the opening of the mitochondrial permeability transition pore. It can also increase conjunctival goblet cell density.¹⁷

Topical Cyclosporin has been used in dry eye treatment for many years to stimulate aqueous production, improve corneal neovascularisation, treat ocular cicatricial pemphigoid and auto-immune corneal melting. It inhibits histamine release from mast cells and basophils through a reduction in IL-5 production, and may reduce eosinophil recruitment as well as effects on the conjunctiva and cornea.¹⁸ Cyclosporin A 1% or 2% can be considered for treatment of moderate to severe VKC and chronic allergy without any side effects (aside from some irritation or burning on installation as experienced by some patients).¹⁹ One drop, two to four times a day, depending on severity, can be used during the allergy season, or for a longer duration, and may have a place for both allergy and dry eye management.²⁰ 

CONCLUSION

Ocular allergy and hay fever can be challenging to manage, especially in the presence of existing dry eye disease. There are many factors to consider when deciding on the best treatment plan for the individual patient. Optometrists are perfectly positioned to advise, inform and manage ocular allergy in their patients.

Dr Jennifer Rayner BAppSc (Optom), GradCertOcTher (UNSW) was a registered nurse before studying optometry. She has practised as an optometrist since 2003 and with her business partner Dr Rene Malingre, established South Australia’s first dedicated dry eye clinic, Alleve Eye Clinic, in 2016.

References 

1. Australia H. Hay fever (allergic rhinitis). www.healthdirect. gov.au. Published July 29, 2019. www.healthdirect.gov.au/ hay-fever 
2. Hay fever – Symptoms and causes. Mayo Clinic. Published 2019. www.mayoclinic.org/diseases-conditions/hay-fever/ symptoms-causes/syc-20373039 
3. Vernal Keratoconjunctivitis – EyeWiki. eyewiki.aao.org. eyewiki.aao.org/Vernal_Keratoconjunctivitis#Signs 
4. Bruce AS, Loughnan MS. Anterior Eye Disease and Therapeutics A-Z. Sidney (Australia) Elsevier; 2011. 
5. Skin Prick Testing Guide for the Diagnosis of Allergic Disease. Australasian Society of Clinical Immunology and Allergy (ASCIA). www.allergy.org.au/hp/papers/skinprick- testing 
6. Administrator. Pollen Allergy. Australasian Society of Clinical Immunology and Allergy (ASCIA). Published 2016. www.allergy.org.au/patients/allergic-rhinitis-hay-fever-andsinusitis/ pollen-allergy 
7. Randall KL, Hawkins CA. Antihistamines and allergy. Australian Prescriber. 2018;41(2):42-45. 
8. Australia H. Hay fever (allergic rhinitis). www.healthdirect. gov.au. Published June 11, 2021. www.healthdirect.gov.au/ hay-fever#diagnosed 
9. Allergic Rhinitis (Hay Fever) and Sinusitis. Australasian Society of Clinical Immunology and Allergy (ASCIA). www.allergy.org.au/patients/allergic-rhinitis-hay-feverand- sinusitis 
10. Ousler GW, Wilcox KA, Gupta G, Abelson MB, Fink K. An evaluation of the ocular drying effects of 2 systemic antihistamines: loratadine and cetirizine hydrochloride. Annals of Allergy, Asthma & Immunology. 2004;93(5):460- 464.
11. Walsh K, Jones L. The use of preservatives in dry eye drops. Clinical Ophthalmology. 2019; Volume 13():1409-1425. 
12. Vane JR, Bakhle YS, Botting RM. CYCLOOXYGENASES 1 AND 2. Annual Review of Pharmacology and Toxicology. 1998;38(1):97-120. 
13. Lin JC, Rapuano CJ, Laibson PR, Eagle RC, Cohen EJ. Corneal Melting Associated With Use of Topical Nonsteroidal Anti-inflammatory Drugs After Ocular Surgery. Archives of Ophthalmology. 2000;118(8):1129-1132. https://jamanetwork.com/journals/jamaophthalmology/ fullarticle/413448 
14. Flach AJ. Corneal melts associated with topically applied nonsteroidal anti-inflammatory drugs. Transactions of the American Ophthalmological Society. 2001;99:205- 210; discussion 210-212. pubmed.ncbi.nlm.nih. gov/11797308 
15. Asai T, Nakagami T, Mochizuki M, Hata N, Tsuchiya T, Hotta Y. Three Cases of Corneal Melting After Instillation of a New Nonsteroidal Anti-Inflammatory Drug. Cornea. 2006;25(2):224-227. 
16. Mian SI, Gupta A, Pineda R. Corneal Ulceration and Perforation With Ketorolac Tromethamine (Acular®) Use After PRK. Cornea. 2006;25(2):232-234. 
17. Kymionis G. Treatment of chronic dry eye: focus on cyclosporine. Clinical Ophthalmology. 2008;2(4):829. 
18. Utine CA, Stern M, Akpek EK. Clinical Review: Topical Ophthalmic Use of Cyclosporin A. Ocular Immunology and Inflammation. 2010;18(5):352-361. 
19. Jameel A, Moin M, Hussain M. Role of Cyclosporine Eye Drops In Allergic Conjunctivitis. Pakistan Journal of Ophthalmology. 2009;25(2):104-109. 
20. Leonardi A, Busca F, Motterle L, et al. Case series of 406 vernal keratoconjunctivitis patients: a demographic and epidemiological study. Acta Ophthalmologica Scandinavica. 2006;84(3):406-410.