What we need to know about ocular allergies

Introduction

Ocular allergy (OA) is a common eye condition encountered in clinical practice (Kari & Saari 2012). OA represents a collection of ocular hypersensitivity disorders affecting the eyelid, conjunctiva, and cornea. OA includes seasonal and perennial allergic conjunctivitis (SAC and PAC), vernal and atopic keratoconjunctivitis (VKC and AKC), and contact blepharoconjunctivitis (CBC). These clinical subtypes may be diagnosed and managed by considering clinical history and signs and symptoms, aided by in vivo and in vitro tests (Leonardi et al., 2019).

Risk factors

Ocular allergic inflammation is a very common event due to frequent contact of the eye with environmental allergens (Doğan & Ağca 2018). Doğan & Ağca 2018 found that prenatal maternal paracetamol exposure and shorter duration of vitamin D supplementation in the postnatal period may play a role in development of SAC, and that patients with SAC were more likely to have asthma, allergic rhinitis and oral allergy syndrome while, their relatives also may demonstrate higher rates of allergic diseases. Allergic conjunctivitis is triggered by allergens such as pollen, dust mites, mold, and pet dander (Ismail & Yuanita 2024). 

Symptoms

OA is a public health concern significantly affecting the quality of life of a large proportion of the population worldwide. The prevalence of this condition has been steadily increasing in both developed and developing countries with children being more frequently affected (Ismail & Yuanita 2024). Accurate diagnosis of allergic conjunctivitis can be challenging, as its symptoms often overlap with other ocular conditions, such as viral or bacterial conjunctivitis. Typical symptoms include itching, redness, watery discharge, and swelling of the conjunctiva, which can significantly impair daily functioning. While a thorough patient history and clinical examination are essential, diagnostic tests such as conjunctival provocation tests and skin prick tests can provide additional support in confirming the allergic etiology of the condition (Ismail & Yuanita 2024). 

In terms of diagnosis, allergic conjunctivitis is often underdiagnosed or mismanaged, particularly by general practitioners, who rely heavily on symptomatology and may not conduct comprehensive allergy testing (Ismail & Yuanita 2024). Patients with multiple allergic conditions may require a more integrated, multidisciplinary approach to care. The interplay between allergic conjunctivitis and other allergic conditions reinforces the need for comprehensive allergy testing and the use of treatments that address multiple allergic pathways simultaneously. This comorbidity association further complicates diagnosis and treatment (Ismail & Yuanita 2024). 

Management

The incorrect management of OA may increase the risk of local and systemic treatment-related side effects (Leonardi et al., 2019). The management of OA involves a combination of pharmacologic and non-pharmacologic treatments.

Pharmacological treatment

Pharmacologically, dual-acting antihistamine-mast cell stabilizers are considered first-line treatments for allergic conjunctivitis. These agents provide rapid relief of symptoms by blocking histamine receptors and stabilizing mast cells, thus preventing further allergic responses. For patients with more severe or persistent symptoms, corticosteroids and mast cell stabilizers are often used. Leonardi et al. (2015) observed that corticosteroids were used in 41% of patients, highlighting their role in managing chronic or more severe cases of AC. However, these treatments are typically reserved for short-term use due to potential side effects such as increased intraocular pressure and cataract formation with prolonged use. In addition to pharmacologic treatments, allergen immunotherapy (AIT) remains a key strategy for longterm management. This approach aims to desensitize patients to the allergens responsible for triggering OA. AIT is particularly beneficial for patients with persistent symptoms who do not respond adequately to other treatments. Immunomodulatory treatments for OA include allergen-specific immunotherapy and biologicals (Ismail & Yuanita 2024). 

There is a wide range of treatment options for OA. Topical drugs for OA can be classified into different pharmacological classes based on their mechanism of action:

Overall,

-          Topical antihistamines and mast cell stabilizers appear to be safe and well tolerated.

-          Topical antihistamines and dual-acting drugs may lead to a quicker onset symptom relief when compared to mast cell stabilizers. Dual-acting agents with combined mast cell stabilizer and antihistaminic function provide better symptom control. The most frequently reported side effects from the use of these agents are burning and stinging sensation, blurred vision and unacceptable aftertaste. To minimize possible toxic effects of preservative compounds on the ocular surface, single-dose preservative-free eye drops should be used whenever possible. (Leonardi et al., 2019).

-          Topical decongestants are frequently used as first-line treatment due to their availability over the counter. They merely alleviate hyperemia, having little to no relief from itching and a short duration of action. They may cause side effects such as rebound redness, chronic follicular conjunctivitis, and tachyphylaxis. Vasoconstrictors alleviate only hyperemia. They should be used with caution and for a short period of 5-7 days because of side effects (Leonardi et al., 2019).

-          Topical NSAIDS are more effective than placebo in reducing ocular itching and redness. NSAIDs are rarely used due to their local side effects, such as burning/stinging after application. NSAIDs are effective for their short-term use but do not target specific inflammatory mechanisms (Leonardi et al., 2019).

-          Topical corticosteroids should not be the first choice of therapy for OA. In clinical practice, they are the most effective anti-inflammatory agents in active OA. Because of potential adverse effects (increased intraocular pressure, with a potential evolution toward glaucoma, cataract formation, bacterial, viral and fungal superinfections), their use must be monitored especially in prolonged treatments. The potency and treatment duration of the topical corticosteroid should be chosen clinically based on the severity of ocular inflammation and corneal involvement. Topical corticosteroids eye drops should be used with caution under ophthalmologist's monitoring and preferably for shorter duration due to the high risk of local and potential blinding side effects (Leonardi et al., 2019).

-          Topical calcineurin inhibitors are the most frequently used treatments as steroid-sparing agents in steroid-dependent cases of VKC and AKC (Leonardi et al., 2019).

Nonpharmacological management

Patients and caregivers should receive educative support regarding the anticipated duration and prognosis of the OA, and possible complications from suboptimal control. The first line of management is the identification of offending allergens and avoidance measures. Particularly during exacerbations in VKC, to minimize the exposure to nonspecific triggering factors, such as sun, wind, and salty water, patients should use measures such as glasses, hats with visors, and swimming goggles (Leonardi et al., 2019). Comert, Karakaya & Kalyoncu (2016) demonstrated that standard wraparound eyeglasses can provide a safe, convenient, and effective measure for protection from pollens in patients with seasonal allergic rhinoconjunctivitis.

Non-pharmacologic approaches, such as the use of cold compresses (CC) and artificial tears (ATs), have been shown to provide significant relief.  CC may provide decongestant effect. Tear substitutes aid in stabilization of the tear film providing a better mucosal barrier against allergens, acting as an eyewash and diluting the concentration of mediators in the tear film in contact with the ocular surface (Leonardi et al., 2019). Bilkhu et al. (2014) demonstrated that CC combined with ATs effectively reduced bulbar conjunctival hyperemia and ocular symptoms, returning temperature to baseline faster than no treatment. Additionally, CC were found to enhance the effect of antihistamine eye drops, indicating that these simple interventions can offer quick symptomatic relief (Ismail & Yuanita 2024).  ATs and CC, either alone or combined, may be considered as front line agents for acute SAC by staff to whom pharmacological treatment options are limited (Kari & Saari 2012).

Products with herbal extracts such as chamomile-containing eye drops should be avoided as they may cross-react with allergens (for example, Artemisia vulgaris) (Leonardi et al., 2019). Frequent hand, face, lid hygiene, and eye washing should also be suggested.

Overall, avoidance of specific and nonspecific triggers is the first step in the prevention of ocular allergy symptoms. Use cold compresses, good eyelid hygiene, and lubricants. Topical antihistamines, mast cell stabilizers, or double-action drugs are the first treatment choice and may be used in combination. They should be used frequently during the day and during the whole season. Systemic anti-allergic drugs should be used when ocular symptoms are associated with other allergic comorbidities. Topical corticosteroids should be used as short, pulsed therapy, in acute exacerbations or when the cornea is involved, under ophthalmologist's monitoring. Topical calcineurin inhibitors, preferentially cyclosporine A (0.1% on-label treatment in the EU), may be used as a steroid-sparing agent in steroid-dependent patients followed in specialized centers; tacrolimus 0.1% eye drops should be reserved for severe VKC and AKC cases refractory to CsA (off-label treatment in the EU). A systemic immunosuppressive treatment should be prescribed in most refractory cases of AKC with visual threat. Cyclosporine is the most frequently used drug. Tacrolimus and mycophenolate mofetil are alternative options (Leonardi et al., 2019).

Treatments of ocular comorbidities and complications

Corneal epithelial erosions, shield ulcers, and plaques, frequently observed in AKC and VKC, occur as a result of mediators released from inflammatory cells and partially by the mechanical trauma from upper tarsal conjunctival giant papillae (GP). Delayed epithelial healing may lead to secondary infections, corneal opacities, and amblyopia (Leonardi et al 2019).

Allergic patients in childhood may develop keratoconus, a progressive, noninflammatory disorder of the cornea characterized by thinning and steepening in the central or paracentral cornea causing irregular astigmatism and subsequent decrease in visual acuity. Corneal cross-linking, consisting in the topical application of a 0.1% riboflavin 5-phosphate solution to the de-epithelized corneal surface followed by exposure to UVA radiation, seems to be a safe and effective surgical option to arrest disease progression, which may be very aggressive in children. Visual rehabilitation in early and moderate stages consists of spectacles, contact lenses, and intracorneal ring implantation. Although the clinical outcome of corneal transplantation in keratoconus with and without VKC is comparable, postoperative complications are more common in VKC. Atopy is a risk factor for complications after corneal grafting (Leonardi et al 2019).

Prolonged treatment with topical steroids should be avoided since glaucoma can occur in all age-groups. Withdrawal of steroids and addition of antiglaucoma medications is effective in controlling IOP in the majority of patients. Glaucoma surgery is rarely necessary (Leonardi et al 2019).

Limbal stem cell deficiency (LSCD) is a rare complication of longstanding VKC and AKC, contributing to severe visual impairment. It is characterized by conjunctival epithelial ingrowth on the cornea, neovascularization, ocular surface inflammation, and/or recurrent corneal epithelial defects. Fibrovascular pannus resection with amniotic membrane transplantation or allolimbal transplantation with systemic immunosuppression has been reported in severe patients (Leonardi et al 2019).

Conclusion

A multifaceted treatment regimen comprising patient education, lifestyle modification, and topical medications may be required in order to manage ocular allergies effectively. The appropriate treatment paradigm is based on the severity of the patients’ signs and symptoms. For moderate-to-severe cases, especially chronic vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis, co-management with an ophthalmologist is recommended (O’Brien 2013). Many patients remain undiagnosed or inadequately treated, highlighting the need for improved awareness, diagnostics, and future research (Ismail & Yuanita 2024). 

REFERENCES

1.      Kari, O., & Saari, K. M. (2012). Diagnostics and new developments in the treatment of ocular allergies. Current allergy and asthma reports, 12(3), 232-239.

2.      Leonardi, A., Silva, D., Perez Formigo, D., Bozkurt, B., Sharma, V., Allegri, P., ... & Fauquert, J. L. (2019). Management of ocular allergy. Allergy, 74(9), 1611-1630.

3.      Doğan, Ü., & Ağca, S. (2018). Investigation of possible risk factors in the development of seasonal allergic conjunctivitis. International Journal of Ophthalmology, 11(9), 1508.

4.  Ismail, I. S., & Yuanita, Y. (2024). The Analysis Study of Prevalence, Diagnosis and Management of Allergic Conjunctivitis: A Comprehensive Systematic Review. The International Journal of Medical Science and Health Research, 6(2), 1-20.

5.      Leonardi, A., Piliego, F., Castegnaro, A., Lazzarini, D., La Gloria Valerio, A., Mattana, P., & Fregona, I. (2015). Allergic conjunctivitis: a cross‐sectional study. Clinical & Experimental Allergy, 45(6), 1118-1125.

6.      Comert, S., Karakaya, G., & Kalyoncu, A. F. (2016, July). Wraparound eyeglasses improve symptoms and quality of life in patients with seasonal allergic rhinoconjunctivitis. In International Forum of Allergy & Rhinology (Vol. 6, No. 7, pp. 722-730).

7.    Bilkhu, P. S., Wolffsohn, J. S., Naroo, S. A., Robertson, L., & Kennedy, R. (2014). Effectiveness of nonpharmacologic treatments for acute seasonal allergic conjunctivitis. Ophthalmology, 121(1), 72-78.

8.   O’Brien, T. P. (2013). Allergic conjunctivitis: an update on diagnosis and management. Current opinion in allergy and clinical immunology, 13(5), 543-549.

9.    Fauquert, J. L. (2019). Diagnosing and managing allergic conjunctivitis in childhood: the allergist’s perspective. Pediatric Allergy and Immunology, 30(4), 405-414.