Allergic conjunctivitis is a common disease and is estimated to affect approximately 25% of the world population.1 The primary symptom of allergic conjunctivitis is ocular itching; other signs include conjunctival hyperemia or redness, chemosis, eyelid swelling, ocular discharge, and lacrimation.2 A wide range of treatments is currently available to the clinician. These include mast cell stabilizers, antihistamines and steroids. Steroids inhibit multiple mediator-induced allergic responses and are effective in controlling symptoms and signs of allergic conjunctivitis; however, possible complications including cataracts and intraocular pressure elevation limit their use. In contrast, mast-cell stabilizers such as cromolyn (cromoglycic acid) inhibit more specific actions such as mast-cell degranulation and mediator release, however these drugs often require up to about a week to obtain satisfactory relief of symptoms. Artificial tears are also often used to wash out allergens from the conjunctival sac.

Oral antihistamines are effective in controlling symptoms such as itching but often induce side effects such as dehydration and drowsiness. Therefore, in patients with predominantly ocular symptoms, topical preparations are preferable. Levocabastine hydrochloride, a second-generation antihistamine, is a non-sedating, highly potent, selective H₁ histamine-receptor antagonist. A 0.025% suspension of levocabastine has been developed in Japan for the treatment of allergic conjunctivitis. In this study, we evaluated whether the early efficacy of levocabastine is superior to the wash-out effect of artificial tears. In this study, the early efficacy of 0.025% levocabastine ophthalmic suspension and that of artificial tears were compared.

Thirty-six patients (10 men and 26 women; mean age, 41.0 ± 15.4 years; range, 20—73 years) with allergic conjunctivitis participated in the study. Patients were examined at the Kozuka Eye Center in Ehime, the Fujishima Eye Clinic in Niigata, or the Nakagawa Eye Clinic in Osaka. The studies were performed from August 2001 to March 2002.

Medical histories were recorded from all patients, and written informed consents were obtained. The following patients were excluded: 1) patients who had any ocular surface diseases other than allergic conjunctivitis, 2) patients who had used systemic or topical medications (e.g. steroids, nonsteroidal anti-inflammatory drugs, anticholinergics, immunosuppressives, mast-cell stabilizers, antihistamines) during the past week, 3) patients younger than 20 years, 4) women who were pregnant or potentially pregnant, and 5) patients who wore contact lenses.

Diagnoses were based on clinical symptoms and slit-lamp examination. Patients were asked to grade their baseline symptoms of ocular itching, conjunctival redness, and foreign body sensation on a scale of 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe). Patients who had pre-treatment symptom grades that differed by more than 1 between their eyes were excluded from the analysis to reduce the bias caused by differences in symptom severity. Objective bulbar conjunctival injection was also graded on a scale of 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe) based on slit-lamp examination. All the data are presented as means ± SD.

All patients were treated with one drop of levocabastine (Livostin^® Eye Drops 0.025%, Santen Pharmaceutical, Osaka, Japan) in one eye, and one drop of artificial tear (Soft Santear^®, Santen Pharmaceutical) in the contralateral eye. In order to avoid evaluation bias, neither the patients nor examiners were notified of the laterality of the eye drops. Symptoms and signs were re-evaluated at 15 and 30 minutes after instillation.

Statistical Analysis—Paired t-tests were used to assess the differences in symptoms before and after treatment, and between levocabastine and artificial tears. P values of less than 0.05 (two-tailed) were considered to indicate statistically significant differences.

Although both levocabastine and artificial tears significantly reduced ocular itching compared with pre-treatment levels, at 15 and 30 minutes (p < 0.001), levocabastine was significantly more effective than artificial tears (p = 0.001 at 15 minutes and p < 0.001 at 30 minutes) (Fig. 1). Levocabastine reduced conjunctival redness at both 15 and 30 minutes (p < 0.001) compared with pretreatment levels, while artificial tears reduced conjunctival redness only at 30 minutes (p = 0.023). Levocabastine was also significantly more effective in reducing conjunctival redness than artificial tears (p < 0.001 at 15 and 30 minutes). Levocabastine also significantly reduced foreign body sensation in the eye compared with pre-treatment levels at 15 (p = 0.001) and 30 minutes (p < 0.001). Treatment with artificial tears did not significantly reduce foreign body sensation. Levocabastine was clearly more effective than artificial tears in reducing foreign body sensation at both 15 (p = 0.005) and 30 minutes (p = 0.001). Although both levocabastine (p < 0.001) and artificial tears (p = 0.017) significantly reduced bulbar conjunctival injection at 30 minutes, levocabastine was more effective than artificial tears (p < 0.001) (Fig. 2). No adverse events were observed during this study.

In this study, artificial tears had a positive effect in reducing symptoms of allergic conjunctivitis. Allergic conjunctivitis is often complicated by dry eye and this relationship has been studied in many studies.3, 4 Although artificial tears do not specifically treat allergy, they augment the tear film, effectively "washing" the ocular surface. This mechanism is useful for removing or reducing the concentration of allergens or proteins that induce inflammation from the ocular surface. Instillation of just one drop was sufficient to bring about this positive effect in our study. This suggests that more frequent instillation or washing with greater volume of artificial tears might be even more effective in improving the signs and symptoms of allergic conjunctivitis.

In this study, we also compared the early efficacy of artificial tears and levocabastine in the same patient by instilling one drug in one eye and the other drug in the other eye. By this method, we excluded bias arising from subjectivity of the patients' evaluation of symptoms and responses to the drugs.5 In our study, topical levocabastine was more effective than artificial tears in reducing ocular itching, conjunctival redness, and foreign body sensation, and also in reducing bulbar conjunctival injection assessed by slit-lamp examination. These results demonstrated that the selective H₁ histamine-receptor antagonist action of levocabastine is rapidly effective in a clinical setting. The reduction of itching and vessel permeability caused by histamine release by levocabastine led to the decreased level of symptoms and signs observed in this study.

In conclusion, our study demonstrated that both artificial tears and levocabastine were effective in reducing acute symptoms of allergic conjunctivitis. Levocabastine however was significantly more effective than artificial tears demonstrating that the selective H₁ histamine-receptor antagonist action of levocabastine is rapidly effective in a clinical setting.

REFERENCES

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Abelson MB, George MA, Garofalo C. Differential diagnosis of ocular allergic disorders. Ann. Allergy 1993; 70: 95-109.
 

2
Leonardi A, Battista MC, Gismondi M, Fregona IA, Secchi AG. Antigen sensitivity evaluated by tear-specific and serum-specific IgE, skin tests, and conjunctival and nasal provocation tests in patients with ocular allergic disease. Eye 1993; 7: 461-464.

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Fujishima H, Toda I, Shimazaki J, Tsubota K. Allergic conjunctivitis and dry eye. Br. J. Ophthalmol. 1996; 80: 994-997.
 

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Toda I, Shimazaki J, Tsubota K. Dry eye with only decreased tear break-up time is sometimes associated with allergic conjunctivitis. Ophthalmology 1995; 102: 302-309.
 

5
Verin P, Easty DL, Secchi A et al. Clinical evaluation of twice-daily emedastine 0.05% eye drops (Emadine eye drops) versus levocabastine 0.05% eye drops in patients with allergic conjunctivitis. Am. J. Ophthalmol. 2001; 131: 691-698.