Treatment of allergic conjunctivitis with
`olopatadine hydrochloride eye drops
`
`R E V I E W
`
`Eiichi Uchio
`Department of Ophthalmology,
`Fukuoka University School of
`Medicine, Fukuoka, Japan
`
`Correspondence: Eiichi Uchio
`Department of Ophthalmology, Fukuoka
`University School of Medicine, 7-45-1
`Nanakuma, Jonan-ku, Fukuoka 814-0180,
`Japan
`Tel +81 92 801 1011
`Fax +81 92 865 4445
`Email: euchio@fukuoka-u.ac.jp
`
`Abstract: Olopatadine hydrochloride exerts a wide range of pharmacological actions such as
`histamine H1 receptor antagonist action, chemical mediator suppressive action, and eosinophil
`infi ltration suppressive action. Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol®)
`was introduced to the market in Japan in October 2006. In a conjunctival allergen challenge
`(CAC) test, olopatadine hydrochloride 0.1% ophthalmic solution signifi cantly suppressed
`ocular itching and hyperemia compared with levocabastine hydrochloride 0.05% ophthalmic
`solution, and the number of patients who complained of ocular discomfort was lower in the
`olopatadine group than in the levocabastine group. Conjunctival cell membrane disruption was
`observed in vitro in the ketotifen fumarate group, epinastine hydrochloride group, and azelastine
`hydrochloride group, but not in the olopatadine hydrochloride 0.1% ophthalmic solution group,
`which may potentially explain the lower discomfort felt by patients on instillation. Many other
`studies in humans have revealed the superiority of olopatadine 0.1% hydrochloride eye drops
`to several other anti-allergic eye drops. Overseas, olopatadine hydrochloride 0.2% ophthalmic
`solution for a once-daily regimen has been marketed under the brand name of Pataday®. It is
`expected that olopatadine hydrochloride ophthalmic solutions may be used in patients with a
`more severe spectrum of allergic conjunctival diseases, such as vernal keratoconjunctivitis or
`atopic keratoconjunctivitis, in the near future.
`Keywords: olopatadine, eye drop, allergic conjunctivitis, anti-histaminergic
`
`Introduction
`The prevalence of allergic conjunctival diseases (ACD) in Japan is estimated to be
`as high as 15%–20% of the population and is on the rise. Cases of seasonal allergic
`conjunctivitis (SAC) due to cedar pollen account for a major part of allergic conjunc-
`tivitis (AC) in Japan. Cedar pollinosis presents not only with nasal symptoms such as
`sneezing and rhinorrhea, but also with severe ocular itching. Ocular itching and nasal
`symptoms adversely affect the quality of life (QoL) of patients. In addition, the recent
`increase in severity of ACD is raising concerns.
`ACD are ocular disorders caused by allergic infl ammation of the ocular surface,
`and include AC, atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC),
`and giant papillary conjunctivitis (GPC). The clinical features of ACD are character-
`ized by their wide variety, and the medical treatment of ACD should be based on the
`clinical characteristics. AC is defi ned as ACD in which the conjunctiva shows no pro-
`liferative change, and is divided into two subcategories, SAC and perennial allergic
`conjunctivitis (PAC), according to the presence of seasonal exacerbation. PAC is a less
`severe ACD, though still uncomfortable for the patient. Signs and symptoms of PAC
`include itching, hyperemia, and tearing. Mucous discharge is clear and transient. AKC
`is a bilateral, chronic hypersensitivity disease of the ocular surface seen in association
`with systemic atopic dermatitis, characterized by lesions of the conjunctiva and cornea
`that vary in severity. Ocular symptoms include intense itching, photophobia, burning,
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`Uchio
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`and the sensation of a foreign body. The clinical signs show
`a wide spectrum, and in the most severe cases, conjunctival
`scarring with subepithelial fi brosis, fornix foreshortening,
`symblepharon and corneal ulceration, and neovasculariza-
`tion may occur. Therefore, it is a sight-threatening condi-
`tion, emerging in the second through the fi fth decade of life
`(Belfort et al 2000). The disease is associated with eczema
`of the lids or other parts of the body. VKC is a recurrent sea-
`sonal disease of childhood, characterized by severe bilateral
`infl ammation of the conjunctiva and by giant papillae of the
`superior tarsal conjunctiva, gelatinous hypertrophy of the
`limbus, and keratopathy. It is associated with intense itching,
`photophobia, and mucous discharge, and is most commonly
`seen in male patients. However, unlike the severe group of
`AKC, it tends to resolve spontaneously after several years.
`The incidence of VKC varies markedly with geographic
`location, with individuals in Italy, Japan, and other areas of
`warm climate being more likely to have the disease (Calonge
`1999; Ono and Abelson 2005).
`For the treatment of ACD, several local ocular drugs, such
`as antihistamines, anti-allergic agents, and corticosteroids,
`have been developed as commercially available eye drops
`recently. Anti-allergic eye drops products which are the
`basic therapy for ACD are classifi ed into 2 types based on
`their pharmacological characteristics: drugs that suppress the
`release of a mediator (eg, disodium cromoglycate) and his-
`tamine H1 antagonists. Especially, histamine H1 antagonists
`are recommended as the fi rst choice of treatment for cases
`with severe nasal symptoms and itching because prompt
`symptom relief is expected.
`As of 2005, 6 mediator release suppression agents
`(disodium cromoglycate, amlexanox, pemirolast potassium,
`tranilast, ibudilast, and acitazanolast hydrate) and 2 histamine
`H1 antagonists (ketotifen fumarate and levocabastine hydro-
`chloride) are used in commercially available anti-allergic eye
`drops products in Japan. Although prescriptions of eye drops
`containing histamine H1 antagonists have recently increased
`because of their superior rapid effect, only 2 eye drops,
`ketotifen fumarate 0.05% and levocabastine hydrochloride
`0.025%, were available at that time in Japan; in contrast, more
`anti-histaminergic eye drops were available worldwide.
`Olopatadine hydrochloride, developed by Kyowa Hakko
`Kogyo Co., Ltd. (Tokyo, Japan), exerts a wide range of phar-
`macological actions such as histamine H1 receptor antagonist
`action, chemical mediator suppressive action, tachykinin
`release inhibitory action, and eosinophil infi ltration suppres-
`sive action. In Japan, a formulation for oral use that is highly
`evaluated by physicians and is indicated for allergic rhinitis,
`
`urticaria, and itching associated with dermatosis (eczema and
`dermatitis, prurigo, pruritus cutaneous, psoriasis vulgaris, and
`erythema exsudativum multiforme) has been marketed since
`March 2001 (Ohmori et al 2002). Alcon Inc. (Hünenberg,
`Switzerland) developed an olopatadine hydrochloride oph-
`thalmic solution under license from Kyowa Hakko Kogyo
`Co., Ltd. Since 1996, the product has been approved in about
`90 countries, including the US, and at present it is widely
`used in clinical practice to treat AC.
`In Japan, olopatadine hydrochloride 0.1% ophthalmic
`solution was introduced to the market in October 2006 as a
`third anti-histaminergic eye drop, in addition ketotifen fuma-
`rate and levocabastine hydrochloride. This article reviews
`the pharmacological actions and clinical effects of the new
`olopatadine hydrochloride ophthalmic solution.
`
`Pharmacological properties
`ACD are mainly caused by type I allergic reactions. When
`IgE antibodies specifi c to pollen or house dust are exces-
`sively produced, an antigen-antibody reaction is induced,
`leading to degranulation of mast cells. Then, mast cells
`release chemical mediators such as histamine, triggering the
`development of symptoms. Although such allergic reactions
`involve various chemical mediators, conjunctival symptoms
`such as ocular itching and conjunctival hyperemia are devel-
`oped by histaminergic actions mainly through H1 receptors
`(Knight 1994).
`Histamine H1 receptor selectivity of olopatadine hydro-
`chloride was examined using brain homogenates from guinea
`pigs and rats. Affi nity for H1, H2, and H3 receptors was exam-
`ined using pyrilamine, tiotidine, and methylhistamine as the
`ligand, respectively. Ki (affi nity) values of the olopatadine
`hydrochloride binding to H1, H2, and H3 receptors were
`4.11 × 10−8 M, 4.34 × 10−5 M, and 1.72 × 10−4 M, respectively,
`indicating that selectivity for H1 receptors is about 1000 times
`that for H2 receptors and 4000 times that for H3 receptors.
`The selectivity of olopatadine hydrochloride is higher than
`that of ketotifen fumarate or levocabastine hydrochloride
`(Sharif et al 1996). Compared with disodium cromoglycate,
`nedocromil, and pemirolast potassium, only olopatadine
`hydrochloride suppressed antigen-induced histamine from
`human conjunctival mast cells in a dose-dependent manner
`(IC50: 6.53 × 10−4 M) (Yanni et al 1997).
`Olopatadine hydrochloride suppressed TNF-α release in
`vitro from human conjunctival mast cells in a concentration-
`dependent manner (IC50: 1.3 ×10−5 M) (Cook et al 2000), as
`well as that of interleukin 6 (IL-6) and IL-8 from conjunc-
`tival epithelial cells (IC50: 5.5 × 10−9 M and 1.7 × 10−9 M,
`
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`respectively) (Yanni et al 1999). The effects of olopatadine
`hydrochloride on type I allergy have also been examined in
`vivo. Guinea pigs were passively sensitized through adminis-
`tration of anti-ovalbumin (OVA) serum into the conjunctival
`sac, and then olopatadine hydrochloride was instilled into their
`eyes. Thirty minutes after the administration, its effect on
`passive anaphylactic reaction was evaluated by intravenously
`administering solution containing OVA and Evans blue. As
`a result, 0.001%–0.1% olopatadine hydrochloride showed a
`dose-dependent suppressive effect, with the 50% effective
`dose (ED50) being 0.0067%. Moreover, the passive anaphylac-
`tic reaction induced in guinea pigs by instillation of the antigen
`after sensitization with anti-OVA serum was signifi cantly
`suppressed when 0.001%–1.0% olopatadine hydrochloride
`was instilled into the eyes 30 minutes before the induction
`(ED50: 0.017%). The effect of olopatadine hydrochloride on
`enhanced vascular permeability induced by histamine in the
`conjunctiva of guinea pigs ranged between concentrations of
`0.00001% to 1.0%. Olopatadine hydrochloride suppressed the
`reaction in a concentration-dependent manner. Signifi cant
`suppression was observed at 0.1% for 24 hours compared
`with that in a control group in which physiological saline was
`instilled into the eyes (Yanni et al 1996).
`Olopatadine hydrochloride is considered as a promising
`dual-action drug with selective and continuous histamine H1
`receptor antagonistic action and mast cell stabilization action.
`
`Clinical trials in Japan
`Olopatadine hydrochloride 0.1% ophthalmic solution is
`marketed worldwide as Patanol® Ophthalmic Solution
`0.1%. In Japan its approved dosage and administration for
`allergic conjunctivitis is 1–2 drops qid. At the beginning of
`its development in Japan, approval for instillation bid at the
`same dosage was considered for convenience of clinical use.
`However, in Japan, most anti-allergic eye drops products are
`used qid, because patients with severe ocular itching caused
`by cedar pollinosis tend to prefer to instill more than twice
`per day. Another reason was that the higher frequency of
`instillations might have a better antigen fl ushing effect. An
`open study was conducted to examine the potential increase
`of adverse reactions with a higher frequency of instilla-
`tion. The study compared a bid group with a qid group, 44
`patients in each, during the cedar-pollen-shedding period
`using an environmental study protocol. Effects on itching
`and hyperemia were comparable in both groups; however,
`the qid group showed slightly lower incidence of adverse
`drug reactions than the bid group (bid group, 15.9%; qid
`group, 9.1%) (Saiga et al 2006). Based on these results and
`
`Olopatadine hydrochloride eye drops in ocular allergy
`
`the aforementioned reasons, the qid regimen was adopted. A
`double-blind phase III study that involved 247 patients with
`Japanese cedar pollen AC was conducted using the environ-
`mental study protocol mentioned above. The study compared
`olopatadine hydrochloride 0.1% ophthalmic solution with
`ketotifen fumarate 0.05% ophthalmic solution (a control
`drug), both at a dose of 2 drops qid for 28 days. Olopatadine
`hydrochloride 0.1% eye drops proved to be as effective (ocu-
`lar itching and conjunctival hyperemia) as ketotifen fumarate
`0.05% eye drops. The incidence of adverse reactions was
`4.8% (6/124 patients) in the olopatadine group and 20.3%
`(25/123 patients) in the ketotifen group (p = 0.0002, Fisher’s
`exact test) (Saiga 2006). Thereafter, a long-term study was
`carried out in 20 patients with AC in which the study drug
`was administered at the same dose but for 70 days (Saiga et al
`2005). The patients were evaluated every 2 weeks using an
`ocular itching and conjunctival hyperemia scale. The ocular
`itching score decreased with time during treatment: 3.55 ±
`1.2 (mean ± SD) at baseline, 2.85 ± 1.5 at 2 weeks, 2.13 ±
`1.4 at 4 weeks, 2.08 ± 1.7 at 6 weeks, 1.75 ± 1.7 at 8 weeks,
`and 1.63 ± 1.7 at 10 weeks. The conjunctival hyperemia score
`showed a similar tendency; signs and symptoms markedly
`improved after the prolonged treatment period. No adverse
`reaction was observed, demonstrating the effi cacy and toler-
`ability of olopatadine hydrochloride 0.1% eye drops in the
`long-term treatment.
`
`Clinical evaluation of olopatadine
`hydrochloride in CAC study
`Conjunctival allergen challenge (CAC) was developed by
`Abelson et al (1990) to evaluate the effi cacy of anti-allergic
`ophthalmic solutions. CAC facilitates the evaluation, because
`in patients confi rmed to have antigen sensitivity, conjuncti-
`val allergic reaction is reproduced by antigen challenge at a
`standardized exact concentration, and then clinical symptoms
`are recorded based on evaluation scales described in the
`protocol. Because it also allows comparison between right
`and left eyes in the same individual, it is less likely to be
`affected by variations in individual differences than conven-
`tional environmental studies. Olopatadine hydrochloride was
`also evaluated for usefulness in terms of duration of action,
`resolution of ocular itching, and comfort upon instillation,
`using the CAC study scheme.
`Abelson and Greiner conducted a double-blind CAC
`study that involved 68 patients (Abelson and Greiner 2004).
`Olopatadine hydrochloride 0.1% eye drops and levocabastine
`hydrochloride 0.05% eye drops were randomly assigned to
`the right and left eyes in an individual, in a double-blind
`
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`Comparison of olopatadine
`hydrochloride with other eye drops
`Brockman et al (2003) examined cytotoxicity of each antihis-
`tamine in a concentration range at which the drug might be
`present after instillation by measuring lactate dehydrogenase
`(LDH), which is released from human conjunctival cells after
`cell membrane disruption. They reported that cell membrane
`disruption was observed in the ketotifen fumarate 0.025%
`group, epinastine hydrochloride 0.05% group, and azelas-
`tine hydrochloride 0.05% group, but not in the olopatadine
`hydrochloride 0.1% ophthalmic solution group, which may
`explain why patients felt less discomfort on instillation. In
`Japan, the aforementioned phase III study showed favorable
`tolerability of olopatadine hydrochloride 0.1% eye drops; in
`addition, Sumi et al (2008) compared the effects and satisfac-
`tion rating in 17 patients with Japanese cedar pollinosis who
`had used other anti-allergic eye drops in the previous year
`(levocabastine hydrochloride ophthalmic solution had been
`used by 10 patients, ketotifen fumarate ophthalmic solution
`by 3 patients, others by 2 patients, and unknown drugs by 2
`patients). These patients used olopatadine hydrochloride 0.1%
`ophthalmic solution after the onset of symptoms, and graded
`their ocular itching according to the visual analog scale (VAS).
`The score decreased from 6.59 at baseline to 3.91 at 2 weeks,
`with statistical signifi cance. The mean difference of the ocular
`itching score from baseline score was 7.38 with olopatadine
`hydrochloride 0.1% ophthalmic solution, which was higher
`than the score reduction obtained in the previous year (4.63).
`The level of satisfaction with treatment was investigated in
`patients who had used the most commonly prescribed levoca-
`bastine hydrochloride eye drops in the previous year; 78% of
`the patients preferred olopatadine eye drops to levocabastine
`
`Olopatadine
`Levocabastine
`
`∗
`
`3
`
`∗
`
`∗
`
`5
`7
`Time after antigen induction
`
`(minutes)
`
`(%)
`100
`
`80
`
`60
`
`40
`
`20
`
`0
`
`Percentage of subjects
`
`Figure 1 Percentage of responders: CAC (conjunctival allergen challenge) study
`comparing olopatadine hydrochloride 0.1% ophthalmic solution with levocabastine
`hydrochloride 0.025% ophthalmic solution. Percentage of responders (n = 20). A
`subject with itching score results of 0 after treatment was defi ned as a responder.
`*p ⬍ 0.05.
`
`Uchio
`
`manner. After treatment, ocular findings induced by a
`positive antigen were compared within 1 hour of dosing.
`Olopatadine hydrochloride 0.1% ophthalmic solution
`signifi cantly suppressed ocular itching (3 and 10 minutes
`after antigen induction, p ⬍ 0.001) and conjunctival
`hyperemia (3, 10, and 20 minutes after antigen induction,
`p ⬍ 0.0001) compared with levocabastine hydrochloride
`0.05% ophthalmic solution. Fewer patients complained
`of ocular discomfort in the olopatadine group than in the
`levocabastine group. Berdy et al (2000) compared ketotifen
`fumarate 0.025% ophthalmic solution with olopatadine
`hydrochloride 0.1% ophthalmic solution in 32 patients. One
`drop of the respective eye drops was instilled and the eye
`was challenged with the antigen 12 hours later. Olopatadine
`hydrochloride signifi cantly reduced the itching score (3,
`5, and 10 minutes after antigen induction, p ⬍ 0.05) and
`comfort score (p ⬍ 0.05) compared with ketotifen fumarate.
`Thus, these CAC study results showed that the effects of
`olopatadine hydrochloride 0.1% ophthalmic solution are
`observed within a few minutes after antigen challenge and
`they last for considerably long period.
`Ohno et al (2007) conducted a CAC study that involved
`20 Japanese (including patients of Japanese descent)
`patients with ACD (including Japanese cedar pollinosis) to
`compare olopatadine hydrochloride 0.1% eye drops with
`levocabastine hydrochloride 0.025% eye drops for effi cacy
`and comfort (Ohno et al 2007). Each eye was challenged
`with the antigen 3.5 hours after any of the two drugs had
`been instilled, and ocular itching was evaluated using
`a 5-grade scale of 0 (absent) to 4 (severe). Olopatadine
`hydrochloride markedly suppressed ocular itching compared
`with levocabastine hydrochloride; the mean score was 42%
`lower in olopatadine hydrochloride-treated eyes than in
`levocabastine hydrochloride-treated eyes. The number of
`responders (subjects with an ocular itching score of 0 after the
`treatment) was signifi cantly higher in the olopatadine group
`than in the levocabastine group (p ⬍ 0.05) (Figure 1). In
`contrast, ocular pain (25%) and burning sensation (20%) were
`observed in the levocabastine group, but no such symptoms
`were reported within the olopatadine group. Seventy-fi ve
`percent (15/20) preferred olopatadine hydrochloride 0.1%
`eye drops to levocabastine hydrochloride 0.025% eye drops
`according to their objective symptoms.
`As described above, the results of CAC studies performed
`both in Japan and other countries have demonstrated the
`effectiveness and usefulness of olopatadine hydrochloride
`0.1% ophthalmic solution in reducing ocular symptoms in
`patients with ACD.
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`eye drops because of higher therapeutic effects and more
`comfortable feeling upon instillation.
`Overseas, double-blind, controlled studies using an
`environmental study protocol have reported favorable effects
`and local tolerability of olopatadine hydrochloride 0.1%
`ophthalmic solution. Artal et al (2000) instilled 1 drop of
`olopatadine hydrochloride 0.1% ophthalmic solution into
`either right or left eye, and 1 drop of ketotifen fumarate 0.05%
`ophthalmic solution into the contralateral eye in 80 patients
`to investigate comfort upon instillation. They reported that all
`patients preferred olopatadine hydrochloride 0.1% to keto-
`tifen fumarate 0.05%. Aguilar (2000) conducted a random-
`ized double-blind controlled study to compare the effi cacy
`of olopatadine hydrochloride 0.1% eye drops and ketotifen
`fumarate 0.05% eye drops, and tolerability in 80 patients with
`allergic conjunctivitis. These drugs were instilled bid for 14
`days. Olopatadine hydrochloride 0.1% ophthalmic solution
`reduced itching as early as 30 minutes after the instillation
`and a higher percentage of patients reported improvement with
`olopatadine hydrochloride 0.1% ophthalmic solution than with
`ketotifen fumarate 0.05% ophthalmic solution. Aguilar (2000)
`also reported that mild reaction of intolerance (stinging) was
`observed in 23% of the ketotifen fumarate 0.05% ophthalmic
`solution group, but not in the olopatadine hydrochloride 0.1%
`ophthalmic solution group. Katelaris et al (2002) conducted a
`6-week, multicenter, randomized controlled study to compare
`the effects of olopatadine hydrochloride 0.1% ophthalmic solu-
`tion and disodium cromoglycate 2% ophthalmic solution on
`itching and hyperemia in 185 patients with seasonal allergic
`conjunctivitis. Group I received olopatadine hydrochloride
`0.1% ophthalmic solution bid and placebo bid, while Group II
`received disodium cromoglycate 2% ophthalmic solution qid
`Itching and hyperemia were suppressed in a signifi cantly higher
`percentage of patients in Group I (p ⬍ 0.05, vs Group II), and
`both groups showed favorable tolerability. They also reported
`that in children less than 11 years old, olopatadine hydrochlo-
`ride 0.1% ophthalmic solution seemed to be more tolerable
`than disodium cromoglycate 2% ophthalmic solution. It has
`been reported that olopatadine 0.1% ophthalmic solution is
`signifi cantly more effective than epinastine hydrochloride
`0.05% ophthalmic solution in controlling itching, redness, and
`chemosis associated with allergic conjunctivitis in the CAC
`model (Lanier et al 2004). Spangler et al (2001) compared the
`effect of olopatadine hydrochloride 0.1% ophthalmic solution
`and azelastine hydrochloride 0.05% in the CAC model, and
`found that both treatments were signifi cantly more effective
`than placebo at reducing itching post challenge; however,
`olopatadine was signifi cantly more effective than azelastine in
`
`Olopatadine hydrochloride eye drops in ocular allergy
`
`reducing itching at 3.5 minutes through 20 minutes post chal-
`lenge (average mean unit difference of –0.31; p ⬍ 0.05). In a
`placebo-controlled, randomized, parallel group, single-center
`study, both olopatadine 0.1% and ketorolac 0.5% ophthalmic
`solutions were found to be effective in alleviating the clinical
`signs and symptoms of SAC compared with placebo. However,
`olopatadine reduces ocular itching signifi cantly more than
`ketorolac (Yaylali et al 2003).
`In contrast, in a 30-day, randomized, double-masked,
`artifi cial tear substitute (ATS)-controlled clinical trial, in both
`active-treatment groups (olopatadine hydrochloride 0.1%
`and ketotifen fumarate 0.025% ophthalmic solutions), the
`improvements in clinical scores (tearing and itching) were
`more pronounced compared with those in the ATS group,
`although the day-30 difference in tearing score between the
`olopatadine and ATS groups was not statistically signifi cant
`(Avunduk et al 2005). Ganz et al (2003) carried out a 3-week
`prospective, randomized, double-masked, parallel-group study
`to compare ketotifen fumarate 0.025% ophthalmic solution
`and olopatadine hydrochloride 0.1% ophthalmic solution in
`66 patients with SAC. The responder rate was higher with
`ketotifen than with olopatadine on day 5 (72% vs 54% for
`patient assessment, 88% vs 55% for investigator assessment)
`and day 21 (91% vs 55%, 94% vs 42%). Global effi cacy rat-
`ings were also higher with ketotifen, and severity scores for
`hyperemia and itching were signifi cantly lower. Although the
`reason for these confl icting results is unclear, differences in
`study design or study population might be the explanation.
`
`Clinical effect of olopatadine
`0.2% eye drops
`Overseas, olopatadine hydrochloride 0.2% ophthalmic solu-
`tion for a once-daily regimen has been marketed under the
`brand name of Pataday®. Its effect lasts 24 hours (Vogelson
`et al 2004). Abelson et al carried out a randomized double-
`blind placebo controlled study using a CAC study protocol
`that involved 23 patients (Abelson et al 2008). Olopatadine
`hydrochloride 0.2% ophthalmic solution was instilled once
`daily into one eye and olopatadine hydrochloride 0.1% oph-
`thalmic solution was instilled twice a dally into the contra-
`lateral eye. They reported that ocular itching was suppressed
`in both treatment groups compared with a placebo group at
`24 hours, and there was no difference in ocular itching sup-
`pression or occurrence of adverse drug reactions between the
`two groups. Mah et al conducted a randomized placebo con-
`trolled study using a CAC study protocol in which 92 subjects
`were distributed into 4 groups: olopatadine hydrochloride vs
`placebo, epinastine hydrochloride vs placebo, olopatadine
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`Uchio
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`hydrochloride vs epinastine hydrochloride, and placebo vs
`placebo (Mah et al 2007). Olopatadine hydrochloride 0.2%
`ophthalmic solution signifi cantly suppressed ocular itching
`by 5–7 minutes after antigen challenge compared with epi-
`nastine hydrochloride 0.05% ophthalmic solution (p = 0.024
`and p = 0.003, respectively), and its effects on conjunctival
`hyperemia and comfort upon instillation were more favorable
`as well (p = 0.003). A placebo-controlled study has also dem-
`onstrated the safety profi le of olopatadine hydrochloride 0.2%
`ophthalmic solution in children and adolescents (Lichtenstein
`et al 2007). Although olopatadine hydrochloride 0.2% eye
`drops cannot be used clinically in Japan, physicians will be
`attracted to the drug in the near future especially because of
`its improved compliance.
`
`Possibility of future optional
`use of olopatadine eye drops
`In Japan among pollinosis patients, treatment for nasal symp-
`toms has been relatively prioritized, while ocular symptoms
`have not been given suffi cient importance (Kakutani et al
`2005). Berger et al conducted a prospective multicenter cross-
`over study that involved 200 patients with allergic rhinitis.
`Of these, 90.5% had some concurrent ocular symptoms, and
`ocular treatment with olopatadine hydrochloride 0.1% eye
`drops combined with nasal treatment improved ocular allergic
`symptoms and their QOL compared with the nasal treatment
`only (Berger et al 2005). From the results in CAC studies, it
`may be possible that olopatadine hydrochloride 0.1% or 0.2%
`ophthalmic solution has an important role if used for these
`multi-organ cases by resolving ocular symptoms promptly and
`potently. Interestingly, it has been reported that olopatadine
`0.2% ophthalmic solution, relative to placebo, signifi cantly
`reduced the frequency of pollen effects on sneezing and itchy
`nose, and reduced the severity of pollen effects on sneezing,
`itchy nose, and runny nose, indicating its additional effect on
`nasal allergy (Abelson et al 2005).
`For patients with a more severe spectrum of ACD, such as
`VKC and AKC, immunosuppressive eye drops (cyclosporine
`or tacrolimus) have been introduced for topical treatment
`in Japan. It has been reported that 2 months’ treatment
`with olopatadine hydrochloride 0.1% relieves the signs and
`symptoms of VKC (Corum et al 2005). Also, it reduces the
`number of goblet cells, which, in turn, decreases the amount
`of mucus discharge in VKC during treatment. Although
`similar reports are limited at present, this research suggests
`that olopatadine 0.1% eye drops may become an important
`option in the treatment of VKC and AKC.
`
`Conclusions
`Olopatadine hydrochloride ophthalmic solution has an
`excellent, strong, and safe anti-allergic effect in vitro and
`it provides superior clinical effectiveness in patients with
`AC compared with other histamine antagonistic ophthalmic
`solutions or non-steroidal anti-infl ammatory eye drops.
`Also, ACD patients feel signifi cantly less discomfort upon
`instillation. Although further clinical evaluation is neces-
`sary, olopatadine hydrochloride eye drops has the potential
`for simultaneous use with nasal drugs for pollinosis, and
`also may be used in patients with more severe conditions,
`such as VKC or AKC, in the near future.
`
`Disclosures
`The author has no confl icts of interest to disclose.
`
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