Conjunctival Allergen Challenge Research Articles

Bepreve TM 1.5% Reduces Rhinorrhea for at Least 16 Hours: An Integrated Analysis of Two Phase 3 Conjunctival Allergen Challenge (CAC) Clinical Trials

Bepreve TM 1.5% Reduces Rhinorrhea for at Least 16 Hours: An Integrated Analysis of Two Phase 3 Conjunctival Allergen Challenge (CAC) Clinical Trials

Bepreve TM 1.5% Reduces Nasal Congestion for at Least 16 Hours: An Analysis of Integrated Data from Two Phase 3 Conjunctival Allergen Challenge (CAC) Clinical Trials

Bepreve TM 1.5% Reduces Nasal Congestion for at Least 16 Hours: An Analysis of Integrated Data from Two Phase 3 Conjunctival Allergen Challenge (CAC) Clinical Trials

Time to onset and duration of action of the antihistamine bepotastine besilate ophthalmic solutions 1.0% and 1.5% in allergic conjunctivitis: A phase III, single-center, prospective, randomized, double-masked, placebo-controlled, conjunctival allergen challenge assessment in adults and children

Background: Bepotastine besilate is a highly selective histamine H 1-receptor antagonist with antihistaminic, mast cell stabilizing, and anti-inflammatory activity. Based on a history of clinical effectiveness and tolerability of oral bepotastine besilate in the treatment of allergic symptoms, bepotastine besilate is being tested as a potential ophthalmic medication for allergic conjunctivitis. Objective: The aim of this study was to assess the effects of bepotastine besilate ophthalmic solution 1.0% and 1.5% for the treatment of ocular itching and conjunctival hyperemia in a conjunctival allergen challenge (CAC) model in adults and children. Methods: This Phase III, single-center, prospective, randomized, double-masked, placebo-controlled, CAC clinical trial enrolled patients ≥10 years of age with a history of allergic conjunctivitis, skin-test reaction, and CAC response. Patients received bepotastine besilate ophthalmic solution 1.0%, bepotastine besilate ophthalmic solution 1.5%, or placebo, 1 drop on each eye on days 14 ± 3 and 28 ± 3. The primary efficacy end points, patient-assessed ocular itching (at 3, 5, and 7 minutes) and investigator-assessed conjunctival hyperemia (at 7, 15, and 20 minutes), were determined after CAC according to standardized 5-point scales (0 = none to 4 = severe). Clinical significance was defined in the protocol as ≥1.0-U between-group difference in mean ocular itching scores at the majority of time points at a study visit and also a ≥0.5-U difference at all time points. Tolerability of the test agent was assessed by visual acuity, slit-lamp biomicroscopy, intraocular pressure, dilated funduscopy, and adverse events. Results: A total of 107 patients (male, 54%; age range, 11–73 years; white race/ethnicity, 93%) received investigational product and comprised the intent-to-treat (ITT) population (bepotastine besilate ophthalmic solution 1.0%, 36 patients; bepotastine besilate ophthalmic solution 1.5%, 35; and placebo, 36). All 107 patients received investigational product at visit 3A (day 0) and were included in the ITT population. Of the 107 patients who were enrolled, 103 completed the study without a protocol deviation or violation. The 1.0% and 1.5% solutions were associated with clinically and statistically significant reductions in mean ocular itching scores compared with placebo on the 15-minute onset-of-action and 8-hour duration-of-action CAC tests (reductions, 1.3–1.5 U and 1.0–1.7 U respectively; all, P < 0.001). Statistically significant reductions in conjunctival hyperemia were achieved with both bepotastine besilate concentrations. Overall, 13 patients experienced a treatmentemergent adverse event considered related to the study drug (bepotastine besilate ophthalmic solution 1.0%, 6 patients; bepotastine besilate ophthalmic solution 1.5%, 4; and placebo, 3). Conclusions: In this CAC model of allergic conjunctivitis in adults and children, bepotastine besilate ophthalmic solutions 1.0% and 1.5% were associated with clinically and statistically significant reductions in ocular itching, but not conjunctival hyperemia, within 15 minutes that were maintained for at least 8 hours after administration. Both solutions were well tolerated. ClinicalTrials.gov identifier: NCT00424398.

Evaluation of desloratadine on conjunctival allergen challenge‐induced ocular symptoms

Allergic conjunctivitis (AC) is frequently associated with allergic rhinitis (AR) and affects up to 91% of patients with AR. Desloratadine, an orally administered, non-sedating second-generation antihistamine, has proven efficacy and safety in the control of nasal and non-nasal--including ocular--symptoms of AR. This randomized-controlled trial is the first to evaluate the effects of continuous oral desloratadine treatment on ocular symptoms after conjunctival allergen challenge. To evaluate the impact of administering oral desloratadine 5 mg daily for 7 days on ocular symptoms in conjunctival allergen-challenged subjects. In this crossover study, adults with a history of seasonal AC and a minimal threshold response to allergen challenge were randomized to receive desloratadine 5 mg daily (n=20) or placebo (n=21) for 7 days after which they underwent a second ocular allergen challenge. After a 2-week washout period, subjects crossed over to the other treatment. The primary efficacy parameter was the intra-subject difference from baseline at end-point in the post-challenge mean composite ocular redness score (the sum of redness scores in ciliary, conjunctival, or episcleral vessel beds). Secondary efficacy parameters included the intra-subject and inter-subject differences in individual symptom scores for ciliary, conjunctival, or episcleral redness; pruritus; chemosis; eyelid swelling; and tearing. The mean composite ocular redness score was reduced at 10, 15, and 20 min post-challenge with desloratadine treatment compared with placebo, though these differences were not statistically significant (P=NS). Desloratadine was significantly more effective than placebo in preventing post-challenge ocular pruritus (P<0.001). Significant improvements post-challenge were also seen in ciliary and episcleral redness, chemosis, eyelid swelling, and tearing (P<0.05 vs. placebo for all comparisons). Desloratadine was well tolerated. Treatment with desloratadine 5 mg daily for 7 days reduced allergic ocular symptoms following allergen challenge.

Bepotastine Besilate Ophthalmic Solution 1.0% Provides Rapid Relief of Rhinorrhea, Total Non-Ocular Symptoms, Tearing, and Ciliary and Episcleral Hyperemia Following Dosing in a Multi-Site Clinical Model of Allergic Conjunctivitis

RATIONALE: To establish the efficacy and safety of bepotastine besilate ophthalmic solution 1.0%, an investigational anti-histamine eye drop, compared to placebo in reducing multiple ocular and non-ocular signs and symptoms using the Conjunctival Allergen Challenge (CAC) model of allergic conjunctivitis at 15 minutes after ophthalmic dosing.

Examination of the Nasal Symptom Response to the Conjunctival Allergen Challenge (CAC) using Subjective and Objective Measures of Nasal Congestion

Examination of the Nasal Symptom Response to the Conjunctival Allergen Challenge (CAC) using Subjective and Objective Measures of Nasal Congestion

A comparison of olopatadine 0.2% ophthalmic solution versus fluticasone furoate nasal spray for the treatment of allergic conjunctivitis

Allergic conjunctivitis is an inflammatory condition of the ocular surface characterized by ocular itching, redness, tearing, chemosis, and eyelid swelling. The purpose of this study was to assess the comparative efficacy of an ophthalmic antihistamine/mast cell stabilizer solution and an intranasal steroid at reducing the signs and symptoms of allergic conjunctivitis induced by the conjunctival allergen challenge (CAC) model. Sixty subjects were enrolled in a single center, randomized, placebo-controlled, parallel-treatment, four-visit CAC study. After titration and confirmation of the allergic reaction at visits 1 and 2, subjects were randomized at visit 3 into one of 4 treatment groups (olopatadine 0.2% ophthalmic solution, fluticasone furoate nasal spray, a tear substitute, or saline nasal spray), dosed with study medication, and challenged 15 minutes later, after which ocular allergic signs and symptoms were assessed. Subjects continued treatment of the assigned medication for 6 days. At visit 4, subjects underwent similar procedures to those performed at visit 3. Fifty-nine subjects completed the study. Olopatadine 0.2% ophthalmic solution showed statistical and clinical superiority over fluticasone furoate nasal spray at all post-CAC time points after a single dose (p < 0.001) and after a 1-week loading period (p < 0.01) for ocular itching, the primary end point. Similarly, olopatadine 0.2% showed statistical and clinical superiority over fluticasone furoate for the majority of time points for ocular redness, tearing, chemosis, and eyelid swelling. Olopatadine 0.2% ophthalmic solution was statistically and clinically superior to fluticasone furoate nasal spray for the relief of signs and symptoms of allergic conjunctivitis.

Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops

Olopatadine hydrochloride exerts a wide range of pharmacological actions such as histamine H(1) receptor antagonist action, chemical mediator suppressive action, and eosinophil infiltration suppressive action. Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol((R))) was introduced to the market in Japan in October 2006. In a conjunctival allergen challenge (CAC) test, olopatadine hydrochloride 0.1% ophthalmic solution significantly 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((R)). 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.

Bioequivalence of two formulations of ketotifen fumarate ophthalmic solution: A single-center, randomized, double-masked conjunctival allergen challenge investigation in allergic conjunctivitis

Background: Ketotifen fumarate ophthalmic solution 0.025% (reference formulation), a topical mast cell stabilizer/antihistamine combination, has been found to be effective and well tolerated in the prevention of ocular itching associated with allergic conjunctivitis (AC). A recently developed formulation of ketotifen fumarate ophthalmic solution 0.025% (test formulation) contains the same active ingredient in the same concentration as the reference formulation, is intended for twice-daily dosing, and may provide a treatment option in patients with AC. Objective: The aim of this study was to determine the clinical bioequivalence of the test and reference formulations using a conjunctival allergen challenge (CAC) model. Methods: This prospective, randomized, double-masked, active- and placebo-controlled CAC study was conducted in a clinical setting (ORA Clinical Research and Development, North Andover, Massachusetts). Patients aged <18 years who had AC, a successful allergen challenge during screening and allergen confirmation visits, a history of ocular allergies, and positive skin-test reactivity were enrolled. Patients' eyes were randomized to receive the test or reference formulation or inactive vehicle (1 drop of 1 study medication per eye per visit). The primary efficacy end point was ocular itching, and the secondary end points were ocular redness, chemosis, lid swelling, tearing, and mucous discharge. Efficacy was assessed following challenge at 8 hours and 15 minutes after instillation. The test and reference formulations were considered bioequivalent if the 95% CIs for the differences in mean ocular itching scores between the 2 groups were within the range of 0.40 to 0.40. Results: There were 108 patients enrolled (61 men, 47 women; mean age, 42 years; 91.7% white). The test and reference formulations both yielded clinically significant results compared with placebo in the prevention of ocular itching at CACs performed 8 hours and 15 minutes after instillation. At the 8-hour posttreatment CAC, the mean ocular itching scores for test formulation-treated eyes were 1.158, 1.265, and 1.305 units lower, respectively, than for eyes at 3, 5, and 7 minutes that were administered placebo. At 15-minute posttreatment CAC, the mean ocular itching scores for reference formulation-treated eyes at 3, 5, and 7 minutes were 1.481, 1.622, and 1.565 units lower, respectively, than for eyes that were administered placebo. With regard to the primary and secondary efficacy variables, no statistically significant differences were observed between test and reference formulations at any post-CAC time point. Conclusions: In this population of patients with AC, the test formulation of ketotifen fumarate ophthalmic solution 0.025% met criteria for bioequivalence to the reference formulation, as established by the protocol. The test and reference formulations were well tolerated in the population studied.

Efficacy of olopatadine ophthalmic solution 0.2% in reducing signs and symptoms of allergic conjunctivitis

Olopatadine hydrochloride ophthalmic solution 0.2% (Pataday, Alcon) is a new formulation of olopatadine hydrochloride ophthalmic solution, the first topical ocular antiallergic agent indicated for once-daily dosing. The aim of this study was to evaluate the safety, efficacy, onset, and duration of action of olopatadine 0.2% in the treatment of allergic conjunctivitis. Using the conjunctival allergen challenge, this double-masked, randomized by eye, parallel-group study included four visits over a 5-week period. Subjects were screened for eligibility (visit 1) and their ocular allergic responses were confirmed at visit 2. The efficacy of olopatadine in reducing the signs and symptoms of allergic conjunctivitis was evaluated at onset of action (visit 4) and 16 hours (visit 3) after masked medication instillation. The primary efficacy parameter was ocular itching. Safety parameters were also evaluated. Ninety subjects were evaluated. Olopatadine 0.2% was significantly (p < 0.001) more effective than placebo in the treatment of ocular itching at all time points at both the onset of action and the 16-hour allergen challenges. Olopatadine 0.2% was significantly (p < 0.03) more effective than placebo in the reduction of conjunctival redness, chemosis, and eyelid swelling at all time points (with the exception of conjunctival redness, which was significantly reduced at five of six time points). There were no serious adverse events and no treatment-related adverse events. Once-daily dosing with olopatadine 0.2% reduced the signs and symptoms of allergic conjunctivitis with a rapid and prolonged duration of action. Safety analyses indicated that olopatadine 0.2% was safe and well tolerated in subjects with a history of allergic conjunctivitis.

Efficacy and comfort of olopatadine 0.2% versus epinastine 0.05% ophthalmic solution for treating itching and redness induced by conjunctival allergen challenge

ABSTRACTBackground: Olopatadine 0.2% (Pataday, Alcon Laboratories Inc., Fort Worth, Texas, USA) and epinastine 0.05% (Elestat, Inspire Pharmaceuticals, Inc., Durham, NC, USA) are topical ocular anti-allergic agents. Both are H1 antihistamine/mast cell stabilizers indicated for the treatment of ocular itching associated with allergic conjunctivitis.Objective: To compare the efficacy and comfort of olopatadine 0.2% with epinastine 0.05%, in the prevention of ocular itching associated with allergic conjunctivitis following conjunctival allergen challenge (CAC).Research design and methods: This was a 7 week, four visit, double-masked, randomized, placebo-controlled CAC study. Visit 1 screened subjects for positive ocular allergic responses and Visit 2 confirmed those responses. At Visit 3, 92 subjects were randomized into one of four treatment groups to receive one drop of study medication in each eye: (1) olopatadine 0.2%/placebo, (2) epinastine 0.05%/placebo, (3) olopatadine 0.2%/epinastine 0.05%, (4) placebo/placebo. Subjects were challenged 12 h after drop instillation to evaluate duration of action. At Visit 4, subjects were challenged 5 min after drop instillation to evaluate onset of action. Drop comfort was assessed at Visit 4.Main outcome measures; results: This article focuses on the results of the onset-of-action challenge (Visit 4). At Visit 4, ocular itching was assessed at 3, 5, and 7 min and redness was assessed at 7, 15, and 20 min post-challenge. Drop comfort was assessed upon instillation, at 30 s, and at 1, 2, and 5 min post-instillation. Olopatadine 0.2%-treated eyes exhibited significantly lower mean ocular itching scores versus epinastine 0.05%-treated eyes at 5 ( p = 0.024) and 7 min ( p = 0.003) post-challenge. Olopatadine 0.2%-treated eyes exhibited significantly lower mean redness scores versus epinastine 0.05%-treated eyes at all time points post-challenge (ciliary: p ≤ 0.013, conjunctival: p ≤ 0.015, episcleral: p ≤ 0.006). Olopatadine 0.2% was rated as significantly more comfortable than epinastine 0.05% at 1 min post-drop instillation ( p = 0.003). All adverse events were non-serious and unrelated to study medication. Although the CAC model reproduces allergic responses that are not environmentally-induced, patients experience varying severities of responses as are seen in real-world situations.Conclusion: Olopatadine 0.2% was superior to epinastine 0.05% in preventing ocular itching and redness at onset when induced by the CAC model.

A Single-Center, Double Masked, Randomized, Placebo Controlled Study to Evaluate the Efficacy of Multiple Doses of 10 mg Montelukast Sodium (Singulair®) on the Signs and Symptoms of Allergic Conjunctivitis Using the Conjunctival Allergen Challenge (CAC) Model

A Single-Center, Double Masked, Randomized, Placebo Controlled Study to Evaluate the Efficacy of Multiple Doses of 10 mg Montelukast Sodium (Singulair®) on the Signs and Symptoms of Allergic Conjunctivitis Using the Conjunctival Allergen Challenge (CAC) Model

Efficacy of Once-Daily Olopatadine 0.2% Ophthalmic Solution Compared to Twice-Daily Olopatadine 0.1% Ophthalmic Solution for the Treatment of Ocular Itching Induced by Conjunctival Allergen Challenge

Olopatadine 0.1% (Patanol®) and olopatadine 0.2% (PatadayTM) ophthalmic solutions are topical ocular anti-allergic agents with antihistaminic and mast cell stabilizing properties. The efficacy of two doses of olopatadine 0.1% was compared to one dose of olopatadine 0.2% in the prevention of ocular itching associated with allergic conjunctivitis over 24 hours. This double-masked conjunctival allergen challenge (CAC) study found no significant difference in the mean itching scores between two drops of olopatadine 0.1% and one drop of olopatadine 0.2%. Both showed significant activity at the 24-hour time point and were statistically superior to placebo. No adverse events occurred while on drug therapy.

Do skin prick and conjunctival provocation tests predict symptom severity in seasonal allergic rhinoconjunctivitis?

In the investigation of seasonal allergic rhinoconjunctivitis (SAR), quantitative skin and conjunctival allergen challenge tests are used to measure individual allergen sensitivity. These tests are reproducible and relate well to prevalence but their relationship to symptom severity is less well established. We wished to determine if quantitative skin prick tests (QSPT) and conjunctival provocation tests (CPTs) using a single grass pollen allergen extract are reproducible and predict symptom severity in SAR. We retrospectively analysed data from 91 participants in a previously published randomized placebo controlled study of low dosage allergen immunotherapy who were randomized to receive placebo treatment. We examined the relationship between pre-seasonal QSPT, CPT and SAR symptoms. We found a high level of reproducibility when repeated measures were compared for both the QSPT (P < 0.001) and the CPT (P < 0.001) and moderate correlation (0.49) between the standard skin prick test (SPT) and the QSPT (P < 0.001). We found weak negative correlation (-0.27) between the QSPT and the CPT (P < 0.001). We found no correlation between seasonal symptom, use of rescue medication or quality of life (QOL) scores and pre-seasonal QSPT or CPT. Conclusion In the assessment of seasonal rhinoconjunctivitis, quantitative skin and conjunctival allergen challenge tests are strongly reproducible, although there is no correlation between these tests and seasonal symptom, use of rescue medication or QOL scores.

Efficacy and response with olopatadine versus epinastine in ocular allergic symptoms: A post hoc analysis of data from a conjunctival allergen challenge study

Objectives: This post hoc analysis used data from a previous study to more precisely evaluate the efficacy of olopatadine hydrochloride and epinastine hydrochloride in alleviating various levels of severity of ocular itching and conjunctival redness and to determine whether there were any significant differences in the number of responders to treatment. Methods: The original study was a randomized, double-masked allergen challenge comparison assessment. Adult patients with allergic conjunctivitis were screened (visits 1 and 2); those who exhibited positive allergic reactions at both visits were randomized to 1 of 3 groups. olopatadine/epinastine, olopatadine/placebo, or epinastine/placebo. At visit 3, each eye was treated with study medication, and then challenged with allergen. Itching, redness, and chemosis assessments were recorded. For the present post hoc analysis, each eye in the olopatadine/epinastine group was separately classified at each time point, based on the pretreatment severity of their symptom (itching) and sign (conjunctival redness) scores, as moderate, moderate/severe, or severe. Data were analyzed to determine responders (eyes with itching and/or conjunctival redness scores of 0 [none]). Results: Of 96 patients screened, 66 were randomized to treatment (36 women, 30 men; mean age, 44.38 years [range, 20–71 years]). Olopatadine-treated eyes exhibited lower mean itching scores than epinastinetreated eyes in the moderate/severe and severe groups at all 3 time points (3, 5, and 7 minutes), with significance in the moderate/severe group at 5 minutes ( P = 0.05) and in the severe group at 5 and 7 minutes ( P = 0.017 and P = 0.02, respectively). Olopatadine-treated eyes had mean conjunctival redness scores similar to epinastine-treated eyes in all severity groups at all time points (10, 15, and 20 minutes) except in the severe group at 10 minutes ( P = 0.03). On response analysis, for itching, the proportion of responders was significantly greater in the olopatadine group versus the epinastine group 7 minutes after challenge (27 [50.9%] vs 14 [26.4%]; P = 0.016). For conjunctival redness, the proportion of responders was significantly greater with olopatadine treatment versus epinastine treatment at 15 and 20 minutes after challenge (15 minutes, 12 [22.6%] vs 1 [1.9%] [ P = 0.002]; 20 minutes, 10 [18.9%] vs 1 [1.9%] [ P = 0.008]).

Efficacy of Levocabastine Hydrochloride Ophthalmic Suspension in the Conjunctival Allergen Challenge Test in Japanese Subjects with Seasonal Allergic Conjunctivitis

This study was conducted to investigate the efficacy and safety of 0.025% levocabastine hydrochloride in Japanese subjects with seasonal allergic conjunctivitis and its duration of action using the conjunctival allergen challenge (CAC) test. Twenty-four asymptomatic subjects were randomized to instill 0.025% levocabastine ophthalmic suspension in one eye and vehicle in the other eye 10 minutes before the CAC test. Signs and symptoms of allergic conjunctivitis were scored 10, 15, and 25 minutes after the CAC test. The duration of drug effects was also evaluated by allergen rechallenge 4 hours after levocabastine administration. The itching score for each eye as the primary efficacy endpoint was assessed 15 minutes after the CAC test using a 5-point scale. The mean itching score in the levocabastine-treated group was 0.08 +/- 0.06, which was significantly lower than the mean score of 1.98 +/- 0.16 in the vehicle group (P < 0.0001). The redness and chemosis of the conjunctiva were also improved significantly compared with the vehicle group. Levocabastine showed prolonged efficacy in inhibiting itching (0.42 +/- 0.12 vs 0.94 +/- 0.17, P < 0.0002) and redness (1.04 +/- 0.18 vs 1.42 +/- 0.22, P < 0.01) of the conjunctiva upon the rechallenge test. No significant topical or systemic adverse safety findings were observed in the levocabastine group. The results indicate that 0.025% levocabastine ophthalmic suspension is effective and safe in the treatment of allergic conjunctivitis with a duration of action of at least 4 h.

A comparison of the clinical efficacy of pheniramine maleate/naphazoline hydrochloride ophthalmic solution and olopatadine hydrochloride ophthalmic solution in the conjunctival allergen challenge model

The signs and symptoms of allergic conjunctivitis include ocular redness and itching. Two treatment options currently indicated for acute ocular allergic reaction are pheniramine maleate 0.3%/naphazoline hydrochloride 0.025% ophthalmic solution, an over-the-counter antihistamine/vasoconstrictor combination; and olopatadine hydrochloride 0.1% ophthalmic solution, a prescription antihistamine/mast cell stabilizer. This study was designed to compare, at onset of action, the relative effectiveness of pheniramine/naphazoline and olopatadine, when administered before conjunctival allergen challenge (CAC), using the ocular allergy index (OAI) as the primary end point. This was a prospective, randomized, double-masked, contralateral, active- and placebo-controlled, single-center study of the CAC model. The first 2 study visits established and confirmed the subjects' ocular allergic reaction (no medication administered). At visit 3, the subjects were randomly assigned to 1 of 3 contralateral (right eye vs left eye) treatment combinations: pheniramine/naphazoline + olopatadine, pheniramine/naphazoline + placebo, or olopatadine + placebo. Medication was given 10 minutes before CAC. The subjects' erythema in the ciliary, conjunctival, and episcleral vessel beds; eyelid swelling; chemosis; and itching were evaluated at 7, 12, and 20 minutes after CAC. The OAI was calculated as a composite score of 6 signs and symptoms of allergic conjunctivitis to assess global severity. Between-treatment differences in OAI scores were used to evaluate efficacy. Subjects were asked their eye drop preference at the conclusion of visit 3. Subjects (n = 83) ranged in age from 20 to 70 years (mean, 42.5 years), 61.4% (n = 51) were female, and 94.0% (n = 78) were white. Both pheniramine/naphazoline and olopatadine were associated with significantly lower OAI scores than placebo at all 3 time points (all, P < 0.001). OAI scores were significantly lower with pheniramine/naphazoline than with olopatadine at 12 and 20 minutes (P = 0.005 and P = 0.001, respectively). In this patient sample, studied in a CAC model of onset of action, prophylactic pheniramine/naphazoline was more effective than olopatadine and placebo in alleviating the signs and symptoms of the acute ocular allergic reaction, as measured by the OAI.

Efficacy and safety of single‐ and multiple‐dose ketotifen fumarate 0.025% ophthalmic solution in a pediatric population

Allergic conjunctivitis can seriously disrupt children's daily activities. This study assessed the efficacy (onset and duration of action) and safety of ketotifen fumarate 0.025% ophthalmic solution compared with vehicle placebo in pediatric subjects after single and multiple dosing. This was a double-masked, multicenter, fellow-eye, placebo-controlled, conjunctival allergen challenge trial. Eligible subjects (8-16-yr-olds) who produced a qualifying reaction to allergen were randomized to a single dose (one drop) of ketotifen fumarate in one eye and vehicle placebo in the fellow eye, followed by an allergen challenge at 15 min and 8 h post-dose. Subjects who had a qualifying reaction to allergen in the placebo-treated eye and a qualifying response to ketotifen in the active-treated eye following the single dose were re-randomized to a multiple-dose treatment period. They were instructed to instill one drop of ketotifen fumarate in one eye and placebo in the other eye twice daily for 4 wk. An allergen challenge was conducted 8 h after the last dose. The primary efficacy assessment was ocular itching, judged by the subject at 3, 7, and 10 min post-allergen challenge after single- and multiple-dose treatments. Other ocular signs and symptoms were assessed at 7, 10, and 15 min post-dose. A total of 133 subjects were randomized to single-dose treatment; 105 were evaluable for efficacy. Of these, 60 were re-randomized to multiple-dose treatment, and 55 were evaluable for efficacy. After single and multiple doses, ketotifen fumarate significantly inhibited ocular itching compared with placebo at all post-challenge timepoints (p < 0.001) and also significantly reduced hyperemia, chemosis, and lid swelling (p = 0.031). No drug-related systemic adverse events were reported, and ocular adverse events were comparable to placebo. No subject discontinued prematurely due to an adverse event. These results indicate that ketotifen fumarate 0.025% ophthalmic solution is an effective and safe treatment option for children with allergic conjunctivitis.

Le Test de provocation conjonctivale allergénique : recommandations pratiques pour le diagnostic des conjonctivites allergiques. Compte-rendu de la table ronde du Groupe Ophtalmo Allergo (GOA) (Journées parisiennes d’allergie, 10 janvier 2004)

Conjunctival allergen challenge (CAC) is the only way to confirm allergen involvement in the diagnosis of allergic conjunctivitis. Implementation of CAC for diagnostic purposes was the subject of a round table discussion during the last meeting of the Group ophthalmoallergo. The main conclusions of the discussion are reported here. After a brief review of the indications for CAC, the group discussed different aspects of CAC: criteria for the diagnosis of sensitisation; safety considerations; the nature and quality of the allergen extracts used; the possibility of avoiding responsible allergens and drugs; contraindications. A consensus was reached regarding the practice of CAC for the diagnosis of allergic conjunctivitis, the dose escalation protocol for allergen instillation, the clinical as well as the complementary criteria for positivity, and interpretation of the results. The group agreed on the need to consider two distinct patient populations, outpatients and inpatients, according to the CAC technique to be used and the follow-up to be considered. Outpatients usually have benign forms of allergic conjunctivitis (acute and seasonal or chronic) due to common allergens (mainly domestic allergens and aeroallergens). In these patients, CAC can be carried out in a medical environment, with an allergist or an ophthalmologist being present, in which case escalation of the allergen dose instilled in the conjunctivae can be rapid and positivity can be assessed by evaluating the pruritus only. Inpatients, affected mainly by vernal keratoconjunctivitis, will have to undergo a more detailed investigation to identify the triggering factor. In these cases, CAC should be carried out by an ophthalmology service. The clinical and biological criteria for positivity are multiple, and a wider variety of allergens may be tested, using a slower dose escalation. In both types of patients, 20 μL of the allergen are instilled every 30 minutes, and the reaction is assessed 15 minutes after each instillation. Emergency measures, including an oral histamine H1 antagonist, an inhalation bronchodilator, and topical and systemic steroids, must be available. Patients must be observed closely until the procedure is completed. If an ocular reaction occurs, an antihistamine should be instilled locally and the patient followed for an additional two hours. In addition, a topical and an oral antihistamine should be prescribed to be used in case the patient has a conjunctival or systemic reaction after discharge. These national guidelines should help practitioners to standardize CAC. They will be reevaluated in three years.

Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model

SUMMARYObjective: To compare the efficacy of olopatadine and levocabastine in reducing ocular allergic itching and vascular hyperemia (redness) induced by conjunctival allergen challenge.Research design and methods: The study was a randomized, double-masked, contralateral study using the conjunctival allergen challenge (CAC) model. At Visit 1, subjects with a positive allergen skin test and a history of allergic conjunctivitis were administered increasing concentrations of allergen until at least a moderate grade 2 ocular itching and conjunctival redness response was obtained in both eyes. Allergic signs were graded on standardized 0–4 scales. Subjects who reacted positively were re-challenged at Visit 2 with the pre-determined concentration of allergen. Subjects who again responded with at least a grade 2 bilateral ocular itching and conjunctival redness score at Visit 2 were eligible for drug evaluation. At Visit 3, subjects received olopatadine in one eye and levocabastine in the contralateral eye according to a computer-generated randomization scheme generated prior to commencement of the study. Ocular discomfort was then graded in both eyes. Subjects were bilaterally challenged with the predetermined concentration of allergen 27 min after topical drug administration, such that the first post-challenge assessment was made 30 min post-drug instillation. Allergic signs and symptoms were evaluated at 3 min, 10 min, and 20 min post-challenge and safety and efficacy analyses were performed.Results: Sixty-eight subjects received study drug and were included in the safety and efficacy analyses. Ocular itching scores for olopatadine were significantly lower than levocabastine at 3 min and 10 min post-challenge ( p < 0.001). Ocular redness scores for olopatadine were significantly lower than levocabastine at all time points post-challenge ( p < 0.0001). Of all subjects, 4.41% reported ocular discomfort in the olopatadine eye and 26.5% in the levocabastine treated eye.Conclusion: Olopatadine treated eyes had significantly less itching and redness than levocabastine treated eyes after conjunctival allergen challenge. Olopatadine was also associated with less discomfort upon instillation than levocabastine.