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

SUMMARY

Objective: 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.     

Clinical efficacy of olopatadine vs epinastine ophthalmic solution in the conjunctival allergen challenge model

SUMMARY

Background: Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol*) and epinastine hydrochloride 0.05% ophthalmic solution (Elestat?) are two topical antiallergic agents. Olopatadine is indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis.

Objective: This study compared the clinical efficacy of olopatadine and epinastine in the prevention of itching and conjunctival redness in the conjunctival allergen challenge (CAC) model.

Research design and methods: This was a prospective, randomized, double-masked, contralaterally-controlled, single center allergen challenge study. Ninety-six subjects with a history of allergic conjunctivitis were screened, and the 66 who responded to conjunctival allergen challenge at visits 1 and 2 were randomized into 1 of 3 treatment groups at visit 3 to receive one drop of study medication in each eye: (1) olopatadine in one eye and epinastine in the fellow eye, (2) olopatadine in one eye and placebo in the fellow eye, and (3) epinastine in one eye and placebo in the fellow eye. Five minutes after study drop instillation, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at Visits 1 and 2. Subjective itching assessments were given at 3?min, 5?min, and 7?min post challenge. Objective redness and chemosis assessments were made at 10?min, 15?min, and 20?min post challenge. Paired sample two-tailed t-tests were performed on the mean scores at each time point to assess statistical significance in the differences between treatments.

Main outcome measures; results: Fifty-three subjects were randomized into the olopatadine/epinastine treatment group, the primary analysis group. Olopatadine treated eyes exhibited significantly lower mean itching and conjunctival redness scores than the contralateral epinastine treated eyes, –0.19 (?p = 0.003) and –0.52 (?p < 0.001), respectively. Olopatadine treated eyes also exhibited significantly less chemosis –0.24 (?p < 0.001), ciliary redness –0.55 (?p < 0.001), and episcleral redness –0.58 (?p < 0.001) than epinastine treated eyes.

Conclusion: Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.

* Patanol is a registered tradename of Alcon Laboratories Inc, Forth Worth, TX, USA     

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

OBJECTIVE: 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 postchallenge 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.     

Clinical efficacy of olopatadine vs epinastine ophthalmic solution in the conjunctival allergen challenge model

BACKGROUND: Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol) and epinastine hydrochloride 0.05% ophthalmic solution (Elestat) are two topical antiallergic agents. Olopatadine is indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis. OBJECTIVE: This study compared the clinical efficacy of olopatadine and epinastine in the prevention of itching and conjunctival redness in the conjunctival allergen challenge (CAC) model. RESEARCH DESIGN AND METHODS: This was a prospective, randomized, double-masked, contralaterally-controlled, single center allergen challenge study. Ninety-six subjects with a history of allergic conjunctivitis were screened, and the 66 who responded to conjunctival allergen challenge at visits 1 and 2 were randomized into 1 of 3 treatment groups at visit 3 to receive one drop of study medication in each eye: (1) olopatadine in one eye and epinastine in the fellow eye, (2) olopatadine in one eye and placebo in the fellow eye, and (3) epinastine in one eye and placebo in the fellow eye. Five minutes after study drop instillation, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at Visits 1 and 2. Subjective itching assessments were given at 3 min, 5 min, and 7 min post challenge. Objective redness and chemosis assessments were made at 10 min, 15 min, and 20 min post challenge. Paired sample two-tailed t-tests were performed on the mean scores at each time point to assess statistical significance in the differences between treatments. MAIN OUTCOME MEASURES; RESULTS: Fifty-three subjects were randomized into the olopatadine/epinastine treatment group, the primary analysis group. Olopatadine treated eyes exhibited significantly lower mean itching and conjunctival redness scores than the contralateral epinastine treated eyes, -0.19 (p = 0.003) and -0.52 (p < 0.001), respectively. Olopatadine treated eyes also exhibited significantly less chemosis -0.24 (p < 0.001), ciliary redness -0.55 (p < 0.001), and episcleral redness -0.58 (p < 0.001) than epinastine treated eyes. CONCLUSION: Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.     

Evaluation of the effects of olopatadine ophthalmic solution, 0.2% on the ocular surface of patients with allergic conjunctivitis and dry eye*

ABSTRACT

Purpose: Olopatadine hydrochloride 0.2% (Pataday^?, Alcon, Fort Worth, USA) is a topical ocular anti-allergic agent that has shown high rates of efficacy in treating ocular itching, the primary symptom of allergic conjunctivitis, and allows for once-daily dosing. Since some patients suffer from signs or symptoms of dry eye in addition to ocular allergy, this study was designed to evaluate the safety of olopatadine 0.2% in a population of patients with both allergic conjunctivitis and dry eye.

Methods: This was a single-center, 3-visit, double-masked, randomized study. Fifty-two patients diagnosed with ocular allergy and mild-to-moderate dry eye were evaluated. After a run-in period, patients were randomized to receive either olopatadine hydrochloride 0.2% or a tear saline, and self-dosed once-daily for 1 week. Outcome measures included tear film break-up time, corneal and conjunctival staining, tear volume and flow as measured by fluorophotometry, Schirmer's test, injection, and symptom evaluations.

Results: No significant differences between the treatment groups were observed (?p > 0.05). No serious adverse events occurred during the trial. Variability in the presentation of dry eye can hinder the observation of treatment effects. Although the study design facilitated the comparison of olopatadine 0.2% against an agent that was certain to not exacerbate dry eye, future comparison of olopatadine 0.2% against other agents in its drug class would provide useful information about relative drug tolerabilities.

Conclusion: As there were no significant changes in the signs and symptoms of dry eye, olopatadine hydrochloride 0.2% is safe to use in ocular allergy patients with mild-to-moderate dry eye.     

A review of olopatadine for the treatment of ocular allergy

Ocular allergy affects > 20% of the general population and many therapeutic preparations are available to individuals experiencing the most common forms – seasonal and perennial allergic conjunctivitis. 0.1% Olopatadine topical ophthalmic solution is currently approved for the treatment of allergic signs and symptoms in patients ≥ 3 years of age. Olopatadine is available in Europe as Opatanol^® and in > 30 other countries as Patanol^®. It inhibits mast cell degranulation and antagonises histamine receptors to manage the itching, redness, chemosis, tearing and lid swelling of the ocular allergic reaction, and its mast cell stabilising ability has been demonstrated both in vitro (using human conjunctival mast cells) and in vivo (human clinical experience). This article reviews both the laboratory and clinical information available on olopatadine, prefaced by a discussion of the current understanding of the ocular allergic reaction and followed by the future implications for this compound. Both laboratory and clinical studies have established the efficacy, safety and comfort of olopatadine in several study design models and comparisons to other antiallergy medications. The application of olopatadine, specifically in the management of lid swelling, an allergic sign recalcitrant to therapy and nasal allergic symptoms has also been established. In the future, a new formulation containing 0.2% olopatadine exhibits a duration of action up to 24 h, supporting once-daily dosing.     

A review of olopatadine for the treatment of ocular allergy

Ocular allergy affects > 20% of the general population and many therapeutic preparations are available to individuals experiencing the most common forms--seasonal and perennial allergic conjunctivitis. 0.1% Olopatadine topical ophthalmic solution is currently approved for the treatment of allergic signs and symptoms in patients > or = 3 years of age. Olopatadine is available in Europe as Opatanol) and in > 30 other countries as Patanol. It inhibits mast cell degranulation and antagonises histamine receptors to manage the itching, redness, chemosis, tearing and lid swelling of the ocular allergic reaction, and its mast cell stabilising ability has been demonstrated both in vitro (using human conjunctival mast cells) and in vivo (human clinical experience). This article reviews both the laboratory and clinical information available on olopatadine, prefaced by a discussion of the current understanding of the ocular allergic reaction and followed by the future implications for this compound. Both laboratory and clinical studies have established the efficacy, safety and comfort of olopatadine in several study design models and comparisons to other antiallergy medications. The application of olopatadine, specifically in the management of lid swelling, an allergic sign recalcitrant to therapy and nasal allergic symptoms has also been established. In the future, a new formulation containing 0.2% olopatadine exhibits a duration of action up to 24 h, supporting once-daily dosing.     

Olopatadine: a drug for allergic conjunctivitis targeting the mast cell

Importance of the field: Ocular allergic diseases are characterized by specific activation of conjunctival mast cells with subsequent release of preformed and newly formed mediators. Mast cells are thus the first therapeutic target of ocular anti-allergic treatments.

Areas covered in this review: In this review, a Medline literature search was conducted on conjunctival mast cells, their role in ocular allergy and mast cell stabilization by ocular anti-allergic compounds.

What the reader will gain: Olopatadine hydrochloride, a mast cell stabilizer and histamine receptor antagonist, has been shown to inhibit mast cell activation in an in vitro model of human mast cell culture, reducing histamine and TNF-α release and upregulating proinflammatory mediators in conjunctival epithelial cells. In the in vivo conjunctival allergen challenge (CAC) model in allergic subjects, combined with objective evaluations of tear mediators and cytology, olopatadine reduced histamine tear levels and all aspects of allergic inflammation, confirming the positive clinical effects observed in active allergic patients.

Take home message: Mast cells play a central role in the pathogenesis of ocular allergy. The CAC model is ideal for assessing the mast cell stabilizing effects of anti-allergic compounds. This review of clinical studies demonstrates the superiority of olopatadine compared with other topical allergic drugs.     

Topical azelastine in perennial allergic conjunctivitis

SUMMARY

Objective: Azelastine is a selective H1-receptor antagonist that inhibits histamine release and interferes with activation of several other mediators of allergic inflammation. Together with demonstrated efficacy in seasonal allergic conjunctivitis, azelastine indicated a therapeutic potential for perennial allergic conjunctivitis (PAC).

The present study aimed to evaluate azelastine eye drops in patients with PAC compared to placebo.

Research design and methods: A multinational trial in 22 centres randomised 139 patients to twice-daily treatment for 6 weeks with masked 0.05% azelastine eye drops, matching masked placebo, or open-label levocabastine. Randomisation required a sum itching and conjunctival redness score of at least 3 (0-6 scale) after 1 week of placebo. The change in sum score was evaluated during treatment.

Results: Azelastine significantly improved itching and conjunctival redness compared to placebo (p?<?0.001) with global tolerability that was not substantially different from placebo. On day 7, the mean symptoms sum score improved with azelastine by 1.9?±?1.1 and with levocabastine by 1.5?±?1.2 compared to placebo (0.6?±?1.1) from baseline values of 3.7-3.8. The sum scores continued to improve up to day 42. Daily patient logs confirmed the clinically assessed scores. Most frequent adverse events following azelastine were bitter taste and application site reaction.

Conclusions: Topical azelastine progressively improved itching and conjunctival redness in PAC patients compared to placebo and was at least as effective as levocabastine. Rapid relief is consistent with H1-receptor antagonist action, while continued improvement up to 6 weeks may be consistent with mechanisms involving other mediators of allergic inflammation.     

Preliminary observations on the use of propionyl-L-carnitine in combination with sildenafil in patients with erectile dysfunction and diabetes

ABSTRACT

Background: Histamine receptor activation and degranulation of mast cells are the mechanisms by which the ocular itching, hyperemia, chemosis, eyelid swelling, and tearing of seasonal allergic conjunctivitis are induced. Some of the topical solutions available as anti-allergy therapies are intended to interfere with these mechanisms, and the body of research regarding the capabilities of these therapeutic molecules continues to expand.

Objective: To review the currently available literature regarding one topical ophthalmic anti-allergy agent, olopatadine (Patanol), and its anti-histaminic and mast cell stabilizing actions, both in pre-clinical and clinical settings.

Design and methods: Relevant research of laboratory, animal model, and clinical trial studies performed using olopatadine was reviewed. MEDLINE literature searches were conducted and supplemented by additional reports which furthered relevant discussion or were necessary to verify the information resulting from original searches.

Results: Olopatadine demonstrates unique properties both pre-clinically and clinically which differentiate it from other therapeutic molecules in its class of dual action mast cell stabilizer/anti-histamine. Its non-perturbation of cell membranes, human conjunctival mast cell stabilization in vivo and in vitro, and superior efficacy as compared to other topical anti-allergic medications including mast cell stabilizers, anti-histamines, and dual action agents, all contribute to olopatadine's profile.

Conclusions: Peer-reviewed literature suggests that olopatadine is clinically superior to the other anti-allergic molecules because of its strong anti-histaminic qualities and its unique ocular mast cell stabilizing properties.     

Olopatadine nasal spray for the treatment of seasonal allergic rhinitis in patients aged 6 years and older

Importance of the field: Allergic rhinitis is an IgE-mediated condition that produces inflammation of the mucosa of the nose, paranasal sinuses and, frequently, of the ocular conjunctiva. Allergic rhinitis causes a significant disease burden in terms of quality of life, lost productivity and medical treatment costs. One of the newest treatments approved by the FDA is Patanase^® (olopatadine hydrochloride) Nasal Spray, 665 μg/spray (OLO). Olopatadine is an antihistamine with selective H₁-receptor antagonist activity.

Areas covered in this review: This review details the basic and clinical research on the olopatadine molecule and OLO nasal spray from 1996 to the present day.

What the reader will gain: The reader will gain a better understanding of the pharmacology of OLO nasal spray, the clinical trial data that have established the efficacy of OLO nasal spray and the overall role of OLO nasal spray in the management of allergic rhinitis.

Take home message: Olopatadine nasal spray is one of the newest treatments approved by the FDA for the management of allergic rhinitis. OLO has a rapid onset of action, efficacy comparable to intranasal steroid sprays and is approved for seasonal allergic rhinitis in patients aged ≥ 6 years.     

Effects of a new formulation of olopatadine ophthalmic solution on nasal symptoms relative to placebo in two studies involving subjects with allergic conjunctivitis or rhinoconjunctivitis

ABSTRACT

Background: A new formulation of olopatadine hydrochloride ophthalmic solution (olopatadine 0.2%) was evaluated in two separate, randomized, placebo-controlled, double-masked, hybrid environmental studies intended to determine efficacy and safety in subjects with histories of seasonal allergic conjunctivitis or rhinoconjunctivitis.

Design and methods: In these 10- and 12-week trials (conducted April–August 2003 and July–December 2001, respectively), subjects assessed their ocular signs and symptoms. Additionally, subjects in the 10-week trial evaluated the frequency of their nasal symptoms while subjects in the 12-week trial evaluated both the frequency and severity of their nasal symptoms. The two trials had a combined enrollment of 500 subjects (217 males, 283 females) including 44 children aged 10–17 years; the combined population was 81.4% Caucasian, 9.2% Black, 2% Hispanic, and 7.4% other. Daily throughout these studies, either ragweed (fall study) or grass (spring study) pollen counts were obtained from each investigative center. Slope analyses were conducted on the nasal symptom assessments by pollen count.

Results: The nasal results from the two clinical trials are presented herein. In the fall study, relative to placebo, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0355) and itchy nose (p = 0.0032), and reduced the severity of pollen effects on sneezing (p = 0.0451), itchy nose (p = 0.0178), and runny nose (p = 0.0327). In the spring study, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0017) and runny nose (p = 0.0031) relative to placebo. In the fall trial, 2 subjects discontinued due to treatment-related adverse events (tachycardia and dry eye), while in the spring study, no subject discontinued due to a treatment-related adverse event. No subject in either study suffered a treatment-related serious adverse event.

Conclusions: For the subjects enrolled in these studies, olopatadine 0.2% appeared to be safe, well-tolerated, and effective in significantly reducing the frequency and/or severity of some effects of pollen on nasal symptoms.     

Efficacy of topical ketorolac tromethamine 0.4% for control of pain or discomfort associated with cataract surgery

SUMMARY

Objective: To evaluate the efficacy of ketorolac 0.4% ophthalmic solution for control of pain and discomfort associated with cataract surgery.

Methods: This was a single-center, double-masked, randomized, fellow-eye placebo-controlled clinical study of 25 patients (mean age 72?years; 76% female) requiring bilateral cataract surgery. Patients received either ketorolac tromethamine 0.4% ophthalmic solution (Acular LS*) or placebo, 1 drop QID for 3?days prior to and 1?day following phacoemulsification and intraocular lens implantation on their first eye, and the other treatment for surgery on the second, fellow eye 1?week–4?weeks later. The physician rated patient cooperation and ocular pain or discomfort during surgery, and patients rated ocular pain or discomfort immediately and 24?h after surgery.

Results: Patients reported significantly less ocular pain during the 24?h following surgery when treated with ketorolac 0.4% than with placebo (?p = 0.02). Ocular pain was reported for only a single ketorolac 0.4%-treated eye (4%) during that period, compared with 39% of placebo-treated eyes (?p = 0.004). No significant differences between eyes treated with ketorolac 0.4% and placebo were observed in patient cooperation, and ocular pain or discomfort during or immediately after surgery. No adverse events occurred during the study.

Limitations: Evaluation of pain is subjective, and the severity of pain experienced in the control, vehicle-treated eyes was low.

Conclusions: The reduction in pain associated with cataract surgery afforded by ophthalmic ketorolac 0.4%, together with its favorable safety profile, make it an important tool to help surgeons meet the high expectations of today's cataract and refractive surgery patients.     

Preservative-free versus preserved brimonidine %0.15 preparations in the treatment of glaucoma and ocular hypertension: short term evaluation of efficacy,safety, and potential advantages

Abstract

Purpose: To compare the efficacy, safety, and potential advantages of the preservative-free versus preserved brimonidine %0.15 preparations in patients with primer open-angle glaucoma (POAG) or ocular hypertension (OHT).

Methods: Forty-two eyes of the 21 treatment-naive patients with POAG or OHT were enrolled in this study. Eyes were randomly assigned to receive brimonidine-purite 0.15% or preservative-free brimonidine 0.15% two times daily. Efficacy of the two eye drops was assessed by measuring the intraocular pressure (IOP) at 9–10 am at baseline and week 4. Safety and potential advantages of the drops were evaluated at weeks 4 in terms of ocular symptoms and tear parameters. Ocular symptom values of the patients were evaluated with a scale of 0–4 (0?=?no discomfort and 4?=?severe discomfort).

Results: Both of the brimonidine tartrate formulations resulted in statistically similar IOP reduction (preserved formulation; ?5.2?mmHg [22.9% reduction] preservative-free formulation; ?5.7?mmHg [24.1% reduction], p?=?0.37). It was found that brimonidine tartrate formulations with and without topical preservatives did not produce a statistically significant difference in pain, stinging, and blurred vision at the upon instillation (p?>?0.05). However, the burning sensation was significantly higher in the preservative-free formulation at the first instillation compared to the preserved formulation (p?=?0.01). Also, there was no statistically significant difference between the two formulations in terms of symptoms (itching, burning, tearing, stinging, and photophobia) and tear parameters during the day (p?>?0.05).

Conclusions: Although topical preservative-free brimonidine tartrate treated eyes had a more burning sensation at the first drop, the two formulations were similar in terms of ocular tolerability in the short term period. Also, both formulations were found to reduce IOP at a similar rate.     

Effectiveness of fluticasone furoate 110 μg once daily in the treatment of nasal and ocular symptoms of seasonal allergic rhinitis in adults and adolescents sensitized to mountain cedar pollen*

ABSTRACT

Background: Fluticasone furoate (FF) is a novel enhanced-affinity corticosteroid for the treatment of allergic rhinitis, delivered by a unique side-actuated device. This study was designed to investigate the efficacy and safety of FF nasal spray (FFNS) 110?μg once daily compared with placebo in adults and adolescents (aged ≥12?years) with seasonal allergic rhinitis (SAR) symptoms caused by mountain cedar (Juniperus ashei) pollen.

Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, phase?III study conducted over a 2-week period (between 10 December 2004 and 19 January 2005) at seven study sites, in Austin, Texas, USA, and San Antonio, Texas, two metropolitan cities in the central Texas Hill Country located approximately 80 miles apart. Adult and adolescent patients (aged ≥12?years) with SAR, who were sensitized to mountain cedar (Juniperus ashei) pollen, were randomized to receive either FFNS 110?μg (n?=?152) or placebo (n?=?150) once daily. Patients rated the severity of each nasal symptom (rhinorrhea, nasal congestion, nasal itching, and sneezing) and ocular symptom (redness, watery eyes, itching and burning) on a 4-point categorical scale (0?=?none, 3?=?severe) in a reflective and instantaneous manner. Patients also rated their overall evaluation of response to therapy.

Results: FFNS significantly improved the nasal symptoms of SAR compared with placebo. The least square (LS) mean difference in the reflective total nasal symptom score (TNSS) was ?0.777 (p?=?0.003). A significant reduction in morning pre-dose instantaneous TNSS was also observed compared with placebo (LS mean difference ?0.902; p?<?0.001). Patients receiving FFNS had significantly greater improvements from baseline in reflective total ocular symptom scores (TOSS) than those receiving placebo (LS mean difference ?0.546; p?=?0.008). Significant improvements in ocular symptoms with FFNS versus placebo were also observed for morning pre-dose instantaneous TOSS (LS mean difference ?0.519; p?=?0.009). FFNS had a favorable safety and tolerability profile: fewer adverse events occurred with FFNS (22%) than with placebo (29%), and no serious adverse events were observed.

Conclusions: FFNS?110?μg once daily demonstrated efficacy in relieving both the nasal and ocular symptoms of SAR in adult and adolescent patients.

Trial registration: ClinicalTrials.gov identifier: NCT00115622.     

Brimonidine purite 0.1% versus brinzolamide 1% as adjunctive therapy to latanoprost in patients with glaucoma or ocular hypertension

ABSTRACT

Objective: To evaluate the efficacy and tolerability of brimonidine purite 0.1% in comparison to brinzolamide 1% when used as adjunctive therapy to latanoprost 0.005% in patients with glaucoma or ocular hypertension.

Methods: Randomized, single-center, investigator-masked, parallel-group clinical study. Patients with IOP?≥?18?mmHg while on once-daily latanoprost were randomized to adjunctive treatment with brimonidine purite TID (n?=?20) or brinzolamide TID (n?=?20) for 3 months. Intraocular pressure (IOP) was measured at 8 a.m., 10 a.m., and 4 p.m. at latanoprost-treated baseline and after 1 and 3 months of latanoprost and adjunctive therapy. A patient questionnaire was administered to evaluate the tolerability of eye drop instillation.

Results: Baseline mean diurnal IOP (± standard deviation, mmHg) on latanoprost was comparable between groups (brimonidine purite: 19.6?±?2.94; brinzolamide: 19.8?±?3.25; p = 0.846). Mean diurnal IOP at Month 3 was 16.3?±?2.63?mmHg with brimonidine purite and 17.8?±?2.19?mmHg with brinzolamide (?p = 0.028). Adjunctive use of brimonidine purite provided greater IOP lowering than brinzolamide at 10 a.m. (?p < 0.001) and 4 p.m. (?p = 0.050) and equivalent IOP lowering to brinzolamide at 8 a.m. (?p = 0.716). Blurred vision at Month 1 and bitter taste at Months 1 and 3 were more common upon instillation of brinzolamide eye drops.

Conclusion: Brimonidine purite 0.1% provided significantly lower IOP compared with brinzolamide 1% when used as adjunctive therapy to latanoprost. Both adjunctive therapies were well tolerated. Limitations of this study include the use of a single site and the sample size. Additional studies are needed to further evaluate these drugs as adjunctive therapy to prostaglandin analogs.     

Efficacy and comfort of olopatadine versus ketotifen ophthalmic solutions: a double-masked,environmental study of patient preference

SUMMARY

Background: Ocular allergies cause itching, redness, chemosis, tearing, and swelling of the eyelids in sensitized individuals. The options available for treatment of ocular allergy include olopatadine 0.1% (Opatanol; Patanol [US]*) and ketotifen 0.025% (Zaditen; Zaditor [US]?). Patient preference for an eye drop can often be a primary factor in determining the level of compliance and satisfaction with any given therapy.

Objective: This study sought patient perspective on eye drop efficacy in controlling signs and symptoms of allergic conjunctivitis and eye drop comfort. Also evaluated were the factors considered by patients when making decisions of preference.

Methods: One hundred patients with previous history and current symptoms of seasonal or perennial allergic conjunctivitis were enrolled at two centers (Athens, Greece, N = 50; Padova, Italy, N = 50) for this two visit, double-masked study. Qualified patients received two masked bottles of medication (one olopatadine, one ketotifen) and were asked to use both medications as needed over the course of four weeks, but not to exceed usage of two drops of medication per eye per day. At the second visit, patients answered five questions comparing the two masked medications in terms of preference, drop comfort, and efficacy in treatment of signs and symptoms. Patients also defined the factors upon which they based these decisions.

Results: A significantly greater percentage of patients (81%) selected olopatadine when asked which medication they preferred; which they found more comfortable; which they found more efficacious in reducing symptoms of allergy; and which they would select if visiting the doctor's office (P < 0.0001). Seventy-six percent (76%) of patients considered both efficacy and comfort when making their preference decisions (P < 0.0001). No adverse events were volunteered or elicited.

Conclusion: In this study, patients preferred to use the anti-allergy eye drop olopatadine over ketotifen after using both drops and evaluating relative efficacy and comfort during the course of four weeks. A significantly greater percentage of the patients preferred to use olopatadine during the study period, found it more efficacious and comfortable, and would select olopatadine if visiting their doctor's office during allergy season.     

Specific IgE for wheat in tear fluid of patients with allergic conjunctivitis

Context: Allergy to hydrolyzed wheat protein in facial soap has become a major social issue in Japan. It has been reported that the most frequent early symptoms of allergy to hydrolyzed wheat protein in soap are allergic conjunctivitis and rhinitis, while wheat-dependent exercise-induced anaphylaxis can be induced by long-term use.

Objective: We evaluated the relation between tear fluid levels of specific IgE for wheat and the features of allergic conjunctivitis.

Methods: A prospective, non-randomized, cross-sectional study was conducted in 103 patients with moderate to severe allergic conjunctivitis (allergic group) and 20 age- and sex-matched healthy control subjects (control group). Specific IgE for wheat was measured in tear fluid with an immunochromatography assay, and a skin prick test (SPT) was also performed. Symptoms (sneezing, rhinorrhea, nasal obstruction, ocular itching, and lacrimation) were assessed in each subject along with the activities of daily living (ADL) score and the total ocular symptom score for allergic conjunctivitis. A severity score (0, 1, 2, or 3) was assigned for various changes of the palpebral and bulbar conjunctiva, as well as for limbal and corneal lesions associated with allergic conjunctivitis.

Results: The IgE positive rate and specific IgE score were both higher in the allergic group than in the control group (71.8% versus 40.0% and 1.9?±?0.7 versus 1.4?±?0.5). A positive SPT for wheat was also more frequent in the allergic group than in the control group (6.8% versus 0.0%). Within the allergic group, patients with a positive SPT had higher specific IgE scores than patients with a negative SPT (3.3?±?0.5 versus 1.8?±?0.6, p?r?=?0.665), tearing (r?=?0.672), and the total ocular symptom score (r?=?0.204). Wheat IgE in tear fluid was also correlated with the severity of rhinitis symptoms, including sneezing (r?=?0.610), nose blowing (r?=?0.640), and nasal obstruction (r?=?0.677). Furthermore, the tear fluid wheat IgE score was correlated with five objective features of allergic conjunctivitis (p?Conclusions: These results suggest that wheat allergy may be involved in the development of allergic conjunctivitis.     

The effect of gatifloxacin 0.3% or moxifloxacin 0.5% on corneal healing,ocular tolerability and toxicity following pterygium surgery

Purpose: To compare the rate of corneal epithelial healing and ocular tolerability following pterygium surgery between gatifloxacin and moxifloxacin.

Methods: In this double masked, prospective, controlled study 40 patients were randomized to receive prophylactic topical gatifloxacin 0.3% or moxifloxacin 0.5% following pterygium surgery. Patients were examined on days 1, 3, 7 and 21 post-operatively or until complete corneal epithelial healing. The primary outcome measure was the area of corneal epithelial defect during the post-operative period. Patients graded post-operative ocular pain, foreign body sensation, tearing, general burning sensation and burning sensation post-antibiotic drops instillation on a scale of 1–5. Conjunctival hyperemia and superficial punctate keratopathy (SPK) were measured on a scale of 0–3.

Results: No significant differences between groups were found in terms of corneal epithelial defect percentage over time (p?=?0.989) and there was no significant difference between groups on each of the post-operative days. No significant differences were noted in terms of post-operative ocular pain, foreign body sensation, tearing, general burning sensation, burning sensation post-antibiotic drops instillation, conjunctival hyperemia and SPK.

Conclusions: Gatifloxacin and moxifloxacin showed equivalent results in terms of corneal epithelial healing and ocular tolerability following pterygium surgery. This study suggests that there was no apparent added epithelial toxicity due to the presence of benzalkonium chloride in the gatifloxacin preparation when compared to moxifloxacin.