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.     

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

ABSTRACT

Background: 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.     

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.     

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     

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.     

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.     

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.     

Ocular allergic disease

Ocular allergy is a common condition that usually affects the conjunctiva of the eye and is therefore often referred to as allergic conjunctivitis. The severity of the disease can range from mild itching and redness, as seen in seasonal allergic conjunctivitis, to the more serious vision threatening forms of ocular allergy which affect the cornea, such as atopic keratoconjunctivitis. The pathogenesis of allergic conjunctivitis involves a complex mechanism which centers around IgE-mediated mast cell degranulation and release of multiple preformed and newly formed inflammatory mediators. The diagnosis of allergic conjunctivitis is usually a clinical one which can be made based on a thorough history and careful examination. Treatment of ocular allergy should begin with conservative measures including allergen avoidance, environmental control, ocular irrigation and cold compresses. Pharmacotherapy of allergic conjunctivitis consists of several classes of drugs. Antihistamines are widely used to treat mild conditions such as seasonal and perennial conjunctivitis and potent new agents such as levocabastine and emedastine are now available. Mast cell stabilizers such as sodium cromoglycate are both safe and effective and are commonly used in ocular allergy. More effective mast cell stabilizers such as nedocromil, lodoxamide and olopatadine are now being used. Nonsteroidal antiinflammatory drugs have demonstrated only limited efficacy and, as such, are not widely used. Topical steroids are very effective in treating signs and symptoms but are reserved for only refractory cases due to their serious side effects. Loteprednol and rimexelone are newer corticosteroids which reportedly have less of an effect on intraocular pressure. Cyclosporine has recently been shown to be highly effective in cases of vernal keratoconjunctivitis and atopic keratoconjunctivitis while producing no adverse effects.     

Topical azelastine in perennial allergic conjunctivitis

OBJECTIVE: Azelastine is a selective H(1)-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 H(1)-receptor antagonist action, while continued improvement up to 6 weeks may be consistent with mechanisms involving other mediators of allergic inflammation.     

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

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.     

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.     

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.     

Comparison of Azelastine Eye Drops with Levocabastine Eye Drops in the Treatment of Seasonal Allergic Conjunctivitis

Summary

A randomised, multicentre parallel group study was undertaken to compare the efficacy and safety of 0.05% azelastine eye drops (101 patients) in an open manner with 0.05% levocabastine eye drops (103 patients) and in a double-blind manner with placebo (103 patients) during a 14-day treatment period involving patients with seasonal allergic conjunctivitis. The three main eye symptoms, scored on a four-point scale, were itching, lacrimation and conjunctival redness; the primary efficacy variable was the responder rate on day 3. Responders were patients whose sum score of the three main eye symptoms decreased by at least three points from a baseline score of at least six points. In addition to these main symptoms, five other symptoms were recorded on days 0, 3, 7 and 14, and patients kept daily diaries of the three main eye symptoms and swollen eyelids. The responder rate after 3 days of treatment was 69% in patients treated with azelastine, 59% in patients treated with levocabastine and 51% in the placebo group. Only the difference in responder rates between azelastine and placebo eye drops was statistically significant (p = 0.02). The improvements in other ocular symptoms and entries in the patients’ diaries closely reflected the changes reported by the investigators. No serious adverse events occurred throughout the study. Nine patients (three in the azelastine, five in the levocabastine and one in the placebo group) terminated the study prematurely due to poor tolerability. Adverse drug reactions, mainly a mild, transient irritation and a bitter or unpleasant taste, were reported in 37% of patients receiving azelastine eye drops, 31% of patients receiving levocabastine and 9% of placebo patients. Overall tolerability was assessed as very good or good in 86% of azelastine- and levocabastinetreated patients, and in 95% of the patients receiving placebo. The results of this study indicate that azelastine possesses a tolerability profile at least comparable to that of levocabastine eye drops, but additionally appears to have a slightly quicker onset of effect, and confirm the therapeutic potential of azelastine eye drops in the treatment of allergic conjunctivitis.     

Comparison of azelastine eye drops with levocabastine eye drops in the treatment of seasonal allergic conjunctivitis

A randomised, multicentre parallel group study was undertaken to compare the efficacy and safety of 0.05% azelastine eye drops (101 patients) in an open manner with 0.05% levocabastine eye drops (103 patients) and in a double-blind manner with placebo (103 patients) during a 14-day treatment period involving patients with seasonal allergic conjunctivitis. The three main eye symptoms, scored on a four-point scale, were itching, lacrimation and conjunctival redness; the primary efficacy variable was the responder rate on day 3. Responders were patients whose sum score of the three main eye symptoms decreased by at least three points from a baseline score of at least six points. In addition to these main symptoms, five other symptoms were recorded on days 0, 3, 7 and 14, and patients kept daily diaries of the three main eye symptoms and swollen eyelids. The responder rate after 3 days of treatment was 69% in patients treated with azelastine, 59% in patients treated with levocabastine and 51% in the placebo group. Only the difference in responder rates between azelastine and placebo eye drops was statistically significant (p = 0.02). The improvements in other ocular symptoms and entries in the patients' diaries closely reflected the changes reported by the investigators. No serious adverse events occurred throughout the study. Nine patients (three in the azelastine, five in the levocabastine and one in the placebo group) terminated the study prematurely due to poor tolerability. Adverse drug reactions, mainly a mild, transient irritation and a bitter or unpleasant taste, were reported in 37% of patients receiving azelastine eye drops, 31% of patients receiving levocabastine and 9% of placebo patients. Overall tolerability was assessed as very good or good in 86% of azelastine- and levocabastine-treated patients, and in 95% of the patients receiving placebo. The results of this study indicate that azelastine possesses a tolerability profile at least comparable to that of levocabastine eye drops, but additionally appears to have a slightly quicker onset of effect, and confirm the therapeutic potential of azelastine eye drops in the treatment of allergic conjunctivitis.     

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.     

A comparison of the fourth-generation fluoroquinolones gatifloxacin 0.3% and moxifloxacin 0.5% in terms of ocular tolerability

PURPOSE: To compare the ocular tolerability of the commercially available ophthalmic solutions of the fourth-generation fluoroquinolones, gatifloxacin 0.3% (Zymar, Allergan, Inc., Irvine, CA) with benzalkonium chloride (BAK) and moxifloxacin 0.5% (Vigamox) without BAK. METHODS: A baseline evaluation was conducted on 30 healthy volunteers for conjunctival hyperemia, conjunctival vascularity, pupil size, and anterior chamber (AC) cell and flare. Pupils were measured under scotopic conditions with a Colvard pupillometer. Conjunctival hyperemia and vascularity, and AC reaction were measured on a Likert-like scale of 0-3. Subjects then received drops in both eyes from masked bottles of gatifloxacin ophthalmic solution 0.3% with BAK (in one eye determined randomly) and moxifloxacin ophthalmic solution 0.5% without BAK (in the contralateral eye) in a double-masked fashion. Subjects graded pain and ocular irritation in each eye on a scale of 1-10 after 5 min with their eyes closed. The examination was then repeated. RESULTS: The average age of this study population was 34.4 years. The groups of eyes receiving moxifloxacin 0.5% demonstrated an increase in mean conjunctival hyperemia (0.21 [range: 0-1] at baseline to 1.52 [range: 0-3] at 5 min.) that was significantly greater (p = 0.0005) compared with that of the group receiving gatifloxacin 0.3% (0.22 [range: 0-1] at baseline to 0.45 [range: 0-2] at 5 min). The group receiving moxifloxacin 0.5% showed an increase in conjunctival vascularity (0.55 [range: 0-1] at baseline to 1.61 [range: 0.5-3] at 5 min.) that was significantly greater (p = 0.0005) compared with that of the group receiving gatifloxacin 0.3% (0.52 [range: 0-1] at baseline to 0.68 [range: 0-2] at 5 min.). Significantly less pain (1.2 vs. 3.2, p = 0.001) and irritation (0.64 vs. 3.42, p = 0.001) occurred with gatifloxacin 0.3% than with moxifloxacin 0.5%. Pupil size was significantly reduced (5.65 mm-5.05 mm) in eyes receiving moxifloxacin 0.5% (p = 0.004) and no significant change occurred in pupil size (5.60 mm-5.65 mm) in eyes that received gatifloxacin 0.3% (p = 0.878). No AC reaction was noted with either medication. CONCLUSIONS: The group of eyes receiving gatifloxacin 0.3% with BAK demonstrated greater ocular tolerability in comparison to the group receiving moxifloxacin 0.5% without BAK. Moxifloxacin-induced pupillary miosis may be due to prostaglandin release in the anterior chamber. A limitation of this study is the relatively young age of the study population.     

Tolerability and safety of 0.1% diclofenac plus 0.3% tobramycin fixed-dose ophthalmic solution: a randomized, comparative, controlled study in healthy volunteers.

The purpose of this double-blind, observer-masked, randomized, crossover trial was to compare the tolerability and safety of a fixed-dose ophthalmic solution of 0.3% tobramycin plus 0.1% diclofenac versus Tobrex (tobramycin sulfate ophth) and Voltaren (diclofenac sodium). Control treatments included a saline solution and a control solution of 0.3% tobramycin prepared by Alcon Cusí. Ten healthy volunteers received three consecutive instillations of 1 drop of a given ophthalmic solution at 08:00, 11:00 and 14:00 h to the same eye; after a washout period of 18 h, the next ophthalmic solution was tested according to a randomized sequence. Occurrence, intensity, and duration of ocular irritation and conjunctival hyperemia at baseline and after the three instillations were recorded. Slit lamp biomicroscopy examination, measurement of intraocular pressure (IOP) changes, visual acuity, and examination of the fundus of the eye were performed after each third instillation by an ophthalmologist. Side effect incidence and patient and investigator opinions were also recorded. Results showed that Voltaren instillation induced statistically significant ocular irritation (p = 0.0077); the remaining ophthalmic solutions tested caused no ocular irritation (Physiological Saline Braun, p = 0.9808; Tobrex, p = 0.8826; control 0.3% tobramycin solution, p = 0.8327; and 0.1% diclofenac plus 0.3% tobramycin, p = 0.5399). None of the ophthalmic solutions tested caused severe conjunctival hyperemia. Analysis of the sum of conjunctival parameters of both eyes for all ophthalmic solutions studied showed no statistically significant differences (p = 0.4688). Moderate superficial punctate keratitis was observed after instillation of Voltaren and of 0.1% diclofenac plus 0.3% tobramycin (1 subject each) that spontaneously resolved within 2 days. Slit lamp biomicroscopy, visual acuity and IOP values showed no statistically significant changes. No systemic side effects related to the study treatments were recorded. In conclusion, the ophthalmic solution containing 0.1% diclofenac plus 0.3% tobramycin was well tolerated under the study conditions. Its tolerability was equivalent to that of Braun physiological saline, Tobrex and a control 0.3% tobramycin solution and was better than that of Voltaren.     

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

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.