Switching patients with glaucoma or ocular hypertension from dual therapy to monotherapy: evaluation of brimonidine as a model.

A multicenter open-label study investigated the clinical effectiveness and economic feasibility of switching 142 patients from dual therapy to twice-daily monotherapy with brimonidine for glaucoma or ocular hypertension. Evaluations were performed at baseline and 2 (visit 2) and 8 (visit 3) weeks after the switch. Patients completed a questionnaire that rated medication-related visual function and satisfaction (comfort, convenience, vision, ease of remembering to use drops) at each visit. At visit 3, investigators, taking into account IOP measurements, safety, and responses on the questionnaire, recommended whether the patient should remain on brimonidine. A pharmacoeconomic analysis, including the number of visits, cost of medication, and success rates, compared the cost of dual therapy with that of switching to brimonidine monotherapy. Of the 131 patients who completed the study, 77 (59%) had no change or a decrease in IOP from baseline, and 53 (41%) had an increase. Investigators recommended that 77% of the study completers continue to take brimonidine monotherapy. Extending treatment with brimonidine for 12 months would achieve a significant cost savings of 16%. Brimonidine monotherapy is an efficacious and cost-effective alternative to dual therapy for glaucoma and ocular hypertension. Appropriate monotherapy may be as effective as dual therapy for many patients, and a clinically relevant trial such as this may be economically advantageous for testing a switch.

Safety and efficacy comparison of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects with allergic conjunctivitis. Emadine Study Group.

PURPOSE: To determine the efficacy and tolerance of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects. METHODS AND MATERIALS: In a randomized, double-masked, parallel controlled study, emedastine 0.05% ophthalmic solution BID was compared to levocabastine 0.05% ophthalmic suspension BID, for control of the signs and symptoms of allergic conjunctivitis in pediatric subjects ages 3-16. Subjects who met all inclusion and exclusion criteria received masked study medication with instructions to instill drops twice daily, in the morning and evening. A diary was completed by the parents four times daily for the first two and last two weeks of the study. Treatment lasted 42 days. Drug efficacy was assessed at the initial administration in the office at Day 0 and after 3, 7, 14, 30 and 42 days. RESULTS: Overall results showed both drugs have an effect and that emedastine was significantly superior (p < 0.05) to levocabastine for the relief of chemosis on Days 14, 30 and 42; of itching on follow-up Days 30 and 42 (p < 0.05); of redness on Days 30 and 42; for eyelid swelling on Days 14 and 30; and for physician's impression score on Days 7, 14, 30 and 42. CONCLUSION: These results confirm previous preclinical and clinical data on the potent and long acting efficacy of this promising new ophthalmic anti-allergic drug, emedastine in pediatric subjects.

An efficacy and tolerance comparison of emedastine difumarate 0.05% and levocabastine hydrochloride 0.05%: reducing chemosis and eyelid swelling in subjects with seasonal allergic conjunctivitis. Emadine Study Group.

PURPOSE: To compare emedastine ophthalmic solution 0.05% BID to levocabastine ophthalmic suspension 0.05% BID in reducing chemosis, eyelid swelling and other signs and symptoms in subjects with seasonal allergic conjunctivitis. METHODS: In a randomized, double-masked, parallel controlled study, emedastine ophthalmic solution 0.05% BID was compared to levocabastine ophthalmic suspension 0.05% BID for control of chemosis, eyelid swelling and other parameters in the environmental allergy study model. RESULTS: At Days 7, 14, 30 and 42, emedastine was significantly better than levocabastine at controlling chemosis and eyelid swelling (p < 0.05). A statistical trend was seen at Day 3 (0.05 < p < 0.10). Results were clinically relevant at Days 30 and 42. Emedastine was also significantly better at reducing redness and itching at Days 7, 14, 30 and 42 (p < 0.05). CONCLUSION: Emedastine is more efficacious than levocabastine in reducing chemosis, eyelid swelling and other efficacy variables associated with seasonal allergic conjunctivitis.

An evaluation of onset and duration of action of patanol (olopatadine hydrochloride ophthalmic solution 0.1%) compared to Claritin (loratadine 10 mg) tablets in acute allergic conjunctivitis in the conjunctival allergen challenge model.

PURPOSE: To compare the clinical efficacy of Patanol (olopatadine hydrochloride ophthalmic solution 0.1%) to Claritin (loratadine 10 mg) tablets, in the conjunctival allergen challenge model. METHODS: This was a randomized, double-masked, single center, contralateral controlled, antigen challenge model study. The concentration of allergen that elicited a positive response was determined at Visits 1 and 2 (itching > or = 2 and redness > or = 2 OU). At Visit 3, 29 subjects were randomized into two groups. Fifteen subjects received Claritin tablet and Patanol ophthalmic solution 0.1% in one eye and placebo in the contralateral eye. Fourteen subjects received placebo tablet and Patanol in one eye and placebo in the contralateral eye. One hour after drug administration, subjects were challenged with the antigen that elicited a positive response. At 3, 7, and 10 minutes, itching was subjectively evaluated. At Visit 4, the same procedure was followed as in Visit 3, but antigen challenge occurred 8 hours after drug instillation. RESULTS: Results were analyzed by eye. Eyes treated with Patanol (concomitant with placebo tablet) had significantly lower ocular itching scores when compared to eyes treated with placebo (concomitant with Claritin) at 3, 7 and 10 minutes in the onset of action evaluation (p < 0.05). Eyes treated with Patanol (concomitant with placebo tablet) had significantly lower ocular itching scores at 7 minutes and there was a statistical trend (0.05 < p < 0.1) at 10 minutes in duration of action evaluation. CONCLUSIONS: Patanol therapy was significantly more efficacious than Claritin in reducing ocular itching related to allergic conjunctivitis.

The added benefit of local Patanol therapy when combined with systemic Claritin for the inhibition of ocular itching in the conjunctival antigen challenge model.

BACKGROUND: Allergic conjunctivitis very often occurs simultaneously with rhinitis in seasonal allergy sufferers. While systemic anti-allergic and antihistaminic agents are effective against many signs and symptoms of allergy, they may not adequately control ocular signs and symptoms in patients with multiple target organ hypersensitivity. Patanol (olopatadine hydrochloride 0.1% ophthalmic solution, Alcon Laboratories, Inc., Fort Worth, TX), a new effective anti-allergic mast cell stabilizer with antihistaminic properties, is approved for the prevention of ocular itching due to allergic conjunctivitis. OBJECTIVE: To determine whether Patanol in combination with the systemic antihistamine Claritin (loratadine, Schering, Kenilworth, NJ) reduces the ocular itching associated with allergic conjunctivitis more effectively than Claritin alone. A topical ocular antigen challenge induced the allergic conjunctivitis in 15 subjects. METHODS: This was a randomized, double-masked study in which the contralateral eye served as the control. On Visit 1, an allergen dose which elicited response scores > 2 for ocular itching was identified. Itching was graded by the subject using a 0 to 4 point scale. At Visit 2, the threshold allergen concentration was confirmed. At Visit 3, the onset of action challenge, in addition to Claritin (10 mg tablet), each subject received Patanol in one eye and placebo in the fellow eye in a randomized, double-masked fashion. Allergen was instilled one hour after dosing, and ocular itching was graded at 3, 7, 10 and 20 minutes after challenge. At Visit 4, the duration of action challenge, the same drug regimen was followed as in Visit 3. However, allergen challenge was performed eight hours after dosing, and itching graded after 3, 7, 10 and 20 minutes. RESULTS: Patient eyes treated with Patanol were significantly less itchy than those treated with systemic Claritin alone at critical time points 3, 7, and 10 minutes after the onset of action challenge (p < 0.05), and at 3 and 7 minutes after the duration of action challenge (p < 0.05). CONCLUSION: The addition of topical Patanol to systemic Claritin therapy significantly reduced ocular itching associated with allergic conjunctivitis compared to treatment with Claritin alone. These findings prove the added benefit of local Patanol therapy in the treatment of ocular allergic symptoms in patients receiving systemic antihistamines for concomitant systemic allergies.

Alteration of mucin in human conjunctival epithelia in dry eye.

PURPOSE: The objective of this study was to determine whether alteration in mucins could be detected in patients with dry eye symptoms by using the monoclonal antibody H185, which recognizes carbohydrate epitopes on mucin molecules. METHODS: Immunohistochemistry and immunoelectron microscopy was used to examine binding of H185 antibody to conjunctival cells obtained by nitrocellulose filter paper stripping (impression cytology). Two study populations were examined. Study I included 22 patients with dry eye symptoms and 13 normal volunteers. Study II included 16 aqueous-deficient dry eye patients and 14 age-matched control subjects. RESULTS: Results of the studies demonstrated significant differences in binding patterns of H185 to conjunctival cells in normal eyes compared with those of patients with dry eye symptoms. In normal eyes, the antibody bound to apical cells in a mosaic pattern, with cells exhibiting either light, medium, or intense binding. A predominant pattern in patients with dry eye symptoms was loss of the mosaic pattern with replacement by a "starry sky" pattern in which there was a lack of apical cell binding (hence, dark sky) but increased binding to goblet cells (hence, stars in the sky). The starry sky pattern correlated with rose bengal staining. CONCLUSIONS: From these studies it is concluded that there is an alteration either in mucin distribution or mucin glycosylation on the surfaces of apical conjunctival cells in dry eye and that glycosylation of goblet cell mucins changes with the disease.

Evaluation of olopatadine, a new ophthalmic antiallergic agent with dual activity, using the conjunctival allergen challenge model.

BACKGROUND: An ophthalmic antiallergic agent with selective H1 antihistaminic and mast cell stabilizing properties has been developed. OBJECTIVES: To evaluate efficacy and safety, determine optimal concentration, and demonstrate onset and duration of action of this new drug, olopatadine. METHODS: This was a placebo-controlled, randomized, double-masked, parallel-group, single-center study with five outpatient visits at least 7 days apart. Ninety-eight healthy, allergy-positive, subjects with a recent history of active allergic conjunctivitis not receiving current treatment participated. Conjunctival allergen challenge (CAC) tests were performed on visits 1 and 2 to identify an allergen and concentration that consistently elicited signs and symptoms of allergic conjunctivitis. On visits 3, 4, and 5, CAC was performed 27 minutes, 8 hours, and 6 hours, respectively, after instillation of one drop of olopatadine (0.01%, 0.05%, 0.1%, or 0.15%) in one eye and placebo in the other. Both eyes were scored for the intensity of itching and redness at 3, 10, and 20 minutes after the CAC. RESULTS: All four concentrations of olopatadine were clinically and statistically superior to placebo in preventing ocular itching at all evaluations and preventing redness at most evaluations from immediately and 8 hours after drug administration. No drug-related adverse events were reported. The 0.1% concentration was found to be most effective. CONCLUSIONS: The results indicate that olopatadine ophthalmic solution is safe and effective in the treatment of allergic conjunctivitis, with the 0.1% concentration of olopatadine being optimal. The rapid onset and at least 8 hour duration of action of olopatadine indicates that the drug can be used twice daily.

Combined analysis of two studies using the conjunctival allergen challenge model to evaluate olopatadine hydrochloride, a new ophthalmic antiallergic agent with dual activity.

PURPOSE: To evaluate the effectiveness and safety of olopatadine hydrochloride and to determine its optimal concentration and the onset and duration of action for treating allergic conjunctivitis. Olopatadine is a new topical ophthalmic antiallergic agent that demonstrates activity as both an antihistamine and a mast cell stabilizer. Two double-masked, randomized, placebo-controlled, contralateral eye comparison studies were conducted using the conjunctival allergen challenge model. METHODS: A total of 169 subjects received 0.05% or 0.1% olopatadine. Study subjects were healthy adult men and women with a history of active allergic conjunctivitis within the previous two seasons but not receiving current treatment. With an allergen dose that produced signs and symptoms of allergic conjunctivitis at visits 1 and 2, the conjunctival allergen challenge was performed 27 minutes after study drug administration at the third visit (onset-of-action challenge) and at 8 hours after study drug administration at the fourth visit (duration-of-action challenge). Olopatadine was administered in one eye and placebo in the opposite eye. Itching and redness were scored for both eyes at 3, 10, and 20 minutes after the conjunctival allergen challenge. RESULTS: Both 0.05% and 0.1% concentrations of olopatadine were significantly (P < .05) more effective than placebo in inhibiting itching and redness at all evaluations when administered 27 minutes or 8 hours before the conjunctival allergen challenge. There were no serious or drug-related ocular or nonocular adverse events in either study. CONCLUSION: These findings demonstrate the rapid and prolonged (at least 8 hours) ocular antiallergic action of olopatadine.

A multicenter comparison of the ocular efficacy and safety of diclofenac 0.1% solution with that of ketorolac 0.5% solution in patients with acute seasonal allergic conjunctivitis.

Only one of several available ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) is currently FDA approved for use in acute seasonal allergic conjunctivitis (SAC). Sixty patients with SAC and moderate itching and bulbar conjunctival injection were enrolled in a multicenter, randomized, double-masked, parallel-group trial comparing diclofenac sodium (DS) with ketorolac tromethamine (KT). Patients instilled 1 drop four times daily while awake for 14 days. Ocular signs and symptoms were evaluated at one and two weeks. The primary efficacy variables were itching and bulbar conjunctival injection. For both treatments, the ocular allergy sign and symptom scores were comparable at baseline. Both treatments evaluated in this study were well tolerated. Significant clinical and statistical reductions from baseline were observed in the primary efficacy variables. Treatment group differences were observed for the pain/soreness score with an advantage observed for the DS group at 30 minutes and at day 7. Our conclusion is that diclofenac sodium and ketorolac tromethamine acted similarly to reduce the ocular signs and symptoms associated with acute seasonal allergic conjunctivitis. There was a statistically significant advantage for the DS group to be free of symptoms at the day 7 visit as compared to the KT group (20.7% vs. 3.2%).

Histaminase activity in patients with vernal keratoconjunctivitis.

PURPOSE: To investigate the activity of histamine-degradating enzymes in tears and plasma of patients with vernal keratoconjunctivitis (VKC). METHOD: Tear and plasma samples were collected from patients with VKC and from age-matched control subjects. Histamine was measured by enzyme-linked immunosorbent assay in acid samples treated with perchloric to deactivate histaminase and in untreated samples. Tear cytology, skin test reactivity to histamine, and the sum clinical score of allergic signs and symptoms in patients with VKC also were evaluated. Nineteen patients with active VKC and six age-matched control subjects participated in this study. RESULTS: In untreated samples, tear histamine (mean +/- standard error of the mean) was 11.15 +/- 2.16 ng/ml in patients with VKC and 0.855 +/- 0.225 ng/ml in control tears (P < 0.001). In treated samples, mean tear histamine was 22.25 +/- 4.17 ng/ml in patients with VKC versus 10.64 +/- 2.85 ng/ml in control subjects (not statistically different). The ratio of histamine in treated to untreated samples (indicating histaminase activity) was significantly lower in patients with VKC (2.30 +/- 0.263) than in control subjects (17.57 +/- 5.97; P = 0.0001). Plasma histamine levels in untreated and treated samples were significantly higher in patients with VKC (untreated, 2.23 +/- 0.334 ng/ml; treated, 4.37 +/- 0.357 ng/ml) than in control subjects (untreated, 0.254 +/- 0.068, P = 0.0002; treated, 2.96 +/- 0.171 ng/ml, P = 0.0082). The enzymatic breakdown of histamine (treated/ untreated) in plasma was significantly decreased in patients with VKC (2.54 +/- 0.447) compared with control subjects (14.78 +/- 4.86; P = 0.0012). Skin reactivity to histamine was not increased in VKC. Tear histamine levels were significantly correlated to tear lymphocyte content in the general population and to tear basophils in the patients with tarsal-vernal VKC only. An increased number of tear eosinophils were correlated with elevated enzyme activity only in patients with tarsal-vernal VKC and to the clinical score only in limbal-vernal patients. CONCLUSION: The enzymatic degradation of histamine was significantly decreased in patients with VKC compared with control subjects in both tears and plasma, suggesting that this dysfunction may be a primary factor in the pathophysiology of VKC.

Evaluation of 0.05% levocabastine versus 4% sodium cromolyn in the allergen challenge model.

PURPOSE: This study was conducted to evaluate the efficacy of 0.05% levocabastine compared with 4% cromolyn for treating allergic conjunctivitis induced by ocular allergen challenge. METHODS: Subjects who met all entry criteria and reacted positively to ocular allergen challenge at two previous visits (n = 50) received placebo in one eye and cromolyn in the fellow eye, four times daily for 2 weeks. On day 18, subjects received the final dose of cromolyn in the pretreated eye and one drop of levocabastine in the fellow eye. Subjects were challenged and evaluated after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and evaluated after 3, 5, and 10 minutes. RESULTS: Levocabastine was significantly more effective than cromolyn in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and 4-hour rechallenge (P < 0.05). CONCLUSION: These results suggest that levocabastine is superior to cromolyn for treating allergen-induced conjunctivitis and has a duration of action of at least 4 hours.

Evaluation of the new ophthalmic antihistamine, 0.05% levocabastine, in the clinical allergen challenge model of allergic conjunctivitis.

The objective of this study was to evaluate the efficacy of 0.05% levocabastine, a new antihistamine formulated for ophthalmic use, compared with the placebo vehicle for the treatment of allergic conjunctivitis induced by ocular allergen challenge. Subjects who reacted. positively in both eyes on two separate occasions to ocular allergen challenge with grass, ragweed, or cat dander (N = 47) received one dose of 1 to 2 drops of 0.05% levocabastine in one eye and its vehicle in the other eye. After 10 minutes, the predetermined dose of allergen was instilled in both eyes. Signs and symptoms of allergic conjunctivitis were evaluated with biomicroscopy and subjective evaluation of itching after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and reevaluated to determine levocabastine's duration of action. Results showed that levocabastine was significantly more effective than placebo in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and in inhibiting all parameters except eyelid swelling after the rechallenge 4 hours later (p < 0.05). These results demonstrate that levocabastine, currently the only ophthalmic antihistamine available that is not combined with a vasoconstrictor, is efficacious in the inhibition of itching, as well as all of the allergic signs of a vascular origin, with a duration of action of at least 4 hours. Because of its strong effects on itching and hyperemia, chemosis, lid swelling, and tearing, levocabastine would be a valuable therapeutic agent to add to the heterogeneous family of antiallergic compounds presently available for the treatment of seasonal allergic conjunctivitis.

Nonsteroidal anti-inflammatory drugs. Current ophthalmic therapy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the treatment of ophthalmic inflammatory disease. Currently four topical preparations are available: flurbiprofen and suprofen for the prevention of miosis during surgery; diclofenac for postoperative inflammation following cataract extraction, and ketorolac for the treatment of itching associated with seasonal allergic conjunctivitis. Caution should be exercised, however, as topical and systemic adverse effects may occur including stinging, photophobia, gastric sensitivity, and increased bleeding time. The mechanism of action of NSAIDs is discussed, complications associated with use, and the current and future roles of therapy.

Levocabastine eye drops: a new approach for the treatment of acute allergic conjunctivitis.

Acute allergic conjunctivitis (AAC) is a common ocular allergic disorder and incident rates as high as 20% have been reported. Although a wide range of therapeutic agents are available for the treatment of AAC, the ideal treatment seems to have remained elusive. Levocabastine, a highly potent specific H1-receptor, appears to offer a promising alternative as a topical single-agent therapy. Levocabastine eye drops have been found to be well tolerated with an adverse-effect profile comparable to placebo and sodium cromoglycate. In addition, ocular levocabastine has been shown to have a rapid onset and long duration of action. The efficacy of levocabastine has been extensively investigated in conjunctival provocation tests and environmental studies. The available data suggest that ocular levocabastine is an effective therapeutic agent. Statistically significant differences in favour of levocabastine have been observed in comparisons with sodium cromoglycate, antazoline/naphazoline and oral terfenadine.