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Efficacy and safety of topical azelastine compared with topical mitomycin C in patients with allergic conjunctivitis.

PURPOSE: To compare the efficacy and safety of topical azelastine with topical mitomycin C (MMC) in patients with allergic conjunctivitis. METHODS: Sixty-three patients (29 male, 29 female; 34 in the age range of 6 to 65 years) with allergic conjunctivitis were enrolled in this study. The patients were randomly assigned to receive topical azelastine 0.02% (n = 31) or topical MMC (0.2 mg/10 mL) (n = 31) four times daily for 3 months. Follow-up examinations were done at 2 weeks to examine side effects of the medications and again at 4 weeks to assess the outcome of treatment. The eyes were examined for relief of symptoms, cure of signs, and the appearance of side effects with use of these drugs. RESULTS: The mean age of the patients in this study was 34.8 +/- 17.3 years. The age of patients in the MMC group was significantly higher than patients in the azelastine group (mean +/- SD, 25.2 +/- 13.5 years). More patients in the MMC group had relief of symptoms like redness [25 (80.7%) in the MMC group versus 19 (55.9%) in the azelastine group; p= 0.033], photophobia [11 (35.5%) in the MMC group versus six (17.7%) in the azelastine group; not significant], discharge [17 (54.8%) in the MMC group versus 11 (32.3%) in the azelastine group; not significant], and foreign body sensation [21 (67.7%) in the MMC group versus 16 (47.1%) in the azelastine group; not significant], while more patients in the azelastine group had relief of lacrimation [14 (41.2%) in the azelastine group versus 10 (32.3%) in the MMC group; not significant] and pain [12 (35.3%) in the azelastine group versus eight (25.8%) in the MMC group; not significant]. The MMC group also showed a greater decrease in follicles [31 (100.0%) in the MMC group versus six (17.7%) in the azelastine group; p= 0.0001] and papillae [29 (93.6%) in the MMC group versus four (11.8%) in the azelastine group; p= 0.0001]. Both drugs were found to be equally effective in relieving itching [18 (58.1%) in the MMC group versus 18 (52.9%) in the azelastine group; not significant]. In the MMC group, 27 (87.1%) patients had conjunctival hyperemia, 28 (90.3%) patients had episcleritis, and 29 (93.6%) patients had irritation. The use of topical azelastine did not cause any adverse event. CONCLUSIONS: Though this was a short-term study, we found topical MMC to be more effective than topical azelastine in the treatment of allergic conjunctivitis both in terms of relief of symptoms and resolution of signs. The use of topical MMC in low doses does not cause any significant adverse effect.

Administration, Topical↗

The effect of topically applied secretory leukocyte protease inhibitor on the eosinophil response in the late phase of allergic conjunctivitis.

PURPOSE: This study examined the effects of secretory leukocyte protease inhibitor (SLPI), a protease inhibitor in tears, in allergic conjunctivitis. METHODS: Conjunctiva of male Hartley guinea pigs sensitized with ovalbumin were treated with SLPI or the vehicle 10 min before antigen challenge or simultaneously. The animals were sacrificed after antigen challenges of 0-24 h duration, and the inhibition of eosinophil conjunctival migration and degranulation by SLPI was analyzed histochemically. The effects of SLPI on mast cell chymase and tryptase were also examined. RESULTS: Treatment of sensitized guinea pigs with SLPI suppressed the conjunctival recruitment and degranulation of eosinophils after antigen challenge for 6 h, inhibiting the development of allergic conjunctivitis. The effects of SLPI were observed at concentrations > or =0.1 microM, with a peak at 5 microM. SLPI inhibited chymase in a dose-dependent manner, but had no effect on tryptase. CONCLUSION: The topical SLPI application may be therapeutic in allergic conjunctivitis.

Administration, Topical↗

A randomized, double-masked, placebo-controlled parallel study of loteprednol etabonate 0.2% in patients with seasonal allergic conjunctivitis.

OBJECTIVE: To evaluate the effects of loteprednol etabonate (LE) 0.2% in reducing the signs and symptoms of seasonal allergic conjunctivitis. DESIGN: Randomized, double-masked, placebo-controlled, parallel group multicenter study of 6 weeks duration. PARTICIPANTS: A total of 135 patients with signs and symptoms of seasonal allergic conjunctivitis participated. INTERVENTION: All patients received either LE 0.2% or placebo (vehicle) four times a day in both eyes for 42 days. MAIN OUTCOME MEASURES: Bulbar conjunctival injection (primary sign) and itching (primary symptom) over the first 2 weeks of treatment was measured. RESULTS: A reduction in severity was seen in both LE and placebo groups for bulbar conjunctival injection (1.5 vs. 1.0 units on a 0-3 scale) and itching (3.4 vs. 3.0 units on a 0-4 scale) over the first 2 weeks. The treatment effect by these measures was -0.5 and -0.4 units in favor of LE (P < or = 0.008). Resolution (i.e., the proportion of patients with signs or symptoms no longer present) at day 14 strongly favored LE-treated patients (36% and 15%; 58% and 38%, for injection and itching, respectively). Both treatments were well tolerated. One patient in each treatment group (1 of 67 and 1 of 68, respectively) had an elevation of intraocular pressure of 10 mmHg or greater during the 6 weeks of treatment. CONCLUSIONS: Loteprednol etabonate 0.2% was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate 0.2% had a safety profile comparable to placebo.

Adult↗

Seasonal allergic conjunctivitis is accompanied by increased mast cell numbers in the absence of leucocyte infiltration.

BACKGROUND: Seasonal allergic conjunctivitis (SAC) is the most common allergic disease to affect the eye, occurring alone or in association with allergic rhinitis. Infiltration with mast cells and eosinophils is characteristic of the chronic forms of allergic conjunctivitis such as vernal and atopic keratoconjunctivitis, and these cell types also contribute significantly to allergic inflammation in the skin. Indirect evidence for a similar pattern of cellular events in SAC comes from studies which demonstrate raised eosinophil and neutrophil numbers in conjunctival scrapings and elevated levels of mast cell tryptase in tears following allergen challenge. OBJECTIVE: To directly characterize the inflammatory cell infiltrate in SAC and to determine its clinical relevance. METHODS: We employed specific immunohistochemical staining to count mast cells, eosinophils and neutrophils in the conjunctival epithelium and lamina propria of eight atopic patients with SAC in, and 12 SAC patients out of the hay fever season. Sixteen patients with no history of ocular allergy were used as control subjects. RESULTS: Mast cells were absent from normal epithelium. During the pollen season median mast cell numbers in the lamina propria were found to be increased by 61% in patients with SAC compared with normals (P=0.012). Eosinophils were found in the lamina propria in less than half of the symptomatic patients with SAC and in only three patients were eosinophils present in the epithelium. The neutrophil numbers in the lamina propria of patients with SAC tended to be higher than normals but these changes did not reach statistical significance. CONCLUSION: These data based on the direct assessment of conjunctival tissue provide evidence that symptoms occur in SAC in the absence of detectable recruitment of eosinophils or neutrophils. This suggests that this disorder is related to mast cell-mediated changes.

Adult↗

Dry eye in allergic conjunctivitis: role of inflammatory infiltrate.

Dry-eye associated symptoms are frequently present in patients affected with allergic conjunctivitis. We evaluated the relationship between ocular inflammation and the tear film parameters in patients affected with chronic allergic conjunctivitis. Eighty-two subjects (age 23.00 &#x00B1; 7.61: range 10-40) affected with chronic allergic conjunctivitis and thirty age- and sex matched healthy controls were enrolled. In all patients tear film qualitative and quantitative tests were performed. To determine the immune activation state, conjunctival biopsies were obtained from the inferior conjunctival fornix. Immunocytochemical markers for CD45RO, CD8, CD20 and EG2 (monoclonal antibody binding eosinophil cationic protein) were evaluated semiquantitatively. All tear film tests were found altered. They were reduced in allergic patients (p&#x003C;0.001). In conjunctival biopsies of allergic patients a very high number of CD45RO+ and EG2+ cells were found (p&#x003C;0.001): a lower number of CD45RO+ cells and no EG2+ cells in control biopsies were found. Multivariate analysis showed a significant relationship between tear tests and conjunctival infiltrate (CD45RO+ and EG2+): The tear film alterations are strictly related to the conjunctival immune infiltration. In particular, the reduction of the mucin-related component of tear film can be related to the toxic effect of the granule cationic proteins released by the conjunctival activated eosinophils (EG2+ cells).

Journal Article↗

Role of substance P in experimental allergic conjunctivitis in guinea pigs.

The role of substance P in experimental allergic conjunctivitis induced by egg albumin was investigated with guinea pigs. Increase in vascular permeability of the conjunctiva induced by antigen was significantly inhibited after repeated application of capsaicin. Substance P contents in the conjunctiva of guinea pig were decreased by topical instillation of antigen to the eyes, suggesting that substance P was released from the conjunctiva due to antigen-antibody reaction. Moreover, subconjunctival injection of substance P resulted in a dose-related conjunctivitis, and vascular permeability in the conjunctiva was also increased by substance P. In substance P-induced conjunctivitis, a significant edema was observed in the bulbar and palpebral conjunctiva, but no hyperemia was noted in all instances. Histamine contents of the conjunctiva and tears were not influenced by subconjunctival injection of substance P. However, topical application of antigen and subconjunctival injection of compound 48/80 caused a significant decrease in histamine content, and content of tear was increased by both treatments. An increase in vascular permeability induced by antigen application was significantly inhibited by intravenous injection of FK-888, which is a specific and potent NK1 receptor antagonist. From these results, it is suggested that substance P is responsible for allergic conjunctivitis to some extent, and the conjunctival hyperpermeability induced by substance P occurs through NK1 receptor on the blood vessels, rather than by the direct action on the conjunctival mast cells during allergic conjunctival reactions.

Animals↗

Daily cost of ophthalmic solutions used to treat allergic conjunctivitis in Japan.

PURPOSE: To estimate the daily cost of various ophthalmic solutions used in Japan for treating allergic conjunctivitis, including nine anti-allergic drugs and six anti-inflammatory drugs. METHODS: The drops contained in one bottle of each solution were counted. The cost per drop was calculated by dividing the government-controlled standard prices by the total number of drops in one bottle, and the daily cost of therapy was calculated by multiplying the cost per drop by the number of drops to be given per day. RESULTS: The total number of drops of the anti-allergic drugs in a bottle ranged from 108 to 169 and that of the anti-inflammatory drugs from 100 to 145. The information in the package insert for these solutions recommends application 2-4 times daily. The price of the antiallergic drugs studied ranged from $6.35 to $8.38 and that of the anti-inflammatory drugs studied from $2.02 to $5.20. The daily cost of the anti-allergic drugs studied varied considerably, from $0.26 to $0.57; for the anti-inflammatory drugs the range was from $0.12 to $0.20. Variations in the total number of drops per bottle and in the recommended dosage affect the daily cost of ophthalmic solutions. CONCLUSIONS: At current prices, the volume of a drop and the dosage had a greater effect on the daily cost than the price of a bottle. Daily cost data may be helpful in selecting ophthalmic products for treating allergic conjunctivitis in settings where the prices of a given drug are relatively uniform.

Anti-Allergic Agents↗

Long-term safety of loteprednol etabonate 0.2% in the treatment of seasonal and perennial allergic conjunctivitis.

PURPOSE: To determine the long-term safety of the topical steroid, loteprednol etabonate 0.2%, in the treatment of seasonal and perennial allergic conjunctivitis. METHODS: A retrospective review of 397 patients from three private ophthalmologic practices treating seasonal and perennial allergic conjunctivitis with long-term loteprednol etabonate 0.2% was performed. Chart review of slitlamp findings and intraocular pressure measurements during follow-up visits was performed to determine the incidence of adverse effects, such as steroid-induced intraocular pressure increase, cataract formation, and any other possible topical steroid-induced adverse event. One hundred fifty-nine of the 397 patients had been continuously using loteprednol for more than 12 months. RESULTS: There were no reported adverse effects of long-term loteprednol etabonate 0.2% use in any of the 159 patients, whose continuous use ranged from a cumulative total of 120 drops per eye to 3,741 drops per eye. CONCLUSIONS: Loteprednol etabonate 0.2% is a safe topical steroid when used on a long-term basis for the treatment of seasonal and perennial allergic conjunctivitis.

Adolescent↗

Efficacy of levocabastine hydrochloride ophthalmic suspension in the conjunctival allergen challenge test in Japanese subjects with seasonal allergic conjunctivitis.

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

Adult↗

[Type I hypersensitivity to gramineae pollen (by tribe), in allergic conjunctivitis patients].

A total of 84 Costa Rican patients with a clinical diagnosis of Allergic Conjuntivitis (with or without other allergic diagnosis) and 100 non atopic subjects were studied by prick tests for all of Poaceae Tribes present in Costa Rica. Positivity was recorded in 70% of the Allergic Conjunctivitis patients for at least one of the tribes (against 2% of controls). An increase in the number of analysed tribes correlated with a higher number of patients allergic to graminean pollens. Guanacaste Province had the highest positivity, and patients aged 11 to 20 years were the most sensitive. Aveneae had the highest positivity except in Alajuela Province, in which Paniceae was highest in positivity. Poaceae pollens are very important in allergic hypersensitivity among Allergic Conjunctivitis patients. Prick tests for all the tribes present in the country are required to fully detect positivity to this family.

Adolescent↗

Clinical evaluation of twice-daily emedastine 0.05% eye drops (Emadine eye drops) versus levocabastine 0.05% eye drops in patients with allergic conjunctivitis.

PURPOSE: The efficacy and safety of emedastine 0.05% eye drops (Emadine; Alcon Laboratories, Inc, Fort Worth, Texas), a new H(1) antagonist, were studied in comparison to levocabastine 0.05% eye drops (Livostin; Janssen-Cilag N V, Berchem, Belgium) during a twice-daily treatment schedule for 6 weeks in adult and pediatric patients with seasonal allergic conjunctivitis. METHODS: In a prospective, multicenter, randomized, double-masked, parallel group study, 222 patients with allergic conjunctivitis were randomized (221 received treatment) to either emedastine or levocabastine, instilled twice daily for 6 weeks. Patient diaries were completed four times daily (before the morning and evening instillations, at noon, and in the afternoon), and clinical examinations were conducted at regular intervals. Primary efficacy variables of ocular redness and itching and secondary efficacy variables of chemosis, eyelid swelling, patient diary data, and physician's global assessment were analyzed. RESULTS: Both emedastine and levocabastine produced a statistically significant (P =.0001) reduction in itching and redness within 5 minutes of the first instillation. All signs and symptoms improved progressively over the 6-week treatment period. After 7 days of use, and throughout the remainder of the study, emedastine was statistically superior to levocabastine (P <.006) in preventing and alleviating the signs and symptoms (itching, redness, chemosis, and eyelid swelling) of allergic conjunctivitis. CONCLUSIONS: Emedastine 0.05% eye drops administered twice daily are more efficacious than levocabastine 0.05% eye drops in the prevention and treatment of the signs and symptoms of allergic conjunctivitis in adults and children of 4 years and above. Both emedastine 0.05% eye drops and levocabastine 0.05% eye drops were well tolerated.

Adolescent↗

Emedastine ophthalmic solution 0.05% versus levocabastine ophthalmic suspension 0.05% in the treatment of allergic conjunctivitis using the conjunctival allergen challenge model.

PURPOSE: To compare a new ocular antihistamine, emedastine difumarate (Emadine Ophthalmic Solution 0.05%; Alcon Laboratories, Fort Worth, Texas), with the marketed ocular antihistamine, levocabastine hydrochloride (Livostin Ophthalmic Suspension 0.05%; CIBA Vision, Atlanta, Georgia), in the treatment of allergic conjunctivitis after conjunctival allergen challenge. METHODS: We performed a prospective, double-masked, randomized, contralateral eye study comparing emedastine 0.05% in one eye with levocabastine 0. 05% or emedastine vehicle (placebo) in the contralateral eye. Efficacy was determined 10 minutes and 2 hours after administration of study medications. Ocular itching and redness scores were recorded 3, 5, and 10 minutes after conjunctival allergen challenge. RESULTS: A total of 97 subjects with a history of allergic conjunctivitis and a positive response to a diagnostic test were evaluable for safety analysis, and 91 subjects were evaluable for the efficacy analysis. Emadastine 0.05% was statistically significantly more effective than levocabastine 0.05% in reducing ocular itching after conjunctival allergen challenge in both the 10-minute and the 2-hour challenge (P <.05). Emedastine 0.05% and levocabastine 0.05% were statistically equivalent in reducing conjunctival redness after conjunctival allergen challenge, although emedastine tended to be more efficacious than levocabastine at every observation time point. CONCLUSIONS: After conjunctival allergen challenge, emadastine 0.05% is significantly more effective than levocabastine 0.05% in reducing ocular itching associated with allergic conjunctivitis. The two compounds are equivalent in controlling the conjunctival redness associated with allergic conjunctivitis.

Adolescent↗

Local ocular immunotherapy for experimental allergic conjunctivitis.

PURPOSE: We studied the efficacy of eyedrops as local ocular immunotherapy against experimental allergic conjunctivitis. METHODS: Guinea pigs were sensitized with an intraperitoneal injection of ovalbumin (OA). Three weeks after the sensitization, a low concentration (10 microg/mL) of OA eyedrops was administered once a day for 3 weeks. Six weeks after the sensitization, an allergic inflammation was provoked with 20 mg/mL of OA eyedrops. RESULTS: In conjunctival clinical scores 30 minutes after the allergen challenge, there was no significant difference between the controls and the treated group. The total number of inflammatory cells in the conjunctiva 8 hours after the allergen challenge was significantly decreased in the treated group (60.8 +/- 23.2 cells/field) compared with the control group (199.1 +/- 83.4 cells/field). Eosinophils in the conjunctiva 24 hours after the allergen challenge were also significantly decreased in the treated group (22.1 +/- 15.5 cells/field) compared with the control group (50.3 +/- 15.0 cells/field). CONCLUSIONS: In this study, local ocular immunotherapy mainly suppressed the late phase reaction of allergic inflammation. These results coincide with previous studies of immunotherapy in which a subcutaneous injection was used. Local ocular immunotherapy is effective against experimental allergic conjunctivitis.

Allergens↗

Platelet activating factor degradation in tear fluid from guinea pigs with allergic conjunctivitis.

The purpose of this study was to investigate the role of platelet-activating factor (PAF) and PAF acetylhydrolase (AH) in conjunctiva. The influence of PAF on conjunctival vascular permeability and the presence of PAF or its metabolites in tears from guinea pigs with allergic conjunctivitis were investigated. We instilled PAF to the eyes of guinea pigs and evaluated vascular permeability. Tear samples were collected from passively sensitized guinea pigs, and the concentration of PAF and its metabolites determined by liquid chromatography-tandem mass spectrometry. Exogenous PAF degradation in tear samples was evaluated with or without diisopropyl fluorophosphate (DFP). Topically applied PAF increased vascular permeability in conjunctiva. In the tear samples from guinea pigs with allergic conjunctivitis, PAF could not be detected. However, 40 +/- 6 ng/ml of lyso-platelet activating factor (lyso-PAF) and 230 +/- 50 ng/ml of 1-alkyl-2-acyl-sn-glycero-3-phosphocholine were detected at 10 min after challenge. Exogenous PAF was rapidly degraded in the tear samples from guinea pigs with allergic conjunctivitis, but not from normal guinea pigs. This PAF degradation was inhibited by DFP. These results suggest that PAF in the tear fluid is quickly hydrolyzed to lyso-PAF by PAF AH, which may be released or activated in allergic conjunctivitis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Comparison of 0.1% bromfenac sodium and 0.1% pemirolast potassium for the treatment of allergic conjunctivitis.

PURPOSE: We compared the efficacy of a new nonsteroidal antiinflammatory drug (NSAID) eye drop, 0.1% bromfenac sodium (Bromfenac), with that of an antiallergic agent, 0.1% pemirolast potassium (Pemirolast), in the treatment of seasonal allergic conjunctivitis in Japanese patients. METHODS: Twenty-two subjects with seasonal allergic conjunctivitis were enrolled in the study. One eye was treated with Bromfenac eye drops and the contralateral eye was treated with Pemirolast eye drops for 1 week. Subjective ocular symptoms and objective ocular signs evaluated by slit-lamp examination were scored and recorded before and after treatment. RESULTS: Both drugs significantly decreased ocular signs after 1 week, but not symptoms. No significant differences in subjective symptoms or objective signs were observed between the two drugs. Ten patients (45.5%) selected Bromfenac as more effective, nine patients (40.9%) selected Pemirolast, and three patients found no difference in efficacy between the two drugs. CONCLUSION: Bromfenac sodium is as safe and effective for the treatment of allergic conjunctivitis as pemirolast potassium.

Adolescent↗