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Nedocromil sodium in golfers with seasonal allergic conjunctivitis.

To evaluate nedocromil sodium 2% ophthalmic solution for the treatment of seasonal allergic conjunctivitis, 24 golfers with documented ragweed-pollen allergy instilled eyedrops twice daily for 4 days prior to golf-course intervention and 15 minutes before playing a round of golf during peak ragweed season. Ocular symptoms were scored at baseline (7 days before golfing), prior to instillation on the day of golf, and 30 minutes, and 1, 4, 8, and 12 hours after tee-off. Physician assessment was performed prior to tee-off, before tee-off on the ninth hole, and at the end of the 18th hole. Itching, burning, grittiness, tearing, redness, and light sensitivity were significantly decreased after nedocromil administration, as were erythema, edema, conjunctival hyperemia, and overall findings in the conjunctiva. Symptom severity scores fell approximately 30 minutes after instillation, with improvements persisting 8 and 12 hours after treatment. Most patients (92%) rated the treatment moderately or completely effective, and 83% were willing to continue its use. Physician assessments of effectiveness agreed with those of the patients. In this open-label study, nedocromil sodium eyedrops relieved the ocular symptoms of seasonal allergic conjunctivitis for up to 12 hours, well beyond a usual round of golf.

Adolescent↗

Dry eye with only decreased tear break-up time is sometimes associated with allergic conjunctivitis.

PURPOSE: The authors' clinical experience has suggested that there is a form of dry eye with only decreased tear break-up time, which is associated with allergic conjunctivitis. The current study was performed to verify this hypothesis. METHOD: The authors recruited patients with two types of dry eye syndrome, those with only decreased tear break-up (BUT type) and those with positive vital staining (staining type). Individuals without any symptoms or signs served as controls. All subjects were compared regarding symptoms, Schirmer and tear clearance test results, conjunctival papillary formation, antigen-specific serum-IgE level (s-IgE), and goblet cell density of the palpebral conjunctiva. Antigen-induced allergic conjunctivitis was produced in guinea pigs, and histopathologic changes of the conjunctiva were examined. RESULTS: Patients with the BUT-type dry eye syndrome were younger and their symptoms were as severe as the staining type. The Schirmer and tear clearance test results were better, and the papillary formation and s-IgE were observed more than in the BUT type. The average goblet cell density in the BUT-type syndrome was 625.4 +/- 193.2/mm2, which was significantly less than 1005.6 +/- 294.5/mm2 in the controls (P < 0.01). The average goblet cell density was significantly decreased in the allergic animals (10.40 +/- 1.11/0.2 mm) compared with that of the controls (16.21 +/- 0.26/0.2 mm) or the anti-allergic drug-treated group (13.69 +/- 0.30/0.2 mm) (P < 0.01). CONCLUSION: These results support the authors' hypothesis that decreased break-up time is in part associated with the decreased goblet cell density caused by allergic conjunctivitis.

Adult↗

Vascular permeability in allergic conjunctivitis in mice lacking histamine H1 receptors.

To clarify the role of histamine H1 receptors in allergic conjunctivitis, changes in vascular permeability of the conjunctiva were measured in histamine H1 receptor deficient mice. Wild-type mice showed a significant increase in vascular permeability of the conjunctiva induced by histamine. However, no such increase was found in histamine H1 receptor deficient mice. On the other hand, no differences were observed between wild-type and histamine H1 receptor deficient mice in response to serotonin. A significant increase in vascular permeability was observed in actively sensitized wild-type mice, whereas no increase was observed in histamine H1 receptor deficient mice. Similar findings were noted in passively sensitized animals. Histamine contents of the conjunctiva were significantly decreased by topical application of antigen in both wild-type and histamine H1 receptor deficient mice after active sensitization with antigen. These findings suggested that vascular permeability in the conjunctiva in allergic conjunctivitis is entirely regulated through histamine H1 receptor.

Animals↗

Nedocromil sodium and astemizole, alone or combined, in the treatment of seasonal allergic conjunctivitis. A multicentre double blind clinical trial.

Two hundred and seven patients with active symptoms of allergic conjunctivitis were studied in a four-week multicentre double blind, double dummy, clinical trial comparing efficacy and safety of nedocromil sodium eye drops with oral astemizole, placebo, and the combined active treatments. Clinical signs were evaluated by clinicians after 1, 2 and 4 weeks, while symptoms were recorded by patients on daily diary cards. Overall opinions were recorded at the end of treatment. Nedocromil sodium eye drops and astemizole, alone or combined, significantly reduced ocular symptoms when compared to placebo (diary card total symptom score and patients' opinion). In the clinicians' opinion nedocromil sodium alone or combined (but not astemizole alone) significantly decreased ocular symptoms when compared to placebo. All treatments were safe and well tolerated, drowsiness being the most frequent side effect observed in patients treated with astemizole. These results indicate the effectiveness of nedocromil sodium eye drops in the treatment of seasonal allergic conjunctivitis.

Adolescent↗

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.

Adolescent↗

Twice daily 4% Sodium Cromoglycate vs. 2% Sodium Cromoglycate used four times daily in seasonal (grass pollen) allergic conjunctivitis.

It is well established that 2% Sodium Cromoglycate is an effective treatment for a number of allergic eye diseases. It has been shown to be non-toxic. It can be used longterm and in serious allergic problems it is a useful adjunctive therapy to steroids. The main problem with Sodium Cromoglycate is that the recommended dosage is a four times daily application and patient non-compliance is common. One of the main objectives of any therapy is to reduce the frequency of dosage and the current study has been designed to investigate the efficacy of a 4% solution of Sodium Cromoglycate, used twice daily, versus a 2% solution used four times daily in seasonal allergic conjunctivitis. A multicentre study, therefore, was carried out to assess the efficacy of both drugs and to assess any possibility of side effects. In addition, a unit dose was used, thus eliminating preservatives and it was used specifically in seasonal allergic conjunctivitis in the pollen season. This study showed that 4% Sodium Cromoglycate used twice daily was at least as affective as 2% Sodium Cromoglycate used four times daily.

Adolescent↗

Comparison of the efficacy and tolerability of topically administered azelastine, sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis.

OBJECTIVE AND SETTING: Azelastine (AZE) in a novel, eye drop, formulation, was compared with topically applied sodium cromoglycate (SCG) and placebo (PLA) in the treatment of seasonal allergic conjunctivitis or rhino-conjunctivitis in a multicentre, parallel group study. RESEARCH DESIGN: 144 subjects ranging in age from 16 to 65 years participated. All had at least a 2-year history of seasonal allergic conjunctivitis and were symptomatic at the time of inclusion. Medications were administered topically either twice daily (AZE/PLA) or four times daily (SCG) over a 2-week treatment period. Method and outcome measures: Azelastine and placebo were compared double-blind; the comparison versus SCG was carried out in an open manner. Itching, redness, flow of tears, eyelid swelling, foreign-body sensation, photophobia, soreness and discharge were scored on a 4-point severity scale. RESULTS: Results for the decrease of main conjunctivitis symptoms (itching, tearing and conjunctival redness) showed a marked effect for both active treatments on day 3 with a sustained improvement on days 7 and 14. A clear response to treatment (an improvement of sum scores for day 3 of >/=3 points compared to baseline) occurred in 85.4% of azelastine-treated patients, 83.0% of sodium cromoglycate patients and 56.3% of placebo patients. Response rates for both active treatments were statistically superior to those for placebo (azelastine p = 0.005; sodium cromoglycate p = 0.007). Global assessment of efficacy was at least 'satisfactory' for 90.0% of azelastine patients, 81.3% of sodium cromoglycate patients and 66.3% of placebo-treated patients. The most frequent adverse effects were transient application site reactions which tended to disappear with increasing duration of treatment, and, less frequently, taste perversion. CONCLUSION: The results of this study indicate that the therapeutic use of azelastine eye drops in patients with seasonal allergic conjunctivitis or rhino-conjunctivitis can be recommended.

Administration, Topical↗

Aggravation of experimental allergic conjunctivitis by environmental chemical and physical factors.

The effects of trichlorfon (DEP, Dipterex, anticholinesterase pesticide) and paraquat dichloride (Gramoxon, inhibitor of superoxide dismutase) on passive anaphylactic reaction in guinea pig conjunctiva using Japanese cedar pollen were quantitatively studied. For estimation of allergic conjunctivitis, Evans blue after i.v. injection was extracted from conjunctiva and measured spectrophotometrically. Allergic conjunctivitis was apparently aggravated by extremely low dosages of organophosphorus pesticide (10(-5) mg/kg) and organochlorine herbicide (10(-4) mg/kg). The aggravation of allergic conjunctivitis was also observed after exposure to cathode ray tubes used in commercial television, possibly due to electromagnetic waves. IgE-mediated allergic reaction could be non-specifically potentiated by such environmental factors.

Allergens↗

Analysis of the interaction between IFN-gamma and IFN-gammaR in the effector phase of experimental murine allergic conjunctivitis.

IFN-gamma acts to promote the severity of experimental allergic conjunctivitis (EC) during the effector phase. To identify the cell source and cell target of this cytokine in the effector phase of EC, we established mice lacking both IFN-gamma and the IFN-gamma receptor (Dbl-KO). Reciprocal adoptive transfer experiments involving wild-type, Dbl-KO, IFN-gamma-lacking and IFN-gammaR-lacking mice were performed. EC was then induced by RW challenge in eye drops. Analysis of the resulting eosinophil infiltration in the six donor/recipient combinations revealed that IFN-gamma produced by both donor and recipient cells plays an important role in the EC effector phase, and that the targets for this cytokine are also both donor and recipient cells. That EC was attenuated when any of the IFN-gamma-IFN-gammaR interactions were disturbed confirms that IFN-gamma promotes the severity of EC during the effector phase. These observations indicate that Dbl-KO mice will be useful for investigating the role(s) IFN-gamma play in inflammatory diseases.

Adoptive Transfer↗

Interleukin-4 and IgE in seasonal allergic conjunctivitis.

We measured interleukin-4 (IL-4) and IgE to study their presence in patients with seasonal allergic conjunctivitis. Twenty patients and 10 normal subjects were enrolled in this study, and their brush cytology samples and peripheral blood lymphocytes (PBL) were cultured for 3 or 24 h. IL-4 levels were measured using ELISA in the supernatants. Measurements of serum IgE were also performed. IL-4 was detected in 4 of 40 brush cytology samples and 10 of 40 PBL samples, but not from the controls. IL-4 positivity rate of patients was significantly higher than normal in 24-hour cultured PBL (p = 0.03). Patients' serum IgE was also significantly higher (p = 0.006). IL-4 may contribute to the development of seasonal allergic conjunctivitis.

Adolescent↗

Two mast cell stabilizers, pemirolast potassium 0.1% and nedocromil sodium 2%, in the treatment of seasonal allergic conjunctivitis: a comparative study.

This randomized, double-masked, active-control, parallel-group trial compared the mast cell stabilizers pemirolast potassium 0.1% and nedocromil sodium 2% in the treatment of seasonal allergic conjunctivitis. Pemirolast is currently indicated for four-times-daily administration, nedocromil, for twice-daily dosing. Both ophthalmic solutions were instilled bilaterally twice a day for 8 weeks. The study involved four office visits and two telephone contacts. Participants evaluated their symptoms daily in take-home diaries (itching was the primary efficacy variable) and completed questionnaires to assess comfort. Of a total enrollment of 80, 78 patients completed the study. No significant differences were found between pemirolast and nedocromil on any signs or symptoms of allergic conjunctivitis (redness, chemosis, itching, eyelid swelling). At each visit, pemirolast was rated significantly more comfortable than nedocromil. A significantly higher percentage of the pemirolast group experienced no signs or symptoms at work or school (58% vs 28%; P = .005). The number of adverse events did not differ significantly between groups. Twice-daily administration of pemirolast potassium was as efficacious and safe as twice-daily nedocromil sodium in the 8-week treatment of ragweed allergic conjunctivitis and was superior to nedocromil in comfort. Increased comfort with pemirolast may increase patient satisfaction and compliance with therapy.

Administration, Topical↗

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.

Administration, Topical↗

Blocking ICAM-1 (CD54) and LFA-1 (CD11a) inhibits experimental allergic conjunctivitis.

Cell adhesion molecules are critical for the homing and migration of leukocytes into inflamed tissues. We investigated the role of ICAM-1 and LFA-1 in a previously described experimental model of ragweed (Rw)-induced allergic conjunctivitis. SWR/J mice were treated intraperitoneally 6 and 1 h prior to topical challenge with Rw with injections of anti-ICAM-1 monoclonal antibody (mAb), anti-LFA-1 mAb, both anti-ICAM-1 and anti-LFA-mAbs, or rat IgG. Blocking ICAM-1 or LFA-1 reduced the clinical signs of allergic conjunctivitis. Treatment with anti-ICAM-1 or anti-LFA-1 mAbs also significantly inhibited cellular infiltration into the conjunctiva. The greatest inhibitory effect was achieved with the combination of antibodies against both cell adhesion molecules. Since antibodies against ICAM-1 and LFA-1 significantly inhibit the development of the clinical and histologic signs of allergic conjunctivitis, they may be useful for treating patients with ocular allergy.

Animals↗