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PubMed2006

Role of VLA-4 in the development of allergic conjunctivitis in mice.

PURPOSE: The severity of allergic conjunctivitis (AC) correlates with the degree of eosinophil infiltration into the conjunctiva, which is believed to be mediated by chemokines and adhesion molecules. The adhesion molecule very late antigen (VLA)-4 and its ligand, vascular cell adhesion molecule (VCAM)-1, are known to play important roles in eosinophil infiltration. However, the expression and function of VLA-4 in AC have not been investigated in detail. We sought to characterize VLA-4-expressing cells in the conjunctivas of mice that are developing experimental AC (EC) and to determine whether the interaction between VLA-4 and VCAM-1 is needed for the infiltration of eosinophils into the conjunctiva in AC. METHODS: EC was induced in Balb/c mice by active immunization with ragweed (RW) or adoptive transfer of RW-primed splenocytes, followed by RW challenge. Twenty-four hours after RW challenge, the conjunctivas were harvested. The conjunctivas from naive mice or mice developing EC were evaluated for VLA-4 and VCAM-1 expression by immunohistochemistry and immunofluorescent analyses. To investigate whether the interaction between VLA-4 and VCAM-1 is needed for the genesis of AC, mice developing EC were treated with anti-VLA-4 or anti-VCAM-1 antibodies two h before and after RW challenge. As a control, EC-developing mice were treated with normal rat IgG. Twenty-four hours after RW challenge, the conjunctivas were harvested for histological analysis. RESULTS: Upon induction of EC, VLA-4-expressing cells infiltrated the conjunctiva but the constitutive VCAM-1 expression around conjunctival vessels was not augmented. Immunofluorescent analyses demonstrated that most of the T cells infiltrating the conjunctiva expressed VLA-4 but only half of the infiltrating eosinophils expressed it. Treatment with both anti-VLA-4 and anti-VCAM-1 antibodies significantly suppressed the infiltration of eosinophils into the conjunctiva that was induced by either active immunization or splenocyte transfer. CONCLUSIONS: These results confirm that VLA-4-expressing cells infiltrate the conjunctiva and that the interaction between VLA-4 and VCAM-1 is needed for the development of EC.

Adoptive Transfer↗
PubMed1994

Evaluation of nedocromil sodium 2% ophthalmic solution for the treatment of seasonal allergic conjunctivitis.

During peak ragweed season, 86 patients with seasonal allergic conjunctivitis participated in a 9-week, multicenter, double-masked, placebo-controlled, group-comparative study testing the efficacy and safety of bid nedocromil sodium, 2% ophthalmic solution. The clinical effectiveness of nedocromil sodium was measured by analyzing the means of patient daily symptom scores and eye examinations after 1, 3, 5, and 8 weeks of treatment. The use of nedocromil sodium during peak ragweed pollen season reduced symptom scores with statistically significant treatment differences as compared with the placebo for itchy eyes, tearing, overall eye condition, and symptom summary score. Clinician assessments also favored the use of nedocromil sodium as indicated by significant improvements in tearing, conjunctival injection, and conjunctival edema. No significant side effects were reported by the patients, allergists, or ophthalmologists. We conclude that nedocromil sodium, 2% ophthalmic solution, administered bid is more effective in the relief of symptoms of seasonal allergic conjunctivitis than placebo and causes no major side effects.

Adolescent↗
PubMed2000

The role of nitric oxide in experimental allergic conjunctivitis.

PURPOSE: To evaluate the role of nitric oxide (NO) in the pathogenesis of allergic conjunctivitis and the effect of NO-synthase (NOS) inhibitors. METHODS: The experimental allergic conjunctivitis was provoked in rabbits and healthy human volunteers by mast cell activators (codeine phosphate, 2.5 mg/mL; compound 48/80, 50 mg/mL; and lipopolysaccharide, 10 ng/eye). NOS inhibitors (aminoguanidine [AG], 1.5%, or N(G)-nitro-L-arginine methyl ester [L-NAME], 200 microg/eye) were applied as a pretreatment. In a rabbit model, concentrations of nitrite plus nitrate in the tear were measured colorimetrically using the Griess reaction after 0.5, 1.5, 3, 6, and 9 h. Immunohistochemical study for NOS was performed. The clinical scoring was performed in human volunteers. The vascular permeability was determined by measuring the albumin content in the tear of the challenged human eyes after 1 h. RESULTS: After the instillation of mast cell activator, the NO level and clinical symptoms were markedly increased within 1.5 h. The NOS inhibitors suppressed the NO level. Vascular permeability was also increased in the activator-treated group. The NO-synthase immunoreactivity has been detected in the conjunctival subepithelial area and stroma for brain and endothelial isoform. L-NAME significantly reduces the immunoreactivity for NOS. CONCLUSION: These results suggest that the expression of NOS mainly contributes to the allergic symptoms. Therefore, NO is an important factor in the induction and progress of the allergic reaction to ocular surface. The NOS inhibitors may have a beneficial effect for allergic conjunctivitis.

Adult↗
PubMed1996

Interaction between nitric oxide and prostaglandin synthesis in the acute phase of allergic conjunctivitis.

Both nitric oxide and prostaglandins induce vasodilatation which is an important feature of local inflammation. The purpose of the study described here was to investigate a possible interaction between these two types of mediators in an experimental model of allergic conjunctivitis. A conjunctival allergic reaction was induced with antigen in sensitized guinea pigs. Conjunctival vascular permeability changes were evaluated with the prophylactic use of an inhibitor of nitric oxide synthase (L-NAME) and a cycloxygenase inhibitor (indomethacin). To study a possible interaction between nitric oxide and prostaglandin synthesis in the acute phase of allergic conjunctivitis, the levels of nitrite and PGE2 were determined in lavage fluid. The prophylactic use of L-NAME on the formation of conjunctival edema in response to topical PGD2 administration was studied by measurement of albumin levels in lavage fluid. Both nitric oxide and PGE2 are synthesized in response to antigen provocation and after histamine administration. Nitric oxide and PGE2 are produced simultaneously in the conjunctiva and they showed identical synthesis profiles in response to antigen provocation. Pretreatment with L-NAME inhibited the synthesis of PGE2 whereas exogenous administration of nitric oxide increased the level of PGE2 in lavage fluid. Prophylactic treatment with L-NAME significantly inhibited the PGD2 induced albumin extravasation. Nitric oxide seems to play an important role in the acute phase of allergic conjunctivitis it may stimulate PGE2 production and acts as a secondary mediator in PGD2 and histamine induced conjunctival edema.

Administration, Topical↗
PubMed1997

Potent inhibitory effect of tetrandrine on experimental allergic conjunctivitis in mice.

This study investigated the effectiveness of tetrandrine (TDR) on experimental allergic conjunctivitis secondary to ragweed pollen. SWR/J mice were divided as follows: group 1, normal controls; group 2, sensitized but untreated; group 3, sensitized, buffered saline (BS)-treated; and group 4, sensitized, TDR-treated. The last three groups were exposed to ragweed through topical contact on the nasal and conjunctival mucosae followed by challenge with the allergen on the conjunctiva. Groups 3 and 4 received doses of BS and TDR, respectively. The allergic conjunctivitis was evaluated by scoring of the clinical signs and histopathology. mRNA gene expression of interleukin 1 beta (IL-1 beta) and IL-5 in the conjunctiva was analyzed by polymerase chain reaction techniques. All mice exposed to ragweed developed allergic conjunctivitis clinically and histologically. The conjunctivitis was significantly modulated by intraperitoneal injection of a new anti-inflammatory agent, TDR. Histopathologic analysis demonstrated that TDR strikingly reduced the conjunctival eosinophil infiltration and the number of intact and degranulating mast cells. IL-1 beta and Il-5 mRNA gene expression in the conjunctiva of TDR-treated mice was dramatically down-regulated compared with untreated and BS-treated controls. The results indicate that TDR may have potential clinical use in the treatment of conjunctivitis.

Alkaloids↗
PubMed2001

Bilateral conjunctival mucosa-associated lymphoid tissue lymphoma misdiagnosed as allergic conjunctivitis.

PURPOSE: This report aimed to discuss two nearly identical cases of primary conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma mimicking allergic conjunctivitis. METHODS: Two patients were referred for intractability to conventional treatment of initial diagnoses of allergic conjunctivitis. On ocular examination, normally pigmented, giant papilla-like lesions were found bilaterally in the upper conjunctiva. Excisional biopsies were performed. RESULTS: Histopathologic and immunohistochemical examination of the conjunctival biopsies indicated MALT lymphoma in both patients. The patients subsequently received radiation therapy and achieved complete remission with no evidence of recurrence during follow-up periods of 13 and 11 months. CONCLUSION: Conjunctival low-grade lymphoma may share similar clinical features with allergic conjunctivitis. Ophthalmologists should be concerned that primary conjunctival low-grade malignant lymphoma can be misdiagnosed as allergic conjunctivitis

Adult↗
PubMed1993

[Participation of environmental chemicals in experimental allergic conjunctivitis].

The effects of organophosphorus pesticides (trichlorfon and fenitrothion) and an organochlorine herbicide (paraquat) on experimental allergic conjunctivitis were studied quantitatively. Guinea pigs were passively immunized with antiserum to Japan cedar pollen. The above chemicals were administered subcutaneously 2 days prior to challenge with cedar pollen in the conjunctival sac, resulting in allergic conjunctivitis. The intensity of the conjunctival allergic reaction was quantitatively estimated by measuring the extravasation of Evans blue in the conjunctiva which had previously been administered intravenously. The allergic conjunctivitis was apparently aggravated by extremely low dosage level of organophosphorus pesticide (10(-4) approximately 10(-5) mg/kg) and organochlorine herbicide (10(-3) approximately 10(-4) mg/kg). The most intensive aggravating reaction was obtained 10(-5) mg/kg of organophosphorus pesticide and at 10(-4) mg/kg of paraquat dichloride. The aggravating effects of organophosphorus pesticide and organochlorine herbicide persisted at least two weeks after the single administration.

Animals↗
PubMedDate not supplied

[Prevalence and risk factors for allergic conjunctivitis in children. Comparative study in two communities].

OBJECTIVE: To determine the prevalence and risk factors for allergic conjunctivitis in childhood populations, in two communities with different urban and industrial development, and population density. METHODS: A questionnaire was applied to childhood from 6 to 14 years old, selected through cluster sampling. This was an epidemiologic study, observational, open, retrospective and cross-sectional. This is a case-control study with cohorts. Statistical analysis consisted in frequency distributions, odds ratios, 95% confidence intervals. Statistical significance was p < 0.05. RESULTS: In the population El Higo, at Veracruz state, where sugar industry is the most important commercial activity, allergic conjunctivitis prevalence was 9.7%; allergic family antecedent was found in 79.74% of patients (p = 0.001, OR = 8.1); nicotinism at home in 12.65% (p = 0.001, OR = 0.34); factory near of patients' house in 65.82% (p = 0.001, OR = 3.5). In Tampico-Madero-Altamira suburb, the prevalence of the pathology was 10.09%; allergic family antecedent 58.89% (p = 0.001, OR = 2.52%); nicotinism at home 36.25% (p = 0.59, OR = 1.06); factory near of house 21.01% (p = 0.03, OR = 1.29). CONCLUSIONS: Results let us to know the problem that health staff will cope when facing allergic conjunctivitis; that results will be important for strategies designing, in order to establish preventive actions to take in the health-disease evolution of this pathology.

Adolescent↗
PubMed2002

Pemirolast potassium 0.1% ophthalmic solution is an effective treatment for allergic conjunctivitis: a pooled analysis of two prospective, randomized, double-masked, placebo-controlled, phase III studies.

Patients with allergic conjunctivitis may experience several debilitating symptoms, particularly ocular itching. The objective of this study was to evaluate the efficacy and safety of pemirolast potassium 0.1% ophthalmic solution (Alamast trade mark ), a novel mast-cell stabilizer, for preventing ocular manifestations of seasonal allergic conjunctivitis. A pooled analysis was performed of data derived from 2 prospective, randomized, double-masked, placebo-controlled, multicenter phase III clinical trials of pemirolast potassium 0.1% in patients with a history of allergic conjunctivitis. Patients having a positive bilateral response to conjunctival allergen challenge (CAC) with ragweed antigen (N = 274) were randomized to receive pemirolast potassium 0.1% or placebo QID, beginning approximately 1-2 weeks before the onset of ragweed season and continuing until after the first killing frost (12-17 weeks duration). Patients recorded their daily evaluations of ocular itching in a diary. After the allergy season, patients underwent a second CAC. Evaluable patients (n = 265) recorded a total of 21,491 patient-days of ocular itching data during allergy season. In every 7-day or 14-day period, patients treated with pemirolast potassium 0.1% reported more days without any ocular itching compared with patients receiving placebo. Differences favoring pemirolast potassium 0.1% were statistically significant in 63% (10/16) of all 7-day periods (p < or = 0.046) and 88% (7/8) of all 14-day periods (p < or = 0.016). After the allergy season, pemirolast potassium 0.1% was significantly superior to placebo in relieving CAC-induced ocular itching, with relief occurring as early as 3 minutes after allergen challenge (p < or = 0.034). Pemirolast potassium 0.1% was well tolerated and had a safety profile similar to that of placebo. In conclusion, pemirolast potassium 0.1% is effective and safe in preventing ocular itching in patients with allergic conjunctivitis during allergy season.

Adolescent↗
PubMed1995

Allergic conjunctivitis and uveitis models: reappraisal with some marketed drugs.

The purpose of this study was to assess the activity of some marketed products in ocular non-immune and immune type I hypersensitivity reactions, and during intra-ocular type III hypersensitivity. In order to compare these activities, we improved and validated three different models of ocular allergic reaction already known for their ability to reproduce allergic conjunctivitis or uveitis. Allergic conjunctivitis was induced by ocular immediate hypersensitivity after instillation of compound 48/80 in the rat, or an active anaphylaxis reaction with ovalbumin immunisation and challenge in the guinea pig. Uveitis was induced by a reverse passive anaphylaxis reaction using intra-vitreal rabbit anti-bovine IgG anti-serum sensitisation and intravenous bovine gamma-globulin challenge in the rabbit. Clinical scores and blood-tissue permeability indices were studied. Using the same schedule of ocular instillation, the effects of Livostin (levocabastine 0.05%), Almide (lodoxamide 0.1%), Opticrom (sodium cromoglycate 2%), Ocufen (flurbiprofen 0.03%), Acular (ketorolac 0.5%) and 0.3% chlorpheniramine maleate were compared to positive and negative controls. We demonstrated the potent activity of chlorpheniramine maleate 0.3% and Livostin in both allergic conjunctivitis models. Significant activity was also evidenced with Almide, which was only active in the non-immune allergy model, while Opticrom was definitely not active in these models. In the uveitis model, Acular and Ocufen are active and potent drugs, while Livostin and Almide were not active. These results are discussed with respect to the models used and the mediators involved.

Anaphylaxis↗
PubMedDate not supplied

Clobetasone treatment of allergic conjunctivitis: a comparative double blind study.

Glucocorticosteroids are often included in the treatment of allergic conjunctivitis. The present study compares the efficacy on clinical and cytological parameters and safety of topical clobetasone butyrate compared to placebo. The trial, designed as double blind, randomized and parallel group treatment, was carried out in 30 patients, suffering from seasonal allergic conjunctivitis due to Grass pollen, during the pollen season (June 1992). Patients received clobetasone butyrate 0.1% eye drops or placebo eye drops, two drops each eye, t.i.d. for 10 days. The clinical and cytological evidences were investigated on admission and at the end of treatment by clinicians and by patients on a dairy card. The steroid group showed a rapid and significant clinical improvement and at the end of the trial a statistically significant difference was evidenced between the active drug treated group and placebo treated group. No serious side effects were observed. The results show the clinical efficacy of clobetasone butyrate in the treatment of pollen-induced allergic conjunctivitis.

Adolescent↗
PubMed2004

[Ketotifen fumarate (Zaditen) eye drops in the treatment of seasonal allergic conjunctivitis].

A group of 25 patients with signs of seasonal allergic conjunctivitis treated during the period of 2 to 6 month with ketotifen fumarate 0.05% eye drops 2-3 times daily (Zaditen eye drops, Novartis Ophthalmic, AG, Switzerland) is described here. As subjective symptoms of itching, stinging, tearing, and mucous discharge were observed and evaluated, as well as objective signs of hyperemia of the conjunctiva and hypertrophy of the tarsal papillae. Similarly the onset of action, duration time, and toleration of the drug were assessed. Subjective symptoms disappeared after 10 days of treatment duration in 60% to 80% patients, after two months of treatment were present in the range 0% to 20%. Objective signs diminished after 10 days of treatment in 60%-72% patients, and after 2 months in 72% to 96% of patients. Hypertrophy of papillae of the tarsal conjunctiva did not totally disappear even after 6 month of treatment with ketotifen fumarate eye drops. Onset of action in all patients was 20 minutes or less, the duration of action was in the range of 8-13 hours. The drug was found as a good tolerable by all patients. Sixteen per cent of patients felt some burning following the instillation. The study states that ketotifen fumarate 0.05% eye drops are effective in a monotherapy of seasonal allergic conjunctivitis. Due to its multiple action, the drug prevents the allergic reaction as well. Subjective symptoms are influenced faster and more effective than the objective signs. The treatment of objective signs needs prolonged use of these drops.

Adult↗
PubMedDate not supplied

Double-masked, paired-comparison clinical study of ketorolac tromethamine 0.5% ophthalmic solution compared with placebo eyedrops in the treatment of seasonal allergic conjunctivitis.

In a multicenter, double-masked, clinical study, we compared the ocular safety and efficacy of ketorolac 0.5% ophthalmic solution with placebo in alleviating the signs and symptoms of allergic conjunctivitis. The study was conducted in 93 patients who received one drop of the appropriate treatments in each eye, four times a day, for seven days. Of these subjects, 74 were evaluated for efficacy. The principal clinical sign of allergic conjunctivitis, conjunctival inflammation, and six allergic symptoms (itching, swollen eyes, burning or stinging, discharge or tearing, foreign body sensation, and photophobia) were evaluated by the investigators at midweek (day 3 or 4) and at the end of the study (day 7 or 8). Ketorolac was superior to placebo in reducing conjunctival inflammation (p = 0.003) and itching (p = 0.020), the principal clinical symptom, at the final examination. In addition, ketorolac was favored over placebo in reducing the other five symptoms evaluated. On the day of final examination, overall therapeutic response evaluated by the investigators rated ketorolac as superior to placebo (p = 0.007). A significant placebo effect was noted in this study, as has been previously reported in clinical studies of allergic conjunctivitis patients. Results of this study demonstrate that 0.5% ketorolac ophthalmic solution used topically four times daily, for seven days, was effective in alleviating the principal sign and the symptoms associated with allergic conjunctivitis.

Adult↗
PubMed1987

The ability of salbutamol and theophylline to suppress immediate allergic conjunctivitis in the guinea pig.

Topically administered salbutamol was extremely effective in suppressing immediate allergic conjunctivitis in the guinea pig; a dose as low as 0.1% elicited 98% inhibition. Topical pretreatment with 1% propranolol completely blocked the suppressant action of 0.1% salbutamol. This was also the case after systemic propranolol (1 mg/kg SC); the beta-adrenoceptor antagonist itself has no effect on antigen-induced inflammation. The effect of 0.1% salbutamol was unaltered by pretreatment with the specific beta 1-adrenoceptor antagonist betaxolol (1 mg/kg SC). In marked contrast, the suppressant action of 0.1% salbutamol was profoundly inhibited by pretreatment with the selective beta 2-adrenoceptor antagonist ICI-118,551 (0.5 mg/kg SC). The experiments employing beta-adrenoceptor antagonists unequivocally demonstrate that the salbutamol suppression of immediate allergic conjunctivitis in the guinea pig is mediated via the activation of beta 2-adrenoceptors. The methylxanthine phosphodiesterase inhibitor theophylline was active after oral administration, 50 mg/kg eliciting an 80% inhibition. Theophylline was inactive topically at 1% and 5%, but this could be due to the fact that the compound was insoluble at these concentrations. Thus, procedures that elevate cyclic-AMP levels suppress immediate hypersensitivity reactions in the guinea pig conjunctiva. Whether or nor this offers an alternative approach to treat allergic conjunctivitis in humans remains to be determined.

Administration, Oral↗