Efficacy of Alcaftadine 0.25% (AGN-229666) for Once-daily Prevention of Cedar-Pollen Allergic Conjunctivitis: A Phase 3 Randomized Study.

Purpose: This study evaluated the efficacy and safety of once-daily Alcaftadine 0.25% (AGN-229666) for prevention of signs and symptoms of Japanese cedar-pollen allergic conjunctivitis.Methods: This was a single-center, placebo-, and comparator-controlled study using the Ora-CAC® model of allergic conjunctivitis. The primary endpoint was ocular itching 16 hours after Alcaftadine 0.25% instillation; efficacy at 16 hours was compared with 0.1% Olopatadine, 4 hours after instillation. Secondary endpoints included conjunctival hyperemia.Results: 263 Japanese subjects were enrolled; 224 completed the trial. Alcaftadine 0.25% was statistically superior to vehicle for relief of ocular itching at 16 hours (p < .0001). Alcaftadine 0.25% at 16 hours was non-inferior to Olopatadine at 4 hours. Alcaftadine 0.25% was significantly better than vehicle for relief of conjunctival hyperemia. All treatments showed a low frequency of ocular adverse events.Conclusion: Once-daily Alcaftadine 0.25% is safe and effective in preventing signs and symptoms of Japanese cedar-pollen allergic conjunctivitis.

Efficacy of epinastine hydrochloride ophthalmic solution in allergic conjunctivitis by conjunctival cedar pollen allergen challenge.

BACKGROUND: Epinastine hydrochloride is a selective histamine H1 receptor antagonist that also inhibits IgE receptor-mediated histamine release from mast cells. OBJECTIVE: To show the superiority of epinastine 0.05% ophthalmic solution (epinastine) to placebo ophthalmic solution (placebo) and noninferiority to olopatadine 0.1% ophthalmic solution (olopatadine) for cedar pollen antigen-induced ocular itching and conjunctival hyperemia. METHODS: The study was conducted in ophthalmologically asymptomatic adult volunteers with seasonal allergic conjunctivitis using a conjunctival allergen challenge test. Subjects were randomized into 3 groups (n = 87) to evaluate superiority to placebo (visits 4 to 6) and 2 groups (n = 86) to evaluate noninferiority to olopatadine (visit 7). At each visit, a single administration of the study medication was instilled at 15 minutes (visit 4), 4 hours (visit 5), 8 hours (visit 6), and 4 hours (visit 7) before the conjunctival allergen challenge test. Ocular itching and conjunctival hyperemia of allergic conjunctivitis were assessed after the conjunctival allergen challenge test. RESULTS: For the primary end point, epinastine showed superiority to placebo for the inhibition of ocular itching and conjunctival hyperemia induced at 4 hours after the dose (equivalent to 4-times-daily dosing). For the secondary end points, epinastine significantly inhibited itching and conjunctival hyperemia induced at 15 minutes and 8 hours after the dose (equivalent to 2-times-daily dosing) compared with placebo. In addition, epinastine demonstrated noninferiority to olopatadine for ocular itching and conjunctival hyperemia. No adverse drug reactions or serious adverse events were reported throughout the study, indicating that epinastine has a good safety profile. CONCLUSION: Epinastine is effective and safe for the treatment of allergic conjunctivitis. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01363700.

Sensitization to Asian dust and allergic rhinoconjunctivitis.

OBJECTIVE: Asian dust storms frequently occur in northeast Asia and the dust occasionally even spreads as far as North America during spring. Asian dust can be harmful to human health and the environment, and thus has become one of the most serious problems for Asian countries. In the present study, we evaluated sensitization to Asian dust in Japanese patients with rhinoconjunctivitis. METHODS: In March 2011, a prospective, non-randomized, cross-sectional study was conducted in 10 patients with allergic rhinoconjunctivitis (allergic group), 3 patients with atopic keratoconjunctivitis (atopic group), and 10 age- and sex-matched healthy control subjects (control group). Skin prick tests (SPT) were performed with untreated Asian dust, Asian dust extract, heat-sterilized Asian dust, silicon dioxide (SiO2), and phosphate-buffered saline (PBS). A panel of 14 allergen extracts was also tested, comprising extracts of pollens (cedar, orchard grass, ragweed, and mugwort), house dust (house dust mixture and Dermatophagoides pteronyssinus), animal dander (cat and dog), fungi (Alternaria tenuis, Candida, and Aspergillus), and foods (milk, egg, and wheat). Then the SPT-positive rate and the mean wheal diameter for each allergen were compared among the three groups. RESULTS: The SPT-positive rates for untreated Asian dust, Asian dust extract, and sterilized Asian dust were significantly higher in the allergic and atopic groups than in the control group (all p<0.05). In the allergic group, there were a significant differences of the SPT-positive rates for untreated Asian dust (70%), Asian dust extract (50%), sterilized Asian dust (20%), SiO2 (20%), and PBS (0%) (p=0.0068). The SPT response to untreated Asian dust was correlated with the mean wheal diameters for four plant pollens (r=0.71, p=0.0104) and for three fungi (r=0.57, p=0.0426). Multivariate logistic regression analysis showed that significant predictors of the SPT reaction to untreated Asian dust were the mean wheal diameter for the four plant pollen (odds ratio=2.54, p=0.0138) and that for the three fungi (odds ratio=1.84, p=0.0273). CONCLUSIONS: Asian dust may act as an adjuvant to promote allergic disease induced by inhaled allergens such as pollen and fungi.

Visante optical coherence tomography and tear function test evaluation of cholinergic treatment response in patients with sjögren syndrome.

PURPOSE: To evaluate tear meniscus changes in patients with Sjögren syndrome (SS) receiving oral pilocarpine with Visante optical coherence tomography (OCT). METHODS: Eight patients with primary SS were recruited in this prospective interventional case series study. Patients received pilocarpine tablets twice a day for 3 months. Visual analog scale assessment for dry eye and dry mouth symptoms was carried out. Patients underwent OCT and slit-lamp microscopy graticule scale tear meniscus height (TMH) measurements, strip meniscometry testing, tear film breakup time measurement, fluorescein and Rose Bengal staining, and the Schirmer 1 test. The data were analyzed 1 week, 1 month, and 3 months after treatment. Mann-Whitney test was performed. RESULTS: Visual analog scale assessment showed a significant time-wise improvement (P < 0.05). OCT and graticule scale TMH measurements significantly improved after 1 week (P < 0.05), 1 month, and 3 months of treatment (P < 0.001). Strip meniscometry, mean tear film stability, and fluorescein and Rose Bengal scores remained improved 3 months after treatment (P < 0.001), whereas Schirmer 1 test values tended to improve without statistical significance. CONCLUSIONS: Visante OCT was effective in monitoring tear meniscus changes during the course of treatment noninvasively and quickly. Oral pilocarpine seemed to be effective in improving TMH, and the signs and symptoms of dryness in patients with SS.

OCT assessment of tear meniscus after punctal occlusion in dry eye disease.

PURPOSE: To evaluate the tear meniscus changes after punctal occlusion in dry eye patients using Visante optical coherence tomography (OCT) in a prospective controlled study. METHODS: Thirty eyes of 15 symptomatic dry eye patients not responding to non-preserved artificial tears received additional upper and lower punctal occlusion with silicone plugs, and 30 eyes of 15 age- and sex-matched dry eye control patients received only non-preserved artificial tears treatment for 1 month. All subjects underwent tear meniscus height (TMH) measurements with Visante OCT. All study participants also underwent slitmicroscopy graticule scale TMH measurement, strip meniscometry testing, tear film break-up time measurement, ocular surface vital staining with fluorescein and Rose Bengal dyes, and the Schirmer-1 test. Both groups, dry eye and control group patients, were examined before and after 1-month treatment. Wilcoxon-matched pair test was performed. The study was conducted in compliance with the Tenets of the Declaration of Helsinki. RESULTS: TMH measurements by OCT and slitlamp graticule scale significantly improved after punctal occlusion (p < 0.001) and remain unchanged in the dry eye control patients. Similarly, strip meniscometry scores, mean tear stability values, Rose Bengal, and fluorescein staining scores showed significant improvement after punctal occlusion (p < 0.05). Schirmer-1 test values tended to be higher after 1 month of treatment in both groups without any statistical significance (p > 0.05). CONCLUSIONS: OCT TMH measurement appears to be effective in monitoring tear meniscus changes after punctal occlusion. OCT can be a valuable non-invasive and quick clinical tool for evaluation of treatment responses in dry eye patients.

Disposable eyelid-warming device for the treatment of meibomian gland dysfunction.

PURPOSE: To assess the clinical efficacy of a newly developed disposable eyelid-warming device (Eye Warmer) for the treatment of meibomian gland dysfunction (MGD). METHODS: The Eye Warmer was applied for 5 minutes to 44 eyes of 22 patients who exhibited decreased tear break-up time (BUT) and dry-eye symptoms. Its efficacy was assessed on the basis of BUT and dry-eye symptoms in the short-term study. In the therapeutic study, the Eye Warmer was applied to 34 eyes of 17 MGD patients with decreased BUT and dry-eye symptoms for 5 minutes once a day for 2 weeks. The 16 eyes of 8 patients served as untreated controls. We examined tear film lipid layer interference patterns, BUT, meibomian gland secretion, and dry-eye symptoms in both groups before and after the treatment. RESULTS: BUT and dry-eye symptoms significantly improved after the treatment in both the short-term and the therapeutic study (P<.01). The incidence of normal tear lipid layer in the treated group was significantly higher after treatment (28 eyes [82.4%]) than before (19 eyes [55.9%]) (P=.036). The incidence of meibomian gland obstruction was significantly decreased after treatment (14 eyes [41.2%]) compared to before treatment (26 eyes [76.5%]) (P=.006). CONCLUSIONS: Warming the eyelids with the Eye Warmer improved the stability and uniformity of the tear lipid layer in MGD patients by melting the meibomian gland lipid. Our study demonstrates the usefulness of the Eye Warmer for the treatment of MGD.

Regulation of prostaglandin endoperoxide synthase-2 and IL-6 expression in mouse bone marrow-derived mast cells by exogenous but not endogenous prostanoids.

Mouse bone marrow-derived mast cells (BMMC), stimulated with stem cell factor, IL-1beta, and IL-10, secrete IL-6 and demonstrate a delayed phase of PGD(2) generation that is dependent upon the induced expression of PG endoperoxide synthase (PGHS)-2. We have examined the potential for exogenous prostanoids, acting in a paracrine fashion, and endogenous prostanoids, acting in an autocrine fashion, to regulate PGHS-2 induction and IL-6 secretion in mouse BMMC. Exogenous PGE(2), which acts through G protein-coupled receptors, and 15-deoxy-Delta(12,14)-PGJ(2), which is a ligand for peroxisome proliferator-activated receptor (PPAR)gamma, elicited a 2- to 3-fold amplification of PGHS-2 induction, delayed-phase PGD(2) generation, and IL-6 secretion in response to stem cell factor, IL-1beta, and IL-10. The effect of PGE(2) was reproduced by the E prostanoid (EP)1 receptor agonist 17-trinor-PGE(2), and the EP1/EP3 agonist, sulprostone, but not the EP2 receptor agonist, butaprost. Although BMMC express PPARgamma, the effects of 15-deoxy-Delta(12,14)-PGJ(2) were not reproduced by the PPARgamma agonists, troglitazone and ciglitazone. PGHS-2 induction, but not IL-6 secretion, was impaired in cPLA(2)-deficient BMMC. However, there was no impairment of PGHS-2 induction in BMMC deficient in hematopoietic PGD synthase or PGHS-1 in the presence or absence of the PGHS-2 inhibitor, NS-398. Thus, although exogenous prostanoids may contribute to amplification of the inflammatory response by augmenting PGD(2) generation and IL-6 secretion from mast cells, endogenous prostanoids do not play a role.