Ocular itch associated with allergic conjunctivitis: latest evidence and clinical management.
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ABSTRACT:
SUBMITTER: Ackerman S
PROVIDER: S-EPMC4707430 | biostudies-literature | 2016 Jan
REPOSITORIES: biostudies-literature
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Ocular itch associated with allergic conjunctivitis: latest evidence and clinical management.
Ackerman Stacey S Smith Lisa M LM Gomes Paulo J PJ
Therapeutic advances in chronic disease 20160101 1
Allergic conjunctivitis is one of the most common allergic conditions worldwide. Its incidence is increasing due to changing climate, pollution, increased pollen loads, and the subject's heightened immunological sensitivity in response to these environmental changes. The pathophysiology predominantly involves immunoglobulin E-related mast-cell activation, with release of histamine and other mediators contributing to the propagation of the response by calling in other immune cells and further inf ...[more]
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Project description:PurposeSeasonal and perennial allergic conjunctivitis represent the majority of cases of ocular allergy. This analysis was designed to evaluate the efficacy and safety of once-daily alcaftadine 0.25% in preventing ocular itching associated with seasonal or perennial allergic conjunctivitis.Subjects and methodsPooled data from two double-masked, multicenter, placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis were analyzed. Subjects randomized to receive treatment with alcaftadine 0.25% or placebo were challenged with seasonal (grass, ragweed, trees) or perennial (cat dander, cat hair, dog dander, dust mites, cockroach) allergens, 16 hours after treatment instillation. The primary efficacy measure was subject-evaluated mean ocular itching at 3 minutes post-CAC. Secondary measures included ocular itching at 5 and 7 minutes post-CAC. The proportion of subjects with minimal itch (itch score <1) and zero itch (itch score =0), and safety were also assessed.ResultsA total of 189 subjects enrolled in the two studies were treated with alcaftadine or placebo. Overall, 129 subjects were challenged with seasonal allergens and 60 subjects were challenged with perennial allergens. Alcaftadine 0.25% achieved a statistically significant reduction in mean itch score at 3, 5, and 7 minutes post-CAC compared with placebo in subjects challenged with seasonal allergens (P<0.0001 at all time points) and those challenged with perennial allergens (P<0.0001 at all time points). A higher percentage of subjects treated with alcaftadine compared with placebo achieved minimal itch (P≤0.001 versus placebo at all time points) and zero itch (P<0.05 at all time points except 7 minutes for perennial) when challenged with either seasonal or perennial allergens. No treatment-related or serious adverse events were reported.ConclusionOnce-daily alcaftadine 0.25% ophthalmic solution was well tolerated and demonstrated effective relief of ocular itching in subjects challenged with allergens classic for triggering either seasonal or perennial allergic conjunctivitis.
| S-EPMC4427074 | biostudies-literature
Project description:IntroductionThe efficacy and safety of the once-daily topical ophthalmic solutions, alcaftadine 0.25% and olopatadine 0.2%, in preventing ocular itching associated with allergic conjunctivitis were evaluated.MethodsPooled analysis was conducted of two double-masked, multicenter, active- and placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis. Subjects were randomized 1:1:1 to receive alcaftadine 0.25%, olopatadine 0.2%, or placebo. The primary efficacy measure was subject-evaluated mean ocular itching at 3 min post-CAC and 16 h after treatment instillation. Secondary measures included ocular itching at 5 and 7 min post-CAC. Ocular itch was determined over all time points measured (3, 5, and 7 min) post-CAC and the proportion of subjects with minimal itch (itch score<1) and zero itch (itch score=0) was also assessed.ResultsA total of 284 subjects were enrolled in the two studies. At 3 min post-CAC and 16 h after treatment instillation, alcaftadine 0.25% achieved a significantly lower mean itch score compared with olopatadine 0.2% (0.50 vs. 0.87, respectively; P=0.0006). Alcaftadine demonstrated a significantly lower mean itch score over all time points compared with olopatadine (0.68 vs. 0.92, respectively; P=0.0390); both alcaftadine- and olopatadine-treated subjects achieved significantly lower overall mean ocular itching scores compared with placebo (2.10; P<0.0001 for both actives). Minimal itch over all time points was reported by 76.1% of alcaftadine-treated subjects compared with 58.1% of olopatadine-treated subjects (P=0.0121). Treatment with alcaftadine 0.25% and olopatadine 0.2% was safe and well tolerated; no serious adverse events were reported.ConclusionOnce-daily alcaftadine 0.25% ophthalmic solution demonstrated greater efficacy in prevention of ocular itching compared with olopatadine 0.2% at 3 min post-CAC (primary endpoint), and over all time points, 16 h post-treatment instillation. Alcaftadine and olopatadine both provided effective relief compared with placebo and were generally well tolerated.
| S-EPMC4209090 | biostudies-literature
Project description:BackgroundClassical understanding of allergic conjunctivitis (ACJ) suggests that ocular itch results from a mast cell-dependent inflammatory process. However, treatments that target inflammatory mediators or immune cells are often unsatisfying in relieving the stubborn itch symptom. This suggests that additional mechanisms are responsible for ocular itch in ACJ. In this study, we aim to determine the role of neuronal FcεRIa in allergic ocular itch.MethodsCalcium imaging was applied to observe the effect of IgE-immune complex in trigeminal neurons. Genomic FcεRIa knockout mice and adeno-associated virus (AAV) mediated sensory neuron FcεRIa knockdown mice were used in conjunction with behavioral tests to determine ocular itch. In addition, immunohistochemistry, Western blot and quantitative RT-PCR were used for in vitro experiments.ResultsWe found that FcεRIα was expressed in a subpopulation of conjunctiva sensory neurons. IgE-IC directly activated trigeminal neurons and evoked acute ocular itch without detectible conjunctival inflammation. These effects were attenuated in both a global FcεRIa-knockout mice and after sensory neuronal-specific FcεRIa-knockdown in the mouse trigeminal ganglion. In an ovalbumin (OVA) induced murine ACJ model, FcεRIα was found upregulated in conjunctiva-innervating CGRP+ sensory neurons. Sensory neuronal-specific knockdown of FcεRIa significantly alleviated ocular itch in the ACJ mice without affecting the immune cell infiltration and mast cell activation in conjunctiva. Although FcεRIα mRNA expression was not increased by IgE in dissociated trigeminal ganglion neurons, FcεRIα protein level was enhanced by IgE in a cycloheximide-resistance manner, with concordant enhancement of neuronal responses to IgE-IC. In addition, incremental sensitization gradually enhanced the expression of FcεRIα in small-sized trigeminal neurons and aggravated OVA induced ocular itch.ConclusionsOur study demonstrates that FcεRIα in pruriceptive neurons directly mediates IgE-IC evoked itch and plays an important role in ocular itch in a mouse model of ACJ. These findings reveal another axis of neuroimmune interaction in allergic itch condition independent to the classical IgE-mast cell pathway, and might suggest novel therapeutic strategies for the treatment of pruritus in ACJ and other immune-related disorders.
| S-EPMC8867756 | biostudies-literature
Project description: Not available
| S-EPMC4826842 | biostudies-literature
Project description:PurposeA contact lens (CL)-based drug delivery system for therapeutic delivery of the antihistamine ketotifen was tested in 2 parallel, conjunctival allergen challenge-based trials.MethodsBoth trials employed the same multicenter, randomized, placebo-controlled protocol. Test lenses were etafilcon A with 0.019 mg ketotifen; control lenses were etafilcon A with no added drug. Subjects were randomized into 3 treatment groups. Group 1 received test lens in one eye and control lens in the contralateral eye; the eye chosen to receive test lens was randomly selected in a 1:1 ratio. Group 2 received test lenses bilaterally, and group 3 received control lenses bilaterally. Allergen challenges were conducted on 2 separate visits: following lens insertion, the subjects were challenged at 15 minutes (to test onset) and 12 hours (to test duration). The primary endpoint was ocular itching measured using a 0 to 4 scale with half-unit steps. Secondary endpoints included ciliary, conjunctival, and episcleral hyperemia.ResultsThe mean itching scores were lower for eyes wearing the test lens as compared to those that received control lenses, indicating that the test lens effectively reduced allergic responses. Mean differences in itching were statistically and clinically significant (mean score difference ≥ 1) at both onset and duration for both trials.ConclusionsThis large-scale assessment (n = 244) is the first demonstration of efficacy for CL delivery of a therapeutic for ocular allergy. Results are comparable to direct topical drug delivery and suggest that the lens/ketotifen combination can provide a means of simultaneous vision correction and treatment for CL wearers with ocular allergies.
| S-EPMC6511424 | biostudies-literature
Project description:CCR7 plays a key role in mobilizing tissue dendritic cells (DCs) to the lymphoid compartment for consequent elicitation of adaptive immunity. Interfering with CCR7 function therapeutically would therefore be anticipated to inhibit the progression of atopic conditions, for example, allergic conjunctivitis (AC). However, the CCR7-CCL19/CCL21 system in the ocular surface is poorly understood as is the precise role of DCs in AC immunopathogenesis. T cells from ovalbumin (OVA)-primed mice were adoptively transferred into wild-type (WT) hosts. Exogenous WT (eGFP(+)) versus CCR7(-/-) DCs were engrafted subconjunctivally (SCJ), and hosts were challenged with OVA (Texas-Red+) eye drops. AC immunopathogenesis was evaluated via clinical examinations, infiltration of mast cells and eosinophils, Th2 reactivity, and serum IgE levels. AC was also assessed in actively immunized mice challenged with OVA eye drops containing 1% anti-CCR7 antibody or isotype control. In eye-draining lymph nodes (LNs), OVA(+) SCJ engrafted WT DCs conferred upregulated CCR7 and caused augmentation of clinical signs. This result was corroborated by increased conjunctival infiltration, Th2 cytokines in LNs, and serum OVA-specific IgE. Strikingly, this was completely reversed with SCJ engrafted CCR7(-/-) DCs in all parameters tested. Furthermore, topical antibody blockade of CCR7 in actively immunized mice significantly inhibited AC. Ocular surface DCs via CCR7 expression contribute to the immunopathogenesis of AC, thereby allowing significant inhibition of this experimental condition via topical CCR7 antibody blockade.
| S-EPMC5691338 | biostudies-literature
Project description:Based on previous findings that ozone can induce an inflammatory response in the ocular surface of an animal model and in cultured human conjunctival epithelial cells, we investigated whether exposure to ozone exacerbates symptoms of allergic conjunctivitis. We evaluated the effects of exposure to ozone on conjunctival chemosis, conjunctival injection, corneal and conjunctival fluorescein staining scores, production of inflammatory cytokines in tears, and aqueous tear production in a mouse model of allergic conjunctivitis. To validate our in vivo results, we used interleukin (IL)-1α-pretreated conjunctival epithelial cells as an in vitro substitute for the mouse model. We evaluated whether exposure to ozone increased the inflammatory response and altered oxidative status and mitochondrial function in IL-1α-pretreated conjunctival epithelial cells. In the in vivo study, ozone induced increases in conjunctival chemosis, conjunctival injection, corneal and conjunctival fluorescein staining scores, and production of inflammatory cytokines, accompanied by a decrease in tear volume. In the in vitro study, exposure to ozone led to additional increases in IL-6 and tumor necrosis factor-α mRNA levels, which were already induced by treatment with IL-1α. Ozone did not induce any changes in cell viability. Pretreatment with IL-1α increased the expression of manganese superoxide dismutase, and exposure to ozone led to additional increments in the expression of this antioxidant enzyme. Ozone did not induce any changes in mitochondrial activity or expression of mitochondrial enzymes and proteins related to mitochondrial function, with the exception of phosphor-mammalian target of rapamycin. Treatment with butylated hydroxyanisole, a free radical scavenger, attenuated the ozone-induced increases in IL-6 expression in IL-1α-pretreated conjunctival epithelial cells. Therefore, we conclude that exposure to ozone exacerbates the detrimental effects on the integrity of the ocular surface caused by conjunctival allergic reactions, and further increases the inflammatory response in IL-1α-pretreated conjunctival epithelial cells.
| S-EPMC5207719 | biostudies-literature
Project description:BackgroundTo explore corneal biomechanical changes, identify related factors and determine early indicators of keratoconus (KC) development risk in allergic conjunctivitis (AC) patients.MethodsA total of 50 patients, including 20 eyes without AC and 30 eyes with AC were enrolled in this study. All patients underwent a complete ocular examination, including evaluations of clinical manifestations of AC, corneal tomography and densitometry by Pentacam, corneal biomechanics by Corvis ST, and corneal and epithelial thickness mapping by RTvue optical coherence tomography (OCT).ResultsThe index of surface variance (ISV), index of vertical asymmetry (IVA), keratoconus index (KI), index of height decentration (IHD) and Belin/Ambrosio enhanced ectasia total deviation index (BAD-D) were significantly higher in the AC group than in the non-allergic conjunctivitis (NAC) group (P < 0.05). The tomography and biomechanical index (TBI) was also significantly higher in the AC group (P = 0.04). The average epithelial thickness in the 2-7 mm annulus was significantly thinner in the AC group than in the NAC group (P < 0.05). The average densitometry of the total cornea and the anterior layer were higher in the AC group than in the NAC group (P < 0.001). The ISV, IVA, KI, IHD and BAD-D were significantly correlated with the TBI and changes in corneal epithelial thickness in AC patients (P < 0.05). The changes in epithelial thickness were closely related to the eye rubbing frequency and allergic sign scores (P < 0.05).ConclusionsAC patients should be advised to routinely undergo corneal tomographic and biomechanical measurements, and the TBI could be used as an indicator of KC development risk in AC patients.Trial registrationCorneal Biomechanical Changes of Allergic Conjunctivitis, NCT04299399 . Registered March 3, 2020 - Retrospectively registered.
| S-EPMC8091662 | biostudies-literature
Project description:Conjunctival intraepithelial lymphocytes, tear soluble molecules and commensal microbiota have important roles in the ocular mucosal immune response in healthy and diseased subjects. For the purpose of this study, the cellular and microbial populations of the conjunctiva and the lacrimal soluble molecules were analyzed to find the main biomarkers in allergic conjunctivitis. A total of 35 healthy subjects, 28 subjects with seasonal allergic conjunctivitis and 32 subjects with perennial allergic conjunctivitis were recruited to obtain peripheral blood, conjunctival brush cytology, tear fluid and microbiota samples. Flow cytometry for lymphocytes, multiplex bead assays for cytokines and high-throughput DNA sequencing for microbiome analysis were used. For perennial allergic conjunctivitis, an increased proportion of Th2 and NKT lymphocytes was found, while CD3+TCRγδ+ lymphocytes and double negative MAIT cells were decreased. In contrast, seasonal allergic conjunctivitis was distinguished by an increase in Th17 and Th22 cell proportions, while the Th1 cell proportion decreased. Among tear fluid, the vast majority of pro-inflammatory cytokines (especially Th2 and Th17 cytokines) in perennial allergies and MMP-9 together with IgA in seasonal allergies were increased. In contrast, TGF-β2 was decreased in both forms of conjunctivitis. Finally, fungal (Malassezia species) and bacterial (Kocuria and Propionobacterium acnes species) colonization were observed in the perennial allergic conjunctivitis group. These results provide the basis for the development of a disease profile for perennial allergic conjunctivitis and open the door to new therapeutic and diagnostic strategies.
| S-EPMC9351602 | biostudies-literature
Project description:PurposeTo explore the role of Th2 signaling pathway in allergic conjunctivitis (AC).MethodsSerum Th2 cytokines IL-4 or IL-13 of patients with AC were detected using the Meso scale discovery assay to verify the correlation of Th2 immunity and AC pathogenesis. Wistar Han rats were intraperitoneally and subcutaneously injected with ovalbumin (OVA) to establish an experimental AC model and the Th2 signaling pathway was blocked by an investigational neutralizing antibody (CM310). Serum IgE and OVA-specific IgE were detected by ELISA. Conjunctivitis inflammation, infiltration of eosinophils, and mast cell degranulation were detected by histological examination. Immortalized human conjunctival epithelial cells, a conjunctival epithelial cell line, and peripheral blood mononuclear cells of patients with AC were used as the target cells to study the impact of IL-4 or IL-13 on AC progression. Finally, a STAT6 reporter gene system was constructed using immortalized human conjunctival epithelial cells to confirm whether the downstream signaling pathway activated by IL-4 or IL-13.ResultsSerum IL-4 or IL-13 were increased in patients with AC versus healthy individuals. In an OVA-induced rat experimental AC model, blocking the Th2 signaling pathway with CM310, an investigational neutralizing antibody, alleviated the conjunctival symptoms, and decreased serum IgE, suppressed infiltration of eosinophils and mast cell degranulation. Further, an in vitro model showed CM310 suppressed the secretion of inflammatory cytokine from both immune cells and epithelial cells in both patients peripheral blood mononuclear cells and cell line.ConclusionsBlocking Th2 signaling pathway alleviates the clinical symptoms and inflammation in AC.
| S-EPMC10382780 | biostudies-literature