Allergic Conjunctival Diseases Research Articles

JACQLQ subjective symptom questionnaire score and clinical test results for patients with allergic conjunctival disease

We investigated the relationship between subjective symptoms and objective findings in patients with allergic conjunctival diseases (ACD) and test results for tear total IgE (t-tIgE), conjunctival eosinophils (c-Eo), serum total IgE (s-tIgE), serum-antigen specific IgE (s-sIgE), and serum eosinophils (s-Eo). Subjective symptoms and objective findings of patients with ACD were evaluated using Japanese Allergic Conjunctival Disease Quality of Life Questionnaire (JACQLQ), which described disability score and emotional score written by patient and clinical findings score written by ophthalmologist. We investigated the relationship between questionnaire scores and laboratory data for t-tIgE, c-Eo, s-tIgE, s-sIgE, and s-Eo. Scores of impediments to life and of moods were highest in vernal keratoconjunctivitis among ACD. Cases with positive pollen-sIgE showed significantly more nasal symptom score than those with negative pollen-sIgE (P < 0.05). Cases with positive t-tIgE or c-Eo showed significantly more objective symptoms’ JACQLQ score than those with negative t-tIgE or c-Eo (P < 0.05), respectively. Cases positive for house dust/mite-sIgE, showed significantly more objective symptoms’ JACQLQ score than those without for house dust/mite-sIgE (P < 0.05). These results indicate that ACD could be analyzed more accurately by the combination of JACQLQ and laboratory data.

Evaluation methods using tear volume in a conjunctivitis mice model

Allergic conjunctival disease is an immune-mediated inflammatory disease of the conjunctiva. To develop clinically useful drugs, it is necessary to develop quantitative evaluation methods that reflect the clinical symptoms in experimental animal models. Allergic conjunctivitis model mice were systemically sensitised with ovalbumin (OVA) administered intraperitoneally and locally sensitised with OVA eye drops between day 14–28. Next, conjunctivitis induced by ocular administration of OVA solution to sensitised mice was evaluated based on tear volume. Additionally, we evaluated increase in tear volume induced by direct ocular instillation of histamine, compound 48/80, and carrageenan. An increase in antigen-induced tear volume was observed in the mice model. Additionally, direct instillation of histamine, compound 48/80, and carrageenan increased tear volume. Furthermore, levocabastine inhibited the increase in tear volume in antigen-induced allergic conjunctivitis and histamine- and compound 48/80-induced conjunctivitis models. In contrast, betamethasone suppressed carrageenan-induced tear volume but not histamine- or compound 48/80-induced tear volume. Histamine may be involved in increased tear volume in allergic conjunctivitis. Betamethasone is not directly involved in the action of histamine and is thought to suppress increase in tear volume. Evaluation of tear volume in a conjunctivitis mice model is highly quantitative; therefore, it is possible to evaluate drug efficacy. This is considered a useful index compared with conventional methods.

Profiles, Distribution, and Functions of Gamma Delta T Cells in Ocular Surface Homeostasis and Diseases.

The ocular surface microenvironment, containing the cornea, conjunctiva, and lacrimal gland, constitutes the mucosal frontline of the eye and houses a myriad of immune cells. As a part of unconventional T cells, gamma delta (γδ) T cells differ in the development and functions from canonical alpha beta (αβ) T cells. They are predominantly situated in mucosal sites throughout the body, including ocular surface tissues. Recent research has elucidated that γδ T cells serve as the primary interleukin-17A (IL-17A) source in the conjunctiva. They play a pivotal role in preserving ocular surface homeostasis and exhibit both protective and pathogenic roles in ocular surface diseases. This review delves into the general profiles of γδ T cells, their distribution in ocular surface tissues, and consolidates current insights into their functions in different conditions including dry eye disease, infectious keratitis, corneal wound healing, anterior chamber-associated immune deviation, allergic conjunctival disease, and diabetic ocular surface disease. The aim is to provide a systemic perspective on γδ T cells in the ocular surface microenvironment and outline potential directions for future studies.

The minimal clinically important difference of app‐based electronic patient‐reported outcomes for hay fever

Hay fever is a common allergic disease, with an estimated worldwide prevalence of 14.4% and a variety of symptoms. This study assessed the minimal clinically important difference (MCID) of nasal symptom score (NSS), non-nasal symptom score (NNSS), and total symptoms score (TSS) for app-based hay-fever monitoring. MCIDs were calculated based on the data from a previous large-scale, crowdsourced, cross-sectional study using AllerSearch, an in-house smartphone application. MCIDs were determined with anchor-based and distribution-based methods. The face scale score of the Japanese Allergic Conjunctival Disease Standard Quality of Life Questionnaire Domain III and the daily stress level due to hay fever were used as anchors for determining MCIDs. The MCID estimates were summarized as MCID ranges. A total of 7590 participants were included in the analysis (mean age: 35.3years, 57.1% women). The anchor-based method produced a range of MCID values (median, interquartile range) for NSS (2.0, 1.5-2.1), NNSS (1.0, 0.9-1.2), and TSS (2.9, 2.4-3.3). The distribution-based method produced two MCIDs (based on half a standard deviation, based on a standard error of measurement) for NSS (2.0, 1.8), NNSS (1.3, 1.2), and TSS (3.0, 2.3). The final suggested MCID ranges for NSS, NNSS, and TSS were 1.8-2.1, 1.2-1.3, and 2.4-3.3, respectively. MCID ranges for app-based hay-fever symptom assessment were obtained from the data collected through a smartphone application, AllerSearch. These estimates may be useful for monitoring the subjective symptoms of Japanese patients with hay fever through mobile platforms.

Positive regulation of innate immune response by miRNA-let-7a-5p.

Background: We have hypothesized that different factors are involved in the severity of ACD and AD because some but not all patients with atopic dermatitis (AD) present with allergic conjunctival disease (ACD) including severe types such as atopic keratoconjunctivitis (AKC) with/without giant papillae. We previously reported that plasma miR-628-3p was up-regulated in AD with severe ACD, but not in severe AD without severe ACD or in our healthy controls. In this study, to investigate the pathogenesis of AD with and without severe ACD, we performed comprehensive plasma miRNA analysis and studied the function of some miRNAs which were significantly up-regulated in ACD. Methods: Transcriptomics analysis of miRNA was performed using the microarray platform from the plasma of nine individuals (AD, severe ACD, controls: n = 3 each). To confirm up-regulation of the 12 miRNAs of the eight miRNA groups we focused on, we performed quantitative miRNA polymerase chain reaction (PCR) assays using 80 plasma samples (AD: 23, severe ACD: 17, controls: 40). To study the function of the eight miRNAs which were significantly up-regulated in ACD, we transfected their mimic to THP-1 cells, a monocyte cell line, and performed comprehensive gene expression analysis of them. The up-regulation of gene expression of interest in transfected THP-1 cells with the hsa-let-7a-5p miRNA mimic was confirmed by quantitative RT-qPCR assay. Results: Quantitative miRNA PCR assays showed that hsa-let-7a-5p, hsa-let-7days-3p, hsa-let-7e-5p, and hsa-miR-151a-5p were significantly up-regulated in both AD-ACD + and AD-ACD - as were hsa-miR-130a-3p, hsa-miR-151a-3p, has-miR-27b-3p, and hsa-miR-146a-5p in AD-ACD + but not in AD-ACD - . The functions of each miRNA were investigated by comprehensive gene expression analysis of THP-1 cells transfected with each miRNA mimic. Of the eight miRNAs, hsa-let-7a-5p, hsa-let-7e-5p, has-miR-27b-3p, and hsa-miR-146a-5p mimic-transfected THP-1 cells showed the up-regulation of CXCL10 (IP-10; interferon gamma-induced protein 10), which might be one of the innate immune-related genes. Quantitative RT-qPCR assays of transfected THP-1 cells with the hsa-let-7a-5p miRNA mimic showed that the 17 genes up-regulated more than 10-fold in the comprehensive gene expression analysis, and TLR3, RIG-I, and MDA5, important innate immune-related genes, were significantly up-regulated. TNFSF13B, AIM2, USP41, STAP1, GBP4, CCL8, and IFI27, reportedly down-regulated by the hsa-miR-628-3p mimic, were also significantly up-regulated in the transfected cells. Conclusion: Hsa-let-7a-5p, which was significantly up-regulated in AD-ACD + and AD-ACD - , could positively regulate the important innate immune-related genes such as TLR3, RIG-I, and MDA5. It is possible that in an allergic disease such as atopic keratoconjunctivitis and/or dermatitis, innate immune responses might be positively regulated by hsa-let-7a-5p in the plasma.

Reliability and Validity of Electronic Patient-Reported Outcomes Using the Smartphone App AllerSearch for Hay Fever: Prospective Observational Study.

BackgroundHay fever is a highly prevalent, heterogenous, and multifactorial disease. Patients may benefit from longitudinal assessments using mobile health (mHealth) principles. We have previously attempted to establish an effective mHealth platform for patients with hay fever through AllerSearch, our in-house smartphone app that assesses electronic patient-reported outcomes through a questionnaire on hay fever and provides evidence-based advice. To be used by the public, an investigation on its reliability and validity is necessary.ObjectiveThe aim of this paper is to assess the reliability and validity of subjective symptom data on hay fever collected through our app, AllerSearch.MethodsThis study used a prospective observational design. The participants were patients aged ≥20 years recruited from a single university hospital between June 2, 2021, and January 26, 2022. We excluded patients who could not use smartphones as well as those with incomplete data records and outlier data. All participants answered the Japanese Allergic Conjunctival Disease Standard Quality of Life Questionnaire (JACQLQ), first in the paper-and-pencil format and subsequently on AllerSearch on the same day. The JACQLQ comprises the following three domains: Domain I, with 9 items on ocular or nasal symptoms; Domain II, with 17 items on daily activity and psychological well-being; and Domain III, with 3 items on overall condition by face score. The concordance rate of each domain between the 2 platforms was calculated. The internal consistency of Domains I and II of the 2 platforms was assessed using Cronbach alpha coefficients, the concurrent validity of Domains I and II was assessed by calculating Pearson correlation coefficients, and the mean differences between the 2 platforms were assessed using Bland-Altman analysis.ResultsIn total, 22 participants were recruited; the data of 20 (91%) participants were analyzed. The average age was 65.4 (SD 12.8) years, and 80% (16/20) of the participants were women. The concordance rate of Domains I, II, and III between the paper-based and app-based JACQLQ was 0.78, 0.85, and 0.90, respectively. The internal consistency of Domains I and II between the 2 platforms was satisfactory (Cronbach alpha of .964 and .919, respectively). Pearson correlation analysis yielded a significant positive correlation between Domains I and II across the 2 platforms (r=0.920 and r=0.968, respectively). The mean difference in Domains I and II between the 2 platforms was 3.35 units (95% limits of agreement: –6.51 to 13.2).ConclusionsOur findings indicate that AllerSearch is a valid and reliable tool for the collection of electronic patient-reported outcomes to assess hay fever, contributing to the advantages of the mHealth platform.

Analysis of Cytokine Production Profiles of Local and Systemic Lymphocytes in Sick Building Syndrome Compared with Ocular Allergy.

PurposeWe have previously studied clinical and allergological aspects of sick building syndrome (SBS) cases with ocular disorders and found that SBS is suggested to be partially induced by an allergic response. We analyzed the cytokine production profiles of conjunctival and peripheral blood lymphocytes in patients with SBS with ocular manifestations to further evaluate the pathophysiology of SBS from an immunological standpoint.MethodsWe obtained conjunctival samples and peripheral blood mononuclear cells (PBMC) from 15 cases of SBS with ocular findings, 49 cases of allergic conjunctival diseases (ACD) (allergic conjunctivitis (AC), atopic keratoconjunctivitis (AKC), and vernal keratoconjunctivitis (VKC)), and normal controls. Frequencies of cytokine-producing T cells were analyzed by flow cytometry based on an intracellular cytokine staining method.ResultsAlthough no significant difference was observed in the percentage of interferon (IFN)-γ-producing CD4+ T cells in PBMC between patients with SBS and controls, the percentage of interleukin (IL)-4-producing PBMC CD4+ T cells in patients with SBS was significantly higher than that in controls. The percentage of IL-4-producing CD4+ T cells in the conjunctiva in patients with SBS was significantly higher than that in controls, whereas it was significantly lower than that in AKC and VKC. A significant correlation was observed between the percentage of IL-4-producing CD4+ T cells in the conjunctiva and clinical score.ConclusionThese results suggest that SBS may be a kind of allergic disorder and that IL-4 plays a role in the development of allergic disorders in SBS ocular lesions.

Combination Therapy of 0.1% Fluorometholone and 0.05% Azelastine in Eyes with Severe Allergic Conjunctival Diseases: A Randomized Controlled Trial.

This study sought to evaluate the efficacy of the isolated use of fluorometholone compared with the combined use of azelastine and fluorometholone for the treatment of severe allergic conjunctival disease (ACD). One hundred and eleven patients with severe ACD were randomized into two groups: one treated with topical 0.1% fluorometholone combined with 0.05% azelastine and the other with 0.1% fluorometholone alone. The Ocular Surface Disease Index (OSDI) and the signs of keratopathy, palpebral conjunctiva papillae and conjunctival congestion were scored before and at one, two and six weeks after treatment and compared between the groups. The intra-ocular pressure (IOP) was also monitored. There were no significant differences between the groups in the baseline mean scores of signs and OSDI scores, which gradually improved at all visits after therapy in both groups. Although the time effect was significant for all the parameters (all p < 0.001), the reduction in corneal involvement scores from week 2 to week 6 was insignificant in both groups (p = 0.460 for the steroids group and p = 0.074 for the combination group). All signs and symptoms were significantly more improved in the combination group than in the isolated group at each control visit. IOP remained stable at all visits (all p < 0.001), except one patient in each group had elevated IOP over 21 mmHg. While both the isolated use of fluorometholone and combined use of azelastine and fluorometholone are effective in alleviating the signs and symptoms of severe ACD, optimal response can be achieved with adjunctive treatment including azelastine.

Dysbiosis of Ocular Surface Microbiota in Patients With Refractive Allergic Conjunctival Diseases.

We investigated ocular surface microbiota dysbiosis in patients with refractory allergic conjunctival diseases (ACDs; stratified into mild and severe groups) treated with topical tacrolimus. Patients (n = 21) with refractory ACDs (including vernal and atopic keratoconjunctivitis) actively treated with topical tacrolimus and 6 healthy controls were evaluated. Based on clinical scores and expression of specific cytokines on the ocular surface, patients with ACDs were divided into mild and severe groups using cluster analysis. The microbial composition of tear specimens collected from patients with mild and severe ACD and control subjects using the Schirmer test paper was determined through next-generation 16S rRNA sequencing analysis. Compared with healthy controls, patients with ACDs exhibited significantly decreased ocular surface microbiota α-diversity. Ocular surface microbiota mainly comprised members of the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria in all groups. The relative abundance of ocular surface microbiota in patients with ACDs was increased for phylum Firmicutes and decreased for phylum Proteobacteria (compared with control subjects). The genera Blautia (vs. mild ACD group) and Morganella (vs. control group) exhibited significantly increased abundance only in the severe ACD group. The ocular surface microbiota in patients with severe ACD exhibited decreased diversity and exacerbation of dysbiosis compared with that in patients with mild ACD and control subjects. Patients with mild refractory ACD also exhibited decreased diversity of these microbiota. These alterations in microbiota indicated a change in the ocular surface of patients with refractory ACD (be it because of disease pathogenesis or topical immunomodulatory treatment).

Difference in the plasma level of miR-628-3p in atopic dermatitis patients with/without atopic keratoconjunctivitis.

IntroductionSome but not all patients with atopic dermatitis (AD) present with allergic conjunctival disease (ACD) including severe types such as atopic keratoconjunctivitis (AKC) with/without giant papillae. We hypothesized that different factors are involved in the severity of ACD and AD. Recently we reported that hsa‐miR‐628‐3p could affect the balance of innate immunity by suppressing pathogen‐associated molecular patterns such as toll‐like receptor 3 (TLR3), RIG‐I, and MDA‐5. We also reported that TLR3 positively regulates ocular surface‐ and skin inflammation such as contact dermatitis and AD. Here we compared the plasma level of miR‐628‐3p in AD patients with severe AKC with giant papillae and/or shield ulcers, with the level in healthy controls and AD patient without AKC or with very mild AKC.MethodsWe used the plasma from 32 AD patients with severe AKC, from 40 healthy controls, and from 23 AD patient without AKC or with very mild AKC without giant papillae nor shield ulcers. Quantitative microRNA PCR assays were used to measure their plasma level of miR‐628‐3p.ResultsWe found that plasma miR‐628‐3p was upregulated in AD with severe AKC, but not in severe AD without severe AKC, nor in our healthy controls.ConclusionOur new findings suggest that the plasma miR‐628‐3p level may represent a marker to predict the presence of severe AKC in AD patients.

The FADS mouse: A novel mouse model of atopic keratoconjunctivitis

Atopic keratoconjunctivitis (AKC) is a chronic allergic conjunctival disease. However, a mouse model of AKC to investigate the underlying mechanism of the therapeutic agents and estimate their efficacy has not been established. We recently generated mice in which Ikk2 is specifically deleted in facial skin fibroblasts and found that these mice spontaneously develop atopic dermatitis (AD)-like facial skin inflammation and scratching behaviors; thus, we named them facial AD with scratching (FADS) mice. We sought to evaluate whether the ocular lesions that FADS mice spontaneously develop are similar to those of patients with AKC and to estimate the efficacy of topical treatments with tacrolimus and betamethasone for FADS mice by using tear periostin, a novel biomarker for allergic conjunctival disease. FADS mice, in which Ikk2 is deleted in dermal fibroblasts, were generated by crossing female Ikk2Flox/Flox mice to male Nestincre; Ikk2Flox/+ mice. We conducted histologic analysis of the ocular lesions in FADS mice. Furthermore, we measured periostin in the tears collected from FADS mice untreated or treated with tacrolimus or betamethasone. The FADS mice exhibited severe blepharitis and scratch behaviors for their faces. In these mice, corneal epithelium and stroma showed hyperplasia and infiltration of eosinophils, mast cells, and TH2/TC2 cells. Periostin was significantly expressed in the lesions and tear periostin was upregulated. Betamethasone showed more suppressive effects than did tacrolimus on severe corneal lesions and increased tear periostin level. The FADS mouse is a novel mouse model of AKC and is useful to examine the therapeutic effects of anti-AKC agents.

Clinical Observation of Allergic Conjunctival Diseases with Portable and Recordable Slit-Lamp Device.

Background: The incidence of allergic conjunctival diseases (ACDs) is gradually increasing worldwide. Both ophthalmologists and non-ophthalmologists prescribe eye drops to treat ACDs; however, there are many cases which are treated without sufficient examination and diagnosis of the eyes. We have invented a portable, recordable, and smartphone-attachable slit-lamp device—Smart Eye Camera (SEC). The purpose of this study was to compare the diagnostic abilities of ACDs between the SEC and the conventional, non-portable slit-lamp microscope. Methods: This prospective observational study included 32 eyes of 17 Japanese patients (mean age: 21.5 ± 14.8 years; range: 11–51 years; female: 5). The severity of 10 objective signs in the palpebral conjunctiva, bulbar conjunctiva, limbus, and cornea were scored on a grading scale of 0 to 4 (0 = normal; 1+ = mild; 2+ = moderate; 3+ = severe), respectively. First, the conventional slit-lamp microscope was used to examine the grade of the ACDs. Second, another ophthalmologist filmed the eyes using the SEC and two other ophthalmologists evaluated the grades on another day. The correlation and inter-rater reproducibility in total scores among the two devices were determined. Results: Total scores of clinical signs, evaluated by the two approaches, correlated significantly (both eyes: r = 0.918 (95% CI: 0.839 to 0.959; p < 0.001)), with substantial inter-rater agreement (weighted κ value = 0.631 (95% CI: 0.601 to 0.661; p < 0.001)). Conclusions: The SEC is as reliable as the conventional non-portable slit-lamp microscope for assessing ACDs.

Long-term outcomes of 0.1% tacrolimus eye drops in eyes with severe allergic conjunctival diseases

BackgroundBecause atopic dermatitis does not heal completely, associated severe atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) often require long-term treatment. This study aims to evaluate the long-term outcomes of using 0.1% tacrolimus eye drops to treat these severe allergic conjunctival diseases.MethodsTwo-hundred-and-seventy eyes of 135 patients diagnosed with AKC or VKC from April 2004 to April 2014 were screened retrospectively. Patient demographics and objective signs were extracted from the electronic medical records. The severity of 10 objective signs, related to the palpebral and bulbar conjunctiva, limbus, and cornea, and intraocular pressure (IOP) were observed at baseline, at 2 weeks, 1, 2, 3, 6, and 12 months after starting treatment, and every 1 year thereafter (average use period: 8.4 ± 2.9 years). Safety was evaluated based on the incidence and severity of adverse events.Results12 patients (AKC; 7 cases, VKC; 5 cases) who were treated with 0.1% tacrolimus eye drops were enrolled in this study. The total score of clinical signs significantly decreased after 2 weeks and remained effective thereafter. Tacrolimus eye drops elicited a statistically significant difference in the mean total clinical scores and IOP over the course of treatment (P < 0.001). Elevated IOP was observed in 2 cases and corneal infection in 1 case; these effects were completely controlled with medication.ConclusionsTopical tacrolimus may provide effective and long-term improvement in clinical signs of severe AKC and VKC cases that refractory to standard conventional treatment.Trial registration: University Hospital Medical Information Network (UMIN) 000034460.

QUANTIFICATION OF CONJUNCTIVAL HYPEREMIA IN RABBITS USING ANALYSIS SOFTWARE

In a method evaluating conjunctival hyperemia using rabbits, it is common to visually grade the degree of vasodilation. However, this method is limited in evaluating consecutive value and in reproducibility. We quantified the degree of conjunctival hyperemia in rabbits as the area ratio of blood vessels by image analysis, and compared the vascular area percentage calculated by image analysis with the hyperemia score. The conjunctiva was photographed before and after the instillation of 0.1% arachidonic acid using a digital medical scope VersaCam® (Nidek Co., Ltd.). Next, the area of the conjunctival blood vessels occupying the area of interest was calculated using hyperemia analysis software. The hyperemia score was visually graded for the degree of conjunctiva vasodilation. Furthermore, the hyperemia score and the vascular area ratio were compared. Fifteen minutes after the instillation of arachidonic acid, the area ratio of the blood vessels in the conjunctiva increased significantly and gradually decreased over time. This trend correlated with the hyperemia score. We found that the degree of conjunctival hyperemia in rabbits can be evaluated numerically and quantitatively. This method is considered to be useful for evaluating conjunctival hyperemia in allergic conjunctival diseases.

Nanotechnology for the Treatment of Allergic Conjunctival Diseases.

Allergic conjunctivitis is one of the most common external eye diseases and the prevalence has been increasing. The mainstay of treatment is topical eye drops. However, low bioavailability, low ocular drug penetration, transient resident time on the ocular surface due to tear turnover, frequent topical applications and dependence on patient compliance, are the main drawbacks associated with topical administration. Nanotechnology-based medicine has emerged to circumvent these limitations, by encapsulating the drugs and preventing them from degradation and therefore providing sustained and controlled release. Using a nanotechnology-based approach to load the drug is particularly useful for the delivery of hydrophobic drugs such as immunomodulatory agents, which are commonly used in allergic conjunctival diseases. In this review, different nanotechnology-based drug delivery systems, including nanoemulsions, liposomes, nanomicelles, nanosuspension, polymeric and lipid nanoparticles, and their potential ophthalmic applications, as well as advantages and disadvantages, are discussed. We also summarize the results of present studies on the loading of immunomodulators or nonsteroidal anti-inflammatory drugs to nano-scaled drug delivery systems. For future potential clinical use, research should focus on the optimization of drug delivery designs that provide adequate and effective doses with safe and satisfactory pharmacokinetic and pharmaco-toxic profiles.

Use of allergen immunotherapy for treatment of allergic conjunctivitis.

The purpose of this article is to provide an overview of the literature pertaining to the use of allergen immunotherapy for treatment of allergic conjunctivitis with an emphasis on recent developments. Both subcutaneous (SCIT) and sublingual (SLIT) immunotherapy continue to show efficacy in treating allergic conjunctival disease, subcutaneous more than sublingual. Adverse effects of sublingual therapy continue to be reported since the FDA's approval of SLIT tablets in 2014. Initial SLIT studies reported high rates of adherence, while real use reports identify rates of nonadherence/discontinuation ranging between 50 and 80%. Studies in polyallergic patients evaluating the efficacy of SLIT combination therapy report encouraging results. Both SCIT and SLIT offers improvement in allergic conjunctival symptom scores and decrease medication utilization. Although SCIT has a higher likelihood of systemic reaction, SLIT has a very high rate of mild-to-moderate adverse events - especially in the first month. Cost-benefit analyses tend to favor SCIT (greater efficacy and less impacted by discontinuation rates).

Roles of Type 2 Immune Response-Initiating Cytokines and Detection of Type 2 Innate Lymphoid Cells in Mouse Models of Allergic Conjunctivitis.

Allergic conjunctivitis is one the most common global diseases and affects many people worldwide. It has been reported that 15% to 20% of the total population in Japan suffers from allergic conjunctival disease. Although TH2 cytokines suchs as interleukin (IL)-4, IL-5, and IL-13 have long been known as causes of allergic conjunctivitis, new cytokines involved in allergic diseases have been identified since 2000. The discovery of type 2 immune response-initiating cytokines, such as IL-25, IL-33, and thymic stromal lymphopoietin, and type 2 innate lymphoid cells has suggested that allergic diseases can arise from not only T cells but also barrier function disruption. In this article, we summarize the results of experiments in mouse models of ragweed-induced experimental allergic conjunctivitis and papain-soaked contact lens-induced conjunctivitis.

Comparison of the efficacy and safety of bepotastine besilate 1.5% and loteprednol etabonate 0.5% ophthalmic solution in patients of vernal keratoconjunctivitis

Vernal keratoconjunctivitis is a chronic, recurrent, bilateral inflammatory disease of cornea and conjunctiva affecting young children. Various treatment modalities of VKC are topical mast cell stabilizers, anti-histaminics, corticosteroids, and immunomodulators. This study compared the efficacy of bepotastine besilate 1.5% and loteprednol etabonate 0.5% topical eye drops in subjects with allergic conjunctival disease. The patients were re-examined after 1 week and 2 weeks. At each follow up visit, best corrected visual acuity, anterior segment examination using slit lamp, tear film examination (Schirmer’s test and tear film breakup time) and intraocular pressure were measured. Patients were scored based on severity of signs and symptoms on day 1, 7 and 15. Itching, tearing, photophobia, upper tarsal papillae, limbus, keratitis and discharge score 1 and 2 for both eyes at day 1, 7 and 15 was significantly more among Bepotastine Besilate 1.5% compared to Loteprednol Etabonate. The mean IOP for both eyes at day 1, 7 and 15 was significantly more among Loteprednol Etabonate 0.5% compared to Bepotastine Besilate 1.5%.: This study demonstrated that LE was more efficacious than B.B in treating patients of VKC, but the mean IOP was found to be more in patients on LE.

Clinical forms of allergic eye manifestations: prospects of therapy

The review presents the main clinical forms of eye allergy. The modern classification of conjunctival allergic diseases (CAD) divides them into several types according to the presence or absence of proliferative changes complicated by atopic dermatitis or mechanical artifactual irritation. These include: 1) allergic conjunctivitis (AC) without proliferative changes, including seasonal allergic conjunctivitis and chronic allergic conjunctivitis, in which the symptoms persist the whole year; 2) atopic keratoconjunctivitis, a chronic allergic conjunctival disease affecting patients with atopic dermatitis, 3) spring keratoconjunctivitis with conjunctival and proliferative changes — papillary conjunctival hyperplasia with the involvement of the cornea (superficial punctate keratitis, erosion, persistent epithelial defect, sterile corneal ulceration), 4) giant papillary conjunctivitis (GPC) accompanied by proliferative changes in the upper lid and the arch of the conjunctiva of the eyeball, caused by mechanical irritation factors (contact lenses, eye prostheses, or surgical sutures). To treat these conditions, the following groups of medications are used: artificial tears; topical antihistamine drugs; mast cell membrane stabilizers; dualaction drugs, preferably without preservatives, nonsteroid anti-inflammatory medications and vasoconstrictors having side effects. Olopatadin 1 mg/1 ml, preservative free (Olofadin -ECO), has certain advantages due to the fact that it combines antihistamine and membrane stabilizing action. Due to the presence of an antihistamine component in the composition, an acute reaction is stopped, while the effect of the drug is accumulated due to the presence of a membrane-stabilizing component. It is safe for long-term therapy.

Potential Biomarkers for Allergic Conjunctival Diseases.

Allergic conjunctival diseases (ACDs) are a group of ocular allergies that include allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Although a large body of information exists on the pathophysiology of ACDs, this has not yet lead to the development of clear recommendations and guidelines for the diagnosis of ACDs or development of conclusive and objective diagnostic tools. Identification of objectively measurable biomarkers that represent the molecular and cellular mechanisms associated with ACDs will be an important step toward achieving these aims. This is a comprehensive review of biological markers that have the potential to become "biomarker(s)" for ACDs and aid in the classification, diagnosis, and development of new therapeutic strategies for these group of allergic conditions.