No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis
Abstract
Background:
Seasonal/perennial allergic conjunctivitis is the most common allergic conjunctivitis, usually with acute manifestations when a person is exposed to allergens and with typical signs and symptoms including itching, redness, and tearing. The clinical signs and symptoms of allergic conjunctivitis are mediated by the release of histamine by mast cells. Histamine antagonists (also called antihistamines) inhibit the action of histamine by blocking histamine H1 receptors, antagonising the vasoconstrictor, and to a lesser extent, the vasodilator effects of histamine. Mast cell stabilisers inhibit degranulation and consequently the release of histamine by interrupting the normal chain of intracellular signals. Topical treatments include eye drops with antihistamines, mast cell stabilisers, non-steroidal anti-inflammatory drugs, combinations of the previous treatments, and corticosteroids. Standard treatment is based on topical antihistamines alone or topical mast cell stabilisers alone or a combination of treatments. There is clinical uncertainty about the relative efficacy and safety of topical treatment.
Objectives:
The objective of this review was to assess the effects of topical antihistamines and mast cell stabilisers, alone or in combination, for use in treating seasonal and perennial allergic conjunctivitis.
Search methods:
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2014, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2014), EMBASE (January 1980 to July 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 17 July 2014. We also searched the reference lists of review articles and relevant trial reports for details of further relevant publications.
Selection criteria:
We included randomised controlled trials (RCTs) comparing topical antihistamine and mast cell stabilisers, alone or in combination, with placebo, no treatment or to any other antihistamine or mast cell stabiliser, or both, that examined people with seasonal or perennial allergic conjunctivitis, or both. The primary outcome was any participant-reported evaluation (by questionnaire) of severity of four main ocular symptoms: itching, irritation, watering eye (tearing), and photophobia (dislike of light), both separately and, if possible, by an overall symptom score. We considered any follow-up time between one week and one year.
Data collection and analysis:
Two review authors independently extracted data and assessed risk of bias. Disagreements were resolved by discussion among review authors and the involvement of a third review author. We followed standard methodological approaches used by Cochrane.
Main results:
We identified 30 trials with a total of 4344 participants randomised, with 17 different drugs or treatment comparisons. The following antihistamines and mast cell stabilisers were evaluated in at least one RCT: nedocromil sodium or sodium cromoglycate, olopatadine, ketotifen, azelastine, emedastine, levocabastine (or levocabastine), mequitazine, bepotastine besilate, combination of antazoline and tetryzoline, combination of levocabastine and pemirolast potassium. The most common comparison was azelastine versus placebo (nine studies).We observed a large variability in reporting outcomes. The quality of the studies and reporting was variable, but overall the risk of bias was low. Trials evaluated only short-term effects, with a range of treatment of one to eight weeks. Meta-analysis was only possible in one comparison (olopatadine versus ketotifen). There was some evidence to support that topical antihistamines and mast cell stabilisers reduce symptoms and signs of seasonal allergic conjunctivitis when compared with placebo. There were no reported serious adverse events related to the use of topical antihistamine and mast cell stabilisers treatment.
Authors' conclusions:
It seems that all reported topical antihistamines and mast cell stabilisers reduce symptoms and signs of seasonal allergic conjunctivitis when compared with placebo in the short term. However, there is no long-term data on their efficacy. Direct comparisons of different antihistamines and mast cell stabilisers need to be interpreted with caution. Overall, topical antihistamines and mast cell stabilisers appear to be safe and well tolerated. We observed a large variability in outcomes reported. Poor quality of reporting challenged the synthesis of evidence.
... Ketotifen fumarate, a selective histamine H₁ receptor antagonist with mast cell-stabilizing properties, is commonly used for allergic conjunctivitis and inflammatory ocular conditions in humans as well as veterinary animal species [5][6][7][8]. It mitigates symptoms like itching, redness, and swelling by inhibiting histamine release and other inflammatory mediators from mast cells and eosinophils while also preventing eosinophil migration to ocular tissues [8][9][10]. Ketotifen fumarate is a Biopharmaceutics Classification System (BCS) class II drug with limited water solubility due to its lipophilic nature (logP 3.49). ...
... As a weak base, it predominantly exists in its ionized (positively charged) form at physiological pH, which affects its solubility, interaction with biological membranes, and overall pharmacokinetics [11,12]. Ketotifen fumarate is available as topical eye drops, oral tablets, and nasal sprays [5,10,12,13]. While ketotifen eye drops (0.025%) are widely used, they require frequent administration due to rapid elimination [2,5]. ...
Ketotifen fumarate is very effective in treating ocular conditions like allergic conjunctivitis. However, its clinical effectiveness is limited by rapid washout, frequent dosing, and poor bioavailability. This study developed a ketotifen fumarate-loaded in situ forming subconjunctival injectable implant (ISFSI) for use in large animal species such as horses and alpacas. ISFSIs were formulated by dispersing ketotifen fumarate in polylactide-co-glycolide (PLGA) combined with different release retarders (Kolliphor® RH 40, Labrasol®, and Maisine®), then characterized for visual appearance, viscosity, solidification time, and in vitro drug release. The changes in the release medium pH and the solidified ISFSI wet weight were monitored for up to 4 weeks. The selected ISFSI, KFM5, was further characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and rheological behavior. The injectability of KFM5 was predicted using the power law for five different syringe and needle dimensions. Cytotoxicity was tested using the Alamar Blue assay and Calcein AM/PI staining on a human corneal epithelial cell line (HCE-T). Results showed that all ISFSI formulations were clear yellowish, with drug recoveries exceeding 95%, varying viscosities, and solidified upon contact with the release medium. KFM5 exhibited a triphasic drug release profile with the lowest burst release (4.91 ± 0.55%) and followed Higuchi kinetics. SEM imaging revealed a "hollow and sponge-like" structure, while DSC confirmed the crystallinity and thermal transitions of ketotifen fumarate within the solidified implant. Rheological analysis indicated shear-thinning fluid behavior with acceptable injection forces. Cytotoxicity assays confirmed >90% cell viability, confirming biocompatibility in the ocular tissue.
... It is medically approved as a dose-dependent mast cell stabilizer that prevents the release of histamine by blocking mast cell degranulation. [117][118][119] Cromoglicic acid is therapeutically used in form of the sodium salt, sodium cromoglicate, or cromolyn sodium. This noncorticosteroid is used as a medicament for asthma. ...
... This noncorticosteroid is used as a medicament for asthma. 120 Various forms of cromoglicic acid are nasal sprays to cure allergic rhinitis, 121 eye drops for allergic conjunctivitis, 117 or in oral form therapeutics for mastocytosis, dermatographic urticaria, and ulcerative colitis. 122 Cromolyn binds with S100P proteins, hence, preventing interaction between S100P and RAGE (receptor for advanced glycation end products). ...
... It is medically approved as a dose-dependent mast cell stabilizer that prevents the release of histamine by blocking mast cell degranulation. [117][118][119] Cromoglicic acid is therapeutically used in form of the sodium salt, sodium cromoglicate, or cromolyn sodium. This noncorticosteroid is used as a medicament for asthma. ...
... This noncorticosteroid is used as a medicament for asthma. 120 Various forms of cromoglicic acid are nasal sprays to cure allergic rhinitis, 121 eye drops for allergic conjunctivitis, 117 or in oral form therapeutics for mastocytosis, dermatographic urticaria, and ulcerative colitis. 122 Cromolyn binds with S100P proteins, hence, preventing interaction between S100P and RAGE (receptor for advanced glycation end products). ...
Natural products have always served as an important source of drugs for treating various diseases. Among various privileged natural product scaffolds, the benzopyrone class of compounds has a substantial presence among biologically active compounds. One of the pioneering anticoagulant drugs, warfarin approved in 1954 bears a benzo‐α‐pyrone (coumarin) nucleus. The widely investigated psoriasis drugs, methoxsalen, and trioxsalen, also contain a benzo‐α‐pyrone nucleus. Benzo‐γ‐pyrone (chromone) containing drugs, cromoglic acid, and pranlukast were approved as treatments for asthma in 1982 and 2007, respectively. Numerous other small molecules with a benzopyrone core are under clinical investigation. The present review discusses the discovery, absorption, distribution, metabolism, excretion properties, and synthetic approaches for the Food and Drug Administration‐approved and clinical‐stage benzopyrone class of compounds. The role of the pyrone core in biological activity has also been discussed. The present review unravels the potential of benzopyrone core in medicinal chemistry and drug development.
... In recent years, significant advancements have been made in understanding immune-mediated conjunctivitis and its diagnostic approaches [1,8]. However, the precise causes and therapeutic approaches for this condition remain areas of focus for numerous ophthalmological specialists. ...
... In terms of treatment, the management of immune-mediated conjunctivitis aims to reduce inflammation, alleviate symptoms, and minimize side effects. Current therapeutic options include the use of topical corticosteroids, immunomodulatory agents, and targeted biologic therapies [8]. Nonetheless, optimizing treatment strategies and achieving long-term remission in refractory cases continue to present ongoing challenges. ...
Background
Immune-mediated conjunctivitis is a prevalent ocular ailment characterized by inflammation and immune reactions in the conjunctiva. However, the precise causes and therapeutic approaches for this condition remain the main focus for numerous ophthalmological specialists. Recently, accumulating evidence from human and mouse experiments has demonstrated the critical involvement of the NLRP3 inflammasome, IL-1β, and IL-18 in the development of allergic diseases. Targeting specific NLRP3 inflammasome and its related inhibitors may hold potential as therapeutic agents for immunologic conjunctivitis. Despite this, there has been no systematic review specifically addressing the treatment of immunologic conjunctivitis related to NLRP3. Therefore, this study aims to conduct a systematic review and meta-analysis of currently published randomized controlled trials (RCTs) on NLRP3-related treatments for immunologic conjunctivitis patients, with the goal of evaluating their efficacy and safety.
Methods
We will conduct a comprehensive search for relevant studies on NLRP3 inflammasome inhibitors or NLRP3-related treatments for immunologic conjunctivitis in various databases including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang. The search will encompass studies from their respective inception dates to July 2023. A meta-analysis will be performed using data extracted from eligible randomized controlled trials (RCTs), focusing on the clinical manifestations of immunologic conjunctivitis, levels of NLRP3-related factors in serum or tear samples, quality of life outcomes, and adverse events. Review Manager 5.4.1 software will be employed for the meta-analysis, and the results will be analyzed using either random-effects or fixed-effects models, depending on the presence of heterogeneity. The reliability and quality of evidence will be evaluated using the Grading of Recommendations, Development, and Evaluation (GRADE) system.
Results
The findings of this study will yield robust and high-quality evidence regarding the efficacy and safety of NLRP3-related treatments for immunologic conjunctivitis. This evidence will contribute significantly to our understanding of the potential benefits and risks associated with such treatments and will assist healthcare professionals in making informed decisions regarding the management of immunologic conjunctivitis.
Conclusion
This study represents the first comprehensive meta-analysis aiming to evaluate the efficacy and safety of NLRP3-related treatments for immunologic conjunctivitis. The findings from this study will provide valuable evidence to guide clinical management strategies for this disease. The results are anticipated to significantly contribute to the understanding of the therapeutic potential and safety profile of NLRP3-related treatments, offering valuable insights for healthcare professionals involved in the care of patients with immunologic conjunctivitis.
Trial registration
Systematic review registration: PROSPERO with registration number CRD42023437076.
... Mast cell stabilizers inhibit mast cell degranulation and, consequently, the release of histamine by interrupting the normal chain of intracellular signals. 4,7 The first line of treatment for this condition includes antihistamines that combine both mechanisms of action: dual-action antihistamines, which present an increased safety and efficacy profile compared with older topical agents used in the treatment of AC. 4 Bepotastine besilate is the latest-generation ophthalmic antihistamine with multiple mechanisms of action in both preclinical and clinical studies. This drug is a highly selective H1 receptor antagonist with potent mast cell-stabilizing action. ...
... A large percentage of patients with AC also present nasal symptoms as a comorbidity, known as allergic rhinoconjunctivitis. 4,5,7 In rhinitis epidemiology studies, it was found that approximately 90% of patients suffering from nasal symptoms also had ocular symptomatology. [14][15][16] The conjunctiva and nasal mucosa share a similar epithelium, leading to a similar reactivity to the same allergens in both tissues. ...
Purpose
To study the efficacy and toxic effects of bepotastine besilate 1.5% preservative-free (BB-PF) and olopatadine 0.2% BAK-preserved (OL-BAK) drops on the ocular surface of patients with allergic conjunctivitis.
Patients and Methods
Ninety-seven patients with allergic conjunctivitis diagnosis participated in a prospective, multicenter, randomized, double-blind, controlled, parallel-group clinical trial. Patients received either BB-PF (n=48) or OL-BAK (n=49), both administered once daily in the morning. The patients were followed for 60 days. Ocular itching was the primary outcome measure. Secondary outcomes included ocular symptoms, signs, and non-ocular symptoms associated with rhinoconjunctivitis. Conjunctival impression cytology (CIC) was performed to evaluate histopathological changes related to the toxic effects of preservatives.
Results
BB-PF treatment was associated with a 1.30 more probability of diminished ocular itching than OL-BAK (odds ratio (OR)=1.30; 95% CI=(0.96–1.7); p=0.086). No statistically significant differences were found between treatments in the resolution of other ocular symptoms or signs, except for tearing, which was superior in the BB-PF (OR=1.37; 95% (1.26–1.47); p<0.0001). BB-PF was superior in terms of the resolution of rhinorrhea (p=0.040) and nasal itching (p=0.037). After 60 days of treatment, the BB-PF group exhibited 2.0 times higher probability of having a lower Nelson scale score compared to the OL-BAK group (OR=2.00; 95% CI=(1.19–3.34); p=0.010).
Conclusion
Both medications presented a similar efficacy in terms of the resolution of ocular signs and symptoms associated with ocular conjunctivitis. BB-PF is superior in the resolution of non-ocular symptoms and safer for the ocular surface than OL-BAK.
... To further clarify the role of the TLR7-mast cell axis in COPD we used treatment with the anti-asthma and mastocytosis drug disodium cromoglycate (DSCG, cromolyn) that inhibits the release of mediators from mast cells 50 . We administered DSCG during weeks 6-8 of CS exposure, when the chronic features emerge to induce experimental COPD. ...
... Low dose imiquimod (50 µg) was used to mimic responses induced by CS exposure rather than viral infection. Acute viral infections induce excessive inflammatory cell infiltrates, cytokine and chemokine responses and virus-induced tissue destruction [50][51][52] . Inflammatory responses induced by CS exposure are chronic and low grade, and CS suppresses anti-viral IFN responses in certain immune cells 38,62,63 . ...
Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.
... Typical signs and symptoms included ocular itching, redness, and tearing, but also is presented with chemosis, lid swelling, and mucous discharge. A large amount of patients with allergic conjunctivitis also present nasal symptoms as a comorbidity, known as allergic rhinoconjunctivitis 2,3 . AC is classified as a type 1, IgE-mediated hypersensitivity immune reaction and occurs in individuals previously exposed to the specific allergen. ...
... Mast cell stabilizers inhibit mast cell degranulation and consequently the release of histamine by interrupting the normal chain of intracellular signals. 2 The first line of treatment of this condition included antihistamines that combine both mechanisms of action. ...
Purpose: To study the efficacy and toxic effects on ocular surface of bepotastine besilate 1,5% preservative-free (BB-PF) in comparison to olopatadine 0,2% BAK-preserved (OL-BAK) eyedrops in patients with allergic conjunctivitis.
Methods: 97 patients with allergic conjunctivitis diagnosis participate in a prospective, multicenter, randomized, double-blind, controlled, parallel-groups clinical trial. Patients received BB-PF (n=48) or OL-BAK (n= 49) both applied once a day at morning. Patients were followed for 60 days of treatment. Primary efficacy outcome was ocular itching. Secondary outcomes included ocular symptoms and signs, non-ocular symptoms associated with rhinoconjunctivitis. Conjunctival impression cytology (CIC) was performed to evaluate histopathology changes related with preservatives toxic effects.
Results: BB-PF treatment was associated with 1.30 more probability to diminished ocular itching in comparison to OL-BAK OR: 1.3 (CI 95% 0.96-1.7) p= 0.086. There were not any statistically significance between treatments in others ocular symptoms or signs, except for tearing that was superior in BB-PF (OR: 1.37 CI 95% 1.26-1.47, p<0.0001). BB-PF was superior in the resolution of rhinorrhea (p=0.040) and nasal itching (p= 0.037). BB-PF treatment was associated with 2.0 more probability to present a lower grade of Nelson scale in comparison to OL-BAK through 60 days of treatment OR: 2.00 (CI 95% 1.19-3.34), p= 0.010).
Conclusions: Both medications under study presented a similar profile in the resolution of ocular signs of symptoms associated with ocular conjunctivitis. BB-PF was superior in the resolution of non-ocular symptoms and was safer for the ocular surface in comparison to OL-BAK.
... Topical antihistamine and mast cell stabilizer are commonly co-administered for treatment of eye allergy [39]. CTZ as an antihistamine provides relief from symptoms before AZE starts working. ...
... AZE inhibits degranulation and the release of histamine. So, the effect of cetirizine in eye allergy can be enhanced by the addition of AZE [39]. ...
A green, simple, quick and economical method is implemented for the first time for the simultaneous estimation of cetirizine (CTZ) and azelastine (AZE) as co-administered eye drops. The method relies on synchronous spectrofluorimetry with ∆λ = 60 nm. Cetirizine can be estimated at 231 nm and AZE can be measured at 294 nm, each at the other’s zero crossing point. All factors affecting the method were studied and properly optimized. Good correlation was obtained in the range of 0.1–2 µg mL⁻¹ for both drugs. The limits of detection were 0.014 and 0.010 µg mL⁻¹ and limits of quantitation were 0.043 and 0.029 µg mL⁻¹ for CTZ and AZE, respectively. Moreover, ICH guidelines were carried out to validate the adopted method. The method was suitable for the analysis of CTZ and AZE in synthetic mixtures, eye drops and aqueous humor. The mean percentage of recoveries of CTZ and AZE in spiked aqueous humor were 99.83 and 99.37, respectively. Furthermore, Green Analytical Procedure Index (GAPI) and analytical Eco-scale approaches were used to evaluate the greenness of the suggested method.
... Current first-line treatments, including topical antihistamines and mast cell stabilizers, provide symptom relief for many patients. However, these therapies often fall short in managing moderate to severe cases, with up to 60% of patients requiring additional interventions to control persistent or severe symptoms [6,7]. For these individuals, topical corticosteroids are frequently used as second-line therapy. ...
Introduction
Seasonal allergic conjunctivitis (SAC) is a hypersensitivity condition characterized by itching, tearing, and redness. It affects over 20% of the general population with limited therapeutic options. Reproxalap, a novel small-molecule aldehyde trap, has emerged as a potential treatment option for SAC by targeting reactive aldehydes involved in inflammation. In this systematic review and meta-analysis, we assessed the efficacy and safety of Reproxalap in treating SAC.
Methods
Multiple databases were searched including PubMed, Cochrane Library, Scopus, and Google Scholar, to identify relevant studies. Clinical trials involving patients diagnosed with SAC and treated with Reproxalap (0.25% or 0.5%) were included. The primary outcomes were symptom relief (efficacy) and side effects (safety). Data extraction and risk of bias assessment were performed independently by two reviewers. Meta-analysis was conducted using RevMan 5.4 software.
Results
Five RCTs involving 625 participants were included. Reproxalap significantly reduced ocular itching compared to control groups for both 0.25% (SMD: -0.31, 95% CI: -0.50 to -0.13, P = .001) and 0.5% concentrations (SMD: -0.31, 95% CI: -0.51 to -0.10, P = 0.004). No significant difference was observed between the two doses (SMD: -0.02, 95% CI: -0.23 to 0.19, P = 0.83). Side effects were more frequent in both Reproxalap groups compared to controls, with odds ratios of 35.31 (95% CI: 17.83 to 69.90, P < 0.00001) for 0.25% and 45.64 (95% CI: 18.49 to 112.66, P < 0.00001) for 0.5%. The 0.5% dose had significantly higher odds of side effects compared to the 0.25% dose (OR: 1.66, 95% CI: 1.10 to 2.51, P = 0.02). Heterogeneity was low for all outcomes (I² = 0%).
Conclusion
Reproxalap reduces ocular itching associated with SAC. While both 0.25% and 0.5% concentrations are effective, safe and tolerable. Further research should focus on the long-term benefits and applicability of Reproxalap on diverse populations.
... Many scholars have repeatedly compared the therapeutic effects of various anti-allergy eye drops on SAC, and although there are slight differences, all can . 3 Scores of the ocular surface symptom questionnaire before and after IPL treatment in the IPL group achieve good results [3][4][5]. In order to control allergic conjunctivitis more effectively, An increasing number of new drugs are being developed, for example, 0.5% epinastine topical eyelid cream may be considered an effective drug to prevent the onset of seasonal allergic conjunctivitis [6]; Bilastine 0.6% ophthalmic solution was effective in reducing ocular symptoms associated with allergic conjunctivitis [7][8]. ...
Objective
To observe the effectiveness of intense pulsed light(IPL) treatment as an adjuvant treatment of refractory seasonal allergic conjunctivitis in children.
Methods
A total of 31 patients with refractory seasonal allergic conjunctivitis who did not respond well to anti-allergic drug treatment were randomly selected to receive drug therapy combined with IPL treatment (17 patients) and drug treatment alone (14 patients) for 1 week, and the ocular surface symptom questionnaire and ocular surface sign score were performed before and after treatment, respectively.
Result
After treatment, the IPL group had significantly lower scores in eye rubbing, blinking, eye itching, discharge, tearing, and total scores than before treatment (P < 0.05), while there was no significant difference in foreign body sense scores before and after treatment (P > 0.05). There were no significant differences in eye rubbing, blinking, eye itching, discharge, foreign body sensation, tearing, and total score between the control group after treatment (P > 0.05). After treatment, the scores of ocular signs in the IPL group and the control group were lower than those before treatment, and the difference was statistically significant (P < 0.01).
Conclusion
IPL therapy is effective in improving ocular surface symptoms in children with refractory seasonal allergic conjunctivitis, especially in suppressing eye itching, with good results.
... The antihistaminic agents prevent histamine release by mast cell stabilization. These medications block the histamine H1 receptor and vasoconstriction in the tissue [15]. Further, studies show that herbal medications like Curcumin inhibits antigen-mediated activation of mast cells and suppress the degranulation and secretion of tumor necrosis factor-α (TNF-α) and interleukin-4 [16]. ...
Background
Mast cell infiltration in oral submucous fibrosis (OSMF) has been drawn in to play a definitive role in initiation, progression, and symptom like burning sensation. Degranulation products of mast cells like tryptase and chymase have been studied through immunochemistry. The presence of mast cells in close to fibroblasts certainly makes them play a pivotal role in initiation of fibrogenesis in oral mucosa. As OSMF involves the oropharynx and esophagus along with the oral mucosa, the role of certain systemic factors might be considered in this spread apart from local factors. Present study was planned to identify the serum concentrations of various mast cell secretions like histamine and chymase using enzyme-linked immunosorbent assay (ELISA). Further, diamine oxidase (DAO), an enzyme that metabolizes histamine, was included to evaluate any correlation with serum histamine.
Methods
Thirty-nine participants were equally divided into 3 groups: OSMF patients, areca chewers without OSMF, and healthy controls. Serum samples collected by drawing blood were estimated for serum histamine, chymase, and diamine oxidase using ELISA kits.
Results
ELISA findings revealed significant differences in the serum values of histamine and chymase while concentration of serum DAO was not significant among the three groups. There was a positive correlation between histamine and DAO levels in all the groups.
Conclusion
Mast cell-related bioactive molecules may render a systemic effect during initiation and progression of OSMF. DAO levels may rise linearly to metabolize histamine as a physiological phenomenon.
... Conventional treatments often include topical ophthalmic drops containing antihistamines, mast cell stabilizers, or dual-action agents, which provide short-term symptom relief by inhibiting histamine activity and preventing mast cell degranulation [5,6]. These medications are effective in reducing symptoms such as itching, redness, and tearing and are commonly used in combination with nonsteroidal anti-inflammatory drugs, corticosteroids, or immunosuppressants, depending on disease severity [6][7][8]. ...
This case report highlights the successful transition from epinastine eye drops to a novel epinastine eyelid cream in managing mild allergic conjunctivitis. A 33-year-old Japanese female with mild allergic conjunctivitis, previously managed with 0.1% epinastine hydrochloride eye drops, requested an alternative formulation due to daily contact lens wear. Treatment was changed to a once-daily application of 0.5% epinastine hydrochloride eyelid cream. Clinical assessment and symptom evaluation were performed at baseline and after 28 days using slit-lamp examination and the Japanese Allergic Conjunctival Disease Quality of Life Questionnaire. Following the transition, the patient's clinical signs (mild conjunctival hyperemia and moderate papillae) and subjective symptoms (itching and mild discomfort) remained stable. Slit-lamp examination showed no corneal or limbal pathology, and tear fluid immunoglobulin E (IgE) testing remained positive, consistent with mild allergic conjunctivitis. No adverse effects or cutaneous reactions were observed. This case suggests that epinastine eyelid cream may serve as an effective once-daily alternative to conventional eye drops in mild allergic conjunctivitis. While this represents the first documented successful transition between delivery methods, larger clinical trials are warranted to confirm these findings and explore applications across various presentations and severities of allergic ocular disease.
... A systematic review of randomized controlled trials (RCTs) of ophthalmic antihistamine formulations (N = 30) published from 1946 to 2014 concluded that, although the trials mainly only evaluated the short-term effects (<8 weeks), they appeared to be safe and well tolerated [25]. To extend the safety analysis to recently developed ophthalmic formulations of antihistamines for the treatment of AC, we searched and reviewed controlled trials published in the past ten years (2014 to 2023 inclusive; see Supplementary Materials for details). ...
Allergic conjunctivitis (AC) is the most common allergic eye disorder. Antiallergic eyedrops are the first line of pharmacological treatment. However, the application of antiallergic eyedrops can potentially alter tear homeostasis and affect the ocular surface, which may result in iatrogenic diseases such as dye eye disease (DED). Long-term treatment of AC with eyedrops containing preservatives and other components may increase the risk of DED and ocular surface damage. Here, we examined 20 clinical trials published during the past ten years with antihistamine ophthalmic formulations in the treatment of AC, to evaluate the extent of evidence about their safety and tolerability. Remarkably, we find that most trials lack an evaluation of the critical ocular surface parameters, such as tear film break-up time, tear volume, corneal and conjunctival damage, and inflammation, to properly assess the state of the ocular surface state after prolonged treatment. There is a need to increase awareness of the use of specific formulations that do not increase the risk of iatrogenic DED.
... Tetryzoline (or tetrahydrozoline) (TZ) (Figure 1b) is 2-(1,2,3,4-tetrahydronaphthalen-1-yl)-4,5-dihydro-1H-imida 25 zole; hydrochloride and was invented in 1954 to be used starting from 1959 as an over-the-counter eye/nasal drop [5]. TZ is mainly an agonist for both alpha-2 receptor and imidazoline receptor I-1 [6]. ...
In this study, the combination of pharmaceutical formulation of tetrahydrozline HCl (TZ) and antazoline HCl (AN) was determined without separating them using smart analytical UV spectrophotometric methods. While the Extended Ratio Subtraction Method (EXRSM) is used to determine AN, the Ratio Subtraction Method (RSM) is utilized to determine TZ and is linked with the ratio subtraction technique. The calibration curves for AN and TZ are linear, ranging from 3.0 to 30.0 µg/mL and 5.0 to 45.0 µg/mL, respectively. Analyzing several laboratory-prepared combinations of the two medications allowed researchers to assess the specificity of the designed methods. The selected drugs' combined dosage form was determined with success using both approaches. Validation was carried out in accordance with ICH requirements, and it was found that repeatability, accuracy, and intermediate precision were all within acceptable limits. Statistical studies showed that both methods can be competitively applied in quality control laboratories. RSM and the EXRSM are complementary to one another, as shown by the determination of AN and TZ without pre-separation. Without any prior separation, the EXRSM was able to differentiate between substances with an extended spectrum using the same characteristics. Therefore, one alternative approach to liquid chromatography techniques is the combination of EXRSM and RSM.
... Os anti-histamínicos tópicos comumente usados incluem olopatadina, cetotifeno e azelastina, enquanto os estabilizadores de mastócitos incluem nedocromil sódico e cromoglicato de sódio. Estudos demonstraram que esses tratamentos são eficazes na redução de sintomas como coceira, vermelhidão e lacrimejamento em curto prazo (CASTILLO et al., 2015, DUDEJA et al., 2019, DARA et al., 2022. Fatores ambientais, particularmente alérgenos e poluentes transportados pelo ar, desempenham um papel significativo na incidência e gravidade da conjuntivite alérgica. ...
Allergic conjunctivitis is an eye condition prevalent among children, characterized by inflammation of the conjunctiva resulting from an allergic reaction to substances such as pollen, dust, dust mites and animal dander. This disease is a manifestation of the immune system and causes symptoms such as intense itching, tearing, hyperemia and a sensation of a foreign body in the eyes. The management of allergic conjunctivitis ranges from simple measures, such as frequent eye washing and avoidance of allergens, to the use of medications such as antihistamines, mast cell stabilizers and topical corticosteroids. In childhood, the management of allergic conjunctivitis faces difficulties such as variability in response to treatment and the impossibility of completely avoiding exposure to allergens. The general objective of this study is to evaluate management strategies for allergic conjunctivitis in childhood, with an emphasis on the effectiveness of available treatments and the identification of factors that influence the response to treatment. Specific objectives include analyzing the effectiveness of different treatments, investigating the influence of environmental and individual factors on disease severity and recurrence, and discussing the management of allergic conjunctivitis. This study is relevant as appropriate management of allergic conjunctivitis can prevent complications and improve children’s well-being. Identifying factors that influence response to treatment can contribute to the development of more personalized and effective therapeutic approaches. Recent literature highlights the need to improve education of parents and caregivers about allergic conjunctivitis to ensure appropriate management of the disease. Studies show that understanding the immunological mechanisms underlying the disease is crucial for developing new therapies. Therefore, this research not only adds to scientific knowledge about childhood allergic conjunctivitis, but also provides valuable insights for clinical practice and health policy formulation.
... Both ARC and urticaria can severely impact the quality of life of patients and caregivers [4,9,11]. First-line treatment of ARC and urticaria includes systemic and topical antihistamines, mast cell stabilizers, anti-inflammatory drugs, and corticosteroids [12][13][14]. ...
Background: Bilastine is a second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis (ARC) and urticaria in adults, adolescents, and children. The pharmacokinetics and safety of oral bilastine 10 mg/d in children aged 2 to 5 years were evaluated. Methods: This was a multicenter, open-label clinical trial in children aged 2 to 5 years with seasonal or perennial ARC or urticaria treated once daily with bilastine 10 mg orodispersible tablets. The safety evaluation included treatment-emergent adverse events (TEAEs), vital signs, and physical examination. Pharmacokinetic data were pooled with data from a prior pediatric study, and pharmacokinetic modeling was performed to assess consistency. Results: A total of 37 children with ARC (81.1%), urticaria (8.1%), or both (10.8%) were included in the study, with a mean (SD) age of 3.7 (1.2) years. The highest plasma concentrations of bilastine were observed 1 hour after administration (634.91 ng/mL). Eight patients (21.6%) experienced 1 TEAE each, none of which was severe. Body weight and age were not covariates of variation in either systemic clearance or the volume of distribution in children aged 2 to 5 years and did not affect the pharmacokinetic parameters of bilastine. Conclusions: The pharmacokinetics of bilastine was linear and consistent with data from a previous trial, suggesting that a 10-mg dose may be used in children (2 to <12 years). No dose adjustments are deemed necessary. Oral once-daily bilastine 10 mg presented a good safety profile in children aged 2 to 5.
... Most commonly, pharmacologic pupillary dilation results from iris parasympathetic receptor blockade. Azelastine is an antihistaminic commonly used in allergic conjunctivitis and it is an over-the-counter drug [2]. It is a second-generation H1 antihistamine with a low affinity for cholinergic receptors. ...
Unilateral pharmacologic mydriasis is one of the differential diagnoses of anisocoria. This is a clinical case of a 37-year-old male patient admitted to the ophthalmology emergency department with unilateral mydriasis, an infrequent side effect of the antihistaminic drug azelastine. A comprehensive medical history including ocular medication was essential to avoid the need for additional tests and to exclude life-threatening conditions responsible for a similar presentation.
... Ophthalmic formulations have a rapid onset of action after instillation (3 to 15 minutes), and in many cases can relieve nasal symptoms as well as ocular symptoms. In patients with allergic conjunctivitis, antihistamines have a more favorable risk-benefit ratio than all the other classes of drugs, including NSAIDs, vasoconstrictors, and corticosteroids [25]. ...
Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non–IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.
... MC stabilizers that inhibit MC degranulation include cromolyn sodium and nedocromil sodium, which are in use as topical, albeit not particularly efficacious, treatments for AR and allergic rhinoconjunctivitis (87). ...
The exponential rise in the prevalence of allergic diseases since the mid-twentieth century has led to a genuine public health emergency and has also fostered major progress in research on the underlying mechanisms and potential treatments. The management of allergic diseases benefits from the biological revolution, with an array of novel immunomodulatory therapeutic and investigational tools targeting players of allergic inflammation at distinct pathophysiological steps. Prominent examples include therapeutic monoclonal antibodies against cytokines, alarmins, and their receptors, as well as small-molecule modifiers of signal transduction mainly mediated by Janus kinases and Bruton's tyrosine kinases. However, the first-line therapeutic options have yet to switch from symptomatic to disease-modifying interventions. Here we present an overview of available drugs in the context of our current understanding of allergy pathophysiology, identify potential therapeutic targets, and conclude by providing a selection of candidate immunopharmacological molecules under investigation for potential future use in allergic diseases.
Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... Topical lubricants such as artificial tears or saline can be used to physically wash out the offending allergens. Mild allergic conjunctivitis can be treated with topical antihistamine agents, preferably second generation topical H1-receptor antagonists [42]. If persistent, ophthalmic drops that have both antihistamine activity and mast cell stabilizing properties, such as azelastine or olopatadine, can be used. ...
Conjunctivitis is a common pediatric problem and is broadly divided into infectious and non-infectious etiologies. Bacterial conjunctivitis makes up the majority of cases in children and often presents with purulent discharge and mattering of the eyelids. Treatment is supportive with an individual approach to antibiotic use in uncomplicated cases since it may shorten symptom duration, but is not without risks. Viral conjunctivitis is the other infectious cause and is primarily caused by adenovirus, with a burning, gritty feeling and watery discharge. Treatment is supportive. Allergic conjunctivitis is largely seasonal and presents with bilateral itching and watery discharge. Treatment can include topical lubricants, topical antihistamine agents, or systemic antihistamines. Other causes of conjunctivitis include foreign bodies and non-allergic environmental causes. Contact lens wearers should always be treated for bacterial conjunctivitis and referred to evaluate for corneal ulcers. Neonatal conjunctivitis requires special care with unique pathogens and considerations. This review covers essential information for the primary care pediatric provider as they assess cases of conjunctivitis.
... These symptoms can be suppressed by blocking the H1 receptor. 4,5 The management of AC includes non-pharmacological treatments, such as lacrimal substitutes and protection of the ocular surface. A standard treatment of AC consists of eye drops containing antihistamines, preferably without additives. ...
Purpose
The objective of this study was to assess the safety and tolerability of preservative-free bilastine 0.6% ophthalmic solution after 8 weeks of once-daily administration in patients with allergic conjunctivitis (AC).
Patients and Methods
Multi-center, international, randomized, double blind, placebo-controlled, parallel-group, phase III study of adult patients with seasonal or perennial AC. The study was conducted in 26 centers of 5 European countries. Duration of daily treatment with bilastine 0.6% ophthalmic solution or placebo was 8 weeks. Safety was evaluated by analyzing incidence of ocular treatment-emergent adverse events (TEAEs); additionally, and as secondary parameters, ocular tolerability was assessed, in addition efficacy was also assessed by the average daily total eye symptoms score (TESS).
Results
A total of 333 randomized patients with AC were included (bilastine, N=218; placebo, N=115). Mean (SD) age of the patients was 39.9 (13.7) and were 63.7% female. Overall, the percentage of ocular related TEAEs was low, and the percentage of patients with ocular related TEAEs was lower in the bilastine ophthalmic solution group (2.8%) than in the placebo group (4.3%). No severe TEAEs were reported. The ocular symptoms and TESS improved during the trial in both treatment groups. Statistically significant treatment differences were observed at Week 8 for the TESS and all individual ocular symptoms, being significantly better in the bilastine ophthalmic solution group than in placebo group.
Conclusion
Bilastine 0.6% ophthalmic solution revealed no safety concerns in patients with AC after 8 weeks of once-daily administration. Bilastine was effective in reducing ocular symptoms associated with AC in response to both seasonal and perennial allergens.
... 92 However, if symptoms are persistent, short-term use of topical antihistamines and mast cell stabiliser drops is recommended. 93 Viral (non-herpetic) conjunctivitis causes redness, discomfort, and watering. Follicles on the palpebral conjunctiva and punctate epithelial lesions on the cornea may also be observed. ...
Artificial tears are the mainstay of dry eye disease management, but also have a role in corneal abrasion and wound healing, pain and inflammation management, conjunctivitis, keratitis, contact lens rewetting and removal, and foreign body removal. A systematic review of randomized controlled trials (PROSPERO registration CRD42022369619) comparing the efficacy of artificial tears in patients with dry eye to inform prescribing choices using Web of Science, PubMed and Medline databases identified 64 relevant articles. There is good evidence that artificial tears improve symptoms of dry eye disease within a month of regular use, applied about four times a day, but signs generally take several months to improve. Not all patients with dry eye disease benefit from artificial tears, so if there is no benefit over a month, alternative management should be considered. Combination formulations are more effective than single active ingredient artificial tears. Artificial tears containing polyethylene glycol are more effective than those containing carboxymethylcellulose/carmellose sodium and hydroxypropyl methylcellulose. Those classified as having evaporative dry eye disease, benefit from artificial tears with liposomes, especially of higher concentration. The data available is limited by the definition of dry eye disease applied in published studies being variable, as well as the disease severity examined and compliance with artificial tears being rarely quantified.
... Studies evaluating olopatadine concluded that it was effective in decreasing histamine levels in the tear film, leading to markedly improved itching, tearing, edema, and chemosis, even in the long term with continued use [112][113][114][115]. These effects are relatively similar across the dual acting agents [116][117][118][119]. The most recently developed drug in this class is bepotastine. ...
Allergic conjunctivitis (AC) is a common condition resulting from exposure to allergens such as pollen, animal dander, or mold. It is typically mediated by allergen-induced crosslinking of immunoglobulin E attached to receptors on primed conjunctival mast cells, which results in mast cell degranulation and histamine release, as well as the release of lipid mediators, cytokines, and chemokines. The clinical result is conjunctival hyperemia, tearing, intense itching, and chemosis. Refractory and chronic cases can result in ocular surface complications that may be vision threatening. Patients who experience even mild forms of this disease report an impact on their quality of life. Current treatment options range from non-pharmacologic therapies to ocular and systemic options. However, to adequately control AC, the use of multiple agents is often required. As such, a precise understanding of the immune mechanisms responsible for this ocular surface inflammation is needed to support ongoing research for potential therapeutic targets such as chemokine receptors, cytokine receptors, non-receptor tyrosine kinases, and integrins. This review utilized several published articles regarding the current therapeutic options to treat AC, as well as the pathological and immune mechanisms relevant to AC. This review will also focus on cellular and molecular targets in AC, with particular emphasis on potential therapeutic agents that can attenuate the pathology and immune mechanisms driven by cells, receptors, and molecules that participate in the immunopathogenesis and immunopathology of AC.
... 8 Clinically, the therapeutic methods for extraocular inflammatory symptoms such as AC mainly include antihistamines and mast cell membrane stabilizers, as well as corticosteroids for patients with severe reactions and high risk of side effects. [9][10][11][12] In this respect, exploration of novel, safe, and effective agents for control of inflammatory response becomes critical. KAT5, also known as TIP60, is a lysine acetyltransferase that modulates acetylation of genes and even proteins. ...
Purpose:
We aimed to explore the effect of lysine acetyltransferase KAT5 on allergic conjunctivitis (AC).
Methods:
The effect of KAT5 on inflammatory response during AC progression was analyzed in the experimental allergic conjunctivitis (EAC) mouse model.
Results:
The clinical score, permeability, total IgE, ovalbumin (OVA)-specific IgE, and IgG1/IgG2a were induced in the EAC mice, in which the overexpression of KAT5 could further enhance but KAT5 inhibitor NU9056 reduce the phenotypes. The eosinophilic infiltration was induced in EAC mice, in which the overexpression of KAT5 was able to further promote but NU9056 attenuate the phenotype. The expression of Eotaxin and RANTES and the inflammatory factors were upregulated in EAC mice and KAT5 overexpression increased, but NU9056 decreased the expression in the model. Significantly, the CD11c+ dendritic cells and CD4+ T cells infiltration in the conjunctiva was enhanced in EAC mice, whereas KAT5 overexpression induced but NU9056 suppressed the effect in the model. Mechanically, the phosphorylation of PI3K and Akt and the levels of histone H3 lysine 27 acetylation (H3K27ac) were enhanced in EAC mice, whereas the overexpression of KAT5 promoted and NU9056 repressed the phenotype in the mice. The enrichment of KAT5 and H3K27ac on PI3K promoter was increased in EAC mice, and the overexpression of KAT5 further enhanced the enrichment in the mice. Significantly, we observed similar results in the KAT5 knockout mice as well. Moreover, PI3K/AKT signaling inhibitor LY294002 reversed KAT5 overexpression-mediated phenotypes and inflammatory response after induction AC in vivo.
Conclusions:
Therefore we concluded that KAT5 inhibition protected against ocular inflammation by mediating the PI3K/AKT pathway in EAC mouse model.
... Systemic antihistamines are especially recommended in the presence of other allergic comorbidities [4,5]. Topical antihistamines and mast cell stabilizers are usually well tolerated and reduce symptoms and signs of allergic conjunctivitis, but there are limited data on their long-term efficacy [6]. Topical ocular antihistamines constitute the first-line treatment in cases of isolated ocular symptoms. ...
IntroductionBilastine is a second-generation H1 antihistamine indicated for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. On the basis of the demonstrated efficacy and safety of the oral formulation, a new ophthalmic formulation of bilastine was recently developed. Previous preclinical studies had indicated that bilastine is mainly absorbed by the conjunctiva and shows low plasma concentration. The objective of this study was to evaluate the pharmacokinetics and safety of ophthalmic bilastine (6 mg/mL) after single and multiple dose administration at steady state in healthy adults.Methods
This was an open-label, single-centre, phase I, bioavailability clinical trial. One drop of the bilastine ophthalmic formulation was administered once daily in each eye of the subjects for 5 days. Bilastine plasma concentrations were measured by HPLC–MS/MS. Adverse drug reactions were recorded for each subject during drug administration and follow-up visits.ResultsTwelve healthy subjects (age 18–55 years) were included in the study. After multiple dose administration, bilastine reached a mean (± SD) maximum blood concentrations of 2682.26 ± 1615.88 pg/mL at a median time of 2.50 h (range 1.25–4.00 h). The half-life of bilastine in plasma was 7.88 ± 6.72 h. Steady state AUC was 19,512.51 ± 9248.76 h·pg/mL. Adverse events were mild and transient, consisting mainly of dysgeusia.Conclusions
Bilastine once-daily ophthalmic formulation 6 mg/mL is absorbed into the bloodstream in low amounts by the ophthalmic route. The bilastine ophthalmic formulation showed a good safety profile after multiple dose administration.
... It mainly acts as a mast cell stabilizer by preventing the release of common inflammatory mediators such as histamine [31]. This medication is used primarily to manage asthma attacks [37,38] together with corticosteroid-based drugs. Additionally, it is very effective in alleviating allergic rhinitis and conjunctivitis symptoms. ...
The COVID-19 pandemic is still active around the globe despite the newly introduced vaccines. Hence, finding effective medications or repurposing available ones could offer great help during this serious situation. During our anti-COVID-19 investigation of microbial natural products (MNPs), we came across α-rubromycin, an antibiotic derived from Streptomyces collinus ATCC19743, which was able to suppress the catalytic activity (IC50 = 5.4 µM and Ki = 3.22 µM) of one of the viral key enzymes (i.e., MPro). However, it showed high cytotoxicity toward normal human fibroblasts (CC50 = 16.7 µM). To reduce the cytotoxicity of this microbial metabolite, we utilized a number of in silico tools (ensemble docking, molecular dynamics simulation, binding free energy calculation) to propose a novel scaffold having the main pharmacophoric features to inhibit MPro with better drug-like properties and reduced/minimal toxicity. Nevertheless, reaching this novel scaffold synthetically is a time-consuming process, particularly at this critical time. Instead, this scaffold was used as a template to explore similar molecules among the FDA-approved medications that share its main pharmacophoric features with the aid of pharmacophore-based virtual screening software. As a result, cromoglicic acid (aka cromolyn) was found to be the best hit, which, upon in vitro MPro testing, was 4.5 times more potent (IC50 = 1.1 µM and Ki = 0.68 µM) than α-rubromycin, with minimal cytotoxicity toward normal human fibroblasts (CC50 > 100 µM). This report highlights the potential of MNPs in providing unprecedented scaffolds with a wide range of therapeutic efficacy. It also revealed the importance of cheminformatics tools in speeding up the drug discovery process, which is extremely important in such a critical situation.
... In addition to the antihistamine effects, recent studies have described the potential of antihistamine drugs against the Ebola virus, Marburg virus (Schafer et al., 2018), and influenza viruses (Xu et al., 2018). Azelastine is an antihistamine and mast cell stabilizer used as nasal spray for hay fever and eye drops for allergic conjunctivitis (Castillo et al., 2015). A recent study have reported that pre-use of azelastine is associated with a decrease in COVID-19 positive test results among susceptible elderly people (Reznikov et al., 2021). ...
A recent study have reported that pre-use of azelastine is associated with a decrease in COVID-19 positive test results among susceptible elderly people. Besides, it has been reported that antihistamine drugs could prevent viruses from entering cells. The purpose of this study is to investigate whether azelastine have antiviral activity against SARS-CoV-2 in vitro and the possible mechanism. Here, we discovered antihistamine azelastine has an affinity to ACE2 by cell membrane chromatography (CMC); Then we determined the equilibrium dissociation constant (KD) of azelastine-ACE2 as (2.58 ± 0.48) × 10⁻⁷ M by surface plasmon resonance (SPR). The results of molecular docking showed that azelastine could form an obvious hydrogen bond with Lys353. The pseudovirus infection experiments showed that azelastine effectively inhibited viral entry (EC50 = 3.834 μM). Our work provides a new perspective for the screening method of drug repositioning for COVID-19, and an attractive and promising drug candidate for anti-SARS-CoV-2.
Allergic conjunctivitis (AC) is a common ophthalmological condition primarily associated with type I and IV allergic responses. Although AC typically does not cause visual impairments, it can significantly reduce the quality of life of individuals, regardless of age, with severe cases possibly affecting the cornea and potentially impairing vision. However, the mechanisms of action of primary therapeutic drugs-antihistamines, mast cell stabilizers, and their combination-remain unclear. This review introduces the pathogenesis of allergic conjunctivitis, including seasonal, perennial, and vernal keratoconjunctivitis. This study found that dual-acting drugs offer advantages over single-agent treatments. Compared to antihistamines or mast cell stabilizers used alone, dual-acting drugs have fewer adverse reactions, avoid side effects such as drowsiness, dizziness, and nausea, and do not cross the blood-brain barrier, thereby preventing potential impacts on learning and memory in both children and adults.
Mast cells (MCs) are bone-marrow-derived haematopoietic cells that are widely distributed in human tissues. When activated, they will release tryptase, histamine and other mediators that play major roles in a diverse array of diseases/disorders, including allergies, inflammation, cardiovascular diseases, autoimmune diseases, cancers and even death. The multiple pathological effects of MCs have made their stabilizers a research hotspot for the treatment of related diseases. To date, the clinically available MC stabilizers are limited. Considering the rapidly increasing incidence rate and widespread prevalence of MC-related diseases, a comprehensive reference is needed for the clinicians or researchers to identify and choose efficacious MC stabilizers. This review analyzes the mechanism of MC activation, and summarizes the progress made so far in the development of MC stabilizers. MC stabilizers are classified by the action mechanism here, including acting on cell surface receptors, disturbing signal transduction pathways and interfering exocytosis systems. Particular emphasis is placed on the clinical applications and the future development direction of MC stabilizers.
This review paper aims to investigate the therapeutic benefits of pemirolast across different medical conditions, including asthma, allergic rhinitis, cancer, conjunctivitis, etc. The prevalence of allergic conditions has risen in recent decades, primarily attributed to environmental factors. This paper explores the role of pemirolast in managing and mitigating these diseases, shedding light on its potential applications in the context of evolving environmental influences.
This review paper investigates the diverse biological activities exhibited by pemirolast, encompassing its roles as an antimicrobial, analgesic, antiviral, anti-inflammatory, antioxidant, antihistamine, mast cell stabilizer, anti-tubercular, anticancer, anti-asthmatic, anti-malarial, diuretic, antianxiety, and antifungal agent. The positive outcomes of pemirolast application in various diseases are highlighted, showcasing its potential across a spectrum of medical conditions.
The pharmacological impact of pemirolast extends to diverse inflammatory mediators, enzymes, and hormones associated with various diseases. Pemirolast demonstrates inhibitory effects on key elements such as eosinophil activation, histamine, leukotriene, IgE, mast cells, basophils, prostaglandin, interleukin, T-helper cells, macrophage T-cells, neutrophils, tryptase, T-lymphocytes, interferons I-III, Amyloid β (Aβ) peptide, dsRNA transcription, GABA, dopamine, serotonin, and norepinephrine. This comprehensive exploration underscores pemirolast inhibitory actions across disorders, emphasizing its potential therapeutic relevance in diverse pathological conditions.
This review paper illuminates pemirolast potassium's versatile biological and therapeutic applications across various diseases. The potential synergies of combining pemirolast with buspirone, ritanserin, theophylline, and capreomycin are explored, showcasing its ability to elicit beneficial responses in addressing diverse ailments.
Conjunctivitis is defined as any inflammatory condition of the membrane that borders the eyelids and covers the exposed sclera. It is the most frequent reason for "red eye." The word "conjunctivitis" refers to a wide range of illnesses that manifest as conjunctival inflammation. Hyper acute, acute, or chronic inflammations are all possible, and their causes might be infectious or noninfectious. Conjunctival injection, sometimes known as "red eye," is a common presentation for various ocular illnesses and can represent up to 1% of all visits to the primary care physician. The presence of these two symptoms may identify 59% of instances with "serious eye conditions," including anterior uveitis and keratitis. Anisocoria and moderate photophobia were substantially related with "serious eye conditions. Before beginning antibiotic therapy, it is preferable to collect swabs from the discharge. The swabs are then cultured in the lab by placing them in different growth media. It is recommended to use Sabouraud agar plates to detect fungus in immunocompromised individuals and those with persistent blepharitis. Additionally, anaerobic culture plates may be beneficial, particularly for individuals who have a history of prior surgery or trauma. A very contagious kind of viral conjunctivitis is acute hemorrhagic conjunctivitis (AHC). It presents with a feeling of a foreign body, excessive weeping, and edema of the eyelids, dilated conjunctival vessels, chemosis, and subconjunctival hemorrhage. When a person is sexually active as an adult or a newborn, Neisseria gonorrhoeae is frequently the cause of hyperacute conjunctivitis. Conjunctiva, eyelids, and cornea can all be impacted by ocular allergies along with other ocular surface areas. Ocular allergy disorders have been divided into three main categories by Leonardi et al based on the immunological mechanism responsible for the final clinical appearance. Patients suffering with viral conjunctivitis have quick onset foreign body feeling, red eyes, irritation, light sensitivity, burning, and watery discharge. Patients with bacterial conjunctivitis have all of the aforementioned symptoms as well as mucopurulent discharge and mattering of the eyelids upon awakening. For individuals with conjunctivitis, general supportive therapies include allergen avoidance (pollens, animals, and dust mites), the use of artificial tears, proper hand hygiene, cold compresses, avoidance of eye rubbing, and mild cleanser to remove any allergens or debris.
The word "elective" refers to medications and procedures undertaken by choice or with a lower grade of prioritization. Patients usually use elective medications or undergo elective procedures to treat pathologic conditions or for cosmetic enhancement, impacting their lifestyle positively and, thus, improving their quality of life. However, those interventions can affect the homeostasis of the tear film and ocular surface. Consequently, they generate signs and symptoms that could impair the patient's quality of life. This report describes the impact of elective topical and systemic medications and procedures on the ocular surface and the underlying mechanisms. Moreover, elective procedures performed for ocular diseases, cosmetic enhancement, and non-ophthalmic interventions, such as radiotherapy and bariatric surgery, are discussed. The report also evaluates significant anatomical and biological consequences of non-urgent interventions to the ocular surface, such as neuropathic and neurotrophic keratopathies. Besides that, it provides an overview of the prophylaxis and management of pathological conditions resulting from the studied interventions and suggests areas for future research. The report also contains a systematic review investigating the quality of life among people who have undergone small incision lenticule extraction (SMILE). Overall, SMILE seems to cause more vision disturbances than LASIK in the first month post-surgery, but less dry eye symptoms in long-term follow up.
Objective: To evaluate and compare the efficacy and safety between tacrolimus, cyclosporine ointment and anti-histamine as single therapy for allergic conjunctivitis. Methods: A comprehensive literature search was conducted through PubMed/MEDLINE, clinicalkey.com and ophtalmologyadvance.com databases. All studies included were interventional or observational reporting the efficacy of tacrolimus, cyclosporine, and antihistamine as monotherapy for all types allergic conjunctivitis. Outcome of this review included number of resolution, duration to resolution, recurrence and complications. Result: Eighteen studies were included in this study. Males predominated, with overall ratio ±2:1 compared to female. Most studies use objective signs and subjective symptom scoring before treatment, during follow up and after treatment for outcome measurement. In the antihistamine group, there was a decrease in itching and redness scores of about 33-75%, especially Bepostatinebesilate solution at a concentration of 1.5% Improvement in conjunctival hyperemia and complete resolution of papillary hypertrophy reported in tacrolimus and cyclosporine group, more than 50% reduction on symptoms and signs severity was found in all patients on tacrolimus and cyclosporine group. Conclusion: Tacrolimus and cyclosporine clinically improved allergic conjunctivitis. Topical cyclosporine and tacrolimus were suggested to be an effective and safe alternative therapy for resistant allergic conjunctivitis.
Ocular itching and eye rubbing are frequent complaints in an ophthalmology practice. Numerous studies address the consequences of eye rubbing, such as keratoconus. However, there are few studies concerning the pathophysiology of itching, its transmission pathways, or its interactions with eye rubbing. Through this literature review, we will address the various clinical, physiological and therapeutic aspects of this pair of symptoms with a variety of ocular consequences. We will then describe the state of the art in itching and scratching in dermatology, in order to draw a parallel between these two vicious cycles. A better understanding of the pathophysiology of ocular itching and eye rubbing, as well as new studies based on dermatological data, might allow more appropriate clinical management of our patients and their symptoms.
A new analytical quality by design-assisted HPLC–UV approach is presented, for the first time, for the concurrent determination of cetirizine (CTZ) and azelastine (AZE) in raw materials, commercial eye drops and aqueous humor. The two drugs are co-administered as eye drops in severe ocular allergies. A 2 ³ full factorial design was adopted for the chromatographic optimization to ensure the best analytical performance and reliability, as well as to save time, effort and solvent consumption. The parameters, including pH, acetonitrile ratio, and flow rate, were selected as independent factors. The responses analyzed were resolution and tailing of peaks. The separation was achieved through isocratic elution on C8 column with mobile phase made up of acetonitrile: 0.3% triethylamine of pH 5 (60:40 v/v) at a flow rate of 1.2 mL min ⁻¹ and detection at 216 nm. The elution time was less than 6 min. The approach was fully validated in accordance with International Council for Harmonization (ICH) guidelines. Good linearity was achieved over the concentration ranges of 1.0–30 and 0.5–10 µg mL ⁻¹ with limits of detection of 0.310 and 0.158 µg mL ⁻¹ and limits of quantification of 0.940 and 0.479 µg mL ⁻¹ for CTZ and AZE, respectively, with correlation coefficients of 0.9998. The intra- and inter-day precisions were lower than 2%. The good sensitivity of the approach permits the analysis of CTZ and AZE in spiked aqueous humor with mean percentage recoveries of 100.93 ± 1.42 and 100.11 ± 1.55, respectively. The statistical comparison between results of the developed method and the comparison method revealed no differences, indicating the accuracy of the method.
Antihistamines and corticosteroids represent the two most commonly used classes of medication for treatment of allergic and immunologic diseases. Specialists in allergy and immunology must recognize the pharmacology of these medications, side effects, dosing strategy, and indications for use.KeywordsHistamineAntihistamineCorticosteroidAllergyInflammationAsthma
Allergic rhinitis is one of the most common diseases (~10%–24% of the population experience allergic rhinitis in the Russian Federation) occurring in the population regardless of sex and age. The urgency of the problem is associated with an increase in the number of patients and the fact that allergic rhinitis is considered a risk factor for the development of asthma. The clinical allergic rhinitis guideline aimed to optimize patient care, up-to-date information about the epidemiology, and disease etiology and pathogenesis. Herein, we present the actual data about the allergic rhinitis classification and its clinical signs and modern (clinical, laboratory, and instrumental) and differential diagnostics. Studies reported allergic rhinitis treatment, rehabilitation, and prevention in the guidelines. The authors describe in detail the existing healthcare options for patients with allergic rhinitis, diagnostic features, and care in partial groups of population (children and pregnant women). The clinical guidelines are recommended for medical doctors (independently from qualification), under-and postgraduate students, universities tutors, residents, and researchers.
Allergic rhinitis (AR) is a prevalent disease worldwide, particularly in developed countries, with estimates of the affected population ranging between 10% and 40%. Persistent AR symptoms not only place a substantial burden on a patient’s quality of life, sleep, activity, and work productivity, but also its impact on health is further augmented by its associated comorbidities, such as conjunctivitis, asthma, sinusitis, ear infections, and nasal polyps. The management of AR includes environmental avoidance measures, implementing pharmacotherapy, and inappropriate cases, administering allergen-specific immunotherapy. The mechanism leading to AR symptoms involves a complex, allergen-driven inflammatory process, modulated by immunoglobulin E, and an interplay between inflammatory cells and vasoactive and proinflammatory mediators, including cytokines. Thus pharmacotherapies used to manage AR symptoms are directed at this inflammatory response with the main treatment goal being symptom relief. The selection of pharmacotherapy is based on the severity and chronicity of symptoms. While the newer-generation antihistamines can be used to treat mild AR, the most effective medication for more persistent symptoms is intranasal glucocorticoids. Several other pharmacotherapies exist as well, including intranasal antihistamines, mast cell stabilizers, leukotriene receptor antagonists, ocular glucocorticoids, and decongestants. There is still a need for newer improved medications, however, as a subset of patients with AR fails to achieve symptom control despite our current arsenal of medications.
Riassunto
La sintomatologia oftalmologica è una ragione frequente di consulto in medicina d’urgenza. La maggior parte delle urgenze oculari può essere gestita da medici di medicina d’urgenza. Tuttavia, è importante sapere come diagnosticare le urgenze immediate che richiedono una consulenza specialistica nel più breve tempo possibile, come le ferite del bulbo, l’endoftalmite o la crisi acuta di chiusura dell’angolo. Questo articolo mette in evidenza le varie patologie oculari più frequenti al Pronto Soccorso, i loro segni clinici, il loro metodo diagnostico e le principali terapie da attuare.
The eye can be affected by immunologically driven inflammation, and this chapter attempts to describe the current state of knowledge regarding the immunologic inflammatory diseases of the conjunctiva, cornea, and sclera. Certain diseases can manifest strictly in the eye while others are ocular manifestations of systemic, potentially lethal disorders. Understanding the mechanism of the various categories of immune reactions can help guide therapy for these diseases.
Conjunctival hyperemia is one of the most common causes for visits to primary care physicians, optometrists, ophthalmologists, and emergency rooms. Despite its high incidence, the treatment options for patients with conjunctival hyperemia are restricted to over-the-counter drugs that provide symptomatic relief due to short duration of action, tachyphylaxis and rebound redness. As our understanding of the immunopathological pathways causing conjunctival hyperemia expands, newer therapeutic targets are also being discovered. These insights have also contributed to the development of animal models for mimicking the pathogenic changes in microvasculature causing hyperemia. Furthermore, this progress has catalyzed the development of novel therapeutics that provide efficacious, long-term relief from conjunctival hyperemia with minimal adverse effects.
2-Imidazoline drugs are used in a variety of applications, such as the treatment of hypertension and opioid withdrawal. It is known these drugs bind to serum proteins and have significant variations within this class of compounds in the overall level of this binding. However, little specific information is available on the interactions of these compounds with the two major transport proteins for many drugs, human serum albumin (HSA) and alpha1-acid glycoprotein (AGP). This study examined binding by 2-imidazolines to these proteins by using 25 mm × 2.1 mm i.d. high-performance affinity microcolumns that contained HSA or AGP. The drugs that were examined were antazoline, clonidine, dexmedetomidine, lofexidine, moxonidine, phentolamine, and tizanidine, which represented a wide range of structures and pharmaceutical applications. The major metabolite of lofexidine, N-(2-aminoethyl)-2-(2,6-dichlorophenoxy) propenamide (LADP), was also examined. All these 2-imidazolines were found to have weak-to-moderate binding to HSA, with global affinities that ranged from 1.62 × 10² to 1.07 × 10⁴ M⁻¹ at pH 7.4 and 37 °C. These compounds had stronger binding with AGP, with global affinities constants ranging from 3.80 × 10² to 1.85 × 10⁴ M⁻¹. No stereoselectivity was observed by HSA for the enantiomers of dexmedetomidine, lofexidine, or LADP. However, AGP did show some stereoselectivity for lofexidine and LADP but not for dexmedetomidine. These results provide a better understanding of interactions of 2-imidazoline with HSA vs AGP in the circulation and of how this binding can change between drugs within this class of compounds.
Purpose: To evaluate and compare the efficacy and tolerance to the topical use of 0.05% ketotifen fumarate and 0.1% olopatadine hydrochloride in the treatment of patients with allergic conjunctivitis. Methods: A masked, randomized clinical study was performed in order to compare the efficacy, safety and side effects of the use of 0.05% ketotifen fumarate and 0.1% olopatadine hydrochloride ophthalmic solutions for the alleviation of symptoms and signs in patients with allergic conjunctivitis. Thirty-four patients, fulfilling the inclusion criteria of the protocol were divided into two groups and received a flask with the masked drug, instilling one drop twice daily in each eye for 30 days. Signs and symptoms of these patients were evaluated on a visit before treatment and on five visits during the treatment (days 1, 2, 7, 14 and 30). Results: Severity of allergic conjunctivitis was the same in both studied groups. Both ketotifen and olopatadine were equivalent and efficient regarding decrease in itching, burning and lacrimation symptoms. Bulbar conjunctival hyperemia was attenuated in both groups. Evaluation of adverse reactions showed the occurrence of burning on administration of both drugs and ketotifen led to occurrence of itching. No hypersensitivity reaction to the studied drugs was observed. Conclusions: This study evidences that 0.05% ketotifen fumarate and 0.1% olopatadine hydrochloride ophthalmic solutions, when instilled twice daily for 30 days, were efficient and safe regarding alleviation of the main symptoms and signs of allergic conjunctivitis.
Background:
The aim of this study was to compare patient-perceived relief of ocular itch, nasal symptoms, and eye drop comfort when allergic conjunctivitis was treated with bepotastine besilate 1.5% versus olopatadine hydrochloride 0.2%.
Methods:
This randomized, observer-masked, single-center, crossover study included 30 patients with ocular itching associated with allergic conjunctivitis accompanied by nasal symptoms. Patients were treated with bepotastine besilate 1.5% twice daily (7 am and 4 pm) or olopatadine hydrochloride 0.2% once daily (7 am) for 14 days. Following a 7-day washout period during which only preservative-free artificial tears were used twice daily, patients were crossed over to the alternative treatment for 14 days. Parameters evaluated by twice-daily patient diaries included each treatment’s ability to relieve ocular itch, ability to relieve itchy/runny nose, ability to relieve ocular allergy symptoms, and eye drop comfort. At the conclusion of the study, patients were also asked to identify which agent provided better all-day relief of ocular itching, better all-day relief of itchy/runny nose, superior comfort, and for which treatment they would prefer a prescription.
Results:
According to the mean daily diary responses, bepotastine besilate 1.5% provided significantly better relief of evening ocular itch, relief of morning and evening itchy/runny nose, and relief of morning and evening ocular allergy symptoms. At study end, 63.3% and 66.7% of patients preferred bepotastine besilate 1.5% for all-day relief of ocular itching and all-day relief of itchy/runny nose, respectively. At study end, there was no significant difference in the number of patients preferring one treatment over the other for comfort. Overall, 66.7% of patients stated that they would prefer to treat their allergic conjunctivitis with bepotastine besilate 1.5% over olopatadine hydrochloride 0.2%.
Conclusion:
Based on their evaluation of therapeutic performance, patients preferred bepotastine besilate 1.5% over olopatadine hydrochloride 0.2% by two-to-one for the treatment of allergic conjunctivitis.
The efficacy and tolerance of topical administration (one drop in each eye q.i.d.) of levocabastine (0.5 mg/ml) was compared with that of sodium cromoglycate (20 mg/ml) and placebo in a 4-week double-blind trial in patients with seasonal allergic conjunctivitis. The investigator rated the treatment as globally good or excellent in significantly more patients treated with levocabastine (89%) than with cromoglycate (67%, P = 0.03) or placebo (48%, P = 0.007). The patients felt that the treatment was more efficacious in 95% (levocabastine), 35% (cromoglycate) and 36% (placebo) of the cases in which they had taken previous antiallergic medication. Total symptom severity according to the patients' diary data was consistently lower with levocabastine than with cromoglycate or placebo for all ocular symptoms. The difference was mainly apparent at the beginning of treatment. The percentage of symptom-free days was higher in the levocabastine group (53%) than in the cromoglycate (31%, P = 0.02) and the placebo group (34%, P = 0.08). Particularly at high-pollen days, levocabastine was superior to cromoglycate in eliminating moderate or severe symptoms. Adverse effects did not occur more frequently with levocabastine or cromoglycate than with placebo. It is concluded that levocabastine is an efficacious, fast-acting and well-tolerated drug in the management of seasonal allergic conjunctivitis.
A pilot study of eye disease was carried out over three months in a general practice at a London community health centre. During the study 223 patients with eye symptoms attended, representing 2.7% of all medical consultations and giving an annual consultation rate for eye disease of 57 per 1000 of the practice population. One hundred and sixty nine of these patients were seen by an ophthalmologist who diagnosed 43 different presenting disorders; seasonal allergic conjunctivitis accounted for 21% of these cases and other disorders of the lids and conjunctiva for 28%. The general practitioner's diagnoses were compared with the ophthalmologist's diagnoses in 30 cases; the principal differences were for specialist areas of external disease, medical retinal disorders, and where ophthalmic symptoms were unrelated to ocular abnormality. A cost analysis showed that an ophthalmic service in a community health centre would be cost effective by reducing attendances at the hospital outpatient department.
The aim of this study was to determine the long-term efficacy and safety of mizolastine, a new second-generation antihistamine with European approval, in the treatment of perennial allergic rhinoconjunctivitis. In this study, 141 patients were treated with once-daily mizolastine 10 mg or 15 mg in a 5-month open-label extension of a 1-month double-blind, placebo-controlled trial, which assessed once-daily mizolastine 10 mg. Mizolastine significantly reduced the nasal subscore (sneezing, rhinorrhoea, itch; end-baseline +/- SD, -2.5 +/- 6.3), nasal obstruction (-1.2 +/- 2.6) and rhinoscopy scores (-1.3 +/- 2.6), and improved ocular and total nasal scores after 6 months' treatment. Improvement was maintained for the duration of the study with no loss of drug efficacy. Adverse effects were mild with no specific effects associated with prolonged use. These results clearly demonstrate that mizolastine is effective and well tolerated in the long-term treatment of perennial allergic rhinoconjunctivitis. The significant clinical improvement in nasal blockade may reflect mizolastine's histamine/5-lipoxygenase dual inhibition.
Allergic conjunctivitis is in actuality a group of diseases affecting the ocular surface and is usually associated with type 1 hypersensitivity reactions. Two acute disorders, seasonal allergic conjunctivitis and perennial allergic conjunctivitis, exist, as do 3 chronic diseases, vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis. The ocular surface inflammation (usually mast cell driven) results in itching, tearing, lid and conjunctival edema-redness, and photophobia during the acute phase and can lead to a classic late-phase response (with associated eosinophilia and neutrophilia) in a subset of individuals. As is the case in other allergic diseases, a chronic disease can also develop, accompanied by remodeling of the ocular surface tissues. In severe cases the patient experiences extreme discomfort and sustains damage to the ocular surface. For such cases, there is no highly effective and safe treatment regimen. Topical administration of corticosteroids is used in severe cases but is associated with an increased risk for the development of cataracts and glaucoma. Thus there is a worldwide search for new biotargets for the treatment of these diseases. Here we provide a brief update of the clinical symptoms associated with these diseases, the rationale for disease classification, recent advances in our understanding of the pathogenesis of the diseases, and an update on both preclinical and clinical advances toward refined therapies for these diseases.
AIM: To evaluate the treatment of Azelastine eye drops in children with allergic conjunctivitis. METHODS: Thirty children patients (60 eyes) with allergic conjunctivitis were enrolled. A randomnized and controlled study was adopted including the control group and the test group. Symptoms and signs were evaluated before and after treatment. The control group used Hyaluronate eye drops and the test group was treated with Hyaluronate plus 0.05% Azelastine eye drops. RESULTS: The respective scores of all symptoms and signs in the control group were 4.60±0.87,4.72±1.53 and 2.53±1.45, 2.40±1.20 before and after treatment, 4.72±0.77, 5.29±1.46 and 1.47±1.48,1.59±1.12 for the test group. The effective rates in the control and test groups were 33% and 73%. There was significant difference between the control and test groups. CONCLUSION: Azelastine eye drops is effective and safe in the treatment of children patients with allergic conjunctivitis.
Ocular allergy is one of the most common conditions encountered by pediatricians and ophthalmologists and is characterized by bilateral injection with itching as the predominant symptom. Risk factors include history of atopy (asthma, eczema, seasonal allergies). Basic and clinical research have provided insight into the immunologic mechanisms, clinical presentation, differential diagnosis, and pharmacologicmanagement of this condition. New pharmacologic agents have improved the efficacy and safety of ocularallergy treatment. This article discusses the classification of ocular allergy diagnosis and management, and addresses clinical symptoms and signs that indicate more severe allergic disease or alternative diagnosis that should prompt expeditious referral to an ophthalmologist.
Aims: To study whether 0.1% olopatadine hydrochloride (OHCL) is more effective and safer than 0.025% ketotifen fumarate (KF) in the management of allergic conjunctivitis. Methods: 83 patients with the sign (hyperemia) and symptoms of allergic conjunctivitis (i.e., tearing, itching and photophobia) were randomized (stratifying by age and sex) 1:1 to receive either 0.1% OHCL or 0.025% KF (one drop in each eye every 12 h). Signs and symptoms were scored before and after 2 weeks of drug therapy using a four-point scale (range: 0-3) while side effects were scored 30 min and 2 weeks after treatment initiation. A composite score of signs and symptoms was defined by adding all measures of signs and symptoms and then subtracting the week 2 sum from the pretreatment sum. Results: Both drugs reduced signs and symptoms of allergic conjunctivitis at 2 weeks from baseline. The treatment with 0.1% OHCL was more effective compared with 0.025% KF, as the mean (SD) composite score of 6.3 (±1.3) for the OHCL group was significantly higher than that of 4.3 (±1.7) for the KF group (p < 0.001, two-sided t-test). KF reduced the mean scores of hyperemia, tearing, itching and photophobia by 64, 63, 55 and 81%, respectively, while OHCL reduced these by 96, 97, 88 and 96%. Relative significant efficacy was achieved for hyperemia, tearing and itching (p ≤ 0.001) but not for photophobia (p = 0.315). No adverse events were observed in the OHCL group while 30% of patients in the KF group showed mild stinging or foreign body sensation after instillation of the first dose. Conclusion: 0.1% OHCl is more effective and safer (in the short term) than 0.025% KF in the management of allergic conjunctivitis.
Purpose: To compare emedastine ophthalmic solution 0.05% BID to levocabastine ophthalmic suspension 0.05% BID in reducing chemosis, eyelid swelling and other signs and symptoms in subjects with seasonal allergic conjunctivitis.
Methods: In a randomized, double-masked, parallel controlled study, emedastine ophthalmic solution 0.05% BID was compared to levocabastine ophthalmic suspension 0.05% BID for control of chemosis, eyelid swelling and other parameters in the environmental allergy study model.
Results: At Days 7, 14, 30 and 42, emedastine was significantly better than levocabastine at controlling chemosis and eyelid swelling (p<0.05). A statistical trend was seen at Day 3 (0.05<p<0.10). Results were clinically relevant at Days 30 and 42. Emedastine was also significantly better at reducing redness and itching at Days 7, 14, 30 and 42 (p<0.05).
Conclusion: Emedastine is more efficacious than levocabastine in reducing chemosis, eyelid swelling and other efficacy variables associated with seasonal allergic conjunctivitis.
Purpose: To determine the efficacy and tolerance of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects.
Methods and Materials: In a randomized, double-masked, parallel controlled study, emedastine 0.05% ophthalmic solution BID was compared to levocabastine 0.05% ophthalmic suspension BID, for control of the signs and symptoms of allergic conjunctivitis in pediatric subjects ages 3–16. Subjects who met all inclusion and exclusion criteria received masked study medication with instructions to instill drops twice daily, in the morning and evening. A diary was completed by the parents four times daily for the first two and last two weeks of the study. Treatment lasted 42 days. Drug efficacy was assessed at the initial administration in the office at Day 0 and after 3, 7, 14, 30 and 42 days.
Results: Overall results showed both drugs have an effect and that emedastine was significantly superior (p<0.05) to levocabastine for the relief of chemosis on Days 14, 30 and 42; of itching on follow-up Days 30 and 42 (p<0.05); of redness on Days 30 and 42; for eyelid swelling on Days 14 and 30; and for physician's impression score on Days 7, 14, 30 and 42.
Conclusion: These results confirm previous preclinical and clinical data on the potent and long acting efficacy of this promising new ophthalmic anti-allergic drug, emedastine in pediatric subjects.
Allergic conjunctivitis (AC) affects an estimated 20% of the population in the Western world, with a large fraction suffering due to seasonal or perennial allergen exposures. Bepotastine besilate ophthalmic solution (BBOS) 1.5%, a dual-acting histamine(H1)receptor antagonist and mast cell stabilizer, is indicated for itching associated with AC. This study was designed to evaluate the efficacy and safety of BBOS 1.5% for reducing ocular itching associated with AC in subjects enrolled in a natural exposure trial. Eligible subjects in a multicenter, double-masked, randomized, parallel-group, placebo-controlled, naturalexposure clinical trial were randomly assigned to either BBOS 1.5% or placebo eyedrops on a 1;1 basis and instilled 1 drop of the test agent into both eyes twice daily for 2 weeks. The mean change from baseline in instantaneous and reflective ocular itching scores at the end of 2 weeks of treatment were evaluated based on subject-assessed severity of instantaneous andreflective itching. Subject-reported adverse events (AEs) were also recorded for safety. Treatment with BBOS 1.5% significantly reduced instantaneous and reflective ocular itching scores from baseline compared with placebo over the 2-week study period (p = 0.007 and p = 0.005, respectively). BBOS 1.5% was well tolerated, and AEs were generally transient and mild. This clinical study indicates BBOS 1.5% effectively and safely treated ocular itching in a natural exposure allergy study and is auseful treatment option for the management of ocular itching associated with AC. (ClinicalTrials.gov identifier number: NCT01174823.).
During the season 65 children, 7–19) yours old, with conjunctivitis due to birch pollinosis were treated with eyedrops, either levocabastine b. i. d. (+ placebo b. i. d.) (n=32), or cromoglycate q. i. d. (n= 33). Beclomethasone was given to children with rhinitis. Symptoms of conjunctivitis and sedation as well as pollen counts were assessed daily. Blood was drawn before and at the end of the treatment. When mean weekly scores for symptoms of conjunctivitis or sedation were evaluated there were no significant differences between the treatments. A dynamic statistical method correlating symptoms with pollen counts on the same and previous days was applied showing that the children treated with levocabastine had a quicker reduction of their conjunctivis symptoms after a pollen peak (p < 0.05) but were tired for a longer period (p < 0.01). Other side effects were few and similar in the groups. No significant changes were seen in the blood safety data. The differences between the groups were small, and from a clinical point of view the conclusion is that levocabastine taken twice daily is as effective and as free of side effects as cromoglycate taken 4 times a day.
Background:
As part of the International Study of Asthma and Allergies in Childhood (ISAAC), prevalence surveys were conducted among representative samples of school children from locations in Europe, Asia, Africa, Australia, North and South America.
Subjects:
257,800 children aged 6-7 years from 91 centres in 38 countries, and 463,801 children aged 13-14 years from 155 centres in 56 countries.
Methods:
Written symptom questionnaires were translated from English into the local language for self-completion by the 13-14-year-olds and completion by the parents of the 6-7-year-olds. Rhinitis was described as a problem with sneezing, or a runny, or blocked nose when you (your child) DID NOT have a cold or the flu. Additional questions were asked about rhinitis associated with itchy-watery eyes, interference with activities and a history of hay fever ever.
Results:
The prevalence of rhinitis with itchy-watery eyes ("rhinoconjunctivitis") in the past year varied across centres from 0.8% to 14.9% in the 6-7-year-olds and from 1.4% to 39.7% in the 13-14-year-olds. Within each age group, the global pattern was broadly consistent across each of the symptom categories. In centres of higher prevalence there was great variability in the proportion of rhinoconjunctivitis labelled as hay fever. The lowest prevalences of rhinoconjunctivitis were found in parts of eastern Europe, south and central Asia. High prevalences were reported from centres in several regions.
Conclusion:
These results suggest substantial worldwide variations in the prevalence and labelling of symptoms of allergic rhinoconjunctivitis which require further study. These differences, if real, may offer important clues to environmental influences on allergy.
We aimed to compare the clinical efficacy and ocular surface variables of olopatadine, ketotifen fumarate, epinastine, emedastine and fluorometholone acetate ophthalmic solutions in preventing the signs and symptoms of seasonal allergic conjunctivitis (SAC).
This was a prospective, randomized, double-blinded and placebo-controlled study. A total of 100 patients with SAC were randomly assigned to one of five groups, in which they were administered olopatadine, ketotifen fumarate, epinastine, emedastine or fluorometholone acetate, instilled twice daily for 2 weeks. One eye of each patient was treated with the study drug and the other was treated with a placebo. Signs and symptoms of allergic conjunctivitis (itching, redness, tearing, chemosis and eyelid swelling) were scored on a 4-point scale. Each symptom was assessed at baseline and then again after 1 and 2 weeks of treatment. Ocular surface variables were assessed by conjunctival impression cytology.
At weeks 1 and 2, all antiallergic agents were significantly more effective than placebo in alleviating itching, redness, tearing, chemosis and eyelid swelling. Fluorometholone acetate was significantly less effective than the other agents in reducing itching and redness at all control visits. Ocular surface findings by impression cytology improved significantly after all treatments compared with placebo.
In patients with SAC, olopatadine, ketotifen, epinastine and emedastine are more efficacious than fluorometholone acetate in preventing itching and redness. All the antiallergic agents gave similar results in terms of reducing tearing, chemosis and eyelid swelling. Our data showed that impression cytology parameters improved after treatment with antiallergic agents in patients with SAC.
To compare the efficacy of olopatadine 0.1 % and ketotifen 0.025 % ophthalmic solutions in the treatment of allergic conjunctivitis.
Forty patients with allergic conjunctivitis were included in the study, they were randomized in two groups: G-I (n = 20) olopatadine 0.1 % and G-II (n = 20) ketotifen 0.025 %, both receiving one drop every 12 hours. We evaluated itching, burning, tearing, redness and chemosis previously and 30 minutes, one, two and four week after.
Age G-I was 19.7 +/- 6.7 years; G-II, 21.05 +/- 8.3 years. When evaluating itching, olopatadine had a significant improvement at 30 minutes and after one week (p < 0.05). In the following weeks, the results were similar in both groups. Olopatadine showed significant improvement in burning at 30 minutes, one and two week (p < 0.05). Tearing significantly decreased at 30 minutes with olopatadine (p < 0.05). There was no difference in redness or chemosis improvement in both groups.
In this study, olopatadine 0.1 % was more effective than topical ketotifen 0.025 % in improving itching, tearing and burning in allergic conjunctivitis patients.
Objective: To assess the cost effectiveness of emedastine, a new antihistamine, versus levocabastine in the treatment of acute allergic conjunctivitis (AAC) in Belgium, France, Germany, The Netherlands, Norway, Portugal and Sweden.
Design and setting: Randomised double-blind multicountry clinical trial followed by economic modelling from the treatment provider perspective.
Patients: A total of 221 patients (109 emedastine, 112 levocabastine) with AAC were included.
Methods: The clinical trial compared the efficacy and safety of emedastine 0.05% and levocabastine 0.05%, both twice daily, for 42 days, using ocular redness, itching, days without symptoms and clinical failure as outcome measures. The cost of first-line treatment failure, including visits, drugs and laboratory examinations, was established in each country from a panel of ophthalmologists and general practitioners. Full sensitivity analyses were conducted.
Results: From day 7 to 42, patients treated with emedastine had less itching (p < 0.001) and less redness (p < 0.001). The failure rate was 10% less (p < 0.02) with emedastine and patients treatedwith emedastine had an incremental 8.5 days (p < 0.01) without symptoms. Emedastine and levocabastine were equally well tolerated. In all European countries, the cost of failurewas lower with emedastine. Emedastine was found to be economically dominant relative to levocabastine, i.e. more effective and less expensive, in Belgium, Germany, Portugal and Sweden; in France, The Netherlands and Norway the incremental cost was low (less than 1 euro per additional symptom-free day).
Conclusion: Through a model based on a randomised clinical trial and cost estimates of treatment failure derived from practitioner interviews, emedastine is a cost-effective treatment of AAC.
The eye represents an ideal and frequent site for the allergic reactions. The term 'allergic conjunctivitis' refers to a collection of disorders that affect the lid, conjunctiva and/or cornea. Even though the diagnosis is essentially clinical, local tests such as cytology, conjunctival provocation and tear mediator analysis can be performed. The immunoglobulin E (IgE)-mediated mechanism does not explain completely the severity and the clinical course of chronic allergic ocular diseases such as vernal (VKC) and atopic keratoconjunctivitis (AKC), which are probably also related to T cell-mediated responses, massive eosinophil attraction and activation and non-specific hypersensitivity. An altered balance between T helper type 1 (Th1) and Th2 cells and between Th1- and Th2-types of cytokines is thought to be responsible of the development of ocular allergic disorders. New findings suggest that a wide range of cytokines, chemokines, proteases and growth factors are involved by complex interwoven interactions rather than distinct and parallel pathways. In addition, several non-specific enzymatic systems may be activated during acute and chronic allergic inflammation, thus contributing to the complex pathogenesis of the disease. Current drug treatment for ocular allergy targets the key mechanisms involved in the development of clinical disease: mast cells with mast cell stabilizers, histamine with histamine receptor antagonists and inflammation with corticosteroids, severe inflammation with immunomodulators. None of these agents lacks side effects and none abolishes signs and symptoms completely. New therapeutic strategies are still needed to respond to the complex pathogenesis of severe forms of ocular allergy such as VKC and AKC.
The aim of this study was to compare short-term (5-minute) ocular comfort and drying effects of 3 topical antihistamine/mast cell stabilizers-epinastine, azelastine, and ketotifen-in patients with allergic conjunctivitis (AC).
Adults with a history of AC, as confirmed on skin testing conducted within the previous 2 years, were enrolled in this single-center, randomized, double-masked crossover study. At visit 1, patients were randomized to receive a single drop of epinastine in 1 eye and either azelastine or ketotifen in the other eye. Ocular comfort was assessed by patients on an 11-point scale (0 = very comfortable to 10 = very uncomfortable) immediately (0 minute) and at 0.5, 1, 2, and 5 minutes after instillation. Patients were also asked to describe how their eyes felt at 3 minutes using a standardized list of positive (soothing, smooth, refreshing, cool, and comfortable), neutral (thick, sticky, and filmy), and negative (stinging, irritating, and burning) descriptor words. At visits 2 to 4, patients were examined for ocular drying and tear-film stability using fluorescein staining and ocular protection index (OPI) evaluation, respectively.
A total of 40 patients (27 women, 13 men; mean age, 40 years [range, 18-73 years]) were included in the study. The mean comfort score was significantly lower (indicating more comfort) with epinastine compared with azelastine at 0.5, 1, 2, and 5 minutes (between-treatment differences, 2.90, 1.85, 1.35, and 0.63, respectively; P < 0.001, P < 0.001, P = 0.001, and P = 0.019) and compared with ketotifen immediately after instillation (between-treatment difference, 1.2; P = 0.014). The mean ocular comfort score was significantly lower with ketotifen compared with azelastine at 0.5, 1, and 2 minutes (between-treatment differences, 2.35, 1.35, and 1.10, respectively; P = 0.001, P = 0.023, and P = 0.028). A majority (85%) of patients chose positive comfort descriptors to describe epinastine versus 34% with azelastine. No significant differences in fluorescein staining or OPI were observed.
In this small study in patients with AC, following administration of a single drop, epinastine was rated as more comfortable than azelastine and ketotifen. None of the tested medications were associated with significant acute ocular drying effects.
A 4 week, multicentre, double-blind, double dummy, placebo controlled group comparative study was carried out during the birch pollen season to compare the efficacy and tolerability of 2% nedocromil sodium eye drops (twice daily) and 2% sodium cromoglycate eye drops (four times daily). Participants with a history of seasonal allergic conjunctivitis (SAC) were randomized to receive nedocromil sodium (60), sodium cromoglycate (61) or placebo (64). Clinical assessment of SAC showed improvement with both active treatments compared to placebo but symptomatology was low and only changes in photophobia and grittiness reached significance (P < 0.05). Patient diaries showed significant control of itching by both active treatments, compared to placebo, with no differences between the active preparations. Patients' opinions indicated a marked placebo effect: 73% of this group reported full or moderate control of symptoms, compared with 75% in sodium cromoglycate and 80% in the nedocromil sodium group. Unusual symptoms were most common (27 patients) with nedocromil sodium eye drops: P < 0.05 vs. placebo (15 patients). There were no serious adverse events. Nedocromil sodium eye drops (b.d.) and sodium cromoglycate eye drops (q.i.d.) were both considered clinically more effective than placebo in controlling symptoms of SAC due to birch pollen.
This was a multicentre, double-blind, randomized group comparative study in which 77 children, aged 6-16 years, received 2% nedocromil sodium eye drops and 72 received placebo, one drop into each eye twice daily. The treatment period was 4 weeks, covering the peak birch pollen season. Prior to the start of the season, patients who had attended the clinic the previous 2 years because of seasonal allergic conjunctivitis (SAC) to birch pollen, entered a one week baseline period during which symptoms were assessed, dairy cards completed, and routine sampling of blood and urine carried out. The double-blind treatment period then commenced at the onset of the birch pollen season. Patients/parents kept daily diary record cards of eye symptom severity and concomitant therapy. Conjunctivitis was mild in both treatment groups but nedocromil sodium was more effective than placebo in controlling symptoms. During the 2-3 weeks of peak pollen counts, this therapeutic effect was statistically significant for itching (P < 0.01), watering (P < 0.05) and total symptom score (P < 0.01), but was not significant for grittiness (P = 0.08) or redness (P = 0.06). Global opinions of efficacy showed no difference between treatments, due to a high placebo effect (however, the diary card data indicated a significant improvement with nedocromil sodium). We therefore conclude that nedocromil sodium 2% eye drops, administered twice daily, is an effective treatment for SAC in children.
The efficacy, tolerability, and adverse-effect profile of the recently developed, topical antihistamine levocabastine were compared with those of sodium cromoglycate in a 4-week double-blind, placebo-controlled trial in 95 patients with seasonal allergic conjunctivitis. At the end of the trial, global therapeutic efficacy was considered to be excellent or good in 87% of levocabastine-treated patients, as compared with 68% of sodium cromoglycate-treated patients (P = 0.006) and 63% of those who received placebo (P = 0.05). After 4 weeks of treatment, levocabastine patients had experienced significantly greater relief from their most severe ocular symptom than patients in the sodium cromoglycate group (P < 0.05). Furthermore, 37% of levocabastine-treated patients were virtually symptom-free for at least 75% of the treatment period, as compared with only 6% of patients in the sodium cromoglycate group (P < 0.01) and 4% of those who received placebo (P < 0.01). Moreover, this trend was maintained on days when the pollen count was high, when the corresponding figures were 33%, 6% (P = 0.02), and 4% (P = 0.02), respectively. Levocabastine was well tolerated. Indeed, the incidence of adverse reactions was no greater in the levocabastine group than in the placebo group. Topical levocabastine is an effective and well-tolerated drug for the prophylaxis and 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.
In a multicenter, double-blind, single-dummy, group-comparative study, 169 patients received ophthalmic sodium cromoglycate 2% four times daily, and 170 patients received 4% ophthalmic sodium cromoglycate twice daily, together with placebo eye-drops twice daily, for the treatment of seasonal allergic conjunctivitis (SAC) to birch pollen. The treatment period was 4 weeks during the birch pollen season. Daily pollen counts were used to identify the peak 14-d period. Clinical examinations were made before the start of treatment, after 1 week of treatment, and at the end of the treatment period. Patients kept daily diary record cards of eye symptom severity and concomitant therapy. Symptoms were generally mild and, except for chemosis (week 4) and soreness (weeks 2 and 3), which were less in the 4% group (P < or = 0.05), no significant treatment differences were seen for symptoms or for antihistamine rescue therapy. Both treatments were considered to be very or moderately effective by more than 90% of patients, and no treatment differences occurred in either clinicians' or patients' opinions of efficacy. The results indicate that the use of 4% sodium cromoglycate eye-drops twice daily is as effective and well tolerated as 2% sodium cromoglycate four times daily in the treatment of birch-pollen conjunctivitis.
Allergic conjunctivitis is one of the most frequent allergic diseases of the anterior eye segment.
This multicentre, clinical trial was an investigation to compare the antiallergic efficacy, local tolerance and safety of Antazolin/Tetryzolin eye drops and Levocabastine eye drops. 69 patients were treated over a 2 weeks course of therapy. The subjective and objective ocular symptoms were documented over the treatment period.
Both eye drops reduced subjective and objective ocular symptoms effective. The difference between the treatments (p = 0.0395) was the faster onset of action of Antazolin/Tetryzolin 30 minutes after administration of the first drop of trial medication.
A fast and effective onset of action is of high clinical relevance. Therefore the benefits of using Antazolin/Tetryzolin eye drops was clearly outweigh.
This double-blind, randomised, placebo-controlled study was carried out to assess the efficacy and safety of 0.025% and 0.05% azelastine eye drops twice daily administered for 14 days to patients with seasonal allergic conjunctivitis or rhinoconjunctivitis. A total of 278 patients were recruited and 226 patients were evaluable for per protocol analysis. The target parameter was the response rate. Four eye symptoms, including the main symptom (itching) were recorded by patients in diaries and eight symptoms were assessed by physicians before and after seven and 14 days of treatment. Severity of symptoms was measured on a four-point scale. The response rates for itching (improvement of at least one score point within the first three days) according to patient assessment were 43% for placebo, 52% for 0.025% and 56% for 0.05% azelastine (NS). However, a more objective assessment of the three main eye symptoms by physicians showed a concentration-dependent improvement in response rate compared with placebo (a decrease of > or = 3 points from a baseline total score of > or = 6), which reached statistical significance for 0.05% azelastine on Day 7 (p < 0.002). In the evaluable patient population, the scores of the three main eye symptoms as well as of all eight recorded eye symptoms, as assessed by the physician, were significantly (p < 0.05) lower in the 0.05% azelastine eye drops group in comparison with the placebo group at Day 7. Inefficacy was the cause of withdrawal in five and three patients on 0.025% and 0.05% azelastine, respectively, and in six patients on placebo. Adverse drug effects, mainly a mild, transient irritation and a bitter or unpleasant taste, were reported by 14% (0.025%), 20% (0.05%) and 15% (placebo) of the patients. No serious side-effects occurred. Azelastine eye drops are effective and well tolerated at a concentration of 0.05% for the treatment of seasonal allergic conjunctivitis.
In a randomised, multicentre study, the effect of azelastine eye drops (n = 51 patients) was compared in a double-blind manner with placebo eye drops (n = 30 patients) and in an open manner with levocabastine eye drops (n = 32 patients) during a 14-day treatment period involving 113 children (aged 4 to 12 years) suffering from seasonal allergic conjunctivitis/rhinoconjunctivitis. The primary variable was the response rate defined as the number of patients showing an improvement after three days of treatment of at least three score points, from a minimum baseline score of six, in the main ocular symptoms of itching, conjunctival redness and lacrimation (each assessed on a four-point scale). Patients discontinuing due to inefficacy were regarded as non-responders. The mean response rate in the azelastine eye drops group (74%) was significantly higher (p < 0.01) than that in the placebo group (39%) and comparable with that in the levocabastine group. The response rates assessed by the patients in their diaries were very similar. Significant differences (p < 0.01) for azelastine compared with placebo were observed on days 3 and 14 in the mean sum scores for the three main symptoms and for a total of eight eye symptoms. The overall assessment of efficacy confirmed the superiority of both active treatments compared with placebo. Adverse drug reactions were reported in 23% of placebo-, 35% of azelastine- and 38% of levocabastine-treated patients. These were mainly local irritant effects. Overall tolerability was assessed as very good or good in 80%, 84% and 91% of placebo-, azelastine- and levocabastine-treated patients, respectively. Azelastine eye drops are effective and well-tolerated in children with seasonal allergic conjunctivitis.
This study was carried out to assess the efficacy of 0.025% and 0.05% azelastine eye-drops in patients with seasonal allergic conjunctivitis of > or = 1 year's duration. A total of 151 patients received 0.025% or 0.05% azelastine eye-drops or placebo b.i.d. for 14 days according to a double-blind, randomized, placebo-controlled, parallel-dosing design; 129 patients completed the study as planned. The three target symptoms, scored on 4-point scales, were itching, lacrimation, and redness of the eyes; responders were patients whose symptom sum score decreased by > or = 3 from a baseline score of > or = 6 by day 3. Mean scores of these and five other symptoms were recorded also on days 7 and 14, and patients kept daily diaries of the three main symptoms and swollen eyelids. Responder rates were 73% for 0.025% (P=0.115 vs placebo) and 82% for 0.05% azelastine eye-drops (P=0.011 vs placebo) and 56% for placebo. The time courses of the mean (investigators' and patients') scores for the three main symptoms reflected the dose-dependent effect of azelastine eye-drops. One patient each from the two azelastine groups and three from the placebo group withdrew because of inefficacy. Adverse drug reactions were reported by 14 and 24 patients receiving 0.025% and 0.05% azelastine eye-drops, respectively, and by eight placebo patients. These reactions were mainly slight application site reactions and taste perversion (bitter or unpleasant taste). Azelastine eye-drops are effective and well tolerated at a dose of 0.05% for the treatment of seasonal allergic conjunctivitis.
The efficacy and safety of twice-daily nedocromil sodium 2% ophthalmic solution and vehicle were compared in the treatment of ragweed seasonal allergic conjunctivitis. Two separate multicenter, randomized, double-masked, placebo-controlled studies were subjected to a combined analysis. Following a one-week baseline period during the beginning of the ragweed pollen season, 189 patients with seasonal allergic conjunctivitis received either nedocromil sodium or vehicle b.i.d. for eight weeks. Efficacy was evaluated by patient diary cards and clinical eye examinations. Safety was assessed by reports of adverse events. Compared with vehicle, nedocromil sodium produced significantly greater decreases in summary symptom score (p = 0.005), itch (p = 0.005), tearing (p = 0.004), overall eye condition (p = 0.001), and clinician-evaluated conjunctival edema (p = 0.018), and significantly better (p = 0.001), and patient (p = 0.001) opinions of treatment effectiveness at the peak pollen period. Additionally, the superiority of nedocromil sodium compared to vehicle approached statistical significance in redness reduction (p = 0.087) and clinician-evaluated conjunctival injection (p = 0.087). There were no serious treatment-related adverse events in either treatment group. In summary, nedocromil sodium 2% ophthalmic solution b.i.d. was found to be effective and to have a favorable safety profile in the treatment of seasonal allergic conjunctivitis.
To compare the ocular comfort of two ophthalmic anti-allergic agents: olopatadine hydrochloride 0.1% and ketotifen fumarate 0.05%.
In a double-masked, multi-centered, randomized trial, 80 subjects were asked to make a 'forced choice' based on ocular comfort between one drop of olopatadine hydrochloride 0.1% instilled in one eye and one drop of ketotifen fumarate 0.05% instilled in the contralateral eye. At one site, the incidence of adverse reactions was also reported.
All subjects (100%) selected olopatadine as the more comfortable formulation. One site (n = 35) reported a 49% incidence of moderate burning and a 49% incidence of mild burning after ketotifen instillation. One subject (2% of population) at this site experienced no ocular discomfort with ketotifen. There were no reports of discomfort associated with olopatadine instillation.
Olopatadine is a more comfortable ophthalmic preparation than ketotifen.
The efficacy and safety of emedastine 0.05% eye drops (Emadine; Alcon Laboratories, Inc, Fort Worth, Texas), a new H(1) antagonist, were studied in comparison to levocabastine 0.05% eye drops (Livostin; Janssen-Cilag N V, Berchem, Belgium) during a twice-daily treatment schedule for 6 weeks in adult and pediatric patients with seasonal allergic conjunctivitis.
In a prospective, multicenter, randomized, double-masked, parallel group study, 222 patients with allergic conjunctivitis were randomized (221 received treatment) to either emedastine or levocabastine, instilled twice daily for 6 weeks. Patient diaries were completed four times daily (before the morning and evening instillations, at noon, and in the afternoon), and clinical examinations were conducted at regular intervals. Primary efficacy variables of ocular redness and itching and secondary efficacy variables of chemosis, eyelid swelling, patient diary data, and physician's global assessment were analyzed.
Both emedastine and levocabastine produced a statistically significant (P =.0001) reduction in itching and redness within 5 minutes of the first instillation. All signs and symptoms improved progressively over the 6-week treatment period. After 7 days of use, and throughout the remainder of the study, emedastine was statistically superior to levocabastine (P <.006) in preventing and alleviating the signs and symptoms (itching, redness, chemosis, and eyelid swelling) of allergic conjunctivitis.
Emedastine 0.05% eye drops administered twice daily are more efficacious than levocabastine 0.05% eye drops in the prevention and treatment of the signs and symptoms of allergic conjunctivitis in adults and children of 4 years and above. Both emedastine 0.05% eye drops and levocabastine 0.05% eye drops were well tolerated.
Olopatadine ophthalmic solution 0.1% (Patanol, Alcon Laboratories, Fort Woth, TX) is approved for the treatment of the signs and symptoms of allergic conjunctivitis. Loratadine 10 mg (Claritin, Schering-Plough, Madison, NJ) is a nonsedating oral antihistamine approved for the treatment of the signs and symptoms of allergic rhinitis.
To compare the efficacy of olopatadine used adjunctively with loratadine versus loratadine alone in patients with seasonal allergic conjunctivitis.
This three-center, observer-masked, treatment-controlled, randomized, parallel-group study involved patients aged 7 to 74 years with seasonal allergic conjunctivitis. Patients were treated for 7 days with either olopatadine twice daily adjunctive to loratadine once daily or only loratadine once daily. Efficacy variables (ocular itching and redness, physician's impression, patient's impression, patient diary ratings of ocular redness and itching), and safety parameters were evaluated during the screening visit and on days 0, 3, and 7. Patients completed the rhinoconjunctivitis quality of life questionnaire on days 0 and 7.
Ninety-four patients received study drug. Patients receiving olopatadine twice daily in addition to loratadine once daily exhibited less ocular itching (P = 0.0436) and rated their ocular condition as more improved compared with those receiving loratadine alone (P < 0.0022). Twenty minutes after initial dosing, olopatadine plus loratadine relieved ocular itching and redness significantly better than loratadine alone (P = 0.001). Both treatment groups showed clinically meaningful improvements in overall quality of life in all but one of the rhinoconjunctivitis quality of life questionnaire domains. Overall, and in most domains, olopatadine plus loratadine also provided significantly better (P < 0.05) quality of life than loratadine alone at day 7.
Compared with loratadine alone, olopatadine adjunctive to loratadine provides greater relief of ocular itching and redness, a better quality of life, and is well tolerated in patients with seasonal allergic conjunctivitis.
Treatments for allergic conjunctivitis have various mechanisms of action. Cromolyn sodium stabilizes conjunctival mast cells by preventing calcium influx across the cell membrane, whereas olopatadine hydrochloride is both an antihistamine and a mast cell stabilizer.
This study compared the efficacy and tolerability of olopatadine and cromolyn in controlling the ocular signs and symptoms of seasonal allergic conjunctivitis.
This was a multicenter, randomized, double-masked, parallel-group trial. One group instilled olopatadine 0.1% ophthalmic solution and placebo BID, and the other instilled cromolyn 2% ophthalmic solution QID, both for 6 weeks. The formulation of cromolyn used in this study is currently available only in Europe and Australia.
The intent-to-treat efficacy and safety analyses included 185 patients, 91 in the olopatadine group and 94 in the cromolyn group. At 30 minutes after the first instillation, respective decreases of approximately 30% and approximately 20% were reported in self-rated ocular itching and redness with both treatments; by 4 hours, itching had decreased by approximately 38% in both groups. Differences between treatments were not statistically significant. At 4 hours, redness had decreased by approximately 38% and approximately 26% in the respective treatment groups. By day 42, both treatments had produced significant reductions from baseline in ocular signs and symptoms; however, the reductions in itching and redness were significantly greater with olopatadine compared with cromolyn (both variables, P < 0.05). The difference in physicians' impression of overall improvement on days 30 and 42 significantly favored olopatadine over cromolyn (both days, P < 0.05). Most patients (62.2%) had reacted positively to grass pollen at baseline. The regression slopes correlating itching and redness with pollen count were 5 times lower for olopatadine compared with cromolyn (P = 0.002 and P = 0.016, respectively), indicating that olopatadine's efficacy increased as the pollen count increased.
Six weeks' instillation of olopatadine 0.19% ophthalmic solution BID had a significantly greater effect on the ocular signs and symptoms of allergic conjunctivitis compared with 6 weeks' instillation of cromolyn 2% ophthalmic solution QID. Both treatments were well tolerated by patients in all age groups; however, olopatadine appeared to have better local tolerability in children aged <11 years.
H1 antihistamines have similar efficacy in the treatment of allergic disorders; however, they differ in terms of their chemical structure, clinical pharmacology, and safety. This review focuses on the clinical pharmacology (pharmacokinetics and pharmacodynamics) of the newer oral H1 antihistamines (acrivastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, and mizolastine). Understanding the pharmacokinetics and pharmacodynamics of these H1 antihistamines provides an objective basis for selection of appropriate dosages and dose intervals. Pharmacokinetic and pharmacodynamic studies provide a rationale for the modified dosage regimens that may be required in special populations, such as the very young, the elderly, those with hepatic or renal dysfunction, or those taking other medications concurrently. Many H1 antihistamines are currently available for use. Clinical pharmacology studies help physicians to select the best H1 antihistamines for their patients.
Azelastine (CAS 58581-89-8) is a selective H1-receptor antagonist that inhibits histamine release and interferes with activation of other mediators of allergic inflammation. The present double-blind study aimed to evaluate azelastine eye drops (Allergodil) in patients with perennial allergic conjunctivitis compared to placebo. A total of 116 patients with an ocular symptoms score for itching and conjunctival redness > or = 3 (0-6 scale) were randomized to twice-daily 0.05% azelastine eye drops treatment (n = 58) or placebo. Patients maintained daily logs and were clinically evaluated after 7, 21 and 42 days of treatment. Azelastine significantly improved itching and conjunctival redness versus placebo (p < 0.001). Tolerability was rated good or better by 97% of patients with only bitter taste and application site reaction notable adverse experiences. On Day 7, ocular symptoms score improved by 1.5 +/- 0.9 (versus 0.5 +/- 0.8 placebo) with score improvement > or = 2 in 55% with azelastine (versus 14% placebo). Itching and redness further improved at Day 42 (score improvement > or = 2 in 95% with azelastine versus 33% placebo) and completely resolved for 47% azelastine patients (versus 10% placebo). Daily patient logs confirmed the clinically assessed scores. Topical azelastine progressively improved itching and conjunctival redness in patients with moderate to severe perennial allergic conjunctivitis. Continued improvement with prolonged use is consistent with mechanisms other than H1-receptor blockade, such as possible down regulation of adhesion molecule receptors.
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.
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.
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.
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.
To study the effectiveness of ketotifen ophthalmic solution (0.25 mg/ml) in seasonal allergic conjunctivitis (SAC) and the impact on the patient's quality of life.
A multicentric, longitudinal, prospective study was designed. 284 Spanish ophthalmologists participated recruiting 1145 patients with SAC. After obtaining the informed consent, a drop of ketotifen ophthalmic solution was instilled. At the visit, clinical symptoms pre and post-treatment were assessed. The patients answered a questionnaire of quality of life (QOL) pre-treatment and minimum one week after initiating the treatment. The qualitative variables were described by the percentage, and the quantitative were described by the average, median, standard deviation, and maximum and minimum values. The effectiveness (change of intensity of the symptoms) and the quality of life were studied by the Wilcoxon test with a significance level of 5% (alpha = 0.05).
Following the instillation of the ketotifen ophthalmic solution the intensity of the ocular symptoms (redness, edema, tearing, secretion, photophobia and visual acuity impairment) decreased significantly. Comparing both QOL, we observed a statistically significant reduction of the limitation perceived by the patients in their daily activities, animic state and ocular symptoms. In 0,7% some adverse event was referred, none was serious and only in one case the probable relationship with the drug was specified.
The results of the ZETA study demonstrate the tolerability and effectiveness of the ketotifen ophthalmic solution for all the symptoms of SAC in clinical practice, observing improvement in the quality of life of the patient.
Ketotifen blocks histamine H(1) receptors, stabilises mast cells, and prevents eosinophil accumulation. These multiple, pharmacological mechanisms provided the rationale for assessing the efficacy and safety of ketotifen 0.025% eye drops in subjects with seasonal allergic conjunctivitis (SAC) in an environmental setting.
This was a double masked, randomised, multicentre trial conducted in Australia. Subjects were randomly assigned to ketotifen fumarate 0.025% ophthalmic solution, placebo (as vehicle), or levocabastine hydrochloride 0.05% ophthalmic suspension, twice daily in each eye for a 4 week period. Subjects were assessed at follow up (days 5-8) and termination (days 25-31) visits. The primary efficacy variable was the responder rate, based on the subjects' assessment of global efficacy at the follow up visit.
519 subjects were randomised to treatment. At the follow up visit, the responder rate, based on subjects' assessment of global efficacy, was significantly greater in the ketotifen group (49.5%) than in the placebo group (33.0%) for subjects with a positive diagnostic test for pollen allergy (p = 0.02). The investigators' assessment of responder rates also showed that ketotifen was superior to placebo (p = 0.001). Ketotifen produced a significantly better outcome than levocabastine (p<0.05) for relief of signs and symptoms of SAC, at both the follow up and the termination visit. The type and frequency of adverse events were similar across treatment groups.
In an environmental setting, ketotifen fumarate 0.025% ophthalmic solution was well tolerated and effective in reducing the signs and symptoms of SAC, and in preventing their recurrence. Ketotifen consistently showed the best efficacy in comparison with both placebo and levocabastine. These results indicate that ketotifen eye drops are a valuable treatment option for this condition.
Ocular allergies cause itching, redness, chemosis, tearing, and swelling of the eyelids in sensitized individuals. The options available for treatment of ocular allergy include olopatadine 0.1% (Opatanol; Patanol [US]) and ketotifen 0.025% (Zaditen; Zaditor [US]). Patient preference for an eye drop can often be a primary factor in determining the level of compliance and satisfaction with any given therapy.
This study sought patient perspective on eye drop efficacy in controlling signs and symptoms of allergic conjunctivitis and eye drop comfort. Also evaluated were the factors considered by patients when making decisions of preference.
One hundred patients with previous history and current symptoms of seasonal or perennial allergic conjunctivitis were enrolled at two centers (Athens, Greece, N = 50; Padova, Italy, N = 50) for this two visit, double-masked study. Qualified patients received two masked bottles of medication (one olopatadine, one ketotifen) and were asked to use both medications as needed over the course of four weeks, but not to exceed usage of two drops of medication per eye per day. At the second visit, patients answered five questions comparing the two masked medications in terms of preference, drop comfort, and efficacy in treatment of signs and symptoms. Patients also defined the factors upon which they based these decisions.
A significantly greater percentage of patients (81%) selected olopatadine when asked which medication they preferred; which they found more comfortable; which they found more efficacious in reducing symptoms of allergy; and which they would select if visiting the doctor's office (P < 0.0001). Seventy-six percent (76%) of patients considered both efficacy and comfort when making their preference decisions (P < 0.0001). No adverse events were volunteered or elicited.
In this study, patients preferred to use the anti-allergy eye drop olopatadine over ketotifen after using both drops and evaluating relative efficacy and comfort during the course of four weeks. A significantly greater percentage of the patients preferred to use olopatadine during the study period, found it more efficacious and comfortable, and would select olopatadine if visiting their doctor's office during allergy season.
Previous studies have suggested that olopatadine hydrochloride ophthalmic solution 0.2% administered once daily is effective for up to 24 hours after instillation and is well tolerated in adults and children aged > or =3 years.
The goal of this study was to evaluate the efficacy and safety profile of olopatadine 0.2% compared with placebo in patients with seasonal allergic conjunctivitis or rhinoconjunctivitis.
This was a 10-week, randomized, placebo-controlled, double-masked environmental study conducted during the spring allergy season (April-August) of 2003. Patients assessed their ocular signs and symptoms in terms of frequency (whole-unit scale from 0 to 5) and severity (half-unit scale from 0 to 4), and grass pollen counts were obtained daily for each investigative site. Responder analyses were conducted by pollen level (frequency based) and pollen period (severity based) to evaluate the clinical significance of differences in ocular itching and redness between treatment groups.
Two hundred sixty patients (137 females, 123 males) were enrolled in the study, including 28 children aged between 11 and 17 years; the overall population was 74% white, 11% black, 4% Hispanic, and 11% other. The frequency-based responder analyses of ocular itching and redness showed that when grass pollen counts were high (>20 gr/m(3) air), a respective 21% and 14% of patients in the olopatadine 0.2% group assessed the frequency of ocular itching and redness as >2, compared with 47% and 31% of patients in the placebo group (P < 0.001 for ocular itching; P < 0.003 for redness). The results of the severity-based responder analyses by peak pollen period were consistent with those of the frequency-based analyses. Compared with placebo, olopatadine 0.2% was associated with significant reductions in calculated mean scores for ocular itching and redness by pollen level and by pollen period. No patient was discontinued from the study because of a treatment-related adverse event, and no patient experienced a treatment-related serious adverse event.
In the patients studied, olopatadine 0.2% appeared to be effective and well tolerated when administered once daily for the treatment of the ocular signs and symptoms of allergic conjunctivitis or rhinoconjunctivitis.