Allergic Conjunctivitis Management: Update on Ophthalmic Solutions.

PURPOSE OF REVIEW: The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface. RECENT FINDINGS: Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage.

Formulation of hesperidin-loaded in situ gel for ocular drug delivery: a comprehensive study.

BACKGROUND: Allergic conjunctivitis is one of the most common eye disorders. Different drugs are used for its treatment. Hesperidin is an active substance isolated from Citrus sinensis L. (Rutaceae) fruit peels, with known anti-inflammatory activity but low solubility. It was complexed with cyclodextrin and encapsulated in situ gel to extend its duration in the eye. RESULTS: The optimized formulation comprised 1% hesperidin, 1.5% hydroxyethyl cellulose, and 16% poloxamer 407. The viscosity at 25 °C was 492 ± 82 cP, and at 35 °C it was 8875 ± 248 cP, the pH was 7.01 ± 0.03, gelation temperature was 34 ± 1.3 °C, and gelation time was 33 ± 1.2 s. There was a 66% in vitro release in the initial 2 h, with a burst effect. A lipoxygenase (LOX) inhibition test determined that hesperidin was active at high doses on leukotyrens seen in the body in allergic diseases. In cell-culture studies, the hesperidin cyclodextrin complex loaded in situ gel, BRN9-CD (poloxamer 16%, hydroxy ethyl cellulose (HEC) 1.5%), enhanced cell viability in comparison with the hesperidin solution. It was determined that BRN9-CD did not cause any irritation in the ocular tissues in the Draize test. CONCLUSION: The findings of this study demonstrate the potential of the in situ gel formulation of hesperidin in terms of ease of application and residence time on the ocular surface. Due to its notable LOX inhibition activity and positive outcomes in the in vivo Draize test, it appears promising for incorporation into pharmaceutical formulations. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Applications of topical immunomodulators enhance clinical signs of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC): a meta-analysis.

PURPOSE: This meta-analysis aimed to review the safety and efficacy of topical cyclosporine A (CsA) and topical tacrolimus in allergic eye disease. METHODS: A systematic search identified thirteen studies and a total of 445 patients for inclusion, making this the largest meta-analysis published on the subject. The current review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Thirteen randomized control trials were included in the meta-analysis. Eleven studies used CsA as the treatment, and two used Tacrolimus. In total, 445 participants were included, of whom 76.6% were male. The mean age of participants across the included studies was 14 years. All studies reported clinical signs as evaluated by an examining clinician. Signs were usually assessed by anatomical region, with the most common regions being the conjunctiva and the cornea, and the most common signs assessed were hyperemia and papillae. Three studies accounted for more than 50% of the meta-analysis's weight. Effect size (d) ranged from - 2.37 to - 0.03, negative values favoring immunomodulators. Fixed Effect Meta-Analysis returned an SMD of - 0.81 (95% CI [- 0.98, - 0.65]). However, there was significant heterogeneity (I2 = 61%, Qw = 30.76) in the outcome measure (P = 0.0021); therefore, a random-effect meta-analysis was also completed in which the pooled SMD was - 0.98 (95% CI [- 1.26, - 0.69], τ2 = 0.16). CONCLUSIONS: This study affirms the current scientific community's stance that immunomodulators effectively treat clinical signs, including blepharitis, conjunctival hyperemia, edema, papillae, and corneal damage in severe ocular allergic disease.

Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops.

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.

The Importance of Preventing and Managing Tear Dysfunction Syndrome in Allergic Conjunctivitis and How to Tackle This Problem.

Tear dysfunction syndrome, also known as dry eye disease (DED), is a multifactorial disease of the ocular surface characterized by the loss of tear film homeostasis. DED shows a significant clinical overlap with ocular allergy (OA), which alters tear film homeostasis, thus predisposing the patient to DED. Both conditions constitute the most common ocular surface disorders and have a potentially severe impact on patients' quality of life. Clinical practice guidelines recommend topical therapies as first-line treatment for OA. However, eye drop formulations may contain additional substances that can contribute to ocular surface damage and the development of DED. Therefore, physicians treating ocular allergy should be aware of problems affecting the tear film, the role of tear film disruption in OA, and topical treatment to prevent or minimize DED. The aim of this review is to present an updated overview of the topic.

Efficacy of Once-Daily Ophthalmic Bilastine for the Treatment of Allergic Conjunctivitis: A Dose-Finding Study.

BACKGROUND AND OBJECTIVE: Bilastine is a nonsedating second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Our study aimed to evaluate the optimal dose, efficacy, and safety of a newly developed once-daily preservative-free ophthalmic formulation of bilastine for allergic conjunctivitis. METHODS: Our phase 2, single-center, double-masked, randomized trial compared the efficacy of 3 doses of a bilastine ophthalmic formulation (0.2%, 0.4%, and 0.6%) with that of vehicle for the treatment of allergic conjunctivitis. The primary efficacy endpoint was the reduction in ocular itching. The Ora-CAC Conjunctival Allergen Challenge model was used to assess ocular and nasal symptoms at the onset of action (15 minutes) and at 8- and 16-hours after treatment. Tolerance and safety were also evaluated. RESULTS: A total of 121 adults with seasonal and/or perennial ocular allergy were randomized. Bilastine ophthalmic formulations 0.2%, 0.4%, and 0.6% were significantly superior (P>.001) to vehicle for the treatment of ocular itching at 3, 5, and 7 minutes after challenge at onset of action (15 minutes) and at 8 hours after treatment. Bilastine 0.6% was also effective at 16 hours after treatment. Treatment differences for bilastine 0.6% were statistically significant (P<.001) compared to vehicle at all timepoints for tearing, eyelid swelling, and nasal symptoms. No relevant adverse events were observed. CONCLUSION: All the tested ophthalmic bilastine doses were efficacious for rapid reduction of ocular itching. The 0.6% formulation was effective up to 16 hours after treatment, making it suitable for once-daily administration. The new formulation was safe and well tolerated.

Lirentelimab for severe and chronic forms of allergic conjunctivitis.

BACKGROUND: Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. OBJECTIVE: We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. METHODS: Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. RESULTS: Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. CONCLUSIONS: Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.

Topical cyclosporine versus allergen specific immunotherapy in perennial allergic conjunctivitis.

PURPOSE: Symptom control in the long-term with less side effects is important in perennial allergic conjunctivitis, since would improve quality of life. This study aimed to assess the clinical efficacies of topical cyclosporin A and subcutaneous allergen immunotherapy (SCIT) in terms of sign control in perennial allergic conjunctivitis. METHODS: This retrospective study included 20 adult patients with perennial allergic conjunctivitis and confirmed sensitization to house dust mites with skin prick test. Patients were assigned to either topical cyclosporine A treatment or SCIT. The participants were followed for 6 months, and signs scores were recorded at 1, 3 and 6 months. RESULTS: Overall, both cyclosporine and immunotherapy groups showed significant improvements in papillary reaction (p = 0.011 and 0.003, respectively), limbal involvement (p = 0.031 and 0.001), and conjunctival hyperemia (p = 0.001 and p < 0.001) scores during the 6-month follow-up. However, only cyclosporine group showed a significant improvement in corneal involvement scores (p = 0.015) during the study period. When scores at different time points were compared, significant improvement in conjunctival hyperemia was evident at 6 months in both groups when compared to baseline (cyclosporine group, 0.7 ± 0.68 vs. 2.4 ± 0.84, 70.8% decrease, p = 0.01; immunotherapy group, 0.3 ± 0.48 vs. 2.3 ± 0.95, 87.0% decrease, p = 0.004), whereas for limbal involvement such an improvement was only evident in the immunotherapy group (0.1 ± 0.32 vs. 1.3 ± 0.95, 92.3% decrease, p = 0.01). CONCLUSIONS: Allergen immunotherapy and cyclosporin A treatment may provide effective sign relief in perennial allergic conjunctivitis. It may represent an encouraging treatment option particularly for cases with perennial allergic conjunctivitis refractive to other treatments and positive skin prick test to a specific allergen (house dust in the present study). Long-term relief by SCIT would reduce the side effects of polypharmacotherapy. Larger studies with longer follow-up are warranted to confirm our findings.

Indication-prescription study for the management of conjunctivitis in a Colombian population.

PURPOSE: Conjunctivitis is one of the most common ocular pathologies. Its treatment depends on its etiology, but an excessive use of antibiotics and corticosteroids, which in many cases are contraindicated, has been described. The objective was to describe the prescription patterns of medications used to treat conjunctivitis in a Colombian population. METHODS: This was a cross-sectional study on the pharmacological treatment of patients diagnosed with conjunctivitis between April 1, 2020, and March 31, 2021; based on a drug-dispensing database of approximately 8.5 million people affiliated with the Colombian Health System. Some sociodemographic and pharmacological variables and comorbidities were considered. A descriptive analysis was performed. RESULTS: A total of 8708 patients were identified; they had a median age of 44.7 years, and 59.3% were women. The most common causes of conjunctivitis were unspecified (53.1%) and allergic (37.4%). The most commonly used drug was olopatadine (26.1%), followed by dexamethasone with neomycin and polymyxin B (25.0%). A total of 97.0% of the patients received ophthalmic prescriptions, while 12.8% received systemic medications. Glucocorticoids (40.3%), antibiotics (37.7%) and antihistamines (31.7%) were the most commonly used groups of ophthalmic drugs. Glucocorticoids and ophthalmic antibiotics were the medications most frequently prescribed by general practitioners for the treatment of viral or bacterial conjunctivitis. CONCLUSIONS: Many patients with conjunctivitis are not being managed according to the recommendations of clinical practice guidelines, which highlights that the widespread use of antibiotics with ophthalmic glucocorticoids could be considered potentially inappropriate prescriptions in many cases.

[Modern possibilities of pathogenetically oriented therapy for dry eye syndrome]. / Sovremennye vozmozhnosti patogeneticheski orientirovannoi terapii sindroma «sukhogo glaza¼.

In recent years, anti-inflammatory therapy has become a significant part of the complex approach to treatment of patients with dry eye syndrome (DES), with cyclosporine preparations becoming increasingly important in the structure of the therapy. Taking into account the immunosuppressive effect of cyclosporine A, which is realized through hindering the activation of T-lymphocytes in the tissues of the ocular surface, its topical application in DES has a pronounced pathogenetic focus. Numerous clinical studies have shown that instillations of cyclosporine into the conjunctival cavity contribute to an increase in total tear production, as well as recovery of the density of goblet cells in the conjunctiva of DES patients. The positive effect of cyclosporine A instillations has been convincingly demonstrated in the complex therapy of patients with vernal and atopic corneal conjunctivitis, Thygeson's superficial punctate keratitis, autoimmune keratitis, meibomian gland dysfunction, etc. However, one significant problem associated with cyclosporine A instillations is the irritating effect of the drug. That prompted the development of a drug that is safe and tolerable during instillations into the conjunctival cavity - preservative-free 0.1% cyclosporine A labelled Ikervis (Santen, Japan). The drug carrier is artificial tear Cationorm (Santen), which has an advantage of stabilizing the tear film and protecting the ocular surface from the irritating effect of cyclosporine. According to numerous clinical studies, Ikervis instillations can improve the effectiveness of complex therapy in patients with DES (especially secondary to Sjögren syndrome, Stevens-Johnson syndrome, graft-versus-host disease), with allergic diseases of the cornea and conjunctiva (spring, atopic corneal conjunctivitis), with corneal transplant disease, and other similar conditions. The high efficacy and safety of Ikervis constitute the reason to recommend it for wide clinical use.

Efficacy of N-acetyl aspartyl glutamic acid versus fluorometholone for treating allergic conjunctivitis in an environmental exposure chamber.

BACKGROUND: Topical mast cell stabilizers were previously shown to treat the signs and symptoms of seasonal and perennial allergic conjunctivitis safely and effectively in active and placebo-controlled trials. However, mast cell stabilizers have not been compared to topical corticosteroids for efficacy. We tested the non-inferiority of a topical mast cell stabilizer, N-acetyl aspartyl glutamic acid (4.9%, NAAGA), compared to fluorometholone (0.1%, FM) during controlled exposures to the airborne birch pollen allergen, Bet v 1, in an environmental exposure chamber (EEC). METHODS: This randomized, cross-over, investigator-blinded study included 24 patients with a history of birch pollen allergic conjunctivitis. Patients were randomized to 5 days of treatment with NAAGA, then FM (n = 12) or FM, then NAAGA (n = 12). After each treatment, patients were exposed to a fixed airborne concentration of Bet v 1 in ALYATEC EEC. The primary endpoint was the amount of allergen required to trigger a conjunctival response (Abelson score ≥5). Groups were compared with a linear model for cross-over studies. Non-inferiority was assumed, when the lower bound of the risk ratio confidence interval (CI) was >0.5. RESULTS: At screening, the mean time-to-conjunctival response was 72.5 ± 35.9 min. NAAGA and FM extended the response time to 114.8 ± 55.0 and 116.6 ± 51.5 min respectively. The mean amounts of allergen required to trigger a conjunctival response were 1.165 ng after NAAGA and 1.193 ng after FM treatment. The risk ratio for the conjunctival response was 0.977 (95% CI: 0.812; 1.174), which indicated non-inferiority. Adverse events occurred less frequently with NAAGA (29.2%) than with FM (58.3%). CONCLUSION: In patients with allergic conjunctivitis to birch pollen, NAAGA was non-inferior to FM in exposures to airborne Bet v 1. The EEC was a good model for simulating real-life airborne allergen exposure and for demonstrating the efficacy and safety of eye drops for treating allergic conjunctivitis. TRIAL REGISTRATION: Not registered.

A comparative study between ciclosporine A eye drop (2%) and tacrolimus eye ointment (0.03%) in management of children with refractory vernal keratoconjunctivitis.

PURPOSE: To compare the effects of ciclosporine A (2%) eye drop and tacrolimus (0.03%) eye ointment on children with vernal keratoconjunctivitis (VKC) who were not responding to corticosteroid eye drops. METHODS: A prospective comparative study was carried out on children who were diagnosed with refractory VKC at the ophthalmology clinic in Benha University, Delta area, Egypt, during the period from October 2019 to February 2020. RESULTS: Fifty-nine patients completed this study. Regarding the individual symptom score, redness, burning, photophobia, and foreign body sensation were significantly reduced in the tacrolimus group compared to those in the ciclosporine A group during the 1st week (p < 0.05). Moreover, the tacrolimus group showed a statistically significant reduction in burning and foreign body sensation at the 4th week (both p = 0.032), and in redness and burning sensation at the 12th week compared to those in the ciclosporine A group (p = 0.005 and 0.048, respectively). The tacrolimus group showed significantly lower mean scores for tarsal conjunctival papillary hypertrophy at the 1st week and 12th week (p = 0.037 and 0.046, respectively), and for punctate erosion and cobblestone papillae at the 1st week (p = 0.029 and 0.037, respectively) than the ciclosporine group. Failure of treatment was observed in 6 patients (19.35%) in the ciclosporine A group and in 5 patients (17.85%) in the tacrolimus group. No serious side effects were detected in any group. CONCLUSION: A higher reduction in inflammatory symptoms and signs as well as compliance with tacrolimus 0.03% eye ointment than with ciclosporine A 2% eye drops was observed. Moreover, long-term medication for refractory cases is needed to control inflammation. Overall, our finding suggested that ciclosporine A eye drops and tacrolimus eye ointment could be considered as corticosteroid-sparing drugs in the management of children with refractory VKC.

Treating refractory corneal hydrops in a male patient with vernal keratoconjunctivitis and mental retardation: a case report.

BACKGROUND: Keratoconus is the most common noninflammatory bilateral corneal ectasia. Vernal keratoconjunctivitis (VKC) and eye rubbing may be associated with keratoconus in children and young adults. Timely management of advanced keratoconus is important to improve visual quality. In addition, it is challenging to carry out VKC treatment with an intent to avoid the occurrence of punctate epithelial keratitis, ulceration, or corneal neovascularization on corneal grafts. CASE PRESENTATION: We report the case of an 18-year-old male patient with a long-term history of mental retardation due to megalencephaly presenting with acute onset of corneal hydrops with prominent bulging and refractory steroid-induced glaucoma of the right eye. The topography of the right eye was unavailable due to advanced ectasia, and that of the left eye revealed central steepening with inferior-superior dioptric asymmetry. According to the clinical findings, the patient was diagnosed with keratoconus. Because of progressive corneal opacity and neovascularization, the patient underwent penetrating keratoplasty (PK) with combination of interrupted and intrastromal running suturing after receiving a preoperative subconjunctival injection of bevacizumab in his right eye, followed by lower eyelid correction. After surgery, the patient was treated with 0.1% tacrolimus dermatological ointment, 0.1% cyclosporine eye drops, artificial tears, and 0.5% loteprednol for keratoplasty and VKC. Repeated education on avoiding eye rubbing was offered to the patient. Two years after PK treatment, his best-corrected visual acuity of the right eye successfully improved from hand motion at 10 cm preoperatively to 6/20 postoperatively. CONCLUSIONS: Large-diameter PK with intrastromal suturing technique for advanced keratoconus could achieve better visual outcomes and avoid suture-related complications. In addition, tacrolimus dermatological ointment rather than tacrolimus topical eye drops or ointment showed satisfactory efficacy when combined with topical cyclosporine and steroid that no significant VKC reactivation were noted after PK.

Allergic Conjunctivitis: An Update.

Conjunctivitis is a frequent disease of the eye with the typical clinical sign being the "red eye" and comprises a very heterogeneous group with different causes. In general, infectious conjunctivitis must be strictly differentiated from non-infectious conjunctivitis. Allergic conjunctivitis is a subtype of non-infectious conjunctivitis and imposes as an acute, intermittent or chronic, inflammation which is most frequently caused by airborne allergens. The leading clinical sign is chemosis, and patients typically complain about itching. Allergic conjunctivitis is often a reaction to topical and systemic drugs or cosmetics as well as animal hairs from cats and/or dogs. Allergic conjunctivitis is sub-classified into the following forms: seasonal allergic conjunctivitis (also termed: hay fever conjunctivitis), atopic conjunctivitis, vernal conjunctivitis, upper limbal (kerato-) conjunctivitis, and conjunctivitis associated with various oculomucocutaneous syndromes. In each form, there are distinctive features in: clinical appearance, generating agent(s), as well as treatment as listed here.

Glucocorticoid receptor modulators CpdX and CpdX-D3 exhibit the same in vivo antiinflammatory activities as synthetic glucocorticoids.

We previously reported that the nonsteroidal compound CpdX, which was initially characterized 20 y ago as a possible gestagen and, shortly afterward, as a possible drug for treatments of inflammatory diseases, selectively triggers the NFκB/AP1-mediated tethered indirect transrepression function of the glucocorticoid receptor (GR), and could therefore be a selective glucocorticoid receptor agonistic modulator (SEGRAM). We now demonstrate that, upon administration to the mouse, CpdX and one of its deuterated derivatives, CpdX-D3, repress as efficiently as a synthetic glucocorticoid (e.g., Dexamethasone) an induced skin atopic dermatitis, an induced psoriasis-like inflammation, a house dust mite (HDM)-induced asthma-like allergic lung inflammation, a collagen-induced arthritis, an induced ulcerative colitis, and an ovalbumin-induced allergic conjunctivitis. Interestingly, in the cases of an HDM-induced asthma-like allergic lung inflammation and of a collagen-induced arthritis, the CpdX antiinflammatory activity was selectively exerted by one of the two CpdX enantiomers, namely, CpdX(eA) or CpdX-D3(eA).

Efficacy of medical treatments for vernal keratoconjunctivitis: A systematic review and meta-analysis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a severe type of allergic conjunctivitis for which treatment strategies are still under debate. OBJECTIVES: This study sought to conduct a systematic review and meta-analysis to evaluate the efficacy of medical treatments for VKC. METHODS: The PubMed, Cochrane Library, Embase, and ScienceDirect databases were searched to assess the efficacy of treatments for VKC. Random-effect meta-analyses on changes in clinical scores of symptoms and signs between baseline and after treatment, stratified on treatment classes, were computed. Meta-regressions were searched for potential influencing parameters. RESULTS: Included were 45 studies (27 randomized controlled trials and 18 prospective cohort studies), 1749 patients (78% were men; mean age, 11.2 years), and 12 different treatment classes. Mast cell stabilizers (MCSs; usually considered as first-line therapy), cyclosporine, and tacrolimus were the most studied drugs (in three-quarters of studies). Overall, all clinical scores improved. Total symptom and sign score decreased for MCSs (effect size, -3.19; 95% CI, -4.26 to -2.13), cyclosporine (effect size, -2.06; 95% CI, -2.72 to -1.40), and tacrolimus (effect size, -2.39; 95% CI, -3.36 to -1.43). No significant differences were shown depending on treatment classes, concentration, age, sex, baseline activity scores, and atopy. Sensitivity analyses demonstrated similar results. CONCLUSIONS: This study confirms the efficacy of MCSs in the treatment of VKC. Efficacy of cyclosporine and tacrolimus did not differ, suggesting that tacrolimus is a good alternative to cyclosporine for severe cases of VKC. Further studies are needed to compare other drugs and their precise place in treatment strategy.

Effects of rAmb a 1-Loaded PLGA-PEG Nanoparticles in a Murine Model of Allergic Conjunctivitis.

Ambrosia artemisiifolia (Amb a) contains many allergens. Allergic conjunctivitis caused by Ambrosia artemisiifolia and its related allergen-specific immunotherapy (AIT) are seldom studied at present. poly(DL-lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) is a very good nano-carrier, which has been applied in the medical field. In this context, we studied the immunotherapy effect and potential mechanism of recombinant Amb a 1 (rAmb a 1)-loaded PLGA-PEG nanoparticles. A mouse allergic conjunctivitis model was established with Ambrosia artemisiifolia crude extract, and the nanoparticles were used for AIT through direct observation of conjunctival tissue, degranulation of mast cells in conjunctival tissue, serum-specific antibodies, cytokines and other assessment models. The treatment of nanoparticles enhanced the secretion of T-helper 1 (Th1) cytokine Interferon-gama (IFN-γ) and the production of immunoglobulin G (IgG)2a (IgG2a), inhibited the secretion of T-helper 2 (Th2) cytokine Interleukin (IL)-13 and IL-4 and the level of IgE. Especially, degranulation of mast cells and expression of mast cell protease-1 (MCP-1) in conjunctival tissue was reduced significantly. In this study, we proved that the nanoparticles prepared by rAmb a 1 and PLGA-PEG have an immunotherapy effect on allergic conjunctivitis in mice.

Clinical characteristics and outcomes of ocular allergy in Thai children.

BACKGROUND: Allergic conjunctivitis (AC) is the most common ocular condition in allergic children. In tropical countries, the study about the clinical features and outcome of treatment is very limited. OBJECTIVE: To review clinical characteristics and outcomes of treatment in children with ocular allergy. METHODS: Children with history of AC were classified to seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). The clinical history and outcome of treatment were recorded. RESULTS: One hundred and sixty-four children were recruited. PAC was the most common type (61.6%), followed by SAC (21.3%), VKC (12.2%), and AKC (4.9%). Male preponderance was found in all groups. Mean age of onset was 6.8 ± 2.8 years. Allergic rhinitis was the most common co-morbidity (97.6%). The common sensitized allergen is house-dust mites (86.1%). Standard treatments in all groups were natural tear and topical olopatadine. Add-on medications were usually needed in severe types of AC (VKC, AKC). History of topical corticosteroid use was 68.8% and 12.5% in VKC and AKC, respectively. All of them can discontinue topical corticosteroid when topical tacrolimus was applied. The overall remission was found 35% in VKC group and 63% in AKC group. The median duration of treatment was 20.5 months in VKC group and 11 months in AKC group. CONCLUSIONS: most Thai children with AC sensitized to house-dust mites. In severe forms of AC, most patients needed addon medication. The use of topical calcineurin inhibitor as an add-on therapy can decrease the use of topical corticosteroid.

Treating Severe Pediatric Keratoconjunctivitis with Topical Cyclosporine A. / Behandlung der chronischen Keratokonjunktivitis im Kindesalter mit topischem Ciclosporin A.

The incidence of chronic keratoconjunctivitis, which potentially causes long-term loss of visual acuity due to corneal opacity, is considerably less common in children than in adults. It is therefore in danger of being overlooked. In children the appropriate treatment is therefore often introduced too late, or to an insufficient extent. In this article we would like to raise awareness about the diagnosis of chronic keratoconjunctivitis in children, and to present an effective treatment plan for severe stages of the disease. There are two forms of chronic keratoconjunctivitis that occur most frequently in children: hyperergic blepharokeratoconjunctivitis (hBKC) and vernal keratoconjunctivitis (VKC). With hBKC, the patient often has a history of recurring hordeolum and also presents with blepharitis; it is characterized by the marked presence of corneal neovascularization in the lower circumference of the cornea. VKC is typically characterized by changes under the upper eyelid, with marked changes to the superior limbus. If there is a risk of complications involving the cornea, or in the presence of such complications, a consistent long-term topical immunosuppressive and anti-inflammatory treatment is required. Both of these properties are combined in the active ingredient cyclosporine A. Other advantages of topical CSA treatment are its steroid-sparing effect and the long-term reduction of exacerbations. Parents need to be informed about the chronic nature of these two diseases and their tendency to recur; because of these characteristics, treatment, in most cases, should be envisaged for at least one year in order to effectively disrupt the complex immunologic processes. This safeguards the child's visual development and prevents amblyopia caused by scarring and astigmatism. We hope that the data presented will lower the barriers related to prescribing CSA for topical eye application in children.

Executive summary: Japanese guidelines for allergic conjunctival diseases 2021.

Allergic conjunctival disease (ACD) is an inflammatory disease of the conjunctiva that is mainly caused by type I hypersensitivity response to allergens and accompanied by subjective symptoms and other findings induced by antigens. ACD is classified as allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. This article summarizes the third edition of the Japanese guidelines for allergic conjunctival diseases published in 2021 and outlines the diagnosis, pathogenesis, and treatment of ACD. Since the introduction of immunosuppressive eye drops, the treatment strategies for severe ACDs have significantly changed. To clarify the recommended standard treatment protocols for ACD, the advantages and disadvantages of these treatments were assessed using clinical questions, with a focus on the use of steroids and immunosuppressive drugs. This knowledge will assist healthcare providers and patients in taking an active role in medical decision making.