• Corticosteroid
• Cyclosporine
• Dupilumab
• Eosinophil
• Immune
• Inflammation
• Montelukast
• Omalizumab
• Tacrolimus
• Vernal keratoconjunctivitis

• Child
• Humans
• Conjunctivitis, Allergic/diagnosis
• Conjunctivitis, Allergic/drug therapy
• Conjunctivitis, Allergic/epidemiology
• Cyclosporine/therapeutic use
• Quality of Life
• Conjunctiva/pathology
• Ophthalmic Solutions/therapeutic use

• Allergy
• Biologics
• IgE
• Omalizumab
• Vernal keratoconjunctivitis

• AKC
• Allergy
• Conjunctivitis
• Cornea
• Eosinophil
• Mediators
• Treatment
• VKC

• benralizumab
• children
• dupilumab
• humanized monoclonal antibodies
• mepolizumab
• off-label
• omalizumab
• paediatrics
• reslizumab

• Antibodies, Monoclonal
• Child
• Drug Labeling
• Humans
• Off-Label Use
• Pediatrics
• Public Health

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.

• Adolescent
• Child
• Child, Preschool
• Conjunctivitis, Allergic/diagnosis
• Eye
• Humans
• Young Adult

A 14-year-old girl with poorly controlled asthma attended the difficult-to-treat asthma clinic for review. Although she has eosinophilia and significantly raised immunoglobulin E levels, she is not currently a candidate for omalizumab (Xolair). She also suffers from chronic urticaria, eosinophilic eosophagitis and severe conjunctivitis. You wonder if omalizumab would be effective in treating her multiple atopic conditions, in particular her troublesome conjunctivitis. PubMed was searched using the following search terms: (Omalizumab) or (Xolair) and (conjunctivitis). Searches were conducted in November 2020. Abstracts were selected for full text review if the study population identified asthma as a comorbidity. Non-paediatric studies and those that were not written in English were excluded. The use of omalizumab has the potential to be effective in the treatment of conjunctivitis associated with asthma and other atopic conditions. However, research is needed to address the question, in the form of multicenter, double-blind randomized control trials.

• Omalizumab
• Conjunctivitis
• Allergy
• Asthma
• Pediatrics
• Atopy

• clinicopathologic correlations
• immunobiologics
• immunomodulators
• pharmacotherapy
• vernal keratoconjunctivitis

• Conjunctival vasculature
• Conjunctivitis
• Hyperemia
• Microcirculation
• Ocular redness

• Humans
• Conjunctivitis, Allergic/drug therapy
• Omalizumab/therapeutic use
• Treatment Outcome

Vernal keratoconjunctivitis (VKC) is a persistent, severe allergic eye disease, mainly occurring in children, that can lead to severe ocular complications including visual loss. The underlying etiology and pathophysiology of VKC remain unclear. Common therapies include topical antihistamines and mast cell stabilizers that are effective in mild-to-moderate forms of VKC but are often ineffective in severe forms that require topical or systemic corticosteroids. Dependence on steroids is common with potential adverse effects both local, as increased intraocular pressure, glaucoma, infection and cataract, as well as systemic ones, as reduction in child growth velocity. Alternative therapies are immunosuppressive drugs, like cyclosporine A and tacrolimus, that usually are effective but may also cause adverse effects. A promising therapeutic option is omalizumab, a recombinant anti-IgE humanized monoclonal antibody, currently used as add-on therapy for moderate to severe uncontrolled allergic asthma and chronic spontaneous urticaria. Here, we report the short-time duration of effective relief of symptoms after the prolonged use of omalizumab in a patient affected by refractory VKC. However, in our case any apparent beneficial effect was short lasting, and we propose that the duration of the disease and the concomitant long-term use of steroids leads to iatrogenic damage; thus, the disease becomes refractory to anti-IgE treatment.

• Corneal ulcer
• Giant papillae
• IgE
• Omalizumab

Allergic eye disease is common, yet often overlooked in North America. In the U.S., up to 40% of the population is deemed to be affected and this number is growing. Symptoms and signs of ocular allergy can lead to decreased productivity and negatively impact quality of life (QoL). Various treatment options exist to achieve symptom control. For allergic conjunctivitis, ophthalmic agents include antihistamines, mast cell stabilizers, dual-activity agents, nonsteroidal anti-inflammatory drugs (NSAIDs), steroids and some off-label treatments. Immunotherapy is recommended as a therapeutic option. This review provides a summary of the forms of ocular allergies, with a focus on symptoms and signs, impact on QoL, physical examination, diagnosis and therapeutic options of allergic conjunctivitis. Through multidisciplinary collaborations, a simplified algorithm for the treatment of allergic conjunctivitis is proposed for Canadian clinical practice.

• Allergic conjunctivitis
• Allergic conjunctivitis diagnosis
• Allergic conjunctivitis treatment algorithm
• Allergic eye disease
• Interprofessional management
• Ocular allergy

• Allergic conjunctivitis
• Allergic inflammation
• Conjunctivitis
• Contact lenses
• Lubrication
• Non-pharmacological treatments
• Ocular allergy
• Ocular surface disease
• Ophthalmic decongestant
• Pharmacotherapy

• Adrenergic alpha-2 Receptor Agonists/therapeutic use
• Animals
• Anti-Allergic Agents/therapeutic use
• Brimonidine Tartrate/therapeutic use
• Conjunctivitis, Allergic/therapy
• Cryotherapy/methods
• Histamine Antagonists/therapeutic use
• Humans
• Ophthalmic Solutions

From its availability for clinical use nearly two decades ago for severe asthma, omalizumab has gained strong evidence of efficacy and safety in the treatment of severe asthma not controlled by standard-of-care therapy. It has been acknowledged by Global Initiative on Asthma guidelines as add-on therapy against severe uncontrolled asthma. Thanks to controlled trials supporting its efficacy, omalizumab has also been licensed for the treatment of chronic spontaneous urticaria. The optimal duration of treatment in either disease has not been established. Despite its high price, omalizumab appears to be cost-effective in severe uncontrolled asthma as well as in chronic urticaria. The literature suggests a wide range of applications for omalizumab in various disorders regardless of allergic or non-allergic pathophysiology.

• anti-IgE antibody
• chronic spontaneous urticaria
• cost-effectiveness
• efficacy
• omalizumab
• safety
• severe asthma

• Anti-Allergic Agents/therapeutic use
• Conjunctivitis, Allergic/drug therapy
• Conjunctivitis, Allergic/immunology
• Cyproheptadine/analogs & derivatives
• Cyproheptadine/therapeutic use
• Humans
• Immunoglobulin E/immunology
• Keratoconjunctivitis/drug therapy
• Keratoconjunctivitis/immunology
• Male
• Middle Aged
• Olopatadine Hydrochloride/therapeutic use
• Omalizumab/therapeutic use

Immunoglobulin E (IgE) plays a key role in the pathogenesis of many allergic diseases. Thus, IgE-mediated immunologic pathways are an attractive target for intervention in allergic diseases. Omalizumab is a recombinant humanized monoclonal antibody that binds IgE and has been used treat allergic asthma for over a decade. Currently, omalizumab is approved for the treatment of both allergic asthma and chronic spontaneous urticaria. Since IgE plays a critical role in other allergic diseases, anti-IgE therapy has been evaluated in other allergic diseases in small clinical trials and case reports. Omalizumab has demonstrated efficacy in treating allergic rhinitis, atopic dermatitis, physical urticarias, mast cell disorders, food allergy, and other allergic diseases. In addition, the use of omalizumab with conventional allergen immunotherapy improves both safety and effectiveness.

• allergy
• asthma
• immunotherapy
• omalizumab
• urticaria

Vernal keratoconjunctivis (VKC) is a severe form of pediatric ocular allergy, characterized by acute and chronic corneoconjunctival inflammation that may lead to visual sequelae. Although topical immunosuppressive drugs such as cyclosporine are usually effective, some severe forms may be refractory and require prolonged steroid therapy. Very few papers report the use of omalizumab in VKC in the literature. In the present study, we describe our clinical experience with omalizumab in severe VKC children.

We retrospectively reviewed the files of four boys treated with omalizumab because of severe VKC, defined as persistent corneal inflammation despite continuous topical 2% cyclosporine and steroid eye drops. We also performed a literature review.

Four boys, aged 7–13 years old, were treated. All children had asthma and one had severe lid eczema. Two patients had required intrapalpebral depot-steroid injections. Omalizumab was administered every 2 weeks by subcutaneous injections, at doses varying from 450 to 600 mg per injection. Three patients out of four responded to the treatment, with a decrease in global symptoms (median symptom rating decreasing from 89 to 29 on a 100-mm visual analog scale), frequency and in duration of the inflammatory flares, and also a decreased need for topical steroid. Their median clinical grade decreased from 4 to 3 (Bonini grading). However, the response was incomplete and they still had inflammatory corneoconjunctival flares despite continuous topical cyclosporine. On the other hand, asthma and lid eczema were completely controlled in these three patients. The fourth child did not respond to omalizumab and needed oral steroids for his VKC and his asthma. Noticeably, this latter patient did not have detectable sensitization to any allergen, contrary to the other cases. The treatment was stopped in this refractory case, but is still ongoing in all other cases, with a median duration of 33 months (range 16–42 months). In the literature (four cases), omalizumab may have a more complete efficacy in some cases, but the results are still variable.

Omalizumab is an interesting treatment in severe refractory forms of VKC, but its efficacy is incomplete in these very severe cases.

• Children
• Cyclosporine
• IgE
• Immunomodulation
• Severe allergy
• Steroids
• VKC

• ABPA
• Anti-IgE
• Atopic dermatitis
• Intrinsic asthma
• Off-label
• Omalizumab
• Xolair

Vernal keratoconjunctivitis (VKC) is a relatively rare, chronic form of ocular allergy that can potentially cause severe visual complications. Affecting mainly children and young adults, it is an IgE- and T cell-mediated disease, leading to a chronic inflammation in which eosinophil, lymphocyte and structural cell activation are involved. Treatment of VKC requires a multiple approach that includes conservative measures and pharmacologic treatment. Patients and parents should be made aware of the long duration of disease, its chronic evolution and possible complications. Treatment should be based on the duration and frequency of symptoms and the severity of corneal involvement. Mast cell stabilizers and antihistamines have been proven to be effective for the treatment of mild to moderate forms of VKC. In the most severe cases, topical steroids can be used as rescue medication to reduce conjunctival and corneal inflammation. Immunomodulators that have been investigated for VKC treatment include topical ocular preparations of cyclosporine A and tacrolimus. Topical cyclosporine A has been proven to be effective in the long-term treatment of VKC, significantly improving signs and symptoms without significant side effects.