Allergy and Clinical Immunology

Current market trends in anterior ocular inflammatory disease landscape Purpose of review In the US anterior ocular inflammatory disease (AOID) composed of the spectrum of ocular allergies, different forms of infectious conjunctivitis, and dry eye diseases, affects over 40% of the population. This review evaluates the current economic costs for AOID associated pharmacotherapies. Recent findings In recent years, with improved understanding in pathophysiology of the AOID, providing novel targets for pharmacotherapy, have led to considerable improvements in outcomes for patients. Despite these advances, there continues to be a need for interventions that inhibit key inflammatory mediators or pathways in the ophthalmic space. In 2018, AOID drugs market represents ∼40% of the costs for the total ophthalmic drugs: dry eye (43%), antiinfectives (15%), antiallergics (13%), and antiinflammatory agents (29%). With increasing treatment costs, the need for improved, cost-effective modalities persists along with treatment algorithms to derive optimal benefits for patients. Summary There has been a dramatic increase in the economic burden of AOID with the annual expenditure for the prescription drugs approaching close to $11 billion in 2018. With increasing prevalence of ocular disease, further investment is required to provide more effective treatment options and deliver improved public health and economic outcomes. Correspondence to Leonard Bielory, MD, 400 Mountain Avenue, Springfield, New Jersey 07081. E-mail: drlbielory@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Office-based ocular procedures for the allergist Purpose The aim of this study is to suggest principles for ocular procedures to be performed by allergists in their offices in helping their diagnosis of ocular diseases and suggest better interactions between allergists and ophthalmologists. Recent findings Diagnosis of ocular allergy is based on clinical history and signs and symptoms, with the support of in-vivo and in-vitro tests for the identification of the specific allergen. Unfortunately, ocular manifestations are frequently misdiagnosed and not properly managed. Summary A multidisciplinary allergist–ophthalmologist approach may improve early differential diagnosis and the prognosis of patients with allergic disease and conjunctivitis through shared management and earlier etiological treatment. Correspondence to Andrea Leonardi, MD, Department of Neuroscience, Ophthalmology Unit, University of Padua, via Giustiniani 2, 35128 Padua, Italy. Fax: +39 049 875 5168; e-mail: andrea.leonardi@unipd.it Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The roles of omega-3 fatty acids and resolvins in allergic conjunctivitis Purpose of review Lipids are one of the most important constituents in our body. Advances of lipidomics are elucidating the new roles of various lipid molecules in allergic diseases. For example, some reports showed anti-inflammatory effects of omega-3 fatty acids (FAs), such as docosahexaenoic acid, eicosapentaenoic acid, and their metabolites, on allergic diseases. Here, we introduce the role of lipid mediators in allergic conjunctivitis mouse model. Recent findings Lipidomics using liquid chromatography–tandem mass spectrometry can profile numerous lipid molecules from small tissue samples such as conjunctival specimens. Lipidomics analysis showed that various inflammatory lipid mediators are produced in the conjunctival tissue of allergic conjunctivitis mouse model. Dietary omega-3 FAs reduced these inflammatory lipid mediators in the conjunctiva and alleviated allergic conjunctivitis symptoms in mouse models. In addition, the roles of specialized proresolving lipid mediators (SPMs) have been reported for allergic inflammation. Summary Lipid mediators have important roles for the pathophysiology of the allergic diseases including allergic conjunctivitis. Omega-3 FAs and SPMs are expected as new treatment tools for allergic conjunctivitis. Correspondence to Akira Matsuda, Laboratory of Ocular Atopic Diseases, Department of Ophthalmology, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. Tel: +81 3 5802 1031; fax: +81 3 5802 5889; e-mail: akimatsu@juntendo.ac.jp Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Role of the ocular surface microbiome in allergic disease Purpose of review The purpose of this review is to provide an update regarding new and emerging data on the role of the ocular surface microbiome in allergic disease. Recent findings Recent findings support the role of the microbiome in the pathophysiology of allergic disease of the ocular surface. Summary Understanding the role of the ocular surface microbiome in allergic disease may provide a new target for the development of therapeutic interventions. Correspondence to Kara M. Cavuoto, MD, 900 NW 17th Street, Miami, FL 33136, USA. Tel.: +1 305 326 6324;. fax: +1 305 547 3675; e-mail: kcavuoto@med.miami.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Biologics and anaphylaxis Purpose of review The use of biologicals as therapeutic agents in oncology and other inflammatory diseases has dramatically increased during the last years. Due to their biological nature and inherent immunological activity, they are able to induce important adverse events, such as cytokine release reactions (rapid release of proinflammatory cytokines), serum sickness disease, and immediate or delayed hypersensitivity reactions, including anaphylaxis. The aim of the current article is to review the state of the art of anaphylaxis because of biological agents. Recent findings Different phenotypes, and potential underlying endotypes, have been described in anaphylactic reactions to biologicals. There seems to be a spectrum from type 1 reactions (IgE or non-IgE-mediated) to cytokine release reactions, with some reactions falling in between both. Management should be directed according to such phenotypes. Summary There is ongoing research to further define immediate adverse reactions to biologicals and to find relevant biomarkers to aid in their diagnosis. Such information will serve in defining their immediate and long term management. Correspondence to Victoria Cardona, MD, PhD, Allergy Section, Department of Internal medicine, Hospital Universitari Vall d'Hebron, Ps. Vall d'Hebron 119-129, 08035 Barcelona, Spain. Tel: +34 93 274 6169; e-mail: vcardona@vhebron.net Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Topical tacrolimus for allergic eye diseases Purpose of review The spectrum of allergic eye diseases includes a variety of conditions, each characterized by complex immunopathologies. Antiallergic drugs, such as antihistamines and mast cell stabilizers, are often insufficient without concomitant topical corticosteroid treatment. The chronic course of the more severe allergic eye diseases, such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC), limits the treatment with topical corticosteroids to short courses. In addition, topical corticosteroid treatment puts patients at high risk of developing severe ocular complications, particularly during childhood when VKC most frequently occurs. The immunopathology of chronic diseases, such as VKC and AKC, involves predominantly T lymphocytes, and as such, immunomodulators that inhibit T-cell activation seem to be the appropriate treatment for these chronic diseases. In the past years, there is an increased incidence of managing chronic allergic eye diseases with the immunomodulator tacrolimus. The current review presents an update of the recent clinical experience with topical tacrolimus for the management of chronic allergic eye diseases. Recent findings Topical tacrolimus significantly improves the symptoms and signs of the various forms of chronic allergic eye disease. Recent studies also demonstrate the efficacy of low concentrations of topical tacrolimus for VKC. Early medical treatment with topical tacrolimus can also prevent the development of serious ocular complications of VKC, such as shield ulcers or limbal stem cell deficiency. Summary Topical tacrolimus has significantly changed the management approaches in severe and chronic allergic eye diseases and has minimized the need for topical corticosteroids. Correspondence to Abraham Solomon, MD, Cornea & Refractive Surgery Service, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. Tel: +972 507874664; e-mail: dr.avi.solomon@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Neurotrophic factors and nerve growth factor in ocular allergy Purpose of review During allergic reaction, nervous and immune systems mutually interact through release of mediators, including neurotrophic factors and nerve growth factor (NGF). These mediators modulate allergic reaction through binding their receptors expressed by immune and structural cells and by stimulating neuropeptide release by nerves. The role of neuropeptides and NGF has been demonstrated in allergic asthma and rhinitis, and, to a lesser extent, in allergic conjunctivitis. The aim of this review are to elucidate the evidence of the role of NGF and neuropeptides in the pathogenesis of allergic conjunctivitis. Recent findings NGF modulates allergic reaction by stimulating release of cytokines, inflammatory mediators and neuropeptides by immune and structural cells and nerve endings at the site of inflammation. Evidence showed that local and systemic NGF levels increase in patients with allergic conjunctivitis, including allergic rhinoconjuncivitis, vernal keratoconjunctivitis and atopic keratoconjunctivitis. We recently described an increase of conjunctival p75NTR expression in patients with allergic rhinoconjuncivitis, and an increase of tear levels of NGF after conjunctival provocation test with allergen. Summary NGF modulates ocular allergic reaction. Increasing understanding of the role of neuropeptides in allergic conjunctivitis may pave the way to the development of novel therapeutic approaches and improvement of patients' management. Correspondence to Professor Alessandro Lambiase, Department of Sense Organs, University Sapienza of Rome, Vilae del Policlinico, 155, 00161 Rome, Italy. Tel: +39 064 997 5357; e-mail: alessandro.lambiase@uniroma1.it Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alexandros Sfakianakis
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