{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:14:40Z","timestamp":1787962480277,"version":"build-2784847793"},"reference-count":215,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T00:00:00Z","timestamp":1625788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Vernal keratoconjunctivitis (VKC) is a complex and chronic, multifactorial Th2 cell-mediated chronic ocular surface inflammatory condition that typically affects predominantly male children in hot or warm climates. The primary symptom is intense ocular pruritus, often significant enough to affect activities of daily living. Clinical features differ from simple forms of allergic conjunctivitis in that they are more-or-less confined to the superior tarsus and limbus. There is also a risk of corneal involvement, which leads to irreversible vision loss in approximately 6% of patients. Right now, there is no standardized treatment protocol, and many of the currently available options are not effective in severe and recurrent cases. As such, it is imperative to understand this complex allergic immune response in order to identify future therapeutic targets. This review will focus on potential drug targets in VKC, with particular emphasis on immunomodulators and immunobiologic agents.<\/jats:p>","DOI":"10.3390\/ph14070658","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T10:50:38Z","timestamp":1625827838000},"page":"658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Immunopharmacology in Vernal Keratoconjunctivitis: Current and Future Perspectives"],"prefix":"10.3390","volume":"14","author":[{"given":"DeGaulle I.","family":"Chigbu","sequence":"first","affiliation":[{"name":"Pennsylvania College of Optometry at Salus University, 8360 Old York Road, Elkins Park, PA 19027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bisant A.","family":"Labib","sequence":"additional","affiliation":[{"name":"Pennsylvania College of Optometry at Salus University, 8360 Old York Road, Elkins Park, PA 19027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1001\/archopht.119.10.1505","article-title":"Gelatinase B in vernal keratoconjunctivitis","volume":"119","author":"Missotten","year":"2001","journal-title":"Arch. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/j.1600-0420.2005.00622.x","article-title":"Case series of 406 vernal keratoconjunctivitis patients: A demographic and epidemiological study","volume":"84","author":"Leonardi","year":"2006","journal-title":"Acta Ophthalmol. Scand."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/j.1398-9995.2008.01858.x","article-title":"Cytokines, matrix metalloproteases, angiogenic and growth factors in tears of normal subjects and vernal keratoconjunctivitis patients","volume":"64","author":"Leonardi","year":"2009","journal-title":"Allergy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1648","DOI":"10.1097\/MD.0000000000001648","article-title":"Dry Eye in Vernal Keratoconjunctivitis: A Cross-Sectional Comparative Study","volume":"94","author":"Villani","year":"2015","journal-title":"Medicine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s40123-013-0019-y","article-title":"Management of Vernal Keratoconjunctivitis","volume":"2","author":"Leonardi","year":"2013","journal-title":"Ophthalmol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/pai.12231","article-title":"Immunogenetic investigation in vernal keratoconjunctivitis","volume":"25","author":"Zicari","year":"2014","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1080\/09286580802573177","article-title":"Prospective, Multicenter Demographic and Epidemiological Study on Vernal Keratoconjunctivitis: A Glimpse of Ocular Surface in Italian Population","volume":"16","author":"Lambiase","year":"2009","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1097\/00006324-199107000-00010","article-title":"Treatment of Vernal Keratoconjunctivitis: A Retrospective Clinical Case Study","volume":"68","author":"Coutu","year":"1991","journal-title":"Optom. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.clae.2010.09.002","article-title":"Ocular surface disease: A case of vernal keratoconjunctivitis","volume":"34","author":"Chigbu","year":"2011","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/00004397-200343010-00007","article-title":"Vernal Keratoconjunctivitis","volume":"43","author":"Leonardi","year":"2003","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0161-6420(98)98034-4","article-title":"Limbal vernal keratoconjunctivitis in the tropics","volume":"105","author":"Tuft","year":"1998","journal-title":"Ophthalmology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Feizi, S., Javadi, M.A., Alemzadeh-Ansari, M., Arabi, A., Shahraki, T., and Kheirkhah, A. (2020). Management of corneal complications in vernal keratoconjunctivitis: A review. Ocul. Surf.","DOI":"10.1016\/j.jtos.2020.10.005"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/S0161-6420(00)00092-0","article-title":"Vernal keratoconjunctivitis revisited: A case series of 195 patients with long-term followup","volume":"107","author":"Bonini","year":"2000","journal-title":"Ophthalmology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/sj.eye.6700675","article-title":"Vernal keratoconjunctivitis","volume":"18","author":"Bonini","year":"2004","journal-title":"Eye"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00417-007-0682-6","article-title":"Preliminary evidence of the efficacy of probiotic eye-drop treatment in patients with vernal keratoconjunctivitis","volume":"246","author":"Iovieno","year":"2008","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.clae.2009.08.002","article-title":"The management of allergic eye diseases in primary eye care","volume":"32","author":"Chigbu","year":"2009","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1755-3768.2008.01347.x","article-title":"Vernal keratoconjunctivitis: A major review","volume":"87","author":"Kumar","year":"2009","journal-title":"Acta Ophthalmol."},{"key":"ref_18","first-page":"242","article-title":"Vernal Keratoconjunctivitis in Nigerians: 109 Consecutive Cases","volume":"33","author":"Ukponmwan","year":"2003","journal-title":"Trop. Dr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"486","DOI":"10.4103\/0301-4738.119431","article-title":"Demographic and clinical profile of vernal keratoconjunctivitis at a tertiary eye care center in India","volume":"61","author":"Saboo","year":"2013","journal-title":"Indian J. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1097\/ACI.0000000000000204","article-title":"Epidemiology of allergic conjunctivitis: Clinical appearance and treatment patterns in a population-based study","volume":"15","author":"Leonardi","year":"2015","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_21","first-page":"157","article-title":"Limbal vernal kerato-conjunctivitis in Yaounde, Cameroon. A clinico-immunology study","volume":"68","author":"McMoli","year":"1991","journal-title":"Rev. Int. Trach. Pathol. Ocul. Trop. Subtrop. Sante Publique"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1076\/0928-6586(200006)721-ZFT149","article-title":"A survey of vernal keratoconjunctivitis and other eosinophil-mediated external eye diseases amongst Palestinians","volume":"7","year":"2000","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/02770909709071200","article-title":"Prevalence of Allergic Diseases and Influencing Factors in Primary-School Children in the Ankara Region of Turkey","volume":"34","author":"Saraclar","year":"1997","journal-title":"J. Asthma"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1824-7288-39-18","article-title":"Allergic conjunctivitis: A comprehensive review of the literature","volume":"39","author":"Lionetti","year":"2013","journal-title":"Ital. J. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1136\/bjo.2007.117812","article-title":"Prevalence of vernal keratoconjunctivitis: A rare disease?","volume":"92","author":"Donadieu","year":"2008","journal-title":"Br. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/pai.12197","article-title":"Vernal keratoconjunctivitis: A severe allergic eye disease with remodeling changes","volume":"25","author":"Vichyanond","year":"2014","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13052-019-0656-4","article-title":"Vernal Keratoconjunctivitis: An update focused on clinical grading system","volume":"45","author":"Zicari","year":"2019","journal-title":"Ital. J. Pediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.ajo.2012.11.018","article-title":"Vernal Keratoconjunctivitis-like Disease in Adults","volume":"155","author":"Leonardi","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.survophthal.2018.12.001","article-title":"Vernal Keratoconjunctivitis","volume":"64","author":"Singhal","year":"2019","journal-title":"Surv. Ophthalmol."},{"key":"ref_30","first-page":"66","article-title":"The Clinical Picture of Vernal Kerato-Conjunctivitis in Uganda","volume":"14","author":"Kawuma","year":"2001","journal-title":"Community Eye Health"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1016\/j.ophtha.2012.03.041","article-title":"Vernal Keratoconjunctivitis in School Children in Rwanda: Clinical Presentation, Impact on School Attendance, and Access to Medical Care","volume":"119","author":"Nkurikiye","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4314\/wajm.v22i1.27971","article-title":"Prevalence of atopic diseases in Nigerian children with vernal kerato-conjunctivitis","volume":"22","author":"Ajaiyeoba","year":"2004","journal-title":"West Afr. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hayilu, D., Legesse, K., Lakachew, N., and Asferaw, M. (2016). Prevalence and associated factors of vernal keratoconjunctivitis among children in Gondar city, Northwest Ethiopia. BMC Ophthalmol., 16.","DOI":"10.1186\/s12886-016-0345-7"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Thanathanee, O., Bhoomibunchoo, C., and Suwan-Apichon, O. (2014). Treatment of asymmetrical vernal keratoconjunctivitis with supratarsal corticosteroid injection. BMJ Case Rep., 2014.","DOI":"10.1136\/bcr-2014-206401"},{"key":"ref_35","first-page":"9","article-title":"Vernal keratoconjunctivitis: An update","volume":"97","author":"Wildner","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.ajo.2007.06.028","article-title":"Development and Testing of the Quality of Life in Children with Vernal Keratoconjunctivitis Questionnaire","volume":"144","author":"Sacchetti","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ophtha.2018.12.027","article-title":"A Randomized, Controlled Trial of Cyclosporine A Cationic Emulsion in Pediatric Vernal Keratoconjunctivitis: The VEKTIS Study","volume":"126","author":"Leonardi","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.sjopt.2011.02.001","article-title":"Ocular complications of severe vernal keratoconjunctivitis (VKC) in Yemen","volume":"25","author":"Bamashmus","year":"2011","journal-title":"Saudi J. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Alemayehu, A.M., Yibekal, B.T., and Fekadu, S.A. (2019). Prevalence of vernal keratoconjunctivitis and its associated factors among children in Gambella town, southwest Ethiopia, June 2018. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215528"},{"key":"ref_40","first-page":"443","article-title":"Intracellular IL-4, IL-5, and IFN-gamma as the main characteristic of CD4+CD30+ T cells after allergen stimulation in patients with vernal keratoconjunctivitis","volume":"21","author":"Aguilar","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_41","first-page":"1515","article-title":"Anti-allergic effects of mapracorat, a novel selective glucocorticoid receptor agonist, in human conjuncti-val fibroblasts and epithelial cells","volume":"19","author":"Cavet","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1097\/ACI.0000000000000202","article-title":"Corneal complications of vernal keratoconjunctivitis","volume":"15","author":"Solomon","year":"2015","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1007\/s11882-003-0098-2","article-title":"Epithelial cells in ocular allergy","volume":"3","author":"Bozkurt","year":"2003","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/cea.12264","article-title":"An essential role for dendritic cells in vernal keratoconjunctivitis: Analysis by laser scanning confocal microscopy","volume":"44","author":"Liu","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.exer.2004.11.006","article-title":"TGF-beta1, IL-1beta, and Th2 cytokines stimulate vascular endothelial growth factor production from conjunctival fibroblasts","volume":"80","author":"Fukagawa","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1046\/j.1365-2222.2000.00699.x","article-title":"Tear levels of interferon-gamma, interleukin (IL)-2, IL-4 and IL-5 in patients with vernal keratoconjunctivi-tis, atopic keratoconjunctivitis and allergic conjunctivitis","volume":"30","author":"Uchio","year":"2000","journal-title":"Clin. Exp. Allergy"},{"key":"ref_47","unstructured":"Chigbu, D.I. (2013). Immunology Relevant to Allergic Ocular Surface Diseases. Allergic Disorders of the Ocular Surface, Nova Science Publishers, Inc."},{"key":"ref_48","unstructured":"Murphy, K.P., Travers, P., and Walport, M. (2012). The Induced Response of Innate Immunity. Janeway\u2019s Immunobiology, Garland Science."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/00004397-200343010-00008","article-title":"Clinical and Immunological Features of Atopic Keratoconjunctivitis","volume":"43","author":"Zhan","year":"2003","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chigbu, D.I., Jain, P., and Khan, Z.K. (2020). Immune Mechanisms, Pathology, and Management of Allergic Ocular Diseases. Advanced Concepts in Human Immunology: Prospects for Disease Control, Springer.","DOI":"10.1007\/978-3-030-33946-3_4"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"76","DOI":"10.33590\/emj\/10312711","article-title":"Immunopathology of allergic conjunctivitis","volume":"3","author":"Chigbu","year":"2018","journal-title":"Eur. Med. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.preteyeres.2005.09.002","article-title":"Role of structural cells of the cornea and conjunctiva in the pathogenesis of vernal keratoconjunctivitis","volume":"25","author":"Kumagai","year":"2006","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_53","first-page":"862","article-title":"Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease","volume":"16","author":"Castellanos","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_54","first-page":"1","article-title":"Eosinophil recruitment is dynamically regulated by interplay among lung dendritic cell subsets after allergen challenge","volume":"24","author":"Yi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_55","unstructured":"Parham, P. (2015). IgE-Mediated Immunity and Allergy. The Immune System, Garland Science."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1365-2222.2007.02886.x","article-title":"The mast cell and allergic diseases: Role in pathogenesis and implications for therapy","volume":"38","author":"Brown","year":"2007","journal-title":"Clin. Exp. Allergy"},{"key":"ref_57","unstructured":"Murphy, K.P., Travers, P., and Walport, M. (2012). Allergy and Allergic Diseases. Janeway\u2019s Immunobiology, Garland Science."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S66","DOI":"10.1097\/01.ico.0000178733.42921.4c","article-title":"Prostaglandin D2 Induces Chemotaxis in Eosinophils via Its Receptor CRTH2 and Eosinophils May Cause Severe Ocular Inflammation in Patients with Allergic Conjunctivitis","volume":"24","author":"Fujishima","year":"2005","journal-title":"Cornea"},{"key":"ref_59","first-page":"114","article-title":"Direct action of platelet activating factor (PAF) induces eosinophil accumulation and enhances expression of PAF receptors in conjunctivitis","volume":"11","author":"Zinchuk","year":"2005","journal-title":"Mol. Vis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S1359-6101(03)00049-2","article-title":"The CC chemokine CCL20 and its receptor CCR6","volume":"14","author":"Schutyser","year":"2003","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.4049\/jimmunol.174.7.4070","article-title":"The Chemokine Receptor CCR7 Activates in Dendritic Cells Two Signaling Modules That Independently Regulate Chemotaxis and Migratory Speed","volume":"174","author":"Torres","year":"2005","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nri2297","article-title":"CCR7 and its ligands: Balancing immunity and tolerance","volume":"8","author":"Rot","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1167\/iovs.09-4122","article-title":"TSLP and Downstream Molecules in Experimental Mouse Allergic Conjunctivitis","volume":"51","author":"Zheng","year":"2010","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2332\/allergolint.11-RAI-0395","article-title":"TSLP Expression: Cellular Sources, Triggers, and Regulatory Mechanisms","volume":"61","author":"Takai","year":"2012","journal-title":"Allergol. Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1006\/exer.1999.0658","article-title":"Histamine Effects on Conjunctival Fibroblasts from Patients with Vernal Conjunctivitis","volume":"68","author":"Leonardi","year":"1999","journal-title":"Exp. Eye Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0014-4835(02)00248-8","article-title":"IL-4-induced cell proliferation and production of extracellular matrix proteins in human conjunctival fibroblasts","volume":"76","author":"Fujitsu","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1167\/iovs.02-0420","article-title":"Effects of Th2 Cytokines on Expression of Collagen, MMP-1, and TIMP-1 in Conjunctival Fibroblasts","volume":"44","author":"Leonardi","year":"2003","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2332\/allergolint.55.121","article-title":"Fibroblasts as Local Immune Modulators in Ocular Allergic Disease","volume":"55","author":"Fukuda","year":"2006","journal-title":"Allergol. Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4049\/jimmunol.166.1.103","article-title":"C-C Chemokine Receptor 4 Expression Defines a Major Subset of Circulating Nonintestinal Memory T Cells of Both Th1 and Th2 Potential","volume":"166","author":"Andrew","year":"2001","journal-title":"J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/978-1-0716-1095-4_17","article-title":"Eosinophil Shape Change and Secretion","volume":"2241","author":"Ochkur","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1177\/112067210301300702","article-title":"Tumor necrosis factor-alpha (TNF-\u03b1) in seasonal allergic conjunctivitis and vernal keratoconjunctivitis","volume":"13","author":"Leonardi","year":"2003","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1136\/bjo.81.12.1099","article-title":"Adhesion molecules in vernal keratoconjunctivitis","volume":"81","author":"Geboes","year":"1997","journal-title":"Br. J. Ophthalmol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1007\/s00417-014-2785-1","article-title":"CCL20\/MIP-3 alpha mRNA expression in the conjunctival epithelium of normal indi-viduals and patients with vernal keratoconjunctivitis","volume":"252","author":"Inada","year":"2014","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/icb.2009.115","article-title":"Eosinophils and Th2 immunity: Contemporary insights","volume":"88","author":"Spencer","year":"2010","journal-title":"Immunol. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.clae.2008.07.003","article-title":"The pathophysiology of ocular allergy: A review","volume":"32","author":"Chigbu","year":"2009","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1067\/mai.2002.126379","article-title":"Active matrix metalloproteinases in the tear fluid of individuals with vernal keratoconjunctivitis","volume":"110","author":"Kumagai","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/00003226-199111000-00011","article-title":"Detection by Brush Cytology of Mast Cells and Eosinophils in Allergic and Vernal Conjunctivitis","volume":"10","author":"Tsubota","year":"1991","journal-title":"Cornea"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/iid3.278","article-title":"Role of ocular cytology in vernal keratoconjunctivitis","volume":"8","author":"Bruschi","year":"2020","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S1350-9462(02)00006-X","article-title":"Vernal keratoconjunctivitis: Pathogenesis and treatment","volume":"21","author":"Leonardi","year":"2002","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"481","DOI":"10.4103\/2008-322X.176904","article-title":"Allergic Conjunctival Granuloma Presenting the Splendore-Hoeppli Phenomenon; Report of Two Cases and Review of Literature","volume":"10","author":"Shahriari","year":"2015","journal-title":"J. Ophthalmic Vis. Res."},{"key":"ref_81","unstructured":"Chigbu, D.I. (2013). Vernal Keratoconjunctivitis. Allergic Disorders of the Ocular Surface, Nova Science Publishers, Inc."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1111\/all.12009","article-title":"Ocular allergy: Recognizing and diagnosing hypersensitivity disorders of the ocular surface","volume":"67","author":"Leonardi","year":"2012","journal-title":"Allergy"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3928\/0191-3913-19970701-20","article-title":"Amblyopia resulting from shield ulcers and plaques of the cornea in vernal keratoconjunc-tivitis","volume":"34","author":"Cameron","year":"1997","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/S0161-6420(95)30925-6","article-title":"Shield ulcers and plaques of the cornea in vernal keratoconjunctivitis","volume":"102","author":"Cameron","year":"1995","journal-title":"Ophthalmology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/00003226-200301000-00020","article-title":"Fungal Keratitis Associated with Vernal Keratoconjunctivitis","volume":"22","author":"Sridhar","year":"2003","journal-title":"Cornea"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1067\/mai.2000.111238","article-title":"Allergic and immunologic disorders of the eye. Part II: Ocular allergy","volume":"106","author":"Bielory","year":"2000","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s40272-016-0185-1","article-title":"An Update on the Therapeutic Approach to Vernal Keratoconjunctivitis","volume":"18","author":"Esposito","year":"2016","journal-title":"Pediatr. Drugs"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1600-0420.1999.tb01165.x","article-title":"Vernal Keratoconjunctivitis","volume":"77","author":"Collum","year":"1999","journal-title":"Acta Ophthalmol. Scand."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1089\/jop.2005.21.400","article-title":"Efficiency of Olopatadine Hydrochloride 0.1% in the Treatment of Vernal Keratoconjunctivitis and Goblet Cell Density","volume":"21","author":"Yeniad","year":"2005","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s10384-008-0577-z","article-title":"Efficacy of topical cyclosporin A 0.05% in conjunctival impression cytology specimens and clinical findings of severe vernal keratoconjunctivitis in children","volume":"52","author":"Keklikci","year":"2008","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1097\/00003226-200405000-00008","article-title":"Perilimbal bulbar conjunctival pigmentation in vernal conjunctivitis: Prospective evaluation of a new clinical sign in an Indian population","volume":"23","author":"Rao","year":"2004","journal-title":"Cornea"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1444-0938.2008.00332.x","article-title":"Unilateral pseudogerontoxon","volume":"92","author":"Read","year":"2009","journal-title":"Clin. Exp. Optom."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.lfs.2015.01.040","article-title":"A comprehensive review on vernal keratoconjunctivitis with emphasis on proteomics","volume":"128","author":"Pattnaik","year":"2015","journal-title":"Life Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/978-1-4419-8056-4_5","article-title":"The role of histamine in ocular allergy","volume":"709","author":"Ohbayashi","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_95","first-page":"119","article-title":"Characterization of the conjunctival vasopermeability response to leukotrienes and their involvement in immediate hypersensitivity","volume":"29","author":"Gary","year":"1988","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_96","first-page":"481","article-title":"Effect of LTD4 on conjunctival vasopermeability and blood-aqueous barrier integrity","volume":"26","author":"Woodward","year":"1985","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4455","DOI":"10.4049\/jimmunol.1000833","article-title":"Conjunctival Goblet Cell Secretion Stimulated by Leukotrienes Is Reduced by Resolvins D1 and E1 To Promote Resolution of Inflammation","volume":"186","author":"Dartt","year":"2011","journal-title":"J. Immunol."},{"key":"ref_98","first-page":"138","article-title":"Studies on the ocular pharmacology of prostaglandin D2","volume":"31","author":"Woodward","year":"1990","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1111\/j.1398-9995.1997.tb00181.x","article-title":"Effects of rapamycin, cyclosporin A, and dexamethasone on interleukin 5-induced eosinophil degranulation and prolonged survival","volume":"52","author":"Meng","year":"1997","journal-title":"Allergy"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.1167\/iovs.14-15496","article-title":"IL-13 Stimulates Proliferation and Expression of Mucin and Immunomodulatory Genes in Cul-tured Conjunctival Goblet Cells","volume":"56","author":"Henriksson","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1046\/j.1523-1747.2000.00874.x","article-title":"Histamine Induces Melanogenesis and Morphologic Changes by Protein Kinase a Activation via H2 Receptors in Human Normal Melanocytes","volume":"114","author":"Yoshida","year":"2000","journal-title":"J. Investig. Dermatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00403-018-1816-x","article-title":"The stem cell factor-stimulated melanogenesis in human melanocytes can be abrogated by interrupting the phosphorylation of MSK1: Evidence for involvement of the p38\/MSK1\/CREB\/MITF axis","volume":"310","author":"Niwano","year":"2018","journal-title":"Arch. Dermatol. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"6166","DOI":"10.4049\/jimmunol.160.12.6166","article-title":"Novel role of transmembrane SCF for mast cell activation and eotaxin production in mast cell-fibroblast interactions","volume":"160","author":"Hogaboam","year":"1998","journal-title":"J. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/sj.eye.6702816","article-title":"Perilimbal conjunctival pigmentation in Chinese patients with vernal keratoconjunctivitis","volume":"22","author":"Luk","year":"2007","journal-title":"Eye"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/APO.0b013e3182795f4d","article-title":"Clinical and Cytologic Evidence of Limbal Stem Cell Deficiency in Eyes with Long-Standing Vernal Keratoconjunctivitis","volume":"2","author":"Saboo","year":"2013","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ghiglioni, D.G., Zicari, A.M., Parisi, G.F., Marchese, G., Indolfi, C., Diaferio, L., Brindisi, G., Ciprandi, G., Marseglia, G.L., and Miraglia del Giudice, M. (2021). Vernal keratoconjunctivitis: An update. Eur. J. Ophthalmol., 31.","DOI":"10.1177\/11206721211022153"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/j.1442-9071.2004.00849.x","article-title":"Pseudogerontoxon","volume":"32","author":"Jeng","year":"2004","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.iac.2010.06.004","article-title":"Atopic Dermatitis and Keratoconjunctivitis","volume":"30","author":"Bielory","year":"2010","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1097\/ACI.0b013e32834a9652","article-title":"Ocular allergy","volume":"11","author":"Friedlaender","year":"2011","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1097\/ACI.0b013e328357a21b","article-title":"Molecular immunology of allergic conjunctivitis","volume":"12","author":"Irkec","year":"2012","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.ajo.2012.09.014","article-title":"Management, Clinical Outcomes, and Complications of Shield Ulcers in Vernal Keratoconjunctivitis","volume":"155","author":"Reddy","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1097\/01.ico.0000121710.58571.c4","article-title":"Surgical management of corneal plaques in vernal keratoconjunctivitis: A clinicopathologic study","volume":"23","author":"Solomon","year":"2004","journal-title":"Cornea"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1097\/01.ico.0000178725.04070.87","article-title":"Rapid healing of vernal shield ulcer after surgical debridement: A case report","volume":"25","author":"Ozbek","year":"2006","journal-title":"Cornea"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1177\/112067210801800123","article-title":"Superficial keratectomy and amniotic membrane patch in the treatment of corneal plaque of vernal keratoconjunctivitis","volume":"18","author":"Pelegrin","year":"2008","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_115","first-page":"217","article-title":"Efficacy of air purifier therapy in allergic rhiniti","volume":"36","author":"Luo","year":"2018","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"408","DOI":"10.2500\/aap.2013.34.3695","article-title":"An algorithm for the management of allergic conjunctivitis","volume":"34","author":"Bielory","year":"2013","journal-title":"Allergy Asthma Proc."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13223-020-0403-9","article-title":"A contemporary look at allergic conjunctivitis","volume":"16","author":"Dupuis","year":"2020","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4103\/0301-4738.179727","article-title":"Systematic approach to managing vernal keratoconjunctivitis in clinical practice: Severity grading system and a treatment algorithm","volume":"64","author":"Gokhale","year":"2016","journal-title":"Indian J. Ophthalmol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/eye.1992.139","article-title":"Effectiveness of nedocromil sodium 2% eyedrops on clinical symptoms and tear fluid cytology of patients with vernal conjunctivitis","volume":"6","author":"Bonini","year":"1992","journal-title":"Eye"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S0002-9394(14)74786-5","article-title":"Efficacy and safety of lodoxamide 0.1% vs cromolyn sodium 4% in patients with vernal keratoconjunctivitis","volume":"113","author":"Caldwell","year":"1992","journal-title":"Am. J. Ophthalmol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1001\/archopht.1977.04450120090009","article-title":"Cromolyn Effects on Vernal Keratoconjunctivitis in Children","volume":"95","author":"Tabbara","year":"1977","journal-title":"Arch. Ophthalmol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1398-9995.1995.tb04252.x","article-title":"Clinical Experience with Tilavist: An Overview of Efficacy and Safety","volume":"50","author":"Kjellman","year":"1995","journal-title":"Allergy"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1136\/bjo.81.1.23","article-title":"Effect of lodoxamide and disodium cromoglycate on tear eosinophil cationic protein in vernal keratoconjunctivitis","volume":"81","author":"Leonardi","year":"1997","journal-title":"Br. J. Ophthalmol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1136\/bjo.2007.122044","article-title":"Systematic review and meta-analysis of randomised clinical trials on topical treatments for vernal keratoconjunctivitis","volume":"91","author":"Mantelli","year":"2007","journal-title":"Br. J. Ophthalmol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1034\/j.1600-0420.2000.078s230042.x","article-title":"Safety and Efficacy Comparison of Emedastine 0.05% Ophthalmic Solution Compared to Levocabastine 0.05% Ophthalmic Suspension in Pediatric Subjects with Allergic Conjunctivitis","volume":"78","author":"Secchi","year":"2000","journal-title":"Acta Ophthalmol. Scand."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/S0002-9394(00)00947-8","article-title":"Clinical evaluation of twice-daily emedastine 0.05% eye drops (emadine eye drops) versus levocabastine 0.05% eye drops in patients with allergic conjunctivitis","volume":"131","author":"Verin","year":"2001","journal-title":"Am. J. Ophthalmol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1001\/archopht.117.5.643","article-title":"Inhibition of Histamine-Induced Human Conjunctival Epithelial Cell Responses by Ocular Allergy Drugs","volume":"117","author":"Yanni","year":"1999","journal-title":"Arch. Ophthalmol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/S0161-6420(00)00538-8","article-title":"Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs","volume":"108","author":"Guidera","year":"2001","journal-title":"Ophthalmology"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"186","DOI":"10.5935\/0004-2749.20170045","article-title":"Supratarsal injection of triamcinolone for severe vernal keratoconjunctivitis in children","volume":"80","author":"Costa","year":"2017","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0002-9394(14)70271-5","article-title":"Supratarsal injection of corticosteroid in the treatment of refractory vernal keratoconjunctivitis","volume":"121","author":"Holsclaw","year":"1996","journal-title":"Am. J. Ophthalmol."},{"key":"ref_131","first-page":"241","article-title":"Supratarsal injection of corticosteroids in the treatment of refractory vernal keratoconjunctivitis","volume":"49","author":"Singh","year":"2001","journal-title":"Indian J. Ophthalmol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s10792-011-9421-4","article-title":"Supratarsal injection of triamcinolone acetonide and childhood allergic keratoconjunctivitis","volume":"32","author":"Zaouali","year":"2012","journal-title":"Int. Ophthalmol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1126\/science.6334364","article-title":"Induction of interleukin 2 messenger RNA inhibited by cyclosporin A","volume":"226","author":"Elliott","year":"1984","journal-title":"Science"},{"key":"ref_134","first-page":"2686","article-title":"Topical cyclosporine inhibits mast cell-mediated conjunctivitis","volume":"37","author":"Whitcup","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1177\/039463201002300322","article-title":"Long-Term Safety and Efficacy of Topical Cyclosporine in 156 Children with Vernal Keratoconjunctivitis","volume":"23","author":"Pucci","year":"2010","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/0002-9394(86)90819-6","article-title":"Cyclosporine Eyedrops for the Treatment of Severe Vernal Keratoconjunctivitis","volume":"101","author":"Benezra","year":"1986","journal-title":"Am. J. Ophthalmol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jaci.2011.07.004","article-title":"Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double-masked, controlled 2-year study","volume":"128","author":"Lambiase","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0002-9394(14)77061-8","article-title":"Topical Use of Cyclosporine in the Treatment of Vernal Keratoconjunctivitis","volume":"110","author":"Secchi","year":"1990","journal-title":"Am. J. Ophthalmol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1097\/ICO.0b013e31828ffdf8","article-title":"Tear cytokine levels in vernal keratoconjunctivitis: The effect of topical 0.05% cyclosporine a therapy","volume":"32","author":"Oray","year":"2013","journal-title":"Cornea"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"507","DOI":"10.11622\/smedj.2015161","article-title":"Efficacy and safety of topical cyclosporine A 0.05% in vernal keratoconjunctivitis","volume":"57","author":"Ulus","year":"2016","journal-title":"Singap. Med. J."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"220","DOI":"10.4103\/0301-4738.95878","article-title":"Oral cyclosporine therapy for refractory severe vernal keratoconjunctivitis","volume":"60","author":"Gokhale","year":"2012","journal-title":"Indian J. Ophthalmol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/eye.2011.75","article-title":"Topical 0.005% tacrolimus eye drop for refractory vernal keratoconjunctivitis","volume":"25","author":"Kheirkhah","year":"2011","journal-title":"Eye"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1089\/jop.2009.0087","article-title":"A Randomized, Placebo-Controlled Clinical Trial of Tacrolimus Ophthalmic Suspension 0.1% in Severe Allergic Conjunctivitis","volume":"26","author":"Ohashi","year":"2010","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"643","DOI":"10.2147\/OPTH.S99157","article-title":"Efficacy and safety of low-dose topical tacrolimus in vernal keratoconjunctivitis","volume":"10","author":"Shoughy","year":"2016","journal-title":"Clin. Ophthalmol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1007\/s11882-013-0345-0","article-title":"Use of Cyclosporine A and Tacrolimus in Treatment of Vernal Keratoconjunctivitis","volume":"13","author":"Vichyanond","year":"2013","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jaci.2003.10.065","article-title":"Vernal keratoconjunctivitisResult of a novel therapy with 0.1% topical ophthalmic FK-506 ointment","volume":"113","author":"Vichyanond","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_147","first-page":"177","article-title":"A double-masked comparison of 0.1% tacrolimus ointment and 2% cyclosporine eye drops in the treatment of vernal keratoconjunctivitis in children","volume":"30","author":"Labcharoenwongs","year":"2012","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_148","first-page":"94","article-title":"Consensus document on allergic conjunctivitis (DECA)","volume":"25","author":"Montero","year":"2015","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jaci.2010.09.034","article-title":"Allergen immunotherapy: A practice parameter third update","volume":"127","author":"Cox","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1111\/all.13786","article-title":"Management of ocular allergy","volume":"74","author":"Leonardi","year":"2019","journal-title":"Allergy"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1111\/all.13317","article-title":"EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis","volume":"73","author":"Roberts","year":"2017","journal-title":"Allergy"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1136\/bjo.2009.165548","article-title":"Intravenous immunoglobulin (IVIg) in the management of severe refractory vernal keratoconjunctivitis","volume":"94","author":"Derriman","year":"2010","journal-title":"Br. J. Ophthalmol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"304","DOI":"10.2500\/ajra.2013.27.3935","article-title":"Perennial is More Effective than Preseasonal Subcutaneous Immunotherapy in the Treatment of Seasonal Allergic Rhinoconjunctivitis","volume":"27","author":"Tworek","year":"2013","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1111\/j.1365-2222.2011.03835.x","article-title":"Sublingual immunotherapy for allergic conjunctivitis: Cochrane systematic review and meta-analysis","volume":"41","author":"Calderon","year":"2011","journal-title":"Clin. Exp. Allergy"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1097\/ACI.0b013e32834cb994","article-title":"Long-term clinical and immunological effects of allergen immunotherapy","volume":"11","author":"Eifan","year":"2011","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1146\/annurev.med.60.041807.123524","article-title":"Immunomodulation of Allergic Disease","volume":"60","author":"Broide","year":"2009","journal-title":"Annu. Rev. Med."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Lin, S.Y., Erekosima, N., Suarez-Cuervo, C., Ramanathan, M., Kim, J.M., Ward, D., Chelladurai, Y., and Segal, J.B. (2013). Allergen-Specific Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and\/or Asthma: Comparative Effectiveness Review, Agency for Healthcare Research and Quality.","DOI":"10.1001\/jama.2013.2049"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1126\/science.277.5322.99","article-title":"Phosphorylation of the Translational Repressor PHAS-I by the Mammalian Target of Rapamycin","volume":"277","author":"Brunn","year":"1997","journal-title":"Science"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ydbio.2010.04.027","article-title":"MAP4K3 regulates body size and metabolism in Drosophila","volume":"344","author":"Bryk","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.cell.2008.06.028","article-title":"p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling","volume":"134","author":"Budanov","year":"2008","journal-title":"Cell"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clim.2018.02.004","article-title":"Rapamycin attenuates Th2-driven experimental allergic conjunctivitis","volume":"190","author":"Shin","year":"2018","journal-title":"Clin. Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.3389\/fimmu.2018.02283","article-title":"Rapamycin Nano-Micelle Ophthalmic Solution Reduces Corneal Allograft Rejection by Potentiating Myeloid-Derived Suppressor Cells\u2019 Function","volume":"9","author":"Wei","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_163","first-page":"CD001186","article-title":"Injection allergen immunotherapy for asthma","volume":"2010","author":"Abramson","year":"2010","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_164","first-page":"969","article-title":"Is allergen immunotherapy effective in asthma? A meta-analysis of randomized controlled trials","volume":"151","author":"Abramson","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1111\/j.1365-2222.2011.03794.x","article-title":"Immunotherapy for allergic rhinitis","volume":"41","author":"Walker","year":"2011","journal-title":"Clin. Exp. Allergy"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0149-2918(00)80037-5","article-title":"Effectiveness of specific immunotherapy in the treatment of asthma: A meta-analysis of prospective, randomized, double-blind, placebo-controlled studies","volume":"22","author":"Ross","year":"2000","journal-title":"Clin. Ther."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"S306","DOI":"10.1016\/j.jaci.2009.10.064","article-title":"Allergen immunotherapy","volume":"125","author":"Frew","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13223-018-0282-5","article-title":"Allergen-specific immunotherapy","volume":"14","author":"Moote","year":"2018","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"5072781","DOI":"10.1155\/2016\/5072781","article-title":"Expression of TSLP and Downstream Molecules IL-4, IL-5, and IL-13 on the Eye Surface of Patients with Various Types of Allergic Conjunctivitis","volume":"2016","author":"Zheng","year":"2016","journal-title":"J. Ophthalmol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1365-2249.2011.04328.x","article-title":"A soluble thymic stromal lymphopoietin (TSLP) antagonist, TSLPR-immunoglobulin, reduces the severity of allergic disease by regulating pulmonary dendritic cells","volume":"164","author":"Zhang","year":"2011","journal-title":"Clin. Exp. Immunol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.4049\/jimmunol.176.4.2238","article-title":"Mast Cells Enhance T Cell Activation: Importance of Mast Cell Costimulatory Molecules and Secreted TNF","volume":"176","author":"Nakae","year":"2006","journal-title":"J. Immunol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"3868","DOI":"10.1172\/JCI33559","article-title":"In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation","volume":"117","author":"Seshasayee","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Reinach, P.S., Mergler, S., Okada, Y., and Saika, S. (2015). Ocular transient receptor potential channel function in health and disease. BMC Ophthalmol., 15.","DOI":"10.1186\/s12886-015-0135-7"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1523\/JNEUROSCI.4643-06.2007","article-title":"TRPV1 Mediates Histamine-Induced Itching via the Activation of Phospholipase A2 and 12-Lipoxygenase","volume":"27","author":"Shim","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1080\/09273948.2016.1231330","article-title":"TRPV1 Antagonist Suppresses Allergic Conjunctivitis in a Murine Model","volume":"26","author":"Kwon","year":"2016","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"148","DOI":"10.18632\/oncotarget.6653","article-title":"The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis","volume":"7","author":"Samivel","year":"2016","journal-title":"Oncotarget"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.jaci.2015.08.047","article-title":"A histamine-independent itch pathway is required for allergic ocular itch","volume":"137","author":"Huang","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.clim.2015.08.004","article-title":"The C-C chemokine receptor 6 (CCR6) is crucial for Th2-driven allergic conjunctivitis","volume":"161","author":"Chung","year":"2015","journal-title":"Clin. Immunol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1016\/j.ajpath.2012.02.015","article-title":"Blocking CCR7 at the ocular surface impairs the pathogenic contribution of dendritic cells in allergic conjunctivitis","volume":"180","author":"Schlereth","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1111\/all.13448","article-title":"Daily allergic multimorbidity in rhinitis using mobile technology: A novel concept of the MASK study","volume":"73","author":"Bousquet","year":"2018","journal-title":"Allergy"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/ACI.0b013e32834a9676","article-title":"Epidemiology of allergic conjunctivitis","volume":"11","author":"Rosario","year":"2011","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/all.13342","article-title":"RItA: The Italian severe\/uncontrolled asthma registry","volume":"73","author":"Maio","year":"2017","journal-title":"Allergy"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1111\/all.13431","article-title":"Higher mortality of adults with asthma: A 15-year follow-up of a population-based cohort","volume":"73","author":"Lemmetyinen","year":"2018","journal-title":"Allergy"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1136\/bjophthalmol-2014-305201","article-title":"Prevalence and risk factors of dry eye disease in a British female cohort","volume":"98","author":"Vehof","year":"2014","journal-title":"Br. J. Ophthalmol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"397","DOI":"10.2500\/ajra.2016.30.4361","article-title":"Dry Eye Disease and Allergic Conditions: A Korean Nationwide Population-Based Study","volume":"30","author":"Kim","year":"2016","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13601-017-0153-z","article-title":"Multi-morbidities of allergic rhinitis in adults: European Academy of Allergy and Clinical Immunology Task Force Report","volume":"7","author":"Cingi","year":"2017","journal-title":"Clin. Transl. Allergy"},{"key":"ref_187","first-page":"3","article-title":"Allergic Conjunctivitis in Patients with Respiratory Allergic Symptoms; a Retrospective Study in Greece","volume":"6","author":"Michailopoulos","year":"2017","journal-title":"Med. Hypothesis Discov. Innov. Ophthalmol. J."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"e6317","DOI":"10.1097\/MD.0000000000006317","article-title":"Prevalence and clinical features of adult atopic dermatitis in tertiary hospitals of China","volume":"96","author":"Wang","year":"2017","journal-title":"Medicine"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1056\/NEJMoa1610020","article-title":"Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis","volume":"375","author":"Simpson","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1016\/S0140-6736(17)31191-1","article-title":"Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): A 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial","volume":"389","author":"Blauvelt","year":"2017","journal-title":"Lancet"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/bjd.17869","article-title":"Conjunctivitis in dupilumab clinical trials","volume":"181","author":"Akinlade","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/j.jaip.2019.10.011","article-title":"Amelioration of conjunctival giant papillae by dupilumab in patients with atopic keratoconjunctivitis","volume":"8","author":"Fukuda","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jtos.2020.05.008","article-title":"Ocular surface disease associated with dupilumab treatment for atopic diseases","volume":"19","author":"Utine","year":"2021","journal-title":"Ocul. Surf."},{"key":"ref_194","first-page":"303","article-title":"Dupilumab-Associated Blepharoconjunctivitis with Giant Papillae","volume":"13","author":"Vingopoulos","year":"2020","journal-title":"Int. Med. Case Rep. J."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12348-020-00234-y","article-title":"Serum IgE reduction and paradoxical eosinophilia associated with allergic conjunctivitis after dupilumab therapy","volume":"11","author":"Kimura","year":"2021","journal-title":"J. Ophthalmic Inflamm. Infect."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s40257-020-00577-1","article-title":"Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma","volume":"22","author":"Bansal","year":"2021","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1365-2222.2008.03121.x","article-title":"Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma","volume":"39","author":"Kopp","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s40123-016-0074-2","article-title":"Omalizumab in Severe Refractory Vernal Keratoconjunctivitis in Children: Case Series and Review of the Literature","volume":"6","author":"Doan","year":"2017","journal-title":"Ophthalmol. Ther."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jaci.2004.06.032","article-title":"Omalizumab-induced reductions in mast cell Fce psilon RI expression and function","volume":"114","author":"Beck","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Taill\u00e9, C., Doan, S., Neukirch, C., and Aubier, M. (2010). Omalizumab for severe atopic keratoconjunctivitis. BMJ Case Rep., 2010.","DOI":"10.1136\/bcr.04.2010.2919"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1001\/jamaophthalmol.2015.5679","article-title":"Omalizumab Treatment of Vernal Keratoconjunctivitis","volume":"134","author":"Heffler","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jaapos.2012.12.153","article-title":"Severe vernal keratoconjunctivitis successfully treated with subcutaneous omalizumab","volume":"17","author":"Biswas","year":"2013","journal-title":"J. AAPOS"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.anai.2018.09.458","article-title":"Omalizumab as single-dose therapy for vernal keratoconjunctivitis","volume":"122","author":"Simpson","year":"2019","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1365-2249.2008.03716.x","article-title":"Allergy and the eye","volume":"153","author":"Leonardi","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1046\/j.1365-2745.2003.01616.x","article-title":"Vernal keratoconjunctivitis: Evidence for immunoglobulin E-dependent and immunoglobulin E-independent eosinophilia","volume":"33","author":"Ono","year":"2003","journal-title":"Clin. Exp. Allergy"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/01.ico.0000114836.13127.45","article-title":"The Relation of Conjunctival and Corneal Findings in Severe Ocular Allergies","volume":"23","author":"Tanaka","year":"2004","journal-title":"Cornea"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1146\/annurev.immunol.24.021605.090720","article-title":"The Eosinophil","volume":"24","author":"Rothenberg","year":"2006","journal-title":"Annu. Rev. Immunol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.5414\/CP202446","article-title":"Characterization of the relationship between dose and blood eosinophil response following subcutaneous administration of mepolizumab","volume":"53","author":"Pouliquen","year":"2015","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.jaci.2008.02.033","article-title":"Anti\u2013IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels","volume":"121","author":"Stein","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fmed.2018.00049","article-title":"Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma","volume":"5","author":"Roufosse","year":"2018","journal-title":"Front. Med."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s40265-016-0583-2","article-title":"Reslizumab: First Global Approval","volume":"76","author":"Markham","year":"2016","journal-title":"Drugs"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2147\/PROM.S146966","article-title":"Impact of reslizumab on outcomes of severe asthmatic patients: Current perspectives","volume":"9","author":"Galo","year":"2018","journal-title":"Patient Relat. Outcome Meas."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1182\/blood-2003-10-3620","article-title":"Safety and efficacy of the monoclonal anti\u2013interleukin-5 antibody SCH55700 in the treatment of patients with hypereosinophilic syndrome","volume":"103","author":"Klion","year":"2004","journal-title":"Blood"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.jaci.2010.04.005","article-title":"Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti\u2013IL-5 receptor \u03b1 antibody, in a phase I study of subjects with mild asthma","volume":"125","author":"Busse","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ajem.2014.09.036","article-title":"A randomized trial of benralizumab, an antiinterleukin 5 receptor \u03b1 monoclonal antibody, after acute asthma","volume":"33","author":"Nowak","year":"2015","journal-title":"Am. J. Emerg. Med."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/7\/658\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:28:31Z","timestamp":1760164111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/7\/658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,9]]},"references-count":215,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ph14070658"],"URL":"https:\/\/doi.org\/10.3390\/ph14070658","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,9]]}}}