Vernal Keratoconjunctivitis: Immunopathological Insights and Therapeutic Applications of Immunomodulators

Abstract

Vernal keratoconjunctivitis (VKC) is a complex and multifactorial disease process that employs Th2 cell-mediated immunologic processes, which involves the overexpression of interleukin 4 (IL-4), IL-5, IL-9, IL-13, and IL-31, and the activation of mast cells that release IL-5 and CCL-11, recruiting eosinophils to the site of inflammation. The disease primarily affects young males and is more common in regions with warm climates. VKC is characterized by persistent and recurrent conjunctival inflammation that can adversely affect the patient’s quality of life, and, when inadequately treated, may lead to a host of ocular complications, such as corneal shield ulcers and scarring. The major distinct forms of VKC include limbal or palpebral, which may occur in combination. The clinicopathological features of VKC include the presence of pseudogerontoxon, limbal gelatinous hyperplasia, and perilimbal hyperpigmentation. Topical immunomodulators are effective anti-steroidal options for controlling severe and chronic cases of VKC. This review will provide a brief overview of topical immunomodulators, including cyclosporin and tacrolimus, and will highlight the clinical manifestations, pathological mechanisms, and fibroproliferative changes in the conjunctiva that can result from recurrent disease.

A Case of Refractory Vernal Keratoconjunctivitis Showing Improvement after the Administration of Upadacitinib for the Treatment of Atopic Dermatitis

“…VKC is a complex and multifactorial disease characterized by Th2 cell-mediated immunologic processes [ 6 ]. Consequently, there is a strong association between VKC and AD, with VKC often occurring concurrently with AD [ 7 , 8 ].…”

“…Recently, various studies have hypothesized that both allergies and autoimmune diseases, as well as oxidative stress, contribute significantly to the origin of the disease [ 5 ]. Traditionally, VKC was considered to be associated with T helper (Th) 2 cell-mediated immunological processes, which involve the overexpression of interleukin 4 (IL-4), IL-5, IL-9, IL-13, and IL-31, along with the activation of mast cells and eosinophils [ 6 ]. VKC is strongly associated with atopic diseases, including atopic dermatitis (AD), characterized by a Th2-shifted immune response [ 7 , 8 ].…”

Allergic Conjunctivitis: Review of Current Types, Treatments, and Trends

“…They inhibit T-lymphocyte activation and proliferation, which prevents histamine release from mast cells and basophils, preventing chronic inflammatory damage to the ocular surface [ 29 , 31 ]. Both cyclosporin A and tacrolimus have been evaluated for safety and efficacy in more severe forms of allergic conjunctivitis including VKC and AKC and have been effective in reducing ocular signs and symptoms [ 63 , 64 , 65 ]. These drugs are calcineurin inhibitors, which allows them to be safe for long-term topical use without lasting side effects [ 29 , 31 ].…”