INTRODUCTION
Vernal keratoconjunctivitis (VKC) is a rare (<1: 10,000) and chronic conjunctivitis that arose in the pediatric population and is often self-limiting during puberty, underlying a possible hormonal correlation 1. Males are affected more than females with an approximate ratio from 4:1 to 2:1.2
Typical phenotypes of VKC disease are: the tarsal one with papillae on the tarsal conjunctiva, the limbal one with limbal papillae covered with Horner Trantas points and the mixed phenotype with characteristics of both the ones above.1
Even if the typical symptoms are in common with allergic conjunctivitis, such as intense photophobia, hyperemia, itching, and tearing and not improved by common therapeutic drugs1, VKC deserves more attention because of its severe complications that can cause permanent eye damage including blindness.
Although many factors have been considered in VKC etiology, the real mechanism supporting chronic ocular inflammation remains a debated topic3,4 VKC was initially defined as an IgE-mediated disease but the presence of atopy, positive SPT, and high serum IgE levels, is reported only in 50% cases.5 Moreover a high percentage of ANA positivity and a family history of autoimmunity is common in VKC.5
Ocular conjunctiva is characterized by a predominantly eosinophil-mediated inflammation where histamine, released from mast cell degranulation in response to environmental allergens, has a key role in keeping active the inflammatory pathways. The local funding of eosinophil cationic protein (ECP) is a marker of this eosinophilic inflammation.6 Besides a Th2 response, many studies have outlined in VKC ocular inflammation several cytokines, such as IL1, 4, 5, 6, 8, 13, and the transforming growth factor-beta 1 (TGFß 1). Also, systemic pro-inflammatory markers, like High-mobility group box 1 (HMGB1) and its receptor for advanced glycation end-product (sRAGE), were found in VKC, underlying a chronic inflammation of the conjunctiva with systemic involvement .3,5,7,8,6
Periostin, produced by fibroblasts and endothelial cells in response to IL-4 or IL-13, resulted in VKC chronic inflammation too.6
Given this crosstalk between allergic Th2-mediated response and inflammatory Th1-mediated one, it is understandable that the lack of efficacy in VKC disease of standard allergic treatments is mostly based on antihistamines.5,7,9,10
The timely use of topical immunosuppressant therapy with cyclosporine A 1% eye drops (CsA) is considered the best treatment for the complete control of ocular symptoms. Furthermore, CsA aims to reduce any future complications, reinforcing the hypothesis of local/systemic inflammation. 11,12,13
Oxidative stress is a well-known mediator that has been identified as a key role in the pathogenesis of many diseases, such as conjunctivitis. In particular, oxidative stress is considered as the pathogenic result of generalized allergy-related inflammation in patients with seasonal allergic conjunctivitis.14
Thus oxidative stress contributes to the onset and persistence of conjunctival damage. A typical example of this condition is common in patients with allergic conjunctivitis, where NADPH oxidase generates superoxide anions that are converted by superoxide dismutase in Hydrogen peroxide (H2O2). This latter oxidative molecule is increased in subjects with allergic conjunctivitis and can contribute to maintaining ocular damage.15
To the best of our knowledge, no study has analyzed oxidative stress in VKC, besides the already well investigated inflammatory cascade.
Therefore, the first aim of this pilot study was to assess if oxidative stress is increased in VKC patients.
Furthermore, previous studies showed that CsA inhibits ROS production16. Thus the second aim of this study was to analyze the effect of CsA on oxidative stress in VKC children.