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.