DISCUSSION
VKC is characterized by a severe inflammatory pattern, generally
resistant to standard anti-inflammatory therapies and sensitive to
topical steroids or immunosuppressants.1,3
Several cytokines and chemokines play a pivotal role in keeping the
inflammatory cascade active, as it results from previous
studies. 3,6,8
The role of oxidative stress has been studied with increasing interest
in several allergic or immune-mediated inflammatory
diseases20, except for VKC.
Ocular oxidative stress has been investigated both in humans and in
animal models in many eye diseases such as uveitis21,
corneal inflammation22, and allergic
keratoconjunctivitis23. To our knowledge in only one
study, Tais H. Wakamatsu et al. 24 evaluated tears and
brush cytology samples in 14 adolescent-young adults with atopic
dermatitis and allergic conjunctivitis, to assess if there were
oxidative-stress related changes in these patients in comparison to
healthy children. The authors24 found higher
percentages of cells positively stained for the early phase lipid
peroxidation marker and the late phase lipid peroxidation marker, in
palpebral conjunctiva and tears, suggesting an increased lipid
peroxidation status in atopic keratoconjunctivitis, leading to
endothelial damage.
Dadaci Z et al., evaluated oxidative stress parameters in 35 patients
with seasonal allergic conjunctivitis (SAC) during the pollen season vs.
38 healthy subjects, demonstrating higher levels of oxidative stress
parameters in SAC compared to controls, outlining a possible role of
oxidative stress in the pathogenesis of this disease.2
This study reports new and intriguing results, never investigated in
VKC, providing the first evidence that oxidative stress characterizes
VKC disease. We found significantly higher levels of hydrogen peroxide
in the serum and in the tears of children in the active phase of disease
compared to VKC treated children and CT. No significant differences were
observed between CT and VKC undergoing CsA. Moreover, a linear
regression analysis reported a significant correlation between serum and
tear H2O2 levels.
The reduction of H2O2 values in tears and the serum of VKC treated
children, could be considered a parameter for the efficacy of CsA
treatment, confirming that this therapy effectively controls both
systemic and local inflammation.
CsA reduces H2O2-induced intracellular generation of reactive oxygen
species, protecting against H2O2-induced cell
injury.25
To confirm the importance of the timely use of CsA, Leonardi A et al.
have conducted a trial where 169 children were randomized to receive CsA
0.1% (1 mg/ml) eye drops with higher dosages compared to lower ones,
reporting a better efficacy of high-dose CsA to improve keratitis,
symptoms and also the quality of life of VKC
children.26
Moreover, CsA can interrupt both the helper T-lymphocyte proliferation
and the IL-2 production, which inhibit the release of histamine from
basophils and mast cells, reducing IL-5 levels.27
This finding leads us to speculate that local immunosuppressive therapy
with CsA may control the ocular immunological response and the systemic
one.5,7
Although eyes are defined as immunological sanctuaries, the finding of
high local H2O2 values lets us speculate that H2O2 could play a key role
in ocular dysfunction and inflammation, which is responsible for the
serious complications typical of VKC. This reinforces the importance of
a prompt start of target therapy with CsA in VKC patients.
Our results must be interpreted, considering some limitations.
First of all, we have studied a small, single-center sample that needs
to be implemented into a larger cohort. The presence of allergic
diseases in 54% of VKC children may interfere with a realistic estimate
of the systemic oxidative stress caused by VKC disease alone, rather
than by other allergic coexisting conditions. However, the randomized
distribution of these patients exceeds a possible risk of bias. Summing
up, this is a pilot study with a cross-sectional design that may reports
only associations between H2O2 mediated oxidative stress and
inflammation in VKC children.
So further studies are warranted to confirm these results in a
long-lasting follow-up.
Several questions remain unsolved, such as the correlation between
oxidative stress and the degree of severity of VKC disease.