Introduction:
Vernal keratoconjunctivitis (VKC) is a chronic, bilateral allergic inflammation of the ocular surface, seasonal or perennial affecting children in the first decade of their life. It can present as limbal, palpebral or as a mixed disease with varying grades of severity, with a small subset bordering on refractory disease not amenable to currently available treatment modalities(1). Being a tropical country, the incidence is high in India and almost 36% children have the perennial form of VKC(2).
The exact etiopathogenesis of allergic disorders is still not completely understood. Pathways involving IgE antibodies or T-cells and inflammatory cytokines(3,4) are well known. However, the ones involving bioactive lipid mediators are still being explored. Of the four classes of immune modulating lipids; platelet activating factor, leukotrienes, prostanoids and sphingolipids, immense focus has been on the sphingolipid group in influencing the pathogenesis of allergic disease as seen in the last decade(5). Sphingolipids (SL) comprise a large family of bioactive lipids containing a sphingoid base (aliphatic amino alcohol) as backbone that is acylated with various fatty acids to form several SL species. Ceramide is the central molecule which is generated by de novo synthesis or formed by degradation from sphingomyelin at plasma membrane level, while sphingosine is formed from ceramide by ceramidase(6). Cytosolic conversion to their respective phosphorylated forms, ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P) and further to other sphingolipids including glycosphingolipids constitute the bioactives that are regulated by the various kinases, phosphatases, hydrolases and lyases (Figure 1) . Activation of the pathway occurs in response to a variety of cellular stresses due to UV radiation, pathogen exposure, allergens and chemotherapeutic agents, leading to the production of the bioactive lipid ceramide(7). Ceramide and sphingosine are interconvertible components of the “sphingolipid rheostat” that regulates immune function(8). These immune modulating sphingolipids accumulate in cell membrane and compartmentalize intracellularly to play a major role in immune cell trafficking, inflammation, barrier cell integrity and cell survival(6,7,9).
In light of the above recent understanding from reports of systemic allergic disorders, we decided to explore such bioactive lipids in the ocular allergic disorder, specifically VKC. The etiopathogenesis of VKC is still being explored. In addition, with the available reports in literature, we are presently unable to explain the etiopathology of refractoriness of this condition, barring reports of higher levels of inflammatory cytokines in these severely affected eyes compared to the less severe ones(10). We therefore specifically studied the sphingolipid metabolism in patients with vernal keratoconjunctivitis.