Association of Tear and Serum Proteomic Profile on Disease Severity in Vernal Keratoconjunctivitis (VKC).
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OBJECTIVE: To study the association of tear and serum proteomic profile with disease severity in vernal keratoconjunctivitis (VKC). METHODS: A prospective, non-randomized, observational study. 50 participants aged 8-16 years were included in the study: 10 Controls (Group 1), 20 in Moderate VKC (Group 2), and 20 in severe VKC (Group 3). The more inflamed eye was selected for tear sampling. Flow cytometry quantified tear and serum cytokines; TIMP1,2, total IgE, and Vitamin D were studied.The Primary outcome measures assessed the correlation between disease severity and tear levels, serum IL-2-10,17, TNF-α, IFN-γ, TNF-α, IFN-α, serum TIMP-1,2, IgE, tear allergen assay, and tear-specific IgE in enrolled patients. Secondary outcome measures assessed disease severity with keratoconus and ocular surface disease index (OSDI). RESULTS: An overall increase in inflammatory mediators in tears was observed in Group 2 compared to Group 1. Higher IL-6 levels were noted in tear samples in groups 2 and 3. Serum IL-10 was elevated in controls compared to diseased patients (p=0.086). Serum IL-17A was detected only in patients with active disease. Keratoconus was present in 15% and 50% of subjects in Groups 2 and 3, respectively (p=0.018). Mean OSDI values in Groups 3, 2, and 1 were 44.70, 26.53, and 5.18, respectively (p<0.001). Serum IgE was elevated in Group 2 and Group 3 patients compared to Group 1 (p< 0.001). DISCUSSION: The diagnosis of VKC is primarily clinical, but immunological tests have been used to explore molecular and cellular mechanisms. Serum and tear inflammatory markers have been studied to identify biomarkers linked to immune responses and potential treatments. This study employed a flow cytometry-based cytokine bead array (CBA) to analyze inflammatory proteins in serum and tears. Overall, cytokine levels were higher in Group 2 than in Group 1, except for TNF-α and IL-10, and in Group 3 than in Group 2, except for IL-6. Significant positive correlations among tear parameters indicated the pro-inflammatory and immune-disturbed nature of VKC. Additionally, correlations between serum and tear parameters supported VKC as a Th2-mediated hypersensitivity. Higher mean OSDI scores (p < 0.001) in Group 3 showed that more severe VKC correlates with worse dry eye. The study also assessed quality of life, finding that 87.5% of patients sometimes rubbed their eyes, 52.5% used eye drops, and 57.5% experienced red eyes and burning sensations in the two weeks before evaluation. Limitations included a small sample size and the use of Schirmer strips for tear collection, which may dilute inflammatory mediators compared with basal tears collected by other methods. CONCLUSION: Tear and serum cytokines are largely associated with diseases severity in VKC patients. New treatment algorithms that involve systemic pathways may be developed.