Background/Purpose: Pediatric chronic anterior uveitis (CAU) leads to sight-threatening complications in approximately 50% of affected children. Among complications, cataract and glaucoma are among the most common ocular complications of CAU. We aim to identify tear-based biomarkers associated with ocular damage in pediatric CAU.

Methods: This cross-sectional study included children ≥5 years old diagnosed with CAU (juvenile idiopathic arthritis-associated (JIA-U) or idiopathic (iCAU)) from our registry at CCHMC. Tear samples were collected from both eyes by Schirmer strips. Ocular complications included cataract, glaucoma, synechiae, band keratopathy, macular edema, epiretinal membrane, and optic disc oedema. Levels of S100A8, A9, and A12 were measured by ELISA, and IL-18, IL-8, CXCL10 (IP-10), MCP-1, RANTES, and sICAM-1 by Luminex assays. Biomarker levels were compared by the number of ocular complications (0, 1, >1). An exploratory Spearman correlation (ρ) analysis was performed and a Heatmap was developed to identify potential significant associations. A p-value < 0.05 was considered significant.

Results: Forty-one children (29 JIA-U; 12 iCAU) with CAU contributed 121 tear samples (86 JIA-U; 35 iCAU) (Table 1), of whom 77 samples are from eyes with complications (51 by JIA-U and 26 by iCAU, χ²2.41, p=0.088). We observed significant differences regarding the number of complications between JIA-U vs iCAU (mean 1.88 vs 2.15, p< 0.001). We observed an increased level of RANTES in children with complications compared to those without complications (0.752 vs 0.389, p=0.028), and when considering the number of complications [0, 1, or >1] (0.389 vs 0.675 vs 0.824 respectively, p=0.022) (Figure 1A). Conversely, CXCL10 was decreased in children with complications (2.82 vs 2.99, p=0.010), and when stratified by the number of complications (2.991 vs 2.881 vs 2.785 respectively, p=0.004, Figure 1B). As shown in Figure 2, there were several significant correlations between the level of candidate biomarkers and ocular parameters: RANTES was positively correlated with the presence of complications (ρ=271, p=0.005) and glaucoma (ρ=306,p=0.015), while CXCL10 was negatively correlated with the presence of complications(ρ=0.27, p=0.005, the number of complications (ρ=0.31,p=0.006), and the presence of macular oedema/and papillitis (ρ=245,p=0.031). Moreover we found a positive correlation between S100A9 and the presence of cataract (ρ=384,p=0.003) and a negative correlation with uveitis activity (ρ=292,p=0.007).

Conclusion: We identified RANTES, CXCL10 and S100A9 as potential tear-based biomarkers associated with ocular damage in pediatric patients with CAU. RANTES appears to be elevated with ocular complications, whereas CXCL10 is decreased. The role of RANTES has been demonstrated in experimental autoimmune uveitis models and patients with uveitis. It has also been shown to differentiate patients with glaucoma. Further, we identified CXCL10 and S100A9 correlations with specific complications. Next steps are to determine biomarkers that are associated with specific ocular complications and differentiate activity from damage (chronicity).

Table 1. Clinical Characteristics of Children with Chronic Anterior Uveitis

Figure 1: Significant differences in complications and A) CXCL10 and B) RANTES with pairwise comparison that indicate differences.

Figure 2: Heatmap representing the correlations among the logarithmic value of cytokines and chemokines and the different variables considered. The significant correlations are identified with one or two stars (0.05 >p>0.009 and p < 0.009 respectively). The blue color represents negative correlations, while red color positive correlations

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rantes-and-cxcl10-as-potential-tear-based-biomarkers-associated-with-ocular-damage-in-pediatric-chronic-anterior-uveitis/