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Effect of intravitreal methotrexate and rituximab on interleukin-10 levels in aqueous humor of treated eyes with vitreoretinal lymphoma.

Raja H, Snyder MR, Johnston PB, O'Neill BP, Caraballo JN, Balsanek JG, Peters BE, Decker PA, Pulido JS - PLoS ONE (2013)

Bottom Line: Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma.Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718.In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%.

View Article: PubMed Central - PubMed

Affiliation: Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, Minnesota, USA.

ABSTRACT
Intraocular cytokines are promising diagnostic biomarkers of vitreoretinal lymphoma. Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma. This is a retrospective case series including 10 patients with lymphoma and 7 patients with uveitis. Non-parametric Mann-Whitney analysis was performed to determine statistical significance of difference in interleukin levels between lymphoma and uveitis. Compared to eyes with uveitis, eyes with lymphoma had higher levels of IL-10 (U = 7.0; two-tailed p = 0.004) and IL-10/IL-6 (U = 6.0; two-tailed p = 0.003), whereas IL-6 levels were more elevated, although insignificant, in those patients with uveitis than in lymphoma (U = 15.0; two-tailed p = ns). Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718. In patients in whom serial interleukin levels were available, regular intravitreal treatment with methotrexate and rituximab was associated with reduction in IL-10 levels over time. In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%. Therefore, these cytokines may serve as a useful adjunct in the diagnosis of lymphoma. While negative IL-10 and IL-10/IL-6 values do not exclude a diagnosis of lymphoma, elevated levels do appear to be consistent with lymphoma clinically. Moreover, elevated levels of IL-10 in the setting of a clinically quiet eye may point to impending disease recurrence. Lastly, once lymphoma is diagnosed, IL-10 levels can be monitored over time to assess disease activity and therapeutic response.

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Empirical ROC curve using IL threshold values.a) IL-10 ROC curve, b) IL-6 ROC curve, c) IL-10/IL-6 ROC curve. The vertical axis represents the true positive rate (sensitivity), and the horizontal axis represents the false positive rate (1-specificity). The curve was generated by dichotomizing IL values into one of two groups (i.e., lymphoma vs. no lymphoma) to determine statistical indices associated with discrete threshold values.
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pone-0065627-g001: Empirical ROC curve using IL threshold values.a) IL-10 ROC curve, b) IL-6 ROC curve, c) IL-10/IL-6 ROC curve. The vertical axis represents the true positive rate (sensitivity), and the horizontal axis represents the false positive rate (1-specificity). The curve was generated by dichotomizing IL values into one of two groups (i.e., lymphoma vs. no lymphoma) to determine statistical indices associated with discrete threshold values.

Mentions: ROC analysis with estimate of areas under the curves was completed to identify threshold values of IL-10 (Fig. 1a), IL-6 (Fig. 1b), and IL-10/IL-6 (Fig. 1c). Area under the ROC curve was 0.900 for IL-10 (95% CI, 0.744–1.0; p = 0.006), 0.786 for IL-6 (95% CI, 0.563–1.0 p = ns), and 0.914 for IL-10/IL-6 (95% CI, 0.751–1.0; p = 0.005). Sensitivity, specificity, and likelihood ratio are reported for discrete threshold values of IL-10 (Table 5), IL-6 (Table 6), and IL-10/IL-6 (Table 7) as derived by GraphPad Prism.


Effect of intravitreal methotrexate and rituximab on interleukin-10 levels in aqueous humor of treated eyes with vitreoretinal lymphoma.

Raja H, Snyder MR, Johnston PB, O'Neill BP, Caraballo JN, Balsanek JG, Peters BE, Decker PA, Pulido JS - PLoS ONE (2013)

Empirical ROC curve using IL threshold values.a) IL-10 ROC curve, b) IL-6 ROC curve, c) IL-10/IL-6 ROC curve. The vertical axis represents the true positive rate (sensitivity), and the horizontal axis represents the false positive rate (1-specificity). The curve was generated by dichotomizing IL values into one of two groups (i.e., lymphoma vs. no lymphoma) to determine statistical indices associated with discrete threshold values.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672178&req=5

pone-0065627-g001: Empirical ROC curve using IL threshold values.a) IL-10 ROC curve, b) IL-6 ROC curve, c) IL-10/IL-6 ROC curve. The vertical axis represents the true positive rate (sensitivity), and the horizontal axis represents the false positive rate (1-specificity). The curve was generated by dichotomizing IL values into one of two groups (i.e., lymphoma vs. no lymphoma) to determine statistical indices associated with discrete threshold values.
Mentions: ROC analysis with estimate of areas under the curves was completed to identify threshold values of IL-10 (Fig. 1a), IL-6 (Fig. 1b), and IL-10/IL-6 (Fig. 1c). Area under the ROC curve was 0.900 for IL-10 (95% CI, 0.744–1.0; p = 0.006), 0.786 for IL-6 (95% CI, 0.563–1.0 p = ns), and 0.914 for IL-10/IL-6 (95% CI, 0.751–1.0; p = 0.005). Sensitivity, specificity, and likelihood ratio are reported for discrete threshold values of IL-10 (Table 5), IL-6 (Table 6), and IL-10/IL-6 (Table 7) as derived by GraphPad Prism.

Bottom Line: Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma.Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718.In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%.

View Article: PubMed Central - PubMed

Affiliation: Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, Minnesota, USA.

ABSTRACT
Intraocular cytokines are promising diagnostic biomarkers of vitreoretinal lymphoma. Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma. This is a retrospective case series including 10 patients with lymphoma and 7 patients with uveitis. Non-parametric Mann-Whitney analysis was performed to determine statistical significance of difference in interleukin levels between lymphoma and uveitis. Compared to eyes with uveitis, eyes with lymphoma had higher levels of IL-10 (U = 7.0; two-tailed p = 0.004) and IL-10/IL-6 (U = 6.0; two-tailed p = 0.003), whereas IL-6 levels were more elevated, although insignificant, in those patients with uveitis than in lymphoma (U = 15.0; two-tailed p = ns). Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718. In patients in whom serial interleukin levels were available, regular intravitreal treatment with methotrexate and rituximab was associated with reduction in IL-10 levels over time. In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%. Therefore, these cytokines may serve as a useful adjunct in the diagnosis of lymphoma. While negative IL-10 and IL-10/IL-6 values do not exclude a diagnosis of lymphoma, elevated levels do appear to be consistent with lymphoma clinically. Moreover, elevated levels of IL-10 in the setting of a clinically quiet eye may point to impending disease recurrence. Lastly, once lymphoma is diagnosed, IL-10 levels can be monitored over time to assess disease activity and therapeutic response.

Show MeSH
Related in: MedlinePlus