Limits...
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.

Show MeSH

Related in: MedlinePlus

Distribution of IL values in patients with uveitis.a) IL-10, b) IL-6, c) IL-10/IL-6. The vertical axis represents IL concentration or, in the case of IL-10/IL-6, the IL-10/IL-6 ratio. Black dots represent data points from individual dates of paracentesis. The dashed line represents the assay’s threshold of sensitivity, which for IL-10 is 1.0 pg/ml and for IL-6 is 4.88 pg/mL.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3672178&req=5

pone-0065627-g003: Distribution of IL values in patients with uveitis.a) IL-10, b) IL-6, c) IL-10/IL-6. The vertical axis represents IL concentration or, in the case of IL-10/IL-6, the IL-10/IL-6 ratio. Black dots represent data points from individual dates of paracentesis. The dashed line represents the assay’s threshold of sensitivity, which for IL-10 is 1.0 pg/ml and for IL-6 is 4.88 pg/mL.

Mentions: Additionally, we analyzed each cytokine marker to see if a significant difference in the distribution of IL values exists between eyes with lymphoma and uveitis. In a rank-sum test, IL-10 values were significantly higher in eyes with lymphoma than uveitis (U = 7.0; two-tailed p = 0.004). Similarly, IL-10/IL-6 levels were significantly elevated in eyes with lymphoma (U = 6.0; two-tailed p = 0.003). Conversely, there was no significant difference in IL-6 levels between the lymphoma and uveitis groups (U = 15.0; two-tailed p = ns). The distribution of all available IL-10, IL-6, and IL-10/IL-6 values for each patient with lymphoma, including multiple data points from the same eye, is graphically depicted in Fig. 2a, Fig. 2b, and Fig. 2c, respectively. Similarly, the distribution of all available IL-10, IL-6, and IL-10/IL-6 levels in uveitis patients is represented in Fig. 3a, Fig. 3b, and Fig. 3c, respectively. However, the Mann-Whitney calculations above were based on the selected data points as outline in the Materials and Methods section.


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)

Distribution of IL values in patients with uveitis.a) IL-10, b) IL-6, c) IL-10/IL-6. The vertical axis represents IL concentration or, in the case of IL-10/IL-6, the IL-10/IL-6 ratio. Black dots represent data points from individual dates of paracentesis. The dashed line represents the assay’s threshold of sensitivity, which for IL-10 is 1.0 pg/ml and for IL-6 is 4.88 pg/mL.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065627-g003: Distribution of IL values in patients with uveitis.a) IL-10, b) IL-6, c) IL-10/IL-6. The vertical axis represents IL concentration or, in the case of IL-10/IL-6, the IL-10/IL-6 ratio. Black dots represent data points from individual dates of paracentesis. The dashed line represents the assay’s threshold of sensitivity, which for IL-10 is 1.0 pg/ml and for IL-6 is 4.88 pg/mL.
Mentions: Additionally, we analyzed each cytokine marker to see if a significant difference in the distribution of IL values exists between eyes with lymphoma and uveitis. In a rank-sum test, IL-10 values were significantly higher in eyes with lymphoma than uveitis (U = 7.0; two-tailed p = 0.004). Similarly, IL-10/IL-6 levels were significantly elevated in eyes with lymphoma (U = 6.0; two-tailed p = 0.003). Conversely, there was no significant difference in IL-6 levels between the lymphoma and uveitis groups (U = 15.0; two-tailed p = ns). The distribution of all available IL-10, IL-6, and IL-10/IL-6 values for each patient with lymphoma, including multiple data points from the same eye, is graphically depicted in Fig. 2a, Fig. 2b, and Fig. 2c, respectively. Similarly, the distribution of all available IL-10, IL-6, and IL-10/IL-6 levels in uveitis patients is represented in Fig. 3a, Fig. 3b, and Fig. 3c, respectively. However, the Mann-Whitney calculations above were based on the selected data points as outline in the Materials and Methods section.

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