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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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IL concentrations and timing of intraocular treatment in a patient with bilateral lymphoma (Case 10).a) IL-10, b) IL-6, c) IL-10/IL-6. The vertical axis represents IL levels. Red arrows indicate intraocular treatment in the right eye, and blue diamonds indicate intraocular treatment in the left eye.
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pone-0065627-g006: IL concentrations and timing of intraocular treatment in a patient with bilateral lymphoma (Case 10).a) IL-10, b) IL-6, c) IL-10/IL-6. The vertical axis represents IL levels. Red arrows indicate intraocular treatment in the right eye, and blue diamonds indicate intraocular treatment in the left eye.

Mentions: A 72-year-old woman, diagnosed with bilateral PVRL by PPV at an outside provider in September 2010, did not receive intraocular treatment prior to her first visit to our clinic in December 2010. Between February and May 2011, IL-10 levels increased markedly in both eyes. In May, the patient again presented to our clinic with worsening vision. Pars plana vitrectomy at that time confirmed PVRL, and intraocular MTX and RTX were administered intraoperatively. Also at this time, the patient was diagnosed with new CNS disease and subsequently underwent six cycles of systemic temozolomide, MTX and RTX with complete response of the CNS lymphoma. The patient underwent PPV in September 2011, followed by treatment with intraocular MTX and RTX in both eyes at her outside provider in November 2011. The patient developed active ocular disease in December 2011 but did not receive intraocular treatment by her provider due to intraocular pressure spike following injections. Interleukin-10, IL-6, and IL-10/IL-6 response to intravitreal treatment is displayed in graph form (Fig. 6a–c).


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)

IL concentrations and timing of intraocular treatment in a patient with bilateral lymphoma (Case 10).a) IL-10, b) IL-6, c) IL-10/IL-6. The vertical axis represents IL levels. Red arrows indicate intraocular treatment in the right eye, and blue diamonds indicate intraocular treatment in the left eye.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065627-g006: IL concentrations and timing of intraocular treatment in a patient with bilateral lymphoma (Case 10).a) IL-10, b) IL-6, c) IL-10/IL-6. The vertical axis represents IL levels. Red arrows indicate intraocular treatment in the right eye, and blue diamonds indicate intraocular treatment in the left eye.
Mentions: A 72-year-old woman, diagnosed with bilateral PVRL by PPV at an outside provider in September 2010, did not receive intraocular treatment prior to her first visit to our clinic in December 2010. Between February and May 2011, IL-10 levels increased markedly in both eyes. In May, the patient again presented to our clinic with worsening vision. Pars plana vitrectomy at that time confirmed PVRL, and intraocular MTX and RTX were administered intraoperatively. Also at this time, the patient was diagnosed with new CNS disease and subsequently underwent six cycles of systemic temozolomide, MTX and RTX with complete response of the CNS lymphoma. The patient underwent PPV in September 2011, followed by treatment with intraocular MTX and RTX in both eyes at her outside provider in November 2011. The patient developed active ocular disease in December 2011 but did not receive intraocular treatment by her provider due to intraocular pressure spike following injections. Interleukin-10, IL-6, and IL-10/IL-6 response to intravitreal treatment is displayed in graph form (Fig. 6a–c).

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