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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 9).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-g005: IL concentrations and timing of intraocular treatment in a patient with bilateral lymphoma (Case 9).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 68-year-old woman with history of breast cancer and CNS lymphoma, diagnosed in July 2009, underwent induction chemotherapy with high-dose MTX to complete remission, followed by consolidation with BEAM conditioning and autologous SCT in January 2010. In December 2009, she was seen by an outside provider for ocular symptoms and treated with corticosteroids for presumed optic neuritis. Upon presenting to us in January 2010, the patient was clinically diagnosed with vitreoretinal lymphoma and initiated on maintenance intraocular MTX and RTX for bilateral disease. Pars plana vitrectomy in the right eye in February 2011 confirmed the diagnosis of diffuse large B cell lymphoma. The IL-10 level in the right eye was markedly elevated at the time of PPV and minimally elevated in the left eye later that month. While receiving intraocular treatment, there was a steady decline in IL-10 to undetectable levels by April 2011 in both eyes. Incidentally, after receiving an intraocular injection in February, the patient developed a self-resolving post-injection sterile endophthalmitis in the left eye. Interleukin-10, IL-6, and IL-10/IL-6 response to intravitreal treatment is displayed in graph form (Fig. 5a–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 9).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-g005: IL concentrations and timing of intraocular treatment in a patient with bilateral lymphoma (Case 9).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 68-year-old woman with history of breast cancer and CNS lymphoma, diagnosed in July 2009, underwent induction chemotherapy with high-dose MTX to complete remission, followed by consolidation with BEAM conditioning and autologous SCT in January 2010. In December 2009, she was seen by an outside provider for ocular symptoms and treated with corticosteroids for presumed optic neuritis. Upon presenting to us in January 2010, the patient was clinically diagnosed with vitreoretinal lymphoma and initiated on maintenance intraocular MTX and RTX for bilateral disease. Pars plana vitrectomy in the right eye in February 2011 confirmed the diagnosis of diffuse large B cell lymphoma. The IL-10 level in the right eye was markedly elevated at the time of PPV and minimally elevated in the left eye later that month. While receiving intraocular treatment, there was a steady decline in IL-10 to undetectable levels by April 2011 in both eyes. Incidentally, after receiving an intraocular injection in February, the patient developed a self-resolving post-injection sterile endophthalmitis in the left eye. Interleukin-10, IL-6, and IL-10/IL-6 response to intravitreal treatment is displayed in graph form (Fig. 5a–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