Effect of Intravitreal Methotrexate and Rituximab on Interleukin-10 Levels in Aqueous Humor of Treated Eyes with Vitreoretinal Lymphoma

Harish Raja, Melissa R. Snyder, Patrick Bruce Johnston, Brian Patrick O'Neill, Juline N. Caraballo, Joseph G. Balsanek, Brian E. Peters, Paul A. Decker, Jose S Pulido

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere65627
JournalPLoS One
Volume8
Issue number6
DOIs
StatePublished - Jun 4 2013

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methotrexate
Aqueous Humor
interleukin-10
lymphoma
Methotrexate
Interleukin-10
Lymphoma
eyes
interleukin-6
Interleukin-6
Uveitis
water
cytokines
Interleukins
interleukins
Cytokines
Rituximab
diagnostic sensitivity
Sensitivity and Specificity
relapse

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Effect of Intravitreal Methotrexate and Rituximab on Interleukin-10 Levels in Aqueous Humor of Treated Eyes with Vitreoretinal Lymphoma. / Raja, Harish; Snyder, Melissa R.; Johnston, Patrick Bruce; O'Neill, Brian Patrick; Caraballo, Juline N.; Balsanek, Joseph G.; Peters, Brian E.; Decker, Paul A.; Pulido, Jose S.

In: PLoS One, Vol. 8, No. 6, e65627, 04.06.2013.

Research output: Contribution to journalArticle

Raja, Harish ; Snyder, Melissa R. ; Johnston, Patrick Bruce ; O'Neill, Brian Patrick ; Caraballo, Juline N. ; Balsanek, Joseph G. ; Peters, Brian E. ; Decker, Paul A. ; Pulido, Jose S. / Effect of Intravitreal Methotrexate and Rituximab on Interleukin-10 Levels in Aqueous Humor of Treated Eyes with Vitreoretinal Lymphoma. In: PLoS One. 2013 ; Vol. 8, No. 6.
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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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