title: Effect of intravitreal methotrexate and rituximab on interleukin-10 levels in aqueous humor of treated eyes with vitreoretinal lymphoma.
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.
authors.affiliation: Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Harish
authors.initials: H
authors.lastname: Raja
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Snyder
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Johnston
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Neill
authors.forename: Juline N
authors.initials: JN
authors.lastname: Caraballo
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Balsanek
authors.forename: Brian E
authors.initials: BE
authors.lastname: Peters
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.forename: Jose S
authors.initials: JS
authors.lastname: Pulido
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism*; D002648:Child; D003937:Diagnosis, Differential; D005134:Eye Neoplasms / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D008223:Lymphoma / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D008875:Middle Aged; D000069283:Rituximab; D014605:Uveitis / Q000175:diagnosis / Q000378:metabolism; D014822:Vitreous Body
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D016753:Interleukin-10; D000069283:Rituximab; D008727:Methotrexate