Intravitreal Management of Ocular Lymphoma Should Use Adjusted Drug Concentrations Not Fixed Dosages

Abstract: Most vitreo-retinal lymphoma are rare high-grade B cell lymphoma of immune privileged sites. As there is considerable heterogeneity, the clinical management hampers the optimisation of treatment protocols. While most patients respond to a fixed intravitreal dose of 400 µg, corneal toxicity is seen in 20 to 50% of patients when administered at short intervals under 1 month. Local recurrence of disease is also seen in about 20% of patients. While systemic chemotherapy is weight or surface dependent, most intraocular treatment protocols follow a fixed dose regimen. By analysing existing published data, we show that both experimentally and clinically, the elimination of intraocular methotrexate follows a first order kinetic model. Starting with an initial concentration of 100 µg/ml of vitreous volume, in most instances, a therapeutic level is present for 3 to 5 days. Systemic therapy alone does not achieve these sustained ocular levels. Furthermore, with vitreous volumes which can vary between 3 and 10 ml, using a fixed Mtx dose can either lead to increased risk of toxicity or under treatment. Future treatment protocols should make use of fixed initial concentrations rather than a fixed dose, thus allowing a better comparison of outcomes. Formulas to adjust the concentration of Mtx to be delivered in a fixed volume are provided.