Effect of intravitreal methotrexate and aqueous humor cytokine levels in refractory retinal vasculitis in Behcet disease

Abstract

PURPOSE: The purpose of this study was to demonstrate the effect of intravitreal methotrexate (MTX) in the treatment of refractory retinal vasculitis due to Behcet disease and to evaluate the changes in aqueous humor cytokines after intravitreal MTX.

METHODS: Seven eyes of seven patients with Behcet disease were assessed. Patients had unilaterally active retinal vasculitis that failed to respond to conventional treatment, together with a history of increased intraocular pressure or intolerance to corticosteroid administration. Intravitreal injection of 400 μg MTX was given monthly until visual acuity and intraocular inflammation were stable. Aqueous humor samples were obtained from the patients before MTX injection and from nine eyes during cataract surgery as a control group. Changes in visual acuity with the Early Treatment Diabetic Retinopathy Study Chart, fluorescein angiographic leakage, and ocular complications associated with intravitreal injection were analyzed. Aqueous humor cytokine levels were measured by proteomic analysis using a multianalyte biochip array system.

RESULTS: Visual acuity improved significantly during a mean follow-up of 24.9 ± 8.2 weeks with a mean improvement from baseline visual acuity of 3.3 ± 2.6 lines after a mean of 4.3 ± 1.0 injections. Six patients (85.7%) showed an increase in visual acuity by 3 or more lines, and 4 patients exhibited a decrease in fluorescein leakage. Change in intraocular pressure after intravitreal MTX was not significant. The aqueous humor levels of interleukin (IL) -6, IL-8, vascular endothelial growth factor, and monocyte chemotactic protein 1 were significantly higher in patients with Behcet disease compared with controls. The levels of IL-6 and IL-8 were significantly reduced at 4 weeks after intravitreal MTX, whereas those of vascular endothelial growth factor and monocyte chemotactic protein 1 were not reduced.

CONCLUSION: Increased intraocular levels of IL-6, IL-8, vascular endothelial growth factor, and monocyte chemotactic protein 1 may be responsible for refractory retinal vasculitis in Behcet disease. Intravitreal MTX was associated with a significant reduction of IL-6 and IL-8 levels and was effective and well tolerated even in steroid responders with refractory retinal vasculitis due to Behcet disease.