Kiichiro Okano

Health- and vision-related quality of life in patients receiving infliximab therapy for Behçet uveitis

Objective To evaluate the changes in health-related and vision-related quality of life (HR-QoL and VR-QoL) in patients with Behçet uveitis (BU) receiving infliximab therapy. Methods Twenty patients with recurrent BU attacks were enrolled. All patients were treated with infliximab. We evaluated the mean number of uveitis attacks and the mean score of extraocular manifestations by Behçet disease current activity form (BDCAF) during the 6 months before and the 6 and 12 months after initiation of infliximab. The EuroQol-5D questionnaire (EQ-5D) and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were self-administered in all patients before treatment and, 6 and 12 months after treatment. Patients’ pre- and post-treatment EQ-5D and NEI VFQ-25 scores were compared. Results By the 6- and 12-month follow-up, the frequency of uveitis attacks and the BDCAF scores was significantly decreased compared with the 6 months before starting infliximab (p<0.0001). Fully completed questionnaires were received from all patients. Infliximab therapy was associated with a significant improvement of the EQ-5D (p<0.0001), NEI VFQ-25 composite score (p=0.0001), general health score (p=0.0001) and mental health score (p=0.0001). This result shows a significant decrease in inflammatory activity of the disease and consequently improvement in HR-QoL and VR-QoL scores with a rising response pattern in all dimensions. Conclusions Relief of uveitis attacks and extraocular manifestations by infliximab therapy significantly improved the HR-QoL and VR-QoL in patients with BU.

Three-year visual outcomes of intravitreal ranibizumab with or without photodynamic therapy for polypoidal choroidal vasculopathy

To compare 3‐year visual outcomes after intravitreal ranibizumab (IVR) monotherapy and combination therapy of photodynamic therapy (PDT) with IVR for polypoidal choroidal vasculopathy (PCV).

Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration.

BackgroundThough accumulating evidence suggests that microglia, resident macrophages in the retina, and bone marrow-derived macrophages can cause retinal inflammation which accelerates photoreceptor cell death, the details of how these cells are activated during retinal degeneration (RD) remain uncertain. Therefore, it is important to clarify which cells play a dominant role in fueling retinal inflammation. However, distinguishing between microglia and macrophages is difficult using conventional techniques such as cell markers (e.g., Iba-1). Recently, two mouse models for visualizing chemokine receptors were established, Cx3cr1GFP/GFP and Ccr2RFP/RFP mice. As Cx3cr1 is expressed in microglia and Ccr2 is reportedly expressed in activated macrophages, these mice have the potential to distinguish microglia and macrophages, yielding novel information about the activation of these inflammatory cells and their individual roles in retinal inflammation.MethodsIn this study, c-mer proto-oncogene tyrosine kinase (Mertk)−/− mice, which show photoreceptor cell death due to defective retinal pigment epithelium phagocytosis, were employed as an animal model of RD. Mertk−/−Cx3cr1GFP/+Ccr2RFP/+ mice were established by breeding Mertk−/−, Cx3cr1GFP/GFP, and Ccr2RFP/RFP mice. The retinal morphology and pattern of inflammatory cell activation and invasion of Mertk−/−Cx3cr1GFP/+Ccr2RFP/+ mice were evaluated using retina and retinal pigment epithelium (RPE) flat mounts, retinal sections, and flow cytometry.ResultsFour-week-old Mertk−/−Cx3cr1GFP/+Ccr2RFP/+ mice showed Cx3cr1-GFP-positive microglia in the inner retina. Cx3cr1-GFP and Ccr2-RFP dual positive activated microglia were observed in the outer retina and subretinal space of 6- and 8-week-old animals. Ccr2-RFP single positive bone marrow-derived macrophages were observed to migrate into the retina of Mertk−/−Cx3cr1GFP/+Ccr2RFP/+ mice. These invading cells were still observed in the subretinal space in 18-week-old animals.ConclusionsCx3cr1-GFP-positive microglia and Ccr2-RFP-positive macrophages were distinguishable in the retinas of Mertk−/−Cx3cr1GFP/+Ccr2RFP/+ mice. In addition, Ccr2 expression in Cx3cr1 positive microglia is a feature of microglial activation in RD. Mertk−/−Cx3cr1GFP/+Ccr2RFP/+ mice enabled observation of microglial activation over time during RD and may be useful for developing inflammation-targeted treatment strategies for RD in the future.