Safety and Efficacy of Ranibizumab and Luseogliflozin Combination Therapy in Patients with Diabetic Macular Edema: Protocol for a Multicenter, Open-Label Randomized Controlled Trial.

INTRODUCTION: Diabetic macular edema (DME) threatens daily life activities such as reading and driving and reduces the patients' quality-of-life. Recently, anti-vascular endothelial growth factor (VEGF) agents have become a first-line therapy in DME. However, therapy with anti-VEGF agents has several problems: repeated invasive injections are required; medical costs are high; and a certain proportion of patients with DME are resistant to treatment with anti-VEGF agents. While sodium-glucose co-transporter 2 (SGLT2) inhibitors have been widely used for the treatment of type 2 diabetes mellitus (T2DM), the effects of a combination therapy with anti-VEGF agent and SGLT2 inhibitor on DME are not yet known. METHODS: This study enrolls subjects with T2DM and DME, randomizes them into either a study agent treatment group (treated with ranibizumab as anti-VEGF agent and luseogliflozin as SGLT2 inhibitor) or a control group (treated with ranibizumab and glimepiride), and observes the subjects for 52 weeks after initiation of treatment. Planned outcomes: The primary endpoint is intergroup difference in the number of intravitreal anti-VEGF injections to the study eye from baseline to week 48. Secondary and exploratory endpoints include safety and ophthalmologic and internal medical clinical parameters. REGISTRATION: This study is registered at the University Hospital Medical Information Network Clinical Trial Registry (UMIN000033961) and Japan Registry of Clinical Trials (jRCTs031180210).

Severe macular edema induced by pioglitazone in a patient with diabetic retinopathy: a case study.

We report a case of severe diabetic macular edema (DME) that developed after pioglitazone was used by a patient with proliferative diabetic retinopathy. A 30-year-old woman with poorly controlled type 2 diabetes mellitus visited our clinic in 2004. She had moderate pre-proliferative diabetic retinopathy OU. Because of the rapid progression of the diabetic retinopathy, she received pan-retinal photocoagulation in both eyes. Two weeks before using pioglitazone, her visual acuity was 0.9 OD and 0.7 OS. On October 2007, pioglitazone was prescribed by her internist because of poorly controlled blood glucose level. Two weeks later, her body weight increased, and her face became edematous. Her visual acuity decreased to 0.5 OU, and ophthlamoscopy showed severe DME in both eyes. Two weeks after stopping pioglitazone, her visual acuity improved to 0.8 OD and 0.5 OS, but the DME was still severe in the optical coherence tomographic images. Then, one half the usual dose (25 mg) of spironolactone, a diuretic, was given and her macular edema was resolved. Her final visual acuity improved to 0.9 OD and 0.7 OS. We recommend that when a patient taking pioglitazone complains of decreased vision, the physician should promptly consult an ophthalmologist.

Pattern visual evoked potentials in Japanese patients with multiple sclerosis without history of visual pathway involvement.

A delay of the peak latency of the pattern visual evoked cortical potentials (pVEP) is accepted as one of the paraclinical evidence for a diagnosis of multiple sclerosis (MS). The purpose of this study was to evaluate the pVEPs in Japanese patients with MS without a history of visual pathway involvement. We studied the medical records of 29 MS patients without any history of visual pathway involvement, and with visual acuity correctable to > or = 20/20. The Goldmann visual fields, pupillary light reflexes, and optic disks were normal in all. pVEPs elicited by 3 rev/s (transient) and 12 rev/s (steady-state) were recorded from the MS patients and compared with those recorded from normal subjects. The latency of the P100 component of the transient pVEPs was significantly prolonged in 9/29 (31%) MS patients. A phase lag in the steady-state pVEPs was found in 6/29 (21%) MS patients, and the mean amplitude was significantly smaller. The incidence of cases with abnormal pVEPs is lower than that reported from Europe and United State. This difference is possibly due to racial differences, and the use of different criteria for diagnosing optic neuritis.