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Ryo Kurobe, Yoshio Hirano, Shuntaro Ogura, Tsutomu Yasukawa, Yuichiro Ogura Department of Ophthalmology & Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanCorrespondence: Yoshio HiranoDepartment of Ophthalmology & Visual Science, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, JapanTel +81-52-8538251Fax +81-52-8419490Email yoshio.hirano@gmail.comPurpose: To investigate whether ultra-widefield (UWF) swept-source optical coherence tomography (SSOCT) system (Silverstone, Nikon Healthcare Japan, Inc, Tokyo, Japan) can obtain OCT images of peripheral retinal degenerations and breaks.Methods: Thirty-seven eyes of 31 consecutive cases (16 men, 15 women; mean age 51 years) who had peripheral retinal degenerations and underwent a UWF-SSOCT imaging were enrolled. The convenience and usefulness were investigated.Results: In all eyes, OCT images were capable and interpretable without any special techniques. The respective findings on OCT were retinal degeneration in 16 eyes: lattice degeneration in 8 eyes, paving stone degeneration in 4 eyes, and unclassified in 4 eyes, retinal tear in 12 eyes, and retinal hole in 9 eyes. The respective locations of the retinal degenerations or breaks were the posterior pole in 0 eyes, mid-periphery in 23 eyes, and far-periphery in 14 eyes. Fifteen eyes had a rhegmatogenous retinal detachment (RRD), one of which was preoperative and the other 14 eyes were postoperative. A buckle was placed in 8 eyes for RRD repair. Subretinal fluid was observed in 9 of 21 eyes with retinal break or retinal hole. Vitreoretinal traction was observed in 10 of 27 eyes without a history of vitrectomy. Inverted artifacts on OCT images were observed in 20 of 37 eyes, which were not related to the location or axial length, but were supposed to be due to the limited scan depth.Conclusion: The UWF-SSOCT system could capture the OCT images of peripheral retinal degenerations and breaks without any special technique.Keywords: ultra-widefield, swept-source optical coherence tomography, peripheral retinal degeneration, retinal break, rhegmatogenous retinal detachment

Yuya Esaki, Yoshio Hirano, Ryo Kurobe, Yusuke Yasuda, Taneto Tomiyasu, Norihiro Suzuki, Tsutomu Yasukawa, Munenori Yoshida, Yuichiro Ogura Department of Ophthalmology & Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanCorrespondence: Yoshio HiranoDepartment of Ophthalmology & Visual Science, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya 467-8601, JapanTel +81 52-8538251Fax +81 52-8419490Email yoshio.hirano@gmail.comPurpose: To classify microaneurysms (MAs) and investigate the relationships with retinal edema in eyes with branch retinal vein occlusion (BRVO).Study Design: Retrospective, observational, consecutive case series.Methods: Eyes with MAs due to BRVO that underwent optical coherence tomography angiography (OCTA) were enrolled. MAs on OCTA images were morphologically classified into six types: focal bulge, saccular, fusiform, mixed (saccular/fusiform), pedunculated, and irregular. The frequency, size, location, and relationships with retinal edema also were investigated.Results: Twenty-four eyes of 23 patients (12 men, 11 women; mean age, 68.0 years) were enrolled. A total of 244 MAs were detected on the OCTA images. The focal bulge and saccular types accounted for over 70% of all MAs. Smaller MAs such as the focal bulge or saccular type also were detected both at the edge of the nonperfused areas (NPAs) and in collateral vessels. In contrast, larger MAs such as the pedunculated or irregular types tended to form at the edges of the NPAs. Older age, the presence of MAs in the collateral vessels, and the absence of pedunculated type were independent predictive factors for retinal edema but not the MA size, or presence in the retinal deep capillary plexus. After treatment, the mean retinal thickness decreased significantly, but the mean MA size remained unchanged.Conclusion: OCTA enables morphologic classification, three-dimensional analysis, and investigation of the longitudinal changes of MAs with noninvasive volumetric quantification, leading to a better understanding of the pathology of MAs in eyes with BRVO.Keywords: microaneurysm, morphology, macular edema, optical coherence tomography angiography, branch retinal vein occlusion

A quantitative understanding of the Li distribution inside all-solid-state Li-ion batteries is important for improving the performance of batteries. We constructed a time-of-flight (TOF) elastic recoil detection analysis (ERDA) system for operando measurements of thin-film Li-ion batteries. The TOF-ERDA measurement provides elementally resolved spectra with a depth resolution much higher than that of conventional stopper-foil ERDA. The Li depth profiles in a cathode film and solid electrolyte were obtained quantitatively to a depth of 100 nm using a 9-MeV Cu ion beam with reflection geometry. In this study, we conducted TOF-ERDA for a thin-film battery having a cathode made from LiCoO2, an oxide-based solid electrolyte [lithium aluminum titanium phosphate (LATP)], and an anode made from Fe2(MoO4)3 to demonstrate the ability of the measurement system and reveal the Li distribution near the interface with improved resolution. The depth resolution at the interface (30 nm from the surface) was estimated to be 12–14 nm. We quantitatively obtained the Li density in the LiCoO2 cathode and the variation in the Li distribution around the LiCoO2/LATP interface and inside the LATP electrolyte upon charging/discharging. TOF-ERDA is thus a powerful tool for the high-resolution quantitative depth analysis of Li in thin-film batteries in operando. [ABSTRACT FROM AUTHOR]

Tetsuyuki Suetsugu,1 Tsutomu Yasukawa,2 Akiyoshi Uemura,1,2 Masahiko Higaki,1 Yuichiro Ogura2 1Department of Ophthalmology, Jyuzen Kinen Hospital, Hamamatsu, Shizuoka, Japan; 2Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan Abstract: We experienced a case of sympathetic ophthalmia in a fellow eye after vitrectomy for subretinal hemorrhage related to polypoidal choroidal vasculopathy. A 60-year-old male consulted us for polypoidal choroidal vasculopathy with subretinal hemorrhage in his left eye. The recurrence of massive subretinal hemorrhage refractory to repeated pars plana vitrectomies leads to phthisis bulbi. Two months later, multiple serous retinal detachments were observed in his right eye. Positive human leukocyte antigen-DR4 and the uveitis were helpful in distinguishing between sympathetic ophthalmia and age-related macular degeneration. High-dose pulse intravenous steroid contributed to recovery of visual acuity after resolution of serous retinal detachment. Keywords: sympathetic ophthalmia, polypoidal choroidal vasculopathy, vitrectomy, vitreous hemorrhage, uveitis

Mihoko Kawamura, Yoshio Hirano, Munenori Yoshida, Takeshi Mizutani, Kazuhiko Sugitani, Tsutomu Yasukawa, Yuichiro Ogura Department of Ophthalmology & Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Purpose: The aim of this study is to report the 6-month results after one intravitreal ranibizumab (IVR) injection followed by pro re nata dosing for macular edema (ME) after branch retinal vein occlusion.Patients and methods: The inclusion criteria included a minimal patient age of 18 years, 20 letters or more best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] score, 77 letters or less), and central retinal thickness (CRT) of 250 microns or more. The primary outcome measure was the mean BCVA change from baseline at month 6; the secondary outcomes were mean changes in CRT, residual ME, and microaneurysm formation.Results: Twenty patients were enrolled from March 2014 through October 2016 at Nagoya City University Hospital. The baseline mean ETDRS letters and CRT were 63.1 and 500 microns, respectively; mean time from symptom onset to initial therapy was 1.80 months; and mean ETDRS gain and CRT reduction were 15.2 letters and 230 microns, respectively. The percentages of patients with Snellen equivalent BCVAs of 20/40 (70 ETDRS letters) or better and 20/20 (85 ETDRS letters) were 90% and 15%, respectively. Residual ME and microaneurysms were observed in 85% and 35% of patients. Microaneurysm formation was associated with delayed initial therapy.Conclusion: Prompt initiation of IVR injection provided a better visual prognosis at month 6 and suppressed the microaneurysm formation. Keywords: branch retinal vein occlusion, macular edema, microaneurysm, ranibizumab, prompt treatment

Amelie Pielen,1,2 W Lloyd Clark,3 David S Boyer,4 Yuichiro Ogura,5 Frank G Holz,6 Jean-Francois Korobelnik,7,8 Brigitte Stemper,9,10 Friedrich Asmus,9 Kay D Rittenhouse,11 Christiane Ahlers,9 Robert Vitti,12 Namrata Saroj,12 Oliver Zeitz,9,13,14 Julia A Haller15 On behalf of the COPERNICUS and GALILEO study group 1Eye Center, University Hospital Freiburg, Eye Hospital, Freiburg, 2Hannover Medical School, University Eye Hospital, Hannover, Germany; 3Palmetto Retina Center, Columbia, SC, USA; 4Retina-Vitreous Associates Medical Group, Beverly Hills, CA, USA; 5Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 6Department of Ophthalmology, University of Bonn, Bonn, Germany; 7Service d’ophtalmologie, CHU de Bordeaux, 8Service d’ophtalmologie, University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team LEHA, UMR 1219, Bordeaux, France; 9Bayer AG, Berlin, 10Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany; 11Bayer US LLC, Whippany, NJ, 12Regeneron Pharmaceuticals, Tarrytown, NY, USA; 13AKH Eye Clinic, Braunschweig, 14Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Augenheilkunde, Hamburg, Germany; 15Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA Objectives: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. Patients and methods: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. Results: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in

Tetsuyuki Suetsugu,1,2 Aki Kato,1 Munenori Yoshida,1 Tsutomu Yasukawa,1 Akiko Nishiwaki,1,3 Norio Hasegawa,1 Hideaki Usui,1 Yuichiro Ogura1 1Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, 2Department of Ophthalmology, General Kamiiida Daiichi Hospital, 3Nishiwaki Eye Clinic, Nagoya, Aichi, Japan Purpose: We aimed to evaluate the prevalence of abnormal peripheral fundus autofluorescence (FAF) in wet age-related macular degeneration (AMD) using wide-field imaging instrument. Patients and methods: A retrospective, case-controlled study involving 66 eyes of 46 Japanese wet AMD patients and 32 eyes of 20 control patients was performed. Wide-field FAF images were obtained for typical AMD (37 eyes/28 patients), polypoidal choroidal vasculopathy (PCV) (22 eyes/20 patients), and retinal angiomatous proliferation (RAP) (seven eyes/four patients). Two masked ophthalmologists independently graded the images for mottled, granular, and nummular patterns. Main outcome measures were abnormal peripheral FAF frequencies and relative risks by disease subgroups and treatments. Results: Abnormal peripheral FAF patterns were found in 51.5% of wet AMD eyes compared with 18.8% of control eyes (P

Munehiro Kitada,1,2 Yoshio Ogura,2 Daisuke Koya1,2 1Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, 2Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan Abstract: Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic nephropathy. Keywords: diabetic nephropathy, rodent model, albuminuria, mesangial matrix expansion, tubulointerstitial fibrosis

Norihiro Suzuki, Yoshio Hirano, Miyu Ichida, Taneto Tomiyasu, Yuya Esaki, Tsutomu Yasukawa, Yuichiro Ogura Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Purpose: The aim of this study was to evaluate the usefulness of preoperative optical coherence tomography (OCT) findings in patients with macular epiretinal membrane (ERM) for the planning of surgical strategy.Patients and methods: One hundred twenty-three eyes of 121 patients (49 men, 72 women; mean age, 66 years) with an idiopathic ERM were enrolled. All patients underwent an ophthalmic examination including indirect ophthalmoscopy and OCT (Cirrus HD-OCT 4000 and/or 5000). OCT images obtained using model 4000 were transferred to the model 5000 system for vitreoretinal interface (VRI) analysis. The retinal thickness in each area, occurrence rate, and locations of the edges and partial detachments of the ERMs were evaluated using OCT.Results: OCT detected identifiable edges in 61 (50%) eyes and partial detachments in 116 (94%) of the 123 eyes. The edges and partial detachments were seen more frequently in the inferior macula. VRI analysis also detected the edges and partial detachments. Excluding the central area, the superior quadrant was the thickest in patients with an ERM. Conclusion: Preoperatively acquired OCT images are useful for planning surgical strategies and performing the surgeries smoothly. Keywords: optical coherence tomography, epiretinal membrane, surgical strategy, membrane edges

Masayo Kimura, Miho Nozaki, Munenori Yoshida, Yuichiro Ogura Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Purpose: Optical coherence tomography angiography (OCTA) is a newly developed technology which allows us to reconstruct the three-dimensional chorioretinal vasculature without dye injection. OCTA is a noninvasive, rapid, and reproducible method to assess retinal ischemia. However, one of its limitations is the size of scanning area. A novel yet simple technique to expand the scan length on optical coherence tomography has been reported as an extended field imaging (EFI) technique. It involves imaging the posterior pole through trial frames fitted with a +20 diopter lens. We applied this technique to OCTA to evaluate retinal vein occlusion.Materials and methods: Ten eyes of nine patients with retinal vein occlusion were studied. The average age was 69.0 years (range: 49–93 years). We obtained OCTA images by using RTVue XR Avanti OCT with AngioVue®. The images of OCTA with scan size of 8×8 mm were obtained with and without EFI, and then they were compared.Results: OCTA with EFI technique was performed successfully in all eyes. The nonperfusion area was well defined in superficial capillary plexus layer. The images with EFI were able to capture the larger area of the fundus by an average of 188.5% than those without EFI. The posterior pole inside the vascular arcade was well covered with this technique. The area of the fundus imaged by OCTA with EFI technique was even larger than that of fluorescein angio­graphy using Heidelberg Retina Angiograph 2, which captured a 30° field.Conclusion: Our results suggested that OCTA with EFI technique is very useful to evaluate the retinal ischemia in retinal vein occlusion. Keywords: optical coherence tomography angiography, OCTA, retinal vein occlusion, RVO, nonperfusion area, wide-field imaging, extended field imaging, EFI

Kazuhito Nakamura,1,2 Norio Watanabe,1 Hiroshi Ohkawa,3 Michiyasu Ando,4 Yukio Ogura,5 Sumito Funabiki,6 Akito Kume,7 Kimihiko Urano,1 Takashi Osada,1 Keiko Yamamura1 1Department of Clinical Pharmacy, School of Pharmacy, Aichi Gakuin University, 2Koyo Pharmacy, 3Ohkawa Clinic, 4Ando Clinic, 5Total Support Clinic, 6Funabiki Clinic, 7Kume Clinic, Aichi, Japan Background: In this study, we evaluated changes in functioning and caregiver burden in Alzheimer’s disease (AD) patients after a dosage increase that was made based on pharmacists’ evaluation of AD patients’ behavior in daily life. Methods: Pharmacists used a checklist, a questionnaire, and the Repetitive Saliva ­Swallowing Test (RSST) to gather data on the daily life of AD patients taking donepezil 5 mg/day and their caregivers. In 27 cases, pharmacists suggested a dosage change to 10 mg/day to AD patients’ physicians. Pharmacists then evaluated these patients for 16 weeks after the increase to determine changes in functional assessment staging, caregiver burden, and swallowing function. Results: During the 16-week study, 20 of the 27 patients showed at least one-stage improvement in relation to the five assessed aspects of daily life (time/place, speech, bathing, dressing, and toileting). The mean score for caregiver burden due to personal strain was significantly lower after the dosage increase than before (5.15±3.76 at baseline; from 3.89±3.42 at week 4 to 3.59±3.90 at week 16; P

Satoshi Ota, Miho Nozaki, Shuichiro Hirahara, Tomoaki Hattori, Munenori Yoshida, Yuichiro Ogura Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Abstract: We experienced a case of retinopathy of prematurity that was successfully treated with pattern scan laser. Pattern scan laser treatment should be considered as one treatment option for Retinopathy of Prematurity. Keywords: retinopathy of prematurity, PASCAL, slit-lamp delivery