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Shigeto Maekawa,1 Kota Sato,1,2 Taiki Kokubun,1 Noriko Himori,1,3 Takeshi Yabana,1 Michiko Ohno-Oishi,1 Ge Shi,1 Kazuko Omodaka,1,4 Toru Nakazawa1,2,4– 6 1Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 2Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 3Department of Aging Vision Healthcare, Tohoku University Graduate School of Biomedical Engineering, Sendai, Miyagi, Japan; 4Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 5Collaborative Program for Ophthalmic Drug Discovery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 6Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Miyagi, JapanCorrespondence: Toru Nakazawa, Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, Miyagi, 980-8574, Japan, Tel +81-22-717-7294, Fax +81-22-717-7298, Email ntoru@oph.med.tohoku.ac.jpPurpose: To investigate the effect of plant-derived antioxidant compounds, identified with primary culture screening, on retinal ganglion cell (RGC) survival in mice under excitotoxic conditions. Additionally, to determine the effect of these compounds on the involvement of calpain inactivation.Materials and Methods: Plant-derived antioxidant compounds including hesperidin, crocetin, and Tamarindus indica were administrated orally to C57BL/6J mice. The levels of lipid oxidation and calpain activation were assessed with a TBARS assay and western blotting. RGC survival was evaluated with a TUNEL assay and RBPMS immunostaining after intravitreal injection of NMDA.Results: Plant-derived antioxidant compounds significantly ameliorated the increase in the level of MDA in the retinas after NMDA injury. Cleaved α-fodrin fragments were detected in the NMDA-injured retinas, and these fragments were significantly lower in mice that received the plant-derived antioxidant compounds. The plant-derived antioxidants also ameliorated increases in TUNEL-positive cells and RGC death after NMDA injection.Conclusion: These results indicate that oral administration of plant-derived antioxidant compounds such as hesperidin, crocetin, and Tamarindus indica suppressed RGC death. This oral supplementation decreased lipid oxidation and excessive calpain activation in NMDA-injured retinas. Thus, our newly developed antioxidant supplement has a potential role in neuroprotective treatment for retinal diseases, such as glaucoma.Keywords: plant-derived antioxidant compounds, oxidative stress, retinal ganglion cells, glaucoma

Noriko Himori,1 Maki Inoue Yanagimachi,1 Kazuko Omodaka,1,2 Yukihiro Shiga,1 Satoru Tsuda,1 Hiroshi Kunikata,1,3 Toru Nakazawa1– 4 1Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, Japan; 3Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Japan; 4Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanCorrespondence: Toru NakazawaDepartment of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho Aoba-ku, Sendai, Miyagi, 980-8574, JapanTel +81-22-717-7294Fax +81-22-717-7298Email ntoru@oph.med.tohoku.ac.jpPurpose: Oxidative stress may be a risk factor for glaucoma, and many previous reports have suggested that antioxidants could be a promising treatment. Here, we investigated the effects of a novel supplement containing three food-derived antioxidants (hesperidin, crocetin, and Tamarindus indica) on markers of oxidative stress in patients with glaucoma.Patients and Methods: This study had a prospective, single arm design. Thirty Japanese glaucoma patients were recruited and given 4 tablets with ample water twice a day for 8 weeks. The treatment was stopped, and the subjects were followed for an additional 8 weeks. We measured biological antioxidant potential (BAP) with a free radical analyzer. We also measured urinary 8-hydroxy-2ʹ-deoxyguanosine (8-OHdG; a marker of oxidative DNA damage). Clinical laboratory data were measured in venous blood samples. Clinical parameters were also recorded. Comparisons used a one-way analysis of variance (ANOVA) followed by Dunnett’s test.Results: The 8-OHdG level was not reduced. We also divided the patients into groups with high or low oxidative stress. In patients with relatively high oxidative stress, the 8-OHdG level was significantly reduced at weeks 4, 8, 12, and 16 (P < 0.001, P < 0.01, P < 0.01, P < 0.01), and BAP was significantly elevated at weeks 8 and 12 (P = 0.03, P = 0.04). In patients with relatively low oxidative stress, the 8-OHdG level was not significantly reduced during supplement intake but was significantly elevated at weeks 12 and 16 (P =0.03, P = 0.04), while BAP was not significantly elevated.Conclusion: An 8-week oral course of antioxidant supplementation was effective in patients with a high oxidative stress level. Dietary supplementation could hold promise in the treatment of systemic oxidative stress-related diseases.Keywords: oxidative stress, supplement, glaucoma, 8-OHdG

Katsuaki Ogushi,1,* Makoto Chuma,1,* Haruki Uojima,2 Hisashi Hidaka,2 Kazushi Numata,1 Satoshi Kobayashi,3 Shunji Hirose,4 Nobuhiro Hattori,5 Tomoaki Fujikawa,6 Takahide Nakazawa,2 Naohisa Wada,2 Shuitirou Iwasaki,2 Taito Fukushima,3 Yusuke Sano,3 Makoto Ueno,3 Kuniyuki Kawano,3 Kota Tsuruya,4 Masako Shomura,4 Tsunamasa Watanabe,5 Kotaro Matsunaga,5 Yosuke Kunishi,7 Yusuke Saigusa,8 Kuniyasu Irie,9 Shogo Iwabuchi,6 Makoto Kako,10 Manabu Morimoto,3 Tatehiro Kagawa,4 Katsuaki Tanaka,11 Shin Maeda9 1Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan; 2Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan; 3Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan; 4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan; 6Department of Gastroenterology, Shonan Fujisawa General Hospital, Fujisawa, Japan; 7Department of Gastroenterology, Kanagawa Prefectural Ashigarakami Hospital, Kanagawa, Japan; 8Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 9Department of Gastroenterology, Yokohama City University Hospital, Yokohama, Japan; 10Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Japan; 11Gastroenterology Division, Hadano Red Cross Hospital, Hadano, Japan*These authors contributed equally to this workCorrespondence: Makoto Chuma Gastroenterological CenterYokohama City University Medical Center, 4-57 Urafune-Cho, Minami-Ku, Yokohama, Kanagawa 2320024, JapanTel +81 45 261 5656Fax +81 45 253 9955Email chuma@yokohama-cu.ac.jpPurpose: To assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC).Methods: Patients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines.Results: Baseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P < 0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥ 0.7 vs < 0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5– 7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment.Conclusion: Lenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.Keywords: lenvatinib, tyrosine kinase inhibitor, hepatocellular carcinoma, Child-Pugh, adverse events, overall survival

Misuzu Takahashi,1 Hiroshi Kunikata,2,3 Keiichi Kato,1 Ayako Kawakami,1 Toru Nakazawa2–5 1Kato Eye Clinic, Taiwa-cho, Japan; 2Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan; 3Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Japan; 4Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 5Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, JapanCorrespondence: Keiichi Kato Kato Eye Clinic 2-8-10, Yoshioka-Higashi, Taiwa-cho, Kurokawa-gun, Miyagi 981-3627, JapanTel +81 22 347 1682Fax +81 22 347 1683Email eye@kato-ganka.comPurpose: To identify new types of clinical findings that could be used to diagnose and treat non-organic visual loss (NOVL).Methods: This study retrospectively examined the records of 191 patients diagnosed with NOVL at the Kato Eye Clinic. Clinical characteristics, including uncorrected visual acuity (UCVA) and complaints of vision loss, were compared in 125 of 191 patients with NOVL and control subjects with organic refractive errors, identified during annual school health checks. If available, familial background data for the NOVL patients were compared with data from a mass population study. Familial background data included the presence of siblings, and whether the mother worked outside the home.Results: Patients with NOVL were more likely to be younger and female (P=0.02, and P

Orie Nakamura,1 Satoru Moritoh,1,2 Kota Sato,1,3 Shigeto Maekawa,1 Namie Murayama,1 Noriko Himori,1 Kazuko Omodaka,1,3 Tetsuya Sogon,4 Toru Nakazawa1–3,5 1Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan; 2Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Miyagi, Japan; 3Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Miyagi, Japan; 4R&D Department, Wakasa Seikatsu Co., Ltd., Kyoto, Japan; 5Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan Purpose: To investigate the effect of bilberry extract anthocyanins on retinal ganglion cell (RGC) survival after optic nerve crush. Additionally, to determine details of the mechanism of the neuroprotective effect of bilberry extract anthocyanins and the involvement of endoplasmic reticulum stress suppression in the mouse retina.Materials and methods: Anthocyanins in bilberry extract (100 mg/kg/day or 500 mg/kg/day) were administrated orally to C57BL/6J mice. The expression levels of various molecular chaperones were assessed with quantitative reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry. RGC survival was evaluated by measuring the gene expression of RGC markers and counting retrogradely labeled RGCs after optic nerve crush.Results: The protein levels of Grp78 and Grp94 increased significantly in mice after bilberry extract administration. Increased Grp78 and Grp94 levels were detected in the inner nuclear layer and ganglion cell layer of the retina, surrounding the RGCs. Gene expression of Chop, Bax, and Atf4 increased in mice after optic nerve crush and decreased significantly after oral bilberry extract administration. RGC survival after nerve crush also increased with bilberry extract administration.Conclusion: These results indicate that oral bilberry extract administration suppresses RGC death. Bilberry extract administration increased Grp78 and Grp94 protein levels, an effect which may underlie the neuroprotective effect of bilberry extract after optic nerve crush. Thus, bilberry extract has a potential role in neuroprotective treatments for retinal injuries, such as those which occur in glaucoma. Keywords: bilberry extract, molecular chaperones, ER stress, retinal ganglion cells, glaucoma

Wataru Kobayashi,1 Shunji Yokokura,1 Takehiro Hariya,1 Toru Nakazawa1–3 1Department of Ophthalmology, 2Department of Retinal Disease Control, Ophthalmology, 3Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: The purpose of this study was to assess the effectiveness of 2% ethylenediaminetetraacetic acid (EDTA) for the treatment of band-shaped keratopathy.Methods: We studied 24 eyes of 16 patients with band-shaped keratopathy who underwent EDTA chelation treatment from April 1, 2011 to December 31, 2012. We compared preoperative and 1 month postoperative logarithm of the minimum angle of resolution (logMAR) best corrected visual acuity, intraocular pressure, and corneal curvature radius (K1, horizontal meridian; K2, vertical meridian; Km, average of K1 and K2). The Mann-Whitney U-test was used to determine the significance of differences.Results: There was a significant difference in preoperative and postoperative logMAR best corrected visual acuity (P=0.01). There were no significant differences in preoperative and postoperative intraocular pressure (P=0.24) or corneal curvature radius (K1, P=0.54; K2, P=0.49; Km, P=0.45).Conclusion: After 2% EDTA chelation treatment, post-operative logMAR best corrected visual acuity improved significantly. Moreover, since there was no significant difference in corneal curvature radius, there was little influence on corneal surface form. We believe that the results of our 2% EDTA chelation treatment were comparable with results obtained with 3.75% EDTA chelation treatment in previous reports. Two percent EDTA chelation is an effective treatment for band-shaped keratopathy and a useful method for any institution. Keywords: ethylenediaminetetraacetic acid, band-shaped keratopathy, phototherapeutic keratectomy, cornea

Ai Shimizu, Kazuichi Maruyama, Yu Yokoyama, Satoru Tsuda, Morin Ryu, Toru Nakazawa Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan Purpose: To investigate the characteristics of uveitic glaucoma (UG) and evaluate surgical treatments.Methods: This study examined a retrospective, nonrandomized comparative interventional case series of 105 UG patients (141 eyes) followed between April 1, 2001 and July 30, 2014 at the outpatient clinic of Tohoku University Hospital. The study group included 47 patients (47 eyes) who underwent glaucoma surgery: trabeculectomy, trabeculotomy, and trabectome surgery. The analysis used Kaplan–Meier life tables, with surgical failure defined as intraocular pressure ≧21 mmHg or the need for additional glaucoma surgery.Results: UG patients represented 9.73% of our database of glaucoma patients. The mean follow-up period was 40.32±32.53 months. Seventy-one patients had granulomatous uveitis (67.62%) and 34 had nongranulomatous uveitis (32.38%). The causes of uveitis included sarcoidosis (n=25), Behçet’s disease (n=11), Vogt–Koyanagi–Harada disease (n=9), Posner–Schlossman syndrome (n=12), herpes simplex virus infectious uveitis (n=7), acute anterior uveitis (n=5), intermediate uveitis (n=4), scleritis (n=4), inflammatory bowel disease (n=4), varicella zoster virus uveitis (n=2), and others (n=6). An additional 16 patients were diagnosed with idiopathic UG. Surgical success rates were 82.86% for trabeculectomy, 62.50% for trabeculotomy, and 75.00% for trabectome. Significant risk factors for surgical failure included male sex (P=0.02), age less than 45 years (P=0.0009), nongranulomatous uveitis (P=0.04), and postoperative inflammation (P=0.01).Conclusion: Young male patients with nongranulomatous uveitis had a significant risk of surgical failure. Moreover, prolonged postoperative inflammation created a susceptibility to surgical failure, indicating the importance of postoperative inflammation reduction. Keywords: uveitic glaucoma, sarcoidosis, Behçet’s disease

Fumihiko Nitta,1 Hiroshi Kunikata,1,2 Naoko Aizawa,1 Kazuko Omodaka,1 Yukihiro Shiga,1 Masayuki Yasuda,1 Toru Nakazawa1–31Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Japan; 3Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanBackground: This study evaluated the effect of intravitreal injection of bevacizumab (IVB) on macular edema associated with diabetic retinopathy (DME) or branch retinal vein occlusion (BRVOME) using laser speckle flowgraphy.Methods: A comparative interventional study of 25 eyes from 22 patients with macular edema (DME group: 12 eyes; BRVOME group: 13 eyes) who underwent IVB. Mean blur rate (MBR) was measured in the retinal artery, retinal vein, optic nerve head (ONH), and choroid before and after IVB. Results: In the BRVOME group, there was no significant change in MBR in the retinal artery, retinal vein or ONH, but choroidal MBR decreased significantly (P=0.04). In the DME group, the MBR in the retinal artery, retinal vein, ONH, and choroid decreased significantly (P=0.02, P=0.04, P

Kenya Yuki,1 Toru Nakazawa,2 Daijiro Kurosaka,3 Tsunehiko Yoshida,4–6 Eduardo C Alfonso,7 Richard K Lee,7 Shigeru Takano,8 Kazuo Tsubota1 1Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan; 2Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan; 3Department of Ophthalmology, Iwate Medical University, Iwate, Japan; 4The House of Representatives of Japan, Tokyo, Japan; 5Nagoya University Hospital, Aichi, Japan; 6Aichi Medical University Hospital, Aichi, Japan; 7Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 8Japan Ophthalmological Association, Tokyo, Japan Purpose: The Great East Japan Earthquake of March 11, 2011 triggered powerful tsunami waves off the northeastern Pacific coast of Japan that destroyed almost all of the built-up areas along the coast. The study reported here examined the role played by the Vision Van, a mobile outpatient ophthalmological clinic, in providing eye care to disaster evacuees. Methods: This was a retrospective case-series study of 2,070 victims (male: 732, female: 1,338) who visited the Vision Van. The subjects' medical records were examined retrospectively and analyzed in terms of age, sex, and date of visit to the Vision Van. Information regarding each patient's chief complaint, diagnosis, medication(s) prescribed, and eyeglasses and contact lenses provided, was also examined. Results: The Vision Van was used to conduct medical examinations on 39 days between April 23 and June 29, 2011. The average number of subjects visiting the Vision Van each day was 53±31 (range: 7–135), with examinations carried out in Miyagi Prefecture and Iwate Prefecture. The most frequent complaint was a need for eye drops (871/2,070 [42.1%]). The second and third most frequent complaints, respectively, were the need for contact lenses (294/2,070 [14.2%]) and eyeglasses (280/2,070 [13.5%]). The most frequent ocular disease diagnosis was cataract (497/2,070 [24.0%]). Eye drops were prescribed to 74.1% of the subjects. Conclusion: Mobile clinics such as the Vision Van provide valuable care, in this case, particularly to individuals who lost or left behind eyeglasses or contact lenses while escaping a natural disaster, and to subjects with chronic eye disease. Keywords: natural disaster, disaster relief, eye care, mobile medical services

Wataru Kobayashi,1 Toshiaki Abe,2 Hiroshi Tamai,1 Toru Nakazawa11Department of Ophthalmology, 2Division of Clinical Cell Therapy, Center for Advanced Medical Research and Development (ART), Tohoku University Graduate School of Medical Science, Sendai, JapanPurpose: This is a report of a case of choroidal excavation accompanied by polypoidal choroidal vasculopathy (PCV) and retinal pigment epithelium detachment (PED).Methods: A 57-year-old Japanese woman who had begun complaining of metamorphopsia in her left eye 7 months earlier underwent spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography (IA), as well as a routine ophthalmological examination.Results: The patient’s intraocular pressure, visual acuity, and visual field were within normal range. Ophthalmoscopy revealed a serous macular detachment, soft drusen, exudates, and a reddish-orange elevated lesion in the macula of the left eye. The right eye was normal. SD-OCT revealed two lesions in the left eye. One was a PED accompanied by a notch sign, and the other was a choroidal excavation. Additionally, FA revealed a window defect in the PED, and IA showed typical PCV. Three monthly injections of antivascular endothelial growth factor preserved visual acuity, but failed to have any visible effect on the lesion during the 6-month follow up period.Conclusions: This is the first report of choroidal excavation accompanied by PED and PCV. The data suggest that choroidal excavation may be associated with various changes that have not been previously reported. Careful observation of such cases may therefore be necessary.Keywords: choroidal excavation, polypoidal choroidal vasculopathy, anti-vascular endothelial growth factor treatment

Tatsuro Otani1, Kanako Yasuda1, Naoko Aizawa2, Fumiaki Sakai3, Toru Nakazawa2, Masahiko Shimura11Department of Ophthalmology, NTT East Japan Tohoku Hospital, 2Department of Ophthalmology, Tohoku University School of Medicine, 3Heisei Ophthalmic Associates P.O., Sendai, Miyagi, JapanAbstract: Coats' disease diagnosed in adulthood is rare; therefore, the treatment options and longer clinical course are not well established. We report on two cases of adult onset Coats' disease, which have been observed for more than 10 years after conventional treatment. In the first case, a 76-year-old man with 9 years of diabetic retinopathy noticed a visual field defect in his left eye. Yellowish subretinal exudation with serous retinal detachment in his superior peripheral retina, and telangiectatic vessels with fluorescein leakage, numerous microaneurysms, and areas of capillary nonperfusion observed in a fluorescein angiography indicated adult Coats' disease, and retinal photocoagulation was applied. Within 1 year, subretinal exudation was regressed and visual acuity was improved from 20/50 to 20/20, and was maintained for the next 11 years. In the second case, a 71-year-old man presented with decreased vision in his right eye. The fundus of his right eye showed multiple telangiectasic vessels and subretinal exudates extended to the fovea, which is diagnosed as adult Coats’ disease. Despite retinal photocoagulation, an increase of exudation and an enlargement of retinal detachment was observed within 1 month, and subsequently, additional treatment of cryotherapy was performed. Two months after these therapies, the exudation was regressed without retinal detachment, and visual acuity was improved to 20/200 which was maintained for the next 10 years. Even with adult Coats’ disease, conventional therapies of retinal photocoagulation and cryotherapy are effective and are the initial choice for improving or maintaining visual function.Keywords: adult onset, Coats’ disease, treatment, follow-up

Yu Yokoyama, Naoko Aizawa, Naoki Chiba, Kazuko Omodaka, Masahiko Nakamura, Takaaki Otomo, Shunji Yokokura, Nobuo Fuse, Toru NakazawaDepartment of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, JapanBackground: Eyes with glaucoma are characterized by optic neuropathy with visual field defects in the areas corresponding to the optic disk damage. The exact cause for the glaucomatous optic neuropathy has not been determined. Myopia has been shown to be a risk factor for glaucoma. The purpose of this study was to determine whether a significant correlation existed between the microcirculation of the optic disk and the visual field defects and the retinal nerve fiber layer thickness (RNFLT) in glaucoma patients with myopic optic disks.Methods: Sixty eyes of 60 patients with myopic disks were studied; 36 eyes with glaucoma (men:women = 19:17) and 24 eyes with no ocular diseases (men:women = 14:10). The mean deviation (MD) determined by the Humphrey field analyzer, and the peripapillary RNFLT determined by the Stratus-OCT were compared between the two groups. The ocular circulation was determined by laser speckle flowgraphy (LSFG), and the mean blur rate (MBR) was compared between the two groups. The correlations between the RNFLT and MBR of the corresponding areas of the optic disk and between MD and MBR of the optic disk in the glaucoma group were determined by simple regression analyses.Results: The average MBR for the entire optic disk was significantly lower in the glaucoma group than that in the control group. The differences of the MBR for the tissue in the superior, inferior, and temporal quadrants of the optic disk between the two groups were significant. The MBR for the entire optic disk was significantly correlated with the MD (r = 0.58, P = 0.0002) and the average RNFLT (r = 0.53, P = 0.0008). The tissue MBR of the optic disk was significantly correlated with the RNFLT in the superior, inferior, and temporal quadrants.Conclusions: Our study suggests that there is a causal relationship between the thinner RNFLT that led to the MD and reduction in the microcirculation in the optic nerve head.Keywords: glaucoma, visual field defects, optic disk, optic neuropathy, myopia, microcirculation, optic nerve head, retinal nerve fiber layer

Naoki Chiba, Kazuko Omodaka, Yu Yokoyama, Naoko Aizawa, Satoru Tsuda, Masayuki Yasuda, Takaaki Otomo, Shunji Yokokura, Nobuo Fuse, Toru Nakazawa Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan Background: The purpose of this study was to investigate the correlations between microcirculation in the optic disc, average peripapillary retinal nerve fiber layer thickness cupping parameters, and visual field defects in glaucoma patients with the generalized enlargement disc type. Methods: A total of 38 eyes from 38 glaucoma patients with the generalized enlargement disc type were included. The microcirculation of the optic nerve head was examined with laser speckle flow graphy, and the mean blur rate in all areas, in vessel area, and in tissue area were calculated using the laser speckle flow graphy analyzer software. Average peripapillary retinal nerve fiber layer thickness was measured using Stratus optical coherence tomography, and cupping parameters were accessed using the Heidelberg retina tomograph. The mean deviation in the Humphrey field analyzer (30-2 SITA standard) was analyzed. The correlation between these parameters was evaluated using the Spearman rank correlation coefficient. Results: The correlation coefficient of mean blur rate in all optic disc area to the average peripapillary retinal nerve fiber layer thickness, vertical C/D, and mean deviation were r = 0.7546 (P < 0.0001), r = –0.6208 (P < 0.0001), and r = 0.6010 (P = 0.0001), respectively. The mean blur rate in tissue area of the optic disc showed r = 0.7305 (P < 0.0001), r = –0.6438 (P < 0.0001), and r = 0.6338 (P < 0.0001). Conclusion: We found that the mean blur rate in the optic disc was significantly correlated with the average peripapillary retinal nerve fiber layer thickness, vertical C/D, and mean deviation in patients with the generalized enlargement disc type of glaucoma. In particular, the mean blur rate in tissue area was more highly correlated than the vessel area with other results of examination in glaucoma patients with the generalized enlargement disc type. Keywords: ocular blood flow, optic disc type, laser speckle flowgraphy, function, structure

Naoko Aizawa, Yu Yokoyama, Naoki Chiba, Kazuko Omodaka, Masayuki Yasuda, Takaaki Otomo, Masahiko Nakamura, Nobuo Fuse, Toru NakazawaDepartment of Ophthalmology, Tohoku University Graduate School of Medicine Sendai, Miyagi, JapanBackground: Laser speckle flowgraphy (LSFG) enables noninvasive quantification of the retinal circulation in glaucoma patients. In this study, we tested the intrasession reproducibility of LSFG-NAVI, a modified LSFG technique.Methods: Sixty-five eyes from 33 subjects (male (M):female (F) = 17:16) with a mean age of 49.4 ± 11.2 years were examined in this study. Two parameters indicating reproducibility – the coefficient of variation (COV) and the intraclass correlation coefficient (ICC) – were analyzed three times on the same day that mean blur rate (MBR) was measured using LSFG-NAVI. The sites analyzed were the retinal artery and vein, the optic disk, and the choroid. Following classification according to the Glaucoma Hemifield Test (GHT; SITA-Standard 30-2 program), the COV and ICC were examined in patients with (GHT+; 38 eyes, M:F = 20:18, average age 48.9 ± 12.8 years) and without (GHT-; 27 eyes, M:F = 13:14, average age 50.1 ± 8.7 years) abnormal glaucomatous visual fields.Results: For all subjects, the intrasession reproducibility of MBR in the optic disk (COV: 3.4 ± 2.0; ICC: 0.95) and choroid (COV: 4.7 ± 3.4; ICC: 0.98) was excellent. The reproducibility for the retinal vein (COV: 8.4 ± 5.6, ICC: 0.90) and retinal artery (COV: 10.9 ± 9.9, ICC: 0.9) was moderate. MBRs in the optic disk had good reproducibility in both the GHT+ group (COV: 3.8 ± 2.0; ICC: 0.97) and the GHT− group (COV: 2.9 ± 2.1; ICC: 0.95). Local assessment of the optic disk in normal or glaucoma patients showed that the COVs of the quadrant optic disk areas were best in the temporal area of MBR (3.4%, 4.2%, respectively).Conclusion: LSFG-NAVI showed favorable reproducibility in evaluation of retinal circulation of glaucoma patients, particularly in the optic disk and choroid.Keywords: ocular circulation, reproducibility, optic nerve, retina

We investigated the applicability of miniature microtremor arrays with a radius of a few meters or less to shallow surveys (up to a few tens of meters). It is shown that the upper limit wavelength normalized by the seismometer separation distance s that is analyzable by a miniature array does not depend on the observation instrument as long as the instrument has a self‐noise level that is sufficiently lower than the microtremor intensities; however, it generally depends on the average S‐wave velocity of the ground. This means that a miniature array is useful at soft‐soil sites but not hard‐soil sites. A statistical study in central Japan showed that the penetration depth by a miniature array with s = 1 m ranges from 6 to 12 m; specifically, the depth exceeds 12 m in one quarter of the cases but remains below 6 m in one quarter of the cases. This large variation is due to the variation in the average S‐wave velocity. A miniature array should thus be used in combination with a larger array with an s value of several meters to 20 m. In urbanized areas with high industrial activity, where the microtremor wavefield is likely isotropic, these arrays can be replaced by a linear array. In environments with extremely low signal‐to‐noise ratios, a less efficient zero‐crossing method should be applied to the larger array. An appropriate observation strategy should be selected for a given geoenvironment. Field examples show that our strategy enables efficient and feasible dense surveys. Plain Language Summary: A microtremor array survey is a non‐destructive, passive method for subsurface exploration. Because such a survey is also easy to conduct and cost‐effective, it is widely used for seismic hazard assessments. It is expected that the benefits can be extended to lunar and planetary exploration. We demonstrate that a miniature microtremor measurement device with a radius of a few meters or less can be used for shallow surveys. The performance of the miniature measurement device does not depend on the observation instrument. This device is effective at soft‐soil sites but not hard‐soil sites. To increase survey feasibility, miniature measurement devices should be used in combination with a larger measurement device. In ground environments with extremely low signal‐to‐noise ratios, larger measurement devices and somewhat less efficient methods must be applied. It is important to select an observation strategy that is appropriate for a given geological environment considering the balance between the efficiency and feasibility of a shallow survey. Key Points: The applicability of a miniature array with a radius of a few meters or less to shallow surveys is reviewed and summarizedThe applicability of a miniature array depends on the average S‐wave velocity of the ground but not on the observation instrumentIllustrative field examples of our strategy, which enables a dense survey to obtain a shallow two‐dimensional velocity section, are shown [ABSTRACT FROM AUTHOR]