Faculty Profiles - MORIZANE Yuki

Papers - MORIZANE Yuki

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Nationwide epidemiological survey of Leber hereditary optic neuropathy in Japan.

Kaori Ueda, Yuki Morizane, Fumio Shiraga, Keigo Shikishima, Hitoshi Ishikawa, Masato Wakakura, Makoto Nakamura

Journal of epidemiology 27 ( 9 ) 447 - 450 2017.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Leber hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy that leads to central loss of vision, predominantly in young males. Most LHON cases have one of three primary point mutations in mitochondrial DNA (mtDNA). The annual incidence and prevalence of LHON in Japan are not known. Thus, we estimated the annual incidence of molecularly confirmed LHON in Japan during 2014. METHODS: Sequential questionnaires were sent to 1397 facilities, which included all of the university hospitals in Japan, and they were certified by either the Japanese Ophthalmological Society or the Japanese Neuro-Ophthalmological Society. We calculated the incidence number (Ir) as the number of patients who developed LHON in 2014 and its 95% confidence interval. RESULTS: We received 861 responses to the first questionnaire, where 49 facilities reported 72 cases (67 were male and 5 were female) of newly developed LHON during 2014. Ir was calculated as 117, and the 95% confidence interval ranged from 81 to 153. For the second questionnaire, responses were received from 30 facilities, where the median age at onset was 38 years for males and 30 years for females, and 86.5% of cases possessed the mtDNA ND4/G11778A mutation. CONCLUSION: Approximately 120 cases of newly developed LHON were reported during 2014 in Japan, and 93.2% were males.

DOI： 10.1016/j.je.2017.02.001

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抗VEGF治療セミナー糖尿病黄斑浮腫に対する硝子体手術

戸島慎二, 森實祐基

あたらしい眼科 34 ( 7 ) 1007 - 1008 2017.7

Language：Japanese Publisher：(株)メディカル葵出版

現在、糖尿病黄斑浮腫に対する治療の第一選択はVEGF阻害薬硝子体内注射であるが、治療に抵抗する症例では他の治療法を考慮する必要がある。本稿では糖尿病黄斑浮腫(DME)の治療における硝子体手術の適応基準、奏効機序と問題点、そして筆者らの施設で行っている新しい術式について概説する。(著者抄録)

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【糖尿病網膜症】糖尿病網膜症に対する硝子体手術の進歩

塩出雄亮, 森實祐基

Diabetes Frontier 28 ( 3 ) 303 - 307 2017.6

Autologous Internal Limiting Membrane Transplants Successfully Close a Large Parafoveal Retinal Hole.

Fumiaki Kumase, Yuki Morizane, Shuhei Kimura, Shinji Toshima, Fumio Shiraga

Acta medica Okayama 71 ( 3 ) 255 - 257 2017.6

Characteristics of successful filtering blebs at 1 year after trabeculectomy using swept-source three-dimensional anterior segment optical coherence tomography.

Akiko Narita, Yuki Morizane, Tomoe Miyake, Jiro Seguchi, Tetsuya Baba, Fumio Shiraga

Japanese journal of ophthalmology 61 ( 3 ) 253 - 259 2017.5

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To identify the cross-sectional characteristics of filtering blebs associated with intraocular pressure (IOP) control at 1 year after trabeculectomy with a square scleral flap and a fornix-based conjunctival flap. METHODS: A retrospective consecutive case series study was conducted. Eighty-four eyes of 79 patients who had undergone primary trabeculectomy were included. Surgical success was defined as IOP ≤15 mmHg and a >20% reduction in IOP without glaucoma medication and without additional glaucoma surgery at 1 year after trabeculectomy. The subjects were classified into two groups according to whether surgery was successful or unsuccessful. Filtering blebs were examined using swept-source three-dimensional anterior segment optical coherence tomography and evaluated for the following quantitative parameters: maximum bleb height, maximum bleb wall thickness, and ratio of hypo-reflective space of the bleb wall. RESULTS: Sixty-six eyes were determined to be successful and 18 eyes unsuccessful. Univariate analysis showed significant differences between the two groups regarding bleb height (P < 0.001), bleb wall thickness (P = 0.011), and ratio of hypo-reflective space of the bleb wall (P = 0.002). Multivariate logistic regression analysis confirmed that the bleb height was significantly associated with success in trabeculectomy [odds ratio 13.996 (95% confidence interval 1.184-165.420); P = 0.036]. CONCLUSION: A tall bleb with a thick hypo-reflective wall may be a feature of the well-functioning bleb.

DOI： 10.1007/s10384-017-0504-2

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全都道府県を対象にした視覚障がい認定の疫学調査

森實祐基, 藤原篤之, 金永圭祐, 坂手澪, 稲垣明日香, 後藤保人, 守本典子, 川崎良, 小椋祐一郎, 白神史雄

日本眼科学会雑誌 121 ( 臨増 ) 202 - 202 2017.3

中心窩の形状が中心窩無血管領域と網膜血管密度に及ぼす影響

藤原篤之, 森實祐基, 木村修平, 熊瀬文明, 細川海音, 塩出雄亮, 平野雅幸, 土居真一郎, 戸島慎二, 細木三佳, 高橋耕介, 白神史雄

日本眼科学会雑誌 121 ( 臨増 ) 193 - 193 2017.3

前眼部光干渉断層計による水晶体および眼内レンズの偏位と傾斜の評価

木村修平, 森實祐基, 熊瀬文明, 細川海音, 塩出雄亮, 土居真一郎, 平野雅幸, 戸島慎二, 高橋耕介, 細木三佳, 藤原篤之, 白神史雄

日本眼科学会雑誌 121 ( 臨増 ) 324 - 324 2017.3

網膜静脈分枝閉塞症に対するラニビズマブ投与(Treat and Extend法)の2年成績

細木三佳, 森實祐基, 熊瀬文明, 土居真一郎, 木村修平, 細川海音, 塩出雄亮, 平野雅幸, 高橋耕介, 藤原篤之, 白神史雄

日本眼科学会雑誌 121 ( 臨増 ) 248 - 248 2017.3

Nitinol loop使用後に見られた網膜神経線維層障害及び傍中心暗点

的場亮, 森實祐基, 木村修平, 戸島慎二, 白神史雄

日本眼科学会雑誌 121 ( 臨増 ) 301 - 301 2017.3

PCVに対するtreat and extend法の治療経過にポリープ病巣退縮の有無が与える影響

細川海音, 森實祐基, 木村修平, 熊瀬文明, 塩出雄亮, 土居真一郎, 平野雅幸, 戸島慎二, 藤原篤之, 細木三佳, 白神史雄

日本眼科学会雑誌 121 ( 臨増 ) 216 - 216 2017.3

Effect of topical isopropyl unoprostone on macular atrophy progression in eyes with exudative age-related macular degeneration. International journal

Chieko Shiragami, Masahiro Miyake, Atsushi Fujiwara, Yuki Morizane, Akitaka Tsujikawa, Ayana Yamashita, Fumio Shiraga

Medicine 96 ( 12 ) e6422 2017.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: To evaluate the efficacy and safety of topical isopropyl unoprostone (IU) in treating macular atrophy in age-related macular degeneration (AMD) patients. METHODS: Fifty-two AMD patients with macular atrophy were included and randomly assigned (1:1) to the treatment (topical 0.15% IU) or placebo group. Subjects used study eye drops 3 times a day for 54 weeks. The macular atrophy was documented on fundus autofluorescence photographs and measured using RegionFinder. The enlargement rate of macular atrophy and the changes in visual acuity were examined statistically between baseline and 54 weeks. RESULTS: Forty-eight subjects were included in the analyses because 4 subjects withdrew from the study. The differences between the IU and placebo groups in mean and median area of macular atrophy were not statistically significant at baseline. The baseline median lesion size of macular atrophy was 2.33 mm in the IU group and 1.63 mm in the placebo group (P = 0.51). The intergroup difference in the enlargement ratio of macular atrophy (21 ± 15% in the IU group and 111 ± 96% in the placebo group) was statistically significant (P < 0.001). Additionally, visual acuity tended to improve over baseline in the IU group. No serious adverse events were observed. CONCLUSIONS: Topical IU therapy is safe and effective for treating macular atrophy in AMD patients.

DOI： 10.1097/MD.0000000000006422

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One-year outcomes of a treat-and-extend regimen of intravitreal aflibercept for polypoidal choroidal vasculopathy.

Mio Hosokawa, Yuki Morizane, Masayuki Hirano, Shuhei Kimura, Fumiaki Kumase, Yusuke Shiode, Shinichiro Doi, Shinji Toshima, Mika Hosogi, Atsushi Fujiwara, Toshiharu Mitsuhashi, Fumio Shiraga

Japanese journal of ophthalmology 61 ( 2 ) 150 - 158 2017.3

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To evaluate the 1-year treatment outcomes of intravitreal aflibercept injections (IVA) using a treat-and-extend regimen for polypoidal choroidal vasculopathy (PCV). METHODS: Thirty-seven eyes with treatment-naive PCV treated with IVA using a treat-and-extend regimen for 1 year were reviewed retrospectively. The main outcome measures were changes in the best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and the treatment interval at 1 year. The predictive factors for patients who could not continue to extend the treatment interval because of poor response to IVA or recurrence were analyzed. RESULTS: The mean logarithm of the minimum angle of resolution BCVA improved from 0.37 at baseline to 0.21 at 1 year (P < 0.001). The mean CRT decreased from 342.3 μm at baseline to 196.6 μm at 1 year (P < 0.001). The mean treatment interval was 9.7 weeks at 1 year (4 weeks in 11 eyes [29.7%], 6 weeks in 1 eye [2.7%], 8 weeks in 2 eyes [5.4%], 10 weeks in 1 eye [2.7%], and 12 weeks in 22 eyes [59.5%]). A larger number of polypoidal lesions at baseline was predictive for patients who could not continue to extend the treatment interval. CONCLUSIONS: IVA using a treat-and-extend regimen is effective for improving BCVA and CRT in eyes with PCV.

DOI： 10.1007/s10384-016-0492-7

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A novel cell exclusion zone assay with a barrier made from room temperature vulcanizing silicone rubber. International journal

Yusuke Shiode, Yuki Morizane, Ryo Matoba, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Ryoichi Araki, Mika Hosogi, Kosuke Takahashi, Yuki Kanzaki, Tomoko Yonezawa, Fumio Shiraga

PloS one 12 ( 12 ) e0190198 2017

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To examine the usefulness of room temperature vulcanizing (RTV) silicone rubber as a barrier material for cell exclusion zone assays. METHODS: We created barriers using three types of RTV silicone rubber with differing viscosities. We then assessed the adherence of these barriers to culture dishes and their ease of removal from the dishes. We tested the effect of the newly created barriers on the extracellular matrix (ECM) protein fibronectin by attaching and then removing them from fibronectin-coated culture dishes. We also conducted cell exclusion zone assays with MIO-M1 cells using this new barrier in order to measure cell migration. We used real time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining to measure the effect of fibronectin on MIO-M1 cell migration and the effect of migration (with fibronectin coating) on basic fibroblast growth factor (bFGF) expression in MIO-M1 cells. RESULTS: Of the three types of RTV silicon rubber tested, KE-3495-T was the best in terms of adherence to the dish and ease of removal from the dish. When barrier attachment and removal tests were performed, this rubber type did not have an effect on the fibronectin that coated the dish. In the cell exclusion assay, removal of the barrier revealed that a cell-free area with a distinct margin had been created, which allowed us to conduct a quantitative assessment of migration. Fibronectin significantly promoted the migration of MIO-M1 cells (P = 0.02). In addition, both real time RT-PCR and immunohistological staining indicated that bFGF expression in migrating MIO-M1 cells was significantly higher than that in non-migrating cells (P = 0.03). CONCLUSIONS: RTV silicone rubber can be used to create an effective barrier in cell exclusion zone assays and allows simple and low-cost multi-parametric analysis of cell migration.

DOI： 10.1371/journal.pone.0190198

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Factors affecting foveal avascular zone in healthy eyes: An examination using swept-source optical coherence tomography angiography. International journal

Atsushi Fujiwara, Yuki Morizane, Mio Hosokawa, Shuhei Kimura, Yusuke Shiode, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Kosuke Takahashi, Mika Hosogi, Fumio Shiraga

PloS one 12 ( 11 ) e0188572 2017

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To examine factors affecting foveal avascular zone (FAZ) area in healthy eyes using swept-source optical coherence tomography angiography (OCTA). METHODS: This prospective, cross-sectional study included 144 eyes of 144 individuals (77 women, 67 men) with a best corrected visual acuity of at least 20/20 and no history of ocular disorders. The area of the superficial FAZ was assessed using OCTA. Age, gender, central retinal thickness (CRT), retinal vascular density, refractive error, and axial length were examined to determine associations with FAZ area. RESULTS: The mean age of the subjects was 42.1 ± 20.2 years (range: 10-79 years). The mean FAZ area was 0.32 ± 0.11 mm2, while the mean retinal vascular density was 35.53 ± 0.92%. Multivariate regression analysis was performed using FAZ area as the dependent variable and age, gender, CRT, retinal vascular density, refractive error, and axial length as independent variables. The results of this analysis demonstrate that CRT and retinal vascular density were significantly associated with FAZ area in our sample (P < 0.001, R2 = 0.425). Age, gender, refractive error, and axial length were not significantly correlated with FAZ area, while CRT and retinal vascular density were negatively correlated with FAZ area (CRT: P < 0.001, R2 = 0.356; retinal vascular density: P < 0.001, R2 = 0.189). CONCLUSIONS: OCTA results suggest that CRT and retinal vascular density negatively affect FAZ area in healthy eyes.

DOI： 10.1371/journal.pone.0188572

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Effect of trabeculectomy on visual field progression in Japanese progressive normal-tension glaucoma with intraocular pressure < 15 mmHg. International journal

Tomoko Naito, Miyuki Fujiwara, Takako Miki, Ryoichi Araki, Atsushi Fujiwara, Yusuke Shiode, Yuki Morizane, Mikio Nagayama, Fumio Shiraga

PloS one 12 ( 8 ) e0184096 2017

Language：English Publishing type：Research paper (scientific journal)

We examined the effectiveness of trabeculectomy in decreasing the slope of mean deviation (MD) in Japanese patients with progressive normal-tension glaucoma (NTG) at low intraocular pressure (IOP) levels. The charts of patients who had undergone initial trabeculectomy with adjunctive mitomycin C for progressive NTG with medically controlled IOP < 15 mmHg in 2010-2013 were retrospectively reviewed. Seventeen eyes of 13 NTG patients who had undergone at least 5 times of visual field (VF) examinations in both of preoperatively and postoperatively with postoperative follow-up of ≥ 2 years were enrolled. Preoperative and postoperative MD slopes were compared to evaluate the effectiveness of trabeculectomy in slowing progression of VF. Mean IOP (8.1 ± 2.9 mmHg) and number of IOP-lowering medications (0.8 ± 1.5) were significantly lower postoperatively than preoperatively (13.9 ± 0.9 mmHg; P < 0.001 and 3.0± 0.4; P < 0.0001). In total, 91.7% of eyes with single-digit IOP postoperatively showed improvement in MD slope, whereas only 20.0% of eyes with IOP ≥ 10 mmHg postoperatively showed the improvement. Three eyes (17.6%) showed a decrease in visual acuity (VA) of ≥ 0.1 unit; this group had a lower mean postoperative IOP (6.0 ± 1.0 vs. 8.6 ± 3.0 mmHg; P = 0.1717) and a higher mean IOP reduction rate (56.2 vs. 38.5%; P = 0.8296) than eyes with a VA decrease of < 0.1 unit or no change. Thus, in this analysis of Japanese NTG patients with medically controlled IOP < 15 mmHg, achieving an IOP < 10 mmHg with trabeculectomy was beneficial for reducing the VF progression rate in progressive NTG at low IOP levels. However, an IOP < 7 mmHg by surgery would be required careful attention to VA decline.

DOI： 10.1371/journal.pone.0184096

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Suppressive effect of AMP-activated protein kinase on the epithelial-mesenchymal transition in retinal pigment epithelial cells. International journal

Ryo Matoba, Yuki Morizane, Yusuke Shiode, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Ryoichi Araki, Mika Hosogi, Tomoko Yonezawa, Fumio Shiraga

PloS one 12 ( 7 ) e0181481 2017

Language：English Publishing type：Research paper (scientific journal)

The epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells plays a central role in the development of proliferative vitreoretinopathy (PVR). The purpose of this study was to investigate the effect of AMP-activated protein kinase (AMPK), a key regulator of energy homeostasis, on the EMT in RPE cells. In this study, EMT-associated formation of cellular aggregates was induced by co-stimulation of cultured ARPE-19 cells with tumor necrosis factor (TNF)-α (10 ng/ml) and transforming growth factor (TGF)-β2 (5 ng/ml). 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), a potent activator of AMPK, significantly suppressed TNF-α and TGF-β2-induced cellular aggregate formation (p < 0.01). Dipyridamole almost completely reversed the suppressive effect of AICAR, whereas 5'-amino-5'-deoxyadenosine restored aggregate formation by approximately 50%. AICAR suppressed the downregulation of E-cadherin and the upregulation of fibronectin and α-smooth muscle actin by TNF-α and TGF-β2. The levels of matrix metalloproteinase (MMP)-2, MMP-9, interleukin-6, and vascular endothelial growth factor were significantly decreased by AICAR. Activation of the mitogen-activated protein kinase and mammalian target of rapamycin pathways, but not the Smad pathway, was inhibited by AICAR. These findings indicate that AICAR suppresses the EMT in RPE cells at least partially via activation of AMPK. AMPK is a potential target molecule for the prevention and treatment of PVR, so AICAR may be a promising candidate for PVR therapy.

DOI： 10.1371/journal.pone.0181481

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Effects of pre-surgical administration of prostaglandin analogs on the outcome of trabeculectomy. International journal

Takako Miki, Tomoko Naito, Miyuki Fujiwara, Ryoichi Araki, Rieko Kiyoi, Yusuke Shiode, Atsushi Fujiwara, Yuki Morizane, Fumio Shiraga

PloS one 12 ( 7 ) e0181550 2017

Language：English Publishing type：Research paper (scientific journal)

For primary open angle glaucoma (POAG), laser treatment or surgery is used when the target intraocular pressure (IOP) cannot be achieved by pharmacological agents, such as prostaglandin (PG) analogs; these drugs also have varied effects. We retrospectively reviewed the medical records of 74 POAG patients (74 eyes) whose IOP was inadequately controlled by PG analogs (bimatoprost [13 eyes], latanoprost [34 eyes], tafluprost [11 eyes], and travoprost [16 eyes]) and underwent primary trabeculectomy. The proportion of patients with no recurrent IOP elevation within 24 months post-trabeculectomy was significantly (P < 0.001) lower in the bimatoprost group (31.3%) than in the latanoprost (83.2%), tafluprost (45.5%), or travoprost groups (65.6%). Deepening of the upper eyelid sulcus (DUES) was observed before trabeculectomy in 18 of 74 eyes (24.3%) treated with bimatoprost (9 eyes; 50.0%), latanoprost (3 eyes; 16.7%), tafluprost (1 eye; 5.5%) and travoprost (5 eyes; 27.8%). The proportion of patients with no recurrent IOP elevation up to 24 months post-trabeculectomy was significantly (P < 0.0001) lower in the DUES(+) group (34.7%) than in the DUES(-) group (74.3%). Multivariate stepwise logistic regression analysis, with no recurrent IOP elevation used as dependent variable, and bimatoprost, latanoprost, travoprost, tafluprost, β-blocker, carbonic anhydrase inhibitor, brimonidine, gender, age, preoperative IOP, mean deviation, duration of PG analog use before surgery, and the number of ophthalmic solutions used as independent variables, identified only bimatoprost as a significant independent factor (P = 0.0368). Thus, the outcome of trabeculectomy varied depending on the PG analog used preoperatively, and bimatoprost use was associated with a high risk of recurrent IOP elevation up to 2 years post-trabeculectomy. This may indicate that the incidence of DUES differed with the PG analog used. Patients with glaucoma who are treated with bimatoprost should be monitored for DUES, and when these patients undergo trabeculectomy, the postoperative course of IOP should be followed carefully.

DOI： 10.1371/journal.pone.0181550

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Assessment of tilt and decentration of crystalline lens and intraocular lens relative to the corneal topographic axis using anterior segment optical coherence tomography. International journal

Shuhei Kimura, Yuki Morizane, Yusuke Shiode, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Atsushi Fujiwara, Fumio Shiraga

PloS one 12 ( 9 ) e0184066 2017

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To investigate the tilt and decentration of the crystalline lens and the intraocular lens (IOL) relative to the corneal topographic axis using anterior segment ocular coherence tomography (AS-OCT). METHODS: A sample set of 100 eyes from 49 subjects (41 eyes with crystalline lenses and 59 eyes with IOLs) were imaged using second generation AS-OCT (CASIA2, TOMEY) in June and July 2016 at Okayama University. Both mydriatic and non-mydriatic images were obtained, and the tilt and decentration of the crystalline lens and the IOL were quantified. The effects of pupil dilation on measurements were also assessed. RESULTS: The crystalline lens showed an average tilt of 5.15° towards the inferotemporal direction relative to the corneal topographic axis under non-mydriatic conditions and 5.25° under mydriatic conditions. Additionally, an average decentration of 0.11 mm towards the temporal direction was observed under non-mydriatic conditions and 0.08 mm under mydriatic conditions. The average tilt for the IOL was 4.31° towards the inferotemporal direction relative to the corneal topographic axis under non-mydriatic conditions and 4.65° in the same direction under mydriatic conditions. The average decentration was 0.05 mm towards the temporal direction under non-mydriatic conditions and 0.08 mm in the same direction under mydriatic conditions. A strong correlation was found between the average tilt and decentration values of the crystalline lens and the IOL under both non-mydriatic and mydriatic conditions (all Spearman correlation coefficients, r ≥ 0.800; all P < 0.001). CONCLUSION: When measured using second generation AS-OCT, both the crystalline lens and the IOL showed an average tilt of 4-6° toward the inferotemporal direction relative to the corneal topographic axis and an average decentration of less than 0.12 mm towards the temporal direction. These results were not influenced by pupil dilation and they showed good repeatability.

DOI： 10.1371/journal.pone.0184066

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特発性黄斑上膜にみられる嚢胞様黄斑浮腫の検討

塩出雄亮, 森實祐基, 木村修平, 熊瀬文明, 細川海音, 平野雅幸, 土居真一郎, 戸島慎二, 細木三佳, 藤原篤之, 白神史雄

眼科臨床紀要 9 ( 10 ) 846 - 846 2016.10

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