研究者詳細 - 細川　海音

論文 - 細川　海音

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INVESTIGATION OF THE PATHOPHYSIOLOGY OF EPIRETINAL MEMBRANE FOVEOSCHISIS: Analysis of Longitudinal Changes in Visual Functions, Retinal Structures, and Retinal Traction Force. 査読国際誌

Ryo Matoba, Yuki Kanzaki, Tetsuro Morita, Yuki Masuda, Shuhei Kimura, Mio M Hosokawa, Yusuke Shiode, Yuki Morizane

Retina (Philadelphia, Pa.) 44 ( 11 ) 1992 - 2000 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Ovid Technologies (Wolters Kluwer Health)

PURPOSE: To analyze the pathophysiology of epiretinal membrane foveoschisis (FS) by evaluating the longitudinal changes in visual function and several optical coherence tomography parameters. METHODS: The medical records of 33 consecutive patients (35 eyes) with untreated epiretinal membrane foveoschisis were retrospectively reviewed. Best-corrected visual acuity, M-CHARTS score, and optical coherence tomography parameters including epiretinal membrane area, maximum depth of retinal folds, FS area, and FS circularity were evaluated. RESULTS: A wide range of FS area changes was observed at the final follow-up visit (59.68%-240.45% of the baseline FS area). In the FS enlargement group, best-corrected visual acuity and mean M-CHARTS scores significantly worsened and maximum depth of retinal folds significantly increased over time, whereas in the FS non-enlargement group, no significant change was observed in the best-corrected visual acuity, mean M-CHARTS scores, or maximum depth of retinal folds during the follow-up period. Multivariate logistic regression analyses revealed that maximum depth of retinal folds (odds ratio: 1.05, 95% confidence interval: 1.00-1.10, P = 0.048) and FS circularity (odds ratio: 0.91, 95% confidence interval: 0.83-1.00, P = 0.043) were significantly associated with FS enlargement. CONCLUSION: Epiretinal membrane foveoschisis encompasses diverse pathophysiologies. Since visual functions do not worsen in some cases, monitoring the changes in visual functions and retinal morphology over time is recommended to determine surgical indications.

DOI： 10.1097/IAE.0000000000004217

MIXED PATHOPHYSIOLOGIES OF LAMELLAR MACULAR HOLES AND RELATED DISEASES 査読

Ryo Matoba, Yuki Kanzaki, Tetsuro Morita, Yuki Masuda, Shuhei Kimura, Mio M. Hosokawa, Yusuke Shiode, Yuki Morizane

Retina 44 ( 10 ) 1785 - 1792 2024年10月

掲載種別：研究論文（学術雑誌）出版者・発行元：Ovid Technologies (Wolters Kluwer Health)

Purpose:

To investigate the characteristics of mixed pathophysiologies in lamellar macular holes (LMHs) and related diseases using multimodal optical coherence tomography.

Methods:

Overall, 126 eyes diagnosed with LMH, epiretinal membrane foveoschisis, or macular pseudohole using the horizontal B-scan image according to the definition proposed by Hubschman et al in 2020 were analyzed using multimodal optical coherence tomography imaging including horizontal and vertical 5-line B-scan, radial scan, and macular three-dimensional volume scan images. If at least two diagnostic criteria for LMH, epiretinal membrane foveoschisis, or macular pseudohole were satisfied in these scans, the patient was diagnosed as having a “mixed type.” Retinal traction force was quantitatively evaluated by measuring the maximum depth of the retinal folds using en-face images.

Results:

Mixed types constituted 34.1% of the cases. The LMH-related mixed group demonstrated intermediate characteristics between the epiretinal membrane foveoschisis/macular pseudohole and true LMH groups in terms of retinal traction and LMH-specific features and had a significant positive correlation between the maximum depth of the retinal folds and mean M-CHARTS scores (P = 0.034).

Conclusion:

A thorough optical coherence tomography analysis is necessary to accurately diagnose LMH and related diseases. A significant positive correlation was observed between the maximum depth of the retinal folds and the degree of metamorphopsia in the LMH-related mixed group.

DOI： 10.1097/iae.0000000000004166

Calcification of a Hydrophilic Acrylic Intraocular Lens after Glaucoma Surgery. 査読

Sara Okamoto, Yusuke Shiode, Shuhei Kimura, Mio Hosokawa, Ryo Matoba, Yuki Kanzaki, Hiroya Kindo, Tetsuro Morita, Akihiro Tsuji, Kosuke Takahashi, Yuki Morizane

Acta medica Okayama 78 ( 3 ) 295 - 300 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

A Japanese woman in her 70s was referred to our hospital for the evaluation and treatment of high intraocular pressure (IOP) in her right eye. She had undergone bilateral cataract surgeries and the insertion of hydrophilic acrylic intraocular lenses (IOLs). We performed trabeculotomy and trabeculectomy to lower her right IOP; thereafter, a circular opacity was observed on the right eye's IOL surface. We removed the right IOL because that eye's vision had decreased due to IOL opacification. The analysis of the removed IOL revealed that the main opacity component was calcium phosphate. This is the first post-glaucoma-surgery IOL calcification case report.

DOI： 10.18926/AMO/67206

Influence of submacular hemorrhage at baseline on the long-term outcomes of aflibercept treatment for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. 査読国際誌

Mio Morizane Hosokawa, Chihiro Ouchi, Yusuke Shiode, Shuhei Kimura, Ryo Matoba, Tetsuro Morita, Yuki Morizane

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 2024年4月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To investigate the influence of submacular hemorrhage (SMH) at baseline on long-term visual outcomes of patients with typical age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept (IVA). METHODS: In this retrospective study, eyes of treatment-naïve patients with tAMD and PCV who initiated IVA under a treat-and-extend regimen and were followed up for ≥ 5 years were classified into the tAMD-SMH ( +), tAMD-SMH (-), PCV-SMH ( +), and PCV-SMH (-) groups based on the presence of SMH at baseline. Best-corrected visual acuity (BCVA) changes and macular fibrosis and atrophy incidences were assessed. RESULTS: This study included 127 eyes (127 patients), including 51 with tAMD and 76 with PCV; 18 eyes had SMH at baseline. In the tAMD-SMH ( +) group (n = 6), the mean logMAR BCVA significantly deteriorated from 0.59 ± 0.45 at baseline to 0.88 ± 0.47 at the final visit (P = 0.024). No significant BCVA changes were observed in the tAMD-SMH (-) (n = 45), PCV-SMH ( +) (n = 12), or PCV-SMH (-) (n = 64) groups (all P > 0.05). The tAMD-SMH ( +) group showed a significantly higher incidence of macular fibrosis at the final visit than did the tAMD-SMH (-) group (P = 0.042). There was no influence of baseline SMH on the macular fibrosis incidence in eyes with PCV and the macular atrophy incidence in eyes with tAMD and PCV. CONCLUSION: The presence of SMH at baseline resulted in poorer long-term visual acuity in eyes with tAMD, even with aflibercept treatment. However, no such influence was observed in eyes with PCV.

DOI： 10.1007/s00417-024-06453-6

ぶどう膜炎所見を呈した肝細胞癌による転移性眼内腫瘍の1例

高須絵理, 塩出雄亮, 金道寛弥, 木村修平, 細川海音, 的場亮, 神崎勇希, 森田哲郎, 足立卓哉, 大塚基之, 森實祐基

日本眼科学会雑誌 128 ( 臨増 ) 287 - 287 2024年3月

Microperimetry-guided inverted internal limiting membrane flap site selection to preserve retinal sensitivity in macular hole with glaucoma. 査読国際誌

Ryo Matoba, Yuki Kanzaki, Tetsuro Morita, Shuhei Kimura, Mio M Hosokawa, Yusuke Shiode, Yuki Morizane

American journal of ophthalmology case reports 33 102007 - 102007 2024年3月

記述言語：英語

PURPOSE: In cases of macular hole (MH) that is difficult to close, including large, chronic, or highly myopic cases, the inverted internal limiting membrane (ILM) flap technique is often preferred and yields favorable surgical outcomes as compared to those yielded by conventional ILM peeling. However, no consensus exists on the optimal location and area for peeling and inverting the ILM, since multiple alternative methods have been reported alongside the original method. Several adverse effects associated with ILM peeling have been documented, including mechanical impairment of the retinal nerve fiber layer and decreased retinal sensitivity. Particularly, when glaucoma is concomitant, the retinal nerve fiber layer is fragile, raising concerns about a decrease in retinal sensitivity. Consequently, in patients with large MH alongside glaucoma, the goal is to select a procedure that maximizes the closure rate of the MH while minimizing any negative impact on glaucomatous visual field impairment. However, a technique for this purpose has not yet been validated. OBSERVATIONS: A woman in her 60s presented with visual impairment (20/50), metamorphopsia, and central scotoma of unknown onset in the right eye. A full-thickness MH accompanied by epiretinal proliferation (EP) was identified, with a minimum diameter of 506 μm. Although a retinal nerve fiber layer defect was not evident on ophthalmoscopy, thinning of the ganglion cell complex (GCC), extending from the superotemporal aspect of the optic disc, was observed on optical coherence tomography. Both microperimetry and static visual field testing revealed reduced retinal sensitivity in the thinned GCC areas. A pars plana vitrectomy combined with cataract surgery was performed to address her condition. The EP was embedded into the foveal cavity. On the basis of the microperimetry results, the ILM within the absolute scotoma region was peeled on the superotemporal side of the fovea to create a flap, which was then placed over the MH. A gas tamponade was applied, and the patient was maintained in a prone position postoperatively. The MH was successfully closed after the surgery, resulting in visual improvement (20/25). No decline in retinal sensitivity after the surgery was observed. CONCLUSIONS AND IMPORTANCE: Determining the location and area of the inverted ILM flap on the basis of microperimetry results is a promising patient-tailored strategy for treating MH concomitant with glaucoma while preventing further ILM peeling-associated reduction in the retinal sensitivity.

DOI： 10.1016/j.ajoc.2024.102007

Evaluation of epiretinal membrane formation after scleral buckling for treating rhegmatogenous retinal detachment: En face optical coherence tomography image-based study. 査読国際誌

Ryo Matoba, Yuki Kanzaki, Tetsuro Morita, Shuhei Kimura, Mio Morizane Hosokawa, Yusuke Shiode, Yuki Morizane

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To assess epiretinal membrane (ERM) formation, severity, and the associated risk factors after scleral buckling using en face optical coherence tomography (OCT) images. METHODS: Medical records of 61 consecutive patients (66 eyes) with rhegmatogenous retinal detachment who underwent scleral buckling were retrospectively reviewed. Posterior vitreous detachment (PVD) was determined based on B-scan OCT images. En face OCT images were used to visualize the ERM and retinal folds. ERM formation was identified by comparing en face images pre- and post-surgery. The maximum depth of the retinal folds (MDRF) was measured using en face imaging to objectively assess traction strength. RESULTS: ERM formation occurred in 15 (22.7%) eyes at the final visit; the foveal pit was preserved in all cases. Parafoveal retinal folds were present in 5 (7.6%) eyes, with a mean MDRF of 21.8 ± 12.6 µm. No significant difference was observed in best-corrected visual acuity (logarithm of the minimal angle of resolution) between the ERM formation (-0.019 ± 0.128) and non-ERM formation (-0.001 ± 0.213) groups at the final visit (P = 0.593; Mann-Whitney U test). Multivariate logistic regression analysis revealed that older age and the presence of PVD were significant risk factors for ERM formation (odds ratio 1.07, 95% confidence interval 1.01-1.14, P = 0.032; odds ratio 5.26, 95% confidence interval 1.06-26.10, P = 0.042; respectively). CONCLUSION: ERM occurred in 22.7% of cases but was mild and did not affect visual acuity. Older age and the presence of PVD are risk factors for ERM formation.

DOI： 10.1007/s00417-023-06285-w

黄斑上膜を剥離する際の内境界膜同時剥離に関連する術前因子の検討

的場亮, 神崎勇希, 木村修平, 細川海音, 塩出雄亮, 森田哲郎, 森實祐基

眼科臨床紀要 16 ( 10 ) 745 - 745 2023年10月

黄斑上膜における網膜内嚢胞様腔と視機能および網膜牽引力との関係

神崎勇希, 的場亮, 木村修平, 細川海音, 塩出雄亮, 森田哲郎, 高須逸平, 森實祐基

眼科臨床紀要 16 ( 10 ) 744 - 745 2023年10月

網膜症増殖糖尿病網膜症に対する硝子体手術後にみられる黄斑上膜に関連する因子の検討

神崎勇希, 知原佑樹, 木村修平, 細川海音, 塩出雄亮, 的場亮, 森田哲郎, 森實祐基

糖尿病合併症 37 ( Suppl.1 ) 136 - 136 2023年9月

Accuracy of ultrasound vs. Fourier-domain optic biometry for measuring preoperative axial length in cases of rhegmatogenous retinal detachment. 査読

Shuhei Kimura, Mio Morizane Hosokawa, Yusuke Shiode, Ryo Matoba, Yuki Kanzaki, Yasuhito Goto, Keisuke Kanenaga, Etsuji Suzuki, Yuki Morizane

Japanese journal of ophthalmology 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To identify a method for accurately measuring preoperative axial length (AL) in cases of rhegmatogenous retinal detachment (RRD). STUDY DESIGN: Retrospective study. METHODS: This retrospective study included 83 eyes of 83 patients who underwent vitrectomy for RRD and had both preoperative and postoperative data for AL. Preoperative AL measurements for the affected eye were obtained using ultrasound (aUS-AL) and compared with those for affected and fellow eyes measured using optical biometry (aOB-AL and fOB-AL, respectively). Absolute differences between preoperative aUS-AL, aOB-AL, or fOB-AL measurements and postoperative AL (aPost-AL) were examined. RESULTS: In the 41 eyes without macular detachment, the absolute difference between aOB-AL and aPost-AL (0.06±0.07 mm) was significantly smaller than between aUS-AL and aPost-AL (0.21±0.18 mm) and that between fOB-AL and aPost-AL (0.29±0.35 mm) (P = 0.017 and P < 0.001, respectively). In the 42 eyes with macular detachment, the absolute difference between aOB-AL and aPost-AL (1.22±2.40 mm) was significantly larger than between aUS-AL and aPost-AL (0.24±0.24 mm) and between fOB-AL and aPost-AL (0.35±0.49 mm) (P = 0.006, P = 0.016, respectively). CONCLUSION: The current findings suggest that aOB-AL is more accurate than aUS-AL or fOB-AL in cases of RRD without macular detachment, while aUS-AL or fOB-AL is more accurate than aOB-AL in cases with macular detachment.

DOI： 10.1007/s10384-023-01018-2

A Case of Acute Zonal Occult Outer Retinopathy in which Oct en Face Imaging Was Useful for Diagnosis and Follow-up. 査読

Ryuki Ono, Yusuke Shiode, Shuhei Kimura, Mio Hosokawa, Ryo Matoba, Yuki Kanzaki, Hiroya Kindo, Tetsuro Morita, Yuki Morizane

Acta medica Okayama 77 ( 4 ) 433 - 437 2023年8月

記述言語：英語

A 23-year-old woman presented with a 1-month history of visual abnormalities in her right eye. A visual field test revealed temporal abnormalities in the right eye. Optical coherence tomography revealed an indistinct ellipsoid zone (EZ) on the B-scan image and hyporeflective areas in the EZ layer on the en face image in the right eye. We diagnosed the patient with acute zonal occult outer retinopathy. Visual field tests and B-scan images improved to almost normal at 6 months, but hyporeflective areas remained on the en face images. Thus, en face images may be more sensitive at detecting abnormalities in the outer retina than other modalities.

DOI： 10.18926/AMO/65756

OCT En face画像を用いた糖尿病黄斑浮腫の分類と黄斑上膜の合併率

森實祐基, 藤原篤之, 神崎勇希, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 的場亮

日本糖尿病眼学会誌 27 116 - 116 2023年5月

A factor for predicting simultaneous internal limiting membrane peeling during epiretinal membrane removal: swept-source optical coherence tomography-based evaluation of epiretinal membrane adhesion to the retina. 査読

Ryo Matoba, Yuki Kanzaki, Shuhei Kimura, Mio M Hosokawa, Yusuke Shiode, Tetsuro Morita, Yuki Morizane

Japanese journal of ophthalmology 2023年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To investigate preoperative factors associated with simultaneous internal limiting membrane (ILM) peeling during epiretinal membrane (ERM) removal. STUDY DESIGN: Observational cross-sectional study. METHODS: We retrospectively reviewed 60 eyes with idiopathic ERM that underwent vitrectomy. The gap between the ERM and ILM was visualized using en face optical coherence tomography. The depth and width of the ERM-ILM gap at the initiation site of ERM removal were measured, and the relationship between preoperative factors including these parameters and simultaneous ILM peeling during ERM removal was investigated. RESULTS: The ILM was simultaneously peeled during ERM removal in 30 eyes, but not in the other 30 eyes. Age was significantly higher (P = 0.017) and the width of the ERM-ILM gap was significantly smaller (P < 0.001) in the simultaneous ILM peeling (+) group than in the simultaneous ILM peeling (-) group. Multivariate logistic regression analysis confirmed the width of the ERM-ILM gap as a significant negative predictor for simultaneous ILM peeling (odds ratio, 0.992; 95% confidence interval, 0.986-0.997; P = 0.003). Receiver operating characteristic curve analysis of the width of the ERM-ILM gap revealed that the optimal cutoff for predicting simultaneous ILM peeling was 187.1 µm. CONCLUSION: The small width of the ERM-ILM gap at the initiation site of ERM removal was significantly associated with simultaneous ILM peeling, indicating that the adhesion strength between the ERM and ILM at the initial ERM grasping site determines whether simultaneous ILM peeling will occur during ERM removal.

DOI： 10.1007/s10384-023-00993-w

IMPACT OF MACULAR INTRARETINAL HEMORRHAGE AND MACULAR HOLE ON THE VISUAL PROGNOSIS OF SUBMACULAR HEMORRHAGE DUE TO RETINAL ARTERIAL MACROANEURYSM RUPTURE. 査読国際誌

Shinichiro Doi, Shuhei Kimura, Shoko Saito, Makoto Inoue, Toshiya Sakurai, Akira Kobori, Toshio Hisatomi, Hisanori Imai, Shoji Kuriyama, Ippei Takasu, Mio Morizane Hosokawa, Yusuke Shiode, Ryo Matoba, Etsuji Suzuki, Yuki Morizane

Retina (Philadelphia, Pa.) 43 ( 4 ) 585 - 593 2023年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To compare the effects of macular intraretinal hemorrhage (IRH) and macular hole (MH) on best-corrected visual acuity (BCVA) after displacement of submacular hemorrhage (SMH) due to retinal arterial macroaneurysm (RAM) rupture. METHODS: This multicenter retrospective study included 48 eyes with SMH due to RAM rupture. Cases underwent vitrectomy to displace SMH and were followed up for 6 months. We classified cases according to the presence of IRH and MH and compared the postoperative BCVA among the groups. RESULTS: We classified the eyes into IRH(+)MH(+) group (10 eyes), IRH(+)MH(-) group (23 eyes), and IRH(-)MH(-) group (15 eyes). The postoperative BCVA was significantly worse in the IRH(+)MH(+) and IRH(+)MH(-) groups than in the IRH(-)MH(-) group (0.91 ± 0.41 in logarithm of the minimal angle of resolution units, Snellen equivalent 20/163, 0.87 ± 0.45, 20/148, and 0.18 ± 0.21, 20/30, respectively; P < 0.001). The postoperative central retinal thickness was significantly lower in the IRH(+) group (IRH(+)MH(+) and IRH(+)MH(-) groups combined) than in the IRH(-) group (IRH(-)MH(-) group) (121.4 ± 70.1 µ m and 174.3 ± 32.9 µ m, respectively, P = 0.008). The postoperative external limiting membrane and ellipsoid zone continuities were significantly discontinuous in the IRH(+) group ( P < 0.001, P = 0.001, respectively). The multiple linear regression analysis showed that both IRH(+)MH(+) and IRH(+)MH(-) were associated with the postoperative BCVA (regression coefficient, 0.799 and 0.711, respectively; P < 0.001 for both). CONCLUSION: Both IRH and MH were poor prognostic indicators in cases with SMH due to RAM rupture.

DOI： 10.1097/IAE.0000000000003725

Quantitative analyses of retinal traction force and metamorphopsia in lamellar macular hole and related diseases 査読

Mai Mino, Ryo Matoba, Yuki Kanzaki, Shuhei Kimura, Mio M. Hosokawa, Yusuke Shiode, Tetsuro Morita, Yuki Morizane

Ophthalmology Science 100305 - 100305 2023年4月

Epiretinal Membrane Impairs the Inner Retinal Layer in a Traction Force-Dependent Manner 査読

Yuki Kanzaki, Ryo Matoba, Shuhei Kimura, Mio M. Hosokawa, Yusuke Shiode, Shinichiro Doi, Tetsuro Morita, Sayumi Kanzaki, Ippei Takasu, Atsuhiro Tanikawa, Yuki Morizane

Ophthalmology Science 100312 - 100312 2023年4月

急速に網膜外層の障害を来した両眼性網膜症の1例

金道寛弥, 塩出雄亮, 木村修平, 細川海音, 的場亮, 森田哲郎, 森實祐基

日本眼科学会雑誌 127 ( 臨増 ) 283 - 283 2023年3月

術後性上顎嚢胞が原因と考えられた前部ぶどう膜炎の1例

今村勇太, 塩出雄亮, 金道寛弥, 木村修平, 細川海音, 的場亮, 森田哲郎, 森實祐基

日本眼科学会雑誌 127 ( 臨増 ) 268 - 268 2023年3月

黄斑下出血を合併したILM下出血に対するILM整復法の術後経過に網膜内出血が及ぼす影響

木村修平, 細川海音, 塩出雄亮, 的場亮, 神崎勇希, 森田哲郎, 森實祐基

日本眼科学会雑誌 127 ( 臨増 ) 256 - 256 2023年3月

OCTを用いた分層黄斑円孔と類縁疾患の多面的解析

的場亮, 神崎勇希, 木村修平, 細川海音, 塩出雄亮, 森實祐基

日本眼科学会雑誌 127 ( 臨増 ) 242 - 242 2023年3月

Protrusion of KCNJ13 Gene Knockout Retinal Pigment Epithelium Due to Oxidative Stress-Induced Cell Death. 査読国際誌

Yuki Kanzaki, Hirofumi Fujita, Keita Sato, Mio Hosokawa, Hiroshi Matsumae, Yuki Morizane, Hideyo Ohuchi

Investigative ophthalmology & visual science 63 ( 12 ) 29 - 29 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: This study was performed to elucidate the mechanisms of morphological abnormalities in a Leber congenital amaurosis 16 (LCA16) cell model using KCNJ13 knockout (KO) retinal pigment epithelial cells derived from human iPS cells (hiPSC-RPE). METHODS: In KCNJ13 KO and wild-type hiPSC-RPE cells, ZO-1 immunofluorescence was performed, and confocal images were captured. The area and perimeter of each cell were measured. To detect cell death, ethidium homodimer III (EthD-III) staining and LDH assay were used. Scanning electron microscopy (SEM) was used to observe the cell surface. The expression levels of oxidative stress-related genes were examined by quantitative PCR. To explore the effects of oxidative stress, tert-butyl hydroperoxide (t-BHP) was administered to the hiPSC-RPE cells. Cell viability was tested by MTS assay, whereas oxidative damage was monitored by oxidized (GSSG) and reduced glutathione levels. RESULTS: The area and perimeter of KCNJ13-KO hiPSC-RPE cells were enlarged. EthD-III-positive cells were increased with more dead cells in the protruded region. The KO RPE had significantly higher LDH levels in the medium. SEM observations revealed aggregated cells having broken cell surfaces on the KO RPE sheet. The KCNJ13-deficient RPE showed increased expression levels of oxidative stress-related genes and total glutathione levels. Furthermore, t-BHP induced a significant increase in cell death and GSSG levels in the KO RPE. CONCLUSIONS: We suggest that in the absence of the Kir.7.1 potassium channel, human RPE cells are vulnerable to oxidative stress and ultimately die. The dying/dead cells form aggregates and protrude from the surviving KCNJ13-deficient RPE sheet.

DOI： 10.1167/iovs.63.12.29

強膜バックリング後に形成された黄斑上膜の検討:OCT en face画像を用いた解析

的場亮, 神崎勇希, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 森實祐基

眼科臨床紀要 15 ( 10 ) 691 - 692 2022年10月

糖尿病黄斑浮腫に対する抗VEGF薬の治療効果に黄斑上膜の合併が及ぼす影響

神崎勇希, 細川海音, 木村修平, 塩出雄亮, 的場亮, 森田哲郎, 森實祐基

糖尿病合併症 36 ( Suppl.1 ) 238 - 238 2022年9月

Bilateral Blunt Ocular Trauma Caused by an Exercise Resistance Band during Muscle Building Exercise for Swimming.

Kanazu Ariyasu, Shuhei Kimura, Ryo Matoba, Mio Morizane Hosokawa, Yusuke Shiode, Shinichiro Doi, Yuki Kanzaki, Yuki Morizane

Acta medica Okayama 76 ( 3 ) 349 - 354 2022年6月

記述言語：英語

An 18-year-old male high school student presented to our clinic with bilateral blunt ocular trauma caused by an exercise resistance band (ERB) during a muscle-building exercise. Best-corrected decimal visual acuities (BCVAs) for right and left eyes were light perception and 0.15, respectively. The right eye was operated 10 days after injury for persistent vitreous hemorrhage, and the left eye 5 months later because of macular hole onset. After 36 months, the right eye showed extensive retinal degeneration (BCVA 0.04), and the left eye macular hole closure (BCVA 1.2). ERBs should be used cautiously as they can cause serious ocular trauma.

DOI： 10.18926/AMO/63747

網膜細動脈瘤破裂による網膜内出血が網膜感度に及ぼす影響

赤塚陸, 土居真一郎, 木村修平, 塩出雄亮, 細川海音, 的場亮, 神崎勇希, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 171 - 171 2022年3月

光干渉断層計en face画像を用いた分層黄斑円孔関連疾患の解析

三野麻以, 的場亮, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 神崎勇希, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 235 - 235 2022年3月

水泳の筋力トレーニング中にエクササイズバンドによって重度の両眼外傷を来した一例

有安奏, 木村修平, 的場亮, 細川海音, 塩出雄亮, 土居真一郎, 神崎勇希, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 283 - 283 2022年3月

黄斑上膜における最大網膜皺襞深度と黄斑局所網膜電図および網膜層厚との関係

神崎勇希, 的場亮, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 谷川篤宏, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 196 - 196 2022年3月

網膜剥離眼における眼軸長の測定法の検討

木村修平, 後藤保人, 金永圭祐, 細川海音, 塩出雄亮, 土居真一郎, 的場亮, 神崎勇希, 鈴木越治, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 219 - 219 2022年3月

水泳の筋力トレーニング中にエクササイズバンドによって重度の両眼外傷を来した一例

有安奏, 木村修平, 的場亮, 細川海音, 塩出雄亮, 土居真一郎, 神崎勇希, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 283 - 283 2022年3月

網膜細動脈瘤破裂による網膜内出血が網膜感度に及ぼす影響

赤塚陸, 土居真一郎, 木村修平, 塩出雄亮, 細川海音, 的場亮, 神崎勇希, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 171 - 171 2022年3月

黄斑上膜における最大網膜皺襞深度と黄斑局所網膜電図および網膜層厚との関係

神崎勇希, 的場亮, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 谷川篤宏, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 196 - 196 2022年3月

網膜剥離眼における眼軸長の測定法の検討

木村修平, 後藤保人, 金永圭祐, 細川海音, 塩出雄亮, 土居真一郎, 的場亮, 神崎勇希, 鈴木越治, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 219 - 219 2022年3月

光干渉断層計en face画像を用いた分層黄斑円孔関連疾患の解析

三野麻以, 的場亮, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 神崎勇希, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 235 - 235 2022年3月

Objective and quantitative estimation of the optimal timing for epiretinal membrane surgery on the basis of metamorphopsia. 国際誌

Yuki Kanzaki, Shinichiro Doi, Ryo Matoba, Sayumi Kanzaki, Shuhei Kimura, Mio M Hosokawa, Yusuke Shiode, Ippei Takasu, Yuki Morizane

Retina (Philadelphia, Pa.) 42 ( 4 ) 704 - 711 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To establish an objective and quantitative biomarker of metamorphopsia in epiretinal membranes (ERMs) and determine the optimal timing for ERM surgery. METHODS: Retrospectively, 172 eyes with ERM were reviewed. Retinal folds due to tangential traction by ERM were visualized by en face optical coherence tomography (OCT). The maximum depth of retinal folds (MDRF) within the parafovea was quantified. Metamorphopsia was quantified by M-CHARTS. The change in the distance between the retinal vessels after ERM surgery and the preoperative total depth of retinal folds between the vessels were quantified using en face OCT and OCT angiography. RESULTS: Significant correlations were observed between preoperative MDRF and M-CHARTS scores before and at 6 months after surgery (r=0.617 and 0.460, respectively; P<0.001) and change in the distance between the retinal vessels after ERM surgery and preoperative total depth of retinal folds between the vessels (r=0.471, P=0.013). The preoperative MDRF values at which M-CHARTS scores were 0.5 before and 6 months after surgery were 69 μm and 118 μm, respectively. CONCLUSION: MDRF is an objective and quantitative biomarker of metamorphopsia in ERM. To maintain patients' quality of vision, ERM surgery may be performed when the preoperative MDRF ranges between 69 and 118 μm.

DOI： 10.1097/IAE.0000000000003401

Sublingual Gland Carcinoma Revealed by Choroidal Metastasis.

Tetsuro Morita, Yusuke Shiode, Shuhei Kimura, Mio Hosokawa, Shinichiro Doi, Kosuke Takahashi, Ryo Matoba, Yuki Kanzaki, Masahiro Tabata, Yuki Morizane

Acta medica Okayama 75 ( 6 ) 741 - 744 2021年12月

記述言語：英語

A 65-year-old man presented with a 1-week history of left eye distortion. An elevated choroidal lesion covering 6 disc diameters was found in the posterior retina of the left eye. Systemic examination revealed sublingual gland carcinoma and multiple lung metastases, and the diagnosis was choroidal metastasis from sublingual gland carcinoma. Following chemotherapy and radiation therapy, the choroidal lesion shrunk and the patient's visual acuity improved. The patient died 23 months after his first visit. To the best of our knowledge, this is the first reported case of choroidal metastasis from sublingual gland carcinoma.

DOI： 10.18926/AMO/62815

Assessment of epiretinal membrane formation using en face optical coherence tomography after rhegmatogenous retinal detachment repair. 国際誌

Ryo Matoba, Yuki Kanzaki, Shinichiro Doi, Sayumi Kanzaki, Shuhei Kimura, Mio Morizane Hosokawa, Yusuke Shiode, Kosuke Takahashi, Yuki Morizane

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 259 ( 9 ) 2503 - 2512 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To investigate epiretinal membrane (ERM) formation using en face optical coherence tomography (OCT) after vitrectomy for rhegmatogenous retinal detachment (RRD). METHODS: We retrospectively reviewed the medical records of 64 consecutive eyes (64 patients) with RRD treated by vitrectomy without ERM and internal limiting membrane peeling. ERMs and retinal folds were detected by B-scan and en face imaging. The maximum depth of retinal folds (MDRF) was quantified using en face imaging. ERM severity was staged using B-scan imaging. Main outcome measures were ERM detection rate with B-scan and en face imaging, MDRF, ERM staging, postoperative best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution), and risk factors for ERM formation. RESULTS: The detection rate for ERM formation was significantly higher with en face imaging (70.3%) than with B-scan imaging (46.9%; P = 0.007). There was no significant difference in postoperative BCVA between eyes with ERM formation (0.06 ± 0.26) and those without ERM formation (0.01 ± 0.14; P = 0.298). Forty of 45 (88.9%) eyes with ERM formation were classified as stage 1. Twenty-seven of 45 (60.0%) eyes with ERM formation developed parafoveal retinal folds. The mean MDRF was 27.4 ± 32.2 μm. Multiple retinal breaks and a maximum retinal break size of ≥ 2 disc diameters were significantly associated with ERM formation (P = 0.033 and P = 0.031, respectively). CONCLUSION: Although ERM formation was observed in 70.3% patients after RRD repair, the formed ERM was not severe and had minimal impact on the postoperative visual acuity.

DOI： 10.1007/s00417-021-05118-y

OCT En face画像を用いた糖尿病黄斑浮腫の分類と黄斑上膜の合併率

森實祐基, 藤原篤之, 神崎勇希, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 的場亮

糖尿病合併症 35 ( Suppl. ) 259 - 259 2021年9月

En Face Image-Based Analysis of Epiretinal Membrane Formation after Surgery for Idiopathic Epiretinal Membrane. 国際誌

Sayumi Kanzaki, Yuki Kanzaki, Shinichiro Doi, Ryo Matoba, Shuhei Kimura, Mio Hosokawa, Yusuke Shiode, Kosuke Takahashi, Atsushi Fujiwara, Ippei Takasu, Yuki Morizane

Ophthalmology. Retina 5 ( 8 ) 815 - 823 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To analyze en face epiretinal membrane (ERM) images constructed using swept-source (SS) OCT and to determine the incidence of ERM formation after ERM surgery and its effects on visual function. DESIGN: Retrospective, consecutive observational study. PARTICIPANTS: Consecutive series of 73 eyes (71 patients) with idiopathic ERM that underwent vitrectomy with both ERM and internal limiting membrane (ILM) peeling. METHODS: We retrospectively reviewed the data of the 73 eyes included in the study. During surgery, the ERM was removed as extensively as possible, and the ILM was removed such that the area of ILM peeling was at least larger than the parafoveal area. All patients underwent comprehensive ophthalmologic examinations, including assessments of best-corrected visual acuity and metamorphopsia, before and at 2 weeks and 6 months after the surgery. En face images constructed using SS OCT were used to investigate ERM formation. MAIN OUTCOME MEASURES: The incidence of ERM formation at 6 months after the surgery, effects of ERM formation on visual function, and the relationship between ERM formation and the extent of ERM and ILM peeling. RESULTS: At 6 months after ERM and ILM peeling, 8 eyes (11.0%) showed ERM formation (formation group). Twenty eyes (27.4%) exhibited remnant ERM without ERM formation (remnant group), whereas 45 eyes (61.6%) showed no ERM (no ERM group). In both the remnant and no ERM groups, best-corrected visual acuity and metamorphopsia showed significant improvements after ERM surgery (both P < 0.01); these improvements were not seen in the formation group (P = 0.067 and P = 0.053, respectively). However, no significant differences were found in preoperative and postoperative best-corrected visual acuities and metamorphopsia among the 3 groups. In the formation group, ERM formation occurred only in the area with residual ILM. Most patients who underwent ILM peeling in which the area of the peeling covered the ERM belonged to the no ERM group (97.7%; P < 0.01). CONCLUSIONS: Epiretinal membrane formation does not affect visual function significantly when the area of ILM peeling is larger than the parafoveal area. When the ILM peeling area covers the ERM area, postoperative ERM formation can be prevented.

DOI： 10.1016/j.oret.2020.10.017

Embedding of Epiretinal Proliferation for a Secondary Lamellar Macular Hole 12 Years after Rhegmatogenous Retinal Detachment Repair.

Miyuki Fujiwara, Shuhei Kimura, Mio Morizane Hosokawa, Yusuke Shiode, Shinichiro Doi, Kosuke Takahashi, Ryo Matoba, Yuki Kanzaki, Yuki Morizane

Acta medica Okayama 75 ( 3 ) 391 - 395 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 58-year-old Japanese man underwent vitrectomy for rhegmatogenous retinal detachment (RRD) in 2002. Twelve years later, optical coherence tomography revealed the development of a lamellar macular hole; the visual acuity was 20/200. Two years later, because metamorphopsia and the foveal retina thinning were aggravated, epiretinal proliferation embedding was performed to restore the foveal structure by transplanting glial cells to the foveal cavity. The patient was followed-up for 4 years, and his macular morphology and visual acuity (20/66) improved. No complications occurred. This appears to be the first report of epiretinal proliferation embedding for a lamellar macular hole post-RRD repair.

DOI： 10.18926/AMO/62236

En face image-based classification of diabetic macular edema using swept source optical coherence tomography. 国際誌

Atsushi Fujiwara, Yuki Kanzaki, Shuhei Kimura, Mio Hosokawa, Yusuke Shiode, Shinichiro Doi, Kosuke Takahashi, Ryo Matoba, Yuki Morizane

Scientific reports 11 ( 1 ) 7665 - 7665 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

This retrospective study was performed to classify diabetic macular edema (DME) based on the localization and area of the fluid and to investigate the relationship of the classification with visual acuity (VA). The fluid was visualized using en face optical coherence tomography (OCT) images constructed using swept-source OCT. A total of 128 eyes with DME were included. The retina was segmented into: Segment 1, mainly comprising the inner nuclear layer and outer plexiform layer, including Henle's fiber layer; and Segment 2, mainly comprising the outer nuclear layer. DME was classified as: foveal cystoid space at Segment 1 and no fluid at Segment 2 (n = 24), parafoveal cystoid space at Segment 1 and no fluid at Segment 2 (n = 25), parafoveal cystoid space at Segment 1 and diffuse fluid at Segment 2 (n = 16), diffuse fluid at both segments (n = 37), and diffuse fluid at both segments with subretinal fluid (n = 26). Eyes with diffuse fluid at Segment 2 showed significantly poorer VA, higher ellipsoid zone disruption rates, and greater central subfield thickness than did those without fluid at Segment 2 (P < 0.001 for all). These results indicate the importance of the localization and area of the fluid for VA in DME.

DOI： 10.1038/s41598-021-87440-3

Endogenous Bacterial Endophthalmitis Caused by Iliopsoas Abscess.

Weiying Sun, Yusuke Shiode, Kazuki Tokumasu, Shuhei Kimura, Mio Hosokawa, Shinichiro Doi, Kosuke Takahashi, Ryo Matoba, Fumio Otsuka, Yuki Morizane

Acta medica Okayama 75 ( 2 ) 249 - 253 2021年4月

記述言語：英語

A 79-year-old woman presented to our hospital with a 10-day history of gradually worsening binocular vision and severe backache. Further investigations revealed poor bilateral best-corrected visual acuities (BCVA), bilateral vitreous opacities, gray-white lesions scattered throughout the retina, and a left iliopsoas abscess on CT that later grew out methicillin-sensitive S. aureus. The abscess was drained and intravenous antibiotics were initiated, but the left eye additionally required intravitreal vancomycin. BCVA for both eyes normalized within 1 year. Intramuscular abscess should be considered as a possible primary lesion in cases of endogenous bacterial endophthalmitis.

DOI： 10.18926/AMO/61909

Effect of rhegmatogenous retinal detachment on preoperative and postoperative retinal sensitivities. 国際誌

Hiroshi Noda, Shuhei Kimura, Mio Morizane Hosokawa, Yusuke Shiode, Shinichiro Doi, Kosuke Takahashi, Ryo Matoba, Yuki Kanzaki, Atsushi Fujiwara, Yuki Morizane

Scientific reports 10 ( 1 ) 21497 - 21497 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

This retrospective study investigated foveal and perifoveal retinal sensitivities using microperimetry before and after surgery for rhegmatogenous retinal detachment (RRD). Consecutive patients with RRD who underwent vitrectomy or scleral buckling were included. Comprehensive ophthalmological examinations, including microperimetry and swept-source optical coherence tomography, were performed before and 6 months after surgery. Pre- and postoperative retinal sensitivities at the fovea and 4 perifoveal measurement points farthest from the fixation point, both vertically and horizontally (superior, inferior, nasal, and temporal) were examined. A total of 34 foveal and 136 perifoveal measurement points in 34 eyes of 34 patients were evaluated. The postoperative retinal sensitivity was significantly higher than the preoperative value at foveal and perifoveal points with (P < 0.001 for both) and without (fovea: P = 0.005, perifovea: P < 0.001) RRD. The postoperative retinal sensitivity was significantly lower at foveal (P < 0.01) and perifoveal (P < 0.001) points with preoperative RRD than at points without preoperative RRD; furthermore, it was significantly better at points with ellipsoid zone (Ez) continuity than at points with Ez discontinuity (fovea: P < 0.01, perifovea: P < 0.001). RRD deteriorates retinal sensitivity, regardless of its presence or absence at the measurement point before surgery. Postoperative Ez continuity is important for good postoperative retinal sensitivity.

DOI： 10.1038/s41598-020-78693-5

Release and extraction of retained subfoveal perfluorocarbon liquid facilitated by subretinal BSS, vibration, and gravity: a case report. 国際誌

Kosuke Takahashi, Shuhei Kimura, Mio Morizane Hosokawa, Yusuke Shiode, Shinichiro Doi, Ryo Matoba, Yuki Kanzaki, Yoshihiro Yonekawa, Yuki Morizane

BMC ophthalmology 20 ( 1 ) 427 - 427 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Perfluorocarbon liquid (PFCL) is an effective surgical adjuvant in performing vitrectomy for severe vitreoretinal pathologies such as proliferative vitreoretinopathy and giant retinal tears. However, subretinal retention of PFCL can occur postoperatively and retained PFCL causes severe visual disorders, particularly when PFCL was retained under the fovea. Although several procedures have been proposed for subfoveal PFCL removal, such as direct aspiration or submacular injection of balanced salt solution (BSS) to dislodge the subfoveal PFCL, the retinal damage associated with these procedures has been a major problem. Here, we report a case of subfoveal retention of PFCL for which we performed a novel surgical technique that attempts to minimize retinal damage. CASE PRESENTATION: A 69-year-old man presented with subfoveal retained PFCL after surgery for retinal detachment. To remove the retained PFCL, the internal limiting membrane overlying the subretinal injection site is first peeled to allow low-pressure (8 psi) transretinal BSS infusion, using a 41-gauge cannula, to slowly detach the macula. A small drainage retinotomy is created with the diathermy tip at the inferior position of the macular bleb, sized to be slightly wider than that of the PFCL droplet. The head of the bed is then raised, and the surgeon gently vibrates the patient's head to release the PFCL droplet to allow it to migrate inferiorly towards the drainage retinotomy. The bed is returned to the horizontal position, and the PFCL, now on the retinal surface, can be aspirated. The subfoveal PFCL is removed while minimizing iatrogenic foveal and macular damage. One month after PFCL removal, the foveal structure showed partial recovery on optical coherence tomography, and BCVA improved to 20/40. CONCLUSION: Creating a macular bleb with low infusion pressure and using vibrational forces and gravity to migrate the PFCL towards a retinotomy can be considered as a relatively atraumatic technique to remove subfoveal retained PFCL.

DOI： 10.1186/s12886-020-01698-1

RELATIONSHIP BETWEEN PREOPERATIVE FOVEAL MICROSTRUCTURE AND VISUAL ACUITY IN MACULA-OFF RHEGMATOGENOUS RETINAL DETACHMENT: Imaging Analysis by Swept Source Optical Coherence Tomography. 国際誌

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

Retina (Philadelphia, Pa.) 40 ( 10 ) 1873 - 1880 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To visualize foveal microstructures in macula-off rhegmatogenous retinal detachment using swept source optical coherence tomography preoperatively and postoperatively and to investigate the relationship between foveal microstructures and postoperative visual acuity. METHODS: We retrospectively analyzed 42 eyes of 42 consecutive patients diagnosed with macula-off rhegmatogenous retinal detachment who underwent anatomically successful repair surgery and were followed up for 6 months. We used swept source optical coherence tomography to investigate the relationship between preoperative and postoperative continuity of both the external limiting membrane (ELM) and ellipsoid zone (Ez) and preoperative and postoperative best-corrected visual acuity. RESULTS: Both preoperative ELM and Ez were continuous in 9 eyes (21%; ELM+/Ez+ eyes), only the ELM was continuous in 25 eyes (60%; ELM+/Ez- eyes), and neither was continuous in 8 eyes (19%; ELM-/Ez- eyes). Postoperative best-corrected visual acuity in ELM+/Ez+ eyes (-0.05 ± 0.04 logarithm of the minimum angle of resolution units, Snellen equivalent 20/18) was significantly better than that in both ELM+/Ez- (0.16 ± 0.16, 20/29; P = 0.03) and ELM-/Ez- (0.86 ± 0.37, 20/145; P < 0.001) eyes. Postoperative best-corrected visual acuity was significantly better in ELM+/Ez- than in ELM-/Ez- eyes (P < 0.001). CONCLUSION: In macula-off rhegmatogenous retinal detachment, preoperative continuity of the ELM and Ez may be a predictor of postoperative best-corrected visual acuity.

DOI： 10.1097/IAE.0000000000002687

EN FACE IMAGE-BASED ANALYSIS OF RETINAL TRACTION CAUSED BY EPIRETINAL MEMBRANE AND ITS RELATIONSHIP WITH VISUAL FUNCTIONS. 国際誌

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

Retina (Philadelphia, Pa.) 40 ( 7 ) 1262 - 1271 2020年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To evaluate the relationship between retinal traction caused by epiretinal membrane and visual functions. METHODS: In this institutional study, en face swept-source optical coherence tomography images of 141 eyes of 130 patients with epiretinal membrane were analyzed to investigate maximum depth of retinal folds, which represents retinal traction strength and the distribution pattern of retinal folds. We investigated the relationships between the maximum depth and distribution pattern of retinal folds and visual functions as well as the effects of membrane peeling. RESULTS: Maximum retinal fold depth was significantly correlated with the metamorphopsia score (P < 0.001). Fifteen eyes showed retinal folds radially extending from the macular epiretinal membrane (radiating folds group), whereas 126 eyes showed a multidirectional pattern of retinal folds (multidirectional folds group). The radiating folds group showed a significantly lower metamorphopsia score (P = 0.014). Multiple regression analysis revealed that the metamorphopsia score was significantly related to maximum retinal fold depth (P = 0.003), distribution pattern (P = 0.015), and central retinal thickness (P < 0.001). One month after membrane peeling, parafoveal retinal folds resolved completely in all cases, and both visual acuity (P < 0.001) and average metamorphopsia score (P = 0.036) were significantly improved. CONCLUSION: Both the strength and the distribution pattern of retinal traction are significantly related to metamorphopsia in epiretinal membrane patients.

DOI： 10.1097/IAE.0000000000002569

KCNJ13 Gene Deletion Impairs Cell Alignment and Phagocytosis in Retinal Pigment Epithelium Derived from Human-Induced Pluripotent Stem Cells. 国際誌

Yuki Kanzaki, Hirofumi Fujita, Keita Sato, Mio Hosokawa, Hiroshi Matsumae, Fumio Shiraga, Yuki Morizane, Hideyo Ohuchi

Investigative ophthalmology & visual science 61 ( 5 ) 38 - 38 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Purpose: The purpose of this study was to establish and analyze a cell model of Leber congenital amaurosis type 16 (LCA16), which is caused by mutations in the KCNJ13 gene encoding Kir7.1, an inward-rectifying potassium ion channel. Methods: The two guide RNAs specific to the target sites in the KCNJ13 gene were designed and KCNJ13 knock-out (KO) human-induced pluripotent stem cells (hiPSCs) were generated using the CRISPR/Cas9 system. The KCNJ13-KO hiPSCs were differentiated into retinal pigment epithelial cells (hiPSC-RPEs). The KCNJ13-KO in hiPSC-RPEs was confirmed by immunostaining. Phagocytic activity of hiPSC-RPEs was assessed using the uptake of fluorescently labeled porcine photoreceptor outer segments (POSs). Phagocytosis-related genes in RPE cells were assessed by quantitative polymerase chain reaction. Results: Most of the translated region of the KCNJ13 gene was deleted in the KCNJ13-KO hiPSCs by the CRISPR/Cas9 system, and this confirmed that the Kir7.1 protein was not present in RPE cells induced from the hiPSCs. Expression of RPE marker genes such as BEST1 and CRALBP was retained in the wild-type (WT) and in the KCNJ13-KO hiPSC-RPE cells. However, phagocytic activity and expression of phagocytosis-related genes in the KCNJ13-null hiPSC-RPE cells were significantly reduced compared to those of WT. Conclusions: We succeeded in generating an RPE model of LCA16 using hiPSCs. We suggest that Kir7.1 is required for phagocytosis of POSs by RPE cells and that impaired phagocytosis in the absence of Kir7.1 would be involved in the retinal degeneration found in LCA16.

DOI： 10.1167/iovs.61.5.38

ADVERSE EFFECT OF MACULAR INTRARETINAL HEMORRHAGE ON THE PROGNOSIS OF SUBMACULAR HEMORRHAGE DUE TO RETINAL ARTERIAL MACROANEURYSM RUPTURE. 国際誌

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

Retina (Philadelphia, Pa.) 40 ( 5 ) 989 - 997 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To investigate the clinical course of submacular hemorrhage associated with ruptured retinal arterial macroaneurysm using swept-source optical coherence tomography. METHODS: This study included 23 eyes of 23 consecutive patients diagnosed with submacular hemorrhage associated with ruptured retinal arterial macroaneurysm. Cases underwent displacement of submacular hemorrhage (vitrectomy + subretinal injection of tissue plasminogen activator + air tamponade) and were followed up for 6 months after surgery. Localization of the preoperative hemorrhage and its effect on preoperative and postoperative best-corrected visual acuity, central retinal thickness, and continuity of the ellipsoid zone were measured. RESULTS: Macular intraretinal hemorrhage (IRH) was observed in 17 eyes (73.9%, IRH [+] group) and was not observed in 6 eyes (26.1%, IRH [-] group). The IRH (+) group showed worse postoperative best-corrected visual acuity values compared with the IRH (-) group (0.89 ± 0.47 in logarithm of the minimal angle of resolution units, Snellen equivalent 20/155 and 0.16 ± 0.23, 20/29, respectively; P < 0.01), smaller central retinal thickness values (97.7 ± 53.5 μm, 173.0 ± 32.3 μm, respectively; P < 0.01), and a higher rate of ellipsoid zone disruption (100%, 33.3%, respectively; P < 0.01). CONCLUSION: Patients with preoperative macular IRH showed lower postoperative visual acuity and worse macular contour after submacular hemorrhage displacement compared with patients without macular IRH.

DOI： 10.1097/IAE.0000000000002460

Interocular symmetry of the foveal avascular zone area in healthy eyes: a swept-source optical coherence tomography angiography study.

Mengxuan Liu, Atsushi Fujiwara, Yuki Morizane, Ryo Kawasaki, Shuhei Kimura, Mio Morizane-Hosokawa, Yusuke Shiode, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Kosuke Takahashi, Mika Hosogi, Xiang Ma, Fumio Shiraga

Japanese journal of ophthalmology 64 ( 2 ) 171 - 179 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To determine the presence or absence of interocular differences in the foveal avascular zone (FAZ) area in healthy eyes. STUDY DESIGN: Cross-sectional study. METHODS: We examined 236 healthy eyes of 118 consecutive subjects (mean age, 39.1 ± 18.9 years). We used swept-source optical coherence tomography angiography (OCTA) images of the FAZ to measure its area from both the superficial capillary plexus (SCP-FAZ) and the whole retinal capillary plexus (WCP-FAZ). We also investigated the relationship between interocular differences in SCP-FAZ and other factors such as: axial length, spherical equivalent, central retinal thickness, and retinal vascular density. RESULTS: There was no significant difference in the FAZ area between the right and left eyes in either the SCP-FAZ (P = 0.61) or WCP-FAZ (P = 0.80), and the FAZ areas of both eyes showed significant positive correlations (SCP-FAZ; P < 0.001, R2 = 0.884, WCP-FAZ; P < 0.001, R2 = 0.856). Bland-Altman plots showed that the mean interocular difference in SCP-FAZ area was 0.002 ± 0.037 mm2 (95% confidence interval, -0.072-0.075 mm2), and in the WCP-FAZ area, 0.050 ± 0.044 mm2 (95% confidence interval, -0.036-0.137 mm2). Multivariate regression analysis showed that none of the investigated factors were significantly associated with interocular differences in SCP-FAZ (P = 0.61, R2 = 0.138). CONCLUSIONS: There was no significant interocular difference in SCP- and WCP-FAZ areas in healthy eyes. The normal range of values for interocular difference in SCP-FAZ area was 0.002 ± 0.037 mm2 and in the WCP-FAZ area, 0.050 ± 0.044 mm2.

DOI： 10.1007/s10384-020-00719-2

Two-year Results of Intravitreal Ranibizumab Injections Using a Treat-and-extend Regimen for Macular Edema due to Branch Retinal Vein Occlusion.

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

Acta medica Okayama 73 ( 6 ) 517 - 522 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

We investigated the effectiveness of a treat-and-extend regimen (TAE) of intravitreal ranibizumab injections for macular edema (ME) due to branch retinal vein occlusion (BRVO). We retrospectively examined 2-year results of 32 eyes of 32 patients who underwent TAE to treat ME due to BRVO. The patients whose treatment interval extended to ≥ 12 weeks were switched to a pro re nata regimen (PRN). For the patients whose treatment interval was <12 weeks, TAE was continued. At 2 years, 10 eyes had required no additional injections after the initial treatment period [recurrence(-) group], whereas the other 22 eyes required additional treatment [recurrence(+) group]. Among the recurrence(+) patients, 11 eyes (34.4% of total) were eventually switched from TAE to PRN; the other 11 eyes (34.4%) continued TAE for 2 years. Visual acuity and central retinal thickness were significantly improved in both the recurrence(+) and (-) groups, and there was no significant betweengroup difference in visual acuity at 2 years. Univariate analyses revealed significant differences in visual acuity (p=0.004), age (p=0.014), and vessel occlusion site (p=0.018) between these groups. Our results suggest that TAE may be effective for BRVO patients with lower visual acuity, older age, and occlusion of a major vein.

DOI： 10.18926/AMO/57716

Outcomes of vitrectomy combined with subretinal tissue plasminogen activator injection for submacular hemorrhage associated with polypoidal choroidal vasculopathy.

Shuhei Kimura, Yuki Morizane, Mio Morizane Hosokawa, Yusuke Shiode, Shinichiro Doi, Mika Hosogi, Atsushi Fujiwara, Toshio Okanouchi, Yasushi Inoue, Fumio Shiraga

Japanese journal of ophthalmology 63 ( 5 ) 382 - 388 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To examine the outcomes of vitrectomy with subretinal tissue plasminogen activator (tPA) injection and postoperative intravitreal antivascular endothelial growth factor (VEGF) injection for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: Retrospective, consecutive case series. METHODS: Patients who underwent vitrectomy for SMH associated with PCV and who were followed up for at least 12 months were included. Surgery consisted of vitrectomy with subretinal tPA and air tamponade. Postoperative intravitreal anti-VEGF was administered pro re nata. The following were examined: best-corrected visual acuity (BCVA) at baseline, at 1 month, and at the final visit; the percentage of patients requiring anti-VEGF postoperatively; and the number of injections administered. RESULTS: This study included 23 eyes of 23 patients (21 men, 2 women) with a mean age of 72.5 ± 9.0 years. The mean duration from disease onset to surgery was 9.0 ± 6.6 days. The mean maximum SMH size was 5.8 ± 4.8 disc diameters. The mean follow-up period was 33 ± 14 months. The BCVA was significantly improved when compared with baseline 1 month after surgery and at the final visit. Postoperative anti-VEGF was required for 91% of the eyes. In eyes that underwent anti-VEGF therapy until the final visit, the mean injection number was 4.1/year. CONCLUSIONS: Vitrectomy with subretinal tPA and air tamponade improved visual acuity in patients with SMH associated with PCV. Postoperative intravitreal anti-VEGF injection maintained the improved BCVA throughout a mean period of 33 months.

DOI： 10.1007/s10384-019-00679-2

The Impact of Prefilled Syringes on Endophthalmitis Following Intravitreal Injection of Ranibizumab. 国際誌

Philip P Storey, Zujaja Tauqeer, Yoshihiro Yonekawa, Bozho Todorich, Jeremy D Wolfe, Sumit P Shah, Ankoor R Shah, Takashi Koto, Ashkan M Abbey, Yuki Morizane, Priya Sharma, Edward H Wood, Mio Morizane-Hosokawa, Pooja Pendri, Maitri Pancholy, Shawn Harkey, Karen W Jeng-Miller, Anthony Obeid, Durga S Borkar, Eric Chen, Patrick Williams, Annabelle A Okada, Makoto Inoue, Fumio Shiraga, Akito Hirakata, Chirag P Shah, Jonathan Prenner, Sunir Garg

American journal of ophthalmology 199 200 - 208 2019年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To compare the rates of infectious endophthalmitis following intravitreal injection of ranibizumab using prefilled syringes vs conventional preparation. DESIGN: Multicenter retrospective cohort study. METHODS: All eyes receiving intravitreal injection of 0.5 mg ranibizumab for retinal vascular diseases at 10 retina practices across the United States (2016 to 2017) and Japan (2009 to 2017) were included. The total numbers of eyes and injections were determined from billing codes. Endophthalmitis cases were determined from billing records and evaluated with chart review. Primary outcome was the rate of postinjection acute endophthalmitis. Secondary outcomes were visual acuity and microbial spectrum. RESULTS: A total of 243 754 intravitreal 0.5 mg ranibizumab injections (165 347 conventional and 78 407 prefilled) were administered to 43 132 unique patients during the study period. In the conventional ranibizumab group, a total of 43 cases of suspected endophthalmitis occurred (0.026%; 1 in 3845 injections) and 22 cases of culture-positive endophthalmitis occurred (0.013%; 1 in 7516 injections). In the prefilled ranibizumab group, 12 cases of suspected endophthalmitis occurred (0.015%; 1 in 6534 injections) and 2 cases of culture-positive endophthalmitis occurred (0.0026%; 1 in 39 204 injections). Prefilled syringes were associated with a trend toward decreased risk of suspected endophthalmitis (odds ratio 0.59; 95% confidence interval 0.31-1.12; P = .10) and a statistically significant decreased risk of culture-positive endophthalmitis (odds ratio 0.19; 95% confidence interval 0.045-0.82; P = .025). Average logMAR vision loss at final follow-up was significantly worse for eyes that developed endophthalmitis from the conventional ranibizumab preparation compared to the prefilled syringe group (4.45 lines lost from baseline acuity vs 0.38 lines lost; P = .0062). Oral-associated flora was found in 27.3% (6/22) of conventional ranibizumab culture-positive endophthalmitis cases (3 cases of Streptococcus viridans, 3 cases of Enterococcus faecalis) compared to 0 cases in the prefilled ranibizumab group. CONCLUSION: In a large, multicenter, retrospective study the use of prefilled syringes during intravitreal injection of ranibizumab was associated with a reduced rate of culture-positive endophthalmitis, including from oral flora, as well as with improved visual acuity outcomes.

DOI： 10.1016/j.ajo.2018.11.023

Successful resolution of coats disease by photodynamic therapy: a case report. 国際誌

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

BMC ophthalmology 18 ( 1 ) 264 - 264 2018年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Coats disease is a retinal disease characterized by exudative retinal detachment due to abnormal retinal blood vessels. Coats disease is generally treated using laser photocoagulation and cryotherapy to ablate the abnormal retinal blood vessels. However, if abnormal blood vessels are present near the posterior pole of the eye and there is a severe exudative change there, it is difficult to perform these standard treatments. We describe a case of Coats disease with severe exudative retinal change and retinal vascular abnormality near the posterior pole for which we performed photodynamic therapy and successfully suppressed the disease and improved vision. CASE PRESENTATION: A 15-year-old Japanese boy presented to hospital with a chief complaint of decreased vision in his right eye. At the initial examination, corrected visual acuity of the right eye was 20/100. On the right fundus, exudative retinal detachment with subretinal haemorrhage was observed from the upper intermediate periphery to the posterior pole. Abnormal telangiectatic vessels and microaneurysms were found at the nasal peripheral retina. From these findings, we diagnosed the case as Coats disease. We conducted photodynamic therapy for the right eye. At 10 months after treatment, both the subretinal haemorrhage and the exudative retinal detachment had disappeared completely. Further, the retinal structure of the macula had recovered, and right vision had improved to 20/20. CONCLUSION: Photodynamic therapy may be an effective and safe treatment for Coats disease in cases that present with abnormal retinal vessels close to the posterior pole of the eye.

DOI： 10.1186/s12886-018-0930-z

Embedding of lamellar hole-associated epiretinal proliferation combined with internal limiting membrane inversion for the treatment of lamellar macular hole: a case report. 国際誌

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

BMC ophthalmology 18 ( 1 ) 257 - 257 2018年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: We recently reported that lamellar macular hole (LMH) with lamellar hole-associated epiretinal proliferation (LHEP) can be effectively treated by embedding the LHEP into the retinal cleavage to improve foveal contour and visual acuity. Here, we report a case of LMH with LHEP for which we performed embedding of the LHEP combined with internal limiting membrane (ILM) inversion. We then evaluated the effects of this surgery on macular morphology and visual functions. CASE PRESENTATION: A 62-year-old man presented with visual disturbance (20/29) and metamorphopsia in his right eye. B-scan optical coherence tomography (OCT) imaging revealed the presence of both partial-thickness defect of the macula with degenerative retinal cleavage and LHEP at the surface of the retina. En face OCT imaging showed the absence of retinal fold. We performed phacoemulsification with intraocular lens implantation, vitrectomy, embedding of LHEP into the retinal cleavage, and ILM inversion. Three months after the surgery, both foveal contour and visual acuity (20/20) were improved and metamorphopsia was reduced. CONCLUSION: Embedding of the LHEP combined with ILM inversion may be an effective treatment for LMH with LHEP.

DOI： 10.1186/s12886-018-0926-8

Impact of Polyp Regression on 2-year Outcomes of Intravitreal Aflibercept Injections: A Treat-and-Extend Regimen for Polypoidal Choroidal Vasculopathy.

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

Acta medica Okayama 72 ( 4 ) 379 - 385 2018年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

We conducted intravitreal aflibercept injections (IVAs) for 37 Japanese patients (28 males, 9 females, mean age 73.4 years) with polypoidal choroidal vasculopathy (PCV), with a treat-and-extend regimen (TER). We evaluated the impact of polyp regression after a loading dose (2-mg IVA 1×/month for 3 months) on the patients' 2-year treatment outcomes. Thirty-seven eyes were treated with IVA by a TER for 2 years. We divided the patients into 2 groups based on their polyp status after the loading dose: polyp regression (PR+) (n=19) and no polyp regression (PR-) (n=18). We compared the groups' best-corrected visual acuity (BCVA), central retinal thickness (CRT), recurrence rate, total number of injections, and final treatment interval. Both the BCVA and CRT were significantly improved by the treatment in both groups, with no between-group difference in the amount of change (p=0.769). In the polyp regression (+) group, recurrence was significantly less common (p=0.03), the mean total number of injections was significantly lower (p=0.013), and the mean treatment interval was significantly longer (0.042). Regarding the 2-year outcomes for PCV, the eyes with post-loading-dose polyp regression demonstrated less frequent recurrence and required fewer numbers of injections compared to the eyes without polyp regression.

DOI： 10.18926/AMO/56175

Assessment of Lamellar Macular Hole and Macular Pseudohole With a Combination of En Face and Radial B-scan Optical Coherence Tomography Imaging. 国際誌

Masayuki Hirano, Yuki Morizane, Shuhei Kimura, Mio Hosokawa, Yusuke Shiode, Shinichiro Doi, Shinji Toshima, Kosuke Takahashi, Mika Hosogi, Atsushi Fujiwara, Ippei Takasu, Toshio Okanouchi, Masaya Kawabata, Fumio Shiraga

American journal of ophthalmology 188 29 - 40 2018年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To investigate lamellar macular hole (LMH) and macular pseudohole (MPH) using a combination of en face and radial B-scan OCT. DESIGN: Retrospective observational case series. METHODS: Setting: Institutional study. PATIENT POPULATION: En face and radial B-scan OCT images of 63 eyes of 60 patients diagnosed with LMH or MPH based on an international classification were reviewed. OBSERVATION PROCEDURES: Cases were classified using en face images based on the presence/absence of epiretinal membrane (ERM), retinal folds, parafoveal epicenter of contractile ERM (PEC-ERM), and retinal cleavage. We compared the en face imaging-based classification system with the international classification system using radial B-scan images. We quantitatively evaluated visual function and macular morphology. MAIN OUTCOME MEASURES: Characterization of multimodal OCT-based subtypes of LMH and MPH. RESULTS: All cases showed ERM and were classified into 4 groups. In the first group, which lacked retinal folds and showed significantly lower visual acuity than the other groups, 81% of eyes had degenerative LMH. In the second group, which lacked PEC-ERM and retinal cleavage and showed significantly lower retinal fold depth, all eyes had MPH. The third group, in which 95% of eyes had symmetric tractional LMH, included eyes with retinal cleavage but without PEC-ERM, and this group showed higher circularity of the foveal aperture and cleavage area than the group with both these features, in which all eyes had asymmetric tractional LMH. CONCLUSIONS: Multimodal OCT enables classification of LMH and MPH based on pathologic conditions. Retinal traction in particular may be useful for determining treatment methods.

DOI： 10.1016/j.ajo.2018.01.016

Results of a Treat-and-Eextend Regimen of Intravitreal Ranibizumab Injection for Macular Edema due to Branch Retinal Vein Occlusion.

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

Acta medica Okayama 72 ( 1 ) 39 - 45 2018年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

To investigate the effectiveness of a treat-and-extend regimen (TAE) of intravitreal ranibizumab injections (IVR) for macular edema (ME) due to branch retinal vein occlusion (BRVO). We retrospectively examined 35 eyes of 35 patients with ME due to BRVO who underwent TAE for 1 year. Patients whose treatment interval extended to 12 weeks were switched to a pro re nata regimen (PRN; TAE to PRN group), while TAE was continued for patients whose treatment interval was less than 12 weeks (continued TAE group). Changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and predictive factors for inclusion in the TAE to PRN group were analyzed. BCVA and CRT both improved significantly at 1 year compared with baseline (p<0.001). Sixteen eyes (45.7%) were included in the TAE to PRN group, while 19 eyes (54.3%) were included in the continued TAE group. BCVA in the TAE to PRN group was significantly better than that in the continued TAE group at 1 year (p=0.047). BCVA at baseline and macular BRVO were significant predictive factors for inclusion in the TAE to PRN group. TAE was effective for improving BCVA and CRT. The TAE to PRN group showed significantly better prognosis.

DOI： 10.18926/AMO/55661

The influence of subretinal injection pressure on the microstructure of the monkey retina. 国際誌

Kosuke Takahashi, Yuki Morizane, Toshio Hisatomi, Takashi Tachibana, Shuhei Kimura, Mio Morizane Hosokawa, Yusuke Shiode, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Ryoichi Araki, Hiroshi Matsumae, Yuki Kanzaki, Mika Hosogi, Atsushi Yoshida, Koh-Hei Sonoda, Fumio Shiraga

PloS one 13 ( 12 ) e0209996 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To investigate the influence of subretinal injection pressure on the microstructure of the retina in a monkey model. METHODS: After vitrectomy, balanced salt solution was injected subretinally into one eye each of four cynomolgus monkeys while controlling the injection pressure. Initially, a pressure of 2 psi was used, and this was gradually increased to determine the minimum required pressure. Subsequent injections were performed at two pressures: minimum (n = 13) and high (n = 6). To compare the influence of these injection pressures on retinal structure, optical coherence tomography (OCT) was performed before surgery and every week afterwards. The monkeys were euthanized and their eyes were enucleated at 1 or 6 weeks after the injections. The eyes were processed for light microscopy and transmission electron microscopy (TEM) as well as for TdT-mediated dUTP nick end labeling. RESULTS: The minimum pressure required to perform subretinal injection was 6 psi. After injection at this pressure, both OCT and microscopy showed that the retinal structure was well-preserved throughout the experimental period at all injection sites. Conversely, after injection at high pressure (20 psi) OCT images at all injection sites showed disruption of the ellipsoid zone (EZ) after 1 week. Microscopy indicated damage to the photoreceptor outer segment (OS) and stratification of the retinal pigment epithelium (RPE). After 6 weeks, OCT demonstrated that the EZ had become continuous and TEM confirmed that the OS and RPE had recovered. Photoreceptor apoptosis was absent after subretinal injection at both pressures. CONCLUSIONS: The retinal damage caused by subretinal injection increases depending on pressure, indicating that clinicians should perform subretinal injection at pressures as low as possible to ensure safety.

DOI： 10.1371/journal.pone.0209996

Retinal sensitivity after displacement of submacular hemorrhage due to polypoidal choroidal vasculopathy: effectiveness and safety of subretinal tissue plasminogen activator.

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

Japanese journal of ophthalmology 61 ( 6 ) 472 - 478 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To investigate the effectiveness of displacement of submacular hemorrhage (SMH) caused by polypoidal choroidal vasculopathy (PCV) by assessing retinal sensitivity using microperimetry. METHODS: We retrospectively reviewed the medical records of 11 consecutive PCV patients with SMH. All patients underwent vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-air exchange, followed by antivascular endothelial growth factor therapy using a pro re nata regimen. The retinal sensitivity was measured by use of microperimetry before and after surgery. RESULTS: The mean (SD) age of the patients was 74.1 ± 9.4 years. The mean SMH diameter was 6.8 ± 5.2 disc diameters. The best-corrected visual acuity (BCVA), mean retinal sensitivity, and mean number of measure points with a sensitivity ≥10 dB before the surgery were 0.94 ± 0.49, 4.2 ± 4.5 dB, and 15.6 ± 15.1 points, respectively. These had significantly improved 6 months after surgery (0.39 ± 0.37, 15.6 ± 7.3 dB, and 50.9 ± 22.2 points, respectively; P < 0.05 for all outcome measures). The mean number of measure points with an absolute scotoma before surgery had decreased significantly 6 months after surgery (from 40.5 ± 15.0 to 9.4 ± 16.0 points; P < 0.001). CONCLUSIONS: Displacement of SMH effectively improves retinal sensitivity as well as BCVA.

DOI： 10.1007/s10384-017-0530-0

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年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

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

Factors Affecting Choroidal Vascular Density in Normal Eyes: Quantification Using En Face Swept-Source Optical Coherence Tomography. 国際誌

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

American journal of ophthalmology 170 1 - 9 2016年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To quantify the vascular density of the choroid of normal eyes and to identify the influencing factors using en face images obtained with swept-source optical coherence tomography (SS OCT). DESIGN: Prospective cross-sectional study. METHODS: One hundred and sixty-three eyes of 163 healthy volunteers (83 female; mean age 42.2 ± 22.6 years) with a corrected visual acuity of ≥1.0 were investigated. En face SS OCT images of the choroid were used for quantitative assessment of the vascular density in the large choroid vessel layer. Relationships between vascular density of the choroid and age, sex, refractive error (RE), axial length (AL), and subfoveal choroidal thickness (SCT) were also investigated. RESULTS: There was a significant negative relationship between vascular density of the choroid and subject age (P < .001). Analysis according to age showed a significant correlation in the group aged >30 years (P < .001), but not in the group aged ≤30 years (P = .225). SCT had a significant positive relationship with vascular density of the choroid (P < .001). However, a significant correlation was not observed between sex, RE, or AL and vascular density of the choroid (P = .981, P = .292, and P = .216, respectively). Multivariable regression analysis with vascular density of the choroid as the dependent variable and age, sex, RE, AL, and SCT as independent variables showed that age and SCT are important determinants of vascular density of the choroid (P < .001). CONCLUSION: Age and SCT affect vascular density of the choroid.

DOI： 10.1016/j.ajo.2016.07.006

Efficacy of vitrectomy and inner limiting membrane peeling in age-related macular degeneration resistant to anti-vascular endothelial growth factor therapy, with vitreomacular traction or epiretinal membrane. 国際誌

Shuhei Kimura, Yuki Morizane, Shinji Toshima, Mika Hosogi, Fumiaki Kumase, Mio Hosokawa, Yusuke Shiode, Atsushi Fujiwara, Fumio Shiraga

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 254 ( 9 ) 1731 - 6 2016年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: We assessed the efficacy of vitrectomy and inner limiting membrane (ILM) peeling, followed by anti-vascular endothelial growth factor (VEGF) therapy, anti-VEGF-resistant age-related macular degeneration (AMD) due to vitreomacular traction (VMT) or epiretinal membrane (ERM). METHODS: We identified six patients with anti-VEGF-resistant AMD due to VMT or ERM amongst a total of 588 patients with AMD (821 eyes) referred to Okayama University Hospital between February 2012 and May 2014. These patients underwent vitrectomy to release the VMT (4 cases) or remove the ERM (2 cases), along with ILM peeling. The regimen used for intravitreal injections of anti-VEGF reagents after surgery was based on the severity of exudative changes in each patient. Preoperative and postoperative best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measurements were compared. RESULTS: After vitrectomy and ILM peeling, all six patients responded to anti-VEGF therapy, which was then able to maintain dry retinas. Mean BCVA did not improve significantly (0.49 ± 0.28 before vs. 0.43 ± 0.38 after surgery, P = 0.538). However, mean CR was significantly decreased after surgery, from 423 ± 83.5 μm to 257 ± 75.8 μm (P = 0.0078). CONCLUSIONS: Vitrectomy and ILM peeling followed by anti-VEGF therapy may be a useful therapeutic option for anti-VEGF-resistant AMD with VMT or ERM.

DOI： 10.1007/s00417-016-3314-1

CLINICAL CHARACTERISTICS OF IDIOPATHIC FOVEOMACULAR RETINOSCHISIS. 国際誌

Ichiro Maruko, Yuki Morizane, Shuhei Kimura, Yusuke Shiode, Mio Hosokawa, Tetsuju Sekiryu, Tomohiro Iida, Fumio Shiraga

Retina (Philadelphia, Pa.) 36 ( 8 ) 1486 - 92 2016年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To describe the clinical features of idiopathic foveomacular retinoschisis not in association with myopia, glaucoma, optic disk pit, or juvenile retinoschisis. METHODS: Retrospective observational case series. Five eyes of five patients with idiopathic foveomacular retinoschisis were included. RESULTS: The patients were 2 men and 3 women (average age, 75.2 years; range, 71-78 years). The average spherical equivalent was +2.40 diopters (range, +0.88 to +5.75 diopters), and the average axial length was 22.0 mm (range, 21.1-23.1 mm). All patients had retinoschisis from the macula to the optic disk in the affected eye. No patients had retinoschisis in the fellow eye. The average best-corrected visual acuity was 20/44 (68 Early Treatment Diabetic Retinopathy Study letter score). CONCLUSION: Idiopathic foveomacular retinoschisis is not inherited or associated with myopia, vitreomacular traction syndrome, optic pit, or glaucoma but is associated with older age, unilaterality, hyperopia with short axial length, complete posterior vitreous detachment, and weak leakage from the optic disk on fluorescein angiography.

DOI： 10.1097/IAE.0000000000000938

A case of radiation retinopathy after carbon ion radiotherapy for adenoid cystic carci - I noma in the sphenoid sinus

Koichiro Watanabe, Shinji Toshima, Kiyo Shibata, Mio Hosokawa, Shinichiro Doi, Hiroshi Noda, Yoshiko Terada, Kazuyuki Hara

Japanese Journal of Clinical Ophthalmology 70 ( 3 ) 387 - 392 2016年3月

記述言語：日本語掲載種別：研究論文（国際会議プロシーディングス）出版者・発行元：Igaku-Shoin Ltd

Purpose: To report a case of radiation retinopathy after carbon ion radiotherapy for adenoid cystic carcinoma in the sphenoid sinus. Case: A 26-year-old female was referred to us for impaired visual acuity in the right eye. She had received carbon ion radiotherapy for adenoid cystic carcinoma in the right sphenoid sinus extending to the right cavernous sinus 19 months before. The dosis of radiation totaled 57.6 GyE. Findings: Corrected visual acuity was 0.8 right and 1.2 left. The right fundus showed a few retinal hemorrhages and cotton-wool spots. Fluorescein angiography showed dry leakage from retinal vessels. Retinal nonperfusion was also present, leading the diagnosis of radiation retinopathy. The right eye developed cataract 32 months later followed by cataract surgery. Retinal neovasucularization developed another 10 months later and was treated by photocoagulation. There has been no recurrence of carcinoma in the sphenoid sinus for 97 months with right visual acuity maintained at 1.0. Conclusion: The present case illustrates that radiation retinopathy may develop years after carbon ion radiotherapy for adenoid cystic carcinoma in the sphenoid sinus.

Surgical Outcome of Idiopathic Epiretinal Membranes with Intraretinal Cystic Spaces. 国際誌

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

PloS one 11 ( 12 ) e0168555 2016年

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: To investigate the occurrence ratio, localization, and surgical outcomes of intraretinal cystic spaces in idiopathic epiretinal membranes (ERMs). METHODS: We retrospectively reviewed the charts of 432 eyes of 398 consecutive patients with idiopathic ERM who underwent vitrectomy and ERM peeling from January 2012 to September 2015. We selected cases with intraretinal cystic space prior to surgery, detected by spectral-domain optical coherence tomography. We then evaluated the effects of ERM peeling on intraretinal cystic spaces, best corrected visual acuity, and central retinal thickness at 6 months after surgery. RESULTS: Twenty-four eyes (5.5%) showed intraretinal cystic spaces before surgery, present in the inner retinal layer (the inner group) in 9 eyes, in the outer retinal layer (the outer group) in 6 eyes, and in both the inner and the outer retinal layers (the combined group) in 9 eyes. Additionally, 30 eyes with ERM but without any presence of intraretinal cystic space were selected randomly and classified as the no cyst group. At 6 months after surgery, the disappearance rate of cystic spaces was significantly greater for the outer group than for the inner group (83.3% and 11.1%, respectively, P = 0.011). The mean best corrected visual acuity improved significantly after surgery in the inner group, the outer group, and the no cyst group (P < 0.05 for all three groups) but did not improve in the combined group (P = 0.58). The mean central retinal thickness decreased significantly after surgery in the inner group, the combined group, and the no cyst group (P < 0.05). CONCLUSIONS: Intraretinal cystic spaces were observed in 5.5% of preoperative idiopathic ERM cases. Following surgery, the cystic spaces in the outer retinal layer disappeared at higher rates than those in the inner retinal layer, suggesting that the pathophysiologies of these cystic spaces are different.

DOI： 10.1371/journal.pone.0168555

COMPARISON OF HALVING THE IRRADIATION TIME OR THE VERTEPORFIN DOSE IN PHOTODYNAMIC THERAPY FOR CHRONIC CENTRAL SEROUS CHORIORETINOPATHY. 国際誌

Yusuke Shiode, Yuki Morizane, Shuhei Kimura, Mio Hosokawa, Tetsuhiro Kawata, Shinichiro Doi, Mika Hosogi, Atsushi Fujiwara, Fumio Shiraga

Retina (Philadelphia, Pa.) 35 ( 12 ) 2498 - 504 2015年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To compare the efficacy and safety of photodynamic therapy using reduced irradiation time or reduced verteporfin dose for chronic central serous chorioretinopathy. METHODS: Between April 2011 and December 2013, 45 eyes with chronic central serous chorioretinopathy (43 consecutive patients) were treated with photodynamic therapy, using either half the irradiation time (18 eyes) or half the verteporfin dose (27 eyes). Outcome measures at follow-up, over at least 3 months, were complete resolution of serous retinal detachment, best-corrected visual acuity, and central retinal thickness. RESULTS: After 3 months, serous retinal detachment had completely resolved in 88.8% of eyes in both treatment groups, which were therefore not significantly different. The logarithm of the minimal angle of resolution best-corrected visual acuity (Snellen equivalent) improved from 0.245 (20/35) to 0.130 (20/27) (P < 0.05, paired t-test) in the reduced time group and from 0.283 (20/38) to 0.138 (20/27) (P < 0.05) in the reduced verteporfin group. Final best-corrected visual acuities in the 2 groups were not significantly different. Central retinal thicknesses dropped from 337.0 μm to 146.6 μm (P < 0.05) in the reduced time group and from 343.5 μm to 166.9 μm (P < 0.05) in the reduced verteporfin group. No ocular or systemic side effects were observed. CONCLUSION: Reduced irradiation time and reduced verteporfin dose were equally effective and safe in photodynamic therapy for chronic central serous chorioretinopathy.

DOI： 10.1097/IAE.0000000000000621

Successful resolution of stromal keratitis and uveitis using canakinumab in a patient with chronic infantile neurologic, cutaneous, and articular syndrome: a case study. 国際誌

Masayuki Hirano, Jiro Seguchi, Masahiro Yamamura, Akiko Narita, Hirotaka Okanobu, Ryuta Nishikomori, Toshio Heike, Mio Hosokawa, Yuki Morizane, Fumio Shiraga

Journal of ophthalmic inflammation and infection 5 ( 1 ) 34 - 34 2015年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS) is a group of rare autoinflammatory diseases, and of these, chronic infantile neurologic, cutaneous, and articular/neonatal-onset multisystem inflammatory disease (CINCA/NOMID) syndrome has the most severe phenotype. Canakinumab, a monoclonal antibody that targets interleukin-1β, has been shown to be an effective treatment for resolving systemic inflammation. However, its efficacy for treating ophthalmic symptoms of this disorder remains unclear. FINDINGS: A 64-year-old female reported episodes of nonpruritic urticaria, fever, aseptic meningitis, and bilateral sensorineural deafness. Her son had experienced similar symptoms. She was initially referred for ophthalmologic treatment for an infectious corneal ulcer. Examination of her right eye by slit lamp biomicroscopy showed diffuse conjunctival injection, corneal infiltrates, a corneal ulcer, and hypopyon. She was therefore treated aggressively with topical and systemic antibiotics in addition to antifungal medications. However, this was ineffective. Genetic analysis detected the heterozygous germline p.Asp303Asn mutation in the NLRP3 gene in both our patient and her son. She was therefore diagnosed with CINCA/NOMID syndrome based on her clinical manifestations. All of the patient's physical and ophthalmic symptoms were resolved within a few days after the initiation of canakinumab treatment. During an 18-month follow-up period, no adverse events or severe infections were observed. CONCLUSIONS: Our case report indicates that canakinumab is effective not only for the treatment of systemic inflammation but also for treating ophthalmic involvement, such as recurrent stromal keratitis and anterior uveitis.

DOI： 10.1186/s12348-015-0065-9

Planned foveal detachment technique for the resolution of diffuse diabetic macular edema.

Yuki Morizane, Shuhei Kimura, Mio Hosokawa, Yusuke Shiode, Masayuki Hirano, Shinichiro Doi, Mika Hosogi, Atsushi Fujiwara, Yasushi Inoue, Fumio Shiraga

Japanese journal of ophthalmology 59 ( 5 ) 279 - 87 2015年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To evaluate the therapeutic efficacy of a novel surgical procedure for diffuse diabetic macular edema (DME), performed in conjunction with conventional vitrectomy. METHODS: This prospective, interventional case series involved 20 eyes of 18 consecutive DME patients with best-corrected visual acuities (BCVAs) between 0.301 and 1.221 logarithm of the minimal angle of resolution (logMAR) units and central retinal thicknesses (CRTs) greater than 275 μm. After vitrectomy, a small retinal detachment was made in the macula by injecting 50-100 μl balanced salt solution into the subretinal space using a 38-gauge needle. Before finishing the surgery, fluid-air exchange was performed. Patients were asked to remain in prone position for 1 day postoperatively. The main outcome measures were CRT and BCVA. RESULTS: The mean CRT of 554.6 ± 152.7 μm before surgery significantly decreased to 295.6 ± 92.5 μm (p < 0.0001) 1 week after surgery and to 185.8 ± 67.4 μm (p < 0.0001) at 6 months after surgery. The CRT was less than 250 μm in 18 eyes (90 %) at 6 months after surgery. The mean BCVA before surgery (0.706 ± 0.348) significantly improved at 6 months after surgery (0.431 ± 0.392, p < 0.0001). Postoperative BCVAs improved by more than 0.3 logMAR units in 13 eyes (65 %), remained unchanged in six eyes (30 %) and worsened in one eye (5 %). Macular edema recurred in three eyes (15 %) 2 months after surgery. CONCLUSIONS: This novel planned foveal detachment technique facilitated a rapid resolution of DME and contributed to improved visual acuity.

DOI： 10.1007/s10384-015-0390-4

Successful displacement of a traumatic submacular hemorrhage in a 13-year-old boy treated by vitrectomy, subretinal injection of tissue plasminogen activator and intravitreal air tamponade: a case report. 国際誌

Shinichiro Doi, Shuhei Kimura, Yuki Morizane, Yusuke Shiode, Mio Hosokawa, Masayuki Hirano, Mika Hosogi, Atsushi Fujiwara, Kazuhisa Miyamoto, Fumio Shiraga

BMC ophthalmology 15 94 - 94 2015年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The natural course of submacular hemorrhage resulting from traumatic choroidal rupture generally has a poor outcome unless treated. The intravitreal injection of gas only or gas with recombinant tissue plasminogen activator (rt-PA) has been reported to be effective, but has also been reported to induce severe complications such as retinal detachment and vitreous hemorrhage. Recently, we reported a safe and effective procedure for treating submacular hemorrhage due to polypoidal choroidal vasculopathy (PCV) with a low dose of rt-PA. Here we report the application of this procedure to a case of traumatic submacular hemorrhage in a 13-year-old boy, which achieved a good visual outcome. CASE PRESENTATION: A 13-year-old Japanese boy presented with a thick submacular hemorrhage in his left eye as a result of blunt trauma from being hit by a sinker. Best-corrected visual acuity (BCVA) was assessed as only able to perceive hand motions. We carried out a vitrectomy, subretinal injection of 4,000 IU rt-PA (6.9 μg) and air tamponade. The day after surgery, most of the submacular hemorrhage had moved to the inferior periphery. One month after the surgery, we observed cataract formation, thin remnants of the submacular hemorrhage and juxtafoveal choroidal rupture. We carried out cataract surgery and injected bevacizumab intravitreally to prevent the development of choroidal neovascularization. Two months after the second surgery, the submacular hemorrhage had totally disappeared and the patient had a BCVA of 20/40. CONCLUSION: Vitrectomy, subretinal injection of rt-PA, and intravitreal air tamponade may be a promising strategy for treating traumatic submacular hemorrhage in young patients.

DOI： 10.1186/s12886-015-0090-3

Six-month results of intravitreal aflibercept injections for patients with polypoidal choroidal vasculopathy. 国際誌

Mio Hosokawa, Fumio Shiraga, Ayana Yamashita, Chieko Shiragami, Aoi Ono, Yukari Shirakata, Shuhei Kimura, Yusuke Shiode, Tetsuhiro Kawata, Mika Hosogi, Atsushi Fujiwara, Yuki Morizane

The British journal of ophthalmology 99 ( 8 ) 1087 - 91 2015年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: This study aims to evaluate the therapeutic effect of intravitreal aflibercept injection for polypoidal choroidal vasculopathy (PCV). METHODS: Eighteen eyes of 17 consecutive patients with PCV received three consecutive monthly intravitreal injections of aflibercept and one additional injection 2 months later (four injections totally). All patients underwent eye examinations, which included best-corrected visual acuity (BCVA), fluorescein angiography, indocyanine green angiography, and optical coherence tomography. The primary endpoint of the study was the regression of polypoidal lesions. The secondary endpoints were BCVA, central retinal thickness (CRT) and changes in retinal exudation. RESULTS: Six months after the first aflibercept injection, the polypoidal lesions were completely resolved in 14 eyes (77.7%) and partially resolved in 4 eyes (22.2%). Although branching choroidal vascular networks were still present in all eyes, retinal exudative changes had completely resolved in 17 eyes (94.4%), and the mean CRT decreased significantly from 407.2±100.1 µm to 229.1±57.2 µm (p<0.0001). BCVA (logarithm of the minimal angle of resolution, logMAR) improved significantly from 0.414±0.384 at baseline to 0.297±0.334 after 6 months (p=0.016). CONCLUSIONS: At 6 months, aflibercept monotherapy effectively reduced polyps, retinal exudation and CRT in patients with PCV.

DOI： 10.1136/bjophthalmol-2014-305275

Case report: successful closure of a large macular hole secondary to uveitis using the inverted internal limiting membrane flap technique. 国際誌

Masayuki Hirano, Yuki Morizane, Tetsuhiro Kawata, Shuhei Kimura, Mio Hosokawa, Yusuke Shiode, Shinichiro Doi, Mika Hosogi, Atsushi Fujiwara, Fumio Shiraga

BMC ophthalmology 15 83 - 83 2015年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Macular holes (MHs) are one of the complications of posterior uveitis that can significantly disturb vision. Conventional MH surgery (vitrectomy, internal limiting membrane (ILM) peeling, and gas tamponade) has been reported to show lower closure rates in patients with MHs secondary to uveitis than in patients with idiopathic MHs. Recently, the inverted ILM flap technique has been reported to be effective for treating refractory MHs. Here, we describe the application of this technique in a patient with a large MH secondary to uveitis, and its successful closure. CASE PRESENTATION: An 80-year-old woman presented with a chronic, large MH secondary to uveitis. The minimum aperture diameter of the MH was 569 μm and extensive post-inflammatory chorioretinal atrophy was present, which included the juxtafoveal region. Vitrectomy with the inverted ILM flap technique assisted by low molecular weight hyaluronic acid was performed. Three days after surgery, the MH was closed successfully, without excessive gliosis. CONCLUSION: The inverted ILM flap technique may be the preferred surgical procedure for the treatment of large MHs secondary to uveitis.

DOI： 10.1186/s12886-015-0072-5

Submacular hemorrhage in polypoidal choroidal vasculopathy treated by vitrectomy and subretinal tissue plasminogen activator. 国際誌

Shuhei Kimura, Yuki Morizane, Mio Hosokawa, Yusuke Shiode, Tetsuhiro Kawata, Shinichiro Doi, Ryo Matoba, Mika Hosogi, Atsushi Fujiwara, Yasushi Inoue, Fumio Shiraga

American journal of ophthalmology 159 ( 4 ) 683 - 9 2015年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To evaluate vitrectomy with subretinal tissue plasminogen activator (t-PA) injection, and air tamponade, followed by intravitreal anti-vascular endothelial growth factor (VEGF) therapy for submacular hemorrhage in polypoidal choroidal vasculopathy (PCV). DESIGN: Prospective, interventional case series. METHODS: setting: Two clinics. PATIENTS: Fifteen eyes of 15 consecutive patients (mean age 72 ± 7 years) with submacular hemorrhage attributable to PCV. INCLUSION CRITERIA: PCV diagnosis with unorganized submacular hemorrhage greater than 500 μm thick. EXCLUSION CRITERIA: Submacular hemorrhage attributable to macular diseases (eg, high myopia, typical age-related macular degeneration, retinal angiomatous proliferation, and angioid streaks). INTERVENTION: Vitrectomy with 4000 IU t-PA injected subretinally and fluid/air exchange. Patients remained facedown for 3 days after surgery. Anti-VEGF drugs were administered as exudative changes required. MAIN OUTCOME MEASURES: Submacular hemorrhage displacement from the macula and changes in best-corrected visual acuities (BCVAs). RESULTS: Mean time from onset to surgery was 9.5 ± 4.5 (range, 5-21) days. Mean follow-up period was 9.4 ± 3.1 (range, 6-17) months. Surgery successfully displaced submacular hemorrhages from the macula in all eyes. Mean BCVA at baseline (0.98 ± 0.44) had improved significantly both 1 month after surgery (0.41 ± 0.25, P < .01) and at final visits (0.23 ± 0.25, P < .001). In all eyes, exudative retinal changes relapsed after surgery but were completely resolved by anti-VEGF injections. No complications occurred in any patients. CONCLUSION: Treating submacular hemorrhage with vitrectomy and subretinal t-PA injection, followed by intravitreal anti-VEGF therapy, is a promising strategy for improving visual acuity in PCV patients warranting further investigation.

DOI： 10.1016/j.ajo.2014.12.020

POEMS syndrome in a 20-year-old patient diagnosed following a complaint of reduced visual acuity.

Shinichiro Doi, Shuhei Kimura, Yuki Morizane, Mika Hosogi, Mio Hosokawa, Yusuke Shiode, Tetsuhiro Kawata, Eisei Kondo, Fumio Shiraga

Acta medica Okayama 68 ( 6 ) 379 - 83 2014年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

We report a case of POEMS syndrome in a 20-year-old patient diagnosed after visiting an eye clinic with a chief complaint of reduced visual acuity. A male university student aged 20 years was referred to our department complaining of blurred vision in both eyes that had persisted for 1 month. He also noted headache, nausea, and paresthesia in the lower extremities around the same time. The visual acuity of his right and left eye was 20/40 and 20/20, respectively. Optic disc edema and serous retinal detachment were present. Brain magnetic resonance imaging showed no intracranial abnormalities, while elevated cerebrospinal fluid pressure, reduced nerve conduction velocity in both lower extremities, hepatosplenomegaly, M proteinemia, high blood VEGF levels, osteoblastic and osteolytic changes in the spine, and atypical plasma cells in bone lesions were noted. From the above findings, the patient was diagnosed with POEMS syndrome. He received high-dose dexamethasone, thalidomide, and radiotherapy on the sacral mass, followed by high-dose melphalan with autologous stem-cell support, and showed subsequent systemic and ophthalmologic improvement. Here, we report the youngest case ever of POEMS syndrome with ocular manifestation. If patients have optic disc edema in both eyes with no intracranial space-occupying lesion, POEMS syndrome should be considered in differential diagnosis, regardless of age.

Autologous transplantation of the internal limiting membrane for refractory macular holes. 国際誌

Yuki Morizane, Fumio Shiraga, Shuhei Kimura, Mio Hosokawa, Yusuke Shiode, Tetsuhiro Kawata, Mika Hosogi, Yukari Shirakata, Toshio Okanouchi

American journal of ophthalmology 157 ( 4 ) 861 - 869 2014年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To determine the effectiveness of autologous transplantation of the internal limiting membrane (ILM) for refractory macular holes. DESIGN: Prospective, interventional case series. PATIENT AND METHODS: Ten eyes of 10 consecutive patients who underwent autologous transplantation of the ILM for the treatment of refractory macular holes were studied. The primary diseases in these patients were large idiopathic macular holes that had existed for more than 1 year (4 eyes), a traumatic macular hole (1 eye), myopic foveoschisis (2 eyes), foveoschisis resulting from pit-macular syndrome (2 eyes), and proliferative diabetic retinopathy (1 eye). Apart from the 5 eyes with idiopathic or traumatic macular holes, macular holes developed in the other 5 eyes after initial vitrectomies with ILM removal. In all eyes, regular macular hole surgery failed to achieve closure. The main outcome measures used in this study were macular hole closure and best-corrected visual acuity (BCVA). RESULTS: Macular holes were closed successfully in 9 eyes (90%) after autologous transplantation of the ILM. The postoperative BCVAs were significantly better than the preoperative BCVAs (P = .007, paired t test). Postoperative BCVAs improved by more than 0.2 logarithm of the minimal angle of resolution units in 8 eyes (80%) and were unchanged in 2 eyes (20%). CONCLUSIONS: Although this is a pilot study, the results suggest that autologous transplantation of the ILM may contribute to improved anatomic and visual outcomes in the treatment of refractory macular holes and may warrant further investigation.

DOI： 10.1016/j.ajo.2013.12.028

Influence of cytochrome P450 (CYP) 3A4*1G polymorphism on the pharmacokinetics of tacrolimus, probability of acute cellular rejection, and mRNA expression level of CYP3A5 rather than CYP3A4 in living-donor liver transplant patients.

Miwa Uesugi, Mio Hosokawa, Haruka Shinke, Emina Hashimoto, Tamotsu Takahashi, Tomoki Kawai, Kazuo Matsubara, Kohei Ogawa, Yasuhiro Fujimoto, Shinya Okamoto, Toshimi Kaido, Shinji Uemoto, Satohiro Masuda

Biological & pharmaceutical bulletin 36 ( 11 ) 1814 - 21 2013年

記述言語：英語掲載種別：研究論文（学術雑誌）

Association between cytochrome P450 (CYP) 3A4*1G genotype of donors (n=412) and/or recipients (n=410), and the pharmacokinetics of tacrolimus and the risk of acute cellular rejection was examined in Japanese living-donor liver transplant patients between 2004 and 2011. The concentration/dose (C/D) ratio of tacrolimus in patients carrying graft liver with CYP3A4*1/*1 was significantly higher during 7 d after surgery than in that with CYP3A4*1/*1G (214 vs. 157 [ng/mL]/[mg/kg/day], p<0.01). After postoperative day 8, no significant difference was observed among CYP3A4*1G genotypes in the graft liver. However, the C/D ratio in CYP3A4*1/*1 of the intestine was significantly higher than that in CYP3A4*1G/*1G for 5 weeks after surgery (postoperative days 1-14; p<0.001, postoperative days 15-35; p<0.01). During postoperative days 14 and 26, acute cellular rejection incidences tended to be lower in the patients with graft liver carrying the CYP3A4*1/*1 allele than in the patients carrying CYP3A4*1G allele (8.7% vs. 14.6%, p=0.0973). However, CYP3A4*1G in the intestine had almost no effect on the incidence of rejection (9.9% in CYP3A4*1/*1 vs. 12.5% in CYP3A4*1G allele, p=0.4824). CYP3A4*1G was significantly related to mRNA expression of CYP3A5 rather than of CYP3A4 in the graft liver and intestine and was strongly linked with the CYP3A5*1. Thus, we elucidated that CYP3A4*1G genotype in the intestine was an important indicator of the pharmacokinetics of tacrolimus, whereas this genotype in the graft liver tended to influence the frequency of acute cellular rejection after transplantation.

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