Faculty Profiles - MORIZANE Yuki

Papers - MORIZANE Yuki

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Relationships among eye dimensions in magnetic resonance images by sex, age, and strabismus type in Japanese patients with acquired strabismus and high myopia. Reviewed

Reika Kono, Ichiro Hamasaki, Fumiko Kishimoto, Takehiro Shimizu, Hiroya Kindo, Kiyo Shibata, Shin Morisawa, Yuki Morizane

Japanese journal of ophthalmology 68 ( 6 ) 641 - 650 2024.11

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

PURPOSE: To investigate the relationships among eye dimensions in magnetic resonance imaging (MRI) scans by sex, age, and strabismus type in Japanese patients with acquired strabismus and high myopia. STUDY DESIGN: Retrospective clinical case series. METHODS: We included 58 eyes of 29 patients with acquired strabismus and high myopia (mean age ± standard deviation: 60.2 ± 14.7 years, axial length [AL]: 28.69 ± 2.12 mm). For all eyes, the equatorial diameter of the globe/AL ratio (EAR) and the globe/orbit volume ratio (GOR) were measured using MRI. EAR and GOR values were compared between the following groups: 9 men vs. 20 women; 8 younger (< 56 years) vs. 21 older (≥ 56 years) patients; and non-esotropia strabismus (NES: 7 patients) vs. esotropia (ET: 13 patients) vs. restrictive strabismus (RS: 9 patients) groups. RESULTS: Female patients had a smaller EAR (0.87 ± 0.07) and larger GOR (0.38 ± 0.04) than male patients (0.92 ± 0.05 and 0.35 ± 0.03, both P < 0.01). Older patients had a smaller EAR (0.87 ± 0.07) than younger ones (0.93 ± 0.04, P < 0.01), without significant differences in GOR. EAR (NES: 0.92 ± 0.06, ET: 0.86 ± 0.06, RS: 0.89 ± 0.09) significantly differed among the three strabismus groups (P = 0.02: post-hoc test: NES vs. ET, P = 0.02; NES vs. RS, P = 0.49; RS vs. ET, P = 0.67), but no significant differences in GOR were found (P = 0.12). CONCLUSIONS: Among patients with acquired strabismus and high myopia, women, older patients, and those with esotropia exhibit a smaller EAR and longer sphere shape with AL as the major axis. The parameter EAR might be useful for evaluating the pathogenesis of strabismus associated with high myopia.

DOI： 10.1007/s10384-024-01133-8

Epiretinal membrane: an overview and update. Reviewed

Ryo Matoba, Yuki Morizane

Japanese journal of ophthalmology 2024.10

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

Epiretinal membrane (ERM) is a frequently diagnosed macular disease associated with aging, characterized by a fibrous membrane forming on the internal limiting membrane (ILM) and leading to visual dysfunctions such as metamorphopsia. Various hypotheses regarding the pathology of metamorphopsia have been proposed; however, the complete pathophysiologic mechanism underlying ERM remains unclear. Optical coherence tomography (OCT) provides detailed images enabling precise diagnosis and characterization of ERM, with several recent studies using the latest OCT imaging techniques. Surgical removal of ERM is the only treatment option; however, criteria for surgical intervention are not established, complicating the decision-making processes. Furthermore, the debate on whether simultaneous peeling of the ILM during ERM surgery enhances outcomes or poses unnecessary risks is ongoing, with no definite conclusion having yet been reached. This review also focuses on epiretinal proliferation, which is different from ERM and is characteristic of lamellar macular hole (LMH). Recently, diagnostic criteria for LMH and related diseases were proposed. Reports on effective surgical procedures for LMH exist, although more research is needed to confirm the long-term outcomes. Thus, this review article aims to provide an overview and updated knowledge of ERM, LMH, and related diseases.

DOI： 10.1007/s10384-024-01127-6

Alteration of treatment choices and the visual prognosis for diabetic macular edema in the era of anti-VEGF drugs: Analysis of the STREAT-DME 2 study. Reviewed International journal

Masahiko Shimura, Takao Hirano, Eiko Tsuiki, Yoshihiro Takamura, Yuki Morizane, Kunihiko Akiyama, Kaori Yamamoto, Taichi Hikichi, Takashi Koto, Takamasa Kinoshita, Sentaro Kusuhara, Shigeo Yoshida, Shin-Ichi Sakamoto, Kazuhiro Kimura, Masahiko Sugimoto, Teruyo Kida, Yoshinori Mitamura, Yoko Takatsuna, Noriaki Washio, Rie Osaka, Tetsuki Ueda, Akira Minamoto, Jiro Kogo, Fumiki Okamoto, Hiroshi Enaida, Yoshihito Sakanishi, Taiji Nagaoka, Fumi Gomi, Mariko Sasaki, Hiroto Terasaki, Tsuyoshi Iwase, Tomoaki Tatsumi, Kosuke Nishi, Kei Shinoda, Shunichiro Ueda, Tomoko Ueda-Consolvo, Hiroyuki Nakashizuka, Toshinori Murata, Shigehiko Kitano, Taiji Sakamoto

Retina (Philadelphia, Pa.) 2024.10

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

PURPOSE: To assess the real-world outcome of best-corrected visual acuity (BCVA) following 2-year intervention for treatment-naïve diabetic macular edema (DME) since the approval of anti-vascular endothelial growth factor (VEGF) therapy. METHODS: A total of 1,780 treatment-naïve eyes with DME for which intervention was initiated between 2015 and 2019, and which were followed for 2 years, were extracted from the longitudinal medical records of 37 retinal disease institutions in Japan. Interventions included anti-VEGF therapy, topical corticosteroid therapy, macular photocoagulation, and vitrectomy. The baseline and final BCVA, and the number and timing of interventions were recorded. Eyes were classified according to the year in which intervention was initiated. RESULTS: Over a 2-year period, BCVA improved annually, finally reaching 7 letters. The proportion of eyes in which good vision was maintained (BCVA >20/40) increased to 73.3% in the latest period. The administration of anti-VEGF therapy remained stable, accounting for approximately 90% of eyes. Notably, the proportion of eyes receiving anti-VEGF drugs as first-line treatment increased dramatically to approximately 80%. CONCLUSION: Anti-VEGF therapy has become the first-line treatment since the approval of anti-VEGF drugs for DME. These findings reflect the evolution of DME treatment and highlight the superiority of anti-VEGF therapy and its increased uptake over time.

DOI： 10.1097/IAE.0000000000004301

MIXED PATHOPHYSIOLOGIES OF LAMELLAR MACULAR HOLES AND RELATED DISEASES Reviewed

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

Retina 44 ( 10 ) 1785 - 1792 2024.10

Publishing type：Research paper (scientific journal) Publisher：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

Investigation of the pathophysiology of epiretinal membrane foveoschisis: An analysis of longitudinal changes in visual functions, retinal structures, and retinal traction force Reviewed International journal

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

Retina 44 ( 11 ) 1992 - 2000 2024.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Ovid Technologies (Wolters Kluwer Health)

Purpose:

To analyze the pathophysiology of epiretinal membrane foveoschisis (ERM-FS) by evaluating the longitudinal changes in visual function and several optical coherence tomography (OCT) parameters.

Methods:

The medical records of 33 consecutive patients (35 eyes) with untreated ERM-FS were retrospectively reviewed. Best-corrected visual acuity (BCVA), M-CHARTS score, and OCT parameters including ERM area, maximum depth of retinal folds (MDRF), 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, BCVA and mean M-CHARTS scores significantly worsened and MDRF significantly increased over time, whereas in the FS non-enlargement group, no significant change was observed in BCVA, mean M-CHARTS scores, or MDRF during the follow-up period. Multivariate logistic regression analyses revealed that MDRF (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:

ERM-FS 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

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

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 2024.6

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

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. Reviewed International journal

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 2024.4

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

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 Reviewed

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 2024.3

OCT画像を用いた機械学習による網膜上膜の最大網膜皺襞深度の予測 Reviewed

森田哲郎, 谷岡真樹, 黒沢飛弾, 的場亮, 神崎勇希, 諸岡健一, 森實祐基

日本眼科学会雑誌 128 ( 臨増 ) 188 - 188 2024.3

アフリベルセプトからファリシマブに切替えた滲出型加齢黄斑変性の1年経過 Reviewed

尾内千容, 細川海音, 塩出雄亮, 木村修平, 的場亮, 神崎勇希, 森田哲郎, 森實祐基

日本眼科学会雑誌 128 ( 臨増 ) 259 - 259 2024.3

Microperimetry-guided inverted internal limiting membrane flap site selection to preserve retinal sensitivity in macular hole with glaucoma. Reviewed International journal

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

American journal of ophthalmology case reports 33 102007 - 102007 2024.3

Language：English

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

Japan-epiretinal membrane (J-ERM) registry: A prospective cohort study protocol investigating the surgical outcome of epiretinal membrane. Reviewed International journal

Yuki Kanzaki, Ryo Matoba, Kenji Ishihara, Tetsuro Morita, Yuki Muraoka, Shuhei Kimura, Takashi Koto, Ryo Kawasaki, Takayuki Baba, Fumiki Okamoto, Makoto Inoue, Taiji Sakamoto, Akitaka Tsujikawa, Yuki Morizane

PloS one 19 ( 2 ) e0297347 2024

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

BACKGROUND: Epiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries. METHODS AND DESIGN: This is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications. DISCUSSION: The results of this study will support the surgical decisions and procedures in ERM practices.

DOI： 10.1371/journal.pone.0297347

Evaluation of epiretinal membrane formation after scleral buckling for treating rhegmatogenous retinal detachment: En face optical coherence tomography image-based study. Reviewed International journal

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 2023.10

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

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 2023.10

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 2023.10

Surgical Management of Full Thickness Macular Holes in Macular Telangiectasia Type 2.A Global Multicenter Study. Reviewed International journal

Jong G Park, Sean D Adrean, Tedi Begaj, Antonio Capone Jr, Steve Charles, San-Ni Chen, Hung-Da Chou, Michael N Cohen, Stephanie Trejo Corona, Lisa J Faia, Sunir J Garg, Bruce R Garretson, Ninel Z Gregori, Julia A Haller, Odette Margit Houghton, Jason Hsu, Jaehyuck Jo, Richard S Kaiser, Chi-Chun Lai, Mohamed Moghazy Mahgoub, Mahsaw Mansoor, Ryo Matoba, Yuki Morizane, Marcio B Nehemy, Paul V Raphaelian, Carl D Regillo, Alan J Ruby, Margaret M Runner, Scott R Sneed, Elliott H Sohn, Marc J Spirn, James F Vander, Taku Wakabayashi, Jeremy D Wolfe, Charles C Wykoff, Yoshihiro Yonekawa, Young Hee Yoon, Tamer H Mahmoud

Ophthalmology 2023.9

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

PURPOSE: To report on macular hole repair in macular telangiectasia type 2 (MacTel). DESIGN: Global, multicenter, retrospective case series. PARTICIPANTS: Patients with surgery for MacTel-associated full thickness macular hole (MTMH). METHODS: A standardized data collection sheet was distributed to all surgeons. MAIN OUTCOME MEASURES: Anatomic closure and visual outcomes of MTMH RESULTS: Sixty-three surgeries in 47 patients with MTMH were included from 30 surgeons. Mean age was 68.1 years, with 62% females, 72% Caucasians, 21% East or South Asians, 2% African American, 2% Hispanic or Latino. Procedures included 34 internal limiting membrane (ILM) peeling alone, 22 ILM flaps, 5 autologous retinal transplantations (ARTs), 1 retinotomy, and 1 subretinal bleb. For ILM peels, preoperative best available visual acuity (VA) was logMAR 0.667 ± 0.423. Minimum hole diameter (MHD) was 305.5 ± 159.4 μm (range 34 - 573 μm). Sixteen of 34 ILM peels resulted in MTMH closure for a 47% success rate. At postoperative month 6 VA was stable at logMAR 0.608 ± 0.516 (P=0.65). VA improved at least 2 lines in 43% and at least 4 lines in 24%. For ILM flaps, preoperative VA was logMAR 0.878 ± 0.552. MHD was 440.8 ± 175.5 μm (range 97 - 697 μm), which was significantly larger than for ILM peels (P<0.01). Twenty of 22 ILM flaps resulted in MTMH closure for a 90% success rate, which was significantly higher for ILM flaps than for ILM peels (P<0.01). At postoperative month 6 VA improved to logMAR 0.555 ± 0.405 (P<0.05). VA improved at least 2 lines in 56% and at least 4 lines in 28%. For ARTs, preoperative VA was logMAR 1.460 ± 0.391. MHD was 390.2 ± 203.7 μm (range 132 - 687 μm). All 5 ARTs resulted in MTMH closure for a 100% success rate. At postoperative month 6 VA was stable at logMAR 1.000 ± 0.246 (P=0.08). VA improved at least 2 lines in 25%. CONCLUSIONS: Surgical closure of macular holes improved VA in 57% of MTMHs. ILM flaps achieved better anatomical and functional outcomes than ILM peeling alone. ART may be an option for refractory MTMHs.

DOI： 10.1016/j.ophtha.2023.08.025

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 2023.9

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

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

Japanese journal of ophthalmology 2023.8

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

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

眼内炎診療における病院総合医の役割

川口満理奈, 大塚勇輝, 副島佳晃, 安藤航, 高木桃李, 大國皓平, 長谷川功, 本多寛之, 萩谷英大, 小比賀美香子, 森田哲郎, 森實祐基, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 142 - 142 2023.8

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

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 2023.8

Language：English

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

黄斑円孔の最新の手術手技の評価

木村修平, 森實祐基

眼科 65 ( 8 ) 733 - 740 2023.8

Language：Japanese Publisher：金原出版(株)

＜文献概要＞黄斑円孔に対して内境界膜(internal limiting membrane:ILM)剥離とガスタンポナーデを併施した硝子体切除が標準術式として行われるようになり,400μm以下の黄斑円孔であれば,ほぼ100%に近い確率で黄斑円孔を閉鎖できるようになった。しかし標準術式では閉鎖が得られにくい難治性の黄斑円孔も存在する。近年,難治性黄斑円孔に対してILM翻転,ILM自家移植,自家感覚網膜移植などの術式が考案され手術成績が報告されている。そこで本稿では,まず標準術式の歴史と問題点について述べ,その後,難治性黄斑円孔に対する術式とその評価について解説する。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00293&link_issn=&doc_id=20230822130009&doc_link_id=10.18888%2Fga.0000003216&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fga.0000003216&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

眼内炎診療における病院総合医の役割

川口満理奈, 大塚勇輝, 副島佳晃, 安藤航, 高木桃李, 大國皓平, 長谷川功, 本多寛之, 萩谷英大, 小比賀美香子, 森田哲郎, 森實祐基, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 142 - 142 2023.8

Analysis of temporal changes in thickness from conjunctiva to sclera after plication of the medial rectus muscle measured by anterior segment optical coherence tomography Reviewed

Takehiro Shimizu, Ichiro Hamasaki, Kiyo Shibata, Shin Morisawa, Reika Kono, Keisuke Kanenaga, Yuki Morizane

Japanese Journal of Ophthalmology 67 ( 5 ) 612 - 617 2023.6

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 2023.5

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.

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

Japanese journal of ophthalmology 2023.4

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

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

A nationwide survey of newly certified visually impaired individuals in Japan for the fiscal year 2019: impact of the revision of criteria for visual impairment certification.

Ryo Matoba, Noriko Morimoto, Ryo Kawasaki, Miyuki Fujiwara, Keisuke Kanenaga, Hidetoshi Yamashita, Taiji Sakamoto, Yuki Morizane

Japanese journal of ophthalmology 2023.4

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

PURPOSE: To determine the status of visual impairment certification in Japan in the fiscal year 2019 and the impact of revising the criteria for visual impairment certification implemented in 2018. STUDY DESIGN: Observational cross-sectional study. METHODS: We requested welfare offices throughout Japan to submit data of age, sex, causative diseases, and visual impairment grades for newly certified visually impaired individuals aged ≥ 18 years during the fiscal year 2019. The certification was based on criteria of the Act on Welfare of Physically Disabled Persons. RESULTS: Altogether, data were collected for 16,504 newly certified visually impaired individuals. The most common age group was 80-89 years (29.6%), followed by 70-79 (28.2%) and 60-69 (15.3%) years. The most common causative disease was glaucoma (40.7%), followed by retinitis pigmentosa (13.0%), diabetic retinopathy (10.2%), and macular degeneration (9.1%). The most common impairment grade was grade 2 (40.8%), followed by 5 (21.2%) and 1 (17.0%). Compared to the fiscal year 2015, there was a considerable increase in the number of individuals certified with glaucoma in the fiscal year 2019. Moreover, there was a significant increase in the number of individuals with certified grades 1 and 2 visual impairment, with a decrease in the number of individuals with certified grade 6 visual impairment. CONCLUSION: The changes revealed in this study were primarily due to the revised certification criteria implemented in July 2018, indicating that it is important to review the certification criteria and to repeat surveys similar to the present study.

DOI： 10.1007/s10384-023-00986-9

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

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

Ophthalmology Science 100305 - 100305 2023.4

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

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 2023.4

Impact of macular intraretinal hemorrhage and macular hole on the visual prognosis of submacular hemorrhage due to retinal arterial macroaneurysm rupture Reviewed International journal

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 43 ( 4 ) 585 - 593 2023.4

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 2023.3

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 2023.3

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 2023.3

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 2023.3

【日本の眼の難病-何がどこまでわかってきたのか?】視覚身体障害者の疫学

的場亮, 森實祐基

臨床眼科 77 ( 1 ) 86 - 90 2023.1

Language：Japanese Publisher：(株)医学書院

＜文献概要＞●視覚障害の原因疾患の第1位が緑内障,第2位が網膜色素変性,第3位が糖尿病網膜症であった。●緑内障を原因とする視覚障害者は高齢であり,障害等級が高かった。●都道府県別の認定者割合は高齢化率および眼科指定医師数と有意に関連した。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01537&link_issn=&doc_id=20221229100015&doc_link_id=10.11477%2Fmf.1410214687&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410214687&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Protrusion of KCNJ13 Gene Knockout Retinal Pigment Epithelium Due to Oxidative Stress-Induced Cell Death. International journal

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

Investigative ophthalmology & visual science 63 ( 12 ) 29 - 29 2022.11

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

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 2022.10

【いま知っておくべき注目の病態名】Epiretinal proliferation(EP)

的場亮, 森實祐基

Retina Medicine 11 ( 2 ) 131 - 135 2022.10

Language：Japanese Publisher：(株)先端医学社

Epiretinal proliferation(EP)は網膜表面にみられる牽引力に乏しい黄白色の膜状組織であり,おもに網膜内層から遊走したMueller細胞からなる.EPは分層黄斑円孔で高率に認められるが,黄斑円孔,黄斑上膜などにおいてもみられる.近年,分層黄斑円孔に対してEPを埋め込む術式の有効性が報告されている.(著者抄録)

Graft Size and Double Scroll Formation Rate in Descemet Membrane Endothelial Keratoplasty. International journal

Hiroshi Matsumae, Takefumi Yamaguchi, Yuki Kusano, Shigeto Shimmura, Akira Kobayashi, Yuki Morizane, Jun Shimazaki

Current eye research 47 ( 9 ) 1246 - 1251 2022.9

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

PURPOSE: This study aimed to evaluate the usefulness of intentional double scroll formation of donor Descemet membrane (DM) inside a glass tube inserter (the Fogla technique) in DM endothelial keratoplasty (DMEK) for controlled insertion and unfolding of grafts. METHODS: Eleven consecutive patients who underwent DMEK were included in this study. We sought to specify graft characteristics in which double scroll configuration was successfully formed using the Fogla technique. We compared donor age, graft size, surgical time, unfolding time, and visual outcomes between patients with and without double scroll configuration. The ability to form double scroll formation of DM grafts of various diameters and unfolding time of DM grafts was evaluated using total seven eye-bank eyes in ex vivo experiments. RESULTS: A double scroll configuration inside a glass tube was successfully obtained in six DMEK grafts (54.5%). When comparing clinical features between those with and without double scroll configuration, only graft size was significantly larger in those with double scroll configuration (7.9 ± 0.2 mm) than in those without (7.4 ± 0.4, P = 0.03). There were no significant differences in other features and clinical outcomes, although unfolding-time was shorter in eyes with double scroll configuration (4.6 ± 2.0 min) compared to those without (8.6 ± 8.1, P = 0.21). Ex vivo experiments showed that unfolding time was significantly shorter in double scroll configuration (2.71 ± 0.49 min) than in single scroll (5.02 ± 0.79, P = 0.01). CONCLUSIONS: A double scroll configuration within a glass tube can be obtained more frequently in larger DMEK grafts (8.0 mm in diameter), which may result in easier and faster DMEK procedures.

DOI： 10.1080/02713683.2022.2104318

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 2022.9

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 2022.9

Reply. International journal

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

Ophthalmology. Retina 6 ( 7 ) 645 - 645 2022.7

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 2022.6

Language：English

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

Postoperative follow-up of submacular hemorrhage displacement treated with vitrectomy and subretinal injection of tissue plasminogen activator: ultrawide-field fundus autofluorescence imaging in gas-filled eyes.

Yosuke Fukuda, Shintaro Nakao, Ri-Ichiro Kohno, Keijiro Ishikawa, Sakurako Shimokawa, Satomi Shiose, Atsunobu Takeda, Yuki Morizane, Koh-Hei Sonoda

Japanese journal of ophthalmology 66 ( 3 ) 264 - 270 2022.5

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

PURPOSE: To investigate the utility of Optos ultrawide-field fundus autofluorescence (UWF-FAF) imaging for postoperative follow-up of gas-filled eyes after vitrectomy with subretinal tissue-plasminogen activator (t-PA) injection for subretinal hemorrhage (SRH) displacement. STUDY DESIGN: Retrospective consecutive case series. METHODS: This study included 24 eyes with SRH. Vitrectomy with subretinal t-PA injection was performed, followed by postoperative prone positioning. FAF images acquired using Optos California were examined and the SRH occupancy in the macula was calculated. The main outcome measures were displacement rate and direction of SRH for 3 days postoperatively, and postoperative best-corrected visual acuity (BCVA). RESULTS: The postoperative BCVA ranged from improvement (23 eyes; 95.8%) to no change (one eye; 4.2%). Analysis was done using postoperative Optos FAF images for 20 eyes (83.3%). Postoperative SRH occupancy was significantly reduced, by 27.4%, compared with the preoperative occupancy (P = 0.03). A statistically significant reduction was found between the preoperative and postoperative day (POD)1 (P = 0.04), but not between POD1 and POD2 (P = 0.7), or between POD2 and POD3 (P = 1.0). CONCLUSION: UWF-FAF imaging is useful for postoperative follow-up of gas-filled eyes after vitrectomy with subretinal t-PA injection for SRH displacement.

DOI： 10.1007/s10384-022-00910-7

Treatment of diabetic macular edema in real-world clinical practice: The effect of aging.

Sentaro Kusuhara, Masahiko Shimura, Shigehiko Kitano, Masahiko Sugimoto, Daisuke Muramatsu, Harumi Fukushima, Yoshihiro Takamura, Makiko Matsumoto, Masahide Kokado, Jiro Kogo, Mariko Sasaki, Yuki Morizane, Takuya Utsumi, Osamu Kotake, Takashi Koto, Hiroto Terasaki, Takao Hirano, Hiroto Ishikawa, Yoshinori Mitamura, Fumiki Okamoto, Takamasa Kinoshita, Kazuhiro Kimura, Kenji Yamashiro, Yukihiko Suzuki, Taiichi Hikichi, Noriaki Washio, Tomohito Sato, Kishiko Ohkoshi, Hiroki Tsujinaka, Mineo Kondo, Hitoshi Takagi, Toshinori Murata, Taiji Sakamoto

Journal of diabetes investigation 13 ( 8 ) 1339 - 1346 2022.4

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

AIMS/INTRODUCTION: In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. MATERIALS AND METHODS: This is a real-world clinical study including 1,552 patients with treatment-naïve center-involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55-64; C3, 65-74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years. RESULTS: From baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were -0.01 in C1, -0.06 in C2, -0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were -136.2 μm in C1, -108.8 μm in C2, -100.6 μm in C3, and -89.5 μm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti-VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001). CONCLUSIONS: Compared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real-world clinical practice.

DOI： 10.1111/jdi.13801

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 2022.3

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 2022.3

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 2022.3

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 2022.3

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 2022.3

2019年度の全国新規視覚障害認定疫学調査

的場亮, 守本典子, 川崎良, 金永圭祐, 坂手澪, 稲垣明日香, 後藤保人, 山下英俊, 坂本泰二, 森實祐基

日本眼科学会雑誌 126 ( 臨増 ) 307 - 307 2022.3

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 2022.3

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 2022.3

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 2022.3

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 2022.3

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 2022.3

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

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 2021.12

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

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 2021.12

Language：English

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

【眼科手術Q&A】網膜・硝子体黄斑下出血に対する硝子体手術について、とくに黄斑円孔合併例への対処法を教えてください

木村修平, 森實祐基

あたらしい眼科 38 ( 臨増 ) 127 - 132 2021.12

Corynebacterium ocular infection after Baerveldt glaucoma implant surgery: treatment involving immediate tube withdrawal and temporary subconjunctival tube placement: a case report. International journal

Naruka Mitsui, Kae Sugihara, Jiro Seguchi, Etsuo Chihara, Yuki Morizane, Akiko Narita

BMC ophthalmology 21 ( 1 ) 368 - 368 2021.10

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

BACKGROUND: We report a case of Corynebacterium endophthalmitis secondary to tube exposure following Baerveldt glaucoma implant surgery that was successfully treated with prompt tube withdrawal and temporary subconjunctival tube placement without removing the glaucoma drainage device. CASE PRESENTATION: A 65-year-old Japanese man with secondary glaucoma underwent glaucoma drainage device surgery with a donor scleral patch graft in the inferonasal quadrant of his right eye. Ten months after surgery, he presented with tube exposure due to dehiscence of the overlying conjunctiva and erosion of the scleral patch graft. Eleven days later, mild inflammation was found in the anterior chamber and anterior vitreous body, with the root of the tube surrounded by a plaque at the site of insertion in the anterior chamber. He was diagnosed with infectious endophthalmitis secondary to tube exposure. Two days later, since medical therapy was ineffective, the tube was withdrawn from the anterior chamber and irrigated with a polyvinyl alcohol-iodine solution, and the tube was tucked into the subconjunctival space. Complete resolution of the infection was achieved 1.5 months later. The tube was reinserted nasally into the anterior chamber and covered with a scleral patch graft and a free limbal conjunctival autograft. Thereafter, there has been no recurrence of infection or tube exposure. Twenty eight months after tube reinsertion, his right best-corrected visual acuity was 20/50 and intraocular pressure was 12 mmHg. CONCLUSION: Prompt tube withdrawal and temporary subconjunctival tube placement followed by tube reinsertion may be effective for endophthalmitis associated with tube exposure after glaucoma drainage device surgery.

DOI： 10.1186/s12886-021-02136-6

Response to the letter to the editor: "Coronal plane OCT imaging and vision in macular pucker". International journal

Ryo Matoba, Yuki Kanzaki, Shinichiro Doi, Yuki Morizane

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 260 ( 7 ) 2381 - 2381 2021.10

網膜細動脈瘤破裂に伴う黄斑下出血において網膜内出血の存在が視力予後に及ぼす影響

土居真一郎, 木村修平, 櫻井寿也, 今井尚徳, 小堀朗, 齋藤翔子, 久冨智朗, 栗山晶治, 井上真, 森實祐基

眼科臨床紀要 14 ( 10 ) 679 - 680 2021.10

網膜細動脈瘤破裂に伴う黄斑下出血において網膜内出血の存在が視力予後に及ぼす影響

土居真一郎, 木村修平, 櫻井寿也, 今井尚徳, 小堀朗, 齋藤翔子, 久冨智朗, 栗山晶治, 井上真, 森實祐基

眼科臨床紀要 14 ( 10 ) 679 - 680 2021.10

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

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 2021.9

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

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

Cytotoxic effects of alteplase, a recombinant tissue plasminogen activator, on human retinal pigment epithelial cells.

Shuhei Kimura, Yuki Morizane, Shinji Toshima, Yusuke Shiode, Shinichiro Doi, Kosuke Takahashi, Ryo Matoba, Yuki Kanzaki, Fumio Shiraga

Japanese journal of ophthalmology 65 ( 5 ) 731 - 739 2021.9

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

PURPOSE: To evaluate the cytotoxic effects of alteplase, a recombinant tissue plasminogen activator, and its additives on human retinal pigment epithelial (hRPE) cells. STUDY DESIGN: Laboratory study. METHODS: We evaluated the cytotoxic effects of alteplase on human fetal RPE (hfRPE) cells, human induced pluripotent stem cell-derived RPE (hiPS-RPE), and ARPE-19 cells, as well as the cytotoxic effects of L-arginine and polysorbate 80, two additives of alteplase, on hfRPE cells. The effects of alteplase on the production of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) from hfRPE cells and the transepithelial resistance (TER) of hiPS-RPE cells were also assessed. The type of cell death induced by alteplase was investigated using ethidium homodimer III and FITC-Annexin V staining and terminal transferase deoxyuridine triphosphatase nick-end labeling. RESULTS: Alteplase reduced the viability of hfRPE cells significantly in a dose- and time-dependent manner. The reaction of hiPS-RPE and ARPE19 cells to alteplase was similar to that of hfRPE cells. Out of L-arginine and polysorbate 80, only treatment with L-arginine significantly reduced the viability of hfRPE cells. Alteplase (83 μg/ml, 6 h) had no significant effect on the production of VEGF and PEDF from hfRPE cells. Alteplase decreased the TER of hiPS-RPE cells in a dose- and time-dependent manner and induced necrosis as the type of cell death. CONCLUSION: Alteplase can be cytotoxic to human RPE cells in a concentration- and time-dependent manner, with L-arginine being a possible causative factor.

DOI： 10.1007/s10384-021-00848-2

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 2021.9

Surgical Treatment of Epiretinal Membrane.

Ryo Matoba, Yuki Morizane

Acta medica Okayama 75 ( 4 ) 403 - 413 2021.8

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

Epiretinal membrane (ERM) is a common retinal disease characterized by cellular proliferation and metaplasia that lead to the formation of a pathological fibrocellular membrane immediately superjacent to the inner retinal surface. The vast majority of ERMs are considered idiopathic. However, ERM formation can result from various primary intraocular diseases, including retinal breaks and detachment, retinal vascular diseases, and vitreoretinal inflammatory conditions. Although ERMs are generally asymptomatic or cause mild metamorphopsia and/or a modest decrease in visual acuity, some can cause severe macular distortion and macular edema, resulting in significantly impaired function. Surgical removal of ERM is the only treatment, and improvements in vitrectomy systems have enabled less invasive treatment. However, there are currently no standardized criteria for ERM surgery, and the indications for surgery are determined from the patient's subjective symptoms. Another problem with ERM surgery is that not all patients show satisfactory postoperative recovery of visual function. Thus, further research is needed to determine the criteria for ERM surgery and methods to improve the postoperative prognosis.

DOI： 10.18926/AMO/62378

Clinical Parameters Reflecting Globe/orbit Volume Imbalances in Japanese Acquired Esotropia Patients with High Myopia but without Abduction Limitations.

Reika Kono, Ichiro Hamasaki, Fumiko Kishimoto, Hiroshi Ohtuski, Kiyo Shibata, Yuki Morizane, Fumio Shiraga

Acta medica Okayama 75 ( 4 ) 447 - 453 2021.8

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

In high myopia, eye dislocation due to increased globe volume or tight orbital volume causes acquired esotro-pia. GOR (globe/orbit volume ratio), an indicator of the degree of progression of this pathology, was investi-gated the relationships among easily obtained clinical parameters. In this retrospective study, 20 eyes from 10 acquired esotropia patients with high myopia but without abduction limitations were examined. The mean age of the patients was 63.7 ± 8.2 years (mean ± standard deviation). Volumes were measured on the three-dimen-sional fast imaging employing steady-state acquisition magnetic resonance imaging images using the vol-ume-measurement function. Correlations between GOR and the displacement angle of the globe (DA), axial length (AL), and equatorial diameter (ED) were investigated. Mean DA, AL, ED, and GOR values were 107.5 ± 8.5°, 28.86 ± 1.92 mm, 25.00 ± 1.16 mm, and 0.36 ± 0.05, respectively. Only AL was correlated with GOR (p < 0.0001, R2 = 0.6649); DA (p = 0.30, R2 = 0.0633) and ED (p = 0.91, R2 = 0.0008) were not. AL was the only clinically available parameter to indicate globe/orbit volume imbalances in acquired esotropia with high myopia but without abduction limitation. AL may be important for the clinical assessment of the progression of this pathology.

DOI： 10.18926/AMO/62396

En Face Image-Based Analysis of Epiretinal Membrane Formation after Surgery for Idiopathic Epiretinal Membrane. International journal

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 2021.8

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

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

黄斑上膜の最新のとらえかた

的場亮, 森實祐基

眼科 63 ( 8 ) 759 - 764 2021.8

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 2021.6

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

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. International journal

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

Scientific reports 11 ( 1 ) 7665 - 7665 2021.4

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

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 2021.4

Language：English

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

Retinal Amyloid Imaging for Screening Alzheimer's Disease. International journal

Koh Tadokoro, Toru Yamashita, Shuhei Kimura, Emi Nomura, Yasuyuki Ohta, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Ryuta Morihara, Yuki Morizane, Koji Abe

Journal of Alzheimer's disease : JAD 83 ( 2 ) 927 - 934 2021

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

BACKGROUND: Cost-effective and noninvasive methods for in vivo imaging of amyloid deposition are needed to screen Alzheimer's disease (AD). Although retinal amyloid is a possible diagnostic marker of AD, there are very few studies on in vivo retinal amyloid imaging. OBJECTIVE: To examine the usefulness of in vivo imaging of retinal amyloid in AD patients. METHODS: To examine amyloid deposition, 30 Japanese subjects (10 normal control (NC), 7 with mild cognitive impairment (MCI), and 13 with AD) underwent a complete ophthalmic examination, including fundus imaging by scanning laser ophthalmoscopy before and after oral curcumin intake. RESULTS: Retinal amyloid deposition was greater in AD than in NC subjects (*p < 0.05) while MCI showed a slight but insignificant increase of retinal amyloid deposition relative to NC subjects. Retinal amyloid deposition was correlated with whole gray matter atrophy (r = 0.51, *p < 0.05) but not with the cognitive score of the Mini-Mental State Examination, nor with medial temporal lobe atrophy. CONCLUSION: The present noninvasive in vivo detection of retinal amyloid deposition is useful for screening AD patients.

DOI： 10.3233/JAD-210327

Effect of rhegmatogenous retinal detachment on preoperative and postoperative retinal sensitivities. International journal

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 2020.12

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

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

Real-world management of treatment-naïve diabetic macular oedema: 2-year visual outcome focusing on the starting year of intervention from STREAT-DMO study. International journal

Masahiko Shimura, Shigehiko Kitano, Daisuke Muramatsu, Harumi Fukushima, Yoshihiro Takamura, Makiko Matsumoto, Masahide Kokado, Jiro Kogo, Mariko Sasaki, Yuki Morizane, Takuya Utsumi, Takashi Koto, Shozo Sonoda, Takao Hirano, Hiroto Ishikawa, Yoshinori Mitamura, Fumiki Okamoto, Takamasa Kinoshita, Kazuhiro Kimura, Masahiko Sugimoto, Kenji Yamashiro, Yukihiko Suzuki, Taiichi Hikichi, Noriaki Washio, Tomohito Sato, Kishiko Ohkoshi, Hiroki Tsujinaka, Sentaro Kusuhara, Mineo Kondo, Hitoshi Takagi, Toshinori Murata, Taiji Sakamoto

The British journal of ophthalmology 104 ( 12 ) 1755 - 1761 2020.12

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

BACKGROUND/AIMS: To investigate the yearly change of real-world outcomes for best corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve diabetic macular oedema (DMO). METHODS: Retrospective analysis of aggregated, longitudinal medical records obtained from 27 retina specialised institutions in Japan from Survey of Treatment for DMO database. A total of 2049 treatment-naïve centre involving DMO eyes of which the initial intervention started between 2010 and 2015, and had been followed for 2 years, were eligible. As interventions, antivascular endothelial growth factor (VEGF) agents, local corticosteroids, macular photocoagulation and vitrectomy were defined. In each eye, baseline and final BCVA, the number of each intervention for 2 years was extracted. Each eye was classified by starting year of interventional treatment. RESULTS: Although baseline BCVA did not change by year, 2-year improvement of BCVA had been increased, and reached to +6.5 letters in the latest term. There is little difference among starting year about proportions of eyes which BCVA gained >15 letters, in contrast to those which lost >15 letters were decreased by year. The proportion of eyes receiving anti-VEGF therapy was dramatically increased, while those receiving the other therapies were gradually decreased. The proportion of eyes which maintained socially good vision of BCVA>20/40 has been increased and reached to 59.0% in the latest term. CONCLUSION: For recent years, treatment patterns for DMO have been gradually but certainly changed; as a result, better visual gain, suppression of worsened eyes and better final BCVA have been obtained. Anti-VEGF therapy has become the first-line therapy and its injection frequency has been increasing.

DOI： 10.1136/bjophthalmol-2019-315726

Concerns about the interpretation of OCT and fundus findings in COVID-19 patients in recent Lancet publication. International journal

Demetrios G Vavvas, David Sarraf, SriniVas R Sadda, Dean Eliott, Justis P Ehlers, Nadia K Waheed, Yuki Morizane, Taiji Sakamoto, Miltiadis Tsilimbaris, John B Miller

Eye (London, England) 34 ( 12 ) 2153 - 2154 2020.12

Evaluation of Blood-filling Patterns in Schlemm Canal for Trabectome Surgery. International journal

Kae Sugihara, Akiko Narita, Naruka Mitsui, Seido Okuda, Jiro Seguchi, Yuki Morizane

Journal of glaucoma 29 ( 12 ) 1101 - 1105 2020.12

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

PRéCIS:: Regardless of the blood-filling patterns in Schlemm canal (SC) before the trabecular meshwork (TM) ablation, the trabectome surgery, combined with phacoemulsification, is effective for mild to moderate primary open-angle glaucoma patients. PURPOSE: The purpose of this study was to evaluate the association between trabectome surgery outcomes and the blood filling patterns in SC before TM ablation. MATERIALS AND METHODS: This retrospective cohort study included 105 eyes of 84 Japanese primary open-angle glaucoma patients who had undergone trabectome surgery in combination with cataract surgery. Provocative gonioscopy was performed before TM ablation to classify the blood filling patterns in SC into 3 groups: no filling (group 1); patchy/irregular filling (group 2); and complete filling (group 3). The subjects were divided into 3 groups according to the blood filling patterns and the trabectome surgery outcomes were compared, including intraocular pressure (IOP), the percentage reduction in IOP, surgical success rate, and the number of glaucoma medications. Success was defined by IOP ≤15 mm Hg and a >20% reduction in IOP with/without glaucoma medication, and without additional glaucoma surgery after trabectome surgery combined with cataract surgery. RESULTS: Twenty-four eyes were assigned to group 1, 48 to group 2, and 33 to group 3. Between-group analyses showed no significant intergroup differences in age (P=0.213), preoperative mean deviation (P=0.505), preoperative and postoperative IOP (P=0.941 and 0.458, respectively), preoperative and postoperative number of glaucoma medications (P=0.805 and 0.077, respectively), percentage IOP reduction (P=0.256), and success rates (P=0.540). CONCLUSION: Trabectome surgery is effective for mild to moderate primary open-angle glaucoma patients, independent of the blood-filling patterns in SC before the TM ablation.

DOI： 10.1097/IJG.0000000000001646

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

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 2020.10

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

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. International journal

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 2020.10

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

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

【眼科救急疾患2020】網膜硝子体強度近視眼の黄斑円孔

松前洋, 森實祐基

眼科 62 ( 11 ) 1239 - 1242 2020.10

Language：Japanese Publisher：金原出版(株)

＜文献概要＞近視は日本を含むアジア諸国に多く,今後も増加が予測されている。近視のなかでも特に強度近視を有する患者が視力低下,歪視の主訴で救急受診した場合には黄斑円孔を疑う必要がある。強度近視眼の黄斑円孔の病態は複雑で,眼球の特殊な形状,脈絡網膜萎縮等が関与しているとされる。そのため,特発性の黄斑円孔の原因と比べて,術後の円孔閉鎖率が低いと報告されており,網膜分離症や黄斑円孔網膜剥離を併発する場合もある。近年,内境界膜翻転法の有用性が報告されており,従来の特発性黄斑円孔の標準術式である内境界膜剥離術と比較した報告では,高い円孔閉鎖率が報告されている。治療に際しては,手術の難易度の高さから網膜硝子体疾患の専門施設への紹介が望ましい。

裂孔原性網膜剥離眼の網膜感度と術前剥離の有無および術後網膜外層構造との関連

野田拓志, 木村修平, 森實祐基, 細川海音, 塩出雄亮, 土居真一郎, 高橋耕介, 的場亮, 神崎勇希, 藤原篤之, 白神史雄

眼科臨床紀要 13 ( 10 ) 679 - 679 2020.10

【疫学研究のアップデート】わかりやすい臨床講座視覚障害の原因疾患の推移

的場亮, 森實祐基

日本の眼科 91 ( 10 ) 1386 - 1390 2020.10

Language：Japanese Publisher：(公社)日本眼科医会

視覚障害は生活の質を著しく低下させ、社会生活の維持にも大きな影響を及ぼす。日本では、厚生労働省が新規視覚障害認定数の全国調査を毎年実施している。しかし、年齢、原因疾患については調査されていない。そこで、これらの項目の実態を把握することを目的として、われわれ(厚生労働省難治性疾患等政策研究事業、網膜脈絡膜・視神経萎縮症に関する調査研究班)は全都道府県の全自治体を対象にした視覚障害の実態調査を2015年度に行った。本稿ではこの調査結果について概説すると共に、わが国の視覚障害の原因疾患の推移について考察する。(著者抄録)

【定着するのか!?最新の術式】黄斑円孔・分層黄斑円孔・黄斑前膜

的場亮, 森實祐基

Retina Medicine 9 ( 2 ) 118 - 123 2020.10

Language：Japanese Publisher：(株)先端医学社

黄斑円孔、分層黄斑円孔、黄斑前膜に対して近年さまざまな術式が考案されている。難治性黄斑円孔に対しては内境界膜や水晶体嚢、自家感覚網膜を活用する術式が考案され、分層黄斑円孔に対しては病態に応じて術式を使い分けることの重要性が提唱されている。黄斑前膜に対しては、内境界膜を剥離することの是非について議論がつづいている。各術式の長所と短所を理解したうえで術式を選択する必要がある。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J06128&link_issn=&doc_id=20201005450004&doc_link_id=%2Fae6retie%2F2020%2F000902%2F005%2F0118-0123%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6retie%2F2020%2F000902%2F005%2F0118-0123%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Real-world management of treatment-naïve diabetic macular oedema in Japan: two-year visual outcomes with and without anti-VEGF therapy in the STREAT-DME study. International journal

Masahiko Shimura, Shigehiko Kitano, Daisuke Muramatsu, Harumi Fukushima, Yoshihiro Takamura, Makiko Matsumoto, Masahide Kokado, Jiro Kogo, Mariko Sasaki, Yuki Morizane, Osamu Kotake, Takashi Koto, Shozo Sonoda, Takao Hirano, Hiroto Ishikawa, Yoshinori Mitamura, Fumiki Okamoto, Takamasa Kinoshita, Kazuhiro Kimura, Masahiko Sugimoto, Kenji Yamashiro, Yukihiko Suzuki, Taiichi Hikichi, Noriaki Washio, Tomohito Sato, Kishiko Ohkoshi, Hiroki Tsujinaka, Sentaro Kusuhara, Mineo Kondo, Hitoshi Takagi, Toshinori Murata, Taiji Sakamoto

The British journal of ophthalmology 104 ( 9 ) 1209 - 1215 2020.9

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

BACKGROUND/AIMS: To investigate real-world outcomes for best-corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve, centr-involving diabetic macular oedema (DME). METHODS: Retrospective analysis of longitudinal medical records obtained from 27 institutions specialising in retinal diseases in Japan. A total of 2049 eyes with treatment-naïve DME commencing intervention between 2010 and 2015 who were followed for 2 years were eligible. Interventions for DME included anti-vascular endothelial growth factor (VEGF) therapy, local corticosteroid therapy, macular photocoagulation and vitrectomy. Baseline and final BCVA (logMAR) were assessed. Eyes were classified by the treatment pattern, depending on whether anti-VEGF therapy was used, into an anti-VEGF monotherapy group (group A), a combination therapy group (group B) and a group without anti-VEGF therapy (group C). RESULTS: The mean 2-year improvement of BCVA was -0.04±0.40 and final BCVA of >20/40 was obtained in 46.3% of eyes. Based on the treatment pattern, there were 427 eyes (20.9%) in group A, 807 eyes (39.4%) in group B and 815 eyes (39.8%) in group C. Mean improvement of BCVA was -0.09±0.39, -0.02±0.40 and -0.05±0.39, and the percentage of eyes with final BCVA of >20/40 was 49.4%, 38.9%, and 52.0%, respectively. CONCLUSION: Following 2-year real-world management of treatment-naïve DME in Japan, BCVA improved by 2 letters. Eyes treated by anti-VEGF monotherapy showed a better visual prognosis than eyes receiving combination therapy. Despite treatment for DME being selected by specialists in consideration of medical and social factors, a satisfactory visual prognosis was not obtained, but final BCVA remained >20/40 in half of all eyes.

DOI： 10.1136/bjophthalmol-2019-315199

Inverted Internal Limiting Membrane Flap versus Internal Limiting Membrane Peeling for Macular Hole Retinal Detachment in High Myopia. International journal

Hiroshi Matsumae, Yuki Morizane, Shin Yamane, Shuichiro Yanagisawa, Toshiya Sakurai, Akira Kobori, Hisanori Imai, Yuki Kanzaki, Etsuji Suzuki, Kazuaki Kadonosono, Atsushi Hayashi, Fumio Shiraga, Shoji Kuriyama

Ophthalmology. Retina 4 ( 9 ) 919 - 926 2020.9

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

PURPOSE: To compare surgical outcomes between the inverted internal limiting membrane (ILM) flap technique and ILM peeling for macular hole retinal detachment (MHRD) in eyes with high myopia. DESIGN: Multicenter cohort study. PARTICIPANTS: We retrospectively reviewed medical records of consecutive patients treated between June 2008 and September 2018 at 7 hospitals and included 100 eyes with MHRD associated with high myopia in our study. All eyes underwent vitrectomy with the inverted ILM flap technique (57 eyes) or ILM peeling (43 eyes) and were followed up for more than 6 months. METHODS: We estimated odds ratios and their 95% confidence intervals (CIs) for macular hole (MH) closure using multivariate logistic regression analysis. We also examined factors associated with the postoperative best-corrected visual acuity (BCVA) at the final visit using multiple linear regression analysis. MAIN OUTCOME MEASURES: Macular hole closure and postoperative BCVA at the final visit. RESULTS: The MH closure rate was significantly higher in the inverted ILM flap group (80.7%) than in the ILM peeling group (37.2%; P < 0.001). Moreover, postoperative BCVA at the final visit was significantly better in the former group (0.88 ± 0.48 vs. 0.99 ± 0.48; P = 0.03). The retinal attachment rate (ILM flap, 91.2%; ILM peeling, 79.5%; P = 0.229) and recovery rates for the external limiting membrane and ellipsoid zone line (ILM flap, 10.9%; ILM peeling, 0%; P = 0.12) showed no significant intergroup differences. After adjustment for age, axis, tamponade substance, and dye for ILM staining, the inverted ILM flap technique was associated strongly and positively with MH closure (odds ratio, 7.14; 95% CI, 2.72-18.7; P = 0.001). Moreover, the inverted ILM flap technique and preoperative BCVA were associated significantly and positively with the postoperative BCVA at the final visit. CONCLUSIONS: Our findings suggest that the MH closure rate and postoperative visual outcome for eyes with high myopia-associated MHRD are better with the inverted ILM flap technique than with ILM peeling. Thus, vitrectomy with the inverted ILM flap technique should be considered as the initial surgery for MHRD associated with high myopia.

DOI： 10.1016/j.oret.2020.03.021

視覚障害認定の全国調査結果の都道府県別検討

森實祐基, 守本典子, 川崎良, 藤原篤之, 的場亮, 山下英俊, 小椋祐一郎, 白神史雄

日本眼科学会雑誌 124 ( 9 ) 697 - 704 2020.9

Language：Japanese Publisher：(公財)日本眼科学会

目的:視覚障害認定の全国調査結果を都道府県別に検討する.対象と方法:2015年度の視覚障害の新規認定の全国調査のデータを用いて,人口10万人あたりの認定者数(認定者割合)と原因疾患を都道府県別に検討した.また,総人口に占める65歳以上の割合(高齢化率),人口10万人あたりの身体障害者福祉法第15条指定医師である眼科医数(指定医師割合),人口10万人あたりの眼科専門医数(専門医割合),県民1人あたりの所得(県民所得),社会福祉費,老人福祉費と認定者割合との関連,および高齢化率と主要な原因疾患による認定者割合との関連について,線形回帰分析を行った.結果:都道府県別の認定者割合の平均(±標準偏差)は13.3±2.6人であった.高齢化率と指定医師割合は認定者割合に有意に関連した(順に,p=0.001,回帰係数0.26,95%信頼区間0.11〜0.41.p=0.023,回帰係数0.31,95%信頼区間0.05〜0.57).専門医割合,県民所得,社会福祉費,老人福祉費は認定者割合に関連しなかった.92.1%の都道府県において原因疾患の1位は緑内障であり,高齢化率は緑内障による認定者割合に有意に関連した(p=0.005,回帰係数0.16,95%信頼区間0.05〜0.27).結論:都道府県別の認定者割合には高齢化率と指定医師割合が関連した.緑内障による認定者割合には高齢化率が関連した.(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01049&link_issn=&doc_id=20200918580003&doc_link_id=%2Fdz1nigan%2F2020%2F012409%2F002%2F0697-0704%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz1nigan%2F2020%2F012409%2F002%2F0697-0704%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

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 2020.7

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

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

Vision loss, tractional retinal detachment, and profound anemia due to rectal carcinoma. International journal

Akira Yamamoto, Yoshito Nishimura, Mikako Obika, Yuki Morizane, Fumio Otsuka

Clinical case reports 8 ( 7 ) 1304 - 1305 2020.7

【サージカルレティナ最前線】黄斑手術における内境界膜剥離の有用性と課題

的場亮, 森實祐基

あたらしい眼科 37 ( 7 ) 797 - 806 2020.7

Risk factors for excessive postoperative exo-drift after unilateral lateral rectus muscle recession and medial rectus muscle resection for intermittent exotropia. International journal

Shin Morisawa, Ichiro Hamasaki, Kiyo Shibata, Takehiro Shimizu, Reika Kono, Manabu Miyata, Takashi Furuse, Satoshi Hasebe, Hiroshi Ohtsuki, Yuki Morizane, Fumio Shiraga

BMC ophthalmology 20 ( 1 ) 216 - 216 2020.6

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

BACKGROUND: To detect significant factors associated with excessive postoperative exo-drift in young patients with intermittent exotropia who had undergone unilateral lateral rectus muscle recession and medial rectus muscle resection. METHODS: We retrospectively examined the records of 64 consecutive patients < 18 years old who underwent surgery between April 2004 and December 2011. We sought risk factors for excessive postoperative exo-drift among patients' demographic and clinical characteristics using univariate and multivariable linear regression analysis. RESULTS: Younger patients (P = 0.007), and those with larger preoperative exo-deviation at distance (P = 0.033), a lower incidence of peripheral fusion at distance (P = 0.021) or a greater postoperative initial eso-deviation (P = 0.001), were significantly more likely to have an excessive postoperative exo-drift (> 20 prism diopters). Univariate analysis revealed significant associations between excessive postoperative exo-drift and age at surgery (P = 0.004), preoperative exo-deviation at distance (P = 0.017) and postoperative initial eso-deviation at distance (P < 0.001). Multivariable linear regression analysis showed that postoperative initial eso-deviation at distance (P = 0.008) was significantly associated with postoperative exo-drift. CONCLUSIONS: Postoperative exodrift in unilateral RR is predicted by the initial postoperative eso-deviation, which may offset the overcorrection. However, the exo-drift is greater in cases with a large preoperative exo-deviation and/or at a younger age, and should be followed carefully.

DOI： 10.1186/s12886-020-01484-z

Formulas to Estimate Appropriate Surgical Amounts of Unilateral Recession-Resection in Intermittent Exotropia with Distance-Near Disparity.

Kiyo Shibata, Ichiro Hamasaki, Shinji Toshima, Takehiro Shimizu, Reika Kono, Manabu Miyata, Shin Morisawa, Takashi Furuse, Satoshi Hasebe, Hiroshi Ohtsuki, Yuki Morizane, Fumio Shiraga

Acta medica Okayama 74 ( 3 ) 229 - 236 2020.6

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

The purpose of this study was to derive new formulas to provide an optimal surgical procedure and optimal amount of recession-resection (RR) surgery in intermittent exotropia (IXT) with a disparity in angle of deviation depending on the fixation distance. The records of 117 consecutive patients with IXT who underwent RR surgery between March 2008 and December 2011 at Okayama University Hospital were retrospectively examined. Multivariable linear regression analysis was performed using the observed corrective angle of deviation at distance or near fixation as the dependent variable, and amounts of lateral rectus muscle (LR) recession (mm) and medial rectus muscle (MR) resection, and age at surgery (years) as independent variables. Two simultaneous formulas were derived: corrective angle of deviation at distance fixation (°)=1.8×recession (mm)+1.6× resection (mm)+0.15×age (years)-6.6, and corrective angle at near fixation (°)=1.5×recession (mm)+1.7× resection (mm)+0.18×age (years)-3.8. Comparisons of coefficient values of the formulas between distance and near fixation revealed that LR recession was more affected by the corrective angle in distance than near fixation. MR resection was more affected at near than distance fixation. We found that our new formulas estimated the appropriate amount of unilateral RR surgery.

DOI： 10.18926/AMO/59956

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

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

Investigative ophthalmology & visual science 61 ( 5 ) 38 - 38 2020.5

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

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. International journal

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 2020.5

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

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 2020.3

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

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

重力と頭部の振動を利用して中心窩下に迷入したパーフルオロカーボンを除去した一例

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

日本眼科学会雑誌 124 ( 臨増 ) 208 - 208 2020.3

内科的治療に支援される硝子体手術黄斑下血腫

森實祐基

日本眼科学会雑誌 124 ( 臨増 ) 141 - 141 2020.3

KCNJ13遺伝子欠損がヒト多能性幹細胞由来網膜色素上皮細胞の貪食能に及ぼす影響

神崎勇希, 藤田洋史, 佐藤恵太, 細川海音, 松前洋, 白神史雄, 森實祐基, 大内淑代

日本眼科学会雑誌 124 ( 臨増 ) 187 - 187 2020.3

網膜橋渡し研究アップデート視覚身体障害の全国調査

森實祐基

眼科 62 ( 3 ) 265 - 272 2020.3

【加齢と眼疾患-健康長寿を目指して】わが国の視覚障害認定の原因疾患の推移

森實祐基

カレントテラピー 38 ( 2 ) 108 - 113 2020.2

Language：Japanese Publisher：(株)ライフメディコム

視覚障害は生活の質(QOL)を著しく低下させ、社会生活の維持にも大きな影響を及ぼす。視覚障害を減らす、もしくは視覚障害の重症化を防ぐためには、病態の解明や有効な治療法の開発に加えて予防が重要であり、医療福祉行政が担う役割は大きい。視覚障害に対する医療福祉行政を推進していくためには、わが国における視覚障害の実態を知り、どの眼疾患を対象として医療福祉行政を行うべきかを見極めることが重要である。われわれ(厚生労働省難治性疾患等政策研究事業、網膜脈絡膜・視神経萎縮症に関する調査研究班)は、2015年度に、本邦で初めてとなる全都道府県の全自治体を対象にした視覚障害の実態調査を行った。本稿ではこの調査結果について概説すると共に、わが国の失明原因の推移について考察する。(著者抄録)

Shape analysis of rectus extraocular muscles with age and axial length using anterior segment optical coherence tomography. International journal

Kiyo Shibata, Atsushi Fujiwara, Ichiro Hamasaki, Takehiro Shimizu, Reika Kono, Keisuke Kanenaga, Masanori Nakazawa, Yuki Morizane

PloS one 15 ( 12 ) e0243382 2020

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

PURPOSE: This study aimed to evaluate the shape of the extraocular muscles (EOMs) in normal subjects using the en-face images of anterior segment optical coherence tomography (AS-OCT). The EOM insertion and the direction of the muscle fibers were investigated. SUBJECTS AND METHODS: A total of 97 healthy normal subjects (194 eyes) at Okayama University Hospital (age, 47.1±21.5 years; range, 8-79 years) participated in the study. A series of 256 tomographic images of the rectus EOMs were captured using the C-scan function of the AS-OCT (CASIA2, TOMEY Co., Japan), and the images were converted to en-face images in multi-TIFF format. The anterior chamber angle to EOM insertion distance (AID) and the angle of the muscle fibers from the insertion site (angle of muscles) were measured from the images. The correlations of AID and angle of muscles with age and axial length were investigated and evaluated. RESULTS: AID and angle of muscles were significantly correlated with age or axial length in some EOMs. The AIDs of medial rectus (MR) (P = 0.000) and superior rectus (SR) (P = 0.005) shortened with age. The AIDs of MR (P = 0.001) and inferior rectus (IR) (P = 0.035) elongated with axial length, whereas lateral rectus (LR) (P = 0.013) shortened. The angles of MR (P = 0.001) and LR (P = 0.000) were found to have a more downward direction toward the posterior in older subjects. CONCLUSION: En-face images can be created by AS-OCT, and the shape of the EOMs in normal subjects using these image measurements was available. With the ability to assess the EOMs, AID and angle of muscles are expected give useful information for treating and diagnosing strabismus-related diseases.

DOI： 10.1371/journal.pone.0243382

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 2019.12

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

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

【中途失明の可能性のある疾患Q&A】中途失明の可能性のある疾患とその検査/治療網膜硝子体黄斑円孔の進行様式と治療について教えてください

木村修平, 森實祐基

あたらしい眼科 36 ( 臨増 ) 141 - 144 2019.11

Results of lamellar macular hole-associated epiretinal proliferation embedding technique for the treatment of degenerative lamellar macular hole. International journal

Kosuke Takahashi, Yuki Morizane, Shuhei Kimura, Yusuke Shiode, Shinichiro Doi, Toshio Okanouchi, Ippei Takasu, Yasushi Inoue, Fumio Shiraga

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 257 ( 10 ) 2147 - 2154 2019.10

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

PURPOSE: To investigate the outcomes of embedding lamellar hole-associated epiretinal proliferation (LHEP) into retinal cleavage for the surgical treatment of degenerative lamellar macular hole (LMH). METHODS: We retrospectively reviewed the medical records of 34 consecutive eyes of degenerative LMH patients who underwent vitrectomy with LHEP embedding and who were followed up for at least 12 months. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and macular structure preoperatively and at the final follow-up were compared. RESULTS: The mean (±SD) follow-up period was 30.0 ± 17.7 months. Twelve patients (35.3%) were men, and the mean age was 69.6 ± 10.1 years. Twenty-three eyes (67.6%) underwent simultaneous cataract surgery. BCVA was significantly improved at the final visit, from 0.31 ± 0.25 logarithm of the minimum angle of resolution units to 0.10 ± 0.25 (P < 0.01). This improvement in mean BCVA at the final postoperative visit occurred regardless of whether the eyes underwent simultaneous cataract surgery, from 0.30 ± 0.26 preoperatively to 0.04 ± 0.16 (P < 0.01) in the "with cataract surgery" group and from 0.32 ± 0.26 preoperatively to 0.21 ± 0.35 (P < 0.05) in the "without cataract surgery" group. CRT was also significantly improved at the final visit, from 123.2 ± 42.6 μm preoperatively to 191.2 ± 42.6 μm (P < 0.01). External limiting membrane and ellipsoid zone defects were detected in 17 (50.0%) and 15 (44.1%) eyes, respectively, but these were resolved in 10 (58.8%) and 7 (46.7%) eyes, respectively, at the final visit. No intraoperative or postoperative complications were observed. CONCLUSIONS: Embedding LHEP may be an effective and safe procedure to treat degenerative LMH.

DOI： 10.1007/s00417-019-04425-9

Twist Knot: A New Sliding Noose in Adjustable Suture Strabismus Surgery.

Kiyo Shibata, Ichiro Hamasaki, Takehiro Shimizu, Reika Kono, Hiroshi Ohtsuki, Yuki Morizane, Fumio Shiraga

Acta medica Okayama 73 ( 5 ) 463 - 468 2019.10

Language：English

To permit noose movement without fraying the sutures following strabismus surgery, we designed a new sliding noose, the "twist knot" and investigated its advantages and disadvantages. We measured the tensile strength required to move the twist knot in a tightly tied state (134±19 gf) and in a loosened state (21±7 gf), and that required to move the conventional sliding noose in a tightly tied state (48±14 gf), and used the Kruskal-Wallis test to compare them. A significant difference was observed among the three tensile strengths (p<0.001). The twist knot technique allowed easy sliding without the multifilament braided suture becoming frayed and a knot to be firmly fixed without slipping. However, if the 2 strings of the pole sutures exit from the sclera at 2 widely separated positions, the sliding noose may become slack. Therefore, the distance between the pole sutures should be small. The simple twist knot technique was found to be an effective approach following adjustable surgery of strabismus.

DOI： 10.18926/AMO/57378

Planned Foveal Detachment Technique for the Resolution of Diabetic Macular Edema Resistant to Anti-Vascular Endothelial Growth Factor Therapy. International journal

Shinji Toshima, Yuki Morizane, Shuhei Kimura, Fumio Shiraga

Retina (Philadelphia, Pa.) 39 Suppl 1 S162-S168 2019.10

黄斑上膜における網膜皺襞と網膜層構造との関係

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

眼科臨床紀要 12 ( 10 ) 781 - 781 2019.10

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 2019.9

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

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

Localization of the ultraviolet-sensor Opn5m and its effect on myopia-related gene expression in the late-embryonic chick eye. International journal

Mutsuko Kato, Keita Sato, Munenori Habuta, Hirofumi Fujita, Tetsuya Bando, Yuki Morizane, Fumio Shiraga, Satoru Miyaishi, Hideyo Ohuchi

Biochemistry and biophysics reports 19 100665 - 100665 2019.9

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

Recent studies show that exposure to ultraviolet (UV) light suppresses ocular elongation, which causes myopia development. However, the specific mechanisms of this process have not been elucidated. A UV-sensor, Opsin 5 (Opn5) mRNA was shown to be present in extraretinal tissues. To test the possibility that UV-signals mediated by Opn5 would have a direct effect on the outer connective tissues of the eye, we first examined the expression patterns of a mammalian type Opn5 (Opn5m) in the late-embryonic chicken eye. Quantitative PCR showed Opn5m mRNA expression in the cornea and sclera. The anti-Opn5m antibody stained a small subset of cells in the corneal stroma and fibrous sclera. We next assessed the effect of UV-A (375 nm) irradiation on the chicken fibroblast cell line DF-1 overexpressing chicken Opn5m. UV-A irradiation for 30 min significantly increased the expression of Early growth response 1 (Egr1), known as an immediate early responsive gene, and of Matrix metalloproteinase 2 (Mmp2) in the presence of retinal chromophore 11-cis-retinal. In contrast, expression of Transforming growth factor beta 2 and Tissue inhibitor of metalloproteinase 2 was not significantly altered. These results indicate that UV-A absorption by Opn5m can upregulate the expression levels of Egr1 and Mmp2 in non-neuronal, fibroblasts. Taken together with the presence of Opn5m in the cornea and sclera, it is suggested that UV-A signaling mediated by Opn5 in the extraretinal ocular tissues could influence directly the outer connective tissues of the chicken late-embryonic eye.

DOI： 10.1016/j.bbrep.2019.100665

Internal Limiting Membrane Transposition for Persistent Macular Holes Using Double Layers of Viscoelastic. International journal

Mohamed Kamel Soliman, Alexander J Lingley, Yuki Morizane, Raman Tuli

Ophthalmic surgery, lasers & imaging retina 50 ( 6 ) 401 - 403 2019.6

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

Internal limiting membrane (ILM) grafting provides a useful option for repair of large and refractory macular holes that fail to close following prior ILM removal. However, current ILM graft techniques are associated with several challenges that may result in failure, most notably the difficulty in maintaining the graft in situ. In this video, the authors describe their modified technique for ILM grafting using a double layer of viscoelastic for stabilization in situ during the procedure. Four of five eyes managed with this technique demonstrated type 1 closure, and all eyes demonstrated improvement in visual acuity.

DOI： 10.3928/23258160-20190605-11

Lights-out Surgery for Strabismus Using a Heads-Up 3D Vision System.

Ichiro Hamasaki, Kiyo Shibata, Takehiro Shimizu, Reika Kono, Yuki Morizane, Fumio Shiraga

Acta medica Okayama 73 ( 3 ) 229 - 233 2019.6

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

During strabismus surgery using illumination from a light source, patients complain of photophobia. The NGENUITYⓇ (Alcon) system is equipped with a high-dynamic-range (HDR) camera. A 4K display viewed by wearing circularly polarized glasses provides clear three-dimensional images of the operative field. A light source is usually required for surgeries of the anterior segment (including strabismic surgery), but the digital processing function of the NGENUITYⓇ system allows image display in relatively dark regions even without a light source. We devised a novel 'lights-out' surgery that does not use a microscope's light source, and we examined the usefulness of this technique in 2 cases of strabismic surgery. We performed strabismus surgery using the NGENUITYⓇ system in two patients between January and June 2018. The HDR function was used, and the aperture was opened to the maximum while the gain was adjusted. Surgery was conducted without using the microscope's light source. We report the 2 cases' results and evaluate the novel method. The surgeries were performed without problem even though the microscope's light source was not used. The patients' photophobia was alleviated. Lights-out surgery is a potentially useful modality for strabismus surgery.

DOI： 10.18926/AMO/56865

Impact of Cataract Surgery on Filtering Bleb Morphology Identified Via Swept-source 3-dimensional Anterior Segment Optical Coherence Tomography. International journal

Akiko Narita, Yuki Morizane, Tomoe Miyake, Kae Sugihara, Tomoko Ishikawa, Jiro Seguchi, Fumio Shiraga

Journal of glaucoma 28 ( 5 ) 433 - 439 2019.5

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

PRéCIS:: Analysis of filtering bleb morphology using swept-source 3-dimensional anterior segment optical coherence tomography (3D AS-OCT) indicates that phacoemulsification can negatively impact the morphology of preexisting filtering blebs. PURPOSE: To identify the cross-sectional morphologic changes in successful filtering blebs after phacoemulsification using swept-source 3D AS-OCT. MATERIALS AND METHODS: In total, 30 phakic eyes of 29 patients with successful filtering blebs after primary trabeculectomy were included in this retrospective cohort study. Success was defined as intraocular pressure (IOP)≤15 mm Hg and a>20% reduction in IOP without glaucoma medication or additional glaucoma surgery after trabeculectomy. The subjects were classified into 2 groups according to whether they had undergone phacoemulsification or not after trabeculectomy: a phaco group and a control group. Filtering blebs were examined using swept-source 3D AS-OCT and evaluated for quantitative parameters, including maximum bleb height, maximum bleb wall thickness, and the ratio of the hyporeflective space of the bleb wall. RESULTS: Sixteen eyes were assigned to the phaco group and 14 eyes to the control group. The eyes in the control group showed no significant differences in IOP or in any of the 3D AS-OCT parameters at any of the follow-up timepoints. In the phaco group, the mean IOP increased significantly after phacoemulsification (P=0.003). Furthermore, the eyes in the phaco group showed a significant decrease in maximum bleb height (P=0.030), maximum bleb wall thickness (P=0.006), and the ratio of the hyporeflective space of the bleb wall (P=0.011) between prephacoemulsification and 1-year postphacoemulsification. CONCLUSION: Phacoemulsification can have a negative impact on filtering bleb morphology, which may lead to an IOP increase.

DOI： 10.1097/IJG.0000000000001204

分層黄斑円孔と黄斑偽円孔のあたらしい捉え方 En face画像を用いた網膜牽引の評価と分類

平野雅幸, 森實祐基

眼科 61 ( 4 ) 387 - 395 2019.4

Language：Japanese Publisher：金原出版(株)

光干渉断層計(OCT)の解像度の向上とともに、黄斑偽円孔(MPH)と似た形態を示す分層黄斑円孔(LMH)との鑑別が難しくなった。現在のLMHとMPHの分類上の問題点を解説したうえで、筆者らが報告したOCTのen face画像を用いたLMHとMPHの新しい分類、さらに分類に基づいた治療法について述べた。牽引型LMHとMPHは、黄斑上膜による網膜牽引が病態に関与し、その強さと方向の均一性によって分類することができると考えられた。

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00293&link_issn=&doc_id=20190426130010&doc_link_id=10.18888%2Fga.0000001129&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fga.0000001129&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

黄斑疾患に対する硝子体手術最近の話題

森實祐基

眼科臨床紀要 12 ( 4 ) 348 - 348 2019.4

黄斑上膜の手術前後における網膜血管移動距離と網膜皺襞深度との関係

神崎勇希, 土居真一郎, 森實祐基, 木村修平, 細川海音, 塩出雄亮, 戸島慎二, 高橋耕介, 藤原篤之, 高須逸平, 白神史雄

日本眼科学会雑誌 123 ( 臨増 ) 206 - 206 2019.3

Surgical retinaの最先端黄斑手術に及ぼすSwept Source OCTの影響(Cutting edge In surgical retina Impact of Swept Source OCT on Macular Surgery)

森實祐基

日本眼科学会雑誌 123 ( 臨増 ) 73 - 73 2019.3

Plication法を用いた短縮術と筋切除術を施行した外斜視の術後1年成績と戻りの比較

柴田貴世, 濱崎一郎, 清水壯洋, 河野玲華, 森澤伸, 古瀬尚, 長谷部聡, 大月洋, 森實祐基, 白神史雄

日本眼科学会雑誌 123 ( 臨増 ) 233 - 233 2019.3

前眼部OCTを用いたPlication法での短縮術の外眼筋の術後評価

清水壯洋, 濱崎一郎, 柴田貴世, 河野玲華, 藤原篤之, 森實祐基, 白神史雄

日本眼科学会雑誌 123 ( 臨増 ) 233 - 233 2019.3

滲出型加齢黄斑変性に対するアフリベルセプトtreat and extend法の4年成績

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

日本眼科学会雑誌 123 ( 臨増 ) 161 - 161 2019.3

The Impact of Prefilled Syringes on Endophthalmitis Following Intravitreal Injection of Ranibizumab. International journal

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 2019.3

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

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

Magnetic resonance imaging findings of age-related distance esotropia in Japanese patients with high myopia. International journal

Reika Kono, Hiroshi Ohtsuki, Fumiko Kishimoto, Ichiro Hamasaki, Yuki Morizane, Fumio Shiraga

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 257 ( 3 ) 657 - 662 2019.3

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

PURPOSE: This study aimed to investigate the characteristics of the extraocular muscles and the orbital connective tissue pulleys in Japanese patients with age-related distance esotropia (ARDE) and high myopia using magnetic resonance imaging (MRI). METHODS: This was a retrospective case-series study. High-resolution coronal MRI scans of 12 orbits were obtained in 6 patients with ARDE and high myopia (age range: 51-69 years). We analyzed the images to determine the positions of the rectus muscle pulleys relative to the center of the globe, the integrity of the lateral rectus-superior rectus muscle (LR-SR) band, and the LR angle (the angle between the major axis of the LR and the vertical plane). RESULTS: The distance esotropia ranged from 4 to 25∆, and 3 cases exhibited vertical deviations. The mean (±standard deviation (SD)) axial length was 28.5 (± 1.6) mm. The mean positions of the medial rectus muscle pulley and LR pulley were 1.3 mm inferior and 1.4 mm inferior, respectively, to those seen in the normal control group in our previous study (P = 0.002 and P = 0.05, respectively). All 12 orbits had abnormal elongated LR-SR bands, and 8 orbits (67%) displayed ruptured LR-SR bands. The LR angle (mean±SD; 18.8° ± 8.5°) increased significantly with the inferior displacement of the LR pulley (R2 = 0.77, P = 0.0002). CONCLUSIONS: Inferior displacement of the LR pulley and abnormal LR-SR bands were seen in Japanese ARDE patients with high myopia, as was found in ARDE patients without high myopia. The LR angle might be useful for judging the degree of LR pulley displacement.

DOI： 10.1007/s00417-019-04250-0

En-face画像を用いた前眼部OCTでの健常者の外眼筋の形状解析

濱崎一郎, 柴田貴世, 清水壯洋, 河野玲華, 藤原篤之, 森實祐基, 白神史雄

日本眼科学会雑誌 123 ( 臨増 ) 301 - 301 2019.3

強膜内陥術後に残存する網膜下液のEn face画像による検討

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

日本眼科学会雑誌 123 ( 臨増 ) 260 - 260 2019.3

Congenital Multiple Ocular Motor Nerve Palsy Complicated by Splitting of the Lateral Rectus Muscle.

Reika Kono, Takehiro Shimizu, Hiroshi Ohtsuki, Ichiro Hamasaki, Kiyo Shibata, Fumiko Kishimoto, Yuki Morizane, Fumio Shiraga

Acta medica Okayama 73 ( 1 ) 67 - 70 2019.2

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

We report a case of congenital multiple ocular motor nerve palsy combined with splitting of the lateral rectus muscle (LR). A 59-year-old Japanese female was investigated for worsening esotropia after corrective surgery. She presented with left hypertropia (35Δ) and esotropia (45-50Δ). Orbital magnetic resonance imaging (MRI) showed reduced belly sizes in the superior rectus, inferior rectus, and superior oblique muscles and splitting of the LR, extending from the origin to the belly, in the left eye. Splitting of the LR belly was detected on MRI in a case of congenital multiple ocular motor nerve palsy.

DOI： 10.18926/AMO/56460

分層黄斑円孔と黄斑偽円孔 En face画像を用いた網膜牽引の評価と分類

平野雅幸, 森實祐基

眼科手術 32 ( 1 ) 65 - 70 2019.1

Language：Japanese Publisher：(公社)日本眼科手術学会

分層黄斑円孔(LMH)もしくは黄斑偽円孔(MPH)と診断された60例63眼を対象として、波長掃引型光干渉断層計を用いてEn face画像を撮影した。En face画像を用いて、網膜(黄斑)上膜(ERM)の有無、網膜皺襞の有無、網膜分層の有無を評価し、この結果に基づいて対象を分類した。その結果、対象は網膜皺襞の有無と網膜分層の有無によって三つのグループに分類された。網膜皺襞と網膜分層をともに認めたグループ(グループA)は、その97%がBスキャン画像に基づく分類における牽引型LMHであった。網膜皺襞を認めたが網膜分層を認めなかったグループ(グループB)は全例がMPHであった。網膜皺襞を認めなかったが、網膜分層を認めたグループ(グループC)はその81%が変性型LMHであった。グループCの視力は、グループAおよびBよりも有意に不良であった。網膜皺襞の深度と黄斑の網膜開口部の真円度を定量評価した結果、グループAはグループBよりも網膜にかかる牽引力が大きく、また牽引の方向に偏りがあることが推察された。以上の結果から、LMHとMPHの病態における網膜牽引の関与が明らかになった。今後、多数例の検討を行い、病態に基づいた診断基準を策定する必要がある。(著者抄録)

Incidence and causes of visual impairment in Japan: the first nation-wide complete enumeration survey of newly certified visually impaired individuals.

Yuki Morizane, Noriko Morimoto, Atsushi Fujiwara, Ryo Kawasaki, Hidetoshi Yamashita, Yuichiro Ogura, Fumio Shiraga

Japanese journal of ophthalmology 63 ( 1 ) 26 - 33 2019.1

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

PURPOSE: To investigate the visual impairment certification status in Japan. STUDY DESIGN: Observational cross-sectional study. METHODS: We asked all welfare offices throughout Japan to submit data concerning age, sex, causative diseases, and visual impairment grades for newly certified visually impaired individuals aged ≥ 18 years in the fiscal year of 2015. The certification was based on criteria of the Act on Welfare of Physically Disabled Persons. RESULTS: In total, data were collected for 12,505 newly certified visually impaired individuals. The most common age group for these individuals was 80-89 years (29.6%), followed by 70-79 (26.3%) and 60-69 (17.3%) years. The most common causative disease was glaucoma (28.6%), followed by retinitis pigmentosa (14.0%), diabetic retinopathy (12.8%), and macular degeneration (8.0%). Glaucoma was the most common causative disease in both sexes (30.2% in men and 27.0% in women). The most common impairment grade was grade 2 (31.8%), followed by grades 5 (24.3%) and grade 1 (16.1%). The number of visually impaired individuals with underlying glaucoma had increased in comparison with the number in the most recent surveys (from fiscal years 2007 to 2009), whereas the number of individuals with underlying diabetic retinopathy and macular degeneration had decreased. CONCLUSION: To our knowledge, this is the first nation-wide complete enumeration survey of newly certified visually impaired individuals in Japan. These findings may contribute to administrative activities concerning medical welfare as well as educational activities for preventing visual impairment.

DOI： 10.1007/s10384-018-0623-4

Four-year follow-up of an elderly Japanese patient with distance Esotropia using magnetic resonance imaging

Reika Kono, Hiroshi Ohtsuki, Ichiro Hamasaki, Jiro Seguchi, Yuki Morizane, Fumio Shiraga

Neuro-Ophthalmology Japan 36 ( 3 ) 349 - 356 2019

Language：English Publishing type：Research paper (scientific journal) Publisher：Neuro-Ophthalmology Society of Japan

This report describes a case involving a Japanese patient with distance esotropia, who was followed-up for 4 years using magnetic resonance imaging (MRI). A 68-year-old woman with high myopia exhibited esotropia of 10 prism diopters (Δ) and right hypotropia of 5Δ
her axial lengths were 31.0 mm oculus dextrus (OD) and 30.7 mm oculus sinister (OS). Bilateral enlarged lateral rectus (LR)-superior rectus (SR) bands and posterior staphylomata were observed on orbital MRI. At the 4-year follow-up, her ocular deviation had deteriorated to esotropia of 18 Δ and right hypotropia of 8Δ
however, her axial lengths had scarcely changed (31.0 mm OD
30.8 mm OS). The enlargement and rupturing of the bilateral LR-SR bands had worsened. Progressive enlargement and rupturing of the LR-SR bands, which are presumably related to aging and possibly linked to progressive connective tissue degeneration, may increase ocular deviation.

DOI： 10.11476/shinkeiganka.36.349

【糖尿病網膜症の検査と最新治療〜失明のリスクが高い糖尿病網膜症を予防するには?〜】日本における視覚障害の原因疾患としての糖尿病網膜症本邦初の全都道府県を対象とした視覚障害の実態調査

森實祐基

月刊糖尿病 10 ( 9 ) 14 - 21 2018.12

光線力学的療法が奏功した15歳男児の網膜血管腫の1例

難波倫江, 塩出雄亮, 藤原美幸, 森實祐基, 木村修平, 細川海音, 平野雅幸, 土居真一郎, 戸島慎二, 高橋耕介, 松前洋, 藤原篤之, 白神史雄

眼科臨床紀要 11 ( 11 ) 835 - 835 2018.11

Successful resolution of coats disease by photodynamic therapy: a case report. International journal

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 2018.10

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

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

PCVによる黄斑下血腫に対するt-PA網膜下注入併用硝子体手術の長期成績

木村修平, 森實祐基, 細川海音, 塩出雄亮, 平野雅幸, 土居真一郎, 戸島慎二, 高橋耕介, 松前洋, 細木三佳, 藤原篤之, 岡野内俊雄, 白神史雄

眼科臨床紀要 11 ( 10 ) 780 - 780 2018.10

【7年前の常識は現在の非常識!-眼科診療の最新標準】網膜・硝子体疾患手術手技黄斑円孔手術

森實祐基

臨床眼科 72 ( 11 ) 256 - 261 2018.10

光線力学的療法後に漿液性網膜剥離が再発した中心性漿液性脈絡網膜症の検討

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

眼科臨床紀要 11 ( 10 ) 776 - 776 2018.10

Differences in the Stability and Amount of Postoperative Exodrift with Age after Unilateral Lateral Rectus Muscle Recession and Medial Rectus Muscle Resection of Intermittent Exotropia.

Ichiro Hamasaki, Kiyo Shibata, Takehiro Shimizu, Shin Morisawa, Shinji Toshima, Manabu Miyata, Takashi Furuse, Satoshi Hasebe, Hiroshi Ohtsuki, Yuki Morizane, Fumio Shiraga

Acta medica Okayama 72 ( 5 ) 487 - 492 2018.10

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

We investigated variances in the stability and amount of postoperative exodrift among age groups of intermittent exotropia (XPT) patients who underwent unilateral lateral rectus muscle recession and medial rectus muscle resection. We analyzed the cases of 110 consecutive patients who underwent the surgery in 2004-2011, dividing the patients into groups by their age at surgery: <10, 10-19, and ≥20 years. We performed a regression analysis (dependent variable: postoperative exodrift (°); independent variable: number of days post-surgery) using the formula of curve lines. When the tangent line slope was = 0.01 (°/days) for each group, we defined the numbers of days until alignment became stable as the 'stable days.' We evaluated the between-group differences in the amount of exodrift calculated for the stable days. The coefficients and coefficients of determination for the fitting curves were: <10 year group: f(x)=12.2 (1-e-0.0183x) (r2=0.588, p<0.05); 10-19 year group: f(x)=10.0 (1-e-0.0178x) (r2=0.453, p<0.05); ≥20 year group: f(x)=3.40 (1-e-0.0382x) (r2=0.217, p<0.05). There were 389 , 388, and 153 stable days, and the estimated postoperative exodrift with long-term follow-up was 11.5±3.7°, 9.3±4.4°, and 4.1±3.6° for the < 10 year, 10-19 year, and ≥ 20 year groups, respectively (≥20 year vs. other 2 groups, p<0.05). Longer periods and more postoperative exodrift were associated with younger age at surgery. The postoperative evaluation was approx. ≥ 1 year post-surgery in patients aged < 20. These findings may contribute to evaluating XPT's success rate and prognoses.

DOI： 10.18926/AMO/56246

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

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 2018.9

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

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 2018.8

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

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

Col4a3ノックアウトマウスにおける網膜の表現型解析

米澤朋子, 松前洋, 神崎勇希, Chuyuan Lou, 前場崇宏, 森實祐基, 美名口順, Miner Jeffrey, 大橋俊孝

日本結合組織学会学術大会プログラム・抄録集 50回 106 - 106 2018.6

Characteristics of early filtering blebs that predict successful trabeculectomy identified via three-dimensional anterior segment optical coherence tomography. International journal

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

The British journal of ophthalmology 102 ( 6 ) 796 - 801 2018.6

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

BACKGROUND/AIMS: To identify the cross-sectional characteristics of filtering blebs at 2 weeks post-trabeculectomy associated with intraocular pressure (IOP) control at 1 year post-trabeculectomy. METHODS: Ninety-nine eyes of 94 patients who had undergone primary trabeculectomy were included in this retrospective consecutive case series study. Surgical success was defined as an IOP ≤15 mm Hg and a >20% reduction in IOP without glaucoma medication or additional glaucoma surgeries at 1 year post-trabeculectomy. Subjects were classified into two groups according to whether surgery was successful or unsuccessful. Blebs were examined using swept-source three-dimensional anterior segment optical coherence tomography and evaluated for quantitative parameters, including maximum height, maximum wall thickness and ratio of hyporeflective space of the wall, as well as qualitative parameters, including multiple parallel hyporeflective layers within the wall (striping phenomenon), decreased visibility of the sclera underlying the bleb (shading phenomenon) and cyst-like structures of the wall. RESULTS: Seventy-seven eyes (77.8%) were assigned to the successful group and 22 (22.2%) to the unsuccessful group. Univariate analysis showed significant differences between the groups regarding maximum bleb height (p=0.044), maximum bleb wall thickness (p=0.017) and the striping phenomenon of the bleb wall (p=0.007). Multivariate logistic regression analysis confirmed that the striping phenomenon at 2 weeks post-trabeculectomy was significantly associated with success at 1 year post-trabeculectomy (OR 3.405; 95% CI 1.059 to 10.947; p=0.040). CONCLUSION: Taller blebs with thicker walls that showed the striping phenomenon at 2 weeks post-trabeculectomy appeared to predict good IOP control at 1 year post-trabeculectomy.

DOI： 10.1136/bjophthalmol-2017-310707

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

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 2018.4

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

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

手術に踏み切るタイミングと手術のコツ網膜下出血

森實祐基

日本眼科学会雑誌 122 ( 臨増 ) 114 - 114 2018.3

細胞外基質が細胞遊走に及ぼす影響の評価を目的とした細胞遊走アッセイ

塩出雄亮, 森實祐基, 平野雅幸, 土居真一郎, 戸島慎二, 荒木亮一, 高橋耕介, 松前洋, 神崎勇希, 細木三佳, 米澤朋子, 白神史雄

日本眼科学会雑誌 122 ( 臨増 ) 226 - 226 2018.3

網膜細動脈瘤破裂による黄斑下血腫において網膜内出血の有無が視力予後に及ぼす影響

土居真一郎, 木村修平, 森實祐基, 細川海音, 塩出雄亮, 平野雅幸, 戸島慎二, 高橋耕介, 松前洋, 神崎勇希, 藤原篤之, 岡野内俊雄, 白神史雄

日本眼科学会雑誌 122 ( 臨増 ) 217 - 217 2018.3

内境界膜剥離を併用した網膜下注入の安全性の検討注入圧の違いが網膜へ及ぼす影響

高橋耕介, 森實祐基, 立花崇, 久冨智朗, 木村修平, 細川海音, 塩出雄亮, 平野雅幸, 土居真一郎, 戸島慎二, 荒木亮一, 園田康平, 白神史雄

日本眼科学会雑誌 122 ( 臨増 ) 219 - 219 2018.3

健常眼の中心窩無血管領域面積の左右差の検討

藤原篤之, Liu Mengxuan, 森實祐基, 細木三佳, 木村修平, 細川海音, 塩出雄亮, 平野雅幸, 土居真一郎, 戸島慎二, 高橋耕介, 松前洋, 神崎勇希, 白神史雄

日本眼科学会雑誌 122 ( 臨増 ) 298 - 298 2018.3

実臨床における糖尿病黄斑浮腫治療の実態 VEGF阻害薬治療

村松大弐, 志村雅彦, 内海卓也, 北野滋彦, 福嶋はるみ, 高村佳弘, 松本牧子, 築城英子, 森實祐基, 厚東隆志, 園田祥三, 石川裕人, 五味文, 香留崇, 三田村佳典, 木村和博, 木下貴正, 杉本昌彦, 近藤峰生, 引地泰一, 鷲尾紀章, 佐藤智人, 竹内大, 辻中大生, 緒方奈保子, 楠原仙太郎, 坂本泰二, J-CREST Study Group

日本眼科学会雑誌 122 ( 臨増 ) 240 - 240 2018.3

実臨床における糖尿病黄斑浮腫治療の実態介入治療開始年度比較

志村雅彦, 内海卓也, 北野滋彦, 福嶋はるみ, 村松大弐, 高村佳宏, 松本牧子, 築城英子, 森實祐基, 厚東隆志, 園田祥三, 石川裕人, 五味文, 香留崇, 三田村佳典, 木村和博, 木下貴正, 杉本昌彦, 近藤峰生, 引地泰一, 鷲尾紀章, 佐藤智人, 竹内大, 辻中大生, 緒方奈保子, 楠原仙太郎, 坂本泰二, J-CREST Group

日本眼科学会雑誌 122 ( 臨増 ) 240 - 240 2018.3

紫外線受容視物質オプシン5のニワトリ胚線維芽細胞における作用

加藤睦子, 佐藤恵太, 藤田洋史, 板東哲哉, 森實祐基, 中山正, 白神史雄, 大内淑代

日本眼科学会雑誌 122 ( 臨増 ) 185 - 185 2018.3

黄斑上膜による網膜牽引が視機能に及ぼす影響

平野雅幸, 神崎勇希, 森實祐基, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 戸島慎二, 高橋耕介, 松前洋, 藤原篤之, 細木三佳, 高須逸平, 白神史雄

日本眼科学会雑誌 122 ( 臨増 ) 220 - 220 2018.3

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 2018.2

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

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

Traumatic Globe Luxation with Complete Optic Nerve Transection Caused by Heavy Object Compression.

Yoshinori Kosaki, Tetsuya Yumoto, Hiromichi Naito, Nobushige Tsuboi, Masahiro Kameda, Masayuki Hirano, Yuki Morizane, Takaya Senoo, Eijirou Tokuyama, Atsunori Nakao

Acta medica Okayama 72 ( 1 ) 85 - 88 2018.2

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

Traumatic eyeball luxation is a rare clinical condition with a dramatic presentation. Here, we describe a unique case of traumatic globe luxation and complete optic nerve transection caused by heavy object compression. A 45-year-old male automobile mechanic was injured when a truck slipped from its supports, crushing his head and face. On arrival, his right eyeball was obviously displaced anteriorly and he had no light perception. Computed tomography revealed complex frontal bone and facial fractures with underlying brain contusion in addition to complete transection of the right optic nerve. The patient was successfully treated using a multidisciplinary approach.

DOI： 10.18926/AMO/55669

Issues with the Specificity of Immunological Reagents for NLRP3: Implications for Age-related Macular Degeneration. International journal

Cassandra Kosmidou, Nikolaos E Efstathiou, Mien V Hoang, Shoji Notomi, Eleni K Konstantinou, Masayuki Hirano, Kosuke Takahashi, Daniel E Maidana, Pavlina Tsoka, Lucy Young, Evangelos S Gragoudas, Timothy W Olsen, Yuki Morizane, Joan W Miller, Demetrios G Vavvas

Scientific reports 8 ( 1 ) 461 - 461 2018.1

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

Contradictory data have been presented regarding the implication of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in age-related macular degeneration (AMD), the leading cause of vision loss in the Western world. Recognizing that antibody specificity may explain this discrepancy and in line with recent National Institutes of Health (NIH) guidelines requiring authentication of key biological resources, the specificity of anti-NLRP3 antibodies was assessed to elucidate whether non-immune RPE cells express NLRP3. Using validated resources, NLRP3 was not detected in human primary or human established RPE cell lines under multiple inflammasome-priming conditions, including purported NLRP3 stimuli in RPE such as DICER1 deletion and Alu RNA transfection. Furthermore, NLRP3 was below detection limits in ex vivo macular RPE from AMD patients, as well as in human induced pluripotent stem cell (hiPSC)-derived RPE from patients with overactive NLRP3 syndrome (Chronic infantile neurologic cutaneous and articulate, CINCA syndrome). Evidence presented in this study provides new data regarding the interpretation of published results reporting NLRP3 expression and upregulation in RPE and addresses the role that this inflammasome plays in AMD pathogenesis.

DOI： 10.1038/s41598-017-17634-1

【黄斑疾患の新しい概念と治療法】黄斑疾患に対する手術手技の新展開内境界膜処理と網膜下注入

森實祐基

日本の眼科 89 ( 1 ) 39 - 44 2018.1

Language：Japanese Publisher：(公社)日本眼科医会

近年、黄斑に対する手術手技について、新たな発想に基づいて手技のバリエーションが生まれる、これまで手技の対象ではなかった疾患が対象となる、といった展開がみられている。例えば黄斑円孔に対して、これまでは内境界膜の剥離除去が行われてきた。しかし、特殊な黄斑円孔に対しては、内境界膜を剥離除去するだけでは円孔が閉鎖しないことが明らかになり、内境界膜弁翻転法や内境界膜自家移植が考案され普及してきている。現時点では、このような新しい黄斑手技の方法や適応は厳密には定まっておらず、術者の経験や好みに基づいて施行されている。今後、手技や適応の標準化に向けた検討が必要である。(著者抄録)

The influence of subretinal injection pressure on the microstructure of the monkey retina. International journal

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

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

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

Comparison of success rates in eye drop instillation between sitting position and supine position. International journal

Tomoko Naito, Keiji Yoshikawa, Koji Namiguchi, Shiro Mizoue, Atsushi Shiraishi, Yuko Ichikawa, Miyuki Fujiwara, Takako Miki, Ryoichi Araki, Yuzo Umeda, Yuki Morizane, Fumio Shiraga

PloS one 13 ( 9 ) e0204363 2018

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

PURPOSE: To compare the success rates of eye drop instillation in the sitting position and supine position among Japanese patients with ocular diseases (cataract, glaucoma, or retinal and vitreous diseases). METHODS: Patients who were hospitalized in Okayama University Hospital for eye surgery were studied. Instillation procedures of each patient in both the sitting and supine positions were recorded using a video camera at the time of instillation. We defined "success" when one drop fell accurately onto the ocular surface at the first attempt. Instillation of two or more drops, drops delivered to a site other than the eye surface, and touching the eyelashes, eyelids, or conjunctiva with the tip of the eye drop bottle were regarded as "failure". We excluded patients with vision below counting finger. RESULTS: One-hundred and two patients (54 males and 58 females, aged 70.2 ± 12.3 years) with ocular disease who were hospitalized for surgery (cataract: 61.8%, glaucoma: 15.7%, retinal and vitreous diseases: 22.5%) were included in this prospective observational study. The mean duration of eye drop use was 3.1 ± 5.2 years. The success rate of eye drop instillation was significantly higher in the supine position than in the sitting position (64.7% vs. 50%, P = 0.0039). The mean age was significantly higher in the failure group than in the success group (74.0 ± 11.5 vs. 67.7 ± 12.4 years, P = 0.0085) for the sitting position, but not significantly different for the supine position (72.3 ± 12.9 vs. 70.1 ± 12.0 years, P = 0.3849). No significant differences in mean duration of drop use, mean corrected VA, and mean spherical equivalent refraction were observed between success and failure groups, for both sitting and supine positions. CONCLUSIONS: In the present study, the success rate of eye drop instillation was significantly higher when applied in the supine position than in the sitting position.

DOI： 10.1371/journal.pone.0204363

【網膜硝子体手術アップデート】難治性の黄斑円孔・糖尿病黄斑浮腫に対する手術

塩出雄亮, 森實祐基

眼科グラフィック 6 ( 6 ) 566 - 575 2017.12

Retinal Nerve Fiber Layer Defect and Paracentral Scotoma after Internal Limiting Membrane Peeling with a Nitinol Loop.

Ryo Matoba, Yuki Morizane, Shuhei Kimura, Shinji Toshima, Fumio Shiraga

Acta medica Okayama 71 ( 6 ) 539 - 542 2017.12

Language：English

Internal limiting membrane (ILM) peeling is an important maneuver in vitrectomy for macular holes (MHs). A nitinol loop is a surgical instrument designed to create an edge on the ILM and peel the ILM safely and consistently. The effect of using a nitinol loop for ILM peeling on the retina is not clear. We report here on a case of an idiopathic full-thickness MH in an adult woman, in whom retinal damage was revealed after her ILM was peeled using a nitinol loop.

DOI： 10.18926/AMO/55592

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 2017.11

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

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

En face optical coherence tomography画像を用いた分層黄斑円孔の解析

平野雅幸, 森實祐基, 木村修平, 熊瀬文明, 細川海音, 塩出雄亮, 土居真一郎, 戸島慎二, 高橋耕輔, 細木三佳, 藤原篤之, 高須一平, 白神史雄

眼科臨床紀要 10 ( 10 ) 841 - 841 2017.10

網膜静脈分枝閉塞症の患眼と僚眼にみられる周辺部網膜血管異常と血管閉塞領域との関連

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

眼科臨床紀要 10 ( 10 ) 855 - 855 2017.10

中心性漿液性脈絡網膜症の治療前後の脈絡膜厚および脈絡膜血管密度の検討

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

眼科臨床紀要 10 ( 10 ) 859 - 859 2017.10

The Role of Inverted Internal Limiting Membrane Flap in Macular Hole Closure. International journal

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

Investigative ophthalmology & visual science 58 ( 11 ) 4847 - 4855 2017.9

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

Purpose: To investigate the mechanism of macular hole (MH) closure following the inverted internal limiting membrane (ILM) technique. Methods: We performed the inverted ILM flap surgical technique as an experimental MH model in monkeys, and investigated the process of MH closure immunohistochemically. We then investigated the effects of type IV collagen, fibronectin, and laminin, which are constituent proteins of the ILM, on the proliferation and migration of cultivated Müller cells (MIO-M1). We also investigated the expression of neurotrophic factors and basic fibroblast growth factor (bFGF) in human ILM and MIO-M1 cells, and the effect of MIO-M1 migration on the expression of these factors, via immunohistochemical staining and the real-time reverse transcription polymerase chain reaction. Results: Ten days after inverted ILM flap surgery, the MH had closed and proliferating glial fibrillary acidic protein (GFAP)-positive cells surrounded the ILM. Type IV collagen, fibronectin, and laminin all enhanced the proliferation of MIO-M1 cells, and type IV collagen and fibronectin enhanced the migration of MIO-M1 cells. Neurotrophic factors and bFGF were present on the surface of the human ILM, and MIO-M1 cells produced these factors. Neurotrophic factors and bFGF were expressed to a significantly greater extent by migrating MIO-M1 cells than by these cells in their static state. Conclusions: During MH closure, the ILM functioned as a scaffold for the proliferation and migration of Müller cells, and may promote Müller cell activation. Neurotrophic factors and bFGF produced by activated Müller cells and present on the surface of the ILM may contribute to MH closure.

DOI： 10.1167/iovs.17-21756

Nationwide epidemiological survey of Leber hereditary optic neuropathy in Japan.

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

Journal of epidemiology 27 ( 9 ) 447 - 450 2017.9

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

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

DOI： 10.1016/j.je.2017.02.001

抗VEGF治療セミナー糖尿病黄斑浮腫に対する硝子体手術

戸島慎二, 森實祐基

あたらしい眼科 34 ( 7 ) 1007 - 1008 2017.7

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

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

【糖尿病網膜症】糖尿病網膜症に対する硝子体手術の進歩

塩出雄亮, 森實祐基

Diabetes Frontier 28 ( 3 ) 303 - 307 2017.6

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

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

Acta medica Okayama 71 ( 3 ) 255 - 257 2017.6

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

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

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

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

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

DOI： 10.1007/s10384-017-0504-2

全都道府県を対象にした視覚障がい認定の疫学調査

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

日本眼科学会雑誌 121 ( 臨増 ) 202 - 202 2017.3

中心窩の形状が中心窩無血管領域と網膜血管密度に及ぼす影響

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

日本眼科学会雑誌 121 ( 臨増 ) 193 - 193 2017.3

前眼部光干渉断層計による水晶体および眼内レンズの偏位と傾斜の評価

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

日本眼科学会雑誌 121 ( 臨増 ) 324 - 324 2017.3

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

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

日本眼科学会雑誌 121 ( 臨増 ) 248 - 248 2017.3

Nitinol loop使用後に見られた網膜神経線維層障害及び傍中心暗点

的場亮, 森實祐基, 木村修平, 戸島慎二, 白神史雄

日本眼科学会雑誌 121 ( 臨増 ) 301 - 301 2017.3

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

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

日本眼科学会雑誌 121 ( 臨増 ) 216 - 216 2017.3

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

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

Medicine 96 ( 12 ) e6422 2017.3

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

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

DOI： 10.1097/MD.0000000000006422

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

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

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

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

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

DOI： 10.1007/s10384-016-0492-7

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

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

PloS one 12 ( 12 ) e0190198 2017

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

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

DOI： 10.1371/journal.pone.0190198

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

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

PloS one 12 ( 11 ) e0188572 2017

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

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

DOI： 10.1371/journal.pone.0188572

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

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

PloS one 12 ( 8 ) e0184096 2017

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

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

DOI： 10.1371/journal.pone.0184096

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

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

PloS one 12 ( 7 ) e0181481 2017

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

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

DOI： 10.1371/journal.pone.0181481

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

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

PloS one 12 ( 7 ) e0181550 2017

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

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

DOI： 10.1371/journal.pone.0181550

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

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

PloS one 12 ( 9 ) e0184066 2017

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

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

DOI： 10.1371/journal.pone.0184066

特発性黄斑上膜にみられる嚢胞様黄斑浮腫の検討

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

眼科臨床紀要 9 ( 10 ) 846 - 846 2016.10

黄斑前膜および黄斑円孔に対する25Gと27G小切開硝子体手術の手術時間の比較

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

眼科臨床紀要 9 ( 10 ) 846 - 847 2016.10

抗VEGF療法に抵抗する糖尿病黄斑浮腫に対する網膜下眼内灌流液注入

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

眼科臨床紀要 9 ( 10 ) 852 - 853 2016.10

網膜静脈分枝閉塞症へのラニビズマブ投与(treat and extend法)1年の再発に関わる因子

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

眼科臨床紀要 9 ( 10 ) 835 - 835 2016.10

ポリープ状脈絡膜血管症に対するアフリベルセプトの治療効果に関連する因子の検討

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

眼科臨床紀要 9 ( 10 ) 838 - 838 2016.10

ポリープ状脈絡膜血管症におけるアフリベルセプト投与後の地図状萎縮

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

眼科臨床紀要 9 ( 10 ) 838 - 838 2016.10

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

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 2016.10

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

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. International journal

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 2016.9

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

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. International journal

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

Retina (Philadelphia, Pa.) 36 ( 8 ) 1486 - 92 2016.8

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

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

Novel Technique for Subretinal Injection Using Local Removal of the Internal Limiting Membrane. International journal

Toshio Okanouchi, Shinji Toshima, Shuhei Kimura, Yuki Morizane, Fumio Shiraga

Retina (Philadelphia, Pa.) 36 ( 5 ) 1035 - 8 2016.5

En faceイメージによる脈絡膜血管の深度別検討

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

日本眼科学会雑誌 120 ( 臨増 ) 187 - 187 2016.3

硝子体手術後に遷延する糖尿病黄斑浮腫に対する網膜下眼内灌流液注入

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

日本眼科学会雑誌 120 ( 臨増 ) 220 - 220 2016.3

滲出型加齢黄斑変性に対するアフリベルセプトtreat and extend法の2年成績

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

日本眼科学会雑誌 120 ( 臨増 ) 177 - 177 2016.3

剥離した内境界膜に含まれる終末糖化産物の定量評価

的場亮, 森實祐基, 木村修平, 米澤朋子, 須野学, 岡野内俊雄, 高畠隆, 三原研一, 佐々木ミチ, 飯島克昌, 白神史雄

日本眼科学会雑誌 120 ( 臨増 ) 185 - 185 2016.3

網膜中心静脈閉塞症へのラニビズマブ投与(Treat & Extend法)1年の再発に関わる因子

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

日本眼科学会雑誌 120 ( 臨増 ) 175 - 175 2016.3

最先端の硝子体手術を検証する難治性黄斑円孔に対する内境界膜翻転法および内境界膜自家移植

森實祐基

日本眼科学会雑誌 120 ( 臨増 ) 10 - 10 2016.3

【OCTを使いこなす2016】網膜硝子体界面症候群

森實祐基

あたらしい眼科 33 ( 2 ) 189 - 195 2016.2

【眼底自発蛍光フル活用】網膜循環障害疾患と眼底自発蛍光

森實祐基

OCULISTA ( 34 ) 61 - 68 2016.1

Language：Japanese Publisher：(株)全日本病院出版会

眼底自発蛍光は、網膜色素上皮細胞や視細胞の機能や代謝状態を反映する。そのため、糖尿病網膜症や網膜静脈および動脈の閉塞症等の網膜循環障害疾患の眼底自発蛍光を検討することは、これらの疾患の病態をより深く理解するために有用であると考えられる。本稿では網膜循環障害疾患に共通してみられる所見として、嚢胞様黄斑浮腫、漿液性網膜剥離、硬性白斑等を取り上げ、その自発蛍光所見の特徴と意義について解説する。また、網膜循環障害疾患の主要な治療法である網膜光凝固における眼底自発蛍光の活用法についても述べる。(著者抄録)

AMPK-Activated Protein Kinase Suppresses Ccr2 Expression by Inhibiting the NF-κB Pathway in RAW264.7 Macrophages. International journal

Fumiaki Kumase, Kimio Takeuchi, Yuki Morizane, Jun Suzuki, Hidetaka Matsumoto, Keiko Kataoka, Ahmad Al-Moujahed, Daniel E Maidana, Joan W Miller, Demetrios G Vavvas

PloS one 11 ( 1 ) e0147279 2016

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

C-C chemokine receptor 2 (Ccr2) is a key pro-inflammatory marker of classic (M1) macrophage activation. Although Ccr2 is known to be expressed both constitutively and inductively, the full regulatory mechanism of its expression remains unclear. AMP-activated protein kinase (AMPK) is not only a master regulator of energy homeostasis but also a central regulator of inflammation. In this study, we sought to assess AMPK's role in regulating RAW264.7 macrophage Ccr2 protein levels in resting (M0) or LPS-induced M1 states. In both M0 and M1 RAW264.7 macrophages, knockdown of the AMPKα1 subunit by siRNA led to increased Ccr2 levels whereas pharmacologic (A769662) activation of AMPK, attenuated LPS-induced increases in Ccr2 expression in an AMPK dependent fashion. The increases in Ccr2 levels by AMPK downregulation were partially reversed by NF-κB inhibition whereas TNF-a inhibition had minimal effects. Our results indicate that AMPK is a negative regulator of Ccr2 expression in RAW264.7 macrophages, and that the mechanism of action of AMPK inhibition of Ccr2 is mediated, in part, through the NF-κB pathway.

DOI： 10.1371/journal.pone.0147279

Surgical Outcome of Idiopathic Epiretinal Membranes with Intraretinal Cystic Spaces. International journal

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

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

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

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

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 2015.12

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

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

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

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 2015.12

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

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

硝子体手術におけるOCT付き手術顕微鏡の有用性

藤原篤之, 森實祐基, 木村修平, 塩出雄亮, 細川海音, 河田哲宏, 土居真一郎, 細木三佳, 白神史雄

眼科臨床紀要 8 ( 11 ) 824 - 824 2015.11

レーベル遺伝性視神経症の新規発症者数に関する疫学調査

上田香織, 森實祐基, 白神史雄, 敷島敬悟, 石川均, 若倉雅登, 中村誠

神経眼科 32 ( 増補1 ) 63 - 63 2015.10

黄斑上膜術後の黄斑浮腫に対するトリアムシノロン後部テノン嚢下投与の効果

塩出雄亮, 木村修平, 森實祐基, 細川海音, 河田哲宏, 土居真一郎, 細木三佳, 藤原篤之, 井上康, 白神史雄

眼科臨床紀要 8 ( 10 ) 745 - 745 2015.10

初回手術で閉鎖が得られなかった陳旧性黄斑円孔に対する内境界膜移植

木村修平, 森實祐基, 細川海音, 塩出雄亮, 河田哲宏, 土居真一郎, 細木三佳, 藤原篤之, 井上康, 白神史雄

眼科臨床紀要 8 ( 10 ) 765 - 766 2015.10

網膜硝子体疾患と治療将来に向かっての展望新しい黄斑手術

森實祐基

眼科臨床紀要 8 ( 10 ) 741 - 741 2015.10

黄斑円孔の術後早期の回復過程

平野雅幸, 河田哲宏, 森實祐基, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 細木三佳, 藤原篤之, 白神史雄

眼科臨床紀要 8 ( 10 ) 744 - 744 2015.10

Inverted ILM flap technique術後の黄斑円孔の閉鎖過程

森實祐基, 河田哲宏, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 細木三佳, 藤原篤之, 井上康, 白神史雄

眼科臨床紀要 8 ( 10 ) 766 - 767 2015.10

Subretinal injection of recombinant tissue plasminogen activator for submacular hemorrhage associated with ruptured retinal arterial macroaneurysm. International journal

Makoto Inoue, Fumio Shiraga, Yukari Shirakata, Yuki Morizane, Shuhei Kimura, Akito Hirakata

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 253 ( 10 ) 1663 - 9 2015.10

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

PURPOSE: To evaluate the surgical outcomes of small-gauge vitrectomy with subretinal injection of recombinant tissue plasminogen activator (rt-PA) for a submacular hemorrhage caused by a ruptured retinal arterial macroaneurysm (RAM). METHODS: Non-comparative, consecutive case-series performed at two ophthalmological institutions. We examined 22 eyes of 22 patients with a submacular hemorrhage associated with a RAM but without a preretinal or sub-internal limiting membrane hemorrhage at the fovea. During 25-gauge vitrectomy, approximately 4000-8000 IU of rt-PA was injected subretinally, followed by the injection of air or 10 % sulfur hexafluoride as a tamponade. The patients maintained an upright position for 1 hour, then turned to a facedown position for 1 to 3 days. The best-corrected visual acuity (BCVA) and postoperative complications were evaluated. RESULTS: The average interval from the onset of symptoms to surgery was 8.4 ± 7.6 days, and the average size of the subretinal hemorrhage was 3.4 ± 1.0 disc diameters. The submacular hemorrhage was displaced from the foveal area in all eyes after 1 week. The mean baseline BCVA was 1.41 ± 0.41 logMAR units, and it improved to 0.91 ± 0.43 at 1 month and to 0.64 ± 0.45 at the final visit (P = 0.0001, P < 0.0001 respectively). A macular hole was detected intraoperatively in two eyes and postoperatively in two eyes, and both were closed by internal limiting membrane peeling or a second vitrectomy. CONCLUSIONS: Small-gauge vitrectomy with subretinal rt-PA injection and gas tamponade were effective in displacing a submacular hemorrhage associated with a RAM.

DOI： 10.1007/s00417-014-2861-6

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 2015.9

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

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. International journal

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 2015.8

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

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. International journal

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 2015.8

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

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. International journal

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 2015.7

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

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

新しい黄斑円孔手術

森實祐基

臨床眼科 69 ( 7 ) 953 - 959 2015.7

Language：Japanese Publisher：(株)医学書院

近年の硝子体手術の進歩とともに,黄斑円孔の治癒率は向上し,現在では90%以上の症例が初回手術で治癒するようになった。しかし一方で,硝子体手術を行っても円孔が閉鎖しない,いわゆる難治性黄斑円孔の存在が明らかとなり,有効な治療法の登場が望まれてきた。近年,難治性黄斑円孔に対して,新しい術式が考案され,良好な手術成績が報告されている。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J01537&link_issn=&doc_id=20150709070002&doc_link_id=10.11477%2Fmf.1410211396&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410211396&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

眼科医の手引難治性黄斑円孔に対する内境界膜自家移植

森實祐基

日本の眼科 86 ( 6 ) 775 - 776 2015.6

Inverted internal limiting membrane flap technique術後の黄斑円孔の閉鎖過程

森實祐基, 河田哲宏, 木村修平, 細川海音, 塩出雄亮, 土居真一郎, 細木三佳, 藤原篤之, 井上康, 白神史雄

日本眼科学会雑誌 119 ( 4 ) 298 - 299 2015.4

Submacular hemorrhage in polypoidal choroidal vasculopathy treated by vitrectomy and subretinal tissue plasminogen activator. International journal

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 2015.4

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

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

網膜静脈分枝閉塞症に対するラニビズマブ投与(Treat and Extend法)の1年治療成績

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

日本眼科学会雑誌 119 ( 臨増 ) 165 - 165 2015.3

【糖尿病網膜症2015年】びまん性糖尿病黄斑浮腫に対する硝子体手術の現状

森實祐基

あたらしい眼科 32 ( 3 ) 361 - 367 2015.3

網膜中心静脈閉塞症に対するラニビズマブ投与(Treat and Extend法)の1年治療成績

細木三佳, 森實祐基, 木村修平, 細川海音, 土居真一郎, 平野雅幸, 藤原篤之, 白神史雄

日本眼科学会雑誌 119 ( 臨増 ) 167 - 167 2015.3

ミュラー細胞の増殖、遊走における4型コラーゲンの役割

塩出雄亮, 森實祐基, 的場亮, 平野雅幸, 土居真一郎, 荒木亮一, 米澤朋子, 白神史雄

日本眼科学会雑誌 119 ( 臨増 ) 168 - 168 2015.3

黄斑下血腫に対するt-PA網膜下注入+液空気置換併用硝子体手術前後の微小視野の検討

木村修平, 森實祐基, 細川海音, 塩出雄亮, 土居真一郎, 平野雅幸, 的場亮, 細木三佳, 藤原篤之, 白神史雄

日本眼科学会雑誌 119 ( 臨増 ) 202 - 202 2015.3

AMPK活性化による網膜色素上皮細胞の上皮間葉転換の抑制

的場亮, 森實祐基, 塩出雄亮, 土居真一郎, 平野雅幸, 荒木亮一, 白神史雄

日本眼科学会雑誌 119 ( 臨増 ) 179 - 179 2015.3

En face OCTイメージによる脈絡膜血管の検討

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

日本眼科学会雑誌 119 ( 臨増 ) 251 - 251 2015.3

早期老化誘導および急性酸化ストレスが網膜色素上皮細胞のMMP産生に及ぼす影響の比較

荒木亮一, 森實祐基, 塩出雄亮, 的場亮, 土居真一郎, 平野雅幸, 白神史雄

日本眼科学会雑誌 119 ( 臨増 ) 332 - 332 2015.3

滲出型加齢黄斑変性に対するアフリベルセプトTreat and Extend法の1年成績

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

日本眼科学会雑誌 119 ( 臨増 ) 200 - 200 2015.3

【最先端の硝子体手術】内境界膜自家移植による難治性黄斑円孔の治療

森實祐基, 白神史雄

あたらしい眼科 32 ( 2 ) 189 - 195 2015.2

抗VEGF治療セミナー加齢黄斑変性に対するTreat and Extend法

細川海音, 森實祐基

あたらしい眼科 32 ( 1 ) 103 - 104 2015.1

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 2014.12

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

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.

【黄斑疾患診療の進歩】最新の黄斑円孔手術内境界膜処理剥離除去から活用する時代へ

森實祐基

眼科 56 ( 12 ) 1415 - 1425 2014.11

【知識が広がる!業務に生かせる!めめ子とトライまるごと眼科クイズ230】(4章)眼科の疾患よく出会う後眼部の疾患(黄斑上膜、黄斑円孔、緑内障、Vogt-小柳-原田病、うっ血乳頭、網膜色素変性症、裂孔原性網膜剥離、網膜細動脈瘤、硝子体出血)

森實祐基

眼科ケア ( 2014夏季増刊 ) 177 - 184 2014.6

Autologous transplantation of the internal limiting membrane for refractory macular holes. International journal

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 2014.4

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

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

滲出型加齢黄斑変性治療後の地図状萎縮に対するウノプロストン0.15%点眼液の有効性

白神千恵子, 藤原篤之, 山下彩奈, 小野葵, 小林守, 真鍋紗季, 森田美沙子, 泉端佐枝子, 三崎佳奈, 馬場哲也, 森實祐基, 白神史雄

日本眼科学会雑誌 118 ( 臨増 ) 297 - 297 2014.3

Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsRNA-induced retinal degeneration Reviewed

Y Murakami, H Matsumoto, M Roh, A Giani, K Kataoka, Y Morizane, M Kayama, A Thanos, S Nakatake, S Notomi, T Hisatomi, Y Ikeda, T Ishibashi, K M Connor, J W Miller, D G Vavvas

Cell Death & Differentiation 21 ( 2 ) 270 - 277 2014.2

EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay. International journal

Kimio Takeuchi, Ryoji Yanai, Fumiaki Kumase, Yuki Morizane, Jun Suzuki, Maki Kayama, Katarzyna Brodowska, Mitsuru Nakazawa, Joan W Miller, Kip M Connor, Demetrios G Vavvas

PloS one 9 ( 3 ) e91849 2014

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

EGFL7 is a secreted angiogenic factor, which in contrast to the well-known secreted angiogenic molecules VEGF and FGF-2, is almost exclusively expressed by endothelial cells and may act in an autocrine fashion. Prior studies have shown EGFL7 to mediate its angiogenic effects by interfering with the Notch pathway and/or via the intronic miR126. Less is known about its effects on VEGF signaling. We wanted to investigate the role of epidermal growth factor-like domain 7 (EGFL7) in VEGF-driven angiogenesis using an ex vivo Matrigel-embedded mouse eye cup assay and siRNA mediated knockdown of EGFL7 by siRNA. Our results suggested that VEGF-induced vascular tube formation was significantly impaired after siRNA downregulation of EGFL7. In addition, knockdown of EGFL7 suppressed VEGF upregulation of phospho-Akt and phospho-Erk(1/2) in endothelial cells, but did not alter VEGFR phosphorylation and neuropilin-1 protein expression or miR126 expression. Thus, in conclusion, EGFL7 is required for VEGF upregulation of the Akt/Erk (1/2) pathway during angiogenesis, and may represent a new therapeutic target in diseases of pathological neovascularization.

DOI： 10.1371/journal.pone.0091849

【抗VEGF薬をどう使う?】PDTとの併用療法

森實祐基, 白神史雄

臨床眼科 67 ( 12 ) 1850 - 1859 2013.11

眼球破裂による眼内凝血塊に対してt-PAを使用し硝子体手術を行った1例

塩出雄亮, 木村修平, 塚本真啓, 細木三佳, 森實祐基

眼科臨床紀要 6 ( 10 ) 840 - 841 2013.10

AMP-dependent kinase inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis by suppressing the dissociation between c-Abl and Prdx1 proteins in endothelial cells. International journal

Kimio Takeuchi, Yuki Morizane, Cynthia Kamami-Levy, Jun Suzuki, Maki Kayama, Wenyi Cai, Joan W Miller, Demetrios G Vavvas

The Journal of biological chemistry 288 ( 28 ) 20581 - 91 2013.7

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

Caveolin-1 is the primary structural component of endothelial caveolae that is essential for transcellular trafficking of albumin and is also a critical scaffolding protein that regulates the activity of signaling molecules in caveolae. Phosphorylation of caveolin-1 plays a fundamental role in the mechanism of oxidant-induced vascular hyper permeability. However, the regulatory mechanism of caveolin-1 phosphorylation remains unclear. Here we identify a previously unexpected role for AMPK in inhibition of caveolin-1 phosphorylation under oxidative stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), inhibited oxidative stress-induced phosphorylation of both caveolin-1 and c-Abl, which is the major kinase of caveolin-1, and endocytosis of albumin in human umbilical vein endothelial cell. These effects were abolished by treatment with two specific inhibitors of AICAR, dipyridamole, and 5-iodotubericidin. Consistently, knockdown of the catalytic AMPKα subunit by siRNA abolished the inhibitory effect of AICAR on oxidant-induced phosphorylation of both caveolin-1 and c-Abl. Pretreatment with specific c-Abl inhibitor, imatinib mesylate, and knock down of c-Abl significantly decreased the caveolin-1 phosphorylation after H2O2 exposure and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Interestingly, knockdown of Prdx-1, an antioxidant enzyme associated with c-Abl, increased phosphorylation of both caveolin-1 and c-Abl and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Furthermore, co-immunoprecipitation experiment showed that AICAR suppressed the oxidant-induced dissociation between c-Abl and Prdx1. Overall, our results suggest that activation of AMPK inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis, and this effect is mediated in part by stabilizing the interaction between c-Abl and Prdx-1.

DOI： 10.1074/jbc.M113.460832

Modified vitreous surgery for symptomatic lamellar macular hole with epiretinal membrane containing macular pigment. International journal

Fumio Shiraga, Ippei Takasu, Kouki Fukuda, Tomoyoshi Fujita, Ayana Yamashita, Kazuyuki Hirooka, Yukari Shirakata, Yuki Morizane, Atsushi Fujiwara

Retina (Philadelphia, Pa.) 33 ( 6 ) 1263 - 9 2013.6

A new syringe adaptor for intravitreal injection of premature eye. International journal

Shuhei Kimura, Masahiro Tsukamoto, Yusuke Shiode, Mika Hosogi, Yuki Morizane

Retina (Philadelphia, Pa.) 33 ( 4 ) 889 - 90 2013.4

黄斑色素を含んだ黄斑上膜を伴う層状黄斑円孔に対する新しい硝子体手術手技

白潟ゆかり, 白神史雄, 高須逸平, 福田恒輝, 藤田智純, 山下彩奈, 廣岡一行, 森實祐基, 藤原篤之

日本眼科学会雑誌 117 ( 臨増 ) 284 - 284 2013.3

マウス網膜色素上皮細胞の細胞遊走におけるAMP依存性キナーゼの役割

森實祐基, 竹内侯雄, 鈴木潤, 吉村武, 塚本真啓, 木村修平, Viollet Benoit, Miller Joan, Vavvas Demetrios

日本眼科学会雑誌 117 ( 臨増 ) 347 - 347 2013.3

ARPE-19の細胞増殖におけるAMP依存性キナーゼの役割

塚本真啓, 木村修平, 米澤朋子, 小阪淳, 森實祐基

日本眼科学会雑誌 117 ( 臨増 ) 352 - 352 2013.3

Aminoimidazole carboxamide ribonucleotide (AICAR) inhibits the growth of retinoblastoma in vivo by decreasing angiogenesis and inducing apoptosis. International journal

Sofia Theodoropoulou, Katarzyna Brodowska, Maki Kayama, Yuki Morizane, Joan W Miller, Evangelos S Gragoudas, Demetrios G Vavvas

PloS one 8 ( 1 ) e52852 2013

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

5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an analog of AMP is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. Recently, we showed that AICAR-induced AMPK activation inhibits the growth of retinoblastoma cells in vitro by decreasing cyclins and by inducing apoptosis and S-phase arrest. In this study, we investigated the effects of AMPK activator AICAR on the growth of retinoblastoma in vivo. Intraperitoneal injection of AICAR resulted in 48% growth inhibition of Y79 retinoblastoma cell tumors in mice. Tumors isolated from mice treated with AICAR had decreased expression of Ki67 and increased apoptotic cells (TUNEL positive) compared with the control. In addition, AICAR treatment suppressed significantly tumor vessel density and macrophage infiltration. We also showed that AICAR administration resulted in AMPK activation and mTOR pathway inhibition. Paradoxically observed down-regulation of p21, which indicates that p21 may have a novel function of an oncogene in retinoblastoma tumor. Our results indicate that AICAR treatment inhibited the growth of retinoblastoma tumor in vivo via AMPK/mTORC1 pathway and by apoptogenic, anti-proliferative, anti-angiogenesis mechanism. AICAR is a promising novel non-chemotherapeutic drug that may be effective as an adjuvant in treating Retinoblastoma.

DOI： 10.1371/journal.pone.0052852

広範囲の網膜分離を伴った成人発症型卵黄様黄斑ジストロフィの1例

細木三佳, 井澤優子, 高畠まゆみ, 森實祐基, 高須逸平

眼科臨床紀要 5 ( 10 ) 963 - 964 2012.10

水晶体皮質が融解・自然吸収した1例

平野雅幸, 森實祐基, 熊瀬文明, 高畠隆, 木村修平, 塚本真啓, 大月洋

臨床眼科 66 ( 9 ) 1359 - 1361 2012.9

Language：Japanese Publisher：(株)医学書院

目的:炎症所見を伴わない水晶体皮質融解の症例の報告。症例:62歳女性が内科でWegener肉芽腫症と診断され,精査のため紹介され受診した。所見と経過:矯正視力は右1.0,左指数弁で,眼圧は正常範囲にあった。左眼では水晶体皮質の大部分が消失し,水晶体嚢と茶褐色の核のみがあった。前房に炎症所見はなかった。水晶体乳化吸引術,水晶体嚢切除,眼内レンズの嚢外固定を行い,6ヵ月後に0.6の視力を得た。眼底に異常所見はなかった。結論:無症状の水晶体皮質融解に対して水晶体再建術を行い,良好な結果を得た。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J01537&link_issn=&doc_id=20120911050018&doc_link_id=10.11477%2Fmf.1410104360&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410104360&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Aminoimidazole carboxamide ribonucleotide ameliorates experimental autoimmune uveitis. International journal

Jun Suzuki, Takeru Yoshimura, Marina Simeonova, Kimio Takeuchi, Yusuke Murakami, Yuki Morizane, Joan W Miller, Lucia Sobrin, Demetrios G Vavvas

Investigative ophthalmology & visual science 53 ( 7 ) 4158 - 69 2012.6

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

PURPOSE: To investigate the anti-inflammatory effect of an adenosine monophosphate (AMP) analog, aminoimidazole carboxamide ribonucleotide (AICAR), in experimental autoimmune uveoretinitis (EAU). METHODS: C57BL/6 mice were injected daily with AICAR (200 mg/kg, intraperitoneally [IP]) from day 0, the day of interphotoreceptor retinoid-binding protein (IRBP) immunization, until day 21. The severity of uveitis was assessed clinically and histopathologically. T-cell proliferation and cytokine production of IFN-γ, IL-17, and IL-10 in response to IRBP stimulation were determined. In addition, regulatory T-cell (Treg) populations were measured. Co-stimulatory molecule expression (CD40, 80, 86, and I-Ab) on dendritic cells (DCs) in EAU and on bone marrow-derived dendritic cells (BMDCs) treated with AICAR was measured. RESULTS: AICAR treatment significantly reduced clinical and histologic severity of EAU as well as ocular cytokine production. An anti-inflammatory effect associated with the inhibition of T-cell proliferation and Th1 and Th17 cytokine production was observed. Increases in the Th2 response and Treg population were not observed with AICAR treatment. AICAR did significantly inhibit BMDC maturation by reducing co-stimulatory molecule expression. CONCLUSIONS: AICAR attenuates EAU by preventing generation of Ag-specific Th1 and Th17 cells. Impaired DC maturation may be an underlying mechanism for this anti-inflammatory effect observed with AICAR.

DOI： 10.1167/iovs.11-9323

Evidence for baseline retinal pigment epithelium pathology in the Trp1-Cre mouse. International journal

Aristomenis Thanos, Yuki Morizane, Yusuke Murakami, Andrea Giani, Dimosthenis Mantopoulos, Maki Kayama, Mi In Roh, Norman Michaud, Basil Pawlyk, Michael Sandberg, Lucy H Young, Joan W Miller, Demetrios G Vavvas

The American journal of pathology 180 ( 5 ) 1917 - 27 2012.5

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

The increasing popularity of the Cre/loxP recombination system has led to the generation of numerous transgenic mouse lines in which Cre recombinase is expressed under the control of organ- or cell-specific promoters. Alterations in retinal pigment epithelium (RPE), a multifunctional cell monolayer that separates the retinal photoreceptors from the choroid, are prevalent in the pathogenesis of a number of ocular disorders, including age-related macular degeneration. To date, six transgenic mouse lines have been developed that target Cre to the RPE under the control of various gene promoters. However, multiple lines of evidence indicate that high levels of Cre expression can be toxic to mammalian cells. In this study, we report that in the Trp1-Cre mouse, a commonly used transgenic Cre strain for RPE gene function studies, Cre recombinase expression alone leads to RPE dysfunction and concomitant disorganization of RPE layer morphology, large areas of RPE atrophy, retinal photoreceptor dysfunction, and microglial cell activation in the affected areas. The phenotype described herein is similar to previously published reports of conditional gene knockouts that used the Trp1-Cre mouse, suggesting that Cre toxicity alone could account for some of the reported phenotypes and highlighting the importance of the inclusion of Cre-expressing mice as controls in conditional gene targeting studies.

DOI： 10.1016/j.ajpath.2012.01.017

Inhibitory effect of aminoimidazole carboxamide ribonucleotide (AICAR) on endotoxin-induced uveitis in rats. International journal

Jun Suzuki, Akrivi Manola, Yusuke Murakami, Yuki Morizane, Kimio Takeuchi, Maki Kayama, Joan W Miller, Lucia Sobrin, Demetrios G Vavvas

Investigative ophthalmology & visual science 52 ( 9 ) 6565 - 71 2011.8

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

PURPOSE. To investigate the anti-inflammatory effect of aminoimidazole carboxamide ribonucleotide (AICAR), an analog of adenosine monophosphate (AMP), in endotoxin-induced uveitis (EIU). METHODS. EIU was induced by subcutaneous injection of lipopolysaccharide (LPS) (200 μg) in Lewis rats. AICAR (50 mg/kg, intraperitoneally) was given 6 hours prior and at the same time as LPS injection. Clinical uveitis scores, number of anterior chamber (AC) infiltrating cells, anterior chamber protein concentration, retinal vessel leukocyte adhesion, and protein leakage were measured 24 hours later. Protein levels of C-C chemokine ligand-2 (CCL-2)/monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) in aqueous humor and retina and nuclear translocation of nuclear factor-κB (NF-κB) in the retina were determined by enzyme-linked immunosorbent assay (ELISA). Both mRNA and protein levels of CD14 in peripheral blood mononuclear cells were also measured. RESULTS. AICAR treatment significantly reduced EIU clinical severity as well as inflammatory cell infiltration and protein concentration in aqueous humor. Similarly, the number of retinal vessel-adherent leukocytes and protein leakage were decreased by AICAR treatment. Protein levels of TNF-α, CCL-2/MCP-1, and ICAM-1 in aqueous humor and CCL-2/MCP-1 and ICAM-1 levels in retina were suppressed with AICAR treatment. AICAR also reduced NF-κB translocation and CD14 expression. CONCLUSIONS. AICAR reduces systemic LPS susceptibility and attenuates intraocular inflammation in a rat EIU model by limiting infiltration of leukocytes, suppressing inflammatory mediators, and inhibiting the NF-κB pathway.

DOI： 10.1167/iovs.11-7331

AMP-activated protein kinase suppresses matrix metalloproteinase-9 expression in mouse embryonic fibroblasts. International journal

Yuki Morizane, Aristomenis Thanos, Kimio Takeuchi, Yusuke Murakami, Maki Kayama, George Trichonas, Joan Miller, Marc Foretz, Benoit Viollet, Demetrios G Vavvas

The Journal of biological chemistry 286 ( 18 ) 16030 - 8 2011.5

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

Matrix metalloproteinase-9 (MMP-9) plays a critical role in tissue remodeling under both physiological and pathological conditions. Although MMP-9 expression is low in most cells and is tightly controlled, the mechanism of its regulation is poorly understood. We utilized mouse embryonic fibroblasts (MEFs) that were nullizygous for the catalytic α subunit of AMP-activated protein kinase (AMPK), which is a key regulator of energy homeostasis, to identify AMPK as a suppressor of MMP-9 expression. Total AMPKα deletion significantly elevated MMP-9 expression compared with wild-type (WT) MEFs, whereas single knock-out of the isoforms AMPKα1 and AMPKα2 caused minimal change in the level of MMP-9 expression. The suppressive role of AMPK on MMP-9 expression was mediated through both its activity and presence. The AMPK activators 5-amino-4-imidazole carboxamide riboside and A769662 suppressed MMP-9 expression in WT MEFs, and AMPK inhibition by the overexpression of dominant negative (DN) AMPKα elevated MMP-9 expression. However, in AMPKα(-/-) MEFs transduced with DN AMPKα, MMP-9 expression was suppressed. AMPKα(-/-) MEFs showed increased phosphorylation of IκBα, expression of IκBα mRNA, nuclear localization of nuclear factor-κB (NF-κB), and DNA-binding activity of NF-κB compared with WT. Consistently, selective NF-κB inhibitors BMS345541 and SM7368 decreased MMP-9 expression in AMPKα(-/-) MEFs. Overall, our results suggest that both AMPKα isoforms suppress MMP-9 expression and that both the activity and presence of AMPKα contribute to its function as a regulator of MMP-9 expression by inhibiting the NF-κB pathway.

DOI： 10.1074/jbc.M110.199398

Distribution of α(IV) collagen chains in the ocular anterior segments of adult mice. International journal

Kenji Saito, Tomoko Yonezawa, Jun Minaguchi, Masae Kurosaki, Shiho Suetsugu, Ai Nakajima, Hiroyuki Nomoto, Yuki Morizane, Yoshikazu Sado, Manabu Sugimoto, Shozo Kusachi, Yoshifumi Ninomiya

Connective tissue research 52 ( 2 ) 147 - 56 2011.4

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

The distribution of the collagen chains from α1(IV) to α6(IV) could serve as a basis for the characterization of type IV collagen. In this study, immunohistochemistry of the ocular anterior segment of adult mice was performed using specific monoclonal antibodies against each chain in the series from α1(IV) to α6(IV). The results show that the components of type IV collagen in vascular basement membranes are α1(IV) and α2(IV) with or without α5(IV) and α6(IV) chains and those in epithelium and muscle basement membranes are α1(IV), α2(IV), α5(IV), and α6(IV) chains. In corneal endothelium, pigmented epithelium of iris and ciliary body, and trabecular meshwork, α3(IV) and α4(IV) chains are also expressed in addition to α1(IV), α2(IV), α5(IV), and α6(IV) chains. Moreover, we investigated the change in molecular composition in ciliary body during postnatal development. α3(IV) and α4(IV) chains were also expressed in addition to α1(IV), α2(IV), α5(IV), and α6(IV) chains in ciliary pigmented epithelium basement membrane from 7 days after birth. This result suggests that the basement membranes gradually change their biochemical features owing to temporal regulation. Taken together, these findings suggest that the different distribution and the developmental expression of α1(IV) to α6(IV) chains are associated with the tissue-specific function of type IV collagen in basement membranes.

DOI： 10.3109/03008207.2010.492062

Heat shock protein 70 (HSP70) is critical for the photoreceptor stress response after retinal detachment via modulating anti-apoptotic Akt kinase. International journal

Maki Kayama, Toru Nakazawa, Aristomenis Thanos, Yuki Morizane, Yusuke Murakami, Sofia Theodoropoulou, Toshiaki Abe, Demetrios Vavvas, Joan W Miller

The American journal of pathology 178 ( 3 ) 1080 - 91 2011.3

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

Photoreceptor apoptosis is a major cause of vision loss in many ocular diseases. Significant progress has been made to elucidate the molecular pathways involved in this process, yet little is known about proteins counteracting these apoptotic pathways. It is established that heat shock proteins (HSPs) function as molecular helper proteins (chaperones) by preventing protein aggregation and facilitating refolding of dysfunctional proteins, critical to the survival of all organisms. Here, we investigated the role of HSP70 on photoreceptor survival after experimental retinal detachment (RD) in mice and rats. We found that HSP70 was up-regulated after RD and associated with phosphorylated Akt, thereby preventing its dephosphorylation and further activation of cell death pathways. Administration of quercetin, which inhibits HSP70 and suppresses Akt phosphorylation significantly increased photoreceptor apoptosis. Similarly, RD-induced photoreceptor apoptosis was augmented in mice carrying hypomorphic mutations of the genes encoding HSP70. On the other hand, administration of geranylgeranylacetone, which induces an increase in HSP70 significantly decreased photoreceptor apoptosis after RD through prolonged activation of Akt pathway. Thus, HSP70 may be a favorable potential target to increase photoreceptor cell survival after RD.

DOI： 10.1016/j.ajpath.2010.11.072

Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis. International journal

George Trichonas, Yusuke Murakami, Aristomenis Thanos, Yuki Morizane, Maki Kayama, Christine M Debouck, Toshio Hisatomi, Joan W Miller, Demetrios G Vavvas

Proceedings of the National Academy of Sciences of the United States of America 107 ( 50 ) 21695 - 700 2010.12

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

Apoptosis has been shown to be a significant form of cell loss in many diseases. Detachment of photoreceptors from the retinal pigment epithelium, as seen in various retinal disorders, causes photoreceptor loss and subsequent vision decline. Although caspase-dependent apoptotic pathways are activated after retinal detachment, caspase inhibition by the pan-caspase inhibitor Z-VAD fails to prevent photoreceptor death; thus, we investigated other pathways leading to cell loss. Here, we show that receptor interacting protein (RIP) kinase-mediated necrosis is a significant mode of photoreceptor cell loss in an experimental model of retinal detachment and when caspases are inhibited, RIP-mediated necrosis becomes the predominant form of death. RIP3 expression, a key activator of RIP1 kinase, increased more than 10-fold after retinal detachment. Morphological assessment of detached retinas treated with Z-VAD showed decreased apoptosis but significantly increased necrotic photoreceptor death. RIP1 kinase inhibitor necrostatin-1 or Rip3 deficiency substantially prevented those necrotic changes and reduced oxidative stress and mitochondrial release of apoptosis-inducing factor. Thus, RIP kinase-mediated programmed necrosis is a redundant mechanism of photoreceptor death in addition to apoptosis, and simultaneous inhibition of RIP kinases and caspases is essential for effective neuroprotection and may be a novel therapeutic strategy for treatment of retinal disorders.

DOI： 10.1073/pnas.1009179107

Glycocalyx degradation in retinal and choroidal capillary endothelium in rats with diabetes and hypertension.

Fumiaki Kumase, Yuki Morizane, Satoshi Mohri, Ippei Takasu, Aiji Ohtsuka, Hiroshi Ohtsuki

Acta medica Okayama 64 ( 5 ) 277 - 83 2010.10

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

Endothelial glycocalyx (GCX) has been reported as a protective factor for vascular endothelial cells (VEC) in diabetes and hypertension. However, the involvement of GCX impairment in ocular vasculopathy remains unclear. We evaluated the changes in the GCX thicknesses of the retinal and choroidal capillaries in rats with diabetes and hypertension by cationic colloidal iron staining using a transmission electron microscope. In the control group, the mean (standard error of the mean) thicknesses of retinal and choroidal GCX were 60.2 (1.5) nm and 84.3 (3.1) nm, respectively. The diabetic rats showed a significant decrease of GCX thickness in the retina, but not in the choroid, compared to controls (28.3 (0.3) nm, p<0.01 and 77.8 (1.4) nm, respectively). In the hypertensive rats, both retinal and choroidal GCX were significantly decreased compared to the control values (10.9 (0.4) nm and 13.2 (1.0) nm, respectively, both p<0.01). Moreover, we could visualize the adhesion of leukocytes and platelets on the luminal surface of VEC, at the site where the GCX was markedly degraded. These findings suggest that the GCX prevents adhesion of leukocytes and platelets to the VEC surface, and this impairment may lead to ocular vasculopathy in diabetes and hypertension.

Retinoblastoma cells are inhibited by aminoimidazole carboxamide ribonucleotide (AICAR) partially through activation of AMP-dependent kinase. International journal

Sofia Theodoropoulou, Paraskevi E Kolovou, Yuki Morizane, Maki Kayama, Fotini Nicolaou, Joan W Miller, Evangelos Gragoudas, Bruce R Ksander, Demetrios G Vavvas

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 ( 8 ) 2620 - 30 2010.8

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

5-Aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), an analog of AMP, is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. We studied the effects of AICAR on the growth of retinoblastoma cell lines (Y79, WERI, and RB143). AICAR inhibited Rb cell growth, induced apoptosis and S-phase cell cycle arrest, and led to activation of AMPK. These effects were abolished by treatment with dypiridamole, an inhibitor that blocks entrance of AICAR into cells. Treatment with the adenosine kinase inhibitor 5-iodotubericidin to inhibit the conversion of AICAR to ZMP (the direct activator of AMPK) reversed most of the growth-inhibiting effects of AICAR, indicating that some of the antiproliferative effects of AICAR are mediated through AMPK activation. In addition, AICAR treatment was associated with inhibition of the mammalian target of rapamycin pathway, decreased phosphorylation of ribosomal protein-S6 and 4E-BP1, down-regulation of cyclins A and E, and decreased expression of p21. Our results indicate that AICAR-induced activation of AMPK inhibits retinoblastoma cell growth. This is one of the first descriptions of a nonchemotherapeutic drug with low toxicity that may be effective in treating Rb patients.

DOI： 10.1096/fj.09-152546

Coats病様眼底変化を生じた網膜色素変性症の1例

秋元悦子, 高畠隆, 森實祐基, 岡部泰史, 濱田禎之, 大月洋

臨床眼科 64 ( 6 ) 895 - 898 2010.6

Language：Japanese Publisher：(株)医学書院

目的:Coats病に似た眼底を呈し,硝子体出血が生じた網膜色素変性症の症例の報告。症例:61歳男性が左眼視力障害で受診した。13歳で夜盲を自覚し,17歳のときに網膜色素変性症と診断された。兄2人と従兄弟1人に網膜色素変性症がある。4年前に白内障手術を受け,左右とも0.04の視力であった。所見:矯正視力は右0.03,左指数弁で,右眼に網膜色素変性症の所見,左眼に硝子体出血と眼底上方に増殖膜があった。左眼に硝子体手術を行い,器質化した増殖膜と新生血管,毛細血管の拡張蛇行があった。一年後の現在,左右眼とも0.03の矯正視力を維持している。結論:本症例でのCoats病様の網膜血管拡張,新生血管,増殖膜形成は,網膜色素変性症に併発したと解釈され,硝子体手術が有効であった。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J01537&link_issn=&doc_id=20100706080015&doc_link_id=10.11477%2Fmf.1410103215&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410103215&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

A novel nonradioactive method to evaluate vascular barrier breakdown and leakage. International journal

George Trichonas, Akrivi Manola, Yuki Morizane, Aristomenis Thanos, Xanthi Koufomichali, Thanos D Papakostas, Sandra Montezuma, Lucy Young, Joan W Miller, Evangelos Gragoudas, Demetrios Vavvas

Investigative ophthalmology & visual science 51 ( 3 ) 1677 - 82 2010.3

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

PURPOSE: To identify a novel, sensitive, nonradioactive leakage assay that can be used in the assessment of retinal vascular permeability in rats and mice. METHODS: Breakdown of the vascular barrier was induced by vascular endothelial growth factor (VEGF), lipopolysaccharide (LPS), or diabetes. Biotinylated bovine serum albumin (bBSA) was administered as a tracer. After perfusion with lactated Ringer's solution, extravasated bBSA was detected with immunoprecipitation and Western blot analysis or sandwich ELISA. The results were then normalized against the final bBSA plasma concentration, the circulation time, and the protein concentration of the tissue. RESULTS: Six hours after VEGF injection, BRB breakdown was quantified in the injected eye and was 2.5-fold higher than in the contralateral phosphate-buffered saline (PBS)-injected eye (n = 6 rats, P < 0.01). Intravitreal LPS injection induced severe inflammation in the directly injected eye and moderate inflammation in the contralateral untreated eye. Leakage was six- and threefold higher, respectively, compared with that in the untreated control animals (n = 5 rats, P < 0.01). Nine-month diabetic rats had a threefold increase in vascular leakage compared with age-matched control animals (n = 6 retinas, P < 0.05). Twenty-four hours after intraperitoneal administration of LPS in mice, the animals showed increased vascular leakage in all tissue organs examined (retina, 1.7-fold; brain, 1.5-fold; and kidney, 1.3-fold). CONCLUSIONS: bBSA can serve as an effective alternative to the current methods used for quantitating vascular leakage and especially the blood-retinal barrier breakdown. It is reasonably easy to perform, low in cost, and adaptable to experiments in mice.

DOI： 10.1167/iovs.09-4193

胎児ヘモグロビン変換率測定による未熟児網膜症発症リスク評価法の開発

森實祐基

医科学応用研究財団研究報告 27 151 - 154 2010.2

Language：Japanese Publisher：(公財)鈴木謙三記念医科学応用研究財団

未熟児網膜症は、低体重出生児への全身管理の際に酸素投与が過剰であった場合に、網膜への酸素供給が必要以上に多くなり、酸素投与を中止したときの変化によって網膜の相対的低酸素状態が惹起され、病的な血管新生によって起こる網膜剥離が原因とされている。本症を起こしやすいリスクファクターは二つに大別され、一つは血管組織側(網膜微小血管)の反応性が高いこと、もう一つは酸素投与時と中止時の末梢酸素供給量の変化が大きいことであると考えられる。本研究では、このうち後者について取り上げ、酸素供給量の変化を規定する赤血球に着目し、ヘモグロビンの酸素親和度と血管の拡張に寄与する一酸化窒素との結合能の生後変化の評価法を確立することを試みた。さらに、酸素運搬体としての赤血球の性質と未熟児網膜症との関係を明らかにするための計測系確立とその応用について展望した。

光線力学療法再施行時におけるトリアムシノロン硝子体内注射の併用効果

森實祐基, 高畠隆, 岡部泰史, 岡本和夫, 中山雅雄

眼科臨床紀要 1 ( 10 ) 1018 - 1018 2008.10

網膜芽細胞腫に対する放射線治療14年後に網膜剥離を生じた1例

岡部泰史, 森實祐基, 高畠隆, 岡本和夫, 中山雅雄

眼科臨床紀要 1 ( 10 ) 1029 - 1029 2008.10

23G・25G硝子体手術システム(Alcon社製)における術後低眼圧の比較

高畠隆, 森實祐基, 岡部泰史, 岡本和夫, 中山雅雄

眼科臨床紀要 1 ( 10 ) 1006 - 1006 2008.10

糖尿病および高血圧による網脈絡膜血管内皮のグリコカリクス障害と白血球の接着

熊瀬文明, 毛利聡, 森實祐基, 高須逸平, 大月洋, 大塚愛二

日本糖尿病眼学会誌 13 100 - 100 2008.9

虹彩の"動き"が瞳孔膜の消退を誘導する

森實祐基

日本眼科学会雑誌 111 ( 11 ) 872 - 880 2007.11

Language：Japanese Publisher：(公財)日本眼科学会

眼球の形成期における水晶体の表面は,瞳孔膜と呼ばれる血管網で覆われている.瞳孔膜は水晶体上皮細胞を栄養した後,光路を保つためアポトーシスにより消退する.しかし,瞳孔膜のアポトーシスを誘導する因子については十分解明されていない.私はラット眼において,瞳孔膜の消退時期に一致して虹彩の運動能(縮瞳・散瞳能)が成熟することに着目し,"虹彩の動き"が瞳孔膜のアポトーシスを誘導しているのではないかと考えた.まず,生体顕微鏡を用いて虹彩運動(縮瞳・散瞳)に伴う瞳孔膜の血流変化を可視化した.その結果,縮瞳時に瞳孔膜の血流が停止し,散瞳時に血流が再開することが明らかになった.次に,散瞳薬を点眼し虹彩運動を持続的に抑制すると,瞳孔膜血管内皮細胞のアポトーシスが対照群に比べて有意に抑制された.以上から,虹彩の動きが瞳孔膜に血流の変化(虚血・再灌流)を起こし,血管内皮細胞のアポトーシスを誘導すると結論した.(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J01049&link_issn=&doc_id=20071113440004&doc_link_id=10019991048&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10019991048&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

[Iris movement mediates pupillary membrane regression].

Yuki Morizane

Nippon Ganka Gakkai zasshi 111 ( 11 ) 872 - 80 2007.11

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

In the course of mammalian lens development, a transient capillary meshwork called as the pupillary membrane (PM) forms. It is located in the pupil area to nourish the anterior surface of the lens, and then regresses to clear the optical path. Although the involvement of the apoptotic process has been reported in PM regression, the initiating factor remains unknown. We initially found that regression of the PM coincided with the development of iris motility, and that iris movement caused cessation and resumption of blood flow within the PM. Therefore, we investigated whether the development of the capacity of the iris to constrict and dilate can function as an essential signal that induces apoptosis in the PM. Continuous inhibition of iris movement with mydriatic agents suppressed apoptosis of the PM and resulted in the persistence of PM in rats. The distribution of apoptotic cells in the regressing PM was diffuse and showed no apparent localization. These results indicated that iris movement induced regression of the PM by changing the blood flow within it. This study suggests the importance of the physiological interactions between tissues-in this case, the iris and the PM-as a signal to advance vascular regression during organ development.

虹彩の動きはラット瞳孔膜の消退時期に血管のアポトーシスを誘導する(Iris movement mediates vascular apoptosis during rat pupillary membrane regression)

森實祐基

日本眼科学会雑誌 111 ( 臨増 ) 147 - 147 2007.3

発育期ラット水晶体におけるα-クリスタリン会合粒子形成と低温白内障消失への関与

中山雅雄, 毛利聡, 森實祐基, 宮坂武寛, 片野坂友紀, 大田昇, 井上勝晶, 大月洋, 成瀬恵治, 八木直人

日本眼科学会雑誌 111 ( 臨増 ) 255 - 255 2007.3

PDT後、再発を繰り返すAMDに伴うCNVの組織学的特徴

熊瀬文明, 高須逸平, 森實祐基, 高畠隆, 岡部泰史, 寺田佳子, 大月洋, 大塚愛二

日本眼科学会雑誌 111 ( 臨増 ) 265 - 265 2007.3

眼科医のための先端医療虹彩の"動き"が瞳孔膜の消退を誘導する虹彩のもうひとつの機能

森實祐基, 毛利聡

あたらしい眼科 23 ( 12 ) 1583 - 1586 2006.12

光線力学療法後のインドシアニングリーン蛍光眼底造影所見の検討

寺田佳子, 森實祐基, 岡本和夫, 細木三佳, 高須逸平

眼科臨床医報 100 ( 10 ) 812 - 812 2006.10

糖尿病網膜症の細胞表面プロテオグリカンの解析

熊瀬文明, 高須逸平, 森實祐基, 中山雅雄, 大月洋, 毛利聡, 大塚愛二

日本眼科学会雑誌 110 ( 臨増 ) 217 - 217 2006.3

Iris movement mediates vascular apoptosis during rat pupillary membrane regression. International journal

Yuki Morizane, Satoshi Mohri, Jun Kosaka, Shigenobu Toné, Takahiko Kiyooka, Takehiro Miyasaka, Juichiro Shimizu, Yasuo Ogasawara, Fumio Shiraga, Yohsuke Minatogawa, Junzo Sasaki, Hiroshi Ohtsuki, Fumihiko Kajiya

American journal of physiology. Regulatory, integrative and comparative physiology 290 ( 3 ) R819-25 2006.3

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

In the course of mammalian lens development, a transient capillary meshwork known as the pupillary membrane (PM) forms, which is located at the pupil area; the PM nourishes the anterior surface of the lens and then regresses to make the optical path clear. Although the involvement of apoptotic process has been reported in the PM regression, the initiating factor remains unknown. We initially found that regression of the PM coincided with the development of iris motility, and iris movement caused cessation and resumption of blood flow within the PM. Therefore, we investigated whether the development of the iris's ability to constrict and dilate functions as an essential signal that induces apoptosis in the PM. Continuous inhibition of iris movement with mydriatic agents from postnatal day 7 to day 12 suppressed apoptosis of the PM and migration of macrophage toward the PM, and resulted in the persistence of PM in rats. The distribution of apoptotic cells in the regressing PM was diffuse and showed no apparent localization. These results indicated that iris movement induced regression of the PM by changing the blood flow within it. This study suggests the importance of the physiological interactions between tissues-in this case, the iris and the PM-as a signal to advance vascular regression during organ development, and defines a novel function of the iris during ocular development in addition to the well-known function, that is, optimization of light transmission into the eye.

A new scleral depressor for premature infants. International journal

Yuki Morizane, Ippei Takasu, Satoshi Mohri, Hiroshi Ohtsuki

Retina (Philadelphia, Pa.) 25 ( 8 ) 1118 - 1118 2005.12

緑内障治療用房水排出インプラントの開発

宮坂武寛, 森實祐基, 山本健一郎, 毛利聡, 高須逸平, 清水壽一郎, 高島征助, 酒井清孝, 大月洋, 梶谷文彦

人工臓器 34 ( 2 ) S - 102 2005.11

虹彩による微小循環調節と血管アポトーシス

毛利聡, 森實祐基, 宮坂武寛, 清水壽一郎, 梶谷文彦

日本バイオレオロジー学会年会抄録集 28回 49 - 49 2005.6

冠微小循環の階層性血管調節機能におけるNOとEDHFの関与

山本岳玄, 廣田真規, 井内洋介, 梶谷昌史, 清岡崇彦, 森本太郎, 岩崎達雄, 森實祐基, 宮坂武寛, 毛利聡, 清水壽一郎, 梶谷文彦

日本生理学雑誌 67 ( 4 ) 165 - 165 2005.4

Autonomic response induces vascular apoptosis during lens development in the rat eye

Y Morizane, S Mohri, J Kosaka, S Tone, T Kiyooka, T Miyasaka, J Shimizu, Y Ogasawara, F Shiraga, Y Minatogawa, J Sasaki, H Ohtsuki, F Kajiya

FASEB JOURNAL 19 ( 5 ) A1672 - A1672 2005.3

正常発生における血管網のアポトーシスにも血流の生理的変化が関与する

森實祐基, 小阪淳, 毛利聡, 刀祢重信, 清岡崇彦, 宮坂武寛, 清水壽一郎, 小笠原康夫, 佐々木順造, 大月洋, 梶谷文彦

解剖学雑誌 80 ( Suppl. ) 137 - 137 2005.3

Direct observation of epicardial coronary capillary hemodynamics during reactive hyperemia and during adenosine administration by intravital video microscopy. International journal

Takahiko Kiyooka, Osamu Hiramatsu, Fumiyuki Shigeto, Hiroshi Nakamoto, Hiroyuki Tachibana, Toyotaka Yada, Yasuo Ogasawara, Masahito Kajiya, Taro Morimoto, Yuki Morizane, Satoshi Mohri, Juichiro Shimizu, Tohru Ohe, Fumihiko Kajiya

American journal of physiology. Heart and circulatory physiology 288 ( 3 ) H1437-43 2005.3

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

Using high-resolution intravital charge-coupled device video microscopy, we visualized the epicardial capillary network of the beating canine heart in vivo to elucidate its functional role under control conditions, during reactive hyperemia (RH), and during intracoronary adenosine administration. The pencil-lens video-microscope probe was placed over capillaries fed by the left anterior descending artery in atrioventricular-blocked hearts of open-chest, anesthetized dogs paced at 60-90 beats/min (n = 17). In individual capillaries under control conditions, red blood cell flow was predominant during systole or diastole, indicating that the watershed between diastolic arterial and systolic venous flows is located within the capillaries. Capillary flow increased during RH and reached a peak flow velocity (2.1 +/- 0.6 mm/s), twice as high as control (1.2 +/- 0.5 mm/s), with enhancement of intercapillary cross-connection flow and enlargement of diameter (by 17%). With adenosine, capillary flow velocity significantly increased (1.8 +/- 0.7 mm/s). However, the increase in volumetric capillary flow with adenosine estimated from red blood cell velocity and diameter was less than the increase in arterial flow, whereas that during RH was nearly equivalent to the increase in arterial flow. There was a time lag of approximately 1.5 s for refilling of capillaries during RH, indicating their function as capacitance vessels. In conclusion, the coronary capillary network functions as 1) the major watershed between diastolic-dominant arterial and systolic-dominant venous flows, 2) a capacitor, and 3) a significant local flow amplifier and homogenizer of blood supply during RH, but with adenosine the increase in capillary flow velocity was less than the increase in arterial flow.

ラットの冠状微小循環のin vivoにおける視覚化階層的血流制御(In Vivo Visualization of Coronary Microcirculation in Rats and Hierarchical Flow Control)

廣田真規, 井内洋介, 梶谷昌史, 清岡嵩彦, 森實祐基, 森本太郎, 岩崎達雄, 宮坂武寛, 毛利聡, 清水壽一郎, 梶谷文彦, 佐野俊二, 麻原仁子, 辻岡克彦

Circulation Journal 68 ( Suppl.III ) 938 - 938 2004.10

冠微小循環の可視化による高血圧および正常血圧ラットの年齢に応じた血管内皮由来弛緩因子の関与

井内洋介, 廣田真規, 清岡崇彦, 梶谷昌史, 森本太郎, 森實祐基, 岩崎達雄, 包金花, 宮坂武寛, 毛利聡, 清水壽一郎, 平松修, 小笠原康夫, 上甲剛, 梶谷文彦

生体医工学 42 ( 2 ) 147 - 147 2004.6

超音波照射による超音波コントラスト剤破壊の微小循環への影響 Land-mine explosion in capillary

清岡崇彦, 島田建永, 平松修, 麻原仁子, 望月精一, 小笠原康夫, 辻岡克彦, 井内洋介, 森本太郎, 梶谷昌史, 森實祐基, 廣田真規, 岩崎達雄, 宮坂武寛, 毛利聡, 清水壽一郎, 梶谷文彦

日本バイオレオロジー学会年会抄録集 27回 22 - 22 2004.5

X-ray diffraction from a left ventricular wall of rat heart. International journal

Naoto Yagi, Juichiro Shimizu, Satoshi Mohri, Jun'ichi Araki, Kazufumi Nakamura, Hiroshi Okuyama, Hiroko Toyota, Taro Morimoto, Yuki Morizane, Mie Kurusu, Tatsushi Miura, Katsushi Hashimoto, Katsuhiko Tsujioka, Hiroyuki Suga, Fumihiko Kajiya

Biophysical journal 86 ( 4 ) 2286 - 94 2004.4

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

We studied x-ray diffraction from the left ventricular wall of an excised, perfused whole heart of a rat using x rays from the third-generation synchrotron radiation facility, SPring-8. With the beam at right angles to the long axis of the left ventricle, well-oriented, strong equatorial reflections were observed from the epicardium surface. The reflections became vertically split arcs when the beam passed through myocardium deeper in the wall, and rings were observed when the beam passed into the inner myocardium of the wall. These diffraction patterns were explained by employing a layered-spiral model of the arrangement of muscle fibers in the heart. In a quiescent heart with an expanded left ventricle, the muscle fibers at the epicardium surface were found to have a (1,0) lattice spacing smaller than in the rest of the wall. The intensity ratio of the (1,0) and (1,1) equatorial reflections decreased on contraction with a similar time course in all parts of the wall. The results show that it is possible to assign the origin of reflections in a diffraction diagram from a whole heart. This study offers a basis for interpretation of x-ray diffraction from a beating heart under physiologically and pathologically different conditions.

超音波照射による超音波コントラスト剤破壊の微小循環への影響 Land-mine explosion in capillary

清岡崇彦, 島田建永, 平松修, 氷見直之, 望月精一, 小笠原康夫, 辻岡克彦, 森本太郎, 森實祐基, 廣田真規, 岩崎達雄, 宮坂武寛, 毛利聡, 清水壽一郎, 梶谷文彦

日本生理学雑誌 66 ( 2 ) 68 - 68 2004.2

ペンシル型CCD生体顕微鏡システムを用いたin vivo肺微小循環と個々の肺胞の同時可視化と機能解析

包金花, 森本太郎, 岩崎達雄, 森實祐基, 梶谷昌史, 清岡崇彦, 宮坂武寛, 毛利聡, 清水壽一郎, 平松修, 小笠原康夫, 梶谷文彦

日本生理学雑誌 66 ( 2 ) 67 - 68 2004.2

ペンシル型CCD生体顕微鏡システムを用いたin vivoラット肺微小循環の観察

岩崎達雄, 森本太郎, 清岡崇彦, 森實祐基, 毛利聡, 清水壽一郎, 平松修, 小笠原康夫, 森田潔, 梶谷文彦

脈管学 43 ( 9 ) 469 - 469 2003.9

CCD生体顕微鏡を用いたラット瞳孔膜微小循環の可視化

森實祐基, 毛利聡, 森本太郎, 清岡崇彦, 廣田真規, 岩崎達雄, 包金花, 井内洋介, 栗栖美絵, 清水壽一郎, 小笠原康夫, 大月洋, 梶谷文彦

電子情報通信学会技術研究報告(MEとバイオサイバネティックス) 103 ( 183 ) 1 - 4 2003.7

Language：Japanese Publisher：(一社)電子情報通信学会

生後8日目のラットに硫酸アトロピン,塩酸ジクロロイソプロテレノール,塩酸フェノキシベンザミンを点眼し,中等度散瞳状態における瞳孔膜血管をペンシルプローブCCD生体顕微鏡で観察した.瞳孔膜の血管網は,瞳孔中央で十文字に吻合する細動静脈と,その間をつなぐ毛細血管網から構成されていた.血管径は,細動脈が21.6μm,細静脈が23.3μm,毛細血管が8.7μmであり,細動脈は向かい合う瞳孔縁の二点から各々瞳孔中央の吻合部に向かって流れ,細静脈は吻合部から向かい合う瞳孔縁の二点に向かって各々流れていた.次に生後3〜14日目のラットで瞳孔膜血管の全分岐点の数を調べたところ,生後8日目までは一定で,14日目に0となった.更に生後12日目のラットで,虹彩の動きに伴う瞳孔膜の形態及び血行動態の変化を観察した.縮瞳時には虹彩によって瞳孔膜血管は強く屈曲し,血流が停止した.散瞳時には瞳孔膜血管が伸展し,血流は再開した

ペンシル型CCD生体顕微鏡システムを用いたin vivo心外膜側毛細管の機能解析

清岡崇彦, 平松修, 重藤史行, 森本太郎, 森實祐基, 毛利聡, 清水壽一郎, 荒木淳一, 梶谷文彦

循環制御 24 ( Suppl. ) 104 - 104 2003.5

ペンシル型CCD生体顕微鏡を用いたin vivoにおけるラット肺微小循環の観察

岩崎達雄, 森本太郎, 清岡崇彦, 森實祐基, 毛利聡, 清水壽一郎, 平松修, 小笠原康夫, 森田潔, 梶谷文彦

循環制御 24 ( Suppl. ) 103 - 103 2003.5

Bilateral Iridocyclitis with Retinal Capillaritis in Juveniles(BIRC)と考えられた小児ブドウ膜炎の2例

岡信宏隆, 岡山英樹, 岡野内俊雄, 佐藤俊介, 森實祐基, 松尾俊彦

眼科臨床医報 97 ( 1 ) 75 - 75 2003.1

特発性網膜血管炎(IRVAN)と考えられた1例

佐藤俊介, 岡山英樹, 岡野内俊雄, 森實祐基, 田中恵子

眼科臨床医報 96 ( 7 ) 815 - 815 2002.7

Selection for inferior limited macular translocation on the basis of distance from the fovea to the inferior edge of the subfoveal choroidal neovascularization. International journal

Yuki Morizane, Fumio Shiraga, Ippei Takasu, Shinya Yumiyama, Toshio Okanouchi, Hiroshi Ohtsuki

American journal of ophthalmology 133 ( 6 ) 848 - 50 2002.6

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

PURPOSE: To assess the visual outcome of inferior limited macular translocation in eyes selected based on the distance from the fovea to the inferior edge of the subfoveal choroidal neovascularization. DESIGN: Interventional case series. METHODS: We performed inferior limited macular translocation in 12 consecutive eyes (12 patients) with age-related macular degeneration or polypoidal choroidal vasculopathy, in which the choroidal neovascularization did not extend for more than half of one disk diameter inferior to the fovea. RESULTS: In all eyes, the choroidal neovascularization was moved to an extrafoveal location. In seven of the 12 eyes, postoperative vision was 20/40 or better. The visual acuity improved by 2 or more lines in 11 eyes. CONCLUSION: Selection for inferior limited macular translocation on the basis of distance from the fovea to the inferior edge of the choroidal neovascularization may be associated with a greater likelihood of visual acuity improvement.

【細菌性感染症】ニューキノロン系抗生物質耐性淋菌による成人発症の淋菌性角結膜炎の1例

森實祐基, 岡山英樹, 岡野内俊雄, 佐藤俊介, 佐々木惠美

社会保険広島市民病院医誌 18 ( 1 ) 47 - 51 2002.3

Language：Japanese Publisher：広島市立広島市民病院

29歳男.右眼に著明な結膜充血,角膜輪部潰瘍がみられ,レボフロキサシンによる初期治療に反応しなかった.眼脂培養の結果,ニューキノロン系抗生物質に耐性を示す淋菌が起因菌であることが判明した.抗生物質をマクロライド系,ペニシリン系及びセフェム系抗生物質に変更し病状は軽快した.重篤な症状を呈する結膜炎の鑑別診断としてニューロキノロン系抗生物質耐性淋菌による結膜炎の可能性を考慮する必要がある

強膜短縮黄斑移動術における術後視力に影響する因子

森實祐基, 白神史雄, 高須逸平, 岡野内俊雄, 弓山真矢, 山本敏広, 大月洋

眼科臨床医報 96 ( 2 ) 195 - 196 2002.2

特発性網膜血管炎(IRVAN)と考えられた1例

佐藤俊介, 岡山英樹, 岡野内俊雄, 森實祐基, 田中恵子

眼科臨床医報 96 ( 2 ) 196 - 196 2002.2

強膜短縮黄斑移動術後の回旋複視

堀川晶代, 平井美恵, 白神史雄, 河野玲華, 長谷部聡, 大月洋, 森實祐基

臨床眼科 55 ( 8 ) 1547 - 1550 2001.8

Language：Japanese Publisher：(株)医学書院

中心窩の脈絡膜新生血管に対して強膜短縮黄斑移動術を行った15例につき,1ヵ月後の回旋複視を検討した.すべて片眼性であり,原疾患は,加齢黄斑変性6例,ポリープ状網脈絡膜新生血管6例,近視性網脈絡膜変性2例,網膜色素線条症1例である.年齢は39歳から78歳,平均65.2±9.9歳である.回旋複視は,70歳以上の高年齢群,左右眼の視力差が小さい群,黄斑移動距離が大きい群,手術眼の固視点での網膜感度が高い群で有意に多かった.手術前の視力,利き眼であるかどうか,眼位,両眼視の有無,他覚的回旋偏位は,術後複視と無関係であった

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2001&ichushi_jid=J01537&link_issn=&doc_id=20010823110012&doc_link_id=10.11477%2Fmf.1410907466&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410907466&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

強膜短縮による中心窩移動術の術後経過

森實祐基, 白神史雄, 高須逸平, 岡野内俊雄, 弓山真矢, 山本敏広, 大月洋, 宮川公博, 岡山英樹, 佐藤俊介

眼科臨床医報 95 ( 6 ) 670 - 671 2001.6

糖尿病網膜症当院での現状と症例

佐藤俊介, 田中恵子, 宮川公博, 岡山英樹, 森實祐基, 橋本克枝

社会保険広島市民病院医誌 17 ( 1 ) 53 - 57 2001.3

強膜短縮による中心窩移動術の術後成績

森實祐基, 白神史雄, 高須逸平, 岡野内俊雄, 弓山真矢, 山本敏広, 大月洋

眼科臨床医報 95 ( 3 ) 333 - 333 2001.3

強膜短縮黄斑移動術の術後視力に影響する因子

森實祐基, 白神史雄, 高須逸平, 岡野内俊雄, 弓山真矢, 山本敏広, 大月洋

眼科手術 14 ( 臨増 ) 219 - 219 2001.1

悪性緑内障を生じた小眼球症の1例

森實祐基, 永山幹夫, 高須逸平, 山口樹一郎, 大月洋, 河西葉子

臨床眼科 54 ( 6 ) 1230 - 1234 2000.6

Language：Japanese Publisher：(株)医学書院

24歳男.小眼球に慢性閉塞隅角緑内障を伴っていた.この患者の両眼に白内障手術を行い,右眼にピロカルピンを点眼し,悪性緑内障を発症した.発症後早期にアトロピン点眼を行うことで前房深度は深くなり,眼圧は正常化した.しかし眼内レンズの瞳孔捕獲が起こり,左眼に比べ前房深度は浅いままとなった.本症例はピロカルピン点眼によって毛様体-水晶体嚢ブロックが起こり,悪性緑内障を発症したと考えられる.また右眼に用いたアクリル3ピースレンズが,左眼に用いたPMMA1ピースレンズに比べて瞳孔捕獲や浅前房を容易にしたと考えた.したがって悪性緑内障を念頭におくべき症例では,眼内レンズの選択が重要である

悪性緑内障をきたした小眼球の1例

森實祐基, 永山幹夫, 高須逸平, 大月洋, 河西洋子

眼科臨床医報 94 ( 1 ) 108 - 108 2000.1

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