Faculty Profiles - HOSOKAWA Mio

Papers - HOSOKAWA Mio

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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