Faculty Profiles - HOSOKAWA Mio

Papers - HOSOKAWA Mio

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

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

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

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

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

DOI： 10.1007/s10384-016-0492-7

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

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

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

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

Japanese Journal of Clinical Ophthalmology 70 ( 3 ) 387 - 392 2016.3

Language：Japanese Publishing type：Research paper (international conference proceedings) Publisher：Igaku-Shoin Ltd

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

Surgical Outcome of Idiopathic Epiretinal Membranes with Intraretinal Cystic Spaces. 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

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

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

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

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

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.

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

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

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

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

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

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

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