KUSUHARA Sentaro | |
Graduate School of Medicine / Faculty of Medical Sciences | |
Associate Professor | |
Medicine |
Oct. 2021 『Ophthalmic Surgery Film Award』 事務局, 2021 Ophthalmic Surgery Film Award (Educational Gold Award), 過熟白内障手術で後悔しないための Visco-Shield technique+α
Apr. 2018 バイエル薬品株式会社, 第3回バイエル レチナ・アワード, 日本国内の大学、医療機関、研究機関等で眼科医学(網膜領域)に関する研究に携わる45歳未満(2017年4月1日時点)の研究者
Others
PURPOSE: To report the characteristics of a case series of ocular inflammatory events following COVID-19 vaccination in Japan. STUDY DESIGN: Retrospective multicenter study METHODS: In this retrospective multicenter survey, a questionnaire was sent to 16 Japanese hospitals that had uveitis specialty clinics. Information on patients who developed ocular inflammatory events within 14 days of COVID-19 vaccination between February 2021 and December 2021 was collected. RESULTS: Thirty-seven patients were diagnosed with ocular inflammatory events following COVID-19 vaccination. The mean age was 53.4 ± 16.4 years (range, 26-86 years), and the mean time to onset after vaccination was 6.3 ± 4.2 days (range, 1-14 days). Vogt-Koyanagi-Harada disease (VKH) was the most common event (n = 17 patients, 46%), followed by anterior uveitis (n = 6), infectious uveitis (n = 3), acute zonal occult outer retinopathy (AZOOR) (n = 2), sarcoidosis-associated uveitis (n = 1), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1), optic neuritis (n = 1), multiple evanescent white dot syndrome (MEWDS) (n = 1), Posner-Schlossman syndrome (n = 1), and unclassified uveitis (n = 4). Twenty-eight cases occurred after BNT162b2 vaccination (Pfizer-BioNTech) and 8 after mRNA-1273 vaccination (Moderna), whilst 1 patient had no information about vaccine type. CONCLUSIONS: COVID-19 vaccination can be related to various types of ocular inflammatory events. When we encounter patients with ocular inflammatory disease, we should consider that it may be an adverse effect of COVID-19 vaccination.
22 Nov. 2022, Japanese journal of ophthalmology, 1 - 8, English, Domestic magazineScientific journal
PURPOSE: We investigated efficacy and safety of adalimumab (ADA) treatment for exacerbation or recurrence of Vogt-Koyanagi-Harada (VKH) patients. METHODS: Medical records of 70 VKH patients who received ADA treatment for more than 6 months were retrospectively investigated. RESULTS: The mean age of VKH patients was 54.8 ± 15.1 years, and male/female ratio was 34/36, and sunset glow fundus was observed in 71.4%. Subfoveal choroidal thickness, indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment for 6 months compared to baseline, while LogMAR and flare counts were also improved without being statistically significant. Adverse events were observed in 17.1%, in which tuberculosis was at 7.14% and psoriasis was at 2.86%; however, ADA treatment was continued in 91.4%. CONCLUSIONS: ADA was shown to be effective to achieve remission of VKH disease refractory to conventional treatments and was generally well tolerated with few serious adverse events.
24 Jun. 2022, Ocular immunology and inflammation, 1 - 9, English, International magazineScientific 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.
07 Apr. 2022, Journal of diabetes investigation, 13 (8), 1339 - 1346, English, Domestic magazineScientific journal
PURPOSE: Non-infectious uveitis associated with Vogt-Koyanagi-Harada (VKH) disease or sarcoidosis is commonly treated with systemic corticosteroids (SCS). We assessed the use of SCS for non-infectious uveitis relapses in Japanese clinical practice. STUDY DESIGN: Multicenter, retrospective chart review (UMIN Clinical Trial Registry; UMIN000032390). METHODS: One hundred fifty-seven patients (15- ≤ 75 years; 103 VKH disease, 54 sarcoidosis) given SCS to treat a relapse of non-infectious intermediate, posterior, or panuveitis accompanying VKH disease or sarcoidosis were studied (August 2011-December 2018). SCS dose and duration, concomitant medications, subsequent relapses, and steroid-related adverse drug reactions (ADRs) were analyzed for 12 months after target relapse treatment. Relationships between background factors and total SCS dose were analyzed (logistic regression). RESULTS: Mean (± SD) total SCS dose over 12 months after target relapse treatment was 3874 ± 2775 mg, and was higher in patients with immunosuppressants than in those without (4575 mg vs 3496 mg). Immunosuppressant use was the only factor significantly associated with higher total SCS dose (p = 0.0196). Mean duration of SCS treatment for relapse was 318.7 ± 89.3 days. Only 29.3% of patients were steroid-free after 12 months; the percentage was higher in patients without immunosuppressants (36.3% vs 16.4%). Subsequent relapse was experienced by 39.5% of patients, and 13.4% had a steroid-related ADR (mostly glaucoma or diabetes). CONCLUSION: In Japanese clinical practice, many patients with recurrent uveitis accompanying VKH disease or sarcoidosis received SCS for relapse for ≥ 300 days, suggesting that reducing corticosteroids is challenging in patients with difficulty suppressing inflammation.
Mar. 2022, Japanese journal of ophthalmology, 66 (2), 130 - 141, English, Domestic magazineScientific journal
AIM: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan. METHODS: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively. RESULTS: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit. CONCLUSIONS: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.
2022, Frontiers in medicine, 9, 999804 - 999804, English, International magazineScientific journal
The aim of this study was to determine the prevalence and progression of diabetic retinopathy (DR) with hyperglycemic disorders during pregnancy (HDPs) in Japan between 2013 and 2018 using two cohorts. The patients with HDPs were classified as those with pre-existing DM (pexD), gestational DM (GDM), and overt DM (ODM). Cohort 1 was obtained from the health claims database whose diseases were classified by the International Classification of Diseases-10. Cohort 2 was derived from a retrospective, multicenter analysis of the medical records of 225 patients from 10 ophthalmological institutions. In Cohort 1, there were 5268 patients with an HDP prevalence of 8.4%. Among them, 73 of 1139 patients had pexD (6.4%) and 61 of 4129 patients with GDM (1.5%) had DR; the overall prevalence of DR was 2.5%. In Cohort 2, 36 of 225 patients (16.0%) had DR, and 149 patients were followed at the early and late stages of pregnancy. Moreover, 10 of the 102 patients with pexD (9.8%) and two of five patients with ODM (40.0%) had a progression of DR. In conclusion, the prevalence and progression of DR in patients with pexD is lower than previously reported. More attention should be given to pexD and ODM.
29 Dec. 2021, Journal of clinical medicine, 11 (1), English, International magazineScientific journal
PURPOSE: To determine the baseline characteristics of patients with central retinal vein occlusion (CRVO) that were significantly associated with the best-corrected visual acuity (BCVA) at the initial examination. METHODS: This was a retrospective multicenter study using the medical records registered in 17 ophthalmological institutions in Japan. Patients with untreated CRVO (≥20-years-of-age) who were initially examined between January 2013 and December 2017 were studied. The patients' baseline factors that were significantly associated with the BCVA at the initial examination were determined by univariate and multivariate linear regression analyses. RESULTS: Data from 517 eyes of 517 patients were analyzed. Univariate analyses showed that an older age (r = 0.194, p < 0.001) and the right eye (r = -0.103, p < 0.019) were significantly associated with poorer BCVA at the initial visit. Multivariate analyses also showed that an older age (β = 0.191, p < 0.001) and the right eye (β = -0.089, p = 0.041) were significantly associated with poorer BCVA at the initial visit. CONCLUSIONS: The results indicate that an older age, a known strong factor, and the right eye were significantly associated with poorer BCVA at the initial visit to the hospital. These results suggest that functional and/or anatomical differences between the right and left eyes may be involved in these results.
29 Nov. 2021, Journal of clinical medicine, 10 (23), English, International magazineScientific journal
Peripherin-2 (PRPH2) is one of the causative genes of inherited retinal dystrophy. While the gene is relatively common in Caucasians, reports from Asian ethnicities are limited. In the present study, we report 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy. We identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. Variants p.R142W and p.V200E were relatively common in the cohort. The age of onset was generally in the 40's; however, some patients had earlier onset (age: 5 years). Visual acuity of the patients ranged from hand motion to 1.5 (Snellen equivalent 20/13). The patients showed variable phenotypes such as retinitis pigmentosa, cone-rod dystrophy, and macular dystrophy. Additionally, intrafamilial phenotypic variability was observed. Choroidal neovascularization was observed in three eyes of two patients with retinitis pigmentosa. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort.
18 Nov. 2021, Genes, 12 (11), English, International magazineScientific journal
PURPOSE: To evaluate the short-term change in choroidal structure following adalimumab (ADA) treatment in refractory noninfectious uveitis. METHODS: This was a retrospective study of 33 eyes from 18 patients with refractory noninfectious uveitis. Subfoveal choroidal thickness (SFCT), the choroidal stromal index (CSI) defined as the proportion of stromal area to the total choroidal area were used as choroidal imaging parameters and were evaluated by enhanced depth imaging optical coherence tomography (EDI-OCT). The change in these parameters in the 2 months following initiation of ADA was analysed. A linear mixed-effect model was used to assess the effect of ADA treatment. RESULTS: The causes of uveitis were Vogt-Koyanagi-Harada disease (VKHD) (42.4%), presumed autoimmune retinopathy (15.2%), others (12.1%) and unclassified (30.3%). In the analysis of all eyes, the SFCT was 309.7 ± 113.1 μm at baseline, 295.7 ± 114.5 μm at 1 month and 275.2 ± 98.8 μm at 2 months after ADA initiation (P < 0.001). The CSI was 0.275 ± 0.050 at baseline, 0.273 ± 0.068 at 1 month and 0.273 ± 0.046 at 2 months (P = 0.785). In the subgroup analysis, the SFCT decreased significantly from baseline to 2 months in VKHD eyes (P = 0.007) and unclassified eyes (P = 0.034). There was no significant change in CSI in either subgroup. CONCLUSIONS: In the assessment of short-term response to ADA treatment in uveitic eyes, using EDI-OCT, the SFCT appears to be more effective as a choroidal imaging biomarker than the CSI, especially in VKHD eyes.
May 2021, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 259 (5), 1273 - 1280, English, International magazineScientific journal
To demonstrate the long-term effect of cystotomy with or without fibrinogen clot removal for treatment-resistant cystoid macular edema (CME) secondary to branch retinal vein occlusion (BRVO). Retrospective clinical study. We retrospectively analyzed medical records of 22 eyes of 22 patients with treatment-resistant CME secondary to BRVO with 12 months observation after cystotomy with or without fibrinogen clot removal. Patients included 11 women and 11 men. The mean ± SD age was 72.7 ± 10.2 years. LogMAR-converted best corrected visual acuity (BCVA) was statistically better at 12 months after surgery (0.30 ± 0.30) than preoperative BCVA (0.39 ± 0.27) (p = 0.01). The central sensitivity of microperimetry (dB) was maintained during follow-up (preoperative sensitivity: 25.4 ± 4.1, postoperative sensitivity at 12 months after the surgery: 25.9 ± 4.2, p = 0.69). Twelve months after surgery, there was a significant improvement in the central retinal thickness (CRT) on optical coherence tomography (OCT) (303.7 ± 80.1) (μm) compared with the preoperative CRT (524.2 ± 114.8) (p < 0.01). In 12 months, CME recurred in 3 of 22 eyes. The preoperative reflectivity in cystoid cavity on OCT was significantly higher in patients with fibrinogen clot removal (n = 5) than in patients without fibrinogen clot removal (n = 17) (p < 0.01). For treatment-resistant CME secondary to BRVO, Cystotomy with or without fibrinogen clot removal may be one of the treatment options.
19 Apr. 2021, Scientific reports, 11 (1), 8460 - 8460, English, International magazine[Refereed]
Scientific journal
Specific postoperative complications, such as tube exposure and conjunctival erosion, have occurred despite the favorable surgical outcomes of tube shunt surgeries for refractory glaucoma. The new autologous scleral pocket technique is performed by inserting the tube into the vitreous cavity without using a donor scleral patch. The purpose of this study was to evaluate the surgical results of Ahmed glaucoma valve (AGV) implantation using this technique for neovascular glaucoma (NVG), which is one of the representative refractory types of glaucoma. This observational retrospective case series included 15 consecutive eyes of 15 patients with NVG who had undergone AGV implantation at Kobe University between January 2018 and December 2019. The mean preoperative intraocular pressure (IOP) was 37.2 ± 13.8 mmHg and the glaucoma drug score was 4.2 ± 2.2. The mean IOP and glaucoma drug score at 1 year postoperatively decreased to 15.0 ± 4.6 mmHg and 1.3 ± 2.0, respectively (p < 0.001). No significant change in the corneal endothelial cell density following surgery was observed (p = 0.09); however, one patient required an additional trabeculectomy at 7 months postoperatively. No cases of tube exposure or conjunctival erosion were observed at 1 year postoperatively. These results indicated the effectiveness and safety of this technique in patients with NVG.
10 Apr. 2021, Journal of clinical medicine, 10 (8), English, International magazine[Refereed]
Scientific journal
This retrospective study was conducted to investigate the clinical factors associated with low-contrast visual acuity after reduced-fluence photodynamic therapy (RFPDT) in patients with resolved central serous chorioretinopathy (CSC) and good baseline visual acuity. A total of 45 eyes of 45 patients with resolved CSC at post-RFPDT and best-corrected visual acuity of >1.0 (logarithm of the minimal angle of resolution [logMAR], 0) at baseline were examined. Visual acuities of both eyes were measured at four contrast levels (100%, 25%, 12%, and 6%) at post-RFPDT. The low-contrast visual acuity (6%, 12%, and 25%) was significantly lower than the 100% contrast visual acuity in the affected eyes. Visual acuities of affected eyes were significantly worse than those of fellow eyes at any contrast levels. The degree of changes in 6% and 100% contrast visual acuities was significantly greater in affected eyes than that in fellow eyes (p < 0.05). The 6% contrast visual acuities in affected eyes at post-RFPDT were significantly associated with the symptom duration (p < 0.05). Patients with a long duration of symptoms might have disturbed low-contrast visual acuities at post-RFPDT even if their baseline visual acuities were good.
28 Mar. 2021, Pharmaceuticals (Basel, Switzerland), 14 (4), English, International magazine[Refereed]
Scientific journal
Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus, Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment.
MDPI AG, 24 Mar. 2021, Pathogens, 10 (4), 390 - 390[Refereed]
Scientific journal
Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the coeffects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of mouse retinas. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same conditions to 8-12 weeks (young) or 45-55 weeks (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to aged WT mice, and subsequent gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision and transcellular barrier functions that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the four age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.
15 Mar. 2021, Antioxidants (Basel, Switzerland), 10 (3), English, International magazine[Refereed]
Scientific journal
[Refereed]
This multicenter retrospective study was conducted to evaluate the 1-year treatment outcome of photodynamic therapy (PDT) combined with anti-vascular endothelial growth factor (VEGF) therapy for pachychoroid neovasculopathy (PNV). A total of 42 eyes of 42 patients with treatment-naïve PNV who were treated with PDT combined with intravitreal injections of an anti-VEGF agent (ranibizumab or aflibercept) for 1 year. All eyes showed exudative and/or hemorrhagic changes that affected the fovea at baseline. After the initial combination therapy, subfoveal choroidal thickness (SCT) and central retinal thickness (CRT) were significantly reduced and were maintained as such for 12 months (P < 0.01 in SCT and CRT). The best-corrected visual acuity (BCVA) (0.19 ± 0.30 at baseline) significantly improved at 3 months (0.15 ± 0.29, P < 0.05) and further improved at 12 months (0.10 ± 0.30, P < 0.01) when compared to that at baseline. After the initial combination therapy, 32 eyes (76.2%) required no additional treatments for 12 months. The mean number of additional PDT and intravitreal injections of anti-VEGF agents was 0.1 ± 0.3 and 0.9 ± 1.9, respectively. Of the 42 eyes included in this study, 22 eyes (52.4%) had polypoidal lesions at baseline. No significant differences in SCT, CRT, or BCVA were observed at any time points between eyes with and without polypoidal lesions. Of 20 eyes without polypoidal lesions, only 1 eye (5.0%) needed additional treatments. PNV, especially without polypoidal lesions, can be treated effectively with PDT combined with anti-VEGF therapy with few sessions.
2021, PloS one, 16 (3), e0248760, English, International magazine[Refereed]
Scientific journal
Aquaporin 9 (AQP9) is an aquaglyceroporin that can transport lactate. Accumulating evidence suggests that astrocyte-to-neuron lactate shuttle (ANLS) plays a critical role in energy metabolism in neurons, including retinal ganglion cells (RGCs). To test the hypothesis that AQP9, in concert with monocarboxylate transporters (MCTs), participates in ANLS to maintain function and survival of RGCs, Aqp9-null mice and wild-type (WT) littermates were subjected to optic nerve crush (ONC) with or without intravitreal injection of an MCT2 inhibitor. RGC density was similar between the Aqp9-null mice and WT mice without ONC, while ONC resulted in significantly more RGC density reduction in the Aqp9-null mice than in the WT mice at day 7. Positive scotopic threshold response (pSTR) amplitude values were similar between the two groups without ONC, but were significantly more reduced in the Aqp9-null mice than in the WT mice 7days after ONC. MCT2 inhibitor injection accelerated RGC death and pSTR amplitude reduction only in the WT mice with ONC. Immunolabeling revealed that both RGCs and astrocytes expressed AQP9, that ONC predominantly reduced astrocytic AQP9 expression, and that MCTs 1, 2, and 4 were co-localized with AQP9 at the ganglion cell layer. These retinal MCTs were also co-immunoprecipitated with AQP9 in the WT mice. ONC decreased the co-immunoprecipitation of MCTs 1 and 4, but did not impact co-immunoprecipitation of MCT2. Retinal glucose transporter 1 expression was increased in Aqp9-null mice. Aqp9 gene deletion reduced and increased the intraretinal L-lactate and D-glucose concentrations, respectively. Results suggest that AQP9 acts as the ANLS to maintain function and survival of RGCs.
04 Aug. 2020, Molecular neurobiology, 57 (11), 4530 - 4548, English, International magazine[Refereed]
Scientific journal
PURPOSE: To show the long-term effect of the cystotomy with or without fibrinogen clot removal for the refractory cystoid macular edema (CME) secondary to diabetic retinopathy (DR). METHODS: Retrospective analyses of the medical records of 30 eyes of 30 patients with refractory CME secondary to DR who had followed-up for 12 months after the surgery were performed. RESULTS: There were 15 men and 15 women. The mean±SD age was 68.4±7.9 years. The best corrected visual acuity (BCVA) (logMAR) at 12 months after the surgery (0.33±0.25, Snellen equivalent (SE), 20/42) was statistically better than the preoperative BCVA (0.45±0.33, SE, 20/56) (p<0.01). The central sensitivity on microperimetry (dB) was not statistically changed between preoperatively (24.0±4.9) and 12 months after the surgery (24.1±4.0) (p=0.75). The central retinal thickness (CRT) on optical coherence tomography (OCT) (μm) at 12 months after the surgery (300.3±99.0) was statistically improved compared with the preoperative CRT (565.6±198.7) (p<0.01). During the follow-up period, CME relapsed in 7 of 30 eyes. The preoperative cystoid cavity reflectivity on OCT in patients with fibrinogen clot removal (n=16) was significantly higher compared with that in patients without fibrinogen clot removal (n=14) (p<0.04). CONCLUSION: The cystotomy with or without fibrinogen clot removal may be a promising treatment option for refractory CME secondary to DR.
21 Jul. 2020, Retina (Philadelphia, Pa.), 41 (4), 844 - 851, English, International magazine[Refereed]
Scientific journal
[Refereed]
PURPOSE: To show the usefulness of the intraoperative three-dimensional fluorescein angiography (3D-FA)-guided pars plana vitrectomy. METHODS: The NGENUITY 3D visualization system was used for the digital assisted vitrectomy. Three-dimensional fluorescein angiography-guided pars plana vitrectomy was performed in three patients with vitreous hemorrhage secondary to proliferative diabetic retinopathy. We investigated both whether several angiographic findings can be successfully displayed on the screen during 3D-FA and whether pars plana vitrectomy can be performed simultaneously on the same screen while implementing 3D-FA. RESULTS: In all cases, the abnormal FA findings including hypofluorescence due to non-perfusion areas, and the hyperfluorescence due to macular edema and fibrovascular proliferative membrane were successfully displayed on the screen. The segmentation and delamination of fibrovascular proliferative membrane and panretinal photocoagulation for detected non-perfusion areas were able to be performed on the same screen while implementing 3D-FA. CONCLUSION: Three-dimensional fluorescein angiography-guided pars plana vitrectomy is a novel approach that fully utilizes the advantages of digital assisted vitrectomy and a promising option for the treatment of proliferative diabetic retinopathy.
17 Apr. 2020, Retina (Philadelphia, Pa.), English, International magazine[Refereed]
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.
13 Mar. 2020, The British journal of ophthalmology, 104 (12), 1755 - 1761, English, International magazine[Refereed]
Scientific journal
OBJECTIVE: To evaluate the usefulness of en face slab optical coherence tomography (OCT) imaging for monitoring diabetic retinal neurodegeneration with supporting animal experimental data. RESEARCH DESIGN AND METHODS: We retrospectively examined 72 diabetic eyes over 3 years using Cirrus-HD OCT. Two-dimensional en face slab OCT images of the innermost retina were reconstructed and graded according to the ratio of dark area to total area, and relative red, green, and blue color area ratios were calculated and used as indexes for each en face slab OCT image. Values from en face OCT images were used for statistical analyses. To obtain insight into the pathogenesis of diabetic retinal neurodegeneration, we used the InsPr-Cre;Pdk1flox/flox diabetic mouse model. RESULTS: Both OCT grade and relative red color area ratio significantly increased with the advancing stage of diabetic retinopathy (p=0.018 and 0.006, respectively). After a mean follow-up period of 4.6 years, the trend was unchanged in the analyses of 42 untreated eyes (p<0.001 and 0.001, respectively). Visual acuity showed a weak but significant negative correlation with the red color ratio on en face slab OCT images, but central retinal thickness did not exhibit a clinically meaningful correlation with values obtained from en face slab OCT images. Immunohistochemical analyses of InsPr-Cre;Pdk1flox/flox diabetic mice demonstrated the loss of ganglion axon bundles and thinning of laminin without apparent retinal vascular change at the age of 20 weeks. CONCLUSIONS: En face slab OCT imaging would be a novel useful modality for the assessment of diabetic retinal neurodegeneration as it could detect subtle optical changes occurring in the innermost retina in diabetic eyes. Our animal experimental data suggest that dark areas observed on en face slab OCT images might be the impairment of the extracellular matrix as well as neurons.
Mar. 2020, BMJ open diabetes research & care, 8 (1), English, International magazine[Refereed]
Scientific journal
This retrospective study was conducted to investigate the predictive factors associated with metamorphopsia after reduced-fluence photodynamic therapy (RFPDT) in patients with central serous chorioretinopathy (CSC) with good baseline visual acuity. A total of 36 eyes of 36 consecutive patients with resolved CSC after RFPDT and best-corrected visual acuity (BCVA) better than 1.0 (logarithm of the minimal angle of resolution (logMAR) 0) at baseline were examined. Metamorphopsia was measured using M-CHARTS at 12 months after RFPDT. An average of the horizontal and vertical M-CHARTS scores was applied for defining the extent of metamorphopsia. The association between M-CHARTS score at 12 months after RFPDT and clinical parameters (age, sex, duration of symptoms, BCVA, and findings of optical coherence tomography (OCT)) was investigated at baseline or 12 months after RFPDT. The M-CHARTS score at 12 months correlated significantly with duration of symptoms (P = 0.005), baseline outer nuclear layer (ONL) thickness (P = 0.009), central foveal thickness (CFT) (P = 0.001) at 12 months, and ONL thickness (P = 0.001) at 12 months after RFPDT. In the multivariate analysis of baseline-related factors, thinner ONL thickness before RFPDT (P = 0.010) was significantly associated with large metamorphopsia at 12 months after RFPDT in CSC patients with good baseline BCVA. Baseline ONL thickness may be a useful predictive factor of metamorphopsia after RFPDT in CSC patients with good baseline BCVA.
2020, PloS one, 15 (10), e0240557, English, International magazineScientific journal
Purpose: Reduced-fluence photodynamic therapy (RFPDT) has proven effective for some patients with chronic central serous chorioretinopathy (cCSC). Several clinicodemographic factors influencing treatment response have been identified, but associations with genetic factors have not been examined. Therefore, we investigated the associations of single nucleotide polymorphisms (SNPs) implicated in cCSC pathogenesis with clinical outcome following RFPDT. Methods: This was a retrospective study of 87 eyes from 87 patients with cCSC who underwent RFPDT and were followed up for more than 12 months. Patients were divided into a good response group (53 patients) and a poor response group (34 patients) based on either persistence or recurrence of subretinal fluid detected with spectral domain optical coherence tomography after the first application of RFPDT. SNPs in the genes encoding age-related maculopathy susceptibility protein 2 (ARMS2, SNP rs10490924) and complement factor H (CFH, SNP rs800292) were genotyped using TaqMan technology. Results: There were no statistically significant differences in the baseline characteristics between the response groups except the degree of hyperfluorescence on indocyanine green angiography (ICGA; p = 0.011). The minor (T) allele frequency of ARMS2 (rs10490924) were statistically significantly lower in the good response group than in the poor response group (24.0% versus 41.0%, p = 0.021). Further, the good response frequency was statistically significantly lower in patients with at least one minor allele (GT or TT) compared to the homozygous major allele group (GG; p<0.05). The baseline best-corrected visual acuity (BCVA) at 12 months after RFPDT was statistically significantly better in the GG carriers than in the GT or TT carriers (p<0.01). Logistic regression analysis showed less intense hyperfluorescence on ICGA, and the T allele of ARMS2 (rs10490924) was statistically significantly associated with poor response to PDT treatment (p = 0.012, p = 0.039, respectively). Conclusions: Carriers of the ARMS2 rs10490924 minor allele (GT or TT) demonstrated a higher subretinal fluid persistence or recurrence rate and poorer visual outcome following RFPDT. In addition to the ICGA findings, genotyping of ARMS2 (rs10490924) may assist in the selection of patients with cCSC most likely to benefit from RFPDT.
2020, Molecular vision, 26, 505 - 509, English, International magazine[Refereed]
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.
29 Nov. 2019, The British journal of ophthalmology, 104 (9), 1209 - 1215, English, International magazine[Refereed]
Scientific journal
[Refereed]
[Refereed]
BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a T-cell-mediated autoimmune disorder characterized by bilateral granulomatous panuveitis with various systemic manifestations. Although VKH disease rarely occurs in the pediatric population, the clinical course tends to be aggressive, and the visual prognosis is worse than that in adult patients due to severe ocular complications secondary to recurrent inflammation. CASE PRESENTATION: A 3-year-old girl with probable VKH was referred to Kobe University Hospital. She had severe bilateral panuveitis with posterior synechiae of the iris, marked optic disk swelling, and serous retinal detachment in both eyes, and her best corrected visual acuities (BCVAs) were 20/200 OD and 20/125 OS. A third course of therapy was administered because serous retinal detachment remained after two courses of therapy. She was treated with three courses of high-dose intravenous corticosteroid therapy, followed by slow tapering of oral corticosteroids. Her BCVAs recovered to 20/16 OU, and relapse of ocular inflammation and side effect of treatment were not observed during the 1.5-year follow-up period. CONCLUSIONS: We experienced a pediatric patient with probable VKH disease who was treated with three courses of high-dose intravenous corticosteroid therapy. With the favorable clinical course in our patient, initial treatment with repeated high-dose intravenous corticosteroid therapy might be beneficial in pediatric VKH disease.
13 Aug. 2019, BMC ophthalmology, 19 (1), 179 - 179, English, International magazine[Refereed]
Scientific journal
Purpose: The present study aimed to assess the ability of en face slab images of maculae to detect residual nerve fiber bundles in eyes with advanced glaucoma. Methods: This study included 36 eyes with diffuse thinning of the ganglion cell and inner plexiform layers (GCL+IPL). Inclusion criterion was GCL+IPL thickness of <1% of the normative database level as detected using optical coherence tomography (OCT). En face slab images (50-μm thickness) were reconstructed from the macular cube scan data using advanced visualization settings. Thereafter, we assessed the agreement of the locations between hyperreflective nerve fiber bundles and normal points in the Humphrey visual field test 10-2 pattern deviation (PD) plots. Additionally, total deviation (TD) corresponding to hyperreflective and hyporeflective areas was compared. Results: Hyperreflective areas were detected in 31 out of 36 eyes; all 31 eyes exhibited at least one normal PD point despite the substantial GCL+IPL thinning in the macular region. Two eyes with abnormalities in all PD points showed no hyperreflective area. The remaining three eyes had normal PD points despite the lack of high reflectivity areas in the slab images. Therefore, 91.7% of eyes showed agreement between en face slab images and PD plots. Moreover, hyperreflective areas demonstrated significantly better TD than hyporeflective areas. Conclusions: En face slab images of maculae were able to reveal the residual nerve fiber bundles in the eyes with advanced glaucoma despite the GCL+IPL thickness in the maculae being diffusely and substantially reduced.
01 Jul. 2019, Investigative ophthalmology & visual science, 60 (8), 2811 - 2821, English, International magazine[Refereed]
目的:続発緑内障に対するテノン開創器を用いた線維柱帯切除術の短期成績を調べること。対象と方法:2016年4月から2017年5月までの期間に神戸大学医学部附属病院で続発緑内障に対してテノン開創器を用いたマイトマイシンC併用線維柱帯切除術が施行された、連続11例12眼を後ろ向きに評価した。本新術式は、1)テノン開創器で強膜とテノン嚢の間に十分なスペースを確保し強膜の後方スペースに広くマイトマイシンC含有スポンジを留置する点、2)強膜フラップ後方を無縫合とする点、3)輪部結膜付近に3mm×6mmのブロッキング糸をかける点が特徴である。治療効果については、手術前後における眼圧および緑内障点眼スコアの変化および術後処置の内容で評価した。結果:続発緑内障の原因は、ブドウ膜炎続発緑内障6眼、血管新生緑内障4眼、落屑緑内障2眼であった。平均眼圧は、術前の34.8±13.8mmHgから術後12ヵ月で18.1±4.0mmHgと、有意に低下していた(p<0.001)。平均点眼スコアについても、術前の4.3±1.2から術後12ヵ月で1.1±1.5と有意に低下していた(p<0.001)。術後結膜下瘢痕に対して濾過胞再建を要した血管新生緑内障の1例を除き、術後処置(レーザー切糸、結膜縫合を含む)を必要とした症例はなかった。結論:続発緑内障に対するテノン開創器を用いた線維柱帯切除術は短期経過では有望な術式であると推測される。(著者抄録)
(公財)日本眼科学会, Feb. 2019, 日眼会誌, 123 (2), 121 - 127, JapaneseTransforming growth factor beta-induced (TGFBI)-associated corneal dystrophies are a group of inherited progressive corneal diseases. One of these TGFBI-associated corneal dystrophies is Avellino corneal dystrophy, an autosomal dominant corneal dystrophy characterized by multiple asymmetric stromal opacities that potentially impair vision. Recently, a case with corneal dystrophy complicated by nephropathy possessing a pathogenic variant of the TGFBI gene was reported for the first time. Here, we report the second case with the same condition and the same mutation in the TGFBI gene. The patient was an 18-year-old male. He and his father had already been diagnosed with corneal dystrophy. Proteinuria was revealed in the patient during urine screening at school. Since his serum creatinine level was raised, a percutaneous renal biopsy was performed. Light microscopy demonstrated oligomeganephronia. Electron microscopy demonstrated an irregular basement membrane. TGFBI was analyzed by direct sequencing. A heterozygous mutation c.371G > A in exon 4, which caused an amino acid substitution from arginine to histidine at codon 124, was identified in the patient and his father. Although only one case of TGFBI-associated corneal dystrophy and nephropathy has been reported, our case's clinical and pathological findings were almost identical to those in that reported case. Further investigations of this new disease entity should be reported to all nephrologists and ophthalmologists.
Feb. 2019, CEN case reports, 8 (1), 14 - 17, English, Domestic magazine[Refereed]
Scientific journal
© 2019 The Author(s). Purpose: Axitinib, an orally administered vascular endothelial growth factor receptors 1, 2, and 3 inhibitor, is widely used as the second-line treatment for metastatic renal cell carcinoma. We present a case of metastatic renal cell carcinoma who developed a novel ocular adverse event, impaired retinal circulation, during axitinib therapy. Methods: This is an observational case report. Results: A 57-year-old male who had been treated with axitinib for metastatic renal cell carcinoma for 2 years presented in August 2015. He complained of sudden-onset abnormal visual field in his right eye. His right eye exhibited multiple soft exudates on fundus photography and a significant fluorescein filling delay of the retinal vessels on fluorescein angiography. His best corrected visual acuity (BCVA) was 20/20 in the right eye, and a cecocentral scotoma was detected by Goldmann perimeter. As axitinib could have been responsible for impaired retinal circulation, axitinib was terminated and switched to temsirolimus. The soft exudates gradually subsided and the patients' symptoms got better, but his right BCVA dropped to 20/63 3 months after the end of axitinib treatment with worsening of his general condition. Conclusion: Clinicians should be aware of retinal circulatory disorder that can occur in patients under axitinib treatment.
01 Jan. 2019, Case Reports in Ophthalmology, 10 (1), 5 - 10[Refereed]
Scientific journal
Purpose: This study aimed to evaluate the long-term efficacy and safety of infliximab (IFX) and cyclosporine (CsA) combination therapy for refractory uveoretinitis in Behçet's disease (BD). Patients and methods: The study involved a retrospective review of the medical records of 11 patients with Behçet's uveoretinitis refractory to conventional treatment who had been treated with IFX+CsA combination therapy. The frequency of ocular inflammatory attacks and a Behçet's disease ocular attack score 24 (BOS24) were used as indices for the evaluation of efficacy during each 6-month period prior to and following initiation of therapy. For the assessment of safety, adverse events (AEs) were recorded throughout the treatment period. Results: The patients had received IFX+CsA combination therapy for 5.6±2.3 years. The frequency of ocular attacks per 6-month period decreased markedly from 2.9±1.6 during the baseline period to 0.6±0.9 during months 1-6, 0.5±0.9 during months 7-12, 0.3±0.5 during months 13-18, 0.3±0.7 during months 19-24, and 0.0±0.0 thereafter (P=0.003). The BOS24 score per ocular attack significantly decreased from 5.2±2.4 during the baseline period to 1.5±2.1 during months 1-6, 1.7±3.1 during months 7-12, 1.6±2.9 during months 13-18, and 0.4±1.0 during months 19-24 (P=0.002). No serious AEs were observed, with the exception of urinary tract infection and cataract progression. Two patients exhibited transient elevation of the serum creatinine level, which was normalized following a reduction in the dose of CsA. Conclusion: For refractory Behçet's uveoretinitis, IFX+CsA combination therapy offers a promising treatment option as it appears to have an acceptable safety profile and can reduce the frequency and severity of ocular inflammatory attacks over a long period of time.
2019, Clinical ophthalmology (Auckland, N.Z.), 13, 521 - 527, English, International magazine[Refereed]
[Refereed]
[Refereed]
Scientific journal
PURPOSE: The purpose of this study was to describe the initial experience, efficacy, and safety of ripasudil hydrochloride hydrate (ripasudil), a Rho-associated kinase inhibitor eye drop, for uveitic glaucoma. METHODS: In this retrospective case series, we retrieved the clinical data of 21 eyes from 19 patients with open-angle uveitic glaucoma who were treated with ripasudil at Kobe University Hospital. We analyzed the median intraocular pressure (IOP) reductions after ripasudil treatment and collected the information on the adverse events that were encountered during the course of this treatment period. RESULTS: The causes of uveitis were sarcoidosis (29%), Behçet's disease (14%), Vogt-Koyanagi-Harada disease (10%), others (15%), and unclassified (33%). Of total, 19 (90%) eyes were treated with topical, periocular, and/or systemic steroid therapies. The median number of glaucoma medications used before ripasudil treatment was 2, and the median follow-up time was 13 months. The median IOPs were 23 mmHg at baseline, 16 mmHg at 1 month, and 18 mmHg at 12 months with significant IOP reductions of - 3 mmHg at 1 month and - 2 mmHg at 12 months (P = 0.0050). Of total, 11 (52%) eyes with an IOP reduction ≥ 3 mmHg at 1 month (responders) showed a significant median IOP decrease at 12 months compared with non-responders (- 5 versus 0 mmHg, P = 0.0242). Two adverse events were observed: rashes on the back and transient conjunctival hyperemia. CONCLUSIONS: Ripasudil appears to be safe and substantially reduce IOP in eyes with uveitic glaucoma if the eye is a responder. Ripasudil could be an option for the treatment of uveitic glaucoma.
Apr. 2018, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 256 (4), 809 - 814, English, International magazine[Refereed]
Scientific journal
A 40-year-old woman with renal dysfunction for 2 years was admitted to our hospital suffering from a headache. Family history revealed that her mother had a headache, renal dysfunction, and brain infarction in younger age. She had a retinal hemorrhage, a retinal atrophy, pitting edema in her lower extremities. Her neurological findings were unremarkable. Brain imaging showed multiple white matter lesions accompanied with calcifications and slightly enhancement. Kidney biopsy showed the thrombotic microangiopathy, Gene analysis demonstrated a causative mutation in three-prime repair exonuclease-1 (TREX1) gene, c.703_704insG (p.Val235GlyfsX6), thereby we diagnosed her as retinal vasculopathy with cerebral leukoencephalopathy (RVCL). RVCL is an autosomal dominant condition caused by C-terminal frame-shift mutation in TREX1. TREX1 protein is a major 3' to 5' DNA exonuclease, which are important in DNA repair. While TREX1 mutations identified in Aicardi-Goutieres syndrome patients lead to a reduction of enzyme activity, it is suggested that mutations in RVCL alter an intracellular location of TREX1 protein. There are no treatments based evidences in RVCL. We administered cilostazol to protect endothelial function, and her brain lesions and renal function have not become worse for 10 months after. It is necessary to consider RVCL associated with TREX1 mutation if a patient has retinal lesions, white matter lesions accompanied with calcifications, and multiple organ dysfunction.
(一社)日本神経学会, Feb. 2018, Rinsho shinkeigaku = Clinical neurology, 58 (2), 111 - 117, Japanese, Domestic magazine[Refereed]
目的:脈絡膜骨腫では,約半数で脈絡膜新生血管などにより視力が低下するとされている。脈絡膜骨腫に続発した脈絡膜新生血管に対し,1回のベバシズマブ硝子体注射と光線力学療法で視力が改善し,長期に維持された症例の報告。症例:17歳の女性が2週間前からの左眼視力低下と中心暗点で紹介受診した。紹介医により左眼黄斑部に漿液性網膜剥離が指摘された。所見と経過:矯正視力は右(1.2),左(0.4)で,右眼に-5D,左眼に-6Dの近視があった。左眼後極部に境界が明瞭な黄白色の病変があった。CTで眼球後壁に石灰化があり,諸検査の結果,脈絡膜新生血管を伴う脈絡膜骨腫と診断した。ベバシズマブ硝子体注射と光線力学的療法を行い,1ヵ月後に出血は消失し,10ヵ月後に視力は(1.2)に改善した。2年後の現在,左眼の眼底病変は沈静化し,(0.8)の視力を維持している。結論:脈絡膜骨腫に続発した脈絡膜新生血管に対する1回のベバシズマブ硝子体注射と光線力学療法で,視力が改善し,以後2年間眼底病変が鎮静化している。(著者抄録)
(株)医学書院, Oct. 2017, 臨床眼科, 71 (10), 1505 - 1511, JapanesePURPOSE: Central serous chorioretinopathy (CSC) is a common choroidal disorder which often affects the vision of young adults. Although the molecular mechanisms associated with CSC remain unknown, correlations between steroid hormone use and CSC have been suspected. We investigated the choroidal status of CSC secondary to corticosteroid use. METHODS: The records of 25 eyes of 25 consecutive acute CSC cases secondary to corticosteroid use were reviewed retrospectively. Central choroidal thickness was measured by optical coherent tomography. Choroidal vessel dilation and choroidal vascular hyperpermeability were evaluated based on indocyanine green angiography findings. The parameters related to secondary CSC were compared with those of 25 eyes of 25 cases with acute idiopathic CSC. RESULTS: The mean central choroidal thickness of secondary CSC was 294.8 ± 95.0 μm, which was significantly thinner than that of idiopathic CSC (409.4 ± 124.7 μm, P = 0.00064). The proportion of the cases exhibiting choroidal vessel dilation was not significantly different between secondary CSC (52%) and idiopathic CSC (64%). The proportion of cases showing choroidal vascular hyperpermeability was significantly smaller in secondary CSC (62%) than idiopathic CSC (92%) (P = 0.028). CONCLUSION: The choroidal status in the acute phase of secondary CSC after corticosteroid use might be different from that of idiopathic CSC, which suggests a complex mechanism for CSC.
Aug. 2017, Retina (Philadelphia, Pa.), 37 (8), 1562 - 1567, English, International magazine[Refereed]
Scientific journal
PURPOSE: The purpose of the study was to evaluate the 1-year visual and anatomical outcomes of combination therapy with intravitreal aflibercept (IVA) and verteporfin photodynamic therapy (vPDT) for polypoidal choroidal vasculopathy (PCV), and to determine the predictors of a good visual outcome. METHODS: This was a prospective case-series study. Twenty eyes from 20 treatment-naïve PCV patients were treated with combination therapy with IVA and vPDT. Best-corrected visual acuity (BCVA) and morphological parameters including polypoidal lesions in indocyanine green angiography (ICGA) were evaluated over 12 months of follow-up. RESULTS: The mean logMAR BCVA was significantly improved from 0.30 at baseline to 0.20 at 3 months and 0.18 at 12 months. The mean central retinal thickness was also significantly improved at 3 months and at 12 months. In ICGA, complete regression of polypoidal lesions was found in 14 out of 20 eyes (70 %) at 3 months and in 14 out of 18 eyes (78 %) at 12 months although no ICGA were done on two eyes. In the multivariate logistic regression analyses, the baseline greatest linear dimension was found as a significant predictive factor for good visual improvement (≧0.3 LogMAR units improvement from baseline) at 12 months. CONCLUSION: In this study, combination therapy with IVA and vPDT gave visual and anatomical improvements to treatment-naïve PCV patients over 12 months of follow-up period.
SPRINGER, Mar. 2017, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 255 (3), 541 - 548, English, International magazine[Refereed]
Scientific journal
In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis. Notably, PC depletion directly induced inflammatory responses in ECs and perivascular infiltration of macrophages, whereby macrophage-derived VEGF and placental growth factor (PlGF) activated VEGFR1 in macrophages and VEGFR2 in ECs. Moreover, angiopoietin-2 (Angpt2) upregulation and Tie1 downregulation activated FOXO1 in PC-free ECs locally at the leaky aneurysms. This cycle of vessel damage was shut down by simultaneously blocking VEGF, PlGF, and Angpt2, thus restoring the BRB integrity. Together, our model provides new opportunities for identifying the sequential events triggered by PC deficiency, not only in DR, but also in various neurological disorders.
09 Feb. 2017, JCI insight, 2 (3), e90905, English, International magazine[Refereed]
Scientific journal
目的:糖尿病黄斑浮腫(DME)に対するranibizumab硝子体注射(IVR)単回投与後の経過に関する検討を行った。対象および方法:対象は2014年3月〜2015年4月にDMEに対してIVR 0.5mgを1回施行し、2ヵ月以上再投与なしで経過観察した連続症例22例26眼(男性17例、女性5例)。光干渉断層計にて計測した平均中心網膜厚(CRT)を、IVR投与前と投与後1、2ヵ月で比較し、その変化量を評価した。結果:平均CRTはIVR前と比較し、IVR後1ヵ月、2ヵ月では有意に減少した(各p=3.4×10^-5、2.1×10^-3)。一方、IVR後1ヵ月と2ヵ月間の平均CRTには有意差を認めなかった(p=0.10)。また、IVR前と比べて、IVR後CRTが30%以上減少した症例の割合は1ヵ月で35.7%、2ヵ月で28.6%であった。結論:DMEに対するIVR単回投与で1ヵ月後には有意なCRTの改善が得られ、2ヵ月後においても治療効果は持続した。(著者抄録)
(株)メディカル葵出版, Feb. 2017, あたらしい眼科, 34 (2), 280 - 282, Japanese[Refereed]
Scientific journal
Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axial length (rs10453441, Pmeta=3.9 × 10(-13)) and corneal curvature (Pmeta=2.9 × 10(-40)) and confirm the previously reported association between GJD2 and myopia. WNT7B significantly associates with extreme myopia in a case-control study with 1,478 Asian patients and 4,689 controls (odds ratio (OR)meta=1.13, Pmeta=0.011). We also find in a mouse model of myopia downregulation of WNT7B expression in the cornea and upregulation in the retina, suggesting its possible role in the development of myopia.
31 Mar. 2015, Nature communications, 6, 6689 - 6689, English, International magazine[Refereed]
Scientific journal
PURPOSE: To compare the response to ranibizumab between patients with typical neovascular age-related macular degeneration (tAMD) and those with polypoidal choroidal vasculopathy (PCV), and to determine the predictors for the outcomes. METHODS: Fifty-nine eyes from 59 consecutive patients (tAMD: 27 eyes, PCV: 32 eyes) were treated with three monthly ranibizumab injections followed by as-needed retreatment. Best-corrected visual acuity (BCVA) and morphological parameters were evaluated over 24 months of follow-up. RESULTS: The mean BCVA in tAMD and PCV patients was significantly improved at 3 months (-0.22 and -0.09 logMAR units, respectively). The improvement in BCVA was sustained up to 24 months in tAMD (p = 0.01) but not in PCV patients. The significant predictor for good response to ranibizumab in tAMD patients was the improvement of BCVA at 3 months, whereas that in PCV patients was the anatomical resolution at 3 months. CONCLUSIONS: Ranibizumab is an effective therapy for tAMD and PCV over 24 months. The predictors for good outcome might be different between tAMD and PCV.
2015, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 234 (1), 33 - 9, English, International magazine[Refereed]
Scientific journal
PURPOSE: Our aim was to use molecular biological methods to study evidence of autoimmune disease in five patients with acute zonal occult outer retinopathy (AZOOR). METHODS: Ophthalmologic data and sera were collected from all patients, who underwent visual field (VF) examination, optical coherence tomography (OCT), and multifocal electroretinogram (mfERG) recording. Serum was prepared from each patient's blood and analyzed for antiretinal antibody activity using immunohistochemistry and Western blot analysis on mouse and human retinas. We also searched for antigen proteins using mass spectrometry. RESULTS: Symptoms were blurred vision in three patients and VF defects in two; all had enlargement of the Mariotte blind spot by VF testing. OCT findings in areas corresponding to the scotoma revealed disruptions of junction borders between inner and outer segment lines. mfERGs amplitudes were reduced in each corresponding scotoma area. Immunohistochemical serum staining revealed the target antigen was present in all photoreceptors of the mouse sensory retina. Western blot analysis using patient serum samples revealed some possible candidate antigens. Mass spectrometry could not determine the causative antigen; however, a list of candidates was discovered. CONCLUSION: We determined that AZOOR could be an autoimmune disease. All AZOOR patients tested using molecular biological methods had antiretinal antigens.
Nov. 2014, Japanese journal of ophthalmology, 58 (6), 462 - 72, English, Domestic magazine[Refereed]
Scientific journal
Since Kelly and Wendel [Arch Ophthalmol 1991;109:654-659] first reported successfully treating macular holes (MHs) using pars plana vitrectomy in 1991, MH surgery has been constantly improved. For example, introducing the removal of the internal limiting membrane considerably increased the closure rate of MHs, and the advent of microincision vitrectomy surgery reduced surgical trauma and decreased patient discomfort after surgery. As modern MH surgery can achieve a higher anatomical success rate and alleviate patients' postoperative distress, postoperative visual outcomes have lately become the primary concern. Informing patients of the expected visual acuity and visual improvement before surgery is ideal, but predicting postoperative visual outcomes is difficult because a large number of factors are associated with them. In this paper, we review previous studies and provide accumulating evidence for the relationship between individual prognostic factors and visual outcomes after MH surgery.
2014, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 231 (3), 125 - 32, English, International magazine[Refereed]
Scientific journal
PURPOSE: To investigate the incidence of and risk factors for a dissociated optic nerve fiber layer (DONFL) appearance after pars plana vitrectomy (PPV). METHODS: We retrospectively reviewed 189 eyes that underwent PPV with internal limiting membrane removal and judged the presence/absence of an apparent DONFL based on en face layer images produced by spectral-domain optical coherence tomography (SD-OCT). RESULTS: An apparent DONFL was observed in 47 (24.9%) eyes. The incidence of an apparent DONFL was significantly higher in the macular hole (MH) group (76.5%) than in the non-MH group (epiretinal membrane, diabetic macular edema, retinal vein occlusion, and others; 4.9%; p < 0.001). In the logistic regression analysis, surgical indication for MH was identified as the most significant DONFL risk factor (odds ratio 63.7; p = 1.05 × 10(-8)). CONCLUSION: Postoperative OCT en face layer imaging clarified that MH eyes are liable to have an apparent DONFL following PPV.
2014, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 232 (3), 170 - 8, English, International magazine[Refereed]
Scientific journal
近視性脈絡膜血管新生(mCNV)に対して、ビスフォスフォネート(BP)薬の内服による2年間の治療効果を抗血管内皮増殖因子(VEGF)療法、光線力学療法(PDT)および無治療群と比較した。抗VEGF群の平均視力は治療開始後3ヵ月時点で有意に改善したが、24ヵ月時点では治療前視力との有意差はなかった。無治療群は有意に平均視力が悪化した。BP群、抗VEGF群、PDT群の平均視力経過はいずれも無治療群よりも有意に良好であった。中心網膜厚の平均はBP群、抗VEGF群、PDT群の全てにおいて24ヵ月後で減少した。BP群の中で4例4眼において24力月の経過中に抗VEGF療法によるブースター治療を行った。BP群の1例で内服開始後約6ヵ月で両眼の虹彩炎を生じ、内服を中止してリンデロン点眼を使用した。虹彩炎は徐々に沈静化し、視力等に影響を及ぼさなかった。BP薬の内服は2年間の視力維持に有効である可能性がある。
(公財)臨床薬理研究振興財団, Jun. 2013, 臨床薬理の進歩, (34), 86 - 92, JapanesePURPOSE: To investigate the effects of reproducibility of optical coherence tomography (OCT) measurements and imaging alignment on predictive performance for visual outcome following macular hole (MH) surgery. METHODS: We retrospectively reviewed 50 eyes that underwent MH surgery. Preoperative cross-sectional images through the center of the MH (on-center image) and through an off-center point (off-center image) were obtained from the OCT data. In each image, the following OCT parameters were either measured or calculated: minimum diameter, base diameter, hole height, temporal and nasal arm length, photoreceptor inner segment/outer segment (IS/OS) defect length, the hole form factor, the macular hole index and the tractional hole index. The IS/OS defect area was also measured. RESULTS: The reproducibility of OCT parameter values was moderate to high, and there was a significant difference in the mean measurement values between the on- and off-center images. Predictive values varied between sessions and raters, and only the preoperative photoreceptor IS/OS defect length consistently showed significant correlation with postoperative visual outcome. CONCLUSIONS: Both the reproducibility and imaging alignment might affect the predictive performance of the OCT parameter for postoperative visual outcome following MH surgery. The preoperative photoreceptor IS/OS defect length seems to be the most useful parameter in this regard.
May 2013, Japanese journal of ophthalmology, 57 (3), 308 - 15, English, Domestic magazine[Refereed]
Scientific journal
BACKGROUND: The effects of intravitreal ranibizumab (IVR) against exudative age-related macular degeneration (AMD) may be different associated with the lesion phenotype. This study was conducted to compare the outcomes of IVR between two different phenotypes of exudative AMD: typical neovascular AMD (tAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This is a retrospective cohort study of 54 eyes from 54 subfoveal exudative AMD patients (tAMD 24, PCV 30 eyes). Three consecutive IVR treatments (0.5 mg) were performed every month, followed by re-injections as needed. Change in the best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were then compared between the tAMD and PCV groups over 12 months of follow-up. RESULTS: The mean BCVA was significantly improved (-0.11 logMAR units) at month 3 after the initial IVR (p <0 .001, Wilcoxon signed-rank test), and was sustained up to 12 months in all AMD patients (p =0.02). In the subgroup analysis, the tAMD group showed a significant improvement in their mean BCVA (-0.06, -0.17, -0.15 and -0.16 logMAR units at 1, 3, 6 and 12 months, respectively), but there was only a slight but non-significant improvement in the PCV group. The improvement in the BCVA was significantly greater in the tAMD group than in the PCV group (p = 0.043, repeated measures ANOVA) over 12 months. Both phenotypes showed significant improvements in the CRT during 12 months after the initial IVR. CONCLUSIONS: IVR is an effective therapy for tAMD and PCV in the BCVA improvement in Japanese patients over 12 months of follow-up. The phenotype of tAMD showed a significantly better outcome with IVR than PCV in terms of BCVA improvement.
04 Apr. 2013, BMC ophthalmology, 13, 10 - 10, English, International magazine[Refereed]
Scientific journal
PURPOSE: Multidrug resistance protein 4 (MRP4) effluxes a wide variety of endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is exclusively expressed in vascular endothelial cells (ECs) of the retina. This study aimed to investigate the role of MRP4 in retinal vascular development. METHODS: The retinal vascular phenotype of Mrp4(-/-) mice was examined by whole-mount immunohistochemistry at P3, P6, and P14. The retinas from P6 pups that received an intraperitoneal injection of either solvent control or forskolin, an inducer of intracellular cAMP formation, at P4 and P5 were analyzed in terms of their vascular formation (vascular length, vascular branching, vascular density, and the number of tip cells), cell proliferation and apoptosis, and vessel stability. RESULTS: The Mrp4(-/-) mice exhibited no overt abnormalities in the development of the retinal vasculature, but retinal vascular development in the Mrp4(-/-) mice was suppressed in response to forskolin administration. There was a significant decrease in the vascular length, vascular branching, and vascular density, and inhibited tip cell formation at the vascular front. The forskolin-treated Mrp4(-/-) mice showed an increased number of Ki67-positive and cleaved caspase 3-positive ECs, a significant decrease in the amount of pericyte coverage, and a reduced number of empty sleeves. In pups exposed to hyperoxia (75% oxygen) from P7 to P12, the Mrp4(-/-) mice showed a significant increase in the unvascularized retinal area. CONCLUSIONS: Mrp4(-/-) mice exhibited suppressed retinal vascular development in response to forskolin treatment. Thus, Mrp4 might have protective roles in retinal vascular development by regulating the intracellular cAMP level.
07 Dec. 2012, Investigative ophthalmology & visual science, 53 (13), 8029 - 35, English, International magazine[Refereed]
Scientific journal
PURPOSE: Sweet's syndrome (SS) is a skin disorder clinically characterized by fever, neutrophilia, and painful edematous plaques that occasionally causes posterior uveitis. We present two cases of SS with panuveitis resembling Behçet's disease (BD). SUBJECTS: Two patients with panuveitis associated with SS. OBSERVATIONS: The patient in case 1 was a 57-year-old Japanese man who developed acute severe iritis with hypopyon in the left eye. Fluorescein angiography (FA) performed 1 month after treatment showed findings observed in posterior uveitis: dye leakage from the optic disc and a petaloid pattern of hyperfluorescence in the macular region. The patient in case 2 was a 64-year-old Japanese man who complained of blurred vision in his left eye. Faint flare and occasional cells were present in the left anterior chamber, 2+ cells in the anterior vitreous, and 2+ vitreous opacification in the left eye. FA demonstrated dye leakage from the optic disc and peripheral capillary vessels in both eyes. Both patients were diagnosed as having SS on the basis of fever, neutrophilia, elevated C-reactive protein, and skin biopsy results of neutrophilic infiltration without vasculitis. CONCLUSIONS: Differentiation of SS from BD based on the ocular manifestations is difficult. Ophthalmologists should bear in mind that SS can exhibit panuveitis resembling BD.
May 2012, Japanese journal of ophthalmology, 56 (3), 268 - 72, English, Domestic magazine[Refereed]
Scientific journal
Purpose. To compare the efficacy of anti-vascular endothelial growth factor (VEGF) therapy versus photodynamic therapy (PDT) for myopic choroidal neovascularization (mCNV). Methods. This study is a retrospective interventional study. Forty-two eyes from 42 patients with mCNV (36 subfoveal, 4 juxtafoveal, and 2 extrafoveal) treated and followed up for more than 6 months were included. Twenty eyes from 20 patients were treated by PDT (PDT group) at 1.5±0.9 months after the symptoms and 22 eyes from 22 patients were treated by anti-VEGF therapy (anti-VEGF group) at 0.9±0.8 months after the symptoms. Photodynamic therapy was performed, followed up, and retreated by standard procedures. Anti-VEGF therapy was repeated as needed. Gender, age, bestcorrected visual acuity (BCVA), greatest linear dimension (GLD), central retinal thickness (CRT), and outer nuclear layer (ONL) thickness at the fovea were then compared between the anti-VEGF and PDT groups. Results. No differences were detected in baseline parameters between the anti-VEGF and PDT groups. The mean BCVA (logMAR) at month 3 and 6 after the initial treatment was improved (-0.30 and -0.29) from baseline in the anti-VEGF group, which was statistically significant (p=0.0048 and 0.021, respectively). In the PDT group, modest improvements were observed in the mean BCVA at the same time periods (-0.05 and -0.10) with no statistical significance (p=0.79 and 0.90, respectively). The mean CRT was significantly reduced from baseline to month 6 in the anti-VEGF and PDT groups. The ONL thickness was significantly reduced in both groups, although the magnitude was significantly greater in the PDT group than the anti-VEGF group. Conclusions. Treatment with anti-VEGF therapy had significantly better visual outcomes than PDT for mCNV. © 2011 Wichtig Editore.
Apr. 2012, European Journal of Ophthalmology, 22 (2), 210 - 215, English[Refereed]
Scientific journal
PURPOSE: To clarify the association of cluster of differentiation 36 (CD36) variants with polypoidal choroidal vasculopathy (PCV) and compare them with those in typical neovascular age-related macular degeneration (tAMD). METHODS: We included 349 Japanese AMD patients (210 PCV, 139 tAMD) and 198 age-matched controls. Four tag single-nucleotide polymorphisms (SNPs)-rs10499862, rs3173798, rs3211883, and rs3173800-in the CD36 region were genotyped using the TaqMan assay. Allelic and genotypic frequencies of the SNPs were tested. RESULTS: Although none of the SNPs tested were associated with PCV, the allelic frequencies of rs3173798 and rs3173800 were significantly different between PCV and tAMD patients. Genotype association analysis demonstrated different associations of these two SNPs between PCV and tAMD in the genotype model. Haplotype analysis revealed that the association of the major haplotype (T-T-T-T) at four selected SNPs in CD36 differed significantly between PCV and tAMD patients. CONCLUSIONS: The CD36 region may be associated with the difference in genetic susceptibility for PCV and tAMD.
2012, Molecular vision, 18, 121 - 7, English, International magazine[Refereed]
Scientific journal
PURPOSE: To clarify the association between cluster of differentiation 36 (CD36) gene polymorphisms and the response to photodynamic therapy (PDT) in polypoidal choroidal vasculopathy (PCV). METHODS: One hundred and thirty-seven patients with PCV were enrolled. The patients were treated with PDT and followed up for more than 6 months. Retreatments were performed every 3 months as needed based on findings from angiography. Patients who showed an improvement in their best-corrected visual acuity at 6 months post-PDT were classified as PDT responders, and the others were defined as non-responders. For the 73 responders and 64 non-responders, 19 single nucleotide polymorphisms (SNPs) across the CD36 region were genotyped using the TaqMan assay. We analyzed the association between these variants and the visual outcomes of PDT. RESULTS: The allelic frequencies of the SNPs rs3211851, rs3173798, and rs3211908 showed nominally significant differences between the PDT responders and non-responders. Genotype association analysis revealed a significant association of SNP rs3173798 with the visual outcome of PDT in a dominant model. The presence of the C allele in rs3173798 was significantly associated with a poor response to PDT after multivariate logistic regression analysis with clinical pre-PDT parameters. The mean best-corrected visual acuity in the group with the TT genotype of rs3173798 was significantly improved over 12 months of follow-up after the initial PDT. CONCLUSIONS: The coding variants in CD36 are possibly associated with the visual outcome of PDT in patients with PCV.
2012, Molecular vision, 18, 2796 - 804, English, International magazine[Refereed]
Scientific journal
BACKGROUND: Drugs inhibiting vascular endothelial growth factor (VEGF) signaling are globally administered to suppress deregulated angiogenesis in a variety of eye diseases. However, anti-VEGF therapy potentially affects the normal functions of retinal neurons and glias which constitutively express VEGF receptor 2. Thus, it is desirable to identify novel drug targets which are exclusively expressed in endothelial cells (ECs). Here we attempted to identify an EC-specific Rho guanine nucleotide exchange factor (GEF) and evaluate its role in retinal angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: By exploiting fluorescence-activated cell sorting and microarray analyses in conjunction with in silico bioinformatics analyses, we comprehensively identified endothelial genes in angiogenic retinal vessels of postnatal mice. Of 9 RhoGEFs which were highly expressed in retinal ECs, we show that Arhgef15 acted as an EC-specific GEF to mediate VEGF-induced Cdc42 activation and potentiated RhoJ inactivation, thereby promoting actin polymerization and cell motility. Disruption of the Arhgef15 gene led to delayed extension of vascular networks and subsequent reduction of total vessel areas in postnatal mouse retinas. CONCLUSIONS/SIGNIFICANCE: Our study provides information useful to the development of new means of selectively manipulating angiogenesis without affecting homeostasis in un-targeted tissues; not only in eyes but also in various disease settings such as cancer.
2012, PloS one, 7 (9), e45858, English, International magazine[Refereed]
Scientific journal
To investigate whether retinal surface imaging by Cirrus high-definition optical coherence tomography (HD-OCT) clearly depicts the development process of a dissociated optic nerve fiber layer (DONFL) appearance after macular hole (MH) surgery. We reviewed the medical records of the patients who underwent MH surgery with internal limiting membrane peeling. The cases were then selected using three principal criteria: (1) surgeries performed by the same surgeon (S. K.), (2) pre- and postoperative Cirrus HD-OCT imaging, and (3) minimal follow-up of 3 months. All cases received a complete ophthalmologic examination. The presence/absence of a DONFL appearance was determined using a retinal surface image provided by Cirrus HD-OCT. Color fundus photographs were also used for determination if available. Fifteen cases met the criteria. A DONFL appearance was identified in 11 (73%) cases during the postoperative course by retinal surface imaging. A DONFL appearance was not detected in any OCT retinal surface image within the first postoperative month, gradually became distinct between 1 and 3 months after surgery, and remained detectable thereafter in all cases but one whose DONFL appearance became less detectable at 12 months. Indentations of the innermost retinal layer became apparent on cross-sectional OCT images as a DONFL appearance developed on OCT retinal surface images. There were two cases in which the DONFL appearance was not observed on color fundus photographs but detected on OCT retinal surface images. Retinal surface imaging provided by Cirrus HD-OCT appeared to be a promising option in evaluating a DONFL appearance after MH surgery.
Oct. 2011, International ophthalmology, 31 (5), 385 - 92, English, International magazine[Refereed]
Scientific journal
PURPOSE: The purpose of this study was to evaluate the intraocular gas dynamics after 23-gauge transconjunctival sutureless vitrectomy (TSV) as compared with 20-gauge pars plana vitrectomy (PPV). METHODS: A consecutive series of 290 eyes that experienced 20-gauge or 23-gauge vitrectomy with 25% sulfur hexafluoride (SF6) gas tamponade were retrospectively reviewed. Intraocular gas bubble size on postoperative Day 1 and Gas50, the interval to dissipate to a 50% gas fill, were evaluated. RESULTS: The mean intraocular bubble size on postoperative Day 1 was 92.0 ± 8.3% in the 20-gauge PPV cases and 83.8 ± 13.7% in the 23-gauge TSV cases (P < 0.001). The mean Gas50 was 8.6 ± 1.6 days in the 20-gauge PPV cases and 6.6 ± 2.2 days in the 23-gauge TSV cases (P < 0.001). Thorough peripheral vitrectomy and 23-gauge TSV were significantly associated with Gas50 ≤ 4 days (odds ratio, 4.62 and 16.8; P = 0.036 and P = 0.007, respectively). Among thoroughly vitrectomized eyes, 13 eyes treated with 23-gauge PPV with intraoperative suture placement at the sclerotomy sites had gas longevity comparative to those with 20-gauge PPV. CONCLUSION: Eyes treated with 23-gauge TSV tend to have earlier gas disappearance or incomplete gas fill. Intraoperative suture placement would be a solution.
Feb. 2011, Retina (Philadelphia, Pa.), 31 (2), 250 - 6, English, International magazine[Refereed]
Scientific journal
PURPOSE: To evaluate the retinal toxicity of intravitreal tissue plasminogen activator (tPA) injection for branch and central retinal vein occlusion (BRVO and CRVO) using the electroretinogram (ERG). PROCEDURES: Ten BRVO patients and 5 CRVO patients were enrolled. A complete examination including full-field ERG, visual acuity, central retinal thickness (CRT), and evaluation of systemic and ocular complications was performed before and after intravitreal tPA injection. RESULTS: No significant differences were found in the amplitude or implicit time of any ERG component after tPA injection, and no systemic or ocular complication was observed. The improvement of visual acuity was significant at month 3 in the BRVO group (p < 0.05) but not in the CRVO group. CRT significantly decreased over the course of 3 months in both groups (p < 0.01). CONCLUSION: Intravitreal tPA injection seems to be a safe and effective treatment option for macular oedema caused by retinal vein occlusions.
2011, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 226 (2), 81 - 6, English, International magazine[Refereed]
Scientific journal
Purpose. To evaluate the early response to intravitreal ranibizumab (IVR) in two different phenotypes of age-related macular degenerations (AMD): typical neovascular AMD (tAMD) and polypoidal choroidal vasculopathy (PCV). Methods. Sixty eyes from 60 patients (tAMD 28, PCV 32 eyes) were recruited. Three consecutive IVR treatments (0.5 mg) were performed every month. Change in the best-corrected visual acuity (BCVA) and central retinal thickness (CRT) was then compared between the tAMD and PCV groups. Results. The mean BCVA logMAR was significantly improved at month 1 and month 3 after the initial IVR in the tAMD group, but there was no change in the PCV group. Both phenotypes showed significant improvements in the CRT during the 3 months after the initial IVR. There were no significant differences in the improvements of the CRT in the tAMD versus the PCV group. In the stepwise analysis, a worse pretreatment BCVA and tAMD lesions were significantly beneficial for a greater improvement of BCVA at 3 months after the initial IVR. Conclusions. The phenotype of tAMD showed a significantly better early response to IVR than PCV in terms of BCVA improvement.
2011, Journal of ophthalmology, 2011, 742020 - 742020, English, International magazine[Refereed]
Scientific journal
PURPOSE: To investigate whether the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2) has a different hereditary contribution in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS: We initially conducted a comparative genetic analysis of neovascular AMD and PCV, genotyping the ARMS2 A69S variant in 181 subjects with neovascular AMD, 198 subjects with PCV, and 203 controls in a Japanese population. Genotyping was conducted using TaqMan technology. Results were then integrated into a meta-analysis of previous studies representing an assessment of the association between the ARMS2 A69S variant and neovascular AMD and/or PCV, comprising a total of 3,828 subjects of Asian descent. The Q-statistic test was used to assess between-study heterogeneity. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a fixed effects model. RESULTS: The genetic effect of the A69S variant was stronger in neovascular AMD (allelic summary OR=3.09 [95% CI, 2.71-3.51], fixed effects p<0.001) than in PCV (allelic summary OR=2.13 [95% CI, 1.91-2.38], fixed effects p<0.001). The pooled risk allele frequency was significantly higher in neovascular AMD (64.7%) than in PCV (55.6%). The population attributable risks for the variant allele were estimated to be 43.9% (95% CI, 39.0%-48.4%) and 29.7% (95% CI, 25.4%-34.0%) for neovascular AMD and PCV, respectively. No significant between-study heterogeneity was observed in any statistical analysis in this meta-analysis. CONCLUSIONS: Our meta-analysis provides substantial evidence that the ARMS2 A69S variant confers a significantly higher risk of neovascular AMD than PCV. Furthermore, there is compelling evidence that the risk attributable to the A69S variant differs between geographic atrophy and neovascular AMD. Together with defining the molecular basis of susceptibility, understanding the relationships between this genomic region and disease subtypes will yield important insights, elucidating the biologic architecture of this phenotypically heterogeneous disorder.
2011, Molecular vision, 17, 3574 - 82, English, International magazine[Refereed]
Scientific journal
BACKGROUND: Genetic variants in the complement component 3 gene (C3) have been shown to be associated with age-related macular degeneration (AMD) in Caucasian populations of European descent. In particular, a nonsynonymous coding variant, rs2230199 (R102G), is presumed to be the most likely causal variant in the C3 locus based on strong statistical evidence for disease association and mechanistic functional evidence. However, the risk allele is absent or rare (<1%) in Japanese and Chinese populations, and the association of R102G with AMD has not been reported in Asian populations. Genetic heterogeneity of disease-associated variants among different ethnicities is common in complex diseases. Here, we sought to examine whether other common variants in C3 are associated with wet AMD, a common advanced-stage manifestation of AMD, in a Japanese population. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 13 tag single nucleotide polymorphisms (SNPs) that capture the majority of common variations in the C3 locus and tested for associations between these SNPs and wet AMD in a Japanese population comprising 420 case subjects and 197 controls. A noncoding variant in C3 (rs2241394) exhibited statistically significant evidence of association (allelic P = 8.32 × 10(-4); odds ratio = 0.48 [95% CI = 0.31-0.74] for the rs2241394 C allele). Multilocus logistic regression analysis confirmed that the effect of rs2241394 was independent of the previously described loci at ARMS2 and CFH, and that the model including variants in ARMS2 and CFH plus C3 rs2241394 provided a better fit than the model without rs2241394. We found no evidence of epistasis between variants in C3 and CFH, despite the fact that they are involved in the same biological pathway. CONCLUSIONS: Our study provides evidence that C3 is a common AMD-associated locus that transcends racial boundaries and provides an impetus for more detailed genetic characterization of the C3 locus in Asian populations.
2011, PloS one, 6 (12), e28847, English, International magazine[Refereed]
Scientific journal
The multidrug resistance protein (MRP) MRP4/ABCC4 is an ATP-binding cassette transporter that actively effluxes endogenous and xenobiotic substrates out of cells. In the rodent retina, Mrp4 mRNA and protein are exclusively expressed in vascular endothelial cells, but the angiogenic properties of Mrp4 are poorly understood so far. This study aims to explore the angiogenic properties of MRP4 in human retinal microvascular endothelial cells (HRECs) utilizing the RNA interference (RNAi) technique. MRP4 expression was decreased at the mRNA and protein levels after stimulation with exogenous vascular endothelial growth factor in a dose-dependent manner. RNAi-mediated MRP4 knockdown in HRECs do not affect cell proliferation but enhances cell migration. Moreover, cell apoptosis induced by serum starvation was less prominent in MRP4 siRNA-treated HRECs as compared to control siRNA-treated HRECs. In a Matrigel-based tube-formation assay, although MRP4 knockdown did not lead to a significant change in the total tube length, MRP4 siRNA-treated HRECs assembled and aggregated into a massive tube-like structure, which was not observed in control siRNA-treated HRECs. These results suggest that MRP4 is uniquely involved in retinal angiogenesis.
01 Oct. 2010, Biochemical and biophysical research communications, 400 (4), 593 - 8, English, International magazine[Refereed]
Scientific journal
PURPOSE: Idiopathic macular holes (MHs) may occur bilaterally, and the spontaneous closure of MHs was documented previously. The median interval between the onset of MHs in each eye was reported to be 17.5 months. METHOD: We report a case of bilateral MHs which occurred and resolved spontaneously over a very short interval. RESULTS: A 48-year-old woman with no history of ocular disease complained of a central scotoma and metamorphopsia in the left eye. Stage 1A MH was diagnosed in the left eye on the initial visit, which resolved spontaneously with vitreofoveal separation after 1 month. After an additional month, she complained of a similar visual disturbance in the right eye. Stage 1B MH was found in the right eye, which showed spontaneous closure after 1 month in the same manner as the left eye. CONCLUSION: We present a unique case of bilateral MHs which occurred and resolved spontaneously within a very short time period. Careful observation of the non-involved eye is needed to address the risk of early onset bilateral MHs.
13 Sep. 2010, Case reports in ophthalmology, 1 (2), 47 - 52, English, International magazine[Refereed]
Scientific journal
[Refereed]
Scientific journal
Purpose. Choroidal neovascularization (CNV) is often associated with age-related macular degeneration (AMD) and pathological myopia (PM). Bisphosphonates, the drug of choice to treat osteoporosis, have been recently reported to have anti-angiogenic effects. The purpose of this study is to investigate the therapeutic effects of oral bisphosphonates for CNV in humans. Methods. Thirty-six consecutive cases with CNV due to AMD or PM who declined anti-VEGF therapy were recruited. The patients were prescribed 5 mg of oral alendronates daily for 6 months. The best-corrected visual-acuity (BCVA), the lesion size in fundus photographs and fluorescein angiography, foveal thickness and total macular volume in optical coherence tomography were compared between pre- and post-treatment. Results. The mean BCVA of the patients was significantly improved after a months with the treatment in the AMD group. In the PM group, the mean BCVA was maintained up to 6 months with the treatment. The mean lesion size was significantly decreased by 3 months in both groups. The averages of foveal thickness and total macular volume were significantly reduced after 1 month of treatment in the AMD group.Conclusions. Oral bisphosphonate should be further investigated as a possible therapeutic and preventive drug for CNV due to AMD and PM.
2010, Journal of ophthalmology, 2010, English, International magazine[Refereed]
Scientific journal
ATP-binding cassette (ABC) transporters at the blood-brain barrier (BBB) are responsible for the majority of the transcellular movement of various substrates, including various drugs, and contribute to the maintenance of brain homeostasis. Clinically, the abnormal expression of efflux transporters at the BBB is known to be associated with brain diseases such as epilepsy. In the retina, vascular endothelial cells outline the inner blood-retinal barrier (BRB) like the BBB, and some ABC efflux transporters are expressed in the adult retina. However, little is known about ABC transporter expression during retinal development or under pathological conditions. Here, we examined ABC transporter expression in the mouse retina, and demonstrated that P-glycoprotein (P-gp)/ABCB1, Mrp4/ABCC4, and Bcrp/ABCG2 were almost uniformly expressed in these blood vessels, including the capillaries and large vessels. This expression persisted throughout the developmental period, and the hyaloid vessels that normally feed the developing eye were immunoreactive for P-gp and Mrp4. Furthermore, we investigated ABC transporter expression in pathological angiogenesis using an oxygen-induced retinopathy model where hypoxia-induced preretinal neovascularization occurred around the central avascular retina. P-gp was prominently immunoexpressed but Mrp4 and Bcrp were weakly immunoexpressed, in the preretinal neovascular tufts. These findings will be helpful for understanding the roles of ABC transporters during both physiological and pathological retinal angiogenesis, and might provide new insights for safe and effective drug administration to infants or patients with angiogenic ocular disease.
04 Aug. 2009, Brain research, 1283, 186 - 93, English, International magazine[Refereed]
Scientific journal
[Refereed]
Scientific journal
PURPOSE: To report a case of familial exudative vitreoretinopathy (FEVR) rapidly resolved by intravitreal injection of bevacizumab. METHODS: A 36-year-old woman complained about floaters and visual field defect. Funduscopic examinations revealed retinal vessel anastomosis located between the equator and ora serrata in both eyes. The right eye was accompanied with slight vitreous hemorrhage. Since the patient declined retinal cryopexy for cosmetic reasons, intravitreal bevacizumab injections (1.25 mg/0.05 ml) were performed in both eyes. RESULTS: Treatment resulted in the rapid regression and the accelerated fibrosis of neovascular tissues. At 4-month follow-up in the right eye and 1-month follow-up in the left, no signs of systemic or ocular complications were detected. CONCLUSIONS: Intravitreal injection of bevacizumab may be considered as an alternative method in treating FEVR.
Dec. 2008, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 246 (12), 1787 - 9, English, International magazine[Refereed]
Scientific journal
Scientific journal
Background/aims: To assess the outcomes of 23-gauge sutureless transconjunctival vitrectomies (TSV), as compared with 25-gauge TSV in macular hole surgeries. Methods: A retrospective, consecutive, interventional case series of 47 eyes with idiopathic macular holes treated by 23- or 25-gauge TSV were analysed. Results: The operative time was 37.2 (SD 8.9) min with 23-gauge TSV and 34.2 (8.7) min with 25-gauge TSV (p = 0.388). The anatomical success rate was 96% with 23-gauge TSV and 92% with 25-gauge TSV (p > 0.999). The logarithm of the minimum angle of resolution of best-corrected visual acuity (BCVA) at the sixth postoperative month was 0.19 (0.16) with 23- gauge TSV and 0.19 (0.25) with 25-gauge TSV (p = 0.521). Postoperative improvement in BCVA was comparable between the two TSVs. IOP on postoperative day 1 was lower with 25-gauge TSV (12.3 (4.9) mm Hg) than with 23-gauge TSV (17.4 (5.8) mm Hg) (p = 0.036). Complications included retinal break, intraoperative bleeding and slippage of the infusion cannula with 23-gauge TSV, while retinal detachment and postoperative hypotony occurred in the 25-gauge TSV group (p = 0.570). Conclusion: 23- gauge TSV appears to be as safe and effective as 25-gauge TSV in macular hole surgery.
B M J PUBLISHING GROUP, Sep. 2008, BRITISH JOURNAL OF OPHTHALMOLOGY, 92 (9), 1261 - 1264, EnglishScientific journal
Purpose To test whether Heidelberg Retina Tomograph (HRT) is applicable to assess the optic nerve head (ONH) configuration of the atrophic phase of non-glaucomatous optic neuropathy when a default set of the reference plane is used. Methods Ten eyes with non-arteritic anterior ischaemic optic neuropathy (NAION), 17 eyes with Leber's hereditary optic neuropathy (LHON), 40 eyes with compressive optic neuropathy (CON) owing to chiasmal tumour, and 241 eyes of control individuals were examined with HRT using the default reference plane. The global values of HRT parameters were evaluated among the groups of patients and controls. The sectoral measurements of the eyes with LHON and CON were compared with controls. To eliminate the influence of disc size and age on HRT measurements, eyes with disc area-and age-matched normal controls were used for comparison with eyes with NAION and LHON. Results Cup parameters in eyes with NAION were similar to those in controls. The retinal nerve fibre layer (RNFL) thickness was significantly thinner in eyes with NAION than that of controls. The eyes with LHON had significantly larger cup parameters, smaller rim volume, and thinner mean RNFL thickness than controls. Eyes with CON had significantly larger rim area and smaller cup parameters but similar RNFL thickness compared with controls. Conclusions When the default reference plane is used, HRT can measure the ONH configuration in eyes with NAION and LHON as expected. However, caution must be made to interpret the parameters obtained from the eyes with CON.
NATURE PUBLISHING GROUP, Sep. 2008, EYE, 22 (9), 1154 - 1160, English[Refereed]
Scientific journal
Aims To assess the changes in macular and peripapillary retinal nerve fibre layer (RNFL) thickness in eyes with unilateral optic atrophy and to evaluate the relationship between retinal thickness and visual function. Methods Enrolled were 22 patients with unilateral optic atrophy. Macular thickness at the divided nine areas and peripapillary RNFL thickness in quadrantic sections were measured by optical coherence tomography. Thickness values in the affected eyes were compared with those in the contralateral unaffected eyes. The correlation of foveal thickness with best-corrected visual acuity (BCVA) was evaluated. The correlation between retinal thickness and the remaining visual field area circumscribed with I-4-e isopter in superior and inferior hemifield was assessed. Results Macular thinning was observed in all areas (P < 0.001 in each area) other than the fovea (P=0.068). Peripapillary RNFL thickness decreased in all quadrantic sections (P < 0.001 in each section). The affected to unaffected eye ratio of retinal thickness was more than 0.6 in each area. BCVA did not correlate with foveal thickness (correlation coefficient 0.094, P=0.668). Although not statistically significant (P=0.281, superior hemifield; P=0.053, inferior hemifield), there was a tendency that eyes with severe visual field loss show more marked retinal thinning. Conclusions Macular thinning with the preserved foveal thickness is a hallmark of eyes with optic atrophy. Together with no correlation between foveal thickness and BCVA, this finding would help in differential diagnosis of macular and optic nerve diseases.
NATURE PUBLISHING GROUP, Aug. 2006, EYE, 20 (8), 882 - 887, English[Refereed]
Scientific journal
The vascular system of the mouse retina provides a useful model for analyzing the molecular and cellular mechanisms regulating angiogenesis because (1) hierarchical vascular networks are newly formed only after birth, (2) the cellular components involved in angiogenesis are well characterized, and (3) all the processes are accessible for monitoring and manipulation. In this article, we present an overview of our current understanding of the process of retinal angiogenesis and describe a number of methodologies applicable to experimental manipulation of the retinal vascular system.
10 Mar. 2006, Experimental cell research, 312 (5), 676 - 83, English, International magazine[Refereed]
Scientific journal
In response to hypoxia, hypoxia-inducible factors act as the primary proangiogenic triggers by regulating transcription levels of target genes, including VEGF. However, little is known about the specific factors that control other components of the angiogenic process, particularly formation of matrix scaffolds that promote adhesion and migration of endothelial cells. We show that in the postnatal mouse retina, the orphan nuclear receptor tailless (Tlx) is strongly expressed in the proangiogenic astrocytes, which secrete VEGF and fibronectin. Tlx expression by retinal astrocytes is controlled by oxygen concentration and rapidly downregulated upon contact with blood vessels. In mice null for Tlx, retinal astrocytes maintain VEGF expression; however, the extracellular assembly of fibronectin matrices by astrocytes is severely impaired, leading to defective scaffold formation and a complete failure of normal retinal vascular development. This work identifies Tlx as an essential component of the molecular network involved in the hypoxia-inducible proangiogenic switch in retinal astrocytes.
Feb. 2006, The Journal of clinical investigation, 116 (2), 369 - 77, English, International magazine[Refereed]
Scientific journal
Background: Optic tract syndrome (OTS) is characterized by incongruous homonymous hemianopia and a perpendicular pattern of bilateral optic atrophy due to the optic tract lesion. However, loss of retinal nerve fiber layer thickness (RNFLT) associated with OTS has not been quantitatively assessed. Case: A 20-year-old woman with blunt head trauma showed normal visual acuity, color vision, ocular motility, and intraocular pressure. Because of a relative afferent pupillary defect in her left eye and left-sided homonymous hemianopia, we suspected right-sided optic tract damage, although magnetic resonance imaging detected no intracranial lesion. Observations: Using optical coherence tomography (OCT), the RNFLT of this case was measured at 31 months after the trauma and compared with age-matched normal controls (n = 41). Nasal, temporal, superior, and inferior quadrant RNFLT was reduced by 22%, 21%, 5%, and 46% in the right eye and 76%, 64%, 25%, and 27% in the left eye, respectively. The reduction was > 3 × the standard deviation of the normal mean values in the nasal and temporal quadrants of the left eye and in the inferior quadrant of the right eye. Conclusions: OCT can determine the RNFLT reduction corresponding to the characteristic patterns of optic atrophy of OTS. © Japanese Ophthalmological Society 2005.
Jul. 2005, Japanese Journal of Ophthalmology, 49 (4), 294 - 296, English[Refereed]
Scientific journal
PURPOSE: To introduce a case of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome with bilateral cystoid macular edema (CME). DESIGN: Interventional case report. METHODS: Temporal changes of serum vascular endothelial growth factor (VEGF) levels and macular thickness were evaluated. RESULTS: A 53-year-old woman with POEMS syndrome was referred complaining of long-standing impaired vision. Typical CME demonstrating petal-like dye pooling was observed in both eyes. After subtenon administrations of triamcinolone acetonide (TA), pars plana vitrectomy, and intraocular TA injection in the right eye, macular thickness decreased. Intraocular VEGF levels were <31 pg/ml at the vitrectomy and intraocular TA injection, whereas serum the VEGF level was >2000 pg/ml throughout the follow-up periods. In the untreated left eye, macular thickness altered related to serum VEGF level. CONCLUSIONS: Based on the low intraocular VEGF level and serum VEGF-related change of macular thickness, elevated serum VEGF might be a cause of CME in POEMS syndrome.
Mar. 2005, American journal of ophthalmology, 139 (3), 563 - 6, English, International magazine[Refereed]
Scientific journal
小児白内障術後の近見・遠見視力発達について検討した.対象は,小児白内障手術を行った30例45眼(男児17例25眼,女児13例20眼)で,片眼は15例15眼,両眼は15例30眼であった.診療録で3歳から7歳まで6ヵ月毎の遠見視力(FV)と近見視力(NV)を片眼,両眼で比較した.その結果,各年齢時で片眼群ではFV,NVとも視力不良が多く,両眼群では良好な経過を辿る例が多かった.経過を通じ,両群ともFVとNVとの間に有意差はなかった.7歳時での視力の中間値は片側群ではFV 0.45,NV 0.35で,両眼群ではFV 1.0,NV 1.0であった.45眼中3眼(7%)でFVとNVに3段階以上の差を認め,2眼(片側群の1眼,両側群の1眼)はNVが良好で,1眼(片側群)はFVが良好であった.術後,大半の症例で調節力のないNVでもFVと同様の発達を認めたが,両者の発達に解離を認める症例も少数あり,FVとともにNVにも注意深い経過観察が必要と考えられた
眼科臨床医報会, Mar. 2005, 眼科臨床医報, 99 (3), 231 - 233, Japanese[Refereed]
Scientific journal
[Refereed]
Scientific journal
OBJECTIVES: To analyze retinal nerve fiber layer (RNFL) thickness in eyes with band atrophy by use of optical coherence tomography (OCT) and to evaluate the ability of OCT to detect this characteristic pattern of RNFL loss. DESIGN: Cross-sectional, retrospective study. PARTICIPANTS: Thirty-four eyes of 18 patients with bitemporal hemianopia caused by optic chiasm compression by chiasmal tumors were studied. All eyes were divided into 3 groups according to visual field loss grading after Goldmann perimetry. INTERVENTIONS: Retinal nerve fiber layer thickness measurements with OCT. MAIN OUTCOME MEASURES: Retinal nerve fiber layer thickness around the optic disc was measured by OCT (3.4-mm diameter circle). Calculation of the changes in OCT parameters, including the horizontal (nasal + temporal quadrant RNFL thickness) and vertical values (superior + inferior quadrant RNFL thickness) was based on data from 160 normal eyes. Comparison between the 3 visual field grading groups was done with the analysis of variance test. The receiver operating characteristic (ROC) curve for the horizontal and vertical value were calculated, and the areas under the curve (AUC) were compared. RESULTS: Retinal nerve fiber layer thickness in eyes with band atrophy decreased in all OCT parameters. The reduction rate in average and temporal RNFL thickness and horizontal value was correlated with visual field grading. The AUC of horizontal value was 0.970+/-0.011, which was significantly different from AUC of vertical value (0.903+/-0.022). CONCLUSIONS: The degree of RNFL thickness reduction correlated with that of visual field defects. Optical coherence tomography was able to identify the characteristic pattern of RNFL loss in these eyes.
Dec. 2004, Ophthalmology, 111 (12), 2278 - 83, English, International magazine[Refereed]
Scientific journal
PURPOSE: To evaluate whether an index based on hole configuration can be used to predict visual outcome in eyes with idiopathic macular holes. DESIGN: Prospective interventional case series. METHODS: Thirty-five eyes of 32 patients with idiopathic stage 2 or 3 macular hole were enrolled in this study. The best-corrected visual acuity (BCVA), cross-sectional image of the macular hole by optical coherence tomography (OCT), and retinal thickness in the central (<1000 microm), inner (1000 to 2220 microm), and outer ring areas (2220 to 3450 microm) as defined by the OCT retinal mapping program were evaluated preoperatively and at 1, 3, 6, and 12 months postoperatively. The change in retinal thickness of the inner ring area at the 6-month postoperative period was used to evaluate the degree of preoperative retinal deformation. The macular hole index (MHI) (ratio of hole height to base diameter of hole) was calculated and correlated with minimum diameter of hole, base diameter of hole, the postoperative decrease in macular thickness, and the postoperative BCVA. The postoperative BCVA was further evaluated in two patient-matched groups. RESULTS: Retinal thickness values in the inner ring area were decreased at the 1-month postoperative period. MHI significantly correlated with the postoperative decrease in macular thickness in the inner ring area at 6 months (correlation coefficient = -0.632, P = .030, Spearman analysis) and with the postoperative BCVA (P = .013, multiple regression analysis). Postoperative BCVA in the MHI >/=0.5 group was better than that in the MHI <0.5 group (P = .032, Mann-Whitney test). CONCLUSIONS: The MHI is a ratio easily calculated from OCT transverse images of the macular area. The MHI represents the preoperative configuration of a macular hole and is a prognostic factor for visual outcome.
Nov. 2004, American journal of ophthalmology, 138 (5), 709 - 16, English, International magazine[Refereed]
Scientific journal
M-CHARTSTMを用いて特発性黄斑上膜(EMM)と中心性漿液性脈絡網膜症(CSC)における視力障害の程度と変視量の関係を解析し,変視の発生機序を検討した.Gass分類grade3のみのEMM(23例27眼,平均62.1歳),CSC(22例22眼,平均46.1歳)を対象とし,視力測定とM-CHARTSTMにて縦横の変視量の測定を行った.その結果,EMMの視力は縦の変視量と相関したが,横の変視量との相関はなく,CSCの視力は縦方向,横方向とも変視量と相関しなかった.また,EMM,CSCともに軽微な視力障害においても変視量の大きい場合が認められた.EMMとCSCでは変視と視力低下の発生に要する条件は異なり,EMMでは定量化された横方向の変視は視力障害よりも自覚症状の検査データとして捉え易く,CSCでは縦・横方向の変視は視力障害よりも出現しやすい視機能障害であると考えられた
日本眼科紀要会, Oct. 2004, 日本眼科紀要, 55 (10), 801 - 803, JapanesePurpose: To investigate the molecular mechanisms for cell growth inhibition or apoptosis in human retinal pigment epithelium (RPE) cells after ionizing radiation. Methods: Cell survival studies, a TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay, and a caspase-3 immunocytochemical analysis were performed on irradiated ARPE-19 cell cultures at different time periods. Transcriptional levels of p53, p21, Bax, Fas/Fas-L, vascular endothelial growth factor (VEGF), and pigment epithelium-derived growth factor (PEDF) were evaluated by semiquantitative reverse transcriptional polymerase chain reaction. Mutations in the p53 gene were analyzcd by DNA sequencing. Protein levels of p53, VEGF, and PEDF were evaluated by Western blot. Results: Cell viability was inversely related to radiation dose. TUNEL-positive cells were detected 6h after radiation exposure. Caspase-3 immunocytochemical analysis revealed increased immunoreactivity in the TUNEL-positive cells. Levels of p53, p21, and Bax mRNA were greatest at the 2-h postradiation period. VEGF and PEDF mRNA and protein levels were constant. Protein levels of p53 were increased at the 4- and 6-h postradiation period. Conclusions: Ionizing radiation induces apoptosis in normal proliferating RPE cells through p53 activation, without affecting expression of VEGF or PEDF. We documented a molecular basis for explaining the decrease in effectiveness of radiation therapy, particularly for age-related macular degeneration. In the clinical setting, selection of appropriate radiation therapy methods and the doses for specific diseases need careful evaluation. © Japanese Ophthalmological Society 2004.
Mar. 2004, Japanese Journal of Ophthalmology, 48 (2), 106 - 114, English[Refereed]
Scientific journal
PURPOSE: To report a novel homozygous RDH5 gene mutation in a 76-year-old fundus albipunctatus who developed macular atrophy with the disappearance of white dots. DESIGN: Observational case report. METHODS: Direct genomic sequencing for RDH5 mutations was done after complete ophthalmic examination. RESULTS: Fundoscopy revealed only macular atrophy with notable absence of white dots. A homozygous G490T (Val164Phe) missense RDH5 gene mutation was detected. CONCLUSIONS: This is the first reported long-term case of fundus albipunctatus demonstrating macular atrophy with fading of the typical white dots. Gene studies may be the only method for distinguishing fundus albipunctatus from other types of macular atrophy in the elderly.
Sep. 2003, American journal of ophthalmology, 136 (3), 572 - 4, English, International magazine[Refereed]
Scientific journal
Bilateral congenital superior oblique palsies manifested in a 4-year-old girl after being hit in the left eye by the nib of a ballpoint pen. Two weeks after the trauma, the best-corrected visual acuity in the left eye was 0.5, and head tilt to the right began to manifest. Two months later, she developed a 14 prism diopter (PD) hypertropia with overaction of the inferior oblique muscle of the left eye. A positive Bielschowsky head-tilt test in both sides was elicited. Three months into occlusion treatment, the left visual acuity improved to 1.0, although a 30 PD hypertropia persisted. Tenotomy of the inferior oblique muscle and recession of the superior rectus muscle in the left eye were performed. There were no noted abnormalities in the point of trauma of the left superior oblique muscle. Post-operatively, the head tilt disappeared and the deviation decreased to 4 PD.
SWETS AND ZEITLINGER B V, 2003, PROGRESS IN STRABISMOLOGY, 125 - 128, English[Refereed]
International conference proceedings
ぶどう膜炎続発緑内障では視野障害の進行スピードが速いことから厳格な眼圧コントロールが必要となる。ぶどう膜炎では炎症と治療薬のステロイドの両方によって隅角部における房水排出が障害されることから、経過観察中に点眼薬のみでの眼圧コントロールが困難になり観血的手術が必要となる症例が多い。また、術後炎症が生じやすいことから術式選択では侵襲の程度が重要となる。筆者の開発したテノン開創器を用いた線維柱帯切除術は低侵襲に十分な眼圧下降効果が期待できることから、ぶどう膜炎続発緑内障の長期視機能維持に貢献できるものと考える。(著者抄録)
(株)北隆館, Feb. 2020, Precision Medicine, 3 (2), 155 - 160, Japanese<文献概要>POINT ●現在わが国で眼疾患に保険適用のある生物学的製剤は4剤であり,抗VEGF薬と抗TNFα薬に大別される。●抗VEGF薬にはラニビズマブとアフリベルセプトがある。いずれも滲出型AMD,DME,RVOに伴う黄斑浮腫,mCNVに適用を有し,多くの患者で視力の向上が期待できる。●抗TNFα薬についてはインフリキシマブとアダリムマブが認可されている。前者はBehcet病による難治性網膜ぶどう膜炎に,後者は既存治療で効果不十分な非感染性の中間部,後部または汎ぶどう膜炎に,それぞれ使用され,患者の視機能予後を改善させることがわかっている。●抗VEGF薬については,頻回投与に伴う高額な治療費や治療抵抗例の存在などが問題となっている。抗TNFα薬については,結核を含む重篤な有害事象や二次無効に対する対策が必要である。
(株)医学書院, Oct. 2019, 臨床眼科, 73 (11), 31 - 38, Japaneseサルコイドーシスは炎症の寛解と増悪をくり返す慢性炎症性疾患であり、良好な視機能と全身状態を長期的に維持することが目標となる。眼サルコイドーシスでは短期的には消炎を得られるが、「どの程度まで炎症をコントロールすべきか?」、「副腎皮質ステロイドをどのように使用するか?」、「合併症対策をどうするか?」といったことで悩むことも多い。患者背景や状況を総合的に勘案して長期的な管理プランを立てることをお勧めしたい。(著者抄録)
(株)先端医学社, Oct. 2019, Retina Medicine, 8 (2), 139 - 144, Japanese自己免疫疾患・膠原病では全身の臓器に炎症・免疫反応が生じることからぶどう膜炎を随伴することがある。ぶどう膜炎は副腎皮質ステロイド点眼のみで改善する軽症のものから適切な治療が行われなければ失明に至る重症のものまで多岐にわたることから、背景にある全身疾患の特徴をよく理解し適切な診断と治療を行うことが重要となる。自己免疫疾患・膠原病では長期管理が必要となることから、随伴するぶどう膜炎だけでなく治療薬の眼副作用にも留意しながら経過観察することが望ましい。(著者抄録)
(株)全日本病院出版会, Apr. 2019, OCULISTA, (73), 47 - 54, Japanese近年の眼底イメージングの進歩により、糖尿病網膜症における細小血管障害の診断技術は飛躍的に向上した。しかし、その背景にある、細胞・分子レベルの異常については、未だ不明な点が多い。そこで我々は、糖尿病網膜症と同様の血管病変をマウスで再現し、生体イメージングを含むさまざまな解析手法を統合することにより、病態解明と新規創薬開発を目指した基礎研究に取り組んできた。1.生体マウス網膜イメージング 糖尿病網膜症の発症・進展過程では、さまざまな細胞がダイナミックに形態を変化させ、網膜組織内を移動すると考えられる。こうした細胞動態を捉えるため、我々は生体マウス網膜におけるリアルタイム・イメージング技術の開発を進めてきた。我々はまず、麻酔下のマウスで進行する白内障を防止し、6時間以上にわたって眼底透見性を維持するコンタクトレンズを開発した。次にこのコンタクトレンズを、共焦点蛍光顕微鏡や二光子励起蛍光顕微鏡と組み合わせることにより、生理的および病的状況における網膜ミクログリアやマクロファージ、さらに網膜循環内の白血球や血流の動態を観察することに成功した。こうした技術を応用することにより、網膜の恒常性維持や疾患における分子メージングも可能になると期待される。2.ペリサイト消失よる網膜血管異常 1960年代に報告されたヒト眼の病理組織解析をもとに、糖尿病網膜症では毛細血管壁のペリサイトが消失することによって、多様な血管障害が発症すると考えられてきた。しかし、高血糖モデル動物ではヒト網膜症と同様の病理変化を再現できないため、ペリサイト消失の病態生理学的意義については十分に解明されていない。こうした問題を克服するため、我々はplatelet-derived growth factor receptorβに対するモノクローナル抗体を新生仔マウスに投与することにより、高血糖を介さずに網膜血管壁のペリサイト集積を阻害する実験モデルを確立した。ペリサイトを消失した網膜では、血管壁が拡張・蛇行するとともに多数の毛細血管瘤が形成され、血管透過性の亢進に伴って浮腫・出血が急速に進行した。さらにペリサイト消失網膜に浸潤したマクロファージと内皮細胞が、vascular endothelial growth factor A、placental growth factor、angiopoietin-2を介した連鎖回路を形成することにより、炎症が遷延し、血管壁バリア機能が不可逆的に破綻することが明らかとなった。これらの結果から、糖尿病網膜症にみられる一連の病理変化が、ペリサイト消失を契機として連続的に進行しうると考えられた。3.虚血網膜における血管再生 増殖糖尿病網膜症では、新生血管が硝子体腔に向かって伸長するため、網膜虚血が一向に改善されない。こうした状況において新生血管を網膜内に誘導し、機能的血管網を再生することができれば、網膜虚血に対する根治療法の開発につながると期待される。そこで我々は、新生仔マウスにおいて新生血管が網膜内に整然と伸長する過程を解析することにより、ニューロン由来のsemaphorin 3E(Sema3E)が内皮細胞のPlexinD1受容体に結合して低分子量G蛋白質RhoJを活性化し、誤った方向に伸長する血管新生を退縮させることを明らかにした。我々はさらに、虚血網膜症モデルマウスの眼内にSema3E蛋白質を投与して、硝子体腔に逸脱する新生血管のPlexinD1を活性化することにより、網膜血管再生に影響を及ぼすことなく、異常血管新生を選択的に阻害することに成功した。これらの結果から、Sema3E-PlexinD1-RhoJシグナルの活性化による、網膜血管再生療法の可能性が示唆された。(著者抄録)
(公財)日本眼科学会, Mar. 2019, 日本眼科学会雑誌, 123 (3), 312 - 336, JapaneseIntroduction scientific journal
Introduction scientific journal
Introduction scientific journal
Introduction scientific journal
Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities-including hyperpermeability, hypoperfusion, and neoangiogenesis-that eventually lead to anatomical and functional alterations in retinal neurons and glial cells. Recent advances in retinal imaging systems using optical coherence tomography technologies and pharmacological treatments using anti-vascular endothelial growth factor drugs and corticosteroids have revolutionized the clinical management of DR. However, the cellular and molecular mechanisms underlying the pathophysiology of DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects of subclinical and early DR. Conversely, non-diabetic mouse models that represent the hallmark vascular disorders in DR, such as pericyte deficiency and retinal ischemia, have provided clues toward an understanding of the sequential events that are responsible for vision-impairing conditions. In this review, we summarize the clinical manifestations and treatment modalities of DR, discuss current and emerging concepts with regard to the pathophysiology of DR, and introduce perspectives on the development of new drugs, emphasizing the breakdown of the blood-retina barrier and retinal neovascularization.
Oct. 2018, Diabetes & metabolism journal, 42 (5), 364 - 376, English, International magazine[Refereed]
Introduction scientific journal
Introduction other
Meeting report
Summary international conference
Meeting report
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目的:経結膜硝子体手術と同時に行う小切開白内障手術での最適な切開の大きさについての報告。対象と方法:過去7ヵ月間に23ゲージ経結膜硝子体手術併用の小切開白内障手術を行った72例72眼を対象とした。42眼では眼内レンズを非wound-assisted法で,30眼ではwound-assisted法で挿入した。これらについてhydrationなしに硝子体手術が可能である白内障手術の切開径を検索した。結果:Hydrationなしで硝子体手術が可能な症例は,2.65mmの切開創による非wound-assisted法で18眼中16眼(89%),2.2mmの切開創によるwound-assisted法で16眼中9眼(56%)であった。結論:経結膜硝子体手術と併用する小切開白内障手術では,非wound-assisted法では2.65mm, wound-assisted法では2.2mmの大きさの角膜切開が適している。(著者抄録)
(株)医学書院, Apr. 2008, 臨床眼科, 62 (4), 559 - 561, JapaneseSummary international conference
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右眼窩先端部症候群の75歳女.1ヵ月前から右三叉神経痛に対して副腎皮質ステロイド薬治療を受けていた.矯正視力は右眼0,左眼1.0であった.磁気共鳴画像検査(MRI)で,右後篩骨洞から眼窩先端部に浸潤性病変があり,真菌感染が疑われた.眼窩前方アプローチによる眼窩生検の結果は炎性偽腫瘍であった.抗真菌薬と副腎皮質ステロイド薬の全身投与と放射線照射で加療したが,初診から5ヵ月後に左眼視力が消失した.経鼻的に篩骨洞と視神経管開放術を行い,右後篩骨洞に大量の真菌塊が発見され,アスペルギルスが同定された.手術の3週後に真菌の脳内浸潤で死亡した
(株)医学書院, Mar. 2002, 臨床眼科, 56 (3), 283 - 287, JapaneseScholarly book
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糖尿病網膜におけるneurovascular unit障害とアストロサイトを標識し2光子顕微鏡を用いたin vivoイメージングを行った。 1. 研究内容:糖尿病マウス網膜におけるneurovascular unit障害の進行を明らかにするためにneurovascular unit構成細胞である、血管内皮細胞、周皮細胞、アストロサイト、網膜神経節細胞、ミクログリア、細胞外マトリックスの変化を免疫染色で経時的(生後4週、12週、20週)に評価しコントロールマウスと糖尿病マウス(InsCre;Pdk1flox/floxマウス)での比較を行ったところ、生後12週から細胞外マトリクスと網膜神経節細胞の変化が出現するがその他の細胞については明らかな形態変化が認められなかった(ミクログリアについては染色が上手くワークしなかったことからCx3cr1-GFPマウスを用いた解析を予定している)。網膜アストロサイトのin vivoイメージングについてはアデノ随伴ウイルスの硝子体注射によってアストロサイトを標識し撮影することに成功しているが予想に反して動きが少なく活動性の評価が難しいと思われた。また網膜像の解像度を向上させるために撮影用コンタクトレンズをさらに改良した。 2. 研究の意義: 実験結果から持続高血糖下では明らかなアストロサイト形態異常が生じる前に網膜神経節細胞障害が生じていることが確認できた。この段階におけるアストロサイトの機能的変化を可視化できれば高血糖におけるneurovascular unit障害を早期に評価できると考える。 3. 研究の重要性:本研究によって糖尿病早期における細胞レベルでの網膜機能評価を可能にするする技術が確立されれば糖尿病網膜症による失明予防に大いに貢献できると考える。
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2010~2017年に血液浄化療法を行った抗アクアポリン4抗体陽性視神経炎患者連続9例15眼の視機能予後を後ろ向きに検討した。いずれもステロイドパルス療法に抵抗性であった。12眼(80%)においてlogMAR換算で0.3以上の視力改善を見た。その大半が1年後にも良好な視力を保ち、早期の血液浄化療法が視神経脊髄炎患者の視機能回復に有効であることを報告した(Mori S, Nakamura M, et al.Jpn J Ophthalmol. 2018;62(4):525-530)。 AQP9 knowkout (KO) マウスにおいて、視神経挫滅後の網膜神経節細胞死が野生型マウスに比べて、有意に多かった。また、免疫沈降とWestern blottingにより、野生型マウスにおいては、網膜や視神経にmonocarboxylate transporter (MCT)4がAQP9と共発現していること、一方、AQP9 KOマウスや視神経挫滅後にはMCT4の発現が代償性に増加することを見出した。網膜においてエネルギー基質である乳酸の輸送を司る二つのtransporter(AQP9とMCT4)が、網膜神経節細胞において共発現していること、ならびにどちらかの一方のみ発現している場合、naiveな網膜神経節細胞の生存は維持できるが、視神経挫滅のようなストレス下では、代償機転は働くものの、生存を維持できない可能性が示唆された。
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Multidrug resistance protein 4 (Mrp4) knockout mice showed a significantly lower retinal vascular density compered with wildtype mice under streptozotocin-induced hyperglycemia. InsCreTg; Pdk1flox/flox mice exhibited thinning of laminin and decrease in the number of retinal nerve fibers prior to obvious manifestations of retinal microvascular abnormality. To evaluate the abnormality of retinal cells in an early stage of diabetes, in vivo mouse retinal imaging system with two-photon microscopy was established. These results seem to be helpful for elucidating the pathogenesis of diabetic retinopathy.
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This study showed Mrp4, an efflux transporter, is intricately associated with physiological retinal angiogenesis by regulating intracellular cAMP level. Additionally, as both the formation of avascular area and extraretinal neovascularization were exacerbated in Mrp4 knockout mice in an oxygen-induced retinopathy model, Mrp4 seems to have a suppressive role in pathological retinal angiogenesis. These results suggest that Mrp4 is a promising therapeutic target for neovascular retinal diseases.
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Multidrug resistance protein 4(MRP4) is a membrane protein that belongs to ABC transporter superfamily. In vitro analysis using human retinal microvascular endothelial cells(HRECs) showed that MRP4 knockdown enhanced cell migration, suppressed apoptosis. Moreover, MRP4 knockdown HRECs assembled and aggregated into a massive tube-like structure in a Matrigel-based tube formation assay. Functional analysis using Mrp4 knockout mice demonstrated abnormal increase in capillary density in developing retina after intraperitoneal injections of forskolin which increase the intracellular level of cAMP, an important substrate for Mrp4. These results suggest that MRP4 has anti-angiogenic properties in retinal angiogenesis.
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