中村 誠 | ![]() |
ナカムラ マコト | |
大学院医学研究科 医科学専攻 | |
教授 | |
医学 |
2011年05月 財団法人日本眼科学会, 日本眼科学会評議員会賞, 第115会日本眼科学会総会評議員会指名講演「緑内障性視神経症への挑戦.その基礎と臨床における三つの仮説の提唱
2007年04月 ロート製薬株式会社, 第12回ロート賞, 網膜内インスリン情報伝達と神経変性眼疾患との関わり
2005年09月 公益信託 須田緑内障治療研究奨励基金, 第18回須田学術奨励賞, Akt is activated via insulin / IGF-1 receptor in rat retina with episcleral vein cauterization. Brain Res 1022: 195-204, 2004
2003年03月 財団法人上原記念生命科学財団, 上原記念生命科学研究奨励, 糖尿病の実験的緑内障眼に及ぼす影響
1997年10月 日本神経眼科学会, 第9回日本神経眼科学会若手奨励賞, Evaluation of bilateral undefined optic neuropathy based on mitochondrial genetics. Neuro-opthalmology 16: 91-97, 1996
BACKGROUND AND OBJECTIVES: This study aimed to compare the efficacy of fluorescein angiography (FA)-guided and indocyanine green angiography (ICGA)-guided half-time photodynamic therapy (PDT) for central serous chorioretinopathy (CSC). SUBJECTS AND METHODS: Medical records of 61 eyes of 61 CSC patients who underwent half-time PDT were retrospectively reviewed. The irradiation area was determined using information from FA or ICGA with physicians' discretion. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SCT), and resolution of subretinal fluid (SRF) were evaluated at baseline and 1, 3, 6, and 12 months after PDT. RESULTS: A total of 29 and 32 eyes received FA-guided PDT (irradiation area, 2898.3 ± 705.7 μm) and ICGA-guided PDT (irradiation area, 4993.8 ± 333.1 μm), respectively. A significant improvement in the mean BCVA was found at 1 month in the FA-guided group (P = 0.02), but not in the ICGA-guided group (P = 0.88). BCVA was significantly improved in both groups at 3, 6, and 12 months with no significant intergroup difference at any time points. CRT and SCT were significantly reduced in both groups at all time points with no significant intergroup differences. No significant intergroup differences were observed in the rate of recurrence and persistent SRF. However, there was a significant difference between groups in the rate of recurrence and/or persistent SRF (P = 0.04). Multivariate analysis revealed that choice of FA-guided was significantly associated with recurrence and/or persistent SRF (P = 0.04). CONCLUSION: Half-time PDT with ICGA-guided irradiation spot might be more effective than that with FA-guided in treating CSC patients in complete resolution of SRF.
2020年08月17日, Photodiagnosis and photodynamic therapy, 101955 - 101955, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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.
2020年08月04日, Molecular neurobiology, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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.
2020年07月21日, Retina (Philadelphia, Pa.), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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.
2020年04月17日, Retina (Philadelphia, Pa.), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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.
2020年03月, BMJ open diabetes research & care, 8 (1), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
PURPOSE: To retrospectively investigate the sensitivity and specificity of weight gain, insulin-like growth factor 1, and neonatal retinopathy of prematurity (WINROP) algorithm for the prediction of severe retinopathy of prematurity (ROP) in a Japanese population of preterm infants. The WINROP algorithm is a tool based on postnatal weight gain. STUDY DESIGN: Retrospective cohort study. METHODS: The medical records of preterm infants born between January 2011 and March 2017 were retrospectively reviewed. Infants born after 33 weeks of gestation were excluded based on the indications of the WINROP algorithm. Postnatal weight was recorded weekly on the WINROP system until postmenstrual week 36. The sensitivity and specificity of the WINROP algorithm were analyzed. RESULTS: In total, 278 infants were included in this study. Based on the WINROP algorithm 110 of these infants were predicted to be at low risk for developing severe ROP and 105 did not develop severe ROP. Based on the WINROP algorithm 168 infants were predicted to be at high risk for developing severe ROP and 27 developed severe ROP. Thus, the sensitivity of the WINROP algorithm was 84.4% and the specificity 42.7%. CONCLUSION: The WINROP algorithm could be used for preterm infants (gestational age of <28 weeks) without a complicated hospital course. Modification of the algorithm will improve its sensitivity and specificity for the Japanese population.
2020年03月, Japanese journal of ophthalmology, 64 (2), 223 - 227, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
OBJECTIVES: To compare the surgical results between air and 20% sulfur hexafluoride (SF6) tamponade in 27-gauge pars plana vitrectomy (27GPPV) for rhegmatogenous retinal detachment (RRD). METHODS: A retrospective, observational, and consecutive study. All patients underwent 27GPPV for RRD were divided into two groups. Group A comprised patients who underwent 20% SF6 gas tamponade. Group B comprised patients who underwent air tamponade. The anatomical success rate, visual outcome, and the type and frequency of complications were investigated and compared between the groups. All patients were followed-up for 12 months after surgery. RESULTS: Seventy eyes were enrolled (Group A: 35 eyes, Group B: 35 eyes). Seventeen eyes in Group A and 13 eyes in Group B had RRD with superior retinal breaks, while 14 eyes in Group A and 19 eyes in Group B had RRD with inferior retinal breaks. There was no statistically difference in preoperative demographic date between the groups. The initial and final anatomical success rates were 97.1% and 100% in Group A and 94.3% and 100% in Group B, respectively. The success rates between the groups were not statistically different (p = 1). The best corrected visual acuity (BCVA) (logMAR) at 12 months after surgery was -0.02 ± 0.14 in Group A and -0.03 ± 0.27 in Group B. The BCVA between the groups was not statistically different (p = 0.27). CONCLUSIONS: The surgical results of air tamponade were not inferior to 20% SF6 tamponade in 27GPPV for RRD irrespective of retinal break locations in the present cohort.
2020年02月, Eye (London, England), 34 (2), 299 - 306, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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年, Molecular vision, 26, 505 - 509, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Objective: To compare the 1-year outcomes of trabeculotomy ab externo (ab externo TLO) and trabeculotomy ab interno using a microhook (ab interno TLO) for glaucoma patients using propensity score analysis. Methods and analysis: The medical charts of 65 consecutive patients who underwent ab externo TLO and those of 69 patients who underwent ab interno TLO were reviewed. Logistic regression analysis was conducted to calculate the propensity score using 1:1 matched analysis, which indicates the likelihood of surgical success at 12 months. We set the outcome-related covariates as age, glaucoma type, mean deviation, preoperative intraocular pressure (IOP), the number of preoperative glaucoma eye drops and the presence or absence of combined cataract surgery. Fifty eyes per each surgery group were subsequently compared. Results: The mean preoperative IOP was 32.5±11.2 mm Hg in the ab externo TLO group and 28.4±7.8 mm Hg in the ab interno TLO group (p=0.08). The mean postoperative IOP at 12 months was 18.3±7.4 mm Hg in the former group and 17.8±6.3 mm Hg in the latter (p=0.91). When surgical success was defined as a postoperative IOP of between 5 and 21 mm Hg with a more than 20% IOP reduction from baseline and no additional glaucoma surgery, the rate at 12 months was 78% in the ab externo TLO group and 74% in the ab interno TLO group (p=1.00). Conclusion: The 1-year success rate was not significantly different between ab externo and ab interno TLO.
2020年, BMJ open ophthalmology, 5 (1), e000446, 英語, 国際誌[査読有り]
BACKGROUND/PURPOSE: To present a case report of retinal metastasis of laryngeal squamous cell carcinoma that was diagnosed by a histopathologic finding from the surgically extracted tumor tissue. METHODS: A 66-year-old man, who was suffered from the treatment-resistant laryngeal carcinoma, was referred to our department because of visual field defect in his right eye. A fundus examination revealed a parafoveal white retinal lesion, which rapidly expanded to the central fovea and decreased the visual acuity. A tissue extraction by 27G pars plana vitrectomy was performed to confirm the diagnosis. RESULTS: The abnormal retinal tissue was extracted en block through 10-mm sclerocorneal tunnel during pars plana vitrectomy. The histopathologic findings revealed that the retinal lesion was retinal metastasis of laryngeal carcinoma. CONCLUSION: We must keep in mind that retinal metastasis can be one of the differential diagnoses for white retinal lesions of unknown cause.
2020年, Retinal cases & brief reports, 14 (2), 127 - 130, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
PURPOSE: To introduce the methodology and outcomes of en bloc removal of the component of cystoid lesion during pars plana vitrectomy as a novel approach for the treatment of cystoid macular edema and show evidence that the component is an aggregation of fibrinogen by mass spectrometry analysis. METHODS: The surgical en bloc extraction of the component of cystoid lesion was performed for cystoid macular edemas secondary to diabetic retinopathy and retinal vein occlusion. Perioperative change of best-corrected decimal visual acuity, and the central retinal thickness and the continuity of subfoveal ellipsoid zone and external limiting membrane on optical coherence tomography were evaluated. Mass spectrometry was performed for the identification of protein constituting the component. RESULTS: Six eyes from six patients were included in the study. In all cases, central retinal thickness was improved after the surgery and remained stable during the follow-up period. Best-corrected decimal visual acuity and the continuity of ellipsoid zone and external limiting membrane were kept in all cases during the follow-up period. The mass spectrometry analysis disclosed that the component was composed of fibrinogen. CONCLUSION: The en block removal of the component of cystoid lesion combined with pars plana vitrectomy may be a promising option for treatment of cystoid macular edema. The component of cystoid lesion is presumably a fibrinogen aggregate.
2020年01月, Retina (Philadelphia, Pa.), 40 (1), 154 - 159, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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PURPOSE: To elucidate the clinical and epidemiologic characteristics of optic neuritis in Japan. DESIGN: Multicenter cross-sectional, observational cohort study. PARTICIPANTS: A total of 531 cases of unilateral or bilateral noninfectious optic neuritis identified in 33 institutions nationwide in Japan. METHODS: Serum samples from patients with optic neuritis were tested for anti-aquaporin-4 antibodies (AQP4-Abs) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) using a cell-based assay and were correlated with the clinical findings. MAIN OUTCOME MEASURES: Antibody positivity, clinical and radiologic characteristics, and visual outcome. RESULTS: Among 531 cases of optic neuritis, 12% were AQP4-Ab positive, 10% were MOG-Ab positive, 77% were negative for both antibodies (double-negative), and 1 case was positive for both antibodies. Pretreatment visual acuity (VA) worsened to more than a median 1.0 logarithm of the minimum angle of resolution (logMAR) in all groups. After steroid pulse therapy (combined with plasmapheresis in 32% of patients in AQP4-Ab-positive group), median VA improved to 0.4 logMAR in the AQP4-Ab-positive group, 0 logMAR in the MOG-Ab-positive group, and 0.1 logMAR in the double-negative group. The AQP4-Ab-positive group showed a high proportion of females, exhibited diverse visual field abnormalities, and demonstrated concurrent spinal cord lesions on magnetic resonance imaging (MRI) in 22% of the patients. In the MOG-Ab-positive group, although posttreatment visual outcome was good, the rates of optic disc swelling and pain with eye movement were significantly higher than those in the AQP4-Ab-positive and double-negative groups. However, most cases showed isolated optic neuritis lesions on MRI. In the double-negative group, 4% of the patients had multiple sclerosis. Multivariate logistic regression analysis of all participants identified age and presence of antibodies (MOG-Ab and AQP4-Ab) as significant factors affecting visual outcome. CONCLUSIONS: The present large-scale cohort study revealed the clinicoepidemiologic features of noninfectious optic neuritis in Japan. Anti-aquaporin-4 antibody-positive optic neuritis has poor visual outcome. In contrast, MOG-Ab positive cases manifested severe clinical findings of optic neuritis before treatment, but few showed concurrent lesions in sites other than the optic nerve and generally showed good treatment response with favorable visual outcome. These findings indicate that autoantibody measurement is useful for prompt diagnosis and proper management of optic neuritis that tends to become refractory.
2019年10月, Ophthalmology, 126 (10), 1385 - 1398, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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PURPOSE: To determine the association of age-related maculopathy susceptibility 2 (ARMS2) gene polymorphisms with the 12-month outcomes of intravitreal aflibercept combined with photodynamic therapy (IVA+PDT) in polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: Interventional cohort study. METHODS: This was a retrospective study of 48 consecutive treatment-naïve PCV patients. The patients underwent IVA+PDT as the initial therapy and were followed up for more than 12 months under a pro re nata regimen. The single nucleotide polymorphism (SNP) at rs10490924 in the ARMS2 gene was genotyped using the TaqMan assay. The clinical characteristics and outcomes of IVA+PDT were compared among the 3 genotypes at rs10490924. Multivariate regression analysis was performed to evaluate the influence of the clinical cofactors on the association of rs10490924 with the visual outcome at 12 months after the first IVA+PDT. RESULTS: No significant difference was found in the baseline characteristics among the 3 genotypes (n = 9, 23, and 16 for the GG, GT, and TT genotypes, respectively). All the patients, regardless of genotype, showed a significant improvement in vision, central retinal thickness, and subfoveal choroidal thickness at all time points measured after the initial IVA+PDT. The number of treatments was significantly smaller in the patients with the GG genotype than in those with the GT or the TT genotype. On multivariate logistic regression analysis, the number of the T allele at rs10490924 was significantly associated with the chance of retreatment after the initial IVA+PDT. CONCLUSION: The presence of the G allele at rs10490924 in the ARMS2 gene is likely associated with a lower chance of retreatment after IVA+PDT in patients with PCV.
2019年09月, Japanese journal of ophthalmology, 63 (5), 389 - 395, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
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.
2019年08月13日, BMC ophthalmology, 19 (1), 179 - 179, 英語, 国際誌[査読有り]
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PURPOSE: To investigate the perioperative clinical factors, which contribute to the postsurgical aqueous flare intensity (AFI) following 27-gauge pars plana vitrectomy (27GPPV) for primary rhegmatogenous retinal detachment (RRD). STUDY DESIGN: Retrospective clinical study. METHODS: We performed retrospective analyses of the medical records of 47 eyes of 47 patients with primary RRD who had undergone 27GPPV with a wide-angle viewing system. AFI was measured preoperatively and 1 week, 1 month, 3 months, 6 months, and 12 months after the surgery. RESULTS: AFI was significantly increased 1 week after the surgery (p<0.01) and then decreased overtime. At 6 months after surgery it was still statistically significantly higher than preoperative AFI (p=0.03). There was no statistical difference between preoperative AFI and that at 12 months following surgery. Multiple regression analyses revealed that the number of retinal photocoagulations and the performance of scleral indentation had significant positive correlation with AFI at 1 week, 1 month, 3 months, and 6 months, and at 1 month and 3 months after the surgery, respectively. CONCLUSION: Intraoperative retinal photocoagulation and scleral indentation are probable causes of increased AFI after 27G PPV for RRD.
2019年07月, Japanese journal of ophthalmology, 63 (4), 317 - 321, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
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.
2019年07月01日, Investigative ophthalmology & visual science, 60 (8), 2811 - 2821, 英語, 国際誌[査読有り]
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研究論文(学術雑誌)
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研究論文(学術雑誌)
Purpose: The purpose of this study was to evaluate the concordance of a temporal raphe architecture estimated using optical coherence tomography (OCT) and MP-3 microperimetry. Methods: We enrolled 25 eyes with either an upper or lower glaucomatous hemifield defect, as detected on the Humphrey visual field 30-2 test. A structural temporal raphe was extrapolated from visible end points of retinal nerve fiber bundles present in a perimetrically normal hemiretina on an en face Spectralis OCT image. A functional temporal raphe was drawn as a line from the fovea to the border of at least a 10-dB difference in sensitivity, at vertically adjacent test points, with at least three consecutive pairs among 25 test points placed at 8° to 18° from the fovea (2° intervals) on the MP-3. An angle determined by the optic disc center, the fovea, and the temporal raphe line (the DFR angle) was calculated. Correlations and agreement of the OCT- and MP-3-derived DFR angles and factors affecting discordance of the two estimates were evaluated. Results: Despite no significant demographic differences, the functional DFR angle (mean ± SD, 171.8° ± 3.5°) was significantly larger than that of the structural DFR angle (166.5° ± 3.2°) in 14 eyes with upper hemifield defects and vice versa in 11 eyes with lower hemifield defects (163.4° ± 3.0° vs. 170.5° ± 3.2°). The mean deviation was significantly associated with the functional and structural DFR angle difference in eyes with only upper hemifield defects. Conclusions: The structural temporal raphe was more deviated to the perimetrically normal hemiretina side than to the functional temporal raphe, thereby suggesting that a structural change may precede a functional loss.
2019年04月01日, Investigative ophthalmology & visual science, 60 (5), 1403 - 1411, 英語, 国際誌[査読有り]
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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, 2019年02月, 日本眼科学会雑誌, 123 (2), 121 - 127, 日本語, 国内誌[査読有り]
研究論文(学術雑誌)
Langerhans cell histiocytosis (LCH) is characterised by tissue destruction caused by the abnormal proliferation of pathogenic dendritic cells. We report a rare case of multi-system LCH with local invasion of the orbital apex.A 56-year-old woman suffered from a decrease of visual acuity in the left eye caused by central scotoma and the limitation of eye movement in all directions. Magnetic resonance imaging revealed an enhanced lesion in the left orbital apex, suggesting optic nerve compression. She had been diagnosed with eosinophilic granuloma 24 years previously. Two weeks after the current presentation, we admitted the patient for optic canal and orbital apex decompression and subtotal tumour resection. Histopathological analysis confirmed the diagnosis of LCH. Post-surgical treatment with low-dose cytarabine was initiated for the residual tumour. However, it was ceased because of myelosuppression-induced pyelonephritis. After surgery, the central scotoma disappeared on day 5 and eye movement palsy resolved by 6 months. After the cessation of cytarabine, she has received low-dose steroid therapy for 2 years with no recurrence. Early surgical intervention with low-dose steroid therapy can lead to recovery of visual acuity and resolve eye movement palsy in patients with lesions of the orbital apex caused by multi-system LCH.
KARGER, 2019年, CASE REPORTS IN OPHTHALMOLOGY, 10 (3), 319 - 326, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
BACKGROUND: Surgical intervention for dense vitreous hemorrhage (DVH) with unclear etiology is often delayed in favor of conservative follow-up despite possible disease progression and the availability of safe minimally invasive vitrectomy. OBJECTIVES: The aim of this study is to investigate the efficacy of early surgical intervention for DVH with unknown etiology. METHODS: Eighty-eight cases (88 eyes) of DVH with unknown origin were retrospectively reviewed. Inclusion criteria were as follows: (1) measured visual acuity (VA) of 20/200 or worse and (2) fundus invisibility requiring B-scan ultrasonography. Eyes with a history of diabetic retinopathy, recent trauma, or likely retinal detachment (RD) as revealed by B-scan ultrasonography were excluded. Outcome measures were a cause of vitreous hemorrhage and final VA following early (≤2 weeks after symptom onset) or delayed vitrectomy. RESULTS: The most frequently occurring causes of DVH were central or branch retinal vein occlusion (30 eyes, 34%) and retinal tear or RD (29 eyes, 33%). logMAR VA significantly improved after treatment (p < 0.001). Final VA was significantly higher for eyes treated within 2 weeks compared with eyes treated later than 2 weeks after symptom onset (p = 0.020). CONCLUSIONS: Surgical intervention within 2 weeks after symptom onset may prevent a lower visual outcome.
2019年, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 242 (4), 234 - 238, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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研究論文(学術雑誌)
© 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.
2019年01月01日, Case Reports in Ophthalmology, 10 (1), 5 - 10, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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年, Clinical ophthalmology (Auckland, N.Z.), 13, 521 - 527, 英語, 国際誌[査読有り]
Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited disease caused by three missense mutations of mitochondrial (mt) DNA, ie, m 3460 G>A, m 11778 G>A, or m 14484 T>C in the greater portion of LHON. m 11778 G>A mutation is especially observed in >90% of the cases in Japanese families. Although spontaneous remission of visual function infrequently occurs, effective treatment for LHON remains unestablished. Transcorneal electrical stimulation has been shown to be efficacious in individuals with optic neuropathy. However, due to potential risk of corneal damage, repeated treatments are not permissible. In this exploratory study, we will be conducting skin electrical stimulation (SES) as an intervention for patients with LHON having 11778 missense mutation and investigate effectiveness and safety of SES. Methods: This is a single-arm, prospective, open-label exploratory trial focused on patients with LHON having 11778 missense mutation. Eleven patients will be enrolled and receive six consecutive SES once every 2 weeks up to 10 weeks. The safety of the SES will be monitored with specular microscopy, slit-lamp biomicroscopy, fundus examinations, and the observation of facial skin. The primary outcome measure will be the averaged l ogarithm of minimum angle resolution (logMAR) converted visual acuity 1 week after the last SES. Secondary outcome measures include changes, in logMAR at 4 and 8 weeks after the last SES, such as visual field indices measured using Humphrey visual field and microperimetry-3, the thickness of peripapillary retinal fiber and macular ganglion cell complex, multifocal visual evoked potentials, critical flicker frequency, and color vision. Discussion: The results of this proposed proof-of-concept feasibility trial will help plan and execute a larger definitive trial to test SES as an effective strategy for LHON and related optic neuropathies and help establish a beneficial treatment for LHON.
2019年, Clinical ophthalmology (Auckland, N.Z.), 13, 897 - 904, 英語, 国際誌[査読有り]
Purpose: To investigate the foveal avascular zone (FAZ) in the eyes of patients with a history of retinopathy of prematurity (ROP) using optical coherence tomography angiography (OCTA) and to identify associated clinical factors. Patients and methods: Overall, 14 children with a history of laser treatment for ROP, 17 children born prematurely without a history of ROP, and 41 age-matched children born at full-term (age range 7-14 years) were included. OCTA was conducted on an area measuring 3 × 3 mm in the central macula. The area of FAZ in the superficial layer was measured. Foveal thickness (FT), ganglion cell complex thickness, and the presence of inner retinal layer (IRL) at the fovea were evaluated. Results: There were significant differences in FT and FAZ size among patients (P < 0.001). The eyes of patients that had been treated for ROP showed the smallest FAZ and greatest FT. Univariate analyses demonstrated that the area of FAZ was not correlated with visual acuity (P=0.078) but with gestational age (GA) (P=0.001), birth weight (P=0.013), the presence of IRL (P < 0.001), and FT (P < 0.001). Multivariate regression analyses showed that the area of FAZ was significantly associated with GA, the presence of IRL, and FT (P=0.03, P=0.01, P < 0.001, respectively). Conclusion: The eyes of preterm children had small FAZ, and this reduction in area was associated with greater FT, the presence of IRL, and lower GA.
2019年, Journal of ophthalmology, 2019, 8340729 - 8340729, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
PURPOSE: This study was prospectively carried out to clarify the effectiveness of visual and anatomical outcomes under combination therapy of intravitreal aflibercept (IVA) and verteporfin photodynamic therapy (vPDT) in over 24 months. STUDY DESIGN: A single-arm prospective exploratory study. METHODS: Twenty-six eyes of 26 treatment naïve PCV patients were enrolled in this study. The primary outcome measures were the changes in best corrected visual acuity (BCVA) and the complete polyp regression rate. The secondary outcome measures included central retinal thickness assessed by optical coherence tomography. RESULTS: The patients showed significant improvement in BCVA by 0.14 logMAR units at 12 months and 0.11 logMAR units at 24 months from baseline (both p < 0.01). The mean central retinal thickness also significantly decreased at 12 months (p < 0.001) and at 24 months (p = 0.001). Complete regression of polypoidal lesions was achieved by 15 out of 20 eyes (75%) at 12 months and 11 out of 20 eyes (55%) at 24 months. The mean treatment number was 2.9 courses of IVA and 1.5 courses of vPDT and the mean retreatment free interval after initial therapy was 12.8 months during follow up of 24 months. The complete data from all predetermined examinations were observed in 17 out of 26 enrolled patients (65%) in this study. CONCLUSION: In this study, combination therapy of IVA and vPDT yielded visual and anatomical improvements in treatment-naïve PCV patients over a 24-month follow-up period.
2019年01月, Japanese journal of ophthalmology, 63 (1), 100 - 108, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
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研究論文(学術雑誌)
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Purpose: To report a rare case of bilateral periphlebitis associated with a pineal germinoma. Observations: A 17-year-old male teenager presented at a local clinic complaining of blurred vision in both eyes. The treating physician identified bilateral uveitis, and prescribed the patient with a local steroid treatment. However, the inflammatory findings did not improve with the treatment, and the patient was referred to our hospital for further examination. At the first visit, his best-corrected visual acuities were 0.3 for the right eye and 0.06 for the left eye; we found no inflammation in the anterior ocular segment, but observed bilateral retinal periphlebitis and a proliferative membrane from the papilla to the macula in the ocular fundus. In addition, we found a tractional serous retinal detachment in the macula. We suspected tuberculous uveitis clinically and initiated treatment with an antituberculous drug. However, the condition of the patient did not improve. Two months after our initial examination, left optic neuritis appeared, and we initiated a steroid pulse therapy. Although the periphlebitis remained, the left optic nerve findings and the visual acuity of both eyes improved. Thus, we reduced the oral steroid dose gradually. However, two months after initiating the dose reduction, the patient suffered a consciousness disturbance, and we detected a pineal tumor by magnetic resonance imaging (MRI). The patient was diagnosed as having a germ cell tumor by pathological examination and underwent radiation and chemotherapy. We noted marked improvements in both the periphlebitis findings and in the visual acuity following the treatment for the pineal tumor. Conclusions and importance: Cases of pineal tumor accompanied with retinal periphlebitis have been reported rarely. Because juvenile retinal vasculitis cases of unknown cause can be associated with pineal germinomas, we recommend brain MRI examinations for such cases.
2018年09月, American journal of ophthalmology case reports, 11, 142 - 145, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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研究論文(学術雑誌)
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研究論文(学術雑誌)
Purpose: To evaluate temporal changes in visual acuity in patients with steroid-resistant optic neuritis (ON) in neuromyelitis optica spectrum disorders (NMOSD) after apheresis. Design: Retrospective observational study, clinical case series Subjects and methods: We reviewed the medical charts of 15 eyes of 9 consecutive patients with ON in NMOSD who underwent apheresis between March 2010 and September 2017. All patients were seropositive for anti-aquaporin 4 (AQP4) antibody and resistant to steroid pulse therapy. Apheresis was performed by either simple plasma exchange or/and immune adsorption therapy. Results: Twelve eyes (80%) showed improvement with logMAR > 0.3 at 1 month after apheresis. Within 1 month after apheresis therapy, logMAR on average significantly decreased, the magnitude of change being greatest within the first week. Thereafter visual acuity became stable in 10 of the 11 eyes, until 12 months. However, two eyes (12%) showed recurrence of visual acuity reduction 3 months after the cessation of apheresis. There were a few serious complications during and after apheresis, but these were completely treatable. Conclusions: Additional apheresis therapy rapidly improves the visual acuity of steroid-resistant seropositive AQP4 ON.
Springer Tokyo, 2018年07月01日, Japanese Journal of Ophthalmology, 62 (4), 525 - 530, 英語[査読有り]
研究論文(学術雑誌)
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研究論文(学術雑誌)
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研究論文(学術雑誌)
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研究論文(学術雑誌)
Central serous chorioretinopathy (CSC) is a common disease affecting younger people and may lead to vision loss. CSC shares phenotypic overlap with age-related macular degeneration (AMD). As recent studies have revealed a characteristic increase of choroidal thickness in CSC, we conducted a genome-wide association study on choroidal thickness in 3,418 individuals followed by TaqMan assays in 2,692 subjects, and we identified two susceptibility loci: CFH rs800292, an established AMD susceptibility polymorphism, and VIPR2 rs3793217 (P = 2.05 × 10-10 and 6.75 × 10-8, respectively). Case-control studies using patients with CSC confirmed associations between both polymorphisms and CSC (P = 5.27 × 10-5 and 5.14 × 10-5, respectively). The CFH rs800292 G allele is reportedly a risk allele for AMD, whereas the A allele conferred risk for thicker choroid and CSC development. This study not only shows that susceptibility genes for CSC could be discovered using choroidal thickness as a defining variable but also, deepens the understanding of differences between CSC and AMD pathophysiology.
2018年06月12日, Proceedings of the National Academy of Sciences of the United States of America, 115 (24), 6261 - 6266, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Purpose: To report a case of temporary bilateral corneal denting in a patient who underwent cardiovascular surgery under general anesthesia. Observations: A 71-year-old male with no history of ophthalmological disease experienced bilateral corneal denting immediately after undergoing surgery for aneurysm of the thoracic aorta under general anesthesia. Anesthesia was induced with propofol and maintained with rocuronium bromide and remifentanil hydrochloride. The initial examination revealed significant denting on the surface of both the corneas and ocular hypotension. Visual evaluation could not be performed due to the patient's low level of consciousness resulting from delayed emergence from anesthesia. After applying tropicamide and phenylephrine ophthalmic solution for fundus examination, the ocular morphology improved. Ocular pressure was normal on the day after surgery, and creasing on the surface of the corneas had disappeared. Conclusions: and Importance: We experienced a patient with bilateral corneal denting following a cardiovascular surgery under general anesthesia. The dents could be attributed to augmentation of ocular hypotension using several types of anesthesia at relatively high doses.
2018年06月, American journal of ophthalmology case reports, 10, 290 - 292, 英語, 国際誌[査読有り]
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.
2018年04月, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 256 (4), 809 - 814, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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研究論文(その他学術会議資料等)
PURPOSE: To compare the postoperative anatomic success rates and the frequency of complications between prone or supine postoperative positioning after transconjunctival sutureless vitrectomy (TSV) for rhegmatogenous retinal detachment (RRD). METHODS: All patients underwent primary 27-gauge TSV for the treatment of primary RRD. Patients were divided into two groups as follows: group A was patients instructed to keep strict postoperative prone positioning for a minimum of 8 days. Group B was patients instructed to keep the prone positioning on the day of the surgery followed by supine positioning for minimum of 7 days from the day after surgery. RESULT: Sixty-two eyes were enrolled (group A: 32, group B: 30). There was no significant difference in baseline data between two groups. The initial and final anatomical success rates were 93.8% and 100% in group A and 93.3% and 100% in group B, respectively (p = 1, p = 1, respectively). Posterior synechia of the iris occurred in one eye in group A and in two eyes in group B (p = 0.61). Macular pucker and retinal fold did not occur in either group. Preoperative intraocular pressure (IOP; mmHg) was 14.5 ± 2.9 in group A and 14.5 ± 2.6 in group B (p = 0.92). Intraocular pressure (IOP) was not statistically different between the groups during the follow-up period (p = 0.36, p = 0.07, respectively). CONCLUSION: Supine positioning may be an option as a postoperative positioning after TSV and gas tamponade for the treatment of RRD.
2018年03月, Acta ophthalmologica, 96 (2), e189-e194 - e194, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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研究論文(学術雑誌)
Purpose: To report a case of polypoidal choroidal vasculopathy associated with optic disc coloboma. Methods: Case report. Results: A 50-year-old woman presented with optic disc coloboma and retinochoroidal coloboma associated with subretinal hemorrhage and serous retinal detachment (SRD) in her left eye. Optical coherence tomography (OCT) confirmed SRD at the macula and showed a sharply elevated retinal epithelial detachment at the choroidal excavation. OCT also revealed choroidal cavitation along the temporal side of the optic coloboma. Fluorescein angiography showed hyperfluorescent dye leakage and indocyanine green angiography revealed polypoidal lesions. We diagnosed polypoidal choroidal vasculopathy (PCV). PCV was located at the end of the choroidal cavitation. Her left eye was treated with an intraocular injection of the anti-vascular endothelial growth factor aflibercept (2 mg). Photodynamic therapy was performed using the standard protocol 1 week after the intravitreal application of aflibercept. One month after the combined treatment, OCT showed completely resolved SRD and her symptoms disappeared. Her best-corrected visual acuity remained stable and no recurrence was found during a 12-month follow-up period. Conclusion: PCV associated with optic disc coloboma has not been previously reported. The morphological abnormality of choroidal cavitation and choroidal excavation connecting with optic disc coloboma may contribute to the development of PCV in this case.
S. Karger AG, 2018年01月23日, Case Reports in Ophthalmology, 9 (1), 92 - 95, 英語[査読有り]
研究論文(学術雑誌)
Purpose Three-dimensional retinal organoids can be differentiated from embryonic stem cells/induced pluripotent stem cells (ES/iPS cells) under defined medium conditions. We modified the serum-free floating culture of embryoid body-like aggregates with quick reaggregation (SFEBq) culture procedure to obtain retinal organoids expressing more rod photoreceptors and S- and M-cone opsins. Methods Retinal organoids differentiated from mouse Nrl-eGFP iPS cells were cultured in various mediums during photoreceptor development. To promote rod photoreceptor development, organoids were maintained in media containing 9-cis retinoic acids (9cRA). To obtain retinal organoids with M-opsin expression, we cultured in medium with 1% fetal bovine serum (FBS) supplemented with T3, BMP4, and DAPT. Section immunohistochemistry was performed to visualize the expression of photoreceptor markers. Results In three-dimensional (3D) retinas exposed to 9cRA, rhodopsin was expressed earlier and S-cone opsins were suppressed. We could maintain 3D retinas up to DD 35 in culture media with 1% FBS. The 3D retinas expressed rhodopsin, S- and M-opsins, but most cone photoreceptors expressed either S- or M-opsins. Conclusion By modifying culture conditions in the SFEBq protocol, we obtained rod-dominated 3D retinas and S- and M-opsin expressing 3D retinas.
Elsevier B.V., 2018年01月22日, Biochemical and Biophysical Research Communications, 495 (4), 2595 - 2601, 英語[査読有り]
研究論文(学術雑誌)
PURPOSE: This study evaluates optical coherence tomography (OCT) findings of the macula in patients with a history of retinopathy of prematurity (ROP). METHODS: We enrolled 112 patients (age: 6-15 years) and categorized them into 3 groups: gestational age (GA) < 36 weeks with or without a history of ROP (ROP group, preterm group) and GA ≥37 weeks. We included 1 eye of each patient and measured the retinal thickness of the macula by OCT. RESULTS: The ROP group demonstrated the worst VA and the shallowest foveal depression. Furthermore, foveal depression significantly correlated with birth weight, GA, ganglion cell layer/inner plexiform layer (GCL-IPL) thickness, and a history of ROP. CONCLUSIONS: This study established a correlation of fovea formation with premature birth, damage of GCL-IPL, and a history of ROP. The retention of the inner retina possibly contributes to abnormal foveal morphology in patients with a history of ROP.
2018年, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 240 (2), 106 - 110, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Purpose: We previously reported that eyes with hypotony maculopathy (HM) after trabeculectomy (TLE) exhibited more reduction of axial length (AL) than those without HM, suggesting that inward collapse of the scleral wall may contribute to the development of HM after TLE. However, we did not evaluate change in choroidal thickness (CT), which could influence AL measures. We compared the magnitude and rate of AL and CT changes in eyes with and without HM by simultaneously measuring these parameters before and after TLE. Methods We enrolled 77 eyes of 77consecutive patients with glaucoma, who underwent TLE between March 2014 and March 2016. Intraocular pressure (IOP), central corneal thickness, keratometry, AL, and CT were measured pre- and postoperatively, up to 6 months. These biometrics were compared in eyes with and without HM. Results The 14 patients who developed HM were significantly younger than those who did not. The eyes with HM exhibited significantly reduced AL (2.8%) compared to those without HM (0.7%). There was no significant difference in CT change between the two groups. The rate of AL reduction was significantly correlated with age, postoperative IOP, and preoperative AL. Post-adjustment logistic regression analysis revealed that eyes with AL reduction rate 2% had 11.67 higher risk for developing HM (95% confidence interval, 1.28–106.6 P = 0.03). Conclusions AL reduction rates 2% were significantly associated with HM. Excessive reduction in AL, which was seen in eyes with HM, was not an artificial measure resulting from choroidal thickening but rather reflected reductions in the anterior-posterior diameter of the eyeball. Inward collapse of the scleral wall leads to redundancy of the chorioretinal tissue, contributing to the development of HM after TLE.
Public Library of Science, 2018年01月01日, PLoS ONE, 13 (1), e0191862, 英語[査読有り]
研究論文(学術雑誌)
Purpose: To assess the combined estimate of retinal ganglion cell (RGC) count developed by Medeiros et al. as a tool for diagnosis of glaucoma in Japanese patients. Study design: Cross-sectional study. Methods: Thirty-one eyes of 19 healthy controls and 106 eyes of 70 glaucoma patients underwent standard automated perimetry (SAP) and three types of spectral domain optical coherence tomography (SD-OCT) imaging using the Cirrus, RTVue, and 3D-OCT instruments. RGC counts derived from SAP and SD-OCT data were estimated using the Harwerth model (SAPrgc and OCTrgc, respectively), from which the combined RGC count estimates (CRGC) were calculated using the formula developed by Medeiros et al. Receiver operating characteristic curve (ROC) analyses were conducted for mean deviation (MD), retinal nerve fiber layer thickness (RNFLT), and CRGC. Results: The mean OCTrgc derived from the Cirrus, RTVue, and 3D-OCT instruments were 1150, 1245, and 1316 (× 1000 cells), respectively, for the control group and 463, 519, and 516 (× 1000 cells), respectively, for the patient group. SAPrgc of the controls’ group was 1526 and the patients’ group, 731 (× 1000 cells), and were consistently greater than OCTrgc in both groups (a generalized estimating equation model, p < 0.001). Partial area under the curve (pAUC) of MD was 0.178, and that of RNFLT and CRGC for the three OCT instruments were 0.185, 0.18, 0.189 and 0.196, 0.196, 0.197, respectively. CRGC had larger pAUC than MD, whereas there was no or marginal difference in pAUC between CRGC and cpRNFLT, irrespective of OCT device used or glaucoma severity. Conclusion: CRGC proved well suited to discriminate glaucoma patients from controls. However, its clinical utility did not seem to overwhelm isolated structural measures in the tested Japanese patients.
Springer Tokyo, 2018年01月01日, Japanese Journal of Ophthalmology, 62 (1), 31 - 40, 英語[査読有り]
研究論文(学術雑誌)
Aim: To compare the anatomic and visual outcomes of 25-gauge (25G), and 27-gauge (27G) transconjunctival sutureless pars plana vitrectomy (TSV) for the management of primary rhegmatogeneous retinal detachment (RRD). Design: A retrospective nonrandomized clinical trial. Methods: A retrospective comparative analysis of 62 consecutive eyes from 62 patients with 6 months of follow-up was performed. Results: Thirty-two patients underwent 25G TSV, and 30 patients underwent 27G TSV for the treatment of primary RRD. There was no significant difference in baseline demographic and preoperative ocular characteristics between the two groups. The initial and final anatomical success rates were 93.8% and 100% in 25G TSV and 96.7% and 100% in 27G TSV, respectively (p=1 and p=1, resp.). Preoperative best-corrected visual acuity (BCVA) (logMAR) was 0.44 ± 0.69 and 0.38 ± 0.61 for 25G and 27G TSV, respectively (p=0.73). The final follow-up BCVA was 0.07 ± 0.25 and -0.02 ± 0.17 for 25G and 27G TSV, respectively (p=0.16). The final BCVA was significantly better than the preoperative BCVA in both groups (p=0.02 and p=0.002, resp.). Preoperative intraocular pressure (IOP) (mmHg) was 13.0 ± 3.5 in 25G TSV and 14.3 ± 2.8 in 27G TSV (p=0.11). IOP did not statistically significantly change in both groups during the follow-up period (p=0.63 and p=0.21, resp.). Conclusion: The 27G TSV system is safe and useful for RRD treatment as 25G TSV.
2018年, Journal of ophthalmology, 2018, 7643174 - 7643174, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
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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, 2017年10月, 臨床眼科, 71 (10), 1505 - 1511, 日本語[査読有り]
研究論文(学術雑誌)
Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy that leads to central loss of vision, predominantly in young males. Most LHON cases have one of three primary point mutations in mitochondrial DNA (mtDNA). The annual incidence and prevalence of LHON in Japan are not known. Thus, we estimated the annual incidence of molecularly confirmed LHON in Japan during 2014. Methods: Sequential questionnaires were sent to 1397 facilities, which included all of the university hospitals in Japan, and they were certified by either the Japanese Ophthalmological Society or the Japanese Neuro-Ophthalmological Society. We calculated the incidence number (Ir) as the number of patients who developed LHON in 2014 and its 95% confidence interval. Results: We received 861 responses to the first questionnaire, where 49 facilities reported 72 cases (67 were male and 5 were female) of newly developed LHON during 2014. Ir was calculated as 117, and the 95% confidence interval ranged from 81 to 153. For the second questionnaire, responses were received from 30 facilities, where the median age at onset was 38 years for males and 30 years for females, and 86.5% of cases possessed the mtDNA ND4/G11778A mutation. Conclusion: Approximately 120 cases of newly developed LHON were reported during 2014 in Japan, and 93.2% were males. (C) 2017 The Authors. Publishing services by Elsevier B.V. on behalf of The Japan Epidemiological Association.
ELSEVIER SCIENCE INC, 2017年09月, JOURNAL OF EPIDEMIOLOGY, 27 (9), 447 - 450, 英語[査読有り]
研究論文(学術雑誌)
PURPOSE: 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.
2017年08月, Retina (Philadelphia, Pa.), 37 (8), 1562 - 1567, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Purpose: To determine the association of age-related maculopathy susceptibility 2 (ARMS2) gene polymorphisms with the 3-year outcomes of photodynamic therapy (PDT) in wet age-related macular degeneration (wet AMD). Methods: The single nucleotide polymorphism (SNP) at rs10490924 in the ARMS2 gene of 65 patients with wet AMD who underwent PDT was genotyped using the TaqMan assay. The clinical characteristics and the outcomes of PDT were compared among the three genotypes at rs10490924. A multivariate regression analysis was performed to evaluate the influence of the clinical cofactors on the association of rs10490924 with the visual outcome at 36 months after the first PDT. Results: A significant difference was found among the genotypes in the age and the baseline lesion size. The patients with the GG genotype showed a significant improvement in vision, and the patients with the TT genotype showed a significant worsening of vision at all time points measured after the initial PDT. In the multivariate regression analysis, the number of the G allele at rs10490924 was associated with a significantly greater improvement in the baseline bestcorrected visual acuity (BCVA) at 36 months after the first PDT. Conclusions: ARMS2 variants are likely associated with the 3-year outcomes of PDT in patients with wet AMD.
MOLECULAR VISION, 2017年07月, MOLECULAR VISION, 23, 514 - 519, 英語[査読有り]
研究論文(学術雑誌)
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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. This was a prospective case-series study. Twenty eyes from 20 treatment-na < ve 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. 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 (ae 0.3 LogMAR units improvement from baseline) at 12 months. In this study, combination therapy with IVA and vPDT gave visual and anatomical improvements to treatment-na < ve PCV patients over 12 months of follow-up period.
SPRINGER, 2017年03月, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 255 (3), 541 - 548, 英語[査読有り]
研究論文(学術雑誌)
Purpose An autoantibody against aquaporin-4 (AQP4 Ab) is highly specific for neuromyelitis optica spectrum disorder and plays a pathogenic role in this disease. The purpose of this study was to investigate the impact of AQP4 Ab on inner retinal structure, function, and the structure -function relationships in eyes with optic neuritis. Methods Thirty five eyes from 25 cases who had received visual function tests and RTVue optical coherence tomography (OCT) measurement at least six months after the latest episode of optic neuritis were enrolled. Patients with multiple sclerosis were excluded. AQP4 Ab was measured using a cell -based assay. Visual acuity, mean deviation (MD) of the Humphrey visual field SITA standard 30-2 tests, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC) thicknesses, and other clinical variables were compared between the AQP4 Ab-positive and-negative groups. Parameters associated with visual functions were evaluated by generalized estimating equation (GEE) models. Results The AQP4 Ab-positive group (20 eyes from 12 cases) had a higher proportion of bilateral involvement and longer duration of follow-up than the AQP4 Ab-negative group (15 eyes from 13 cases). Linear mixed effect models revealed worse MD and visual acuity in AQP4 Ab-positive eyes than those in AQP4 Ab-negative eyes after adjusting for within -patient inter-eye dependence, whereas there were no differences in RNFL and GCC thickness between the two groups. In seropositive eyes, GEE regression analyses revealed that depending on age and the number of recurrences of ON episodes, OCT parameters correlated strongly with MD and more weakly with visual acuity. Conclusions Reductions in RNFL and GCC thickness were proportional to the visual field defect in eyes with AQP4 Ab but not in eyes without AQP4 Ab. The presence of AQP4 Ab probably plays a critical role in retinal ganglion cell loss in optic neuritis.
PUBLIC LIBRARY SCIENCE, 2017年02月, PLOS ONE, 12 (2), e0171880, 英語[査読有り]
研究論文(学術雑誌)
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, 2017年02月, あたらしい眼科, 34 (2), 280 - 282, 日本語[査読有り]
研究論文(学術雑誌)
Background: To compare the 12-month outcomes of intravitreal ranibizumab (IVR) between two angiographic subtypes of polypoidal choroidal vasculopathy (PCV). Methods: This is a retrospective cohort study of 38 treatment-naive PCV cases. Three consecutive IVR and retreatments as needed were performed. Subsequently, the PCV cases were classified into two phenotypes (18 type 1 and 20 type 2) according to the status of branching vascular network. The best-corrected visual acuity (BCVA) was evaluated in each PCV subtype up to 12 months after the initial IVR. Results: The mean BCVA was significantly improved from baseline in type 1 PCV while not in type 2 PCV. In type 2 PCV, 3 cases showed severe visual loss after 6 months from the initial IVR. The mean retreatment number was 1.9 +/- 1.7 in type 1 PCV and 1.2 +/- 1.3 in type 2 PCV. Conclusions: The outcomes of IVR may be different between two angiographic subtypes of PCV. (C) 2017 S. Karger AG, Basel
KARGER, 2017年, OPHTHALMOLOGICA, 237 (3), 123 - 127, 英語[査読有り]
研究論文(学術雑誌)
Aims. To compare the surgical outcome of pars plana vitrectomy (PPV) for full-thickness macular hole (FTMH) with and without lamellar hole-associated epiretinal proliferation (LHEP). Methods. This retrospective study included 158 eyes of 158 patients with FTMH treated with PPV. The following variables were analyzed: sex, age, preoperative best corrected visual acuity (pre-BCVA), BCVA 6 months after the surgery (6M-BCVA), the axial length of eye, the minimum diameter of FTMH, the diameter of basal side of FTMH, postoperative continuity of subfoveal ellipsoid zone (EZ) and external limiting membrane (ELM), and the preoperative presence of LHEP. Results. Twenty-eight eyes had FTMH with LHEP and 130 without LHEP. The mean +/- SD age (years) was 72.6 +/- 7.9 and 68.6 +/- 8.7, respectively (p = 0 02). 6M-BCVA was 0.38 +/- 0.30 and 0.26 +/- 0.25, respectively (p = 0 03). The diameter of basal side of FTMH (mu m) was 901.5 +/- 404.9 and 658.9 +/- 288.1, respectively (p = 0 00027). EZ was disrupted in 24 eyes and 63 eyes, respectively (p = 0 00071). ELM was disrupted in 15 eyes and 23 eyes, respectively (p = 0 00015). The FTMH diameters and the presence of LHEP were inversely correlated with the continuity of EZ and ELM. Conclusion. The preoperative appearance of LHEP could be one of the prognostic factor for the treatment of FTMH.
HINDAWI LTD, 2017年, JOURNAL OF OPHTHALMOLOGY, 英語[査読有り]
研究論文(学術雑誌)
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© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd Purpose: To report the 5-year incidence of visual impairment after mitomycin C-augmented trabeculectomy (MMC trabeculectomy) and the risk factors for visual impairment. Methods: This is a multicentre prospective observational cohort study. Among glaucoma patients registered in the Collaborative Bleb-related Infection Incidence and Treatment Study performed in Japan, the patients with eyes meeting the following qualifications were included: eyes with primary open-angle glaucoma; eyes with primary angle-closure glaucoma; eyes with exfoliative glaucoma; eyes with ≥3/60 in blindness analysis; and eyes with ≥20/60 in low-vision analysis and visual acuity loss analysis. The patients were followed at 6-month intervals for 5 years. The entry data and follow-up data were analysed to determine the incidence of blindness (<3/60), low vision (≥3/60 and <20/60) and visual acuity loss (≥0.2 logMAR) during the follow-up period. Risk factors for visual impairment were also analysed. Results: A total of 694 eyes of 694 or 559 eyes of 559 glaucoma patients were subjected to the blindness analysis or the low-vision and visual acuity loss analysis, respectively. Visual acuity significantly deteriorated (p < 0.0001): 12.2% (95%CI: 9.8–14.7%) of the patients became blind; 12.1% (95%CI: 9.4–14.9%) were judged to have low vision at the final examination; 28.3% (95%CI: 24.5–32.0%) were judged to have visual acuity loss. Glaucoma subtypes, poor preoperative visual function and postoperative complications are the main risk factors for visual impairment. Conclusions: Visual acuity was significantly reduced after MMC trabeculectomy in 5 years, and we identified several risk factors associated with this complication.
2016年11月01日, Acta Ophthalmologica, 94 (7), e561 - e570, 英語[査読有り]
研究論文(学術雑誌)
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研究論文(学術雑誌)
Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that predominantly attacks the optic nerve and spinal cord. This study evaluated the effect of administration of human IgG (hIgG) into the caudal vein on optic nerve degeneration in a rodent model of NMO. The optic nerves were exposed to AQP4-Ab-positive sera, and the administration of intravenous immunoglobulin (IVIG) was performed immediately, at 7 days (cohort A) or at 7 days and 10 days (cohort B) after exposure to the sera. A reference group, similarly exposed to the serum, was treated with saline. Retinal ganglion cells (RGCs) labeled by the injection of Fluoro-Gold into the superior colliculus were counted in whole-mounted retina. RGCs labeled by the injection of Fluoro-Gold into the superior colliculus were counted in the whole-mounted retina. The number of RGCs 14 days after optic nerve exposure to sera from patients with NMO was 1455 +/- A 192/mm(2) (n = 7) in cohort A, 1657 +/- A 192/mm(2) (n = 4) in cohort B, and 981 +/- A 182/mm(2) (n = 10) in the saline-treated reference group (p < 0.001). Western blotting revealed that the content of neurofilament in the optic nerve of the hIgG-treated group in cohort A was significantly greater than that in the reference group (p = 0.037). IVIG administration reduced optic nerve degeneration in a rat model of NMO-optic neuritis. IVIG could be used as a treatment in the acute phase of NMO.
SPRINGER JAPAN KK, 2016年09月, JAPANESE JOURNAL OF OPHTHALMOLOGY, 60 (5), 419 - 423, 英語[査読有り]
研究論文(学術雑誌)
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Background: It has been hypothesized that dysfunction of the solute carrier family 1, member1 gene (SLC1A1), which encodes the glutamate aspartate transporter, may play a role in normal tension glaucoma. In this study we investigate whether SLC1A1 is associated with normal tension glaucoma in Japanese patients.Methods: A total of 292 Japanese patients with normal tension glaucoma and 500 healthy control subjects were recruited. We genotyped 12 single-nucleotide polymorphisms in SLC1A1. We also performed an imputation analysis to evaluate the potential association of un-genotyped SLC1A1 single-nucleotide polymorphisms, and 165 single-nucleotide polymorphisms were imputed.Results: We observed an increased frequency of the G allele of rs10739062 in patients compared to controls (p = 0.043, OR = 1.25). The rs10739062 polymorphism exhibited a dominant effect: individuals with genotype GG and GC showed a 1.91-fold increase in risk compared to genotype CC (p = 0.0082). However, the statistical significance disappeared after Bonferroni correction for multiple testing (pc > 0.05). We did not find any significant association between any of the remaining 176 single-nucleotide polymorphisms and disease risk.Conclusions: Our study showed a lack of association between SLC1A1 variants and normal tension glaucoma in Japanese patients, suggesting that the SLC1A1 gene does not play a critical role in the development of the disorder in this patient population. However, further genetic studies with larger sample sizes are needed to clarify whether SLC1A1 may make some contribution that affects the risk of developing normal tension glaucoma.
Taylor and Francis Ltd, 2016年04月02日, Ophthalmic Genetics, 37 (2), 194 - 200, 英語[査読有り]
研究論文(学術雑誌)
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研究論文(学術雑誌)
Purposes: To evaluate the effects of axial length and age on the circumpapillary retinal nerve fiber layer (cpRNFL) and the inner macular parameters measured using 3 spectral-domain optical coherence tomography (OCT) instruments. Methods: A total of 102 normal eyes (1 eye per subject) were imaged using Cirrus, RTVue, and 3D-OCT. The cpRNFL and the macular retinal nerve fiber layer (mRNFL), the ganglion cell layer+inner plexiform layer (GCLIPL), and the mRNFL+GCLIPL ganglion cell complex, GCC thicknesses were analyzed. The correlations between these values and the axial length or age were evaluated using a partial correlation analysis. These correlations were corrected using the axial length-related magnification effect. Results: All but the nasal quadrant cpRNFL thicknesses and GCC thicknesses obtained using the 3 OCT instruments were significantly correlated with age. The average cpRNFL thickness and GCC thickness measured using the Cirrus and RTVue, but not by the 3D-OCT, had a negative correlation with the axial length. The temporal quadrant cpRNFL thickness measured using the 3 instruments was positively correlated with the axial length. The magnification correction made the most correlations positive. Conclusions: The average cpRNFL and GCC thicknesses measured using these 3 instruments decreased with age. The axial length affected the cpRNFL and GCC thicknesses as measured using the Cirrus and RTVue this effect likely depended on the fundus area of analyses.
Lippincott Williams and Wilkins, 2016年, Journal of Glaucoma, 25 (4), 383 - 389, 英語[査読有り]
研究論文(学術雑誌)
Background: Cytomegalovirus (CMV) is the most common congenital infection, and chorioretinitis is the most common ophthalmic manifestation of congenital CMV infection. We experienced a unique case of CMV retinopathy showing unusual retinal vessels. Case presentation: An infant boy weighing 1860 g was born at 36 weeks. He was diagnosed with severe symptomatic congenital CMV infection, which was confirmed by positive CMV-DNA in urine and whole blood, and he was referred to our ophthalmology department on his first day of life. Ophthalmoscopic examination and fluorescein angiography revealed no chorioretinitis but major retinal vascular occlusions and arterio-venous anastomosis associated with CMV detection in the aqueous humor. These findings regressed within a week after treatment with systemic gancyclovir administration. Conclusions: To our knowledge, there are no reports of these ocular issues associated with congenital CMV infection. These findings may be useful for the early and rapid diagnosis of congenital CMV infection.
BioMed Central Ltd., 2016年, BMC Ophthalmology, 16 (1), 81, 英語[査読有り]
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PURPOSE. Optical coherence tomography (OCT) instruments do not embed a normative database from highly myopic normal (HMN) eyes. The abilities of three OCT instruments to detect early glaucoma with high myopia were compared using the two controls with or without high myopia. METHODS. A total of 52 early glaucomatous eyes (mean deviation > -6.0 dB) with high myopia (spherical equivalent <= -6.0 diopters [HMG]), 54 HMN eyes, and 90 nonhighly myopic normal (NHMN) eyes were enrolled. Each participant was imaged using Cirrus, RTVue, and Topcon 3D OCT to evaluate the thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL), the macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL/IPL), and mRNFL + GCL/IPL (GCC). The covariate-adjusted areas under the receiver operating characteristic curves (AUCs) for detecting HMG were compared among the instruments and between the two normal groups (HMN or NHMN). RESULTS. Highly myopic normal eyes showed higher AUCs for the temporal quadrant cpRNFL thickness but lower AUCs for the superior and inferior RNFL thicknesses compared with NHMN. We found the AUCs for the GCC thickness showed no significant difference between the two control groups, but the GCL/IPL and mRNFL thicknesses had differences. CONCLUSIONS. The abilities of the three OCT instruments to detect early glaucomatous eyes with high myopia were different if the normal eyes were associated with high myopia or not. A normative database that includes data from patients with high myopia should be established for accurate diagnosis of glaucoma with high myopia. (www.umin.ac.jp/ctr number, UMIN000006900.)
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2015年10月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 56 (11), 6573 - 6580, 英語[査読有り]
研究論文(学術雑誌)
Purpose In previous studies, we applied receiver operating characteristic curve analysis to the signal-to-noise ratio distributions in the signal and noise windows of multifocal VEP (mfVEP) response. The areas under the curve thus obtained (SNR-AUC) were found to quantitatively detect glaucomatous visual field damage. The present study evaluated the reproducibility of SNR-AUC and the Humphrey visual field (HVF) global indices in 37 eyes with primary open angle glaucoma (POAG; POAG group) and in 30 controls (control group) within a 2-year period. Methods The HVF SITA standard 24-2 and mfVEP were recorded at three separate sessions for each individual. The intersession variability for SNR-AUC, mean deviation (MD), and pattern standard deviation (PSD) was evaluated using the repeated measures of analysis of variance and Bland-Altman plots. The logarithmically converted coefficients of variation (CV) of PSD and SNR-AUC were compared between the control and POAG groups. Linear regression analyses were performed on the logarithmic CV of SNR-AUC against the average MD, PSD, and SNR-AUC. Results SNR-AUC in the POAG group was significantly lower and its CV was greater compared with the control group (P < 0.0001). MD value recorded at the third visit had significantly improved than that at the first visit in the control group (analysis of variance, P = 0.03), whereas PSD value was significantly worse in the POAG group (P = 0.024). In the POAG group, SNR-AUC CV increased as the glaucoma stage became more advanced when evaluated by any functional parameters tested (i.e., MD, PSD, or SNR-AUC). Conclusions The SNR-AUC of mfVEP showed a high reproducibility in control group, whereas it fluctuated more in the POAG group according to the disease severity. MD in the control group and PSD in POAG group fluctuated among sessions during the 2-year period.
SPRINGER, 2015年10月, DOCUMENTA OPHTHALMOLOGICA, 131 (2), 115 - 124, 英語[査読有り]
研究論文(学術雑誌)
Background/aims Chiasmal compression affects the crossed nerve fibres originating from the nasal hemiretina, as opposed to the uncrossed fibres from the temporal hemiretina. The objectives were to evaluate circumpapillary retinal nerve fibre layer (cpRNFL) thickness by spectral-domain optical coherence tomography in eyes with band atrophy (BA) accompanying temporal hemianopia due to chiasmal damage and to estimate the distribution pattern of cpRNFL from the nasal hemiretina. Methods This cross-sectional study included 53 eyes with optic neuropathy due to chiasmal lesions and 72 normal eyes. Visual field sensitivity (VFS) was evaluated by standard automated perimetry. Eyes with abnormalities in the nasal visual hemifield were excluded. The structure-function relationships (cpRNFL thickness and VFS in the temporal hemifield) were evaluated in eyes with BA. The base levels composed of only non-neuronal elements and cpRNFL from the temporal hemiretina were estimated in the average and 12 sector-cpRNFL thicknesses using regression analysis. Results The base level in the average cpRNFL thickness was 71.2 mm in eyes with BA, which corresponded to 70% of average thickness of normal controls. However, the estimated base level of 12 sector-cpRNFL thicknesses represented the unique distribution pattern, in which base level-thickness localised at the 1 o'clock and 5 o'clock sectors was extensively reduced, with an even distribution of base levels at other sectors. Conclusions The RNFL originating from the nasal hemiretina is estimated to enter into the optic disc predominantly at the 1 o'clock and 5 o'clock angles.
BMJ PUBLISHING GROUP, 2015年10月, BRITISH JOURNAL OF OPHTHALMOLOGY, 99 (10), 1419 - 1423, 英語[査読有り]
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研究論文(学術雑誌)
[査読有り]
Background: Rebamipide with mucin secretagogue activity was recently approved for the treatment of dry eye. The efficacy and safety in the treatment of rebamipide were shown in two pivotal clinical trials. It was the aim of this study to evaluate the effect of 2 % rebamipide ophthalmic suspension in patients with dry eye and analyze relevant factors for favorable effects of rebamipide in clinical practice. Methods: This was a retrospective cohort study of 48 eyes from 24 patients with dry eye treated with 2 % rebamipide ophthalmic suspension. Dry eye-related symptom score, tear film break-up time (TBUT), fluorescein ocular surface staining score (FOS) and the Schirmer test were used to collect the data from patients at baseline, and at 2, 4, 8, and 12 week visits. To determine the relevant factors, multiple regression analyses were then performed. Results: Mean dry eye-related symptom score showed a significant improvement from the baseline (14.5 points) at 2, 4, 8 and 12 weeks (9.80, 7.04, 7.04 and 7.83 points, corrected P value <0.001, respectively). Median FOS showed a significant improvement from the baseline (3.0 points) at 2, 4, 8 and 12 weeks (2.0, 2.0, 1.0 and 1.0 points, corrected P value <0.001, respectively). TBUT and Schirmer test values were not significantly improved after the treatment. For ocular symptoms, three parameters (foreign body sensation, dry eye sensation and ocular discomfort) showed significant improvements at all visits. The multiple regression analyses showed that the fluorescein conjunctiva staining score was significantly correlated with the changes of dry eye-related symptom score at 12 weeks (P value = 0.017) and dry eye-related symptom score was significantly correlated with independent variables for the changes of FOS at 12 weeks (P value = 0.0097). Conclusions: Two percent rebamipide ophthalmic suspension was an effective therapy for dry eye patients. Moreover the fluorescein conjunctiva staining score and dry eye-related symptom score might be good relevant factors for favorable effects of rebamipide.
BIOMED CENTRAL LTD, 2015年06月, BMC OPHTHALMOLOGY, 15, 58, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
Aquaporin 9 (AQP9), an aquaglyceroporin, is not only permeable to water but also to non-charged solutes, such as lactate. Lactate can be an energy source for retinal neurons. This study aimed to evaluate the effect of the downregulation of AQP9 expression on the survival rates and reactive oxygen species accumulation in RGC-5 cells cultured in a medium containing lactate. The Live/Dead assay revealed that the cell death rate of RGC-5 cells transfected with the control siRNA (siControl) was 3.65%±0.75% in the 5-mM glucose medium. The death rate was significantly increased by five-fold in the no glucose and 10-mM d-lactate media but not in the 10-mM l-lactate medium. In comparison, the death rate of cells transfected with siRNA targeting AQP9 (siAQP9) was 8.07%±1.01% in the 5-mM glucose medium, which was significantly increased by two-fold in the other medium conditions, indicating that the downregulation of AQP9 expression eliminated the prosurvival effect of l-lactate. Few RGC-5 cells transfected with siControl showed dichlorofluorescein (DCF) fluorescence when cultured in 5-mM glucose and 10-mM l-lactate media. However, approximately 70% of those showed DCF fluorescence when cultured in the no glucose and 10-mM d-lactate media. The downregulation of AQP9 significantly increased the DCF fluorescence rate to 50.44%±6.13% in the 10-mM l-lactate medium, whereas, it did not increase the rate in the other medium conditions. These results demonstrate that AQP9 expression is required for l-lactate to maintain retinal neuronal survival.
2015年03月04日, Neuroscience letters, 589, 185 - 90, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[査読有り]
[査読有り]
[査読有り]
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. (C) 2015 S. Karger AG, Basel
KARGER, 2015年, OPHTHALMOLOGICA, 234 (1), 33 - 39, 英語[査読有り]
研究論文(学術雑誌)
To compare the relationship between visual field sensitivity (VFS) and macular parameters measured using three spectral-domain optical coherence tomography (SD-OCT) instruments and to determine a base level (=floor effect) for macular parameters. We imaged 127 glaucomatous eyes (1 eye per subject) using three different OCT instruments, i.e., the Cirrus, RTVue and 3D OCT devices; 76 normal eyes were evaluated as controls using the same instruments. The thicknesses of the macular retinal nerve fiber layer (mRNFL), ganglion cell layer+inner plexiform layer (GCL/IPL), and mRNFL+GCL/IPL (GCC) were analyzed. The VFS of the area analyzed by OCT was expressed in decibels and the 1/Lambert scale. For each parameter, the structure-function relationship and the base level were evaluated by regression analysis. The strength of the correlations between the instruments was compared by the bootstrapping method. All of the macular parameters evaluated exhibited statistically significant correlations with VFS. The average GCC measured by all three SD-OCT instruments and the average mRNFL thickness measured by the Cirrus and 3D OCT instruments had similar correlations with VFS. The average GCL/IPL thickness measured by the Cirrus OCT instrument was better correlated with VFS that was measured by the 3D OCT instrument (p = 0.031). The base level GCC thickness measured by all three instruments was approximately 65 % of that of normal eyes. The base level mRNFL thickness measured with the Cirrus and OCT instruments was 52 and 48 %, respectively, of that of normal eyes. The base level GCL/IPL thickness measured with the Cirrus and 3D instruments was 71 and 75 %, respectively, of that of normal eyes. The three SD-OCT instruments evaluated showed similar structure-function relationships in terms of GCC and mRNFL measurements. The base levels of the macular parameters determined by the three instruments differed, due, at least partly, to the scanning area defined by each instrument.
SPRINGER JAPAN KK, 2015年01月, JAPANESE JOURNAL OF OPHTHALMOLOGY, 59 (1), 55 - 64, 英語[査読有り]
研究論文(学術雑誌)
The impairment of mitochondrial function is an important pathogenic factor in glaucoma and other optic neuropathies in which retinal ganglion cell (RGC) death is the fundamental pathology. Syntaphilin was recently discovered as a docking protein that affects mitochondrial mobility. However, no reports have investigated the involvement of syntaphilin in the visual system. We investigated the expression of syntaphilin in the rat retina, optic nerve and brain. The expression of syntaphilin exhibited varying patterns in the visual system. Syntaphilin was expressed in retinal ganglion cells in the retina, in the cell bodies of neurons in the superior colliculus and was abundant in the astrocytes of rat optic nerves (similar to the findings that syntaphilin is expressed in human optic nerves). After optic nerve transection, which caused RGC death and axonal degeneration, quantitative real-time RT-PCR was used to assess changes in gene expression in the rat retina and optic nerve. Syntaphilin gene and protein expression in the optic nerve was downregulated 3 and 7 days after optic nerve transection. Our study suggests that syntaphilin expression in astrocytes at the optic nerve might be involved in axonal injury. (C) 2014 Elsevier Ltd. All rights reserved.
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2014年12月, EXPERIMENTAL EYE RESEARCH, 129, 38 - 47, 英語[査読有り]
研究論文(学術雑誌)
Purpose: Our aim was to investigate the efficacy and prognostic factors of intraocular injections of bevacizumab as needed in patients with macular edema secondary to central retinal vein occlusion (CRVO). Methods: This is a retrospective study including 28 eyes of 27 consecutive patients with macular edema due to CRVO and followed for at least 6 months. The mean age of the patients was 66.3 years. The patients underwent an intravitreal injection of bevacizumab (1.25 mg) at the initial visit. Retreatments were performed when macular edema was persistent or worsened (as-needed regimen). The primary outcome measure was the mean change in best-corrected visual acuity (BCVA). The change in central retinal thickness (CRT) was evaluated as the secondary outcome. Finally, the factors useful for predicting BCVA outcome were determined. Results: The mean number of injections was 1.8 over a period of 6 months. The mean BCVA (logarithm of minimum angle of resolution) was significantly improved at 1 (-0.097), 3 (-0.14), and 6 months (-0.25) after the initial injection (P< 0.05, < 0.01, and < 0.001, respectively). The mean CRT was also improved significantly at 1 (-250.4), 3 (-150.0), and 6 months (-187.2) (P< 0.001 each). Earlier treatment and better improvement in BCVA at 1 month after the initial treatment were the prognostic factors significantly associated with better visual outcomes at 6 months (P=0.047 and 0.029, respectively). Conclusion: Intravitreal injection of bevacizumab as needed significantly improved visual acuity and macular edema in CRVO patients. Time before the treatment and early response to the treatment were important factors for the visual outcome.
Dove Medical Press Ltd, 2014年11月19日, Clinical Ophthalmology, 8, 2301 - 2305, 英語[査読有り]
研究論文(学術雑誌)
PURPOSE. To assess the diagnostic performance of the macular parameters detected by spectral-domain optical coherence tomography (SD-OCT) in band atrophy (BA) eyes. METHODS. Forty-nine BA eyes with permanent temporal hemianopia and 89 normal eyes were enrolled. Any patients who had nasal visual field loss were excluded. Each participant was imaged by three-dimensional (3D) OCT-2000, and 10 3 10 grids in the macula were automatically allocated. The thickness of the macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL) + (GCL+inner plexiform layer [IPL]), and GCL++ (RNFL+GCL+IPL) in both nasal and temporal hemiretina was calculated and compared between the BA and normal eyes. The areas under the receiver operating characteristic curves (AUCs) in these parameters were compared between the nasal hemiretina and the temporal hemiretina. RESULTS. All the parameters in the BA eyes were significantly thinner than those in the normal eyes. The AUCs for the mRNFL, GCL+, and GCL++ thickness in the nasal hemiretina were 0.890, 0.988, and 0.981, respectively. The parameters in the nasal hemiretina showed significantly higher AUCs than those parameters in the temporal hemiretina. In the temporal hemiretina, the damaged grids in the mRNFL were located in the arcuate areas in each hemifield. CONCLUSIONS. The inner macular parameters in the nasal hemiretina exhibited high diagnostic abilities to detect BA. The GCL+ was more affected than mRNFL. The characteristic pattern of mRNFL and GCL+ thinning was implicated in the anatomical architecture regarding the nasotemporal overlap of the crossed and uncrossed fibers around the fovea. (www.umin.ac.jp/ctr number, UMIN000006900.)
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2014年07月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 55 (7), 4667 - 4672, 英語[査読有り]
研究論文(学術雑誌)
We have previously reported that the degree of signal-to-noise ratio (SNR) distribution overlaps between a signal window and a noise window in multifocal VEP (mfVEP) responses, which is determined by the area under the receiver-operating characteristic curve termed SNR-AUC, can quantitatively detect glaucomatous visual functional damage. However, the effect of high myopia on this parameter is not yet known. SNR-AUC, total deviation, and retinal sensitivity on the Humphrey visual field (HVF) test were compared among 34 eyes >-6 diopters (control) and 21 eyes a parts per thousand currency signa'6 diopters (high myopia), both of which were ophthalmoscopically normal and had a best-corrected visual acuity of 20/20. The mfVEP and HVF parameters were obtained from stimulus areas that corresponded to both HVF 24-2 and 10-2 programs. Both the HVF 24-2 total deviation and the SNR-AUC obtained from 60 sectors in high-myopia patients were significantly lower compared with controls (P = 0.045 and P = 0.003, respectively). The SNR-AUC obtained from the central 36 sectors that corresponded to the HVF 10-2 area in high-myopia patients was also significantly lower than that of the controls (P = 0.01). Multiple regression analyses demonstrated that age and refractive error were significantly associated with retinal sensitivity on the HVF 24-2 and SNR-AUC for the whole field and central field, respectively. High myopia reduces the SNR-AUC of mfVEP responses, even with refractive correction. A normative database should be separately established for high myopes to evaluate the mfVEP responses obtained from highly myopic glaucoma patients.
SPRINGER, 2014年06月, DOCUMENTA OPHTHALMOLOGICA, 128 (3), 179 - 189, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Histones are DNA-binding proteins and are involved in chromatin remodeling and regulation of gene expression. Histones can be released after tissue injuries, and the extracellular histones cause cellular damage and organ dysfunction. Regardless of their clinical significance, the role and relevance of histones in ocular diseases are unknown. We studied the role of histones in eyes with retinal detachment (RD). Vitreous samples were collected during vitrectomy, and the concentration of histone H3 was measured by enzyme-linked immunosorbent assay. The location of the histones and related molecules was examined in a rat RD model. The release of histones and their effects on rat retinal progenitor cells R28 and ARPE-19 were evaluated in vitro. In addition, the protective role of the vitreous body against histones was tested. The intravitreal concentration of histones was higher in eyes with RD (mean, 30.9 +/- 9.8 ng/ml) than in control eyes (below the limit of detection, P<0.05). In the rat RD model, histone H3 was observed on the outer side of the detached retina and was associated with photoreceptor death. Histone H3 was released from cultured R28 by oxidative stress. Histones at a concentration 10 mu g/ml induced the production of interleukin-8 in ARPE-19 cells (2.5-fold increase, P<0.05) that was mediated through the ERK1/2- and p38 MAPK-dependent pathways and Toll-like receptor 4. Histones were toxic to cells at concentrations of >= 20 mu g/ml. Vitreous body or hyaluronan decreased toxicity of histones by inhibiting diffusion of histones. These results indicate that histones are released from retinas with RD and may modulate the subretinal microenvironment by functioning as damage-associated molecular pattern molecules, thereby inducing proinflammatory cytokines or cell toxicity. In addition, the important role of the vitreous body and hyaluronan in protecting the retina from these toxic effects is suggested.
NATURE PUBLISHING GROUP, 2014年05月, LABORATORY INVESTIGATION, 94 (5), 569 - 585, 英語[査読有り]
研究論文(学術雑誌)
To establish a rat glaucoma model with chronic intraocular pressure (IOP) elevation induced by microbeads suspended in sodium sulfate-sodium hyaluronate. Chronic elevation of IOP was induced unilaterally by injecting polystyrene microbeads, suspended in 4 % sodium sulfate and 3 % sodium hyaluronate, into the anterior chamber. The microbead suspension was injected through either the clear corneal (CC) or sclerocorneal (SC) tunnel. IOP changes were monitored up to 8 weeks after injection. The loss of retinal ganglion cells (RGCs) was assessed using fluorogold retrograde labeling of RGCs. RGC axons were evaluated by immunohistochemistry and immunoblotting. The resulting IOP elevation was maintained up to 3 weeks after the intracameral injection of microbeads through the CC route and up to 4 weeks after injection through the SC route. The density of RGCs was significantly reduced at 4 weeks after injection, with the SC route leading to more RGC loss than the CC route (p = 0.037). The neurofilament immunoreactivity and protein levels in the optic nerve were also significantly reduced at 4 weeks after injection. Some eyes in the SC route cohort received re-injection of the microbead suspension at 4 weeks after the initial injection, which led to an elevated IOP more than 8 weeks after the initial injection, and eventually a 27.5 % loss of RGC density compared with the control eyes. The intracameral injection of microbeads suspended in hyaluronate effectively produced chronic IOP elevation and subsequent RGC degeneration in rat eyes. The sclerocorneal tunnel approach yielded a longer period of IOP elevation than the clear corneal approach. Our modified microbead injection offers a reliable high-pressure glaucoma model.
SPRINGER JAPAN KK, 2014年05月, JAPANESE JOURNAL OF OPHTHALMOLOGY, 58 (3), 290 - 297, 英語[査読有り]
研究論文(学術雑誌)
To measure changes in axial length before and after trabeculectomy with noncontact, partial coherence laser interferometry and identify patient factors that lead to the development of hypotony maculopathy and axial length shortening in 25 eyes with intraocular pressure (IOP) a parts per thousand currency sign6 mmHg at 4 weeks after mitomycin C-augmented trabeculectomy. A retrospective comparative case series. Hypotony maculopathy was identified with both ophthalmoscopy and spectral-domain optical coherence tomography. Axial length and IOP were serially measured pre- and postoperatively. Logistic regression analysis was performed to identify factors associated with the presence of hypotony maculopathy at 4 weeks after trabeculectomy and multiple regression analysis to identify factors associated with axial length changes. Ten eyes exhibited hypotony maculopathy, whereas the remaining 15 did not. Patients with hypotony maculopathy were significantly younger (47.7 +/- A 6.2 years) compared with those without it (63.3 +/- A 9.6 years, P = 0.0002, unpaired t test). The percent reduction of axial length after trabeculectomy was significantly larger in the former group (5.91 +/- A 2.76 %) compared with the latter group (1.51 +/- A 0.91 %) (P = 0.0001, Mann-Whitney U test). Multivariate analyses showed that only age was associated with the presence of hypotony maculopathy, with an odds ratio of 0.82 (P = 0.0075), when age, sex, type of glaucoma, lens status, percent changes in axial length and IOP before and after trabeculectomy, and central corneal thickness were included as independent variables (R (2) = 0.543, P = 0.003). Age-dependent axial length reduction is a risk factor for the development of hypotony maculopathy after trabeculectomy.
SPRINGER JAPAN KK, 2014年05月, JAPANESE JOURNAL OF OPHTHALMOLOGY, 58 (3), 267 - 275, 英語[査読有り]
研究論文(学術雑誌)
Neuromyelitis optica (NMO) is an autoimmune inflammatory, neurodestructive disease primarily targeting the optic nerve and spinal cord. An autoantibody against water channel protein aquaporin-4 (AQP4), which is expressed at endofeet of astrocytes has been implicated in the pathogenesis of NMO. We evaluated the impact of sera of seropositive patients with NMO spectrum disorders (NMOSDs) on the rodent optic nerve and retina. Serum was obtained either from patients with seropositive NMOSD (AQP4+), seronegative patient with idiopathic optic neuritis (AQP4), and healthy volunteers (control). Anti-AQP4 antibody in a serum was measured by a previously established cell-based assay. The patients' sera were applied on the optic nerve after de-sheathed. Immunohistochemistry showed that at 7 days after the treatment, the area of the optic nerve exposed to the AQP4+ sera lost expression of both AQP4 and glial fibrillary acidic protein. Also, Human-IgG immunoreactivity and marked invasion of inflammation cells were observed in the optic nerve treated with AQP4+ serum. Immnoreactivity of neurofilament was reduced at 14 days after the treatment, not 7 days. Real-time polymerase chain reaction revealed the reduced gene expression of neurofilament in retina from the eye that was exposed to the AQP4+ sera at 14 days. Retrograde fluorogold-labeling on the retinal flatmount disclosed the significantly reduced number of retinal ganglion cells when the AQP4+ sera were applied. The present model has demonstrated that the sera from patients with seropositive NMOSDs led to the regional astrocytic degeneration and inflammatory cell invasion in the optic nerve, resulting in the ultimate loss of RGCs and their axons at areas beyond the injury site. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2014年02月, EXPERIMENTAL EYE RESEARCH, 119, 61 - 69, 英語[査読有り]
研究論文(学術雑誌)
[査読有り][招待有り]
研究論文(学術雑誌)
PURPOSE. We compared the ability of circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macular parameters obtained by three spectral-domain optical coherence tomography (SD-OCT) instruments to detect glaucoma. METHODS. We enrolled 87 normal eyes and 145 glaucomatous eyes (75 early glaucomatous eyes (EGs), mean deviation > -6 dB). Each participant was imaged using Cirrus, RTVue, and 3D-OCT to evaluate the average and quadrant cpRNFL thicknesses. The macular retinal nerve fiber layer (mRNFL), ganglion cell layer plus inner plexiform layer (GCL/IPL), and mRNFL + GCL/IPL (ganglion cell complex [GCC]) thicknesses were analyzed. The areas under the receiver operating characteristic curves (AUCs) were compared among the instruments. RESULTS. These instruments revealed similar AUCs for the average cpRNFL and GCC thicknesses in EGs, and total all-stage glaucomatous eyes (TGs). RTVue showed better performance in the nasal cpRNFL thickness than Cirrus and 3D-OCT, and better performance in the temporal cpRNFL thickness than 3D-OCT in TGs. RTVue had a higher AUC for the superior GCC thickness compared to Cirrus and 3D-OCT in EGs, and TGs. Cirrus had higher AUCs for GCL/IPL parameters in TGs, and lower AUCs for the mRNFL parameters in EGs and TGs compared to 3D-OCT. CONCLUSIONS. The average cpRNFL and GCC thicknesses measured using these OCT instruments exhibited similar abilities in the diagnosis of glaucoma, and RTVue exhibited better diagnostic abilities than Cirrus and 3D-OCT for nasal cpRNFL, and superior GCC thicknesses. The diagnostic performance of Cirrus and 3D-OCT was different for GCL/IPL and mRNFL parameters. (http://www.umin.ac.jp/ctr number, UMIN000006900.)
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2013年07月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 54 (7), 4478 - 4484, 英語[査読有り]
研究論文(学術雑誌)
[査読有り][招待有り]
研究論文(学術雑誌)
Purpose: To compare the relationships of parapapillary retinal nerve fibre layer (RNFL) thickness among three spectral-domain optical coherence tomography (SD-OCT) instruments with visual field sensitivity (VFS). Methods: One hundred and thirteen eyes of 113 Japanese subjects with glaucoma (mean deviation in standard automated perimetry = -8.9 +/- 6.7 dB) were imaged by Cirrus, RTVue and 3D OCT. The average hemi-superior and hemi-inferior RNFL thicknesses were obtained. In addition, the structure-function relationship using two retinotopic maps that consisted of six or nine sectors was also evaluated. Decibel (dB) scale and 1/Lamert (1/L) were used to express VFS. RNFL thickness correlation with corresponding VFS in visual field sectors was compared among the three instruments. Background RNFL thickness (non-neuronal tissue) for each instrument was estimated using a linear regression model at 1/L = 0. Results: The correlation between the average hemi-superior and hemi-inferior RNFL thickness in the three SD-OCT instruments with corresponding VFS was similar. In the analysis of retinotopic maps, 3D OCT showed a higher correlation in superotemporal sectors than RTVue, whereas RTVue had a stronger relationship in the nasal sector than Cirrus. The background RNFL thickness extrapolated was approximately 60% that of normal eyes in all the instruments. Conclusions: The three SD-OCT showed similar overall correspondence with VFS with a partially discordant retinotopic relationship. RNFL measured with any SD-OCT devices likely contains non-neuronal tissue, comprising 60% of its thickness.
WILEY-BLACKWELL, 2013年05月, ACTA OPHTHALMOLOGICA, 91 (3), E196 - E202, 英語[査読有り]
研究論文(学術雑誌)
Aquaporin 9 (AQP9), an aquaglyceroporin belonging to the AQP water channel family, is permeable not only to water but also to noncharged solutes such as lactate. In neurons, Lactate presumably acts as an energy substrate and as a source of NADH (the reduced form of nicotinamide adenine dinucleotide), a scavenger of reactive oxygen species (ROS). We previously reported that retinal ganglion cells (RGCs) express AQP9 and that elevated intraocular pressure reduces AQP9 expression and increases death of neurons in the retinal ganglion cell Layer of rodents. In the present study, we investigated the association of AQP9 expression with serum deprivation-induced death of RGC-5 cells and with death of neurons in the rat retinal ganglion cell layer after optic nerve transection (ONT). The effect of AQP9 RNA interference on serum deprivation-induced apoptosis, ROS accumulation, and the NAD(+)/NADH ratio in RGC-5 cells was examined. Both serum deprivation and ONT significantly reduced AQP9 protein expression in RGCs and increased the rate of RGC death. Retinal AQP9 gene expression also declined after ONT. Down-regulation of AQP9 significantly increased apoptosis, ROS accumulation, and the NAD(+)/NADH ratio in the RGC-5 cells. These findings suggest that AQP9 Loss adversely affects survival of RGCs, at least partly because of decreased transport of Lactate as a substrate for energy and/or ROS scavenger.
ELSEVIER SCIENCE INC, 2013年05月, AMERICAN JOURNAL OF PATHOLOGY, 182 (5), 1727 - 1739, 英語[査読有り]
研究論文(学術雑誌)
光干渉断層計(optical coherence tomography:OCT)は眼科学に生体病理学ともいえる新しい分野を形成し,黄斑疾患や緑内障の診療に革新的な情報をもたらしている.緑内障の診断には他の視神経・視路疾患との鑑別が必要である.そこでOCTの視神経・視路疾患における有用性について検討した.次いで,視神経疾患の中で最も頻度の高い緑内障性視神経症(glaucomatous optic neuropathy:GON)の病態についてアクアポリン(aquaporin:AQP)の動態に焦点を当てて検討した.I 光干渉断層計による視神経・視路疾患の評価 交互点滅対光反射試験(swinging flashlight test)は相対的瞳孔求心路障害(relative afferent pupillary defect:RAPD)を検出する容易で敏感な他覚的検査である.片眼性視神経萎縮20症例でswinging flashlight testにおけるRAPD量とOCTで測定した網膜神経線維層厚(retinal nerve fiber layer thickness:RNFLT)の両眼間の比には有意の相関がみられた.OCTによりRAPDという両眼の視神経機能障害の差を,構造的な差として把握することができた.外傷性視神経症4例において受傷直後よりRNFLTおよび神経節細胞複合体(ganglion cell complex:GCC)の経時変化を観察した.OCTによりRNFLT,GCCは受傷後2週から20週の間に急速に減少することが分かった.視交叉症候群34眼でRNFLTを測定すると,視神経乳頭周囲の水平方向では垂直方向に比してRNFLTは有意に減少していた.このことは視交叉症候群にみられる視神経乳頭の帯状萎縮が,OCTにより量的に把握できることを示した.視索症候群でRNFLTを測定すると,患側では視神経乳頭の垂直方向の水平方向に対する菲薄化が,対側では水平方向の垂直方向に対する菲薄化が確認された.またGCCでは患側の中心窩から耳側半側の菲薄化,対側眼では鼻側半側の菲薄化を示した.これらは視索症候群における患側視神経乳頭の砂時計状萎縮,対側における帯状萎縮,また同名半盲を構造的に捉えていることを示す.OCTはこのように視神経・視路疾患の評価にも有用であったが,限界もある.視交叉症候群ではOPTvue 100とCirrusで測定したRNFLTの非薄部位はまったく逆の結果を示した.これはRTVue 100のほうがCirrusに比較して視神経乳頭鼻側の薄いRNFL評価に優れているためであった.OCTの評価には機種の特性を考慮する必要がある.II 視神経におけるアクアポリンの動態 AQPは細胞膜を水が効率よく通過できるための水チャンネルを構成する膜蛋白質である.従来,視神経にはAQP-4が発現していることが報告されていたが,AQP-4は球後の有髄神経部位にのみ発現し,視神経乳頭に発現するAQPについては不明であった.我々はラット,サル,ヒトで視神経におけるAQPの発現を検討した.無髄神経部位の前篩状板部,篩状板部ではAQP-9のみが発現し,有髄神経部位ではAQP-4とAQP-9が発現していることを認めた.これらはglial fibrillary acidic proteinと共発現したことから,アストロサイトに発現していることが分かった.ラットにおいて高眼圧眼を作製するとAQP-4の発現は変化がなかったが,AQP-9の発現は著明に減少した.この現象はサル高眼圧眼,ヒト緑内障眼でも同様であった.AQP-9は水のほか,乳酸などの溶質も輸送するアクアグリセロポリンに属する.近年,神経科学の分野ではアストロサイトから神経細胞への乳酸の輸送が神経細胞のエネルギー基質になっているというastrocyte-to-neuron lactate shuttle hypothesisが提唱されている.眼圧上昇による視神経乳頭におけるAQP-9の発現低下はGONの発症に深くかかわっている可能性がある.(著者抄録)
(公財)日本眼科学会, 2013年03月, 日本眼科学会雑誌, 117 (3), 187 - 211, 日本語[査読有り]
PURPOSE. We determined the cause of sterile endophthalmitis after intravitreal triamcinolone acetonide (IVTA). METHODS. The clinical records of 21 eyes that had sterile endophthalmitis after IVTA were reviewed. Cytologic studies were performed, and cytokine and chemokine profiles in the aqueous humor were determined. The effects of a direct contact of triamcinolone acetonide (TA) particles with cultured lens epithelial cells (B3) or retinal pigment epithelial cells (ARPE-19) on cytokine production were determined. Noncontact culture studies were performed in a Boyden chamber; 11-deoxycortisol was used for nonbioactive particles. RESULTS. Inflammation appeared one day after the IVTA, and the incidence of severe sterile endophthalmitis was 13.0% (6/46), which was reduced to 4.3% (2/47) after switching to preservative-free TA. Most cells found in the aqueous humor were granulocytes. The concentrations of IL-6 (447.8-<5000 pg/mL) and IL-8 (47.2-<5000 pg/mL) were increased significantly, but IL-1 beta, IL-10, IL-12p70, and TNF-alpha were not significantly changed. In B3 cells, the level of IL-8 increased significantly when the cells made direct contact with TA particles (1.33 times that of PBS, P < 0.05, Student's t-test), but not in noncontact cultures. Similar reaction pattern was found in ARPE-19 cells. These effects also were observed when the cells were exposed to 11-deoxycortisol. CONCLUSIONS. Sterile endophthalmitis after IVTA is characterized by an immediate granulocytic infiltration and an increase of IL6/IL-8 in the aqueous humor. Preservatives may be a factor causing this condition, and mechanical/rheologic stress by particles presumably might be a new causative factor by increasing IL-6/IL-8. (Invest Ophthalmol Vis Sci. 2013; 54:1758-1766) DOI:10.1167/iovs.12-11247
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2013年03月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 54 (3), 1758 - 1766, 英語[査読有り]
研究論文(学術雑誌)
Unilateral injury of the optic tract leads to asymmetrical optic atrophy in both eyes derived from the crossing of the nerve fibers at the chiasm. This report demonstrates unique imaging appearances of optic atrophy due to this uncommon condition detected by spectral-domain optical coherence tomography (SD-OCT). Cirrus and RTVue measurements were performed in four cases of optic tract syndrome. Circumpapillary retinal nerve fiber layer (cpRNFL) thickness was obtained from both instruments and ganglion cell complex (GCC) integrity was obtained from RTVue. The presumable reduction rates of quadrant cpRNFL thickness were calculated from the published normative database and compared between eyes with temporal hemianopia and those with nasal hemianopia. Both devices showed significant reduction of cpRNFL thickness, but did not have statistical difference in the reduction rates at temporal or nasal quadrant cpRNFL between contralateral and ipsilateral eyes to the lesion. Color-coded maps helped to visualize the unique pattern of cpRNFL and GCC thinning. SD-OCT can be used as a diagnostic tool for the optic tract syndrome.
SPRINGER, 2013年02月, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 251 (2), 591 - 595, 英語[査読有り]
研究論文(学術雑誌)
研究論文(その他学術会議資料等)
The caveolin 1 to caveolin 2 (CAV1-CAV2) gene region on chromosome 7q31 has been reported to be associated with susceptibility to primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) in previous studies. We investigated whether genetic variants in the CAV1-CAV2 region are associated with NTG in Japanese patients. Two hundred and ninety-two Japanese patients with NTG and 352 Japanese healthy controls were recruited. We genotyped three single-nucleotide polymorphisms that is, rs1052990, rs4236601, and rs7795356, in the CAV1-CAV2 gene region and assessed the allelic diversity among cases and controls. The frequency of the minor allele (G) of rs1052990 was significantly decreased in NTG cases compared with controls (P=0.014, OR=0.71), whereas NTG or POAG cases had a significantly higher frequency of the allele than controls in previous studies. Conversely, rs7795356 did not show any significant association with NTG cases, and rs4236601 was monomorphic in the Japanese study population. Our findings did not correspond with previous positive results, suggesting that CAV1-CAV2 variants studied in the present study are not important risk factors for NTG susceptibility in all populations. Further studies are needed to elucidate the possible contribution of the CAV1-CAV2 region to the development of glaucoma. © 2013 Macmillan Publishers Limited All rights reserved.
Nature Publishing Group, 2013年, Eye (Basingstoke), 27 (8), 979 - 983, 英語[査読有り]
研究論文(学術雑誌)
PURPOSE. To compare the ability of circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macular parameters obtained by three spectral-domain optical coherence tomography (SD-OCT) instruments to detect highly myopic glaucoma. METHODS. In this study, 84 glaucomatous eyes, 53 normal eyes with high myopia, and 86 normal eyes (not highly myopic) were enrolled. Each participant was imaged using Cirrus, RTVue, and 3D OCT to evaluate the average and quadrant cpRNFL thicknesses. The macular retinal nerve fiber layer (mRNFL), ganglion cell layer {thorn} inner plexiform layer (GCL/IPL), and mRNFL {thorn} GCL/IPL (GCC) thicknesses were analyzed. The areas under the receiver operating characteristic curves (AUCs) were compared between the instruments. In addition, the best parameters for the AUC were compared between the cpRNFL parameters and macular parameters in each instrument. RESULTS. These analyses revealed similar AUCs for the average cpRNFL and GCC thicknesses between the instruments. RTVue displayed a significantly higher AUC in the nasal cpRNFL thickness than both Cirrus (P = 0.0004) and 3D OCT (P = 0.0006). 3D OCT showed higher AUCs than Cirrus in the mRNFL parameters. There were no significant differences between the best cpRNFL parameters and macular parameters in each instrument. CONCLUSIONS. The average cpRNFL and GCC thicknesses that were measured using these OCT instruments exhibited similar abilities for diagnosing highly myopic glaucoma, and RTVue exhibited better diagnostic abilities than Cirrus and 3D OCT for nasal cpRNFL. 3D OCT had better ability than Cirrus in the mRNFL. Both cpRNFL and GCC in each instrument were comparable, and their measurements offered good ability for diagnosing glaucoma with high myopia. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
2013年, Investigative Ophthalmology and Visual Science, 54 (9), 6025 - 6032, 英語[査読有り]
研究論文(学術雑誌)
Purpose. Using spectral-domain optical coherence tomography (SD-OCT), we assessed the ability of cluster analyses, based on the grid-pattern of macular parameters, to detect glaucoma. Methods. We enrolled 75 normal eyes, 64 early glaucomatous eyes (EG), and 40 preperimetric glaucomatous eyes (PPG). Each participant was imaged using 3-dimensional optical coherence tomography (3D-OCT) to examine the macular retinal nerve fiber layer (mRNFL) and the thickness of the ganglion cell layer, together with the inner plexiform layer (GCL/IPL). Diagnostic criteria based on the clustering of abnormal grids from the mRNFL and GCL/IPL measurements were applied. The sensitivity and specificity of glaucoma detection were compared between the cluster criteria (CC) and the average thickness criteria (ATC) of total and hemiretinal sectors, and the cut-off criteria were determined using receiver operating characteristic (ROC) curve analyses from our normal controls. Results. The specificity values of CC and ATC from mRNFL measurements were 97% and 100%, respectively. The sensitivity of CC was 94% for EG and 68% for PPG. The sensitivity of ATC was 81% for EG and 38% for PPG. The specificity values of CC and ATC from GCL/IPL measurements were 96% and 100%, respectively. The sensitivity values of CC and ATC were 92% for EG and 63% for PPG. The sensitivity of ATC was 84% for EG and 25% for PPG. When compared to ATC and ROC-based cut-off criteria, CC showed a higher diagnostic capability. Conclusions. Judging abnormality based on a clustering of abnormal grids from macular OCT parameters may be a reliable approach for diagnosing early glaucoma. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
2013年, Investigative Ophthalmology and Visual Science, 54 (9), 6401 - 6408, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
研究論文(その他学術会議資料等)
To assess the agreement and diagnostic performance between retinal nerve fiber layer (RNFL) thickness measurements obtained using the Cirrus (Carl Zeiss Meditec) and RTVue (Optovue Inc.) devices for detection of band atrophy (BA) in patients with permanent temporal hemianopia. In this retrospective study, 26 eyes with BA and 64 control eyes were enrolled. The Cirrus optic disc cube protocol and the RTVue optic nerve head map protocol were used. The Cirrus measurements were extracted and regrouped to be topographically matched with the RTVue measurements. Concordance correlation and 95 % limits of agreement were assessed. Areas under the receiver operating characteristic curves (AUC) and the Spearman's correlation coefficient between average Humphrey total deviation in the temporal hemifield and average RNFL thickness were calculated. RTVue measured consistently thicker values than Cirrus in controls, whereas in eyes with BA, nasal segment measurements from the RTVue were thinner than those obtained using the Cirrus. Each quadrant showed moderate to close agreement in controls, whereas in eyes with BA, the nasal and temporal quadrants exhibited poor agreement. The RTVue measurements demonstrated significantly higher AUCs for nasal segments just above (0.95) and below (0.96) the horizontal meridian than Cirrus measurements (0.80 and 0.66, respectively) and a significant correlation with visual field loss (r(s) = 0.46, P = 0.02 for RTVue vs. r(s) = 0.26, P = 0.22 for Cirrus). The RTVue RNFL thickness measurements in nasal sectors showed better diagnostic performance in detecting BA and higher correlations with temporal hemianopia than the Cirrus measurements.
SPRINGER, 2012年10月, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 250 (10), 1499 - 1507, 英語[査読有り]
研究論文(学術雑誌)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
[査読有り]
研究論文(学術雑誌)
To evaluate the effects of ocular rotation on parapapillary retinal nerve fiber layer (RNFL) thickness measured by spectral-domain optical coherence tomography (SD-OCT). Eighty-eight normal and 205 glaucomatous eyes were studied. RNFL thickness was measured by 3D OCT. Ocular rotation angle was measured from a fundus image obtained by a non-mydriatic fundus camera equipped with 3D OCT. The average, hemi-superior, and hemi-inferior RNFL thicknesses as well as those in the 4 quadrants and the 16-segmented superotemporal (ST-1) and inferotemporal (IT-4) sectors were compared both before and after correcting for ocular rotation. Receiver operating characteristic curves and the areas under the curve (AUC) for the RNFL thicknesses were calculated on the basis of the data from glaucomatous and control eyes. The relationships between RNFL thickness and retinal sensitivity in the corresponding visual field were analyzed using a Humphrey field analyzer. Correction for ocular rotation did not affect the AUCs of the hemi-superior and hemi-inferior RNFL thicknesses. RNFL thicknesses in all of the quadrants and in ST-1 and IT-4 were significantly changed by correcting for ocular rotation. The correlations between all RNFL sectors and retinal sensitivity were not changed by correcting for the ocular rotation angle. Ocular rotation compensation affected RNFL thickness measurement with 3D OCT. However, the effect was clinically negligible in the diagnosis of glaucoma.
SPRINGER TOKYO, 2012年07月, JAPANESE JOURNAL OF OPHTHALMOLOGY, 56 (4), 354 - 361, 英語[査読有り]
研究論文(学術雑誌)
Backgrounds/aims To evaluate the agreement of parapapillary retinal nerve fibre layer (RNFL) thickness among three spectral-domain optical coherence tomography (OCT) instruments. Methods Two hundred and three glaucomatous eyes and 88 normal eyes were imaged by Cirrus, RTVue and 3D OCT. The average and the four quadrant RNFL thicknesses were evaluated. Agreement among RNFL measurements was evaluated using Bland-Altman analysis and linear regression analysis. The percentage of each quadrant in the average RNFL thickness value was compared among the three instruments. Results Cirrus showed significantly smaller thickness values than RTVue (difference=8.8 mu m, p<0.0001) and 3D OCT (difference=8.1 mu m, p<0.0001). Although RNFL measurements among the instruments were highly correlated, the Bland-Altman analysis revealed proportional biases for most of the pair-wise agreements. Additionally, 3D OCT showed strong proportional biases with RTVue and 3D OCT. RTVue had a smaller occupied proportion of nasal quadrants (30.2%) and a larger proportion of inferior quadrants (32.4%) compared with Cirrus and 3D OCT. Conclusions RNFL measurements among the instruments were well correlated but had different values for thickness. The measurement circle of RTVue might be more superior-temporally located compared with the other instruments. Differences in the measurement protocols might be affected by the disagreements. These instruments should not be used interchangeably.
BMJ PUBLISHING GROUP, 2012年06月, BRITISH JOURNAL OF OPHTHALMOLOGY, 96 (6), 832 - 837, 英語[査読有り]
研究論文(学術雑誌)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
Purpose/Aim: To determine whether amniotic membrane transplantation (AMT) at trabeculectomy affects intrableb structures and which intrableb parameters are significantly correlated with the long-term intraocular pressure (IOP) control. Materials and Methods: Enrolled were 64 eyes of 56 glaucoma patients who underwent trabeculectomy without (36 eyes) or with (28 eyes) AMT. Bleb structure was evaluated by ultrasound biomicroscopy (UBM) at least one year after surgery. IOP control was defined as good when the eyes had a more than 30% decrease in the preoperative IOP and an IOP value < 18 mmHg if the preoperative IOP was higher than 21 mmHg. Logistic regression analyses were conducted to identify factors significantly associated with IOP control. Results: Intervals between surgery and the timing of the UBM examinations (median; 2.5 years) and the overall frequency of good IOP control (28/36 in the eyes without AMT and 17/28 in those with AMT; chi-square test, P = 0.2276) were similar in the two groups. The eyes with AMT had a significantly lower number of type H (high reflective) or L (low reflective) blebs and a higher number of type E (encapsulated) blebs compared to those without AMT (P < 0.0001). Among independent variables, which included age, sex, glaucoma type, lens status, the number of ocular hypotensives, and previous intraocular surgeries, only type F (flattened) bleb in eyes without AMT (P = 0.0008, odds ratio [ OR] = 0.0256) and no or limited intrableb fluid-filled space in eyes with AMT were significantly associated with poor IOP control (P = 0.0026, OR = 0.0111, and 0.0071, 0.0167, respectively). Conclusions: Intrableb structures after trabeculectomy alone versus AMT-assisted trabeculectomy were distinct. The bleb wall reflectivity in the former and the extent of the subconjunctival fluid-filled space in the latter were factors associated with long-term IOP control.
INFORMA HEALTHCARE, 2012年03月, CURRENT EYE RESEARCH, 37 (3), 239 - 250, 英語[査読有り]
研究論文(学術雑誌)
Purpose: To preliminarily test whether aquaporin (AQP)-9 is expressed in the primate and human optic nerve and whether glaucoma reduces its expression. Methods: The expression of AQP-4 and AQP-9 was immunohistochemically studied in the optic nerves of monkey eyes (an angle-laser-induced ocular hypertensive (OH) eye and a control fellow eye) and of human donor eyes (one control eye and one glaucomatous eye). Results: AQP-9 was immunoreactive throughout the entire region of the optic nerve in the monkey and human control eyes and was co-labeled with glial fibrillary acidic protein. In both the monkey OH and human glaucomatous optic nerves, the level of AQP-9 immunoreactivity was substantially reduced. AQP-4 was immunoreactive only in the retrobulbar region in both the monkey and human control optic nerves, whereas neither OH nor glaucoma affected the AQP-4 expression pattern. Conclusions: As has been shown in rats, the optic nerve head in monkeys and humans expresses AQP-9 but not AQP-4. Elevated intraocular pressure or glaucoma reduces AQP-9 expression in the optic nerve. The decrease in the astrocytic expression of AQP-9 in the optic nerve could be implicated in the development of glaucomatous optic neuropathy.
INFORMA HEALTHCARE, 2011年11月, CURRENT EYE RESEARCH, 36 (11), 1064 - 1067, 英語研究論文(学術雑誌)
To test whether multifocal visual evoked potential (mfVEP) recording using two perpendicularly placed channels, as previously reported, to measure the degree of signal-to-noise ratio (SNR) distribution overlap between a signal window and a noise window would efficiently detect and quantify glaucomatous damage. Humphrey visual field (HVF) and mfVEP were recorded from 56 patients with primary open-angle glaucoma and mean deviation less than -15 dB and 62 age-matched ophthalmologically normal individuals. Areas under the receiver-operating characteristic curve (SNR-AUC) were calculated based on the proportion of mfVEP responses that exceeded a specific SNR criterion for both windows. Abnormal sectors with an SNR deviated from the previously established norm with P<5% and 1% were counted. Diagnostic accuracy of the SNR-AUC was similar to that of the average total deviation (TD) of the HVF. The hemifield agreement to detect a defect in mfVEP and HVF was 77.1-87.3%, which was similar to previous reports using multiple channels. Correlation coefficients between SNR-AUC and average TD (0.74 in the upper hemifield and 0.65 in the lower) were significantly higher than those between the sums of abnormal locations on the mfVEP and HVF probability plots (0.27 and 0.33, respectively). Two perpendicular channels can detect and quantify functional damage due to glaucoma. The SNR-AUC may be used as a global index to quantify diffuse glaucomatous functional loss.
SPRINGER, 2011年10月, DOCUMENTA OPHTHALMOLOGICA, 123 (2), 93 - 108, 英語[査読有り]
研究論文(学術雑誌)
Diabetes pathology derives from the combination of hyperglycemia and hypoinsulinemia or insulin resistance leading to diabetic complications including diabetic neuropathy, nephropathy and retinopathy. Diabetic retinopathy is characterized by numerous retinal defects affecting the vasculature and the neuro-retina, but the relative contributions of the loss of retinal insulin signaling and hyperglycemia have never been directly compared. In this study we tested the hypothesis that increased retinal insulin signaling and glycemic normalization would exert differential effects on retinal cell survival and retinal physiology during diabetes. We have demonstrated in this study that both subconjunctival insulin administration and systemic glycemic reduction using the sodium-glucose linked transporter inhibitor phloridzin affected the regulation of retinal cell survival in diabetic rats. Both treatments partially restored the retinal insulin signaling without increasing plasma insulin levels. Retinal transcriptomic and histological analysis also clearly demonstrated that local administration of insulin and systemic glycemia normalization use different pathways to counteract the effects of diabetes on the retina. While local insulin primarily affected inflammation-associated pathways, systemic glycemic control affected pathways involved in the regulation of cell signaling and metabolism. These results suggest that hyperglycemia induces resistance to growth factor action in the retina and clearly demonstrate that both restoration of glycemic control and retinal insulin signaling can act through different pathways to both normalize diabetes-induced retinal abnormality and prevent vision loss.
PUBLIC LIBRARY SCIENCE, 2011年10月, PLOS ONE, 6 (10), 英語[査読有り]
研究論文(学術雑誌)
To determine if asymmetrical postural change-induced elevations in intraocular pressure (IOP) in eyes of patients with primary open-angle glaucoma (POAG) were associated with asymmetries in functional and structural damage. Enrolled were 132 eyes of 66 patients with POAG (male/female = 22/44, age = 55.2 +/- 13.4 years). IOP was first measured in a seated position and then in a supine position at 10-minute intervals over a 60-minute period using a TonoPen XL. The Humphrey visual field 30-2 program and a fast retinal nerve fiber layer (RNFL) thickness acquisition protocol of Stratus optical coherence tomography (OCT) were performed. Mean deviation (MD) and average total RNFL thickness were compared between eyes with the greater magnitude of postural change-induced IOP elevation (Delta IOP) and those with the smaller magnitude of Delta IOP. The MDs of the eyes with larger Delta IOP (6.21 +/- 3.18 mmHg) and smaller Delta IOP (3.02 +/- 0.37 mmHg) were -12.31 +/- 7.63 dB and -9.67 +/- 6.80 dB respectively (p = 0.0176). The average total RNFL thickness was 64.33 +/- 17.83 mu m in the former and 68.56 +/- 15.10 mu m in the latter (p = 0.049). The MDs and RNFL thickness were not significantly different between the eyes that had higher and lower IOP values measured in the seated position. In patients with asymmetrical POAG, the magnitude of IOP elevation induced by postural changes may be related to differences in the severity of both functional and structural damage between the eyes.
SPRINGER, 2011年06月, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 249 (6), 879 - 885, 英語[査読有り]
研究論文(学術雑誌)
Purpose: To investigate whether the solute carrier family 1, member 3 (SLC1A3) gene, which encodes the glutamate aspartate transporter, is associated with normal tension glaucoma (NTG) in Japanese patients. Methods: Two hundred and ninety-five Japanese patients with NTG and 518 Japanese healthy controls were recruited. Patients exhibiting comparatively early NTG onset were selected because early onset suggests that genetic factors may show stronger involvement. We genotyped 5 single-nucleotide polymorphisms (SNPs) in SLC1A3 and assessed the allelic and genotypic diversity among cases and controls. Results: There were no statistically significant differences in the frequency of SLC1A3 alleles and genotypes between cases and controls. Conclusions: Our study showed no association between SLC1A3 and NTG, suggesting that the SLC1A3 gene may not be an associated factor in NTG pathogenesis.
MOLECULAR VISION, 2011年03月, MOLECULAR VISION, 17 (89-90), 792 - 796, 英語研究論文(学術雑誌)
Diabetes redistributes the expression of glial aquaporin (AQP) water channels in the retina. However, it is not known whether diabetes also affects retinal AQP-0 expression. This study examined the effects of the development of diabetes on the expression of retinal AQP-0 in spontaneously diabetic Toni (SDT) rats. Male SDT rats at 10 and 40 weeks of age and age-matched male Sprague-Dawley (SD) rats were used. The localization of AQP-0 was assessed immunohistochemically using sagittal cryosections of the rats' retinas and optic nerves. Fold changes in AQP-0 gene expression relative to controls were assessed by real-time RT-PCR. All SDT rats spontaneously developed diabetes by 40 weeks of age (the mean hemoglobin (Hb) A1c levels were 2.8 +/- 0.2% and 11.2 +/- 1.0% at 10 and 40 weeks, respectively). SD rats did not develop diabetes (the HbA1c levels were 2.7 +/- 0.2% and 2.6 +/- 0.3% at 10 and 40 weeks, respectively). In the retinas of SD rats and in those of SDT rats at 10 weeks of age, immunoreactivity for AQP-0 was confined predominantly to the inner nuclear layer and to the border between the inner plexiform layer and the ganglion cell layer (GCL), where AQP-0 colocalized with protein kinase C-e. AQP-0 immunoreactivity was also observed in the GCL to a lesser degree, which colocalized with the neuronal nuclei. In the 40-week-old SDT rat retinas, additional AQP-0 immunoreactivity was observed in the GCL and colocalized with neurofilaments, indicating expression of AQP-0 in ganglion cell axons. However, the axonal AQP0 immunoreactivity was restricted to the retinal nerve fibers, whereas the optic nerve axons were devoid of AQP-0. Retinal blood vessels did not express AQP-0. AQP-0 gene expression was 3.4-fold higher in SDT rat retinas than in SD rat retinas at 40 weeks of age. AQP-0 was predominantly expressed in the bipolar cells of the non-diabetic rat retinas, whereas it was also expressed in the retinal nerve fibers of diabetic rat retinas. The disrupted water transport between astrocytes and retinal nerve fibers may be associated with the known accelerated apoptosis of retinal ganglion cells induced by diabetes. (C) 2011 Elsevier Ltd. All rights reserved.
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2011年03月, EXPERIMENTAL EYE RESEARCH, 92 (3), 195 - 201, 英語研究論文(学術雑誌)
The purpose of this study was to establish optimal conditions for recording multifocal visual evoked potentials (mVEPs) in Japanese individuals, whose skull frame presumably differs from Caucasians. The scalp point that was extended from the calcarine fissure was identified using magnetic resonance imaging scans of 200 subjects. MVEPs were recorded from 56 individuals using three single channels and combinations of vertical and horizontal channels. Five electrodes were placed at the inion, 4 cm above the inion, 2.5 cm below the inion, 4 cm to the left or 4 cm to the right of the inion. The signal-to-noise ratio (SNR) was obtained by measuring the root-mean-square (RMS) amplitude of a signal window (45-150 ms) from each of 60-local responses that was divided by the average of the 60 RMS amplitudes of the noise window (325-430 ms). Receiver operating characteristic (ROC) analyses were performed based on the proportion of mVEP responses that exceeded a specific SNR criterion, calculated for both the signal window and the noise window. The position of the calcarine fissure relative to the inion was significantly lower than the value reported for Caucasians. The ROC analyses disclosed that bi-channel combinations (one vertical and one horizontal) had significantly better performance to discriminate signal from noise in 60-local mVEP responses compared to any single channel and performed similarly to the tri-channel combination. Two sets of perpendicular channels should be simultaneously used in recording mVEP responses from Japanese people, among whom skull frame characteristics differ from those observed in Caucasians.
SPRINGER, 2011年02月, DOCUMENTA OPHTHALMOLOGICA, 122 (1), 29 - 37, 英語[査読有り]
研究論文(学術雑誌)
Stromal cell-derived factor-1 (SDF-1) causes chemotaxis of CXCR4-expressing bone marrow-derived cells. SDF-1 is involved in the pathogenesis of various vascular diseases, including those of the eye. However, the role of SDF-1 in neuronal diseases is not completely understood. Here, we show higher SDF-1 levels in the vitreous humor of patients with retinal detachment (RD) compared with normal patients. SDF-1 correlated positively with the duration as well as the extent of RD. Furthermore, SDF-1 correlated significantly with levels of interleukin-6 and interleukin-8, but not with vascular endothelial growth factor. Western blot analysis results showed significant SDF-1 up-regulation in detached rat retinas compared with normal animals Immunohistochemistry data showed that SDF-1 was co-localized with the glial cells of the detached retina. SDF-1 blockade with a neutralizing antibody increased photoreceptor cell loss and macrophage accumulation in the subretinal space. The retinal precursor cell line R28 expressed CXCR4. SDF-1 rescued serum starvation-induced apoptosis in R28 cells and enhanced their ability to participate in wound closure in a scratch assay. Our results indicate a surprising, protective role for SDF-1 in RD. This effect may be mediated directly or indirectly through other cell types. (Am J Pathol 2010, 177:2268-2277 DOI: 10.2353/ajpath.2010.100134)
AMER SOC INVESTIGATIVE PATHOLOGY, INC, 2010年11月, AMERICAN JOURNAL OF PATHOLOGY, 177 (5), 2268 - 2277, 英語研究論文(学術雑誌)
PURPOSE. To investigate the effect of chronically elevated intraocular pressure (IOP) on the expression of water channel aquaporins (AQPs) 1, 4, and 9 in the optic nerve and retina in rats. METHODS. Three episcleral veins were cauterized to elevate IOP in the left eyes of Sprague-Dawley rats. IOPs were monitored with a rebound tonometer. At 2 and 4 weeks after surgery, eyeballs with the attached optic nerve were enucleated for cryosectioning with immunohistochemistry, or dissected retinas and desheathed optic nerves were subjected to gene expression analyses. RESULTS. IOP was significantly increased after surgery up to 4 weeks (P = 0.0008). In the control optic nerve, the unmyelinated portion showed only AQP9 immunoreactivity, whereas the myelinated portion expressed both AQP4 and AQP9 immunoreactivities colabeled for glial fibrillary acidic protein but not for neurofilament. In the control retina, AQP1 was expressed in the outer nuclear layer and photoreceptors, AQP4 was expressed in Muller cell endfeet, and AQP9 was expressed primarily in NeuN-positive cells in the ganglion cell layer (GCL). Elevated IOPs substantially reduced AQP9 expression in the optic nerve head (ONH) and the GCL and decreased the retinal gene expression, but not immunoreactivity, of AQP1. CONCLUSIONS. AQP9 was the only water channel expressed in the unmyelinated portion of the ONH and in the GCL whose expression was reduced after IOP elevation. Given that AQP9 presumably acts as a channel for metabolites to pass from astrocytes to neurons, the reduced expression of AQP9 at these specific sites may be implicated in the pathogenesis of glaucomatous optic neuropathy. (Invest Ophthalmol Vis Sci. 2010; 51: 4618-4626) DOI: 10.1167/iovs.09-4712
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2010年09月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 51 (9), 4618 - 4626, 英語[査読有り]
研究論文(学術雑誌)
Purpose: Normal tension glaucoma (NTG) is a subtype of glaucoma in which intraocular pressure is within the statistically normal range. NTG may be associated with an immune disorder. The aim of this study was to determine whether specific alleles in the human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 genes correlated with NTG in Japanese patients. Methods: We genotyped the HLA-DRB1 and HLA-DQB1 alleles in 113 Japanese patients with NTG and in 184 healthy Japanese control subjects using the polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) Luminex method. We assessed the allelic diversity in patients and controls. Results: There were no statistically significant differences in the allele frequency of HLADRB1 and HLA-DQB1 between NTG patients and control subjects, and no HLA-DRB1-HLA-DQB1 haplotypes demonstrated any significant association with NTG. Conclusions: Our findings suggest that HLA-DRB1 and HLA-DQB1 polymorphisms have no significant effect on the development of NTG in Japanese patients.
MOLECULAR VISION, 2010年09月, MOLECULAR VISION, 16 (203), 1874 - 1879, 英語[査読有り]
研究論文(学術雑誌)
Purpose: To investigate whether the GLC1F locus is associated with normal tension glaucoma (NTG) in Japanese patients. Methods: We recruited 242 unrelated Japanese subjects, including, 141 NTG patients and 101 healthy controls. The patients exhibiting a comparatively early onset were selected as they suggest that genetic factors may show stronger involvement. Genotyping and assessment of allelic diversity was performed on 11 highly polymorphic microsatellite markers in and around the GLC1F locus. Results: Individuals carrying the 163 allele of D7S1277i had a statistically significant increased risk of NTG (p=0.0013, pc=0.016, OR=2.47, 95% CI=1.42-4.30). None of the other markers identified significant loci (pc>0.05) after Bonferroni's correction. Conclusions: These findings suggested that the genes in the GLC1F locus may be associated with the pathogenesis of NTG.
MOLECULAR VISION, 2010年03月, MOLECULAR VISION, 16 (51-52), 462 - 466, 英語研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Evidence is mounting that not only microangiopathy, but also neurodegenerative events occur in the retinas of humans and rodents with early diabetes. Diverse pathologies are known to alter the amount and/or location of glial expression of the water-selective channels aquaporins (AQPs) 1 and 4. However, the temporal relationships among glial activation, the altered expression of the AQP proteins and neuronal death in the retinas of diabetic animals remains to be investigated. Male spontaneously diabetic Torii (SDT) rats reportedly develop diabetes by 40 weeks of age at the latest and manifest proliferative diabetic retinopathy at 50 weeks or later. This study compared temporal changes in neuroretinal apoptosis, glial fibrillary acidic protein (GFAP) expression and the expression of AQPs 1 and 4 between SDT rat retinas and age-matched Sprague-Dawley (SD) rat retinas. Cell death was detected by terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate nick end-labeling on retinal flatmounts and activated caspase 3 immunofluorescence of retinal cryosections. The expression of GFAP and AQPs 1 and 4 was assessed by immunohistochemistry of cryosections and retinal flatmounts. Diabetes started to develop around 15 weeks in SDT rats. Apoptotic cells in the ganglion cell layer and the inner nuclear layer were significantly more numerous in 40-week-old SDT rat retinas than in either age-matched SD rat retinas or 10-week-old SDT rats. GFAP immunoreactivity was confined to the nerve fiber layer both in SD and SDT rats at 10 weeks, whereas it spanned the whole retina in SDT rats, but not in 5D rats, at 40 weeks. AQP1 was expressed in the outer retina, whereas AQP4 was expressed in the perivascular and end feet of Muller cells and astrocytes in the inner retina in the control SD rats and the SDT rats at 10 weeks. The perivascular AQPs shifted from AQP4 to AQP1 in 40-week-old SDT rats that exhibited marked hyperglycemia. Thus, the development of diabetes increases neuroretinal apoptosis, and this coincides with an altered expression pattern of GFAP and water-selective channels AQPs 1 and 4 in SDT rats. (C) 2009 Elsevier Ltd. All rights reserved.
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2010年01月, EXPERIMENTAL EYE RESEARCH, 90 (1), 17 - 25, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Purpose: Toll-like receptor 2 (TLR2) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands, and interacts with heat-shock proteins, which are reportedly involved in normal tension glaucoma (NTG). We investigated whether TLR2 polymorphisms are associated with NTG. Methods: 200 Japanese patients with NTG and 128 healthy Japanese controls were recruited. We genotyped five single-nucleotide polymorphisms (SNPs) in the TLR2 gene and assessed the allele and haplotype diversities between cases and controls for all SNPs. Results: No significant differences in the frequency of TLR2 alleles and haplotypes in the NTG cases were detected, compared with the controls. Conclusions: Our study showed no evidence for an association between TLR2 polymorphisms and NTG. TLR2 polymorphisms may not play an important role in NTG pathogenesis in the Japanese population.
MOLECULAR VISION, 2009年12月, MOLECULAR VISION, 15 (306-07), 2905 - 2910, 英語[査読有り]
研究論文(学術雑誌)
To investigate whether tafluprost, which is a prostaglandin-related compound and an anti-glaucoma drug, has a direct anti-apoptotic effect in cultured retinal ganglion cells (RGCs) and rat RGCs in retinas with optic nerve crush (ONC). RGC-5 cells were induced to undergo apoptosis by a serum deprivation and by exogenous glutamate. The level of cell death with or without tafluprost was monitored by an XTT assay and by immunocytochemistry with activated caspase-3. Changes in intracellular calcium ([Ca(2+)]i) levels were measured with fluo-4 fluorescence. Rat RGCs were degenerated by ONC. After topical instillation of tafluprost for 7 and 14 days, the numbers of retrograde-labeled RGCs were counted. Retinal flatmounts were subjected to terminal dUTP nick end labeling (TUNEL) staining to detect apoptotic cells. Tafluprost dose-dependently promoted RGC-5 cell viability with an optimum concentration of 3 mu M (p = 0.006). Tafluprost significantly reduced caspase-3-positive cells and suppressed [Ca(+2)]i evoked by exogenous glutamate. The cGMP-dependent protein kinase inhibitor and KT-5823 partially blocked the rescue effect of tafluprost (p = 0.002). The survival rate of RGCs significantly increased in eyes treated with tafluprost (p = 0.01), and the prevalence of TUNEL-positive cells was significantly decreased 14 days after ONC (p < 0.001). These data suggest that tafluprost has an anti-apoptotic effect in RGCs.
SPRINGER, 2009年10月, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 247 (10), 1353 - 1360, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Objective: To evaluate which of the 3 clinically used Visual field indices including mean deviation (MD), Advanced Glaucoma Intervention Study (AGIS) score, and Collaborative Initial Glaucoma Treatment Study (CIGTS) score are best in evaluating functional damage of glaucomatous optic neuropathy. Methods: In 213 glaucomatous eyes, peripapillary retinal nerve fiber layer thickness (RNFLT) and optic disc configuration were measured with Stratus optical coherence tomography and Heidelberg Retina Tomograph-2, respectively. Visual field was measured with standard automated perimetry 30-2. Correlations of the structural parameters compared with the 3 VF indices using second polynomial regression were calculated. In addition, these correlations were analyzed among eyes of 3 different stages of glaucoma, as defined by MD score (early, MD >= - 6 dB; moderate, - 12 dB <= MD < - 6 dB; advanced, MD < - 12 dB). Results: Among structure-function relationships in all subjects, the highest correlation determination (R(2)) was MD with RNFLT ( = 0.298). CIGTS score showed better R(2) than MD or AGIS score with rim area, but these values were not higher than any R(2) with RNFLT. In analyses of 3 groups depending on MD, statistically significant structure-function correlations were observed only in patients with an advanced stage. Conclusions: No clear difference was found among MD and AGIS/CIGTS scores in expressing functional damage of glaucomatous eyes. MD is suggested to be no worse than others in monitoring glaucoma in clinical setting.
LIPPINCOTT WILLIAMS & WILKINS, 2009年06月, JOURNAL OF GLAUCOMA, 18 (5), 379 - 384, 英語[査読有り]
研究論文(学術雑誌)
We investigated whether latanoprost has a direct anti-apoptotic effect in retinal ganglion cell (RGC) line and RGCs in the rat. RGC-5 cells were induced to undergo apoptosis by serum deprivation and exogenous glutamate. The level of cell death with or without latanoprost acid was monitored by an XTT assay and by immunocytochemistry with activated caspase-3. Changes in the level of intracellular calcium ([Ca(2+)](i)) were measured with fluo-4 fluorescence. The XTT assay revealed that latanoprost acid increased RGC-5 cell viability. Latanoprost acid significantly reduced caspase-3 positive cells and suppressed [Ca(2+)](i)evoked by glutamate. 00126, a mitogen-activated protein/extracellular signal-regulated kinase 1 and 2 inhibitor, partially blocked the rescue effect of latnanoprost acid (p = 0.013). In vivo, rat RGCs were degenerated by optic nerve crush. After topical instillation of latanoprost for 7 days, RGCs labeled with fluorogold were significantly. Retinal flatmounts were subjected to terminal dUTP nick end labeling (TUNEL) staining to detect apoptotic cells. TUNEL-positive cells were significantly decreased in eyes with topically instilled latanoprost (p = 0.015). These data suggest that latanoprost has an neuroprotective ability in RGCs. (C) 2008 Elsevier Ltd. All rights reserved.
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2009年03月, EXPERIMENTAL EYE RESEARCH, 88 (3), 535 - 541, 英語[査読有り]
研究論文(学術雑誌)
High-mobility group box 1 (HMGB1) protein is a multifunctional protein, which is mainly present in the nucleus and is released extracellularly by dying cells and/or activated immune cells. Although extracellular HMGB1 is thought to be a typical danger signal of tissue damage and is implicated in diverse diseases, its relevance to ocular diseases is mostly unknown. To determine whether HMGB1 contributes to the pathogenesis of retinal detachment (RD), which involves photoreceptor degeneration, we investigated the expression and release of HMGB1 both in a retinal cell death induced by excessive oxidative stress in vitro and in a rat model of RD-induced photoreceptor degeneration in vivo. In addition, we assessed the vitreous concentrations of HMGB1 and monocyte chemoattractant protein 1 (MCP-1) in human eyes with RD. We also explored the chemotactic activity of recombinant HMGB1 in a human retinal pigment epithelial (RPE) cell line. The results show that the nuclear HMGB1 in the retinal cell is augmented by death stress and upregulation appears to be required for cell survival, whereas extracellular release of HMGB1 is evident not only in retinal cell death in vitro but also in the rat model of RD in vivo. Furthermore, the vitreous level of HMGB1 is significantly increased and is correlated with that of MCP-1 in human eyes with RD. Recombinant HMGB1 induced RPE cell migration through an extracellular signal-regulated kinase-dependent mechanism in vitro. Our findings suggest that HMGB1 is a crucial nuclear protein and is released as a danger signal of retinal tissue damage. Extracellular HMGB1 might be an important mediator in RD, potentially acting as a chemotactic factor for RPE cell migration that would lead to an ocular pathological wound-healing response.
NATURE PUBLISHING GROUP, 2009年03月, LABORATORY INVESTIGATION, 89 (3), 278 - 289, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
BACKGROUND: To investigate whether the GPDS1 locus, a potential causative locus of pigment-dispersion syndrome, is associated with normal-tension glaucoma (NTG) in Japanese patients. MATERIALS AND METHODS: We used polymerase chain reaction amplification with sequence-specific primers to analyze 20 polymorphic microsatellite markers in and around the GPDS1 locus with an automated DNA analyzer and automated fragment detection by fluorescent-based technology. The DNA samples used for these analyses were obtained from ethnicity- and gender-matched patients, including 141 Japanese patients with NTG and 101 healthy controls. Patients exhibiting a comparatively early onset were selected as this suggests that genetic factors may show stronger involvement. RESULTS: One allele of D7S2462 exhibited a frequency that was significantly decreased in NTG cases compared to controls (P = 0.0013, Pc = 0.019, OR = 0.48, 95% CI = 0.30-0.75). Alleles at another six microsatellite loci were positively or negatively associated with NTG, but these associations did not retain statistical significance after Bonferroni correction (P < 0.05, Pc > 0.05). CONCLUSION: Our study showed a significant association between the GPDS1 locus and NTG, suggesting that there may be some genetic risk factor(s) in the development of NTG.
2009年, Clinical ophthalmology (Auckland, N.Z.), 3, 307 - 12, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Purpose: To compare the morphologic alterations between upper and lower sectors of the optic nerve head (ONH) in eyes with primary open-angle glaucoma (POAG) that have hemifield Visual field defects and to evaluate the correlation between this sectoral ONH damage and visual field sensitivity loss within the corresponding clustered test points of standard automated perimetry. Methods: Visual field testing with Humphrey Field Analyzer and imaging with Heidelberg Retina Tomograph (HRT) were performed in 87 eyes from 87 Japanese patients with POAG and 150 eves, from 150 normal subjects. Global and segmental HKT topographic parameters were compared among POAG patients with Superior hemifield defects, those with interior hemifield defects, and controls. The correlation between the sectoral HRT measurements and the sum of total deviation Value, ill the corresponding clustered visual field test points was analyzed in the 2 POAG groups. Results: The HRT measurements in both POAG groups were significantly different from those of controls, not only in the sectors corresponding to abnormal hemifield. but also in the sectors corresponding to the normal Visual hemifield. There was a linear correlation between the sectoral HRT parameters and clustered Visual field sensitivities in the affected hemifield areas. Conclusions: The present study indirectly supports the notion that the relationship between structural and functional damage of glaucomatous optic neuropathy is not linear when evaluated with the currently available techniques and instruments.
LIPPINCOTT WILLIAMS & WILKINS, 2009年01月, JOURNAL OF GLAUCOMA, 18 (1), 62 - 68, 英語[査読有り]
研究論文(学術雑誌)
Objective: To establish the structure-function relationship between peripapillary retinal nerve fiber layer (RNFL) thickness and visual field (VF) test points in standard automated perimetry. Methods: We included 213 eyes with open-angle glaucoma and VF loss in this cross-sectional study. Correlations between individual VF sensitivity at 52 test points and peripapillary RNFL thickness divided into 16 sectors were calculated. The RNFL thickness was measured by Stratus optical coherence tomography. A new VF cluster map corresponding to RNFL sectors was generated by grouping the VF test points with the highest relation to each RNFL sector. Results: The VF sensitivity at each test point was significantly correlated with the sectoral RNFL thickness. The highest coefficient of determination (R-2) for a superotemporal RNFL sector and VF sensitivity at an inferotemporal test point (9 degrees temporal and 15 degrees inferior from the center) in standard automated perimetry was 0.500 (P <.001). Clustered VF test points most highly related to the RNFL sectors were asymmetrically located between the upper and lower hemifields. A newly developed map revealed significant structure-function relationships. Conclusions: We describe an association between VF sensitivity at test points and sectoral RNFL thickness. Nine clustered VF test points corresponding to 9 RNFL regions were demonstrated from the structure-function relationships.
AMER MEDICAL ASSOC, 2008年11月, ARCHIVES OF OPHTHALMOLOGY, 126 (11), 1500 - 1506, 英語[査読有り]
研究論文(学術雑誌)
Photoreceptor apoptosis is a critical process of retina degeneration in retinitis pigmentosa (RP), a group retinal degenerative diseases that result from rod and cone photoreceptor cell death and represent a major cause of adult blindness. We previously demonstrated the efficient prevention of photoreceptor apoptosis by intraocular gene transfer of pigment epithelium-derived factor (PEDF) in animal models of RP; however, the underlying mechanism of the neuroprotective activity of PEDF remains elusive. In this study, we show that an apoptosis-inducing factor (AIF)-related pathway is an essential target of PEDF-mediated neuroprotection. PEDF rescued serum starvation-induced apoptosis, which is mediated by AIF but not by caspases, of R28 cells derived from the rat retina by preventing translocation of AIF into the nucleus. Nuclear translocation of AIF was also observed in the apoptotic photoreceptors of Royal College of Surgeons rats, a well-known animal model of RP that carries a mutation of the Merik gene. Lentivirus-mediated retinal gene transfer of PEDF prevented the nuclear translocation of AIF in vivo, resulting in the inhibition of the apoptotic loss of their photoreceptors in association with up-regulated Bcl-2 expression, which mediates the mitochondrial release of A-IF. These findings clearly demonstrate that AIF is an essential executioner of photoreceptor apoptosis in inherited retinal degeneration and provide a therapeutic rationale for PEDF-mediated neuroprotective gene therapy for individuals with RP. (Am J Pathol 2008, 173:1326-1338; DOI: 10.2353/ajpath.2008.080466)
AMER SOC INVESTIGATIVE PATHOLOGY, INC, 2008年11月, AMERICAN JOURNAL OF PATHOLOGY, 173 (5), 1326 - 1338, 英語[査読有り]
研究論文(学術雑誌)
Background/aims: To evaluate to what extent the optic nerve head (ONH) parameters as measured with Heidelberg Retina Tomograph (HRT) differed from those measured with optical coherence tomography (OCT) in eyes with compressive optic neuropathy (CON) that had band atrophy (BA) of the optic disc. Methods: A total of 30 eyes from 19 patients with BA due to chiasmal tumour and 162 eyes from 162 normal subjects were examined with HRT and Stratus OCT using the fast optic nerve scan protocol. Parameters measured by the two devices, including the disc area, cup/disc (C/D) area ratio, cup area, cup volume, rim area and rim volume, were compared between the eyes of BA patients and controls. Bland-Altman plots were used to evaluate agreement for each parameter between OCT and HRT in both groups of eyes. Intermethod discrepancy of the measurements for each parameter was compared between the two groups of eyes. Results: Eyes with BA had smaller cup and larger rim parameters than control eyes when measured with HRT, whereas they had significantly larger cup and significantly smaller rim parameters than control eyes when measured with OCT. HRT measurements tended to be consistently lower in the C/D area ratio and cup area and higher in the rim area and rim volume than OCT measurements for both control eyes and eyes with BA. The intermethod discrepancy for all the parameters except the disc area was significantly larger in eyes with BA than in control eyes. Conclusion: The increased optic disc excavation was detected with OCT but not with HRT in CON eyes with BA of the optic disc. Thus, the distinct algorithms used by these two modalities affected the measurements of ONH parameters, particularly when assessing optic discs with temporal rim thinning.
B M J PUBLISHING GROUP, 2008年10月, BRITISH JOURNAL OF OPHTHALMOLOGY, 92 (10), 1382 - 1386, 英語[査読有り]
研究論文(学術雑誌)
PURPOSE. Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands and interacts with heat shock proteins, which are reportedly involved in normal tension glaucoma (NTG). This study was undertaken to investigate whether TLR4 polymorphisms are associated with NTG. METHODS. Two hundred fifty Japanese patients with NTG and 318 Japanese healthy control subjects were recruited. Eight single-nucleotide polymorphisms (SNPs) in the TLR4 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects. RESULTS. Strong linkage disequilibrium was observed among all SNPs (D' >= 0.85), which were located in one haplotype block. With respect to allelic diversity, the minor allele of three SNPs (rs10759930, rs1927914, and rs7037117) carried a significantly increased risk of NTG. With regard to genotypic diversity, individuals with the minor allele of six SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, and rs7037117) had a 1.47- to 1.65-fold increased risk of NTG. rs7037117, located in the 3'-untranslated region of TLR4, was most strongly associated with NTG, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 0.0038, P(c) = 0.0095). CONCLUSIONS. Multiple SNPs in the TLR4 gene are associated with the risk of NTG. This finding suggests that the ligands and/or cytokines involved in the TLR4 signaling network may be risk factors for the development of NTG.
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2008年10月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 49 (10), 4453 - 4457, 英語[査読有り]
研究論文(学術雑誌)
Aims: The aim of this study was to investigate the association between normal tension glaucoma and the candidate disease locus glaucoma 1, open angle, B (GLC1B) on chromosome 2. There are many reports describing the results of association or linkage studies for primary open angle glaucoma (POAG), with GLC1B as one of the loci associated with normal or moderately elevated intraocular pressure. However, there are few reports about the association of genes or defined genomic regions with normal tension glaucoma, which is the leading type of glaucoma in Japan. The GLC1B locus is hypothesized to be a causative region for normal tension glaucoma. Methods: Genomic DNA was extracted from whole blood of normal tension glaucoma (n= 143) and healthy controls (n= 103) of Japanese origin. Results: Fifteen microsatellite markers within and/or near to the GLC1B locus were genotyped, and their association with normal tension glaucoma was analysed. Two markers D2S2264 and D2S176 had significant positive associations. Conclusion: The D2S176 marker had the strongest significant association and it is located 24 kb from the nearest gene NCK2, which now becomes an important new candidate gene for future studies of its association with normal tension glaucoma.
B M J PUBLISHING GROUP, 2008年09月, BRITISH JOURNAL OF OPHTHALMOLOGY, 92 (9), 1293 - 1296, 英語[査読有り]
研究論文(学術雑誌)
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, 2008年09月, EYE, 22 (9), 1154 - 1160, 英語[査読有り]
研究論文(学術雑誌)
Background To report long-term results of amniotic membrane transplantation (AMT)-assisted bleb revision for intractable late-onset bleb leak. Methods Retrospective medical record review of six consecutive patients who underwent AMT-assisted bleb revision for late-onset bleb leak at the Kobe University hospital between December 2001 and March 2004. Results The median (range) of age was 60 (20-77) years. All patients had a history of trabeculectomy with adjunctive use of 0.4 mg/ml mitomycin C. The median (range) of interval between the prior trabeculectomy and bleb leak was 15 (4-54) months. Preoperative intraocular pressure (IOP) was lower than 10 mmHg in two cases, while it was 25 mmHg or higher in three patients, who had a localized, ischemic, thin-wall leaking bleb circumscribed with extensively scarred tissue. The median (range) of follow-up after the AMT-assisted bleb revision was 49 (41-67) months. Postoperative IOP was well controlled in all patients without medication or with a maximum of three glaucoma medications. No patients presented recurrence of the bleb leak or AMT-related complications during entire follow-up. All patients showed at final visit a diffuse bleb which extended posteriorly beyond the conjunctival incision line. Conclusion AMT-assisted bleb revision successfully treated intractable late-onset bleb leak. Further comparative studies are needed to confirm the present result.
SPRINGER, 2008年04月, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 246 (4), 567 - 571, 英語研究論文(学術雑誌)
Aims: To investigate the influence of age, disc size and axial length on the retinal nerve fibre layer (RNFL) thickness measurements of Heidelberg Retina Tomograph (HRT) and optical coherence tomography (OCT). Methods: A total of 162 eyes of 162 Japanese normal subjects aged between 20 and 83 were enrolled in this study. The disc area and mean RNFL thickness were measured with HRT. The disc area was also measured using the fast optic nerve scan protocol, and the average RNFL thickness was measured using the fast RNFL thickness scan mode with Stratus OCT. The correlations of age, disc area and axial length with RNFL thickness measured with HRT and OCT were analysed. The associations between axial length and disc area measured with HRT and OCT were also calculated. Results: RNFL thickness measured with the two instruments decreased with age. There was a significantly negative correlation between the mean RNFL thickness and disc area measured with HRT. The RNFL thickness measured with OCT correlated positively with the disc area measured with OCT, but not with the disc area measured with HRT. Both RNFL thickness and disc area measured with OCT were inversely correlated with axial length, whereas the two parameters measured with HRT had no association with axial length. Conclusion: In addition to the effect of ageing, the disc size affected the RNFL thickness measured with HRT, whereas the axial length influenced the RNFL thickness and disc area measured with OCT. These variables must be taken into consideration when measuring eyes with the lower or upper boundary of the normal range.
B M J PUBLISHING GROUP, 2008年02月, BRITISH JOURNAL OF OPHTHALMOLOGY, 92 (2), 186 - 190, 英語研究論文(学術雑誌)
Purpose: To investigate if nipradilol has an anti-apoptotic effect in serum-deprived RGC-5 cells and in the streptozotocin-induced diabetic rat retina. Methods: Apoptosis was quantified by activated caspase-3 immunohistochemistry or terminal dUTP nick end-labeling assay. Results: Nipradilol dose-dependently suppressed apoptosis in a protein kinase A- and G-dependent manner and counteracted glutamate-induced calcium entry in the RGC-5 cells and reduced apoptotic cells in the retinal ganglion cell layer of 4- and 12-week diabetic retinas compared to controls when instilled for 5 days. Removal of the nitric oxide moiety from nipradilol blocked these effects. Conclusions: Nipradilol protects RGCs from apoptosis induced by serum-deprivation in vitro and by diabetes in vivo. The NO-related signaling pathway mediates the anti-apoptotic ability of nipradilol.
INFORMA HEALTHCARE, 2008年, CURRENT EYE RESEARCH, 33 (8), 683 - 692, 英語[査読有り]
研究論文(学術雑誌)
Aim: The relative afferent pupillary defect (RAPD) is an important clinical sign of asymmetrical retinal ganglion cell and axonal damage. Although glaucoma essentially affects bilateral eyes, a subset of patients manifests asymmetrical glaucomatous optic neuropathy (GON), which exhibits an RPAD in the more advanced eyes. However, the degree to which axonal loss occurs before an RAPD is clinically detectable has not been substantiated. The purpose of this study is to assess the relationship between the depth of a clinically detectable RAPD and the reduction ratio of retinal nerve fiber layer (RNFL) thickness in the more advanced eyes relative to that in the contralateral less advanced eyes of patients with asymmetrical GON. Methods: Enrolled were 29 consecutive glaucoma patients with the clinically detectable RAPD. An RAPD was quantified by placing log-scaled neutral density filters over the less advanced eyes while performing the swinging flashlight test. Average RNFL thickness was determined using the Fast RNFL thickness programme of optical coherence tomography 3000. Correlation coefficient and Linear regression analyses were used in assessing the relationship between the RAPD and the ratio of RNFL thickness in the more advanced eyes relative to that in the less advanced. Results: RAPD ranged from 0.6 to 2.4 log units. The log-scaled RAPD had a statistically significantly inversed correlation with the average RNFL thickness ratio (r(s) = 20.729, p, 0.0001). Linear regression analysis found an equation that the average RNFL thickness ratio in the more affected eyes relative to that in the less advanced (%) = (0.8272-0.1696 x RAPD (log units)) 6100 (R-2 = 0.557, p, 0.0001). Conclusions: When an RAPD is clinically detected, the RNFL thickness in the more advanced eyes was in average reduced to about 73% of that in the less advanced.
B M J PUBLISHING GROUP, 2007年05月, BRITISH JOURNAL OF OPHTHALMOLOGY, 91 (5), 633 - 637, 英語[査読有り]
研究論文(学術雑誌)
Purpose: Although central corneal thickness (CCT) can be measured by several methods, interchangeability of different modalities has not been fully investigated. CCT is known to correlate with intraocular pressure (IOP). The aim of this study was to evaluate the agreement of Pentacam Scheimpflug system with noncontact specular microscopy (NCSM) and ultrasound (US) pachymetry in measuring CCT and the relation between IOP taken with Goldmann applanation tonometer (GAT) and the CCT measured with these three methods. Methods: The right eyes of 135 enrolled persons without antiglaucoma drug use (100 females and 35 males), who comprised 32 patients with primary open-angle glaucoma, 14 with ocular hypertension, 45 with primary angle-closure glaucoma, and 44 controls, were studied. Intermethod comparison of CCT was made by the 95% limits of agreement analysis according to Bland and Altman. Linear regression analysis was used to assess the relationship between IOP and CCT taken with each modality. Results: The mean CCT (+/-SD) taken with Scheimpflug, US, and NCSM was 559.49 +/- 38.44 mu m, 553.01 +/- 39.33 mu m, and 552.04 +/- 42.95 mu m, respectively. The average values of CCT taken with the three instruments were not significantly different (one-factor ANOVA; p = 0.26), although the marginal mean difference between Scheimpflug and US or NCSM was statistically significant (paired t test; p = 0.0009 and 0.005, respectively). The 95% limits of agreement were 6.47 +/- 43.21 mu m between Scheimpflug and US, 7.45 +/- 58.86 mu m between Scheimpflug and NCSM, and 0.98 +/- 51.69 mu m between US and NCSM. There was a positive association between IOP and CCT measured with US or NCSM, whereas there was no correlation between IOP and CCT measured with Scheimpflug. Conclusions: Although CCT values measured with Scheimpflug, US, and NCSM are closely similar, clinicians should keep in mind that these methods are not simply interchangeable.
TAYLOR & FRANCIS INC, 2007年02月, CURRENT EYE RESEARCH, 32 (2), 89 - 94, 英語[査読有り]
研究論文(学術雑誌)
Nitric oxide (NO) is cytoprotective to certain types of neuronal cells. The neuroprotective ability of NO in the retina was reportedly mediated by the cyclic GMP (cGMP) to protein kinase G (PKG) pathway. Cyclic AMP-responsive element binding protein (CREB) plays an essential role in the NO/cGMP/PKG-mediated survival of rat cerebellar granule cells. We tested whether CREB transduces the NO/cGMP/PKG anti-apoptotic cascade in R28 neuro-glial progenitor cells. Apoptosis was induced in R28 cells by serum deprivation for 24 h. Varying concentrations of two NO donors, sodium nitroprusside (SNP) and nipradilol, were added to medium with or without an NO scavenger, a soluble guanylyl cyclase inhibitor, or a PKG inhibitor. The cells were immunostained against activated caspase-3 and counterstained with Hoechst 33258. Apoptosis was quantified by counting activated caspase-3 positive or pyknotic cells. SNP and nipradilol rescued R28 cells from apoptosis in a dose-dependent manner, at an optimal concentration of 1.0 mu M and 10 mu M, respectively. Higher concentrations were cytotoxic. The NO scavenger and the inhibitors decreased the anti-apoptotic effect of the NO donors. Intracellular cGMP levels were increased after exposure to SNP and nipradilol. Western blotting showed that both NO donors increased CREB phosphorylation, which was blocked when pre-exposed to the inhibitors. Transfection with a dominant negative CREB construct defective of phosphorylation at Ser-133 interfered with the anti-apoptotic activity of SNP. These results indicate that CREB at least in part mediates the cGMP/PKG-dependent anti-apoptotic signal induced by NO in R28 cells. (c) 2006 Elsevier Ltd. All rights reserved.
ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD, 2007年01月, EXPERIMENTAL EYE RESEARCH, 84 (1), 152 - 162, 英語[査読有り]
研究論文(学術雑誌)
This study tested whether once weekly instillation of latanoprost exerts the similar IOP lowering effect as once daily instillation in the same individuals. Latanoprost was administered on right eyes of eight healthy male volunteers once daily first for 24 days, which was followed by the 31-day washout and the subsequent once weekly instillation for another 24 days. The mean baseline IOP was 12.06 ± 1.50 (range, 10.0 to 14.0) mmHg, whereas the mean IOP during once daily treatment was 9.87 ± 1.71 mmHg, which was significantly lower than the former (p=0.025). The mean washout IOP was 12.56 ± 2.16 mmHg, which was similar to the baseline IOP. The mean IOP during once weekly instillation of latanoprost was 11.34 ± 1.51 mmHg, which was not statistically different from the washout IOP. Four of the 8 subjects showed 15% or more reduction in IOP both during once daily and once weekly instillations, two of whom were overlapped. Since the magnitude of the IOP reduction with once daily use was higher than that with once weekly use even in the responders, the current protocol of once daily instillation should be respected.
2007年, Kobe Journal of Medical Sciences, 53 (6), 297 - 304, 英語[査読有り]
研究論文(学術雑誌)
A relative afferent pupillary defect (RAPD) is known to develop only when more than 25% of retinal ganglion cells are ablated in monkeys' eyes. However, there was no prior study to estimate biometrically the degree of retinal nerve fiber layer (RNFL) thickness reduction leading to the development of RAPD in live human eyes. The purpose of this study was to examine the correlation between the amount of RNFL thickness reduction and the depth of a clinically detectable RAPD in patients with unilateral optic atrophy. Enrolled were 20 patients with optic atrophy of various etiologies. We quantified RAPD by performing the swinging flashlight test with log-scaled neutral density filters placed over the unaffected eye. Average RNFL thickness was measured by OCT3000 with the average RNFL thickness program. Linear regression analysis was used in assessing the relationship between RAPD and the ratio of affected to unaffected average RNFL thickness. The mean of average RNFL thickness was 95.6 +/- 17.3 mu m in the unaffected eyes and 50.7 +/- 19.3 mu m in the affected eyes (P < 0.001). Regression analysis between RAPD and the ratio of affected to unaffected average RNFL thickness revealed a correlation coefficient R-2=0.48 (P=0.0007). The regression line intersected the y-axis at 0.77. RAPD was not clinically detected until at least approximately 25% of the retinal nerve fibers were lost when compared with the unaffected eyes. Substantial retinal ganglion cell damage is required for the development of RAPD.
SPRINGER, 2006年11月, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 244 (11), 1480 - 1484, 英語[査読有り]
研究論文(学術雑誌)
The purpose of this study was to investigate whether latanoprost, a prostaglandin F2 alpha analogue, has a direct anti-apoptotic effect both in retinal neuro-glial cells in culture and in diabetic retina. R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24 h serum deprivation. Serum withdrawal made up to 15% of R28 cells pyknotic and activated caspase-3 immunoreactive, and latanoprost acid suppressed apoptosis with dose dependency at an optimum concentration of 1.0 mu M (P < 0.001). UO126, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) 1 and 2 inhibitor reversed this effect. Streptozotocin induced one- or three-month diabetic rats received balanced-salt-solution (BSS) in the left eye and latanoprost eye drops in the right for 5 days. Retinal wholemount was subjected to terminal dUTP nick end labeling (TUNEL) staining, whereas eyeballs were enucleated for cleaved caspase-3 immunofluorescence. Retinal homogenates were probed for phospho- or total p44/p42 MAPK and Akt. One- and three-month diabetic retina had 30.2 +/- 15.3 and 23.6 +/- 9.0 TUNEL positive cells per 0.5 CM, respectively, whereas control retina had few TUNEL positive cells. Latanoprost instillation significantly reduced these cells (10.0 +/- 3.1 and 11.3 +/- 3.1 cells per 0.5 cm(2) for 1 M and 3 M, respectively, P < 0.01), whereas BSS did not. Latanoprost also significantly reduced cleaved caspase-3 immunoreactive cells in ganglion cell and inner nuclear layers (P < 0.05). Latanoprost increased phosphorylated to total protein ratio of p44/p42 MAPK (P < 0.05), but not of Akt. Taken together, the present findings suggest that latanoprost rescues retinal neurons and/or glial cells from apoptosis, which is probably mediated by p44/p42 MAPK through caspase-3 inhibition. (c) 2006 Elsevier Ltd. All rights reserved.
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2006年11月, EXPERIMENTAL EYE RESEARCH, 83 (5), 1108 - 1117, 英語研究論文(学術雑誌)
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, 2006年08月, EYE, 20 (8), 882 - 887, 英語[査読有り]
研究論文(学術雑誌)
PURPOSE: To evaluate the agreement of iCare rebound tonometer in measuring intraocular pressure (IOP) with Goldmann applanation tonometer (GAT), Tonopen XL, and noncontact tonometer, and the influence of the central corneal thickness (CCT) on IOP measurements made with these four tonometers in 45 (12 control and 33 glaucomatous or ocular hypertensive) eyes. DESIGN: Clinically relevant experimental study. METHODS: Tonometer intermethod agreement was assessed by the Bland-Altman method. The relations of CCT with absolute IOP values and intertonometer differences were analyzed by linear regression. RESULTS: The mean differences (95% limits of agreement) in IOP readings between iCare and GAT, Tonopen XL, and noncontact tonometer were 1.40 +/- 4.29, 0.00 +/- 4.78, and 2.22 +/- 4.19 mm Hg, respectively. All tonometries had a marked association with CCT. As the CCT got thicker, iCare considerably overestimated GAT and Tonopen XL. CONCLUSIONS: Although influenced by CCT, iCare agrees well with applanation tonometers.
ELSEVIER SCIENCE INC, 2006年08月, AMERICAN JOURNAL OF OPHTHALMOLOGY, 142 (2), 332 - 334, 英語研究論文(学術雑誌)
Diabetic retinopathy is characterized by early onset of neuronal cell death. We previously showed that insulin mediates a prosurvival pathway in retinal neurons and that normal retina expresses a highly active basal insulin receptor/Akt signaling pathway that is stable throughout feeding and fasting. Using the streptozotocin-induced diabetic rat model, we tested the hypothesis that diabetes diminishes basal retinal insulin receptor signaling concomitantly with increased diabetes-induced retinal apoptosis. The expression, phosphorylation status, and/or kinase activity of the insulin receptor and downstream signaling proteins were investigated in retinas of age-matched control, diabetic, and insulin-treated diabetic rats. Four weeks of diabetes reduced basal insulin receptor kinase, insulin receptor substrate (IRS)-1/2-associated phosphatidylinositol 3-kinase, and Akt kinase activity without altering insulin receptor or IRS-1/2 expression or tyrosine phosphorylation. After 12 weeks of diabetes, constitutive insulin receptor autophosphorylation and IRS-2 expression were reduced, without changes in p42/p44 mitogen-activated protein kinase or IRS-1. Sustained systemic insulin treatment of diabetic rats prevented loss of insulin receptor and Akt kinase activity, and acute intravitreal insulin administration restored insulin receptor kinase activity. Insulin treatment restored insulin receptor-beta autophosphorylation in rat retinas maintained ex vivo, demonstrating functional receptors and suggesting loss of ligand as a cause for reduced retinal insulin receptor/Akt pathway activity. These results demonstrate that diabetes progressively impairs the constitutive retinal insulin receptor signaling pathway through Akt and suggests that loss of this survival pathway may contribute to the initial stages of diabetic retinopathy.
AMER DIABETES ASSOC, 2006年04月, DIABETES, 55 (4), 1148 - 1156, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Background: The aim was to compare the ability of confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP), and optical coherence tomography (OCT) to discriminate eyes with ocular hypertension (OHT), glaucoma-suspect eyes (GS) or early glaucomatous eyes (EG) from normal eyes. Methods: Ocular hypertension, GS, and EG were defined as normal disc with intraocular pressure > 21 mmHg, glaucomatous disc without visual field loss, and glaucomatous disc accompanying the early glaucomatous visual filed loss respectively. Ninety-three normal eyes, 26 OHT, 55 GS, and 67 EG were enrolled. Optic disc configuration was analyzed by CSLO (version 3.04), whereas retinal nerve fiber layer thickness was analyzed by SLP (GDx-VCC; version 5.3.2) and OCT-1 (version A6X1) in each individual. The measurements were compared in the four groups of patients. Receiver operating characteristic curve (ROC) and area under the curve (AUC) discriminating OHT, GS or EG from normal eyes were compared for the three instruments. Results: Most parameters in GS and EG eyes showed significant differences compared with normal eyes. However, there were few significant differences between normal and OHT eyes. No significant differences were observed in AUCs between SLP and OCT. In EG eyes, the greatest AUC parameter in OCT (inferior-120; 0.932) had a higher AUC than that in CSLO (vertical cup/disc ratio; 0.845; P=0.017). In GS, the greatest AUC parameter in OCT (average retinal nerve fiber layer [RNFL] thickness; 0.869; P=0.002) and SLP (nerve fiber indicator [NFI]; 0.875; P=0.002) had higher AUC than that in CSLO (vertical cup/disc ratio; 0.720). Conclusions: Three instruments were useful in identifying GS and EG eyes. For glaucomatous eyes with or without early visual field defects, SLP and OCT performed similarly or had better discriminating abilities compared with CSLO.
SPRINGER, 2006年01月, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 244 (1), 58 - 68, 英語研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
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 eve 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 eve, respectively. The reduction was > 3 x the standard deviation of the normal mean values in the nasal and temporal quadrants of the left eve 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.
ELSEVIER SCIENCE INC, 2005年07月, JAPANESE JOURNAL OF OPHTHALMOLOGY, 49 (4), 294 - 296, 英語研究論文(学術雑誌)
Although glaucoma is known to alter glial reactivity, the long-term effect of elevated intraocular pressure (IOP) on glial change has not been fully elucidated. This study aimed to examine how chronically elevated IOP induced by episcleral vein cauterization (EVC) in unilateral eyes affect reactivities of astrocytes and Muller cells of rats in the treated as well as contralateral eyes over time. EVC in unilateral eyes of Sprague-Dawley rats were performed to produce chronically elevated IOP. Flat mounted retina preparations were made at several points until 6 months, which were subjected to immunostaining for glial fibrillary acidic protein (GFAP). Retinal homogenates were one- or two-dimensionally electrophoresed, followed by GFAP immunoblotting. EVC significantly increased IOPs up to 27.8 from 13.1 mmHg, which gradually decreased over time. In flat mounted retinas, astrocytes lost but Muller cells gained GFAP immunoreactivity at 3 days after cauterization. The glial changes were partially reversed over time but last even after IOP normalization. In the contralateral eyes, similar glial changes gradually appeared at 1 month after EVC and thereafter. Immunoblotting demonstrated not only molecular size shifts but also alteration of isoelectric focusing of GFAP both in treated and contralateral retina as compared with age-matched control retina. EVC led to opposite reactions in astrocytes and Muller cells in terms of GFAP immunoreactivity. Late-onset glial reactivity also occurred in the contralateral retina. (c) 2005 Elsevier Ltd. All rights reserved.
ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD, 2005年07月, EXPERIMENTAL EYE RESEARCH, 81 (1), 48 - 56, 英語研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
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, 2005年03月, 眼科臨床医報, 99 (3), 231 - 233, 日本語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Purpose. Unoprostone isopropyl is an ocular hypotensive that was originally produced as a prostaglandin F2alpha analogue and is eventually recognized as a synthetic docosanoid. The compound is recently suggested to have potent neuroprotective ability in the retina. The purpose of this study is to test whether and how the biologically active metabolites of unoprostone isopropyl rescue retinal neuro-glial progenitor cells from apoptosis. Methods. R28 cells were deprived of serum for 24 hr with or without varying concentrations of unoprostone metabolite M1 or M2 or vehicle in the presence or absence of specific inhibitors against several types of signal transduction proteins. Immunocytochemistry against activated caspase-3 with Hoechst nuclear staining was performed. Results. Up to 15% of R28 cells became pyknotic and activated caspase-3 immunoreactive after 24-hr serum withdrawal. M1, but not M2, significantly reduced apoptotic cells in a dose-dependent fashion with a maximal effect at 100 muM (p < .0001). LY294002, the phosphatidylinositol 3-OH kinase (PI3K) inhibitor, and KT5823, the protein kinase G (PKG) inhibitor, reversed the antiapoptotic effect of M1. Conclusions. The unoprostone metabolite M1 protects retinal neuro-glial progenitor R28 cells from apoptosis induced by serum deprivation via the PI3K and PKG pathways.
SWETS ZEITLINGER PUBLISHERS, 2004年12月, CURRENT EYE RESEARCH, 29 (6), 457 - 464, 英語[査読有り]
研究論文(学術雑誌)
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. Ophthalmology 2004;111:2278-2283 (C) 2004 by the American Academy of Ophthalmology.
ELSEVIER SCIENCE INC, 2004年12月, OPHTHALMOLOGY, 111 (12), 2278 - 2283, 英語[査読有り]
研究論文(学術雑誌)
The Akt serine/threonine kinase mediates pro-survival signalings in retina and was reported to be activated in a response to some retinal and optic nerve injuries. Human and experimental glaucoma induce apoptosis of retinal ganglion cells (RGCs). The purpose of this study is to test whether episcleral vein cauterization (EVC) to chronically elevate intraocular pressures (IOPs) in rats increase apoptosis of RGCs and affect activation of Akt and its upstream insulin-like growth factor (IGF)-1 receptor/Insulin receptor. Three episcleral veins in left eyes of Sprague-Dawley rats were cauterized to elevate IOPs. Up to 6 months, IOPs were monitored and the retina was dissected at several time points. The numbers of terminal dUTP nick end labeling (TUNEL)-positive cells and those of RGCs labeled with fluorogold were counted in flat-mounted retina. Immunohistochemistry and immunoblotting were performed to identify cells expressing phosphorylated Akt and to quantify the phospho- to total ratios of Akt and IGF-1 receptor/insulin receptor. EVC significantly elevated ION up to 2 months, increased TUNEL-positive cells in an IOP-dependent fashion, and reduced 34.5% of RGCs at 6 months (P<0.001) compared with contralateral retinas. Phosphorylated Akt was specifically expressed in RGCs until 1 month after cauterization. Akt (P=0.036) and IGF-1 receptor/Insulin receptor (P=0.003) were transiently phosphorylated at 3 days. Intrinsic activation of the IGF-1 receptor/Insulin receptor to Akt pathway may occur in RGCs in retina with EVC. (C) 2004 Elsevier B.V. All rights reserved.
ELSEVIER SCIENCE BV, 2004年10月, BRAIN RESEARCH, 1022 (1-2), 195 - 204, 英語[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
[査読有り]
研究論文(学術雑誌)
研究論文(学術雑誌)
A 17-year-old girl presented with bilateral angle-closure glaucoma associated with spherophakia. A previous bilateral laser iridotomy failed to control intraocular pressure (IOP). Goniosynechialysis with lens aspiration and posterior chamber intraocular lens implantation were performed in both eyes. Peripheral iridoplasty was performed 3 days later. The postoperative IOP was controlled without medication for 12 months in the right eye and 24 months in the left eye. By restructuring the physiologic aqueous outflow route, goniosynechialysis safely and effectively treated secondary glaucoma from spherophakia.
ELSEVIER SCIENCE INC, 2004年02月, JOURNAL OF CATARACT AND REFRACTIVE SURGERY, 30 (2), 513 - 516, 英語[査読有り]
研究論文(学術雑誌)
Purpose. Diabetes mellitus (DM) is a risk factor for open-angle glaucoma, although the mechanistic interrelationship of the two is debatable. The purpose of this study is to test whether DM augments neural apoptosis in rat retina with chronically elevated intraocular pressure (IOP). Methods. Sprague-Dawley rats were made diabetic by intraperitoneal injection of streptozotocin (STZ). At one month after STZ injection, three episcleral veins in one eye were cauterized to elevate IOP Rats without STZ injection were treated likewise as diabetic controls. At 2 weeks, 1 month, and 2 months after cauterization, the retina was dissected, flat-mounted, and subjected to terminal dUTP nick end labeling (TUNEL) staining. TUNEL positive cells per unit area of the whole retina were measured. Results. DM did not affect base line IOP or augment IOP elevation due to episcleral vein cauterization. TUNEL positive cells, which primarily consisted of the neurons and glial cells in the inner retina including retinal ganglion cell (RGC), were counted consistently eight times more in the diabetic retina without IOP elevation than diabetic controls (n = 9, p < 0.001). The cauterization significantly elevated IOP up to 28.9 mmHg (p < 0.001), which was reduced over time, and substantially induced apoptosis in a IOP-dependent fashion (p < 0.001). Ocular hypertensive retinas with DM had significantly more TUNEL positive cells-than those without DM despite of the similar time course of IOP changes (p < 0.001). Conclusions. DM has an additive effect on apoptosis induction by chronic elevation of IOR Diabetes may act as a risk factor of open-angle glaucoma by increasing susceptibility of retinal cells including retinal ganglion cells to apoptosis triggered by additional stresses such as elevated IOP.
SWETS ZEITLINGER PUBLISHERS, 2004年01月, CURRENT EYE RESEARCH, 28 (1), 47 - 54, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
[査読有り]
研究論文(学術雑誌)
Purpose: To evaluate the relationship between age and retinal nerve fiber layer (RNFL) thickness in normal subjects, as measured by optical coherence tomography (OCT). Methods: One hundred and forty-four normal subjects (144 eyes), ranging from 16 to 84 years of age, were enrolled in this cross-sectional study. The RNFL thickness was determined using OCT with three circle scans 3.4 mm in diameter. Results: The average RNFL thickness was inversely correlated with age (r = -0.348, p < 0.001). Analyzing the quadrants as a parameter, RNFL thickness in the superior, temporal and inferior quadrants also decreased with age. Using 30-degree segments, there were significant correlations between age and the RNFL thickness of temporal segments (7-11 o'clock). The average RNFL thickness had the highest correlation among all parameters (r = -0.348, p < 0.001). Regarding nasal quadrant thickness, RNFL ratios (average, superior, temporal and inferior RNFL thickness relative to the nasal quadrant thickness) were not significant-
KARGER, 2003年07月, OPHTHALMOLOGICA, 217 (4), 273 - 278, 英語[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
PURPOSE: To present a case of occult macular dystrophy accompanying normal-tension glaucoma. DESIGN: Observational case report. METHODS: Visual function and ophthalmoscopic and electroretinographic findings in a 56 year,old man suffering from gradually progressive photophobia and visual dysfunction were followed up over 4 years. RESULTS: Best-corrected visual acuity was below 20/200, and intraocular pressures remained in the low teens in both eyes. A wedge-shaped visual field defect in the right eye, corresponding to the enlarged disk cupping, and a relative central scotoma in the left were detected. Ophthalmoscopy and fluorescein angiography detected no apparent abnormality at the macular region in either eye. Severely attenuated multifocal electroretinographic responses were recorded from only the central areas, with normal full field responses. CONCLUSION: Clinicians must took for additional pathos logic conditions in patients with normal tension glaucoma who have unexplained central visual dysfunction. (Am J Ophthalmol 2003;135:715-717. (C) 2003 by Elsevier Inc. All rights reserved.).
ELSEVIER SCIENCE INC, 2003年05月, AMERICAN JOURNAL OF OPHTHALMOLOGY, 135 (5), 715 - 717, 英語[査読有り]
研究論文(学術雑誌)
PURPOSE: To evaluate the relationship between visual field and retinal nerve fiber layer (RNFL) thickness measured by optical coherent tomography (OCT) and to assess the diagnostic ability of OCT to distinguish between early glaucomatous or glaucoma-suspect eyes from normal eyes. DESIGN: Retrospective, non-randomized, cross-sectional study. METHODS: A total of 160 eyes of 120 normal Japanese adults, 23 eyes of 16 patients with ocular hypertension, 38 eyes of 35 glaucoma-suspect patients, and 237 glaucomatous eyes of 140 glaucoma patients were enrolled in the study. The glaucoma group included 89 early glau, comatous eyes. Thickness of the RNFL around the optic disk was determined with three 3.4-mm diameter circle OCT scans. Average and segmental RNFL thickness values were compared among all groups. The correlation between mean deviation and RNFL thickness in glaucomatous eyes was also analyzed. Receiver operating characteristic (ROC) curve area was calculated to discriminate normal eyes from early glaucomatous or glaucoma suspect eyes. RESULTS: A significant relationship existed between the mean deviation and RNFL thickness in all parameters excluding the 3-o'clock area. The average RNFL thickness had the strongest correlation in all parameters (r = -0.729, P < .001). Retinal nerve fiber layer thickness at the 7-o'clock inferotemporal segment had the widest areas under the ROC curves in all parameters for early glaucomatous eyes (0.873). CONCLUSION: Measurement of RNFL thickness by OCT is useful in detecting early RNFL damage. Furthermore, OCT measurements of RNFL thickness may provide clinically relevant information in monitoring glaucomatous changes. (C) 2003 by Elsevier Science Inc. All rights reserved.
ELSEVIER SCIENCE INC, 2003年04月, AMERICAN JOURNAL OF OPHTHALMOLOGY, 135 (4), 513 - 520, 英語[査読有り]
研究論文(学術雑誌)
Purpose. The changes in short wavelength sensitive (S-) cone electroretinograms (ERGs) to ganzfeldt flash stimuli were examined in patients with Posner-Schlossman syndrome to study the differences in S-cone action in both the acute attack phase and the remission phase. Methods. Ganzfeldt colour flashes under bright white background illumination were used to elicit short wavelength (S-), and mixed long- (L) and middle- (M) wavelength sensitive cone ERGs. Three subjects with unilateral Posner-Schlossman syndrome and 18 age-matched normal controls were compared. To compare the media opacity we obtained the L,M-cone balance, namely, the log density units of the neutral density filter required to produce the L,M-cone b-wave elicited with red stimuli which is identical to those with blue stimuli. Results. Selective reduction of the S-cone ERG b-wave in acute attacks of Posner-Schlossman syndrome was found. Two of three cases showed the recovery of the S-cone b-wave with a decrease in the intraocular pressure. With regard to the implicit time, significant delay of the S-cone b-wave could not be detected in all subjects. Conclusion. Selective reduction of the S-cone component of the ERG during raised intraocular pressure was found. The S-cone pathway is thought to be more vulnerable to damage than the L,M-cone systems following elevations of intraocular pressure.
Royal College of Ophthalmologists, 2001年, Eye, 15 (2), 163 - 167, 英語[査読有り]
研究論文(学術雑誌)
PURPOSE: To report a case of zoster sine herpete with bilateral ocular involvement. METHOD: Case report. RESULTS: A 65-year-old man showed bilateral iridocyclitis with sectoral iris atrophy and elevated intraocular pressure unresponsive to steroid treatment. No cutaneous eruption was manifest on the forehead. A target region of varicella-zoster virus DNA sequence was amplified from the aqueous sample from the left eye by polymerase chain reaction. Bilateral iridocyclitis resolved promptly after initiation of systemic and topical acyclovir treatment. Secondary glaucoma was well controlled by bilateral trabeculectomy. CONCLUSIONS: Zoster sine herpete should be considered and polymerase chain reaction performed on an aqueous sample to detect varicella-zoster virus DNA for rapid diagnosis whenever anterior uveitis accompanies the characteristic iris atrophy, even in the case of bilateral involvement. © 2000 Elsevier Science Inc.
2000年, American Journal of Ophthalmology, 129 (6), 809 - 810, 英語[査読有り]
研究論文(学術雑誌)
Optic perineuritis is a rare syndrome characterized by bilateral, sometimes unilateral, optic disc swelling without a raised cerebrospinal fluid (CSF) pressure and visual dysfunction except for big blind spots, which are presumed to be an inflammation of the optic nerve sheaths. Syphilitic infection is known to be most commonly associated with optic perineuritis. We present three cases of optic perineuritis without syphilitic infection. Two of them showed disc swelling and blind spot enlargement bilaterally, which subsided in a good response to the corticosteroid therapy. In the remaining one case, the left eye exhibited disc swelling without visual disturbance as in the other cases, while anterior ischemic optic neuropathy occurred and produced the permanent visual field defect in the right eye, presumably due to the coincidental existence of optic disc hypoplasia. CSF in all cases showed normal pressure and lymphocytosis, which faded in response to the corticosteroid therapy. A lumbar puncture was a critical maneuver for the correct diagnosis. Despite the overall favorable outcome, immediate treatment should be considered for optic perineuritis patients, especially those who have a local anatomical vulnerability of the disc.
1999年, Neuro-Ophthalmology, 21 (3), 135 - 145, 英語[査読有り]
研究論文(国際会議プロシーディングス)
[招待有り]
記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
研究発表ペーパー・要旨(国際会議)
目的:本邦における緑内障診療データの管理・共通化の現状について調査し,今後の緑内障診療・研究の向上のための課題と方向性について明らかにすること.対象と方法:日本緑内障学会内に設置されたデータ共通化委員会に参画し,緑内障診療に積極的に取り組んでいる14大学に対して文書によってアンケート調査を行った.結果:すべての大学において病院情報システムが導入され,3社の眼科部門カルテによる診療データの電子化が行われていた.しかしながら,電子カルテから電子的な診療データ提供体制が整っていた大学は30.8%にとどまり,データの二次利用が具体的に進んでいる大学眼科は14.3%のみであった.地域医療機関との電子データによる診療連携を進めている大学眼科は35.7%であり,眼科内で診療データの電子的管理を行っていたのは42.9%にとどまっていた.結論:アンケートの結果から診療データの管理や共通化について多くの課題が明らかになった.(著者抄録)
(公財)日本眼科学会, 2016年08月, 日本眼科学会雑誌, 120 (8), 540 - 547, 日本語[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[招待有り]
記事・総説・解説・論説等(学術雑誌)
目的:カラーコンタクトレンズ(CL)による両眼角膜潰瘍の報告。症例:16歳女性がカラーCLを装着したまま就寝後に両眼の眼痛,充血を自覚し,数日後に当院へ紹介となった。初診時の矯正視力は左右眼とも0.6であった。両眼の上方角膜に弓状に配列する多数の潰瘍と毛様充血を認めた。それまでの抗菌薬点眼に反応が乏しいことからCLへの炎症反応の可能性を考え,ステロイド点眼と内服を併用したところ,徐々に上皮化し視力改善が得られた。本症例ではカラーCLの角膜側に偏在した色素による直接的な障害と色素に対するアレルギー反応である可能性が推定された。結論:カラーCLによる角膜潰瘍で抗菌薬点眼の効果が乏しい場合には,ステロイド治療を検討すべきと考えられた。(著者抄録)
(株)医学書院, 2016年05月, 臨床眼科, 70 (5), 741 - 745, 日本語[査読有り]
速報,短報,研究ノート等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
[査読有り]
速報,短報,研究ノート等(学術雑誌)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
[招待有り]
記事・総説・解説・論説等(学術雑誌)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[査読有り]
記事・総説・解説・論説等(学術雑誌)
[査読有り][招待有り]
記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
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その他
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記事・総説・解説・論説等(学術雑誌)
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書評論文,書評,文献紹介等
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
緑内障性視神経症は緑内障における視機能障害の本態とされる.しかし,眼圧を筆頭とするさまざまな危険因子がどのようにして緑内障性視神経症を引き起こすのか,未だ十分に解明されていない.また,視機能障害の評価に用いられる静的・動的視野検査は心理物理学に基づく自覚的検査であるため,客観的な他覚的検査法の導入が望まれてきた.本研究において我々は緑内障性視神経症の病態と他覚的視機能解析方法に関して検討を行った.アクアポリン(aquaporin:AQP)水チャンネルは,ホモないしヘテロ四量体として主に細胞膜に存在し,細胞内外への双方向性の水輸送を担っている.AQPによる水輸送は,神経細胞が活動電位を迅速に繰り返し発生させるのに不可欠である.既報の13のアイソフォームのうちAQP-4が球後視神経には発現するが,視神経乳頭部には発現していないことが知られていた.我々は,ラット視神経のアストロサイトは,無髄・有髄領域にかかわらずAQP-9を発現していることを見出した.上強膜静脈焼灼による慢性高眼圧によって,AQP-9の免疫染色性と遺伝子発現が著しく減弱したが,球後のAQP-4の発現に変化はなかった.同様の変化は,隅角レーザー誘発高眼圧サル眼やヒト緑内障眼の視神経でも確認された.さらにAQP-9は正常ラットでは網膜神経節細胞の細胞体にも発現していたが,慢性高眼圧眼ではその発現が有意に減弱していた.すなわち,慢性高眼圧は,視神経乳頭のアストロサイトと網膜神経節細胞の細胞体という,緑内障性視神経症の発症に深く関与している細胞ならびに部位におけるAQP-9の発現を減弱させていた.近年,神経科学の分野では,解糖系によりブドウ糖から代謝されて産生された乳酸がエネルギー基質としてアストロサイトから神経細胞へ供給されると考えられるようになった(astrocyte-to-neuron lactate shuttle hypothesis).AQP-9は,水以外に乳酸などの溶質も輸送するアクアグリセロポリンに属する.AQP-9のdown-regulationにより,エネルギー基質である乳酸が網膜神経節細胞とその軸索へ正常に供給されなくなることが,緑内障性視神経症の発症に関与している可能性がある.多局所視覚誘発電位(multifocal visual evoked potential:mfVEP)は一度に60ヶ所の局所網膜に対応する視覚誘発電位を記録することのできる他覚的視野検査である.同時に複数のチャンネルから記録することで,信号雑音比(signal-to-noise ratio:SNR)は向上した.しかし,これまでの研究対象はおおむね白人であったため,骨格の異なる日本人に適した記録方法はまだ確立されていなかった.200例の頭部磁気共鳴画像(magnetic resonance imaging:MRI)から鳥距溝の後頭結節に対する相対位置関係を計測したところ,白人に比べ,その相対位置関係は約1cm有意に低かった.次いで,3チャンネルからのmfVEP同時記録ならびに信号窓と雑音窓におけるSNR分布の受信者操作特性(receiver-operating characteristic:ROC)曲線解析を行った.その結果,日本人においては,後頭結節を挟む水平チャンネルと二組の垂直チャンネルのいずれかを組み合わせた2チャンネルを用いてmfVEP記録すると,ROC曲線下面積(area under the ROC curve:AUC)が最も大きくなることを見出した.次にHumphrey視野計の平均偏差が-15dB未満の初期から中期緑内障56眼ならびに正常62眼において,このSNR-AUCがHumphrey視野計のトータル偏差に対して,同等の緑内障診断能ならびに高い相関を示すことを見出した.一方,確率プロットに基づく,Humphrey視野とmfVEP間の障害部位のトポグラフィカルな一致率は中程度であった.従来検討されてきたSNRの確率プロットのクラスター判定が局所の感度低下の診断に有用であるのに対して,SNR-AUCは,平均偏差に類似した,緑内障性視神経症のびまん性機能障害を定量するグローバル・インデックスとして用いることができる可能性がある.(著者抄録)
(公財)日本眼科学会, 2012年03月, 日本眼科学会雑誌, 116 (3), 298 - 346, 日本語[査読有り][招待有り]
記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
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記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
[査読有り]
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
速報,短報,研究ノート等(学術雑誌)
教科書・概説・概論
学術書
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学術書
学術書
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学術書
学術書
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学術書
教科書・概説・概論
教科書・概説・概論
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
教科書・概説・概論
学術書
学術書
教科書・概説・概論
学術書
学術書
学術書
学術書
学術書
学術書
学術書
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ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
公開講演,セミナー,チュートリアル,講習,講義等
口頭発表(一般)
口頭発表(一般)
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
公開講演,セミナー,チュートリアル,講習,講義等
口頭発表(一般)
口頭発表(一般)
ポスター発表
口頭発表(一般)
口頭発表(一般)
ポスター発表
公開講演,セミナー,チュートリアル,講習,講義等
公開講演,セミナー,チュートリアル,講習,講義等
公開講演,セミナー,チュートリアル,講習,講義等
公開講演,セミナー,チュートリアル,講習,講義等
公開講演,セミナー,チュートリアル,講習,講義等
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
口頭発表(一般)
口頭発表(一般)
シンポジウム・ワークショップパネル(指名)
公開講演,セミナー,チュートリアル,講習,講義等
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
公開講演,セミナー,チュートリアル,講習,講義等
公開講演,セミナー,チュートリアル,講習,講義等
公開講演,セミナー,チュートリアル,講習,講義等
公開講演,セミナー,チュートリアル,講習,講義等
口頭発表(一般)
公開講演,セミナー,チュートリアル,講習,講義等
公開講演,セミナー,チュートリアル,講習,講義等
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(招待・特別)
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
口頭発表(一般)
ポスター発表
口頭発表(一般)
口頭発表(一般)
公開講演,セミナー,チュートリアル,講習,講義等
口頭発表(一般)
口頭発表(一般)
[招待有り]
シンポジウム・ワークショップパネル(指名)
口頭発表(一般)
公開講演,セミナー,チュートリアル,講習,講義等
口頭発表(一般)
[招待有り]
シンポジウム・ワークショップパネル(指名)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
公開講演,セミナー,チュートリアル,講習,講義等
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
[招待有り]
シンポジウム・ワークショップパネル(指名)
口頭発表(一般)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
公開講演,セミナー,チュートリアル,講習,講義等
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
その他
口頭発表(一般)
口頭発表(一般)
その他
その他
口頭発表(一般)
口頭発表(一般)
その他
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
[招待有り]
口頭発表(招待・特別)
その他
その他
口頭発表(一般)
その他
口頭発表(一般)
口頭発表(一般)
その他
その他
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
シンポジウム・ワークショップパネル(公募)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
競争的資金
競争的資金
競争的資金
競争的資金
競争的資金
競争的資金
競争的資金
競争的資金
競争的資金
競争的資金