Publications by authors named "Eri Nakano"

21 Publications

  • Page 1 of 1

Acute Megakaryoblastic Leukemia Harboring a Subclone Expressing BCR-ABL1 Fusion Gene Product.

Intern Med 2021 May 29. Epub 2021 May 29.

Department of Hematology, Suzuka Kaisei Hospital, Japan.

Acute myeloid leukemia (AML) with BCR-ABL1, also termed Philadelphia chromosome-positive AML (Ph+ AML), is a rare leukemia subtype classified by the World Health Organization in 2016. The characteristics of Ph+ AML have not been fully identified yet. We herein report a patient with Ph+ AML who phenotypically exhibited megakaryoblastic characteristics, FAB:M7 and harbored a subclone expressing BCR-ABL1 gene fusion products. This case suggests that BCR-ABL1 was acquired as a subclone due to a secondary event that might have occurred late during leukemia evolution. Our findings may aid in deciphering the mechanism underlying Ph+ AML development in future studies.
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http://dx.doi.org/10.2169/internalmedicine.7335-21DOI Listing
May 2021

Use of a Novel Fluorescent Catheter to Locate the Ureters during Total Laparoscopic Hysterectomy.

J Minim Invasive Gynecol 2021 Jul 19;28(7):1420-1424. Epub 2021 Apr 19.

Department of Obstetrics and Gynecology (Drs. Fujita, Nakagawa, Katano, Nakano, Kitayama, and Tanaka), Medical Park Shonan, Kanagawa, Japan; Department of Obstetrics and Gynecology (Dr. Kikuchi), Medical Park Yokohama, Kanagawa, Japan.

Ureteral injury can occur during total laparoscopic hysterectomy. This report documents our experience in using the near-infrared ray catheter (NIRC), a newly developed fluorescent ureteral catheter made of material that contains a fluorescent dye to improve visualization of the ureters. We have used the device in 3 patients between 40 and 50 years of age (mean, 46.3 ± 4.5 years) undergoing total laparoscopic hysterectomy and bilateral salpingectomy for uterine myomas. The time of catheter insertion ranged from 4 minutes and 9 seconds to 10 minutes and 57 seconds. A number of intraoperative procedures were performed near the ureters, namely, identification and ligation of the uterine arteries, dissection of the cardinal ligament, incision of the vaginal canal, and suturing of the vaginal stump. The abovementioned fluorescent ureteral catheter appears green on a monitor when illuminated by near-infrared light, and this facilitated real-time confirmation of the ureter positions, increasing surgical safety. The patients were followed up for 6 months postoperatively, and no urinary tract infection or injury was found. Prophylactic use of the fluorescent ureteral catheter may improve visualization of the ureters in patients considered to be at high risk of ureteral injury, such as those expected to exhibit ureteral deviation due to severe adhesions or an enlarged uterus and when the surgeon has little experience in laparoscopic surgery.
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http://dx.doi.org/10.1016/j.jmig.2021.04.004DOI Listing
July 2021

Early central nervous system relapse of monomorphic epitheliotropic intestinal T-cell lymphoma after cord blood transplantation.

Int J Hematol 2021 Jul 1;114(1):129-135. Epub 2021 Mar 1.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare subtype of intestinal T-cell lymphoma that occurs mostly in Asia. CHOP-like therapy is usually selected, but the prognosis is very poor. This report concerns a 43-year-old woman with newly diagnosed stage IVA MEITL. The patient obtained a partial response after 4 cycles of GDP (gemcitabine, dexamethasone, cisplatin) and achieved a complete response (CR) after cord blood transplantation (CBT) conditioned with total body irradiation, cyclophosphamide, and cytarabine. Seven months after transplantation, the patient experienced cognitive impairment. Magnetic resonance imaging of the brain showed a high-intensity lesion in the right cerebral peduncle and internal capsule. A cerebrospinal fluid examination confirmed central nervous system (CNS) relapse of MEITL. After 3 cycles of MPV (methotrexate, procarbazine, vincristine) followed by whole-brain radiotherapy, her cognitive impairment improved. Due to disease progression, she died 6 months after CNS relapse. Given the CNS relapse after achieving a CR with GDP and CBT in this patient, CNS prophylaxis during first-line therapy may be beneficial in the treatment of MEITL.
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http://dx.doi.org/10.1007/s12185-021-03107-9DOI Listing
July 2021

Relationship between Intraocular Pressure and Coffee Consumption in a Japanese Population without Glaucoma: The Nagahama Study.

Ophthalmol Glaucoma 2021 May-Jun;4(3):268-276. Epub 2020 Nov 5.

Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Purpose: To evaluate the association between daily coffee consumption and intraocular pressure (IOP) in healthy persons without glaucoma and the association between daily coffee consumption and history of glaucoma.

Design: Cross-sectional study.

Participants: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016.

Methods: All participants underwent a standardized ophthalmic examination. Self-reporting questionnaires were completed by all participants. First, the association between habitual coffee consumption and IOP among nonglaucoma individuals was evaluated by a multivariate linear regression analysis, adjusting for possible confounders. Second, the association between habitual coffee consumption and history of glaucoma also was evaluated using a multivariate logistic regression analysis.

Main Outcome Measures: The association between habitual coffee consumption and IOP among nonglaucoma individuals.

Results: Of 9850 participants, 9418 did not have history of glaucoma. Among these participants, the mean ± standard deviation IOP of both eyes was 14.7 ± 2.9 mmHg. The multivariate regression analysis revealed that habitual coffee consumption was associated significantly with IOP (P < 0.001): the higher the consumption of coffee, the lower the IOP of an individual. The IOP of the group who consumed coffee most frequently (3 times daily or more) was 0.4 mmHg lower (95% confidence interval, 0.2-0.5 mmHg lower) than that of the group that consumed coffee least frequently (less than once daily). However, the logistic regression analysis showed that habitual coffee consumption was not associated significantly with history of glaucoma (P = 0.53).

Conclusions: Frequent coffee consumption was associated with a slightly lower IOP in people without glaucoma but was not associated with a decreased risk of glaucoma developing. Additional experimental studies are needed to examine the effects of coffee on IOP and glaucoma risk.
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http://dx.doi.org/10.1016/j.ogla.2020.09.019DOI Listing
November 2020

Longitudinal changes in superficial microvasculature in glaucomatous retinal nerve fiber layer defects after disc hemorrhage.

Sci Rep 2020 12 16;10(1):22058. Epub 2020 Dec 16.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Glaucoma is a multifactorial optic neuropathy, possibly involving vascular dysfunction, leading to the death of retinal ganglion cells and their axons. Disc hemorrhage (DH) is known to be closely associated with the widening of retinal nerve fiber layer defect (NFLD); however, it has not been well elucidated how DH affects retinal microvasculature. We aimed to investigate the association between DH history and longitudinal changes in superficial retinal microvasculature in NFLD. We enrolled 15 glaucoma patients with DH history (32 glaucomatous NFLD locations, with or without DH history). NFLD-angle, superficial retinal vessel density (VD), and decreased superficial retinal microvasculature (deMv)-angle were assessed using optical coherence tomography angiography for at least three times over time. The mean follow-up period and OCT/OCTA scan interval were 21.3 ± 5.4 months (range, 12-28) and 6.8 ± 0.4 months (range, 2-18), respectively. Linear mixed-effects models showed that the presence of DH history was significantly associated with an additional NFLD-angle widening of 2.19 degree/year (P = 0.030), VD decrease of 1.88%/year (P = 0.015), and deMv-angle widening of 3.78 degree/year (P < 0.001). These changes were significantly correlated with each other (P < 0.001). Thus, the widening of NFLD was closely associated with deMv, and DH was associated with a subsequent decrease in superficial retinal microvasculature in NFLD.
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http://dx.doi.org/10.1038/s41598-020-79151-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744505PMC
December 2020

Analysis of Retinal Nerve Fibre Thickening in Progressive and Non-progressive Non-arteritic Anterior Ischaemic Optic Neuropathy Using Optical Coherence Tomography.

Neuroophthalmology 2020 25;44(5):307-314. Epub 2020 Jun 25.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

The study aims to investigate the longitudinal changes in the circumpapillary retinal nerve fibre layer thickness (cpRNFLT) in progressive and non-progressive non-arteritic anterior ischaemic optic neuropathy (NAION). This retrospective observational case series study analysed 17 eyes with NAION. Patients sustaining any additional visual loss (additional decrease in visual acuity (VA) ≥0.2 logMAR) within two months after initial onset of symptoms were classified as having progressive NAION. Of the 17 eyes with NAION, 13 (76.5%) were diagnosed as non-progressive and 4 (23.5%) were diagnosed as progressive. Compared with control eyes, eyes with non-progressive NAION showed greater cpRNFLT in all four optic disc quadrants at the initial visit (temporal and superior: < .001; nasal and inferior: = .002). In contrast, compared with control eyes, eyes with progressive NAION showed greater cpRNFLT in the superior and nasal quadrants (.004 and 0.028, respectively), but not in the temporal and inferior quadrants. During progression, eyes with progressive NAION showed a significant increase in cpRNFLT in the inferior quadrants; furthermore, there was significant increase in cpRNFLT in the nasal sector before visual loss developed after the initial visit. Progressive NAION showed development of the disc swelling from the superior to inferior portion of optic disc via the nasal swelling, suggesting that swollen axons in one ischaemic part may lead to secondary vascular infarction in another part of the optic disc. This enlargement could constitute the earliest sign of progressive NAION.
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http://dx.doi.org/10.1080/01658107.2020.1755991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518333PMC
June 2020

Atopic dermatitis as a risk factor for severe visual field loss in youth-a retrospective cohort study of glaucoma under steroid treatment.

Graefes Arch Clin Exp Ophthalmol 2021 Jan 16;259(1):129-136. Epub 2020 Sep 16.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Purpose: To assess the characteristics of glaucoma patients who received systemic or topical steroid treatment.

Methods: Patients who received steroid treatment were selected from a total of 4256 patients at our tertiary referral center of glaucoma management between August 2011 and October 2017. Clinical characteristics of the subjects were extracted from clinical records. To evaluate the factors influencing highest intraocular pressure during observation (max-IOP) or mean deviations (MDs) of visual field at the first and last visits, univariate and multivariate regression analyses were performed using a generalized estimating equation.

Results: Three hundred and eighty-two eyes of 196 patients were included in this study. The most frequent disease as the reason for steroid treatment was atopic dermatitis (58 eyes) followed by autoimmune diseases. The patients with atopic dermatitis were significantly younger (38.0 ± 11.2 years old, p < 0.001) and had lower MD (- 9.3 ± 9.1 dB at first visit, p = 0.01; - 10.6 ± 9.2 dB at last visit, p = 0.004) than those with other diseases. In multivariate regression analysis, age and MD at first visit, max-IOP, and atopic dermatitis were correlated with MD at last visit.

Conclusions: The results of the present study suggest that patients with atopic dermatitis carry the risk of irreversible visual field loss even in youth. For earlier detection of high intraocular pressure, reinforcement of ophthalmological screening in management of atopic dermatitis should be recommended.
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http://dx.doi.org/10.1007/s00417-020-04925-zDOI Listing
January 2021

Myopia Prevalence and Ocular Biometry Features in a General Japanese Population: The Nagahama Study.

Ophthalmology 2021 04 27;128(4):522-531. Epub 2020 Aug 27.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Purpose: To describe the distribution of ocular biometry and refraction in Japanese adults.

Design: Cross-sectional analysis of a prospective cohort study.

Participants: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. Participants were between 34 and 80 years of age.

Methods: All participants underwent axial length (AL; in millimeters), anterior chamber depth (ACD; in millimeters), corneal diameter (white to white; in millimeters), and central corneal thickness (CCT; in micrometers) measurement (IOL Master; Carl Zeiss Meditec, Dublin, CA) and refraction (spherical equivalent [SE]; in diopters [D]) and corneal curvature (CC; in millimeters) measurement (ARK-530A; Nidek, Aichi, Japan). Distribution of these ocular biometric parameters and prevalence of myopia, high myopia, and extreme myopia were summarized.

Main Outcome Measures: Distribution of ocular biometry and refraction.

Results: After standardization to the national population of 2015, estimates of mean AL and SE were 24.21 mm and -1.44 D, respectively. Estimates of mean CC, corneal diameter, CCT, and ACD were 7.69 mm, 12.01 mm, 543.96 μm, and 3.21 mm, respectively. After standardization of age and gender, the prevalence of myopia (SE, ≤-0.5 D) and high myopia (SE, ≤-6.0 D) were 49.97% and 7.89%, respectively. Approximately 70% of the younger participants (34-59 years of age) showed myopia, whereas high myopia was observed in approximately 10%. Although the number of individuals with myopia or high myopia was higher in the younger age groups, the prevalence of more extreme phenotypes remained stable across all ages, especially in women. Axial length of more than 30 mm was observed only in older women (n = 5 [0.05%]).

Conclusions: We showed detailed distributions of various ocular biometry and refraction parameters using a large general Japanese cohort. Prevalences of myopia and high myopia from 2013 through 2016 were higher than those in earlier studies, which reflects recent environmental change. However, constant prevalence of extreme myopia across all ages suggests high genetic predisposition of the extreme phenotype.
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http://dx.doi.org/10.1016/j.ophtha.2020.08.023DOI Listing
April 2021

Keratoconus-susceptibility gene identification by corneal thickness genome-wide association study and artificial intelligence IBM Watson.

Commun Biol 2020 07 31;3(1):410. Epub 2020 Jul 31.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely STON2 rs2371597 (P = 2.32 × 10), and confirmed a significant association between STON2 rs2371597 and keratoconus development (P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM's Watson question answering computer system (P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development.
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http://dx.doi.org/10.1038/s42003-020-01137-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395727PMC
July 2020

Azathioprine Hypersensitivity Syndrome during Treatment of Severe Interstitial Lung Disease with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.

Case Rep Pulmonol 2020 3;2020:8852441. Epub 2020 Jul 3.

Department of Internal Medicine, Suwa Central Hospital, Chino, Nagano 391-8503, Japan.

Azathioprine is used to treat anti-neutrophil cytoplasmic antibody- (ANCA-) associated vasculitis. Azathioprine hypersensitivity syndrome is often missed. An 81-year-old man undergoing treatment for interstitial pneumonia developed a high fever and was diagnosed with ANCA-associated vasculitis based on an elevated myeloperoxidase- (MPO-) ANCA titer and renal biopsy findings. After induction therapy, his clinical symptoms improved, but his MPO-ANCA remained elevated (>300 U·L) and hematuria persisted. Prednisolone plus azathioprine was administered as maintenance therapy. Three exacerbations of the inflammatory response occurred during the subsequent 3 months. In each instance, we suspected opportunistic infection or a flare-up of vasculitis. The first exacerbation was treated with an increased prednisolone dose and antibiotics. At the onset of the second exacerbation, which was accompanied by systemic erythema, we stopped azathioprine and administered antibiotics. The third exacerbation, which occurred the day after restarting azathioprine, involved a fever with chills and an acute inflammatory reaction; we therefore suspected an azathioprine allergy. A drug provocation test was performed, and a hyperinflammatory response was observed. The patient received prednisolone (15 mg·day) monotherapy; no further fever was observed during the subsequent 2 months. We therefore diagnosed azathioprine hypersensitivity syndrome. Under treatment with prednisolone (5 mg·day) and mycophenolate mofetil (1 g·day) (replacing the azathioprine), no signs of relapse or infection have occurred for more than two years. Renal function and the pulmonary lesions are stable, although the high MPO-ANCA titer and hematuria persist. The diagnosis of azathioprine hypersensitivity is often delayed because of the difficulty in identifying the relationship between immunosuppressive agents and hypersensitivity and in distinguishing this from infection or relapse of the primary disease. The misdiagnosis of azathioprine hypersensitivity leads to unnecessary treatment; thus, clinicians should consider allergic reactions specific to azathioprine when switching from induction to maintenance therapy.
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http://dx.doi.org/10.1155/2020/8852441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355349PMC
July 2020

Correlation between metamorphopsia and disorganization of the retinal inner layers in eyes with diabetic macular edema.

Graefes Arch Clin Exp Ophthalmol 2019 Sep 22;257(9):1873-1878. Epub 2019 Jun 22.

Department of Ophthalmology, Otsu Red Cross Hospital, 1-1-35 Nagara, Otsu, Shiga, 520-8511, Japan.

Purpose: To investigate factors associated with the severity of metamorphopsia secondary to diabetic macular edema (ME) by evaluating optical coherence tomography (OCT) parameters including disorganization of the retinal inner layers (DRIL).

Methods: We retrospectively reviewed medical records of 37 eyes of 37 consecutive patients with diabetic ME or resolved diabetic ME, who underwent spectral-domain OCT examination and metamorphopsia assessment with M-CHARTS on the same day between November 2017 and March 2018. Age, sex, visual acuity, lens status, treatment history, and factors analyzed on OCT examination including DRIL length were evaluated in association with M-CHARTS scores.

Results: Metamorphopsia was detected in 20 eyes (54%). The patients with metamorphopsia were relatively older than those without it (P = 0.060), and DRIL length was relatively longer in eyes with metamorphopsia (P = 0.065), while visual acuity was significantly better in eyes without metamorphopsia (P = 0.048). In correlation analyses to the severity of metamorphopsia, the DRIL length was the only OCT parameter associated with the M-CHARTS score (P = 0.035), while age, visual acuity, and ME were not significantly associated with the severity of metamorphopsia (P = 0.051, 0.060, and 0.344, respectively).

Conclusion: The DRIL length was significantly associated with the severity of metamorphopsia secondary to diabetic ME. The inner retinal layer plays a key role in the development of metamorphopsia in eyes with diabetic ME. Metamorphopsia should be carefully considered when treating diabetic ME since its severity has been found to be independent of visual acuity and ME status.
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http://dx.doi.org/10.1007/s00417-019-04393-0DOI Listing
September 2019

Anterior Segment Optical Coherence Tomography Angiography Imaging of Conjunctiva and Intrasclera in Treated Primary Open-Angle Glaucoma.

Am J Ophthalmol 2019 12 16;208:313-322. Epub 2019 May 16.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Purpose: To investigate conjunctival and intrascleral vasculature in glaucoma eyes using anterior segment (AS)-optical coherence tomography angiography (OCTA) and assess the factors contributing to the vessel density in AS-OCTA images.

Design: Prospective, cross-sectional study.

Methods: Thirty-four patients with primary open-angle glaucoma and 20 healthy subjects were included. A swept-source OCT system was used to obtain the AS-OCTA images of the corneoscleral limbus at the nasal and temporal quadrants. Vessel densities were measured in the superficial (from the conjunctival epithelium to a depth of 200 μm) and deep (from a depth of 200 to 1000 μm) layers. The vessel density was compared between healthy and glaucoma eyes, and the associations of the vessel density with possible confounding factors were analyzed using univariable and multivariable analyses.

Results: The vessel density was not significantly different between healthy eyes and eyes with glaucoma. There was a significant association of superficial vessel density with the use of a prostaglandin analog (P = .007) and with nasal location (P = .016) in eyes with glaucoma. Deep vessel density was significantly smaller with advancing age (P = .029) in healthy eyes and greater with higher intraocular pressure (P = .021) in eyes with treated glaucoma.

Conclusions: AS-OCTA images may be useful for the objective assessment of conjunctival hyperemia and helpful for understanding the pathophysiology of post-trabecular aqueous humor outflow.
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http://dx.doi.org/10.1016/j.ajo.2019.05.008DOI Listing
December 2019

A Case of Alveolar Bleeding from Clotting Abnormality by Cefmetazole.

Case Rep Med 2019 21;2019:3574064. Epub 2019 Jan 21.

Department of Internal Medicine, Suwa Central Hospital, Chino, Nagano, Japan.

Cephalosporins are one of the most commonly used first-line antibiotics. In this report, we describe the case of a patient who developed alveolar bleeding due to clotting abnormality following the use of cefmetazole, one of cephalosporins containing an -methylthiotetrazole (NMTT) side chain. Compared to other antibiotics, cephalosporins with an NMTT side chain cause a higher degree of bleeding events. The bleeding tendency is caused by the depletion of vitamin K-dependent clotting factors via inhibition of the vitamin K epoxide reductase. This mechanism of action is the same as warfarin. Recent years have seen an increase in the number of patients using direct oral anticoagulants that do not require coagulation tests. As a consequence, there may be an increase in the number of bleeding events due to anticoagulant drugs and such antibiotics coprescription. Therefore, this case is an instructive lesson.
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http://dx.doi.org/10.1155/2019/3574064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360626PMC
January 2019

One-Year Outcome Predictors of Strabismus Surgery from Anterior Segment Optical Coherence Tomography with Multiple B-Scan Averaging.

Sci Rep 2019 02 21;9(1):2523. Epub 2019 Feb 21.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Strabismologists are eager to identify preoperative or intraoperative strabismus surgery outcome predictors because of the variable effects in each patient. Conjunctival closure position recession after rectus muscle recession is effective for correcting large angle strabismus. The elasticity of the conjunctiva and Tenon's capsule is important for strabismus surgery management. In this longitudinal study, we evaluated the prognosis of conjunctiva and Tenon's capsule thickness (CTT) near the limbus 1 year after strabismus surgery with a limbal conjunctival incision using swept-source anterior segment optical coherence tomography with multiple B-scan averaging. Also, we identified preoperative and/or intraoperative parameters associated with corrective effects 1 year after surgery in 15 consecutive treatment-naïve patients with exotropia or esotropia who underwent recession and resection. The 1-year CTT was greater than the preoperative CTT on the resection side (269 ± 111 vs 183 ± 53 μm, P < 0.001) but was smaller on the recession side (137 ± 54 vs 183 ± 71 μm, P = 0.02). The corrective effect of surgery (1.6 ± 0.3°/mm) was most strongly correlated with preoperative CTT on the recession side (P = 0.005, β = -0.73). Hence, CTT on the recession side may provide adjunctive information for strabismus treatment.
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http://dx.doi.org/10.1038/s41598-019-39361-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385243PMC
February 2019

Disorganization of the Retinal Inner Layers after Anti-VEGF Treatment for Macular Edema due to Branch Retinal Vein Occlusion.

Ophthalmologica 2018 8;240(4):229-234. Epub 2018 Aug 8.

Purpose: To evaluate the association between disorganization of the retinal inner layers (DRIL) and visual acuity (VA) after anti-VEGF treatment for macular edema (ME) due to branch retinal vein occlusion (BRVO).

Methods: Sixty eyes of 60 patients were retrospectively investigated. Baseline characteristics and factors analyzed on optical coherence tomography (OCT) examination at the final visit were evaluated in association with VA at the final visit.

Results: DRIL was detected in 39 eyes at the final visit. The central subfield thickness was significantly higher in the eyes with DRIL. While DRIL length at the final visit showed a significant association with final VA on univariable analysis, only age and ellipsoid zone disruption on OCT at the final visit were found to be significantly associated with VA on multivariable analysis.

Conclusions: DRIL had only a minor role in determining VA after anti-VEGF treatment for ME due to BRVO.
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http://dx.doi.org/10.1159/000490809DOI Listing
January 2019

Quantitative comparison of disc rim color in optic nerve atrophy of compressive optic neuropathy and glaucomatous optic neuropathy.

Graefes Arch Clin Exp Ophthalmol 2016 Aug 26;254(8):1609-1616. Epub 2016 Apr 26.

Department of Ophthalmology and Visual Sciences, Kyoto University, 54 Shougoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Purpose: The purpose was to investigate an objective and quantitative method to estimate the redness of the optic disc neuroretinal rim, and to determine the usefulness of this method to differentiate compressive optic neuropathy (CON) from glaucomatous optic neuropathy (GON).

Methods: In our study there were 126 eyes: 40 with CON, 40 with normal tension glaucoma (NTG), and 46 normal eyes (NOR). Digital color fundus photographs were assessed for the redness of disc rim color using ImageJ software. We separately measured the intensity of red, green, and blue pixels from RGB images. Three disc color indices (DCIs), which indicate the redness intensity, were calculated through existing formulas.

Results: All three DCIs of CON were significantly smaller than those of NOR (P < 0.001). In addition, when compared with NTG, DCIs were also significantly smaller in CON (P < 0.05). A comparison of mild CON and mild NTG (mean deviation (MD) > -6 dB), in which the extent of retinal nerve fiber layer thinning is comparable, the DCIs of mild CON were significantly smaller than those of mild NTG (P < 0.05). In contrast, DCIs did not differ between moderate-to-severe stages of CON and NTG (MD ≤ -6 dB), though the retinal nerve fibers of CON were more severely damaged than those of NTG. To differentiate between mild CON and mild NTG, all AUROCs for the three DCIs were above 0.700.

Conclusions: A quantitative and objective assessment of optic disc color was useful in differentiating early-stage CON from GON and NOR.
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http://dx.doi.org/10.1007/s00417-016-3366-2DOI Listing
August 2016

Transient Ciliochoroidal Detachment After Ab Interno Trabeculotomy for Open-Angle Glaucoma: A Prospective Anterior-Segment Optical Coherence Tomography Study.

JAMA Ophthalmol 2016 Mar;134(3):304-11

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Shogoin, Sakyo-ku, Kyoto, Japan.

Importance: Although trabeculotomy is a glaucoma surgical procedure for modest intraocular pressure (IOP) reduction, some eyes exhibit very low IOP during the early postoperative period. To our knowledge, the reason and its effect have not been investigated.

Objectives: To investigate ciliochoroidal detachment (CCD) immediately after ab interno trabeculotomy and evaluate its effect on IOP immediately after surgery.

Design, Setting, And Participants: This prospective, observational, case series was conducted at Kyoto University Hospital, Kyoto, Japan. Patients with open-angle glaucoma who underwent ab interno trabeculotomy using a microsurgical device by a single surgeon between July 1, 2014, and May 31, 2015, were included. Thirty-seven consecutive patients were enrolled, 33 of whom were included in the analysis. The dates of the analysis were August 1 to August 15, 2015.

Intervention: Imaging of CCD using anterior-segment optical coherence tomography (AS-OCT).

Main Outcomes And Measures: The incidence of CCD immediately after ab interno trabeculotomy and its effect on IOP in the early postoperative period.

Results: The study cohort comprised 33 patients. Their mean (SD) age was 69.4 (13.2) years, and 19 (58%) were male. At postoperative day 3, CCD was detected in 14 of 33 eyes (42%) (CCD group) using AS-OCT. The CCD group had shorter axial length (mean [SD], 23.66 [1.67] vs 25.16 [1.59] mm) and thinner central corneal thickness (mean [SD], 505.9 [35.8] vs 533.9 [39.1] μm) than the non-CCD group. Only 5 eyes had CCD at postoperative day 10, and 4 of these eyes had CCD at 1 month after surgery. The postoperative IOPs at all follow-up periods were lower in the CCD group than in the non-CCD group, but the difference in the postoperative IOPs between the groups decreased as time passed. The mean (SD) IOPs for the CCD group vs the non-CCD group were 9.1 (3.0) vs 14.2 (5.8) mm Hg at day 1, 8.4 (2.4) vs 13.4 (5.0) mm Hg at day 3, 11.0 (3.0) vs 15.5 (6.3) mm Hg at day 10, 13.4 (2.4) vs 15.5 (3.3) mm Hg at 1 month, and 13.9 (3.4) vs 15.5 (4.0) mm Hg at 3 months. In several eyes in the CCD group, the AS-OCT images revealed a connection between the CCD and the anterior chamber via the trabeculotomy site.

Conclusions And Relevance: Ciliochoroidal detachment after ab interno trabeculotomy was not rare and was associated with low IOP immediately after surgery. Postoperative CCD may be partially attributed to the transient increase in uveoscleral aqueous outflow via the trabeculotomy site.
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http://dx.doi.org/10.1001/jamaophthalmol.2015.5765DOI Listing
March 2016

Wilms' tumor gene WT1 promotes homologous recombination-mediated DNA damage repair.

Mol Carcinog 2015 Dec 21;54(12):1758-71. Epub 2014 Nov 21.

Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.

The Wilms' tumor gene WT1 is overexpressed in leukemia and various types of solid tumors and plays an oncogenic role in these malignancies. Alternative splicing at two sites yields four major isoforms, 17AA(+)KTS(+), 17AA(+)KTS(-), 17AA(-)KTS(+), and 17AA(-)KTS(-), and all the isoforms are expressed in the malignancies. However, among the four isoforms, function of WT1[17AA(-)KTS(+)] isoform still remains undetermined. In the present study, we showed that forced expression of WT1[17AA(-)KTS(+)] isoform significantly inhibited apoptosis by DNA-damaging agents such as Doxorubicin, Mitomycin, Camptothesisn, and Bleomycin in immortalized fibroblast MRC5SV and cervical cancer HeLa cells. Knockdown of Rad51, an essential factor for homologous recombination (HR)-mediated DNA repair canceled the resistance to Doxorubicin induced by WT1[17AA(-)KTS(+)] isoform. GFP recombination assay showed that WT1[17AA(-)KTS(+)] isoform alone promoted HR, but that three other WT1 isoforms did not. WT1[17AA(-)KTS(+)] isoform significantly upregulated the expression of HR genes, XRCC2, Rad51D, and Rad54. Knockdown of XRCC2, Rad51D, and Rad54 inhibited the HR activity and canceled resistance to Doxorubicin in MRC5SV cells with forced expression of WT1[17AA(-)KTS(+)] isoform. Furthermore, chromatin immunoprecipitation (ChIP) assay showed the binding of WT1[17AA(-)KTS(+)] isoform protein to promoters of XRCC2 and Rad51D. Immunohistochemical study showed that Rad54 and XRCC2 proteins were highly expressed in the majority of non-small-cell lung cancer (NSCLC) and gastric cancer, and that expression of these two proteins was significantly correlated with that of WT1 protein in NSCLCs. Our results presented here showed that WT1[17AA(-)KTS(+)] isoform had a function to promote HR-mediated DNA repair.
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http://dx.doi.org/10.1002/mc.22248DOI Listing
December 2015

Optimal impedance control for task achievement in the presence of signal-dependent noise.

J Neurophysiol 2004 Aug 31;92(2):1199-215. Epub 2004 Mar 31.

ATR Computational Neuroscience Labs., 2-2-2 Hikaridai, Seika-cho, Soraku-gun, Kyoto 619-0288, Japan.

There is an infinity of impedance parameter values, and thus different co-contraction levels, that can produce similar movement kinematics from which the CNS must select one. Although signal-dependent noise (SDN) predicts larger motor-command variability during higher co-contraction, the relationship between impedance and task performance is not theoretically obvious and thus was examined here. Subjects made goal-directed, single-joint elbow movements to either move naturally to different target sizes or voluntarily co-contract at different levels. Stiffness was estimated as the weighted summation of rectified EMG signals through the index of muscle co-contraction around the joint (IMCJ) proposed previously. When subjects made movements to targets of different sizes, IMCJ increased with the accuracy requirements, leading to reduced endpoint deviations. Therefore without the need for great accuracy, subjects accepted worse performance with lower co-contraction. When subjects were asked to increase co-contraction, the variability of EMG and torque both increased, suggesting that noise in the neuromotor command increased with muscle activation. In contrast, the final positional error was smallest for the highest IMCJ level. Although co-contraction increases the motor-command noise, the effect of this noise on the task performance is reduced. Subjects were able to regulate their impedance and control endpoint variance as the task requirements changed, and they did not voluntarily select the high impedance that generated the minimum endpoint error. These data contradict predictions of the SDN-based theory, which postulates minimization of only endpoint variance and thus require its revision.
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http://dx.doi.org/10.1152/jn.00519.2003DOI Listing
August 2004

Internal forward models in the cerebellum: fMRI study on grip force and load force coupling.

Prog Brain Res 2003 ;142:171-88

ATR Human Information Science Laboratories, 2-2-2, Hikaridai, Seika-cho, Soraku-gun, Kyoto 619-0288, Japan.

Internal models are neural mechanisms that can mimic the input-output or output-input properties of the motor apparatus and external objects. Forward internal models predict sensory consequences from efference copies of motor commands. There is growing acceptance of the idea that forward models are important in sensorimotor integration as well as in higher cognitive function, but their anatomical loci and neural mechanisms are still largely unknown. Some of the most convincing evidence that the central nervous system (CNS) makes use of forward models in sensory motor control comes from studies on grip force-load force coupling. We first present a brief review of recent computational and behavioral studies that provide decisive evidence for the utilization of forward models in grip force-load force coupling tasks. Then, we used functional magnetic resonance imaging (fMRI) to measure the brain activity related to this coupling and demonstrate that the cerebellum is the most likely site for forward models to be stored.
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http://dx.doi.org/10.1016/S0079-6123(03)42013-XDOI Listing
May 2003

A Kendama Learning Robot Based on Bi-directional Theory.

Neural Netw 1996 Nov;9(8):1281-1302

ATR Human Information Processing Research Laboratories, Kyoto, Japan

A general theory of movement-pattern perception based on bi-directional theory for sensory-motor integration can be used for motion capture and learning by watching in robotics. We demonstrate our methods using the game of Kendama, executed by the SARCOS Dextrous Slave Arm, which has a very similar kinematic structure to the human arm. Three ingredients have to be integrated for the successful execution of this task. The ingredients are (1) to extract via-points from a human movement trajectory using a forward-inverse relaxation model, (2) to treat via-points as a control variable while reconstructing the desired trajectory from all the via-points, and (3) to modify the via-points for successful execution. In order to test the validity of the via-point representation, we utilized a numerical model of the SARCOS arm, and examined the behavior of the system under several conditions. Copyright 1996 Elsevier Science Ltd.
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http://dx.doi.org/10.1016/s0893-6080(96)00043-3DOI Listing
November 1996
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