Yasuo Kurimoto - Academia.edu (original) (raw)

Papers by Yasuo Kurimoto

Investigative Ophthalmology & Visual Science, Jun 11, 2015

Scientific Reports, May 3, 2022

This study aimed to evaluate the distribution of retinal pigment epithelium (RPE) melanin in pati... more This study aimed to evaluate the distribution of retinal pigment epithelium (RPE) melanin in patients with retinitis pigmentosa (RP) using entropy measurements by custom-made polarizationsensitive optical coherence tomography (PS-OCT) images, and compare entropy with the intensity of short-wavelength (SW) and near-infrared (NIR) autofluorescence (AF). We retrospectively reviewed the retinal images, including PS-OCT, SW-AF, and NIR-AF of patients with RP who had a hyperautofluorescent ring on AF. A total of 12 eyes of 12 patients (8 women and 4 men; mean age: 37.9 years) were included. There was a strong positive correlation between entropy value and NIR-AF intensity (r = 0.626, p < 0.001), and there was a very weak negative correlation between entropy value and SW-AF (r = − 0.197, p = 0.001). The mean values of the entropy in the foveal, temporal (2 mm from the fovea), and nasal (2 mm from the fovea) sections were 0.41 (± 0.09), 0.29 (± 0.08), and 0.26 (± 0.08), respectively. The entropy was significantly higher in the foveal section than in the temporal and nasal sections (p = 0.002 and p = 0.003, respectively). There was no significant difference between the entropies values for the temporal and nasal sections (p = 0.157). Age, logMAR best-corrected visual acuity, ellipsoid zone width, and central retinal thickness were not correlated with foveal entropy. We presented RPE melanin imaging in patients with RP using PS-OCT for the first time. PS-OCT can be a useful tool for monitoring patients with RP. Retinitis pigmentosa (RP) is the most common hereditary retinal dystrophy with a worldwide prevalence of approximately 1 in 4,000 individuals 1. The clinical course of RP is characterized by night blindness and progressive loss of the visual field due to degeneration and loss of photoreceptors. For typical RP, rod photoreceptors are primarily affected, followed by the loss of secondary cone photoreceptors and retinal pigment epithelium (RPE). While, RPE dysfunction leads to photoreceptor function impairment and results in the loss of photoreceptors in RP with several causative genes, including MER proto-oncogene, tyrosine kinase (MERTK), RPE65, LRAT , and bestrophin 1 (BEST1) 2. The RPE is an indispensable partner of the neural retina. Located between the neural retina and choroid, the RPE plays an essential role in the survival and function of photoreceptors 3. Three major pigments, lipofuscin, melanin, and melanolipofuscin, are present in the RPE. Clinically, autofluorescence (AF) imaging has been used to evaluate RPE. Short-wavelength AF (SW-AF; 488 nm excitation) originates from lipofuscin in the RPE 4 , whereas near-infrared AF (NIR-AF; 785 nm excitation) originates from melanin in the RPE, with a smaller contribution from the choroid 5. Characteristic hyperautofluorescent rings are often observed in patients with RP, and

Clinical Ophthalmology, Jun 1, 2017

The purpose of this study was to investigate the occurrence of outer retinal tubulation (ORT) amo... more The purpose of this study was to investigate the occurrence of outer retinal tubulation (ORT) among patients with different types of choroidal neovascularization (CNV) over time. Materials and methods: In this retrospective chart review, disease type was classified as typical age-related macular degeneration (t-AMD), polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), or myopic CNV (mCNV). Spectral domain-optical coherence tomography (SD-OCT) images were evaluated for the appearance of ORT and subretinal fibrosis and fluid. Furthermore, the association of the presence of ORT with clinical data and OCT findings was investigated. Results: Among the 136 eyes studied, the overall rates of occurrence of ORT were 7.8%, 18.8%, and 31.6% after 12, 24, and 36 months from baseline, respectively. Among patients with t-AMD, RAP, and mCNV, the occurrence of ORT increased soon after the initial visit. In contrast, among patients with PCV, the occurrence of ORT increased slowly over time. Patients with and without ORT-ORT(+) and ORT(−) groups, respectively-differed significantly in terms of sex ratio and presence of intraretinal fluid at the initial visit and presence of subretinal fibrosis at 3 years from baseline. The ORT(+) group exhibited lower visual acuity (VA; 0.67±0.43) than that of the ORT(−) group (0.41±0.36; P,0.001). Conclusion: The occurrence of ORT tended to increase more slowly among eyes diagnosed with PCV than among eyes with other types of CNV.

Japanese Journal of Ophthalmology, Sep 3, 2015

Purpose Our aim was to investigate predictive factors associated with efficacy and recurrence aft... more Purpose Our aim was to investigate predictive factors associated with efficacy and recurrence after intravitreal bevacizumab (IVB) therapy for macular edema (ME) in patients with branch retinal vein occlusion (BRVO). Methods Fifty-two eyes of 52 patients who underwent IVB as a primary treatment against ME associated with BRVO were included retrospectively. Based on the postoperative central retinal thickness (CRT), the patients were classified into two groups: an effective group in which the CRT decreased to B250 lm within postoperative 3 months and an ineffective group in which the CRT remained [250 lm throughout the first 3 months. The effective group was then divided into two subgroups: a recurrent group in which ME had once resolved but recurred afterward, and a nonrecurrent group in which the resolution of ME was maintained throughout the follow-up period without additional injections. Preoperative factors such as age, gender, estimated elapsed time from disease onset to IVB, visual acuity, and CRT were compared between groups. Results There was no significant difference between effective (n = 37) and ineffective (n = 15) groups in all preoperative factors. Between recurrent (n = 26) and nonrecurrent (n = 11) groups, elapsed time was significantly different (29.7 ± 29.5 vs. 15.7 ± 8.9 weeks, respectively; P = 0.036), and there were no significant differences in the remaining factors. Conclusions Early IVB treatment against BRVO may suppress ME recurrence.

Investigative Ophthalmology & Visual Science, Jan 13, 2017

PURPOSE. To develop a clinically applicable transplantation device and surgical procedure for ext... more PURPOSE. To develop a clinically applicable transplantation device and surgical procedure for extracellular matrix-scaffold-supported human-induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) cell sheet transplantation for clinical use. METHODS. The developed surgical device consisted of a custom-designed hand piece and a cannula. The subretinal transplantation of hiPSC-RPE cell sheets was performed in 12 rabbits. The results evaluated were the graft condition (damage or fold), side (front or back), position (center, near, far), and direction (anterior, posterior, right, left) immediately after surgery and the graft condition (shrinking or fold) 2 weeks after surgery. These results were evaluated by fundus photography and optical coherence tomography, followed by immersion-fixed histology. RESULTS. All grafts could be transplanted without obvious damage. The transplanted grafts included 2 of 12 folded grafts, 12 of 12 front side, 12 of 12 center position, 10 of 12 anterior direction, and 2 of 12 right direction immediately after surgery, whereas transplantation with a distance between an inlet and an outlet greater than graft and the coaxial direction of the flow paths and the insertion device posed the correct condition and direction. Two weeks after the surgery, the transplanted grafts included two folded grafts and four shrunken grafts; however, complete drainage of subretinal fluid for adhesion between the graft and the host prevented shrunken grafts. CONCLUSIONS. A developed surgical device and procedure allow grafts to be transplanted into the targeted transplantation site safely and reproducibly. This surgical method will provide additional information on the advancement of future RPE transplantation therapies.

Eye, 2022

OBJECTIVE: To predict the visual prognosis of cataract surgery in patients with retinitis pigment... more OBJECTIVE: To predict the visual prognosis of cataract surgery in patients with retinitis pigmentosa by measuring ellipsoid zone (EZ) width using spectral-domain optical coherence tomography. METHODS: This retrospective study included patients with retinitis pigmentosa who underwent uncomplicated cataract surgery between December 2017 and June 2020. Preoperative best-corrected visual acuity (BCVA) and the best postoperative BCVA during follow-up were collected. EZ width was measured on preoperative cross-sectional optical coherence tomography images along the horizontal/vertical meridian through the fovea. RESULTS: Thirty-eight eyes of 38 patients (22 female; mean [±standard deviation] age, 62.1 ± 11.8 years) were included. The median preoperative logarithm of the minimum angle of resolution BCVA of 0.52 (range, 0.00-3.00) significantly improved to 0.07 (range, −0.18-3.00) after surgery (P < 0.001). On preoperative spectral-domain optical coherence tomography images, the median horizontal, vertical, and average EZ widths were 783 (range, 0-9837), 761 (range, 0-10 250), and 769 (range, 0-10 043) μm, respectively. Postoperative BCVA significantly correlated with the horizontal (r = −0.784, P < 0.001), vertical (r = −0.777, P < 0.001), and average EZ widths (r = −0.777, P < 0.001). The area under the receiver operating characteristic curve for the ability of the horizontal, vertical, and average EZ widths to discriminate eyes with and without postoperative BCVA ≤ 0.3 was 0.971, 0.960, and 0.963, respectively, with best cutoff values of 513, 608, and 515 μm, respectively. CONCLUSIONS: EZ width measurement can help predict the visual prognosis of cataract surgery in patients with retinitis pigmentosa. A preferable visual acuity prognosis can be expected in patients with an EZ width of approximately 600 μm.

Scientific Reports, May 6, 2020

transplantation of autologous human induced pluripotent stem cell-derived retinal pigment epithel... more transplantation of autologous human induced pluripotent stem cell-derived retinal pigment epithelial (hipSc-Rpe) sheets is a promising therapy for age-related macular degeneration (AMD). As melanin content is a representative feature of healthy RPE, we used polarization-sensitive optical coherence tomography (pS-oct) to estimate the relative melanin content of Rpe in diseased and non-diseased area, and in human iPSC-RPE sheets in vitro and in vivo by evaluating the randomness of polarization (entropy). Two aged Japanese women, one with neovascular AMD that underwent transplantation of an autologous hiPSC-RPE cell sheet and another with binocular dry AMD, were selected for this study. Entropy value was minimal in cells containing no melanin, whereas that of human RPE and hiPSC-RPE sheets was high. En face entropy of the cultured hiPSC-RPE sheet was compared with its grey-scale photo and its values were found to be inversely correlated with the extent of absence of pigmentation in vitro. en face entropy maps were compared to colour fundus photographs, fundus autofluorescence images, and fluorescein angiography images from patients. Entropy values of intact and defective RPEs and of iPSC-RPE transplant areas were determined in vivo using PS-OCT B-scan images. PS-OCT was found to be applicable in the estimation of relative melanin content of cultured and transplanted Rpes in regenerative medicine. Age-related macular degeneration (AMD) is a major cause of vision loss in the aging population of developed countries 1. Although anti-vascular endothelial growth factor (anti-VEGF) therapy for AMD is effective in reducing the activity of choroidal neovascular membrane (CNV) and resolving exudation 2 , it does not restore the lost or damaged retinal cells, including retinal pigment epithelial (RPE) or photoreceptor cells. Since RPE is essential for the survival and function of photoreceptor cells 3 , supplementation by healthy RPE may be a promising approach for treating AMD with anatomical or functional loss of RPE. As reported previously, a sheet of RPE cells, differentiated from autologous human induced pluripotent stem cells (hiPSCs), was transplanted in a patient with neovascular AMD in September 2014 4,5. We observed no signs of rejection or tumorigenicity, consistent with the safety of pluripotent stem cell-based transplantation therapies 4,5. Although we observed stability of the pigment sheet for over 4 years with no recurrence of the background disease and stabilised visual function, we detected no improvement in visual function after surgery, partly because the eye had an advanced AMD at the time of CNV removal and hiPSC-RPE transplantation. However, structure

Scientific Reports, 2022

The retinal pigment epithelium (RPE) is essential for the survival and function of retinal photor... more The retinal pigment epithelium (RPE) is essential for the survival and function of retinal photoreceptor cells. RPE dysfunction causes various retinal diseases including age-related macular degeneration (AMD). Clinical studies on ES/iPS cell-derived RPE transplantation for RPE dysfunction-triggered diseases are currently underway. Quantification of the diseased RPE area is important to evaluate disease progression or the therapeutic effect of RPE transplantation. However, there are no standard protocols. To address this issue, we developed a 2-step software that enables objective and efficient quantification of RPE-disease area changes by analyzing the early-phase hyperfluorescent area in fluorescein angiography (FA) images. We extracted the Abnormal region. This extraction was based on deep learning-based discrimination. We scored the binarized extracted area using an automated program. Our program’s performance for the same eye from the serial image captures was within 3.1 ± 7.8% ...

Investigative Ophthalmology & Visual Science, 2010

Journal of Clinical Medicine, 2021

Age-related macular degeneration (AMD) is a highly prevalent irreversible impairment in the elder... more Age-related macular degeneration (AMD) is a highly prevalent irreversible impairment in the elderly population worldwide. Stem cell therapies have been considered potentially viable for treating AMD through the direct replacement of degenerated cells or secretion of trophic factors that facilitate the survival of existing cells. Among them, the safety of pluripotent stem cell-derived retinal pigment epithelial (RPE) cell transplantation against AMD, and some hereditary retinal degenerative diseases, has been discussed to a certain extent in clinical studies of RPE cell transplantation. Preparations are in progress for its clinical application. On the other hand, clinical trials using somatic stem cells are also being conducted, though these had controversial outcomes. Retinal regenerative medicine using stem cells is expected to make steady progress toward practical use while new technologies are incorporated from various fields, thereby making the role of ophthalmologists in this f...

International Journal of Molecular Sciences, 2020

Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-ma... more Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (iPSC-RPE) cells in patients with age-related macular degeneration. However, there was an issue regarding immune rejection after transplantation. In this study, we established a preoperational in vitro “drug–lymphocytes–grafts immune reaction (Drug-LGIR)” test to determine the medication for immune rejection using host immunocompetent cells (lymphocytes) and transplant cells (target iPSC-RPE cells) together with different medications. The adequacy of the test was assessed by in vivo transplantation in monkey models together with medication based on in vitro data. In the results of Drug-LGIR tests, some drugs exhibited significant suppression of RPE cell-related allogeneic reactions, while other drugs did not, and the efficacy of each drug differed among the recipient monkeys. Based on the results of D...

Ophthalmology and Therapy, 2019

Introduction: The use of optical coherence tomography (OCT) images is increasing in the medical t... more Introduction: The use of optical coherence tomography (OCT) images is increasing in the medical treatment of age-related macular degeneration (AMD), and thus, the amount of data requiring analysis is increasing. Advances in machine-learning techniques may facilitate processing of large amounts of medical image data. Among deep-learning methods, convolution neural networks (CNNs) show superior image recognition ability. This study aimed to build deep-learning models that could distinguish AMD from healthy OCT scans and to distinguish AMD with and without exudative changes without using a segmentation algorithm. Methods: This was a cross-sectional observational clinical study. A total of 1621 spectral domain (SD)-OCT images of patients with AMD and a healthy control group were studied. The first CNN model was trained and validated using 1382 AMD images and 239 normal images. The second transfer-learning model was trained and validated with 721 AMD images with exudative changes and 661 AMD images without any exudate. The attention area of the CNN was described as a heat map by class activation mapping (CAM). In the second model, which classified images into AMD with or without exudative changes, we compared the Enhanced Digital Features To view enhanced digital features for this article, go to https://doi.org/10.6084/ m9.figshare.8977010.

Stem Cell Reports, 2016

There is an ongoing controversy as to whether major histocompatibility complex (MHC) matching is ... more There is an ongoing controversy as to whether major histocompatibility complex (MHC) matching is a solution for allogeneic stem cell transplantation. In the present study, we established retinal pigment epithelial (RPE) cells from induced pluripotent stem cells (iPSCs) in MHC homozygote donors. We observed no rejection signs in iPSC-derived RPE allografts of MHC-matched animal models without immunosuppression, whereas there were immune attacks around the graft and retinal tissue damage in MHC-mismatched models. In an immunohistochemical examination of MHC-mismatched allografts, the transplanted RPE sheets/cells were located in the subretinal space, but the RPE exhibited inflammatory and hypertrophic changes, and many inflammatory cells, e.g., Iba1 + cells, MHC class II + cells, and CD3 + T cells, invaded the graft area. Conversely, these inflammatory cells poorly infiltrated the area around the transplanted retina if MHC-matched allografts were used. Thus, cells derived from MHC homozygous donors could be used to treat retinal diseases in histocompatible recipients.

Clinical ophthalmology (Auckland, N.Z.), 2017

To evaluate the response to and dependence on aflibercept or ranibizumab in patients with age-rel... more To evaluate the response to and dependence on aflibercept or ranibizumab in patients with age-related macular degeneration (AMD). We retrospectively reviewed AMD patients who received induction therapy with aflibercept or ranibizumab for the following parameters: whether complete resolution of the retinal fluid ("good response") was achieved and whether recurrence was observed within 3 months ("dependent") after the induction treatment. With aflibercept treatment, treatment-naïve eyes with a good response/non-dependence were recommended a pro re nata regimen, and other eyes were recommended a proactive bimonthly regimen, followed by monitoring of visual acuity (VA) for 12 months. The measured values of the groups were compared using one-way analysis of variance with Tukey's test to evaluate the difference between baseline and postinjection VA. Among the treatment-naïve eyes, 76% had a good response to aflibercept and 37% of these were aflibercept-dependent, w...

The New England journal of medicine, Mar 16, 2017

We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells di... more We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] nu...

Japanese Journal of Ophthalmology, 2015

Ophthalmic Surgery, Lasers and Imaging Retina, 2010

Background and Objective: To assess the efficacy and safety of the newly developed three-step inc... more Background and Objective: To assess the efficacy and safety of the newly developed three-step incision method of performing 23-gauge vitrectomy. Patients and Methods: A retrospective comparative study in which a consecutive series of 45 eyes that underwent the three-step incision type of 23-gauge vitrectomy was compared with a series of 27 consecutive eyes that had previously undergone the oblique incision type of 23-gauge vitrectomy. Results: No cases of postoperative hypotony (< 6 mm Hg) were noted in the three-step group compared with 3 cases (11%) in the oblique group ( P = .05). The three-step incision resulted in a significantly higher mean intraocular pressure than the conventional incision on postoperative day 1 (14.1 ± 6.7 mm Hg vs 10.9 ± 3.7 mm Hg; P = .05), but there was no significant difference after 1 week. Conclusion: The three-step incision for performing 23-gauge vitrectomy effectively prevented postoperative hypotony and demonstrated a safety profile comparable ...