網膜静脈分枝閉塞症に伴う黄斑浮腫眼おける光干渉断層計での中心窩視細胞内節外節ラインの隆起 (foveal bulge) の評価

PURPOSE: To determine whether a significant correlation exists between the presence of a bulge in the photoreceptor inner segment/outer segment (IS/OS) line and the best-corrected visual acuity (BCVA) in eyes with resolved macular edema associated with branch retinal vein occlusion (BRVO). DESIGN: Retrospective, observational case series. METHODS: We retrospectively reviewed the medical records of patients who had a complete resolution of macular edema and had an intact IS/OS line in the central fovea in the spectral-domain optical coherence tomographic (SDOCT) images. Thirty-one eyes with macular edema associated with BRVO (BRVO group) and 31 unaffected fellow eyes (control group) of 31 patients were evaluated. In normal eyes, the intact IS/OS line determined by SDOCT has a bulge at the central fovea, called the foveal bulge. The eyes in the BRVO group were classified by the presence or absence of foveal bulge, and the characteristics of the 2 groups were compared. RESULTS: A foveal bulge was present in 7 of 31 eyes in the BRVO group. The incidence of a foveal bulge was significantly lower in the BRVO group (22.6%) than in the control group (100%; P < .0001). All 7 eyes with foveal bulge had a decimal BCVA of ≥1.0 at the final visit. The incidence of a foveal bulge was significantly higher in eyes with BCVA of ≥1.0 (77.8%) than in the eyes with BCVA of <1.0 (0%; P < .0001). CONCLUSIONS: The foveal bulge is a good marker of the functional properties of the fovea in eyes with resolved macular edema associated with BRVO.博士（医学）・乙第1416号・平成30年3月15日Copyright © 2014 Elsevier Inc. All rights reserved

白内障手術既往のある高齢者は視力と独立して高い認知機能を維持する : 平城京コホート研究横断解析

Cataract surgery improves visual acuity and drastically increases the capacity for light reception to the retina. Although previous studies suggested that both light exposure and visual acuity were associated with cognitive function, the relationships between cataract surgery, visual acuity, and cognitive function have not been evaluated in large populations. In this cross-sectional study, we measured cognitive function using the Mini-Mental State Examination and best-corrected visual acuity in pseudophakic (previous cataract surgery) and phakic (no previous cataract surgery) elderly individuals. Of 945 participants (mean age 71.7 years), 166 (17.6%) had pseudophakia and 317 (33.5%) had impaired cognitive function (score ≤26). The pseudophakic group showed significantly better visual acuity than the phakic group (p = 0.003) and lower age-adjusted odds ratio (ORs) for cognitive impairment (OR 0.66; p = 0.038). Consistently, in multivariate logistic regression models, after adjusting for confounding factors, including visual acuity and socioeconomic status, ORs for cognitive impairment were significantly lower in the pseudophakic group than in the phakic group (OR 0.64; 95% confidence interval 0.43-0.96; p = 0.031). This association remained significant in sensitivity analysis, excluding participants with low cognitive score ≤23 (n = 36). In conclusion, in a general elderly population, prevalence of cognitive impairment was significantly lower in pseudophakic individuals independently of visual acuity. The association was also independent of several major causes of cognitive impairment such as aging, gender, obesity, socioeconomic status, hypertension, diabetes, sleep disturbances, depressive symptoms, and physical inactivity.博士（医学）・甲第666号・平成29年3月15日© Mary Ann Liebert, Inc.This is a non-final version of an article published in final form in "http://dx.doi.org/10.1089/rej.2015.1718

Deep Collaborative Filtering Approaches for Context-Aware Venue Recommendation

In recent years, vast amounts of user-generated data have being created on Location-Based Social Networks (LBSNs) such as Yelp and Foursquare. Making effective personalised venue suggestions to users based on their preferences and surrounding context is a challenging task. Context-Aware Venue Recommendation (CAVR) is an emerging topic that has gained a lot of attention from researchers, where context can be the user's current location for example. Matrix Factorisation (MF) is one of the most popular collaborative filtering-based techniques, which can be used to predict a user's rating on venues by exploiting explicit feedback (e.g. users' ratings on venues). However, such explicit feedback may not be available, particularly for inactive users, while implicit feedback is easier to obtain from LBSNs as it does not require the users to explicitly express their satisfaction with the venues. In addition, the MF-based approaches usually suffer from the sparsity problem where users/venues have very few rating, hindering the prediction accuracy. Although previous works on user-venue rating prediction have proposed to alleviate the sparsity problem by leveraging user-generated data such as social information from LBSNs, research that investigates the usefulness of Deep Neural Network algorithms (DNN) in alleviating the sparsity problem for CAVR remains untouched or partially studied

高齢者における視機能と認知機能障害の関連 : 藤原京アイスタディより

Both visual impairment and cognitive impairment are essential factors that determine the quality of life in the aged population. The aim of this study was to determine if a correlation existed between visual acuity and cognitive impairment in an elderly Japanese population. The Fujiwara-kyo Eye Study was a cross-sectional study of individuals aged ≥68 years who lived in Nara Prefecture of Japan. Participants underwent ophthalmological examinations and cognitive function test. A mild visual impairment was defined as having a best corrected visual acuity (BCVA) >0.2 logarithm of the minimum angle of resolution (logMAR) units in the better eye. Cognitive impairment was defined as having a Mini-Mental State Examination (MMSE) score of ≤23 points. A total to 2818 individuals completed the examinations. The mean age of the participants was 76.3 ± 4.8 years (mean ± standard deviation). The mean BCVA of the better eye was -0.02 ± 0.13 logMAR units and 6.6% subjects were classified as being mildly visually impaired. The mean MMSE score was 27.3 ± 2.3 and 5.7% subjects were classified as being cognitively impaired. The proportion of subjects with cognitive or moderate visual impairment increased with age, and there was a significant correlation between the visual acuity and MMSE score (r = -0.10, p < 0.0001). Subjects with mild visual impairments had 2.4 times higher odds of having cognitive impairment than those without visual impairment (odds ratio 2.4, 95% confidence interval, 1.5-3.8, p < 0.001) after adjusting for age, sex, and length of education. We conclude that it may be important to maintain good visual acuity to reduce the risk of having cognitive impairment.博士（医学）・乙第1396号・平成29年3月15日© Masashi Mine et al. 2016; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

網膜へのレーザー凝固により惹起される脈絡膜新生血管はヘッジホッグシグナル系因子を発現する。

Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration.博士（医学）・甲第653号・平成28年7月8日Copyright © 2016 The Japan Society of Histochemistry and Cytochemistry（日本組織細胞化学会）J-STAGEへのリンク：http://doi.org/10.1267/ahc.1503

Effect of optical correction on choroidal structure

The aim of this study was to assess the effect of wearing optical correction on the choroidal structure in eyes of children with anisohypermetropic amblyopia. This study was conducted at the Nara Medical University Hospital and at the Tokushima University Hospital. Twenty-nine anisohypermetropic amblyopic eyes and their fellow eyes of 29 amblyopic patients (mean age, 5.7 ± 1.7 years, range 3- to 8-years) and twenty eyes of 20 age-similar control children (4.9 ± 0.8 years, range 4- to 6-years) were studied. All patients wore optical correction and 15 patients had both optical correction and patching. The values at the baseline were compared to that at one year later. The binarization method was used to determine the total, luminal, and stromal areas of the choroid in the enhanced depth imaging optical coherence tomographic images. The best-corrected visual acuity (BCVA) of the amblyopic eyes was significantly improved after the one-year period. A large luminal area was characteristic of the amblyopic eye at the baseline, and it was significantly reduced after the optical treatment. The stromal area widened significantly in the amblyopic and fellow eyes after one year whereas there were no significant changes in the choroid of the control eyes after one year. After one-year of optical correction, the luminal/stromal ratios in the amblyopic and fellow eyes were decreased and were then not significantly different from that of the normal control eyes. There was a significant and positive correlation between the improvement of the BCVA and the stromal area at the baseline (r = 0.64, P = 0.001). Wearing corrective lenses on the amblyopic eyes improves the BCVA, and the choroidal structure of the amblyopic eye becomes closer to that of the control eyes. The narrowed luminal area is a specific response of the amblyopic eye associated with the correction of the refractive error. The larger stromal area in the amblyopic eyes at the baseline is a predictive factor for improvements of the BCVA

ヒト網膜色素上皮はヒドロキノンと最終糖化産物の共刺激により、VEGF遺伝子の発現上昇を伴って増殖する

Although recent research showed that advanced glycation endproduct (AGE) and hydroquinone (HQ) are related to the pathogenesis of age-related macular degeneration (AMD), the mechanism how AGE and HQ induce or accelerate AMD remains elusive. In the present study, we examined the effects of AGE and HQ on changes of human retinal pigment epithelial (RPE) cell numbers and found that the viable cell numbers were markedly reduced by HQ by apoptosis and that AGE prevented the decreases of HQ-treated cell numbers by increased replicative DNA synthesis of RPE cells without changing apoptosis. Real-time RT-PCR revealed that vascular endothelial growth factor (VEGF)-A mRNA was increased by HQ treatment and the addition of HQ+AGE resulted in a further increment. The increase of VEGF secretion was confirmed by ELISA, and inhibition of VEGF signaling by chemical inhibitors and small interfering RNA decreased the HQ+AGE-induced increases in RPE cell numbers. The deletion analysis demonstrated that −102 to −43 region was essential for the VEGF-A promoter activation. Site-directed mutaions of specificity protein 1 (SP1) binding sequences in the VEGF-A promoter and RNA interference of SP1 revealed that SP1 is an essential transcription factor for VEGF-A expression. These results indicate that HQ induces RPE cell apoptosis, leading to dry AMD, and suggest that AGE stimulation in addition to HQ enhances VEGF-A transcription via the AGE-receptor for AGE pathway in HQ-damaged cells. As a result, the secreted VEGF acts as an autocrine/paracrine growth factor for RPE and/or adjacent vascular cells, causing wet AMD.博士（医学）・甲第640号・平成27年11月27日Copyright © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Optical correction and the choroidal thickness in children with anisohypermetropic amblyopia

The purpose of this study was to determine the effect of optical correction on the best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (CT) in the eyes of children with anisohypermetropic amblyopia. Twenty-four anisohypermetropic amblyopic eyes and their fellow eyes of 24 patients and twenty-three eyes of 23 age-matched control children were studied. After one year of optical correction, the BCVA in the anisohypermetropic amblyopic eyes was significantly improved. Before the treatment, the mean subfoveal CT in the amblyopic eyes was 351.9 ± 59.4 μm which was significantly thicker than that of control eyes at 302.4 ± 63.2 μm. After the treatment, the amount of change in the subfoveal CT in the amblyopic and fellow eyes was greater than that in the control eyes. The amblyopic and fellow eyes with thicker choroids had a greater thinning of the choroid whereas eyes with thinner choroids had a greater thickening of the choroid. We conclude that wearing corrective lenses improves the visual acuity, and induces changes of the subfoveal CT in eyes with anisohypermetropic amblyopia

IOP elevation after STTA

Purpose To evaluate real-world evidence for intraocular pressure (IOP) elevation after subtenon triamcinolone acetonide injection (STTA) in 1252 Japanese patients (1406 eyes) in the Japan Clinical REtina STudy group (J-CREST). Methods This was a multicentre retrospective study of the medical records of 1252 patients (676 men (758 eyes); mean age: 63.8 ± 12.9 years) who received STTA in participating centres between April 2013 and July 2017. Results IOP elevation was observed in 206 eyes (14.7%) and IOP increase ≥ 6 mmHg was found in 328 eyes (23.3%). In total, 106 eyes (7.5%) needed medication and two eyes (0.14%) needed surgical procedures. Younger age, higher baseline IOP, and steroid dose were risk factors associated with IOP elevation. Risk factors associated with IOP increase ≥ 6 mmHg were younger age, lower baseline IOP, steroid dose, and higher incidences of diabetic macular oedema (DME) and uveitis. In contrast, with steroid dose fixed at 20 mg, a lower incidence of DME was a risk factor for increased IOP, suggesting that STTA had dose-dependent effects on IOP increase, especially in patients with DME. Conclusion Our real-world evidence from a large sample of Japanese patients who received STTA showed that the incidence of IOP elevation after STTA was 14.7%, and was associated with younger age, higher baseline IOP, and steroid dose. Thus, IOP should be monitored, especially in patients with younger age, higher baseline IOP, and higher incidences of DME and uveitis