{"title":"[Age-related Macular Degeneration in the Japanese].","authors":"Nagahisa Yoshimura","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) in the Japanese often shows different clinical features from those described in Caucasians. For example, we often observe choroidal neovascularization (CNV) in elderly patients without drusen in the fundus. The high incidence of polypoidal choroidal vasculopathy (PCV) in AMD among Japanese is well-known. The reason why such differences occur in clinical manifestations of AMD has been one of my main interests. In this review article, I will discuss the characteristics of AMD in the Japanese population, as found in our recent study. I. Prevalence and clinical characteristics of AMD in the Japanese population. Cohort studies are important to determine the prevalence and incidence of diseases. In Japan, cohort studies began to be carried out rather late compared with Western countries. Although good cohort studies from Japan are reported in the literature, the size of the cohorts was not sufficiently large to determine the prevalence of AMD. However, a recent meta-analysis of Asian cohorts has shown that the prevalence of late AMD in Asians is not different from that reported in Caucasians. On the other hand, the prevalence of early AMD appears lower in the Japanese than in Caucasians. Recently, we have published the results of the Nagahama Cohort study. In this cohort study, we found a high prevalence of drusen. It seems that the incidence of dry AMD is likely to increase among Japanese. In Japan, most retina specialists classify AMD into three categories : typical AMD, PCV, and retinal angiomatous proliferation (RAP). However, there are no definite diagnostic criteria to distinguish between the three conditions. To compare the clinical features of Japanese and Western cases of AMD, and to determine the incidence of the three types of AMD, we exchanged data about 100 consecutive cases between Kyoto University and Centre d'Ophtalmologie de Paris, France. Interestingly, the diagnoses made by the two institutes were not always in agreement. We also found more cases of PCV among the Japanese than among the French. II. PCV. About 50% of exudative AMD cases in the Japanese population are PCV. Because of its peculiar angiographic findings, PCV has long been considered to be a distinct clinical entity different from the usual exudative AMD. Also, there have been serious discussions on the nature of PCV. In our analyses, about 20% of PCV cases show rather large lesion sizes that exceed the vascular arcade. Scar formation in the macula and compromised vision are frequent findings in such cases. The occurrence of PCV in the inferior staphyloma or in angioid streaks shows heterogeneity in PCV. These findings suggest that PCV may be a finding on indocyanine green angiography rather than a distinct clinical entity. Spectral domain OCT examination shows that the branching vascular network of PCV is located between the retinal pigment epithelium and Bruch's membrane. In cases with retinal pigment epithelial detachment, C","PeriodicalId":19670,"journal":{"name":"Nippon Ganka Gakkai zasshi","volume":"120 3","pages":"163-88; discussion 189"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34471676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[To Protect Corneal Transparency against Diseases].","authors":"Tomohiko Usui","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To protect corneal transparency, we tried to develop a new therapeutic strategy for corneal neovascularization, corneal scar, and TGFBI-related corneal dystrophy using nucleic acid drug. 1. The expression of angiopietin-like protein 2 (Angptl2) markedly increased in the neovascularized corneas compared to the normal cornea, and Angtpl2 was(a potent inducer of inflammatory corneal neovascularization. We have produced a single-stranded proline-modified short hairpin anti-Angptl2 ribonucleric acid interference (RNAi) molecule that is carried in a lipid nanoparticle for topical application. We have found this agent can penetrate all layers of the cornea. Angptl2 mRNA expression and corneal neovascularization were inhibited in a mouse alkari injury model by topical application of this agent. Thus, this modified RNAi agent is a new topical formulation for use against corneal neovascularization and scar. 2. Human umbilical vein endothelial cells (HUVECs) were cultured with human corneal keratocytes under serum-free conditions. We performed microarray gene-expression analysis in the coculture system and selected angiopoietin-like protein 7 (Angptl7). In vivo, intrastromal injections of an anti-Angptl7 RNAi agent into the avascular corneal stroma of mice resulted in the growth of blood vessels. Further, we examined the effects of Angptl7 on corneal nerves using culture rat trigeminal cells and this molecule had neurotrophic property on the cornea. Thus, Angpt17 is a unique molecule, which contain its bilateral character (anti-angiogenic and neurotrophic) in the cornea; an agonistic nucleic acid drug for Angptl7 may be a new therapeutic tool for protecting corneal transparency. 3. We examined local gene editing for TGFBI-related corneal dystrophy using CRISPR-Cas9 mediated homology directed repair (HDR). Cultured corneal keratocytes were obtained from a patient of R124H granular dystrophy. The R124H gene arrangement was corrected by a tranfection of guide RNA and HDR repair template single strand DNA in vitro. Thus, CRISPR-Cas9 medi-ated HDR could be a future radical treatment for TGFBI-related corneal dystrophy.</p>","PeriodicalId":19670,"journal":{"name":"Nippon Ganka Gakkai zasshi","volume":"120 3","pages":"246-62; discussion 263"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34376315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Humphrey Perimetry and Retinal Diseases].","authors":"Hiroyuki Iijima","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Since, in most eyes with retinal diseases quality of vision is greatly affected by visual field defects including paracentral scotoma and inferior field defects, visual function should be assessed by central 30- or 10-degrree automated static perimetry as well as visual acuity testing. The reduction of light sensitivity, demonstrated in the results of Humphrey central 10-2 perimetry, is more apparent than visual acuity loss in eyes with central serous chorioretinopathy (CSC), in which patients complain of dimness in the visual field of the affected eye. While reduced light sensitivity in eyes with acute CSC is well correlated with the height of subretinal fluid, marked and irreversible light sensitivity loss is demonstrated in the absence of subretinal fluid in eyes with chronic CSC due to structural damage in the photoreceptors. Various degrees of light sensitivity loss are seen in eyes wih age-related macular degeneration corresponding to intraretinal or subretinal pathology including intra- or subretinal fluid, fibrous scarring containing choroidal neovascularization and atrophic changes. The mean deviation (MD) of Humphrey central 10-2 perimetry is useful in predicting the visual outcome in eyes with exudative AMD after photodynamic therapy or intravitreal injection of anti-vascular endothelial growth factor. The progression of retinitis pigmentosa is well assssed with MD of Humphrey central 10-2 perimetry, which decreases linearly in the stage of residual visual field of 10 degrees or less. The age of patients with visual loss below 0.5 is delayed in eyes showing pencil-like configuration of \"Traquair's island of visual field\", in which a small area of normal light sensitivity around the fixation point is surrounded by absolute scotoma. With less visual acuity loss compared with that seen in eyes with central retinal artery occlusion; eyes with branch retinal artery occlusion show marked visual field defects, which are permanent and profound simulating the nasal-step pattern seen in eyes with glaucoma. Non-perfusion areas in fluorescein angiograms of eyes with branch retinal vein occlusion generally demonstrate reduced light sensitivity in the results of Humphrey central 30-2 perimetry, the degree of which tends to correlate with severity of non-perfusion. The light sensitivity in the area of detached retina in eyes with rhegmatogenous retinal detachment is generally reduced to show absolute scotoma, yet these eyes recover greatly after successful surgical repair.</p>","PeriodicalId":19670,"journal":{"name":"Nippon Ganka Gakkai zasshi","volume":"120 3","pages":"190-208; discussion 209"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34471677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Retinal Cell Therapy Using iPS Cells].","authors":"Masayo Takahashi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Progress in basic research, starting with the work on neural stem cells in the middle 1990's to embryonic stem (ES) cells and induced pluripotent stem (iPS) cells at present, will lead the cell therapy (regenerative medicine) of various organs, including the central nervous system to a big medical field in the future. The author's group transplanted iPS cell-derived retinal pigment epithelial (RPE) cell sheets to the eye of a patient with exudative age-related macular degeneration (AMD) in 2014 as a clinical research. Replacement of the RPE with the patient's own iPS cell-derived young healthy cell sheet will be one new radical treatment of AMD that is caused by cellular senescence of RPE cells. Since it was the first clinical study using iPS cell-derived cells, the primary endpoint was safety judged by the outcome one year after surgery. The safety of the cell sheet has been confirmed by repeated tumorigenisity tests using immunodeficient mice, as well as purity of the cells, karyotype and genetic analysis. It is, however, also necessary to prove the safety by clinical studies. Following this start, a good strategy considering cost and benefit is needed to make regenerative medicine a standard treatment in the future. Scientifically, the best choice is the autologous RPE cell sheet, but autologous cell are expensive and sheet transplantation involves a risky part of surgical procedure. We should consider human leukocyte antigen (HLA) matched allogeneic transplantation using the HLA 6 loci homozyous iPS cell stock that Prof. Yamanaka of Kyoto University is working on. As the required forms of donor cells will be different depending on types and stages of the target diseases, regenerative medicine will be accomplished in a totally different manner from the present small molecule drugs. Proof of concept (POC) of photoreceptor transplantation in mouse is close to being accomplished using iPS cell-derived photoreceptor cells. The shortest possible course for treatment is now being investigated in preclinical research. Among the mixture of rod and cone photoreceptors in the donor cells, the percentage of cone photoreceptors is still low. Donor cells with more. cone photoreceptors will be needed. If that will work well, photoreceptor transplantation will be the first example of neural network reconstruction in the central nervous system. These efforts will reach to variety of retinal cell transplantations in the future.</p>","PeriodicalId":19670,"journal":{"name":"Nippon Ganka Gakkai zasshi","volume":"120 3","pages":"210-24; discussion 225"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34471678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Future Innovative Medicine for Corneal Diseases].","authors":"Kohji Nishida","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Japan faces an aging population and a declining birth rate, so medical professionals and the public are seeking next-generation ophthalmological treatments to preserve and restore visual function. Two fields lie at the heart of this future concept of ophthalmological treatments. The first is predictive medicine and early intervention and treatment. This field is based on precision medicine to treat chronic conditions such as keratoconus, glaucoma, and macular degeneration while the condition is latent or soon after it has developed. The second field is regenerative therapy. This field includes cell therapy, regenerative medicine, artificial corneas and retinal implants. Precision medicine is the concept of examining the effects of genomic information and environmental factors on the onset or progression of a condition. Precision medicine involves dividing patients with a given condition into subgroups and then developing an appropriate method of preventing or treating that condition for each group. This may prove useful in treating corneal conditions such as keratoconus and dry eye. To accomplish that goal, however, overarching genomic, imaging, and biomarker studies must be conducted. Markers related to the onset or progression of a condition must also be identified. This paper describes results of preliminary study of 2 types of markers: biomarkers, and genetic markers. These markers have been used in efforts to predict the onset or progression of keratoconus. The development of regenerative medicine requires basic studies of stem cells and microenvironments (niches) in which to sustain those cells. N-cadherin is a cell adhesion molecule, and the current authors are the first to contend that this molecule plays an important role in the corneal epithelial stem cell niche. In addition, the current authors are the first to report that corneal endothelial cells expressing p75 may potentially be corneal endothelial precursor cells. Capitalizing on the results of that basic study, the current authors have also worked to develop regenerative therapies for the corneal epithelium and the corneal endothelium. The current authors developed the world's first autologous oral mucosal cell sheets to treat corneal epithelial stem cell deficiency. Having conducted a first-in-human clinical study and a multi-center clinical study, the current authors have initiated a physician-led clinical trial of this therapy. In order to identify ways to better restore visual acuity, the current authors are using iPS cells to develop a regenerative therapy with autologous corneal epithelium. Furthermore, the current authors are working to develop a regenerative therapy for corneal endothelium using allogeneic corneal endothelial cells derived from iPS cells. Making medicine of the future a current reality is not easy. Innovations that benefit patients are developed over decades. The current authors hope to pass this baton of scientific innovation on to future generation","PeriodicalId":19670,"journal":{"name":"Nippon Ganka Gakkai zasshi","volume":"120 3","pages":"226-44; discussion 245"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34376314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Clinical Results of Diffractive Multifocal Intraocular Lens Implantation after Laser In Situ Keratomileusis].","authors":"Mami Yoshino, Keiichiro Minami, Manabu Hirasawa, Shinichi Oki, Hiroko Bissen-Miyajima","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the visual performance in eyes with diffractive intraocular lenses (IOLs) after laser in situ keratomileusis (LASIK).</p><p><strong>Methods: </strong>This single-center retrospective study evaluated eyes that had diffractive multifocal IOL implantation after previous LASIK or not treated with LASIK (controls). The outcomes' measures were the visual acuities (VAs) at distance and near, spherical equivalent (SE) and contrast sensitivity at one month postoperatively.</p><p><strong>Results: </strong>The study evaluated 40 eyes of 33 patients. The mean uncorrected logMAR VAs were -0.05 ± 0.13/0.00 ± 0.14 (LASIK group/control group) at distance and 0.10 ± 0.13/0.16 ± 0.18 at near. There was no statistically significant difference between the 2 groups at the VAs. The SE of the LASIK group was -0.06 ± 0.39 D, significantly lower than the control group (0.22 ± 0.45 D) (p < 0.05). The contrast sensitivity of the LASIK group at high spatial frequency was lower than the control group (p < 0.05).</p><p><strong>Conclusion: </strong>After LASIK, the diffractive multifocal IOL provided good uncorrected distance and near VAs. However, decrease in contrast sensitivity should be considered.</p>","PeriodicalId":19670,"journal":{"name":"Nippon Ganka Gakkai zasshi","volume":"119 9","pages":"613-8"},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34094746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Long-Term Follow-up of Age-related Strabismus Patients 50 Years-old and Over].","authors":"Akihiko Oohira","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize age-related strabismus by long term observation.</p><p><strong>Methods: </strong>Clinical Characteristics were collected at two institutions from patients 50 years-old and over with age-related strabismus, who complained of diplopia and were followed up longer than 2 years without surgical intervention.</p><p><strong>Results: </strong>The cohort consisted of one case of near exotropia (convergence insufficiency, exotropia angle at near was 11.3 degrees), eight cases of distance esotropia (divergence insufficiency, average esotropia angle at distance was 5.8 degrees), and 15 cases of hypertropia (average hypertropia angle at distance was 3.6 degrees). In 14 patients more than one year passed from the onset of diplopia to date of visiting one of the two clinics. The strabismus angle slowly increased (0.3 per year in average; Wicoxon signed-rank test, p < 0.01). 17 patients successfully used prism incorporated glasses. Diplopia was intermittent at first and became more frequent in most cases. Hypertropic patients often showed extorsion of the lower eye.</p><p><strong>Conclusion: </strong>Age-related strabismus eyes slowly develop diplopia and very slowly get worse in deviation angle. Prism incorporated glasses are useful in this condition.</p>","PeriodicalId":19670,"journal":{"name":"Nippon Ganka Gakkai zasshi","volume":"119 9","pages":"619-24"},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34096239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Bilateral Endogenous Fungal Subretinal Abscesses due to Scedosporium prolificans: a Case Report].","authors":"Satoru Inoda, Yukihiro Sato, Yusuke Arai, Hiroto Obata, Jun Suzuki, Toshikatsu Kaburaki, Katsuhiko Kamei","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>We report a case with bilateral endogenous fungal subretinal abscesses. To our knowledge, this is the first report from Japan in which Scedosporium prolificans (S. prolificans) was cultured from intraocular tissue.</p><p><strong>Case: </strong>A 74-year-old man, receiving chemotherapy for acute myeloid leukemia, complained of visual loss in both eyes. Best-corrected visual acuity was hand motion in the right and 2/200 in the left eye. His right eye showed exophthalmos, inflammation in the anterior chamber and iris neovascularization. Funduscopy revealed no details as there was vitreous opacity in the right eye, and irregular round yellowish-white subretinal lesions involving the macula in the left eye. Blood culture was negative, and C-reactive protein (CRP) and β-D glucan titers were high. An antifungal drug and broad-spectrum antibiotics were initiated. Two days after the initial visit, right visual acuity had deteriorated to light perception. Enucleation of the right eye was performed for diagnosis and treatment. Fungi were cultured from the subretinal lesion, confirming a diagnosis of S. prolificans infection. After systemic administration and intravitreal injections of antifungal agents, the subretinal abscess in the left eye gradually diminished. At present, six months after the first visit, left visual acuity is 20/200.</p><p><strong>Conclusion: </strong>Although S. prolificans endophthalmitis can be intractable, this case suggests that repeated intravitreal antifungal agent injections can be effective.</p>","PeriodicalId":19670,"journal":{"name":"Nippon Ganka Gakkai zasshi","volume":"119 9","pages":"632-9"},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34096241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}