記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

目的:広義原発開放隅角緑内障(POAG)におけるカルテオロール/ラタノプロスト配合点眼剤(以下、CAR/LAT)単独への変更による1年間の眼圧下降効果を後ろ向きに検討する。対象および方法:プロスタグランジン関連薬(以下、PG)単剤または異種のPG/β遮断薬配合剤(以下、PG/β)単独からの切り替えで、CAR/LATを新規に処方した広義POAG患者のうち、緑内障手術歴のない連続65例を対象とした。変更前と変更1ヵ月後、3ヵ月後、6ヵ月後、12ヵ月後の眼圧をそれぞれ比較した。結果:PGからの変更では、眼圧(平均±標準偏差)は、変更前14.9±3.2mmHgに対して変更12ヵ月後12.8±2.1mmHgで、変更前と比べて変更後のすべての時点で有意な眼圧下降を認めた(p<0.05)。異種のPG/βからの変更では、有意な変化はなかった(p=0.30)。結論:広義POAGにおいて、PG単剤からCAR/LATへの変更では、1年間有意な眼圧下降が得られ、また、異種のPG/β単独からの変更では有意な眼圧変化はない。(著者抄録)

researchmap

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01784&link_issn=&doc_id=20220624100023&doc_link_id=%2Fah9atgke%2F2022%2F003906%2F020%2F0830-0834%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fah9atgke%2F2022%2F003906%2F020%2F0830-0834%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Maternally inherited diabetes and deafness (MIDD) is caused by a heteroplasmic m.3243A>G mutation in the mitochondrial DNA. The main ocular feature in MIDD is macular dystrophy. The purpose of this study was to identify the phenotypical characteristics of a patient with MIDD by multimodal high-resolution imaging analyses.Methods: A detailed history and ophthalmic examination were performed on a 39-year-old patient with MIDD. Multi-modal imaging included fundus photography, fundus autofluorescence imaging, fluorescein angiography, spectral-domain optical coherence tomography, OCT-angiography, and adaptive optics imaging. The PCR-invader and whole exome sequencing (WES) methods were performed on the DNA of the patient.Results: A 39-year-old woman with sensorineural hearing loss, diabetes mellitus presented with atrophic perifoveal changes and MIDD was suspected. The PCR-invader and WES methods showed that the patient had a m.3243A>G mutation in the mitochondrial DNA with 29% and 16.7% of the heteroplasmy in the peripheral blood, respectively. Morphological analyses revealed that the areas of photoreceptor degeneration and chorioretinal atrophy were present mainly in the perifoveal region. Multifocal ERGs showed that the perifoveal responses were reduced. Goldmann visual field was significant for a cecocentral scotoma in the right eye and an enlarged blind spot in the left eye. The central isopter was constricted bilaterally. The results of high-resolution retinal imaging by AO revealed that the densities of the cone photoreceptor were significantly reduced in the fovea where no obvious atrophy of the RPE and choroid was observed.Conclusions: Our findings indicate that WES analysis can be used to detect the m.3243A>G mutation in the mtDNA. The results of multimodal imaging analyses indicated that the primary dysfunction of the photoreceptors in the fovea might precede the dysfunction of the RPE in patient with MIDD.

DOI： 10.1080/13816810.2021.1881978

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Little is known about genotype-phenotype correlations of RP1-associated retinal dystrophies in the Japanese population. We aimed to investigate the genetic spectrum of RP1 variants and provide a detailed description of the clinical findings in Japanese patients. METHODS: In total, 607 patients with inherited retinal diseases were examined using whole-exome/whole-genome sequencing (WES/WGS). PCR-based screening for an Alu element insertion (c.4052_4053ins328/p.Tyr1352AlafsTer9) was performed in 18 patients with autosomal-recessive (AR)-retinitis pigmentosa (RP) or AR-cone dystrophy (COD)/cone-rod dystrophy (CORD), including seven patients with heterozygous RP1 variants identified by WES/WGS analysis, and 11 early onset AR-RP patients, in whom no pathogenic variant was identified. We clinically examined 25 patients (23 families) with pathogenic RP1 variants, including five patients (five families) with autosomal-dominant (AD)-RP, 13 patients (11 families) with AR-RP, and seven patients (seven families) with AR-COD/CORD. RESULTS: We identified 18 pathogenic RP1 variants, including seven novel variants. Interestingly, the Alu element insertion was the most frequent variant (32.0%, 16/50 alleles). The clinical findings revealed that the age at onset and disease progression occurred significantly earlier and faster in AR-RP patients compared to AD-RP or AR-COD/CORD patients. CONCLUSIONS: Our results suggest a genotype-phenotype correlation between variant types/locations and phenotypes (AD-RP, AR-RP, and AR-COD/CORD), and the Alu element insertion was the most major variant in Japanese patients with RP1-associated retinal dystrophies.

DOI： 10.3390/jcm10112265

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The hexokinase 1 (HK1) gene encodes one of the four human hexokinases that play essential roles in glucose metabolism. Recently, several cases of E847K mutation in the HK1 gene were reported to cause inherited retinal dystrophy. The purpose of this study was to identify the phenotypical characteristics of patients with a recurrent E847K mutation in the HK1 gene. METHODS: Three generations of one family with autosomal dominant retinitis pigmentosa were examined. Whole exome sequencing was performed on the DNA. Fundus imaging by an adaptive optics fundus camera was used to obtain high-resolution photoreceptor images. RESULTS: Fundus examination of the proband showed degeneration of the mid-peripheral retina, and SD-OCT images showed an absence of the ellipsoid zone (EZ) and interdigitation zone (IZ) in the parafovea and more peripherally. SD-OCT images of the mother of the proband showed an absence of the EZ and IZ, and fundus autofluorescence images showed hypo-autofluorescence surrounding the macular region. One daughter of the proband had only mild night blindness, however, the density of the cone photoreceptors was reduced in the parafoveal region. Whole exome sequencing identified a heterozygous variant, E847K, in the HK1 gene. This variant was found to co-segregate with the disease in three family members. CONCLUSIONS: Although the systemic phenotypes were found to be associated with the HK1 mutations, only the E847K mutation can cause a non-syndromic photoreceptor degeneration. Our study strengthened the hypothesis that the amino acid E847 might play a critical role in the maintenance of the morphology and function of the photoreceptors.

DOI： 10.1080/13816810.2020.1810284

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The GUCY2D (guanylate cyclase 2D) gene encodes a photoreceptor guanylate cyclase (GC-E), that is predominantly expressed in the cone outer segments. Mutations in the GUCY2D lead to severe retinal disorders such as autosomal dominant cone-rod dystrophy (adCRD) and autosomal recessive Leber congenital amaurosis type 1. The purpose of this study was to identify the phenotype of a Japanese patient with a probably pathogenic GUCY2D variant. METHODS: Detailed ophthalmic examinations were performed, and whole exome sequencing was performed on DNA obtained from the patient. The variants identified by exome sequencing and targeted analysis were further confirmed by direct sequencing. RESULTS: A 47-year-old man had atrophic and pigmentary changes in the macula of both eyes. Amplitudes and implicit times on full-field electroretinograms (ERGs) were within normal limits; however, the densities of multifocal ERGs in the central area were reduced in both eyes. Whole exome sequencing identified heterozygous variant c.2527G>C, p.Glu843Gln in the GUCY2D gene within the mutation hot spot for adCRD. The allelic frequencies of this variant are extremely low and, according to American College of Medical Genetics and Genomics standards and guidelines, the variants are classified as likely pathogenic. CONCLUSIONS: This is the first report of a heterozygous variant, c.2527G>C, p.Glu843Gln, in the GUCY2D, in a patient presenting with mild macular dystrophy without a general reduction in cone function. Our findings expand the spectrum of the clinical phenotypes of GUCY2D-adCRD and help clarify the morphological and functional changes caused by defects of dimerization of GC-E in the phototransduction cascade.

DOI： 10.1272/jnms.JNMS.2020_87-207

PubMed

researchmap

記述言語：日本語   出版者・発行元：眼科臨床紀要会  

researchmap

記述言語：日本語   出版者・発行元：眼科臨床紀要会  

researchmap

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

researchmap