研究者詳細 - 西口　康二

Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases

Goto, K; Koyanagi, Y; Akiyama, M; Murakami, Y; Fukushima, M; Fujiwara, K; Iijima, H; Yamaguchi, M; Endo, M; Hashimoto, K; Ishizu, M; Hirakata, T; Mizobuchi, K; Takayama, M; Ota, J; Sajiki, A; Kominami, T; Ushida, H; Fujita, K; Kaneko, H; Ueno, S; Hayashi, T; Terao, C; Hotta, Y; Murakami, A; Kuniyoshi, K; Kusaka, S; Wada, Y; Abe, T; Nakazawa, T; Ikeda, Y; Momozawa, Y; Sonoda, KH; Nishiguchi, KM

JOURNAL OF MEDICAL GENETICS 2024年3月

記述言語：英語出版者・発行元：Journal of Medical Genetics

Background As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP–allied diseases. Methods We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines. Results A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases. Conclusion A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.

DOI： 10.1136/jmg-2023-109750

Genetic and Clinical Features of ABCA4-Associated Retinopathy in a Japanese Nationwide Cohort.

Mizobuchi K, Hayashi T, Tanaka K, Kuniyoshi K, Murakami Y, Nakamura N, Torii K, Mizota A, Sakai D, Maeda A, Kominami T, Ueno S, Kusaka S, Nishiguchi KM, Ikeda Y, Kondo M, Tsunoda K, Hotta Y, Nakano T

American journal of ophthalmology 264 巻頁： 36 - 43 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Ophthalmology

Purpose: To clarify the genetic and clinical features of Japanese patients with ABCA4-associated retinopathy. Design: Retrospective, multicenter cohort study. Methods: Patients with retinal degeneration and biallelic ABCA4 variants were recruited from 13 different hospitals. Whole exome sequencing analysis was used for genetic testing. Comprehensive ophthalmic examinations were performed on matched patients. The primary outcome measure was identifying multimodal retinal imaging findings associated with disease progression. Results: This study included 63 patients: 19 with missense/missense, 23 with missense/truncation, and 21 with truncation/truncation genotypes. In total, 62 variants were identified, including 29 novel variants. Six patients had a mild phenotype characterized by foveal-sparing or preserved foveal structure, including 4 with missense/missense and 2 with missense/truncation genotypes. The p.Arg212His variant was the most frequent in patients with mild phenotypes (4/12 alleles). Clinical findings showed a disease duration-dependent worsening of the phenotypic stage. Patients with the truncation/truncation genotype exhibited rapid retinal degeneration within a few years and definite fundus autofluorescence imaging patterns, including hyper autofluorescence at the macula and few or no flecks. Conclusions: Our results indicate that missense/missense or missense/truncation genotypes, including the p.Arg212His variant, are associated with a relatively mild phenotype. In contrast, the truncation/truncation genotype causes rapid and severe retinal degeneration in Japanese patients with ABCA4-associated retinopathy. These data are vital in predicting patient prognosis, guiding genetic counseling, and stratifying patients for future clinical trials.

DOI： 10.1016/j.ajo.2024.03.007

Secondary Angle Closure Caused by Anterior Displacement of Capsular Tension Ring and Intraocular Lens Due to Aqueous Misdirection

Goto, K; Tomita, R; Hiraiwa, J; Kawabe, M; Nishiguchi, KM; Yuki, K

CUREUS JOURNAL OF MEDICAL SCIENCE 16 巻 ( 3 ) 頁： e55716 2024年3月

特集先端医療を先取りしよう-日本にはない海外の医療企画にあたって

西口康二

臨床眼科 78 巻 ( 2 ) 頁： 159 - 159 2024年2月

Accuracy of pattern deviation in estimating the glaucomatous damage in the central 10° visual field in eyes with glaucoma and cataract

Tomita, R; Asaoka, R; Hirasawa, K; Fujino, Y; Nakakura, S; Murata, H; Omura, T; Shoji, N; Obana, A; Nishiguchi, KM; Tanito, M

BRITISH JOURNAL OF OPHTHALMOLOGY 108 巻 ( 1 ) 頁： 78 - 83 2024年1月

記述言語：英語出版者・発行元：British Journal of Ophthalmology

Background/aims The accuracy of pattern deviation (PD) in estimating the damage to the glaucomatous visual field (VF) in the central 10° in eyes with glaucoma and cataract is unclear. Methods This retrospective study includes 63 eyes of 52 glaucoma patients who successfully underwent cataract surgery or cataract surgery plus iStent implantation. Using the Humphrey Field Analyser 10-2 test, VF was measured within 6 months preoperatively and postoperatively (VF pre and VF post, respectively). The mean total deviation values in VF post (mTD post) indicates glaucomatous damage without cataract and the difference between this value and mean PD values in VF pre (mPD pre) was evaluated (ϵmPD). The effect of cataract was then evaluated as the difference between mTD post and mTD pre ( "mTD), while the effects of mTD post and "mTD on ϵmPD were also assessed. In addition, based on preoperative visual acuity (VA pre) and VF pre, the optimal model for predicting mTD post was identified. The error of this method (ϵOptimalModel) was estimated as the difference against mTD post, which was compared with ϵmPD. Results Compared with mTD pre, there was a significant improvement in mTD post (p=0.028). A significant difference was observed between mPD pre and mTD post (p<0.001). Further, ϵmPD significantly increased with the increase of mTD post or "mTD (p<0.001 and p=0.0444, respectively). The absolute ϵOptimalModel was significantly smaller than the absolute ϵmPD (p<0.001). Conclusions This study warns clinicians that PD of the central 10° VF might underestimate the glaucomatous VF damage with the progression of glaucoma and overestimate it as a cataract progresses.

DOI： 10.1136/bjo-2022-322274

Identification of OPTN p.(Asn51Thr): A novel pathogenic variant in primary open-angle glaucoma.

Shiga Y, Hashimoto K, Fujita K, Maekawa S, Sato K, Kubo S, Kawase K, Tokumo K, Kiuchi Y, Mori S, Nakamura M, Iwata T, Nishiguchi KM, Nakazawa T

Genetics in medicine open 2 巻頁： 100839 - 100839 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Genetics in Medicine Open

Purpose: Pathogenic variants in TBK1, MYOC, and OPTN are associated with primary open-angle glaucoma (POAG) with severe visual field defects. This study aims to understand further POAG-related pathogenic variant(s) based on a cohort of East Asian populations that have not been well-characterized. Methods: We conducted a comprehensive screening of TBK1, MYOC, and OPTN variants in 174 POAG Japanese patients, followed by 8380 population-specific genome sequencing data references, segregation analysis, and functional protein assays to determine pathogenic variants. Results: Despite the small sample size, 4 variants were novel, 2 of which p.(Cys5Trp) and p.(Thr293Met) were in the MYOC gene, and 2 p.(Asn51Thr), and p.(Gln142His) were in the OPTN. Notably, the OPTN p.(Asn51Thr) missense variant adjacent to the p.(Glu50Lys) variant, a well-known POAG pathogenic variant, was segregated from all proband's family members with POAG. Moreover, in silico and in vitro analyses revealed that the OPTN p.(Asn51Thr) protein increased binding instability, interactions of the OPTN-TBK1 complex, and enhanced protein insolubility, likewise the p.(Glu50Lys) protein. Conclusion: Our findings may provide further genetic insights into rare variants of POAG and support the clear conclusion that OPTN p.(Asn51Thr) is a novel likely pathogenic variant.

DOI： 10.1016/j.gimo.2023.100839

Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases

網膜遺伝子治療の夜明け～いま何が問題か？～

西口康二

日本視能訓練士協会誌 54 巻 ( 0 ) 頁： 1 - 6 2024年

記述言語：日本語出版者・発行元：公益社団法人日本視能訓練士協会

2008年に先天性に発症する重症な網膜ジストロフィに対する遺伝子治療の成功が初めて報告されて15年が経過し、2023年に同治療がルクスターナTMとして本邦で薬事承認された。これによって、眼科領域でも本格的にゲノム医療の時代が幕を開けた。しかし、同治療により、高度に低下していた網膜感度が大幅に改善させることが可能となった一方で、低視力の問題は解決しないことや術後に網脈絡膜萎縮が発症することなどの課題が報告されている。また、保険診療で遺伝病に対する遺伝子特異的な治療を行うにあたっては、保険診療のもとで広く遺伝子検査を実施するシステムの整備が必要となる。本稿では、本邦での網膜遺伝子治療に関する諸問題について考察する。

DOI： 10.4263/jorthoptic.54t001

CiNii Research

Kensuke Goto, Yoshito Koyanagi, Masato Akiyama, Yusuke Murakami, Masatoshi Fukushima, Kohta Fujiwara, Hanae Iijima, Mitsuyo Yamaguchi, Mikiko Endo, Kazuki Hashimoto, Masataka Ishizu, Toshiaki Hirakata, Kei Mizobuchi, Masakazu Takayama, Junya Ota, Ai Fujita Sajiki, Taro Kominami, Hiroaki Ushida, Kosuke Fujita, Hiroki Kaneko, Shinji Ueno, Takaaki Hayashi, Chikashi Terao, Yoshihiro Hotta, Akira Murakami, Kazuki Kuniyoshi, Shunji Kusaka, Yuko Wada, Toshiaki Abe, Toru Nakazawa, Yasuhiro Ikeda, Yukihide Momozawa, Koh-Hei Sonoda, Koji M. Nishiguchi

2023年11月

出版者・発行元：Cold Spring Harbor Laboratory

Abstract

Background

As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)–related genes in a large number of Japanese RP patients by applying the standardized variant interpretation guidelines for Japanese IRD patients (J-IRD-VI guidelines) built upon ACMG/AMP rules and assess the contribution of these genes in RP-allied diseases.

Methods

We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, all newly analyzed), including Usher syndrome, Leber congenital amaurosis, and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines.

Results

A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 RP patients. This led to a genetic diagnostic rate in 38.6% of RP patients, withEYSaccounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for CRD patients was 28.2%, with RP-related genes significantly contributing over other allied diseases.

Conclusion

A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the unique genetic findings for Japanese IRD patients; these findings serve as a foundation for the clinical application of gene-specific therapies.

DOI： 10.1101/2023.11.09.23297953

Abilities of circumpapillary retinal nerve fiber layer thickness and vascular density to discriminate stages in primary open-angle glaucoma 国際誌

Yamaguchi, K; Tomita, R; Koyanagi, Y; Kawase, K; Asaoka, R; Terasaki, H; Iwase, T; Nishiguchi, KM

GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 262 巻 ( 4 ) 頁： 1221 - 1229 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Graefe's Archive for Clinical and Experimental Ophthalmology

Purpose: To clarify the abilities of circumpapillary retinal nerve fiber layer thickness (cpRNFLT) obtained by optical coherence tomography (OCT) and circumpapillary vessel density (cpVD) measured by OCT-angiography to distinguish different stages in primary open-angle glaucoma determined by 24–2 or 30–2 static visual field (VF) testing. Methods: This retrospective study includes 25 healthy normal eyes of 25 subjects and 87 primary open-angle glaucoma eyes of 87 patients. Areas under the receiver operating characteristic curves (AUROC) were evaluated for determining glaucoma stages using cpRNFLT and cpVD. The absolute errors of the estimated mean total deviation (mTD) using optimal models with cpRNFLT and cpVD were also compared. Results: The AUROCs for discriminating glaucomatous eyes from normal eyes was significantly higher for cpRNFLT than the respective AUROCs for cpVD (0.969 [95% CI 0.939 to 0.998] vs. 0.872 [95% CI 0.806 to 0.938], p = 0.006), whereas cpVD had significantly higher AUROC for discriminating severe glaucoma eyes from moderate glaucoma eyes than cpRNFLT (0.771 [95% CI 0.655 to 0.886] vs. 0.578 [95% CI 0.420 to 0.736], p = 0.022). The mean absolute error in estimating mTD using both cpRNFLT and cpVD was significantly less than the error using cpRNFLT alone (4.56 ± 3.76 dB vs. 5.39 ± 4.00 dB, p = 0.027). Conclusion: Our results suggest that cpVD is better for follow-ups after moderate stage. The combination of cpRNFLT and cpVD may improve VF estimation compared to cpRNFLT alone.

DOI： 10.1007/s00417-023-06302-y

Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis

Yamada, K; Tazaki, A; Ushio-Watanabe, N; Usui, Y; Takeda, A; Matsunaga, M; Suzumura, A; Shimizu, H; Zheng, H; Ariefta, NR; Yamamoto, M; Hara, H; Goto, H; Sonoda, KH; Nishiguchi, KM; Kato, M; Nishikawa, Y; Toyokuni, S; Kaneko, H

REDOX BIOLOGY 67 巻頁： 102890 2023年11月

記述言語：英語出版者・発行元：Redox Biology

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer 57Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.

DOI： 10.1016/j.redox.2023.102890

Ornithine aminotransferase(OAT)遺伝子の複合ヘテロ接合性変異による脳回状脈絡網膜萎縮症の男児例

中野裕太, 安田小百合, 溝渕圭, 池田麻衣子, 濱島崇, 上野真治, 西口康二, 林孝彰

日本眼科学会雑誌 127 巻 ( 11 ) 頁： 1069 - 1080 2023年11月

記述言語：日本語出版者・発行元：(公財)日本眼科学会

目的:脳回状脈絡網膜萎縮症(GACR)は,本邦ではまれな常染色体潜性遺伝(劣性遺伝)の先天性代謝異常症で,ビタミンB6(VitB6)依存性オルニチンアミノ基転移酵素活性の低下による高オルニチン血症を特徴とし,進行性の脈絡網膜変性を来す.今回,GACR症例を報告するとともに,過去の日本人GACR報告例の遺伝学的解析結果と比較検討した.症例:3歳,男児.外斜視の精査を目的に紹介受診となった.以前より夜盲を呈していたが,明らかな眼底異常はなく経過観察となった.6歳時の眼底検査で両眼の耳側網膜周辺部に特徴的な脳回状の網脈絡膜萎縮がみられた.全視野刺激網膜電図の杆体系・錐体系反応はいずれも消失していた.高オルニチン血症を認め,GACRが疑われたため,VitB6投与を開始したが,血中オルニチン値は低下しなかった.低蛋白質食治療を併用したところ血中オルニチン値は低下した.最終的に必須アミノ酸を補った蛋白質制限とVitB6投与によって血中オルニチン値の低下が維持された.全エクソーム解析を行い,ornithine aminotransferase(OAT)遺伝子に複合ヘテロ接合性変異(p.Arg271Lysとp.Arg426Ter)が検出された.8歳時の眼底検査で網脈絡膜萎縮は明らかに拡大していた.結論:低蛋白質食治療とVitB6投与の併用によって血中オルニチン値の低下が維持されたが,網脈絡膜萎縮は進行性に拡大した.本症例も含め,過去の日本人GACR症例(13例)のOAT遺伝子変異をまとめた結果,p.Arg426Terが高頻度変異(27%,7/26アレル)であることが見出された.(著者抄録)

今月の表紙中心性漿液性脈絡網膜症のEn face画像

稲垣恵子, 西口康二

臨床眼科 77 巻 ( 10 ) 頁： 1234 - 1234 2023年10月

Association Between Torque Teno Virus and Systemic Immunodeficiency in Patients With Uveitis With a Suspected Infectious Etiology 査読有り国際誌

Sajiki, A; Koyanagi, Y; Ushida, H; Kawano, K; Fujita, K; Okuda, D; Kawabe, M; Yamada, K; Suzumura, A; Kachi, S; Kaneko, H; Komatsu, H; Usui, Y; Goto, H; Nishiguchi, KM

AMERICAN JOURNAL OF OPHTHALMOLOGY 254 巻頁： 80 - 86 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Ophthalmology

PURPOSE: To determine the correlation between the presence of torque teno virus (TTV) in the aqueous humor of patients with uveitis and clinical information, including immunodeficiency history. DESIGN: Multicenter, retrospective, cross-sectional study. METHODS: Fifty-eight patients with uveitis with a suspected infectious etiology and 24 controls with cataract or age-related macular degeneration were included. We used quantitative polymerase chain reaction to test all subjects for TTV and multiplex polymerase chain reaction to test uveitis subjects for common ocular pathogens. When possible, both serum and aqueous humor samples were tested. Ocular TTV positivity was compared with age, sex, and a history of systemic immunodeficiency with logistic analysis. RESULTS: Ocular TTV positivity was found in 23%, 11%, and 0% of patients with herpetic uveitis, nonherpetic uveitis, and controls, respectively. Among patients with herpes infection, positivity for ocular TTV was found in 43%, 8%, 14%, and 50% of patients with cytomegalovirus retinitis, iridocyclitis, acute retinal necrosis, and Epstein–Barr virus–positive uveitis, respectively. Patients with cytomegalovirus retinitis showed a significantly higher rate of ocular TTV infection than controls (P =.008). Serum analysis revealed TTV positivity in 90% of patients with uveitis and in 100% of controls. Age- and gender-adjusted logistic analysis revealed a correlation between ocular TTV positivity and systemic immunodeficiency (P =.01), but no correlations between ocular TTV and age, gender, or viral pathogenic type. CONCLUSIONS: These findings suggest that positivity for ocular TTV was correlated with a clinical history of systemic immunodeficiency.

DOI： 10.1016/j.ajo.2023.06.012

Pathogenic variants of MFRP and PRSS56 genes are major causes of nanophthalmos in Japanese patients

Ota, J; Inooka, T; Okado, S; Maeda, N; Koyanagi, Y; Kominami, T; Nishiguchi, KM; Ueno, S

OPHTHALMIC GENETICS 44 巻 ( 5 ) 頁： 423 - 429 2023年9月

記述言語：英語出版者・発行元：Ophthalmic Genetics

Background: Nanophthalmos (NNO) is a rare condition with significantly shorter axial length than normal. Several genes are known to cause NNO, among them the MFRP and PRSS56 genes have been reported to cause majority of NNOs. The purpose of this study was to determine the genetic basis of Japanese patients with NNO. Materials and Methods: We studied seven patients with NNO. Whole exome sequencing (WES) and Sanger sequencing were performed to determine the variants causing the NNO. We also reviewed the medical charts of the patients to determine the phenotype of these seven patients. Results: WES revealed that four patients from three families carried homozygous frameshift variants of the PRSS56 gene (c.1066dupC). Two novel variants of the MFRP gene were detected in the other two patients: one proband had a homozygous missense variant (c.1486 G>A) and the other had a compound heterozygous variant (c.1486 G>A and c.662_663insT). The axial length of the eight eyes with the PRSS56 variant was 15.69 ± 0.48 mm (mean ± SD) and that for the 4 eyes with the MFRP variant was 15.63 ± 0.69 mm. Three of the six cases with the PRSS56 or MFRP variant had the uveal effusion syndrome. Conclusions: NNOs in Japanese patients are caused by variants of the PRSS56 and MFRP genes as in other ethnic populations. In addition, two new variants of the MFRP gene were found in our cohort. The phenotypes and anomalies in Japanese patients with NNO were similar to those reported for other ethnic populations.

DOI： 10.1080/13816810.2023.2208220

Predictive factors for outcomes of half-dose photodynamic therapy combined with aflibercept for pachychoroid neovasculopathy

Takeuchi, J; Ota, H; Nakano, Y; Horiguchi, E; Taki, Y; Ito, Y; Terasaki, H; Nishiguchi, KM; Kataoka, K

GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 261 巻 ( 8 ) 頁： 2235 - 2243 2023年8月

記述言語：英語出版者・発行元：Graefe's Archive for Clinical and Experimental Ophthalmology

Purpose: To assess the effects of half-dose photodynamic therapy (PDT) combined with an intravitreous aflibercept (IVA) injection for pachychoroid neovasculopathy (PNV) and its predictive factors. Methods: Clinical information of 43 patients (43 eyes) with PNV obtained before and 6 months after treatment with half-dose PDT combined with IVA was retrospectively analyzed. Patients were categorized into the sufficient (25 eyes, 58.1%) or insufficient (18 eyes, 41.9%) group based on resolution or persistence/recurrence of subretinal fluid (SRF), respectively, and clinical data were compared. Macular neovascularization (MNV) change was studied in 30 cases with available pre- and post-treatment optical coherence tomography angiography images. Results: The sufficient group included younger patients with better baseline best-corrected visual acuity (BCVA), more treatment-naïve eyes, and smaller MNV lesions at baseline than the insufficient group (all, P < 0.047). Complete SRF resolution was 81.8% in treatment-naïve eyes and only 33.3% in previously treated eyes. MNV expanded after half-dose PDT was combined with IVA regardless of the treatment outcome (P = 0.003). Conclusion: Half-dose PDT combined with IVA was effective for PNV treatment, especially for younger patients with good baseline BCVA, treatment-naïve eyes, and small MNV sizes at baseline. MNV expanded after treatment regardless of the treatment outcomes.

DOI： 10.1007/s00417-023-06030-3

Genetic characteristics of retinitis pigmentosa and allied diseases in 2063 Japanese patients

Nishiguchi, KM; Koyanagi, Y; Akiyama, M; Murakami, Y; Iijima, H; Endo, M; Ueno, S; Hayashi, T; Hotta, Y; Murakami, A; Wada, Y; Abe, T; Nakazawa, T; Ikeda, Y; Sonoda, KH; Goto, K

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 64 巻 ( 8 ) 2023年6月

遺伝性網膜ジストロフィにおける遺伝学的検査のガイドライン

池田康博, 堀田喜裕, 近藤寛之, 西口康二, 前田亜希子, 藤波芳, 大石明生, 三宅正裕, 秋山雅人, 厚生労働科学研究費補助金難治性疾患政策研究事業網膜脈絡膜・視神経萎縮症に関する調査研究班遺伝性網膜ジストロフィにおける遺伝学的検査のガイドライン作成ワーキンググループ

日本眼科学会雑誌 127 巻 ( 6 ) 頁： 628 - 632 2023年6月

Assessment of factors affecting flicker ERGs recorded with RETeval from data obtained from health checkup screening 国際誌

Inooka, T; Kominami, T; Yasuda, S; Koyanagi, Y; Ota, J; Okado, S; Tomita, R; Ito, Y; Iwase, T; Terasaki, H; Nishiguchi, KM; Ueno, S

PLOS ONE 18 巻 ( 4 ) 頁： e0284686 2023年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PLoS ONE

Purpose To determine the factors significantly associated with the amplitudes and implicit times of the flicker electroretinograms (ERGs) recorded with the RETeval system by analyzing the comprehensive data obtained during a health checkup screening. Methods Flicker ERGs were recorded with the RETeval system from 373 individuals who had a normal fundus and optical coherence tomography images. The sex, age, anthropometric, ophthalmologic, and hematologic data were collected from all participants who were 40- to 89- years-of-age. Univariable and multivariable linear mixed effects regression analyses were performed to identify factors that were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. Results Univariable linear mixed effects regression analysis showed significant correlations between the implicit times and the best-corrected visual acuity, the age, the axial length, the blood sugar level, and the blood urea nitrogen level. Analyses by multivariable linear mixed effects regression identified that the axial length (β = 0.28), the age (β = 0.24), and the blood sugar level (β = 0.092) were three independent factors that were significantly correlated with the implicit times of the RETeval flicker ERGs. Univariable linear mixed effects regression analysis also showed significant correlations between the amplitudes of the RETeval flicker ERGs and the age, the platelet count, and the creatinine level. Multivariable linear mixed effects regression models identified the age (β = -0.092), the platelet count (β = 0.099), and the creatinine level (β = -0.12) as three independent factors that were significantly correlated with the amplitudes of the RETeval flicker ERGs. However, the smoking habits, body mass index, and the blood pressure were not significantly correlated with either the implicit times or amplitudes of the RETeval flicker ERGs. Conclusions Our results indicate that the age and some ophthalmologic and hematologic findings but not the anthropometric findings were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. Thus, clinicians should remember these factors when analyzing the RETeval flicker ERGs.

DOI： 10.1371/journal.pone.0284686