Development and clinical application of quantitative visual evaluation with comprehensive light emitting diode stimulation for patients with severe visual impairment.

2020 Fiscal Year Annual Research Report

• Project/Area Number: 18K16943
• Research Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター)
• Principal Investigator: 藤波 優 独立行政法人国立病院機構(東京医療センター臨床研究センター), 視覚研究部, 研究員 (50815173)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 視機能評価

Outline of Annual Research Achievements

重症網膜疾患に起因する重度視覚障害は生活の質に直結する重篤な症状を呈し、改善必須の社会問題となって久しい。近年、分子細胞生物学の発展に伴い、重度視覚障害に関する治療導入が実現に向かう反面、先鋭的治療導入は実臨床に届いていない。その大きな要因として、治療の適応判断と効果判定に関する有用な評価法が存在しない事実が挙げられる。

本研究の目的は、治療導入・展開が見込まれる重度視覚障害患者に対して、東京医療センター・臨床研究センター(NISO)、英国UCL Institute of Ophthalmology(UCL IoO)、Cambridge Research Systems (CRS)との密な連携下で最新の統合型LEDモニタ刺激技術を用いて刺激アルゴリズを構築する事で、従来の視力検査では定量的な測定が困難であった重度視覚障害患者群に対して、視力や視野等の病状、さらには病気メカニズムに即した様々な刺激パターンを用いた包括的・定量的評価系を確立し、その臨床応用を実践する事である。

令和２年度では、重症網膜疾患における機能評価の実践、有用性の評価が行われた。重度視覚障害において最も頻度が高いといわれている網膜色素変性症をはじめとする重症網膜疾患を有する患者12眼において包括的視機能評価が実践された。東京医療センターにて患者リクルートが行われ、段階２で構築された刺激アルゴリズム・検査プロトコルによる検査が実施された。また、検査結果は、重度視力障害の視機能レベルを定量的に示す形となり、その重症度は、視覚障害質問票を用いた生活・視覚の質評価などのパラメタと比較され、その関連が確認された。上記結果を受け、それぞれの重度視覚障害の病状・病態に対する刺激アルゴリズム・検査プロトコルの適応・有効性が示唆された。

Research Products

• [Int'l Joint Research] Seoul National University(韓国)
  • Country Name: KOREA (REP. OF KOREA)
  • Counterpart Institution: Seoul National University
• [Int'l Joint Research] Southwest Hospital/Peking union medical college hospital/Henan Eye Institute(中国)
  • Country Name: CHINA
  • Counterpart Institution: Southwest Hospital/Peking union medical college hospital/Henan Eye Institute
  • # of Other Institutions: 2
• [Int'l Joint Research] Universidad de Chile(チリ)
  • Country Name: CHILE
  • Counterpart Institution: Universidad de Chile
• [Int'l Joint Research] University College London, London(英国)
  • Country Name: UNITED KINGDOM
  • Counterpart Institution: University College London, London
• [Int'l Joint Research] ohannes Kepler University Linz/Medical University of Graz(オーストリア)
  • Country Name: AUSTRIA
  • Counterpart Institution: ohannes Kepler University Linz/Medical University of Graz
• [Int'l Joint Research]
  • # of Other Countries: 4
• [Journal Article] Prediction of causative genes in inherited retinal disorder from fundus photography and autofluorescence imaging using deep learning techniques (2021)
  • Author(s): Fujinami-Yokokawa Y, Ninomiya H, Liu X, Yang L, Pontikos N, Yoshitake K, Iwata T, Sato Y, Hashimoto T, Tsunoda K, Miyata H, Fujinami K; Japan Eye Genetics Study (JEGC) Group.
  • Journal Title: Br J Ophthalmol Volume: bjophthalmol-2020-318544 Pages: NA
  • DOI: 10.1136/bjophthalmol-2020-318544
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] KCNV2-associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints - KCNV2 Study Group Report 2 (2021)
  • Author(s): Georgiou M, Fujinami K,,..., Fujinami-Yokokawa Y, Leo SM, Liu X, Tsunoda K, Hayashi T, Jimenez-Rolando B, Martin-Merida MI, Avila-Fernandez A, Carre?o E, Garcia-Sandoval B, Carmen A, Sharon D, Kohl S, Huckfeldt RM, Boon CJF, Banin E, Pennesi ME, Wissinger B, Webster AR, H?on E, Khan AO, Zrenner E, Michaelides M.
  • Journal Title: Am J Ophthalmol Volume: S0002-9394(21) Pages: 00117-3
  • DOI: 10.1016/j.ajo.2021.03.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-term follow-up of a Chinese patient with KCNV2-retinopathy (2021)
  • Author(s): Lie H, Wang G, Liu X, Meng X, Long Y, Ren J, Yang L, Fujinami-Yokokawa Y, Kurihara T, Tsubota K, Fujinami K, Li S.
  • Journal Title: Ophthalmic Genet Volume: 42(2) Pages: 144-149
  • DOI: 10.1080/13816810.2020.1861307
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spatial Functional Characteristics of East Asian Patients With Occult Macular Dystrophy (Miyake Disease); EAOMD Report No. 2 (2021)
  • Author(s): Yang L, Joo K, Tsunoda K, Kondo M, Fujinami-Yokokawa Y, Arno G, Pontikos N, Liu X, Nakamura N, Kurihara T, Tsubota K, Iwata T, Li H, Zou X, Wu S, Sun Z, Ahn SJ, Kim MS, Mun YS, Park KH, Robson AG, Miyake Y, Woo SJ, Sui R, Fujinami K; East Asia Inherited Retinal Disease Society Study Group.
  • Journal Title: Am J Ophthalmol Volume: 221 Pages: 169-180
  • DOI: 10.1016/j.ajo.2020.07.025
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1 (2020)
  • Author(s): Georgiou M, Robson AG, Fujinami K, ..., Fujinami-Yokokawa Y, et al.
  • Journal Title: Am J Ophthalmol Volume: 225 Pages: 95-107
  • DOI: 10.1016/j.ajo.2020.11.022
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] RP2-associated retinal disorder in a Japanese cohort: Report of novel variants and a literature review, identifying a genotype-phenotype association (2020)
  • Author(s): Fujinami K, Liu X, Ueno S, Mizota A, Shinoda K, Kuniyoshi K, Fujinami-Yokokawa Y, Yang L, Arno G, Pontikos N, Kameya S, Kominami T, Terasaki H, Sakuramoto H, Nakamura N, Kurihara T, Tsubota K, Miyake Y, Yoshiake K, Iwata T, Tsunoda K; Japan Eye Genetics Consortium Study Group.
  • Journal Title: Am J Med Genet C Semin Med Genet Volume: 184(3) Pages: 675-693
  • DOI: 10.1002/ajmg.c.31830
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and genetic characteristics of Stargardt disease in a large Western China cohort: Report 1 (2020)
  • Author(s): Liu X, Meng X, Yang L, Long Y, Fujinami-Yokokawa Y, Ren J, Kurihara T, Tsubota K, Tsunoda K, Fujinami K, Li S; East Asia Inherited Retinal Disease Society Study Group.
  • Journal Title: Am J Med Genet C Semin Med Genet Volume: 184(3) Pages: 694-707
  • DOI: 10.1002/ajmg.c.31838
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and Genetic Characteristics of 15 Affected Patients From 12 Japanese Families with GUCY2D-Associated Retinal Disorder (2020)
  • Author(s): Liu X, Fujinami K, Kuniyoshi K, Kondo M, Ueno S, Hayashi T, Mochizuki K, Kameya S, Yang L, Fujinami-Yokokawa Y, Arno G, Pontikos N, Sakuramoto H, Kominami T, Terasaki H, Katagiri S, Mizobuchi K, Nakamura N, Yoshitake K, Miyake Y, Li S, Kurihara T, Tsubota K, Iwata T, Tsunoda K; Japan Eye Genetics Consortium.
  • Journal Title: Transl Vis Sci Technol Volume: 9(6) Pages: 2
  • DOI: 10.1167/tvst.9.6.2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and genetic characteristics of 10 Japanese patients with PROM1-associated retinal disorder: A report of the phenotype spectrum and a literature review in the Japanese population (2020)
  • Author(s): Fujinami K, Oishi A, Yang L, Arno G, Pontikos N, Yoshitake K, Fujinami-Yokokawa Y, Liu X, Hayashi T, Katagiri S, Mizobuchi K, Mizota A, Shinoda K, Nakamura N, Kurihara T, Tsubota K, Miyake Y, Iwata T, Tsujikawa A, Tsunoda K; Japan Eye Genetics Consortium study group.
  • Journal Title: Am J Med Genet C Semin Med Genet Volume: 184(3) Pages: 656-674
  • DOI: 10.1002/ajmg.c.31826
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and Genetic Characteristics of 18 Patients from 13 Japanese Families with CRX-associated retinal disorder: Identification of Genotype-phenotype Association (2020)
  • Author(s): Fujinami-Yokokawa Y, Fujinami K, Kuniyoshi K, Hayashi T, Ueno S, Mizota A, Shinoda K, Arno G, Pontikos N, Yang L, Liu X, Sakuramoto H, Katagiri S, Mizobuchi K, Kominami T, Terasaki H, Nakamura N, Kameya S, Yoshitake K, Miyake Y, Kurihara T, Tsubota K, Miyata H, Iwata T, Tsunoda K; Japan Eye Genetics Consortium.
  • Journal Title: Sci Rep Volume: 10(1) Pages: 9531
  • DOI: 10.1038/s41598-020-65737-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic Spectrum of EYS-associated Retinal Disease in a Large Japanese Cohort: Identification of Disease-associated Variants with Relatively High Allele Frequency (2020)
  • Author(s): Yang L, Fujinami K, Ueno S, Kuniyoshi K, Hayashi T, Kondo M, Mizota A, Naoi N, Shinoda K, Kameya S, Fujinami-Yokokawa Y, Liu X, Arno G, Pontikos N, Kominami T, Terasaki H, Sakuramoto H, Katagiri S, Mizobuchi K, Nakamura N, Mawatari G, Kurihara T, Tsubota K, Miyake Y, Yoshitake K, Iwata T, Tsunoda K; JEGC study group.
  • Journal Title: Sci Rep Volume: 10(1) Pages: 5497
  • DOI: 10.1038/s41598-020-62119-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Ethnicity of pathogenic variants in the ABCA4 gene: analysis of allele frequency in the general population. (2020)
  • Author(s): Fujinami Yokokawa Y, Naka I, Pontikos N, Arno G, Yang L, Liu X, Li S, Woo SJ, Moya R, Tsunoda K, Miyata H, Ohashi J, Strauss RQ, Scholl H, Michaelides M, Fujinami K
  • Organizer: The Association for Research in Vision and Ophthalmology (ARVO) 2020 Conference
  • Int'l Joint Research
• [Presentation] Electrically Evoked Responses Elicited by Transcorneal Electrical Stimulation in Patients with Retinitis Pigmentosa. (2020)
  • Author(s): Fujinami Yokokawa Y, Suzuki Y, Yang L, Liu X, Miyata H, Farmer J, Shinoda K, Tsunoda K, Miyake Y, Fujinami K.
  • Organizer: The 58th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
  • Int'l Joint Research
• [Presentation] Full-Field Scotopic Thresholds for Color Stimuli in patients with Retinitis Pigmentosa. (2020)
  • Author(s): Suzuki Y, Yang L, Fujinami Yokokawa Y, Liu X, Farmer J, Tsunoda K, Fujinami K
  • Organizer: The 58th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
  • Int'l Joint Research
• [Presentation] Spectrum of Occult Macular Dysfunction Syndrome (OMDS): Investigation of RP1L1-positive Occult Macular Dystrophy and RP1L1-negative OMDS; EAOMD Report 5. (2020)
  • Author(s): Yang L, Joo K, Tsunoda K, Fujinami Yokokawa Y, Pontikos N, Arno G, Kondo M, Liu Z, Kurihara T, Tsubota K, Yoshitake K, Iwata T, Yamazawa K, Zuo X, Li H, Park KH, Kim MS, Mum YS, Robson AG, Miyake Y, Woo SJ, Sui R, Fujinami K
  • Organizer: The 58th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
  • Int'l Joint Research
• [Presentation] The clinical and genetic spectrum of cone-dominated retinal dystrophies with normal funduscopic appearance (2020)
  • Author(s): Fujinami K, Ueno S, Hayashi T, Kunitoshi K, Kondo M, Mizota A, Shinoda K, Mochizuki K, Kameya S, Ideta R, Naoi N, Ikeda Y, Fujinami Yokokawa Y, et al.
  • Organizer: The 58th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
  • Int'l Joint Research
• [Presentation] Electrophysiological findings of patients with RPGR-associated retinal disorder. (2020)
  • Author(s): Nakamura N, Fujinami K, Naoi N, Ikeda Y, Hayashi T, Ueno S, Terasaki H, Kuniyoshi K, Mizota A, Shinoda K, Yang L, Fujinami Yokokawa Y, Liu X, Kominami T, Komori S, Sakuramoto H, Katagiri S, Mizobuchi K, Mawatari G, Miyake Y, Yoshitake K, Iwata K, Tsunoda K, Japan Eye Genetics Consortium study group
  • Organizer: The 58th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
  • Int'l Joint Research
• [Presentation] Oguchi disease caused by a homozygous novel SAG splicing alteration associated with the multiple evanescent white dot syndrome: A 15-month follow-up. (2020)
  • Author(s): Liu X, Gao L, Yang L, Fujinami Yokokawa Y, Wang G, Long Y, Ren J, Fujinami K, Meng X, Li S
  • Organizer: The 58th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
  • Int'l Joint Research
• [Presentation] Genotype-phenotype Association in East Asian Patients with Occult Macular Dystrophy (Miyake’s disease); EAOMD Report No.4. (2020)
  • Author(s): Fujinami Yokokawa Y, Yang L, Joo K, Tsunoda K, Kondo M, Arno G, N, Pontikos N, Liu X, Kurihara T, Tsubota K, Iwata T, Zou X, Li H, Park KH, Naka I, Ohashi J, Miyake Y, Miyata H, Woo SJ, Sui R, Fujinami K; on behalf of East Asian Inherited Retinal Disease society.
  • Organizer: The 2nd Symposium of East Asia Inherited Retinal Disease Society
  • Int'l Joint Research
• [Presentation] Spectrum of Occult Macular Dysfunction Syndrome (OMDS): Investigation of RP1L1-associated Occult Macular Dystrophy and non-RP1L1 OMDS; EAOMD Report 5. (2020)
  • Author(s): Yang L, Joo K, Liu X, Tsunoda K, Fujinami Yokokawa Y, Pontikos N, Arno G, Nakamura N, Kondo M, Kurihara T, Tsunoda K, Iwata T, Yamzawaki K, Zou X, Li H, We S, Sun Z, Ahn SJ, Kim MS, Mun YS, Park KH, Robon AG, Miyake Y, Li S, Woo SJ, Sui R, Fujinami K; EAIRDs study group.
  • Organizer: The 2nd Symposium of East Asia Inherited Retinal Disease Society
  • Int'l Joint Research
• [Presentation] Investigation of RP1L1-associated Macular Dystrophy in Southwest China. (2020)
  • Author(s): Liu X, Meng X, Yang L, Long Y, Fujinami Yokokawa Y, Ren J, Kurihara T, Tsubota K, Tsunoda K, Fujinami K, Li S; East Asia Inherited Retinal Disease Society study group.
  • Organizer: The 2nd Symposium of East Asia Inherited Retinal Disease Society
  • Int'l Joint Research
• [Presentation] Clinical and genetic characteristics of ABCA4-associated retinal disease in Japan. (2020)
  • Author(s): Fujinami K, Liu X, Mizota A, Shinoda K, Takaaki H, Kuniyoshi K, Kondo M, Ueno S, Yang L, Fujinaim-Yokokawa Y, Miyake Y, Iwata T, Tsunoda K.
  • Organizer: The 2nd Symposium of East Asia Inherited Retinal Disease Society
  • Int'l Joint Research
• [Presentation] Clinical and genetic characteristics of Stargardt disease in a large Western China cohort:report 1. (2020)
  • Author(s): Liu X, Meng H, Yang L, Long Y, Fujinami Yokokawa Y, Ren J, Kurihara T, Tsubota K, Tsunoda K, Fujinami K, Li S; East Asia Inherited Retinal Disease Society study group.
  • Organizer: The 2nd Symposium of East Asia Inherited Retinal Disease Society
  • Int'l Joint Research
• [Presentation] Genetic Spectrum of EYS-associated Retinal Disease in a Japanese Cohort: Identification of Variants with Relatively High Allele Frequency. (2020)
  • Author(s): Yang L, Fujinami K, Ueno S, Kuniyoshi K, Hayashi T, Kondo M, Mizota A, Naoi N, Shinoda K, Kameya S, Fujinami Yokokawa Y, Liu X, Arno G, Pontikos N, Kominami T, Terasaki H, Sakuramoto H, Katagiri S, Mizobuchi K, Nakamura N, Mawatari G, Kurihara T, Tsubota K, Miyake Y, Yoshitake K, Iwata T, Tsunoda K; JEGC study group.
  • Organizer: The 2nd Symposium of East Asia Inherited Retinal Disease Society
  • Int'l Joint Research
• [Presentation] Electrophysiological Findings of Japanese Patients with RPGR-associated Retinal Disorder. (2020)
  • Author(s): Yang L, Nakamura N, Fujinami K, Naoi N, Ikeda Y, Hayashi T, Ueno S, Terasaki H, Kuniyoshi K, Mizota A, Shinota K, Fujinami Yokokawa Y, Liu X, Kominami T, Komori S, Sakurai H, Katagiri S, Mizobuchi K, Mawatari G, Miyake Y, Yoshitake K, Iwata T, Tsunoda K; JEGC study group.
  • Organizer: The 2nd Symposium of East Asia Inherited Retinal Disease Society
  • Int'l Joint Research
• [Presentation] A Japanese case diagnosed with bradyopsia: clinical, electrophysiological, and genetic features. (2020)
  • Author(s): Fujinami K, Fujinami Yokokawa Y, Kondo M, Lizhu Y, Liu X, Uji Y, Iwata T, Tsunoda K
  • Organizer: The 2nd Symposium of East Asia Inherited Retinal Disease Society
  • Int'l Joint Research
• [Presentation] Clinical and genetic characteristics of USH2A-associate retinal disease in Japan. (2020)
  • Author(s): Fujinami K, Yang L, Ueno S, Kuniyoshi K, Takaaki H, Kondo M, Mizota A, Shinoda K, Naoi N, Sekiryu T, Fujinami Yokokawa Y, Liu X, Miyake Y, Iwata T, Tsunoda K; JEGC study group.
  • Organizer: The 2nd Symposium of East Asia Inherited Retinal Disease Society
  • Int'l Joint Research
• [Presentation] Ethnicity of pathogenic variants in the ABCA4 gene: analysis of allele frequency in the general population. (2020)
  • Author(s): Fujinami Yokokawa Y, Naka I, Pontikos N, Arno G, Yang L, Liu X, Li S, Woo SJ, Moya R, Tsunoda K, Miyata H, Ohashi J, Strauss RQ, Scholl H, Michaelides M, Fujinami K.
  • Organizer: The 2nd Symposium of East Asia Inherited Retinal Disease Society
  • Int'l Joint Research
• [Presentation] Spatial Functional Characteristics of East Asian Patients with Occult Macular Dystrophy (Miyake disease); EAOMD Report No.2. (2020)
  • Author(s): Yang L, Tsunoda K, Kondo M, Fujinami Yokokawa Y, Tsubota K, Iwata T, Miyake Y, Woo SJ, Sui R, Fujinami K; on behalf of East Asia Inherited Retinal Disease Society.
  • Organizer: 第68回日本視覚電気生理学会
• [Presentation] Electrophysiological characteristics of Stargardt disease in a large Western China cohort. (2020)
  • Author(s): Liu X, Meng X, Yang L, Ren J, Kurihara T, Tsubota K, Tsunoda K, Fujinami K, Li S; on behalf of East Asia Inherited Retinal Disease Society.
  • Organizer: 第68回日本視覚電気生理学会
• [Presentation] 遺伝性網膜疾患における全視野ERG を用いた自動診断支援システムの構築 (2020)
  • Author(s): 藤波（横川）優,鈴木泰賢,劉霄,楊麗珠,角田和繁,宮田裕章,藤波芳, JEGC Study Group.
  • Organizer: 第68回日本視覚電気生理学会
• [Book] 眼科診療ビジュアルラーニング5網膜，硝子体 (2020)
  • Author(s): 藤波 芳, 藤波 優, 鈴木 泰賢
  • Total Pages: 5
  • Publisher: 株式会社中山書店