Investigation of clinical and molecular genetic characteristics of inherited macular diseases for treatment approach

• Project/Area Number: 25861662
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• 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: FUJINAMI Kaoru 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), 視覚生理学研究室, 研究員 (60646206)
• Research Collaborator: TSUNODA Kazushige ; IWATA Takeshi ; AKAHORI Masakazu ; MIYAKE Yozo ; KONDO Mineo ; ANDREW Webster ; MOORE Anthony
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 遺伝性網膜疾患 / 黄斑部遺伝性疾患 / 眼遺伝学

Outline of Final Research Achievements

We studied the clinical and molecular genetic characteristics of inherited macular diseases for treatment approaches. The cohort established till March of 2015 included 167 subjects from 143 families; occult macular dystrophy (64 families), cone (-rod) dystrophy (42), Stargardt disease (34), and Best disease (3). Genetic diagnosis was obtained in 29 families; 17 families with RP1L1, 3 with ABCA4, 2 with BEST1, 2 with GUCA1A, 2 with GUCY2D, 1 with ADAMTS18, 1 with PDE6C, and 1 with RPGR. In the two subsets with RP1L1-related retinal disease and ABCA4-related retinal disease, the genotype-phenotype association was studied. There was no significant association between disease severity and types of mutations in RP1L1-related retinal disease. A significant genotype-phenotype association was revealed in ABCA4-related retinal disease in collaboration with a British team, suggesting the treatment approaches are recommended for such patients.

Research Products

• [Journal Article] Clinical and Molecular Characteristics of Childhood-onset Stargardt Disease. (2015)
  • Author(s): Fujinami K, Jana Zernant, Ravinder K Chana, Genevieve A Wright, Tsunoda K, Ozawa Y, Tsubota K, Anthony G Robson, Graham E Holder, Rando Allikmets, Michel Michaelides, FACS; Anthony T Moore.
  • Journal Title: Ophthalmology. Volume: 122 Issue: 2 Pages: 326-334
  • DOI: 10.1016/j.ophtha.2014.08.012
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Longitudinal Follow-up of Siblings with a Discordant Stargardt Disease Phenotype. (2014)
  • Author(s): Singh R, Fujinami K, Chen LL, Michaelides M, Moore AT.
  • Journal Title: Acta Ophthalmol. Volume: 92 Issue: 4
  • DOI: 10.1111/aos.12280
  • Peer Reviewed
• [Journal Article] Fundus auofluorescence imaging in patient with juvenile form of galactosialidosis (2014)
  • Author(s): Yamazaki R, Tsunoda K, Fujinami K, Noda T et al.
  • Journal Title: Ophthalmic Surgery Lasers & Imaging Retina Volume: in press Issue: 3 Pages: 259-61
  • DOI: 10.3928/23258160-20140425-01
  • Peer Reviewed
• [Journal Article] Branch Retinal Artery Occlusion Secondary to Prepapillary Arterial Loop. (2014)
  • Author(s): Singh R, Fujinami K, Moore AT
  • Journal Title: Retin Cases Brief Rep. Volume: 8 Issue: 2 Pages: 124-6
  • DOI: 10.1097/icb.0000000000000020
  • Peer Reviewed
• [Journal Article] Clinical course of focal choroidal excavation in Vogt-Koyanagi-Harada disease. (2014)
  • Author(s): Nishikawa Y, Fujinami K, Watanabe K, Noda T, Tsunoda K, Akiyama K.
  • Journal Title: Clin Ophthalmol. Volume: 8 Pages: 2461-5
  • DOI: 10.2147/opth.s75558
  • Peer Reviewed
• [Journal Article] Clinical and molecular analysis of Stargardt disease with preserved foveal structure and function (2013)
  • Author(s): Fujinami K, Sergouniotis PI, Tsunoda K, et al
  • Journal Title: Am J Ophthalmol Volume: 156(3) Issue: 3 Pages: 487-501
  • DOI: 10.1016/j.ajo.2013.05.003
  • Peer Reviewed
• [Journal Article] Molecular characteristics of four Japanese cases with KCNV2 retinopathy: Report of novel disease-causing variants (2013)
  • Author(s): Kaoru Fujinami, Kazushige Tsunoda, Natsuko Nakamura, Yu Kato, Toru Noda, Kei Shinoda, Kaoru Tomita, Tetsuhisa Hatase, Tomoaki Usui, Masakazu Akahori, Takeshi Itabashi, Takeshi Iwata, Yoko Ozawa, Kazuo Tsubota, Yozo Miyake
  • Journal Title: Molecular Vision Volume: 19 Pages: 1580-1590
  • Peer Reviewed
• [Journal Article] ABCA4 Gene Screening by Next-Generation Sequencing in a British Cohort (2013)
  • Author(s): Fujinami K, Zernant J, Tsunoda K et al.
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 54(10) Issue: 10 Pages: 6662-74
  • DOI: 10.1167/iovs.13-12570
  • Peer Reviewed
• [Presentation] Stargardt Disease with Foveal Sparing Phenotype. (2015)
  • Author(s): Fujinami K.
  • Organizer: Asia-ARVO 2015
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2015-02-16 – 2015-02-19
  • Invited
• [Presentation] 加齢性黄斑変性症の再発予測における網膜色素上皮下病変測定の有用 性． (2014)
  • Author(s): 加藤悠、佐々木真理子、平形寿彬、藤波芳、渡辺健、秋山邦彦、 角田和繁、野田徹．
  • Organizer: 第 68 回日本臨床眼科学会
  • Place of Presentation: 神戸
  • Year and Date: 2014-11-13 – 2014-11-16
• [Presentation] 簡易型フリッカー網膜電位計（レチバル）による錐体機能評価. (2014)
  • Author(s): 中村奈津子、藤波芳、水野嘉信、野田徹、角田和繁.
  • Organizer: 第 68 回日本臨床眼科学会
  • Place of Presentation: 神戸
  • Year and Date: 2014-11-13 – 2014-11-16
• [Presentation] 滲出型加齢黄斑変性に対するアフリベルセプト硝子体内注射の 1 年成 績. (2014)
  • Author(s): 平形寿彬、加藤悠、藤波芳、渡辺健、秋山邦彦、角田和繁、野田徹、 佐々木真理子.
  • Organizer: 第 68 回日本臨床眼科学会
  • Place of Presentation: 神戸
  • Year and Date: 2014-11-13 – 2014-11-16
• [Presentation] GUCY2D 遺伝子変異を伴う錐体杆体ジストロフィーの 2 例 (2014)
  • Author(s): 中村奈津子、藤波芳、野田徹、岩田岳、角田和繁.
  • Organizer: 第 62 回日本臨床視覚電気生理学会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] 黄斑分離の自然消失と伴に改善を認めた黄斑部局所律動様小波. (2014)
  • Author(s): 平形寿彬、藤波芳、中村奈津子、加藤悠、福井正樹、野田徹、角田和繁、 三宅養三
  • Organizer: 第 62 回日本臨床視覚電気生理学会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] 中心窩機能温存型黄斑ジストロフィ. (2014)
  • Author(s): 藤波芳、後藤総、赤堀正和、小沢洋子、坪田一男、野田徹、岩田岳、三 宅養三、角田和繁.
  • Organizer: 第 62 回日本臨床視覚電気生理学会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] ABCA4-related retinal disorder -up to date (2014)
  • Author(s): Fujinami K.
  • Organizer: Genetic Conference, Edward Howkins Institute, Columbia University
  • Place of Presentation: New York, NY, U.S.A.
  • Year and Date: 2014-07-29
  • Invited
• [Presentation] Novel Funduscopic Features in Oguchi’s Disease; Relationship between Retinal Arteries and Golden Metallic Refrex (2014)
  • Author(s): Kato Y, Tsunoda K, Fujinami K, Noda T, Oguchi Y
  • Organizer: The International Society of Clinical Electrophysiology and Vision (ISCEV), 52nd International Symposium
  • Place of Presentation: Boston, Massachusetts U.S.A.
  • Year and Date: 2014-07-20 – 2014-07-24
• [Presentation] Unilateral Cone-rod Dysfunction associated with Electronegative bright flash Electroretinography. (2014)
  • Author(s): Hirakata T, Fujinami K, Kato Y, Nakamura N, Noda T, Hirakata A, Ueno S, Ohguro H, Miyake Y, Tsunoda K.
  • Organizer: The International Society of Clinical Electrophysiology and Vision (ISCEV), 52nd International Symposium
  • Place of Presentation: Boston, Massachusetts U.S.A.
  • Year and Date: 2014-07-20 – 2014-07-24
• [Presentation] Clinical and Genetic Characteristics of Childhood-onset Stargardt Disease. (2014)
  • Author(s): Fujinami K, Zernant J, Robson AG, Tsunoda K, Ozawa Y, Tsubota K, Allikmets R, Michaelides M, Moore AT, Holder GE.
  • Organizer: The International Society of Clinical Electrophysiology and Vision (ISCEV), 52nd International Symposium
  • Place of Presentation: Boston, Massachusetts U.S.A.
  • Year and Date: 2014-07-20 – 2014-07-24
• [Presentation] 黄斑ジストロフィ～機能・構造異常からみる病態生理～ (2014)
  • Author(s): 藤波芳
  • Organizer: 第 3 回日本視野学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-06-28 – 2014-06-29
  • Invited
• [Presentation] A Case of Occult Macular Dystrophy with Foveal Detachment by Vitreomacular Traction (2014)
  • Author(s): Kato Y, Fujinami K, Noda T, Akahori M, Iwata T, Miyake Y, Tsunoda K.
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
  • Place of Presentation: Orlando, Florida, U.S.A
  • Year and Date: 2014-05-03 – 2014-05-07
• [Presentation] Efficacy of Aflibercept in Japanese Patients with Neovascular Age-related Macular Degeneration and Poor Response to Ranibizumab. (2014)
  • Author(s): Hirakata T, Nishikawa Y, Fujinami K, Watanabe K, Tsunoda K, Noda T, Akiyama K.
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
  • Place of Presentation: Orlando, Florida, U.S.A
  • Year and Date: 2014-05-03 – 2014-05-07
• [Presentation] Clinical and Genetic Characteristics of Childhood-onset Stargardt Disease. (2014)
  • Author(s): Fujinami K, Zernant J, Ozawa Y, Tsubota K, Robson AG, Holder GE, Webster AR, Allikmets R, Michaelides M, Moore AT
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
  • Place of Presentation: Orlando, Florida, U.S.A
  • Year and Date: 2014-05-03 – 2014-05-07
• [Presentation] Fundus Manifestations of Hereditary Hemorrhagic Telangiectasia (2014)
  • Author(s): Kato Y, Fujinami K, Noda T, Miyake Y, Tsunoda K.
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2014-04-02 – 2014-04-06
• [Presentation] Case report of Monocular rod-cone dystrophy, which suspected Melanoma associated retinopathy (2014)
  • Author(s): Hirakata T, Fujinami K, Tsunoda K, Hirakata A, Miyake Y.
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2014-04-02 – 2014-04-06
• [Presentation] Choroidal Excavation in Vogt-Koyanagi-Harada Disease. (2014)
  • Author(s): Nishikawa Y, Fujinami K, Watanabe K, Akiyama K, Noda T
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2014-04-02 – 2014-04-06
• [Presentation] Siblings with Childhood-Onset Stargardt Disease Associated with External Limiting Membrane Thickening. (2014)
  • Author(s): Iehisa I, Fujinami K, Nakamura N, Noda T, Tsunoda K
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2014-04-02 – 2014-04-06
• [Presentation] A Longitudinal Study of Stargardt Disease: Quantitative Assessment of Fundus Autofluorescence, Progression and Genotype Correlations. (2013)
  • Author(s): Fujinami K, Lois N, Mukhopadhyay R, McBain, VA, Tsunoda K, Tsubota K, Fitzke FW, Moore AT, Webster AR, Michaelides M.
  • Organizer: The Association for Research in Vision and Ophthalmology (ARVO) annual meeting 2013
  • Place of Presentation: Seattle, USA
• [Presentation] Clinical and Molecular Findings in Japanese Cases with KCNV2- retinopathy: Report of Novel Variants. (2013)
  • Author(s): Kato Y, Fujinami K, Nakamura N, Akahori M, Iwata T, Tsunoda K
  • Organizer: The Association for Research in Vision and Ophthalmology (ARVO) annual meeting 2013
  • Place of Presentation: Seattle, USA
• [Presentation] Clinical and Molecular Analysis of Stargardt Disease with Preserved Foveal Structure and Function. (2013)
  • Author(s): Fujinami K, Sergouniotis PI, Tsunoda K, Tsubota K, Robson AG, Moore AT, Michaelides M, Webster AR, Holder GE.
  • Organizer: International Society for Clinical Electrophysiology of Vision (ISCEV) symposium 2013
  • Place of Presentation: Chongqing, China
• [Presentation] Clinical and Molecular Analysis of Macular Dystrophy with Preserved Foveal Structure and Function. (2013)
  • Author(s): Goto S, Fujinami K, Akahori M, Iwata T, Noda T, Miyake Y, Tsunoda K.
  • Organizer: International Society for Clinical Electrophysiology of Vision (ISCEV) symposium 2013
  • Place of Presentation: Chongqing, China
• [Presentation] Genotype-phenotype correlations in Inherited Retinal Disease (2013)
  • Author(s): Kaoru Fujinami
  • Organizer: Retina updated meeting
  • Place of Presentation: Chongqing, China.
  • Invited
• [Presentation] Phenotype and Genotype of Stargardt Disease -updated- (2013)
  • Author(s): Kaoru Fujinami
  • Organizer: Ophthalmic Genetics Conference
  • Place of Presentation: Ljubljana, Slovenia
  • Invited
• [Presentation] Genotype-Phenotype Correlation in Macular Dystrophy (2013)
  • Author(s): Kaoru Fujinami
  • Organizer: Electrophysiology Course
  • Place of Presentation: Pavia, Italy
  • Invited
• [Presentation] Genotype-Phenotype Correlation in Inherited Retinal Disease (2013)
  • Author(s): Kaoru Fujinami
  • Organizer: Medical Retina Meeting
  • Place of Presentation: Monza, Italy
  • Invited
• [Book] 新版 どうとる？どう読む？ERG IV どう読む？/先天性疾患 錐体（杆体）ジストロフィ (2015)
  • Author(s): 藤波芳、中村奈津子.
  • Publisher: メジカルビュー社
• [Book] 新版 どうとる？どう読む？ERG IV どう読む？/先天性疾患 Stargardt 病（ABCA4-related retinal disease） (2015)
  • Author(s): 藤波芳.
  • Publisher: メジカルビュー社
• [Book] 眼科 57(4) 硝子体・網膜病変の診かた－私はこう診る－/ 1.症状と鑑別診断 5)羞 明・昼盲の鑑別疾患. (2015)
  • Author(s): 藤波芳
  • Publisher: 金原出版株式会社
• [Book] 眼科 57(4) 硝子体・網膜病変の診かた－私はこう診る－/ 3.所見と病態 3)Stargardt 病 (2015)
  • Author(s): 藤波芳
  • Publisher: 金原出版株式会社
• [Book] 眼科 56(4) 電気生理学的検査 黄斑部局所 ERG. (2014)
  • Author(s): 藤波芳
  • Publisher: 金原出版株式会社
• [Book] 眼科 56(5) 【眼と遺伝】黄斑ジストロフィ(三宅病を含めて). (2014)
  • Author(s): 角田和繁、藤波芳.
  • Publisher: 金原出版株式会社