Tokyo Medical Center | Fujinamilab

Japanese / 日本語

National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center
National Institute of Sensory Organs
Since 2003, it has been established as a highly specialized medical facility for sensory organ diseases (Sensory Organ Centre), including clinical medical research, basic medical research and policy medicine.

We have been treating and researching intractable diseases such as hereditary retinal diseases, hereditary deafness and congenital visual and auditory double disorders.

National Hospital Organization, Tokyo Medical Center

Division of Vision Research

Section chief　Kazushige Tsunoda

Laboratory of Visual Physiology/Ophthalmic Genetics　（Laboratory head：Kaoru Fujinami）

Laboratory of Low Vision（Laboratory head：Toru Noda）

Laboratory of Ophthalmic Epidemiology （Laboratory head ： Kazushige Tsunoda）

Ophthalmology Clinic

Chief Medical Officer：Toru Noda

Medical Director：Kunihiko Akiyama

(1)　Outpatient of Vitreous Retina（Kunihiko Akiyama・Ken Watanabe・Takaaki Matsuki）

(2)　Outpatient of Macular Transformation（Mariko Sasaki）

(3)　Outpatient of Retinal degeneration（Kazushige Tsunoda・Kaoru Fujinami・Natsuko Nakamura（Part-time））

(4)　Outpatient of Cornea（Shota Fujii）

(5)　Excimer laser surgery・Outpatient of Refractive correction（Shota Fujii、Kazuno Negishi・Kenji Ono・Masateru Iwanami（Part-time））

(6)　Outpatient of Green cataracts（Asako Naruo）

(7)　Outpatient of Ophthalmic Formation Surgery（Katsuhiko Kuwahara（Part-time））

(8)　Laboratory of Low Vision（Yoshiko Ogawa、Junko Nomura（Visual Trainer））

Laboratory of Visual Physiology/Ophthalmic Genetics

Laboratory Head　Kaoru Fujinami

1998-2004 Nagoya University Faculty of Medicine, Department of Medicine

2004-2006 Nagoya First Red Cross Hospital, Aichi, Japan

2006-2009 Tokyo Medical Center　Ophthalmology Resident
（Paediatric training：Seiiku Medial Center）

2009-2013 Moorfields Eye Hospital, London, UK （Clinical Fellow）

University College London, London, UK （assistant）

2013-2016 Tokyo Medical Center Retina team・Keio University Collaborative Graduate School (RCB)

2016-2017 Moorfields Eye Hospital・Institute of Ophthalmology, University of London Genetics Senior Researcher

2017- 　Tokyo Medical Center・National Institute of Sensory Organs　Laboratory of Visual Physiology/Ophthalmic Genetics　

LLaboratory head

＜concurrent post＞

2016- Keio University　Ophthalmology Classroom　Part-time lecturer

2018- Moorfields Eye Hospital　Division of Inherited Retinal Diseases　Visiting Adviser

2020- University College LondonInstitute of Ophthalmology　Genetics　Visiting Professor

Laboratory of Visual Physiology/Ophthalmic Genetics　

Since 2017, Dr. Kaoru Fujinami has been a head of the laboratory, and he is working to elucidate the pathogenesis and introduce treatment for hereditary retinal diseases by using various research methods such as electrophysiology, clinical genetics, genetic biology and clinical epidemiology.
In order to apply the results of his research to clinical practice, he will open an outpatient clinic specialising in the treatment of hereditary retinal diseases (Ophthalmology: Outpatient Clinic for Hereditary Ophthalmic Diseases, Clinical Genetics Centre: Outpatient Clinic for Hereditary Retinal Diseases) in 2020.
We are promoting translational basic and clinical research by introducing the latest technology from an international perspective in order to realize the evaluation and development of various diseases and the introduction of treatment, including the launch of gene replacement therapy as a part of personalized medicine for hereditary retinal diseases ahead of other Asian countries.

AI　LAB

-National Hospital Artificial Intelligence Diagnostic Support Centre
（laboratory① in front of Institutional Headquarters 2018-）

Ophthalmic genetics lab

-Genotyping and Phenotyping Laboratory（６F Laboratory①、2017-）

-Retinal Electrophysiology Laboratory（６F Laboratory②、Darkroom、2017-）

Novel therapies

-Centre for the introduction of new treatments①（６F Laboratory②、受託Laboratory・治験対応、2017-）

-Centre for the introduction of new treatments②（Hospital ward３rd floor Electrophysiology room
Commissioned Research・Clinical Trial Support、2020-）

-Ophthalmology Gene Therapy Centre（７th floor Laboratory①②
Commissioned Research・Clinical Trial Support、2021-）

AI　LAB

-National Hospitals Artificial Intelligence Diagnostic Support Centre
（in front of Institutional Headquarters①、2018-）

The National Hospital Organization network is being used to its full potential to create an ophthalmic care support system.
The system is based on the application of machine diagnosis using artificial intelligence (AI).

For the construction of the application, the medical information platform to be established

in the Department of Health Policy and Management of Keio University will be the basis for the solution

to the problems of mechanical remote diagnosis, medical information integration and individualisation

of medical care.

Ophthalmic genetics lab

In Japan, with the support of the AMED Research for Practical Application of Intractable Diseases, we are collaborating with the Laboratory of Molecular and Cellular Biology (Dr. Iwata, Director) on a large cohort study using a joint database with 38 institutions in Japan.

The UK-Japan collaborative study is ongoing, with the UK (UCL institute of Ophthalmology) playing a central role. The UK-Japan collaborative study is continuing vigorously, with the UK (UCL institute of Ophthalmology) playing a central role in the establishment of an international consortium of 27 countries on 6 continents.

-Genotyping and Phenotyping Laboratory（６F Laboratory①、2017-）

We are responsible for a wide range of services from diagnosis to genetic analysis, including patient data and specimen storage, as follows.

・Clinical diagnosis (including electrophysiological assessment)

　It maintains data on family history, visual acuity, fundus photographs, OCT examinations, visual fields, full-field ERG, multifocal ERG and focal macular ERG.

・Sample collection (peripheral blood/saliva/RNA)

　Maintains peripheral blood (and in some cases saliva samples) and other biological material obtained from patients.

・DNA extraction (in house/subcontracting)

For urgent cases, the extraction is done in-house, but for quality assurance, the extraction is done at SRL/BML/Kazusa DNA Laboratory. gDNA (UK, Korea, Chile, Australia, Kenya) and other samples are managed and the quality of the DNA is controlled.

・Quality check (in house/companies)

Quality control is outsourced, but can also be carried out in-house.

・Sequencing (in house/subcontracting)

Whole exome sequencing(WES)、Whole genome sequencing(WGS)、Target sequencing (35 genes panel)、Microarray SNP6、Direct sequencing、custumized sequencing

・Pipeline analysis (in house/phenopolis)

WES, WGS (Iwata Lab, Phenopolis)、WES, WGS original pipeline (Illumina Dragen, in house)、ABI SNP6 data analysis software、Merged data browser

・Variant detection (in house/subcontracting)

Pathogenisity confirmation Custom filtration

・Familial segregation (in house/subcontracting)

Single site analysis (outsourced)、Direct sequencing（Some are outsourced）

-Retinal Electrophysiology Laboratory（６F Laboratory②、Darkroom2017-）

Electrophysiological tests for deep phenotyping are carried out.

The electrodes used are mainly DTL electrodes and rarely skin electrodes, with the aim of reducing patient burden.

The tests detailed below are selected according to the medical condition and individualised tests are selected.

All ISCEV Extended ERG Protocols
Red Flash ERG
Multi Focal ERG
Pattern ERG
Photopic negativeresponse
Pattern VEP
Flash VEP
EER
EOG
Pupillometry
FST

Novel therapies lab

In recent years there has been a rapid increase in the development of gene therapy and we have started to choice a treatment based on the mechanism or the stage of disease.

Drug therapy, gene therapy (supplementation, editing and transduction), RNA therapy, compound therapy, electrical retinal stimulation, artificial retina transplantation and regenerative cell transplantation are being investigated for the treatment of inherited retinal diseases.

Many of these therapies have reached the clinical trial stage in the world, and we are greatly expected to start pioneering therapies in Asia.

In the Novel therapies lab, research and clinical trials for novel therapies are being conducted under contract to pharmaceutical companies from Japan and overseas.

-Centre for the introduction of new treatments①（６F laboratory②、outsoursed research・Clinical Trial Support、2017-）

-Centre for the introduction of new treatments②（Hospital ward３F Electrophysiology room outsoursed research・Clinical Trial Support 2020-）

-Ophthalmology Gene Therapy Centre（７F Laboratory①②、outsoursed research・Clinical Trial Support 2021-）

・Clinical Trial

Phase　０

・Development of a comprehensive visual function assessment method

for people with severe visual impairment

（https://www.clinicaltrials.gov/ct2/show/NCT03281005）

Phase　３

An unshielded single-arm study to determine the efficacy and safety

of subretinal injection of voretigene neparvovec in Japanese patients

with hereditary retinal dystrophy due to bilateral allelic RPE65 mutations.

Study of Efficacy and Safety of Voretigene Neparvovec in Japanese

Patients With Biallelic RPE65 Mutation-associated Retinal Dystrophy.

https://clinicaltrials.gov/ (NCT04516369)

The process from diagnosis to treatment

Clinical diagnosisA multidisciplinary ophthalmological examination including optical coherence tomography (OCT), full-field light threshold test (FST), electrophysiological tests and consultation with an ophthalmologist are carried out here.
If the patient agrees to proceed the next process, with genetic counselling, gene finding for clinical diagnosis or research purposes is considered.
Comprehensive gene searchPathogenicity interpretation is carried out here for IRD-related genes. If possible, parents and relatives are tested in parallel.
Genetic diagnosis in expert panelsGenetic diagnosis in expert panels is proceeded based on The American College of Medical Genetics and Genomics (ACMG) guidelines. In some cases, the ClinGENE evidence score will also be considered.
Introduction to therapeutic trialsOn the basis of the results of the genotypic phenotyping, the indication for a therapeutic trial is discussed and a detailed explanation of the trial is given by the ophthalmic geneticist, clinical trial coordinator and genomic medical research coordinator.
After obtaining the patient's consent, tests and interventional treatments will be carried out according to the trial protocol.
Determination of treatment efficacy
The treatment is evaluated according to the clinical trial protocol, an that time, an additional functional tests are carried out as the situation demands to assess safety and efficacy and to verify the most appropriate endpoints.