Dystrophy Electrophysiology Genetics Imaging Retina

Journal

The British journal of ophthalmology
ISSN: 1468-2079
Titre abrégé: Br J Ophthalmol
Pays: England
ID NLM: 0421041

Informations de publication

Date de publication:
18 Oct 2023
Historique:
received: 27 03 2023
accepted: 15 09 2023
medline: 19 10 2023
pubmed: 19 10 2023
entrez: 18 10 2023
Statut: aheadofprint

Résumé

To investigate genotype-phenotype associations in patients with Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants. Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials.

Sections du résumé

BACKGROUND/AIMS OBJECTIVE
To investigate genotype-phenotype associations in patients with
METHODS METHODS
Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of
RESULTS RESULTS
Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants.
CONCLUSIONS CONCLUSIONS
Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials.

Identifiants

pubmed: 37852740
pii: bjo-2023-323640
doi: 10.1136/bjo-2023-323640
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: MG and MM consult for MeiraGTx. KF consults for Astellas Pharma, Kubota Pharmaceutical Holdings, Acucela, Novartis AG and Janssen Pharmaceuticals. Ester Carreño consults for Active Biotech and Alimera. EZ consults for Acucela, IVERIC bi, Janssen Pharmaceuticals, ProQR Therapeutics N.V., Gyroscope Therapeutics and Biogen MA. AV consults for Adverum Biotechnologies. MEP consults for Spark Therapeutics. Susanne Kohl consults for Novartis AG. CA consults for Novartis AG, Janssen Pharmaceuticals and Santen. The rest of the authors have no conflicts of interest to disclose.

Auteurs

Thales A C de Guimaraes (TAC)

Institute of Ophthalmology, University College London, London, UK.
Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Michalis Georgiou (M)

Institute of Ophthalmology, University College London, London, UK.
Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Anthony G Robson (AG)

Institute of Ophthalmology, University College London, London, UK.
Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Kaoru Fujinami (K)

Institute of Ophthalmology, University College London, London, UK.
Moorfields Eye Hospital NHS Foundation Trust, London, UK.
Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, Tokyo, Japan.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

Ajoy Vincent (A)

Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada.

Fadi Nasser (F)

Centre for Ophthalmology, University Hospital Tubingen Institute for Ophthalmic Research, Tubingen, Germany.

Samer Khateb (S)

Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel.

Omar A Mahroo (OA)

Institute of Ophthalmology, University College London, London, UK.
Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Nikolas Pontikos (N)

Institute of Ophthalmology, University College London, London, UK.
Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Maurício E Vargas (ME)

Genetic Eye Therapies, Ventura, California, USA.

Alberta A H J Thiadens (AAHJ)

Department of Opthalmology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.

Emanuel R de Carvalho (ER)

Institute of Ophthalmology, University College London, London, UK.
Department of Ophthalmology, Amsterdam University Medical Centres, Amsterdam, The Netherlands.

Xuan-Than-An Nguyen (XT)

Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.

Gavin Arno (G)

Institute of Ophthalmology, University College London, London, UK.
Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Yu Fujinami-Yokokawa (Y)

Institute of Ophthalmology, University College London, London, UK.
Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, Tokyo, Japan.
Department of Health Policy and Management, Keio University School of Medicine, Tokyo, Japan.

Xiao Liu (X)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, Tokyo, Japan.

Kazushige Tsunoda (K)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, Tokyo, Japan.

Takaaki Hayashi (T)

Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.

Belén Jiménez-Rolando (B)

Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Spain.

Maria Inmaculada Martin-Merida (MI)

Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Spain.
Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.

Almudena Avila-Fernandez (A)

Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Spain.
Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.

Ester Carreño Salas (EC)

Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Spain.

Blanca Garcia-Sandoval (B)

Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Spain.

Carmen Ayuso (C)

Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Spain.
Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.

Dror Sharon (D)

Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel.

Susanne Kohl (S)

Centre for Ophthalmology, University Hospital Tubingen Institute for Ophthalmic Research, Tubingen, Germany.

Rachel M Huckfeldt (RM)

Department of Ophthalmology, Massachusetts Eye and Ear, Harvard, Massachusetts, USA.

Eyal Banin (E)

Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel.

Mark E Pennesi (ME)

Department of Ophthalmology, Oregon Health & Science University - Casey Eye Institute, Portland, Oregon, USA.

Arif O Khan (AO)

Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.
Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.

Bernd Wissinger (B)

Centre for Ophthalmology, University Hospital Tubingen Institute for Ophthalmic Research, Tubingen, Germany.

Andrew R Webster (AR)

Institute of Ophthalmology, University College London, London, UK.
Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Elise Heon (E)

Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada.

Camiel J F Boon (CJF)

Department of Ophthalmology, Amsterdam University Medical Centres, Amsterdam, The Netherlands.
Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.

Eberhard Zrenner (E)

Centre for Ophthalmology, University Hospital Tubingen Institute for Ophthalmic Research, Tubingen, Germany.

Michel Michaelides (M)

Institute of Ophthalmology, University College London, London, UK michel.michaelides@ucl.ac.uk.
Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Classifications MeSH