KCNV2 -associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3.

Autor:	de Guimaraes TAC; Institute of Ophthalmology, University College London, London, UK.; Moorfields Eye Hospital NHS Foundation Trust, London, UK., Georgiou M; Institute of Ophthalmology, University College London, London, UK.; Moorfields Eye Hospital NHS Foundation Trust, London, UK., Robson AG; Institute of Ophthalmology, University College London, London, UK.; Moorfields Eye Hospital NHS Foundation Trust, London, UK., 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., Vincent A; Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada., Nasser F; Centre for Ophthalmology, University Hospital Tubingen Institute for Ophthalmic Research, Tubingen, Germany., Khateb S; Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel., Mahroo OA; Institute of Ophthalmology, University College London, London, UK.; Moorfields Eye Hospital NHS Foundation Trust, London, UK., Pontikos N; Institute of Ophthalmology, University College London, London, UK.; Moorfields Eye Hospital NHS Foundation Trust, London, UK., Vargas ME; Genetic Eye Therapies, Ventura, California, USA., Thiadens AAHJ; Department of Opthalmology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands., Carvalho ER; Institute of Ophthalmology, University College London, London, UK.; Department of Ophthalmology, Amsterdam University Medical Centres, Amsterdam, The Netherlands., Nguyen XT; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands., Arno G; Institute of Ophthalmology, University College London, London, UK.; Moorfields Eye Hospital NHS Foundation Trust, London, UK., 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., Liu X; Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, Tokyo, Japan., Tsunoda K; Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, Tokyo, Japan., Hayashi T; Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan., Jiménez-Rolando B; Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Spain., 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., 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., Salas EC; Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Spain., Garcia-Sandoval B; Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Spain., Ayuso C; Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Spain.; Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain., Sharon D; Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel., Kohl S; Centre for Ophthalmology, University Hospital Tubingen Institute for Ophthalmic Research, Tubingen, Germany., Huckfeldt RM; Department of Ophthalmology, Massachusetts Eye and Ear, Harvard, Massachusetts, USA., Banin E; Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel., Pennesi ME; Department of Ophthalmology, Oregon Health & Science University - Casey Eye Institute, Portland, Oregon, USA., 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., Wissinger B; Centre for Ophthalmology, University Hospital Tubingen Institute for Ophthalmic Research, Tubingen, Germany., Webster AR; Institute of Ophthalmology, University College London, London, UK.; Moorfields Eye Hospital NHS Foundation Trust, London, UK., Heon E; Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada., Boon CJF; Department of Ophthalmology, Amsterdam University Medical Centres, Amsterdam, The Netherlands.; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands., Zrenner E; Centre for Ophthalmology, University Hospital Tubingen Institute for Ophthalmic Research, Tubingen, Germany., Michaelides M; Institute of Ophthalmology, University College London, London, UK michel.michaelides@ucl.ac.uk.; Moorfields Eye Hospital NHS Foundation Trust, London, UK.
Jazyk:	angličtina
Zdroj:	The British journal of ophthalmology [Br J Ophthalmol] 2024 Jul 23; Vol. 108 (8), pp. 1137-1144. Date of Electronic Publication: 2024 Jul 23.
DOI:	10.1136/bjo-2023-323640
Abstrakt:	Background/aims: To investigate genotype-phenotype associations in patients with KCNV2 retinopathy. 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 KCNV2 variants-two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)-and parameters were compared. 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: 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. Competing Interests: 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. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
Databáze:	MEDLINE
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