Abstract
Original language | English |
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Pages (from-to) | 1-11 |
Number of pages | 11 |
Journal | American Journal of Ophthalmology |
Volume | 230 |
DOIs | |
Publication status | Published - 1 Oct 2021 |
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In: American Journal of Ophthalmology, Vol. 230, 01.10.2021, p. 1-11.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - KCNV2-Associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints—KCNV2 Study Group Report 2
AU - Georgiou, Michalis
AU - Fujinami, Kaoru
AU - Vincent, Ajoy
AU - Nasser, Fadi
AU - Khateb, Samer
AU - Vargas, Mauricio E.
AU - Thiadens, Alberta A. H. J.
AU - de Carvalho, Emanuel R.
AU - Nguyen, Xuan-Thanh-An
AU - de Guimarães, Thales Antônio Cabral
AU - Robson, Anthony G.
AU - Mahroo, Omar A.
AU - Pontikos, Nikolas
AU - Arno, Gavin
AU - Fujinami-Yokokawa, Yu
AU - Leo, Shaun Michael
AU - Liu, Xiao
AU - Tsunoda, Kazushige
AU - Hayashi, Takaaki
AU - Jimenez-Rolando, Belen
AU - Martin-Merida, Maria Inmaculada
AU - Avila-Fernandez, Almudena
AU - Carreño, Ester
AU - Garcia-Sandoval, Blanca
AU - Ayuso, Carmen
AU - Sharon, Dror
AU - Kohl, Susanne
AU - Huckfeldt, Rachel M.
AU - Boon, Camiel J. F.
AU - Banin, Eyal
AU - Pennesi, Mark E.
AU - Wissinger, Bernd
AU - Webster, Andrew R.
AU - Héon, Elise
AU - Khan, Arif O.
AU - Zrenner, Eberhart
AU - Michaelides, Michel
N1 - Funding Information: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Funding/Support: M.G. is supported by the Onassis Foundation and Leventis Foundation. M.M., A.R.W., O.A.M., and A.G.R. are supported by grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, and Moorfields Eye Charity. M.M. is supported by The Wellcome Trust (099173/Z/12/Z), Retina UK, and the Foundation Fighting Blindness (FFB, USA). N.P. is supported by a Moorfields Eye Charity Career Development Award (R190031A). G.A. is supported by a Fight for Sight (United Kingdom) Early Career Investigator Award (5045/46). O.A.M. is supported by The Wellcome Trust (206619/Z/17/Z). M.P. is supported by an unrestricted grant from Research to Prevent Blindness to Casey Eye Institute, and NIH P30EY010572. A.C. is supported by the Instituto de Salud Carlos III (ISCIII) from the Spanish Ministry of Health FIS (PI16/00425), FIS (PI19/00321); the regional government of Madrid RAREGenomics-CM (CAM, B2017/BMD-3721); the Spanish National Organization of the Blind (ONCE); and the Ramon Areces Foundation. This work was supported by a grant from the Foundation Fighting Blindness USA (BR-GE-0214-0639-TECH) to D.S. and E.B. R.M.H. is supported by an FFB Career Development Award (CD-CMM-0918-0747-MEEI). This work was also supported by the Excellence Program of the German Government (DFG EXC 307, Center for Integrative Science) to E.Z.; the Tistou and Charlotte Kerstan Foundation to Fadi Nasser; and the German Research Council (DFG, KFO134) and the German Ministry of Education and Research (01GM0850) to B.W. A.V. is supported by the Foundation Fighting Blindness (USA; CD-CL-0617-0727-HSC). E.H. is supported by Henry Brent Chair and Fighting Blindness Canada. The views expressed are those of the authors and not the funding organizations. Financial Disclosures: M.G. and M.M. consult for MeiraGTx. K.F. consults for Astellas Pharma Inc, Kubota Pharmaceutical Holdings Co, Ltd, Acucela Inc, Novartis AG, and Janssen Pharmaceuticals. E. C. consults for AbbVie and Alimera. E.Z. consults for Acucela Inc, IVERIC bio Inc, Janssen Pharmaceuticals, ProQR Therapeutics N.V., Gyroscope Therapeutics Ltd, and Biogen MA Inc. A.V. consults for Adverum Biotechnologies Inc. M.E.P. consults for Spark Therapeutics. S.K. consults for Novartis AG. The rest of the authors have no conflicts of interest to disclose. All authors attest that they meet the current ICMJE criteria for authorship. Funding Information: Acknowledgment: M.M. E.Z. S.K, and C.B. are members of the European Reference Network for Rare Eye Diseases (ERN-EYE). All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Funding/Support: M.G. is supported by the Onassis Foundation and Leventis Foundation. M.M. A.R.W. O.A.M. and A.G.R. are supported by grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, and Moorfields Eye Charity. M.M. is supported by The Wellcome Trust (099173/Z/12/Z), Retina UK, and the Foundation Fighting Blindness (FFB, USA). N.P. is supported by a Moorfields Eye Charity Career Development Award (R190031A). G.A. is supported by a Fight for Sight (United Kingdom) Early Career Investigator Award (5045/46). O.A.M. is supported by The Wellcome Trust (206619/Z/17/Z). M.P. is supported by an unrestricted grant from Research to Prevent Blindness to Casey Eye Institute, and NIH P30EY010572. A.C. is supported by the Instituto de Salud Carlos III (ISCIII) from the Spanish Ministry of Health FIS (PI16/00425), FIS (PI19/00321); the regional government of Madrid RAREGenomics-CM (CAM, B2017/BMD-3721); the Spanish National Organization of the Blind (ONCE); and the Ramon Areces Foundation. This work was supported by a grant from the Foundation Fighting Blindness USA (BR-GE-0214-0639-TECH) to D.S. and E.B. R.M.H. is supported by an FFB Career Development Award (CD-CMM-0918-0747-MEEI). This work was also supported by the Excellence Program of the German Government (DFG EXC 307, Center for Integrative Science) to E.Z.; the Tistou and Charlotte Kerstan Foundation to Fadi Nasser; and the German Research Council (DFG, KFO134) and the German Ministry of Education and Research (01GM0850) to B.W. A.V. is supported by the Foundation Fighting Blindness (USA; CD-CL-0617-0727-HSC). E.H. is supported by Henry Brent Chair and Fighting Blindness Canada. The views expressed are those of the authors and not the funding organizations. Financial Disclosures: M.G. and M.M. consult for MeiraGTx. K.F. consults for Astellas Pharma Inc, Kubota Pharmaceutical Holdings Co, Ltd, Acucela Inc, Novartis AG, and Janssen Pharmaceuticals. E. C. consults for AbbVie and Alimera. E.Z. consults for Acucela Inc, IVERIC bio Inc, Janssen Pharmaceuticals, ProQR Therapeutics N.V. Gyroscope Therapeutics Ltd, and Biogen MA Inc. A.V. consults for Adverum Biotechnologies Inc. M.E.P. consults for Spark Therapeutics. S.K. consults for Novartis AG. The rest of the authors have no conflicts of interest to disclose. All authors attest that they meet the current ICMJE criteria for authorship. Publisher Copyright: © 2021 The Authors
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Purpose: To describe the detailed retinal phenotype of KCNV2-associated retinopathy. Study design: Multicenter international retrospective case series. Methods: Review of retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), including qualitative and quantitative analyses. Results: Three distinct macular FAF features were identified: (1) centrally increased signal (n = 35, 41.7%), (2) decreased autofluorescence (n = 27, 31.1%), and (3) ring of increased signal (n = 37, 44.0%). Five distinct FAF groups were identified based on combinations of those features, with 23.5% of patients changing the FAF group over a mean (range) follow-up of 5.9 years (1.9-13.1 years). Qualitative assessment was performed by grading OCT into 5 grades: (1) continuous ellipsoid zone (EZ) (20.5%); (2) EZ disruption (26.1%); (3) EZ absence, without optical gap and with preserved retinal pigment epithelium complex (21.6%); (4) loss of EZ and a hyporeflective zone at the foveola (6.8%); and (5) outer retina and retinal pigment epithelium complex loss (25.0%). Eighty-six patients had scans available from both eyes, with 83 (96.5%) having the same grade in both eyes, and 36.1% changed OCT grade over a mean follow-up of 5.5 years. The annual rate of outer nuclear layer thickness change was similar for right and left eyes. Conclusions: KCNV2-associated retinopathy is a slowly progressive disease with early retinal changes, which are predominantly symmetric between eyes. The identification of a single OCT or FAF measurement as an endpoint to determine progression that applies to all patients may be challenging, although outer nuclear layer thickness is a potential biomarker. Findings suggest a potential window for intervention until 40 years of age.
AB - Purpose: To describe the detailed retinal phenotype of KCNV2-associated retinopathy. Study design: Multicenter international retrospective case series. Methods: Review of retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), including qualitative and quantitative analyses. Results: Three distinct macular FAF features were identified: (1) centrally increased signal (n = 35, 41.7%), (2) decreased autofluorescence (n = 27, 31.1%), and (3) ring of increased signal (n = 37, 44.0%). Five distinct FAF groups were identified based on combinations of those features, with 23.5% of patients changing the FAF group over a mean (range) follow-up of 5.9 years (1.9-13.1 years). Qualitative assessment was performed by grading OCT into 5 grades: (1) continuous ellipsoid zone (EZ) (20.5%); (2) EZ disruption (26.1%); (3) EZ absence, without optical gap and with preserved retinal pigment epithelium complex (21.6%); (4) loss of EZ and a hyporeflective zone at the foveola (6.8%); and (5) outer retina and retinal pigment epithelium complex loss (25.0%). Eighty-six patients had scans available from both eyes, with 83 (96.5%) having the same grade in both eyes, and 36.1% changed OCT grade over a mean follow-up of 5.5 years. The annual rate of outer nuclear layer thickness change was similar for right and left eyes. Conclusions: KCNV2-associated retinopathy is a slowly progressive disease with early retinal changes, which are predominantly symmetric between eyes. The identification of a single OCT or FAF measurement as an endpoint to determine progression that applies to all patients may be challenging, although outer nuclear layer thickness is a potential biomarker. Findings suggest a potential window for intervention until 40 years of age.
UR - http://www.scopus.com/inward/record.url?scp=85108876875&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ajo.2021.03.004
DO - https://doi.org/10.1016/j.ajo.2021.03.004
M3 - Article
C2 - 33737031
SN - 0002-9394
VL - 230
SP - 1
EP - 11
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
ER -