KCNV2-Associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints—KCNV2 Study Group Report 2

Michalis Georgiou, Kaoru Fujinami, Ajoy Vincent, Fadi Nasser, Samer Khateb, Mauricio E. Vargas, Alberta A.H.J. Thiadens, Emanuel R. de Carvalho, Xuan Thanh An Nguyen, Thales Antônio Cabral De Guimarães, Anthony G. Robson, Omar A. Mahroo, Nikolas Pontikos, Gavin Arno, Yu Fujinami-Yokokawa, Shaun Michael Leo, Xiao Liu, Kazushige Tsunoda, Takaaki Hayashi, Belen Jimenez-RolandoMaria Inmaculada Martin-Merida, Almudena Avila-Fernandez, Ester Carreño, Blanca Garcia-Sandoval, Carmen Ayuso, Dror Sharon, Susanne Kohl, Rachel M. Huckfeldt, Camiel J.F. Boon, Eyal Banin, Mark E. Pennesi, Bernd Wissinger, Andrew R. Webster, Elise Héon, Arif O. Khan, Eberhart Zrenner, Michel Michaelides*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalAmerican Journal of Ophthalmology
Publication statusPublished - 1 Oct 2021

Bibliographical note

Funding Information:
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.

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