TY - JOUR
T1 - KCNV2-Associated Retinopathy
T2 - Genetics, Electrophysiology, and Clinical Course—KCNV2 Study Group Report 1
AU - Georgiou, Michalis
AU - Robson, Anthony G.
AU - Fujinami, Kaoru
AU - Leo, Shaun M.
AU - Vincent, Ajoy
AU - Nasser, Fadi
AU - Cabral De Guimarães, Thales Antônio
AU - Khateb, Samer
AU - Pontikos, Nikolas
AU - Fujinami-Yokokawa, Yu
AU - Liu, Xiao
AU - Tsunoda, Kazushige
AU - Hayashi, Takaaki
AU - Vargas, Mauricio E.
AU - Thiadens, Alberta A.H.J.
AU - de Carvalho, Emanuel R.
AU - Nguyen, Xuan Thanh An
AU - Arno, Gavin
AU - Mahroo, Omar A.
AU - Martin-Merida, Maria Inmaculada
AU - Jimenez-Rolando, Belen
AU - Gordo, Gema
AU - Carreño, Ester
AU - Carmen, Ayuso
AU - Sharon, Dror
AU - Kohl, Susanne
AU - Huckfeldt, Rachel M.
AU - Wissinger, Bernd
AU - Boon, Camiel J.F.
AU - Banin, Eyal
AU - Pennesi, Mark E.
AU - Khan, Arif O.
AU - Webster, Andrew R.
AU - Zrenner, Eberhart
AU - Héon, Elise
AU - Michaelides, Michel
N1 - Publisher Copyright:
© 2020 The Author(s)
PY - 2021/5
Y1 - 2021/5
N2 - Purpose: To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults. Study design: This was a multicenter international clinical cohort study. Methods: Review of clinical notes and molecular genetic testing. Full-field electroretinography (ERG) recordings, incorporating the international standards, were reviewed and quantified and compared with age and recordings from control subjects. Results: In total, 230 disease-associated alleles were identified from 117 patients, corresponding to 75 different KCNV2 variants, with 28 being novel. The mean age of onset was 3.9 years old. All patients were symptomatic before 12 years of age (range, 0-11 years). Decreased visual acuity was present in all patients, and 4 other symptoms were common: reduced color vision (78.6%), photophobia (53.5%), nyctalopia (43.6%), and nystagmus (38.6%). After a mean follow-up of 8.4 years, the mean best-corrected visual acuity (BCVA ± SD) decreased from 0.81 ± 0.27 to 0.90 ± 0.31 logarithm of minimal angle of resolution. Full-field ERGs showed pathognomonic waveform features. Quantitative assessment revealed a wide range of ERG amplitudes and peak times, with a mean rate of age-associated reduction indistinguishable from the control group. Mean amplitude reductions for the dark-adapted 0.01 ERG, dark-adapted 10 ERG a-wave, and LA 3.0 30 Hz and LA3 ERG b-waves were 55%, 21%, 48%, and 74%, respectively compared with control values. Peak times showed stability across 6 decades. Conclusion: In KCNV2-associated retinopathy, full-field ERGs are diagnostic and consistent with largely stable peripheral retinal dysfunction. Report 1 highlights the severity of the clinical phenotype and established a large cohort of patients, emphasizing the unmet need for trials of novel therapeutics.
AB - Purpose: To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults. Study design: This was a multicenter international clinical cohort study. Methods: Review of clinical notes and molecular genetic testing. Full-field electroretinography (ERG) recordings, incorporating the international standards, were reviewed and quantified and compared with age and recordings from control subjects. Results: In total, 230 disease-associated alleles were identified from 117 patients, corresponding to 75 different KCNV2 variants, with 28 being novel. The mean age of onset was 3.9 years old. All patients were symptomatic before 12 years of age (range, 0-11 years). Decreased visual acuity was present in all patients, and 4 other symptoms were common: reduced color vision (78.6%), photophobia (53.5%), nyctalopia (43.6%), and nystagmus (38.6%). After a mean follow-up of 8.4 years, the mean best-corrected visual acuity (BCVA ± SD) decreased from 0.81 ± 0.27 to 0.90 ± 0.31 logarithm of minimal angle of resolution. Full-field ERGs showed pathognomonic waveform features. Quantitative assessment revealed a wide range of ERG amplitudes and peak times, with a mean rate of age-associated reduction indistinguishable from the control group. Mean amplitude reductions for the dark-adapted 0.01 ERG, dark-adapted 10 ERG a-wave, and LA 3.0 30 Hz and LA3 ERG b-waves were 55%, 21%, 48%, and 74%, respectively compared with control values. Peak times showed stability across 6 decades. Conclusion: In KCNV2-associated retinopathy, full-field ERGs are diagnostic and consistent with largely stable peripheral retinal dysfunction. Report 1 highlights the severity of the clinical phenotype and established a large cohort of patients, emphasizing the unmet need for trials of novel therapeutics.
UR - http://www.scopus.com/inward/record.url?scp=85101977838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101977838&partnerID=8YFLogxK
U2 - 10.1016/j.ajo.2020.11.022
DO - 10.1016/j.ajo.2020.11.022
M3 - Article
C2 - 33309813
AN - SCOPUS:85101977838
SN - 0002-9394
VL - 225
SP - 95
EP - 107
JO - American journal of ophthalmology
JF - American journal of ophthalmology
ER -