Moorfields Eye Hospital, London, United Kingdom; University College London Institute of Ophthalmology, London, United Kingdom.
Moorfields Eye Hospital, London, United Kingdom; University College London Institute of Ophthalmology, London, United Kingdom; Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Ontario, Japan.
Am J Ophthalmol. 2021 May;225:95-107. doi: 10.1016/j.ajo.2020.11.022. Epub 2020 Dec 11.
To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults.
This was a multicenter international clinical cohort study.
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.
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.
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.
研究 KCNV2 相关视网膜病变在儿童和成人队列中的遗传学、电生理学和临床过程。
这是一项多中心国际临床队列研究。
回顾临床记录和分子遗传学检测。审查并量化全视野视网膜电图（ERG）记录，采用国际标准，并与年龄和对照受试者的记录进行比较。
总共从 117 名患者中鉴定出 230 个疾病相关等位基因，对应于 75 种不同的 KCNV2 变体，其中 28 种是新的。平均发病年龄为 3.9 岁。所有患者在 12 岁之前出现症状（范围 0-11 岁）。所有患者均存在视力下降，其他 4 种症状常见：色觉减退（78.6%）、畏光（53.5%）、夜盲（43.6%）和眼球震颤（38.6%）。在平均 8.4 年的随访后，平均最佳矫正视力（BCVA ± SD）从 0.81 ± 0.27 下降至 0.90 ± 0.31 最小角分辨率对数。全视野 ERG 显示出特征性的波形特征。定量评估显示 ERG 幅度和峰值时间范围广泛，与对照组相比，年龄相关的降低率无明显差异。暗适应 0.01 ERG、暗适应 10 ERG a 波和 LA 3.0 30 Hz 和 LA3 ERG b 波的平均振幅降低分别为 55%、21%、48%和 74%，与对照值相比。峰值时间在 6 个十年跨度内保持稳定。
在 KCNV2 相关视网膜病变中，全视野 ERG 具有诊断价值，与周围视网膜功能障碍基本稳定一致。报告 1 强调了临床表型的严重性，并建立了一个大型患者队列，强调了对新型治疗药物试验的迫切需求。
