Spatial and temporal resolution of the photoreceptors rescue dynamics after treatment with voretigene neparvovec.
Spatial and temporal resolution of the photoreceptors rescue dynamics after treatment with voretigene neparvovec.
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DOI：
10.1136/bjophthalmol-2020-318286
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发表时间：
2022-06
影响因子：
4.1
通讯作者：
Stingl, Katarina
中科院分区：
文献类型：
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作者：
Stingl, Krunoslav;Kempf, Melanie;Bartz-Schmidt, Karl U.;Dimopoulos, Spyridon;Reichel, Felix;Jung, Ronja;Kelbsch, Carina;Kohl, Susanne;Kortuem, Friederike Charlotte;Nasser, Fadi;Peters, Tobias;Wilhelm, Barbara;Wissinger, Bernd;Wozar, Fabian;Zrenner, Eberhart;Fischer, M. Dominik;Stingl, Katarina
Voretigene neparvovec是一种基因治疗剂，用于治疗由双等位基因RPE65突变引起的视网膜营养不良。在这项研究中，我们报告了一种新的和客观的评价视网膜异位光感受器抢救。对5例双等位基因RPE65突变患者（14、21、23、24、36岁，1男，4女）7眼进行了voretigene neparvovec治疗。临床检查包括视力测试、暗适应全场刺激阈值（FST）、暗适应30度网格色度周长（DAC）、30度网格暗位光致色度瞳孔测量（CPC）。在基线、1个月和3个月进行所有评估和光谱域光学相干断层扫描。除年龄最大的患者外，所有患者在1个月时通过FST， DAC或scotopcpc评估杆状体功能均有可测量的改善。所有眼睛的视力略有改善或保持稳定。三眼视锥细胞功能明显改善。蓝色FST和DAC刺激（青色）的暗适应阈值的增益与年龄有很强的相关性（R2 >.7）。暗位CPC患者的瞳孔反应改善与基线局部视网膜体积相关（R2=0.5）。提出的方案允许评估基因治疗效果的个体空间和时间效应。此外，我们还探讨了与治疗成功相关的参数。CPC和DAC提供了新的和快速的方法来评估视杆和视锥功能的功能变化，测量视网膜功能的互补方面。
Voretigene neparvovec is a gene therapeutic agent for treatment of retinal dystrophies caused by bi-allelic RPE65 mutations. In this study, we report on a novel and objective evaluation of a retinotopic photoreceptor rescue. Seven eyes of five patients (14, 21, 23, 24, 36 years, 1 male, 4 females) with bi-allelic RPE65 mutations have been treated with voretigene neparvovec. The clinical examinations included visual acuity testing, dark-adapted full-field stimulus threshold (FST), dark-adapted chromatic perimeter (DAC) with a 30-degree grid, and a 30 degrees grid scotopic and photopic chromatic pupil campimetry (CPC). All evaluations and spectral domain optical coherence tomography were performed at baseline, 1 month and 3 months. All except the oldest patient had a measurable improvement of the rod function assessed via FST, DAC or scotopic CPC at 1 month. The visual acuity improved slightly or remained stable in all eyes. A cone function improvement as measured by photopic CPC was observed in three eyes. The gain of the dark-adapted threshold with blue FST and the DAC stimuli (cyan) average correlated strongly with age (R2>0.7). The pupil response improvement in the scotopic CPC correlated with the baseline local retinal volume (R2=0.5). The presented protocols allow evaluating the individual spatial and temporal effects of gene therapy effects. Additionally, we explored parameters that correlated with the success of the therapy. CPC and DAC present new and fast ways to assess functional changes in retinotopic maps of rod and cone function, measuring complementary aspects of retinal function.
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DOI：
10.1038/mt.2009.277
发表时间：
2010-03
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
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影响因子：
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作者：
Jacobson, Samuel G.;Cideciyan, Artur V.;Ratnakaram, Ramakrishna;Heon, Elise;Schwartz, Sharon B.;Roman, Alejandro J.;Peden, Marc C.;Aleman, Tomas S.;Boye, Sanford L.;Sumaroka, Alexander;Conlon, Thomas J.;Calcedo, Roberto;Pang, Ji-Jing;Erger, Kirsten E.;Olivares, Melani B.;Mullins, Cristina L.;Swider, Malgorzata;Kaushal, Shalesh;Feuer, William J.;Iannaccone, Alessandro;Fishman, Gerald A.;Stone, Edwin M.;Byrne, Barry J.;Hauswirth, William W.
通讯作者：
Hauswirth, William W.
影响因子：
3
作者：
Kelbsch, Carina;Stingl, Katarina;Stingl, Krunoslav
通讯作者：
Stingl, Krunoslav
影响因子：
13.7
作者：
Lorenz, B;Wabbels, B;Preising, MN
通讯作者：
Preising, MN