Real-world outcomes of voretigene neparvovec treatment in pediatric patients with RPE65-associated Leber congenital amaurosis.
Real-world outcomes of voretigene neparvovec treatment in pediatric patients with RPE65-associated Leber congenital amaurosis.
复制标题
DOI：
10.1007/s00417-021-05508-2
复制
发表时间：
2022-05
影响因子：
2.7
通讯作者：
Besirli, Cagri G.
中科院分区：
文献类型：
--
作者：
Deng, Callie;Zhao, Peter Y.;Branham, Kari;Schlegel, Dana;Fahim, Abigail T.;Jayasundera, Thiran K.;Khan, Naheed;Besirli, Cagri G.
目的：探讨双等位基因RPE65致病变异的儿童患者接受奈帕伏韦克基因治疗的安全性和有效性。对14例(27只眼)RPE65相关性Leber先天性黑色素患者进行了回顾性研究，观察了术后并发症和视网膜下注射voretgene neparvovec后光感受器功能的纵向变化。分别于术前和术后12个月进行全场刺激阈值测试(FST)、Goldmann视野(GVF)、最佳矫正视力(BCVA)和光学相干断层扫描(OCT)中央亚场厚度(CST)检查。通过6~12个月的随访，获得7例13只眼的FST和GVF资料。治疗后每只眼的FST平均改善2.1个对数单位(P<；.001)，GVF每只眼平均改善221个和度(P<；.001)。BCVA从基线的logMAR 0.98改善到最后一次随访的logMAR 0.83(P<；.001)。在纳入CST分析的10名患者的19只眼中，从基线到最后一次随访，平均CST有微小但有统计学意义的9微米的下降(P<；.001)。术后最常见的问题包括眼压升高(59%)，持续性眼内炎症(15%)和玻璃体混浊(26%)，这些问题在几个月内消失。这份报告提供了一些最早的纵向真实世界证据，使用视网膜的多种功能和结构测量来证明voretgene neparvovec的儿科安全性和有效性。结果显示视觉功能显著改善，与临床试验结果一致。
To investigate real-world safety and efficacy of voretigene neparvovec gene therapy administration in pediatric patients with biallelic RPE65 disease-causing variants. A retrospective study of 27 eyes of 14 patients with RPE65-associated Leber congenital amaurosis examined post-operative complications and longitudinal changes in photoreceptor function following treatment with subretinal injection of voretigene neparvovec. Full-field stimulus threshold testing (FST), Goldmann visual fields (GVF), best corrected visual acuity (BCVA), and central subfield thickness (CST) on optical coherence tomography (OCT) scans were collected pre-operatively and up to 12 months post-treatment. Baseline through 6-12 month follow-up FST and GVF data were obtained for 13 eyes of 7 patients. FST improved for each eye after treatment with mean improvement of 2.1 log-units (P < .001) and GVF improved for each eye with mean improvement of 221 sum-degrees (P <.001). BCVA improved from logMAR 0.98 at baseline to logMAR 0.83 at last follow-up (P < .001). Across 19 eyes of 10 patients included in CST analysis, there was a small but statistically significant 9 micron decrease in mean CST from baseline to last follow-up (P < .001). The most common postoperative issues included elevation in intraocular pressure (59%), persistent intraocular inflammation (15%) and vitreous opacities (26%) that resolved over a period of months. This report provides some of the earliest longitudinal real-world evidence of the pediatric safety and efficacy of voretigene neparvovec using multiple functional and structural measures of the retina. Outcomes demonstrate significant improvements in visual function consistent with clinical trial results.
登录
查看更多内容
影响因子：
17.8
作者：
Berger, Wolfgang;Kloeckener-Gruissem, Barbara;Neidhardt, John
通讯作者：
Neidhardt, John
DOI：
10.2147/opth.s231804
发表时间：
2020
期刊：
Clinical ophthalmology (Auckland, N.Z.)
影响因子：
--
作者：
Gao J;Hussain RM;Weng CY
通讯作者：
Weng CY
影响因子：
4.6
作者：
Fujiwara K;Ikeda Y;Murakami Y;Tachibana T;Funatsu J;Koyanagi Y;Nakatake S;Yoshida N;Nakao S;Hisatomi T;Yoshida S;Yoshitomi T;Ishibashi T;Sonoda KH
通讯作者：
Sonoda KH
影响因子：
4.2
作者：
Chung, Daniel C.;Bertelsen, Mette;Reape, Kathleen Z.
通讯作者：
Reape, Kathleen Z.
影响因子：
4
作者：
Chung, Daniel C.;McCague, Sarah;High, Katherine A.
通讯作者：
High, Katherine A.